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Biomedicines, Volume 9, Issue 11 (November 2021) – 246 articles

Cover Story (view full-size image): Natural killer (NK) cells are essential effector cells in cancer immunotherapy. One possible strategy to trigger their cytotoxicity toward malignant cells is by using bi- or better poly-valent molecules mediating NK cell recognition. To activate NK cells, we prepared a pHPMA-based copolymer decorated via a complementary coiled coil interaction with NK cell-activating ligand B7-H6 and anti-CAIX tumor-targeting scFv. This chimeric biopolymer is a promising precursor for targeted cancer immunotherapy.View this paper
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Review
Bisphenol A and Its Analogues Deteriorate the Hormones Physiological Function of the Male Reproductive System: A Mini-Review
Biomedicines 2021, 9(11), 1744; https://doi.org/10.3390/biomedicines9111744 - 22 Nov 2021
Cited by 2 | Viewed by 924
Abstract
BPA is identified as an endocrine-disrupting chemical that deteriorates the physiological function of the hormones of the male reproductive system. Bisphenol F (BPF), bisphenol S (BPS), and bisphenol AF (BPAF) are actively explored as substitutes for BPA and are known as BPA analogues [...] Read more.
BPA is identified as an endocrine-disrupting chemical that deteriorates the physiological function of the hormones of the male reproductive system. Bisphenol F (BPF), bisphenol S (BPS), and bisphenol AF (BPAF) are actively explored as substitutes for BPA and are known as BPA analogues in most manufacturing industries. These analogues may demonstrate the same adverse effects as BPA on the male reproductive system; however, toxicological data explaining the male reproductive hormones’ physiological functions are still limited. Hence, this mini-review discusses the effects of BPA and its analogues on the physiological functions of hormones in the male reproductive system, focusing on the hypothalamus-pituitary-gonad (HPG) axis, steroidogenesis, and spermatogenesis outcomes. The BPA analogues mainly show a similar negative effect on the hormones’ physiological functions, proven by alterations in the HPG axis and steroidogenesis via activation of the aromatase activity and reduction of spermatogenesis outcomes when compared to BPA in in vitro and in vivo studies. Human biomonitoring studies also provide significant adverse effects on the physiological functions of hormones in the male reproductive system. In conclusion, BPA and its analogues deteriorate the physiological functions of hormones in the male reproductive system as per in vitro, in vivo, and human biomonitoring studies. Full article
(This article belongs to the Section Cell Biology and Pathology)
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Review
Somatostatin and Its Receptor System in Colorectal Cancer
Biomedicines 2021, 9(11), 1743; https://doi.org/10.3390/biomedicines9111743 - 22 Nov 2021
Cited by 1 | Viewed by 698
Abstract
Somatostatin (SST)/somatotropin release-inhibiting factor (SRIF) is a well-known neuropeptide, widely distributed in the central and peripheral nervous systems, that regulates the endocrine system and affects neurotransmission via interaction with five SST receptors (SST1-5). In the gastrointestinal tract, the main SST-producing cells include intestinal [...] Read more.
Somatostatin (SST)/somatotropin release-inhibiting factor (SRIF) is a well-known neuropeptide, widely distributed in the central and peripheral nervous systems, that regulates the endocrine system and affects neurotransmission via interaction with five SST receptors (SST1-5). In the gastrointestinal tract, the main SST-producing cells include intestinal enteroendocrine cells (EECs) restricted to the mucosa, and neurons of the submucosal and myenteric plexuses. The action of the SRIF system is based on the inhibition of endocrine and exocrine secretion, as well as the proliferative responses of target cells. The SST1–5 share common signaling pathways, and are not only widely expressed on normal tissues, but also frequently overexpressed by several tumors, particularly neuroendocrine neoplasms (NENs). Furthermore, the SRIF system represents the only peptide/G protein-coupled receptor (GPCR) system with multiple approved clinical applications for the diagnosis and treatment of several NENs. The role of the SRIF system in the histogenesis of colorectal cancer (CRC) subtypes (e.g., adenocarcinoma and signet ring-cell carcinoma), as well as diagnosis and prognosis of mixed adenoneuroendocrine carcinoma (MANEC) and pure adenocarcinoma, is poorly understood. Moreover, the impact of the SRIF system signaling on CRC cell proliferation and its potential role in the progression of this cancer remains unknown. Therefore, this review summarizes the recent collective knowledge and understanding of the clinical significance of the SRIF system signaling in CRC, aiming to evaluate the potential role of its components in CRC histogenesis, diagnosis, and potential therapy. Full article
(This article belongs to the Special Issue Neuropeptides in Biomedicines)
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Article
Origins and Function of VL30 lncRNA Packaging in Small Extracellular Vesicles: Implications for Cellular Physiology and Pathology
Biomedicines 2021, 9(11), 1742; https://doi.org/10.3390/biomedicines9111742 - 22 Nov 2021
Viewed by 547
Abstract
Long non-coding RNAs (lncRNAs) have emerged during the post-genomic era as significant epigenetic regulators. Viral-like 30 elements (VL30s) are a family of mouse retrotransposons that are transcribed into functional lncRNAs. Recent data suggest that VL30 RNAs are efficiently packaged in small extracellular vesicles [...] Read more.
Long non-coding RNAs (lncRNAs) have emerged during the post-genomic era as significant epigenetic regulators. Viral-like 30 elements (VL30s) are a family of mouse retrotransposons that are transcribed into functional lncRNAs. Recent data suggest that VL30 RNAs are efficiently packaged in small extracellular vesicles (SEVs) through an SEV enrichment sequence. We analysed VL30 elements for the presence of the distinct 26 nt SEV enrichment motif and found that SEV enrichment is an inherent hallmark of the VL30 family, contained in 36 full-length elements, with a widespread chromosomal distribution. Among them, 25 elements represent active, present-day integrations and contain an abundance of regulatory sequences. Phylogenetic analysis revealed a recent spread of SEV-VL30s from 4.4 million years ago till today. Importantly, 39 elements contain an SFPQ-binding motif, associated with the transcriptional induction of oncogenes. Most SEV-VL30s reside in transcriptionally active regions, as characterised by their distribution adjacent to candidate cis-regulatory elements (cCREs). Network analysis of SEV-VL30-associated genes suggests a distinct transcriptional footprint associated with embryonal abnormalities and neoplasia. Given the established role of VL30s in oncogenesis, we conclude that their potential to spread through SEVs represents a novel mechanism for non-coding RNA biology with numerous implications for cellular homeostasis and disease. Full article
(This article belongs to the Special Issue Non-coding RNAs in Health and Disease)
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Article
Energy Metabolism and Intracellular pH Alteration in Neural Spheroids Carrying Down Syndrome
Biomedicines 2021, 9(11), 1741; https://doi.org/10.3390/biomedicines9111741 - 22 Nov 2021
Viewed by 717
Abstract
Brain diseases including Down syndrome (DS/TS21) are known to be characterized by changes in cellular metabolism. To adequately assess such metabolic changes during pathological processes and to test drugs, methods are needed that allow monitoring of these changes in real time with minimally [...] Read more.
