Imperatorin Improves Obesity-Induced Cardiac Sympathetic Nerve Injury Mediated by P2X4 Receptor in Stellate Sympathetic Ganglion.

Obesity can activate the inflammatory signal pathway, induce in the body a state of chronic inflammation, and increase the excitability of the sympathetic nervous system, which may induce sympathetic neuropathic injury. The stellate sympathetic ganglia (SG) can express the P2X4 receptor, and the abnormal expression of the P2X4 receptor is related to inflammation. Imperatorin (IMP) is a kind of furan coumarin plant which has anti-inflammatory effects. This project aimed to investigate whether IMP can affect the expression of P2X4 receptors in the SG of obese rats to display a protective effect from high-fat-triggered cardiac sympathetic neuropathic injury. Molecular docking through homology modelling revealed that IMP had good affinity for the P2X4 receptor. Our results showed that compared with the normal group, the administration of IMP or P2X4 shRNA decreased sympathetic excitement; reduced the serum levels of triglyceride, total cholesterol, and lactate dehydrogenase; downregulated the expression of P2X4 receptors in SG; and inhibited the expression of inflammatory factors in the SG and serum of obese rats significantly. In addition, the expression of factors associated with the cell pyroptosis GSDMD, caspase-1, NLRP-3, and IL-18 in obese rats were significantly higher than those of the normal rats, and such effects were decreased after treatment with IMP or P2X4 shRNA. Furthermore, IMP significantly reduced the ATP-activated currents in HEK293 cells transfected with P2X4 receptor. Thus, the P2X4 receptor may be a key target for the treatment of obesity-induced cardiac sympathetic excitement. IMP can improve obesity-induced cardiac sympathetic excitement, and its mechanism of action may be related to the inhibition of P2X4 receptor expression and activity in the SG, suppression of cellular pyroptosis in the SG, and reduction of inflammatory factor levels.

Gallic Acid Alleviates Visceral Pain and Depression via Inhibition of P2X7 Receptor.

Chronic visceral pain can occur in many disorders, the most common of which is irritable bowel syndrome (IBS). Moreover, depression is a frequent comorbidity of chronic visceral pain. The P2X7 receptor is crucial in inflammatory processes and is closely connected to developing pain and depression. Gallic acid, a phenolic acid that can be extracted from traditional Chinese medicine, has been demonstrated to be anti-inflammatory and anti-depressive. In this study, we investigated whether gallic acid could alleviate comorbid visceral pain and depression by reducing the expression of the P2X7 receptor. To this end, the pain thresholds of rats with comorbid visceral pain and depression were gauged using the abdominal withdraw reflex score, whereas the depression level of each rat was quantified using the sucrose preference test, the forced swimming test, and the open field test. The expressions of the P2X7 receptor in the hippocampus, spinal cord, and dorsal root ganglion (DRG) were assessed by Western blotting and quantitative real-time PCR. Furthermore, the distributions of the P2X7 receptor and glial fibrillary acidic protein (GFAP) in the hippocampus and DRG were investigated in immunofluorescent experiments. The expressions of p-ERK1/2 and ERK1/2 were determined using Western blotting. The enzyme-linked immunosorbent assay was utilized to measure the concentrations of IL-1ß, TNF-α, and IL-10 in the serum. Our results demonstrate that gallic acid was able to alleviate both pain and depression in the rats under study. Gallic acid also reduced the expressions of the P2X7 receptor and p-ERK1/2 in the hippocampi, spinal cords, and DRGs of these rats. Moreover, gallic acid treatment decreased the serum concentrations of IL-1ß and TNF-α, while raising IL-10 levels in these rats. Thus, gallic acid may be an effective novel candidate for the treatment of comorbid visceral pain and depression by inhibiting the expressions of the P2X7 receptor in the hippocampus, spinal cord, and DRG.

Reversal of Functional Brain Activity Related to Gut Microbiome and Hormones After VSG Surgery in Patients With Obesity.

CONTEXT: Vertical sleeve gastrectomy (VSG) is becoming a prioritized surgical intervention for obese individuals; however, the brain circuits that mediate its effective control of food intake and predict surgical outcome remain largely unclear. OBJECTIVE: We investigated VSG-correlated alterations of the gut-brain axis. METHODS: In this observational cohort study, 80 patients with obesity were screened. A total of 36 patients together with 26 normal-weight subjects were enrolled and evaluated using the 21-item Three-Factor Eating Questionnaire (TFEQ), MRI scanning, plasma intestinal hormone analysis, and fecal sample sequencing. Thirty-two patients underwent VSG treatment and 19 subjects completed an average of 4-month follow-up evaluation. Data-driven regional homogeneity (ReHo) coupled with seed-based connectivity analysis were used to quantify VSG-related brain activity. Longitudinal alterations of body weight, eating behavior, brain activity, gastrointestinal hormones, and gut microbiota were detected and subjected to repeated measures correlation analysis. RESULTS: VSG induced significant functional changes in the right putamen (PUT.R) and left supplementary motor area, both of which correlated with weight loss and TFEQ scores. Moreover, postprandial levels of active glucagon-like peptide-1 (aGLP-1) and Ghrelin were associated with ReHo of PUT.R; meanwhile, relative abundance of Clostridia increased by VSG was associated with improvements in aGLP-1 secretion, PUT.R activity, and weight loss. Importantly, VSG normalized excessive functional connectivities with PUT.R, among which baseline connectivity between PUT.R and right orbitofrontal cortex was related to postoperative weight loss. CONCLUSION: VSG causes correlated alterations of gut-brain axis, including Clostridia, postprandial aGLP-1, PUT.R activity, and eating habits. Preoperative connectivity of PUT.R may represent a potential predictive marker of surgical outcome in patients with obesity.

Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention.

Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese individuals. We identified obesity-associated gut microbial species linked to changes in circulating metabolites. The abundance of Bacteroides thetaiotaomicron, a glutamate-fermenting commensal, was markedly decreased in obese individuals and was inversely correlated with serum glutamate concentration. Consistently, gavage with B. thetaiotaomicron reduced plasma glutamate concentration and alleviated diet-induced body-weight gain and adiposity in mice. Furthermore, weight-loss intervention by bariatric surgery partially reversed obesity-associated microbial and metabolic alterations in obese individuals, including the decreased abundance of B. thetaiotaomicron and the elevated serum glutamate concentration. Our findings identify previously unknown links between intestinal microbiota alterations, circulating amino acids and obesity, suggesting that it may be possible to intervene in obesity by targeting the gut microbiota.

Glycated Hemoglobin is Independently Associated with Albuminuria in Young Nondiabetic People with Obesity: A Cross-Sectional Study.

BACKGROUND The aim of this study was to explore the association between glycated hemoglobin (HbA1c) level and albuminuria in young nondiabetic people with obesity. MATERIAL AND METHODS A total of 537 young nondiabetic people with obesity were enrolled in this cross-sectional study, which was approved by the Rui-jin Hospital Ethics Committee. Albuminuria was defined as a urinary albumin-to-creatinine ratio (ACR) ≥30 mg/g. Multivariate logistic regression was used to analyze the association between HbA1c level and albuminuria. RESULTS Urinary ACR progressively increased across the tertiles of HbA1c level (P for trend <0.05). HbA1c levels were positively associated with the risk of albuminuria in the logistic regression analysis after adjustment for confounding factors. The adjusted odds ratio (OR) for albuminuria was 3.72 (95% confidence interval [CI], 1.25-11.00; P=0.017) when comparing between the highest (≥5.7%) and lowest tertiles of HbA1c level (≤5.3%). Moreover, an increment of 1 SD in HbA1c level increased the risk of albuminuria in a fully adjusted model (OR, 1.73; 95% CI, 1.25-2.46). CONCLUSIONS These data suggest that HbA1c level was independently associated with albuminuria in young nondiabetic people with obesity.

Pd(II)-Catalyzed Direct ortho-C-H Acylation of Aromatic Ketones by Oxidative Decarboxylation of α-Oxocarboxylic Acids.

A Pd-catalyzed decarboxylative acylation of aromatic ketones with α-oxocarboxylic acids was developed, and 1,2-diacylbenzenes were formed in up to 90% yield with excellent ortho-selectivity. This work demonstrates the first successful attempt to direct C-H acylation of aromatic ketones without the need for prederivatization to imines. The acylation reaction was inhibited by radical scavengers such as TEMPO, and 2,2,6,6-tetramethylpiperidin-1-yl benzoate, the adduct of TEMPO and a benzoyl radical, has been isolated and characterized. This finding is compatible with the intermediacy of acyl radicals. A mechanism involving the reaction of the palladacyclic complexes of aryl ketones with acyl radicals is proposed.

Prevalence of polycystic ovary syndrome in Chinese obese women of reproductive age with or without metabolic syndrome.

OBJECTIVE: To compare the prevalence of polycystic ovary syndrome (PCOS) and related clinical characteristics between metabolically unhealthy obese (MUO) and metabolically healthy obese (MHO) women of reproductive age. DESIGN: Cross-sectional clinical study. SETTING: Tertiary hospital. PATIENT(S): We studied 299 MUO and 122 MHO Chinese women matched on body mass index. Metabolically healthy obese was defined as obesity with no more than one metabolic abnormality. Diagnosis of PCOS was based on the revised Rotterdam criteria. INTERVENTION(S): Each subject underwent physical examination, laboratory evaluation, and gynecologic ultrasound for a diagnosis of PCOS or metabolic syndrome (MetS). MAIN OUTCOME MEASURE(S): Prevalence of PCOS was calculated in both groups. Insulin resistance was determined by homeostasis model assessment of insulin resistance or by the insulin sensitivity index derived from Bergman's minimal model. Fat distribution was measured with computerized tomography scan. RESULT(S): Prevalence of PCOS and its components did not differ between MUO and BMI-matched MHO groups (67.89% and 66.96%, respectively). In logistic regression analysis, MetS did not predict the presence of PCOS after adjusting for confounding factors. The MHO group had lower visceral adipose tissue, relatively higher insulin sensitivity, and better ß-cell function, compared with those in the MUO group; but there were no significant differences in sex hormones (except for free T and sex hormone-binding globulin) and ultrasound manifestations between MHO and MUO women. CONCLUSION(S): For the first time, our findings suggest that MetS does not add additional risk for PCOS. In addition, we found that both MUO and MHO are associated with insulin resistance to some extent.

