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1.
Int J Cancer ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34792202

RESUMO

Biomarkers for early detection of pancreatic cancer are in urgent need. To explore systematic circulating metabolites unbalance and identify potential biomarkers for pancreatic cancer in prospective Chinese cohorts, we conducted an untargeted metabolomics study in subjects with incident pancreatic cancer and matched controls (n=192) from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. We characterized 998 metabolites in baseline serum and calculated 156 product-to-precursor ratios based on the KEGG database. The identified metabolic profiling revealed systematic metabolic network disorders before pancreatic cancer diagnosis. Forty-five metabolites or product-to-precursor ratios showed significant associations with pancreatic cancer (P < 0.05 and FDR < 0.1), revealing abnormal metabolism of amino acids (especially alanine, aspartate and glutamate), lipids (especially steroid hormone, vitamins, nucleotides and peptides. A novel metabolite panel containing aspartate/alanine (OR [95% CI]: 1.97 [1.31-2.94]), androstenediol monosulfate (0.69 [0.49-0.97]) and glycylvaline (1.68 [1.04-2.70]) was significantly associated with risk of pancreatic cancer. Area under the receiver operating characteristic curves (AUCs) was improved from 0.573 (reference model of CA 19-9) to 0.721. The novel metabolite panel was validated in an independent cohort with AUC improved from 0.529 to 0.661. These biomarkers may have a potential value in early detection of pancreatic cancer. This article is protected by copyright. All rights reserved.

2.
Chem Biol Drug Des ; 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34811888

RESUMO

The present study deals with developing novel 1,3,5-triazine-nicotinohydrazide derivatives as potent CDK9 inhibitors in a straightforward synthetic route with potent anti-osteosarcoma activity. The most potent CDK9 inhibitor compound 5k inhibits proliferation of MG-63 cells via induction of apoptosis and G2/M cell cycle arrest. It reduces tumor progression in the patient-derived orthotopic xenograft (PDOX) mouse model with significant antioxidant and anti-inflammatory activity. In tumor tissue homogenates, it caused significant inhibition of CDK9 and inhibited the phosphorylation of RNAPII ser2 and reduced MCL-1 expression in western blot analysis. Compound 5k also showed considerable bioavailability in SD mice. Our results demonstrated that compound 5k inhibits growth of OS in-vitro and in-vivo via inhibition of CDK9 which attenuated the downstream phosphorylation of RNAPII ser2 and represses expression of the anti-apoptotic protein, MCL-1 for the induction of apoptosis in OS.

3.
Diabetes Metab Syndr Obes ; 14: 4497-4503, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34785919

RESUMO

Objective: This study aims to explore the factors influencing the renal glucose threshold (RTG) in patients with newly diagnosed type 2 diabetes mellitus (T2DM). Methods: A cross-sectional study was conducted on 1009 hospitalized patients with T2DM using stratified random sampling. Blood glucose was monitored using a dynamic blood glucose monitor to obtain the mean blood glucose (MBG), which is used to calculate the RTG. The factors influencing the RTG were then analyzed. Results: The mean RTG in patients with newly diagnosed T2DM was 203.58 ± 55.22 mg/dl. The correlation between the RTG and the various variables was analyzed, and the results demonstrated that the RTG was correlated with the patient's age (r = -0.14539, P = 0.0001); MBG (r = -0.35009, P = 0.0001); renal long neck (r = 0.16762, P = 0.0001); homeostatic model assessment for insulin resistance (r = -0.38322, P = 0.0001); homeostatic model assessment for beta-cell function (r = -0.22770, P = 0.0001); and the levels of glycated hemoglobin (HbA1c; r = 0.98994, P = 0.0001), blood urea nitrogen (r = -0.11093, P = 0.0004), creatinine (r = -0.26414, P = 0.0001), uric acid (r = -0.20149, P = 0.0001), total cholesterol (r = 0.13192, P = 0.0001), low-density lipoprotein (r = 0.12466, P = 0.0001), thyroid-stimulating hormone (r = -0.06346, P = 0.0460), beta-2 microglobulin (r = -0.08884, P = 0.0056), and 24-hour urine glucose (r = 0.32115, P = 0.0001). Multiple linear stepwise regression analysis revealed that the HbA1c, 24-hour urine glucose, estimated glomerular filtration rate (eGFR), D-dimer, and body mass index (BMI) should be included in the final model, and HbA1c had the greatest impact on the RTG followed in descending order by the 24-hour urine glucose, eGFR, D-dimer, and BMI (P < 0.05). Conclusion: The RTG increases in most patients with newly diagnosed diabetes. The risk factors for the RTG are HbA1c, 24-hour urine glucose, eGFR, D-dimer, and BMI.