Brain diseases including Down syndrome (DS/TS21) are known to be characterized by changes in cellular metabolism. To adequately assess such metabolic changes during pathological processes and to test drugs, methods are needed that allow monitoring of these changes in real time with minimally invasive effects. Thus, the aim of our work was to study the metabolic status and intracellular pH of spheroids carrying DS using fluorescence microscopy and FLIM. For metabolic analysis we measured the fluorescence intensities, fluorescence lifetimes and the contributions of the free and bound forms of NAD(P)H. For intracellular pH assay we measured the fluorescence intensities of SypHer-2 and BCECF. Data were processed with SPCImage and Fiji-ImageJ. We demonstrated the predominance of glycolysis in TS21 spheroids compared with normal karyotype (NK) spheroids. Assessment of the intracellular pH indicated a more alkaline intracellular pH in the TS21 spheroids compared to NK spheroids. Using fluorescence imaging, we performed a comprehensive comparative analysis of the metabolism and intracellular pH of TS21 spheroids and showed that fluorescence microscopy and FLIM make it possible to study living cells in 3D models in real time with minimally invasive effects. Full article
(This article belongs to the Section Neurobiology and Neurologic Disease)
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Review
Counting on COVID-19 Vaccine: Insights into the Current Strategies, Progress and Future Challenges
Biomedicines 2021, 9(11), 1740; https://doi.org/10.3390/biomedicines9111740 - 22 Nov 2021
Cited by 8 | Viewed by 1505
Abstract
The emergence of a novel coronavirus viz., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019 and its subsequent substantial spread produced the coronavirus disease 2019 (COVID-19) pandemic worldwide. Given its unprecedented infectivity and pathogenicity, the COVID-19 pandemic had a devastating impact [...] Read more.
The emergence of a novel coronavirus viz., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019 and its subsequent substantial spread produced the coronavirus disease 2019 (COVID-19) pandemic worldwide. Given its unprecedented infectivity and pathogenicity, the COVID-19 pandemic had a devastating impact on human health, and its clinical management has been a great challenge, which has led to the development and speedy trials of several vaccine candidates against SARS-CoV-2 at an exceptional pace. As a result, several COVID-19 vaccines were made commercially available in the first half of 2021. Although several COVID-19 vaccines showed promising results, crucial insights into their epidemiology, protective mechanisms, and the propensities of reinfection are not largely reviewed. In the present report, we provided insights into the prospects of vaccination against COVID-19 and assessed diverse vaccination strategies including DNA, mRNA, protein subunits, vector-based, live attenuated, and inactivated whole/viral particle-based vaccines. Next, we reviewed major aspects of various available vaccines approved by the World Health Organization and by the local administrations to use against COVID-19. Moreover, we comprehensively assessed the success of these approved vaccines and also their untoward effects, including the possibility of reinfection. We also provided an update on the vaccines that are under development and could be promising candidates in the future. Conclusively, we provided insights into the COVID-19 vaccine epidemiology, their potency, and propensity for SARS-CoV-2 reinfection, while a careful review of their current status, strategies, success, and future challenges was also presented. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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Article
The Role of Neuropeptide Y in Adipocyte-Macrophage Crosstalk during High Fat Diet-Induced Adipose Inflammation and Liver Steatosis
Biomedicines 2021, 9(11), 1739; https://doi.org/10.3390/biomedicines9111739 - 22 Nov 2021
Viewed by 621
Abstract
Obesity is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD), which is initiated by adipocyte-macrophage crosstalk. Among the possible molecules regulating this crosstalk, we focused on neuropeptide Y (NPY), which is known to be involved in hypothalamic appetite and adipose [...] Read more.
Obesity is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD), which is initiated by adipocyte-macrophage crosstalk. Among the possible molecules regulating this crosstalk, we focused on neuropeptide Y (NPY), which is known to be involved in hypothalamic appetite and adipose tissue inflammation and metabolism. In this study, the NPY−/− mice showed a marked decrease in body weight and adiposity, and lower free fatty acid and adipose inflammation without food intake alteration during a high fat diet (HFD). Moreover, NPY deficiency increased the thermogenic genes expression in brown adipose tissue. Notably, NPY-mRNA expression was upregulated in macrophages from the HFD mice compared to that from the mice on a standard diet. The NPY-mRNA expression also positively correlated with the liver mass/body weight ratio. NPY deletion alleviated HFD-induced adipose inflammation and liver steatosis. Hence, our findings point toward a novel intracellular mechanism of NPY in the regulation of adipocyte-macrophage crosstalk and highlight NPY antagonism as a promising target for therapeutic approaches against obesity and NAFLD. Full article
(This article belongs to the Special Issue Neuropeptides in Biomedicines)
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Article
Clinical Effects of Oral Bacteriotherapy on Anal HPV Infection and Related Dysplasia in HIV-Positive MSM: Results from the “HPVinHIV” Trial
Biomedicines 2021, 9(11), 1738; https://doi.org/10.3390/biomedicines9111738 - 22 Nov 2021
Viewed by 714
Abstract
Background. Anal HPV infection, anal dysplasia and, ultimately, anal cancer are particularly common in HIV-infected men who have sex with men. Treatment of anal dysplasia, aiming to prevent evolution to squamous cell carcinoma of the anus, is currently limited to direct ablation and/or [...] Read more.
Background. Anal HPV infection, anal dysplasia and, ultimately, anal cancer are particularly common in HIV-infected men who have sex with men. Treatment of anal dysplasia, aiming to prevent evolution to squamous cell carcinoma of the anus, is currently limited to direct ablation and/or application of topical therapy. The aim of the present study is to investigate the effect of oral bacteriotherapy (Vivomixx® in EU, Visbiome® in USA) on anal HPV infection and HPV-related dysplasia of the anal canal in HIV-infected men who have sex with men. Methods. In this randomized, placebo-controlled, quadruple-blinded trial (NCT04099433), HIV-positive men who have sex with men with anal HPV infection and HPV-related dysplasia were randomized to receive oral bacteriotherapy or placebo for 6 months. Anal HPV test, anal cytology and high resolution anoscopy with biopsies of anal lesions were performed at baseline and at the end of the study. Safety and tolerability of oral bacteriotherapy were also evaluated. Interim analysis results were presented. Results. 20 participants concluded the study procedures to date. No serious adverse events were reported. In respect to participants randomized to placebo, individuals in the experimental arm showed higher rate of anal dysplasia regression (p = 0.002), lower rate of onset of new anal dysplasia (p = 0.023) and lower rates of worsening of persistent lesions (p = 0.004). Clearance of anal HPV infection was more frequently observed in the bacteriotherapy group (p = 0.067). Conclusion. Being an interim analysis, we limit ourselves to report the preliminary results of the current study. We refer the conclusions relating to the possible effectiveness of the intervention to the analysis of the definitive data. Full article
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Article
Design of α/β-Hybrid Peptide Ligands of α4β1 Integrin Equipped with a Linkable Side Chain for Chemoselective Biofunctionalization of Microstructured Materials
Biomedicines 2021, 9(11), 1737; https://doi.org/10.3390/biomedicines9111737 - 21 Nov 2021
Cited by 2 | Viewed by 656
Abstract
Arg-Gly-Asp (RGD)-binding integrins, e.g., αvβ3, αvβ1, αvβ5 integrins, are currently regarded as privileged targets for the delivery of diagnostic and theranostic agents, especially in cancer treatment. In contrast, scarce attention has been paid so far to the diagnostic opportunities promised by integrins that [...] Read more.
