Nf-κb Inhibition Rescues Cardiac Function By Remodeling Calcium Genes In A Duchenne Muscular Dystrophy Model

Duchenne muscular dystrophy (DMD) is a neuromuscular disorder causing progressive muscle degeneration. Although cardiomyopathy is a leading mortality cause in DMD patients, the mechanisms underlying heart failure are not well understood. Previously, we showed that NF-κB exacerbates DMD skeletal muscle pathology by promoting inflammation and impairing new muscle growth. Here, we show that NF-κB is activated in murine dystrophic (mdx) hearts, and that cardiomyocyte ablation of NF-κB rescues cardiac function. This physiological improvement is associated with a signature of upregulated calcium genes, coinciding with global enrichment of permissive H3K27 acetylation chromatin marks and depletion of the transcriptional repressors CCCTC-binding factor, SIN3 transcription regulator family member A, and histone deacetylase 1. In this respect, in DMD hearts, NF-κB acts differently from its established role as a transcriptional activator, instead promoting global changes in the chromatin landscape to regulate calcium genes and cardiac function

The Association of Thyroid Autoimmunity and Lipid Profile in Hypothyroidism: A Cross-sectional Study

Introduction: Thyroid disorders, particularly hypothyroidism, are the most common thyroid disorders in India, affecting one in ten adults. Autoimmunity may play a significant role in the progression of hyperlipidaemia, which is one of the recurrent issues associated with thyroid disorders. Although serum lipids have been proven to control immunological and inflammatory responses, little is known about their relationship to thyroid autoimmunity. Aim: To investigate the association between Thyroid Peroxidase Antibody (anti-TPO) and serum lipid parameters among patients diagnosed with hypothyroidism. Materials and Methods: A hospital-based cross-sectional study was conducted at Parul Sevashram Hospital in Vadodara, Gujarat from November 2022 to May 2023. A total of 103 patients with hypothyroidism were included in the study. All patients underwent estimation of thyroid function parameters such as triiodothyronine (T3), thyroxine (T4), and ThyroidStimulating Hormone (TSH), as well as anti-TPO levels and selected lipid profile parameters such as Total Cholesterol (TC), Triglycerides (TG), High-Density Lipoproteins (HDL), and LowDensity Lipoproteins (LDL). The association between anti-TPO and lipid levels was further analysed. Statistical analysis was performed using the Chi-square test. Results: Among the 103 hypothyroid patients, 83 (80.6%) were females, while only 20 (19.4%) were males. Positive serum antiTPO antibodies were found in 79 (76.7%) patients, whereas negative Anti-TPO cases accounted for 24 (23.3%). The total serum cholesterol, with a mean of 226.88±37.44 mg/dL, and serum LDL, with 145.31±34.60 mg/dL, were significantly increased (p-value<0.01), whereas the serum TG with a mean of 181.06±52.13 mg/dL, and serum HDL, with 44.61±7.87 mg/ dL, were found to be non significant (p-value>0.05). Conclusion: Hypothyroid patients positive for anti-TPO antibodies are at risk of experiencing disrupted lipid levels. There was a significant association between positive anti-TPO status and TC and LDL in the present study

Association of Insulin Resistance with Hepatitis B and Hepatitis C Infection: A Cross-sectional Study

Introduction: Hepatitis B and C viruses (HBV and HCV) are the most common causes of chronic viral hepatitis in the United States and worldwide. As several studies have shown that some viral infections promote Insulin Resistance (IR), it becomes imperative to investigate the effect of HBV and HCV on the same. Aim: To investigate the association between IR and Hepatitis C and Hepatitis B infection. Materials and Methods: The present cross-sectional study was conducted in the Department of Paramedical and Health Sciences, Parul Institute of Paramedical and Health Sciences, Faculty of Medicine, Parul University, Vadodara, Gujarat, India, from November 2022 to June 2023. The study comprised 100 consecutive patients, with 55% testing positive for Hepatitis B and 45% for Hepatitis C. Biochemical parameters such as fasting blood sugar, fasting insulin and IR via the Homeostasis Model Assessment (HOMA-IR) were determined. Statistical analysis was performed using International Business Machines (IBM) Statistical Package for Social Sciences (SPSS) software version 26.0. The z-test of proportion was calculated and a Z-score calculator was used for p-value. Results: In the present study, out of 100 consecutive patients, 76 were males and 24 were females. The mean insulin level for HBV patients was found to be high, with values of 28.94±2.22 mU/L in 23.63% of cases, whereas in HCV cases, 68.8% of patients were found to have higher levels, with mean values of 34.52±9.00 mU/L. The mean HOMA-IR values for HBV patients were found to be high, at 4.84±2.32 in 47.27% of cases, whereas in HCV cases, 77.7% of patients were found to have higher values of HOMA-IR, with a mean of 7.94±4.83. Conclusion: Insulin resistance can be a consequence of the inability of insulin to induce the appropriate effect on glucose metabolism and is the principal indication for the development of metabolic syndrome and diabetes mellitus. In the current study, HCV-positive patients showed more IR compared to HBV-positive cases

