Life | Editor’s choice

Review

17 pages, 1108 KiB

Open AccessEditor’s ChoiceReview

Interleukin-1 Blockers: A Paradigm Shift in the Treatment of Recurrent Pericarditis

by Emilia Lazarou, Christos Koutsianas, Panagiotis Theofilis, George Lazaros, Dimitrios Vassilopoulos, Charalambos Vlachopoulos, Costas Tsioufis, Massimo Imazio, Antonio Brucato and Dimitris Tousoulis

Life 2024, 14(3), 305; https://doi.org/10.3390/life14030305 - 26 Feb 2024

Cited by 2 | Viewed by 1632

Abstract

Recurrent pericarditis is a problematic clinical condition that impairs the quality of life of the affected patients due to the need for repeated hospital admissions, emergency department visits, and complications from medications, especially glucocorticoids. Unfortunately, available treatments for recurrent pericarditis are very limited, [...] Read more.

Recurrent pericarditis is a problematic clinical condition that impairs the quality of life of the affected patients due to the need for repeated hospital admissions, emergency department visits, and complications from medications, especially glucocorticoids. Unfortunately, available treatments for recurrent pericarditis are very limited, including only a handful of medications such as aspirin/NSAIDs, glucocorticoids, colchicine, and immunosuppressants (such as interleukin-1 (IL-1) blockers, azathioprine, and intravenous human immunoglobulins). Until recently, the clinical experience with the latter class of medications was very limited. Nevertheless, in the last decade, experience with IL-1 blockers has consistently grown, and valid clinical data have emerged from randomized clinical trials. Accordingly, IL-1 blockers are a typical paradigm shift in the treatment of refractory recurrent pericarditis with a clearly positive cost/benefit ratio for those unfortunate patients with multiple recurrences. A drawback related to the above-mentioned medications is the absence of universally accepted and established treatment protocols regarding the full dose administration period and the need for a tapering protocol for individual medications. Another concern is the need for long-standing treatments, which should be discussed with the patients. The above-mentioned unmet needs are expected to be addressed in the near future, such as further insights into pathophysiology and an individualized approach to affected patients. Full article

(This article belongs to the Special Issue Interdisciplinarity in Cardiovascular Diseases: From Pathophysiology to Diagnosis and Treatment—2nd Edition)

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37 pages, 2103 KiB

Open AccessEditor’s ChoiceReview

Integrating Artificial Intelligence for Drug Discovery in the Context of Revolutionizing Drug Delivery

by Anita Ioana Visan and Irina Negut

Life 2024, 14(2), 233; https://doi.org/10.3390/life14020233 - 7 Feb 2024

Cited by 19 | Viewed by 9898

Abstract

Drug development is expensive, time-consuming, and has a high failure rate. In recent years, artificial intelligence (AI) has emerged as a transformative tool in drug discovery, offering innovative solutions to complex challenges in the pharmaceutical industry. This manuscript covers the multifaceted role of [...] Read more.

Drug development is expensive, time-consuming, and has a high failure rate. In recent years, artificial intelligence (AI) has emerged as a transformative tool in drug discovery, offering innovative solutions to complex challenges in the pharmaceutical industry. This manuscript covers the multifaceted role of AI in drug discovery, encompassing AI-assisted drug delivery design, the discovery of new drugs, and the development of novel AI techniques. We explore various AI methodologies, including machine learning and deep learning, and their applications in target identification, virtual screening, and drug design. This paper also discusses the historical development of AI in medicine, emphasizing its profound impact on healthcare. Furthermore, it addresses AI’s role in the repositioning of existing drugs and the identification of drug combinations, underscoring its potential in revolutionizing drug delivery systems. The manuscript provides a comprehensive overview of the AI programs and platforms currently used in drug discovery, illustrating the technological advancements and future directions of this field. This study not only presents the current state of AI in drug discovery but also anticipates its future trajectory, highlighting the challenges and opportunities that lie ahead. Full article

(This article belongs to the Special Issue Revolutionizing Drug Delivery: Innovations in Targeted Therapeutic Nanocarriers)

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21 pages, 1149 KiB

Open AccessEditor’s ChoiceReview

Mitochondria in Alzheimer’s Disease Pathogenesis

by Allison B. Reiss, Shelly Gulkarov, Benna Jacob, Ankita Srivastava, Aaron Pinkhasov, Irving H. Gomolin, Mark M. Stecker, Thomas Wisniewski and Joshua De Leon

Life 2024, 14(2), 196; https://doi.org/10.3390/life14020196 - 30 Jan 2024

Cited by 3 | Viewed by 4454

Abstract

Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disorder that primarily affects persons aged 65 years and above. It causes dementia with memory loss and deterioration in thinking and language skills. AD is characterized by specific pathology resulting from the accumulation in [...] Read more.

Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disorder that primarily affects persons aged 65 years and above. It causes dementia with memory loss and deterioration in thinking and language skills. AD is characterized by specific pathology resulting from the accumulation in the brain of extracellular plaques of amyloid-β and intracellular tangles of phosphorylated tau. The importance of mitochondrial dysfunction in AD pathogenesis, while previously underrecognized, is now more and more appreciated. Mitochondria are an essential organelle involved in cellular bioenergetics and signaling pathways. Mitochondrial processes crucial for synaptic activity such as mitophagy, mitochondrial trafficking, mitochondrial fission, and mitochondrial fusion are dysregulated in the AD brain. Excess fission and fragmentation yield mitochondria with low energy production. Reduced glucose metabolism is also observed in the AD brain with a hypometabolic state, particularly in the temporo-parietal brain regions. This review addresses the multiple ways in which abnormal mitochondrial structure and function contribute to AD. Disruption of the electron transport chain and ATP production are particularly neurotoxic because brain cells have disproportionately high energy demands. In addition, oxidative stress, which is extremely damaging to nerve cells, rises dramatically with mitochondrial dyshomeostasis. Restoring mitochondrial health may be a viable approach to AD treatment. Full article

(This article belongs to the Special Issue Mitochondria: Biological Targets for Fighting Disease)

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0 pages, 1342 KiB

Open AccessEditor’s ChoiceReview

Cutaneous Hyalohyphomycosis and Its Atypical Clinical Presentations in Immunosuppressed Patients

by Nikola Ferara, Sanja Špoljar, Liborija Lugović-Mihić, Ana Gverić Grginić, Violeta Rezo Vranješ, Iva Bešlić, Judita Perović and Tihana Regović Džombeta

Life 2024, 14(1), 154; https://doi.org/10.3390/life14010154 - 21 Jan 2024

Viewed by 1815

Abstract

There has been a substantial increase in the number of cases of invasive fungal infections worldwide, which is associated with a growing number of immunosuppressed patients and a rise in antifungal resistance. Some fungi that were previously considered harmless to humans have become [...] Read more.

