METHODS: The ATGL-predicted protein structure, verified by PROCHECK, was determined using AlphaFold. Molecular docking, molecular dynamics simulation, and prime molecular mechanic-generalized born surface area were performed using LigPrep, Desmond, and prime MM-GBSA modules of Schrödinger software release 2021-2, respectively. For pharmacological validation, immunoblotting was performed to assess ATGL protein expression. The fluorescence intensity and glycerol concentration were quantified to evaluate the efficiency of phillyrin in inhibiting ATGL.
AIM OF THE STUDY: This study explores the anti-inflammatory effect of TPTQ in silico, in vitro, and in vivo.
MATERIALS AND METHODS: In silico testing used the Gnina application, opened via Google Colab. The TPTQ structure was docked with the nuclear factor kappa B (NF-ĸB) protein (PDB: 2RAM). In vitro testing began with testing the cytotoxicity of TPTQ against Raw 264.7 cells, using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) method. A phagocytic activity test was carried out using the neutral red uptake method, and interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) secretion tests were carried out using the enzyme-linked immunosorbent assay (ELISA) method. In vivo, tests were carried out on mice by determining cluster of differentiation 8+ (CD8+), natural killer cell (NK cell), and IL-6 parameters, using the ELISA method.
RESULTS: TPTQ has a lower binding energy than the native ligand and occupies the same active site as the native ligand. TPTQ decreased the phagocytosis index and secretion of IL-6 and TNF-α experimentally in vitro. TPTQ showed significant downregulation of CD8+ and slightly decreased NK cells and IL-6 secretion in vivo.
CONCLUSION: The potent inhibitory effect of TPTQ on the immune response suggests that TPTQ can be developed as an anti-inflammatory agent, especially in the treatment of Covid-19.
AIM OF THE STUDY: To investigate the ability of CB to ameliorate H2O2-induced oxidative stress in testes and sperm in mice and prevent H2O2-induced oxidative in human sperm.
MATERIALS AND METHODS: Oxidative stress was induced in male mice by pre-exposure to 2% H2O2 orally for seven consecutive days, followed by 100 and 200 mg/kg b. w. administration. CB for another seven days. At the end of treatment, mice were sacrificed and testes and epididymal sperm were harvested. Serum FSH, LH and testosterone levels were measured and sperm parameters were obtained. Meanwhile, oxidative stress levels in mice testes and sperm, steroidogenesis and spermatogenesis markers in mice testes were assessed by molecular biological techniques. In another experiment, sperm from thirty-two healthy fertile men were incubated with 200 μM H2O2 and CB (100 and 200 μg/ml) simultaneously and were then evaluated for sperm parameter changes.
RESULTS: In mice, CB administration ameliorates persistent increases in oxidative stress and decreases in anti-oxidative enzyme levels in testes and sperm following H2O2 pre-exposure. Additionally, CB also helps to ameliorate deterioration in sperm parameters and testicular steroidogenesis and spermatogenesis and restores the serum FSH, LH and testosterone levels near normal in mice. In humans, CB helps to prevent deterioration in sperm parameters following H2O2 exposure.
CONCLUSION: CB is potentially useful to preserve the male reproductive capability and subsequently male fertility in high oxidative stress conditions.
PURPOSE: The present study seeks to determine if TLP would prevent HFD-induced NAFLD in vivo and its underlying mechanisms from the perspectives of gut microbiota, metabolites, and hepatic inflammation.
METHODS: TLP was subjected to extraction and chemo-profiling, and in vivo evaluation in HFD-fed rats on hepatic lipid and inflammation, intestinal microbiota, short-chain fatty acids (SCFAs) and permeability, and body weight and fat content profiles.
RESULTS: The TLP was primarily constituted of gallic acid, corilagin and chebulagic acid. Orally administered HFD-fed rats with TLP were characterized by the growth of Ligilactobacillus and Akkermansia, and SCFAs (acetic/propionic/butyric acid) secretion which led to increased claudin-1 and zonula occludens-1 expression that reduced the mucosal permeability to migration of lipopolysaccharides (LPS) into blood and liver. Coupling with hepatic cholesterol and triglyceride lowering actions, the TLP mitigated both inflammatory (ALT, AST, IL-1β, IL-6 and TNF-α) and pro-inflammatory (TLR4, MYD88 and NF-κB P65) activities of liver, and sequel to histopathological development of NAFLD in a dose-dependent fashion.
CONCLUSION: TLP is promisingly an effective therapy to prevent NAFLD through modulating gut microbiota, mucosal permeability and SCFAs secretion with liver fat and inflammatory responses.
OBJECTIVE: This study aims to identify and compare photoaging rat models exposed to UVA and UVB.
METHODS: This research method compared macroscopic (scoring degree of wrinkling) and microscopic (histology) signs and symptoms on skin samples of rat exposed to UVA and UVB for 4 weeks at a radiation dose of 840mJ/cm2.
RESULTS: The results of this study indicated that the degree of wrinkling was highest in rat skin exposed to UVB rays by 51% (p<0.05). UVB histological results showed that the epidermis layer (40 µm, p<0.05) was thickened and the dermis layer (283 µm, p<0.05) was thinned in the skin of mice exposed to UVB light. The UVB group, showed the density of collagen in the dermis with a mean value of 55% (p<0.05).
CONCLUSION: Our results suggest that short-term exposure to UVB radiation (in the acute, subacute or subchronic phase) induces more rapid and pronounced damage to rat skin when compared to UVA radiation exposure.