The objective was to investigate the hypoglycemic action of catalpol in spontaneous diabetes db/db mice. 40 db/db mice were randomly divided into fi ve groups: model control gourp; db/db plus catalpol 40, 80, 120 mg/kg body wt. groups and db/db plus metformin 250 mg/kg group. Age-matched db/m mice were selected as normal control group. The mice were administered with corresponding drugs or solvent by gavage for 4 weeks. The oral glucose tolerance test was carried out at the end of 3rd week. After 4 weeks of treatment, the concentrations of fasting blood glucose (FBG), glycated serum protein (GSP), insulin (INS), triglyceride (TG), total cholesterol (TC) and adiponection (APN) in serum were detected. The protein expressions of phosphorylation-AMPKα1/2 in liver, phosphorylation-AMPKα1/2 and glucose transporter-4 (GLUT-4) in skeletal muscle and adipose tissues were detected by western blot. Real time RT-PCR was used to detect the mRNA expressions of acetyl-CoA carboxylase (ACC) and Hydroxymethyl glutaric acid acyl CoA reductase (HMGCR) in liver. Our results showed that catalpol could significantly improve the insulin resistance, decrease the serum concentrations of INS, GSP, TG, and TC. The concentrations of APN in serum, the protein expression of phosphorylation-AMPKα1/2 in liver, phosphorylation-AMPKα1/2 and GLUT-4 in peripheral tissue were increased. Catalpol could also down regulate the mRNA expressions of ACC and HMGCR in liver. In conclusion, catalpol ameliorates diabetes in db/db mice. It has benefi t eff ects against lipid/glucose metabolism disorder and insulin resistance. The mechanism may be related to up-regulating the expression of phosphorylation-AMPKα1/2.

No abstract

The serum total protein levels of the elderly possibly decrease gradually with aging. However, serum total protein levels are not suitable as a uniform reference standard for the elderly at different ages and genders. Thus, we investigated the total serum protein distribution in different gender and age groups of 11,453 elderly individuals aged ≥60 years and without liver or renal disease from Lianyungang, Jiangsu, China. The total protein levels (TPL) of these individuals exhibited normal distribution (Z = 1.206, P = 0.109), whereas the reference range (95% CI) was 54.1 g/L to 82.3 g/L. TPL was higher in females than in males for those aged between 60 and 75 years, whereas no significant difference was observed for those aged between 80 and 95 years. TPL was negatively correlated with age in males (r = −0.1342, P<0.05), females (r = −0.304, P<0.05), and the total group (r = −0.2136, P<0.05). TPL also decreased with aging and showed a faster rate in women than in men. These results indicated that an appropriate range of serum total protein based on age and gender differences should be used for clinical applications.

Atherosclerosis is a chronic inflammatory disease implicated in oxidative stress and endothelial dysfunction. Protein disulfide-isomerase A3 (PDIA3) has been reported to regulate oxidative stress and suppress inflammation. This study aimed to explore the function of PDIA3 in atherosclerosis and the underlying mechanisms. PDIA3 expression in oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) was detected using RT-qPCR and Western blotting. Following PDIA3 knockdown through transfection with small interfering RNA targeting PDIA3, cell viability, oxidative stress and inflammation in ox-LDL-induced HUVECs was examined using a Cell Counting Kit-8, corresponding kits and ELISA, respectively. The levels of CD31, α-smooth muscle, iNOS, p-eNOS, eNOS and NO were assessed using RT-qPCR, Western blotting and an NO kit to reflect endothelial dysfunction in ox-LDL-induced HUVECs. The relationship between PDIA3 and the activating transcription factor 2 (ATF2) was confirmed using co-immunoprecipitation. In addition, ATF2 expression was examined following PDIA3 silencing. The results indicated that PDIA3 was highly expressed in ox-LDL-induced HUVECs. PDIA3 silencing increased cell viability, and reduced oxidative stress and inflammation, as evidenced by the decreased levels of reactive oxygen species, malondialdehyde, TNF-α, IL-1β and IL-6, and increased superoxide dismutase and glutathione peroxidase activity. In addition, PDIA3 deletion improved endothelial dysfunction. PDIA3 interacted with ATF2, and PDIA3 deletion downregulated ATF2 expression. Furthermore, ATF2 overexpression reversed the effects of PDIA3 knockdown on ox-LDL-induced damage of HUVECs. Collectively, PDIA3 knockdown was found to attenuate ox-LDL-induced oxidative stress, inflammation and endothelial dysfunction in HUVECs by downregulating ATF2 expression, showing promise for the future treatment of atherosclerosis.

BackgroundThe incidence of atrial fibrillation (AF)-related stroke increases with aging. Natriuretic peptides (NPs) family, including Corin-B type natriuretic peptide (BNP)-neprilysin (NEP) protein levels increased with age and are risk markers of cardiovascular and cerebrovascular diseases, such as AF and cardioembolic stroke. Aging is also linked to epigenetics, specifically DNA methylation. However, only a few studies have investigated the effect of DNA methylation on the NP system. Thus, the present study aimed to investigate whether the Corin-BNP-NEP protein pathway is involved in the pathogenesis of AF-stroke and CpG methylation in the promoter region of the Corin protein gene has an effect on AF-related ischemic stroke.MethodsA total of 82 patients hospitalized with acute ischemic strokes were enrolled in this study. The differences in clinical information were compared between the AF-stroke (n = 37) and no AF-stroke groups (n = 45). Plasma-soluble Corin and NEP were detected using an ELISA kit. CpG methylation in the promoter region of the gene was assessed by a next-generation sequencing-based bisulfite sequencing polymerase chain reaction (BSP).Results(1) Patients in AF-stroke were older, had higher initial NIHSS score, 90-day mRs, higher D2-dimer, INR, and APTT, and low TG, TC, and HbA1c (all p &lt; 0.05). (2) Serum levels of Corin and BNP in the AF-stroke group were significantly higher than that in the no AF-stroke group (p &lt; 0.05). No significant difference was detected in the serum levels of NEP between the two groups. (3) The levels of CpG methylation in the promoter region of the Corin protein gene in the AF-stroke group was significantly lower than that in the no AF-stroke group (p &lt; 0.05). The CpG sites with maximal methylation differences between the two groups were CORIN:678, CORIN:682, CORIN:694, and CORIN:700.ConclusionThe current findings raise the possibility that the Corin–BNP–NEP protein pathway may be involved in the pathogenesis of AF-related ischemic stroke. Deficient CpG methylation in the promoter region of the Corin protein gene is associated with AF-related ischemic stroke.

