Assessing Performance of Martins's and Sampson's Formulae for Calculation of LDL-C in Indian Population: A Single Center Retrospective Study.

Various formulae had been derived to calculate the LDL-C from other lipid profile parameters to supplant the need for direct estimation. Martin's, Sampson's, and Cordova's formulae are recently derived formulae for calculating LDL-C. However, no study has been undertaken till now to verify the newer formulae viz. Martins's and Sampson's in Indian population. The retrospective cross-sectional study was carried out after obtaining approval from the Institutional Ethics Committee on human subject research. The lipid profile data were collected for a period of 17 months from January 2020 to May 2021. The formulae proposed by Friedewald, Cordova, Anandaraja, Martin, and Sampson were used to assess calculated LDL-C. Intraclass correlations were performed to assess the effectiveness of each formula when compared with direct estimation. In our study, we observed that LDL-C calculated using Martin was observed to be closer to that of direct estimation. The bias observed was lowest for Martin's formulae, followed by Sampson's. Intraclass correlation analysis for absolute agreement demonstrated Cordova, Martin, and Sampson to have an average ICC > 0.9, with Martin, and Sampson having a p value < 0.05. Martin fared superior to other formulae in intraclass correlation in patients with LDL > 70. In patients with TG below 200 mg/dL, Martin, and Sampson had a significant correlation with comparable average ICC. However, in patients with TG > 300 mg/dL, Cordova appears to fare better than all other formulae. Our study demonstrated a distinctly superior performance of Martin's formula over Friedewald's formula in the Indian patient population.

Association of Klotho with Neuropsychiatric Disorder: A Meta-Analysis.

Neuropsychiatric disorders are mainly concerned with the behavioural, emotional and cognition symptoms that may be due to disturbed cerebral functions or extracerebral disease. Klotho protein is an antiaging protein that is mostly associated with cognitive changes in these disorders and thus this meta-analysis is conducted in order to find Klotho proteins association with these disorders. We searched related topics in pubmed, by using the key word i.e. Klotho and related disorder from neuropsychiatry e.g. Klotho levels and schizophrenia, Klotho levels and parkinsonism etc. Total 82 studies were found till 9th February 2021 after extensive search and 10 studies were selected for further analysis. The meta-analysis of studies was performed using the Random effect model. The forest plot represented each study in the meta-analysis, so as to make the comparison of SMD value across studies. The meta-analysis outcome demonstrated that overall schizophrenia had higher klotho levels as compared with bipolar disorder, psychosocial stress, parkinsonism, multiple sclerosis, depression, Alzheimer's disease, and healthy controls, followed by MS. The meta-analysis also found that bipolar disorder and Alzheimer's disease were associated with low klotho levels as compared to schizophrenia. The results indicate a significant association of the klotho levels and schizophrenia. Further studies are needed to characterize the potential biological roles of klotho levels in psychiatric disorders.

Exploring Micronutrient Dynamics in COVID-19 Severity and Mortality: Unraveling the Roles of Vitamin D, Calcium, Phosphorus, Magnesium and ALP.

The COVID-19 pandemic has underscored the critical importance of understanding the intricate relationship between micronutrient levels and disease outcomes. This study explores the impact of Vitamin D, calcium, phosphorus, magnesium, and alkaline phosphatase (ALP) on COVID-19 severity and mortality. The study involves 200 participants (100 COVID-19 patients, 100 controls), we meticulously analyzed micronutrient dynamics. Calcium, phosphorus, magnesium and ALP was measured spectrophotometrically. Vitamin D was measured using Chemiluminescent method. The study reveals that diminished levels of calcium, phosphorus, magnesium, and with elevated ALP, are significantly associated with COVID-19 cases. Whereas the Vitamin D levels in severe group was increased when compared to mild cases but decreased than control group. Disease severity correlated with declining calcium (r = - 0.35, p < 0.01), phosphorus (r = - 0.26, p < 0.05), and magnesium (r = - 0.21, p < 0.05), and increased ALP (r = 0.42, p < 0.001). Post-discharge, calcium (p < 0.05) and phosphorus (p < 0.01) showed positive trends, while ALP (p < 0.001) decreased. Notably, calcium (OR = 0.63, p < 0.05) and ALP (OR = 1.87, p < 0.001) emerged as significant predictors of disease severity. The findings not only illuminate potential therapeutic avenues but also emphasize the need to optimize nutrient levels, including magnesium, for COVID-19 prevention and management. Given the complexities of these relationships, further rigorous exploration, including well-designed trials and understanding underlying mechanisms, is imperative to unravel the dynamics of these nutrient interactions in the context of COVID-19. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-024-01225-9.