4.
J Colloid Interface Sci ; 608(Pt 2): 1481-1488, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34742067

RESUMO

In aqueous zinc-based batteries, the reaction by-product Zn4SO4(OH)6·xH2O is commonly observed when cycling vanadium-based and manganese-based cathodes. This by-product obstructs ion transport paths, resulting in enhanced electrochemical impedance. In this work, we report a hybrid aqueous battery based on a Na0.44MnO2 cathode and a metallic zinc foil anode. The surfactant sodium lauryl sulfate is added to the electrolyte as a modifier, and the performance before and after modification is compared. The results show that sodium lauryl sulfate can generate an artificial passivation film on the electrode surface. This passivation film reduces the generation of Zn4SO4(OH)6·xH2O and inhibits the dissolution of Na0.44MnO2 in the electrolyte. Therefore, the reaction kinetics and cycle stability of the battery are significantly enhanced. A battery with this electrolyte additive delivers an initial discharge capacity of 235 mA h g-1 at a current density of 0.1 A g -1. At the same time, the battery has excellent rate performance. Under the high-rate condition of 1 A g-1, the battery still maintains a capacity retention rate of 93% after 1500 cycles. Finally, the functional mechanism of by-product inhibition by the electrolyte additive is discussed.

5.
Foods ; 10(11)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34828932

RESUMO

Aristolochic acid (AA) toxicity has been shown in humans regarding carcinogenesis, nephrotoxicity, and mutagenicity. Monitoring the AA content in drug homologous and healthy foods is necessary for the health of humans. In this study, a monoclonal antibody (mAb) with high sensitivity for aristolochic acid I (AA-I) was prepared. Based on the obtained mAb, a chemiluminescent immunoassay (CLEIA) against AA-I was developed, which showed the 50% decrease in the RLUmax (IC50) value of 1.8 ng/mL and the limit of detection (LOD) of 0.4 ng/mL. Carbon dots with red emission at 620 nm, namely rCDs, were synthesized and employed in conventional indirect competitive enzyme-linked immunosorbent assay (icELISA) to improve the assay sensitivity of a fluoroimmunoassay (FIA). Oxidized 3,3'',5,5''-tetramethylbenzidine dihydrochloride (oxTMB) can quench the emission of the rCDs through the inner-filter effect; therefore, the fluorescence intensity of rCDs can be regulated by the concentration of mAb. As a result, the assay sensitivity of FIA was improved by five-fold compared to CLEIA. A good relationship between the results of the proposed assays and the standard ultra-high performance liquid chromatography-triple quadrupole mass spectrometer (UPLC-QQQ-MS/MS) of real samples indicated good accuracy and practicability of CLEIA and FIA.