Arg-Gly-Asp (RGD)-binding integrins, e.g., αvβ3, αvβ1, αvβ5 integrins, are currently regarded as privileged targets for the delivery of diagnostic and theranostic agents, especially in cancer treatment. In contrast, scarce attention has been paid so far to the diagnostic opportunities promised by integrins that recognize other peptide motifs. In particular, α4β1 integrin is involved in inflammatory, allergic, and autoimmune diseases, therefore, it represents an interesting therapeutic target. Aiming at obtaining simple, highly stable ligands of α4β1 integrin, we designed hybrid α/β peptidomimetics carrying linkable side chains for the expedient functionalization of biomaterials, nano- and microparticles. We identified the prototypic ligands MPUPA-(R)-isoAsp(NHPr)-Gly-OH (12) and MPUPA-Dap(Ac)-Gly-OH (13) (MPUPA, methylphenylureaphenylacetic acid; Dap, 2,3-diamino propionic acid). Modification of 12 and 13 by introduction of flexible linkers at isoAsp or Dap gave 49 and 50, respectively, which allowed for coating with monolayers (ML) of flat zeolite crystals. The resulting peptide–zeolite MLs were able to capture selectively α4β1 integrin-expressing cells. In perspective, the α4β1 integrin ligands identified in this study can find applications for preparing biofunctionalized surfaces and diagnostic devices to control the progression of α4β1 integrin-correlated diseases. Full article
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Article
Pattern of Repetitive Element Transcription Segregate Cell Lineages during the Embryogenesis of Sea Urchin Strongylocentrotus purpuratus
Biomedicines 2021, 9(11), 1736; https://doi.org/10.3390/biomedicines9111736 - 21 Nov 2021
Viewed by 668
Abstract
Repetitive elements (REs) occupy a significant part of eukaryotic genomes and are shown to play diverse roles in genome regulation. During embryogenesis of the sea urchin, a large number of REs are expressed, but the role of these elements in the regulation of [...] Read more.
Repetitive elements (REs) occupy a significant part of eukaryotic genomes and are shown to play diverse roles in genome regulation. During embryogenesis of the sea urchin, a large number of REs are expressed, but the role of these elements in the regulation of biological processes remains unknown. The aim of this study was to identify the RE expression at different stages of embryogenesis. REs occupied 44% of genomic DNA of Strongylocentrotus purpuratus. The most prevalent among these elements were the unknown elements—in total, they contributed 78.5% of REs (35% in total genome occupancy). It was revealed that the transcription pattern of genes and REs changes significantly during gastrulation. Using the de novo transcriptome assembly, we showed that the expression of RE is independent of its copy number in the genome. We also identified copies that are expressed. Only active RE copies were used for mapping and quantification of RE expression in the single-cell RNA sequencing data. REs expression was observed in all cell lineages and they were detected as population markers. Moreover, the primary mesenchyme cell (PMC) line had the greatest diversity of REs among the markers. Our data suggest a role for RE in the organization of developmental domains during the sea urchin embryogenesis at the single-cell resolution level. Full article
(This article belongs to the Special Issue Theoretical Approaches to Developmental Biology)
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Review
Acne Syndromes and Mosaicism
Biomedicines 2021, 9(11), 1735; https://doi.org/10.3390/biomedicines9111735 - 21 Nov 2021
Viewed by 793
Abstract
Abnormal mosaicism is the coexistence of cells with at least two genotypes, by the time of birth, in an individual derived from a single zygote, which leads to a disease phenotype. Somatic mosaicism can be further categorized into segmental mosaicism and nonsegmental somatic [...] Read more.
Abnormal mosaicism is the coexistence of cells with at least two genotypes, by the time of birth, in an individual derived from a single zygote, which leads to a disease phenotype. Somatic mosaicism can be further categorized into segmental mosaicism and nonsegmental somatic mosaicism. Acne is a chronic illness characterized by inflammatory changes around and in the pilosebaceous units, commonly due to hormone- and inflammatory signaling-mediated factors. Several systemic disorders, such as congenital adrenal hyperplasia, polycystic ovarian syndrome, and seborrhoea-acne-hirsutism-androgenetic alopecia syndrome have classically been associated with acne. Autoinflammatory syndromes, including PAPA, PASH, PAPASH, PsAPASH, PsaPSASH, PASS, and SAPHO syndromes include acneiform lesions as a key manifestation. Mosaic germline mutations in the FGFR2 gene have been associated with Apert syndrome and nevus comedonicus, two illnesses that are accompanied by acneiform lesions. In this review, we summarize the concept of cutaneous mosaicism and elaborate on acne syndromes, as well as acneiform mosaicism. Full article
(This article belongs to the Special Issue Somatic Mosaicism in Skin Disorders)
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Review
Special delEVery: Extracellular Vesicles as Promising Delivery Platform to the Brain
Biomedicines 2021, 9(11), 1734; https://doi.org/10.3390/biomedicines9111734 - 20 Nov 2021
Cited by 5 | Viewed by 1019
Abstract
The treatment of central nervous system (CNS) pathologies is severely hampered by the presence of tightly regulated CNS barriers that restrict drug delivery to the brain. An increasing amount of data suggests that extracellular vesicles (EVs), i.e., membrane derived vesicles that inherently protect [...] Read more.