Genetic and Epigenetic Basis of Drug-Induced Liver Injury.

Drug-induced liver injury (DILI) is a rare but severe adverse drug reaction seen in pharmacotherapy and a major cause of postmarketing drug withdrawals. Advances in genome-wide studies indicate that genetic and epigenetic diversity can lead to inter-individual differences in drug response and toxicity. It is necessary to identify how the genetic variations, in the presence of environmental factors, can contribute to development and progression of DILI. Studies on microRNA, histone modification, DNA methylation, and single nucleotide polymorphisms related to DILI were retrieved from databases and were analyzed for the current research and updated to develop this narrative review. We have compiled some of the major genetic, epigenetic, and pharmacogenetic factors leading to DILI. Many validated genetic risk factors of DILI, such as variants of drug-metabolizing enzymes, HLA alleles, and some transporters were identified. In conclusion, these studies provide useful information in risk alleles identification and on implementation of personalized medicine.

Role of Klotho Protein in Neuropsychiatric Disorders: A Narrative Review.

Neuropsychiatric disorders are comprised of diseases having both the neurological and psychiatric manifestations. The increasing burden of the disease on the population worldwide makes it necessary to adopt measures to decrease the prevalence. The Klotho is a single pass transmembrane protein that decreases with age, has been associated with various pathological diseases, like reduced bone mineral density, cardiac problems and cognitive impairment. However, multiple studies have explored its role in different neuropsychiatric disorders. A comprehensive search was undertaken in the Pubmed database for articles with the keywords "Klotho" and "neuropsychiatric disorders". The available literature, based on the above search strategy, has been compiled in this brief narrative review to describe the emerging role of Klotho in various neuropsychiatric disorders. The Klotho levels were decreased in various neuropsychiatric disorders except for bipolar disorder. A suppressed Klotho protein levels induced oxidative stress and incited pro-inflammatory conditions significantly contributing to the pathophysiology of neuropsychiatric disorder. The increasing evidence of altered Klotho protein levels in cognition-decrement-related disorders warrants its consideration as a biomarker in various neuropsychiatric diseases. However, further evidence is required to understand its role as a therapeutic target.

Association of Serum Complement C3 Levels with Severity and Mortality in COVID 19.

The severe acute respiratory distress syndrome-associated coronavirus-2 infection can activate innate and adaptive immune responses which may lead to harmful tissue damage, both locally and systemically. C3, a member of complement system of serum proteins, is a major component of innate immune and inflammatory responses. This study is aimed to assess serum C3 as a marker of COVID-19 severity and a predictor of disease progression. A total of 150 COVID-19 patients, confirmed by RT-PCR, and 50 healthy controls were recruited. Serum C3 levels were determined by using direct colorimetric method. Median levels of serum C3 in total cases and controls were 157.8 and 165.7 mg/dL respectively. Serum C3 although not significantly decreased, they were lower in cases when compared to controls. Similarly, significant differences were found between the groups, with severe group (140.6 mg/dL) having low levels of serum C3 protein when compared to mild (161.0 mg/dL) and moderate group (167.1 mg/dL). Interestingly, during hospitalization, significant difference between baseline (admission) and follow-up (discharge) was observed only in patients with moderate disease. Based on our results, lower levels of C3, with an increase in IL-6 and d-dimer levels, are associated with higher odds of mortality. Therefore, we would like to emphasize that measuring serum C3 levels along with other inflammatory markers might give an added advantage in early identification of patients who are prone to having a severe disease course and can help in a more effective follow-up of disease progression. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-023-01148-x.