7.
Front Endocrinol (Lausanne) ; 12: 717069, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671316

RESUMO

Objectives: Nationwide studies focusing on the impact of early-onset type 2 diabetes and obesity on the development of cardiovascular diseases (CVD) are limited in China. We aimed to investigate the association between age at diagnosis of type 2 diabetes and the risk of CVD, and to further examine the modifying effect of obesity on this association among Chinese adults. Methods: This study included 23,961 participants with previously diagnosed diabetes from a large nationwide population-based cohort study across mainland China. With an interviewer-assisted questionnaire, we collected detailed information on CVDs. Logistic regression analysis was used to evaluate the risk of CVDs associated with age at diagnosis of diabetes. Results: Compared with patients with late-onset diabetes (≥60 years), those with earlier-onset diabetes had increased risks for CVD, with adjusted ORs (95% CIs) of 1.72 (1.36-2.17), 1.52 (1.31-1.75) and 1.33 (1.19-1.48) for patients diagnosed aged <40, 40-49 and 50-59 years, respectively. Each 5-year earlier age at diagnosis of type 2 diabetes was significantly associated with 14% increased risk of CVD (OR, 1.14; 95%CI, 1.11-1.18). This association was more prominent for patients with obesity than those with normal body mass index (BMI). Significant interaction was detected between age at diagnosis and BMI categories on CVD risk (P for interaction=0.0457). Conclusion: Early-onset type 2 diabetes was significantly associated with higher risk of CVD, and this association was more prominent among patients with obesity.

8.
Neurotox Res ; 39(6): 1800-1811, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34655374

RESUMO

Microglia-mediated neuroinflammation in response to injurious self and non-self-stimuli exerts detrimental effects on neurons, which may lead to cognitive impairment. Luteolin, a typical kind of natural flavonoid in honeysuckle, chrysanthemum, and Herba Schizonepetae, is widely recognized to be anti-inflammatory and antioxidant against peripheral inflammation. However, its protective effect against inflammation-induced cognitive impairment is currently unknown. In this paper, we investigated the relief potential of luteolin against lipopolysaccharide (LPS)-induced cognitive impairment and neuroinflammation and its possible anti-inflammatory mechanisms in lipopolysaccharide-stimulated BV2 microglia cells. In this study, luteolin ameliorated LPS-induced cognitive impairments, indicated by behavioral performance of neuroinflammatory model mice in Morris water maze tests. Protein analyses and histological examination also revealed protective effect of luteolin against neuronal damage, through inhibiting overproduction of inflammatory cytokines in both hippocampus and cortex of mice. We also observed luteolin in vitro significantly suppressed the levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-1 ß (IL-1ß), and inflammatory mediators like nitric oxide. Taken together, these results demonstrated luteolin was effective in alleviating cognitive impairment and limited neuronal damage via inhibiting the release of inflammatory mediators, suggesting luteolin is potential for further therapeutic research of neuroinflammation-related neurodegenerative diseases.

9.
Metabolism ; 124: 154874, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34517014

RESUMO

AIMS/HYPOTHESIS: We aimed to evaluate the effect of NAFLD on the risk of incident cardiovascular disease (CVD) and estimated glomerular filtration rate (eGFR)-based chronic kidney disease (CKD), and further test the joint effects and interactions between NAFLD status and individual metabolic element, as well as the total 'ABCs' metabolic goal achievement, on the CVD and CKD risk among 101,296 patients with prediabetes or diabetes from a prospective cohort study. METHODS: We conducted the study based on the China Cardiometabolic Disease and Cancer Cohort (4C) study, a large-scale, population-based prospective cohort. After excluding alcohol abuse and other cause of hepatic diseases, we used fatty liver index (FLI) ≥ 60 as a proxy of NAFLD and stratified the probability of fibrosis by aspartate transaminase/alanine transaminase ratio (AAR) with cut-offs of 0.8 and 1.4. 'ABCs' metabolic goal was defined as subjects who had HbA1c < 6.5% (A), SBP/DBP < 130/80 mmHg (B), and LDL-C < 100 mg/dL (C). During 3.8 years follow-up, we validated 2340 CVD events based on medical records and identified 1943 participants developed CKD based on centrally tested eGFR. RESULTS: The multivariable adjusted hazard ratios (HRs) were 1.15 (95% confidence interval (CI), 1.05-1.27) for CVD events and 1.33 (95% CI, 1.20-1.48) for CKD among NAFLD patients, compared with participants without NAFLD. Of NAFLD patients, relative to individuals with low AAR (<0.8), those with high AAR (≥1.4) were more likely to experience CVD events [1.62 (1.21-2.18)] and CKD [1.63 (1.17-2.28)]. Participants with NAFLD and comorbid poorly controlled metabolic risk factors had higher risk of CVD events or CKD than having either alone, with a significant interaction between poor glycemic control and NAFLD on the risk of vascular complications. CONCLUSIONS: NAFLD was associated with incident CVD and CKD among patients with prediabetes or diabetes. Such associations were substantially modified by the comprehensive achievement of metabolic goal.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34427675

