bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of Cytochrome P450 2a5 by Artemisia capillaris and 6,7-Dimethylesculetin in Mouse Hepatocytes
Authors: Kim Sangsoo Daniel , Morgan Larry , Hargreaves Elyse , Zhang Xiaoying , Jiang Zhihui , Antenos Monica , Li Ben , Kirby Gordon M. 
Published: November 2021

Jaundice is a potentially fatal condition resulting from elevated serum bilirubin levels. For centuries, herbal remedies containing Artemisia capillaris Thunb. including the compound 6,7-dimethylesculetin (DE) have been used in Asia to prevent and treat jaundice in neonates. DE activates an important regulator of bilirubin metabolism, the constitutive androstane receptor (CAR), and increases bilirubin clearance. In addition, murine cytochrome P450 2a5 (Cyp2a5) is known to be involved in the oxidative metabolism of bilirubin. Moreover, treatment of mice with phenobarbital, a known inducer of both CAR and Cyp2a5, increases expression of Cyp2a5 suggesting a potential relationship between CAR and Cyp2a5 expression. The aim of this study is to investigate the influence of Artemisia capillaris and DE on the expression and regulatory control of Cyp2a5 and the potential involvement of CAR. Treatment of mouse hepatocytes in primary culture with DE (50 μM) significant increased Cyp2a5 mRNA and protein levels. In mice, Artemisia capillaris and DE treatment also increased levels of hepatic Cyp2a5 protein. Luciferase reporter assays showed that CAR increases Cyp2a5 gene transcription through a CAR response element in the Cyp2a5 gene promoter. Moreover, DE caused nuclear translocation of CAR in primary mouse hepatocytes and increased Cyp2a5 transcription in the presence of CAR. These results identify a potential CAR-mediated mechanism by which DE regulates Cyp2a5 gene expression and suggests that DE may enhance bilirubin clearance by increasing Cyp2a5 levels. Understanding this process could provide an opportunity for the development of novel therapies for neonatal and other forms of jaundice.
Cinacalcet Targets the Neurokinin-1 Receptor and Inhibits PKCδ/ERK/P65 Signaling to Alleviate Dextran Sulfate Sodium-Induced Colitis
Authors: Chen Yuehong , Liu Huan , Zhang Qiuping , Luo Yubin , Wu Liang , Zhong Yutong , Tang Zhigang , Pu Yaoyu , Lu Chenyang , Yin Geng , Xie Qibing 
Published: November 2021

Objective: Inflammatory bowel disease is an immune-mediated chronic inflammatory disease of the gastrointestinal tract for which curative drugs are currently not available. This study was performed to assess the therapeutic effects of cinacalcet on dextran sulfate sodium (DSS)-induced colitis.Methods: Primary macrophages obtained from bone marrow and the macrophage cell line RAW264.7 were used to examine the inhibitory effect of cinacalcet on cytokine production, the PKCδ/ERK/P65 signaling pathway, and NF-κB P65 translocation. Colitis was induced using DSS to assess the treatment effect of cinacalcet. Bioinformatics approaches were adopted to predict potential targets of cinacalcet, and a drug affinity responsive target stability (DARTs) assay was performed to confirm binding between cinacalcet and potential target.Results:In vivo analysis showed that cinacalcet reduced the disease activity score, prevented shortening of the colon, diminished inflammatory cell infiltration, and protected the structural integrity of the intestinal wall. Cinacalcet also reduced production of the inflammatory cytokines TNFα, IL-1β, and IL-6 in the colon and sera of mice with DSS-induced colitis. In vitro studies revealed that cinacalcet suppressed the translocation of P65 and inhibited production of the inflammatory cytokines IL-1β and IL-6. Mechanistic studies revealed that the target of cinacalcet was neurokinin-1 receptor (NK1R) and their binding was confirmed by a DARTs assay. Furthermore, the inhibition of NK-κB P65 activation was found to occur via the suppression of PKCδ/ERK/P65 signaling mediated by cinacalcet.Conclusion: Cinacalcet inhibits the activation of NF-κB and reduces the production of inflammatory cytokines by suppressing the PKCδ/ERK/P65 signaling pathway via targeting NK1R, suggesting that it can be used to treat inflammatory diseases, particularly colitis.
HR-MS Based Untargeted Lipidomics Reveals Characteristic Lipid Signatures of Wilson’s Disease
Authors: Zhi Yixiao , Sun Yujiao , Jiao Yonggeng , Pan Chen , Wu Zeming , Liu Chang , Su Jie , Zhou Jie , Shang Dong , Niu Junqi , Hua Rui , Yin Peiyuan 
Published: November 2021

