Restarting of anticoagulation in patients with atrial fibrillation after major bleeding: A meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Benefits and risks of restarting oral anticoagulants (OACs) in patients with atrial fibrillation after major bleeding remain unknown. A meta-analysis was performed to systematically evaluate the effects of restarting OACs on thromboembolism and bleeding events in these patients. METHODS: Relevant studies were obtained via systematically search of PubMed, Cochrane's Library and Embase databases. A randomized-effect model was used to pool the results. Subgroup analyses according to the types of OACs and sites of reoccurred bleeding were performed. RESULTS AND DISCUSSION: Seven retrospective cohort studies with 12 197 patients were included. Restarting OACs was associated with reduced risk of thromboembolism (risk ratio [RR]: 0.61, 95% confidence interval [CI]: 0.42-0.87; P = .007). Subgroup analyses showed that restarting warfarin reduced risk of thromboembolism (RR = 0.59, P = .05), but not for the new oral anticoagulants (NOACs; RR = 1.37, P = .18). Moreover, restarting OACs did not affect the risk of reoccurred bleeding (RR = 0.98, 95% CI: 0.74-1.30, P = .89). Similar results were found for warfarin and NOACs, as well as for reoccurred intracranial haemorrhage or gastrointestinal bleeding. In addition, restarting OACs was associated with significantly reduced risk of all-cause mortality (RR = 0.42, 95% CI: 0.33-0.52, P < .001). Consistent results were found for warfarin and NOACs. WHAT IS NEW AND CONCLUSION: Restarting of OACs after major bleeding in AF patients may be associated with reduced risks of thromboembolism and mortality without increasing reoccurrence of bleeding.

Impact of Various Ration Energy Levels on the Slaughtering Performance, Carcass Characteristics, and Meat Qualities of Honghe Yellow Cattle.

Consumers are increasing their daily demand for beef and are becoming more discerning about its nutritional quality and flavor. The present objective was to evaluate how the ration energy content (combined net energy, Nemf) impacts the slaughter performance, carcass characteristics, and meat qualities of Honghe yellow cattle raised in confinement. Fifteen male Honghe yellow cattle were divided into three groups based on a one-way design: a low-energy group (LEG, 3.72 MJ/kg), a medium-energy group (MEG, 4.52 MJ/kg), and a high-energy group (HEG, 5.32 MJ/kg). After a period of 70 days on these treatments, the animals were slaughtered and their slaughter performance was determined, and the longissimus dorsi muscle (LD) and biceps femoris (BF) muscles were gathered to evaluate meat quality and composition. Increasing the dietary energy concentration led to marked improvements (p < 0.05) in the live weight before slaughter (LWBS), weight of carcass, backfat thickness, and loin muscle area. HEG also improved the yield of high-grade commercial cuts (13.47% vs. 10.39%) (p < 0.05). However, meat quality traits were not affected by treatment except for shear force, which was affected by dietary energy. A significant improvement (p < 0.05) in the intramuscular fat (IMF) content was observed in the HEG. Little effect on the amino acid profile was observed (p > 0.05), except for a tendency (p = 0.06) to increase the histidine concentration in the BF muscle. Increasing dietary energy also reduced C22:6n-3 and saturated fatty acids (SFAs) and enhanced C18:1 cis-9 and monounsaturated fatty acids (MUFAs, p < 0.05). Those results revealed that increasing energy levels of diets could enhance slaughter traits and affect the meat quality and fatty acid composition of different muscle tissues of Honghe yellow cattle. These results contribute to the theoretical foundation to formulate nutritional standards and design feed formulas for the Honghe yellow cattle.

Long-term baicalin administration ameliorates metabolic disorders and hepatic steatosis in rats given a high-fat diet.

AIM: Baicalin, one of the major flavonoids in Scutellaria baicalensis, possesses antioxidant and anti-inflammatory properties. However, the effects of baicalin on metabolic disorders and hepatic steatosis have not been investigated. METHODS: Body weight was examined in high-fat diet (HFD)-fed rats with or without baicalin treatment. At the end of the experiment, serum biochemical parameters, liver histology and lipid profile were analyzed to assess whether the animals were suffering from metabolic disorders or hepatic steatosis. In the liver, the phosphorylation of AMP activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) and the gene expression of some enzymes involved in lipogenesis were examined. The effects of baicalin on the phosphorylation of AMPK and lipid accumulation induced by high glucose in human hepatoma HepG2 cells were also examined. RESULTS: Baicalin (80 mg/kg) administered ip for 16 weeks suppressed body weight gain in HFD-fed rats. Weight reduction was accompanied by the reduction of visceral fat mass. Baicalin significantly decreased the elevated serum cholesterol, free fatty acid and insulin concentrations caused by the HFD. Baicalin also suppressed systemic inflammation by reducing the serum level of tumor necrosis factor alpha. Baicalin reduced hepatic lipid accumulation, enhanced the phosphorylation of AMPK and ACC and down-regulated genes involved in lipogenesis, including fatty acid synthase and its upstream regulator SREBP-1c. In HepG2 cells, baicalin (5 and 10 micromol/L) increased the phosphorylation of AMPK and decreased lipid accumulation following the addition of high glucose. CONCLUSION: Our study suggests that baicalin might have beneficial effects on the development of hepatic steatosis and obesity-related disorders by targeting the hepatic AMPK.