RESUMO

OBJECTIVES: To investigate the associations between individual and combined cardiometabolic morbidities and incident cardiovascular events in Chinese adults. DESIGN: A prospective, nationwide, and population-based cohort study. PARTICIPANTS: 133572 participants aged ≥ 40 years were included in the study. MAIN OUTCOME MEASURES: Cardiovascular disease (CVD) events. RESULTS: Compared with participants without diabetes, hypertension and dyslipidemia, participants with only diabetes (hazard ratio [HR], 1.58; 95% confidence interval [CI], 1.32-1.90) or only hypertension (2.04; 1.82-2.28) exhibited significantly higher risk for CVD events, while participants with only dyslipidemia (0.97; 0.84-1.12) exhibited no significantly higher risk for CVD events. When analyzed collectively, participants with diabetes plus hypertension (HR, 2.67; 95%CI, 2.33-3.06), diabetes plus dyslipidemia (1.57; 1.32-1.87), and hypertension plus dyslipidemia (2.12; 1.88-2.39) exhibited significantly higher risk for CVD. Moreover, participants with the combination of diabetes, hypertension and dyslipidemia exhibited the highest risk for CVD events (HR, 3.06; 95%CI, 2.71-3.46). Multivariable-adjusted HRs (95% CIs) for CVD associated with diabetes based on fasting glucose ≥7.0 mmol/L, oral glucose tolerance test-2h glucose ≥11.1 mmol/L, and hemoglobin A1c ≥6.5% were 1.64 (1.51-1.78), 1.57 (1.45-1.69), and 1.54 (1.42-1.66), respectively; associated with hypertension based on systolic blood pressure ≥140 mmHg and diastolic blood pressure ≥90 mmHg were 1.89 (1.76-2.03) and 1.74 (1.60-1.88), respectively; associated with dyslipidemia based on total cholesterol ≥6.22 mmol/L, low-density lipoprotein cholesterol ≥4.14 mmol/L, high-density lipoprotein cholesterol <1.04 mmol/L, and triglycerides ≥2.26 mmol/L were 1.18 (1.08-1.30), 1.30 (1.17-1.44), 1.00 (0.92-1.09), and 1.10 (1.01-1.20), respectively. CONCLUSIONS: Diabetes, hypertension and dyslipidemia showed additive associations with the risk of CVD events in middle-aged and elderly Chinese adults.

11.
Theranostics ; 11(16): 7829-7843, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335967

RESUMO

Aims/hypothesis: MicroRNAs (miRNAs) are known to contribute to many metabolic diseases, including type 2 diabetes. This study aimed to investigate the roles and molecular mechanisms of miR-185-5p in the regulation of hepatic gluconeogenesis. Methods: MicroRNA high-throughput sequencing was performed to identify differentially expressed miRNAs. High-fat diet-induced obese C57BL/6 mice and db/db mice, a genetic mouse model for diabetes, were used for examining the regulation of hepatic gluconeogenesis. Quantitative reverse transcriptase PCR and Western blotting were performed to measure the expression levels of various genes and proteins. Luciferase reporter assays were used to determine the regulatory roles of miR-185-5p on G6Pase expression. Results: Hepatic miR-185-5p expression was significantly decreased during fasting or insulin resistance. Locked nucleic acid (LNA)-mediated suppression of miR-185-5p increased blood glucose and hepatic gluconeogenesis in healthy mice. In contrast, overexpression of miR-185-5p in db/db mice alleviated blood hyperglycemia and decreased gluconeogenesis. At the molecular level, miR-185-5p directly inhibited G6Pase expression by targeting its 3'-untranslated regions. Furthermore, metformin, an anti-diabetic drug, could upregulate miR-185-5p expression to suppress G6Pase, leading to hepatic gluconeogenesis inhibition. Conclusions/interpretation: Our findings provided a novel insight into the role of miR-185-5p that suppressed hepatic gluconeogenesis and alleviated hyperglycemia by targeting G6Pase. We further identified that the /G6Pase axis mediated the inhibitory effect of metformin on hepatic gluconeogenesis. Thus, miR-185-5p might be a therapeutic target for hepatic glucose overproduction and fasting hyperglycemia.


