METHODS: The cytoprotective role of AEIA was measured on mouse hepatocytes by cell viability assay followed by Hoechst staining and flow cytometric assay. The effect on ROS production, lipid peroxidation, protein carbonylation, intracellular redox status were measured after incubating the hepatocytes with Pb-acetate (6.8 μM) along with AEIA (400 μg/ml). The effects on the expressions of apoptotic signal proteins were estimated by western blotting. The protective role of AEIA was measured by in vivo assay in mice. Haematological, serum biochemical, tissue redox status, Pb bioaccumulation and histological parameters were evaluated to estimate the protective role of AEIA (100 mg/kg) against Pb-acetate (5 mg/kg) intoxication.

RESULTS: Pb-acetate treated hepatocytes showed a gradual reduction of cell viability dose-dependently with an IC50 value of 6.8 μM. Pb-acetate treated hepatocytes exhibited significantly enhanced levels (p < 0.01) of ROS production, lipid peroxidation, protein carbonylation with concomitant depletion (p < 0.01) of antioxidant enzymes and GSH. However, AEIA treatment could significantly restore the aforementioned parameters in murine hepatocytes near to normalcy. Besides, AEIA significantly reversed (p < 0.05-0.01) the alterations of transcription levels of apoptotic proteins viz. Bcl 2, Bad, Cyt C, Apaf-1, cleaved caspases [caspase 3, caspase 8 and caspase 9], Fas and Bid. In in vivo bioassay, Pb-acetate treatment caused significantly high intracellular Pb burden and oxidative pressure in the kidney, liver, heart, brain and testes in mice. In addition, the haematological and serum biochemical factors were changed significantly in Pb-acetate-treated animals. AEIA treatment restored significantly the evaluated-parameters to the near-normal position.

METHODS: This is a prospective cohort study, where cognitive assessments were done 1-day before surgery, at discharge, and during 6 weeks of follow-up. Sample size calculation, accounting for an estimated 20% dropout rate, determined a minimum of 170 subjects were required for the study. Reduction of MMSE score of more than 2.5 was considered as having POCD. Score differences between groups were analysed using T-test and analysis of variance (ANOVA), while consistency between tools was analysed using correlation and regression.

RESULTS: A total of 188 patients completed the study, with a POCD prevalence of 20.2% and 6.9% at discharge and at the 6 week follow up, respectively. All cognitive tools show a significant difference between preoperative and postoperative scores. All tests show a significant moderate correlation with MMSE.

METHODS: Electronic health records were linked to echocardiography data between 2015 and 2021 from patients in Tayside, Scotland (population~450 000). Incident HF diagnosis was classified into inpatient or outpatient and stratified by ejection fraction (EF). A non-HF comparator group with normal left ventricular function was also defined. The primary outcome was time to cardiovascular death or hHF within 12 months of diagnosis.

RESULTS: In total, 5223 individuals were identified, 4231 with HF (1115 heart failure with reduced ejection fraction (HFrEF), 666 heart failure with mildly reduced ejection fraction, 1402 heart failure with preserved ejection fraction and 1048 HF with unknown EF) and 992 with non-HF comparators. Of the 4231 HF patients, 2169 (51.3%) were diagnosed as inpatients. The primary outcome was observed in 1193 individuals with HF (28.1%) and 32 (3.2%) non-HF comparators and was significantly more likely to occur in individuals diagnosed as inpatients than outpatients (809 vs 384 events; adjusted HR: 1.62 (1.39-1.89), p<0.001), and this was consistent regardless of EF. For HFrEF patients first diagnosed as inpatients, those discharged on ≥2 GDMT had a reduced incidence of the primary outcome compared with those discharged on <2 GDMT (303 vs 175 events; adjusted HR: 0.72 (0.55-0.94), p=0.016).

OBJECTIVES: The novel objective of this study is to examine the effects of TRF with low carbohydrate and high protein and fat (LCHPF) diet on control and management of body weight, blood sugar and good cholesterol.

METHODOLOGY: This retrospective cohort study was performed at Clinixero in Kuala Lumpur between February 2021 and August 2023. In an open-label trial, all participants were assigned to one of two intervention groups with varying intervention durations (3 months or 6 months). Three month intervention group consists of Phase 1 TRF of 1.5 months (7 weeks) of a 16:8 h fasting-to-feeding ratio followed by another 1.5 months (7 weeks) of a 23:1 h ratio, whereas in six month intervention group phase 1 TRF comprises 3 months (13 weeks) of a 16:8 h fasting-to-feeding ratio followed by another 3 months (13 weeks) of a 23:1 h ratio. Individual BMI was measured along with fasting blood glucose, HbA1c and lipid profile before and after intervention.

RESULTS: We show that miR-15a is increased in the plasma of diabetic patients, correlating with disease severity. miR-15 plays an important role in insulin production in pancreatic β-cells. By culturing rat pancreatic β-cells (INS-1) cells in high-glucose media, we identified a source of increased miR-15a in the blood as exosomes secreted by pancreatic β-cells. We postulate that miR-15a, produced in pancreatic β-cells, can enter the bloodstream and contribute to retinal injury. miR-15a overexpression in Müller cells can be induced by exposing Müller cells to exosomes derived from INS-1 cells under high-glucose conditions and results in oxidative stress by targeting Akt3, which leads to apoptotic cell death. The in vivo relevance of these findings is supported by results from high-fat diet and pancreatic β-cell-specific miR-15a-/- mice.

INNOVATION: This study highlights an important and underappreciated mechanism of remote cell-cell communication (exosomal transfer of miRNA) and its influence on the development of T2D complications.

OBJECTIVE: The aim of the in silico study was to establish protocols to predict the most effective flavonoid from prenylated and pyrano-flavonoid classes for AChE inhibition linking to the potential treatment of Alzheimer's disease.

METHODOLOGY: Three flavonoids isolated from Artocarpus anisophyllus Miq. were selected for the study. With these compounds, Lipinski filter, ADME/Tox screening, molecular docking and quantitative structure-activity relationship (QSAR) were performed in silico. In vitro activity was evaluated by bioactivity staining based on the Ellman's method.

RESULTS: In the Lipinski filter and ADME/Tox screening, all test compounds produced positive results, but in the target fishing, only one flavonoid could successfully target AChE. Molecular docking was performed on this flavonoid, and this compound gained the score as -13.5762. From the QSAR analysis the IC50 was found to be 1659.59 nM. Again, 100 derivatives were generated from the parent compound and docking was performed. The derivative compound 20 was the best scorer, i.e. -31.6392 and IC50 was predicted as 6.025 nM.