Does dehydroepiandrosterone sulfate have a role in COVID-19 prognosis and treatment?

The pathophysiology of COVID comprises an exaggerated pro-inflammatory response. Hypothalamic-pituitary-adrenal (HPA) axis has a crucial role in various inflammatory conditions and modulated immunological response. Limited evidence is available regarding the incidence and the effect of HPA dysfunction in COVID-19. Although the cortisol levels have only been estimated in a few studies, the dehydroepiandrosterone sulfate (DHEAS) release from the adrenal gland has not been explored yet. In this mini review, the authors discuss the role of dehydroepiandrosterone (DHEA) and DHEAS in the acute stress response and immunological modulation. Various effects of DHEAS have been demonstrated in different diseases. The specific inhibitory effect of DHEA on interleukin 6 (IL-6) could be of paramount importance in COVID-19. Further, DHEA supplementation has already been proposed in inflammatory conditions, like rheumatoid arthritis. DHEAS levels in COVID-19 may help to understand the HPA axis dysfunction as well as the possibility of repurposing DHEA as a drug for mitigating the pro-inflammatory COVID-19.

Association of Vitamin D Status with COVID-19 Infection and Mortality in the Asia Pacific region: A Cross-Sectional Study.

COVID-19 has been declared a global pandemic by WHO on 11 March 2020. Still, very little is known about the potential protective dietary factors for the prevention of infection and mortality due to COVID-19. Keeping in view the scarcity of literature/studies available, in this regards present study was undertaken to assess if there is any correlation between mean levels of Vitamin D in various Asia Pacific countries with the infection and mortality caused by COVID-19. We collected data for mean levels of Vitamin D for 37 Asia Pacific countries for which we have also got the data regarding the morbidity and mortality of COVID-19. The mean levels of Vitamin D were found to have a significant association with the number of cases/million(r = - 0.394, p value = 0.016) and a weak association with the number of deaths/ million (r = - 0.280, p value = 0.093) due to COVID-19. In conclusion, we found a significant relationship between Vitamin D levels with the number of COVID-19 cases. So further clinical trial/study with a large sample size is needed to elucidate the protective role of Vitamin D in COVID-19.

Trace Elements as Immunoregulators in SARS-CoV-2 and Other Viral Infections.

Nutritional deficiency is associated with impaired immunity and increased susceptibility to infections. The complex interactions of trace elements with the macromolecules trigger the effective immune response against the viral diseases. The outcome of various viral infections along with susceptibility is affected by trace elements such as zinc, selenium, iron, copper, etc. due to their immuno-modulatory effects. Available electronic databases have been comprehensively searched for articles published with full text available and with the key words "Trace elements", "COVID-19", "Viral Infections" and "Immune Response" (i.e. separately Zn, Se, Fe, Cu, Mn, Mo, Cr, Li, Ni, Co) appearing in the title and abstract. On the basis of available articles we have explored the role of trace elements in viral infections with special reference to COVID-19 and their interactions with the immune system. Zinc, selenium and other trace elements are vital to triggerTH1 cells and cytokine-mediated immune response for substantial production of proinflammatory cytokines. The antiviral activity of some trace elements is attributed to their inhibitory effect on viral entry, replication and other downstream processes. Trace elements having antioxidants activity not only regulate host immune responses, but also modify the viral genome. Adequate dietary intake of trace elements is essential for activation, development, differentiation and numerous functions.

Beyond the basics: Sigma scores in laboratory medicine with variable total allowable errors (TEa).

