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1.
J Hypertens ; 39(4): 808-812, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649283
2.
Neurochem Int ; 145: 105010, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33684544

RESUMO

To determine whether voluntary wheel running could improve cognitive function from both the young and middle-aged APP/PS1 mice and the underlying mechanisms involved in. Young (9-weeks old) and middle-aged (24-weeks old) APP/PS1 mice were randomly assigned into control and exercise groups, respectively. Mice from exercise group had free and unlimited access to the running wheel for a total of 16 weeks. Voluntary exercise only improved cognitive function from young but not the middle-aged APP/PS1 mice. This might be owing to that in young APP/PS1 mice voluntary exercise reduced tau phosphorylation via inhibiting p-GSK3ß activity, as well as reduced neuro-inflammation and elevated key proteins involved in synaptic plasticity. Additionally, exercise also elevated circulating L-Valine, Glucosamine, Formylanthranilic acid, Myristic acid level and improved gut microbiota profiles (i.e. elevated Oscillibacter, EF097061_g, EU454870_g, EU504554_g, EU505046_g and EF096172_g and reduced Alistipes). Improved circulating metabolites and intestinal microbiome might also contribute to improved learning and memory abilities post exercise. For the middle-aged APP/PS1 mice, exercise reduced ADAM10 and GFAP protein expression in hippocampus, with no notable alterations in circulating metabolites; additionally, mice from exercise group had markedly reduced abundance of the phyla Proteobacteria and Tenericutes, genera Bacteroides and Faecalibacterium, and elevated abundance of the genera Allobaculum. It is suggested that voluntary exercise should be initiated at an early adulthood period rather than at late stage in order to prevent cognitive decline or Alzheimer's disease.

3.
BMC Cardiovasc Disord ; 21(1): 141, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731001

RESUMO

BACKGROUND: The predictive importance of visit-to-visit blood pressure variability (VVV) for high blood pressure (HBP) in a pediatric population has been largely unsettled. We aimed to evaluate it based on Health Promotion Program for Children and Adolescents (HPPCA), a school-based surveillance conducted from 2012 to 2018 in Suzhou, China. METHODS: A total of 330,618 participants had BP measurement in 2018 and ≥ 3 BP records during 2012-2017, were recruited from HPPCA. Absolute BP values (in mmHg) were converted into age-, sex- and height- normalized z-scores. VVV was expressed as standard deviation (SD), coefficient of variation (CV) or average real variability (ARV) of BP z-scores during 2012-2017. Logistic regression models were used to assess the associations between VVV and HBP in 2018. RESULTS: In 2018, 42,554 (12.87%) subjects were defined as HBP. VVV, except for SBP-CV and DBP-CV, was significantly higher in the HBP group than normotensives group. After adjusting for covariates including mean BP values from 2012 to 2017, SBP-SD, SBP-ARV, DBP-SD and DBP-ARV, increased the risk of HBP by 5.70 [95% confidence interval (95% CI) 5.54-5.87], 4.10 (95% CI 4.01-4.20), 4.70 (95% CI 4.50-4.90) and 3.39 (95% CI 3.28-3.50) times, respectively. Notably, SBP-SD significantly improved risk discrimination of HBP based on other risk variables (c-statistics, net reclassification index and integrated discrimination improvement significantly increased). CONCLUSIONS: Higher SD or ARV of BP, was independently related with higher probability of HBP in Chinese pediatric population. SBP-SD could be potentially helpful for detecting HBP. Future researches investigating the predictive value of VVV are warrant.

