GALNT14 in association with GDF-15 promotes stemness and drug resistance through ß-catenin signalling pathway in breast cancer.

BACKGROUND: Altered glycosylation plays a role in carcinogenesis. GALNT14 promotes cancer stem-like properties and drug resistance. GDF-15 is known to induces drug resistance and stemness markers for maintenance of breast cancer (BC) stem-like cell state. Currently there is lack of data on association of GDF-15 and GALNTs. In this study, the expression and interaction of GALNT14 and GDF-15 with stemness (OCT4 and SOX2) and drug resistance (ABCC5) markers were evaluated in BC. METHODS: We investigated tumour tissue from 30 BC patients and adjacent non-tumour tissues. Expression of serum GALNT14 from BC patients and matched healthy controls was evaluated. Expression of GALNT14, GDF-15, OCT4, SOX2, ABCC5, and ß-catenin in BC tissue was determined by RT-PCR. Knockdown of GALNT14 and GDF-15 in the MCF-7 cell line was done through siRNA, gene expression and protein expression of ß-catenin by western blot were determined. RESULTS: A significant increase in the expression of GALNT14, GDF-15, OCT4, SOX2, ABCC5, and ß-catenin was observed in BC tumour tissues compared to adjacent non-tumour tissues. The serum level of GALNT14 was significantly high in BC patients (80.7 ± 65.3 pg/ml) compared to healthy controls (12.2 ± 9.12 pg/ml) (p < 0.000). To further analyse the signalling pathway involved in BC stemness and drug resistance, GALNT14 and GDF-15 were knocked down in the MCF-7 cell line, and it was observed that after knockdown, the expression level of OCT4, SOX2, ABCC5, and ß-catenin was decreased, and co-knockdown with GALNT14 and GDF-15 further decreased the expression of genes. CONCLUSION: It can be concluded that GALNT14, in association with GDF-15, promotes stemness and intrinsic drug resistance in BC, possibly through the ß-catenin signalling pathway.

Extracellular Vesicles in Malaria: Shedding Light on Pathogenic Depths.

Malaria, a life-threatening infectious disease caused by Plasmodium falciparum, remains a significant global health challenge, particularly in tropical and subtropical regions. The epidemiological data for 2021 revealed a staggering toll, with 247 million reported cases and 619,000 fatalities attributed to the disease. This formidable global health challenge continues to perplex researchers seeking a comprehensive understanding of its pathogenesis. Recent investigations have unveiled the pivotal role of extracellular vesicles (EVs) in this intricate landscape. These tiny, membrane-bound vesicles, secreted by diverse cells, emerge as pivotal communicators in malaria's pathogenic orchestra. This Review delves into the multifaceted roles of EVs in malaria pathogenesis, elucidating their impact on disease progression and immune modulation. Insights into EV involvement offer potential therapeutic and diagnostic strategies. Integrating this information identifies targets to mitigate malaria's global impact. Moreover, this Review explores the potential of EVs as diagnostic biomarkers and therapeutic targets in malaria. By deciphering the intricate dialogue facilitated by these vesicles, new avenues for intervention and novel strategies for disease management may emerge.

Non-invasive detection of renal disease biomarkers through breath analysis.

Breath biomarkers are substances found in exhaled breath that can be used for non-invasive diagnosis and monitoring of medical conditions, including kidney disease. Detection techniques include mass spectrometry (MS), gas chromatography (GC), and electrochemical sensors. Biosensors, such as GC-MS or electronic nose (e-nose) devices, can be used to detect volatile organic compounds (VOCs) in exhaled breath associated with metabolic changes in the body, including the kidneys. E-nose devices could provide an early indication of potential kidney problems through the detection of VOCs associated with kidney dysfunction. This review discusses the sources of breath biomarkers for monitoring renal disease during dialysis and different biosensor approaches for detecting exhaled breath biomarkers. The future of using various types of biosensor-based real-time breathing diagnosis for renal failure is also discussed.

