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Resveratrol (Res) is a natural polyphenolic compound found in several plants and reported as a promising biological molecule with effective anti-fibrosis and anti-inflammatory activities. However, the underlying mechanism of Res on systemic sclerosis (SSc) remains unclear. In the study, we identified the key cellular signaling pathways involved in the Res regulatory process on SSc.

Res-targeted genes interaction network was constructed using the STITCH database, and the shared Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in both SSc and Res-targeted genes were then identified. The top five enriched KEGG pathways were visualized by GOplot. KEGG pathways associated with Res-targeted genes were established by Pathway Builder Tool 2.0. Quantitative real-time PCR (qRT-PCR) was used to assess the expression of sirtuin 1 (SIRT1), mammalian targeted of rapamycin (mTOR), and cytokines.

Enrichment analysis of Res-targeted genes showed 79 associated pathways, 27 of which were also involved in SSc. Particularly, SIRT1/mTOR signaling was found as one of the crucial regulatory pathways. In vitro results suggested that SIRT1-mediated mTOR degradation ameliorated bleomycin (BLM)-induced fibrosis and inflammation. Res was capable of elevating the SIRT1 level in fibroblasts and partially reversing mTOR-dependent induction of fibrosis and inflammation.

These results indicated that Res is a feasible and effective choice for SSc and therapeutic target of mTOR could be a potential alternative for treatment of SSc.

These results indicated that Res is a feasible and effective choice for SSc and therapeutic target of mTOR could be a potential alternative for treatment of SSc.

The present work aimed at challenging the efficacy of natural gums, karaya and locust bean gum, as matrix-forming polymers for the formulation of sustained-release tablets of diltiazem, a model drug.

Central design composite was adopted for the formulation and optimization of tablet formulations. The two gums have been selected as independent variables. click here The dependent factors chosen were the amount of drug released in 1st hour (Y1), amount of drug released after 12 h (Y2), diffusion exponent (Y3), and time for half of the total drug released (T

) (Y4). Wet granulation approach was used for the formulation of tablets. FT-IR, DSC, in vitro dissolution, swelling-erosion investigations, SEM, and stability studies were carried out.

It was evident that the release pattern from the prepared formulations was significantly influenced by the quantity of gum(s) in the tablet. FT-IR and DSC results confirm drug-polymer compatibility. Polynomial equations were used for the prediction of quantitative impact of independent factors at different levels on response variables. After ANOVA analysis, the significant factors were considered for constrained optimization to get the optimized formula. The optimized formula generated by the response surface methodology was evaluated both for in vitro and in vivo properties. The optimized formula and a sustained-release marketed product were subjected to in vivo studies in rabbits and the results of the

-test demonstrated insignificant variation in pharmacokinetic parameters among the two formulations, confirming that the prepared tablet showed sustained-release profile.

The results indicated that karaya and locust bean gum can be effectively used to formulate sustained-release tablets.

The results indicated that karaya and locust bean gum can be effectively used to formulate sustained-release tablets.

Glioma is the most common malignant tumor of the nervous system, which accounts for more than 45% of central nervous system tumors and seriously threatens our health. Because of high mortality rate, limitations, and many complications of traditional treatment methods, new treatment methods are urgently needed. β-Mangostin is a natural compound derived from the fruit of

L. and it has anticancer activity in several types of cancer cells. However, the antitumor effect of β-mangostin in glioma has not been clarified. Hence, this study aimed to investigate its therapeutic effects on gliomas.

To study the effect of β-mangostin on glioma cells, cell viability assay, reactive oxygen species production, cell cycle, apoptosis, and mitochondrial membrane potential were evaluated in the C6 cell line in vitro. Immunofluorescence and Western blotting were used to analyze protein expression and phosphorylation to study its mechanism of action. A subcutaneous xenograft model was used to investigate the effect of β-mangostin on tumorigenesis in vivo.

We found that β-mangostin can inhibit glioma cell growth and induce oxidative damage in vitro. In addition, it reduces the phosphorylated form levels of PI3K, AKT and mTOR. Furthermore, the phosphorylated form levels of PI3K, AKT and mTOR were increased after the PI3K inhibitor was added. In vivo experiments showed that β-mangostin can inhibit tumor growth as shown by its reduced size and weight.

This study suggests that β-mangostin can inhibit cell proliferation and induce oxidative damage in cells. It is the first study to demonstrate that β-mangostin induces oxidative damage in glioma cells by inhibiting the PI3K/AKT/mTOR signaling pathway.

This study suggests that β-mangostin can inhibit cell proliferation and induce oxidative damage in cells. It is the first study to demonstrate that β-mangostin induces oxidative damage in glioma cells by inhibiting the PI3K/AKT/mTOR signaling pathway.

To investigate the effects of sildenafil citrate (SC) on live birth rates (LBR) during women undergoing their first frozen embryo transfers (FET) with hormone replacement therapy (HRT).

This retrospective cohort study included a total of 10,069 infertile women with adequate endometrial thickness (≥7 mm when progesterone was initiated) in their first FET cycle with hormone replacement therapy. Women received either vaginal SC or no adjuvant during their first transfer cycle depending on patient or physician preference. In the sildenafil group, 1098 women underwent HRT FET with adjuvant vaginal use of SC, and 8971 women were included as controls. The primary outcome measure was LBR, defined as the likelihood of live birth per transfer cycle. Endometrial thickness (EMT), implantation, chemical pregnancy, clinical pregnancy, miscarriage, ongoing pregnancy, birth weight and preterm delivery (PTB) were also recorded.

Baseline characteristics were comparable between the two groups. In the crude analysis, the unadjusted LBR was significantly higher in the vaginal SC group (scHRT-FET) than in the control group (HRT-FET) (40.