The treatment of central nervous system (CNS) pathologies is severely hampered by the presence of tightly regulated CNS barriers that restrict drug delivery to the brain. An increasing amount of data suggests that extracellular vesicles (EVs), i.e., membrane derived vesicles that inherently protect and transfer biological cargoes between cells, naturally cross the CNS barriers. Moreover, EVs can be engineered with targeting ligands to obtain enriched tissue targeting and delivery capacities. In this review, we provide a detailed overview of the literature describing a natural and engineered CNS targeting and therapeutic efficiency of different cell type derived EVs. Hereby, we specifically focus on peripheral administration routes in a broad range of CNS diseases. Furthermore, we underline the potential of research aimed at elucidating the vesicular transport mechanisms across the different CNS barriers. Finally, we elaborate on the practical considerations towards the application of EVs as a brain drug delivery system. Full article
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Review
Deep Learning for Human Disease Detection, Subtype Classification, and Treatment Response Prediction Using Epigenomic Data
Biomedicines 2021, 9(11), 1733; https://doi.org/10.3390/biomedicines9111733 - 20 Nov 2021
Cited by 2 | Viewed by 1001
Abstract
Deep learning (DL) is a distinct class of machine learning that has achieved first-class performance in many fields of study. For epigenomics, the application of DL to assist physicians and scientists in human disease-relevant prediction tasks has been relatively unexplored until very recently. [...] Read more.
Deep learning (DL) is a distinct class of machine learning that has achieved first-class performance in many fields of study. For epigenomics, the application of DL to assist physicians and scientists in human disease-relevant prediction tasks has been relatively unexplored until very recently. In this article, we critically review published studies that employed DL models to predict disease detection, subtype classification, and treatment responses, using epigenomic data. A comprehensive search on PubMed, Scopus, Web of Science, Google Scholar, and arXiv.org was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Among 1140 initially identified publications, we included 22 articles in our review. DNA methylation and RNA-sequencing data are most frequently used to train the predictive models. The reviewed models achieved a high accuracy ranged from 88.3% to 100.0% for disease detection tasks, from 69.5% to 97.8% for subtype classification tasks, and from 80.0% to 93.0% for treatment response prediction tasks. We generated a workflow to develop a predictive model that encompasses all steps from first defining human disease-related tasks to finally evaluating model performance. DL holds promise for transforming epigenomic big data into valuable knowledge that will enhance the development of translational epigenomics. Full article
(This article belongs to the Special Issue Bioinformatics and Its Application in Biomedicine)
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Review
Acute Respiratory Distress Syndrome: Focus on Viral Origin and Role of Pulmonary Lymphatics
Biomedicines 2021, 9(11), 1732; https://doi.org/10.3390/biomedicines9111732 - 20 Nov 2021
Viewed by 692
Abstract
Acute respiratory distress syndrome (ARDS) is a serious affection of the lung caused by a variety of pathologies. Great interest is currently focused on ARDS induced by viruses (pandemic influenza and corona viruses). The review describes pulmonary changes in ARDS and specific effects [...] Read more.
Acute respiratory distress syndrome (ARDS) is a serious affection of the lung caused by a variety of pathologies. Great interest is currently focused on ARDS induced by viruses (pandemic influenza and corona viruses). The review describes pulmonary changes in ARDS and specific effects of the pandemic viruses in ARDS, and summarizes treatment options. Because the known pathogenic mechanisms cannot explain all aspects of the syndrome, the contribution of pulmonary lymphatics to the pathology is discussed. Organization and function of lymphatics in a healthy lung and in resorption of pulmonary edema are described. A future clinical trial may provide more insight into the role of hyaluronan in ARDS but the development of promising pharmacological treatments is unlikely because drugs play no important role in lymphedema therapy. Full article
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Review
MiRNAs as New Tools in Lesion Vitality Evaluation: A Systematic Review and Their Forensic Applications
Biomedicines 2021, 9(11), 1731; https://doi.org/10.3390/biomedicines9111731 - 20 Nov 2021
Cited by 6 | Viewed by 590
Abstract
Wound vitality demonstration is one of the most challenging fields in forensic pathology. In recent years, researchers focused on the application of histological and immunohistochemical staining in this sphere of study. It is based on the detection of inflammation, red cell infiltration, and [...] Read more.
Wound vitality demonstration is one of the most challenging fields in forensic pathology. In recent years, researchers focused on the application of histological and immunohistochemical staining in this sphere of study. It is based on the detection of inflammation, red cell infiltration, and tissue alterations at the histological examination, all of which are supposedly present in antemortem rather than post-mortem wounds. Nevertheless, some doubts about the reliability of those markers have arisen. Furthermore, the lack of a standardized protocol and the operator dependency of this approach make the proper interpretation of its results difficult. Moreover, a differential miRNAs expression has been demonstrated in antemortem and post-mortem wounds. Herein, a systematic review concerning the current knowledge about the use of miRNAs in lesion vitality evaluation is carried out, to encourage researchers to deepen this peculiar study area. A compendium about the potential miRNAs that may be further investigated as vitality markers is also provided. The aim is to collect all available data about this topic to direct further studies on this field and highlight the future applications of miRNAs in forensic pathology. We found 20 articles and a total of 51 miRNAs that are involved in inflammation and wound healing. Further studies are certainly needed to deepen the role of miRNAs in inflammatory processes in lesioned skin and to evaluate their reliability in distinguishing between antemortem and post-mortem lesions. Full article
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Review
Association of Mutations Identified in Xanthinuria with the Function and Inhibition Mechanism of Xanthine Oxidoreductase
Biomedicines 2021, 9(11), 1723; https://doi.org/10.3390/biomedicines9111723 - 20 Nov 2021
Cited by 1 | Viewed by 862
Abstract
Xanthine oxidoreductase (XOR) is an enzyme that catalyzes the two-step reaction from hypoxanthine to xanthine and from xanthine to uric acid in purine metabolism. XOR generally carries dehydrogenase activity (XDH) but is converted into an oxidase (XO) under various pathophysiologic conditions. The complex [...] Read more.
Xanthine oxidoreductase (XOR) is an enzyme that catalyzes the two-step reaction from hypoxanthine to xanthine and from xanthine to uric acid in purine metabolism. XOR generally carries dehydrogenase activity (XDH) but is converted into an oxidase (XO) under various pathophysiologic conditions. The complex structure and enzymatic function of XOR have been well investigated by mutagenesis studies of mammalian XOR and structural analysis of XOR–inhibitor interactions. Three XOR inhibitors are currently used as hyperuricemia and gout therapeutics but are also expected to have potential effects other than uric acid reduction, such as suppressing XO–generating reactive oxygen species. Isolated XOR deficiency, xanthinuria type I, is a good model of the metabolic effects of XOR inhibitors. It is characterized by hypouricemia, markedly decreased uric acid excretion, and increased serum and urinary xanthine concentrations, with no clinically significant symptoms. The pathogenesis and relationship between mutations and XOR activity in xanthinuria are useful for elucidating the biological role of XOR and the details of the XOR reaction process. In this review, we aim to contribute to the basic science and clinical aspects of XOR by linking the mutations in xanthinuria to structural studies, in order to understand the function and reaction mechanism of XOR in vivo. Full article
(This article belongs to the Special Issue Hypouricemia)
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Case Report
Clinical and Radiological Deterioration in a Case of Creutzfeldt–Jakob Disease following SARS-CoV-2 Infection: Hints to Accelerated Age-Dependent Neurodegeneration
Biomedicines 2021, 9(11), 1730; https://doi.org/10.3390/biomedicines9111730 - 19 Nov 2021
Cited by 2 | Viewed by 951
Abstract
Systemic inflammation and the host immune responses associated with certain viral infections may accelerate the rate of neurodegeneration in patients with Creutzfeldt–Jakob disease (CJD), a rare, transmissible neurodegenerative disease. However, the effects of the newly emerged SARS-CoV-2 infection on the pathogenesis of CJD [...] Read more.