CaMKKß is involved in AMP-activated protein kinase activation by baicalin in LKB1 deficient cell lines.

AMP-activated protein kinase (AMPK) plays an important role in mediating energy metabolism and is controlled mainly by two upstream kinases, LKB1 or Ca(2+)/calmodulin-dependent protein kinase kinase-ß (CaMKKß). Previously, we found that baicalin, one of the major flavonoids in a traditional Chinese herb medicine, Scutellaria baicalensis, protects against the development of hepatic steatosis in rats feeding with a high-fat diet by the activation of AMPK, but, the underlying mechanism for AMPK activation is unknown. Here we show that in two LKB1-deficient cells, HeLa and A549 cells, baicalin activates AMPK by α Thr-172 phosphorylation and subsequent phosphorylation of its downstream target, acetyl CoA carboxylase, at Ser-79, to a similar degree as does in HepG2 cells (that express LKB1). Pharmacologic inhibition of CaMKKß by its selective inhibitor STO-609 markedly inhibits baicalin-induced AMPK activation in both HeLa and HepG2 cells, indicating that CaMKKß is the responsible AMPK kinase. We also show that treatment of baicalin causes a larger increase in intracellular Ca(2+) concentration ([Ca(2+)](i)), although the maximal level of [Ca(2+)](i) is lower in HepG2 cells compared to HeLa cells. Chelation of intracellular free Ca(2+) by EDTA and EGTA, or depletion of intracellular Ca(2+) stores by the endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin abrogates baicalin-induced activation of AMPK in HeLa cells. Neither cellular ATP nor the production of reactive oxygen species is altered by baicalin. Finally, in HeLa cells, baicalin treatment no longer decreases intracellular lipid accumulation caused by oleic acid after inhibition of CaMKKß by STO-609. These results demonstrate that a potential Ca(2+)/CaMKKß dependent pathway is involved in the activation of AMPK by baicalin and suggest that CaMKKß likely acts as an upstream kinase of AMPK in response to baicalin.

Heat shock protein 90 acts as a molecular chaperone in late-phase activation of extracellular signal-regulated kinase 1/2 stimulated by oxidative stress in vascular smooth muscle cells.

AIM: To investigate whether cytosolic heat shock protein 90 (HSP90) acts as a molecular chaperone on the activated extracellular signal-regulated kinase 1/2 (ERK1/2) and cell proliferation stimulated by reactive oxygen species (ROS) in rat vascular smooth muscle cells (VSMC). METHODS: VSMC were exposed to 1 micromol/L LY83583 (6-anilinoquinoline-5,8-quinolinedione, producer of ROS) for 120 min in the presence or absence of 5 micromol/L geldanamycin, a specific inhibitor of HSP90. Then the total, soluble, and insoluble proteins of the cells were collected. HSP90, ERK1/2, and phosphor-ERK1/2 in the cell lysate were measured by Western blotting. The interaction of HSP90 and phosphor-ERK1/2 was analyzed by immunoprecipitation assay, and the nuclear phosphor-ERK1/2 was measured by Western blotting and immunofluorescence. Cell proliferation was tested by cell counting and 3-(4,5-dimethylthiazol-2-y1)-3,5-di-phenyltetrazolium bromide (MTT). RESULTS: The cytosolic HSP90 of VSMC was upregulated by LY83583 in a time-dependent manner with the peak at 120 min, which is consistent with the late peak of phosphor-ERK1/2. Immunoprecipitation and Western blotting analyses showed that LY83583 increased the interaction of HSP90 with phosphor-ERK1/2, the phosphor-ERK1/2 level, and the soluble phosphor-ERK1/2 level by 1.8-, 2.5-, and 2.9-fold, respectively. In contrast, the insoluble phosphor-ERK1/2 of VSMC was decreased. Interestingly, LY83583 treatment promoted the nuclear phosphor-ERK1/2 by 7.6-fold as confirmed by Western blotting and immunofluorescence assays. Furthermore, cell counting and the MTT assay showed that LY83583 stimulated VSMC proliferation with the increased expression of HSP90 and levels of soluble and nuclear phosphor-ERK1/2. Pretreatment of geldanamycin antagonized the effect of LY83583. CONCLUSION: HSP90 could mediate the oxidative stress-stimulated, late-phase activation of ERK1/2 and VSMC proliferation by promoting the ERK1/2 phosphorylation, the association of itself with phosphor-ERK1/2, and the solubility and nuclear translocation of phosphor-ERK1/2.