Role of thrombospondin-1 in high-salt-induced mesenteric artery endothelial impairment in rats.

The matrix glycoprotein thrombospondin-1 (THBS1) modulates nitric oxide (NO) signaling in endothelial cells. A high-salt diet induces deficiencies of NO production and bioavailability, thereby leading to endothelial dysfunction. In this study we investigated the changes of THBS1 expression and its pathological role in the dysfunction of mesenteric artery endothelial cells (MAECs) induced by a high-salt diet. Wild-type rats, and wild-type and Thbs1-/- mice were fed chow containing 8% w/w NaCl for 4 weeks. We showed that a high salt diet significantly increased THBS1 expression and secretion in plasma and MAECs, and damaged endothelium-dependent vasodilation of mesenteric resistance arteries in wild-type animals, but not in Thbs1-/- mice. In rat MAECs, we demonstrated that a high salt environment (10-40 mM) dose-dependently increased THBS1 expression accompanied by suppressed endothelial nitric oxide synthase (eNOS) and phospho-eNOS S1177 production as well as NO release. Blockade of transforming growth factor-ß1 (TGF-ß1) activity by a TGF-ß1 inhibitor SB 431542 reversed THBS1 up-regulation, rescued the eNOS decrease, enhanced phospho-eNOS S1177 expression, and inhibited Smad4 translocation to the nucleus. By conducting dual-luciferase reporter experiments in HEK293T cells, we demonstrated that Smad4, a transcription promoter, upregulated Thbs1 transcription. We conclude that THBS1 contributes to endothelial dysfunction in a high-salt environment and may be a potential target for treatment of high-salt-induced endothelium dysfunction.

Phylogenetic and Evolutionary Comparison of Mitogenomes Reveal Adaptive Radiation of Lampriform Fishes.

Lampriform fishes (Lampriformes), which primarily inhabit deep-sea environments, are large marine fishes varying from the whole-body endothermic opah to the world's longest bony fish-giant oarfish, with species morphologies varying from long and thin to deep and compressed, making them an ideal model for studying the adaptive radiation of teleost fishes. Moreover, this group is important from a phylogenetic perspective owing to their ancient origins among teleosts. However, knowledge about the group is limited, which is, at least partially, due to the dearth of recorded molecular data. This study is the first to analyze the mitochondrial genomes of three lampriform species (Lampris incognitus, Trachipterus ishikawae, and Regalecus russelii) and infer a time-calibrated phylogeny, including 68 species among 29 orders. Our phylomitogenomic analyses support the classification of Lampriformes as monophyletic and sister to Acanthopterygii; hence, addressing the longstanding controversy regarding the phylogenetic status of Lampriformes among teleosts. Comparative mitogenomic analyses indicate that tRNA losses existed in at least five Lampriformes species, which may reveal the mitogenomic structure variation associated with adaptive radiation. However, codon usage in Lampriformes did not change significantly, and it is hypothesized that the nucleus transported the corresponding tRNA, which led to function substitutions. The positive selection analysis revealed that atp8 and cox3 were positively selected in opah, which might have co-evolved with the endothermic trait. This study provides important insights into the systematic taxonomy and adaptive evolution studies of Lampriformes species.

[Expression of tumor necrosis factor-alpha and caspase-3 protein in monocytes adjacent to the invaded Echinococcus multilocularis in liver].

OBJECTIVE: To investigate the expression and its significance of tumor necrosis factor-alpha (TNF-alpha) and caspase-3 protein in monocytes adjacent to the invaded Echinococcus multilocularis in liver. METHODS: 40 female Kunming mice were randomly divided into experimental group (n=20) and sham operation (control) group (n=20). Mice in experimental group were infected with 20% E. multilocularis suspension (0.1 ml per mouse) through abdominal opening injection in liver and the mice in control group were injected with equal physiological saline. The mice were sacrificed at 6 months post-infection for observing the growth and metastasis of E. multilocularis. Pathological changes were observed by HE staining. The expression of TNF-alpha and caspase-3 protein in hydatid cyst and metastasis tissue were detected by immunohistochemistry staining and the apoptosis of the monocytes was measured by TUNEL. RESULTS: After 6 months post-infection, E. multilocularis were spread over the liver of the mice in experimental group. Metastasis rate of lymph nodes was 45.0% (9/20). Infiltration of monocytes was observed around E. multilocularis in liver and lymph nodes with metastasis by HE staining. Immunohistochemistry showed that the positive expression rate of TNF-alpha and caspase-3 protein in monocytes was 100% and 100%, and 95% and 100% respectively around the cyst in experimental group, while the expression rate was only 5% and 0 respectively in the liver of the control mice (P<0.01). The monocytes showed significant apoptosis by TUNEL in experimental group with a positive expression rate of 100%, with a significant difference between experiment group and the control (P<0.01). CONCLUSION: In the process of alveolar Echinococcus infection, the high expression of TNF-alpha protein might be associated with the apoptosis of monocytes, which may inhibit the host immunological function.