Search

Meibomian gland dysfunction (MGD), complicated by type 2 diabetes, is associated with a high incidence of ocular surface disease, and no effective drug treatment exists. Diabetes mellitus (DM) MGD shows a notable disturbance in lipid metabolism. Er-Dong-Xiao-Ke decoction (EDXKD) has important functions in nourishing yin, clearing heat, and removing blood stasis, which are effective in the treatment of DM MGD. To observe the therapeutic effect of EDXKD on DM MGD and its underlying molecular mechanism. After establishing a type 2 DM (T2DM)-induced MGD rat model, different doses of EDXKD and T0070907 were administered. The chemical constituents of EDXKD were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the molecular mechanism of EDXKD in treating DM MGD was predicted using network pharmacology. Lipid metabolism in DM meibomian glands (MGs) was analyzed using LC-MS/MS, and lipid biomarkers were screened and identified. Histological changes and lipid accumulation in MGs were detected by staining, and Peroxisome proliferator-activated receptor gamma (PPARG) expression in MG acinar cells was detected by immunofluorescence. The expression of lipid metabolism-related factors was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) or western blotting. EDXKD reduced lipid accumulation in the MGs and improved the ocular surface index in DM MGD rats. The main active components of EDXKD had advantages in lipid regulation. Additionally, the PPARG signaling pathway was the key pathway of EDXKD in the treatment of DM MGD. Twelve lipid metabolites were biomarkers of EDXKD in the treatment of DM MGD, and glycerophospholipid metabolism was the main pathway of lipid regulation. Moreover, EDXKD improved lipid deposition in the acini and upregulated the expression of PPARG. Further, EDXKD regulated the PPARG-mediated UCP2/AMPK signaling network, inhibited lipid production, and promoted lipid transport. EDXKD is an effective treatment for MGD in patients with T2DM. EDXKD can regulate lipids by regulating the PPARG-mediated UCP2/AMPK signaling network, as it reduced lipid accumulation in the MGs of DM MGD rats, promoted lipid metabolism, and improved MG function and ocular surface indices. [Display omitted] • Meibomian glands play a key role in maintaining homeostasis of the ocular surface • Hyperglycemia leads to abnormal lipid metabolism in meibomian gland • PPARG is an important regulator of glucose and lipid metabolism • Er-Dong-Xiao-Ke Decoction is an effective treatment for type 2 diabetes mellitus meibomian gland dysfunction [ABSTRACT FROM AUTHOR]

Objective. To study the mechanism of curcumol affecting the proliferation and apoptosis of liver cancer cells through the DJ-1/PTEN/PI3K/AKT pathway. Method. HepG2 cells were cultured in vitro, treated with curcumol at concentrations of 10, 30, and 100 μg/mL, and DMSO was used as a control. The levels of cell proliferation and apoptosis were measured by CCK-8 and flow cytometry, respectively. RT-PCR and western blot were used to detect PTEN, p-AKT, DJ-1, and PI3K gene and protein expression changes. Result. (1) Compared with the DMSO blank control group, the proliferation level of liver cancer cells in the 10 μg/mL curcumol group decreased, and the proportion of apoptosis increased (p <0.05). (2) Compared with the blank control group and the 10 and 30 μg/mL concentration groups, the proliferation level of liver cancer cells in the 100 μg/mL curcumol group was significantly reduced, and the proportion of cell apoptosis was significantly increased (p < 0.05). (3) Curcumol can significantly increase the expression of PTEN gene and protein in liver cancer cells and reduce the expression of DJ-1 and PI3K genes and protein in liver cancer cells (p < 0.05). Conclusion. Curcumol can regulate DJ-1, PTEN, PI3K, and AKT signal transduction pathways, inhibit cell proliferation, and cause a significant increase in the proportion of cell apoptosis, and the pharmacodynamic effect of curcumol is dependent on the time and dose of action. [ABSTRACT FROM AUTHOR]

Erxian Decoction (EXD) has been used empirically for more than 70 years to treat premature ovarian failure (POF), but more research is needed to understand how it works. The study aims to ascertain both in vivo and in vitro rewards of EXD. EXD is composed of Curculiginis Rhizoma, Epimedii Folium, Morindae Officinalis, Angelicae Sinensis, Anemarrhenae Rhizoma, and Phellodendri Chinensis Cortex. UPLC/MS analysis was used to investigate the components of EXD. Using a POF model created by administering cisplatin to rats intraperitoneally, the pharmacodynamic effects of EXD were investigated. Three dose groups of EXD were garaged into rats: high (15.6 g/kg), medium (7.8 g/kg), and low (3.9 g/kg). By using a vaginal smear, the impact of EXD on the rat estrous cycle was evaluated. An ELISA test was used to measure the anti-Mullerian hormone (AMH), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels in the serum of rats. By using HE stains, pathological alterations in the ovaries may be seen. MDA and SOD levels in ovarian samples were used to measure the degree of ovarian oxidation. TUNEL labeling of ovarian sections was used to find apoptosis levels. By using ATP, energy production was evaluated. The relative expression of proteins connected to aging and the RAGE pathway was assessed using Western blot. Then, using H 2 O 2 , a model of senescent human ovarian granulosa cells (KGN) was created in vitro. The impact of EXD and H 2 O 2 on cellular senescence was discovered using-galactosidase staining. Cell apoptosis levels were found using PI/Hoechest33342. By using DCFH-DA, intracellular ROS was examined. MDA and SOD concentrations were used to measure the degree of cellular oxidation. RAGE-related mRNA and protein expression were evaluated using RT-qPCR and western blotting. Using UPLC/MS analysis, 39 chemicals in EXD were found. Rats' estrous cycles were enhanced by EXD, which increased ovarian index and follicle count and reduced the proportion of atretic follicles in the rats. EXD reduced LH and FSH output while restoring AMH and E2 secretion. In ovarian tissues, EXD reduced the amount of apoptosis and MDA while raising SOD activity and ATP levels. The protein levels of p16, p21, p53, and Lamin A/C were among the senescence-related proteins that EXD lowered, along with the levels of RAGE, PI3K, BAX, and CASPASE 3. Anti-apoptotic protein BCL-2 was also raised in the RAGE pathway. Senescence, apoptosis, ROS, and MDA levels in the KGN cells were lowered in vitro by EXD. Additionally, EXD increased the anti-apoptotic potential by changing the expression of CAT, SOD2, and SIRT1. RAGE, BAX, BCL-2, CASPASE 3, and p38 expression levels were altered by EXD, enhancing its anti-apoptotic capability. EXD boosted the ovary's antioxidant and anti-apoptotic capabilities while enhancing the estrous cycle and hormone output. These findings strongly suggested that EXD may contribute to the alleviation of POF and ovarian granulosa cells senescence. [Display omitted] • This study verified the protective effect of Erxian decoction on premature ovarian failure in vivo and in vitro. • Erxian decoction could protect senescent ovarian granulosa cells. Erxian decoction could regulate the RAGE pathway. [ABSTRACT FROM AUTHOR]

Highlights: [•] TCDD induces inflammatory activation by increasing levels of Ca2+ in microglial cells. [•] TCDD upregulates the expression and secretion of TNF-α in HAPI microglial cells. [•] TCDD activates NF-κB signaling pathways in HAPI microglial cells. [•] TCDD causes a rapid activation of cPLA2 and COX-2 in HAPI microglial cells [Copyright &y& Elsevier]