bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of head-down tilt on clinical outcome and cerebral perfusion in ischemic stroke patients: A case series
Authors: Zhao Zi-Ai , Zhang Nan-Nan , Tao Lin , Cui Yu , Li Meng , Qi Shou-Liang , Chen Hui-Sheng 
Published: September 2022

BackgroundThe effect of head position on stroke is not clear. The current study aimed to observe the effect of head-down tilt on acute ischemic stroke (AIS) patients with large vessel occlusion.MethodsWe observed the influence of head-down tilt position on clinical outcomes, myocardial enzymogram and N-terminal pro b-type Natriuretic Peptide in 4 AIS patients who suffered early neurological deterioration (END). Cerebral perfusion imaging was performed in 3 patients using arterial spin labeling.ResultsIn series of AIS patients with END, head down tilt (-20°) prevented further neurological deterioration and improved clinical outcomes. An increase in cerebral blood flow was observed by arterial spin labeling after head down tilt treatment. No obvious adverse events occurred.ConclusionThe case series suggest that head-down tilt may improve clinical outcome in AIS patients through increasing the cerebral perfusion with no obvious adverse events. The finding needs to be confirmed in future clinical trials.
Effectiveness of transcranial direct current stimulation over dorsolateral prefrontal cortex in patients with prolonged disorders of consciousness: A systematic review and meta-analysis
Authors: Liu Siwei , Gao Qiang , Guan Min , Chen Yi , Cheng Shuhai , Yang Lin , Meng Wei , Lu Chunyan , Li Bingqian 
Published: September 2022

BackgroundTranscranial direct current stimulation (tDCS) has been widely studied for treatment of patients with prolonged disorders of consciousness (PDOC). The dorsolateral prefrontal cortex (DLPFC) is a hot target for intervention, but some controversies remain.PurposeThis review aimed to systematically investigate the therapeutic effects of DLPFC-anodal-tDCS for patients with PDOC through a meta-analysis approach.Data sourcesSearches for relevant articles available in English were conducted using EMBASE, Medline, Web of Science, EBSCO, and Cochrane Central Register of Controlled Trials from inception until March 26, 2022.Study selectionAll randomized parallel or cross-over controlled trials comparing the effect of intervention with active-tDCS and Sham-tDCS on Coma Recovery Scale Revised (CRS-R) score in individuals with PDOC were included.Data extractionTwo authors independently extracted data, assessed the methodological quality, and rated each study.Data synthesisTen randomized parallel or cross-over controlled trials were eligible for systematic review, and eight of the studies involving 165 individuals were identified as eligible for meta-analysis. Compared with Sham-tDCS, the use of anode-tDCS over DLPFC improved the CRS-R score (SMD = 0.71; 95% CI: 0.47–0.95, I2 = 10%). Patients with PDOC classified as MCS and clinically diagnosed as CVA or TBI may benefit from anode-tDCS.LimitationsFailure to evaluate the long-term effects and lack of quantitative analysis of neurological examination are the main limitations for the application of anode-tDCS.ConclusionsAnodal-tDCS over the left DLPFC may be advantageous to the recovery of patients with MCS and clinically diagnosed with CVA or TBI. There is a lack of evidence to support the duration of the disease course will limit the performance of the treatment. Further studies are needed to explore the diversity of stimulation targets and help to improve the mesocircuit model.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=279391, identifier: CRD42022279391.
The effect of montelukast, a leukotriene receptor antagonist, on the acetic acid-induced model of colitis in rats: Involvement of NO-cGMP-KATP channels pathway
Authors: Ghorbanzadeh Behnam , Behmanesh Mohammad Amin , Mahmoudinejad Roya , Zamaniyan Mehdi , Ekhtiar Shadi , Paridar Yousef 
Published: September 2022

