Life | Editor’s choice Articles

15 pages, 1706 KB

Open AccessEditor’s ChoiceReview

Liver Transplantation in People Living with HIV: Still an Experimental Procedure or Standard of Care?

by Erica Nicola Lynch and Francesco Paolo Russo

Life 2023, 13(10), 1975; https://doi.org/10.3390/life13101975 - 27 Sep 2023

Cited by 4 | Viewed by 3639

Liver transplantation (LT) is the only curative treatment for various liver diseases, including acute liver failure, end-stage liver disease, and selected unresectable liver malignancies. Combination antiretroviral therapy has improved outcomes for people living with HIV (PLWH), transforming the status of acquired immune deficiency [...] Read more.

Liver transplantation (LT) is the only curative treatment for various liver diseases, including acute liver failure, end-stage liver disease, and selected unresectable liver malignancies. Combination antiretroviral therapy has improved outcomes for people living with HIV (PLWH), transforming the status of acquired immune deficiency syndrome from a fatal disease to a chronic and manageable condition. These powerful antiviral therapies have not only increased the number of HIV+ enlisted patients by improving their survival but also made the use of HIV+ organs a viable option. In this review, we summarise current knowledge on the peculiarities of liver transplantation in PLWH. In particular, we focus on the indications, contraindications, specific considerations for treatment, and outcomes of LT in PLWH. Finally, we present available preliminary data on the use of HIV+ liver allografts. Full article

(This article belongs to the Special Issue New Scenarios in Liver Transplantation)

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13 pages, 765 KB

Open AccessEditor’s ChoiceArticle

Occupational Exposure during Pregnancy and Effects on Newborns: A Nested Case-Control Study

by Gabriele Donzelli, Beatriz Marcos-Puig, Isabel Peraita-Costa, Juan Llopis-Morales and María Morales-Suarez-Varela

Life 2023, 13(10), 1962; https://doi.org/10.3390/life13101962 - 26 Sep 2023

Cited by 3 | Viewed by 3082

Abstract

Background: The protection of pregnant workers should be based on evidence regarding the risks to reproductive health from exposure to specific work environments and conditions. The objective of this study was to identify the effects on mothers and newborns resulting from environmental exposure [...] Read more.

Background: The protection of pregnant workers should be based on evidence regarding the risks to reproductive health from exposure to specific work environments and conditions. The objective of this study was to identify the effects on mothers and newborns resulting from environmental exposure to various occupational risks. Methods: The study cohort was composed of 399 women admitted to the Obstetrics/Postpartum ward at Hospital La Fe in Valencia, Spain. Face-to-face interviews were conducted to establish associations between workplace exposure during pregnancy and its effects on maternal and newborn health. Sex, anthropometric characteristics, and blood gas analysis in arterial and venous umbilical cord blood at delivery were collected. Results: A total of 138 women were exposed to biological and/or chemical risks, 122 to physical risks, and 139 at no risk of exposure. In the group with chemical and/or biological risks, the frequency of women who resorted to in vitro fertilization to achieve the studied pregnancy is less than half of the group exposed to physical risks, with statistically significant differences (p = 0.047). The mean values for the arterial analysis in both exposure groups were within average values, with similar pH values between them, but the mean values of PCO2 and PO2 were lower in the group of neonates of mothers exposed to physical risks, with a significant difference for arterial PO2 (p = 0.027). Conclusion: Our analysis contributes evidence for planning and prioritizing preventive actions to protect women’s reproductive health. The results suggest the continuation of a future project that would consider more factors and potentially increase the sample size. Full article

(This article belongs to the Section Epidemiology)

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22 pages, 3698 KB

Open AccessEditor’s ChoiceSystematic Review

The Role of Bifidobacterium in COVID-19: A Systematic Review

by Clarissa Reginato Taufer and Pabulo Henrique Rampelotto

Life 2023, 13(9), 1847; https://doi.org/10.3390/life13091847 - 31 Aug 2023

Cited by 6 | Viewed by 5330

Abstract

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, mainly causes respiratory and intestinal symptoms and changes in the microbiota of patients. We performed a systematic search in major databases using “Bifidobacterium” and “COVID-19” or “SARS-CoV-2” as key terms to assess the [...] Read more.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, mainly causes respiratory and intestinal symptoms and changes in the microbiota of patients. We performed a systematic search in major databases using “Bifidobacterium” and “COVID-19” or “SARS-CoV-2” as key terms to assess the relationship of the genus to COVID-19. After the selection steps, 25 articles were analyzed. Of these, eighteen were observational, and seven were interventional articles that evaluated the use of Bifidobacterium alone or in mix as probiotics for additional treatment of patients with COVID-19. All stages and severities were contemplated, including post-COVID-19 patients. Overall, Bifidobacterium was associated with both protective effects and reduced abundance in relation to the disease. The genus has been found to be abundant in some cases and linked to disease severity. The studies evaluating the use of Bifidobacterium as probiotics have demonstrated the potential of this genus in reducing symptoms, improving pulmonary function, reducing inflammatory markers, alleviating gastrointestinal symptoms, and even contributing to better control of mortality. In summary, Bifidobacterium may offer protection against COVID-19 through its ability to modulate the immune response, reduce inflammation, compete with pathogenic microbes, and maintain gut barrier function. The findings provide valuable insights into the relationship between the disease and the genus Bifidobacterium, highlighting the potential of microbiota modulation in the treatment of COVID-19. Full article

(This article belongs to the Collection Feature Papers in Microbiology)

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12 pages, 4743 KB

Open AccessEditor’s ChoiceArticle

Novel Compounds Derived from DFPM Induce Root Growth Arrest through the Specific VICTR Alleles of Arabidopsis Accessions

by Seojung Kim, Miri Cho and Tae-Houn Kim

Life 2023, 13(9), 1797; https://doi.org/10.3390/life13091797 - 23 Aug 2023

Viewed by 1542

Abstract

The small compound [5-(3,4-dichlorophenyl) furan-2-yl]-piperidine-1-ylmethanethione (DFPM) inhibits ABA responses by activating effector-triggered immune signal transduction in Arabidopsis. In addition to the known function of DFPM as an antagonist of ABA signaling, DFPM causes accession-specific root growth arrest in Arabidopsis Columbia-0 via the TIR-NLR [...] Read more.

The small compound [5-(3,4-dichlorophenyl) furan-2-yl]-piperidine-1-ylmethanethione (DFPM) inhibits ABA responses by activating effector-triggered immune signal transduction in Arabidopsis. In addition to the known function of DFPM as an antagonist of ABA signaling, DFPM causes accession-specific root growth arrest in Arabidopsis Columbia-0 via the TIR-NLR protein VICTR (VARIATION IN COMPOUND TRIGGERED ROOT growth response) in an EDS1/PAD4/RAR1/SGT1B-dependent manner. Although DFPM could control the specific steps of various cellular responses, the functional residues for the activity of DFPM or the existence of a stronger version of DFPM modification have not been characterized thoroughly. This study analyzed twenty-two DFPM derivatives during root growth arrest, inhibition of ABA signaling, and induction of biotic signal transduction to determine critical residues that confer the specific activity of DFPM. Furthermore, this study identified two more Arabidopsis accessions that generate significant root growth arrest in response to DFPM derivatives dependent on multiple amino acid polymorphisms in the coding region of VICTR. The isolation of novel compounds, such as DFPM-5, and specific amino acid polymorphisms critical for the compound-induced responses will help determine the detailed regulatory mechanism for how DFPM regulates abiotic and biotic stress signaling interactions. Full article

(This article belongs to the Special Issue Abiotic Stress in Plants_Life)

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22 pages, 1361 KB

Open AccessEditor’s ChoiceReview

Extracellular Vesicles as Surrogates for Drug Metabolism and Clearance: Promise vs. Reality

by Anna Gagliardi, Gzona Bajraktari-Sylejmani, Elisabetta Barocelli, Johanna Weiss and Juan Pablo Rigalli

Life 2023, 13(8), 1745; https://doi.org/10.3390/life13081745 - 14 Aug 2023

Cited by 5 | Viewed by 2937

Abstract

Drug-metabolizing enzymes (DMEs) and transporters play a major role in drug efficacy and safety. They are regulated at multiple levels and by multiple factors. Estimating their expression and activity could contribute to predicting drug pharmacokinetics and their regulation by drugs or pathophysiological situations. [...] Read more.

Drug-metabolizing enzymes (DMEs) and transporters play a major role in drug efficacy and safety. They are regulated at multiple levels and by multiple factors. Estimating their expression and activity could contribute to predicting drug pharmacokinetics and their regulation by drugs or pathophysiological situations. Determining the expression of these proteins in the liver, intestine, and kidney requires the collection of biopsy specimens. Instead, the isolation of extracellular vesicles (EVs), which are nanovesicles released by most cells and present in biological fluids, could deliver this information in a less invasive way. In this article, we review the use of EVs as surrogates for the expression and activity of DMEs, uptake, and efflux transporters. Preliminary evidence has been provided for a correlation between the expression of some enzymes and transporters in EVs and the tissue of origin. In some cases, data obtained in EVs reflect the induction of phase I-DMEs in the tissues. Further studies are required to elucidate to what extent the regulation of other DMEs and transporters in the tissues reflects in the EV cargo. If an association between tissues and their EVs is firmly established, EVs may represent a significant advancement toward precision therapy based on the biotransformation and excretion capacity of each individual. Full article

(This article belongs to the Special Issue New Insights into Extracellular Vesicles in Health and Disease)

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12 pages, 2023 KB

Open AccessEditor’s ChoiceArticle

Evaluation of Rapid Multiplex Reverse Transcription-Quantitative Polymerase Chain Reaction Assays for SARS-CoV-2 Detection in Individual and Pooled Samples

by Young-Hyun Baek, Min-Young Park, Ho-Jae Lim, Dong-Jae Youm, Youngshin You, Seojin Ahn, Jung-Eun Park, Min-Jin Kim, Sun-Hwa Lee, Yong-Hak Sohn and Yong-Jin Yang

Life 2023, 13(8), 1717; https://doi.org/10.3390/life13081717 - 10 Aug 2023

Viewed by 1839

Abstract

Although coronavirus disease 2019 (COVID-19) is no longer a Public Health Emergency of International Concern (PHEIC), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has had a vast impact to date. Hence, continuous management is required, given the uncertainty caused by the potential [...] Read more.

Although coronavirus disease 2019 (COVID-19) is no longer a Public Health Emergency of International Concern (PHEIC), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has had a vast impact to date. Hence, continuous management is required, given the uncertainty caused by the potential evolution of SARS-CoV-2. Reverse transcription-quantitative PCR (RT-qPCR) diagnosis has been fundamental in overcoming this issue. In this study, the performances of two rapid RT-qPCR assays (Real-Q Direct SARS-CoV-2 Detection Kit and Allplex™ SARS-CoV-2 fast PCR Assay) with short PCR times were comparatively evaluated using a STANDARD M nCoV Real-Time Detection Kit (STANDARD M, conventional RT-qPCR assay). All kits showed a limit of detection values (10²–10³ copies/reaction). The evaluation showed that the two rapid assay tests had ≥97.89% sensitivity and ≥99.51% specificity (κ = 0.98) for individual samples and ≥97.32% sensitivity and ≥97.67% specificity for pooled samples compared to STANDARD M. These results indicate that the two rapid RT-qPCR kits, which showed significant time reduction in performance, are as effective as a conventional RT-qPCR assay. They are likely to increase not only the number of tests that can be performed but also the efficiency of sustainable management of COVID-19 in the long term. Full article

(This article belongs to the Special Issue COVID-19 and SARS-CoV-2 Investigations: Characteristics, Clinical Course, Prevention, Treatment and Prognosis)

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14 pages, 2314 KB

Open AccessEditor’s ChoiceArticle

Unexpected Adverse Events of Immune Checkpoint Inhibitors

by Walid Shalata, Alexander Yakobson, Aharon Y. Cohen, Iris Goldstein, Omar Abu Saleh, Yulia Dudnik and Keren Rouvinov

Life 2023, 13(8), 1657; https://doi.org/10.3390/life13081657 - 29 Jul 2023

Cited by 8 | Viewed by 3371

Abstract

The introduction of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment standards and significantly enhanced patient prognoses. However, the utilization of these groundbreaking therapies has led to the observation and reporting of various types of adverse events, commonly known as immune-related adverse events [...] Read more.

