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1.
Am J Physiol Cell Physiol ; 327(1): C74-C96, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38738303

ABSTRACT

Activation of incretin receptors by their cognate agonist augments sustained cAMP generation both from the plasma membrane as well as from the endosome. To address the functional outcome of this spatiotemporal signaling, we developed a nonacylated glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor dual agonist I-M-150847 that reduced receptor internalization following activation of the incretin receptors. The incretin receptor dual agonist I-M-150847 was developed by replacing the tryptophan cage of exendin-4 tyrosine substituted at the amino terminus with the C-terminal undecapeptide sequence of oxyntomodulin that placed lysine 30 of I-M-150847 in frame with the corresponding lysine residue of GIP. The peptide I-M-150847 is a partial agonist of GLP-1R and GIPR; however, the receptors, upon activation by I-M-150847, undergo reduced internalization that promotes agonist-mediated iterative cAMP signaling and augments glucose-stimulated insulin exocytosis in pancreatic ß cells. Chronic administration of I-M-150847 improved glycemic control, enhanced insulin sensitivity, and provided profound weight loss in diet-induced obese (DIO) mice. Our results demonstrated that despite being a partial agonist, I-M-150847, by reducing the receptor internalization upon activation, enhanced the incretin effect and reversed obesity.NEW & NOTEWORTHY Replacement of the tryptophan cage (Trp-cage) with the C-terminal oxyntomodulin undecapeptide along with the tyrosine substitution at the amino terminus converts the selective glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 to a novel GLP-1R and GIPR dual agonist I-M-150847. Reduced internalization of incretin receptors upon activation by the GLP-1R and GIPR dual agonist I-M-150847 promotes iterative receptor signaling that enhances the incretin effect and reverses obesity.


Subject(s)
Glucagon-Like Peptide-1 Receptor , Incretins , Mice, Inbred C57BL , Obesity , Animals , Obesity/metabolism , Obesity/drug therapy , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptide-1 Receptor/metabolism , Mice , Male , Incretins/pharmacology , Incretins/metabolism , Protein Transport/drug effects , Glycemic Control/methods , Mice, Obese , Receptors, Gastrointestinal Hormone/agonists , Receptors, Gastrointestinal Hormone/metabolism , Insulin-Secreting Cells/metabolism , Insulin-Secreting Cells/drug effects , Humans , Diet, High-Fat/adverse effects , Blood Glucose/metabolism , Blood Glucose/drug effects , Insulin/metabolism , Exenatide/pharmacology , Signal Transduction/drug effects , Cyclic AMP/metabolism
2.
J Biochem Mol Toxicol ; 37(1): e23221, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36094808

ABSTRACT

Following its accumulation in the body, cadmium (Cd) exposure is associated with devastating effects on multiple organ system of the human body. The immune system is one of the sensitive targets for Cd-induced toxicity. Recently, studies have demonstrated a significant role of Cd in inducing epigenetic alterations. With this background, the present study was planned to study the changes in candidate microRNA (miRNA) expression associated with immune regulation in occupationally Cd-exposed workers. One hundred individuals involved in welding and metal handicraft manufacturing, while 80 apparently healthy subjects without any prior history of occupational exposure were recruited for the study. Blood Cd level was determined by atomic absorption spectrometry. Serum cytokine levels were measured using an enzyme-linked immunosorbent assay and serum miRNA expression of candidate miRNAs (miR-146a, miR-210, and miR-222) were determined by real-time polymerase chain reaction. The median Cd level (2.40 µg/L) in the occupationally exposed workers was significantly higher than the nonexposed subjects (0.90 µg/L). Among the cytokines, interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-α) were significantly higher while IL-2 and IL-10 were significantly lower in the exposed. The expression level of miR-146a and miR-222 were significantly different between the groups with the former showing downregulation and later showing upregulation. Correlation analysis revealed a positive and negative association of miR-222 and miR-146a with blood cadmium level, IL-17 as well as TNF-α, respectively. Furthermore, the in-silico analysis revealed a significant role of the studied miRNAs in various cellular and genetic pathways. The findings of the present study demonstrate significant involvement of Cd-induced alteration in miRNAs in varied immune regulatory changes in exposed individuals.