Designing a Multi-Epitope Subunit Vaccine against VP1 Major Coat Protein of JC Polyomavirus.

The JC polyomavirus virus (JCPyV) affects more than 80% of the human population in their early life stage. It mainly affects immunocompromised individuals where virus replication in oligodendrocytes and astrocytes may lead to fatal progressive multifocal encephalopathy (PML). Virus protein 1 (VP1) is one of the major structural proteins of the viral capsid, responsible for keeping the virus alive in the gastrointestinal and urinary tracts. VP1 is often targeted for antiviral drug and vaccine development. Similarly, this study implied immune-informatics and molecular modeling methods to design a multi-epitope subunit vaccine targeting JCPyV. The VP1 protein epitopic sequences, which are highly conserved, were used to build the vaccine. This designed vaccine includes two adjuvants, five HTL epitopes, five CTL epitopes, and two BCL epitopes to stimulate cellular, humoral, and innate immune responses against the JCPyV. Furthermore, molecular dynamics simulation (100 ns) studies were used to examine the interaction and stability of the vaccine protein with TLR4. Trajectory analysis showed that the vaccine and TLR4 receptor form a stable complex. Overall, this study may contribute to the path of vaccine development against JCPyV.

Mechanism of Immune Evasion in Mosquito-Borne Diseases.

In recent decades, mosquito-borne illnesses have emerged as a major health burden in many tropical regions. These diseases, such as malaria, dengue fever, chikungunya, yellow fever, Zika virus infection, Rift Valley fever, Japanese encephalitis, and West Nile virus infection, are transmitted through the bite of infected mosquitoes. These pathogens have been shown to interfere with the host's immune system through adaptive and innate immune mechanisms, as well as the human circulatory system. Crucial immune checkpoints such as antigen presentation, T cell activation, differentiation, and proinflammatory response play a vital role in the host cell's response to pathogenic infection. Furthermore, these immune evasions have the potential to stimulate the human immune system, resulting in other associated non-communicable diseases. This review aims to advance our understanding of mosquito-borne diseases and the immune evasion mechanisms by associated pathogens. Moreover, it highlights the adverse outcomes of mosquito-borne disease.

In silico analysis of differentially expressed-aberrantly methylated genes in breast cancer for prognostic and therapeutic targets.

Breast cancer (BC) is the leading cause of death among women across the globe. Abnormal gene expression plays a crucial role in tumour progression, carcinogenesis and metastasis of BC. The alteration of gene expression may be through aberrant gene methylation. In the present study, differentially expressed genes which may be regulated by DNA methylation and their pathways associated with BC have been identified. Expression microarray datasets GSE10780, GSE10797, GSE21422, GSE42568, GSE61304, GSE61724 and one DNA methylation profile dataset GSE20713 were downloaded from Gene Expression Omnibus database (GEO). Differentially expressed-aberrantly methylated genes were identified using online Venn diagram tool. Based on fold change expression of differentially expressed-aberrantly methylated genes were chosen through heat map. Protein-protein interaction (PPI) network of the hub genes was constructed by Search Tool for the Retrieval of Interacting Genes (STRING). Gene expression and DNA methylation level of the hub genes were validated through UALCAN. Overall survival analysis of the hub genes was analysed through Kaplan-Meier plotter database for BC. A total of 72 upregulated-hypomethylated genes and 92 downregulated-hypermethylated genes were obtained from GSE10780, GSE10797, GSE21422, GSE42568, GSE61304, GSE61724, and GSE20713 datasets by GEO2R and Venn diagram tool. PPI network of the upregulated-hypomethylated hub genes (MRGBP, MANF, ARF3, HIST1H3D, GSK3B, HJURP, GPSM2, MATN3, KDELR2, CEP55, GSPT1, COL11A1, and COL1A1) and downregulated-hypermethylated hub genes were constructed (APOD, DMD, RBPMS, NR3C2, HOXA9, AMKY2, KCTD9, and EDN1). All the differentially expressed hub genes expression was validated in UALCAN database. 4 in 13 upregulated-hypomethylated and 5 in 8 downregulated-hypermethylated hub genes to be significantly hypomethylated or hypermethylated in BC were confirmed using UALCAN database (p < 0.05). MANF, HIST1H3D, HJURP, GSK3B, GPSM2, MATN3, KDELR2, CEP55, COL1A1, APOD, RBPMS, NR3C2, HOXA9, ANKMY2, and EDN1 were significantly (p < 0.05) associated with poor overall survival (OS). The identified aberrantly methylated-differentially expressed genes and their related pathways and function in BC can serve as novel diagnostic and prognostic biomarkers and therapeutic targets.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 4 Given name: [Jeewan Ram] Last name [Vishnoi]. Also, kindly confirm the details in the metadata are correct.It is correct.