Background and Aims: The diagnosis of Wilson’s disease (WD) is challenging by clinical or genetic criteria. A typical early pathological change of WD is the increased liver lipid deposition and lowered serum triglyceride (TG). Therefore, the contents of serum lipids may provide evidence for screening of biomarkers for WD.Methods: 34 WD patients, 31 WD relatives, and 65 normal controls were enrolled in this study. Serum lipidomics data was acquired by an ultra-high-performance liquid chromatography high-resolution mass spectrometry system, and the data were analyzed by multivariate statistical methods.Results: Of all 510 identified lipids, there are 297 differential lipids between the WD and controls, 378 differential lipids between the relatives and controls, and 119 differential lipids between the patients and relatives. In WD, the abundances of most saturated TG were increased, whereas other unsaturated lipids decreased, including phosphatidylcholine (PC), sphingomyelin (SM), lysophosphatidylcholine (LPC), ceramide (Cer), and phosphatidylserine (PS). We also found many serum lipid species may be used as biomarkers for WD. The areas under the receiver operating characteristic curve (AUC) of PS (35:0), PS (38:5), and PS (34:0) were 0.919, 0.843, and 0.907. The AUCs of TG (38:0) and CerG1 (d42:2) were 0.948 and 0.915 and the AUCs of LPC (17:0) and LPC (15:0) were 0.980 and 0.960, respectively. The lipid biomarker panel exhibits good diagnostic performance for WD. The correlation networks were built among the different groups and the potential mechanisms of differential lipids were discussed. Interestingly, similar lipid profile of WD is also found in their relatives, which indicated the changes may also related to the mutation of the ATP7B gene.Conclusions: Lipid deregulation is another important hallmark of WD besides the deposition of copper. Our lipidomic results provide new insights into the diagnostic and therapeutic targets of WD.
Efficacy of Ligustrazine Injection as Adjunctive Therapy in Treating Acute Cerebral Infarction: A Systematic Review and Meta-Analysis
Authors: Shao Huikai , He Xia , Zhang Lijuan , Du Shan , Yi Xiaoqing , Cui Xiaojiao , Liu Xinxia , Huang Shengfeng , Tong Rongsheng 
Published: November 2021

Background: Ligustrazine injection has been widely used as adjunctive therapy in the treatment of acute cerebral infarction (ACI) during the past decades in China, but its clinical efficacy is not yet well confirmed. This study aims to evaluate the efficacy of ligustrazine injection as adjunctive therapy for ACI.Methods: Databases including China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), PubMed, Medline, Google Scholar, Chinese Biomedical Literature Database, Cochrane Library, Embase, Sino-Med, Wanfang Database, and Chinese Science Citation Database were systematically searched for the published randomized controlled trials (RCTs) on ligustrazine injection in the treatment of ACI until November 2020. Meta-analysis was performed on the primary outcome measure (i.e., clinical effective rate) and the secondary outcome measure [i.e., neurological deficit score (NDS), fibrinogen, low shear blood viscosity (LBV), and high shear blood viscosity (HBV)]. The quality of the included RCTs was assessed according to the M scoring system (the refined Jadad scale). Sensitivity analysis and subgroup analysis were conducted according to the methodological quality, years of publication, and sample size.Results: Nineteen RCTs, containing 2022 patients, were included in this study. Meta-analysis indicated that ligustrazine injection combined with Western medicine could achieve a better effect in the treatment of ACI than using Western medicine alone in terms of clinical effective rate (RR = 1.24; 95% CI, 1.19–1.29), NDS (MD = −3.88; 95%CI, −4.51 to −3.61), fibrinogen (MD = −0.59; 95% CI, −0.76 to −0.42), LBV (MD = −2.11; 95% CI, −3.16 to −1.06), and HBV (MD = −0.88; 95% CI, −1.20 to −0.55).Conclusions: This research indicated that ligustrazine injection as adjunctive therapy seemed to be more effective than using western medicine alone in treating ACI. However, more evidence is required to confirm the efficacy of ligustrazine injection due to the low methodological quality of the included RCTs.
A Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine Exposure
Authors: Bedrossiantz Juliette , Bellot Marina , Dominguez-García Pol , Faria Melissa , Prats Eva , Gómez-Canela Cristian , López-Arnau Raul , Escubedo Elena , Raldúa Demetrio 
Published: November 2021