BACKGROUND: To diagnose diseases, track the effectiveness of treatments and make well-informed clinical decisions, doctors rely on results from laboratories. Accurate and precise results minimize the necessity for additional testing, saving time and money while enhancing patient satisfaction.. Internal quality control and an external quality assurance scheme(EQAS) are metrics used to evaluate a clinical laboratory's performance. One of the numerous quality indicators that can be used to gauge the amount of errors is sigma metrics. To calculate the sigma scores bias%, CV%, and Total Error Allowable (TEa) are needed. Total Error allowable(TEa) is a crucial benchmark that establishes allowed limits on the degree of deviation from the target value for a certain analyte. Nevertheless, a proper consensus for establishing a TEa goal has not been reached and the impact of this limiting factor in standard laboratory practice and sigma calculation has not been sufficiently established. Choosing the right Total Error allowable(TEa) goal is one of the greatest challenges when employing sigma metrics as depending on the source, several measurands of TEa values may exhibit alteration. MATERIAL AND METHODS: Our study aims to determine the sigma scores of 20 routine chemistry parameters using six different TEa sources: Clinical Laboratory Improvement Amendment (CLIA 88'), CLIA(Clinical Laboratory Improvement Amendment) 24, BDV (Biological Variation Desirable), RCPA(Royal College of Pathologists of Australasia), RiliBak(Guideline of the German Medical Association for Quality Assurance of Laboratory Medical Examinations), and EMC/Spain(Measurement and Control Scheme) over a 12-month period using the bias percent from the External Quality Assessment Scheme (EQAS) and coefficient of variation (CV) from the Internal Quality Control (IQC). Detection system was automated, multi-channel, selective analyzer, the Beckman Coulter AU680 which works on the principle of spectrophotometry. To compute the Sigma metrics, formula used was Sigma = (TEa - Bias%) / CV%. By comparing the sigma values from the different TEa sources, TEa variance on the evaluation of the sigma metric was ascertained after which an internal quality control plan and QGI(Quality Goal Index) for underperforming parameters were devised. RESULTS: The study discovered that the sigma values of common chemical parameters varied significantly based on the TEa sources used. Maximum parameters in the above three-sigma zone were TBil, HDL, CK, ALP, amylase and uric acid in CLIA'88 while RCPA and Biological variation were determined to be the most severe, with the highest performing parameters falling below three sigma zones. Rilibaek was the most liberal, with only sodium in the lower three sigma zones along with CLIA'88. The findings indicate that there is the substantial influence of various Total Error Allowable (TEa) sources on the sigma metric evaluation. A quality control plan was devised depending on different sigma scores of the analytes using biorad unity 2.0 software(westgard sigma multirules). The origins of errors that resulted in low sigma ratings liked enhanced cleaning of electrodes, electrode replacement, ageing of reagents, instrument maintainence were pinpointed and addressed. CONCLUSION: The study highlights the necessity of harmonizing and standardizing sigma metrics, stressing the significance of choosing suitable total error allowable goals (TEa). The creation of worldwide standards and recommendations for total error allowable (TEa) can lead to its harmonization. Establishing a consensus on the acceptable levels of error for various laboratory tests would necessitate the cooperation of specialists from many nations and organizations in order to set such guidelines and standards.

Unveiling Novel Drug Targets and Emerging Therapies for Rheumatoid Arthritis: A Comprehensive Review.

Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disease, that causes joint damage, deformities, and decreased functionality. In addition, RA can also impact organs like the skin, lungs, eyes, and blood vessels. This autoimmune condition arises when the immune system erroneously targets the joint synovial membrane, resulting in synovitis, pannus formation, and cartilage damage. RA treatment is often holistic, integrating medication, physical therapy, and lifestyle modifications. Its main objective is to achieve remission or low disease activity by utilizing a "treat-to-target" approach that optimizes drug usage and dose adjustments based on clinical response and disease activity markers. The primary RA treatment uses disease-modifying antirheumatic drugs (DMARDs) that help to interrupt the inflammatory process. When there is an inadequate response, a combination of biologicals and DMARDs is recommended. Biological therapies target inflammatory pathways and have shown promising results in managing RA symptoms. Close monitoring for adverse effects and disease progression is critical to ensure optimal treatment outcomes. A deeper understanding of the pathways and mechanisms will allow new treatment strategies that minimize adverse effects and maintain quality of life. This review discusses the potential targets that can be used for designing and implementing precision medicine in RA treatment, spotlighting the latest breakthroughs in biologics, JAK inhibitors, IL-6 receptor antagonists, TNF blockers, and disease-modifying noncoding RNAs.

Seasonal variation and Vitamin-D status in ostensibly healthy Indian population: An experience from a tertiary care institute.