4.
Neuromodulation ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33538043

RESUMO

OBJECTIVES: Intestinal electrical stimulation (IES) has been proposed for treating diabetes; however, its parameters need to be further systematically optimized. This study aimed to optimize the parameters of IES and investigate its possible mechanisms involving glucagon-like peptide-1 (GLP-1) in diabetic rats. MATERIALS AND METHODS: Thirty-six high-fat diet-induced diabetic rats were chronically implanted with a pair of bipolar electrodes at the duodenum for IES. The oral glucose tolerance test (OGTT) was performed in a number of sessions with IES using different parameters and biphasic charge-balanced waveforms to derive the best values for train on-time, pulse frequency, and pulse width. Incretin hormones such as GLP-1 were assessed and the GLP-1 antagonist Exendin 9-39 was used to assess the role of GLP-1 in the ameliorating effect of IES on hyperglycemia. RESULTS: The most effective IES parameters in reducing blood glucose (BG) during the OGTT were derived: 1.2 sec on, 0.3 sec off, 80 Hz, 3 msec. IES with these parameters reduced BG level by at least 29% from 15 min to 180 min (p < 0.05 for all points, N = 10). IES with these stimulation parameters increased plasma GLP-1 level at 30 min, 60 min, 90 min and gastric inhibitory peptide (GIP) level at 30 min (N = 8). Exendin 9-39 blocked the inhibitory effect of IES on BG (p > 0.05, IES + Exendin 9-39 vs. sham-IES, N = 8). CONCLUSION: IES with the most effective parameters derived in this study improves hyperglycemia in diabetic rats. The ameliorating effect of IES on hyperglycemia is attributed to the enhanced release of GLP-1. IES has great potential for treating diabetes.

5.
J Hum Hypertens ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33589762

RESUMO

The 2017 American College of Cardiology/American Heart Association guideline recommends a lowered threshold for hypertension diagnosis. Nonetheless, the association of blood pressure (BP) groups defined by the new guideline and all-cause mortality has not been fully estimated, especially in general Chinese. Based on the China Health and Retirement Longitudinal Study (CHARLS) during 2011-2018, 12,964 participants aged 45 years or older at baseline were enrolled for a follow-up of 7 years. Cox proportional hazards models were used to examine the relationship of BP classifications with all-cause mortality, with normal BP (<120/80 mmHg) as a reference. Afterwards, eligible studies shed light in this field were searched in public databases, and meta-analysis was conducted. In CHARLS, there were 41.21% and 16.08% individuals with stage 2 hypertension and stage 1 hypertension, respectively. During the follow-up, 1293 death occurred. The redefined stage 1 (130-139/80-89 mmHg) and stage 2 hypertension (≥140/≥90 mmHg) were found to have increased risk of death in the crude model, but only stage 2 hypertension maintained statistically significance after adjustment. Furthermore, meta-analysis including CHARLS and nine other prospective studies, with a total of 290,609 participants followed up for 3,081,532 person-years, resulted in similar results (combined hazard ratio (95% confidence interval) was 1.07 (0.99-1.15) for stage 1 hypertension, and 1.39 (1.25-1.53) for stage 2 hypertension). The present study detected that individuals with stage 2 and stage 1 hypertension had increased likelihood to die from any cause, but only the former association achieved statistically significance. Further cohorts with long-term follow-up duration are warranted, especially in China.

6.
BMC Pregnancy Childbirth ; 21(1): 155, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33618715

RESUMO

BACKGROUND: Associations between trajectories of systolic blood pressure (SBP) during pregnancy and pregnant outcomes remain unclear and disparate. METHODS: Data of 20,353 mothers without chronic hypertension and who delivered live singletons between January, 2014 and November, 2019, was extracted from Taicang register-based cohort. Based on SBP measured during 10 to 40 weeks of gestation, SBP trajectories were explored using latent class growth mixture model, and their associations with maternal and neonatal outcomes were assessed by logistic regression analyses. RESULTS: Six heterogeneous SBP trajectories were identified: low delayed-increasing (7.47%), low reverse-increasing (21.88%), low-stable (19.13%), medium-stable (21.64%), medium reverse-increasing (16.47%), and high stable (13.41%) trajectories. The high-stable trajectory had SBP around 125 mmHg in the 10th gestational week, and increased slightly onwards. When compared with the low-stable trajectory, the high-stable trajectory had maximally adjusted odds ratio (95% confidence interval) of 5.28 (2.76-10.10), 1.30 (1.13-1.50), 1.53 (1.12-2.08), 1.32 (1.06-1.65) and 1.64 (1.08-2.48) for gestational hypertension (GH), early-term delivery (ETD), preterm delivery (PTD), small for gestational age and low birth weight (LBW), respectively. Besides, the medium reverse-increasing trajectory showed significantly increased risk of GH and ETD, while the medium-stable trajectory had significantly elevated risk of ETD and PTD. Notably, SBP trajectories slightly but significantly improved risk discrimination of GH, ETD and LBW, over traditional risk factors. CONCLUSION: Women with different SBP trajectories were at varied risk of adverse maternal and fetal outcomes. Meanwhile, our study suggested that BP monitoring during pregnancy is necessary, especially for women with high SBP in early pregnancy or upward trajectory.