Inflammatory bowel disease is a chronic autoimmune disorder that may involve entire gastrointestinal tract. The leukotrienes have a role as mediators in the pathophysiology of colitis. Here, we investigated the effect of a leukotriene receptor antagonist, montelukast, and also the role of the NO-cGMP-KATP channel pathway in acetic acid-induced colitis. Rectal administration of acetic acid (4%) was used for induction of colitis in rats. To investigate our hypothesis, the rats were intraperitoneally pre-treated with L-NAME (NOS inhibitor), L-arginine, sildenafil, methylene blue, glibenclamide, or diazoxide 15 min before treatment with montelukast (5–20 mg/kg, i. p.), for three consecutive days. Then, microscopic, macroscopic, and inflammatory parameters were evaluated. Montelukast reduced the microscopic and macroscopic damage induced by acetic acid. Montelukast also reduced the level of IL-1β and TNF-α. We also showed that the effects of montelukast were significantly attenuated by L-NAME, methylene blue (guanylate cyclase inhibitor), and an ATP-sensitive potassium channel blocker (glibenclamide). Also, the administration of L-arginine, sildenafil, and diazoxide before montelukast produced protective effect. In conclusion, the pathway of the NO-cGMP-KATP channel is involved in the protective effect of montelukast in acetic acid-induced colonic tissue damage.
Upregulation of TLR4/MyD88 pathway in alcohol-induced Wernicke’s encephalopathy: Findings in preclinical models and in a postmortem human case
Authors: Moya Marta , Escudero Berta , Gómez-Blázquez Elena , Rebolledo-Poves Ana Belen , López-Gallardo Meritxell , Guerrero Carmen , Marco Eva M. , Orio Laura 
Published: September 2022

Wernicke’s encephalopathy (WE) is a neurologic disease caused by vitamin B1 or thiamine deficiency (TD), being the alcohol use disorder its main risk factor. WE patients present limiting motor, cognitive, and emotional alterations related to a selective cerebral vulnerability. Neuroinflammation has been proposed to be one of the phenomena that contribute to brain damage. Our previous studies provide evidence for the involvement of the innate immune receptor Toll-like (TLR)4 in the inflammatory response induced in the frontal cortex and cerebellum in TD animal models (animals fed with TD diet [TDD] and receiving pyrithiamine). Nevertheless, the effects of the combination of chronic alcohol consumption and TD on TLR4 and their specific contribution to the pathogenesis of WE are currently unknown. In addition, no studies on TLR4 have been conducted on WE patients since brains from these patients are difficult to achieve. Here, we used rat models of chronic alcohol (CA; 9 months of forced consumption of 20% (w/v) alcohol), TD hit (TDD + daily 0.25 mg/kg i.p. pyrithiamine during 12 days), or combined treatment (CA + TDD) to check the activation of the proinflammatory TLR4/MyD88 pathway and related markers in the frontal cortex and the cerebellum. In addition, we characterized for the first time the TLR4 and its coreceptor MyD88 signature, along with other markers of this proinflammatory signaling such as phospo-NFκB p65 and IκBα, in the postmortem human frontal cortex and cerebellum (gray and white matter) of an alcohol-induced WE patient, comparing it with negative (no disease) and positive (aged brain with Alzheimer’s disease) control subjects for neuroinflammation. We found an increase in the cortical TLR4 and its adaptor molecule MyD88, together with an upregulation of the proinflammatory signaling molecules p-NF-ĸB and IĸBα in the CA + TDD animal model. In the patient diagnosed with alcohol-induced WE, we observed cortical and cerebellar upregulation of the TLR4/MyD88 pathway. Hence, our findings provide evidence, both in the animal model and the human postmortem brain, of the upregulation of the TLR4/MyD88 proinflammatory pathway in alcohol consumption–related WE.
Association between antibiotics and dementia risk: A retrospective cohort study
Authors: Kim Minseo , Park Sun Jae , Choi Seulggie , Chang Jooyoung , Kim Sung Min , Jeong Seogsong , Park Young Jun , Lee Gyeongsil , Son Joung Sik , Ahn Joseph C. , Park Sang Min 
Published: September 2022

Background: The possible relation between antibiotic exposure and the alteration of gut microbiota, which may affect dementia risk, has been revealed. However, the association between antibiotics and dementia incidence has rarely been studied. We aimed to determine the association between antibiotic exposure and the risk of dementia.Methods: This population-based retrospective cohort study used data from the National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) in South Korea. Exposure was the cumulative days of antibiotic prescription from 2002 to 2005. Newly diagnosed overall dementia, Alzheimer’s disease (AD), and vascular dementia (VD) were identified based on diagnostic codes and prescriptions for dementia-related drugs. The follow-up investigation was carried out from 1 January 2006 to 31 December 2013. The Cox proportional hazards regression was used to assess the association between cumulative antibiotic prescription days and dementia incidence.Results: A total of 313,161 participants were analyzed in this study. Compared to antibiotic non-users, the participants who used antibiotics for 91 or more days had an increased risk of overall dementia [adjusted hazard ratio (aHR), 1.44; 95% confidence interval (CI), 1.19–1.74], AD (aHR, 1.46; 95% CI, 1.17–1.81), and VD (aHR, 1.38; 95% CI, 0.83–2.30). Those who used five or more antibiotic classes had higher risks of overall dementia (aHR, 1.28; 95% CI, 1.00–1.66) and AD (aHR, 1.34; 95% CI, 1.00–1.78) than antibiotic non-users.Conclusion: Antibiotic exposure may increase the risk of dementia in a cumulative duration-dependent manner among adult participants. Future studies are needed to assess the causality between the long-term prescription of antibiotics and dementia risk.
NOX1 promotes myocardial fibrosis and cardiac dysfunction via activating the TLR2/NF-κB pathway in diabetic cardiomyopathy
Authors: Zhang Dandan , Li Yilan , Wang Weijie , Lang Xueyan , Zhang Yanxiu , Zhao Qianqian , Yan Jingru , Zhang Yao 
Published: September 2022

