Interplay of precision therapeutics and MD study: Calocybe indica's potentials against cervical cancer and its interaction with VEGF via octadecanoic acid.

The evolving landscape of personalized medicine necessitates a shift from traditional therapeutic interventions towards precision-driven approaches. Embracing this paradigm, our research probes the therapeutic efficacy of the aqueous crude extract (ACE) of Calocybe indica in cervical cancer treatment, merging botanical insights with advanced molecular research. We observed that ACE exerts significant influences on nuclear morphology and cell cycle modulation, further inducing early apoptosis and showcasing prebiotic attributes. Characterization of ACE have identified several phytochemicals including significant presence of octadeconoic acid. Simultaneously, utilizing advanced Molecular Dynamics (MD) simulations, we deciphered the intricate molecular interactions between Vascular Endothelial Growth Factor (VEGF) and Octadecanoic acid to establish C.indica's role as an anticancer agent. Our study delineates Octadecanoic acid's potential as a robust binding partner for VEGF, with comprehensive analyses from RMSD and RMSF profiles highlighting the stability and adaptability of the protein-ligand interactions. Further in-depth thermodynamic explorations via MM-GBSA calculations reveal the binding landscape of the VEGF-Octadecanoic acid complex. Emerging therapeutic innovations, encompassing proteolysis-targeting chimeras (PROTACs) and avant-garde nanocarriers, are discussed in the context of their synergy with compounds like Calocybe indica P&C. This convergence underscores the profound therapeutic potential awaiting clinical exploration. This study offers a holistic perspective on the promising therapeutic avenues facilitated by C. indica against cervical cancer, intricately woven with advanced molecular interactions and the prospective integration of precision therapeutics in modern oncology.

Retinal Nerve Fibre Layer Thinning in Patients with Thalassaemia, Iron Deficiency Anaemia, and Anaemia of Chronic Diseases.

PURPOSE: Retinal nerve fibre layer (RNFL) is a sensitive structure, which is affected by anaemia due to hypoxia. A timely detection of RNFL thinning may aid preventing devastating complications. Optical coherence tomography (OCT) measures RNFL thinning with accuracy and helps in detecting thinning of the retinal layer in anaemic patients. This study was destined to evaluate thinning of RNFL in anaemic patients and their correlation with the haemoglobin level. METHODS: It was a prospective comparative study. Total of 151 patients were included in this study. Patients with retinal diseases were excluded from this study. After initial evaluation, haematological and ophthalmological parameters were measured. RNFL was measured with OCT and corroborated with the Hb level and analysed accordingly. EPI and SPSS softwares were used for detail analysis and the correlation between RNFL thinning and the Hb level. Initially, each eye was separately assigned a value (0, 1, and 2) (normal, borderline, and abnormal, respectively) as per the severity of thinning, and then, the sum of the scores of both eyes were considered as a separate variable, and a multiple linear regression analysis was performed with the independent variables. RESULTS: RNFL thinning was found to be significant in each group of patients. There was a strong correlation of RNFL thinning with degree of anaemia. CONCLUSIONS: Thalassaemia, iron deficiency anaemia, and anaemia of chronic diseases are associated with the significant damage to RNFL. Degree of anaemia is the most important parameter for such thinning of the RNFL layer.

Tropical Milky White Mushroom, Calocybe indica (Agaricomycetes): An Effective Antimicrobial Agent Working in Synergism with Standard Antibiotics.

Synergistic effect of mushroom extracts with standard antibiotics against pathogenic bacteria is beneficial for treating infectious diseases. The present investigation tested the antibacterial activity and synergistic effect from an edible mushroom, Calocybe indica, with standard antibiotics. The minimum inhibitory concentration (MIC) of different extracts from C. indica was checked against pathogenic and opportunistic pathogenic bacteria such as Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, S. epidermidis, and Bacillus subtilis using the broth dilution and agar well diffusion method. The agar disc diffusion method, checkerboard study, and growth curve analysis were used to test synergism. The preliminary mechanism of action regarding cellular morphology, membrane permeability, and damage to protein and DNA were evaluated. Maximum antimicrobial activity was found in the methanolic crude extract (MCE) from C. indica, with a MIC value ranging from 5 to 10 mg/mL. It showed a significant increase in the efficiency of ciprofloxacin (CIP) acting synergistically. The fractional inhibitory concentration index (FICI) of MCE was significant for E. coli and S. aureus with values of 0.46 and 0.45 respectively. Results showed an increase in the loss of cell viability, damage to cell membrane permeability, and damage to bacterial protein and DNA as the probable synergistic mechanism of action for the MCE and the antibiotic. HR-LCMS analysis of the MCE showed the presence of phenolic acid, terpenoids, fatty acid ester, and carboxylic acid, which, in combination, increased the bacterial susceptibility. The present study is significant because it considered the methanolic crude extract from C. indica as complementary medicine for infectious diseases.