There has been a substantial increase in the number of cases of invasive fungal infections worldwide, which is associated with a growing number of immunosuppressed patients and a rise in antifungal resistance. Some fungi that were previously considered harmless to humans have become emerging pathogens. One of them is Purpureocillium lilacinum, a ubiquitous filamentous fungus commonly found in the environment, especially in the air and soil. P. lilacinum belongs to a bigger group of hyaline fungi that cause hyalohyphomycosis, a fungal infection caused by fungi with colorless hyphae. Although this is a heterogeneous group of fungi, there are similarities regarding their ubiquity, ways of transmission, affected patients, and difficulties in diagnostics and treatment. In hyalohyphomycosis, the skin is one of the most affected organs, which is why the involvement of dermatologists is crucial for the initial assessment, since the timely recognition and early diagnosis of this condition can prevent life-threatening infections and death. In this review, we covered cutaneous hyalohyphomycosis caused by P. lilacinum and other fungi in the same group, including Fusarium, Penicilium, Scedosporium, Scopulariopsis, Acremonium, and Trichoderma genera. Full article

(This article belongs to the Section Microbiology)

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13 pages, 1239 KiB

Open AccessEditor’s ChoiceReview

Connectome-Based Neurosurgery in Primary Intra-Axial Neoplasms: Beyond the Traditional Modular Conception of Brain Architecture for the Preservation of Major Neurological Domains and Higher-Order Cognitive Functions

by Marcello Magnani, Arianna Rustici, Matteo Zoli, Constantin Tuleasca, Bipin Chaurasia, Enrico Franceschi, Caterina Tonon, Raffaele Lodi and Alfredo Conti

Life 2024, 14(1), 136; https://doi.org/10.3390/life14010136 - 18 Jan 2024

Cited by 1 | Viewed by 1493

Abstract

Despite the therapeutical advancements in the surgical treatment of primary intra-axial neoplasms, which determined both a significative improvement in OS and QoL and a reduction in the incidence of surgery-induced major neurological deficits, nowadays patients continue to manifest subtle post-operative neurocognitive impairments, preventing [...] Read more.

Despite the therapeutical advancements in the surgical treatment of primary intra-axial neoplasms, which determined both a significative improvement in OS and QoL and a reduction in the incidence of surgery-induced major neurological deficits, nowadays patients continue to manifest subtle post-operative neurocognitive impairments, preventing them from a full reintegration back into social life and into the workforce. The birth of connectomics paved the way for a profound reappraisal of the traditional conception of brain architecture, in favour of a model based on large-scale structural and functional interactions of a complex mosaic of cortical areas organized in a fluid network interconnected by subcortical bundles. Thanks to these advancements, neurosurgery is facing a new era of connectome-based resections, in which the core principle is still represented by the achievement of an ideal onco-functional balance, but with a closer eye on whole-brain circuitry, which constitutes the foundations of both major neurological functions, to be intended as motricity; language and visuospatial function; and higher-order cognitive functions such as cognition, conation, emotion and adaptive behaviour. Indeed, the achievement of an ideal balance between the radicality of tumoral resection and the preservation, as far as possible, of the integrity of local and global brain networks stands as a mandatory goal to be fulfilled to allow patients to resume their previous life and to make neurosurgery tailored and gentler to their individual needs. Full article

(This article belongs to the Section Medical Research)

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16 pages, 1845 KiB

Open AccessEditor’s ChoiceReview

Breast Reconstruction following Mastectomy for Breast Cancer or Prophylactic Mastectomy: Therapeutic Options and Results

by Laurentiu Simion, Ina Petrescu, Elena Chitoran, Vlad Rotaru, Ciprian Cirimbei, Sinziana-Octavia Ionescu, Daniela-Cristina Stefan, Dan Luca, Dana Lucia Stanculeanu, Adelina Silvana Gheorghe, Horia Doran and Ioana Mihaela Dogaru

Life 2024, 14(1), 138; https://doi.org/10.3390/life14010138 - 18 Jan 2024

Cited by 3 | Viewed by 2170

Abstract

(1) Importance of problem: Breast cancer accounted for 685,000 deaths globally in 2020, and half of all cases occur in women with no specific risk factor besides gender and age group. During the last four decades, we have seen a 40% reduction in [...] Read more.

(1) Importance of problem: Breast cancer accounted for 685,000 deaths globally in 2020, and half of all cases occur in women with no specific risk factor besides gender and age group. During the last four decades, we have seen a 40% reduction in age-standardized breast cancer mortality and have also witnessed a reduction in the medium age at diagnosis, which in turn means that the number of mastectomies performed for younger women increased, raising the need for adequate breast reconstructive surgery. Advances in oncological treatment have made it possible to limit the extent of what represents radical surgery for breast cancer, yet in the past decade, we have seen a marked trend toward mastectomies in breast-conserving surgery-eligible patients. Prophylactic mastectomies have also registered an upward trend. This trend together with new uses for breast reconstruction like chest feminization in transgender patients has increased the need for breast reconstruction surgery. (2) Purpose: The purpose of this study is to analyze the types of reconstructive procedures, their indications, their limitations, their functional results, and their safety profiles when used during the integrated treatment plan of the oncologic patient. (3) Methods: We conducted an extensive literature review of the main reconstructive techniques, especially the autologous procedures; summarized the findings; and presented a few cases from our own experience for exemplification of the usage of breast reconstruction in oncologic patients. (4) Conclusions: Breast reconstruction has become a necessary step in the treatment of most breast cancers, and many reconstructive techniques are now routinely practiced. Microsurgical techniques are considered the “gold standard”, but they are not accessible to all services, from a technical or financial point of view, so pediculated flaps remain the safe and reliable option, along with alloplastic procedures, to improve the quality of life of these patients. Full article

(This article belongs to the Special Issue Advances in Breast Cancer Research and Treatment)

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13 pages, 1125 KiB

Open AccessEditor’s ChoiceReview

Primary Role of the Kidney in Pathogenesis of Hypertension

by Gheun-Ho Kim

Life 2024, 14(1), 119; https://doi.org/10.3390/life14010119 - 14 Jan 2024

Cited by 1 | Viewed by 3428

Abstract

Previous transplantation studies and the concept of ‘nephron underdosing’ support the idea that the kidney plays a crucial role in the development of essential hypertension. This suggests that there are genetic factors in the kidney that can either elevate or decrease blood pressure. [...] Read more.