Hyperthermia is a common confounding factor for assessing the neurotoxic effects of methamphetamine (METH) in mammalian models. The development of new models of methamphetamine neurotoxicity using vertebrate poikilothermic animals should allow to overcome this problem. The aim of the present study was to develop a zebrafish model of neurotoxicity by binge-like methamphetamine exposure. After an initial testing at 20 and 40 mg/L for 48 h, the later METH concentration was selected for developing the model and the effects on the brain monoaminergic profile, locomotor, anxiety-like and social behaviors as well as on the expression of key genes of the catecholaminergic system were determined. A concentration- and time-dependent decrease in the brain levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT) was found in METH-exposed fish. A significant hyperactivity was found during the first hour of exposure, followed 3 h after by a positive geotaxis and negative scototaxis in the novel tank and in the light/dark paradigm, respectively. Moreover, the behavioral phenotype in the treated fish was consistent with social isolation. At transcriptional level, th1 and slc18a2 (vmat2) exhibited a significant increase after 3 h of exposure, whereas the expression of gfap, a marker of astroglial response to neuronal injury, was strongly increased after 48 h exposure. However, no evidences of oxidative stress were found in the brain of the treated fish. Altogether, this study demonstrates the suitability of the adult zebrafish as a model of METH-induced neurotoxicity and provides more information about the biochemical and behavioral consequences of METH abuse.
Mechanical Power Correlates With Lung Inflammation Assessed by Positron-Emission Tomography in Experimental Acute Lung Injury in Pigs
Authors: Scharffenberg Martin , Wittenstein Jakob , Ran Xi , Zhang Yingying , Braune Anja , Theilen Raphael , Maiello Lorenzo , Benzi Giulia , Bluth Thomas , Kiss Thomas , Pelosi Paolo , Rocco Patricia R. M. , Schultz Marcus J. , Kotzerke Jörg , Gama de Abreu Marcelo , Huhle Robert 
Published: November 2021

Background:Mechanical ventilation (MV) may initiate or worsen lung injury, so-called ventilator-induced lung injury (VILI). Although different mechanisms of VILI have been identified, research mainly focused on single ventilator parameters. The mechanical power (MP) summarizes the potentially damaging effects of different parameters in one single variable and has been shown to be associated with lung damage. However, to date, the association of MP with pulmonary neutrophilic inflammation, as assessed by positron-emission tomography (PET), has not been prospectively investigated in a model of clinically relevant ventilation settings yet. We hypothesized that the degree of neutrophilic inflammation correlates with MP.Methods:Eight female juvenile pigs were anesthetized and mechanically ventilated. Lung injury was induced by repetitive lung lavages followed by initial PET and computed tomography (CT) scans. Animals were then ventilated according to the acute respiratory distress syndrome (ARDS) network recommendations, using the lowest combinations of positive end-expiratory pressure and inspiratory oxygen fraction that allowed adequate oxygenation. Ventilator settings were checked and adjusted hourly. Physiological measurements were conducted every 6 h. Lung imaging was repeated 24 h after first PET/CT before animals were killed. Pulmonary neutrophilic inflammation was assessed by normalized uptake rate of 2-deoxy-2-[18F]fluoro-D-glucose (KiS), and its difference between the two PET/CT was calculated (ΔKiS). Lung aeration was assessed by lung CT scan. MP was calculated from the recorded pressure–volume curve. Statistics included the Wilcoxon tests and non-parametric Spearman correlation.Results:Normalized18F-FDG uptake rate increased significantly from first to second PET/CT (p= 0.012). ΔKiSsignificantly correlated with median MP (ρ = 0.738,p= 0.037) and its elastic and resistive components, but neither with median peak, plateau, end-expiratory, driving, and transpulmonary driving pressures, nor respiratory rate (RR), elastance, or resistance. Lung mass and volume significantly decreased, whereas relative mass of hyper-aerated lung compartment increased after 24 h (p= 0.012,p= 0.036, andp= 0.025, respectively). Resistance and PaCO2were significantly higher (p= 0.012 andp= 0.017, respectively), whereas RR, end-expiratory pressure, and MP were lower at 18 h compared to start of intervention.Conclusions:In this model of experimental acute lung injury in pigs, pulmonary neutrophilic inflammation evaluated by PET/CT increased after 24 h of MV, and correlated with MP.
Myoelectric Activity and Fatigue in Low-Load Resistance Exercise With Different Pressure of Blood Flow Restriction: A Systematic Review and Meta-Analysis
Authors: de Queiros Victor Sabino , de França Ingrid Martins , Trybulski Robert , Vieira João Guilherme , dos Santos Isis Kelly , Neto Gabriel Rodrigues , Wilk Michal , Matos Dihogo Gama de , Vieira Wouber Hérickson de Brito , Novaes Jefferson da Silva , Makar Piotr , Cabral Breno Guilherme de Araújo Tinoco , Dantas Paulo Moreira Silva 
Published: November 2021