The introduction of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment standards and significantly enhanced patient prognoses. However, the utilization of these groundbreaking therapies has led to the observation and reporting of various types of adverse events, commonly known as immune-related adverse events (irAEs). In the following article, we present four patients who encountered uncommon toxicities induced by ICIs. The first patient was a 59-year-old female diagnosed with stage 4 lung adenocarcinoma. She received immunotherapy (pembrolizumab) together with chemotherapy and subsequently developed autonomic neuropathy (AN). The next two patients also received chemo-immunotherapy (pembrolizumab) and were both 63-year-old males with stage 4 lung adenocarcinoma. One of the two experienced palmoplantar keratoderma, while the other presented with Reiter’s syndrome (urethritis, conjunctivitis and arthritis). The 4th patient, an 80-year-old male with stage 4 squamous cell carcinoma of the lung, received chemo-immunotherapy (pembrolizumab) and developed myasthenia gravis. Full article

(This article belongs to the Special Issue Drug Interactions in Cancer Therapy)

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43 pages, 1636 KB

Open AccessEditor’s ChoiceReview

The Cytotoxic Properties of Extreme Fungi’s Bioactive Components—An Updated Metabolic and Omics Overview

by Attila Kiss, Farhad Hariri Akbari, Andrey Marchev, Viktor Papp and Iman Mirmazloum

Life 2023, 13(8), 1623; https://doi.org/10.3390/life13081623 - 25 Jul 2023

Cited by 5 | Viewed by 4012

Abstract

Fungi are the most diverse living organisms on planet Earth, where their ubiquitous presence in various ecosystems offers vast potential for the research and discovery of new, naturally occurring medicinal products. Concerning human health, cancer remains one of the leading causes of mortality. [...] Read more.

Fungi are the most diverse living organisms on planet Earth, where their ubiquitous presence in various ecosystems offers vast potential for the research and discovery of new, naturally occurring medicinal products. Concerning human health, cancer remains one of the leading causes of mortality. While extensive research is being conducted on treatments and their efficacy in various stages of cancer, finding cytotoxic drugs that target tumor cells with no/less toxicity toward normal tissue is a significant challenge. In addition, traditional cancer treatments continue to suffer from chemical resistance. Fortunately, the cytotoxic properties of several natural products derived from various microorganisms, including fungi, are now well-established. The current review aims to extract and consolidate the findings of various scientific studies that identified fungi-derived bioactive metabolites with antitumor (anticancer) properties. The antitumor secondary metabolites identified from extremophilic and extremotolerant fungi are grouped according to their biological activity and type. It became evident that the significance of these compounds, with their medicinal properties and their potential application in cancer treatment, is tremendous. Furthermore, the utilization of omics tools, analysis, and genome mining technology to identify the novel metabolites for targeted treatments is discussed. Through this review, we tried to accentuate the invaluable importance of fungi grown in extreme environments and the necessity of innovative research in discovering naturally occurring bioactive compounds for the development of novel cancer treatments. Full article

(This article belongs to the Collection Bacterial Infections, Treatment and Antibiotic Resistance)

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13 pages, 1707 KB

Open AccessEditor’s ChoiceReview

Cerebral Vasomotor Reactivity in COVID-19: A Narrative Review

by Zahra Ghotbi, Mehrdad Estakhr, Melika Hosseini and Reza Bavarsad Shahripour

Life 2023, 13(7), 1614; https://doi.org/10.3390/life13071614 - 24 Jul 2023

Cited by 4 | Viewed by 3472

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the respiratory system but can also lead to neurological complications. Among COVID-19 patients, the endothelium is considered the Achilles heel. A variety of endothelial dysfunctions may result from SARS-CoV-2 infection and subsequent endotheliitis, such [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the respiratory system but can also lead to neurological complications. Among COVID-19 patients, the endothelium is considered the Achilles heel. A variety of endothelial dysfunctions may result from SARS-CoV-2 infection and subsequent endotheliitis, such as altered vascular tone, oxidative stress, and cytokine storms. The cerebral hemodynamic impairment that is caused is associated with a higher probability of severe disease and poor outcomes in patients with COVID-19. This review summarizes the most relevant literature on the role of vasomotor reactivity (VMR) in COVID-19 patients. An overview of the research articles is presented. Most of the studies have supported the hypothesis that endothelial dysfunction and cerebral VMR impairment occur in COVID-19 patients. Researchers believe these alterations may be due to direct viral invasion of the brain or indirect effects, such as inflammation and cytokines. Recently, researchers have concluded that viruses such as the Human Herpes Virus 8 and the Hantavirus predominantly affect endothelial cells and, therefore, affect cerebral hemodynamics. Especially in COVID-19 patients, impaired VMR is associated with a higher risk of severe disease and poor outcomes. Using VMR, one can gain valuable insight into a patient’s disease progression and make more informed decisions regarding appropriate treatment options. A new pandemic may develop with the COVID-19 virus or other viruses, making it essential that healthcare providers and researchers remain focused on developing new strategies for improving survival in such patients, particularly those with cerebrovascular risk factors. Full article

(This article belongs to the Special Issue Stroke and COVID-19: Pathophysiological Links, Clinical Implications and Stroke Care in Times of the Pandemic)

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14 pages, 1436 KB

Open AccessEditor’s ChoiceReview

Current Nuclear Engineering Strategies in the Green Microalga Chlamydomonas reinhardtii

by Federico Perozeni and Thomas Baier

Life 2023, 13(7), 1566; https://doi.org/10.3390/life13071566 - 15 Jul 2023

Cited by 13 | Viewed by 4054

Abstract

The green model microalga Chlamydomonas reinhardtii recently emerged as a sustainable production chassis for the efficient biosynthesis of recombinant proteins and high-value metabolites. Its capacity for scalable, rapid and light-driven growth in minimal salt solutions, its simplicity for genetic manipulation and its “Generally [...] Read more.

The green model microalga Chlamydomonas reinhardtii recently emerged as a sustainable production chassis for the efficient biosynthesis of recombinant proteins and high-value metabolites. Its capacity for scalable, rapid and light-driven growth in minimal salt solutions, its simplicity for genetic manipulation and its “Generally Recognized As Safe” (GRAS) status are key features for its application in industrial biotechnology. Although nuclear transformation has typically resulted in limited transgene expression levels, recent developments now allow the design of powerful and innovative bioproduction concepts. In this review, we summarize the main obstacles to genetic engineering in C. reinhardtii and describe all essential aspects in sequence adaption and vector design to enable sufficient transgene expression from the nuclear genome. Several biotechnological examples of successful engineering serve as blueprints for the future establishment of C. reinhardtii as a green cell factory. Full article

(This article belongs to the Special Issue Algae Biotechnology: Green Chemistry for High-Value Products)

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17 pages, 1612 KB

Open AccessEditor’s ChoiceArticle

Variation of Circulating Brain-Derived Neurotrophic Factor (BDNF) in Depression: Relationships with Inflammatory Indices, Metabolic Status and Patients’ Clinical Features

by Valentina Falaschi, Lionella Palego, Donatella Marazziti, Laura Betti, Laura Musetti, Alessandra Maglio, Valerio Dell’Oste, Simona Sagona, Antonio Felicioli, Barbara Carpita, Alberto Brogi, Federico Mucci, Enrico Massimetti, Liliana Dell’Osso and Gino Giannaccini

Life 2023, 13(7), 1555; https://doi.org/10.3390/life13071555 - 13 Jul 2023

Cited by 7 | Viewed by 3008

Abstract

This study seeks to offer a contribution to the method of subtyping major depressed patients by exploring the possible relationships between circulating brain-derived neurotrophic factor (BDNF), different peripheral inflammatory/metabolic markers in the blood and clinical characteristics. Thirty-nine patients, thoroughly diagnosed according to the [...] Read more.

This study seeks to offer a contribution to the method of subtyping major depressed patients by exploring the possible relationships between circulating brain-derived neurotrophic factor (BDNF), different peripheral inflammatory/metabolic markers in the blood and clinical characteristics. Thirty-nine patients, thoroughly diagnosed according to the DSM-5 criteria, underwent a comprehensive set of evaluations encompassing structured interviews, rating scales and a panel of blood tests. Correlation and comparison analyses were carried out by means of non-parametric statistical tests. Concurrently, a principal component analysis was performed to explain biochemical variance. The findings of our research unveiled that leukocyte counts, their ratios and other inflammatory parameters are positively correlated with depression scores. Moreover, we found variations within the BDNF pools of depressed patients. Specifically, higher levels of platelet-poor plasma BDNF (PPP-BDNF) were correlated with augmented inflammatory markers in patients showing specific episode characteristics, whereas reduced platelet BDNF (PLT-BDNF) provided a better indication of the changes that were linked to a diagnosis of long-term depression. Our findings suggest that PPP-BDNF and PLT-BDNF might differentiate depression conditions. They also imply usefulness in appraising peripheral biomarker profiles in patients for a deeper characterization of major depressive episodes. At the same time, it is plausible that they might constitute novel avenues for developing more tailored therapeutic strategies for patients with MDs. Full article

(This article belongs to the Section Pharmaceutical Science)

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11 pages, 260 KB

Open AccessEditor’s ChoiceReview

Pathophysiology of Acute Coronary Syndromes—Diagnostic and Treatment Considerations

by Panagiotis Theofilis, Evangelos Oikonomou, Christos Chasikidis, Konstantinos Tsioufis and Dimitris Tousoulis

Life 2023, 13(7), 1543; https://doi.org/10.3390/life13071543 - 12 Jul 2023

Cited by 16 | Viewed by 9372

Abstract

Coronary artery disease and acute coronary syndromes are accountable for significant morbidity and mortality, despite the preventive measures and technological advancements in their management. Thus, it is mandatory to further explore the pathophysiology in order to provide tailored and more effective therapies, since [...] Read more.

Coronary artery disease and acute coronary syndromes are accountable for significant morbidity and mortality, despite the preventive measures and technological advancements in their management. Thus, it is mandatory to further explore the pathophysiology in order to provide tailored and more effective therapies, since acute coronary syndrome pathogenesis is more varied than previously assumed. It consists of plaque rupture, plaque erosion, and calcified nodules. The advancement of vascular imaging tools has been critical in this regard, redefining the epidemiology of each mechanism. When it comes to acute coronary syndrome management, the presence of ruptured plaques almost always necessitates emergent reperfusion, whereas the presence of plaque erosions may indicate the possibility of conservative management with potent antiplatelet and anti-atherosclerotic medications. Calcified nodules, on the other hand, are an uncommon phenomenon that has largely gone unexplored in terms of the best management plan. Future studies should further establish the importance of detecting the underlying mechanism and the role of various treatment plans in each of these distinct entities. Full article

(This article belongs to the Section Medical Research)

7 pages, 348 KB

Open AccessEditor’s ChoiceCase Report

A Case of Delirious Mania Treated with Electroconvulsive Therapy

by Beniamino Tripodi, Manuel Glauco Carbone, Irene Matarese, Lorenzo Lattanzi and Pierpaolo Medda

Life 2023, 13(7), 1544; https://doi.org/10.3390/life13071544 - 12 Jul 2023

Cited by 2 | Viewed by 2492

Abstract

(1) Background: Delirious mania is a neuropsychiatric condition characterized by the rapid onset of delirium, psychosis, and mania. Due to the presence of catatonic signs and symptoms, some authors considered this syndrome to be a specific excited catatonia subtype. Usually, delirious mania is [...] Read more.

(1) Background: Delirious mania is a neuropsychiatric condition characterized by the rapid onset of delirium, psychosis, and mania. Due to the presence of catatonic signs and symptoms, some authors considered this syndrome to be a specific excited catatonia subtype. Usually, delirious mania is responsive to intravenous benzodiazepines (BZDs) or to electroconvulsive therapy (ECT). (2) Methods: In the present study, we describe the case of a 64-year-old woman with a diagnosis of recurrent major depressive disorder. We assessed the severity of the clinical picture and the response to ECT treatment with the Bush–Francis Catatonia Rating Scale (BFCRS). (3) Results: After eleven sessions of ECT, the patient presented a reduced BFCRS total score, with a resolution of the autonomic abnormalities (temperature, respiratory, and heart rate). (4) Conclusions: These data demonstrate how important it is to diagnose this syndrome as soon as possible to set up an effective therapy, avoiding the use of antipsychotic drugs and preventing potentially fatal complications. The initial administration of BZDs IV and the subsequent ECT application, associated with intensive care of life-threatening general medical conditions, guaranteed us a good level of efficacy in obtaining a complete resolution of the clinical picture. Full article

(This article belongs to the Special Issue What Is New in Psychiatry and Psychopharmacology?)

23 pages, 4607 KB

Open AccessEditor’s ChoiceArticle

Novel Hydrogenated Derivatives of Chemically Modified Curcumin CMC2.24 Are Potent Inhibitors of Melanogenesis in an In Vitro Model: Influence of Degree of Hydrogenation

by Shilpi Goenka

Life 2023, 13(6), 1373; https://doi.org/10.3390/life13061373 - 12 Jun 2023

Cited by 4 | Viewed by 2750

Abstract

Chemically modified curcumin, CMC2.24, is a promising therapeutic that has shown efficacy in ameliorating excessive pigmentation in our previous studies. However, its inherent disadvantages of color, stability, solubility, and cytotoxicity to melanocytes and keratinocytes at concentrations > 4 µg/mL posed challenges in its [...] Read more.