7.
PLoS One ; 15(12): e0243227, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33270788

RESUMO

Fewer studies have focused on the independent association between mean corpuscular volume (MCV) and cognitive performance. This study was designed to characterize the cross-sectional association between MCV and cognitive performance in a large sample of Chinese residents (age≥45 years) from the China Health and Retirement Longitudinal Study (CHARLS). A total of 4023 male and 4173 female adults with MCV ≥ 80 fl were included for analysis. By multivariable linear regression analysis, for the total subjects, MCV level was significantly negatively associated with global cognitive function and episodic memory. When adjusted by sex, only in male subjects, higher MCV level was associated with reduced scores for global cognitive function, episodic memory and mental status. Via binary logistic regression analysis, the higher MCV level (MCV>100 fl) was associated with poor global cognitive function (OR = 1.601; 95% CI = 1.198-2.139; p = 0.001), episodic memory (OR = 1.679; 95% CI = 1.281-2.201; p<0.001), and mental status (OR = 1.422; 95% CI = 1.032-1.959; p = 0.031) for the whole participants. When testing this association by sex, the significant relationship between higher MCV level with worse episodic memory was observed both in male (OR = 1.690; 95% CI = 1.211-2.358; p = 0.002) and female (OR = 1.729; 95% CI = 1.079-2.770; p = 0.023) subjects; while the association between higher MCV level and poor global cognitive function (OR = 1.885; 95% CI = 1.329, 2.675; p<0.001) and mental status (OR = 1.544; 95% CI = 1.034, 2.306; p = 0.034) only existed in male subjects. Further studies are warranted to clarify the association between MCV level and cognitive performance by considering sex into consideration both cross-sectionally and longitudinally.

8.
J Affect Disord ; 280(Pt A): 442-449, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33242715

RESUMO

BACKGROUND: To assess the potential incremental utility of multiple biomarkers reflecting several pathological pathways for the risk prediction of depression after stroke. METHODS: We used data from the China Antihypertensive Trial in Acute Ischemic Stroke, and a panel of 13 circulating biomarkers were measured. The study outcome was depression (24-item Hamilton Depression Rating Scale score≥8) at 3 months after ischemic stroke. Logistic regression models were performed to evaluate the risk of depression associated with multiple biomarkers. Discrimination and risk reclassification for depression were analyzed. RESULTS: Among 631 included ischemic stroke patients, elevated growth differentiation factor-15, anticardiolipin antibodies, antiphosphatidylserine antibodies and matrix metalloproteinase-9 were individually associated with increased risks of depression after stroke. The multiple biomarker analysis showed a clear gradient in the risk of depression with increasing numbers of elevated biomarkers, and multivariate adjusted odds ratio (95% confidence interval) of patients with 4 elevated biomarkers was 6.52 (2.24-18.95) compared with those without elevation in any of 4 biomarkers. The simultaneous inclusion of all 4 biomarkers to the conventional model significantly improved discrimination (C statistic increased from 0.702 to 0.748, P=0.004) and risk reclassification (net reclassification improvement 45.0%; integrated discrimination improvement 6.2%; both P<0.001) for depression after stroke. LIMITATIONS: We selected biomarkers that had previously been reported to be promising predictors of depression after stroke, while other novel biomarkers not tested might have additional predictive value. CONCLUSIONS: Simultaneously adding multiple biomarkers from several pathophysiological pathways to traditional risk factors provided substantial incremental utility of the risk stratification for depression after stroke.

