Recent studies have demonstrated that myocardial calpain triggers caspase-3 activation and myocardial apoptosis in models of sepsis, whereas the inhibition of calpain activity down-regulates myocardial caspase-3 activation and apoptosis. However, the mechanism underlying this pathological process is unclear. Therefore, in this study, our aim was to explore whether the Hsp90/Akt signaling pathway plays a role in the induction of myocardial calpain activity, caspase-3 activation and apoptosis in the septic mice.

The class of adhesion G protein–coupled receptors (aGPCRs), with 33 human homologs, is the second largest family of GPCRs. In addition to a seven‐transmembrane α‐helix—a structural feature of all GPCRs—the class of aGPCRs is characterized by the presence of a large N‐terminal extracellular region. In addition, all aGPCRs but one (GPR123) contain a GPCR autoproteolysis–inducing (GAIN) domain that mediates autoproteolytic cleavage at the GPCR autoproteolysis site motif to generate N‐ and a C‐terminal fragments (NTF and CTF, respectively) during protein maturation. Subsequently, the NTF and CTF are associated noncovalently as a heterodimer at the plasma membrane. While the biological function of the GAIN domain–mediated autocleavage is not fully understood, mounting evidence suggests that the NTF and CTF possess distinct biological activities in addition to their function as a receptor unit. We discuss recent advances in understanding the biological functions, signaling mechanisms, and disease associations of the aGPCRs.

Background: Dilated cardiomyopathy (DCM) has been extensively investigated for many years, but its pathogenesis remains uncertain. The ACTC1 gene was the first sarcomeric gene whose mutation was shown to cause DCM; recent studies have indicated that the HSPB7 and ZBTB17 genes are also associated with DCM. To assess the potential role of these three genes in DCM, we examined 11 single nucleotide polymorphisms (SNPs) in the ZBTB17, HSPB7 and ACTC1 genes: namely, rs10927875 in ZBTB17; rs1739843, rs7523558, and rs6660685 in HSPB7; rs533021, rs589759, rs1370154, rs2070664, rs3759834, rs525720 and rs670957 in ACTC1. Methods: A total of 97 DCM patients and 189 controls were included in the study. All SNPs were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Results: The genotype of SNP rs10927875 in ZBTB17 (OR=5.19, 95% CI =1.00 to 27.03, P=0.05) was associated with DCM in a Han Chinese population. There was no difference in genotype or allele frequencies in ACTC1 or HSPB7 between DCM patients and control subjects. Conclusion: The ZBTB17 polymorphism rs10927875 appears to play a role in the susceptibility of the Han Chinese population to DCM.

BACKGROUND: The estimated glucose disposal rate (eGDR) is a validated surrogate marker of insulin resistance. However, its association with stroke and dementia in nondiabetic populations remains insufficiently investigated. METHODS: This prospective cohort study included nondiabetic participants from the UK Biobank. The outcomes in this study were stroke, ischemic stroke, hemorrhagic stroke, all-cause dementia, vascular dementia, and Alzheimer disease. Multivariable Cox regression and restricted cubic splines were used to examine the associations between eGDR and outcomes. Polygenic risk score analyses were applied to investigate interactions between eGDR and genetic risk. RESULTS: Overall, 430 093 participants were included. During a follow-up of around 13.5 years, 10 307 stroke cases and 11 137 all-cause dementia cases were recorded. Restricted cubic splines analyses indicated nonlinear associations between eGDR and the risks of stroke and vascular dementia. Below specific thresholds (<7.64 for stroke, <7.60 for ischemic stroke, <7.75 for hemorrhagic stroke, and <8.31 for vascular dementia), eGDR levels were not significantly associated with these outcomes except a modest inverse association with overall stroke risk (hazard ratio [HR] 0.97 [95% CI, 0.95–0.99]; P =0.012). In contrast, above these thresholds, higher eGDR levels were associated with significantly reduced risks of stroke (HR, 0.80 [95% CI, 0.78–0.82]; P <0.001), ischemic stroke (HR, 0.80 [95% CI, 0.78–0.81]; P <0.001), hemorrhagic stroke (HR, 0.81 [95% CI, 0.78–0.84]; P <0.001), and vascular dementia (HR, 0.89 [95% CI, 0.84–0.94]; P <0.001). A linear inverse relationship was observed between eGDR and all-cause dementia and Alzheimer disease. The HR in the highest versus lowest quartile was 0.81 (95% CI, 0.75–0.88) for all-cause dementia and 0.73 (95% CI, 0.64–0.84) for Alzheimer disease. Stratified polygenic risk score analyses revealed a synergistic interaction between reduced eGDR and elevated genetic susceptibility. CONCLUSIONS: eGDR exhibited nonlinear associations with stroke and vascular dementia risk and linear inverse associations with all-cause dementia and Alzheimer disease in nondiabetic populations.