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The present study aimed to investigate the effect of benzoxime on leukemia RBL-1 cell proliferation and a leukemic Sprague-Dawley rat model. Proliferation of RBL-1 cells was determined using an MTT assay. Sprague-Dawley rats were assigned randomly into three groups of 10 animals each, where the positive control group was administered an intravenous injection of normal saline, the negative control group was administered 1×106 RBL-1 cells and the treatment group was administered with 1×106 RBL-1 cells and then benzoxime (50 mg/kg/day) for 1 week. Increased dosage of benzoxime reduced RBL-1 cell viability from 92 at 2 µM to ٢١٪ at ١٢ µM after ٢٤ h. Benzoxime treatment prevented the loss of body weight in the rats with leukemia. Compared with the negative control rats, the body weight was determined to be significantly reduced (P<0.05) in the positive control rats. The weight of the spleen and liver was determined to be significantly increased (P<0.02) in the positive control rats and the benzoxime-treated rats compared with that in the negative control group on day 35 of RBL-1 cell implantation. Analysis of leukocytes in rats on day 35 demonstrated a significant reduction (P<0.05) in the cluster of differentiation (CD)11b and CD45 level in the positive control group compared with that in the negative control group. The level of CD11b and CD45 was determined to be similar in the rats in the benzoxime treatment and negative control groups. Analysis of the level of serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase and blood urea nitrogen indicated that all three components exhibited no significant changes in the rats following treatment with benzoxime compared with the component levels in the negative control group. The levels of these three components were in the normal range in rats treated with benzoxime on day 35 of cell implantation. These data demonstrated that the liver and kidneys are not influenced by benzoxime in rats with leukemia. In summary, the present study demonstrated that benzoxime efficiently prevents leukemia growth without inducing any harmful effects in rat models through targeting CD11b and CD45 level; thus, benzoxime should be evaluated further regarding its use in the treatment of leukemia. [ABSTRACT FROM AUTHOR]

The clinical efficacy and mechanism of Pralatrexate (PTX) combined with Palbociclib Isethionate (PAL) in the treatment of bladder cancer patients was investigated. A retrospective analysis of medical records of 82 bladder cancer patients admitted to Shengjing Hospital of China Medical University from February 2015 to February 2018 was performed. Patients treated with PTX combined with PAL served as study group (42 cases) and patients with conventional GC (gemcitabine plus cisplatin) chemotherapy regimen were the control group (40 cases). Changes in liver function indexes before and after treatment were observed, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil). RT-qPCR was used for detection of relative expression levels of serum dihydrofolate reductase (DHFR) and vascular endothelial growth factor (VEGF) before and after treatment in the two groups. The clinical efficacy after treatment and adverse reactions during treatment were observed in the two groups. There was no significant difference in the clinical remission rate (RR) nor in the serum ALT, AST, ALP and TBil levels between the study and the control groups (P>0.05). Concentrations of serum ALT, AST, ALP and TBil were significantly higher than those before treatment in both groups (P<0.05). Serum ALT, AST, ALP and TBil concentrations in study group were significantly lower than those in control group (P<0.05). There was no significant difference in the incidence of thrombocytopenia and leukopenia between the two groups (P>0.05). There was no significant difference in relative expression levels of serum DHFR mRNA and VEGF mRNA before treatment between the study and control groups (P>0.05). Those after treatment were significantly lower than those before treatment in both groups (P<0.05), and those after treatment in study group were significantly lower than those in control group (P<0.05). PTX combined with PAL can reduce adverse reactions of nausea and vomiting and liver function impairment during treatment and suppress tumor neovascularization. This is achieved possibly by inhibiting expression levels of DHFR and VEGF, thereby killing cancer cells. PTX combined with PAL may become a new method for the treatment of bladder cancer patients. DHFR and VEGF are expected to become novel therapeutic targets for the treatment of bladder cancer. [ABSTRACT FROM AUTHOR]

Isopsoralen (IPRN), which comes from the fruit of Psoralea corylifolia, has been identified as a kind of phytoestrogen and has been proven to be effective for the treatment of osteoporosis (OP). However, the mechanisms underlying IPRN's anti-OP effects, especially the anti-postmenopausal osteoporosis (PMOP) effects, remain indistinct. Thus, this study aimed to investigate the effects and mechanisms of IPRN's anti-PMOP activity. In this study, the bioinformatics results predicted that IPRN could resist PMOP by targeting EGFR, AKT1, SRC, CCND1, ESR1 (ER-α), AR, PGR, BRCA1, PTGS2, and IGF1R. An ovariectomized (OVX) mice model and a H 2 O 2 -induced bone marrow mesenchyml stem cells (BMSCs) model confirmed that IPRN could inhibit the bone loss induced by OVX in mice and promote the osteogenic differentiation in H 2 O 2 -induced BMSCs by inhibiting oxidative stress and apoptosis. Moreover, IPRN could significantly produce the above effects by upregulating ESR1. IPRN might be a therapeutic agent for PMOP by acting as an estrogen replacement agent and a natural antioxidant., (© 2022 John Wiley & Sons Ltd.)

Background: This study was designed to elucidate the role of DNMT3a and PPARγ functions in postmenopausal osteoporosis. Materials & methods: Mice were ovariectomized to establish an in vivo osteoporosis model and MC3T3-E1-14 osteoblasts were induced to differentiate. Gain- or loss-of-function approaches were used to manipulate the expression of PPARγ , DNMT3a  and SCD1 , followed by an evaluation of their role in postmenopausal osteoporosis both in vivo and in vitro . Results: DNMT3a induced methylation of the PPARγ promoter region, consequently stimulating osteoblast differentiation. PPARγ elevated SCD1 , which decreased GLUT1 and inhibited osteoblast differentiation. Inhibition of PPARγ reduced SCD1 while increasing GLUT1 expression, thus alleviating postmenopausal osteoporosis in mice. Conclusion: DNMT3a promotes osteoblast differentiation and prevents postmenopausal osteoporosis by regulating the PPARγ / SCD1 / GLUT1 axis.

Multi-drug resistance (MDR) is one of the obstacles for leukemia therapy, the major cause is an overexpression of P-glycoprotein (P-gp) leading to increased drug efflux. We investigated the reversion of multi-drug resistance and the possible mechanism by which the proteasome inhibitor bortezomib affects the expression of the multi-drug resistance gene mdrl in the K562/DNR cell line. The drug resistance of the cells and the cellular toxicity of bortezomib were confirmed by MTT. Intracellular drug concentrations and cell apoptosis were detected by flow cytometry. The expression of mdrl mRNA was examined by fluorescence quantitative PCR. The expression levels of nuclear factor-kappa B (NF-kappaB), inhibitor of NF-kappaB (IkappaB) and P-gp were detected by western blotting, and NF-kappaB activity was detected by ELISA. DNR-induced apoptosis increased in a dose-dependent manner after adding bortezomib. Bortezomib decreased IkappaB degradation, decreased NF-kappaB and NF-kappaB p65 activity, reduced P-gp/mdr1 mRNA expression, and increased the intracellular DNR concentration in K562/DNR cells in vitro. The bortezomib reversed leukemic multi-drug resistance in a dose-dependent manner as the result of decreasing IkappaB degradation, thus preventing the translocation of NF-kappaB into the nucleus and leading the down-regulation of mdr1 and a reduction in P-gp expression. Therefore, the intracellular drug concentration increased, and then apoptosis was induced.