Diabetic cardiomyopathy (DCM) is a prevalent complication in patients with diabetes, resulting in high morbidity and mortality. However, the molecular mechanisms of diabetic cardiomyopathy have yet to be fully elucidated. In this study, we investigated a novel target, NOX1, an isoform of superoxide-producing NADPH oxidase with key functional involvement in the pathophysiology of DCM. The DCM rat model was established by a high-fat diet combined with streptozotocin injections. DCM rats elicited myocardial fibrosis exacerbation, which was accompanied by a marked elevation of NOX1 expression in cardiac tissue. In particular, a specific NOX1 inhibitor, ML171, effectively decreased myocardial fibrosis and protected against cardiac dysfunction in DCM rats. Rat neonatal cardiac fibroblasts were incubated with high glucose (HG, 33 mM) as an in vitro model of DCM. We also observed that the expression of NOX1 was upregulated in HG-cultured cardiac fibroblasts. Silencing of NOX1 was found to attenuate myocardial fibrosis and oxidative stress in HG-induced cardiac fibroblasts. Furthermore, the upregulation of NOX1 by hyperglycemia induced activation of the TLR2/NF-κB pathway both in vitro and in vivo, whereas these effects were significantly attenuated with NOX1 gene silencing and further enhanced with NOX1 gene overexpression. In summary, we demonstrated that NOX1 induced activation of the TLR2/NF-κB pathway and increased reactive oxygen species production accumulation, which ultimately increased myocardial fibrosis and deteriorated cardiac function in diabetic cardiomyopathy. Our study revealed that NOX1 was a potential therapeutic target for DCM.
Macrophage malfunction in Triptolide-induced indirect hepatotoxicity
Authors: Qin Tingting , Hasnat Muhammad , Zhou Yang , Yuan Ziqiao , Zhang Wenzhou 
Published: September 2022

Background and Objective: Indirect hepatotoxicity is a new type of drug-induced hepatotoxicity in which the character of a drug that may induce its occurrence and the underlying mechanism remains elusive. Previously, we proved that Triptolide (TP) induced indirect hepatotoxicity upon LPS stimulation resulting from the deficiency of cytoprotective protein of hepatocyte. However, whether immune cells participated in TP-induced indirect hepatotoxicity and the way immune cells change the liver hypersensitivity to LPS still need to be deeply investigated. In this study, we tried to explore whether and how macrophages are involved in TP-induced indirect hepatotoxicity.Method: Firstly, TP (500 μg/kg) and LPS (0.1 mg/kg) were administrated into female C57BL/6 mice as previously reported. Serum biochemical indicators, morphological changes, hepatic macrophage markers, as well as macrophage M1/M2 markers were detected. Secondly, macrophage scavenger clodronate liposomes were injected to prove whether macrophages participated in TP-induced indirect hepatotoxicity. Also, the ability of macrophages to secrete inflammatory factors and macrophage phagocytosis were detected. Lastly, reverse docking was used to find the target of TP on macrophage and the possible target was verified in vivo and in RAW264.7 cells.Results: TP pretreatment increased the liver hypersensitization to LPS accompanied by the recruitment of macrophages to the liver and promoted the transformation of macrophages to M1 type. Depletion of hepatic macrophages almost completely alleviated the liver injury induced by TP/LPS. TP pretreatment increased the secretion of pro-inflammatory factors and weakened the phagocytic function of macrophages upon LPS exposure. Reverse docking results revealed that MerTK might be the real target of TP.Conclusion: TP disrupts inflammatory cytokines profile and phagocytic function of hepatic macrophages, resulting in the production of massive inflammatory factors and the accumulation of endotoxin in the liver, ultimately leading to the indirect hepatotoxicity of TP. MerTK might be the target of TP on the macrophage, while the binding of TP to MerTK should be investigated in vivo and in vitro.
Toxicity evaluation induced by single and 28-days repeated exposure of withametelin and daturaolone in Sprague Dawley rats
Authors: Baig Muhammad Waleed , Majid Muhammad , Nasir Bakht , Hassan Syed Shams ul , Bungau Simona , Haq Ihsan-ul 
Published: September 2022

