bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sitagliptin Reduces Endothelial Dysfunction and Apoptosis Induced by High-Fat Diet and Palmitate in Thoracic Aortas and Endothelial Cells via ROS-ER Stress-CHOP Pathway
Authors: Cao Qiongqiong , Xu Dongmei , Chen Yong , Long Yueming , Dai Fang , Gui Li , Lu Yunxia 
Published: September 2021

Macrovascular disease is tightly associated with obesity-induced metabolic syndrome. Sitagliptin (SIT), an orally stable selective inhibitor of Dipeptidyl peptidase-4 (DPP-4), has protective effects on endothelium. However, the mechanisms enabling SIT to exhibit resistance to diet-induced obesity (DIO) related with reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress in the aorta and endothelial cells have not been reported yet. Therefore, the present study was conducted to determine if SIT exerts protective role in the thoracic aortas isolated from the high-fat diet (HFD)-treated rats and palmitate (PA)-treated endothelial cells by alleviating ROS and ER stress. Male Sprague Dawley rats were randomly divided into standard chow diet (SCD), HFD and HFD plus sitagliptin administration (HFD + SIT) groups. The rats of latter two groups were given HFD fodder for 12 weeks, then the HFD + SIT rats were treated with SIT (10 mg/kg/d) by intragastric administration for another 8 weeks. The body mass, vascular tension, serum oxidative stress indices and inflammatory parameters, pathological changes, protein expression of endothelial nitric oxide synthase (eNOS), the genes associated with ER stress and apoptosis in the thoracic aorta were measured. Furthermore, cell proliferation, ROS and the protein expression associated with ER stress (especially CHOP) and apoptosis were assessed in human umbilical vein endothelial cells (HUVECs) incubated with SIT and PA. Compared to the SCD rats, the HFD rats had higher serum lipid levels, decreased vascular tension, increased inflammation, oxidative and ER stress, and apoptosis of endothelial cells. PA promoted ROS generation, ER stress and apoptosis, inhibited cell proliferation in HUVECs. SIT treatment obviously ameliorated apoptosis via alleviating ROS and ER stress in the thoracic aortas isolated from HFD-fed rats and PA-treated HUVECs. The results suggest that SIT improved endothelial function via promoting cell proliferation and alleviating ROS-ER stress-CHOP pathway both in vivo and in vitro.
Safety Assessment of Acer tegmentosum Maxim. Water Extract: General Toxicity Studies in Sprague–Dawley Rats and Beagle Dogs With Re-evaluation of Genotoxic Potentials
Authors: Park Jin-Sung , Kwon Euna , Kim Yun-Soon , Kim Sang-Moo , Kim Dae-Sun , Jang Ja-June , Yun Jun-Won , Kang Byeong-Cheol 
Published: September 2021

Acer tegmentosum Maxim., commonly known as Manchurian stripe maple, is a deciduous tree belonging to the family of Aceraceae and has been traditionally used in folk medicine for its remedial effects in liver diseases and traumatic bleedings. With a growing body of experimental evidence for its pharmacological efficacies, such as neuroprotective, hepatoprotective, antioxidant, and anti-inflammatory activities, A. tegmentosum has gradually gained popularity as a health supplement and functional food. However, the large part of essential toxicity information still remained lacking despite the possibility of mutagenic potentials as previously suggested, posing safety concerns for human consumption. In this study, we evaluated 90-day repeated oral toxicity of A. tegmentosum Maxim. water extract (ATWE) in SD rats with acute toxicity assessment in beagle dogs, and reevaluated genotoxicity using a combination of in vitro and in vivo assays. During the oral study period, ATWE did not cause toxicity-related clinical signs and mortality in rodents without adverse effects observed in the analysis of hematology, serum biochemistry, and histopathology, establishing &gt;5,000 mg/kg BW as the NOAEL. In addition, doses up to 5,000 mg/kg BW did not cause acute toxicity in beagle dogs. When assessed for genotoxicity using bacterial reverse mutation, chromosome aberration, and micronucleus formation, ATWE showed lack of mutagenicity and clastogenicity. These results demonstrated that AWTE was safe in the present preclinical study for systemic toxicity and genotoxicity at the tested doses, providing a guideline for safe use in humans.
Creation of an Anti-Inflammatory, Leptin-Dependent Anti-Obesity Celastrol Mimic with Better Druggability
Authors: Zhou Bo , Yuan Yaxia , Shi Le , Hu Sheng , Wang Dong , Yang Yang , Pan Yuanhu , Kong Dexin , Shikov Alexander N. , Duez Pierre , Jin Moonsoo , Li Xiaohua , Hu Xuebo 
Published: September 2021

