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.

Correlation Between Severity of Schizophrenia with Certain Trace Elements and TNF-α Gene Expression and Its Circulatory Level in the Population of Western India.

This cross-sectional study aimed to assess serum trace element (TE) concentrations, TNF-α gene expression, protein levels in schizophrenia (SZ) patients, and their correlation with disease severity measured by Positive and Negative Syndrome Scale (PANSS) scores. Forty SZ cases and 40 healthy controls aged 18-60 were recruited. Forty (n = 40) cases who meet ICD-10 criteria for SZ and 40 (n = 40) healthy individuals (controls) between 18 and 60 years of age were recruited in the study. Sandwich enzyme-linked immunosorbent assay (ELISA) and RT-qPCR (quantitative real-time PCR) were used to estimate pro-inflammatory cytokine TNF-α protein and gene expression. Inductively coupled plasma-optical emission spectroscopy (ICP-OES) and graphite furnace atomic absorption spectroscopy (GFAAS) were used to assess serum levels of trace elements (TEs): Fe, Zn, Cu, Mg, and Se. Compared to healthy controls, cases had significantly higher levels of TNF-α protein, as well as Fe, Cu, and Se (p < 0.05). Cu correlated positively with TNF-α protein level (rho = 0.234; p = 0.048) and gene expression (rho = 0.333; p = 0.041) and with PANSS negative (rho = 0.531), general (rho = 0.643), and total (rho = 0.541) scores. Additionally, Zn negatively correlated with serum Mg (rho = - 0.426, p < 0.01) and positively with serum Se (rho = 0.343, p < 0.05). In conclusion, elevated Cu levels could potentially contribute to the development of SZ. Elevated Cu levels in cases and their correlation with the TNF-α gene and protein and PANSS score indicate Cu's potential role in exacerbating SZ severity through inflammatory cytokines. This suggests the involvement of metals and cytokines in the pathophysiology of SZ.

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.

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.

Gene expression, levels and polymorphism (Ala16Val) of mitochondrial superoxide dismutase in tuberculosis patients of Rajasthan.

BACKGROUND: Infectious diseases cause redox imbalance and oxidative stress (OS) in host. Superoxide Dismutases(SOD) decrease this OS. SOD2 gene polymorphism can influence the expression and levels of enzyme. AIM: To investigate the association of genetic polymorphism of MnSOD with enzyme levels and mRNA expression in TB patients. METHODS: A total of 87 TB patients and 85 healthy individuals participated in the study. The serum SOD2 levels were measured by ELISA. Gene polymorphism was analysed using PCR-RFLP with BsaW1 as the restriction enzyme. Expression was studied by Real-TimePCR. Statistical significance was determined using the Mann-Whitney, Chi-square and Kruskal-Wallis tests and p value < 0.05 was considered statistically significant. RESULTS: The median(IQR) serum SOD2 levels of TB patients were lower than those of healthy subjects (4.64(6.48) vs 11.35(20.36)ng/mL respectively,p < 0.001). SOD2 expression was significantly down-regulated in TB patients with a fold change value of 0.312. The Val/Val genotype was higher in the patient group than healthy subjects (36.8% vs 23.5%). However, the difference observed between serum SOD2 levels and mRNA expression in the different genotypes were statistically non-significant. CONCLUSION: Significant difference was found between levels and expression of SOD2 in TB patients and healthy controls, but not for SOD2 gene polymorphism.

Role of interleukin-22 in tuberculosis patients.