9.
Hypertens Res ; 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895496

RESUMO

To investigate the potential associations between visit-to-visit blood pressure variability (VVV) and adverse birth outcomes in pregnancies, 48,209 pregnant women without proteinuria or chronic hypertension before 20 weeks of gestation who delivered live singletons between January 2014 and November 2019 in Taizhou or Taicang cities were recruited. VVV was estimated as the standard deviation and coefficient of variation of blood pressure [i.e., systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP)] measured from 20 weeks of gestation onwards. Pregnant women were classified into four groups according to the corresponding quartiles for each VVV index. It was found that VVV was significantly higher in women with small for gestational age (SGA) or low birth weight (LBW) infants than in their counterparts. Graded associations between VVV categories and poor birth outcomes were observed. In particular, when comparing the women with the highest to the lowest quartiles of standard deviation and coefficient variation of DBP, the odds ratios (95% confidence interval) for SGA was 1.15 (1.06-1.26) and 1.14 (1.05-1.25), respectively. Interestingly, the addition of DBP-VVV to established risk factors improved risk prediction of SGA; DBP-VVV demonstrated modestly superior predictive performance to VVV obtained from SBP or MAP. Similar results were found even among normotensive pregnancies. Our findings indicated that VVV during pregnancy, especially DBP-VVV, was independently associated with poor birth outcomes of pregnancies in East China. The inclusion of DBP-VVV with established risk factors may help in identifying pregnancies at high risk of SGA. Validations are needed.

10.
Neurogastroenterol Motil ; 32(10): e13916, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32537873

RESUMO

BACKGROUND: The mucosal barrier damage is recognized as one of the key factors in the pathogenesis of colitis. While sacral nerve stimulation (SNS) was reported to have therapeutic potential for colitis, its mechanisms of actions on colonic permeability remained largely unknown. METHODS: In this study, colitis was induced by intrarectal administration of TNBS in rats. Five days later, they were treated with SNS or sham-SNS for 10 days. The effects of SNS on colonic permeability were assessed by measuring the expression of tight-junction proteins involved in regulating permeability and the FITC-dextran test. The mechanism of actions of SNS was investigated by studying the function of the enteric nervous system (ENS) cells and analyzing the autonomic nervous system. KEY RESULTS: SNS decreased the disease activity index, microscopic and macroscopic scores, myeloperoxidase activity, and pro-inflammatory cytokines (TNF-α, IL-6). SNS increased the expression of Zonula Occludens-1, Occludin, Claudin-1, and Junctional adhesion molecule-A in the colon tissue. The FITC-dextran test showed that the colonic permeability was lower with SCS than sham-SNS. SNS increased ChAT, pancreatic polypeptide, and GDNF and reduced norepinephrine NGF, sub-P, and mast cell overactivation in the colon tissue. Concurrently, SNS increased acetylcholine in colon tissues and elevated vagal efferent activity. CONCLUSIONS & INFERENCES: SNS ameliorates colonic inflammation and enhances colonic barrier function with the proposed mechanisms involving the increase in parasympathetic activity and modulation of the activity of the ENS and immune system, including mast cells.

11.
J Hypertens ; 38(6): 1090-1102, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32371799

RESUMO

OBJECTIVE: The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline recommended a lower threshold (130/80 mmHg) for hypertension in nonpregnant adults. However, the influence of this guideline in Chinese pregnant women is not well characterized. METHODS: Data of 32 742 and 14 479 mothers who had blood pressure (BP) less than 130/80 mmHg and no proteinuria before 20 gestational weeks and delivered live singletons between 1 January 2014 and 30 November 2019 were extracted from Taizhou and Taicang register-based cohorts, respectively. The average measured BP in the third trimester was obtained and categorized according to the 2017 ACC/AHA guideline. The association between BP and risk of adverse birth outcomes was assessed by multivariate logistic regression analysis. RESULTS: In the third trimester, 331 (1.01%) and 378 (2.61%) women had mean BP at least 140/90 mmHg, but 2435 (7.44%) and 1054 (7.28%) had stage 1 hypertension (130-139/80-89 mmHg) in Taizhou and Taicang, respectively. Significant associations between stage 1 hypertension and small for gestational age [odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.14-1.52] and low birth weight (OR = 1.81, 95% CI = 1.46-2.25) were observed in the Taizhou population. Consistent results were also shown in the Taicang population [OR (95% CI), of 1.46 (1.18-1.79) and 1.50 (1.07-2.11), respectively]. CONCLUSION: Stage 1 hypertension in the third trimester defined by the 2017 ACC/AHA guideline was associated with an increased risk for adverse birth outcomes in Eastern Chinese pregnant women, suggesting that this guideline may improve the detection of high BP and surveillance of adverse neonatal outcomes in China.