Previous transplantation studies and the concept of ‘nephron underdosing’ support the idea that the kidney plays a crucial role in the development of essential hypertension. This suggests that there are genetic factors in the kidney that can either elevate or decrease blood pressure. The kidney normally maintains arterial pressure within a narrow range by employing the mechanism of pressure-natriuresis. Hypertension is induced when the pressure-natriuresis mechanism fails due to both subtle and overt kidney abnormalities. The inheritance of hypertension is believed to be polygenic, and essential hypertension may result from a combination of genetic variants that code for renal tubular sodium transporters or proteins involved in regulatory pathways. The renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS) are the major regulators of renal sodium reabsorption. Hyperactivity of either the RAAS or SNS leads to a rightward shift in the pressure-natriuresis curve. In other words, hypertension is induced when the activity of RAAS and SNS is not suppressed despite increased salt intake. Sodium overload, caused by increased intake and/or reduced renal excretion, not only leads to an expansion of plasma volume but also to an increase in systemic vascular resistance. Endothelial dysfunction is caused by an increased intracellular Na⁺ concentration, which inhibits endothelial nitric oxide (NO) synthase and reduces NO production. The stiffness of vascular smooth muscle cells is increased by the accumulation of intracellular Na⁺ and subsequent elevation of cytoplasmic Ca⁺⁺ concentration. In contrast to the hemodynamic effects of osmotically active Na⁺, osmotically inactive Na⁺ stimulates immune cells and produces proinflammatory cytokines, which contribute to hypertension. When this occurs in the gut, the microbiota may become imbalanced, leading to intestinal inflammation and systemic hypertension. In conclusion, the primary cause of hypertension is sodium overload resulting from kidney dysregulation. Full article

(This article belongs to the Special Issue Pulmonary Hypertension: From Bench to Bedside: 2nd Edition)

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16 pages, 374 KiB

Open AccessEditor’s ChoiceReview

The Most Recent Insights into the Roots of Gastric Cancer

by Lorena Elena Meliț, Cristina Oana Mărginean and Reka Borka Balas

Life 2024, 14(1), 95; https://doi.org/10.3390/life14010095 - 8 Jan 2024

Cited by 2 | Viewed by 1735

Abstract

Helicobacter pylori (H. pylori) is the most common bacterial infection worldwide, usually being acquired during childhood, and its persistence into adulthood represents one of the main contributors of gastric carcinogenesis. Based on these statements, it would be of great importance to [...] Read more.

Helicobacter pylori (H. pylori) is the most common bacterial infection worldwide, usually being acquired during childhood, and its persistence into adulthood represents one of the main contributors of gastric carcinogenesis. Based on these statements, it would be of great importance to know if the most early premalignant transformation occurs in children or later since, this would enable the development of effective anti-tumorigenesis strategies. The interplay between H. pylori virulence factors, the host’s responses modified by this infection, and the gastric microecology are complex and eventually lead to the development of gastric cancer in susceptible individuals. Several biomarkers were identified as major contributors of this long-lasting process, such as pepsinogens, gastrin 17, lipid-, glucose- and iron-metabolism parameters, immunity players, aberrant bacterial DNA methylation, H. pylori virulence factors, and hallmarks of gastric dysbiosis. Several of these biomarkers were also identified in children with H. pylori infection, independently of the presence of premalignant lesions, which were also proven to be present in a subgroup of H. pylori-infected children, especially those carrying extremely virulent strains. Therefore, the most incipient premalignant gastric changes might indeed occur early during childhood, opening a promising research gate for further studies to delineate the border between infection and cancer. Full article

(This article belongs to the Special Issue Helicobacter pylori)

27 pages, 447 KiB

Open AccessEditor’s ChoiceReview

Traditional Therapeutics and Potential Epidrugs for CVD: Why Not Both?

by Lauren Rae Gladwell, Chidinma Ahiarah, Shireen Rasheed, Shaikh Mizanoor Rahman and Mahua Choudhury

Life 2024, 14(1), 23; https://doi.org/10.3390/life14010023 - 22 Dec 2023

Cited by 1 | Viewed by 2321

Abstract

Cardiovascular disease (CVD) is the leading cause of death worldwide. In addition to the high mortality rate, people suffering from CVD often endure difficulties with physical activities and productivity that significantly affect their quality of life. The high prevalence of debilitating risk factors [...] Read more.

Cardiovascular disease (CVD) is the leading cause of death worldwide. In addition to the high mortality rate, people suffering from CVD often endure difficulties with physical activities and productivity that significantly affect their quality of life. The high prevalence of debilitating risk factors such as obesity, type 2 diabetes mellitus, smoking, hypertension, and hyperlipidemia only predicts a bleak future. Current traditional CVD interventions offer temporary respite; however, they compound the severe economic strain of health-related expenditures. Furthermore, these therapeutics can be prescribed indefinitely. Recent advances in the field of epigenetics have generated new treatment options by confronting CVD at an epigenetic level. This involves modulating gene expression by altering the organization of our genome rather than altering the DNA sequence itself. Epigenetic changes are heritable, reversible, and influenced by environmental factors such as medications. As CVD is physiologically and pathologically diverse in nature, epigenetic interventions can offer a ray of hope to replace or be combined with traditional therapeutics to provide the prospect of addressing more than just the symptoms of CVD. This review discusses various risk factors contributing to CVD, perspectives of current traditional medications in practice, and a focus on potential epigenetic therapeutics to be used as alternatives. Full article

(This article belongs to the Section Pharmaceutical Science)

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11 pages, 771 KiB

Open AccessEditor’s ChoiceReview

Advances in Identifying the Mechanisms by Which Microorganisms Improve Barley Salt Tolerance

by Zhiwei Chen, Zhenzhu Guo, Longhua Zhou, Hongwei Xu, Chenghong Liu and Xin Yan

Life 2024, 14(1), 6; https://doi.org/10.3390/life14010006 - 19 Dec 2023

Viewed by 1213

Abstract

As the global human population continues to increase, the use of saline–alkali land for food production is an important consideration for food security. In addition to breeding or cultivating salt-tolerant crop varieties, microorganisms are increasingly being evaluated for their ability to improve plant [...] Read more.