Systemic inflammation and the host immune responses associated with certain viral infections may accelerate the rate of neurodegeneration in patients with Creutzfeldt–Jakob disease (CJD), a rare, transmissible neurodegenerative disease. However, the effects of the newly emerged SARS-CoV-2 infection on the pathogenesis of CJD are unknown. In this study, we describe the case of an elderly female patient with sporadic CJD that exhibited clinical deterioration with the emergence of seizures and radiological neurodegenerative progression following an infection with SARS-CoV-2 and severe COVID-19. Despite efforts to control the progression of the disease, a dismal outcome ensued. This report further evidences the age-dependent neurological effects of SARS-CoV-2 infection and proposes a vulnerability to CJD and increased CJD progression following COVID-19. Full article
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Review
Antibody-Based Immunotoxins for Colorectal Cancer Therapy
Biomedicines 2021, 9(11), 1729; https://doi.org/10.3390/biomedicines9111729 - 19 Nov 2021
Cited by 3 | Viewed by 859
Abstract
Monoclonal antibodies (mAbs) are included among the treatment options for advanced colorectal cancer (CRC). However, while these mAbs effectively target cancer cells, they may have limited clinical activity. A strategy to improve their therapeutic potential is arming them with a toxic payload. Immunotoxins [...] Read more.
Monoclonal antibodies (mAbs) are included among the treatment options for advanced colorectal cancer (CRC). However, while these mAbs effectively target cancer cells, they may have limited clinical activity. A strategy to improve their therapeutic potential is arming them with a toxic payload. Immunotoxins (ITX) combining the cell-killing ability of a toxin with the specificity of a mAb constitute a promising strategy for CRC therapy. However, several important challenges in optimizing ITX remain, including suboptimal pharmacokinetics and especially the immunogenicity of the toxin moiety. Nonetheless, ongoing research is working to solve these limitations and expand CRC patients’ therapeutic armory. In this review, we provide a comprehensive overview of targets and toxins employed in the design of ITX for CRC and highlight a wide selection of ITX tested in CRC patients as well as preclinical candidates. Full article
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Review
Genetic Determinants of Plasma Low-Density Lipoprotein Cholesterol Levels: Monogenicity, Polygenicity, and “Missing” Heritability
Biomedicines 2021, 9(11), 1728; https://doi.org/10.3390/biomedicines9111728 - 19 Nov 2021
Viewed by 680
Abstract
Changes in plasma low-density lipoprotein cholesterol (LDL-c) levels relate to a high risk of developing some common and complex diseases. LDL-c, as a quantitative trait, is multifactorial and depends on both genetic and environmental factors. In the pregenomic age, targeted genes were used [...] Read more.
Changes in plasma low-density lipoprotein cholesterol (LDL-c) levels relate to a high risk of developing some common and complex diseases. LDL-c, as a quantitative trait, is multifactorial and depends on both genetic and environmental factors. In the pregenomic age, targeted genes were used to detect genetic factors in both hyper- and hypolipidemias, but this approach only explained extreme cases in the population distribution. Subsequently, the genetic basis of the less severe and most common dyslipidemias remained unknown. In the genomic age, performing whole-exome sequencing in families with extreme plasma LDL-c values identified some new candidate genes, but it is unlikely that such genes can explain the majority of inexplicable cases. Genome-wide association studies (GWASs) have identified several single-nucleotide variants (SNVs) associated with plasma LDL-c, introducing the idea of a polygenic origin. Polygenic risk scores (PRSs), including LDL-c-raising alleles, were developed to measure the contribution of the accumulation of small-effect variants to plasma LDL-c. This paper discusses other possibilities for unexplained dyslipidemias associated with LDL-c, such as mosaicism, maternal effect, and induced epigenetic changes. Future studies should consider gene–gene and gene–environment interactions and the development of integrated information about disease-driving networks, including phenotypes, genotypes, transcription, proteins, metabolites, and epigenetics. Full article
(This article belongs to the Special Issue Advances in the Genetics of Plasma Cholesterol Levels)
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Article
Enpp2 Expression by Dendritic Cells Is a Key Regulator in Migration
Biomedicines 2021, 9(11), 1727; https://doi.org/10.3390/biomedicines9111727 - 19 Nov 2021
Cited by 1 | Viewed by 610
Abstract
Enpp2 is an enzyme that catalyzes the conversion of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), which exhibits a wide variety of biological functions. Here, we examined the biological effects of Enpp2 on dendritic cells (DCs), which are specialized antigen-presenting cells (APCs) characterized by [...] Read more.
Enpp2 is an enzyme that catalyzes the conversion of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), which exhibits a wide variety of biological functions. Here, we examined the biological effects of Enpp2 on dendritic cells (DCs), which are specialized antigen-presenting cells (APCs) characterized by their ability to migrate into secondary lymphoid organs and activate naïve T-cells. DCs were generated from bone marrow progenitors obtained from C57BL/6 mice. Enpp2 levels in DCs were regulated using small interfering (si)RNA or recombinant Enpp2. Expression of Enpp2 in LPS-stimulated mature (m)DCs was high, however, knocking down Enpp2 inhibited mDC function. In addition, the migratory capacity of mDCs increased after treatment with rmEnpp2; this phenomenon was mediated via the RhoA-mediated signaling pathway. Enpp2-treated mDCs showed a markedly increased capacity to migrate to lymph nodes in vivo. These findings strongly suggest that Enpp2 is necessary for mDC migration capacity, thereby increasing our understanding of DC biology. We postulate that regulating Enpp2 improves DC migration to lymph nodes, thus improving the effectiveness of cancer vaccines based on DC. Full article
(This article belongs to the Special Issue Modulation of Innate Immunity in Cancer Immunotherapy)
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Review
Cell and Cell Free Therapies in Osteoarthritis
Biomedicines 2021, 9(11), 1726; https://doi.org/10.3390/biomedicines9111726 - 19 Nov 2021
Cited by 2 | Viewed by 1090
Abstract
Osteoarthritis (OA) is the most common articular disease in adults and has a current prevalence of 12% in the population over 65 years old. This chronic disease causes damage to articular cartilage and synovial joints, causing pain and leading to a negative impact [...] Read more.
