Genistin Represses the Proliferation and Angiogenesis While Accelerating the Apoptosis of Glioma Cells by Modulating the FOXC1-Mediated Wnt Signaling Pathway.

BACKGROUND: Glioma is a tumor originating from glial cells and is the most common primary brain tumor. At present, the main treatment methods for glioma include surgical resection and radiotherapy and chemotherapy, but the treatment effect is not very ideal. Genistin (GS) inhibits breast cancer cell growth while promoting apoptosis, but its effect and detailed molecular mechanism on glioma are yet to be defined. In addition, forkhead box C1 (FOXC1) has been found to be involved in the growth, invasion, and angiogenesis processes of glioma cells. METHODS: Human glioma cells in the Control, GS-6.25, GS-12.5, and GS25 (GS) groups were treated with 0, 6.25, 12.5, and 25 µM of Genistin, respectively, for 72 hours, and cells in the GS + NC (negative control) and GS + FOXC1 groups were transfected with negative control or forkhead box C1 (FOXC1) overexpression plasmids, respectively, prior to Genistin (25 µM) treatment for 72 hours. Next, the viability, proliferation, apoptosis, and angiogenesis of treated glioma cells were detected using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'deoxyuridine (EdU) proliferation, flow cytometry, and tube formation assays. Meanwhile, the half-maximal inhibitory concentration (IC50) of Genistin in the treated glioma cells was calculated. Afterwards, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot quantified the levels of FOXC1, Wnt1, Wnt3a, glycogen synthase kinase-3ß (GSK3ß), and phosphorylated GSK3ß (p-GSK3ß). RESULTS: Genistin inhibited viability, proliferation, and angiogenesis while promoting the apoptosis of glioma cells (p < 0.05, p < 0.001). Also, Genistin decreased the levels of FOXC1, Wnt1, and Wnt3a while increasing p-GSK3ß levels in glioma cells (p < 0.05, p < 0.01, p < 0.001). FOXC1 was up-regulated in glioma cells and tissues, and overexpressed FOXC1 overturned the effects of Genistin on the abovementioned factors in glioma cells (p < 0.05, p < 0.001). CONCLUSIONS: Genistin inhibits viability, proliferation, and angiogenesis while accelerating glioma cell apoptosis by modulating the FOXC1-mediated Wnt signaling pathway.

Toxicity of Melastoma dodecandrum Lour. and its effects on lipopolysaccharide-induced inflammation and oxidative stress.

Melastoma dodecandrum Lour. (MDL) is component used in traditional Chinese medicine that is widely distributed throughout southern China. MDL has been long utilized in clinical treatment for various conditions, such as inflammation. However, the toxicity and underlying anti-inflammatory mechanism of MDL remain to be elucidated. In the present study, Sprague-Dawley rats received intragastric administration of MDL for 2 months, and the toxicity of MDL was investigated. The rats were treated with lipopolysaccharide (LPS) for 8 h to determine the potential anti-inflammatory mechanism of MDL. The results demonstrated that MDL alone did not affect the expression levels of factors associated with inflammation (IL-1ß, IL-6 and TNF-α) and oxidative stress [malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO)] in the rat serum and exerted no effects on rat liver and kidneys. By contrast, MDL attenuated LPS-induced inflammation and oxidative stress by regulating specific cytokines, such as IL-1ß, IL-6, TNF-α, MDA, SOD and NO in the rat serum and alleviated LPS-induced liver and kidney damage. Additionally, compared with the LPS group, MDL inhibited CD4+ T cell differentiation into Th1 and Th17 cells and enhanced CD4+ T cell differentiation into Th2 and Treg cells. MDL also suppressed reactive oxygen species (ROS) production and mitochondrial apoptosis by modulating mitochondrial apoptosis-related proteins in spleen CD4+ T cells. In conclusion, the results of the present study demonstrated the non-toxic nature of MDL and revealed that it alleviated LPS-induced inflammation and oxidative stress by regulating differentiation and ROS production in CD4+ T cells.

The effect of Bailemian on neurotransmitters and gut microbiota in p-chlorophenylalanine induced insomnia mice.

Bailemian (BLM) is reportedly used for the treatment of insomnia as a traditional Chinese medicine in China for many years. However, the anti-insomnia mechanisms of BLM are still unknown. The present study aims to investigate the anti-insomnia activity of BLM by evaluating its influence on the relevant neurotransmitters and gut microbiota in p-chlorophenylalanine (PCPA) induced insomnia mice. The results indicated that the level of GABA, 5-HT, DA, and NE is significantly decreased in the PCPA-induced insomnia model group compared with the control group, while the level of Glu is higher than the control group. Treatment with BLM could ameliorate the symptoms of insomnia and significantly modulate the levels of the neurotransmitters mentioned above in brain and colonic faeces. Furthermore, the structure and composition of gut microbiota were changed after the administration of BLM and can increase the percentage of beneficial bacterial species in gut microbiota. These results indicated that Bailemian could ameliorate the symptoms of insomnia, and its effects may be through modification of the neurotransmitters levels and gut microbiota composition.

Liuwei Dihuang exhibits antidiabetic effects through inhibiting α-amylase and α-glucosidase.

