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Background and Purpose: Glial cell‐derived neurotrophic factor (GDNF) maintains gut homeostasis. Dopamine promotes GDNF release in astrocytes. We investigated the regulation by dopamine of colonic GDNF secretion. Experimental Approach: D1 receptor knockout (D1R−/−) mice, adeno‐associated viral 9‐short hairpin RNA carrying D2 receptor (AAV9‐shD2R)‐treated mice, 6‐hydroxydopamine treated (6‐OHDA) rats and primary enteric glial cells (EGCs) culture were used. Incubation fluid from colonic submucosal plexus and longitudinal muscle myenteric plexus were collected for GDNF and ACh measurements. Key Results: D2 receptor‐immunoreactivity (IR), but not D1 receptor‐IR, was observed on EGCs. Both D1 receptor‐IR and D2 receptor‐IR were co‐localized on cholinergic neurons. Low concentrations of dopamine induced colonic GDNF secretion in a concentration‐dependent manner, which was mimicked by the D1 receptor agonist SKF38393, inhibited by TTX and atropine and eliminated in D1R−/− mice. SKF38393‐induced colonic ACh release was absent in D1R−/− mice. High concentrations of dopamine suppressed colonic GDNF secretion, which was mimicked by the D2 receptor agonist quinpirole, and absent in AAV‐shD2R‐treated mice. Quinpirole decreased GDNF secretion by reducing intracellular Ca2+ levels in primary cultured EGCs. Carbachol (ACh analogue) promoted the release of GDNF. Quinpirole inhibited colonic ACh release, which was eliminated in the AAV9‐shD2R‐treated mice. 6‐OHDA treated rats with low ACh and high dopamine content showed decreased GDNF content and increased mucosal permeability in the colon. Conclusion and Implications: Low concentrations of dopamine promote colonic GDNF secretion via D1 receptors on cholinergic neurons, whereas high concentrations of dopamine inhibit GDNF secretion via D2 receptors on EGCs and/or cholinergic neurons. [ABSTRACT FROM AUTHOR]

Background Although many studies have shown that herbs containing aristolochic acids can treat various human diseases, AAΙ in particular has been implicated as a nephrotoxic agent. Methods and results Here, we detail the nephrotoxic effect of AAΙ via an approach that integrated 1H NMR-based metabonomics and network pharmacology. Our findings revealed renal injury in mice after the administration of AAΙ. Metabolomic data confirmed significant differences among the renal metabolic profiles of control and model groups, with significant reductions in 12 differential metabolites relevant to 23 metabolic pathways. Among them, there were seven important metabolic pathways: arginine and proline metabolism; glycine, serine, and threonine metabolism; taurine and hypotaurine metabolism; ascorbate and aldehyde glycolate metabolism; pentose and glucosinolate interconversion; alanine, aspartate, and glutamate metabolism; and glyoxylate and dicarboxylic acid metabolism. Relevant genes, namely, nitric oxide synthase 1 (NOS1), pyrroline-5-carboxylate reductase 1 (PYCR1), nitric oxide synthase 3 (NOS3) and glutamic oxaloacetic transaminase 2 (GOT2), were highlighted via network pharmacology and molecular docking techniques. Quantitative real-time PCR findings revealed that AAI administration significantly downregulated GOT2 and NOS3 and significantly upregulated NOS1 and PYCR1 expression and thus influenced the metabolism of arginine and proline. Conclusion This work provides a meaningful insight for the mechanism of AAΙ renal injury. [ABSTRACT FROM AUTHOR]

Relativistic multichannel theory has been used to calculate the even-parity Rydberg states and odd-parity autoionizing (AI) Rydberg spectrum converging to the limit of second and third excited core states of selenium (Se), taking into account the ionic core dipole polarization effect caused by the Rydberg electron. Six even-parity Rydberg series 4 s 2 4 p 3 ( ​ 4 S o ) n p 3 P 0 , 1 , 2 and 4 s 2 4 p 3 ( ​ 4 S o ) n p 5 P 1 , 2 , 3 are calculated, along with AI Rydberg states converging to 4 s 2 4 p 3 ( ​ 2 D 3 / 2 o ) or 4 s 2 4 p 3 ( ​ 2 D 5 / 2 o ) in J π = (1) − , (2) − or (3) − symmetry. In general, there is less than a 0.05 difference between calculated and experimental quantum defects. The influence of the perturbers on quantum defects and peak profiles has all been investigated. The accuracy of our calculations allows us to provide a reliable the assignment of the measured AI Rydberg states and the accompanying total angular momentum. [ABSTRACT FROM AUTHOR]

