BACKGROUND: Hepcidin-25, a polypeptide hormone, plays a major role in iron metabolism and is found to be reduced during iron deficiency; therefore, testing for hepcidin can be utilized as an ...indicator of bioavailability of iron. Globally, reference range values for hepcidin have been established in different communities. The aim of the present study was to establish the normal reference range values of serum hepcidin in Indian blood donors to fathom the baseline and reference point of hepcidin.
MATERIALS AND METHODS: A total of 90 donors fulfilling the eligibility criteria were recruited in the study consisting of 28 males and 62 females. Blood samples collected were used to execute hemoglobin (Hb), serum ferritin, and hepcidin assays. Serum hepcidin-25 isoform was detected by a commercial competitive enzyme-linked immunosorbent assay kit according to the manufacturer's instructions. Hb and ferritin were evaluated by the standard methods.
RESULTS: The mean ± standard deviation (SD) of Hb level in males was 14.62 ± 1.34 g/dL and females was 13.33 ± 0.76 g/dL. The mean ± SD of ferritin level in males was 113 ± 56.12 ng/mL and females was 62.65 ± 40.8 ng/mL. Similarly, the mean ± SD of hepcidin level in male donors was 22.18 ± 12.17 ng/mL and female donors was 10.95 ± 6.06 ng/mL. The established reference range values of Hepcidin were 6.32-46.06 ng/mL for males and 3.44-24.78 for females.
CONCLUSION: These findings suggest that further studies with larger groups of donors are mandatory to produce reference values of hepcidin that can be précised to the whole populace in India.
Background
Alcohol use disorders (AUDs) leading to liver disease is major concern over other spectrum of disorder. Excessive alcohol consumption resulting in leaky gut syndrome is attributed to ...alcohol-induced liver injury through portal translocation of bacterial endotoxin. Susceptibility to alcoholic liver disease (ALD) in AUD patients could be dependent upon genes responsible for inflammation and alcohol metabolism. The pattern recognition receptor CD14 gene is a major player in endotoxin-mediated inflammation and susceptibility to ALD. This study investigated the genetic association of CD14 polymorphisms and other mechanisms relevant to altered inflammatory responses leading to ALD.
Methods
Patients with alcohol use disorder with ALD (n
=
128) and without liver disease (ALC, n = 184) and controls without alcohol use disorder (NALC, n = 152) from North India were enrolled. The CD4 gene polymorphisms in the North Indian population were evaluated by RFLP and sequencing. Secretory CD14 (sCD14), LBP, TLR4, MD2, TNFα, IL1b, IFNγ, IL6, IL10, and IL4 levels in serum were measured by ELISA among groups. The influence of polymorphisms on CD14 gene promoter activity and circulatory bacterial DNA level was determined.
Results
The CD14 gene promoter and exonic region SNPs were found to be monomorphic, except for SNP rs2569190 for the North Indian population. The genetic association of SNP rs2569190(C/T) with the risk of developing ALD was found significant for TT genotype OR
TT
, 95% CI = 2.19, 1.16–4.13 for ALD vs. ALC and OR, 2.09, 1.18–3.72 for ALD vs. NALC. An increased sCD14 level was observed in AUD patients compared to NALC control. Increased levels of LBP, TLR4, TNFα, IL1β, IFNγ, and IL6 and reduced levels of MD2, IL10, and IL4 were observed among the ALD patients compared to the other two control groups. Elevated levels of pro-inflammatory and reduced levels of anti-inflammatory cytokines were observed in the risk genotype TT groups of ALD patients and the ALC group compared to NALC. Promoter activity was observed in the intronic region flanking SNPs and risk genotype can influence reporter activity, indicating CD14 gene expression.