Chemically modified curcumin, CMC2.24, is a promising therapeutic that has shown efficacy in ameliorating excessive pigmentation in our previous studies. However, its inherent disadvantages of color, stability, solubility, and cytotoxicity to melanocytes and keratinocytes at concentrations > 4 µg/mL posed challenges in its use in cosmetic formulations. To overcome these limitations, chemical reduction by hydrogenation of CMC2.24 (compound 1) was developed to yield products at different time points of hydrogenation (1 h, 2 h, 4 h, and 24 h) referred to as partially (2, 3, 4) or fully hydrogenated (5) products, and the effects of the degree of hydrogenation on melanogenesis in vitro were explored. Compound 1 and products 2–5 were evaluated using mushroom tyrosinase activity assays with two substrates (L-tyrosine and L-DOPA), then cellular assays using B16F10 mouse melanoma cells, MNT-1 human melanoma cells, and physiological normal human melanocytes (HEMn-DP cells). The cytotoxicity, melanin contents, cellular tyrosinase activities, and cellular oxidative stress were evaluated. Moreover, the recovery of melanin contents in HEMn-DP cells was also studied. Our results provide novel insights into the role of the degree of hydrogenation of compound 1 on the biological effects of melanogenesis, which were dependent on cell type. To the best of our knowledge, this is the first study to show that in HEMn-DP cells, the anti-melanogenic efficacy of the yellow-colored CMC2.24 is retained as early as 1 h after its hydrogenation; this efficacy is enhanced with longer durations of hydrogenation, with a robust efficacy achieved for the 24 h hydrogenated product 5 at the lowest concentration of 4 µg/mL. A similar potency could be achieved for product 4 at higher concentrations, although interestingly, both differ only by a minor amount of dihydro-CMC2.24. Our results indicate promise for using products 4 & 5 as a skin-lightener in cosmetic formulations with the advantages of lack of color combined with a potency much greater than that of the parent compound 1 at lower concentrations and reversibility of the effects on melanocytes. This, along with the easy synthesis and scale-up of the hydrogenation method for CMC2.24 and the documented higher solubility, stability, and bioavailability of tetrahydrocurcumin, provides further impetus to incorporating these derivatives in cosmetic formulations. The results of this study can help to extend the therapeutic window of the lead compound CMC2.24 by providing options for selecting partially or fully hydrogenated derivatives for cosmetic applications where a trade-off between color and efficacy is needed. Thus, the degree of hydrogenation can be tuned for desired biological effects. Further studies are warranted to evaluate the efficacy of products 4 & 5 at suppressing pigmentation in 3D skin-tissue equivalents and in vivo models. Full article

(This article belongs to the Collection The Role of Bioactive Natural Compounds in the Treatment of Diseases)

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20 pages, 1847 KB

Open AccessEditor’s ChoiceArticle

Effect of Adherence to the Mediterranean Diet on Maternal Iron Related Biochemical Parameters during Pregnancy and Gestational Weight Gain

by María Morales-Suárez-Varela, Isabel Peraita-Costa, Alfredo Perales-Marín, Beatriz Marcos Puig, Juan Llopis-Morales and Yolanda Picó

Life 2023, 13(5), 1138; https://doi.org/10.3390/life13051138 - 8 May 2023

Cited by 9 | Viewed by 3272

Abstract

Gestation is a crucial life stage for both women and offspring, and outcomes are affected by many environmental factors, including diet. The Mediterranean dietary pattern (MD) is considered a healthy eating pattern that can provide the nutritional requirements of pregnancy. Meanwhile, iron deficiency [...] Read more.

Gestation is a crucial life stage for both women and offspring, and outcomes are affected by many environmental factors, including diet. The Mediterranean dietary pattern (MD) is considered a healthy eating pattern that can provide the nutritional requirements of pregnancy. Meanwhile, iron deficiency anemia is one of the most frequent complications related to pregnancy. This study aimed to evaluate how the level of adherence to the MD influences maternal gestational weight gain and specific iron-related maternal biochemical parameters during the pregnancy. Accordingly, an observational, population-based study using data from pregnant women conducted over the entire course of their pregnancy was carried out. Adherence to the MD was assessed once using the MEDAS score questionnaire. Of the 506 women studied, 116 (22.9%) were classified as demonstrating a high adherence, 277 (54.7%) a medium adherence, and 113 (22.3%) a low adherence to the MD. No differences were observed in gestational weight gain among the MD adherence groups but the adequacy of weight gain did vary among the groups, with the proportions of inadequate (insufficient or excessive) weight gain presenting the most notable differences. Total anemia prevalence was 5.3%, 15.6%, and 12.3%, respectively, during the first, second, and third trimesters. For iron-related biochemical parameters, no differences are observed among the adherence groups during pregnancy. With high adherence to the MD as the reference group, the crude odds of iron deficiency diagnosis are significant in the first trimester for both the medium [OR = 2.99 (1.55–5.75)] and low [OR = 4.39 (2.15–8.96)] adherence groups, with deficient adherence to the Mediterranean dietary pattern being responsible for 66.5% (35.5–82.6) and 77.2% (53.5–88.8) of the risk of iron deficiency diagnosis for medium and low adherence, respectively. However, adjusted odds ratios were not significant, possibly due to the small sample size. Our data suggest that MD adherence could be related to gestational weight gain adequacy and that optimal adherence could reduce iron deficiency and/or anemia during pregnancy in the studied population. Full article

(This article belongs to the Special Issue Nutrition and Dietary Pattern Associated with Diseases)

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16 pages, 2623 KB

Open AccessEditor’s ChoiceArticle

Detection of Enterotoxigenic Escherichia coli and Clostridia in the Aetiology of Neonatal Piglet Diarrhoea: Important Factors for Their Prevention

by Nikolaos Tsekouras, Eleftherios Meletis, Polychronis Kostoulas, Georgia Labronikou, Zoi Athanasakopoulou, Georgios Christodoulopoulos, Charalambos Billinis and Vasileios G. Papatsiros

Life 2023, 13(5), 1092; https://doi.org/10.3390/life13051092 - 27 Apr 2023

Cited by 12 | Viewed by 3430

Abstract

This study aimed to research the involvement of enterotoxigenic E. coli (ETEC) and C. difficile or C. perfringens type C in the aetiology of neonatal piglet diarrhoea in Greece and to identify preventive factors for them. A total of 78 pooled faecal samples [...] Read more.

This study aimed to research the involvement of enterotoxigenic E. coli (ETEC) and C. difficile or C. perfringens type C in the aetiology of neonatal piglet diarrhoea in Greece and to identify preventive factors for them. A total of 78 pooled faecal samples were collected randomly from 234 suckling piglets (1–4 days of age) with diarrhoea from 26 pig farms (3 piglets × 3 litters × 26 farms = 234 piglets = 78 faecal pool samples). The collected samples were initially screened for the presence of E. coli and C. difficile or C. perfringens via cultivation on MacConkey and anaerobic blood agar, respectively. Subsequently, the samples were pooled on ELUTE cards. From samples tested, 69.23% of those in the farms were ETEC F4-positive, 30.77% were ETEC F5-positive, 61.54% ETEC were F6-positive, 42.31% were ETEC F4- and E. coli enterotoxin LT-positive, 19.23% were ETEC F5- and LT-positive, 42.31% were ETEC F6- and LT-positive, while LT was found in 57.69% of those in the farms. C. difficile was involved in many cases and identified as an emerging neonatal diarrhoea etiological agent. Specifically, Toxin A of C. difficile was found in 84.62% and Toxin B in 88.46% of those in the farms. Antibiotic administration to sows in combination with probiotics or acidifiers was revealed to reduce the detection of antigens of ETEC and the enterotoxin LT of E. coli. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnosis, Prevention and Control of Zoonotic and Livestock Bacteria)

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32 pages, 5406 KB

Open AccessEditor’s ChoiceReview

Advancement in Solubilization Approaches: A Step towards Bioavailability Enhancement of Poorly Soluble Drugs

by Lakshmi Kumari, Yash Choudhari, Preeti Patel, Ghanshyam Das Gupta, Dilpreet Singh, Jessica M. Rosenholm, Kuldeep Kumar Bansal and Balak Das Kurmi

Life 2023, 13(5), 1099; https://doi.org/10.3390/life13051099 - 27 Apr 2023

Cited by 132 | Viewed by 23660

Abstract

A drug’s aqueous solubility is defined as the ability to dissolve in a particular solvent, and it is currently a major hurdle in bringing new drug molecules to the market. According to some estimates, up to 40% of commercialized products and 70–90% of [...] Read more.

A drug’s aqueous solubility is defined as the ability to dissolve in a particular solvent, and it is currently a major hurdle in bringing new drug molecules to the market. According to some estimates, up to 40% of commercialized products and 70–90% of drug candidates in the development stage are poorly soluble, which results in low bioavailability, diminished therapeutic effects, and dosage escalation. Because of this, solubility must be taken into consideration when developing and fabricating pharmaceutical products. To date, a number of approaches have been investigated to address the problem of poor solubility. This review article attempts to summarize several conventional methods utilized to increase the solubility of poorly soluble drugs. These methods include the principles of physical and chemical approaches such as particle size reduction, solid dispersion, supercritical fluid technology, cryogenic technology, inclusion complex formation techniques, and floating granules. It includes structural modification (i.e., prodrug, salt formation, co-crystallization, use of co-solvents, hydrotrophy, polymorphs, amorphous solid dispersions, and pH variation). Various nanotechnological approaches such as liposomes, nanoparticles, dendrimers, micelles, metal organic frameworks, nanogels, nanoemulsions, nanosuspension, carbon nanotubes, and so forth have also been widely investigated for solubility enhancement. All these approaches have brought forward the enhancement of the bioavailability of orally administered drugs by improving the solubility of poorly water-soluble drugs. However, the solubility issues have not been completely resolved, owing to several challenges associated with current approaches, such as reproducibility in large scale production. Considering that there is no universal approach for solving solubility issues, more research is needed to simplify the existing technologies, which could increase the number of commercially available products employing these techniques. Full article

(This article belongs to the Special Issue New Trends in Pharmaceutical Science: 2nd Edition)

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29 pages, 10722 KB

Open AccessEditor’s ChoiceReview

Modern Trends in Natural Antibiotic Discovery

by Anna A. Baranova, Vera A. Alferova, Vladimir A. Korshun and Anton P. Tyurin

Life 2023, 13(5), 1073; https://doi.org/10.3390/life13051073 - 23 Apr 2023

Cited by 18 | Viewed by 10209

Abstract

Natural scaffolds remain an important basis for drug development. Therefore, approaches to natural bioactive compound discovery attract significant attention. In this account, we summarize modern and emerging trends in the screening and identification of natural antibiotics. The methods are divided into three large [...] Read more.

Natural scaffolds remain an important basis for drug development. Therefore, approaches to natural bioactive compound discovery attract significant attention. In this account, we summarize modern and emerging trends in the screening and identification of natural antibiotics. The methods are divided into three large groups: approaches based on microbiology, chemistry, and molecular biology. The scientific potential of the methods is illustrated with the most prominent and recent results. Full article

(This article belongs to the Special Issue Bacteriocin, Antimicrobial Peptide, and Antibiotics: Current Insights and Application)

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11 pages, 414 KB

Open AccessEditor’s ChoiceArticle

Comparing the Impact of COVID-19 on Vaccinated and Unvaccinated Patients Affected by Myasthenia Gravis

by Elena Scarsi, Sara Massucco, Pilar M. Ferraro, Arianna Cella, Stefano G. Grisanti, Andrea Assini, Alessandro Beronio, Fabio Della Cava, Chiara Gemelli, Fabio Bandini, Carlo Serrati, Massimo Del Sette, Angelo Schenone, Luana Benedetti, Valeria Prada and Marina Grandis

Life 2023, 13(4), 1064; https://doi.org/10.3390/life13041064 - 21 Apr 2023

Cited by 3 | Viewed by 2331

Abstract

We evaluated 13 patients affected by myasthenia gravis (MG) who had coronavirus disease 2019 (COVID-19) before vaccination and 14 myasthenic patients who contracted severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection after vaccination to evaluate factors related to different COVID-19 outcomes. We compared the two [...] Read more.