12.
Neurogastroenterol Motil ; 32(6): e13825, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32115817

RESUMO

BACKGROUND: Vagal nerve stimulation has been reported to treat inflammation with promising results. The aims of our study were to optimize sacral nerve stimulation (SNS) methodologies for colonic inflammation in a rodent model of colitis and to investigate autonomic and cytokine mechanisms. METHODS: Three major efforts were made in optimizing SNS: (a) to determine the best stimulation duration: SNS-0.5h daily, SNS-1h daily, and SNS-3h daily with the parameters set at 5 Hz, 10 seconds on, 90 seconds off; (b) to determine the best stimulation position: bilateral, bipolar, and unipolar stimulation; (c) to determine the best stimulation parameters: our 5 Hz intermittent stimulation vs 14 Hz-210 µs continuous stimulation. Inflammatory responses were assessed by the disease activity index (DAI), histological analyses, and the myeloperoxidase (MPO) activity. Levels of inflammatory cytokines, norepinephrine (NE), and pancreatic polypeptide (PP) in both plasma and colon tissues were assessed. KEY RESULTS: Both SNS-1h and SNS-3h significantly ameliorated intestinal inflammation; SNS-1h was superior to SNS-3h. Bipolar but not bilateral or unipolar stimulation improved the inflammation in colitis. SNS with 5 Hz intermittent stimulation but not the 14 Hz continuous SNS was better for treating colitis in rats. SNS with the optimized stimulation parameters increased vagal activity and decreased sympathetic activity. CONCLUSION & INFERENCES: Bipolar stimulation for 1 hour daily using intermittent 5 Hz parameters is most effective in improving colonic inflammation in TNBS-treated rats by inhibiting pro-inflammatory cytokines and increasing anti-inflammatory cytokines via the modulation of the autonomic function.

13.
Am J Physiol Gastrointest Liver Physiol ; 318(4): G624-G634, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32068444

RESUMO

Sacral nerve stimulation (SNS) was reported to improve 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. The aim of this study was to investigate whether the SNS anti-inflammatory effect is mediated via the local sacral splanchnic nerve or the spinal afferent-vagal efferent-colon pathway. Under general anesthesia, rats were administrated with TNBS intrarectally, and bipolar SNS electrodes were implanted unilaterally at S3. The sacral and vagal nerves were severed at different locations for the assessment of the neural pathway. SNS for 10 days improved colonic inflammation only in groups with intact afferent sacral nerve and vagus efferent nerve. SNS markedly increased acetylcholine and anti-inflammatory cytokines (IL-10) and decreased myeloperoxidase and proinflammatory cytokines (IL-2, IL-17A, and TNF-α) in colon tissues. SNS increased the number of c-fos-positive cells in the brain stem and normalized vagal activity measured by spectral analysis of heart rate variability. SNS exerts an anti-inflammatory effect on TNBS-induced colitis by enhancing vagal activity mediated mainly via the spinal afferent-brain stem-vagal efferent-colon pathway.NEW & NOTEWORTHY Our findings support that there is a possible sacral afferent-vagal efferent pathway that can transmit sacral nerve stimulation to the colon tissue. Sacral nerve stimulation can be carried out by spinal cord afferent to the brain stem and then by the vagal nerve (efferent) to the target organ.