Prevalence of Subclinical Hypothyroidism in Acute Coronary Syndrome in Nondiabetics: Detailed Analysis from Consecutive 1100 Patients from Eastern India.

BACKGROUND: The association between subclinical thyroid dysfunction (defined by no symptoms or clinical features of hypothyroidism but biochemically TSH level in the range of above 5 miu/ml but below 10 miu/ml with normal FT4 level) and Acute Coronary Syndrome (ACS) is not known so far. This study was done to calculate the prevalence of subclinical thyroid dysfunction in patients with ACS. METHODS: A retrospective chart review of 1100 consecutive patients was done who presented to Emergency Department with symptoms suggestive of ACS and admitted. They were later classified in 3 categories that includes Acute ST Elevated Myocardial Infarction (STEMI), Unstable Angina (UA), and Acute Non-ST Elevated Myocardial Infarction (NSTEMI). Thyroid function test (FT4, TSH) and antithyroid peroxidase (TPO) were done and evaluated properly. RESULTS: Of 1100 consecutive patients 168 (15.27%) patients had the biochemical features of subclinical thyroid dysfunction. These 168 patients include 60 STEMI, 66 NSTEMI, and 42 Unstable Angina patients. There were no statistically significant differences in terms of left ventricular ejection fraction (LVEF) and catheterisation results considering thyroid dysfunction. CONCLUSIONS: Subclinical thyroid dysfunction is quite prevalent in ACS patients. There are no significant associations between STEMI, Unstable Angina, or NSTEMI patients in terms of thyroid dysfunction neither in single vessel versus multivessel disease involvement. The causative role and outcomes of treatment are still uncertain and need further follow-up.

Correlation of oxidant status with oxidative tissue damage in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a debilitating autoimmune disease whose etiology remains unknown, but studies have consistently implicated a plethora of inflammatory mechanisms culminating in chronic symmetric and erosive synovitis. Importantly, reactive oxygen species (ROS) have been attributed to directly contribute towards the destructive, proliferative synovitis evident in RA. Accordingly, this study aimed to establish whether the degree of oxidative stress and disease activity score (DAS28) correlated with the downstream effects of oxidative damage. The redox status of neutrophils sourced from synovial fluid (SF) was measured by flow cytometry in terms of total ROS and hydroxyl radicals. Among the molecular damage markers, protein carbonylation and lipid peroxidation were detected by spectrophotometry and S-nitrosothiols by fluorimetry. Neutrophils constituted the major cellular component of the SF of patients with RA and their levels of ROS and hydroxyl radicals correlated strongly with protein carbonylation and lipid peroxidation. However, all the oxidative damage markers correlated positively with DAS28. Taken together, in patients with RA, the strong correlation between levels of ROS and DAS28 with markers of oxidative damage suggests that measurement of oxidative stress could serve as a biomarker for monitoring disease severity in RA.

Oxidative stress as a potential biomarker for determining disease activity in patients with rheumatoid arthritis.

Rheumatoid arthritis is an inflammatory, autoimmune disease where oxidative stress has been proposed to contribute to the joint tissue damage. To establish whether measurement of the redox status in blood mirrors the oxidant status at sites of inflammation in patients with rheumatoid arthritis, we concomitantly examined their oxidant status by spectrophotometry and/or flow cytometry. The basal levels of total reactive oxygen species (ROS), superoxide and hydroxyl radicals were significantly raised in neutrophils sourced from peripheral blood and synovial infiltrate, as also showed a strong positive correlation; however, there was no major increase in the reactive nitrogen species RNS generated in monocytes from both sources. Furthermore, raised levels of superoxide in neutrophils of synovial infiltrate showed a positive correlation with NADPH oxidase activity in synovial fluid. Additionally, as ROS generated in both peripheral blood and synovial infiltrate correlated positively with both DAS 28 and CRP/anti-CCP levels, its measurement can serve as an indirect measure of the degree of inflammation in patients with RA.