Salvianolic acid B alleviates diabetic endothelial and mitochondrial dysfunction by down-regulating apoptosis and mitophagy of endothelial cells.

Endothelial dysfunction is a critical mediator in the pathogenesis of vascular complications of diabetes. Herein, this study was conducted to investigate the therapeutic effects of Salvianolic acid B (Sal B) on diabetes-induced endothelial dysfunction and the underlying mechanisms. Diabetic models were established both in db/db mice and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs). Moreover, HUVECs were exposed to carbonyl cyanide m-chlorophenyl hydrazone (CCCP) to induce endothelial cell damage. Following Sal B treatment, pathological changes of thoracic aorta were investigated by hematoxylin and eosin, alcian blue (AB), elastic fiber, Masson, and reticular fiber staining. BCL2-associated X (BAX), B-cell lymphoma-2 (Bcl-2), Beclin1, Parkin and PTEN Induced Kinase 1 (Pink1) expression was detected by Western blot, immunohistochemistry, and immunofluorescence in thoracic aorta, HG- and CCCP-induced HUVECs. Cell scratch test, MitoTracker Red CMXRos staining and Flou-4 AM staining were separately presented to detect migration, mitochondrial activity and intracellular Ca2+ in HUVECs. Our results showed that Sal B significantly ameliorated hyperlipidemia, hyperglycemia, hyperinsulinemia, and insulin resistance in db/db mice. Furthermore, it significantly alleviated diabetes-induced vascular endothelial dysfunction according to histopathology analysis. In diabetic thoracic aorta, HG- and CCCP-induced HUVECs, Sal B distinctly increased Bcl-2 expression and reduced BAX, Beclin1, Parkin and Pink1 expression, thereby protecting endothelial cells from apoptosis and mitophagy. Moreover, Sal B markedly enhanced migration, mitochondrial activity and intracellular Ca2+ levels both in HG- and CCCP-induced HUVECs. Collectively, Sal B exhibited a potential to improve diabetes-induced endothelial and mitochondrial dysfunction through down-regulating apoptosis and mitophagy of endothelial cells.Abbreviations: DM: diabetes mellitus; T2DM: type 2 diabetes mellitus; Sal B: Salvianolic acid B; HG: high glucose; FBG: fasting blood glucose; TC: total cholesterol; TG: triglycerides; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; FINS: fasting insulin; HOMA-IR: homeostasis model assessment insulin resistance; QUICKI: quantitative insulin-sensitivity check index; H&E: hematoxylin and eosin; HUVECs: human umbilical vein endothelial cells; IHC: immunohistochemistry; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; FCM: flow cytometry; CCK-8: cell counting kit-8.

Self-Inclusion and Dissociation of a Bridging ß-Cyclodextrin Triplet.

To understand the self-inclusion and the dissociation in a branched ß-cyclodextrin (CD) system, we designed and synthesized a ß-CD trimer in which each CD group is connected to one of bridging arms of a planar triphenylbenzene core through a CuAAC click reaction. Only one rather than two or all of the three host CDs was demonstrated to be in a self-including state in water, while no self-inclusion was observed to occur in dimethylsulfoxide (DMSO) via the characterization of 1H and NOESY NMR spectra. The configuration structures of the CD groups in the self-included state were evaluated, and the dissociation to free state in water was investigated under various conditions like heating, increased acidity, and discharging versus the addition of competitive guests. While raised temperature and increased acidity did not break the self-inclusion, two adamantane guest molecules were found to show capability in driving the equilibrium to get back to free state against the self-inclusion. The inclusion process of the added guests was believed to involve in the dissociation of the self-inclusion and the occupation of the guests in CD cavity. The results of host-guest interaction study indicated that the stable combination of guests was favorable for blocking the structural overturning of glucose toward trapping the bridging group into the cavity.

A supramolecular approach of modified polyoxometalate polymerization and visualization of a single polymer chain.

An anthracene modified Anderson-Evans polyoxometalate was polymerized via supramolecular inclusion and then covalent coupling with the support of γ-cyclodextrin (γ-CD) under UV light irradiation. The formed main chain polymers of the inorganic polyanions self-assembled into fibrous bundles and single-strand chains were visualized and characterized via TEM and other techniques.

[Establishment of an undifferential orchitis model in rats and changes of spermatogenic epithelium].

OBJECTIVE: To explore the changes of rat testicular spermatogenic epithelium stimulated by bacterial lipopolysaccharide (LPS) in vivo. METHODS: Twenty Wistar rats were divided into two groups: control group and experimental group. The control group was treated with pyrogen-free saline (1 ml/kg) and the experimental group was injected ip with saline containing LPS (1 mg/kg) once every two days. Two groups were operated after ten days in order to investigate the testicular pathological changes by HE staining and the expression of proliferating cell nuclear antigen( PCNA), alpha-catenin in spermatogenic epithelium by immunohistochemistry assay. RESULTS: The testes of the experimental group showed inflammatory changes. The positive expression of PCNA in seminiferous epithelium was significantly lower than that of control group. The number of positive cells in every seminiferous, in which only spermatogonia were stained in experimental group were 59 +/- 5 and it showed significant decrease compared with the control (P < 0.01). Furthermore, the percentage of such seminiferous tubules was 0.673 +/- 0.054 and increased apparently (P < 0.01). The expression of alpha-catenin in testicular tissue of the experimental group declined (P < 0.01), and cellular positive granular light density was 0.150 +/- 0.014. CONCLUSION: The ability of spermatogonium proliferation and the function of conglutination of cells under inflammatory condition of the testes declined, which may be one of the etiologies of male infertility.

[Progresses on macrophages of male reproductive tract].

The review summarized the recent progress on macrophages of male reproductive tract and the action of macrophages on male reproductive physiology and pathology. The close correlation and effect between testicular macrophages and Leydig cells, Sertoli cells, germ cells, hypothalamic-pituitary-gonadal axis were introduced, respectively. At the same time, it pointed out the changes of macrophages' morphology and function in immune orchitis, and their regulation on the development of orchitis. So the complex immune regulation network in testes and testicular macrophages playing an important role on spermatogenesis and the stableness of spermatogenetic microenvironment in testes were further illuminated, which can provide theoretical basis for clinic therapy.