[Tianma Gouteng Decoction regulates MFN2 expression to delay vascular aging in spontaneously hypertensive rats].

We studied the effect of Tianma Gouteng Decoction on vascular aging in spontaneously hypertensive rats(SHRs) to explore the molecular mechanism of the decoction in improving arterial vascular aging by regulating the expression of mitofusin 2(MFN2).Twenty 64-weeks-old SHRs were randomly assigned into the aging group and the treatment group(Tianma Gouteng Decoction 5.48 mg·kg~(-1)).Wistar-Kyoto(WKY) rats of 64 weeks old were taken as the normal group and SHR rats of 14 weeks old as the young group.The intervention with Tianma Gouteng Decoction lasted for 12 weeks.We then employed HE staining and Masson staining to observe the morphology of thoracic aorta under an electron microscope and measured the malondialdehyde(MDA) content, superoxide dismutase(SOD) activity, respiratory chain complex Ⅲ level, and thioredoxin peroxidase(TPX) activity.The vascular aging was detected via the biomarker senescence-associated beta-galactosidase(SA-ß-Gal).The expression levels of MFN2 and aging marker proteins silent information regulator 1(SIRT1), Klotho, p21, and p53 in thoracic aorta were detected by immunohistochemistry/fluorescence, qRT-PCR, and Western blot.Compared with the young group and the normal group, the aging group had risen blood pressure, lumen stenosis caused by thickened intima of blood vessels, decreased SOD and TPX activities, increased MDA and mitochondrial respiratory chain complex Ⅲ levels, down-regulated expression of MFN2, SIRT1, and Klotho, and up-regulated expression of p21 and p53(P<0.01 or P<0.05).The treatment with Tianma Gouteng Decoction significantly lowered blood pressure, mitigated vascular intimal thickening, increased SOD and TPX activities, and decreased MDA and mitochondrial respiratory chain complex Ⅲ levels, thus alleviating vascular aging.At the same time, the decoction up-regulated the expression of MFN2, SIRT1, and Klotho, while down-regulated that of p21 and p53(P<0.01 or P<0.05).In summary, Tianma Gouteng Decoction can significantly delay the vascular aging in hypertension.Specifically, it may up-regulate the expression of MFN2 and regulate the expression of aging-related proteins to alleviate oxidative stress.

Herbal NF-κB Inhibitors Sensitize Rituximab-Resistant B Lymphoma Cells to Complement-Mediated Cytolysis.

BACKGROUND: Drug resistance remains a serious challenge to rituximab therapy in B-NHL (B cell non-Hodgkin's lymphoma). CDC (complement-dependent cytotoxicity) has been proposed as a major antitumor mechanism of rituximab, and direct abrogation of CD59 function partially restores rituximab sensitivity with high efficacy. However, universal blockade of CD59 may have deleterious effects on normal cells. Sp1 regulates constitutive CD59 expression, whereas NF-κB and CREB regulate inducible CD59 expression. METHODS: Immunohistochemistry (IHC) assay was used to detect the expression levels of CD59 and other related molecules. Quantitative Real-time PCR (RT-PCR) analysis was used to explore the levels of transcripts in the original and resistant cells. We chose LY8 cells to test the effects of NF-κB and CBP/p300 inhibition on CD59 expression using flow cytometry (FACS). Immunoblotting analysis was employed to detect the effects of curcumin and POH. The in vitro and in vivo experiments were used to evaluate the toxicity and combined inhibitory effect on tumor cells of curcumin and POH. RESULTS: We demonstrated that herbal (curcumin and perillyl alcohol) blockade of NF-κB specifically suppresses the expression of inducible CD59 but not CD20, thus sensitizing resistant cells to rituximab-mediated CDC. Moreover, activation of NF-κB and CREB is highly correlated with CD59 expression in B-NHL tissues. CONCLUSIONS: Our findings suggest the potential of CD59 expression as a predictor of therapeutic efficacy of NF-κB inhibitors in clinical application as well as the rationality of a NF-κB inhibitor-rituximab regimen in B-NHL therapy.

Comparative transcriptomic analysis revealed novel potential therapeutic targets of traditional Chinese medicine (Pinggan-Qianyang decoction) on vascular remodeling in spontaneously hypertensive rats.