Safe preclinical dose determination is predictive of human toxicity and can have a profound impact on the overall progress of the compound in early drug discovery process. In this respect, current study sought to investigate for the first time the acute and subacute oral toxicity of two pharmacologically active natural compounds i.e., withametelin and daturaolone in Sprague Dawley rats following OECD guideline 420 and 407, respectively. As per acute toxicity studies, withametelin and daturaolone were characterized as Globally Harmonized System (GHS) category 4 and 5 compounds, respectively. Sub-acute daily dose of withametelin was 5, 2.5, and 1.25 mg/kg but, for daturaolone, it was 10, 5, and 2.5 mg/kg. High dose (5 and 2.5 mg/kg) withametelin groups showed dose dependent changes in the general, hematological, biochemical and histopathological parameters in both sexes, the most prominent being hyperthyroidism while no toxicity was observed at lower doses (1.25 and 0.75 mg/kg), No Observable Adverse Effect Level (NOAEL) being 1.25 mg/kg. Daturaolone was comparatively safer and showed dose dependent significant changes in hepatic enzyme (Alanine Transaminase), bilirubin, creatinine, and glucose levels while histological changes in testes were also observed. Lower doses (5, 2.5, and 1.25 mg/kg) of daturaolone showed no significant toxic effects and 5 mg/kg was declared as its NOAEL. Depending upon our findings, starting effective oral dose levels of 1.25 mg/kg/day for withametelin and 5 mg/kg/day for daturaolone are proposed for repeated dose (up to 28 days) preclinical pharmacological evaluation models. Long term studies with more behavioral, biochemical, histopathological and hormonal parameters are proposed to strengthen the findings.
The effect of regular aerobic exercise on renal function in patients with CKD: A systematic review and meta-analysis
Authors: Ma Qirui , Gao Ye , Lu Jiandong , Liu Xinhong , Wang Ruolin , Shi Yajun , Liu Jingqi , Su Hao 
Published: September 2022

Objective: To evaluate the effect of regular aerobic exercise on the improvement of renal function in patients with chronic kidney disease through meta-analysis and to provide targeted exercise recommendations for patients with CKD.Methods: PubMed, Web of Science, EBSCO, China National Knowledge Infrastructure (CNKI), and other databases were searched, and randomized controlled trials on the effects of regular aerobic exercise on renal function-related indexes in patients with CKD were collected according to the inclusion and exclusion criteria. The methodological quality of the included literature was evaluated using the Cochrane evaluation tool second generation, and statistical analysis was performed using R analysis software.Results: A total of 12 randomized controlled trials (RCTs) with a total of patients with CKD were included, and the results of the meta-analysis showed that regular aerobic exercise significantly improved the estimated glomerular filtration rate SMD = 0.65, 95% CI [0.30, 1.00], serum creatinine SMD = -0.63, 95% CI [-0.86, -0.40], 24-h urine protein volume in patients with CKD SMD = -0.41, 95% CI [-0.70, -0.11], and serum urea nitrogen SMD = -0.66, 95% CI [-1.20, -0.12]. Single exercise session longer than 30 min significantly improved the estimated glomerular filtration rate in CKD patients (p &lt; 0.01), and walking and running as exercise modalities significantly improved CKD patients’ SCr levels were significantly improved by walking and running as exercise modalities (p &lt; 0.05), and the improvement effect was not significant when cycling was selected as an exercise modality.Conclusion: Regular aerobic exercise has a significant effect on the estimated glomerular filtration rate, serum creatinine, 24-h urine protein amount, and blood urea nitrogen in CKD patients. Aerobic exercise with a single exercise duration longer than 30 min has a more significant effect on the estimated glomerular filtration rate, and aerobic exercise by walking or running can more effectively improve the serum creatinine in CKD patients.
Association between interindividual variability in training volume and strength gain
Authors: Ema Ryoichi , Saito Itaru , Akagi Ryota 
Published: September 2022