Obesity is characterized by an excessive body mass, but is also closely associated with metabolic syndrome. And, so far, only limited pharmacological treatments are available for obesity management. Celastrol, a pentacyclic triterpenoid from a traditional Chinese medicine (Tripterygium wilfordii Hook.f.), has shown remarkable potency against obesity, inflammation and cancer, but its high toxicity, low natural abundance and tedious chemical synthesis hindered its translation into clinics. In the present work, a triterpenoid library was screened for compounds with both high natural abundance and structural similarity to celastrol; from this library, glycyrrhetinic acid (GA), a compound present in extremely high yields in Glycyrrhiza uralensis Fisch. ex DC., was selected as a possible scaffold for a celastrol mimic active against obesity. A simple chemical modification of GA resulted in GA-02, a derivative that suppressed 68% of food intake in diet-induced obesity mice and led to 26.4% weight loss in 2 weeks. GA-02 plays a role in obesity treatment by re-activating leptin signaling and reducing systemic and, more importantly, hypothalamic inflammation. GA-02 was readily bioavailable with unnoticeable in vitro and in vivo toxicities. The strategy of scaffold search and modification on the basis of bio-content and structural similarity has proved to be a green, economic, efficient and practical way of widening the medicinal applications of “imperfect” bioactive natural compounds.
Selective Myeloid Depletion of Galectin-3 Offers Protection Against Acute and Chronic Lung Injury
Authors: Humphries Duncan C. , Mills Ross , Dobie Ross , Henderson Neil C. , Sethi Tariq , Mackinnon Alison C. 
Published: September 2021

Rationale:Galectin-3 (Gal-3) is an immune regulator and an important driver of fibrosis in chronic lung injury, however, its role in acute lung injury (ALI) remains unknown. Previous work has shown that global deletion of galectin-3 reduces collagen deposition in a bleomycin-induced pulmonary fibrosis model (MacKinnon et al., Am. J. Respir. Crit. Care Med., 2012, 185, 537–46). An inhaled Gal-3 inhibitor, GB0139, is undergoing Phase II clinical development for idiopathic pulmonary fibrosis (IPF). This work aims to elucidate the role of Gal-3 in the myeloid and mesenchymal compartment on the development of acute and chronic lung injury.Methods:LgalS3fl/flmice were generated and crossed with mice expressing the myeloid (LysM) and mesenchymal (Pdgfrb) cre drivers to yieldLysM-cre+/-/LgalS3fl/flandPdgfrb-cre+/-/LgalS3fl/flmice. The response to acute (bleomycin or LPS) or chronic (bleomycin) lung injury was compared to globally deficientGal-3−/−mice.Results:Myeloid depletion of Gal-3 led to a significant reduction in Gal-3 expression in alveolar macrophages and neutrophils and a reduction in neutrophil recruitment into the interstitium but not into the alveolar space. The reduction in interstitial neutrophils corelated with decreased levels of pulmonary inflammation following acute bleomycin and LPS administration. In addition, myeloid deletion decreased Gal-3 levels in bronchoalveolar lavage (BAL) and reduced lung fibrosis induced by chronic bleomycin. In contrast, no differences in BAL Gal-3 levels or fibrosis were observed inPdgfrb-cre+/-/LgalS3fl/flmice.Conclusions:Myeloid cell derived Galectin-3 drives acute and chronic lung inflammation and supports direct targeting of galectin-3 as an attractive new therapy for lung inflammation.
Is Targeting Nerve Growth Factor Antagonist a New Option for Pharmacologic Treatment of Low Back Pain? A Supplemental Network Meta-Analysis of the American College of Physicians Guidelines
Authors: Cao Ziqin , Li Qiangxiang , Guo Jia , Li Yajia , Wu Jianhuang 
Published: September 2021