Complete mitochondrial genome of the African pompano Alectis ciliaris (Perciformes: Carangidae).

The African pompano Alectis ciliaris (Perciformes: Carangidae) is an economic fish species distributed throughout the tropical oceans and seas of the world. In this study, we assembled the complete mitochondrial genome of A. ciliaris from contiguous, overlapping segments amplified by polymerase chain reactions. The complete mitogenome sequence was 16,570 bp in length, consisting of 37 typical animal mitochondrial genes and 1 control region, same with the typical vertebrate mitochondrial gene arrangement. There were 10 regions of gene overlaps totaling 30 bp and 12 intergenic spacer regions totaling 67 bp. The overall base composition of the heavy strand was 28.32% for A, 26.77% for T, 16.16% for G, 28.75% for C with a slight AT bias of 55.09%.

Whole mitogenome of the Japanese scad Decapterus maruadsi (Perciformes: Carangidae).

The Japanese scad (Decapterus maruadsi) is one of the most commercially important fish species that is popularly harvested in tropical and temperate seas in South East Asian countries. In the present study, we obtained the whole mitochondrial genome sequence of D. maruadsi by overlapped polymerase chain reactions. The entire sequence was 16,541 bp in length, with a gene content (13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 2 non-coding regions: the control region and the light strand replication origin) and organization similar to most of the other vertebrates. Overall base composition of the genome was 27.5% of A, 30.2% of C, 25.5% of T and 16.8% of G, showing an obvious anti G bias commonly observed in teleosts. The sequence data of D. maruadsi could provide useful information for the studies on conservation genetics and molecular phylogenetics.

The complete mitochondrial genome of longfin yellowtail S. rivoliana (Perciformes: Carangidae).

The complete mitochondrial genome of the longfin yellowtail Seriola rivoliana (Perciformes: Carangidae) was obtained in this study. The entire genome was sequenced via primer walking after long PCRs. The size of the genome was 16,530 bp in length, containing the usual 2 rRNA genes, 13 protein-coding genes, 22 tRNA genes, and one non-coding control region. The genome composition and gene order were similar to most vertebrates. Most mitochondrial genes (excepted for ND6 and eight tRNA genes) were encoded on the heavy strand. The complete mitogenome of S. rivoliana could provide a basic data for studies on species identification, molecular systematics and conservation genetics.

Serum CYFRA 21-1 in Biliary Tract Cancers: A Reliable Biomarker for Gallbladder Carcinoma and Intrahepatic Cholangiocarcinoma.

BACKGROUND: Biliary tract cancers encompass gallbladder carcinoma, and intrahepatic, perihilar and distal cholangiocarcinoma. Upregulated serum CYFRA 21-1 has been reported in intrahepatic cholangiocarcinoma. AIMS: The present study aimed to explore the clinical significance of serum CYFRA 21-1 in all biliary tract cancer subtypes. METHODS: Serum CYFRA 21-1, carbohydrate antigen 19-9 and carcinoembryonic antigen were quantitated preoperatively, postoperatively and during follow-up in 134 malignant and 52 benign patients. Receiver operator characteristic curves of biomarkers were analyzed. Level of CYFRA 21-1 was correlated with patients' clinicopathological features and follow-up data. RESULTS: CYFRA 21-1 was significantly upregulated in biliary malignancies, and expressional difference existed between these subtypes. Based on the maximal Youden's index, cutoff values were selected (ng/mL): 2.61 for biliary tract cancers (sensitivity 74.6 % and specificity 84.6 %); 3.27 for intrahepatic cholangiocarcinoma (75.6 and 96.2 %) and gallbladder carcinoma (93.7 and 96.2 %); 2.27 for perihilar cholangiocarcinoma (71.0 and 71.2 %); and 2.61 for distal cholangiocarcinoma (63.3 and 84.6 %). CYFRA 21-1 showed better diagnostic performance than other biomarkers in gallbladder carcinoma and intrahepatic cholangiocarcinoma; its performance was not inferior to that of the combination of these three biomarkers and declined after curative resection and re-elevated when tumor recurred, which was correlated with tumor aggressiveness and TNM stage; it was an independent predictor for 1-year recurrence-free survival and overall survival on multivariate analysis. CONCLUSION: Serum CYFRA 21-1 represents a reliable biomarker for gallbladder carcinoma and intrahepatic cholangiocarcinoma.