Gut microbiome profile of Chinese hypertension patients with and without type 2 diabetes mellitus.

BACKGROUND: The coexistence of hypertension and type 2 diabetes mellitus (T2DM) may largely increase the risk for cardiovascular disease. However, there is no clear consensus on the association between hypertension and the risk of diabetes. Gut microbiota plays important roles in the development of hypertension and T2DM, but whether there is difference between hypertension patients with or without T2DM has not been explored yet. METHODS: We recruited 101 hypertension patients in this study (72 patients without T2DM named HT group and 29 patients with T2DM named HT-T2DM group). Their blood samples were collected for testing clinical characteristics and fecal samples were tested for bacterial DNA using 16 S ribosomal RNA gene sequencing targeting the V3 and V4 region. The data of 40 samples were downloaded from project PRJNA815750 as health control (HC group) in this study. The community composition and structure of the microbiome, taxonomic difference, co-occurrence network and functional enrichment were analyzed by alpha/beta diversity, LEfSe, Fruchterman Reingold's algorithm and PICRUSt2 functional analysis, respectively. RESULTS: Alpha and beta diversity analysis showed significant differences in microbial community richness and composition among the three groups. The HC group had a significantly higher Simpson index and a distinct microbiota community compared to the HT and HT-T2DM groups, as demonstrated by significant differences in unweighted and weighted UniFrac distances. The LEfSe analysis identified specific taxa that had significantly different abundance among the groups, such as Bacteroides uniformis, Blautia wexlerae, Alistipes putredinis, and Prevotella stercorea in the HC group, Prevotella copri and Phascolarctobacterium faecium in the HT group, and Klebsiella pneumoniae in the HT-T2DM group. Co-occurrence network analysis indicates that Prevotella copri, Mediterraneibacter gnavus, Alistipes onderdonkii and some unidentified species act as key nodes in the network. Differentially functional pathway identified by PICRUSt2 were concentrated in nutrition and energy metabolism, as well as the biosynthesis of other secondary metabolites. CONCLUSIONS: Our study found significant differences in microbial community richness, composition, and function among the healthy controls, hypertension patients with and without T2DM. Some specific taxa may explain this difference and serve as potential therapeutic targets for hypertension, T2DM, and their coexistence.

NAD+ precursor nutritional supplements sensitize the brain to future ischemic events.

Nicotinamide adenine dinucleotide (NAD+) is a redox cofactor critical for oxidative phosphorylation. Nicotinamide (NAM) and nicotinamide riboside (NR) are NAD+ precursors widely used as nutritional supplements to augment oxidative phosphorylation. Indeed, NAD+ precursors have been reported to improve outcomes in ischemic stroke when administered as a rescue therapy after stroke onset. However, we have also reported that enhanced reliance on oxidative phosphorylation before ischemia onset might worsen outcomes. To address the paradox, we examined how NAD+ precursors modulate the outcome of middle cerebral artery occlusion in mice, when administered either 20 minutes after reperfusion or daily for three days before ischemia onset. A single post-ischemic dose of NAM or NR indeed improved tissue and neurologic outcomes examined at 72 hours. In contrast, pre-ischemic treatment for three days enlarged the infarcts and worsened neurological deficits. As a possible explanation for the diametric outcomes, a single dose of NAM or NR augmented tissue AMPK, PGC1α, SIRT1, and ATP in both naïve and ischemic brains, while the multiple-dose paradigm failed to do so. Our data suggest that NAD+ precursor supplements may sensitize the brain to subsequent ischemic events, despite their neuroprotective effect when administered after ischemia onset.

Acute Treatment with Nicotinamide Riboside Chloride Reduces Hippocampal Damage and Preserves the Cognitive Function of Mice with Ischemic Injury.