Objectives: In this study we aimed to assess the clinicopathological characteristics and long‐term prognosis of patients with nonalcoholic fatty liver disease (NAFLD) having distinct steatosis distribution patterns. Methods: Clinicopathological data of 238 individuals with biopsy‐confirmed NAFLD were collected. Nonalcoholic steatohepatitis‐clinical research network (NASH‐CRN) and steatosis, activity and fibrosis (SAF)/fatty liver inhibition of progression (FLIP) algorithm were used. Cumulative incidence of liver‐related events (LREs) was compared by Kaplan–Meier analysis. Univariate and multivariate logistic regression analyses were used to identify independent predictors for steatosis distribution. Results: Eligible patients were categorized into three groups based on their steatosis distribution, including azonal steatosis (AS) (62 [26.1%]), perivenular steatosis (PVS) (147 [61.8%]), and the pan‐acinar steatosis (PAS) groups (29 [12.1%]). There were significantly higher ballooning grade and disease activity (P < 0.05), more severe fibrosis (P < 0.001), and a higher cumulative incidence of LREs (hazard ratio [HR] 8.0, 95% confidence interval [CI] 2.34–27.35, P < 0.0001) in the AS group than in the PVS and PAS groups after a median of 3.6‐year follow‐up. Multivariate logistic regression analysis revealed age (odds ratio [OR] 1.11, 95% CI 1.06–1.16, P < 0.001) might be independently associated with AS distribution, and PNPLA3 rs738409 CG/GG genotype (OR 3.36, 95% CI 0.98–11.47, P = 0.053) might also play a role. Conclusions: AS is associated with more severe disease activity and fibrosis stage in NAFLD, and predisposes toward poor prognosis. Age might be an independent predictor for AS in NAFLD, while PNPLA3 rs738409 CG/GG genotype might also play a role. [ABSTRACT FROM AUTHOR]

Stroke is the third most common cause of death and also causes seizures and disability. Biomarkers are abnormal signal indicators at the biological level that are present before the organism is seriously affected and are more sensitive to early diagnosis than are traditional imaging methods. Early diagnosis of stroke can prevent the progression of the disease. However, there are currently no widely accepted biomarkers for stroke that have been applied clinically. A serum metabonomics method based on ultra-high-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (UPLC-Q-TOF/MS) was used to identify potential biomarkers and metabolic pathways of cerebral infarction. The receiver-operating characteristic (ROC) curve was used to verify the diagnostic and classification abilities of the biomarkers, and a support vector machine (SVM) model was developed for the prediction of cerebral infarction. Principal component analysis revealed a clear separation between the normal and cerebral infarction groups. A total of 13 potential serum biomarkers were identified, which were mainly involved in linoleic acid metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; tyrosine metabolism; arachidonic acid metabolism; and fatty acid biosynthesis. The ROC curve analysis showed that the potential biomarkers had high specificity and sensitivity for the diagnosis of cerebral infarction. The SVM model had good diagnostic ability and could accurately distinguish the control group from the cerebral infarction group. The metabonomics approach may be a useful bioanalytical method for understanding the pathophysiology of cerebral infarction and may provide an experimental basis for the development of clinical biomarkers for stroke. [ABSTRACT FROM AUTHOR]

In the presence of a chiral spiro phosphoric acid catalyst, the asymmetric reaction of disubstituted ketenes with N–H pyrroles occurred to afford enantioenriched C-acylated pyrroles bearing α-stereogenic carbon centres. The described reaction constitutes a rare example of a catalytic asymmetric reaction of ketenes with carbon-based nucleophiles. [ABSTRACT FROM AUTHOR]

Myocardial ischemia-reperfusion injury (MIRI) has high morbidity and mortality worldwide. Increasing evidence has shown that electroacupuncture (EA) plays a critical role in alleviating MIRI. The aim of this study is to investigate whether glutamatergic neurons in the lateral hypothalamus (LH) have vital effect on MIRI as well as the underlying mechanism during the EA pretreatment. The MIRI model was established by ligating the left anterior descending (LAD) coronary artery for 30 min followed by reperfusion for 2 h. Chemogenetics, electrocardiogram (ECG) recording, ELISA, multichannel physiology recording, and immunofluorescence staining methods were combined to demonstrate that firing frequencies of neurons in the LH and expression of c-Fos decreased by EA pretreatment. Meanwhile, EA preconditioning significantly reduced the percentage of infarct size and the levels of cardiac troponin I (cTnI) and creatine kinase isoenzymes (CK-MB) were similar to inhibition of glutamatergic neurons in LH, also attenuated morphology of myocardial tissue was induced by MIRI. However, activation of glutamatergic neurons in LH weakened the above effects of EA pretreatment. NEW & NOTEWORTHY This study demonstrates that EA preconditioning can attenuate myocardial injury for MIRI, which is similar to inhibition of glutamatergic neurons in LH. However, chemical activation of glutamatergic neurons in LH attenuates the protective effect of EA pretreatment. These findings help better understand the mechanisms of EA to regulate cardiac function.

Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders of pregnancy and can cause short- and long-term adverse effects in both pregnant women and their offspring. However, the etiology and pathogenesis of GDM are still unclear. As a metabolic disease, GDM is well suited to metabolomics study, which can monitor the changes in small molecular metabolites induced by maternal stimuli or perturbations in real time. The application of metabolomics in GDM can be used to discover diagnostic biomarkers, evaluate the prognosis of the disease, guide the application of diet or drugs, evaluate the curative effect, and explore the mechanism. This review provides comprehensive documentation of metabolomics research methods and techniques as well as the current progress in GDM research. We anticipate that the review will contribute to identifying gaps in the current knowledge or metabolomics technology, provide evidence-based information, and inform future research directions in GDM., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest for this manuscript., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)