We evaluated 13 patients affected by myasthenia gravis (MG) who had coronavirus disease 2019 (COVID-19) before vaccination and 14 myasthenic patients who contracted severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection after vaccination to evaluate factors related to different COVID-19 outcomes. We compared the two groups’ previous stability of MG and the severity of SARS-CoV-2 infection. Vaccinated and non-vaccinated patients were comparable in terms of severity of the previous MG course (mean maximum myasthenia gravis Foundation of America–MGFA–Class III) and during SARS-CoV-2 infection (mean MGFA Class II). In non-vaccinated patients, the hospitalization and severe course percentages were 61.5%, while the mortality reached 30.8%. The hospitalization, severe course, and mortality percentages in vaccinated patients were 7.1%. In deceased, non-vaccinated patients, greater myasthenia severity in the past clinical history, but not at the time of infection, was observed. Similarly, older age at MG onset and at the time of infection correlated with a more severe COVID-19 course in non-vaccinated patients (p = 0.03 and p = 0.04), but not in the group of vaccinated patients. In summary, our data support a protective role of vaccination in myasthenic patients, even if anti-CD20 therapy might be associated with a poor immune response to vaccines. Full article

(This article belongs to the Special Issue COVID-19 Prevention and Treatment: 2nd Edition)

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20 pages, 1775 KB

Open AccessEditor’s ChoiceReview

Left Ventricular Assist Device as a Destination Therapy: Current Situation and the Importance of Patient Selection

by María Melendo-Viu, David Dobarro, Sergio Raposeiras Roubin, Carmen Llamas Pernas, Candela Moliz Cordón, Miriam Vazquez Lamas, Miguel Piñón Esteban, Maria Ángela Varela Martínez, Emad Abu Assi, Rafael Pita Romero, Juan José Legarra Calderón and Andrés Íñiguez Romo

Life 2023, 13(4), 1065; https://doi.org/10.3390/life13041065 - 21 Apr 2023

Cited by 10 | Viewed by 8403

Abstract

Advanced heart failure is a growing problem for which the best treatment is cardiac transplantation. However, the shortage of donors’ hearts made left ventricular assist devices as destination therapy (DT-LVAD) a highly recommended alternative: they improved mid-term prognosis as well as patients’ quality [...] Read more.

Advanced heart failure is a growing problem for which the best treatment is cardiac transplantation. However, the shortage of donors’ hearts made left ventricular assist devices as destination therapy (DT-LVAD) a highly recommended alternative: they improved mid-term prognosis as well as patients’ quality of life. Current intracorporeal pumps with a centrifugal continuous flow evolved in the last few years. Since 2003, when first LVAD was approved for long-term support, smaller device sizes with better survival and hemocompatibility profile were reached. The most important difficulty lies in the moment of the implant. Recent indications range from INTERMACS class 2 to 4, with close monitoring in intermediate cases. Moreover, a large multiparametric study is needed for considering the candidacy: basal situation, with a special interest in frailty, comorbidities, including renal and hepatic dysfunction, and medical background, considering every prior cardiac condition, must be evaluated. In addition, some clinical risk scores can be helpful to measure the possibility of right heart failure or morbi-mortality. With this review, we sought to summarize all the device improvements, with their updated clinical results, as well as to focus on all the patient selection criteria. Full article

(This article belongs to the Special Issue Advanced Heart Failure Therapy and Mechanical Circulatory Support)

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15 pages, 2733 KB

Open AccessEditor’s ChoiceArticle

Afamelanotide Is Associated with Dose-Dependent Protective Effect from Liver Damage Related to Erythropoietic Protoporphyria

by Anna-Elisabeth Minder, Xiaoye Schneider-Yin, Henryk Zulewski, Christoph E. Minder and Elisabeth I. Minder

Life 2023, 13(4), 1066; https://doi.org/10.3390/life13041066 - 21 Apr 2023

Cited by 6 | Viewed by 4218

Abstract

In animal models, melanocyte-stimulating hormones (MSHs) protect the liver from various injuries. Erythropoietic protoporphyria (EPP), a metabolic disorder, leads to the accumulation of protoporphyrin (PPIX). In addition to the most prominent symptom of incapacitating phototoxic skin reactions, 20% of EPP patients exhibit disturbed [...] Read more.

In animal models, melanocyte-stimulating hormones (MSHs) protect the liver from various injuries. Erythropoietic protoporphyria (EPP), a metabolic disorder, leads to the accumulation of protoporphyrin (PPIX). In addition to the most prominent symptom of incapacitating phototoxic skin reactions, 20% of EPP patients exhibit disturbed liver functioning and 4% experience terminal liver failure caused by the hepatobiliary elimination of excess PPIX. Skin symptoms are mitigated through the application of the controlled-release implant afamelanotide, an α-MSH analog, every sixty days. Recently, we showed that liver function tests (LFTs) improved during afamelanotide treatment when compared to before treatment. The present study investigated whether this effect is dose-dependent, as the evidence of dose dependency would support a beneficial influence of afamelanotide. Methods: In this retrospective observational study, we included 2933 liver-function tests, 1186 PPIX concentrations and 1659 afamelanotide implant applications in 70 EPP patients. We investigated whether the number of days since the preceding afamelanotide dose or the number of doses during the preceding 365 days had an effect on LFTs and PPIX levels. In addition, we assessed the effect of global radiation. Results: Inter-patient differences exerted the most prominent effect on PPIX and LFTs. In addition, PPIX increased significantly with an increase in the number of days since the last afamelanotide implant (p < 0.0001). ALAT and bilirubin decreased significantly with an increasing number of afamelanotide doses in the preceding 365 days (p = 0.012, p = 0.0299, respectively). Global radiation only influenced PPIX (p = 0.0113). Conclusions: These findings suggest that afamelanotide ameliorates both PPIX concentrations and LFTs in EPP in a dose-dependent manner. Full article

(This article belongs to the Special Issue Heme Metabolism and Porphyria)

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20 pages, 2737 KB

Open AccessEditor’s ChoiceArticle

Impact of Light and Dark Treatment on Phenylpropanoid Pathway Genes, Primary and Secondary Metabolites in Agastache rugosa Transgenic Hairy Root Cultures by Overexpressing Arabidopsis Transcription Factor AtMYB12

by Thi Minh Hanh Do, Minsol Choi, Jae Kwang Kim, Ye Jin Kim, Chanung Park, Chang Ha Park, Nam Il Park, Changsoo Kim, Ramaraj Sathasivam and Sang Un Park

Life 2023, 13(4), 1042; https://doi.org/10.3390/life13041042 - 19 Apr 2023

Cited by 11 | Viewed by 3401

Abstract

Agastache rugosa, otherwise called Korean mint, has a wide range of medicinal benefits. In addition, it is a rich source of several medicinally valuable compounds such as acacetin, tilianin, and some phenolic compounds. The present study aimed to investigate how the Tartary [...] Read more.

Agastache rugosa, otherwise called Korean mint, has a wide range of medicinal benefits. In addition, it is a rich source of several medicinally valuable compounds such as acacetin, tilianin, and some phenolic compounds. The present study aimed to investigate how the Tartary buckwheat transcription factor AtMYB12 increased the primary and secondary metabolites in Korean mint hairy roots cultured under light and dark conditions. A total of 50 metabolites were detected by using high-performance liquid chromatography (HPLC) and gas chromatography–time-of-flight mass spectrometry (GC-TOFMS). The result showed that the AtMYB12 transcription factor upregulated the phenylpropanoid biosynthesis pathway genes, which leads to the highest accumulation of primary and secondary metabolites in the AtMYB12-overexpressing hairy root lines (transgenic) than that of the GUS-overexpressing hairy root line (control) when grown under the light and dark conditions. However, when the transgenic hairy root lines were grown under dark conditions, the phenolic and flavone content was not significantly different from that of the control hairy root lines. Similarly, the heat map and hierarchical clustering analysis (HCA) result showed that most of the metabolites were significantly abundant in the transgenic hairy root cultures grown under light conditions. Principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) showed that the identified metabolites were separated far based on the primary and secondary metabolite contents present in the control and transgenic hairy root lines grown under light and dark conditions. Metabolic pathway analysis of the detected metabolites showed 54 pathways were identified, among these 30 were found to be affected. From these results, the AtMYB12 transcription factor activity might be light-responsive in the transgenic hairy root cultures, triggering the activation of the primary and secondary metabolic pathways in Korean mint. Full article

(This article belongs to the Special Issue Development of Genetic Engineering Technologies for Crops)

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24 pages, 3324 KB

Open AccessEditor’s ChoiceArticle

Acai Berry (Euterpe sp.) Extracts Are Neuroprotective against L-Glutamate-Induced Toxicity by Limiting Mitochondrial Dysfunction and Cellular Redox Stress

by Maryam N. ALNasser, Ayman M. AlSaadi, Alison Whitby, Dong-Hyun Kim, Ian R. Mellor and Wayne G. Carter

Life 2023, 13(4), 1019; https://doi.org/10.3390/life13041019 - 15 Apr 2023

Cited by 10 | Viewed by 4334

Abstract

Aberrant accumulation of the neurotransmitter L-glutamate (L-Glu) has been implicated as a mechanism of neurodegeneration, and the release of L-Glu after stroke onset leads to a toxicity cascade that results in neuronal death. The acai berry (Euterpe oleracea) is a potential [...] Read more.

Aberrant accumulation of the neurotransmitter L-glutamate (L-Glu) has been implicated as a mechanism of neurodegeneration, and the release of L-Glu after stroke onset leads to a toxicity cascade that results in neuronal death. The acai berry (Euterpe oleracea) is a potential dietary nutraceutical. The aim of this research was to investigate the neuroprotective effects of acai berry aqueous and ethanolic extracts to reduce the neurotoxicity to neuronal cells triggered by L-Glu application. L-Glu and acai berry effects on cell viability were quantified using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, and effects on cellular bioenergetics were assessed via quantitation of the levels of cellular ATP, mitochondrial membrane potential (MMP), and production of reactive oxygen species (ROS) in neuroblastoma cells. Cell viability was also evaluated in human cortical neuronal progenitor cell culture after L-Glu or/and acai berry application. In isolated cells, activated currents using patch-clamping were employed to determine whether L-Glu neurotoxicity was mediated by ionotropic L-Glu-receptors (iGluRs). L-Glu caused a significant reduction in cell viability, ATP, and MMP levels and increased ROS production. The co-application of both acai berry extracts with L-Glu provided neuroprotection against L-Glu with sustained cell viability, decreased LDH production, restored ATP and MMP levels, and reduced ROS levels. Whole-cell patch-clamp recordings showed that L-Glu toxicity is not mediated by the activation of iGluRs in neuroblastoma cells. Fractionation and analysis of acai berry extracts with liquid chromatography-mass spectrometry identified several phytochemical antioxidants that may have provided neuroprotective effects. In summary, the acai berry contains nutraceuticals with antioxidant activity that may be a beneficial dietary component to limit pathological deficits triggered by excessive L-Glu accumulations. Full article

(This article belongs to the Collection The Role of Bioactive Natural Compounds in the Treatment of Diseases)

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25 pages, 3684 KB

Open AccessEditor’s ChoiceReview

Cardiac Reverse Remodeling in Ischemic Heart Disease with Novel Therapies for Heart Failure with Reduced Ejection Fraction

by Sabina Andreea Leancă, Irina Afrăsânie, Daniela Crișu, Iulian Theodor Matei, Ștefania Teodora Duca, Alexandru Dan Costache, Viviana Onofrei, Ionuţ Tudorancea, Ovidiu Mitu, Minerva Codruța Bădescu, Lăcrămioara Ionela Șerban and Irina Iuliana Costache

Life 2023, 13(4), 1000; https://doi.org/10.3390/life13041000 - 13 Apr 2023

Cited by 8 | Viewed by 8818

Abstract

Despite the improvements in the treatment of coronary artery disease (CAD) and acute myocardial infarction (MI) over the past 20 years, ischemic heart disease (IHD) continues to be the most common cause of heart failure (HF). In clinical trials, over 70% of patients [...] Read more.

Despite the improvements in the treatment of coronary artery disease (CAD) and acute myocardial infarction (MI) over the past 20 years, ischemic heart disease (IHD) continues to be the most common cause of heart failure (HF). In clinical trials, over 70% of patients diagnosed with HF had IHD as the underlying cause. Furthermore, IHD predicts a worse outcome for patients with HF, leading to a substantial increase in late morbidity, mortality, and healthcare costs. In recent years, new pharmacological therapies have emerged for the treatment of HF, such as sodium-glucose cotransporter-2 inhibitors, angiotensin receptor-neprilysin inhibitors, selective cardiac myosin activators, and oral soluble guanylate cyclase stimulators, demonstrating clear or potential benefits in patients with HF with reduced ejection fraction. Interventional strategies such as cardiac resynchronization therapy, cardiac contractility modulation, or baroreflex activation therapy might provide additional therapeutic benefits by improving symptoms and promoting reverse remodeling. Furthermore, cardiac regenerative therapies such as stem cell transplantation could become a new therapeutic resource in the management of HF. By analyzing the existing data from the literature, this review aims to evaluate the impact of new HF therapies in patients with IHD in order to gain further insight into the best form of therapeutic management for this large proportion of HF patients. Full article

(This article belongs to the Special Issue Ischemic Heart Disease in the Context of Different Comorbidities, Volume II)

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28 pages, 32710 KB

Open AccessEditor’s ChoiceArticle

Morphology of Penicillium rubens Biofilms Formed in Space

by Megan Hupka, Raj Kedia, Rylee Schauer, Brooke Shepard, María Granados-Presa, Mark Vande Hei, Pamela Flores and Luis Zea

Life 2023, 13(4), 1001; https://doi.org/10.3390/life13041001 - 13 Apr 2023

Cited by 11 | Viewed by 5328

Abstract

Fungi biofilms have been found growing on spacecraft surfaces such as windows, piping, cables, etc. The contamination of these surfaces with fungi, although undesirable, is highly difficult to avoid. While several biofilm forming species, including Penicillium rubens, have been identified in spacecraft, [...] Read more.