Background: 25-hydroxy vitamin-D (25(OH)D) deficiency is prevalent worldwide including India. Earlier some cross-sectional studies have discussed 25(OH)D deficiency and its prevalence. The correlation of 25(OH)D with seasonal variation has been reported rarely in India. To determine the 25(OH)D levels and seasonal changes of 25(OH)D status at a tertiary care hospital in North-western India. Materials and methods: 25(OH)D assessments performed in laboratories between 2018 and 2020 was acquired using hospital records. A total of 11,428 assays of serum 25(OH)D were analyzed in the study. Subjects were divided into three groups based on the International Endocrine Society's recommendation for serum 25(OH)D level. The 25(OH)D deficiency <20 ng/ml, insufficiency 20-29 ng/mL and sufficiency ≥30 ng/mL was defined. The months have been separated into the following seasons to analyze seasonal trends: Summer/monsoon (April-September), and winter/spring (October-March). Results: The median 25(OH)D was 17.2 ng/mL. We observed the prevalence of 60 %, 24.1 % & 15.9 % of 25(OH)D deficiency, 25(OH)D insufficiency, and sufficiency respectively in the total number of individuals tested. 56 % male and 63 % females were 25(OH)D deficient. Notably, the lowest median 25(OH)D value was found in the 21-30 age group (14.8 ng/mL). A significant difference in 25(OH)D levels between the summer (18.7 ng/mL) and winter (15.8 ng/mL) seasons has been noticed. Discussion: Current study revealing that 25(OH)D deficiency is common in all age groups and genders, according to our findings. Surprisingly, the lowest levels were reported in young adults. Seasonal variation has an impact on 25(OH)D status, however in all seasons 25(OH)D levels are lower than reference intervals. These findings suggest that the criteria for determining the state of 25(OH)D insufficiency and deficiency in the Indian population should be reconsidered.

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.

The Differentially Expressed Genes Responsible for the Development of T Helper 9 Cells From T Helper 2 Cells in Various Disease States: Immuno-Interactomics Study.