Assuntos
Vias Eferentes/fisiologia , Inflamação/terapia , Sacro/inervação , Nervos Espinhais/fisiologia , Nervo Vago/fisiologia , Animais , Colite/induzido quimicamente , Masculino , Ratos , Ratos Sprague-Dawley , Ácido Trinitrobenzenossulfônico/toxicidade
14.
Obes Surg ; 30(3): 948-956, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31898050

RESUMO

BACKGROUND: Vagal nerve stimulation (VNS) has recently been indicated as a novel method for treating obesity. However, the optimal stimulation parameters were unknown and mechanisms were poorly understood. The aim of this study was to investigate the effects of VNS on food intake and body weight in diet-induced obesity (DIO) rats and its possible mechanism involving autonomic functions and gut hormones. METHODS: Ten control rats and 16 DIO rats were chronically implanted with one pair of electrodes in the subdiaphragmatic vagal nerve. VNS with different stimulation parameters and sham-VNS were performed in control rats. In a chronic study, 8 DIO rats were applied with VNS and another 8 DIO rats were treated with sham-VNS for 4 weeks. Food intake, body weight, gastric emptying, heart rate variability (HRV), and gut hormones were evaluated. RESULTS: In DIO rats, the food intake (p < 0.001) and body weight (p < 0.001) were significantly decreased in the VNS group, compared with the sham-VNS group. VNS decreased the sympathovagal ratio (p = 0.003) and increased vagal activity (p = 0.032) assessed from the spectral analysis of HRV. It also increased plasma levels of glucagon-like peptide-1 (p = 0.012), polypeptide YY (p = 0.008), and pancreatic polypeptide (p = 0.008) in DIO rats. Physiologically, VNS delayed solid gastric emptying (p < 0.001) and increased gastric volume (p = 0.004). CONCLUSION: VNS with appropriate parameters reduced food intake and body weight by delaying gastric emptying mediated via the enhancement of vagal activity and release of anorexigenic hormones.

15.
J Neurogastroenterol Motil ; 26(1): 147-159, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31917917

RESUMO

Background/Aims: Gastroparesis is commonly seen in patients with diabetes and functional dyspepsia with no satisfactory therapies. Dysautonomia is one of the main reasons for the imbalanced motility. We hypothesized that spinal cord stimulation (SCS) is a viable therapy for gastroparesis via the autonomic modulation to improve gastric motility. The aim is to find an optimal method of SCS for treating gastroparesis. Methods: Eight healthy-female dogs were implanted with a gastric cannula, a duodenal cannula, 2 multi-electrode spinal leads, and an implantable pulse generator. Gastric motility index (MI) was used to determine the best stimulation location/parameters of SCS. Optimized SCS was used to improve glucagon-induced gastroparesis. Results: With fixed parameters, SCS at Thoracic 10 (T10) was found most effective for increasing gastric MI (37.8%, P = 0.013). SCS was optimized with different parameters (pulse width: 0.05-0.6 msec, frequency: 5-500 Hz, motor threshold: 30-90%) on T10. Our findings revealed that 0.5 msec, 20 Hz with 90% motor threshold at T10 were the best parameters in increasing MI. Glucagon significantly delayed gastric emptying, and this inhibitory effect was partially blocked by SCS. Gastric emptying at 120 minutes was 25.6% in the control session and 15.7% in glucagon session (P = 0.007 vs control), while it was 22.9% with SCS session (P = 0.041 vs glucagon). SCS with the optimal parameters was found to maximally enhance vagal activity and inhibit sympathetic activity assessed by the spectral analysis of heart rate variability. Conclusions: SCS with optimized stimulation location and parameters improves gastric motility in healthy-dogs and accelerates gastric emptying impaired by glucagon via enhancing vagal activity.