Fungi biofilms have been found growing on spacecraft surfaces such as windows, piping, cables, etc. The contamination of these surfaces with fungi, although undesirable, is highly difficult to avoid. While several biofilm forming species, including Penicillium rubens, have been identified in spacecraft, the effect of microgravity on fungal biofilm formation is unknown. This study sent seven material surfaces (Stainless Steel 316, Aluminum Alloy, Titanium Alloy, Carbon Fiber, Quartz, Silicone, and Nanograss) inoculated with spores of P. rubens to the International Space Station and allowed biofilms to form for 10, 15, and 20 days to understand the effects of microgravity on biofilm morphology and growth. In general, microgravity did not induce changes in the shape of biofilms, nor did it affect growth in terms of biomass, thickness, and surface area coverage. However, microgravity increased or decreased biofilm formation in some cases, and this was incubation-time- and material-dependent. Nanograss was the material with significantly less biofilm formation, both in microgravity and on Earth, and it could potentially be interfering with hyphal adhesion and/or spore germination. Additionally, a decrease in biofilm formation at 20 days, potentially due to nutrient depletion, was seen in some space and Earth samples and was material-dependent. Full article

(This article belongs to the Special Issue Gravitational Microbiology Research and Applications)

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22 pages, 5283 KB

Open AccessEditor’s ChoiceArticle

Evaluation of Drought Responses in Two Tropaeolum Species Used in Landscaping through Morphological and Biochemical Markers

by Diana M. Mircea, Roberta Calone, Rashmi Shakya, Javier Zuzunaga-Rosas, Radu E. Sestras, Monica Boscaiu, Adriana F. Sestras and Oscar Vicente

Life 2023, 13(4), 960; https://doi.org/10.3390/life13040960 - 6 Apr 2023

Cited by 4 | Viewed by 2163

Abstract

One of the most important challenges horticultural crops confront is drought, particularly in regions such as the Mediterranean basin, where water supplies are usually limited and will become even scarcer due to global warming. Therefore, the selection and diversification of stress-tolerant cultivars are [...] Read more.

One of the most important challenges horticultural crops confront is drought, particularly in regions such as the Mediterranean basin, where water supplies are usually limited and will become even scarcer due to global warming. Therefore, the selection and diversification of stress-tolerant cultivars are becoming priorities of contemporary ornamental horticulture. This study explored the impact of water stress on two Tropaeolum species frequently used in landscaping. Young plants obtained by seed germination were exposed to moderate water stress (half the water used in the control treatments) and severe water stress (complete withholding of irrigation) for 30 days. Plant responses to these stress treatments were evaluated by determining several growth parameters and biochemical stress markers. The latter were analysed by spectrophotometric methods and, in some cases, by non-destructive measurements using an optical sensor. The statistical analysis of the results indicated that although the stress responses were similar in these two closely related species, T. minus performed better under control and intermediate water stress conditions but was more susceptible to severe water stress. On the other hand, T. majus had a stronger potential for adaptation to soil water scarcity, which may be associated with its reported expansion and naturalisation in different regions of the world. The variations in proline and malondialdehyde concentrations were the most reliable biochemical indicators of water stress effects. The present study also showed a close relationship between the patterns of variation of flavonoid and chlorophyll contents obtained by sensor-based and spectrophotometric methods. Full article

(This article belongs to the Special Issue Abiotic Stress Signaling and Responses in Plants)

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21 pages, 5177 KB

Open AccessEditor’s ChoiceArticle

Bioactive Compounds and Signaling Pathways of Wolfiporia extensa in Suppressing Inflammatory Response by Network Pharmacology

by Juri Jin, Md. Helal Uddin Chowdhury, Md. Hafizur Rahman, Ki-Young Choi and Md. Adnan

Life 2023, 13(4), 893; https://doi.org/10.3390/life13040893 - 27 Mar 2023

Cited by 6 | Viewed by 3324

Abstract

Wolfiporia extensa (WE) is a medicinal mushroom and an excellent source of naturally occurring anti-inflammatory substances. However, the particular bioactive compound(s) and mechanism(s) of action against inflammation have yet to be determined. Here, we studied anti-inflammatory bioactive compounds and their molecular mechanisms through [...] Read more.

Wolfiporia extensa (WE) is a medicinal mushroom and an excellent source of naturally occurring anti-inflammatory substances. However, the particular bioactive compound(s) and mechanism(s) of action against inflammation have yet to be determined. Here, we studied anti-inflammatory bioactive compounds and their molecular mechanisms through network pharmacology. Methanol (ME) extract of WE (MEWE) was used for GC-MS analysis to identify the bioactives, which were screened by following Lipinski’s rules. Public databases were used to extract selected bioactives and inflammation-related targets, and Venn diagrams exposed the common targets. Then, STRING and Cytoscape tools were used to construct protein-protein (PPI) network and mushroom-bioactives-target (M-C-T) networks. Gene Ontology and KEGG pathway analysis were performed by accessing the DAVID database and molecular docking was conducted to validate the findings. The chemical reactivity of key compounds and standard drugs was explored by the computational quantum mechanical modelling method (DFT study). Results from GC-MS revealed 27 bioactives, and all obeyed Lipinski’s rules. The public databases uncovered 284 compound-related targets and 7283 inflammation targets. A Venn diagram pointed to 42 common targets which were manifested in the PPI and M-C-T networks. KEGG analysis pointed to the HIF-1 signaling pathway and, hence, the suggested strategy for preventing the onset of inflammatory response was inhibition of downstream NFKB, MAPK, mTOR, and PI3K-Akt signaling cascades. Molecular docking revealed the strongest binding affinity for “N-(3-chlorophenyl) naphthyl carboxamide” on five target proteins associated with the HIF-1 signaling pathway. Compared to the standard drug utilized in the DFT (Density Functional Theory) analysis, the proposed bioactive showed a good electron donor component and a reduced chemical hardness energy. Our research pinpoints the therapeutic efficiency of MEWE and this work suggests a key bioactive compound and its action mechanism against inflammation. Full article

(This article belongs to the Special Issue New Trends in Pharmaceutical Science: 2nd Edition)

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13 pages, 3794 KB

Open AccessEditor’s ChoiceArticle

Vitamin D₃ Supplementation: Comparison of 1000 IU and 2000 IU Dose in Healthy Individuals

by Eva Dědečková, Roman Viták, Michal Jirásko, Markéta Králová, Ondřej Topolčan, Ladislav Pecen, Tomáš Fürst, Pavel Brož and Radek Kučera

Life 2023, 13(3), 808; https://doi.org/10.3390/life13030808 - 16 Mar 2023

Cited by 8 | Viewed by 11356

Abstract

Background: Scientific studies point to a significant global vitamin D deficiency. The recommended dose of vitamin D for the adult population in Central Europe is 800–2000 IU/day. The aim of our study was to determine whether doses of 1000 IU or 2000 IU [...] Read more.

Background: Scientific studies point to a significant global vitamin D deficiency. The recommended dose of vitamin D for the adult population in Central Europe is 800–2000 IU/day. The aim of our study was to determine whether doses of 1000 IU or 2000 IU of vitamin D₃ are adequate to achieve the sufficiency reference values of [25(OH)D]. Methods: Seventy-two healthy volunteers, average age twenty-two, took part in the study. The study was conducted from October to March in order to eliminate intra-dermal vitamin D production. Vitamin D₃ in an oleaginous mixture was used. The participants used either 1000 IU or 2000 IU/daily for two 60-day periods with a 30-day break. Results: The dose of 1000 IU, taken for 60 days, increased vitamin D levels relatively little. Furthermore, serum vitamin D levels decreased in the 30 days following the cessation of supplementation. Taking 2000 IU daily led to a sharp increase in serum levels which plateaued 30 days after the subjects stopped using vitamin D₃ drops. Conclusions: Both doses, taken daily, can help maintain adequate vitamin D levels during the winter months. A daily dose of 2000 IU, however, maintained the desired levels of vitamin D for a longer period. Full article

(This article belongs to the Special Issue Feature Papers in Medical Research)

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16 pages, 599 KB

Open AccessEditor’s ChoiceReview

Tissue Culture—A Sustainable Approach to Explore Plant Stresses

by Akila Wijerathna-Yapa and Jayeni Hiti-Bandaralage

Life 2023, 13(3), 780; https://doi.org/10.3390/life13030780 - 14 Mar 2023

Cited by 44 | Viewed by 15435

Abstract

Plants are constantly faced with biotic or abiotic stress, which affects their growth and development. Yield reduction due to biotic and abiotic stresses on economically important crop species causes substantial economic loss at a global level. Breeding for stress tolerance to create elite [...] Read more.

Plants are constantly faced with biotic or abiotic stress, which affects their growth and development. Yield reduction due to biotic and abiotic stresses on economically important crop species causes substantial economic loss at a global level. Breeding for stress tolerance to create elite and superior genotypes has been a common practice for many decades, and plant tissue culture can be an efficient and cost-effective method. Tissue culture is a valuable tool to develop stress tolerance, screen stress tolerance, and elucidate physiological and biochemical changes during stress. In vitro selection carried out under controlled environment conditions in confined spaces is highly effective and cheaper to maintain. This review emphasizes the relevance of plant tissue culture for screening major abiotic stresses, drought, and salinity, and the development of disease resistance. Further emphasis is given to screening metal hyperaccumulators and transgenic technological applications for stress tolerance. Full article

(This article belongs to the Special Issue Bioengineering for Improving the Stress Tolerance of Plants)

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19 pages, 7846 KB

Open AccessEditor’s ChoiceArticle

The Abundant Phytocannabinoids in Rheumatoid Arthritis: Therapeutic Targets and Molecular Processes Identified Using Integrated Bioinformatics and Network Pharmacology

by Arijit Nandi, Anwesha Das, Yadu Nandan Dey and Kuldeep K. Roy

Life 2023, 13(3), 700; https://doi.org/10.3390/life13030700 - 5 Mar 2023

Cited by 14 | Viewed by 4143

Abstract

The endocannabinoid system consists of several phytocannabinoids, cannabinoid receptors, and enzymes that aid in numerous steps necessary to manifest any pharmacological activity. It is well known that the endocannabinoid system inhibits the pathogenesis of the inflammatory and autoimmune disease rheumatoid arthritis (RA). To [...] Read more.

The endocannabinoid system consists of several phytocannabinoids, cannabinoid receptors, and enzymes that aid in numerous steps necessary to manifest any pharmacological activity. It is well known that the endocannabinoid system inhibits the pathogenesis of the inflammatory and autoimmune disease rheumatoid arthritis (RA). To the best of our knowledge, no research has been done that explains the network-pharmacology-based anti-rheumatic processes by focusing on the endocannabinoid system. Therefore, the purpose of this study is to further our understanding of the signaling pathways, associated proteins, and genes underlying RA based on the abundant natural endocannabinoids. The knowledge on how the phytocannabinoids in Cannabis sativa affect the endocannabinoid system was gathered from the literature. SwissTarget prediction and BindingDB databases were used to anticipate the targets for the phytocannabinoids. The genes related to RA were retrieved from the DisGeNET and GeneCards databases. Protein–protein interactions (high confidence > 0.7) were carried out with the aid of the string web server and displayed using Cytoscape. The Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis was used to perform enrichment analyses on the endocannabinoid–RA common targets. ShinyGO 0.76 was used to predict the biological processes listed in the Gene Ontology (GO) classification system. The binding affinity between the ligand and the receptors was precisely understood using molecular docking, induced-fit docking, and a molecular dynamics simulation. The network pharmacology analyses predicted that processes like response to oxygen-containing compounds and peptodyl-amino acid modification are related to the potential mechanisms of treatment for RA. These biological actions are coordinated by cancer, neuroactive ligand–receptor interaction, lipids and atherosclerosis, the calcium signaling pathway, and the Rap1 signaling pathway. According to the results of molecular docking, in the context of RA, phytocannabinoids may bind to important target proteins such PIK3CA, AKT1, MAPK9, PRKCD, BRAF, IGF1R, and NOS3. This entire study predicted the phytocannabinoids’ systemic biological characteristics. Future experimental research is needed, however, to confirm the results so far. Full article

(This article belongs to the Special Issue Endocannabinoid System in Health and Disease)

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20 pages, 1654 KB

Open AccessEditor’s ChoiceReview

Neurotrophins and Other Growth Factors in the Pathogenesis of Alzheimer’s Disease

by Tadahiro Numakawa and Ryutaro Kajihara

Life 2023, 13(3), 647; https://doi.org/10.3390/life13030647 - 26 Feb 2023

Cited by 39 | Viewed by 5529

Abstract

The involvement of the changed expression/function of neurotrophic factors in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD), has been suggested. AD is one of the age-related dementias, and is characterized by cognitive impairment with decreased memory function. Developing evidence demonstrates that [...] Read more.

