Search

Introduction: Non Alcoholic Fatty Liver Disease (NAFLD) is one of the major leading causes of liver diseases, comprising a spectrum of conditions ranging from simple steatosis to cirrhosis. In the era of preventive medicine, it is of utmost importance to recognise the subset of NAFLD patients at high risk of progressing to liver cirrhosis. A newly emerging concept of myosteatosis is now suspected to be an early manifestation of NAFLD disease progression. Aim: To find the correlation between myosteatosis and liver fibrosis among patients with NAFLD. Materials and Methods: This was a cross-sectional study conducted in the Department of Radiodiagnosis and Department of Gastroenterology at Amala Institute of Medical Sciences in Thrissur, Kerala, India, from January 2021 to June 2022. A total of 57 subjects with Magnetic Resonance Imaging-proven (MRI) NAFLD were included in the study. Body weight and height were measured. Liver fat and myosteatosis were measured using the MRI-derived Proton Density Fat Fraction (PDFF) method {Iterative Decomposition of Water and Fat with Echo (IDEAL-IQ sequence)}. Liver fibrosis was assessed using 2D shear wave elastography. The proportion of myosteatosis and liver fibrosis among NAFLD patients was estimated. Partial correlation, controlling for gender, was evaluated using partial Spearman's rho correlation coefficients. An Reciever Operating Characteristic (ROC) curve was plotted to assess muscle fat fraction in predicting liver fibrosis outcome among patients. Results: Out of the 57 subjects studied, 17 were females and 40 were males. The median Interquartile Range (IQR) age of the subjects was 43.0 (16.5). The median MRI hepatic fat fraction was 10.8. The median muscle PDFF in males was 8.4, and in females, it was 16.9. The median H-PDFF was 18.8. Myosteatosis correlated positively with liver fibrosis (r=0.558; p<0.001). It also negatively correlated with hepatic steatosis (r=-0.321; p=0.02). A statistically significant correlation was not found between liver fat and liver fibrosis. An ROC curve was plotted to predict the liver fibrosis outcome by muscle fat fraction {Area Under Curve (AUC: 0.605; p-value: 0.204)}, which showed a sensitivity of 0.615 and a specificity of 0.389 at a cutoff score of 10.43. Conclusion: Myosteatosis positively correlated with liver fibrosis and negatively with liver steatosis. [ABSTRACT FROM AUTHOR]

The objective of the present study was the bioprospection of bioactive compounds from endophytic Thielaviopsis basicola with therapeutic applications, isolated from Ximenia americana, Western Ghats of Karnataka, India. The fresh and healthy leaves and roots of Ximenia americana were collected from the forests of Western Ghats of Karnataka, India. The collected explants were submerged for the enumeration and purification of fungal endophytes by using selective, and different media. Isolated fungal endophytes were processed for the production, extraction, phytochemical analysis, purification and evaluation of bioactive compounds by referring standard protocols. At a glance, endophyte derived bioactive compounds were used in in-vitro antagonistic, antioxidant antiurolithisis, and anticancer activity. A total of 32 pure isolates were obtained, 8 morphologically distinct fungal endophytes were identified from 200 explants of X. americana. Endophytic Thielaviopsis basicola was a core candidate identified and cultivated in solid-state fermentation on corn bran under the dark condition at 25° ± 2° for 15 days. Obtained 5.30g of aqueous crude extract per 100g of cornmeal were processed for qualitative phytochemical analysis, in alkaloids, terpenoids, flavonoids, phenols, tannins, and glycosides were found. The aqueous crude extract showed 0.761g of phenol and 0.276g of flavonoids content. From these crude extract TbCC1 and TbCC2, two fractions were purified by column chromatography and spotted potent bioactive compounds on thin layer chromatography. The FTIR data of TbCC1 and TbCC2 showed different functional groups such as alcohol, phenols, alkanes, alkenes, aromatic, alkyl halides, amines, ether, and nitrile. The TbCC1 exhibited prominent antagonistic activity and MIC against Staphylococcus aureus (24mm with 100µg/mL) and Candida albicans (22mm with 75µg/mL) while TbCC2 exhibited against Salmonella typhi (22mm with 75µg/mL) and Aspergillus fumigatus (18mm with 75µg/mL). The TbCC1 showed potent antioxidant activity (86.24±0.35) with 5.26µg/mL of IC50 value as compared with TbCC2. The maximum antiurolithiasis activity showed with 100% concentration at the rate of 67.5±1.49 of aqueous crude extract. The Sulphorodamine B assay showed MCF7 human breast cancer cell line viability 98.39±0.0250 at 100µg concentration and 40.81±0.0470 at 500µg with an IC50 value of 459.60µg. This is the first innovative report of endophytic Thielaviopsis basicola for their phytochemicals detection and prominent in-vitro activities from the selected plants. [ABSTRACT FROM AUTHOR]