OBJECTIVES: Disease progression of tuberculosis (TB) depends on the balance between the microorganism's virulence and the host defense systems (mainly T cell-mediated immune response). Interleukin-22 (IL-22) helps in cell proliferation and regeneration and provides protection against microbial diseases. The IL-22-producing T cells can migrate into the granulomas during TB infection. However, disparity exists in literature regarding its role. The present study aims to compare serum IL-22 levels and its' expression in TB patients and healthy controls. METHODS: 87 TB patients and 85 healthy subjects were enrolled in the study. Under aseptic conditions, venous blood was withdrawn. Serum IL-22 levels were estimated using enzyme-linked immunosorbent assay, and its gene expression was assessed using SYBR green-based quantitative PCR technology. A statistical analysis was performed using SPSS. RESULTS: The median (interquartile range) of serum IL-22 levels was significantly lower in TB patients (18.55 (5.08) pg/mL) when compared to controls (49.38 (162.88) pg/mL) (p<0.0001). The IL-22 expression was significantly upregulated with a fold change value of 29.44 in TB patients. CONCLUSIONS: The IL-22 levels were found to be significantly decreased in patients, contradictory to its expression, which is upregulated. It plays a crucial role for the modulation of tissues in response to TB infection.

Klotho: A Possible Role in the Pathophysiology of Nephrotic Syndrome.

Klotho, encoded by the klotho gene, is associated with phosphate homeostasis. Klotho acts as a co-receptor for FGF23 for binding to its receptors. With FGF23, klotho regulates the systemic mineral homeostasis by regulation of vitamin D and parathyroid hormone. The anti-inflammatory, antifibrotic and antioxidant properties of klotho give it a cardinal role in the development of various renal diseases. The protective effect of klotho has been evident in different types of nephropathy, including diabetic nephropathy, cyclosporine A-induced nephropathy, Calcineurin inhibitors-induced nephropathy, and renal ischemic-reperfusion injury. Nephrotic syndrome is distinguished by hypoproteinemia, proteinuria, and hypercholesterolemia as a result of the aberration of the glomerular filtration barrier. The various factors and pathways associated with the pathophysiology of the nephrotic syndrome have similarities with other types of nephropathy. Despite these similarities, the role of klotho in the pathology of nephrotic syndrome remains still unexplored. This minireview builds the case for the possible role of klotho in nephrotic syndrome. The review explores the possible pathways where klotho can play a major role by identifying the similarities in the pathophysiology of nephrotic syndrome and other types of nephropathy.

Efficacy and safety of vitamin D in tuberculosis patients: a systematic review and meta-analysis.

BACKGROUND: Evidence from the basic research and epidemiological studies indicates a beneficial effect of vitamin D in the treatment of tuberculosis (TB). However, the evidence from randomized controlled trials (RCTs) is inconsistent. OBJECTIVES: This systematic review and meta-analysis was performed to synthesize evidence regarding role of vitamin D versus placebo for the management of TB. MATERIALS AND METHODS: We searched PubMed and Cochrane Clinical Trial Registry for RCTs comparing vitamin D versus placebo for the treatment of TB. RCTs enrolling adult patients with TB receiving vitamin D in addition to standard treatment were included. Data were pooled using random effects model. The study was conducted according to PRISMA guidelines and protocol was registered with PROSPERO (CRD42016052841). RESULTS: Of 605 identified references, 12 RCTs were included. The overall risk of bias in included studies was low or unclear. There was no significant difference between vitamin D and placebo group for any outcomes of efficacy (time to culture conversion, time to smear conversion, rate of culture conversion, and rate of smear conversion) or safety (mortality, serious adverse events, and nonserious adverse events). CONCLUSION: Vitamin D administered with standard treatment has no beneficial effect in the TB patients as compared to the placebo.

Modified PVA membrane for separation of micro-emulsion.

Release of liquefied hydrocarbons in domestic and industrial effluents, along with oil spills cause significant adverse effects on the soil, water, aquatic ecosystem, and humans. Thus, selective and cost-effective technology to address this challenge is highly desirable. Here, we report the fabrication of electrospun polyvinyl alcohol (PVA) membrane, modified with glutaraldehyde (GA) and a device thereof, for treatment of oil emulsions and recovery of precious fossil fuel. The modified PVA membranes are super-oleophobic with a high static underwater oil contact angle of 163 ± 3° for motor oil. Investigation of wetting properties suggests that the membrane can efficiently separate different oils such as sesame oil, motor oil, mustard oil, and sunflower oil from their emulsions. The motor oil emulsion with separation efficiency of >99% at an excellent permeate flux of 5128 L/m2·h·bar has been achieved. Thus, the prepared modified PVA membrane construes an easy solution for not only effective treatment of oily wastewater but also for oil recovery with high flux.