Assuntos
Gluconeogênese/genética , MicroRNAs/genética , Regiões 3' não Traduzidas , Animais , Glicemia/análise , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Feminino , Gluconeogênese/fisiologia , Glucose/metabolismo , Glucose-6-Fosfatase/metabolismo , Hiperglicemia/metabolismo , Insulina/metabolismo , Resistência à Insulina/genética , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , MicroRNAs/metabolismo , Obesidade/genética
12.
Front Neurol ; 12: 522513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34408715

RESUMO

Objective: To identify the gene mutation of Stormorken syndrome and review the published Stromal Interaction Molecule 1 (STIM1) mutation phenotype. Methods: We described the clinical and molecular aspects of a Chinese female with Stormorken syndrome by laboratory tests, muscle biopsies, and genetic analysis. We used this information to summarize all the mutation sites reported in the literature. We also reviewed the clinical features of published cases with a gain of function mutations of STIM1. Results: A 12-year-old Chinese female presented with skin purpura in the lower limbs and stroke-like episodes. Muscle biopsy and microscopic examination revealed atrophy in her skeletal muscle. Genetic analysis identified a novel heterozygous missense mutation, a c.1095G>C transition (NM_003156.3), which caused a p.K365N amino acid substitution in the protein and affected a STIM1-orai1-activation region (SOAR). Conclusions: The novel variant c.1095G>C transition (NM_003156.3) was located in the SOAR, which expands the phenotypic spectrum of STIM1 variants in human disorders and may define the molecular basis of Stormorken syndrome.

13.
Cell Death Discov ; 7(1): 224, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34455417

RESUMO

Hepatocellular carcinoma (HCC) is a heterogeneous tumor with an increased incidence worldwide accompanied by high mortality and dismal prognosis. Emerging evidence indicates that mesenchymal stem cells (MSCs)-derived exosomes possess protective effects against various human diseases by transporting microRNAs (miRNAs or miRs). We aimed to explore the role of exosomal miR-15a derived from MSCs and its related mechanisms in HCC. Exosomes were isolated from transduced MSCs and co-incubated with Hep3B and Huh7 cells. miR-15a expression was examined by RT-qPCR in HCC cells, MSCs, and secreted exosomes. CCK-8, transwell, and flow cytometry were used to detect the effects of miR-15a or spalt-like transcription factor 4 (SALL4) on cell proliferative, migrating, invasive, and apoptotic properties. A dual-luciferase reporter gene assay was performed to validate the predicted targeting relationship of miR-15a with SALL4. Finally, in vivo experiments in nude mice were implemented to assess the impact of exosome-delivered miR-15a on HCC. The exosomes from MSCs restrained HCC cell proliferative, migrating, and invasive potentials, and accelerated their apoptosis. miR-15a was expressed at low levels in HCC cells and could bind to SALL4, thus curtailing the proliferative, migrating, and invasive abilities of HCC cells. Exosomes successfully delivered miR-15a to HCC cells. Exosomal miR-15a depressed tumorigenicity and metastasis of HCC tumors in vivo. Overall, exosomal miR-15a from MSCs can downregulate SALL4 expression and thereby retard HCC development.

14.
HLA ; 98(5): 488-490, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34390544

RESUMO

The HLA-DRB3*02:02:19 allele differs from DRB3*02:02:01:02 by a single nucleotide change in exon 2.