OBJECTIVE: Liuwei Dihuang (LWDH) is a famous traditional herbal medicine formula in China that may regulate the balance of kidney yin yang and has been used to restore functional insufficiency of the kidney for a long time in China. METHODS: In this study, the water extract of LWDH was tested for its α-Amylase and α-Glucosidase inhibitory activities, and its anti-diabetic property in streptozotocin (STZ)-induced diabetic mice was also analyzed. RESULTS: LWDH extract inhibited α-Glucosidase and α-Amylase activities in a dose- dependent manner. Treatment of streptozotocin-induced diabetic mice with LWDH extract decreased camp, fasting blood glucose, TC, TG, LDL-c, HbA1C, Urine volume levels and Urine sugar, increased HDL-c level when compared to STZ induced diabetic mice. CONCLUSION: This study demonstrates that extract of LWDH can inhibit α-amylase and α-glucosidase activities and shows anti-diabetic effect in a mice preclinical model.

Clinical efficacy and safety of tripterygium glycosides in treatment of stage IV diabetic nephropathy: A meta-analysis.

The aim of this meta-analysis was to evaluate the clinical efficacy and safety of tripterygium glycosides in treatment of stage IV diabetic nephropathy. Methods Through searching the PubMed and CNKI databases, the open published clinically controlled trials related to efficacy and safety of tripterygium glycosides in the treatment of stage IV diabetic nephropathy were collected. The pooled total efficacy, 24h urinary protein, serum creatinine and tripterygium glycosides related toxicity were calculated using Stata 11.0 software. Results Fourteen publications including 992 subjects (512 in the experimental group and 480 in the control group) were included in this study. Eight studies reported the total clinical efficacy comparing the experiment and control groups. No significant statistical heterogeneity was found in total efficacy (I2=24.9%, p>0.05). Thus, the combined odds ratio (OR) was pooled by fixed effect model. The pooled OR=4.16 with its 95% CI 2.71~6.37 (p<0.05), which indicated the total efficacy in the experiment group, was significant higher than that of control group (p<0.05); Thirteen studies reported the post-treatment 24h urinary protein value. Statistical heterogeneity analysis indicated significant heterogeneity across studies (I2=91.1%, p<0.05); that data was pooled by a random effects model. The combined standardized mean difference (SMD) was -1.55 with its 95% I -2.06~1.03, (p<0.05). The results indicated that post-treatment 24h urinary protein in the experiment group was significant lower than that in control group (p<0.05); Ten studies reported the post-treatment serum creatinine. Significant heterogeneity existed across those studies (I2=82.3%, p<0.05). Thereafter, the data was pooled by a random effect model. The combined standardized mean difference (SMD) was -0.24 with its 95%CI -0.40~0.09, (p<0.05). The results indicated that the post-treatment serum creatinine in experiment group was significant lower than that of control group (p<0.05); Eight studies reported tripterygium glycoside-associated toxicity such as liver function damage, gastrointestinal reactions and menstrual disorders. With no statistical heterogeneity among the studies, the data was pooled by fixed effect model. The pooled OR=6.42 (95%CI 2.23~18.48, p<0.05). The pooled results showed the tripterygium glycoside- associated toxicity incidence rate was significant higher in the experiment group than that of the control group (p<0.05); There were no publication bias for effect size of total efficacy, 24h urinary protein, and serum creatinine. However, for tripterygium glycoside-related toxicity, the publication bias was significant (t=-3.55, p<0.05). Conclusion The present evidence shows that tripterygium glycosides can improve clinical efficacy, reduce the 24h urinary protein and serum creatinine, but that they increase the tripterygium glycoside-related toxicity in treatment of stage IV diabetic nephropathy.

Azithromycin Reduces the Production of α-hemolysin and Biofilm Formation in Staphylococcus aureus.

Staphylococcus aureus causes a broad range of life-threatening diseases in humans. This bacterium produces a large number of extracellular virulence factors that are closely associated with specific diseases which are controlled by quorum sensing. In this study, we show that azithromycin was active against methicillin-resistant Staphylococcus aureus (MRSA) strains with MICs ranged from 32 to 64 µg/mL. Azithromycin at subinhibitory concentration, markedly reduced the production of α-hemolysin at (1/16MIC, 1/8MIC) and biofilm formation at (1/16MIC, 1/8MIC), respectively. The results indicated that sub-inhibitory concentrations of azithromycin decreased the production of α-hemolysin and biofilm formation in MRSA in a dose-dependent manner. Therefore, azithromycin may be useful in the treatment of α-hemolysin producing and biofilm formation MRSA infections.

Antibiotic resistance profiles and quorum sensing-dependent virulence factors in clinical isolates of pseudomonas aeruginosa.

Pseudomonas aeruginosa produces multiple virulence factors that have been associated with quorum sensing. The aim of this study was to evaluate the prevalence of drug resistant profiles and quorum sensing related virulence factors. Pseudomonas aeruginosa were collected from different patients hospitalized in China, the isolates were tested for their susceptibility to different common antimicrobial drugs and detected QS-related virulence factors. We identified 170 isolates displaying impaired phenotypic activity, approximately 80 % of the isolates were found to exhibit the QS-dependent phenotypes, among them, 12 isolates were defective in AHLs production, and therefore considered QS-deficient strains. Resistance was most often observed to Cefazolin (81.2 %), followed by trimethoprim-sulfamethoxazole (73.5 %), ceftriaxone (62.4 %) and Cefotaxime, Levofloxacin, Ciprofloxacin (58.8 %), and to a lesser extent Meropenem (20.0 %), Cefepime (18.8 %), and Cefoperazone/sulbactam (2.4 %) The QS-deficient isolates that were negative for virulence factor production were generally less susceptible to the antimicrobials. The results showed a high incidences of antibiotic resistance and virulence properties in P. aeruginosa, and indicate that the clinical use of QS-inhibitory drugs that appear superior to conventional antimicrobials by not exerting any selective pressure on resistant strains.