Efficacy of procalcitonin and pentraxin-3 as early biomarkers for differential diagnosis of pleural effusions.

OBJECTIVES: Pleural effusion, defined as an abnormal accumulation of fluid in pleural space, can be of two types: transudative and exudative. The primary aim of the study was to assess the predictive accuracy of procalcitonin (PCT) and pentraxin-3 (PTX-3) in comparison to other biochemical markers such as C-reactive protein (CRP), and adenosine deaminase (ADA) in the differential diagnosis of pleural effusions. METHODS: A cross-sectional analytical study was conducted on patients with pleural effusion. Multiple comparisons and receiver-operating characteristics (ROC) analyses were made to evaluate the diagnostic significance of biochemical markers. RESULTS: Sixty-six patients with exudative pleural effusion classified as malignant, tuberculous, and parapneumonic effusions (malignant pleural effusion [MPE], tuberculous [TPE], and parapneumonic [PPE]) were included. Significant differences in pleural fluid levels in both PCT (p-value: 0.001) and PTX-3(p-value: 0.001), as well as serum levels of PCT (p-value: 0.001), were observed between the three groups. ROC analysis showed both PTX-3 and PCT having favorable discrimination ability with high sensitivity (≥90%) and specificity to predict PPE from TPE and MPE. CONCLUSIONS: Evaluation of serum and pleural fluid PCT and levels of PTX-3 in the pleural fluid may be used as an early biomarker to differentiate the etiology of pleural effusion.

Adverse Events Reported From COVID-19 Vaccine Trials: A Systematic Review.

COVID-19 infection originated in Wuhan, China in December 2019 and crippled human health globally in no time. The public health emergency required urgent efforts to develop and test the efficacy and safety of vaccines to combat the COVID-19 pandemic. The emergency use approval has been granted to COVID-19 vaccines before the completion of conventional phases of clinical trials. However, there is no comprehensive review of safety data reported from the vaccine trials, which is critical information to inform the policies in order to improve uptake of COVID-19 vaccines and mitigate the risk aversion perceived due to the COVID-vaccine side effects. This study aims to systematically review and synthesize the evidence on the safety data from the published COVID-19 vaccine trials. This study followed PRISMA guidelines. We searched three major electronic databases (PubMed, Embase, and Google Scholar) for published studies between Dec 2019 and 2020. Eligible study designs were randomized trials and pre-and post-intervention evaluations. Descriptive findings of included studies were reported stratified by target population, setting, outcomes, and overall results. From PubMed, Embase, WHO database, and Google Scholar screened titles and abstracts, 11 studies were identified in this review. Most of the reactions reported were mild to moderate whereas a few with severe intensity. All reactions resolved within 3-4 days. The commonly reported local adverse events were pain at the site of injection, swelling, and redness. The systemic reactions included fever, fatigue, myalgia, and headache. Some trials also reported laboratory derangements  like decreased hemoglobin, increased bilirubin, altered SGOT and SGPT. None of these alterations were clinically manifested and were self-limiting. Few clinical trials reported serious adverse events, but they were unrelated to vaccination. This systematic review indicates that COVID-19 vaccines can be safe with no serious adverse events. However, long-term post-marketing surveillance data, particularly in high-risk vulnerable populations (elderly and those with co-morbidities, pregnant women, and children) is warranted to ensure the safety of COVID-19 vaccines.

Immunomodulation by epigenome alterations in Mycobacterium tuberculosis infection.

Mycobacterium tuberculosis (MTB) has co-evolved with humans for decades and developed several mechanisms to evade host immunity. It can efficiently alter the host epigenome, thus playing a major role in immunomodulation by either activating or suppressing genes responsible for mounting an immune response against the pathogen. Epigenetic modifications such as DNA methylation and chromatin remodelling regulate gene expression and influence several cellular processes. The involvement of epigenetic factors in disease onset and development had been overlooked upon in comparison to genetic mutations. It is now believed that assessment of epigenetic changes hold great potential in diagnosis, prevention and treatment strategies for a wide range of diseases. In this review, we unravel the principles of epigenetics and the numerous ways by which MTB re-shapes the host epigenetic landscape as a strategy to overpower the host immune system for its survival and persistence.