Conclusion
Enhanced CD14 expression associated with inflammatory responses increases susceptibility to ALD in the TT genotype of AUD patients.
is a pathogenic bacterium that causes gastritis and gastric carcinoma. Besides gastric complications its potential link with gut-brain axis disruption and neurological disorders has also been ...reported. The current study investigated the plausible role and its associated molecular mechanism underlying
mediated gut-brain axis disruption and neuroinflammation leading to neurological modalities like Alzheimer's disease (AD). We have chosen the antimicrobial resistant and susceptible
strains on the basis of broth dilution method. We have observed the increased inflammatory response exerted by
strains in the gastric as well as in the neuronal compartment after treatment with
derived condition media (HPCM). Further, elevated expression of STAT1, STAT3, and AD-associated proteins- APP and APOE4 was monitored in HPCM-treated neuronal and neuron-astrocyte co-cultured cells. Excessive ROS generation has been found in these cells. The HPCM treatment to LN229 causes astrogliosis, evidenced by increased glial fibrillary acidic protein. Our results indicate the association of STAT3 as an important regulator in the
mediated pathogenesis in neuronal cells. Notably, the inhibition of STAT3 by its specific inhibitor, BP-1-102, reduced the expression of pSTAT3 and AD markers in neuronal compartment induced by HPCM. Thus, our study demonstrates that
infection exacerbates inflammation in AGS cells and modulates the activity of STAT3 regulatory molecules.
secretome could affect neurological compartments by promoting STAT3 activation and inducing the expression of AD-associated signature markers. Further, pSTAT-3 inhibition mitigates the
associated neuroinflammation and amyloid pathology.
The ongoing COVID-19 vaccine drives across the world, including India, may have caused people to adopt risky behavior such as decreased or non-adherence to COVID-appropriate social behavior. Such ...phenomenon in which people are more likely to engage in risky behavior when security measures have been mandated is termed as the "Peltzman Effect" and apart from the emergence of various variants, it may have contributed to the recent upsurge in the number of new COVID-19 cases across the world, including in India. To make the worldwide COVID-19 vaccine drive successful, it is important to acknowledge, understand and minimize the potential harms from Peltzman Effect.
Small cell lung carcinomas (SCLC) are aggressive tumors with high propensity to metastasize. Recent NCCN guidelines have incorporated immunotherapy in extensive stage SCLC. Limited benefit in few ...patients compounded by side effects of unwonted immune-checkpoint-inhibitor (ICPI) usage necessitates identification of potential biomarkers predicting response to ICPIs. Attempting this, we analysed expression of various immunoregulatory molecules in tissue biopsies and paired blood samples of SCLC patients. In 40 cases, immunohistochemistry for expression of immune inhibitory receptors CTLA-4, PD-L1 and IDO1 was performed. Matched blood samples were quantified for IFN-γ, IL-2, TNF-α and sCTLA-4 levels using immunoassay and additionally for IDO1 activity (Kynurenine/Tryptophan ratio) using LC-MS. Immunopositivity for PD-L1, IDO1 and CTLA-4 was identified in 9.3%, 6.2% and 71.8% cases, respectively. Concentration of serum IFN-γ (p-value < 0.001), TNF-α (p-value = 0.025) and s-CTLA4 (p-value = 0.08) were higher in SCLC patients while IL-2 was lower (p-value = 0.003) as compared to healthy controls. IDO1 activity was significantly elevated in SCLC cohort (p-value = 0.007). We proffer that SCLC patients show immune suppressive milieu in their peripheral circulation. Analysis of CTLA4 immunohistochemical expression along with s-CTLA4 levels appears prospective as biomarkers for predicting responsiveness to ICPIs. Additionally, evaluation of IDO1 appears cogent both as prognostic marker and potential therapeutic target as well.
The gut–brain axis is a bidirectional communication network connecting the gastrointestinal tract and central nervous system. The axis keeps track of gastrointestinal activities and integrates them ...to connect gut health to higher cognitive parts of the brain. Disruption in this connection may facilitate various neurological and gastrointestinal problems. Neurodegenerative diseases are characterized by the progressive dysfunction of specific populations of neurons, determining clinical presentation. Misfolded protein aggregates that cause cellular toxicity and that aid in the collapse of cellular proteostasis are a defining characteristic of neurodegenerative proteinopathies. These disorders are not only caused by changes in the neural compartment but also due to other factors of non-neural origin. Mounting data reveal that the majority of gastrointestinal (GI) physiologies and mechanics are governed by the central nervous system (CNS). Furthermore, the gut microbiota plays a critical role in the regulation and physiological function of the brain, although the mechanism involved has not yet been fully interpreted. One of the emerging explanations of the start and progression of many neurodegenerative illnesses is dysbiosis of the gut microbial makeup. The present understanding of the literature surrounding the relationship between intestinal dysbiosis and the emergence of certain neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis, is the main emphasis of this review. The potential entry pathway of the pathogen-associated secretions and toxins into the CNS compartment has been explored in this article at the outset of neuropathology. We have also included the possible mechanism of undelaying the synergistic effect of infections, their metabolites, and other interactions based on the current understanding.