As the global human population continues to increase, the use of saline–alkali land for food production is an important consideration for food security. In addition to breeding or cultivating salt-tolerant crop varieties, microorganisms are increasingly being evaluated for their ability to improve plant salt tolerance. Barley is one of the most important and salt-tolerant cereal crops and is a model system for investigating the roles of microorganisms in improving plant salt tolerance. However, a comprehensive review of the mechanisms by which microorganisms improve barley salt tolerance remains lacking. In this review, the mechanisms of barley salt tolerance improvement by microorganisms are summarized, along with a discussion of existing problems in current research and areas of future research directions. In particular, with the development of sequencing technology and the great reduction of prices, the use of omics can not only comprehensively evaluate the role of microorganisms but also evaluate the impact of the microbiome on plants, which will provide us with many opportunities and challenges in this research area. Full article

(This article belongs to the Special Issue Cereals: Stress Resistance and Breeding)

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13 pages, 501 KiB

Open AccessEditor’s ChoiceReview

Dermatophyte Infections Worldwide: Increase in Incidence and Associated Antifungal Resistance

by Caroline Kruithoff, Ahmed Gamal, Thomas S. McCormick and Mahmoud A. Ghannoum

Life 2024, 14(1), 1; https://doi.org/10.3390/life14010001 - 19 Dec 2023

Cited by 4 | Viewed by 5493

Abstract

The increase in incidence of superficial fungal infections combined with the emergence of antifungal resistance represents both a global health challenge and a considerable economic burden. Recently, dermatophytes, the main culprit causing superficial fungal infections, have started to exhibit antifungal resistance. This can [...] Read more.

The increase in incidence of superficial fungal infections combined with the emergence of antifungal resistance represents both a global health challenge and a considerable economic burden. Recently, dermatophytes, the main culprit causing superficial fungal infections, have started to exhibit antifungal resistance. This can be observed in some of the most common species such as Trichophyton rubrum and Trichophyton mentagrophytes. Importantly, the new subspecies, known as Trichophyton indotineae, has been reported to show high resistance to terbinafine, a first-line treatment for dermatophyte infections. Compounding these issues is the realization that diagnosing the causative infectious agents requires using molecular analysis that goes beyond the conventional macroscopic and microscopic methods. These findings emphasize the importance of conducting antifungal susceptibility testing to select the appropriate antifungal necessary for successful treatment. Implementing these changes may improve clinical practices that combat resistant dermatophyte infections. Full article

(This article belongs to the Special Issue Fungal Disease Epidemiology: Current State and Future Prospects)

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18 pages, 8612 KiB

Open AccessEditor’s ChoiceReview

The Cavernous Nerve Injury Rat Model: A Pictorial Essay on Post-Radical Prostatectomy Erectile Dysfunction Research

by Silviu Constantin Latcu, Dorin Novacescu, Victor-Bogdan Buciu, Cristina-Stefania Dumitru, Raluca Amalia Ceausu, Marius Raica, Talida Georgiana Cut, Razvan Ilina, Daniel Claudiu Malita, Cristi Tarta and Alin Adrian Cumpanas

Life 2023, 13(12), 2337; https://doi.org/10.3390/life13122337 - 13 Dec 2023

Cited by 2 | Viewed by 2065

Abstract

Understanding and addressing post-radical prostatectomy (RP) erectile dysfunction (ED) is of paramount importance for clinicians. Cavernous nerve (CN) injury rat model studies have provided consistently promising experimental data regarding regaining erectile function (EF) after nerve damage-induced ED. However, these findings have failed to [...] Read more.

Understanding and addressing post-radical prostatectomy (RP) erectile dysfunction (ED) is of paramount importance for clinicians. Cavernous nerve (CN) injury rat model studies have provided consistently promising experimental data regarding regaining erectile function (EF) after nerve damage-induced ED. However, these findings have failed to translate efficiently into clinical practice, with post-RP ED therapeutic management remaining cumbersome and enigmatic. This disparity highlights the need for further standardization and optimization of the elaborate surgical preparation protocols and multifaceted reporting parameters involved in reliable CN injury rat model experimentation. Even so, despite its technical complexity, this animal model remains instrumental in exploring the functional implications of RP, i.e., surgical lesions of the neurovascular bundles (NVBs). Herein, besides cavernous nerve (CN) dissection, injury, and electrostimulation, multiple pressure measurements, i.e., mean arterial pressure (MAP) and intra-cavernosal pressure (ICP), must also be achieved. A transverse cervical incision allows for carotid artery cannulation and MAP measurements. Conversely, ICP measurements entail circumcising the penis, exposing the ischiocavernous muscle, and inserting a needle into the corporal body. Finally, using an abdominal incision, the prostate is revealed, and the major pelvic ganglia (MPG) and CNs are dissected bilaterally. Specific surgical techniques are used to induce CN injuries. Herein, we provide a narrative and illustrative overview regarding these complex experimental procedures and their particular requirements, reflecting on current evidence and future research perspectives. Full article

(This article belongs to the Special Issue Prostate Cancer: 3rd Edition)

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28 pages, 1858 KiB

Open AccessEditor’s ChoiceReview

Point-of-Care Testing for Hepatitis Viruses: A Growing Need

by Matthew D. Pauly and Lilia Ganova-Raeva

Life 2023, 13(12), 2271; https://doi.org/10.3390/life13122271 - 28 Nov 2023

Cited by 1 | Viewed by 3120

Abstract

Viral hepatitis, caused by hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), or hepatitis E virus (HEV), is a major global public health problem. These viruses cause millions of infections each year, and chronic infections [...] Read more.

Viral hepatitis, caused by hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), or hepatitis E virus (HEV), is a major global public health problem. These viruses cause millions of infections each year, and chronic infections with HBV, HCV, or HDV can lead to severe liver complications; however, they are underdiagnosed. Achieving the World Health Organization’s viral hepatitis elimination goals by 2030 will require access to simpler, faster, and less expensive diagnostics. The development and implementation of point-of-care (POC) testing methods that can be performed outside of a laboratory for the diagnosis of viral hepatitis infections is a promising approach to facilitate and expedite WHO’s elimination targets. While a few markers of viral hepatitis are already available in POC formats, tests for additional markers or using novel technologies need to be developed and validated for clinical use. Potential methods and uses for the POC testing of antibodies, antigens, and nucleic acids that relate to the diagnosis, monitoring, or surveillance of viral hepatitis infections are discussed here. Unmet needs and areas where additional research is needed are also described. Full article

(This article belongs to the Section Epidemiology)

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18 pages, 342 KiB

Open AccessEditor’s ChoiceReview

Gut Microbiota, Inflammation, and Probiotic Supplementation in Fetal Growth Restriction—A Comprehensive Review of Human and Animal Studies

by Naser A. Alsharairi and Li Li

Life 2023, 13(12), 2239; https://doi.org/10.3390/life13122239 - 21 Nov 2023

Cited by 2 | Viewed by 2046

Abstract

Fetal growth restriction (FGR) is a pathological state that represents a fetus’s inability to achieve adequate growth during pregnancy. Several maternal, placental, and fetal factors are likely associated with FGR etiology. FGR is linked to severe fetal and neonatal complications, as well as [...] Read more.