The involvement of the changed expression/function of neurotrophic factors in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD), has been suggested. AD is one of the age-related dementias, and is characterized by cognitive impairment with decreased memory function. Developing evidence demonstrates that decreased cell survival, synaptic dysfunction, and reduced neurogenesis are involved in the pathogenesis of AD. On the other hand, it is well known that neurotrophic factors, especially brain-derived neurotrophic factor (BDNF) and its high-affinity receptor TrkB, have multiple roles in the central nervous system (CNS), including neuronal maintenance, synaptic plasticity, and neurogenesis, which are closely linked to learning and memory function. Thus, many investigations regarding therapeutic approaches to AD, and/or the screening of novel drug candidates for its treatment, focus on upregulation of the BDNF/TrkB system. Furthermore, current studies also demonstrate that GDNF, IGF1, and bFGF, which play roles in neuroprotection, are associated with AD. In this review, we introduce data demonstrating close relationships between the pathogenesis of AD, neurotrophic factors, and drug candidates, including natural compounds that upregulate the BDNF-mediated neurotrophic system. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanisms in Neurodegenerative Diseases)

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30 pages, 1572 KB

Open AccessEditor’s ChoiceReview

Bioactive Compounds from Kalanchoe Genus Potentially Useful for the Development of New Drugs

by Luana Beatriz dos Santos Nascimento, Livia Marques Casanova and Sônia Soares Costa

Life 2023, 13(3), 646; https://doi.org/10.3390/life13030646 - 26 Feb 2023

Cited by 24 | Viewed by 8850

Abstract

The genus Kalanchoe Adans. (Crassulaceae) is native to Madagascar and comprises 145 species, being naturalized in the tropics and cultivated worldwide. In addition to having ornamental value, several Kalanchoe species are commonly used in popular medicine for the treatment of inflammatory conditions, wounds, [...] Read more.

The genus Kalanchoe Adans. (Crassulaceae) is native to Madagascar and comprises 145 species, being naturalized in the tropics and cultivated worldwide. In addition to having ornamental value, several Kalanchoe species are commonly used in popular medicine for the treatment of inflammatory conditions, wounds, gastric ulcers, and other diseases. The great importance of the genus is reflected on its acknowledgment by traditional and alternative health systems and organizations, as well as on the growing number of papers reporting pharmacological properties of extracts and isolated compounds from Kalanchoe. Among these properties, we highlight anti-inflammatory, antitumor, wound healing, antiulcer, and muscle relaxing properties. These activities are attributed mostly to flavonoids and bufadienolides, the main secondary metabolites reported in Kalanchoe extracts. While bufadienolides are generally related to cytotoxic and muscle relaxing activities, flavonoids are commonly reported as anti-inflammatory and wound healing agents. This review provides up to date information and perspectives on bioactive compounds from the Kalanchoe genus that are potentially useful for the development of new drugs. It includes not only a discussion on the advantages of the Kalanchoe species as source of bioactive compounds, but also the gaps, opportunities, and challenges to translate the acquired knowledge into innovation for drug development. Full article

(This article belongs to the Collection The Role of Bioactive Natural Compounds in the Treatment of Diseases)

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13 pages, 1067 KB

Open AccessEditor’s ChoiceReview

Assessment of Exercise Capacity in Post-COVID-19 Patients: How Is the Appropriate Test Chosen?

by Rodrigo Torres-Castro, Rodrigo Núñez-Cortés, Santiago Larrateguy, Xavier Alsina-Restoy, Joan Albert Barberà, Elena Gimeno-Santos, Agustin Roberto García, Oriol Sibila and Isabel Blanco

Life 2023, 13(3), 621; https://doi.org/10.3390/life13030621 - 23 Feb 2023

Cited by 19 | Viewed by 6873

Abstract

There is a wide range of sequelae affecting COVID-19 survivors, including impaired physical capacity. These sequelae can affect the quality of life and return to work of the active population. Therefore, one of the pillars of following-up is the evaluation of physical capacity, [...] Read more.

There is a wide range of sequelae affecting COVID-19 survivors, including impaired physical capacity. These sequelae can affect the quality of life and return to work of the active population. Therefore, one of the pillars of following-up is the evaluation of physical capacity, which can be assessed with field tests (such as the six-minute walk test, the one-minute standing test, the Chester step test, and the shuttle walking test) or laboratory tests (such as the cardiopulmonary exercise test). These tests can be performed in different contexts and have amply demonstrated their usefulness in the assessment of physical capacity both in post-COVID-19 patients and in other chronic respiratory, metabolic, cardiologic, or neurologic diseases. However, when traditional tests cannot be performed, physical function can be a good substitute, especially for assessing the effects of an intervention. For example, the Short Physical Performance Battery assessment and the Timed Up and Go assessment are widely accepted in older adults. Thus, the test should be chosen according to the characteristics of each subject. Full article

(This article belongs to the Collection COVID-19 and Life)

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11 pages, 419 KB

Open AccessEditor’s ChoiceArticle

Sexually Transmitted Infections Prevalence and Cascade of Care among Undocumented Sex Workers: A Twenty-Year-Long Experience

by Alessandra Donisi, Agnese Colpani, Beatrice Zauli, Andrea De Vito, Vito Fiore, Sergio Babudieri and Giordano Madeddu

Life 2023, 13(3), 606; https://doi.org/10.3390/life13030606 - 22 Feb 2023

Cited by 5 | Viewed by 2600

Abstract

Undocumented migrant sex-workers (SW) are vulnerable to Sexually Transmitted Infections (STIs). However, data regarding prevalence and linkage-to-care are lacking. Defining epidemiology is crucial to implement preventive measures. We report data from SW attending a facility for migrants in Piacenza, Italy. We collected medical [...] Read more.

Undocumented migrant sex-workers (SW) are vulnerable to Sexually Transmitted Infections (STIs). However, data regarding prevalence and linkage-to-care are lacking. Defining epidemiology is crucial to implement preventive measures. We report data from SW attending a facility for migrants in Piacenza, Italy. We collected medical records from 1999 until 2021. Quantitative variables were summarized as mean and standard deviation (SD), and qualitative ones by absolute and relative frequencies. Logistic regression analysis was performed to assess the relationship between sociodemographic, clinical variables, positive testing, and loss to follow-up (LFU). Overall, 1035 STI episodes were collected, 917 in cisgender-females (CF), and 118 in transgender-females (TF). Overall, 474 diagnoses were made. Three-hundred-ninety-two/474 (82.7%) started therapy, and 264/474 (55.7%) complied with a follow-up. Only 51.5% of HBV and 30.8% of HIV were linked to care. Having symptoms (OR 1.70 (95% CI 1.06–2.73), p = 0.028) and previous STIs (OR 1.36 (95% CI 1.04–1.77), p = 0.022) were associated with a higher chance of STIs, while at-risk intercourse to lower risk (OR 0.19 (95% CI 0.07–0.49), p = 0.001). TF had higher odds of bloodborne infections and syphilis (OR 2.61 (95% CI 1.17–5.80), p = 0.019). Regarding follow-up, the older the patient, the higher the LFU (OR 1.05 (95% CI 1.01–1.10), p = 0.021). Our data showed a high prevalence of STIs and LFU among undocumented SW. TF are even more vulnerable. Further efforts should be put into targeted interventions. Full article

(This article belongs to the Special Issue Exploration of the Unmet Needs of Aging People Living with HIV)

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16 pages, 732 KB

Open AccessEditor’s ChoiceReview

Exploring the Protective Effect of Food Drugs against Viral Diseases: Interaction of Functional Food Ingredients and SARS-CoV-2, Influenza Virus, and HSV

by Andrea Ricci and Giovanni N. Roviello

Life 2023, 13(2), 402; https://doi.org/10.3390/life13020402 - 1 Feb 2023

Cited by 22 | Viewed by 5819

Abstract

A complex network of processes inside the human immune system provides resistance against a wide range of pathologies. These defenses form an innate and adaptive immunity, in which certain immune components work together to counteract infections. In addition to inherited variables, the susceptibility [...] Read more.

A complex network of processes inside the human immune system provides resistance against a wide range of pathologies. These defenses form an innate and adaptive immunity, in which certain immune components work together to counteract infections. In addition to inherited variables, the susceptibility to diseases may be influenced by factors such as lifestyle choices and aging, as well as environmental determinants. It has been shown that certain dietary chemical components regulate signal transduction and cell morphologies which, in turn, have consequences on pathophysiology. The consumption of some functional foods may increase immune cell activity, defending us against a number of diseases, including those caused by viruses. Here, we investigate a range of functional foods, often marketed as immune system boosters, in an attempt to find indications of their potential protective role against diseases caused by viruses, such as the influenza viruses (A and B), herpes simplex virus (HSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in some cases mediated by gut microbiota. We also discuss the molecular mechanisms that govern the protective effects of some functional foods and their molecular constituents. The main message of this review is that discovering foods that are able to strengthen the immune system can be a winning weapon against viral diseases. In addition, understanding how the dietary components function can aid in the development of novel strategies for maintaining human bodily health and keeping our immune systems strong. Full article

(This article belongs to the Special Issue Nutrition and Dietary Pattern Associated with Diseases)

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14 pages, 3224 KB

Open AccessEditor’s ChoiceArticle

Antiobesity and Antioxidative Effect of Fermented Brown Rice Using In Vitro with In Vivo Caenorhabditis elegans Model

by Kaliyan Barathikannan, Akanksha Tyagi, Lingyue Shan, Nam-Hyeon Kim, Deuk-Sik Lee, Jong-Soon Park, Ramachandran Chelliah and Deog-Hwan Oh

Life 2023, 13(2), 374; https://doi.org/10.3390/life13020374 - 29 Jan 2023

Cited by 7 | Viewed by 3547

Abstract

Naturally occurring phytochemicals from plants or grains are crucial in reducing various metabolic disorders. Bioactive phytonutrients are abundant in the Asian dietary staple, brown rice. This research evaluated the impact of lactic acid bacteria (LABs) bioconversion and fermentation on antioxidant and antiobesity activities [...] Read more.

Naturally occurring phytochemicals from plants or grains are crucial in reducing various metabolic disorders. Bioactive phytonutrients are abundant in the Asian dietary staple, brown rice. This research evaluated the impact of lactic acid bacteria (LABs) bioconversion and fermentation on antioxidant and antiobesity activities and ferulic acid content in brown rice. The combination of bioconversion with Pediococcus acidilactici MNL5 among all LABs used showed a synergistic impact with 24 h of solid-state brown rice fermentation. The 24-h MNL5 fermented brown rice (FBR) demonstrated the most potent pancreatic lipase inhibitory activity (85.5 ± 1.25%) compared to raw brown rice (RBR) (54.4 ± 0.86%). The antioxidant potential of MNL5-FBR was also found to be highest in the DPPH assay (124.40 ± 2.40 mg Trolox Equiv./100 g, DW), ABTS assay (130.52 ± 2.32 mg Trolox Equiv./100 g, DW), and FRAP assay (116.16 ± 2.42 mg Trolox Equiv./100 g, DW). Based on higher antioxidant and antiobesity activities, samples were quantified for ferulic acid content using the HPLC-MS/MS approach. Furthermore, C. elegans supplementation with FBR showed enhanced life span and lipid reduction in fluorescence microscope analysis compared to the control. Our results indicate that the expression study using the C. elegans model (N2 and Daf-2 models) fat gene was conducted, showing a lowering of obesity ability in FBR-fed worms. Our study indicates that FBR has improved antioxidant and antiobesity actions, especially in MNL5-FBR, and can be employed to develop functional foods that combat obesity. Full article

(This article belongs to the Special Issue The Discovery and Application of Phytochemicals and Bio Actives)

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14 pages, 1182 KB

Open AccessEditor’s ChoiceReview

Robotic Bronchoscopy: Review of Three Systems

by Maxwell J. Diddams and Hans J. Lee

Life 2023, 13(2), 354; https://doi.org/10.3390/life13020354 - 28 Jan 2023

Cited by 27 | Viewed by 13534

Abstract

Robotic bronchoscopy (RB) has been shown to improve access to smaller and more peripheral lung lesions, while simultaneously staging the mediastinum. Pre-clinical studies demonstrated extremely high diagnostic yields, but real-world RB yields have yet to fully matched up in prospective studies. Despite this, [...] Read more.