Association between Iron Indices and Dyslipidemia among Patients with Iron Deficiency Anaemia: A Cross-sectional Study

Introduction: Iron Deficiency Anaemia (IDA) is a major public health problem in India. Iron plays a role in hepatic lipogenesis, being an integral part of some enzymes and transporters involved in lipid metabolism. Since information on the association between iron metabolism and dyslipidemia in adults is limited, it is important to assess the lipid status in iron-deficient patients. Aim: To study the association of iron indices with the lipid profile among patients with iron deficiency anaemia. Materials and Methods: This hospital-based cross-sectional study was conducted at the Department of Paramedical and Health Sciences, Parul Institute of Paramedical and Health Sciences, Faculty of Medicine, Parul University, Vadodara, Gujarat, India, from December 2022 to May 2023. In the present study, 100 IDA patients aged between 25-45 years were included. All the participants underwent different tests including Total Cholesterol (TC), Triglyceride (TG), High Density Lipoprotein-Cholesterol (HDL-C), and Low Density Lipoprotein-Cholesterol (LDL-C). Furthermore, the association between IDA patients and lipid levels was analysed. The data were statistically analysed using Pearson’s correlation test and Chi-square test. Results: In the present study, out of a total of 100 patients, 38 were males and 62 were females. The majority of IDA patients had lower levels of TC, TG, and LDL-C. Low levels of TC and LDL were found in 52 (83.87%) of females and 30 (78.94%) of males. A total of 28 (73.68%) of males and 52 (83.87%) of females had lower values for TG levels. In contrast to TC and TG, a substantial correlation between Haemoglobin (Hb) levels and HDL-C and LDL-C was found. However, Hb had a positive association with TG, HDL-C, and LDL-C and a negative correlation with TC. These results also suggest a substantial correlation between Serum Iron (SI) and TC, TG, and HDL-C, but not a significant correlation with LDL-C. Conclusion: When observed for dyslipidemia, IDA patients showed significantly lower levels of TC, TG, and HDL-C with respect to their SI levels

SARS-CoV-2 Spike Mutations, L452R, T478K, E484Q and P681R, in the Second Wave of COVID-19 in Maharashtra, India

As the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic expands, genomic epidemiology and whole genome sequencing are being used to investigate its transmission and evolution. Against the backdrop of the global emergence of “variants of concern” (VOCs) during December 2020 and an upsurge in a state in the western part of India since January 2021, whole genome sequencing and analysis of spike protein mutations using sequence and structural approaches were undertaken to identify possible new variants and gauge the fitness of the current circulating strains. Phylogenetic analysis revealed that newly identified lineages B.1.617.1 and B.1.617.2 were predominantly circulating. The signature mutations possessed by these strains were L452R, T478K, E484Q, D614G and P681R in the spike protein, including within the receptor-binding domain (RBD). Of these, the mutations at residue positions 452, 484 and 681 have been reported in other globally circulating lineages. The structural analysis of RBD mutations L452R, T478K and E484Q revealed that these may possibly result in increased ACE2 binding while P681R in the furin cleavage site could increase the rate of S1-S2 cleavage, resulting in better transmissibility. The two RBD mutations, L452R and E484Q, indicated decreased binding to select monoclonal antibodies (mAbs) and may affect their neutralization potential. Further in vitro/in vivo studies would help confirm the phenotypic changes of the mutant strains. Overall, the study revealed that the newly emerged variants were responsible for the second wave of COVID-19 in Maharashtra. Lineage B.1.617.2 has been designated as a VOC delta and B.1.617.1 as a variant of interest kappa, and they are being widely reported in the rest of the country as well as globally. Continuous monitoring of these and emerging variants in India is essential

Prabhjot Singh1, Prija Ponnan1,2, Shibu Krishnan3, Tapesh Kumar Tyagi1,

Protein acyltransferase function of purified calreticulin. Part 1: characterization of propionylation of protein utilizing propoxycoumarin as the propionyl group dono