Background: Low-load resistance exercise (LL-RE) with blood flow restriction (BFR) promotes increased metabolic response and fatigue, as well as more pronounced myoelectric activity than traditional LL-RE. Some studies have shown that the relative pressure applied during exercise may have an effect on these variables, but existing evidence is contradictory.Purpose: The aim of this study was to systematically review and pool the available evidence on the differences in neuromuscular and metabolic responses at LL-RE with different pressure of BFR.Methods: The systematic review and meta-analysis was reported according to PRISMA items. Searches were performed in the following databases: CINAHL, PubMed, Scopus, SPORTDiscus and Web of Science, until June 15, 2021. Randomized or non-randomized experimental studies that analyzed LL-RE, associated with at least two relative BFR pressures [arterial occlusion pressure (AOP)%], on myoelectric activity, fatigue, or metabolic responses were included. Random-effects meta-analyses were performed for MVC torque (fatigue measure) and myoelectric activity. The quality of evidence was assessed using the PEDro scale.Results: Ten studies were included, all of moderate to high methodological quality. For MVC torque, there were no differences in the comparisons between exercise with 40–50% vs. 80–90% AOP. When analyzing the meta-analysis data, the results indicated differences in comparisons in exercise with 15–20% 1 repetition maximum (1RM), with higher restriction pressure evoking greater MVC torque decline (4 interventions, 73 participants; MD = −5.05 Nm [95%CI = −8.09; −2.01], p = 0.001, I2 = 0%). For myoelectric activity, meta-analyses indicated a difference between exercise with 40% vs. 60% AOP (3 interventions, 38 participants; SMD = 0.47 [95%CI = 0.02; 0.93], p = 0.04, I2 = 0%), with higher pressure of restriction causing greater myoelectric activity. This result was not identified in the comparisons between 40% vs. 80% AOP. In analysis of studies that adopted pre-defined repetition schemes, differences were found (4 interventions, 52 participants; SMD = 0.58 [95%CI = 0.11; 1.05], p = 0.02, I2 = 27%).Conclusion: The BFR pressure applied during the LL-RE may affect the magnitude of muscle fatigue and excitability when loads between 15 and 20% of 1RM and predefined repetition protocols (not failure) are prescribed, respectively.Systematic Review Registration: [http://www.crd.york.ac.uk/prospero], identifier [CRD42021229345].
Recovery Education for Adults Transitioning From Homelessness: A Longitudinal Outcome Evaluation
Authors: Durbin Anna , Nisenbaum Rosane , Wang Ri , Hwang Stephen W. , Kozloff Nicole , Stergiopoulos Vicky 
Published: November 2021

Objective: Grounded in principles of adult education, Recovery Education Centres (RECs) hold promise in promoting recovery for adults with mental health challenges, but research on recovery outcomes for hard-to-reach populations participating in RECs is scant. This quasi-experimental study compares 12-month recovery outcomes of adults with histories of homelessness and mental health challenges enrolled in a REC, to those of participants of other community services for this population.Methods: This pre-post quasi-experimental study compared participants enrolled in a REC for people with histories of homelessness and mental health challenges (n = 92) to an age-and-gender frequency matched control group participating in usual services (n = 92) for this population in Toronto, Ontario. Changes from program enrollment to 12 months in personal empowerment (primary outcome), disease specific quality of life, recovery, health status, health related quality of life, and mastery were assessed. Post-hoc analyses compared subgroups with 1–13 h (n = 37) and 14+ h (n = 37) of REC participation during the study period to the control group. Linear mixed models estimated mean changes and differences in mean changes and 95% confidence intervals.Results: Mean change in perceived empowerment from program enrollment to 12 months in the intervention group [0.10 (95% CI: 0.04, 0.15)] was not significantly different from the control group [0.05 (−0.01, 0.11)], mean difference, 0.05 [(−0.03, 0.13), P = 0.25]. In the post-hoc analysis, the mean change in perceived empowerment for the intervention subgroup with 14+ h of REC participation [0.18 (0.10, 0.26)] was significantly different than in the control group [0.05 (−0.01, 0.11)] mean difference, 0.13 [(0.03, 0.23), P &lt; 0.01]. Mean change in mastery was also significantly different for the intervention subgroup with 14+ h of REC participation [2.03 (1.04, 3.02)] vs. controls [0.60 (−0.15, 1.35)], mean difference, 1.43 [(0.19, 2.66), P = 0.02]. There were no significant differences in other outcomes.Conclusion: With sufficient hours of participation, recovery education may be a helpful adjunct to health and social services for adults with mental health challenges transitioning from homelessness.
Influence of Clinical Markers of Dopaminergic Behaviors on Depressive Symptoms During Withdrawal in Cocaine Users
Authors: Cabé Julien , Brousse Georges , Pereira Bruno , Cabé Nicolas , Karsinti Emily , Zerdazi El-Hadi , Icick Romain , Llorca Pierre M. , Bloch Vanessa , Vorspan Florence , De Chazeron Ingrid 
Published: November 2021