Robotic bronchoscopy (RB) has been shown to improve access to smaller and more peripheral lung lesions, while simultaneously staging the mediastinum. Pre-clinical studies demonstrated extremely high diagnostic yields, but real-world RB yields have yet to fully matched up in prospective studies. Despite this, RB technology has rapidly evolved and has great potential for lung-cancer diagnosis and even treatment. In this article, we review the historical and present challenges with RB in order to compare three RB systems. Full article

(This article belongs to the Special Issue Interventional Pulmonology – Review and Updates)

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17 pages, 3317 KB

Open AccessEditor’s ChoiceArticle

Addition of Arbuscular Mycorrhizal Fungi Enhances Terpene Synthase Expression in Salvia rosmarinus Cultivars

by Emily Leggatt, Alistair Griffiths, Simon Budge, Anthony D. Stead, Alan C. Gange and Paul F. Devlin

Life 2023, 13(2), 315; https://doi.org/10.3390/life13020315 - 23 Jan 2023

Cited by 3 | Viewed by 3017

Abstract

Culinary herbs are commercially cultivated for their wide range of volatile compounds that give characteristic aromas and tastes. Rosemary (Salvia rosmarinus Spenn.) is an excellent model for assessment of methods improvement of volatile production as cultivars offer a wide variety of aromatic [...] Read more.

Culinary herbs are commercially cultivated for their wide range of volatile compounds that give characteristic aromas and tastes. Rosemary (Salvia rosmarinus Spenn.) is an excellent model for assessment of methods improvement of volatile production as cultivars offer a wide variety of aromatic profiles due to the large family of terpene synthase genes. Arbuscular mycorrhizal fungi (AMF) associations have been shown to improve essential oil production in aromatic plants and offer one approach to enhance aroma in commercial herb production. Changes in the expression of seven different terpene synthases were compared in six rosemary cultivars in response to addition of AMF to a peat substrate. Addition of AMF profoundly influenced terpene synthase expression in all cultivars and did so without impacting the optimised plant size and uniformity achieved in these conditions. In addition, two methods for AMF application, developed with the horticultural industry in mind, were tested in this study. Uniform incorporation of AMF mixed into the growing substrate prior to planting of a root plug produced the most consistent root colonisation. Overall, our findings demonstrate the potential for the use of AMF in the improvement of aroma in culinary herbs within a commercial setting but show that outcomes are likely to greatly vary depending on variety. Full article

(This article belongs to the Special Issue Plants as a Promising Biofactory for Bioactive Compounds)

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12 pages, 644 KB

Open AccessEditor’s ChoiceArticle

Inflammation as Prognostic Hallmark of Clinical Outcome in Patients with SARS-CoV-2 Infection

by Diana Fuzio, Angelo Michele Inchingolo, Vitalba Ruggieri, Massimo Fasano, Maria Federico, Manuela Mandorino, Lavinia Dirienzo, Salvatore Scacco, Alessandro Rizzello, Maurizio Delvecchio, Massimiliano Parise, Roberto Rana, Nicola Faccilongo, Biagio Rapone, Francesco Inchingolo, Antonio Mancini, Maria Celeste Fatone, Antonio Gnoni, Gianna Dipalma and Giovanni Dirienzo

Life 2023, 13(2), 322; https://doi.org/10.3390/life13020322 - 23 Jan 2023

Cited by 9 | Viewed by 2842

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often characterized by a life-threatening interstitial pneumonia requiring hospitalization. The aim of this retrospective cohort study is to identify hallmarks of in-hospital mortality in patients affected by Coronavirus Disease 19 (COVID-19). A total of 150 [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often characterized by a life-threatening interstitial pneumonia requiring hospitalization. The aim of this retrospective cohort study is to identify hallmarks of in-hospital mortality in patients affected by Coronavirus Disease 19 (COVID-19). A total of 150 patients admitted for COVID-19 from March to June 2021 to “F. Perinei” Murgia Hospital in Altamura, Italy, were divided into survivors (n = 100) and non-survivors groups (n = 50). Blood counts, inflammation-related biomarkers and lymphocyte subsets were analyzed into two groups in the first 24 h after admission and compared by Student’s t-test. A multivariable logistic analysis was performed to identify independent risk factors associated with in-hospital mortality. Total lymphocyte count and CD3⁺ and CD4⁺ CD8⁺ T lymphocyte subsets were significantly lower in non-survivors. Serum levels of interleukin-6 (IL-6), lactate dehydrogenase (LDH), C-reactive protein (CRP) and procalcitonin (PCT) were significantly higher in non-survivors. Age > 65 years and presence of comorbidities were identified as independent risk factors associated with in-hospital mortality, while IL-6 and LDH showed a borderline significance. According to our results, markers of inflammation and lymphocytopenia predict in-hospital mortality in COVID-19. Full article

(This article belongs to the Special Issue COVID-19 Prevention and Treatment)

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22 pages, 601 KB

Open AccessEditor’s ChoiceSystematic Review

A Critical Review of the Psychomotor Agitation Treatment in Youth

by Beniamino Tripodi, Irene Matarese and Manuel Glauco Carbone

Life 2023, 13(2), 293; https://doi.org/10.3390/life13020293 - 20 Jan 2023

Cited by 4 | Viewed by 5756

Abstract

(1) Background: To systematically review evidence on the safety and efficacy of psychopharmacological treatments available for psychomotor agitation (PA) in children and adolescents. (2) Methods: Studies assessing the safety and efficacy of psychopharmacological treatments for acute PA in children and adolescents that were [...] Read more.

(1) Background: To systematically review evidence on the safety and efficacy of psychopharmacological treatments available for psychomotor agitation (PA) in children and adolescents. (2) Methods: Studies assessing the safety and efficacy of psychopharmacological treatments for acute PA in children and adolescents that were published between January 1984 and June 2022 on PubMed were systematically reviewed. We included: (i) papers that presented a combination of the search terms specified in the “Search strategy” sub-paragraph; (ii) manuscripts in English; (iii) original papers; (iv) prospective or retrospective/observational studies and experimental or quasi-experimental reports. The exclusion criteria were: (i) review papers; (ii) non-original studies including editorials and book reviews; (iii) studies not specifically designed and focused on the selected topic. (3) Results: We selected 42 papers: 11 case series (11/42, 26.19%), 8 chart reviews (8/42, 19.05%), 8 case reports (8/42, 19.05%), 6 double-blind placebo-controlled randomized studies (6/42, 14.29%), 4 double-blind controlled randomized studies (4/42, 9.52%), 4 open-label trials (4/42, 9.52%) and 1 case control (1/42, 2.38%). (4) Conclusions: The drugs most frequently used to treat agitation in children and adolescents were ziprasidone, risperidone, aripiprazole, olanzapine and valproic acid. Further studies are needed to evaluate the efficacy/safety ratio, considering the limited number of observations in this field. Full article

(This article belongs to the Special Issue What Is New in Psychiatry and Psychopharmacology?)

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30 pages, 2406 KB

Open AccessEditor’s ChoiceReview

Biofilm Lifestyle in Recurrent Urinary Tract Infections

by Amr S. Abu Lila, Azza A. H. Rajab, Marwa H. Abdallah, Syed Mohd Danish Rizvi, Afrasim Moin, El-Sayed Khafagy, Shams Tabrez and Wael A. H. Hegazy

Life 2023, 13(1), 148; https://doi.org/10.3390/life13010148 - 4 Jan 2023

Cited by 89 | Viewed by 11699

Abstract

Urinary tract infections (UTIs) represent one of the most common infections that are frequently encountered in health care facilities. One of the main mechanisms used by bacteria that allows them to survive hostile environments is biofilm formation. Biofilms are closed bacterial communities that [...] Read more.

Urinary tract infections (UTIs) represent one of the most common infections that are frequently encountered in health care facilities. One of the main mechanisms used by bacteria that allows them to survive hostile environments is biofilm formation. Biofilms are closed bacterial communities that offer protection and safe hiding, allowing bacteria to evade host defenses and hide from the reach of antibiotics. Inside biofilm communities, bacteria show an increased rate of horizontal gene transfer and exchange of resistance and virulence genes. Additionally, bacterial communication within the biofilm allows them to orchestrate the expression of virulence genes, which further cements the infestation and increases the invasiveness of the infection. These facts stress the necessity of continuously updating our information and understanding of the etiology, pathogenesis, and eradication methods of this growing public health concern. This review seeks to understand the role of biofilm formation in recurrent urinary tact infections by outlining the mechanisms underlying biofilm formation in different uropathogens, in addition to shedding light on some biofilm eradication strategies. Full article

(This article belongs to the Special Issue Urinary Microbiome and Genitourinary System Disorders)

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14 pages, 4212 KB

Open AccessEditor’s ChoiceReview

Gut Microbiome Composition in Patients with Chronic Urticaria: A Review of Current Evidence and Data

by Mirela Krišto, Liborija Lugović-Mihić, Melba Muñoz, Maja Rupnik, Aleksander Mahnic, Petar Ozretić, Morana Jaganjac, Diana Ćesić and Matea Kuna

Life 2023, 13(1), 152; https://doi.org/10.3390/life13010152 - 4 Jan 2023

Cited by 21 | Viewed by 10179

Abstract

Recent studies have linked gut microorganism composition and chronic urticaria (CU); however, the underlying mechanisms responsible for this connection are unknown. Since the human immune system is in homeostasis with microbiota, and the composition of the microbiome regulates the development and function of [...] Read more.

Recent studies have linked gut microorganism composition and chronic urticaria (CU); however, the underlying mechanisms responsible for this connection are unknown. Since the human immune system is in homeostasis with microbiota, and the composition of the microbiome regulates the development and function of the immune system, it is likely that an alteration of microbiota components (a dysbiosis) could influence the course of chronic spontaneous urticaria (CSU), including disease severity, patient quality of life and treatment outcome. To date, several studies have identified changes in the gut microbiota composition of patients with CSU, though only a few have exhibited metabolic abnormalities associated with gut dysbiosis. The studies on CSU patients predominantly showed that the relative abundance of beneficial bacteria was decreased (Firmicutes and Bacteroides), while that of opportunistic bacteria was increased (Enterobacteria and Proteobacteria). In addition, serum metabolome analysis revealed that gut microbiota-associated alterations in unsaturated fatty acids and the butanoate metabolism pathway may play a role in CSU. These findings are potentially associated with inflammation mediated by the imbalance of Th1/Th2/Th17 cytokines, which might contribute to CSU pathogenesis. Further research in this field could improve clinical, diagnostic, and therapeutic approaches to patients with CSU. By applying new knowledge on gut microbial communities and metabolomics, future CSU therapies could modify the microbiota composition using agents such as probiotics or other similar agents, which, in combination with current standard therapies, could hopefully lead to a reduction in symptoms and an improved quality of life for CSU patients. Full article

(This article belongs to the Section Microbiology)

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26 pages, 1834 KB

Open AccessEditor’s ChoiceReview

Clinical Guideline on Perioperative Management of Patients with Advanced Chronic Liver Disease

by Lidia Canillas, Amalia Pelegrina, Juan Álvarez, Elena Colominas-González, Antonio Salar, Lluís Aguilera, Fernando Burdio, Antonio Montes, Santiago Grau, Luis Grande and José A. Carrión

Life 2023, 13(1), 132; https://doi.org/10.3390/life13010132 - 3 Jan 2023

Cited by 15 | Viewed by 12561

Abstract

(1) Background: Patients with advanced chronic liver disease (ACLD) are living longer with more comorbidities because of improved medical and surgical management. However, patients with ACLD are at increased risk of perioperative morbidity and mortality; (2) Methods: We conducted a comprehensive review of [...] Read more.

(1) Background: Patients with advanced chronic liver disease (ACLD) are living longer with more comorbidities because of improved medical and surgical management. However, patients with ACLD are at increased risk of perioperative morbidity and mortality; (2) Methods: We conducted a comprehensive review of the literature to support a narrative clinical guideline about the assessment of mortality risk and management of perioperative morbidity in patients with ACLD undergoing surgical procedures; (3) Results: Slight data exist to guide the perioperative management of patients with ACLD, and most recommendations are based on case series and expert opinion. The severity of liver dysfunction, portal hypertension, cardiopulmonary and renal comorbidities, and complexity of surgery and type (elective versus emergent) are predictors of perioperative morbidity and mortality. Expert multidisciplinary teams are necessary to evaluate and manage ACLD before, during, and after surgical procedures; (4) Conclusions: This clinical practice document updates the available data and recommendations to optimize the management of patients with advanced chronic liver disease who undergo surgical procedures. Full article

(This article belongs to the Special Issue Clinical Guidelines in the Health Area)

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10 pages, 250 KB

Open AccessEditor’s ChoiceArticle

Cytogenetic Effects in Patients after Computed Tomography Examination

by Elizaveta Neronova and Sergei Aleksanin

Life 2022, 12(12), 1983; https://doi.org/10.3390/life12121983 - 27 Nov 2022

Cited by 2 | Viewed by 2504

Abstract

Millions of people around the world are exposed to low doses of ionizing radiation from diagnostic computed tomography (CT) scans. Currently available data on the potential cancer risk after CT scans are contradictory and therefore demand further investigations. The aim of the current [...] Read more.