Fetal growth restriction (FGR) is a pathological state that represents a fetus’s inability to achieve adequate growth during pregnancy. Several maternal, placental, and fetal factors are likely associated with FGR etiology. FGR is linked to severe fetal and neonatal complications, as well as adverse health consequences in adulthood. Numerous randomized controlled trials (RCTs) have demonstrated improved growth in FGR fetuses with promising treatment strategies such as maternal micronutrient, amino acid, and nitric oxide supplementation. Elevated inflammation in pregnant women diagnosed with FGR has been associated with an imbalance between pro- and anti-inflammatory cytokines. Gut microbiota dysbiosis may result in increased FGR-related inflammation. Probiotic treatment may relieve FGR-induced inflammation and improve fetal growth. The aim of this review is to provide an overview of the gut microbiota and inflammatory profiles associated with FGR and explore the potential of probiotics in treating FGR. Full article

(This article belongs to the Special Issue From Stem Cells to Embryos, Congenital Anomalies and Epidemiology)

15 pages, 897 KiB

Open AccessEditor’s ChoiceReview

Celebrating Versatility: Febuxostat’s Multifaceted Therapeutic Application

by Krasimir Iliev Kraev, Mariela Gencheva Geneva-Popova, Bozhidar Krasimirov Hristov, Petar Angelov Uchikov, Stanislava Dimitrova Popova-Belova, Maria Ilieva Kraeva, Yordanka Mincheva Basheva-Kraeva, Nina Staneva Stoyanova and Vesela Todorova Mitkova-Hristova

Life 2023, 13(11), 2199; https://doi.org/10.3390/life13112199 - 11 Nov 2023

Cited by 2 | Viewed by 2285

Abstract

Febuxostat, initially developed as a xanthine oxidase inhibitor to address hyperuricemia in gout patients, has evolved into a versatile therapeutic agent with multifaceted applications. This review provides a comprehensive overview of febuxostat’s mechanism of action, its effectiveness in gout management, its cardiovascular safety [...] Read more.

Febuxostat, initially developed as a xanthine oxidase inhibitor to address hyperuricemia in gout patients, has evolved into a versatile therapeutic agent with multifaceted applications. This review provides a comprehensive overview of febuxostat’s mechanism of action, its effectiveness in gout management, its cardiovascular safety profile, renal and hepatic effects, musculoskeletal applications, safety considerations, and emerging research prospects. Febuxostat’s primary mechanism involves selective inhibition of xanthine oxidase, resulting in reduced uric acid production. Its pharmacokinetics require personalized dosing strategies based on individual characteristics. In gout management, febuxostat offers a compelling alternative, effectively lowering uric acid levels, relieving symptoms, and supporting long-term control, especially for patients intolerant to allopurinol. Recent studies have demonstrated its cardiovascular safety, and it exhibits minimal hepatotoxicity, making it suitable for those with liver comorbidities. Febuxostat’s potential nephroprotective effects and kidney stone prevention properties are noteworthy, particularly for gout patients with renal concerns. Beyond gout, its anti-inflammatory properties hint at applications in musculoskeletal conditions and a broader spectrum of clinical contexts, including metabolic syndrome. Emerging research explores febuxostat’s roles in cardiovascular health, neurological disorders, rheumatoid arthritis, and cancer therapy, driven by its anti-inflammatory and antioxidative properties. Future directions include personalized medicine, combination therapies, mechanistic insights, and ongoing long-term safety monitoring, collectively illuminating the promising landscape of febuxostat’s multifaceted therapeutic potential. Full article

(This article belongs to the Section Medical Research)

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19 pages, 689 KiB

Open AccessEditor’s ChoiceReview

The Therapeutic Potential of Amphetamine-like Psychostimulants

by Bruno Pires, Luana M. Rosendo, Ana Teresa Brinca, Ana Y. Simão, Mário Barroso, Tiago Rosado and Eugenia Gallardo

Life 2023, 13(11), 2180; https://doi.org/10.3390/life13112180 - 8 Nov 2023

Cited by 2 | Viewed by 3332

Abstract

This review delves into the therapeutic applications of amphetamine-type stimulants such as lisdexamphetamine dimesylate, mixed amphetamine salts, 3,4-methylenedioxymethamphetamine (MDMA), dextroamphetamine, and phentermine. These compounds have been investigated for their potential in treating a range of psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), [...] Read more.

This review delves into the therapeutic applications of amphetamine-type stimulants such as lisdexamphetamine dimesylate, mixed amphetamine salts, 3,4-methylenedioxymethamphetamine (MDMA), dextroamphetamine, and phentermine. These compounds have been investigated for their potential in treating a range of psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), drug dependence, post-traumatic stress disorder (PTSD), and obesity. Lisdexamphetamine dimesylate has shown promise in effectively treating ADHD symptoms in both children and adults. Additionally, it has been explored as a potential treatment for drug dependency and withdrawal, demonstrating encouraging results. Mixed amphetamine salts have also exhibited efficacy in reducing ADHD symptoms in adults. Future research should explore their potential use in treating bipolar disorder and cocaine dependence, considering the associated risks and benefits. MDMA-assisted psychotherapy has emerged as an innovative approach to treating PTSD, leading to sustained reductions in symptoms and even promoting post-traumatic growth. Furthermore, it has shown promise in managing anxiety related to life-threatening illnesses. Dextroamphetamine and phentermine have demonstrated efficacy in treating cocaine and opioid dependence, ADHD, and obesity. However, careful consideration and monitoring by medical professionals are essential due to the potential risks and benefits associated with them. In conclusion, amphetamine-type stimulants present a promising avenue for therapeutic interventions in various psychiatric conditions. Nevertheless, further research is necessary to comprehensively understand their mechanisms of action, dosage requirements, and long-term effects in different patient populations. Full article

(This article belongs to the Special Issue The Implication of Psychoactive Substance Consumption)

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19 pages, 22552 KiB

Open AccessEditor’s ChoiceReview

Pityriasis Versicolor—A Narrative Review on the Diagnosis and Management

by Nina Łabędź, Cristian Navarrete-Dechent, Honorata Kubisiak-Rzepczyk, Monika Bowszyc-Dmochowska, Anna Pogorzelska-Antkowiak and Paweł Pietkiewicz

Life 2023, 13(10), 2097; https://doi.org/10.3390/life13102097 - 22 Oct 2023

Cited by 5 | Viewed by 6452

Abstract

This narrative review presents a comprehensive overview of the diagnosis and management of pityriasis versicolor (PV), a common superficial fungal infection caused by the yeast Malassezia. PV is characterised by scaly hypopigmented or hyperpigmented patches, primarily affecting the upper trunk, neck, and upper [...] Read more.

