Effect of moxibustion combined with intraperitoneal injection of benazepril on endoplasmic reticulum stress-related protein phosphorylation in rats with chronic heart failure. / è‰¾ç¸è”åˆè´é‚£æ™®åˆ©å¯¹æ ¢æ€§å¿ƒåŠ›è¡°ç«­å¤§é¼ å¿ƒè‚Œå† è´¨ç½‘åº”æ¿€ç›¸å ³è›‹ç™½ç£·é ¸åŒ–è¡¨è¾¾çš„å½±å“.

OBJECTIVES: To observe the effect of moxibustion at "Xinshu"(BL15) and "Feishu"(BL13) combined with intraperitoneal injection of benazepril on cardiac function and phosphorylation of protein kinase R-like endoplasmic reticulum kinase (PERK) and eukaryotic initiation factor 2α (elF2α) proteins in myocardium of rats with chronic heart failure (CHF), so as to explore its potential mechanism underlying improvement of CHF. METHODS: A total of 42 male SD rats were randomly assigned to blank control (n=10), CHF model (n=7), medication (benazepril, n=8), moxibustion (n=8) and moxibustion+benazepril (n=9) groups, after cardiac ultrasound model identification and elimination of the dead. The CHF model was established by intraperitoneal injection of doxorubicin hydrochloride (DOX), once every week for 6 weeks. Mild moxibustion was applied to bilateral BL15 and BL13 regions for 20 min, once daily for 3 weeks. The rats of the medication group and moxibustion+benazepril group (benazepril was given first, followed by moxibustion) received intraperitoneal injection of benazepril (0.86 mg/kg) solution once daily for 3 weeks . The cardiac ejection fraction (EF) and left ventricular fractional shortening (FS) were measured using echocardiography. Histopathological changes of the cardiac muscle tissue were observed under light microscope after hematoxylin-eosin (H.E.) staining. Serum contents of B-type brain natriuretic peptide (BNP) and angiotensin Ⅱ (AngⅡ) were measured by enzyme-linked immunosorbent assay (ELISA). The expressions of phospho-PERK (p-PERK) and phospho-elF2α (p-elF2α) in the myocardium were detected by Western blot. RESULTS: Compared with the blank control group, the EF and FS of the left cardiac ventricle were significantly decreased (P<0.01), while the contents of serum BNP and AngⅡ, and expression levels of p-PERK and p-eIF2α significantly increased in the model group (P<0.01). In comparison with the model group, both the decreased EF and FS and the increased BNP and AngⅡ contents as well as p-PERK and p-elF2α expression levels were reversed by moxibustion, medication and moxibustion+benazepril (P<0.01). The effects of moxibustion+benazepril were markedly superior to those of simple moxibustion and simple medication in raising the levels of EF and FS rate and in down-regulating the contents of BNP, Ang Ⅱ, levels of p-PERK and p-elF2α (P<0.01, P<0.05). Outcomes of H.E. staining showed irregular arrangement of cardiomyocytes, cell swelling, vacuole and inflammatory infiltration in the model group, which was relatively milder in the 3 treatment groups. The effects of moxibustion+benazepril were superior to those of moxibustion or benazepril. CONCLUSIONS: Moxibustion combined with Benazepril can improve the cardiac function in CHF rats, which may be related to its functions in down-regulating the expression levels of myocardial p-PERK and p-elF2α to inhibit endoplasmic reticulum stress response.

An extraordinary fossil captures the struggle for existence during the Mesozoic.

Dinosaurs and mammals have coexisted for the last ~ 230 million years. Both groups arose during the Late Triassic and diversified throughout the Mesozoic and into the Cenozoic (the latter in the form of birds). Although they undoubtedly interacted in many ways, direct fossil evidence for their interaction is rare. Here we report a new fossil find from the Lujiatun Member of the Lower Cretaceous Yixian Formation of China, showing a gobiconodontid mammal and psittacosaurid dinosaur locked in mortal combat. We entertain various hypothesized explanations for this association, but the balance of the evidence suggests that it represents a predation attempt on the part of the smaller mammal, suddenly interrupted by, and preserved within, a lahar-type volcanic debris flow. Mesozoic mammals are usually depicted as having lived in the shadows of their larger dinosaurian contemporaries, but this new fossil convincingly demonstrates that mammals could pose a threat even to near fully-grown dinosaurs. The Yixian Formation-and the Chinese fossil Jehol Biota more broadly-have played a particularly important role in revealing the diversity of small-bodied dinosaurs and other fauna. We anticipate that the volcanically derived obrution deposits specific to the Lujiatun Member will likewise continue to yield evidence for biotic interactions otherwise unknown from the rest of the fossil record.

Protective role of autophagy in palmitate-induced INS-1 beta-cell death.

Autophagy, a vacuolar degradative pathway, constitutes a stress adaptation that avoids cell death or elicits the alternative cell-death pathway. This study was undertaken to determine whether autophagy is activated in palmitate (PA)-treated beta-cells and, if activated, what the role of autophagy is in the PA-induced beta-cell death. The enhanced formation of autophagosomes and autolysosomes was observed by exposure of INS-1 beta-cells to 400 microm PA in the presence of 25 mm glucose for 12 h. The formation of green fluorescent protein-LC3-labeled structures (green fluorescent protein-LC3 dots), with the conversion from LC3-I to LC3-II, was also distinct in the PA-treated cells. The phospho-mammalian target of rapamycin level, a typical signal pathway that inhibits activation of autophagy, was gradually decreased by PA treatment. Blockage of the mammalian target of rapamycin signaling pathway by treatment with rapamycin augmented the formation of autophagosomes but reduced PA-induced INS-1 cell death. In contrast, reduction of autophagosome formation by knocking down the ATG5, inhibition of fusion between autophagosome and lysosome by treatment with bafilomycin A1, or inhibition of proteolytic degradation by treatment with E64d/pepstatin A, significantly augmented PA-induced INS-1 cell death. These findings showed that the autophagy system could be activated in PA-treated INS-1 beta-cells, and suggested that the induction of autophagy might play an adaptive and protective role in PA-induced cell death.