Millions of people around the world are exposed to low doses of ionizing radiation from diagnostic computed tomography (CT) scans. Currently available data on the potential cancer risk after CT scans are contradictory and therefore demand further investigations. The aim of the current study was to obtain estimations of genome damage after CT scans in 42 non-cancer patients and to conduct a comparison of the results with 22 control subjects. The frequency of dicentric ring chromosomes and chromosome breaks was significantly increased in irradiated patients compared to the controls. The distribution of dicentrics among the cells demonstrated non-Poisson distribution that reflected non-uniform and partial-body radiation exposure. A fraction of patients followed Poisson distribution, which is typical for uniform whole-body exposures. Some patients demonstrated a level of dicentrics similar to the control subjects. The individual variations in the frequency and dicentric distribution suggested complex mechanisms of chromosome aberration induction and elimination that could be associated with individual radiosensitivity, as well as previous diagnostics that used ionizing radiation or the redistribution of small fractions of irradiated lymphocytes within the circulatory pull. In conclusion, CT scans may cause genome damage and possible increases in cancer risk. The introduction of a specific follow-up of such patients, especially in the case of repeated CT scans, is suggested. Full article

(This article belongs to the Special Issue State-of-the-Art in Biomedicine in Russia Federation)

14 pages, 1341 KB

Open AccessEditor’s ChoiceReview

Fine-Needle Aspiration Cytology for Parotid Tumors

by Masataka Taniuchi, Tetsuya Terada and Ryo Kawata

Life 2022, 12(11), 1897; https://doi.org/10.3390/life12111897 - 15 Nov 2022

Cited by 11 | Viewed by 4680

Abstract

Fine-needle aspiration (FNA) cytology is widely used in clinical practice as a simple and minimally invasive test for parotid tumors that allows for preoperative estimation of benignancy and malignancy, histological type, and malignancy grade and can be performed on an outpatient basis. In [...] Read more.

Fine-needle aspiration (FNA) cytology is widely used in clinical practice as a simple and minimally invasive test for parotid tumors that allows for preoperative estimation of benignancy and malignancy, histological type, and malignancy grade and can be performed on an outpatient basis. In recent years, cell blocks prepared with core needle biopsy (CNB) and liquid-based cytology (LBC) have increased the reliability of immunostaining and molecular biological testing, leading to improved diagnostic accuracy. In 2018, the Milan System for Reporting Salivary Gland Cytology was introduced, but it does not include malignancy grade or histological type, so we proposed the Osaka Medical College classification as a more clinically based cell classification that includes both types of information, and we have reported on its usefulness. This review gives an overview of the history and use of FNA and describes CNB and LBC and the two classification systems. Full article

(This article belongs to the Special Issue New Insights into Diagnosis and Pitfalls in the Treatment of Parotid Tumors)

19 pages, 996 KB

Open AccessEditor’s ChoiceReview

Acute Respiratory Distress Syndrome and the Use of Inhaled Pulmonary Vasodilators in the COVID-19 Era: A Narrative Review

by Adeel Nasrullah, Shiza Virk, Aaisha Shah, Max Jacobs, Amina Hamza, Abu Baker Sheikh, Anam Javed, Muhammad Ali Butt and Swathi Sangli

Life 2022, 12(11), 1766; https://doi.org/10.3390/life12111766 - 2 Nov 2022

Cited by 9 | Viewed by 6049

Abstract

The Coronavirus disease (COVID-19) pandemic of 2019 has resulted in significant morbidity and mortality, especially from severe acute respiratory distress syndrome (ARDS). As of September 2022, more than 6.5 million patients have died globally, and up to 5% required intensive care unit treatment. [...] Read more.

The Coronavirus disease (COVID-19) pandemic of 2019 has resulted in significant morbidity and mortality, especially from severe acute respiratory distress syndrome (ARDS). As of September 2022, more than 6.5 million patients have died globally, and up to 5% required intensive care unit treatment. COVID-19-associated ARDS (CARDS) differs from the typical ARDS due to distinct pathology involving the pulmonary vasculature endothelium, resulting in diffuse thrombi in the pulmonary circulation and impaired gas exchange. The National Institute of Health and the Society of Critical Care Medicine recommend lung-protective ventilation, prone ventilation, and neuromuscular blockade as needed. Further, a trial of pulmonary vasodilators is suggested for those who develop refractory hypoxemia. A review of the prior literature on inhaled pulmonary vasodilators in ARDS suggests only a transient improvement in oxygenation, with no mortality benefit. This narrative review aims to highlight the fundamental principles in ARDS management, delineate the fundamental differences between CARDS and ARDS, and describe the comprehensive use of inhaled pulmonary vasodilators. In addition, with the differing pathophysiology of CARDS from the typical ARDS, we sought to evaluate the current evidence regarding the use of inhaled pulmonary vasodilators in CARDS. Full article

(This article belongs to the Special Issue Challenges in Stroke Care)

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19 pages, 729 KB

Open AccessEditor’s ChoiceReview

The Overview of Perspectives of Clinical Application of Liquid Biopsy in Non-Small-Cell Lung Cancer

by Aleksandra Bożyk and Marcin Nicoś

Life 2022, 12(10), 1640; https://doi.org/10.3390/life12101640 - 19 Oct 2022

Cited by 9 | Viewed by 3408

Abstract

The standard diagnostics procedure for non-small-cell lung cancer (NSCLC) requires a pathological evaluation of tissue samples obtained by surgery or biopsy, which are considered invasive sampling procedures. Due to this fact, re-sampling of the primary tumor at the moment of progression is limited [...] Read more.

The standard diagnostics procedure for non-small-cell lung cancer (NSCLC) requires a pathological evaluation of tissue samples obtained by surgery or biopsy, which are considered invasive sampling procedures. Due to this fact, re-sampling of the primary tumor at the moment of progression is limited and depends on the patient’s condition, even if it could reveal a mechanism of resistance to applied therapy. Recently, many studies have indicated that liquid biopsy could be provided for the noninvasive management of NSCLC patients who receive molecularly targeted therapies or immunotherapy. The liquid biopsy of neoplastic patients harbors small fragments of circulating-free DNA (cfDNA) and cell-free RNA (cfRNA) secreted to the circulation from normal cells, as well as a subset of tumor-derived circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA). In NSCLC patients, a longitudinal assessment of genetic alterations in “druggable” genes in liquid biopsy might improve the follow-up of treatment efficacy and allow for the detection of an early progression before it is detectable in computed tomography or a clinical image. However, a liquid biopsy may be used to determine a variety of relevant molecular or genetic information for understanding tumor biology and its evolutionary trajectories. Thus, liquid biopsy is currently associated with greater hope for common diagnostic and clinical applications. In this review, we would like to highlight diagnostic challenges in the application of liquid biopsy into the clinical routine and indicate its implications on the metastatic spread of NSCLC or monitoring of personalized treatment regimens. Full article

(This article belongs to the Special Issue Thoracic Malignancies: From Prevention and Diagnosis to Late Stages)

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12 pages, 993 KB

Open AccessEditor’s ChoiceArticle

Identification of Universally Applicable and Species-Specific Marker Peptides for Bacillus anthracis

by Natalie Witt, Domenico Galante, Sandro Andreotti, Mostafa Abdel Glil, Antonio Fasanella, David Meierhofer and Herbert Tomaso

Life 2022, 12(10), 1549; https://doi.org/10.3390/life12101549 - 6 Oct 2022

Viewed by 3028

Abstract

Anthrax is a zoonotic infection caused by the bacterium Bacillus anthracis (BA). Specific identification of this pathogen often relies on targeting genes located on two extrachromosomal plasmids, which represent the major pathogenicity factors of BA. However, more recent findings show that these plasmids [...] Read more.

Anthrax is a zoonotic infection caused by the bacterium Bacillus anthracis (BA). Specific identification of this pathogen often relies on targeting genes located on two extrachromosomal plasmids, which represent the major pathogenicity factors of BA. However, more recent findings show that these plasmids have also been found in other closely related Bacillus species. In this study, we investigated the possibility of identifying species-specific and universally applicable marker peptides for BA. For this purpose, we applied a high-resolution mass spectrometry-based approach for 42 BA isolates. Along with the genomic sequencing data and by developing a bioinformatics data evaluation pipeline, which uses a database containing most of the publicly available protein sequences worldwide (UniParc), we were able to identify eleven universal marker peptides unique to BA. These markers are located on the chromosome and therefore, might overcome known problems, such as observable loss of plasmids in environmental species, plasmid loss during cultivation in the lab, and the fact that the virulence plasmids are not necessarily a unique feature of BA. The identified chromosomally encoded markers in this study could extend the small panel of already existing chromosomal targets and along with targets for the virulence plasmids, may pave the way to an even more reliable identification of BA using genomics- as well as proteomics-based techniques. Full article

(This article belongs to the Special Issue Emerging Themes in Anthrax)

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16 pages, 621 KB

Open AccessEditor’s ChoiceReview

The Interplay between Anti-Angiogenics and Immunotherapy in Colorectal Cancer

by Brigida Anna Maiorano, Alessandro Parisi, Evaristo Maiello and Davide Ciardiello

Life 2022, 12(10), 1552; https://doi.org/10.3390/life12101552 - 6 Oct 2022

Cited by 6 | Viewed by 3244

Abstract

Angiogenesis, a hallmark of cancer, plays a fundamental role in colorectal cancer (CRC). Anti-angiogenic drugs and chemotherapy represent a standard of care for treating metastatic disease. Immune checkpoint inhibitors (ICIs) have changed the therapeutic algorithm of many solid tumors. However, the efficacy of [...] Read more.

Angiogenesis, a hallmark of cancer, plays a fundamental role in colorectal cancer (CRC). Anti-angiogenic drugs and chemotherapy represent a standard of care for treating metastatic disease. Immune checkpoint inhibitors (ICIs) have changed the therapeutic algorithm of many solid tumors. However, the efficacy of ICIs is limited to mCRC patients carrying microsatellite instability (MSI-H), which represent approximately 3–5% of mCRC. Emerging evidence suggests that anti-angiogenic drugs could exhibit immunomodulatory properties. Thus, there is a strong rationale for combining anti-angiogenics and ICIs to improve efficacy in the metastatic setting. Our review summarizes the pre-clinical and clinical evidence regarding the combination of anti-angiogenics and ICIs in mCRC to deepen the possible application in daily clinical practice. Full article

(This article belongs to the Special Issue New Insights into the Treatment of Colorectal Cancer in the Era of Precision Medicine)

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13 pages, 738 KB

Open AccessEditor’s ChoiceReview

Microbiome in Chronic Kidney Disease

by Theodoros Tourountzis, Georgios Lioulios, Asimina Fylaktou, Eleni Moysidou, Aikaterini Papagianni and Maria Stangou

Life 2022, 12(10), 1513; https://doi.org/10.3390/life12101513 - 28 Sep 2022

Cited by 18 | Viewed by 5412

Abstract

The gut microbiome is a complex collection of microorganisms with discrete characteristics and activities. Its important role is not restricted to food digestion and metabolism, but extends to the evolution, activation and function of the immune system. Several factors, such as mode of [...] Read more.

The gut microbiome is a complex collection of microorganisms with discrete characteristics and activities. Its important role is not restricted to food digestion and metabolism, but extends to the evolution, activation and function of the immune system. Several factors, such as mode of birth, diet, medication, ageing and chronic inflammation, can modify the intestinal microbiota. Chronic kidney disease (CKD) seems to have a direct and unique effect, as increased urea levels result in alteration of the gut microbiome, leading to overproduction of its metabolites. Therefore, potentially noxious microbial uremic toxins, which have predominantly renal clearance, including p-cresyl sulfate, indoxyl sulfate and N-oxide of trimethylamine [Trimethylamine-N-Oxide (TMAO)], accumulate in human’s body, and are responsible not only for the clinical implications of CKD, but also for the progression of renal failure itself. Certain changes in gut microbiome are observed in patients with end stage renal disease (ESRD), either when undergoing hemodialysis or after kidney transplantation. The purpose of this review is to summarize the changes of gut microbiome and the protein bound uremic toxins which are observed in CKD and in different kidney replacement strategies. In addition, we attempt to review the connection between microbiome, clinical implications and immune response in CKD. Full article

(This article belongs to the Section Medical Research)

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