This study aimed to examine the association between interindividual variability in strength changes and in training volume. A total of 26 untrained men completed 4-weeks of isometric knee extension (KE group, n = 12) and hip flexion (HF group, n = 14) training. Each training session comprised four sets of ten isometric contractions, 3-s contractions every 20 s. Training volume, which was defined as impulse during contractions, and maximal voluntary contraction (MVC) torque during KE and HF were evaluated. Based on the magnitude of MVC torque changes, the participants were divided into the high and low responders (n = 13; KE = 6 and HF = 7 per responders). The MVC torque changes (KE, 20.8%; HF, 22.4%) and total training volume did not significantly differ between the two groups. A higher training volume was demonstrated in the low responders than the high responders. The total training volume was positively associated with the MVC torque changes in low responders (r = 0.869%, 95% confidence interval [0.610, 0.960], p &lt; 0.001), but not in high responders [r = 0.229, 95% confidence interval (−0.368, 0.693), p = 0.451], KE or HF group. Results showed that training volume was an important factor in determining the magnitude of strength gains in low responders, and MVC torque could improve by approximately 20% with the use of the study protocol regardless of joint actions involved during training.
Effects of different exercise types on visceral fat in young individuals with obesity aged 6–24 years old: A systematic review and meta-analysis
Authors: Wang Rong , Zhang Xiaoyuan , Ren Hong , Zhou Huixuan , Yuan Yaqing , Chai Yunlong , Hou Xiao 
Published: September 2022

Introduction: The prevalence of pediatric obesity remains high all over the world. Various exercise interventions have been applied to decrease the visceral fat in young individuals with obesity. But the evidence remains controversial on the effect of the exercise on visceral fat. Moreover, it is unclear which type of the exercise is the most effective for young individuals with overweight or obesity to reduce visceral fat.Objective: The objective of this review and meta-analysis is to evaluate and compare the effectiveness of different exercise interventions on visceral fat in young individuals with overweight or obesity.Methods: Four databases consisting of PubMed, Web of Science, EBSCO, and Cochrane Library were searched prior to May 2022. Fifteen studies with a total of 30 data points involving 1,134 participants were included in this meta-analysis. And the interventions were limited to 4 exercise types [i.e., aerobic exercise (AE), resistance exercise (RE), aerobic exercise combined with resistance exercise (CE), and high-intensity interval training (HIIT)].Data Synthesis: The results showed that AE (Standardized Mean Difference = −0.32; 95% CI = −0.50 to −0.13; p = 0.0007; I2 = 37%) and HIIT (SMD = −0.59; 95% CI = −0.87 to −0.31; p &lt; 0.0001; I2 = 0%) had a significant reduction effect on visceral fat. And the effect of HIIT seemed better than AE. However, RE (SMD = −0.58; 95% CI = −1.34 to 0.17; p = 0.13; I2 = 76%) and CE (SMD = −0.21; 95% CI = −0.81 to 0.38; p = 0.48; I2 = 63%) had a non-significant effect on visceral fat decline. Additionally, compared with the control group, exercise interventions had a significant effect on reducing visceral fat in adolescents (SMD = −0.54; 95% CI = −0.82 to −0.26; p = 0.0001; I2 = 64%) and young adults (SMD = −0.42; 95% CI = −0.69 to −0.15; p = 0.003; I2 = 0%) rather than children (SMD = −0.15; 95% CI = −0.32 to 0.02; p = 0.08; I2 = 0%). And the gender-based subgroup analysis indicated that the effectiveness of the exercise on the reduction of visceral fat was more significant in males (SMD = −1.27; 95% CI = −1.67 to −0.87; p &lt; 0.00001; I2 = 0%) than that in females (SMD = −0.31; 95% CI = −0.48 to −0.14; p = 0.0004; I2 = 0%).Conclusion: This review and meta-analysis demonstrates that exercise interventions are efficient to decrease visceral fat in adolescents (12–18 years old) and young adults (18–24 years old). Among different exercise types, AE and HIIT are helpful for young individuals with overweight or obesity to reduce visceral fat and HIIT appears to be the most effective exercise intervention. In addition, the effect of exercise interventions on the consumption of visceral fat is more significant in males than that in females.Systematic Review Registration: [http://www.crd.york.ac.uk/PROSPERO], identifier [CRD42022310878].