Short-term orlistat therapy improves fatty infiltration indices and liver fibrosis scores in patients with non-alcoholic fatty liver disease and metabolic syndrome

Background and study aimsPatients with non-alcoholic fatty liver disease (NAFLD) exhibit features of metabolic syndrome, including a high body mass index, central obesity, high blood pressure, and abnormal lipid profile values. Orlistat, an intestinal lipase enzyme inhibitor, improves insulin resistance. We aimed to investigate the effects of short-term therapy with orlistat on the components of metabolic syndrome associated with NAFLD and explore its effect on liver fibrosis scores.Patients and methodsAn open-label placebo-controlled clinical study using orlistat for 12 weeks was carried out on 50 patients with NAFLD. They were divided into a placebo group (Group I) and an orlistat treatment group (120 mg per day, Group II). The diagnosis of NAFLD was made by ultrasonography and laboratory investigations. Anthropometric and blood pressure measurements and hepatic liver enzymes, fasting lipids, and blood glucose levels were determined before and after treatment. Lipid indices including cholesterol (Chol-I), triglyceride (TG-I), triglyceride-glucose (TYG-I), and the scores for lipid fibrosis using the NAFLD fibrosis score (NFS) and Fibrosis-4 score (Fib-4) were also determined.ResultsOrlistat significantly improved the anthropometric and metabolic indices (TG-I, TYG-I) and liver enzymes. Orlistat demonstrated a favorable impact on the NAS and Fib-4 scores for liver fibrosis.ConclusionOrlistat improves the components of metabolic syndrome, leading to the improvement of insulin resistance and thereby improves fatty infiltration of the liver. To a lesser extent, orlistat improved the liver fibrosis scores.     

Discovery of Novel Peptidomimetics as Irreversible CHIKV NsP2 Protease Inhibitors Using Quantum Mechanical‐Based Ligand Descriptors

Chikungunya virus (CHIKV) is a mosquito‐borne alphavirus. Recent outbreaks of CHIKV infections have been reported in Asia, Africa, and Europe. The symptoms of CHIKV infection include fever, headache, nausea, vomiting, myalgia, rash, and chronic persistent arthralgia. To date, no vaccines or selective antiviral drugs against this important emerging virus have been reported. In this study, the design, synthesis, and antiviral activity screening of new topographical peptidomimetics revealed three potential prototype agents 3a , 4b, and 5d showing 93–100% maximum inhibition of CHIKV replication in cell‐based assay having EC₉₀ of 8.76–9.57 μg/mL. Intensive molecular modeling studies including covalent docking, lowest unoccupied molecular orbital energies, and the atomic condensed Fukui functions calculations strongly suggested the covalent binding of peptidomimetics 3a , 4b, and 5d to CHIKV nsP2 protease leading to permanent enzyme inactivation via Michael adduct formation between α/β‐unsaturated ketone functionality in our designed peptidomimetics and active site catalytic cysteine1013. Furthermore, small molecular weight peptidomimetics 3a and 4b satisfied the Lipinski rule of five for drug‐likeness and showed promising intestinal absorption and aqueous solubility via computational admet studies making them promising hits for further optimization.     

Laser-Assisted High Speed Machining of 316 Stainless Steel: The Effect of Water-Soluble Sago Starch Based Cutting Fluid on Surface Roughness and Tool Wear

Laser-assisted high speed milling is a subtractive machining method that employs a laser to thermally soften a difficult-to-cut material’s surface in order to enhance machinability at a high material removal rate with improved surface finish and tool life. However, this machining with high speed leads to high friction between workpiece and tool, and can result in high temperatures, impairing the surface quality. Use of conventional cutting fluid may not effectively control the heat generation. Besides, vegetable-based cutting fluids are invariably a major source of food insecurity of edible oils which is traditionally used as a staple food in many countries. Thus, the primary objective of this study is to experimentally investigate the effects of water-soluble sago starch-based cutting fluid on surface roughness and tool’s flank wear using response surface methodology (RSM) while machining of 316 stainless steel. In order to observe the comparison, the experiments with same machining parameters are conducted with conventional cutting fluid. The prepared water-soluble sago starch based cutting fluid showed excellent cooling and lubricating performance. Therefore, in comparison to the machining using conventional cutting fluid, a decrease of 48.23% in surface roughness and 38.41% in flank wear were noted using presented approach. Furthermore, using the extreme learning machine (ELM), the obtained data is modeled to predict surface roughness and flank wear and showed good agreement between observations and predictions.     

Toxicity of fungicides to Pisum sativum: a study of oxidative damage,growth suppression,cellular death and morpho-anatomical changes

Considering the fungicidal threat to the sustainable agro-environment, the toxicological impacts of three fungicides, namely kitazin, hexaconazole and carbendazim, on the biological, chemical and morpho-anatomical changes of peas were assessed. Fungicide applications in general caused a slow but gradual reduction in growth, symbiosis and yields of peas, which, however, varied appreciably among species and concentrations of the three fungicides. Of the three fungicides, carbendazim had the most lethal effect, in which it delayed seed germination and also diminished the overall pea growth. Carbendazim at 3000 μg kg⁻¹ maximally reduced the germination, SVI, size of roots and shoots and total dry matter accumulation in roots, shoots and whole plants distinctly by 40%, 84%, 72%, 73%, 68%, 75% and 73% (p ≤ 0.05), respectively. Hexaconazole at 120 μg kg⁻¹ significantly (p ≤ 0.05) declined total chlorophyll, carotenoids, grain yields, grain protein, root P and shoot N by 19%, 28%, 46%, 69%, 48% and 51%, respectively, over the control. The synthesis of stress biomarkers and oxidative stress were increased with increasing dosage rates of fungicides. Proline content in roots, shoots, leaves and grains, MDA, electrolyte leakage and H₂O₂ of plants grown in soil treated with 288 μg kg⁻¹ kitazin were increased significantly (p ≤ 0.05) by 73%, 52%, 41%, 24%, 59%, 40% and 27%, respectively, relative to the control. Antioxidant defence enzymes were greater in pea foliage. The SEM and CLSM images revealed an obvious alteration in root tips, enhanced cellular damage and cell death when plants were raised under fungicide stress. Also, morpho-anatomical variations in fungicide-treated foliage were visible in the SEM images. Overall, the present study suggests that a careful and secure strategy should be adopted before fungicides are chosen for enhancing pulse production in different agro-climatic regions.

Considering the fungicidal threat to the sustainable agro-environment, the toxicological impacts of three fungicides, namely kitazin, hexaconazole and carbendazim, on the biological, chemical and morpho-anatomical changes of peas were assessed.