Analyzing the Association of Visceral Adipose Tissue Growth Differentiation Factor-15 and MicroRNA in Type 2 Diabetes Mellitus.

Background: Growth differentiation factor-15 (GDF-15) is involved in insulin resistance and diabetes. In this study, we determine the associations of GDF-15 with miR-181b-5p, miR-330-3p, mothers against decapentaplegic homolog 7 (SMAD7), and insulin resistance in visceral adipose tissue (VAT) and peripheral blood mononuclear cells (PBMCs) in type 2 diabetes mellitus (T2DM) patients. Methods: Sixty patients, equally divided into those with T2DM and non-diabetic controls, were recruited for gene expression analysis. Protein-protein interaction (STRING), target prediction (miRNet), and functional enrichment were conducted accordingly. Results: Our study showed that VAT and PBMCs had similar expression profiles, where GDF-15 and miR-181b-5p were upregulated, whereas SMAD7 and miR-330-3p were downregulated. Serum GDF-15 could differentiate between T2DM and non-diabetic patients (P<0.001). Target prediction revealed a microRNA (miRNA)-messenger RNA regulatory network, transcription factors, and functional enrichment for the miRNA that suggested involvement in T2DM pathogenesis. Conclusion: VAT GDF-15 is associated with insulin resistance and is possibly regulated by miR-181b-5p, miR-330-3p, and SMAD7 in T2DM.

Metformin mediates MicroRNA-21 regulated circulating matrix metalloproteinase-9 in diabetic nephropathy: an in-silico and clinical study.

Metformin is commonly used as an oral hypoglycaemic agent in type 2 diabetes mellitus (T2DM). MicroRNA-21 is widely studied in diabetic and diabetic nephropathy (DN) patients. Matrix metalloproteinase-9 (MMP9) is involved in extracellular matrix degradation and tissue repair processes. However, the effect of metformin administration on hsa-miR-21-5p and MMP9 has not been evaluated in T2DM and DN patients. The study subjects were divided into three groups (Healthy controls = 36, T2DM = 38, DN = 35). Anthropometric measurements were taken and biochemical tests were carried out on fasting blood samples. Reverse transcriptase PCR was employed for whole blood gene expression analysis of hsa-miR-21-5p and MMP9. Bioinformatics analyses including drug-gene interaction, protein-protein interaction, functional enrichment analyses and co-expression networks were performed. In the present study, MMP9 and hsa-miR-21-5p levels were downregulated and upregulated respectively in T2DM and DN patients when compared with healthy controls. However, in metformin-treated group, a downregulation of hsa-miR-21-5p and upregulation of MMP9 was observed. In-silico analysis revealed the target genes involved in the miR-21 and MMP9 interaction network. Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.

Acute kidney injury in COVID 19 - an update on pathophysiology and management modalities.