Background: During cocaine withdrawal, transient depressive symptoms that do not meet the criteria for depression, but promote relapse, are frequently observed. Their temporality could evoke a role of dopamine, especially since the underlying mechanism of these depressive symptoms is not well understood. We hypothesized that variation in the dopaminergic activity profile, modeled from clinical markers, could be implicated in the development of depressive symptoms during cocaine withdrawal.Methods: We compared patients reporting depressive symptoms (RDS+) or not (RDS–) during cocaine withdrawal. We evaluated dopaminergic activity through indirect clinical markers based on the known dopaminergic behaviors. A combined criterion was constructed for hyper and hypo dopaminergic models according to the O'Brien method and illustrated by the Hedges' effect-size and forest-plot graph. A multidimensional factorial analysis was carried out to determine which parameters discriminate RDS+/RDS– patients.Results: 313 patients were included, and 77% reported depressive symptoms during cocaine withdrawal. Hyperdopaminergic variables used to discriminate the two groups had a large overall effect size (−0.669) and included psychotic symptoms (−0.524), hallucinations (−0.548), and delusions (−0.528). The overall effect of the hypodopaminergic component was considerable (−0.604) with a large effect size for the severity of dependence (−0.616), withdrawal symptoms (−0.578), and anhedonia (−0.528). The combined model including hyperdopaminergic and hypodopaminergic components had the largest effect size (−0.785).Conclusion: The dopaminergic activities profile, assessed by indirect clinical markers, seems to characterize patients with depressive symptoms very well during cocaine withdrawal. RDS+ patients reported moreover higher levels of psychotic symptoms and more severe cocaine use disorder than RDS–.
Comparison of Surgical Outcomes Between Separation Surgery and Piecemeal Spondylectomy for Spinal Metastasis: A Retrospective Analysis
Authors: Xu Lun , Huang Wending , Cai Weiluo , Sun ZhengWang , Fang Meng , Ji Yingzheng , Wang Shuoer , Zhang Jianing , Hu Tu , Cheng Mo , Yan Wangjun 
Published: November 2021

Objective: This study aimed to compare the outcomes between piecemeal spondylectomy and separation surgery for patients with spinal metastasis.Summary of Background Data: Piecemeal spondylectomy and separation surgery are two widely-used treatment options for spinal metastasis. However, no studies have compared the surgical outcomes between both treatment modalities.Methods: Patients with spinal metastasis who underwent piecemeal spondylectomy or separation surgery between August 2017 and April 2020 at our spine center were recruited. Demographic, preoperative, perioperative, and follow-up data were collected and analyzed. Kaplan–Meier analysis and the log-rank test were used to analyze overall survival (OS) and progression-free survival (PFS) in patients with spinal metastasis.Results: Overall, 26 patients were treated with piecemeal spondylectomy, and 29 underwent separation surgery with postoperative stereotactic radiosurgery. Both groups showed significant postoperative improvements in neurological status. The piecemeal spondylectomy group had significantly more blood loss (1784.62 ± 833.64 vs. 1165.52 ± 307.38 ml) and required longer operative time (4.76 ± 0.93 vs. 3.73 ± 1.15 h) than the separation surgery group. No significant difference in OS was found between the groups (P = 0.064); however, patients in the separation surgery group experienced less local recurrence than those in the piecemeal spondylectomy group (P = 0.0014). Notably, significant differences were detected in the development of complications between the groups (P = 0.029).Conclusion: Separation surgery led to less blood loss and reduced complications and had shorter operation time than piecemeal spondylectomy. Although no significant differences were found in OS between the groups, separation surgery was associated with better PFS compared with piecemeal spondylectomy. These findings suggest that separation surgery has some advantages over piecemeal spondylectomy for patients with spinal metastatic disease.