Osteoarthritis (OA) is the most common articular disease in adults and has a current prevalence of 12% in the population over 65 years old. This chronic disease causes damage to articular cartilage and synovial joints, causing pain and leading to a negative impact on patients’ function, decreasing quality of life. There are many limitations regarding OA conventional therapies—pharmacological therapy can cause gastrointestinal, renal, and cardiac adverse effects, and some of them could even be a threat to life. On the other hand, surgical options, such as microfracture, have been used for the last 20 years, but hyaline cartilage has a limited regeneration capacity. In recent years, the interest in new therapies, such as cell-based and cell-free therapies, has been considerably increasing. The purpose of this review is to describe and compare bioregenerative therapies’ efficacy for OA, with particular emphasis on the use of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP). In OA, these therapies might be an alternative and less invasive treatment than surgery, and a more effective option than conventional therapies. Full article
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Article
In Vitro Replication Inhibitory Activity of Xanthorrhizol against Severe Acute Respiratory Syndrome Coronavirus 2
Biomedicines 2021, 9(11), 1725; https://doi.org/10.3390/biomedicines9111725 - 19 Nov 2021
Cited by 1 | Viewed by 968
Abstract
In spite of the large number of repositioned drugs and direct-acting antivirals in clinical trials for the management of the ongoing COVID-19 pandemic, there are few cost-effective therapeutic options for severe acute respiratory syndrome (SARS) coronavirus 2 (SCoV2) infection. In this paper, we [...] Read more.
In spite of the large number of repositioned drugs and direct-acting antivirals in clinical trials for the management of the ongoing COVID-19 pandemic, there are few cost-effective therapeutic options for severe acute respiratory syndrome (SARS) coronavirus 2 (SCoV2) infection. In this paper, we show that xanthorrhizol (XNT), a bisabolane-type sesquiterpenoid compound isolated from the Curcuma xanthorrhizza Roxb., a ginger-line plant of the family Zingiberaceae, displays a potent antiviral efficacy in vitro against SCoV2 and other related coronaviruses, including SARS-CoV-1 (SCoV1) and a common cold-causing human coronavirus. XNT reduced infectious SCoV2 titer by ~3-log10 at 20 μM and interfered with the replication of the SCoV1 subgenomic replicon, while it had no significant antiviral effects against hepatitis C virus and noroviruses. Further, XNT exerted similar antiviral functions against SCoV2 variants, such as a GH clade strain and a delta strain currently predominant worldwide. Neither SCoV2 entry into cells nor the enzymatic activity of viral RNA polymerase (Nsp12), RNA helicase (Nsp13), or the 3CL main protease (Nsp5) was inhibited by XNT. While its CoV replication inhibitory mechanism remains elusive, our results demonstrate that the traditional folk medicine XNT could be a promising antiviral candidate that inhibits a broad range of SCoV2 variants of concern and other related CoVs. Full article
(This article belongs to the Section Drug Discovery)
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Article
Tryptophan Metabolites, Cytokines, and Fatty Acid Binding Protein 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Biomedicines 2021, 9(11), 1724; https://doi.org/10.3390/biomedicines9111724 - 19 Nov 2021
Cited by 4 | Viewed by 2942
Abstract
Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) differ for triggers, mode of start, associated symptoms, evolution, and biochemical traits. Therefore, serious attempts are underway to partition them into subgroups useful for a personalized medicine approach to the disease. Here, we investigated clinical and [...] Read more.
Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) differ for triggers, mode of start, associated symptoms, evolution, and biochemical traits. Therefore, serious attempts are underway to partition them into subgroups useful for a personalized medicine approach to the disease. Here, we investigated clinical and biochemical traits in 40 ME/CFS patients and 40 sex- and age-matched healthy controls. Particularly, we analyzed serum levels of some cytokines, Fatty Acid Binding Protein 2 (FAPB-2), tryptophan, and some of its metabolites via serotonin and kynurenine. ME/CFS patients were heterogeneous for genetic background, trigger, start mode, symptoms, and evolution. ME/CFS patients had higher levels of IL-17A (p = 0.018), FABP-2 (p = 0.002), and 3-hydroxykynurenine (p = 0.037) and lower levels of kynurenine (p = 0.012) and serotonin (p = 0.045) than controls. Changes in kynurenine and 3-hydroxykynurenine were associated with increased kynurenic acid/kynurenine and 3-hydroxykynurenine/kynurenine ratios, indirect measures of kynurenine aminotransferases and kynurenine 3-monooxygenase enzymatic activities, respectively. No correlation was found among cytokines, FABP-2, and tryptophan metabolites, suggesting that inflammation, anomalies of the intestinal barrier, and changes of tryptophan metabolism may be independently associated with the pathogenesis of the disease. Interestingly, patients with the start of the disease after infection showed lower levels of kynurenine (p = 0.034) than those not starting after an infection. Changes in tryptophan metabolites and increased IL-17A levels in ME/CFS could both be compatible with anomalies in the sphere of energy metabolism. Overall, clinical traits together with serum biomarkers related to inflammation, intestine function, and tryptophan metabolism deserve to be further considered for the development of personalized medicine strategies for ME/CFS. Full article
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Article
Obesity-Associated Metabolic Disturbances Reverse the Antioxidant and Anti-Inflammatory Properties of High-Density Lipoproteins in Microglial Cells
Biomedicines 2021, 9(11), 1722; https://doi.org/10.3390/biomedicines9111722 - 19 Nov 2021
Cited by 1 | Viewed by 668
Abstract
High-density lipoproteins (HDLs) play an important role in reverse cholesterol transport and present antioxidant properties, among others. In the central nervous system (CNS), there are HDLs, where these lipoproteins could influence brain health. Owing to the new evidence of HDL functionality remodeling in [...] Read more.
High-density lipoproteins (HDLs) play an important role in reverse cholesterol transport and present antioxidant properties, among others. In the central nervous system (CNS), there are HDLs, where these lipoproteins could influence brain health. Owing to the new evidence of HDL functionality remodeling in obese patients, and the fact that obesity-associated metabolic disturbances is pro-inflammatory and pro-oxidant, the aim of this study was to investigate if HDL functions are depleted in obese patients and obesity-associated microenvironment. HDLs were isolated from normal-weight healthy (nwHDL) and obese men (obHDL). The oxHDL level was measured by malondialdehyde and 4-hydroxynoneal peroxided products. BV2 microglial cells were exposed to different concentrations of nwHDL and obHDL in different obesity-associated pro-inflammatory microenvironments. Our results showed that hyperleptinemia increased oxHDL levels. In addition, nwHDLs reduced pro-inflammatory cytokines’ release and M1 marker gene expression in BV2 microglial cells. Nevertheless, both nwHDL co-administered with LPS+leptin and obHDL promoted BV2 microglial activation and a higher pro-inflammatory cytokine production, thus confirming that obesity-associated metabolic disturbances reverse the antioxidant and anti-inflammatory properties of HDLs in microglial cells. Full article
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Article
Protective Role of Combined Polyphenols and Micronutrients against Influenza A Virus and SARS-CoV-2 Infection In Vitro
Biomedicines 2021, 9(11), 1721; https://doi.org/10.3390/biomedicines9111721 - 19 Nov 2021
Cited by 7 | Viewed by 1217
Abstract
Polyphenols have been widely studied for their antiviral effect against respiratory virus infections. Among these, resveratrol (RV) has been demonstrated to inhibit influenza virus replication and more recently, it has been tested together with pterostilbene against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [...] Read more.