16.
Dis Markers ; 2019: 7284691, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827641

RESUMO

Background and Objectives: Type 2 diabetes mellitus (T2DM) is an epidemic disease that endangers human health seriously. Recently, a large number of reports have revealed that macrophage-inhibiting cytokine-1 (MIC-1) is linked with T2DM, but the results were inconclusive. The aim of this study was to perform bioinformatics analysis of the association between MIC-1 and T2DM. Material and Methods: Datasets and relevant literatures were searched in Gene Expression Omnibus (GEO), PubMed, Google Scholar, and Web of Science till September 20, 2019. Expression levels of MIC-1 were extracted, pooled, and compared between T2DM cases and controls. Results: In summary, 11 GEO datasets and 3 articles with 421 T2DM cases and 711 controls were finally included. The expression level of MIC-1 was significantly higher in T2DM patients compared with controls, with a standard mean difference (SMD) of 0.54 and a 95% confidence interval (95% CI) of 0.24-0.83; in blood samples, the difference was still significant (SMD = 0.65; 95%CI = 0.24-1.06). Meanwhile, the expression level of MIC-1 plays a significant role in differentiating T2DM cases from controls; the combined sensitivity, specificity, and odds ratio were 0.83 (95%CI = 0.72-0.90), 0.59 (95%CI = 0.45-0.72), and 1.64 (95%CI = 1.35-1.99), respectively. The summary receiver operating characteristic (SROC) curve demonstrated that the area under the curve (AUC) was 0.81 (95%CI = 0.77-0.84). Conclusion: Our results suggested that the expression levels of MIC-1 were significantly higher in T2DM patients in multiple tissues including blood samples.


Assuntos
Diabetes Mellitus Tipo 2/patologia , Fator 15 de Diferenciação de Crescimento/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Prognóstico
18.
Am J Physiol Gastrointest Liver Physiol ; 317(5): G609-G617, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31411502

RESUMO

Although sacral nerve stimulation (SNS) has been applied for treating constipation, its parameters were adopted from SNS for fecal incontinence, its effects are limited, and mechanisms are largely unknown. We investigated the effects and mechanism of SNS with appropriate parameters on constipation in rats treated with loperamide. First, using rectal compliance as an outcome measure, an experiment was performed to derive effective SNS parameters. Then, a 7-day SNS was performed in rats with constipation induced by loperamide. Autonomic functions were assessed by spectral analysis of heart rate variability (HRV) derived from an electrocardiogram. Serum levels of pancreatic polypeptide (PP), norepinephrine (NE), and acetylcholine (ACh) in colon were assessed. 1) Acute SNS at 5 Hz, 100 µs was found effective in enhancing rectal compliance and accelerating distal colon transit (P < 0.05 vs. sham SNS). 2) The 7-day SNS normalized loperamide-induced constipation, assessed by the number, weight, and water content of fecal pellets, and accelerated the distal colon transit (29.4 ± 3.7 min with sham SNS vs. 16.4 ± 5.3 min with SNS but not gastric emptying or intestinal transit. 3) SNS significantly increased vagal activity (P = 0.035) and decreased sympathetic activity (P = 0.012), assessed by spectral analysis of HRV as well as by the serum PP. 4) SNS increased ACh in the colon tissue; atropine blocked the accelerative effect of SNS on distal colon transit. We concluded that SNS with appropriate parameters improves constipation induced by loperamide by accelerating distal colon motility, mediated via the autonomic-cholinergic function.NEW & NOTEWORTHY Although sacral nerve stimulation (SNS) has been applied for treating constipation, its parameters were adopted from SNS for fecal incontinence, effects are limited, and mechanisms are largely unknown. This paper shows that SNS with appropriate parameters improves constipation induced by loperamide by accelerating distal colon motility mediated via the autonomic-cholinergic function.


Assuntos
Colo/fisiologia , Constipação Intestinal/terapia , Terapia por Estimulação Elétrica/métodos , Trânsito Gastrointestinal , Plexo Lombossacral/fisiologia , Acetilcolina/metabolismo , Animais , Sistema Nervoso Autônomo/fisiologia , Colo/inervação , Colo/metabolismo , Constipação Intestinal/etiologia , Loperamida/toxicidade , Masculino , Norepinefrina/sangue , Polipeptídeo Pancreático/sangue , Ratos , Ratos Sprague-Dawley
19.
Neurogastroenterol Motil ; 31(10): e13676, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31327175