Subject(s)
Cytokines , MicroRNAs , Humans , Cytokines/metabolism , Cadmium/toxicity , Tumor Necrosis Factor-alpha/metabolism , MicroRNAs/metabolism , Down-Regulation
3.
Int Arch Occup Environ Health ; 96(9): 1257-1266, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37572134

ABSTRACT

BACKGROUND: Occupational and environmental exposure to lead (Pb) is a persistent health problem majorly in developing countries and has been implied to cause epigenetic alterations. Its effect on histone post-translational modifications is not explored in human population. MicroRNAs are epigenetic modulators reported to be differentially expressed under Pb exposure. The present study was targeted to find plausible association between the role of hsa-miR-146a and global histone (H3) acetylation in Pb-induced inflammation in occupationally exposed workers. MATERIALS AND METHODS: A total of 100 occupationally exposed individuals working in different industries were recruited for the study and divided into 2 groups based on the median Pb levels [low Pb group (Pb < 5 µg/dL) and High Pb group (Pb > 5 µg/dL)]. The Pb levels were measured in whole blood using atomic absorption spectrometry to confirm Pb exposure. Histone H3 acetylation and serum interleukin-6 (IL-6) levels were measured using colorimetric methods and enzyme-linked immunosorbent assay (ELISA), respectively. MicroRNA-146a expression was quantified using TaqMan assay. RESULTS: The median BLL of the study population was 5 µg/dL. BLL, IL-6, and Histone (H3) acetylation increased significantly with the duration of exposure. BLL level showed a significant positive correlation with IL-6 and histone H3 acetylation level. We also found that hsa-miR-146a exhibited significantly increased expression in the high Pb group compared to the low Pb group (Fold change: 2.56; P = 0.014). The linear regression model suggested that BLL has significantly predicted histone H3 acetylation, hsa-miR-146a, and IL-6 in the study subjects. CONCLUSION: The finding that hsa-miR146a was significantly upregulated in individuals with high BLL and had a significant negative correlation with serum IL-6 suggests that Pb-induced oxidative stress likely activates H3 acetylation, which then releases inflammatory cytokines like IL-6.

4.
Indian J Clin Biochem ; 38(1): 13-21, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36684492

ABSTRACT

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.

5.
Crit Rev Clin Lab Sci ; 59(1): 19-39, 2022 01.
Article in English | MEDLINE | ID: mdl-34592888

ABSTRACT

Depression is one of the most common neuropsychiatric disorders in the world. While conventional pharmaceutical therapy targets monoaminergic pathway dysfunction, it has not been totally successful in terms of positive outcomes, remission, and preventing relapses. There is an increasing amount of evidence that neuroinflammation may play a significant part in the pathophysiology of depression. Among the key components of the neuroinflammatory pathways already known to be active are the T helper (Th) cells, especially Th17 cells. While various preclinical and clinical studies have reported increased levels of Th17 cells in both serum and brain tissue of laboratory model animals, contradictory results have argued against a pertinent role of Th17 cells in depression. Recent studies have also revealed a role for more pathogenic and inflammatory subsets of Th17 in depression, as well as IL-17A and Th17 cells in non-responsiveness to conventional antidepressant therapy. Despite recent advances, there is still a significant knowledge gap concerning the exact mechanism by which Th17 cells influence neuroinflammation in depression. This review first provides a short introduction to the major findings that led to the discovery of the role of Th cells in depression. The major subsets of Th cells known to be involved in neuroimmunology of depression, such as Th1, Th17, and T regulatory cells, are subsequently described, with an in-depth discussion on current knowledge about Th17 cells in depression.


Subject(s)
Depression , Th17 Cells , Animals , Humans , Neuroinflammatory Diseases , T-Lymphocytes, Regulatory
6.
Toxicol Ind Health ; 38(1): 1-10, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34874211