Acute kidney injury (AKI), characterised by fluid imbalance and overload, is prevalent in severe disease phenotypes of coronavirus disease 2019 (COVID-19). The elderly immunocompromised patients with pre-existing comorbidities being more risk-prone to severe COVID-19, the importance of early diagnosis and intervention in AKI is imperative. Histopathological examination of COVID-19 patients with AKI reveals viral invasion of the renal parenchyma and evidence of AKI. The definitive treatment for AKI includes renal replacement therapy and renal transplant. Immunosuppressant regimens and its interactions with COVID-19 have to be further explored to devise effective treatment strategies in COVID-19 transplant patients. Other supportive strategies for AKI patients include hemodynamic monitoring and maintenance of fluid balance. Antiviral drugs should be meticulously monitored in the management of these high-risk patients. We have focussed on the development of renal injury provoked by the SARS-CoV-2, the varying clinical characteristics, and employment of different management strategies, including renal replacement therapy, alongside the emerging cytokine lowering approaches.

A clinical and in-silico study of microRNA-21 and growth differentiation factor-15 expression in pre-diabetes, type 2 diabetes and diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN), a microvascular complication associated with long-standing diabetes, is a major cause of the end-stage renal disease (ESRD). Our in-silico analysis indicates several enrichment analyses involved in glucose metabolism to be affected by GDF15 transcription factors. METHODS: In-silico analysis was used to identify GDF15 and Insulin related protein-protein interaction (PPI) network and a common set of GDF15 regulating transcription factors by various databases. Common targeting miRNA of GDF15 regulating transcription factors were investigated in miRNet and TargetScan. Further, healthy controls (N.=30) and patients with pre-type-2 diabetes mellitus (pre-diabetes) (N.=30), T2DM (N.=30) and DN (N.=30) were included for analysis of routine biochemical tests, serum GDF15 levels by ELISA and to evaluate the Fold change expression (FCE) of circulating hsa-miR-21 by RT-PCR. RESULTS: MicroRNA-21 was found to directly target GDF15 downregulating transcription factors KLF4, TP53, and CEBPB. A significant difference in the levels of serum GDF15 was observed in Pre-diabetes (708.56±76.37), T2DM (1528.87±140.75) and DN patients (10-fold higher; 5507.90±503.88) when compared to healthy controls (567.36±69.99). The FCE of circulating hsa-miR-21 was 6.19 (pre-diabetes), 8.22 (T2DM), 9.19 (DN), folds higher in cases as compared to controls, reflecting an increasing trend and several folds higher levels of hsa-miR-21 in patients. CONCLUSIONS: We suggest the potential of serum GDF15 and circulating-hsa-miR-21 to serve as clinically important biomarkers and therapeutic targets for controlling advancement of diabetes to DN.

Growth Differentiation Factor-15 as a Candidate Biomarker in Gynecologic Malignancies: A Meta-analysis.

Growth differentiation factor-15 (GDF-15), though emerged as a novel marker in gynecological cancers, is yet to be recognized in clinical diagnostics. Eligible studies were sorted from multiple online databases, namely PubMed, Cochrane, ClinicalTrials.gov, Google Scholar, Web of Science, Embase, Scopus, LILACS, and Opengrey. From six studies, histopathologically diagnosed cases without prior treatment, and with diagnostic accuracy data for GDF-15 in gynecological cancers, were included. Our meta-analysis shows that GDF-15 has pooled diagnostic odds ratio of 12.74 at 80.5% sensitivity and 74.1% specificity, and an area under the curve of 0.84. Hence, GDF-15 is a potential marker to differentiate gynecological malignancy from non-malignant tumors.

Multi-omics integration and interactomics reveals molecular networks and regulators of the beneficial effect of yoga and exercise.