RESUMO

BACKGROUND: Vagal nerve stimulation (VNS) was reported to have a therapeutic potential for inflammatory bowel disease (IBD). This study was designed to determine effects and mechanisms of SNS on colonic inflammation of in rodent models of IBD and compare the difference among SNS, VNS, and SNS plus VNS. METHODS: Intestinal inflammation in rats was induced by intrarectal administration of TNBS (2,4,6-Trinitrobenzenesulfonic acid) on the first day. Five days after intrarectal TNBS, the rats were treated with sham-VNS, VNS, Sham-SNS, SNS, and SNS + VNS for 10 days. In another experiment, after 10 days of 4% DSS (dextran sodium sulfate) in drinking water, rats were treated with 10-day sham-SNS and SNS. Various inflammatory responses were assessed; mechanisms involving autonomic functions and inflammatory cytokines were investigated. KEY RESULTS: (a) VNS, SNS, and VNS + SNS significantly and equally decreased the disease activity index and macroscopic scores, and normalized colon length; (b) IL-10 was decreased by TNBS but increased with SNS, VNS, and SNS + VNS; pro-inflammatory cytokines, IL-6, IL-17A, MCP-1 and TNF-α, were increased by TNBS but decreased with SNS, VNS, and SNS + VNS (P < .05); MPO activity was decreased by SNS, VNS, and SNS + VNS; (c) SNS, VNS, and SNS + VNS remarkably increased vagal activity that was suppressed by TNBS (P < .05); (d) smilar SNS effects were noted in rats with DSS-induced colitis. CONCLUSIONS & INFERENCES: SNS presents similar anti-inflammatory effects as VNS by inhibiting pro-inflammatory cytokines and increasing anti-inflammatory cytokines via the autonomic pathway. Similar to VNS, SNS may also have a therapeutic potential for colonic inflammation.


Assuntos
Sistema Nervoso Autônomo , Colite/imunologia , Colo/imunologia , Citocinas/imunologia , Plexo Lombossacral , Estimulação do Nervo Vago , Animais , Colite/induzido quimicamente , Colo/inervação , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Terapia por Estimulação Elétrica , Inflamação/imunologia , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/terapia , Ratos , Ácido Trinitrobenzenossulfônico/toxicidade
20.
Obes Surg ; 29(9): 2869-2877, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31222497

RESUMO

BACKGROUND: Vagal nerve stimulation (VNS) has been reported to reduce body weight and improve sympathovagal imbalance in both basic and clinical studies. Its effects on glycemic control were however unclear. The aims of this study were to investigate the effects of VNS with various parameters on blood glucose and its possible mechanisms in rats. METHODS: A hyperglycemic rodent model induced by glucagon was used initially to optimize the VNS parameters; then, a type 2 diabetic rodent model induced by high-fat diet combined with streptozotocin was used to validate the VNS method. The VNS electrodes were implanted at the dorsal subdiaphragmatic vagus; three subcutaneous electrodes were implanted at the chest area for recording electrocardiogram in rats induced by glucagon. RESULTS: (1) VNS with short pulse width of 0.3 ms but not 3 ms reduced blood glucose during an oral glucose tolerance test (OGTT), with a 38.4% reduction at 15 min and 26.9% at 30 min (P < 0.05, vs. sham-VNS respectively). (2) VNS at low frequency of 5 Hz but not 14 Hz or 40 Hz reduced blood glucose during the OGTT (P < 0.05, vs. sham-VNS). (3) Intermittent VNS was more potent than continuous VNS (P < 0.01). (4) No difference was found between unilateral VNS and bilateral VNS. (5) VNS enhanced vagal activity (P = 0.005). (6) The hypoglycemic effect of VNS was blocked by glucagon-like peptide-1 (GLP-1) antagonist exendin-4. CONCLUSIONS: VNS at 5 Hz reduces blood glucose in diabetic rats by enhancing vagal efferent activity and the release of GLP-1.


Assuntos
Glicemia/fisiologia , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Estimulação do Nervo Vago , Animais , Glicemia/análise , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/terapia , Ratos
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