Polyphenols have been widely studied for their antiviral effect against respiratory virus infections. Among these, resveratrol (RV) has been demonstrated to inhibit influenza virus replication and more recently, it has been tested together with pterostilbene against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the present work, we evaluated the antiviral activity of polydatin, an RV precursor, and a mixture of polyphenols and other micronutrients, named A5+, against influenza virus and SARS-CoV-2 infections. To this end, we infected Vero E6 cells and analyzed the replication of both respiratory viruses in terms of viral proteins synthesis and viral titration. We demonstrated that A5+ showed a higher efficacy in inhibiting both influenza virus and SARS-CoV-2 infections compared to polydatin treatment alone. Indeed, post infection treatment significantly decreased viral proteins expression and viral release, probably by interfering with any step of virus replicative cycle. Intriguingly, A5+ treatment strongly reduced IL-6 cytokine production in influenza virus-infected cells, suggesting its potential anti-inflammatory properties during the infection. Overall, these results demonstrate the synergic and innovative antiviral efficacy of A5+ mixture, although further studies are needed to clarify the mechanisms underlying its inhibitory effect. Full article
(This article belongs to the Special Issue Inhibitors of Key Targets of SARS-CoV-2 and Other Coronaviruses)
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Article
The Safety and Feasibility of Laparoscopic Surgery for Very Low Rectal Cancer: A Retrospective Analysis Based on a Single Center’s Experience
Biomedicines 2021, 9(11), 1720; https://doi.org/10.3390/biomedicines9111720 - 19 Nov 2021
Viewed by 521
Abstract
In this work we intend to validate the long-term oncologic outcomes for very low rectal cancer over the past 20 years and to determine whether laparoscopic procedures are useful options for very low rectal cancer. A total of 327 patients, who electively underwent [...] Read more.
In this work we intend to validate the long-term oncologic outcomes for very low rectal cancer over the past 20 years and to determine whether laparoscopic procedures are useful options for very low rectal cancer. A total of 327 patients, who electively underwent laparoscopic rectal cancer surgery for a lesion within 5 cm from the anal verge, were enrolled in this study and their long-term outcomes were reviewed retrospectively. Of 327 patients, 70 patients underwent laparoscopic low anterior resection (LAR), 164 underwent laparoscopic abdominal transanal proctosigmoidocolectomy with coloanal anastomosis (LATA), and 93 underwent laparoscopic abdominoperineal resection (APR). The conversion rate was 1.22% (4/327). The overall postoperative morbidity rate was 26.30% (86/327). The 5-year disease free survival (DFS), 5-year overall survival (OS), and 3-year local recurrence (LR) were 64.3%, 79.7%, and 9.2%, respectively. The CRM involvement was a significant independent factor for DFS (p = 0.018) and OS (p = 0.042) in multivariate analysis. Laparoscopic APR showed poorer 5-year DFS (47.8%), 5-year OS (64.0%), and 3-year LR (17.6%) than laparoscopic LAR (74.1%, 86.4%, 1.9%) and laparoscopic LATA (69.2%, 83.6%, 9.2%). Laparoscopic procedures for very low rectal cancer including LAR, LATA, and APR could be good surgical options in selective patients with very low rectal cancer. Full article
(This article belongs to the Special Issue Colorectal Cancer: New Diagnostic and Therapeutic Approaches)
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Article
Bioactive Flavonoids Icaritin and Icariin Protect against Cerebral Ischemia–Reperfusion-Associated Apoptosis and Extracellular Matrix Accumulation in an Ischemic Stroke Mouse Model
Biomedicines 2021, 9(11), 1719; https://doi.org/10.3390/biomedicines9111719 - 19 Nov 2021
Viewed by 721
Abstract
Stroke, which is the second leading cause of mortality in the world, is urgently needed to explore the medical strategies for ischemic stroke treatment. Both icariin (ICA) and icaritin (ICT) are the major active flavonoids extracted from Herba epimedii that have been regarded [...] Read more.
Stroke, which is the second leading cause of mortality in the world, is urgently needed to explore the medical strategies for ischemic stroke treatment. Both icariin (ICA) and icaritin (ICT) are the major active flavonoids extracted from Herba epimedii that have been regarded as the neuroprotective agents in disease models. In this study, we aimed to investigate and compare the neuroprotective effects of ICA and ICT in a middle cerebral artery occlusion (MCAO) mouse model. Male ICR mice were pretreated with both ICA and ICT, which ameliorated body weight loss, neurological injury, infarct volume, and pathological change in acute ischemic stroke mice. Furthermore, administration of both ICA and ICT could also protect against neuronal cell apoptotic death, oxidative and nitrosative stress, lipid peroxidation, and extracellular matrix (ECM) accumulation in the brains. The neuroprotective effects of ICT are slightly better than that of ICA in acute cerebral ischemic stroke mice. These results suggest that pretreatment with both ICA and ICT improves the neuronal cell apoptosis and responses of oxidative/nitrosative stress and counteracts the ECM accumulation in the brains of acute cerebral ischemic stroke mice. Both ICA and ICT treatment may serve as a useful therapeutic strategy for acute ischemic stroke. Full article
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Article
Genomic and Phylogenetic Analysis of Lactiplantibacillus plantarum L125, and Evaluation of Its Anti-Proliferative and Cytotoxic Activity in Cancer Cells
Biomedicines 2021, 9(11), 1718; https://doi.org/10.3390/biomedicines9111718 - 19 Nov 2021
Cited by 3 | Viewed by 904
Abstract
Lactiplantibacillus plantarum is a diverse species that includes nomadic strains isolated from a variety of environmental niches. Several L. plantarum strains are being incorporated in fermented foodstuffs as starter cultures, while some of them have also been characterized as probiotics. In this study, [...] Read more.
