OBJECTIVE: To examine the effect of the aqueous extract of Ligustrum robustum on tumor growth in vitro and in vivo and explore the possible molecular mechanisms. METHODS: In in vitro study, cell viabilities of human cervical carcinoma cells (HeLa), human breast cancer cells (MCF-7), human prostate cancer cells (PC-3), human hepatoma cells (7721) and human colon carcinoma cells (SW480) were evaluated with cell counting kit-8. For L. robustum-treated Hela cells, early or late apoptosis were evaluated by annexin V/PI staining. Mitochondrial membrane potential was measured by staining cells with JC-1. Apoptosis was monitored by nuclear morphology based on chromatin condensation and fragmentation by 4',6-diamidino-2-phenylinole (DAPI) staining. Caspase-3 and -8 activity levels were measured by a colorimetric assay. In vivo, to evaluate the possible mechanism of L. robustum-mediated antitumor effect, nude mouse xenograft study was also conducted. RESULTS: In in vitro study, L. robustum was found to be toxic to HeLa, MCF-7, PC-3, 7721, SW480, with an half maximal inhibitory concentration value of 2-5 mg/mL (P<0.05). Moreover, externalization of phosphatidylserine, loss of mitochondrial membrane potential, DNA fragmentation and activation of caspase-3 and -8 were detected in L. robustum-treated Hela cells. Using a nude mouse model bearing Hela xenografts, we found that L. robustum reduced tumor volume and tumor weight (P<0.05), but had no effect on body weight and histological damage of important organs. Intraperitoneal injection of L. robustum caused a significant reduction in serum aspartate transaminase and alanine transaminase levels (P<0.05). Furthermore, cleaved caspase-3-positive and terminal nucleotidyl transferase-mediated nick end labeling (TUNEL)-positive cells were observed in L. robustum-treated tumor tissues. CONCLUSIONS L. robustum inhibits tumor cell growth both in vitro and in vivo by inducing apoptosis in a caspase-dependent way without apparent hepatic toxicity and histological damage, which may offer partial scientific support for the ethnopharmacological claims of L. robustum as a herbal tea for its antitumor activity.

Obesity is an important risk factor for cardiovascular diseases, which can lead to a variety of cardiovascular diseases including myocardial remodeling. Obesity may induce myocardial dysfunction by affecting hemodynamics, inducing autonomic imbalance, adipose tissue dysfunction, and mitochondrial dyshomeostasis. The key necessary biochemical functions for metabolic homeostasis are performed in mitochondria, and mitochondrial homeostasis is considered as one of the key determinants for cell viability. Mitochondrial homeostasis is regulated by dynamic regulation of mitochondrial fission and fusion, as well as mitochondrial cristae remodeling, biogenesis, autophagy, and oxidative stress. The mitochondrial fission-fusion and morphological changes of mitochondrial cristae maintain the integrity of the mitochondrial structure. The mitochondria maintain a "healthy" state by balancing biogenesis and autophagy, while reactive oxygen species can act as signaling molecules to regulate intracellular signaling. The excessive accumulation of lipids and lipid metabolism disorder in obesity leads to mitochondrial dyshomeostasis, which activate the apoptotic cascade and lead to myocardial remodeling. In this review, we provide an overview of the recent research progress on obesity-induced myocardial remodeling and its possible mechanism of mitochondrial dyshomeostasis.
Humans ; Mitochondria ; pathology ; Mitochondrial Dynamics ; Myocardium ; pathology ; Obesity ; physiopathology ; Reactive Oxygen Species

Near-infrared spectroscopy (NIRS) combined with chemometrics can achieve rapid detection in process analysis. After variable selection, the redundant information is effectively removed and the characteristic variables related to the response values are selected. Compared with global model, the complexity is significantly reduced and the prediction accuracy is also improved. In this study, near-infrared spectroscopy analysis combined with different variable selection methods was applied to achieve the rapid detection of baicalin in the extraction process of Scutellaria baicalensis. Data sets were divided based on sample set portioning based on joint x-y distance (SPXY) method. Competitive adaptive weighted resampling method (CARS), random frog (RF) and successive projections algorithm (SPA) were applied to variable selection. Partial least squares (PLS) models were constructed based on above three methods, and the prediction results were compared. After CARS, RF and SPA method, 92, 10 and 17 variables were screened out respectively. According to the performance of the models, CARS method is found to be more effective and suitable than RF and SPA. Furthermore, the characteristic variables selected by CARS method have a better correspondence with the chemical structure of baicalin. The root mean square error (RMSEC) of the calibration set and the root mean square error (RMSEP) of the prediction set are 0.528 2 and 0.720 2 respectively. Compared with the global PLS model, the correlation coefficient of the calibration set (Rc) is increased to 0.979 9 from 0.917 0, and the relative standard errors of prediction (RSEP) is reduced to 5.59% from 10.58%.