Background
Parkinson's disease (PD) is an increasingly common neurodegenerative condition, which causes movement dysfunction and a broad range of non-motor symptoms. There is no molecular or ...biochemical diagnosis test for PD. The miRNAs are a class of small non-coding RNAs and are extensively studied owing to their altered expression in pathological states and facile harvesting and analysis techniques.
Methods
A total of 48 samples (16 each of PD, aged-matched, and young controls) were recruited. The small extracellular vesicles (sEVs) were isolated and validated using Western blot, transmission electron microscope, and nanoparticle tracking analysis. Small RNA isolation, library preparation, and small RNA sequencing followed by differential expression and targeted prediction of miRNA were performed. The real-time PCR was performed with the targeted miRNA on PD, age-matched, and young healthy control of plasma and plasma-derived sEVs to demonstrate their potential as a diagnostic biomarker.
Results
In RNA sequencing, we identified 14.89% upregulated (fold change 1.11 to 11.04,
p
< 0.05) and 16.54% downregulated (fold change −1.04 to −7.28,
p
< 0.05) miRNAs in PD and controls. Four differentially expressed miRNAs (miR-23b-3p, miR-29a-3p, miR-19b-3p, and miR-150-3p) were selected. The expression of miR-23b-3p was “upregulated” (
p
= 0.002) in plasma, whereas “downregulated” (
p
= 0.0284) in plasma-derived sEVs in PD than age-matched controls. The ROC analysis of miR-23b-3p revealed better AUC values in plasma (AUC = 0.8086,
p
= 0.0029) and plasma-derived sEVs (AUC = 0.7278,
p
= 0.0483) of PD and age-matched controls.
Conclusion
We observed an opposite expression profile of miR-23b-3p in PD and age-matched healthy control in plasma and plasma-derived sEV fractions, where the expression of miR-23b-3p is increased in PD plasma while decreased in plasma-derived sEV fractions. We further observed the different miR-23b-3p expression profiles in young and age-matched healthy control.
This study was planned to evaluate triceps skinfold thickness (TSFT), mid-arm muscle circumference (MAMC) and bioelectrical impedance analysis (BIA) for assessing body composition using dual-energy ...X-ray absorptiometry (DEXA) (reference) and to predict fat mass (FM) and fat-free mass (FFM) in patients with cirrhosis.
FM and FFM were assessed by using DEXA and BIA. Skin-fold calliper was used for measuring TSFT, and MAMC was calculated. Bland–Altman plot was used to determine agreement and linear regression analysis for obtaining equations to predict FM and FFM.
Patients with cirrhosis (n = 302, 241 male, age 43.7 ± 12.0 years) were included. Bland–Altman plot showed very good agreement between BIA and DEXA for the estimation of FM and FFM. Majority of patients were within the limit of agreement: FM (98%) and FFM (96.4%). BIA shows a positive correlation with DEXA:FM (r = 0.73, P ≤ 0.001) and FFM (r = 0.86, P ≤ 0.001). DEXA (FM and FFM) shows a positive correlation with TSFT (r = 0.69, P ≤ 0.01) and MAMC (r = 0.61, P ≤ 0.01). The mean difference between the observed and predicted value of FM and FFM by BIA in the developmental set was 0.01 and 0.05, respectively; whereas in the validation set, it was −0.13 and 0.86, respectively. The mean difference between the observed and predicted value of TSFT and MAMC in the developmental set was 0.43 and 0.07; whereas, in the validation set, it was 0.16 and 0.48, respectively.
Anthropometry (TSFT and MAMC) and BIA are simple and easy to use and can be a substitute of DEXA for FM and FFM assessment in routine clinical settings in patients with cirrhosis.
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