BACKGROUND: T helper (Th) 9 cells are a novel subset of Th cells that develop independently from Th2 cells and are characterized by the secretion of interleukin (IL)-9. Studies have suggested the involvement of Th9 cells in variable diseases such as allergic and pulmonary diseases (eg, asthma, chronic obstructive airway disease, chronic rhinosinusitis, nasal polyps, and pulmonary hypoplasia), metabolic diseases (eg, acute leukemia, myelocytic leukemia, breast cancer, lung cancer, melanoma, pancreatic cancer), neuropsychiatric disorders (eg, Alzheimer disease), autoimmune diseases (eg, Graves disease, Crohn disease, colitis, psoriasis, systemic lupus erythematosus, systemic scleroderma, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, atopic dermatitis, eczema), and infectious diseases (eg, tuberculosis, hepatitis). However, there is a dearth of information on its involvement in other metabolic, neuropsychiatric, and infectious diseases. OBJECTIVE: This study aims to identify significant differentially altered genes in the conversion of Th2 to Th9 cells, and their regulating microRNAs (miRs) from publicly available Gene Expression Omnibus data sets of the mouse model using in silico analysis to unravel various pathogenic pathways involved in disease processes. METHODS: Using differentially expressed genes (DEGs) identified from 2 publicly available data sets (GSE99166 and GSE123501) we performed functional enrichment and network analyses to identify pathways, protein-protein interactions, miR-messenger RNA associations, and disease-gene associations related to significant differentially altered genes implicated in the conversion of Th2 to Th9 cells. RESULTS: We extracted 260 common downregulated, 236 common upregulated, and 634 common DEGs from the expression profiles of data sets GSE99166 and GSE123501. Codifferentially expressed ILs, cytokines, receptors, and transcription factors (TFs) were enriched in 7 crucial Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology. We constructed the protein-protein interaction network and predicted the top regulatory miRs involved in the Th2 to Th9 differentiation pathways. We also identified various metabolic, allergic and pulmonary, neuropsychiatric, autoimmune, and infectious diseases as well as carcinomas where the differentiation of Th2 to Th9 may play a crucial role. CONCLUSIONS: This study identified hitherto unexplored possible associations between Th9 and disease states. Some important ILs, including CCL1 (chemokine [C-C motif] ligand 1), CCL20 (chemokine [C-C motif] ligand 20), IL-13, IL-4, IL-12A, and IL-9; receptors, including IL-12RB1, IL-4RA (interleukin 9 receptor alpha), CD53 (cluster of differentiation 53), CD6 (cluster of differentiation 6), CD5 (cluster of differentiation 5), CD83 (cluster of differentiation 83), CD197 (cluster of differentiation 197), IL-1RL1 (interleukin 1 receptor-like 1), CD101 (cluster of differentiation 101), CD96 (cluster of differentiation 96), CD72 (cluster of differentiation 72), CD7 (cluster of differentiation 7), CD152 (cytotoxic T lymphocyte-associated protein 4), CD38 (cluster of differentiation 38), CX3CR1 (chemokine [C-X3-C motif] receptor 1), CTLA2A (cytotoxic T lymphocyte-associated protein 2 alpha), CTLA28, and CD196 (cluster of differentiation 196); and TFs, including FOXP3 (forkhead box P3), IRF8 (interferon regulatory factor 8), FOXP2 (forkhead box P2), RORA (RAR-related orphan receptor alpha), AHR (aryl-hydrocarbon receptor), MAF (avian musculoaponeurotic fibrosarcoma oncogene homolog), SMAD6 (SMAD family member 6), JUN (Jun proto-oncogene), JAK2 (Janus kinase 2), EP300 (E1A binding protein p300), ATF6 (activating transcription factor 6), BTAF1 (B-TFIID TATA-box binding protein associated factor 1), BAFT (basic leucine zipper transcription factor), NOTCH1 (neurogenic locus notch homolog protein 1), GATA3 (GATA binding protein 3), SATB1 (special AT-rich sequence binding protein 1), BMP7 (bone morphogenetic protein 7), and PPARG (peroxisome proliferator-activated receptor gamma, were able to identify significant differentially altered genes in the conversion of Th2 to Th9 cells. We identified some common miRs that could target the DEGs. The scarcity of studies on the role of Th9 in metabolic diseases highlights the lacunae in this field. Our study provides the rationale for exploring the role of Th9 in various metabolic disorders such as diabetes mellitus, diabetic nephropathy, hypertensive disease, ischemic stroke, steatohepatitis, liver fibrosis, obesity, adenocarcinoma, glioblastoma and glioma, malignant neoplasm of stomach, melanoma, neuroblastoma, osteosarcoma, pancreatic carcinoma, prostate carcinoma, and stomach carcinoma.

Association of circulatory Klotho levels and its expression with miRNA- 339 in patients with schizophrenia.

Schizophrenia is one of the major neuropsychiatric disorders affecting 1% of the population worldwide. Neuroinflammation, neurodevelopment, and oxidative stress are some of the crucial factors that can contribute to the pathogenesis of Schizophrenia. Klotho gene is an antiaging gene whose dysregulated expression can lead to Schizophrenia and aging-like symptoms in patients. Klotho gene expression is regulated by miRNA- 339, which might lead to expression changes of the klotho gene in schizophrenia patients. This study aimed to determine the Role of miRNA- 339-5p in the Regulation of Klotho Gene Expression and its Circulatory Levels in Schizophrenia. In this study total of 60 cases, schizophrenia patients and 30 healthy controls were recruited, and written informed consent was obtained from all the study subjects. The klotho gene and miRNA - 339-5p expressions were done using a reverse transcription polymerase chain reaction. And relative fold change expression was calculated by Livaak's method, that is 2^-double delta ct. It was found that the klotho gene is around 2.08 times upregulated as compared to healthy control, and miRNA- 339-5p was downregulated and showed an inverse relationship. The present study is the first to evaluate the klotho gene expression and correlate it with miRNA- 339-5p. Further confirmation of the results study should be planned with a large sample size and with drug naïve patients.