Background: Acitretin and matrine have been used in the treatment of psoriasis in China. This study was designed to investigate the role and related mechanisms of matrine alone and in combination with acitretin in the treatment of psoriasis in vitro and in vivo. Methods: HaCaT cells were treated with matrine at different concentrations of 0 (blank control), 0.2, 0.4, 0.8, and 1.6 mg/mL for 24, 48, 72 h, respectively. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium cell viability assay was used to assess the growth and proliferation of HaCaT cells. Cell cycle and apoptosis were detected by flow cytometry. Expression of protein was detected by Western blotting. Autophagy was observed by transmission electron microscopy. Then HaCaT cells were assigned to normal saline (NS) control group, matrine (0.4 mg/mL) group, acitretin (10 μmol/L) group, and matrine plus acitretin group, and the above methods were repeated. In animal experiments, the cumulative score (erythema, scaling, thickening) as a measure of the severity of inflammation was used to measure the skin performance of mice after treated with matrine 50 mg/kg, acitretin 4.5 mg/kg or combination of the two drugs on the psoriasis-like mouse models, respectively. Pathological findings of the lesions were observed, and the protein expressions in the lesions were detected by immunohistochemistry. Results: Cell proliferation inhibition was seen in HaCaT cells with treatment of matrine in a dose- and time-dependent manner (P < 0.01, respectively). Cell cycle G0/G1 phase arrest was observed in a dose-dependent way (P < 0.01). The expression of p21 (P < 0.05), LC3II/I (P < 0.01), and Beclin 1 (P < 0.01) increased and the expression of cyclin D1 (P < 0.05) decreased with increasing doses of matrine. Compared with the blank control, more autophagosomes were seen in HaCaT cells treated with matrine at 0.4 mg/mL by transmission electron microscopy (2.667 ± 1.202 vs. 21.33 ± 1.453, t = 9.899, P < 0.01). Cell proliferation inhibition and degree of the G0/G1 phase arrest was significantly higher in matrine plus acitretin group than those in matrine, acitretin, or the NS control group (P < 0.01, respectively). Compared with matrine or acitretin group, the expression of p21 (P < 0.05, P < 0.05) and LC3II/I (P < 0.01, P < 0.05) in matrine plus acitretin group increased significantly and the expression of cyclin D1 (P < 0.01, P < 0.05) and p62 (P < 0.05, P < 0.05) was reduced significantly. Compared with matrine or acitretin, matrine plus acitretin significantly down-regulated the phosphorylation of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway (P < 0.05) and its downstream p-p70S6K (P < 0.05). In addition, the cumulative score of mice in the matrine plus acitretin group was significantly better than that in the matrine or acitretin group (1.480 ± 0.230 vs. 2.370 ± 0.241, P < 0.01; 1.480 ± 0.230 vs. 2.888 ± 0.341, P < 0.01). The expression of LC3 protein in the matrine plus acitretin group was also higher than that in the matrine, acitretin, or the NS control group (P < 0.05, respectively). Conclusions Matrine has therapeutic potentials for psoriasis. Matrine and acitretin show synergistic effect via cell cycle arrest and autophagy induction by PI3K/Akt/mTOR pathway.

Objective To investigate the effect of fibronectin type Ⅲ and SPRY domain containing 1 (FSD1) protein on the invasion of glioma stem cells (GSCs), so as to probe into the new biomarkers or potential therapeutic targets for gliomas. Methods The Cancer Genome Altas (TCGA) database data were used to analyze and compare the FSD1 gene expression (the FSD1 mRNA level) in the glioblatoma (also known as glioblastoma multiforme, GBM) and normal brain tissues as well as in the different grade glioma tissues, and the correlation of the FDS1 gene expression (mRNA level) with the survival prognosis of patients was also analyzed using the TCGA database data. The lentivirus was used to overexpress the FSD1 protein in the GSCs, T4121 and D456. The effect of the overexpressed FSD1 protein on the invasive ability of the GSCs, T4121 and D456 was evaluated by Transwell invasion assay. Results The FSD1 gene expression (mRNA level) was significantly lower in GBM than in normal brain (P＜0.01). The FSD1 gene expression (the mRNA level) in gliomas significantly decreased with the increase of the gliomas grade (gradeⅡvs Ⅲ, P＜0.05;gradeⅢvs Ⅳ, P＜0.01). The survival prognosis of patients with gilomas was well associated with the level of FSD1 gene expression (the FSD1 mRNA level), as indicated by the overall survival rate of the patients, which was significantly lower in the patients with the low FSD1 mRNA level than in the patients with the high FSD1 mRNA level (P＜0.01). In the Transwell invasion assay, the count of the invasive cell numbers significantly decreased in the FSD1 protein-overexpressed T421 and D456 groups than in the corresponding control group (P＜0.01 in both T4121 and D456 cell lines). Conclusion There is a clinical relevance of the FSD1 expression for the malignant progression of gliomas (the grade of gliomas). The low level FSD1 is favorable for keeping the invasive ability in GSCs.