Assuntos
Nucleotídeos , Alelos , Éxons/genética , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB3/genética , Teste de Histocompatibilidade , Humanos
16.
J Diabetes ; 13(12): 949-959, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34427386

RESUMO

BACKGROUND: Gestational hyperglycemia increases the risk of diabetes in later life. However, the risk of future cardiovascular diseases (CVD) related to gestational hyperglycemia remains inconclusive. The purpose of this study was to investigate the impact of gestational hyperglycemia on the subsequent risk of CVD and its modifying factors among elderly Chinese women. METHODS: We conducted a case-control study of elderly women from the baseline survey of Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study. Women with gestational hyperglycemia (n = 82), and controls matched by age and study site (n = 410) were included. Information on CVD, including reported coronary heart disease, stroke, or myocardial infarction, was collected through an interviewer-assisted questionnaire. RESULTS: Women with gestational hyperglycemia were more likely to develop diabetes (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.50-4.18) and CVD (OR, 1.98; 95% CI, 1.05-3.74). Even without progressing to type 2 diabetes, gestational hyperglycemia was associated with an increased risk of CVD (OR, 2.88; 95% CI, 1.18-7.00). However, subgroup analysis indicated that compared with those without gestational hyperglycemia or hypertension, women with both gestational hyperglycemia and hypertension had higher risk of CVD (OR, 3.98; 95% CI, 1.65-9.58), whereas the risk estimate did not significantly change in women with gestational hyperglycemia alone (OR, 2.15; 95% CI, 0.71-6.57). Stratified analysis indicated that among those with overweight/obesity, inactive physical activity, or unhealthy dietary habits, gestational hyperglycemia increased the risk of CVD. CONCLUSIONS: In elderly Chinese women, gestational hyperglycemia was associated with an increased risk of CVD in later life. This association was independent of the progression to diabetes and might be modified by lifestyle factors and hypertension.

17.
Diabetes Metab Res Rev ; : e3489, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344058

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is now regarded as the hepatic manifestation of metabolic syndrome (MetS). Recent research has suggested that serum creatinine (SCr) may be an indicator of MetS and its related diseases. We aimed to investigate the association between SCr and NAFLD in Chinese adults. METHODS: A cross-sectional sample of 8862 subjects aged 40 years or older (40-73 years) from China were analysed in this study. The anthropometric measurements, laboratory tests, and hepatic ultrasonography were conducted. NAFLD presence was defined by hepatic ultrasound in the absence of other liver diseases. RESULTS: NAFLD subjects had higher SCr than those without NAFLD (66.8 µmol/L vs. 65.6 µmol/L, p < 0.001). Moreover, SCr levels were correlated with alanine aminotransferase (ß = 0.099, p < 0.001), aspartate aminotransferase (ß = 0.135, p < 0.001), γ-glutamyltransferase (ß = 0.039, p < 0.001), and insulin resistance (ß = 0.027, p = 0.014) after adjusted for potential covariates. In the multivariable-adjusted logistic regression analyses, compared to the first SCr quintile, the odds ratio for NAFLD was 1.35 (95% confidence interval 1.14-1.60, p < 0.001) for the fifth quintile after adjusting multiple measured confounders. CONCLUSION: SCr concentration is independently associated with NAFLD in a middle aged and older Chinese population. Elevated SCr levels, even within normal ranges, were associated with higher risk of NAFLD.