This narrative review presents a comprehensive overview of the diagnosis and management of pityriasis versicolor (PV), a common superficial fungal infection caused by the yeast Malassezia. PV is characterised by scaly hypopigmented or hyperpigmented patches, primarily affecting the upper trunk, neck, and upper arms. Regarding commensal interactions, Malassezia utilises nutrient sources without affecting the human host. In cases of pathogenicity, Malassezia can directly harm the host via virulence factors or toxins, or indirectly by triggering damaging host responses. The diagnosis typically relies on recognising characteristic clinical features. Due to the wide variability in its clinical presentation, recognising the differential diagnosis is critical. In this paper, we discuss the clinical differentials, with their dermatoscopic presentation, but also describe a range of helpful diagnostic techniques (microscopy, conventional and ultraviolet-induced fluorescence dermatoscopy, and confocal microscopy). Topical therapies are the primary treatment for PV, encompassing non-specific antifungal agents like sulphur with salicylic acid, selenium sulphide 2.5%, and zinc pyrithione. Additionally, specific topical antifungal medications with either fungicidal or fungistatic properties may also be incorporated into the topical treatment regimen, such as imidazoles, allylamines, and ciclopirox olamine. Systemic therapies might occasionally be used. Patient education and the promotion of good personal hygiene are pivotal to reduce the risk of recurrence. In recurrent cases, particularly during warmer and more humid periods, prolonged prophylaxis with topical agents should be considered. Full article

(This article belongs to the Special Issue Applications of Dermatoscopy in Skin Diseases)

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15 pages, 1706 KiB

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 1 | Viewed by 1938

Abstract

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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22 pages, 1361 KiB

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 3 | Viewed by 1748

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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43 pages, 1636 KiB

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 2 | Viewed by 2231

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 KiB

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 3 | Viewed by 2520

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 KiB

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 8 | Viewed by 2417

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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11 pages, 260 KiB

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 6 | Viewed by 4965

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)

32 pages, 5406 KiB

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 29 | Viewed by 10604

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 KiB

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 9 | Viewed by 6009

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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20 pages, 1775 KiB

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 4 | Viewed by 6388

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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25 pages, 3684 KiB

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 4 | Viewed by 5703

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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16 pages, 599 KiB

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 11 | Viewed by 7936

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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20 pages, 1654 KiB

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 15 | Viewed by 3281

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 KiB

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 11 | Viewed by 4607

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 KiB

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 7 | Viewed by 4535

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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16 pages, 732 KiB

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 14 | Viewed by 4266

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, 1182 KiB

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 11 | Viewed by 7812

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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30 pages, 2406 KiB

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 40 | Viewed by 5692

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 KiB

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 10 | Viewed by 5087

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 KiB

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 10 | Viewed by 7213

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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14 pages, 1341 KiB

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 4 | Viewed by 3257

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 KiB

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 4 | Viewed by 3621

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 KiB

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 5 | Viewed by 2596

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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16 pages, 621 KiB

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 3 | Viewed by 2448

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 KiB

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 11 | Viewed by 3880

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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19 pages, 1249 KiB

Open AccessEditor’s ChoiceReview

Exosomes and Biomaterials: In Search of a New Therapeutic Strategy for Multiple Sclerosis

by Doddy Denise Ojeda-Hernández, Mercedes A. Hernández-Sapiéns, Edwin E. Reza-Zaldívar, Alejandro Canales-Aguirre, Jordi A. Matías-Guiu, Jorge Matías-Guiu, Juan Carlos Mateos-Díaz, Ulises Gómez-Pinedo and Francisco Sancho-Bielsa

Life 2022, 12(9), 1417; https://doi.org/10.3390/life12091417 - 11 Sep 2022

Cited by 9 | Viewed by 3910

Abstract

Current efforts to find novel treatments that counteract multiple sclerosis (MS) have pointed toward immunomodulation and remyelination. Currently, cell therapy has shown promising potential to achieve this purpose. However, disadvantages such as poor survival, differentiation, and integration into the target tissue have limited [...] Read more.

Current efforts to find novel treatments that counteract multiple sclerosis (MS) have pointed toward immunomodulation and remyelination. Currently, cell therapy has shown promising potential to achieve this purpose. However, disadvantages such as poor survival, differentiation, and integration into the target tissue have limited its application. A series of recent studies have focused on the cell secretome, showing it to provide the most benefits of cell therapy. Exosomes are a key component of the cell secretome, participating in the transfer of bioactive molecules. These nano-sized vesicles offer many therapeutical advantages, such as the capacity to cross the blood-brain barrier, an enrichable cargo, and a customizable membrane. Moreover, integrating of biomaterials into exosome therapy could lead to new tissue-specific therapeutic strategies. In this work, the use of exosomes and their integration with biomaterials is presented as a novel strategy in the treatment of MS. Full article

(This article belongs to the Special Issue Multiple Sclerosis: Research in Remyelination, the Next Step)

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13 pages, 1295 KiB

Open AccessEditor’s ChoiceReview

HER2 in Metastatic Colorectal Cancer: Pathology, Somatic Alterations, and Perspectives for Novel Therapeutic Schemes

by Mariia Ivanova, Konstantinos Venetis, Elena Guerini-Rocco, Luca Bottiglieri, Mauro Giuseppe Mastropasqua, Ornella Garrone, Nicola Fusco and Michele Ghidini

Life 2022, 12(9), 1403; https://doi.org/10.3390/life12091403 - 9 Sep 2022

Cited by 9 | Viewed by 2957

Abstract

HER2 is an emerging biomarker in colorectal cancer (CRC). This oncogene plays an essential role in regulating cell proliferation, differentiation, migration, and, more in general, tumorigenesis and tumor progression. The most frequent types of HER2 alterations in CRC include gene amplification and missense [...] Read more.

HER2 is an emerging biomarker in colorectal cancer (CRC). This oncogene plays an essential role in regulating cell proliferation, differentiation, migration, and, more in general, tumorigenesis and tumor progression. The most frequent types of HER2 alterations in CRC include gene amplification and missense mutations in 7–8% of CRC, often being mirrored by HER2 protein overexpression, representing founder events in solid tumors, including CRC. There are currently no approved HER2-targeted therapy guidelines for CRC; however, several studies have shown that HER2 can be effectively targeted in meta-static CRC settings. In this review, we discuss the current knowledge of HER2 testing in CRC and the immediate future perspectives for HER2 targeting in the metastatic setting. 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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17 pages, 535 KiB

Open AccessEditor’s ChoiceReview

Up-Date on Diabetic Nephropathy

by Maria Chiara Pelle, Michele Provenzano, Marco Busutti, Clara Valentina Porcu, Isabella Zaffina, Lucia Stanga and Franco Arturi

Life 2022, 12(8), 1202; https://doi.org/10.3390/life12081202 - 8 Aug 2022

Cited by 43 | Viewed by 6370

Abstract

Diabetes is one of the leading causes of kidney disease. Diabetic kidney disease (DKD) is a major cause of end-stage kidney disease (ESKD) worldwide, and it is linked to an increase in cardiovascular (CV) risk. Diabetic nephropathy (DN) increases morbidity and mortality among [...] Read more.