ABSTRACT

Occupational exposure to heavy metals like lead (Pb) and cadmium (Cd) is associated with the development of several diseases. The objective of this study was to determine the effect of occupational co-exposure to Pb and Cd on the blood levels of selected immune-modulatory cytokines related to T helper (Th), that is, Th1, interleukin-2 (IL-2), Th2, (IL-4 and IL-10), and Th17, (IL-17) cells. The study comprised 207 individuals divided into two groups: exposed (n = 110) and nonexposed (n = 97). Blood Pb and Cd were determined using Graphite Furnace Atomic Absorption Spectroscopy, and serum levels of cytokines were measured using enzyme-linked immunosorbent assay (ELISA). The study revealed significantly higher blood Pb and Cd levels in the exposed group. A significant decrease in Th1 cytokine-IL-2 and Th2 cytokine-IL-10 was found, while IL-4 (Th2 cytokine) and IL-17 (Th17) levels were higher in the exposed group. In the mixed exposure analysis, among all the selected cytokines, IL-4 levels were significantly different between individuals having higher levels of both Pb and Cd versus lower levels of Pb and Cd. While IL-2 levels were highest among the low Pb and Cd group, the IL-17 levels were highest among individuals with higher Cd levels. The study demonstrated that co-exposure to low levels of Pb and Cd might have an immune-modulatory effect. The data suggested a metal-induced pro-inflammatory immune response.


Subject(s)
Cadmium/analysis , Cytokines/blood , Immunity , Lead/analysis , Occupational Exposure/analysis , Adult , Cadmium/toxicity , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Humans , Lead/toxicity , Male , Spectrophotometry, Atomic
7.
Indian J Clin Biochem ; 37(2): 218-223, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35463106

ABSTRACT

Occupational and environmental exposure to Lead (Pb) has profound detrimental effects on human health. The underlying mechanism of lead toxicity is not fully understood but antioxidant imbalance is suggested to be a key player in its pathogenesis. Selenium (Se) being a vital component of antioxidant system in the body, has been linked to many health benefits in humans. Selenium levels in occupationally Pb exposed individuals has not been explored in Indian setup. The aim of the present study is to find out the association of Se with blood lead levels (BLL) in occupationally Pb exposed individuals. In the present study 91 occupationally Pb exposed workers employed in handicraft and paint industries were recruited after taking informed consent. The demographic details were noted on self-generated questionnaire. The BLL and Se were measured using GFAAS (Thermofisher Scientific, Waltham, USA). Samples were run in duplicate after ensuring quality control. The mean Pb and Se levels in the study population were 5.5 ± 5.6 µg/dl (0.42-31.76 µg/dl) and 105.5 ± 23.8 µg/dl (46.4-189.6 µg/dl) respectively. BLL was significantly higher in tobacco chewers and those occupationally exposed to Pb for more than 5 years. Significantly low Se levels were observed in individuals with high BLL. Statistically significant negative linear relationship was noted between BLL and Se. The negative correlation of Se with BLL indicates the antagonistic relationship between these metals.

8.
Indian J Clin Biochem ; 37(3): 294-302, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35873607

ABSTRACT

Lead (Pb) is profoundly used heavy metal despite its known toxic effects. Children in particular are more susceptible to Pb toxicity. Thus, the present study was carried out to estimate the prevalence of lead toxicity in Indian children, to observe serum levels of biochemical parameters and to evaluate psychopathological implications of Pb toxicity using population specific scale-Childhood Psychopathological Measurement Schedule (CPMS) in children. Children between 9 and 15 years of age were included in the study (N = 70). Demographic details and information regarding the source of lead exposure were collected using a self-made questionnaire. All biochemical investigations were performed in Beckman Coulter Auto-analyser AU680 and Blood Lead Levels (BLL) were estimated by Graphite Furnace Atomic Absorption Spectrophotometer. The neurobehavioral state of the children was assessed by a population-specific scale i.e., CPMS, which evaluates for neurobehavior under 8 factors, titled, Low intelligence with behavioural problems, Conduct disorder, Anxiety, Depression, Psychotic symptoms, Special symptoms, Physical illness with emotional problems, and Somatization. The median BLL of the study population was 4.9 µg/dL. Habit of frequently consuming roadside food, proximity of residence to vehicular traffic and educational status of the mother were observed to be significant contributing factors for high BLL (≥ 5 µg/dL). Serum alkaline phosphatase (P = 0.02) and phosphorous levels (P = 0.04) were significantly lower in children belonging to high BLL group. A significantly high adverse neurobehavioral score was observed in high BLL group children compared to low BLL group (P < 0.05). There was high prevalence of Pb toxicity with 50% of children having BLL > 5 µg/dL. Further, certain lifestyle characteristics such as proximity of residence to vehicular traffic, frequent consumption of roadside food and lower educational status of the mother could be possible risk factors for higher Pb exposure in children. Evaluation of neurobehavior in children with high BLL revealed a high prevalence of adverse neurobehavior in them when compared to children in low BLL group.