Lactiplantibacillus plantarum is a diverse species that includes nomadic strains isolated from a variety of environmental niches. Several L. plantarum strains are being incorporated in fermented foodstuffs as starter cultures, while some of them have also been characterized as probiotics. In this study, we present the draft genome sequence of L. plantarum L125, a potential probiotic strain presenting biotechnological interest, originally isolated from a traditional fermented meat product. Phylogenetic and comparative genomic analysis with other potential probiotic L. plantarum strains were performed to determine its evolutionary relationships. Furthermore, we located genes involved in the probiotic phenotype by whole genome annotation. Indeed, genes coding for proteins mediating host–microbe interactions and bile salt, heat and cold stress tolerance were identified. Concerning the potential health-promoting attributes of the novel strain, we determined that L. plantarum L125 carries an incomplete plantaricin gene cluster, in agreement with previous in vitro findings, where no bacteriocin-like activity was detected. Moreover, we showed that cell-free culture supernatant (CFCS) of L. plantarum L125 exerts anti-proliferative, anti-clonogenic and anti-migration activity against the human colon adenocarcinoma cell line, HT-29. Conclusively, L. plantarum L125 presents desirable probiotic traits. Future studies will elucidate further its biological and health-related properties. Full article
(This article belongs to the Special Issue Microbial Ecology in Health and Disease 2.0)
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Article
808-nm Photobiomodulation Affects the Viability of a Head and Neck Squamous Carcinoma Cellular Model, Acting on Energy Metabolism and Oxidative Stress Production
Biomedicines 2021, 9(11), 1717; https://doi.org/10.3390/biomedicines9111717 - 18 Nov 2021
Cited by 8 | Viewed by 889
Abstract
Photobiomodulation (PBM) is a form of low-dose light therapy that acts through energy delivery from non-ionizing sources. During the recent two decades, there has been tremendous progress with PBM acceptance in medicine. However, PBM effects on potential stimulation of existing malignant or pre-malignant [...] Read more.
Photobiomodulation (PBM) is a form of low-dose light therapy that acts through energy delivery from non-ionizing sources. During the recent two decades, there has been tremendous progress with PBM acceptance in medicine. However, PBM effects on potential stimulation of existing malignant or pre-malignant cells remain unknown. Thus, the primary endpoint was to assess the safety of PBM treatment parameters on head and neck squamous cell carcinoma (HNSCC) proliferation or survival. The secondary endpoint was to assess any putative anti-cancer effects of PBM treatments. Cell viability, energy metabolism, oxidative stress, and pro- and anti-apoptotic markers expression were investigated on a Human Head and Neck Squamous Cell Carcinoma cellular model (OHSU-974 FAcorr cell line). PBM therapy was administered through the 810 nm diode laser (GaAlAs) device (Garda Laser, 7024 Negrar, Verona, Italy) at the powers of 0, 0.25, 0.50, 0.75, 1.00, or 1.25 W in continuous wave (CW) mode for an exposure time of 60 s with a spot-size of 1 cm2 and with a distance of 1.86 cm from the cells. Results showed that 810-nm PBM affected oxidative phosphorylation in OHSU-971 FAcorr, causing a metabolic switch to anaerobic glycolysis. In addition, PBM reduced the catalase activity, determining an unbalance between oxidative stress production and the antioxidant defenses, which could stimulate the pro-apoptotic cellular pathways. Our data, at the parameters investigated, suggest the safeness of PBM as a supportive cancer therapy. Pre-clinical and clinical studies are necessary to confirm the in vitro evidence. Full article
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Review
Epigenetic Mechanisms of Endocrine-Disrupting Chemicals in Obesity
Biomedicines 2021, 9(11), 1716; https://doi.org/10.3390/biomedicines9111716 - 18 Nov 2021
Cited by 3 | Viewed by 849
Abstract
The incidence of obesity has dramatically increased over the last decades. Recently, there has been a growing interest in the possible association between the pandemics of obesity and some endocrine-disrupting chemicals (EDCs), termed “obesogens”. These are a heterogeneous group of exogenous compounds that [...] Read more.
The incidence of obesity has dramatically increased over the last decades. Recently, there has been a growing interest in the possible association between the pandemics of obesity and some endocrine-disrupting chemicals (EDCs), termed “obesogens”. These are a heterogeneous group of exogenous compounds that can interfere in the endocrine regulation of energy metabolism and adipose tissue structure. Oral intake, inhalation, and dermal absorption represent the major sources of human exposure to these EDCs. Recently, epigenetic changes such as the methylation of cytosine residues on DNA, post-translational modification of histones, and microRNA expression have been considered to act as an intermediary between deleterious effects of EDCs and obesity development in susceptible individuals. Specifically, EDCs exposure during early-life development can detrimentally affect individuals via inducing epigenetic modifications that can permanently change the epigenome in the germline, enabling changes to be transmitted to the next generations and predisposing them to a multitude of diseases. The purpose of this review is to analyze the epigenetic alterations putatively induced by chemical exposures and their ability to interfere with the control of energy metabolism and adipose tissue regulation, resulting in imbalances in the control of body weight, which can lead to obesity. Full article
(This article belongs to the Special Issue Epigenetic Mechanisms of Environmental Diseases)
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Article
Oxidized LDL Increase the Proinflammatory Profile of Human Visceral Adipocytes Produced by Hypoxia
Biomedicines 2021, 9(11), 1715; https://doi.org/10.3390/biomedicines9111715 - 18 Nov 2021
Cited by 2 | Viewed by 617
Abstract
Background: Little is known about the effects of hypoxia on scavenger receptors (SRs) levels in adipocytes. We analyzed the effect of morbid obesity and hypoxia on SRs and inflammation markers in human visceral adipocytes and whether ox-LDL modify the inflammatory profile produced by [...] Read more.
Background: Little is known about the effects of hypoxia on scavenger receptors (SRs) levels in adipocytes. We analyzed the effect of morbid obesity and hypoxia on SRs and inflammation markers in human visceral adipocytes and whether ox-LDL modify the inflammatory profile produced by hypoxia. Methods: We studied in 17 non-obese and 20 subjects with morbid obesity (MO) the mRNA expression of HIF-1α, SRs (LOX-1, MSR1, CL-P1 and CXCL16), IL6 and TNFα in visceral adipocytes and the effect of hypoxia with or without ox-LDL on visceral in vitro-differentiated adipocytes (VDA). Results: HIF-1α, TNFα, IL6, LOX-1, MSR1 and CXCL16 expression in adipocytes was increased in MO when compared with those in non-obese subjects (p < 0.05). The expression of most of the inflammatory markers and SRs gene correlated with HIF-1α. In VDA, hypoxia increased TNFα, IL6, MSR1, CXCL16 and CL-P1 (p < 0.05) in non-obese subjects, and TNFα, IL6, MSR1 and CXCL16 (p < 0.05) in MO. Silencing HIF-1α prevented the increase of TNFα, IL6, LOX-1, MSR1, CL-P1 and CXCL16 expression (p < 0.05). The combination of hypoxia and ox-LDL produced higher TNFα expression (p = 0.041). Conclusions: Morbid obesity and hypoxia increased SRs and inflammatory markers in visceral adipocytes. In a hypoxic state, ox-LDL increased the proinflammatory response of visceral adipocytes to hypoxia. Full article
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