Ginsenoside-Rg1 combined with a conditioned medium from induced neuron-like hUCMSCs alleviated the apoptosis in a cell model of ALS through regulating the NF-κB/Bcl-2 pathway / 中国天然药物

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons in the brain and spinal cord. One important aspect of ALS pathogenesis is superoxide dismutase 1 (SOD1) mutant-mediated mitochondrial toxicity, leading to apoptosis in neurons. This study aimed to evaluate the neural protective synergistic effects of ginsenosides Rg1 (G-Rg1) and conditioned medium (CM) on a mutational SOD1 cell model, and to explore the underlying mechanisms. We found that the contents of nerve growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor significantly increased in CM after human umbilical cord mesenchymal stem cells (hUCMSCs) were exposed to neuron differentiation reagents for seven days. CM or G-Rg1 decreased the apoptotic rate of SOD1G93A-NSC34 cells to a certain extent, but their combination brought about the least apoptosis, compared with CM or G-Rg1 alone. Further research showed that the anti-apoptotic protein Bcl-2 was upregulated in all the treatment groups. Proteins associated with mitochondrial apoptotic pathways, such as Bax, caspase 9 (Cas-9), and cytochrome c (Cyt c), were downregulated. Furthermore, CM or G-Rg1 also inhibited the activation of the nuclear factor-kappa B (NF-κB) signaling pathway by reducing the phosphorylation of p65 and IκBα. CM/G-Rg1 or their combination also reduced the apoptotic rate induced by betulinic acid (BetA), an agonist of the NF-κB signaling pathway. In summary, the combination of CM and G-Rg1 effectively reduced the apoptosis of SOD1G93A-NSC34 cells through suppressing the NF-κB/Bcl-2 signaling pathway (Fig. 1 is a graphical representation of the abstract).

Efficacy of mesalazine in combination with bifid triple viable capsules on ulcerative colitis and the resultant effect on the inflammatory factors

Present investigation is conducted to investigate the clinical efficacy of mesalazine in combination with the Bifid Triple Viable Capsules on the ulcerative colitis [UC] and the resultant effect on the inflammatory factors [TNF-alpha, IL-8 and IL-10] of UC patients. A total of 120 UC patients who were admitted to this hospital for treatment between May 2014 and February 2018 were enrolled in this study and divided randomly into the research group and control group, with 60 patients in each group. For patients in the two groups, they underwent medication via mesalazine, while those in the research group additionally received the medication by Bifid Triple Viable Capsules. Following treatment, we evaluated the clinical efficacy, as well as the disease activity index [DAI] of UC, score of clinical symptoms, changes in the inflammatory factors [TNF-alpha, IL-8 and IL-10] and the adverse reactions to drugs before and after treatment. The total effectiveness rate in the research group was 90.0%, significantly higher than 72.5% in the control group, and the difference had statistical significance [P < 0.05]. Before treatment, we assessed the UCDAI and clinical symptoms, and found that there were no statistically significant differences in these indicators between two groups [P>0.05]; however, after treatment, both of UCDAI and clinical symptoms scores were decreased evidently in two groups [P<0.05], while the decreases in the research group were more significant [P < 0.05]. In addition, following treatment, the levels of TNFalpha and IL-8 were all decreased in two groups, with an acute increase in IL-10 [all P<0.01], and the alterations in these indicators in the research group were much more significant than those in the control group [all P <0.05]. For adverse reactions, the incidence rate in the research group was 6.67%, significantly lower than 33.33% in the control group [P <0.05]. Mesalazine in combination with Bifid Triple Viable Capsules shows a magnificent protective effect on the mucosa of UC patients, and curb the UC-related inflammatory reactions effectively. Thus, it is a safe and reliable method that is worthy of being promoted in clinical practice

Inhibition of Toll-like receptor 9 activation in microglia after oxygen-glu-cose deprivation and reoxygenation protects neurons from damage / 中国病理生理杂志

AIM:To observe the Toll-like receptor 9 (TLR9) activation in microglia BV-2 cells after oxygen-glucose deprivation and reoxygenation ( OGDR) , and its effects on neuronal apoptosis.METHODS:The BV-2 cell super-natants were collected after the corresponding treatment and added to mouse primary cortical neurons after OGDR for 4 h, followed by normal culture for 24 h.The cells were divided into normal BV-2 group, NC-siRNA group, TLR9-siRNA group, OGDR group, OGDR+NC-siRNA group, OGDR+TLR9-siRNA group and control group (without adding BV-2 cell supernatant) .The changes of the neuronal morphology were observed under an inverted phase-contrast microscope, and the neuronal apoptosis was detected by TUNEL.The protein expression of cleaved caspase-3 was detected by Western blot-ting.RESULTS:After OGDR, the axon turned thin, twisted and broken, and neuronal swelling, decrease in refraction and vacuolar degeneration were observed.The green-stained apoptotic bodies in the neurons in all groups were positive. Compared with control group, the caspase-3 protein levels in other groups were increased.Compared with the normal BV-2 group, the caspase-3 protein in OGDR group and TLR9-siRNA group was increased.Compared with OGDR+TLR9-siRNA group, the caspase-3 protein in TLR9-siRNA group and OGDR group was decreased.CONCLUSION: After OGDR, TLR9 activation in BV-2 cells induces neuronal apoptosis with the increase in caspase-3 protein level.Inhibition of TLR9 expression reduces neuronal damage.