9.
Indian J Clin Biochem ; 37(4): 423-431, 2022 Oct.
Article in English | MEDLINE | ID: mdl-34812224

ABSTRACT

SARS-CoV-2, a novel coronavirus, emerged a year ago in Wuhan, China causing a new pandemic. Convalescent plasma therapy has been applied previously to many infectious diseases and has shown a successful result. This study was planned to assess the Anti-SARS-CoV-2 IgG antibody levels in convalescent COVID-19 patients. In this study, serum samples from 210 persons infected by SARS-CoV-2, treated and discharged from the hospital were collected. Anti-SARS-CoV-2 IgG antibody levels were detected using a chemiluminescence assay. A directory of convalescent plasma donors was created. Anti-SARS-CoV-2 IgG antibody levels vary substantially in the study population with a mean of 51.2 AU/ml. On comparing the serum anti-SARS-CoV-2 IgG antibody levels, a significant difference was observed between the subjects who had cough and those who did not (p = 0.0004). Similar significant findings were found with total protein and globulin levels on comparing the individuals with different antibody status (positive, negative and equivocal). The middle-aged and old age people had high Ab titres compared to younger individuals and the duration of the hospital stay was found to be positively correlated with the anti-SARS-CoV-2 IgG antibody. Cough, age and duration of the hospital stay was found to play a significant role in the development of Anti-SARS-CoV-2 IgG levels. Further, the data suggests that blood groups have a lesser impact on the severity of disease and the development of antibodies. Patients who present with the cough are more likely to develop antibodies.

10.
Environ Geochem Health ; 43(1): 185-193, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32813162

ABSTRACT

Occupational exposure to heavy metals like lead and cadmium causes a wide range of biological effects and may elevate the risk of genetic damage. Heavy metal toxicity is now becoming a significant public health problem. There are many discrepancies in the results of the studies on the genotoxicity of heavy metals. Therefore, the study aimed to estimate lead, cadmium, and 8-OHdG levels (8-hydroxy-2-deoxyguanosine) and expression of DNA repair gene OGG1 (8-oxoguanine DNA glycosylase 1) in occupationally heavy metal exposed workers. The study comprised 100 workers, occupationally exposed to lead and cadmium from different factories and 100 controls without history of metal exposure. The lead and cadmium mean ± SD were 5.69 ± 12.07 µg/dL and 3.44 ± 1.33 µg/L in the cases and 1.27 ± 1.10 µg/dL and 1.07 ± 0.67 µg/L in the controls. The 8-OHdG concentration was significantly higher in the cases than the controls. Cadmium showed a significant positive correlation with 8-OHdG in the cases. The expression of OGG1 was significantly down-regulated in the cases compared to the controls. Lead levels did not show any significant correlation with OGG1, whereas cadmium level had a significant positive correlation with OGG1 in the cases. To conclude, the exposure to heavy metals is associated with increased oxidative DNA damage and impaired expression of the DNA repair gene, OGG1.


Subject(s)
8-Hydroxy-2'-Deoxyguanosine/blood , Cadmium/blood , DNA Damage , DNA Glycosylases/genetics , Environmental Pollutants/blood , Lead/blood , Occupational Exposure/analysis , Adolescent , Adult , Aged , DNA Glycosylases/metabolism , Gene Expression , Humans , India , Middle Aged , Young Adult
11.
Indian J Clin Biochem ; 36(1): 100-107, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33505134

ABSTRACT

In spite of the established knowledge regarding their toxicities, occupational exposure to heavy metals like lead and cadmium still continues because of their wide distribution in environment. Due to lack of awareness, most of the workers usually eat, smoke, drink at their workplace which may aggravate the metal exposure. The present study was planned to assess the blood levels of lead and cadmium in occupationally exposed workers of Jodhpur (India). A total of 110 individuals working in different industrial set ups (furniture, metal handicraft, welders) of Jodhpur district (exposed group), aged between 20 and 60 years and 97 apparently healthy people (controls) with no history of occupational heavy metal exposure aged between 25 and 60 were recruited. Details of personal habits and demographics were recorded by means of self-developed questionnaire. 5 ml of whole blood was drawn from every individual. Metal levels were measured by graphite furnace atomic absorption spectrophotometer. Statistical analysis was done using GraphPad Prism Software. Results showed that Blood Lead Level and Blood Cadmium Level (CdB) were significantly higher in the exposed group as compared to the non-exposed group. Significant age and gender-based differences were found in terms of blood cadmium levels but no such difference was observed in case of blood lead. The study also revealed that higher blood levels of these metals in workers are influenced by their occupational practices, lack of protection against workplace environment pollutants, thus increasing their susceptibility to metal toxicity.