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.

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.

The Clinical Laboratory: A Key Player in Diagnosis and Management of COVID-19.

The Coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had emerged as a pandemic affecting almost all countries in the world in a short span after it was first reported in December. Clinical laboratory have a crucial role in mitigating this new pandemic. Timely and accurate diagnosis of COVID-19 is of paramount importance for detecting cases early and to prevent transmission. Clinical Laboratories have adopted different test modalities and processes to tackle this unprecedented situation with directives from regulatory bodies such as the WHO. The varying presentations, as well as complications attributed to comorbidities in COVID-19, have created hurdles in the management of these patients. Various clinical laboratory parameters have been investigated for their potential for diagnosis and prognosis of the disease, prediction of complications and monitoring of treatment response. Different routine and uncommon parameters have been shown to have the diagnostic and prognostic capacity. This update discusses the role of the laboratory in diagnosis, prognosis and monitoring of treatment response. Different methodologies for diagnostic testing as well as various clinical laboratory parameters having diagnostic and predictive powers have been discussed. This compilation organises relevant available information on various clinical laboratory parameters and their role in COVID-19 mitigating pandemic.

Snapshot of COVID-19 Related Clinical Trials in India.

Many interventions are being explored for the prophylaxis and treatment of COVID-19 in all over the world including India. There was a need of systematic data about the COVID-19 related clinical trials conducted in India. The aim of the present study was to analyze various clinical trials registered in Clinical Trial Registry of India (CTRI) exploring the interventions for COVID 19. The data of various clinical trials being conducted in India was obtained from CTRI. Different trial characteristics were extracted in the predesigned proforma and analyzed. Values were expressed in frequency and percentages. As of 11th July, 2020, a total of 203 trials were registered in the CTRI. The majority of the trials (61%) were related to the AYUSH interventions. Only 3 trials were international while the others were national. A major portion of public and private funding were dedicated to the AYUSH trials. More number of trials were for treatment as compared to prophylaxis. Maharashtra and Delhi are having highest number of trial sites. There is a good progress regarding AYUSH clinical trials, and a similar progress is expected for allopathic interventions.

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.

Analysis of Association of Angiotensin II Type 1 Receptor Gene A1166C Gene Polymorphism with Essential Hypertension.

The A/C transversion at 1166 of the angiotensin II Type 1 Receptor (AT1R) gene per se does not characterize any functional diversity but has been associated with expression of the AT1R, consequently molecular variants of the gene may modulate the possible risk of essential hypertension. The present study was performed to determine the genotypic frequency of the A1166C polymorphism of the AT1R gene in essential hypertensive patients with the aim to assess the effect of variants of this polymorphism in hypertension. AT1R gene amplification was performed by PCR and A1166C polymorphism was determined by enzyme digestion methodologies in 224 consecutively enrolled essential hypertensive patients and 257 controls. Suitable descriptive statistics was used for different variables. Results revealed that genotype and allele distribution of the A1166C variant differed significantly in hypertensives and normotensives. Allele frequency at the A1166C position was 61%A and 39%C for control and 52%A and 48%C for patients. Observed frequencies were compatible with HWE expected frequencies in cases as well as in controls. rs5186 was found to be associated with hypertension (95% CI 1.1453-2.7932, p: 0.0106). The difference remained statistically significant after the multivariate adjustment (p < 0.05), with C/C variant conferring a risk of 1.74-fold of essential hypertension. This association was confirmed by inter-genotypic variations in the mean systolic and diastolic blood pressure in patients. In conclusion, genetic variation at the AT1R gene influences the risk of hypertension stratification and might serve as a predictive marker for the susceptibility to hypertension among affected families.