Background: Limb‑girdle muscular dystrophy (LGMD) is the most common adult‑onset class of muscular dystrophies in India, but a majority of suspected LGMDs in India remain unclassified to the genetic subtype level. The next‑generation sequencing (NGS)‑based approaches have allowed molecular characterization and subtype diagnosis in a majority of these patients in India. Materials and Methods: (I) To select probable dysferlinopathy (LGMD2B) cases from other LGMD subtypes using two screening methods (i) to determine the status of dysferlin protein expression in blood (peripheral blood mononuclear cell) by monocyte assay (ii) using a predictive algorithm called automated LGMD diagnostic assistant (ALDA) to obtain possible LGMD subtypes based on clinical symptoms. (II) Identification of gene pathogenic variants by NGS for 34 genes associated with LGMD or LGMD like muscular dystrophies, in cases showing: absence of dysferlin protein by the monocyte assay and/or a typical dysferlinopathy phenotype, with medium to high predictive scores using the ALDA tool. Results: Out of the 125 patients screened by NGS, 96 were confirmed with two dysferlin variants, of which 84 were homozygous. Single dysferlin pathogenic variants were seen in 4 patients, whereas 25 showed no variants in the dysferlin gene. Conclusion: In this study, 98.2% of patients with absence of the dysferlin protein showed one or more variants in the dysferlin gene and hence has a high predictive significance in diagnosing dysferlinopathies. However, collection of blood samples from all over India for protein analysis is expensive. Our analysis shows that the use of the “ALDA tool” could be a cost‑effective alternative method. Identification of dysferlin pathogenic variants by NGS is the ultimate method for diagnosing dysferlinopathies though follow‑up with the monocyte assay can be useful to understand the phenotype in relation to the dysferlin protein expression and also be a useful biomarker for future clinical trials. [ABSTRACT FROM AUTHOR]

Background: Dihydropyrimidine dehydrogenase (DPD) encoded by DPYD gene is the major enzyme involved in metabolism of 5-flurouracil (5-FU), a pyrimidine analogue used in cancer chemotherapy. Although very effective as a cancer therapeutic drug, if not rapidly metabolized, 5-FU may prove lethal. Single nucleotide variants (SNVs) within DPYD that modulate DPD enzyme activity contribute to 5-FU toxicity. Study: This study looked for DPYD SNVs common in the Indian population that might be associated with variable DPD activity and drug toxicity. To achieve this, sequencing analysis was performed of all 23 exons and flanking intronic regions of the DPYD gene in a cohort of 50 healthy adult Indians. This study detected 22 SNVs including intronic, synonymous and non-synonymous changes in the DPYD gene, of which six have not been documented before. Allelic frequency was calculated for the observed variants and linkage disequilibrium (LD) analysis was performed on variants with frequency ≥0.1 to identify haplotypes. Conclusions: This study provides a brief overview of the genetic polymorphism in DPYD in Indians and emphasizes the need for a large scale extensive study to establish markers associated with the frequently observed variable drug metabolism. [ABSTRACT FROM AUTHOR]

South Asian Indians represent a sixth of the world's population and are a racially, geographically, and genetically diverse people. Their unique anthropological structure, prevailing caste system, and ancient religious practices have all impacted the genetic composition of most of the current-day Indian population. With the evolving socio-religious and economic activities of the subsects and castes, endogamous and consanguineous marriages became a commonplace. Consequently, the frequency of founder mutations and the burden of heritable genetic disorders rose significantly. Specifically, the incidence of certain autosomal-recessive disorders is relatively high in select Indian subpopulations and communities that share common recent ancestry. Although today clinical genetics and molecular diagnostic services are making inroads in India, the high costs associated with the technology and the tests often keep patients from an exact molecular diagnosis, making more customized and tailored tests, such as those interrogating the most common and founder mutations or those that cater to select sects within the population, highly attractive. These tests offer a quick first-hand affordable diagnostic and carrier screening tool. Here, we provide a comprehensive catalog of known common mutations and founder mutations in the Indian population and discuss them from a molecular, clinical, and historical perspective., (© 2014 WILEY PERIODICALS, INC.)

Cytidine deaminase (CDA) is the major enzyme involved in metabolism of gemcitabine, a pyrimidine analog widely used for chemotherapy of solid tumors. While only low amounts of administered gemcitabine undergo intracellular phosphorylation into active forms and involve in antineoplastic activities, majority of it is rapidly inactivated by CDA and excreted to avoid drug toxicity. Knowledge of the genetic polymorphisms mildly effecting cellular activity of the enzyme CDA is therefore crucial to understanding drug-induced toxicities associated with gemcitabine. Functional significance and allele frequencies for common SNPs including 79A>C (*2) and 208G>A (*3) have been reported in various ethnic populations including Caucasian, African, Korean and Japanese. However, such studies have not been reported in any Indian sub-population. In the present study, conventional polymerase chain reaction (PCR) based amplification using gene specific primers and Sanger sequencing were performed to identify CDA variants in 50 healthy individuals from Indian sub-population. Established common variant 79A>C known to reduce CDA activity was observed at a frequency of 0.14 in the study cohort. In addition to other known variants, one novel variant, c.325-209T>C was detected at a frequency of 0.06. Genetic variants in CDA gene and their frequencies established in our study hold value in pharmacogenetics., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Introduction: Clinical heterogeneity of limb-girdle muscular dystrophies (LGMDs, 24 known subtypes), which includes overlapping phenotypes and varying ages of onset and morbidity, adds complexity to clinical and molecular diagnoses., Methods: To diagnose LGMD subtype, protein analysis, using immunohistochemistry (IHC) and immunoblotting, was followed by gene sequencing through a panel approach (simultaneous sequencing of known LGMD genes) in 9 patients from unrelated families of the Indian Agarwal community. Haplotype studies were performed by targeted SNP genotyping to establish mutation segregation., Results: We identified 2 founder mutations in CAPN3, a missense (c.2338G>C; p.D780H) and a splice-site (c.2099-1G>T) mutation, on 2 different haplotype backgrounds. The patients were either heterozygous for both or homozygous for either of these mutations., Conclusions: Founder mutations have immediate clinical application, at least in selected population groups. Clinically available gene panels may provide a definitive molecular diagnosis for heterogeneous disorders such as LGMD., (Copyright © 2012 Wiley Periodicals, Inc.)