Diabetes is one of the leading causes of kidney disease. Diabetic kidney disease (DKD) is a major cause of end-stage kidney disease (ESKD) worldwide, and it is linked to an increase in cardiovascular (CV) risk. Diabetic nephropathy (DN) increases morbidity and mortality among people living with diabetes. Risk factors for DN are chronic hyperglycemia and high blood pressure; the renin-angiotensin-aldosterone system blockade improves glomerular function and CV risk in these patients. Recently, new antidiabetic drugs, including sodium–glucose transport protein 2 inhibitors and glucagon-like peptide-1 agonists, have demonstrated additional contribution in delaying the progression of kidney disease and enhancing CV outcomes. The therapeutic goal is regression of albuminuria, but an atypical form of non-proteinuric diabetic nephropathy (NP-DN) is also described. In this review, we provide a state-of-the-art evaluation of current treatment strategies and promising emerging treatments. Full article

(This article belongs to the Special Issue Hyperglycemia: From Pathophysiology to Therapeutics)

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23 pages, 1338 KiB

Open AccessEditor’s ChoiceReview

Left Ventricular Remodeling after Myocardial Infarction: From Physiopathology to Treatment

by Sabina Andreea Leancă, Daniela Crișu, Antoniu Octavian Petriș, Irina Afrăsânie, Antonia Genes, Alexandru Dan Costache, Dan Nicolae Tesloianu and Irina Iuliana Costache

Life 2022, 12(8), 1111; https://doi.org/10.3390/life12081111 - 24 Jul 2022

Cited by 39 | Viewed by 10102

Abstract

Myocardial infarction (MI) is the leading cause of death and morbidity worldwide, with an incidence relatively high in developed countries and rapidly growing in developing countries. The most common cause of MI is the rupture of an atherosclerotic plaque with subsequent thrombotic occlusion [...] Read more.

Myocardial infarction (MI) is the leading cause of death and morbidity worldwide, with an incidence relatively high in developed countries and rapidly growing in developing countries. The most common cause of MI is the rupture of an atherosclerotic plaque with subsequent thrombotic occlusion in the coronary circulation. This causes cardiomyocyte death and myocardial necrosis, with subsequent inflammation and fibrosis. Current therapies aim to restore coronary flow by thrombus dissolution with pharmaceutical treatment and/or intravascular stent implantation and to counteract neurohormonal activation. Despite these therapies, the injury caused by myocardial ischemia leads to left ventricular remodeling; this process involves changes in cardiac geometry, dimension and function and eventually progression to heart failure (HF). This review describes the pathophysiological mechanism that leads to cardiac remodeling and the therapeutic strategies with a role in slowing the progression of remodeling and improving cardiac structure and function. Full article

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

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16 pages, 4808 KiB

Open AccessEditor’s ChoiceReview

Pathogenesis of Distal Symmetrical Polyneuropathy in Diabetes

by Sasha Smith, Pasha Normahani, Tristan Lane, David Hohenschurz-Schmidt, Nick Oliver and Alun Huw Davies

Life 2022, 12(7), 1074; https://doi.org/10.3390/life12071074 - 19 Jul 2022

Cited by 13 | Viewed by 4468

Abstract

Distal symmetrical polyneuropathy (DSPN) is a serious complication of diabetes associated with significant disability and mortality. Although more than 50% of people with diabetes develop DSPN, its pathogenesis is still relatively unknown. This lack of understanding has limited the development of novel disease-modifying [...] Read more.

Distal symmetrical polyneuropathy (DSPN) is a serious complication of diabetes associated with significant disability and mortality. Although more than 50% of people with diabetes develop DSPN, its pathogenesis is still relatively unknown. This lack of understanding has limited the development of novel disease-modifying therapies and left the reasons for failed therapies uncertain, which is critical given that current management strategies often fail to achieve long-term efficacy. In this article, the pathogenesis of DSPN is reviewed, covering pathogenic changes in the peripheral nervous system, microvasculature and central nervous system (CNS). Furthermore, the successes and limitations of current therapies are discussed, and potential therapeutic targets are proposed. Recent findings on its pathogenesis have called the definition of DSPN into question and transformed the disease model, paving the way for new research prospects. Full article

(This article belongs to the Special Issue Peripheral Diabetic Neuropathy: Symptoms, Causes and Treatment)

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13 pages, 1218 KiB

Open AccessEditor’s ChoiceReview

Cardio-Oncology Rehabilitation—Present and Future Perspectives

by Boaz Elad, Manhal Habib and Oren Caspi

Life 2022, 12(7), 1006; https://doi.org/10.3390/life12071006 - 7 Jul 2022

Cited by 7 | Viewed by 3667

Abstract

Recent advances in cancer therapy have led to increased survival rates for cancer patients, but also allowed cardiovascular complications to become increasingly evident, with more than 40% of cancer deaths now being attributed to cardiovascular diseases. Cardiotoxicity is the most concerning cardiovascular complication, [...] Read more.

Recent advances in cancer therapy have led to increased survival rates for cancer patients, but also allowed cardiovascular complications to become increasingly evident, with more than 40% of cancer deaths now being attributed to cardiovascular diseases. Cardiotoxicity is the most concerning cardiovascular complication, one caused mainly due to anti-cancer drugs. Among the harmful mechanisms of these drugs are DNA damage, endothelial dysfunction, and oxidative stress. Cancer patients can suffer reduced cardiorespiratory fitness as a secondary effect of anti-cancer therapies, tumor burden, and deconditioning. In the general population, regular exercise can reduce the risk of cardiovascular morbidity, mortality, and cancer. Exercise-induced modifications of gene expression result in improvements of cardiovascular parameters and an increased general fitness, influencing telomere shortening, oxidative stress, vascular function, and DNA repair mechanisms. In cancer patients, exercise training is generally safe and well-tolerated; it is associated with a 10–15% improvement in cardiorespiratory fitness and can potentially counteract the adverse effects of anti-cancer therapy. It is well known that exercise programs can benefit patients with heart disease and cancer, but little research has been conducted with cardio-oncology patients. To date, there are a limited number of effective protective treatments for preventing or reversing cardiotoxicity caused by cancer therapy. Cardiac rehabilitation has the potential to mitigate cardiotoxicity based on the benefits already proven in populations suffering from either cancer or heart diseases. Additionally, the fact that cardiotoxic harm mechanisms coincide with similar mechanisms positively affected by cardiac rehabilitation makes cardiac rehabilitation an even more plausible option for cardio-oncology patients. Due to unstable functional capacity and fluctuating immunocompetence, these patients require specially tailored exercise programs designed collaboratively by cardiologists and oncologists. As the digital era is here, with the digital world and the medical world continuously intertwining, a remote, home-based cardio-oncology rehabilitation program may be a solution for this population. Full article