12.
Indian J Clin Biochem ; 36(4): 427-439, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33814753

ABSTRACT

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.

13.
Indian J Clin Biochem ; 36(4): 440-450, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34177139

ABSTRACT

COVID-19 has emerged as a global pandemic. It is mainly manifested as pneumonia which may deteriorate into severe respiratory failure. The major hallmark of the disease is the systemic inflammatory immune response characterized by Cytokine Storm (CS). CS is marked by elevated levels of inflammatory cytokines, mainly interleukin-6 (IL-6), IL-8, IL-10, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Of these, IL-6 is found to be significantly associated with higher mortality. IL-6 is also a robust marker for predicting disease prognosis and deterioration of clinical profile. In this review, the pivotal role played by IL-6 in the immuno-pathology of COVID-19 has been illustrated. The role of IL-6 as a pleiotropic cytokine executing both pro and anti-inflammatory activities has been reviewed. ADAM 10, a metalloproteinase switches the anti-inflammatory pathway of IL-6 to pro inflammatory hence blocking the action of ADAM 10 could be a new therapeutic strategy to mitigate the proinflammatory action of IL-6. Furthermore, we explore the role of anti-IL6 agents, IL-6 receptor antibodies which were being used for autoimmune diseases but now are being repurposed for the therapy of COVID-19.

14.
Indian J Clin Biochem ; 36(1): 108-111, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33162692

ABSTRACT

COVID-19 is caused by a novel coronavirus which was first reported in Wuhan city, China. The pandemic has led to considerable mortality globally. India, at present has the second largest burden of COVID-19 cases globally. Clinical trials with new interventions, including new vaccine candidates are being explored in the scientific world. Countries like China and India, with a rich history of traditional medicine, are exploring the effectiveness of traditional medicines to treat COVID-19. This study included 725 patients from an Isolation center, of which 230 (31.7%) were excluded due to reasons like incorrect phone numbers, no response on phone, or denying consent to participate. Finally, 495 participants had responded, of which 367 (74.1%) had not used any Complementary and Alternative Medicine (CAM) product or home remedies while 128 (25.8%) people used 161 CAM products and home remedies during the treatment and even afterward. More than half of the participants (59.6%) among them had consumed Ayurvedic Kadha. Many respondents consumed more than one CAM products or home remedies but there were no reported acute or severe adverse effects with these products. However, it is essential to ensure the safety of these interventions on long-term use because patients with other comorbidities can have a detrimental effect due to these products or due to drug herb interaction with their ongoing medications. Hence, long-term follow-up studies of recovered patients are crucial in determining the effects of medications or CAM products on organ functions due to disease or interventions.

15.
Am J Physiol Cell Physiol ; 319(3): C500-C509, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32687406

ABSTRACT

Severe acute respiratory syndrome coronavirus (SARS-CoV), an enveloped virus with a positive-sense single-stranded RNA genome, facilitates the host cell entry through intricate interactions with proteins and lipids of the cell membrane. The detailed molecular mechanism involves binding to the host cell receptor and fusion at the plasma membrane or after being trafficked to late endosomes under favorable environmental conditions. A crucial event in the process is the proteolytic cleavage of the viral spike protein by the host's endogenous proteases that releases the fusion peptide enabling fusion with the host cellular membrane system. The present review details the mechanism of viral fusion with the host and highlights the therapeutic options that prevent SARS-CoV-2 entry in humans.