18.
Toxicol Appl Pharmacol ; 429: 115701, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34453990

RESUMO

Gut dysbiosis and dysregulation of gut-brain communication have been identified in hypertensive patients and animal models. Previous studies have shown that probiotic or prebiotic treatments exert positive effects on the pathophysiology of hypertension. This study aimed to examine the hypothesis that the microbiota-gut-brain axis is involved in the antihypertensive effects of curcumin, a potential prebiotic obtained from Curcuma longa. Male 8- to 10-week-old spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were divided into four groups: WKY rats and SHRs treated with vehicle and SHRs treated with curcumin in dosage of 100 or 300 mg/kg/day for 12 weeks. Our results show that the elevated blood pressure of SHRs was markedly decreased in both curcumin-treated groups. Curcumin treatment also altered the gut microbial composition and improved intestinal pathology and integrity. These factors were associated with reduced neuroinflammation and oxidative stress in the hypothalamus paraventricular nucleus (PVN). Moreover, curcumin treatment increased butyrate levels in the plasma, which may be the result of increased butyrate-producing gut microorganisms. In addition, curcumin treatment also activated G protein-coupled receptor 43 (GPR 43) in the PVN. These results indicate that curcumin reshapes the composition of the gut microbiota and ameliorates the dysregulation of the gut-brain communication to induce antihypertensive effects.

19.
Cardiovasc Toxicol ; 21(10): 820-834, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34269955

RESUMO

Long-term maternal salt intake induces the hypertension in offspring. Numerous studies have also indicated that high-salt diet causes the inflammation and an imbalance in neurotransmitters in the paraventricular nucleus (PVN) which increases the blood pressure and sympathetic activity. This study aimed to explore whether maternal salt intake induces hypertension in their male offspring by increasing the inflammation and changing the neurotransmitters balance in the paraventricular nucleus of offspring. This study includes two parts: Part I to explore the effect of high-salt diet on pregnant rats and the changes in inflammation and neurotransmitters in their male offspring PVN; Part II to reveal the influence on their offspring of bilateral PVN infusion of c-Src inhibitor dasatinib (DAS) in pregnant rats fed a high-salt diet. Maternal high-salt diet intake during copulation, pregnancy, and lactation impacted the offspring mean arterial pressure (MAP) and elevated the offspring PVN levels of p-Src, proinflammatory cytokines, and excitatory neurotransmitters. Bilateral PVN infusion of a c-Src inhibitor combined with maternal high-salt diets decreased MAP in the offspring. The infusion was also shown to suppress the Src-induced MAPK/NF-κB signaling pathway (p38 MAPK, JNK, Erk1/2), which attenuates inflammatory reactions. Finally, bilateral PVN infusion of the Src inhibitor in pregnant rat with high-salt diets improved the levels of inhibitory neurotransmitters in offspring PVN, which restored the excitatory-inhibitory neurotransmitter balance in male offspring. High-salt diets increase sympathetic activity and blood pressure in adult offspring, probably by activating the c-Src/MAPKs/NF-κB signaling pathway-induced inflammation. Moreover, NF-κB disrupts the downstream excitatory-inhibitory neurotransmitter balance in the PVN of male offspring.

20.
ACS Appl Mater Interfaces ; 13(29): 34349-34356, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34279899

RESUMO

A power supply with the characteristics of portability and safety will be one of the dominating mainstreams for future wearable electronics and implantable biomedical devices. The conventional energy storage devices with typical sandwich structures have complicated components and low mechanical properties, suffering from the apparent performance degradation during deformation and hindering the possibility of implanting biomedical units. Herein, a novel all-in-one structure ″paper-like″ zinc ion battery (ZIB) was designed and assembled from an electrospun polyacrylonitrile (PAN) nanomembrane (as the separator) with in situ deposited anode (zinc nanosheets) and cathode (MnO2 nanosheets), which ensures the monolith under different bending states by avoiding the relative sliding and detaching between the integrated layers. Benefiting from the well-designed all-in-one construction and electrodes, the resultant all-in-one ZIB (AZIB) features an ultrathin thickness (about 97 µm), superior specific capacity of 353.8 mAh g-1 (at 0.1 mA cm-2), and outstanding cycling stability (98.7% capacity retention after 500 cycles at 1 A cm-2). And the achieved volumetric energy density is as high as 17.5 mWh cm-3 at a power density of 116.4 mW cm-3. Impressively, the concept of wearable electronic applications of the obtained AZIB was fully demonstrated with excellent flexibility and remarkable temperature resistance under various severe conditions. Our AZIB may provide a versatile strategy for applying and developing flexible wearable electronics and implantable biomedical devices.

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