(This article belongs to the Special Issue Cardio-oncology: From Basic Mechanisms and research to Clinical Practice)

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22 pages, 1052 KiB

Open AccessEditor’s ChoiceReview

Cancer Cachexia and Antitumor Immunity: Common Mediators and Potential Targets for New Therapies

by Konstantinos Rounis, Dimitrios Makrakis, Ioannis Gioulbasanis, Simon Ekman, Luigi De Petris, Dimitris Mavroudis and Sofia Agelaki

Life 2022, 12(6), 880; https://doi.org/10.3390/life12060880 - 12 Jun 2022

Cited by 3 | Viewed by 2764

Abstract

Cancer cachexia syndrome (CCS) is a multifactorial metabolic syndrome affecting a significant proportion of patients. CCS is characterized by progressive weight loss, alterations of body composition and a systemic inflammatory status, which exerts a major impact on the host’s innate and adaptive immunity. [...] Read more.

Cancer cachexia syndrome (CCS) is a multifactorial metabolic syndrome affecting a significant proportion of patients. CCS is characterized by progressive weight loss, alterations of body composition and a systemic inflammatory status, which exerts a major impact on the host’s innate and adaptive immunity. Over the last few years, the development of immune checkpoint inhibitors (ICIs) transformed the treatment landscape for a wide spectrum of malignancies, creating an unprecedented opportunity for long term remissions in a significant subset of patients. Early clinical data indicate that CCS adversely impairs treatment outcomes of patients receiving ICIs. We herein reviewed existing evidence on the potential links between the mechanisms that promote the catabolic state in CCS and those that impair the antitumor immune response. We show that the biological mediators and processes leading to the development of CCS may also participate in the modulation and the sustainment of an immune suppressive tumor microenvironment and impaired anti-tumor immunity. Moreover, we demonstrate that the deregulation of the host’s metabolic homeostasis in cancer cachexia is associated with resistance to ICIs. Further research on the interrelation between cancer cachexia and anti-tumor immunity is required for the effective management of resistance to immunotherapy in this specific but large subgroup of ICI treated individuals. Full article

(This article belongs to the Collection Tumor Progression, Microenvironments, and Therapeutics)

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17 pages, 760 KiB

Open AccessEditor’s ChoiceReview

Acute and Long-Term Consequences of COVID-19 on Arterial Stiffness—A Narrative Review

by Ioana Mădălina Zota, Cristian Stătescu, Radu Andy Sascău, Mihai Roca, Larisa Anghel, Alexandra Maștaleru, Maria Magdalena Leon-Constantin, Cristina Mihaela Ghiciuc, Sebastian Romica Cozma, Lucia Corina Dima-Cozma, Irina Mihaela Esanu and Florin Mitu

Life 2022, 12(6), 781; https://doi.org/10.3390/life12060781 - 25 May 2022

Cited by 11 | Viewed by 3884

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global coronavirus (COVID-19) pandemic. Although initially viewed as an acute respiratory illness, COVID-19 is clearly a complex multisystemic disease with extensive cardiovascular involvement. Emerging evidence shows that the endothelium plays [...] Read more.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global coronavirus (COVID-19) pandemic. Although initially viewed as an acute respiratory illness, COVID-19 is clearly a complex multisystemic disease with extensive cardiovascular involvement. Emerging evidence shows that the endothelium plays multiple roles in COVID-19 physiopathology, as both a target organ that can be directly infected by SARS-CoV-2 and a mediator in the subsequent inflammatory and thrombotic cascades. Arterial stiffness is an established marker of cardiovascular disease. The scope of this review is to summarize available data on the acute and long-term consequences of COVID-19 on vascular function. COVID-19 causes early vascular aging and arterial stiffness. Fast, noninvasive bedside assessment of arterial stiffness could optimize risk stratification in acute COVID-19, allowing for early escalation of treatment. Vascular physiology remains impaired at least 12 months after infection with SARS-CoV-2, even in otherwise healthy adults. This raises concerns regarding the extent of arterial remodeling in patients with preexisting vascular disease and the potential development of a persistent, chronic COVID-19 vasculopathy. Long-term follow up on larger cohorts is required to investigate the reversibility of COVID-19-induced vascular changes and their associated prognostic implications. Full article

(This article belongs to the Section Medical Research)

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14 pages, 703 KiB

Open AccessEditor’s ChoiceReview

Regulatory Effects of Statins on SIRT1 and Other Sirtuins in Cardiovascular Diseases

by Danial Khayatan, Seyed Mehrad Razavi, Zahra Najafi Arab, Maryam Khanahmadi, Saeideh Momtaz, Alexandra E. Butler, Fabrizio Montecucco, Yuliya V. Markina, Amir Hossein Abdolghaffari and Amirhossein Sahebkar

Life 2022, 12(5), 760; https://doi.org/10.3390/life12050760 - 20 May 2022

Cited by 10 | Viewed by 6051

Abstract

Adverse cardiovascular disease (CVD) outcomes, such as sudden cardiac death, acute myocardial infarction, and stroke, are often catastrophic. Statins are frequently used to attenuate the risk of CVD-associated morbidity and mortality through their impact on lipids and they may also have anti-inflammatory and [...] Read more.

Adverse cardiovascular disease (CVD) outcomes, such as sudden cardiac death, acute myocardial infarction, and stroke, are often catastrophic. Statins are frequently used to attenuate the risk of CVD-associated morbidity and mortality through their impact on lipids and they may also have anti-inflammatory and other plaque-stabilization effects via different signaling pathways. Different statins, including atorvastatin, rosuvastatin, pravastatin, pitavastatin, and simvastatin, are administered to manage circulatory lipid levels. In addition, statins are potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase via modulating sirtuins (SIRTs). During the last two decades, SIRTs have been investigated in mammals and categorized as a family of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases (HDACs) with significant oxidative stress regulatory function in cells—a key factor in extending cell lifespan. Recent work has demonstrated that statins upregulate SIRT1 and SIRT2 and downregulate SIRT6 in both in vitro and in vivo experiments and clinical trials. As statins show modulatory properties, especially in CVDs, future investigations are needed to delineate the role of SIRT family members in disease and to expand knowledge about the effects of statins on SIRTs. Here, we review what is currently known about the impact of statins on SIRTs and how these changes correlate with disease, particularly CVDs. Full article

(This article belongs to the Section Pharmaceutical Science)

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