Nicotinamide adenine dinucleotide (NAD) is a critical cosubstrate for enzymes involved in supplying energy to the brain. Nicotinamide riboside (NR), an NAD+ precursor, emerges as a neuroprotective factor after chronic brain insults. However, researchers have not determined whether it improves cognition after acute ischemia. In the present study, mice with middle cerebral artery occlusion were treated with NR chloride (NRC, 300 mg/kg, IP., 20 min after reperfusion). The results of the Morris water maze test revealed better recovery of learning and memory function in the NRC-treated group. Acute NRC treatment decreased hippocampal infarct volume, reduced neuronal loss and apoptosis in the hippocampus. Western blot and high-performance liquid chromatography assays of hippocampal tissues revealed that the activation of Sirtin-1 and adenosine 5' monophosphate-activated protein kinase was increased, the NAD content was elevated, and the production of adenosine triphosphate was strengthened by NRC. Collectively, acute NRC treatment increased the energy supply, reduced the neuronal loss and apoptosis, protected the hippocampus and ultimately promoted the recovery of cognitive function after brain ischemia.

Galectin-1 Contributes to Vascular Remodeling and Blood Flow Recovery After Cerebral Ischemia in Mice.

Galectin-1 is found in the vasculature and has been confirmed to promote angiogenesis in several cancer models. Furthermore, galectin-1 has been demonstrated to improve the recovery of cerebral ischemia. However, whether vascular remodeling contributes to this improvement is still unknown. In the present study, photochemical cerebral ischemia was induced in both galectin-1-treated (2 µg/day, i.c.v, 3 days) and galectin-1 knockout mice. Laser speckle imaging and immunofluorescent staining demonstrated that circulation and vascular remodeling in the ischemic cortex were improved by galectin-1 treatment but disrupted in galectin-1 knockout mice. Western blot analysis showed that the expression of matrix metallopeptidase-9 and vascular endothelial growth factor (VEGF) was regulated by galectin-1 in vivo. To determine how galectin-1 influences endothelial cells, the expression of galectin-1 in bEnd.3 cells was increased by transfection with an expression plasmid and knocked down by siRNA. As demonstrated by quantitative RT-PCR and western blot analysis, the expression of metallopeptidase-9, VEGF, and VEGF receptors was upregulated by galectin-1 overexpression but downregulated after galectin-1 knockdown. Flow cytometry, Transwell assay, and capillary-like tube formation assay were performed on cells after gene manipulation as well as cells treated by exogenous galectin-1 after anoxia. It demonstrated that galectin-1 potentiated the cell proliferation, migration capacity, and tube formation ability. Taken together, these data suggest that by targeting vascular remodeling, galectin-1 contributes to the restoration of blood flow, which promotes the recovery of mice after cerebral ischemic insults.

A case report of successful atrioventricular junction pacing in Ebstein's anomaly.

We report a case of atrioventricular junction (AVJ) pacing in a patient with Ebstein's anomaly (EA). The patient was a 68-year-old man who suffered from pacemaker syndrome and complained of heart failure symptoms. He was initially diagnosed with EA in his thirties and received right ventricular (RV) apex pacing for safe during a surgery because of low heart rate atrial fibrillation (AF) 9 years ago. However, since the patient felt discomfort, the pacing rate was then programed down to 45-55 per/min. During recent years, he was often admitted for dyspnea, dizziness, or edema and was advised to undergo intracardiac repair, but he rejected this due to the high risk of the surgery. We believed that the patient's low heart rate and ventricular pacing burden (47.8%) might be important causes of the symptoms. Therefore, we suggested that the patient undergo an upgrade of the pacing mode. In consideration of possible abnormal cardiac coronary veins, we tried His bundle pacing (HBP) to upgrade pacing. However, the SelectSecure 3830 lead was fixed at the AVJ region and obtained steady pacing parameters. After the upgrading of the AVJ pacing mode. The patient's symptoms, exercise capacity and quality of life were all improved at the 2-year follow-up. Thus, we presented the first case of AVJ pacing in a patient with EA.