Epigenetics regulation of prostate cancer: Biomarker and therapeutic potential.

Prostate cancer (CaP) is the second leading cause of cancer death and displays a broad range of clinical behavior from relatively indolent to aggressive metastatic disease. The etiology of most cases of CaP is not understood completely, which makes it imperative to search for the molecular basis of CaP and markers for early diagnosis. Epigenetic modifications, including changes in DNA methylation patterns, histone modifications, miRNAs, and lncRNAs are key drivers of prostate tumorigenesis. These epigenetic defects might be due to deregulated expression of the epigenetic machinery, affecting the expression of several important genes like GSTP1, RASSF1, CDKN2, RARRES1, IGFBP3, RARB, TMPRSS2-ERG, ITGB4, AOX1, HHEX, WT1, HSPE, PLAU, FOXA1, ASC, GPX3, EZH2, LSD1, etc. In this review, we highlighted the most important epigenetic gene alterations and their variations as a diagnostic marker and target for therapeutic intervention of CaP in the future. Characterization of epigenetic changes involved in CaP is obscure and adequate validation studies are still required to corroborate the present results that would be the impending future of transforming basic research settings into clinical practice.

Comparative Analysis of Serum Zinc, Copper and Magnesium Level and Their Relations in Association with Severity and Mortality in SARS-CoV-2 Patients.

The deficiencies of trace elements and infectious diseases often coexist and exhibit complex interactions. Several trace elements such as zinc (Zn), copper (Cu) and magnesium (Mg) have immunomodulatory functions and thus influence the susceptibility to the course and outcome of a variety of viral infections. So, this present study was aimed to study relations of trace metals in association with severity and mortality in SARS-CoV-2 patients. A total of 150 individuals infected with COVID-19 and 50 healthy individuals were recruited. Cases were divided based on severity (mild, moderate and severe) and outcome (discharged or deceased). Serum Zn, Mg and Cu levels were analysed by direct colourimetric method. Both serum Cu and Zn levels were significantly decreased in cases when compared to those in controls (p < 0.005 and p < 0.0001). Serum magnesium levels although not significant were found to be slightly decreased in controls. On comparing the trace elements between the deceased and discharged cases, a significant difference was found between serum copper and zinc levels, but for magnesium, both groups have similar levels. The receiver operating characteristic (ROC) curve results indicate that a serum Cu/Zn ratio along with the age of patient provides some reliable information on COVID-19 course and survival odds by yielding an AUC of 95.1% with a sensitivity of 93.8% and specificity of 89.8%. Therefore, we would like to emphasize that measuring the serum copper and zinc along with their ratio can be used as routine investigations for COVID-19 patients in proper identification and management of severe cases in upcoming new waves of COVID-19.

Validation of a novel method for determination of low-density lipoprotein cholesterol levels in Indian patients with type 2 diabetes.

BACKGROUND AND AIMS: LDL-cholesterol (LDL-C), being the primary predictor of cardiovascular disease in Type 2 diabetes (T2D), is associated with cardiovascular risk stratification and requires to be estimated with better accuracy with minimal bias. Different formulae have been devised to calculate the LDL-C from the measured lipid profile parameters. METHODS: In this analytical cross-sectional study, a total of 150 patients with T2D were studied, and blood samples were subjected for lipid profile analysis at the Central Biochemistry laboratory. Different formulae assessed calculated LDL-C. RESULTS: We observed that all formulae, except Ahmadi, underestimated the LDL-C compared to direct assay. A significant difference was observed between all calculated LDL-C and directly measured LDL-C. On linear regression analysis, the newer formula Martin's has a better approximation with direct assay (slope: 0.9708) than Friedewald (slope: 0.9477). Similarly, Martin's formula exhibited lesser bias (-13.56) in calculating LDL-C in patients with T2D compared with Friedewald's formula. CONCLUSIONS: The study demonstrated that in patients with T2D, all formulae except Ahmadi significantly underestimated the LDL-C when compared with the direct assay. The newer Martin's formula appeared to more precisely calculate LDL-C in T2D when compared with the traditional Friedewald's formula.

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.

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.