Background: Yoga is a multifaceted spiritual tool that helps in maintaining health, peace of mind, and positive thoughts. In the context of asana, yoga is similar to physical exercise. This study aims to construct a molecular network to find hub genes that play important roles in physical exercise and yoga. Methodology: We combined differentially expressed genes (DEGs) in yoga and exercise using computational bioinformatics from publicly available gene expression omnibus (GEO) datasets and identified the codifferentially expressed mRNAs with GEO2R. The co-DEGs were divided into four different groups and each group was subjected to protein-protein interaction (PPI) network, pathways analysis, and gene ontology. Results: Our study identified immunological modulation as a dominant target of differential expression in yoga and exercise. Yoga predominantly modulated genes affecting the Th1 and NK cells, whereas Cytokines, Macrophage activation, and oxidative stress were affected by exercise. We also observed that while yoga regulated genes for two main physiological functions of the body, namely Circadian Rhythm (BHLHE40) and immunity (LBP, T-box transcription factor 21, CEACAM1), exercise-regulated genes involved in apoptosis (BAG3, protein kinase C alpha), angiogenesis, and cellular adhesion (EPH receptor A1). Conclusion: The dissimilarity in the genetic expression patterns in Yoga and exercise highlights the discrete effect of each in biological systems. The integration and convergences of multi-omics signals can provide deeper and comprehensive insights into the various biological mechanisms through which yoga and exercise exert their beneficial effects and opens up potential newer research areas.

Growth Differentiation Factor-15 as a Biomarker of Obese Pre-diabetes and Type 2 Diabetes Mellitus in Indian Subjects: A Case-control Study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is an ever-growing epidemic in India and poses significant morbidity, mortality, and socioeconomic burden. INTRODUCTION: Growth differentiation factor-15 (GDF15) is a stress-responsive cytokine, increased in T2DM patients compared to control subjects without the disease. We aimed to assess whether serum GDF15 and adipose tissue GDF15 expression can differentiate between obese pre-diabetes and T2DM and control populations. METHODOLOGY: We recruited 156 individuals including 73 type 2 diabetes, 30 pre-diabetes, and 53 healthy controls. Clinical history, anthropometric measurements and biochemical profiling were taken. Insulin resistance indices were calculated following HOMA models. Serum GDF15 was measured by sandwich ELISA. Visceral adipose tissue (VAT) expression of GDF15 was observed in 17 T2DM patients and 29 controls using SYBR Green chemistry in RT-PCR using GAPDH as the housekeeping gene. The data were analyzed on R programming platform using RStudio. RESULTS: Serum GDF15 was significantly higher (p<0.001) in T2DM subjects (median 1445.47 pg/mL) compared to pre-diabetes (627.85 pg/mL) and healthy controls (609.01 pg/mL). Using the ΔΔCt method, the VAT GDF15 expression was 1.54 fold and 1.57 fold upregulated in T2DM (n=17) compared to control subjects (n=29), and obese (n=12) compared to non-obese (n=34)subjects, respectively. The optimal cut-off point following Youden's index method was found to be 868.09 pg/mL. ROC curve analysis revealed that serum GDF15 had a sensitivity, specificity, and area under the curve (AUC) of 90.41%, 79.52%, and 0.892 respectively. GDF15 levels were significantly associated with age, BMI, HbA1c, fasting blood sugar, and insulin resistance indices. CONCLUSION: Hence, serum GDF15 is a biomarker for T2DM patients in our study population from Western India. However, larger prospective cohorts are necessary to validate this claim.

Critical appraisal of epigenetic regulation of galectins in cancer.

Galectins are defined as the glycan-binding protein containing either one or two carbohydrate-binding domains and participate in various biological functions such as developmental processes, vascularisation programs, cell migration, and immune-regulation and apoptosis. Galectins are also linked to many diseases, including cancer. They are widely spread in extracellular and intracellular spaces, and their altered expression in cancer leads to tumor progression, metastasis, angiogenesis and stemness through different signalling pathways. Promoter methylation, microRNA, and histone modification constitute the epigenetic changes that regulate galectin activity in cancer. Our review discusses the concept of epigenetics in cancer and how the aforementioned factors i.e., promoter methylation, histone modification, change in miRNAs expression affect the glycomic changes in malignancies.