BACKGROUND: Both experimental and clinical studies have revealed satisfactory effects with the traditional Chinese formula Pinggan Qianyang decoction (PGQYD) for improving vascular remodeling caused by essential hypertension. The present study explored various therapeutic targets of PGQYD using mRNA transcriptomics. METHODS: In this study, rats were randomly divided into three groups: Wistar-Kyoto (WKY; normal control), spontaneously hypertensive (SHR), and PGQYD-treated rat groups. After 12 weeks of PGQYD treatment, behavioral tests were employed and the morphology of thoracic aortas were examined with hematoxylin-eosin (HE) and Masson staining and electron microscopy. The mRNA expression profiles were identified with RNA-Seq and quantitative real-time PCR to validate changes in gene expression observed with microarray analysis. The gene ontology and pathway enrichment analyses were carried out to predict gene function and gene co-expressions. Pathway networks were constructed to identify the hub biomarkers, which were further validated by western blotting and immunofluorescence analysis. RESULTS: After PGQYD treatment, the behavioral tests and histological and morphological findings of vascular remodeling were obviously meliorated compared with the SHR group. In the rat thoracic aorta tissues, 626 mRNAs with an exact match were identified. A total of 129 of mRNAs (fold change > 1.3 and P-value < 0.05) were significantly changed in the SHR group compared to the WKY group. Among them, 16 mRNAs were markedly regulated by PGQYD treatment and validated with quantitative real-time PCR. Additionally, target prediction and bioinformatics analyses revealed that these mRNAs could play therapeutic roles through biological processes for regulating cell metabolic processes (such as glycation biology), biological adhesions, rhythmic processes, and cell autophagy. The cellular signaling pathways involved in autophagy may be AGE-RAGE/PI3K/Akt/mTOR signaling pathway. CONCLUSION: The present study provides novel insights for future investigations to explore the mechanisms by which PGQYD may effectively inhibit vascular remodeling by activating the AGE-RAGE/PI3K/Akt/mTOR signal pathway in cell autophagy biology.

Efficacy of Weikang Pian in Patients with Functional Dyspepsia: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: FD (functional dyspepsia) is a common functional gastrointestinal disorder, which lacks effective and safe treatment. Chinese herbal medicine (CHM) has been applied in FD treatment for thousands of years with satisfactory clinical outcomes. Zhishi is a classical traditional Chinese medicine used to treat FD. Weikang pian (WKP) is made of flavonoids extracted from zhishi which could effectively alleviate the symptoms of FD. This research aimed to assess the efficacy and safety of WKP in FD treatment. METHODS: This was a randomized, double-blinded and placebo-controlled clinical trial. The patients were diagnosed as FD according to RomeIII criteria. Then, FD patients were selected and assigned randomly to either WKP or placebo group. The subjects randomly received WKP or placebo for 4 weeks with 4 tablets each time, 3 times daily. The single dyspepsia symptom (SDS) scale and the gastric emptying function were measured before and after the treatment. Moreover, the safety of the trial and patient compliance were evaluated. RESULTS: A total of 60 FD patients were eventually enrolled in the trial, among them 45 patients in the WKP group and 15 patients in the placebo group. The primary outcome was the SDS scale, including assessments of postprandial distension, early satiety, epigastric burning, and pain. The secondary outcome was the gastric emptying function. Compared with the placebo group, the symptoms of FD in the WKP group were relieved after 4 weeks of treatment (P < 0.05). Some minor changes appeared in the four groups, but there were no significant differences in gastric emptying parameters of GER (2-hour gastric emptying rate) and GET/2 (gastric semiempty time) (P > 0.05). Severe adverse events were absent. The compliance to treatment was 94%-96%, and there was no significant difference between the groups. CONCLUSION: WKP can relieve FD symptoms to some extent. This trial is registered with Chinese Clinical Trial Registry (ChiCTR): CTR 20132482.

[Effect of simvastatin on the reserve of heart function and endothelial function in X-syndrome].

OBJECTIVE: To determine the therapeutic effect of simvastatin combined with traditional medicine on patients with X-syndrome, and on the reserve of heart function and endothelial function. METHODS: Forty patients with X-syndrome were recruited from September 2006 to September 2007 and randomly divided into 2 groups (a simvastatin group and a control group). The control group received routine treatment including beta receptor blocker, calcium-channel blocker (CCB) and long active nitrate. The simvastatin group received simvastatin and the routine treatment. The clinical condition and exercise test (TET) were performed before and after the treatment.The levels of triglyeride (TG), total cholesterol (TC), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C), endothelin-1 (ET-1) and nitric oxide (NO) were measured. RESULTS: The frequencies of chest pain in the simvastatin group were lower than those in the control group. The levels of ET-1, ET-1/NO, TG, TC, and LDL-C were significantly decreased in the simvastatin group as compared with the control group after the treatment. The levels of HDL-C and NO were significantly increased in the simvastatin group as compared with the control group after the treatment. The time in TET was significantly increased in the simvastatin group as compared with the control group. The frequencies of chest pain were positively related to the level of ET-1/NO and negatively related to the time in TET. CONCLUSION: Simvastatin is effective for patients with X-syndrome and may improve the endothelial function and the reserve of heart function.