Subject(s)
Betacoronavirus/metabolism , Cell Membrane/metabolism , Coronavirus Infections/metabolism , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/metabolism , Pneumonia, Viral/prevention & control , Viral Fusion Proteins/metabolism , Amino Acid Sequence , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus/drug effects , COVID-19 , Cell Membrane/drug effects , Cell Membrane/virology , Humans , Peptidyl-Dipeptidase A/metabolism , Protease Inhibitors/pharmacology , Protease Inhibitors/therapeutic use , Protein Binding/drug effects , Protein Binding/physiology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/metabolism , Viral Fusion Proteins/drug effects
16.
Toxicol Ind Health ; 36(10): 816-822, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32816651

ABSTRACT

Metallothioneins (MTs) are low molecular weight cysteine-rich, metal-binding proteins. They are involved in transportation and detoxification of heavy metals, homeostasis of essential metals, and as antioxidation against reactive oxygen species. Polymorphisms in a gene may increase or decrease the expression efficiency of a gene. This study aimed to determine the genetic effect of MT1A rs8052394 on lead (Pb), cadmium (Cd), zinc (Zn), and aluminum (Al) levels in factory workers. The study included 100 occupationally heavy metal exposed workers from different factories around Jodhpur. Pb, Cd, Zn, and Al levels were measured by atomic absorption spectrophotometry. Individuals with the GG genotype had lower Pb, Zn, and Al levels and higher Cd levels than AA and AG genotypes. The genotyping of MT1A rs8052394 was done by the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). The mean ± standard deviation of Pb, Cd, Zn, and Al was 5.88 ± 13.28 µg/dL, 3.52 ± 1.25 µg/L, 16.45 ± 16.69 µg/dL, and 58.92 ± 58.91 µg/L, respectively. A significant association was found between single-nucleotide polymorphisms (SNPs) of MT1A gene and Cd (p = 0.006) and with Zn levels (p = 0.031) but no association found with Pb and Al levels. Among the study population, 78 participants were homozygote major (AA), 19 were heterozygote (AG), and 3 were homozygote minor (GG). The χ 2 test presented the genotypic distribution of all three genotypes under the Hardy-Weinberg equilibrium (p > 0.05). The frequency of the A allele was 87.5% (175) and the G allele was 12.5% (25). To conclude, polymorphism in rs8052394 of the MT1A gene is associated with increased metal accumulation which in turn may lead to increased toxic effects in the exposed individuals. Factory workers thus, should be more cautious about protecting their health against the toxic effects of heavy metals.


Subject(s)
Aluminum/blood , Cadmium/blood , Copper/blood , Lead/blood , Metallothionein/genetics , Metals, Heavy/blood , Zinc/blood , Adolescent , Adult , Aged , Female , Genetic Variation , Genotype , Humans , India , Male , Metal Workers , Middle Aged , Occupational Exposure/adverse effects , Paint/adverse effects , Polymorphism, Single Nucleotide , Young Adult
17.
Indian J Clin Biochem ; 35(3): 260-273, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32641873

ABSTRACT

The novel Coronavirus Disease 2019 (COVID-19), that began in Wuhan Province, China was labelled as an International Public Health Emergency on January 30, 2020 and later was declared a pandemic by the World Health Organisation (WHO) on March 11, 2020. The causative agent, SARS-CoV-2 was the third coronavirus responsible for causing major disease outbreaks in human population after Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) caused by SARS-CoV and MERS-CoV respectively. The patients of COVID-19 present with a clinical feature resembling mild form of viral pneumonia which in certain cases progress to a severe form characterised by adult respiratory distress syndrome (ARDS) and/or multiorgan failure leading to death. The transition from mild to severe form of COVID-19 is affected by a lot of factors like age, co-morbidities etc. In the absence of an absolute cure, it is essential to explore the molecular pathogenesis of the disease to identify people at risk of developing severity so that alternative treatment modalities may be planned. The aim of this review is to provide an update on the general characteristics of SARS-CoV-2 and highlight the inflammatory changes and immune dysregulation that may help in identification of molecular predictors of disease severity.

18.
Indian J Clin Biochem ; 35(4): 418-422, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32837035

ABSTRACT

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.

19.
Indian J Clin Biochem ; 35(4): 497-501, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32837037

ABSTRACT

The present study explores the association between weather and COVID-19 pandemic in Delhi, India. The study used the data from daily newspaper releases from the Ministry of Health and Family Welfare, Government of India. Linear regression was run to understand the effect of the number of tests, temperature, and relative humidity on the number of COVID-19 cases in Delhi. The model was significantly able to predict number of COVID-19 cases, F (4,56) = 1213.61, p < 0.05, accounting for 99.4% of the variation in COVID-19 cases with adjusted R2 = 98.8%. Maximum Temperature, average temperature and average relative humidity did not show statistical significance. The only number of tests was significantly associated with COVID-19 cases.

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