[Objectives]To observe the clinical effects of the immediate implant placement of Zimmer dental implant sys-tem in the mandibular posterior region.[Methods]67 cases with a total of 89 mandible posterior teeth to deal with immediate implantion which selected to be treated with Zimmer dental implant system.76 teeth between implant and tooth socket bone wall were simultaneously filled with Bio-oss Collagen.The upper structure was repaired with PFM porcelain crown after the postoperative phase I of 3~6 months.All the patients were followed up for 6~24 months.[Results]During the clinical follow up,the implant survival rate was 100%. In 67 patients,89 implants was successfully loaded,with stable implants,good condition in synosteosis and without adverse subjective symptoms. All of the 67 patients had achieved good synosteosis and success loads clinically and radiologically.[Conclusion]A good osseointegration is obtained in the mandibular posterior re-gion with Zimmer dental implant system,Correctly dealing with Bio-oss Collagen between implant and tooth socket bone wall.At the same time,it can shorten the time of therapy,simplify the procedure,so that the clinical results are more satis-factory.

Objective To study the relationship between phosphodiesterase 4D (PDE4D) gene rs966221 single nucleotide polymorphisms (SNPs) and ischemic stroke (IS) in Guangxi Zhuang population.Methods One hundred and one IS patients from Guangxi Zhuang Autonomous Region served as IS pgroup and 104 healthy subjects undergoing physical ecamination served as control group in this study.Their PDE4D gene rs966221 SNPs were detected by SNaPshot technique.The genotypes and frequencies of alleles were compared between the two groups and the relationship between PDE4D gene rs966221 SNPs and IS was analyzed.Results No significant difference was found in the GG,GA,AA genotypes and in the frequencies of G and A alleles between the two groups (0.99％ vs 3.85％,29.70％ vs 21.15％,69.31％ vs 75.00％,P＞0.05;15.84％ vs 14.42％,84.16％ vs 85.58％,P＞0.05).Univariate and multivariate logistic regression analysis showed that the PDE4D gene rs966221 SNPs were not related with the risk of IS in dominant AA vs GG+GA,recessive GG vs AA+GA and additive GG vs AA genetic models (P＞0.05).Conclusion The PDE4D gene rs966221 SNPs are not related with IS in Guangxi Zhuang population.

Objective To study the effect of Pirin(an iron-binding nuclear protein)on the proliferation and self-renewal of glioma stem cell(GSC)so as to provide a potential therapy target for malignant glioma.Methods PLKO.1-shPirin lentiviral plasmids were constructed to stably knock down Pirin in GSC by using lentivirus infection system.The interference efficiency of Pirin short hair?pin RNA(shRNA)was detected by Western blotting. The capacity of GSC was examined by the assessment of cell viability. Tumor sphere formation assay was used to detect the effect of Pirin on GSC self-renewal capacity. Results Pirin was highly expressed in GSC.Consistently,the protein level of Pirin in the conditioned medium from GSC was much higher than that from the corresponding non-stem tumor cell(NSTC).Gene-sequencing analysis demonstrated that PLKO.1-shPirin lentiviral plasmids were successfully con?structed.Pirin shRNA transfection significantly inhibited the expression of Pirin in GSC and suppressed the cell viability and ability of tumorsphere formation.Conclusion Knocking down Pirin significantly inhibites the cell proliferation and self-renewal of GSC.

Ischemic heart disease (IHD) is the life-threatening cardiovascular disease. Mitochondria have emerged as key participants and regulators of cellular energy demands and signal transduction. Mitochondrial quality is controlled by a number of coordinated mechanisms including mitochondrial fission, fusion and mitophagy, which plays an important role in maintaining healthy mitochondria and cardiac function. Recently, dysfunction of each process in mitochondrial quality control has been observed in the ischemic hearts. This review describes the mechanism of mitochondrial dynamics and mitophagy as well as its performance linked to myocardial ischemia. Moreover, in combination with our study, we will discuss the effect of vagal nerve on mitochondria in cardio-protection.