Effect of implantation site of the His bundle pacing leads on pacing parameters: a single-center experience.

BACKGROUND: HB pacing is a promising approach to achieve physiological pacing, but its efficacy and long-term effects require further validation. In current study, we deemed to investigate the effect of the His bundle pacing (HBP) lead location on pacing parameters. METHODS: 2D echocardiography imaging was performed after successful implantation, according to which the patients were divided into groups A (whose His lead tips were at the atrial side) and B (whose His lead tips were at the ventricular side). The capture thresholds, sensing values, and H-V intervals between the two groups were compared. RESULTS: Thirteen patients were in group A and 16 patients were in group B. The average capture thresholds during, 1 month, and 1 year after operation were 1.20 ± 0.34, 0.69 ± 0.29, and 0.92 ± 0.80 V/0.5 ms for group A and 1.14 ± 0.43, 0.81 ± 0.39, and 0.98 ± 0.59 V/0.5 ms for group B, respectively. The difference between the two groups was not significant. The threshold values in both groups decreased significantly in 1 month and slightly increased in 1 year. The sensing values of group A were 1.87 ± 0.82, 1.95 ± 0.76, and 1.88 ± 0.75 mV, while those of group B were 4.53 ± 1.37, 4.69 ± 1.38, and 4.59 ± 1.42 mV. The difference among the three time points was not significant. However, the sensing values in group A were consistently significantly lower than those in group B. The HV interval in group A was significantly longer than that in group B. CONCLUSIONS: The implantation site of HBP leads has a significant effect on sensing values for that His leads crossing the tricuspid annulus toward the ventricle are associated with higher sensing values, compared to a more proximal location. Meanwhile, lead location has no evident effect on capture thresholds that is improved significantly shortly after operation.

Monocytic cell junction proteins serve important roles in atherosclerosis via the endoglin pathway.

The formation of atherosclerosis is recognized to be caused by multiple factors including pathogenesis in monocytes during inflammation. The current study provided evidence that monocytic junctions were significantly altered in patients with atherosclerosis, which suggested an association between cell junctions and atherosclerosis. Claudin­1, occludin­1 and ZO­1 were significantly enhanced in atherosclerosis, indicating that the tight junction pathway was activated during the pathogenesis of atherosclerosis. In addition, the gene expression of 5 connexin members involved in the gap junction pathway were quantified, indicating that connexin 43 and 46 were significantly up­regulated in atherosclerosis. Furthermore, inflammatory factors including endoglin and SMAD were observed, suggesting that immune regulative factors were down­regulated in this pathway. Silicon­based analysis additionally identified that connexins and tight junctions were altered in association with monocytic inflammation regulations, endoglin pathway. The results imply that reduced expression of the immune regulation pathway in monocytes is correlated with the generation of gap junctions and tight junctions which serve important roles in atherosclerosis.

The Correlation Between 9p21 Chromosome rs4977574 Polymorphism Genotypes and the Development of Coronary Artery Heart Disease.

Our aim is to investigate the correlation between 9p21 chromosome rs4977574 polymorphism genotypes and the development of coronary artery heart disease (CHD). Two hundred and eighty-nine patients with angiography-confirmed CHD were recruited as the CHD group, while 338 subjects without CHD symptoms were enrolled as the control group. For all participating subjects, the genotypes of rs4977574 polymorphism were examined by the real-time PCR analysis. Analyses acquired from single-locus technique showed that genotype distribution of rs4977574 polymorphism was significantly different (p = 0.041) between CHD group and the control group. Logistic regression analysis demonstrated that rs4977574 polymorphism in a dominant mode significantly increased (p = 0.038) the risk of CHD, where odds ratio (OR) was 0.71 and the 95 % confidence interval (CI) 0.58-0.97 was applied. 9p21 chromosome rs4977574 polymorphism genotypes are associated with the incidence and development of CHD. The presence of C allele may reduce the risk of CHD.