Background and purpose Cerebral small vessel disease (CSVD) is a common cause of stroke and senile vascular cognitive impairment, imposing a heavy burden on public health care systems worldwide. Hypertension and 24-hour blood pressure variability (BPV), known to be significant risk factors for cognitive dysfunction, have been found to be associated with cognitive function in CSVD patients in previous studies. However, as a derived part of BPV, there are few studies on the relationship between circadian rhythm of blood pressure and cognitive dysfunction in CSVD patients, and the relationship between them is still unclear. Thus, this study aimed to investigate whether the disturbance of circadian rhythm of blood pressure can affect the cognitive function of patients with CSVD. Methods A total of 383 CSVD patients hospitalized in the Geriatrics Department of the Lianyungang Second People’s Hospital between May 2018 and June 2022 were enrolled in this study. The clinical information and parameters of 24-hour ambulatory blood pressure monitoring were compared between the cognitive dysfunction group (n = 224) and the normal group (n = 159). Finally, a binary logistic regression model was used to assess the relationship between circadian rhythm of blood pressure and cognitive dysfunction in patients with CSVD. Results (1) Patients in the cognitive dysfunction group were older, had lower blood pressure on admission, and had a greater number of previous cardiovascular and cerebrovascular diseases (P < 0.05). (2) More patients in the cognitive dysfunction group had circadian rhythm abnormalities in blood pressure, especially the non-dipper and reverse-dipper types (P < 0.001). (3) In the elderly, there was a statistical difference in the circadian rhythm of blood pressure between the cognitive dysfunction group and the normal group, but this phenomenon did not exist in the middle-aged. (4) Binary logistic regression analysis showed that after adjusting for confounding factors, the risk of cognitive dysfunction in CSVD patients with non-dipper type was 4.052 times higher than that of dipper type (95% CI, 1.782–9.211; P = 0.001), and reverse-dipper type was 8.002 times higher than those with dipper type (95% CI, 3.367–19.017; P<0.001). Conclusions The disturbance of circadian rhythm of blood pressure may affect the cognitive function of patients with CSVD, and the risk of cognitive dysfunction in non-dipper and reverse-dipper types are higher.

This study aimed to investigate whether fecal microbiota transplantation (FMT) provides protection for stroke injury in obese patients. Rats were fed high-fat diet (HFD) for 4 weeks and subjected to middle cerebral artery occlusion (MCAO). After FMT for 30 days, body weight, serum total cholesterol (TC) and triglyceride (TG) levels, neurological score, brain water content, and cerebral infarction volume were measured. Brain reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA) were detected and the levels of Bcl-2, Bax and cleaved caspase-3 were examined. Rats fed with HFD had higher body weight and higher serum TC and TG levels. Neurological score was lower, brain water content and cerebral infarction volume were higher in obese rats following MCAO, but FMT improved neurological deficit. Moreover, oxidative stress was enhanced in obese rats following MCAO, but FMT attenuated oxidative stress. Brain Bcl-2 level was lower while Bax and cleaved caspase-3 levels were higher in obese rats following MCAO, but FMT increased brain Bcl-2 level and decreased Bax and cleaved caspase-3 levels.In conclusion, FMT attenuated cerebral ischemic injury in obese rats and the beneficial effects of FMT may be mediated by the attenuation of oxidative stress and apoptosis in the brain.

Objective To investigate the impact of N-terminal pro-B-type natriuretic peptide (NT-proBNP) on CTP infarct core volume and poor 90-day functional outcomes in acute ischemic stroke (AIS). Methods A total of 403 hospitalized patients with AIS in the Stroke Center of the First Hospital Affiliated to Soochow University were enrolled from March 2018 to January 2021. The association between NT-proBNP and clinical outcomes in acute ischemic patients was assessed by logistic regression and adjusted for confounding factors. Also, subgroup analyses were conducted based on treatment decisions. Results NT-proBNP was positively correlated with CTP ischemic volume (p < 0.001), infarct core volume (p < 0.001), and ischemic penumbra volume (p < 0.001). Univariate analysis showed that the influence of NT-proBNP and functional outcomes were statistically significant in model 1 (p = 0.002). This phenomenon was persistent after adjusted for age, sex, and body mass index in model 2 (p = 0.011), adjusted for SBP, current smoking, family history of stroke, hypertension, and diabetes mellitus in model 3 (p < 0.001), and adjusted for TnI, D-dimer, PLT, Cr, TC, TG, HDL-C, treatment decisions, and NIHSS score in model 4 (p = 0.027). A high NT-proBNP was associated with a high 90-days mRS score among the total population, IV rt-PA, and standardized treatment groups, but not in IV rt-PA + EVT, EVT, and EVT/IV rt-PA + EVT groups. Conclusion Elevated NT-proBNP levels reveal large CTP infarct core volume and poor 90-day functional outcome in AIS. NT-pro BNP is an independent risk factor for functional outcomes.