MicroRNAs based regulation of cytokine regulating immune expressed genes and their transcription factors in COVID-19.

BACKGROUND: Coronavirus disease 2019 is characterized by the elevation of a broad spectrum of inflammatory mediators associated with poor disease outcomes. We aimed at an in-silico analysis of regulatory microRNA and their transcription factors (TF) for these inflammatory genes that may help to devise potential therapeutic strategies in the future. METHODS: The cytokine regulating immune-expressed genes (CRIEG) were sorted from literature and the GEO microarray dataset. Their co-differentially expressed miRNA and transcription factors were predicted from publicly available databases. Enrichment analysis was done through mienturnet, MiEAA, Gene Ontology, and pathways predicted by KEGG and Reactome pathways. Finally, the functional and regulatory features were analyzed and visualized through Cytoscape. RESULTS: Sixteen CRIEG were observed to have a significant protein-protein interaction network. The ontological analysis revealed significantly enriched pathways for biological processes, molecular functions, and cellular components. The search performed in the miRNA database yielded ten miRNAs that are significantly involved in regulating these genes and their transcription factors. CONCLUSION: An in-silico representation of a network involving miRNAs, CRIEGs, and TF, which take part in the inflammatory response in COVID-19, has been elucidated. Thus, these regulatory factors may have potentially critical roles in the inflammatory response in COVID-19 and may be explored further to develop targeted therapeutic strategies and mechanistic validation.

A clinical and in-silico study exploring the association of CASP-3, NF-kB, miR-187, and miR-146 in pre-eclampsia.

INTRODUCTION: Apoptosis is involved in pathogenesis of Pre-eclampsia (PE), further research is needed to determine its molecular mechanism. METHODS: The study recruited two groups (controls; 09, PE; 11). Biochemical tests, RT-PCR and ELISA were employed for analysis of genes and MicroRNAs (miRNA). Bioinformatics tools were employed for interactomics analysis. RESULTS: There was increased apoptosis in maternal placental tissue (MPT) and Maternal Blood Cells (MBC) as demonstrated by expression of CASP3 and NF-κB1. miR-146-5p and 187-5p were downregulated in MBC and MPT but upregulated in fetal placental tissue (FPT).. DISCUSSION: An increased apoptosis in MBC and MPT is a significant contributory factor for PE in pregnancy, while FPT is immune to the aforementioned effects.

Leptin DNA Methylation and Its Association with Metabolic Risk Factors in a Northwest Indian Obese Population.

BACKGROUND: It is well established that obesity is a major health risk in diabetes and associated diseases. Epigenetic changes, specially DNA methylation, play an important role in regulation of adipokines. The objective of the present study was to evaluate the DNA methylation status at the promoter region of the leptin gene in obese individuals and its association with metabolic risk factors. METHODS: The study included obese (n=100) and non-obese (n=75) individuals aged 25-45 years, and measured their physical, biochemical parameters (glucose, insulin, and lipid profiles) and leptin, DNA methyltransferase 1 (DNMT1), and DNA methyltransferase 3 beta (DNMT3b) mRNA expressions with real-time reverse transcription-polymerase chain reaction (qRT-PCR). DNA methylation of the leptin gene at the promoter region was analyzed by methyl-specific qPCR . RESULTS: The study found that the DNA methylation level at the promoter area of the leptin gene was negatively associated with weight in obese subjects. Furthermore, study findings showed that the DNA methylation level was negatively associated with fasting insulin, glucose, homeostatic model assessment for insulin resistance, and total cholesterol. There was also a higher expression of DNMT1 and DNMT-3b in obese subjects as compared with non-obese subjects. CONCLUSION: The leptin epigenetic profile may be associated with obesity and its associated metabolic risk factors.

MicroRNA 21 Emerging Role in Diabetic Complications: A Critical Update.

BACKGROUND: Diabetes Mellitus is a multifactorial disease encompassing various pathogenic pathways. To avoid morbidity and mortality related to diabetic complications, early detection of disease complications as well as targeted therapeutic strategies are essential. INTRODUCTION: MicroRNAs (miRs) are short non-coding RNA molecules that regulate eukaryotic posttranscriptional gene expression. MicroRNA-21 has diverse gene regulatory functions and plays a significant role in various complications of Type 2 diabetes mellitus (T2DM). METHODS: The study included electronic database searches on Pubmed, Embase, and Web of Science with the search items MicroRNA21 and each of the diabetic complications. The search was carried out up to November, 2019. RESULTS: MicroRNA-21 modulates diabetic cardiomyopathy by affecting vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. At the renal tubules, miR-21 can regulate the mesangial expansion, interstitial fibrosis, macrophage infiltration, podocyte loss, albuminuria and fibrotic and inflammatory gene expression related to diabetic nephropathy. Overexpression of miR-21 has been seen to play a pivotal role in the pathogenesis of diabetic retinopathy by contributing to diabetes-induced endothelial dysfunction as well as low-grade inflammation. CONCLUSION: Considering the raised levels of miR-21 in various diabetic complications, it may prove to be a candidate biomarker for diabetic complications. Further, miR-21 antagonists have shown great potential in the treatment of diabetic cardiomyopathy, diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy related complications in the future. The current review is the first of its kind encompassing the roles miR-21 plays in various diabetic complications, with a critical discussion of its future potential role as a biomarker and therapeutic target.

Viricidal treatments for prevention of coronavirus infection.

Coronavirus disease 2019 (COVID-19), which causes severe acute respiratory syndrome and lung failure, is caused by the novel coronavirus, also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to high transmission rates from individual to individual, it has progressed to a pandemic. However, indirect transmission from inanimate objects or surfaces that have come in contact with a patient poses an even more significant threat as it is difficult to trace the source of infection in these cases. Therefore, these surfaces and objects require disinfection with chemicals having potent viricidal activity. These include alcohols, aldehydes, quaternary ammonium compounds, chlorhexidine, and chlorine-based disinfectants, among others. They vary in their viricidal activity depending on their structure, concentrations, and mechanism of action. Several studies have looked into these agents and the transmission of the virus related to it. Moreover, certain viricides, if used as constituents of commercially available oral disinfectants, can further aid in preventing ventilator-associated pneumonia and maintain oral hygiene. However, these chemicals are not entirely free of potential hazards. In this review, we have compiled and critically appraised some commonly used viricidal agents in healthcare settings and the role they can play in the prevention of SARS-CoV-2 transmission.

Perspectives on the role of PTEN in diabetic nephropathy: an update.

Phosphatase and tensin homolog (PTEN) is a potent tumor suppressor gene that antagonizes the proto-oncogenic phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway and governs basic cellular metabolic processes. Recently, its role in cell growth, metabolism, architecture, and motility as an intramolecular and regulatory mediator has gained widespread research interest as it applies to non-tumorous diseases, such as insulin resistance (IR) and diabetic nephropathy (DN). DN is characterized by renal tubulointerstitial fibrosis (TIF) and epithelial-mesenchymal transition (EMT), and PTEN plays a significant role in the regulation of both. Epigenetics and microRNAs (miRNAs) are novel players in post-transcriptional regulation and research evidence demonstrates that they reduce the expression of PTEN by acting as key regulators of autophagy and TIF through activation of the Akt/mammalian target of rapamycin (mTOR) signaling pathway. These regulatory processes might play an important role in solving the complexities of DN pathogenesis and IR, as well as the therapeutic management of DN with the help of PTEN K27-linked polyubiquitination. Currently, there are no comprehensive reviews citing the role PTEN plays in the development of DN and its regulation via miRNA and epigenetic modifications. The present review explores these facets of PTEN in the pathogenesis of IR and DN.