Objective: It has been found that targeting nerve growth factor antagonists (ANGF) have excellent effects in the treatment of chronic pain, and the current pharmacologic treatments have very limited effects on low back pain (LBP). Thus we conducted this network meta-analysis (NMA) to study the efficacy and safety of ANGF for the treatment of LBP, and to guide for clinical practice and further research.Method: PubMed, Scopus, Embase, CNKI, and the Cochrane Library were searched from January 1980 to March 2021. A frequentist framework network meta-analysis with a random-effect model was performed. Ranking effects were calculated by surface under the cumulative ranking analysis (SUCRA) and clusterank analysis.Results: This NMA identified 30 studies, involving 9,508 patients with LBP. ANGF reported both superior effect on pain relief {SUCRA 82.1%, SMD 0.89, 95% CI [(0.26,1.51)]} and function improvement {SUCRA 77.3%, SMD 0.93, 95% CI [(0.27,1.58)]} than placebo, and did not showed any higher risk of treatment-emergent adverse effects {RR 1.11, 95% CI [(0.97,1.27)]} or serious adverse effects {RR 1.03, 95% CI [(0.54,1.97)]}, but it was associate with a special risk of rapidly progressive osteoarthritis. ANGF displayed the greatest potential to be the most effective and safest treatment (cluster-rank value for function improvement and safety: 4266.96, for pain relief and safety: 4531.92).Conclusion: ANGF could relieve pain and improve function effectively and are superior to other traditional drugs recommended by guidelines. Although no significant difference in tolerability and safety between ANGFs and placebo was found, the rapid progression of original osteoarthritis which may be related to the use of ANGFs still needs special attention and furtherly verification by clinical trials.Systematic Review Registration: PROSPERO, identifier [CRD42021258033].
LncRNA GAS5 Competitively Combined With miR-21 Regulates PTEN and Influences EMT of Peritoneal Mesothelial Cells via Wnt/β-Catenin Signaling Pathway
Authors: Fan Yi , Zhao Xingxu , Ma Jianfei , Yang Lina 
Published: September 2021

ObjectiveEpithelial-mesenchymal transition (EMT) is an important factor leading to peritoneal fibrosis (PF) in end-stage renal disease (ESRD) patients. The current research aimed to evaluate the effect of long non-coding RNA growth arrest-specific 5 (lncRNA GAS5) in human peritoneal mesothelial cells (HPMCs) EMT and explore the potential molecular mechanisms.Materials and MethodsHPMCs were cultured under control conditions or with high glucose (HG). The cells were then treated with lncRNA GAS5, lncRNA GAS5 siRNA, with or without miR-21 inhibitor and PTEN transfection. Expression of lncRNA GAS5, miR-21, α-SMA, Vimentin, E-cadherin, phosphatase and tensin homolog deleted on chromosome ten (PTEN), Wnt3a, and β-catenin were measured by real time PCR and Western blotting. Bioinformatics analyses were used to test the specific binding sites between the 3′ UTR of the PTEN gene, miR-21, and lncRNA GAS5. Rescue experiments were performed to confirm the lncRNA GAS5/miR-21/PTEN axis in HPMC EMT.ResultsWe found that HG-induced EMT decreased lncRNA GAS5 and that overexpression of lncRNA GAS5 can attenuate EMT in HPMCs. In addition, lncRNA GAS5 regulated HG-induced EMT through miR-21/PTEN. Cotransfection of miR-21 inhibitors remarkably increased PTEN expression and attenuated EMT in lncRNA GAS5 knockdown HPMCs. Moreover, rescue experiments showed that overexpression of PTEN attenuated the EMT effects of lncRNA GAS5 siRNA in HPMCs. We also confirmed that the Wnt/β-catenin pathway was stimulated in lncRNA GAS5/miR-21/PTEN-mediated EMT.ConclusionOur research showed that lncRNA GAS5 competitively combined with miR-21 to regulate PTEN expression and influence EMT of HPMCs via the Wnt/β-catenin signaling pathway. This study provides novel evidence that lncRNA GAS5 may be a potential therapeutic target for HPMC EMT.
The Gaps Between the Self and Professional Evaluation in Mental Health Assessment of COVID-19 Cluster Cases
Authors: Liu Ligai , Wang Xin , Hao Yiwei , Yang Jingming , Yang Di , Duan Xuefei , Fang Gaoli , Han Bing , Jiang Chunguo , Li Junnan , Liu Yao , Wang Yang , Song Rui 
Published: September 2021

Objective: To analyze the discrepancy between self-rating and professional evaluation of mental health status in coronavirus disease 2019 (COVID-19) cluster cases.Method: A total of 65 COVID-19 cluster cases admitted to Beijing Ditan Hospital Capital Medical University from June 14, 2020 to June 16, 2020 were included in the study. Mental health assessment was completed by self-rating and professional evaluation. The gaps between self-rating and professional evaluation in different demographic characteristics were compared.Results: The results of self-rating were inconsistent with those of professional evaluation. The gap was statistically different among certain demographic subgroups. As for anxiety, the gaps had remarkable statistics differences in subgroups of sex, monthly income, infection way, and anxiety/depression medical history. Similarly, in the terms of depression, the gaps had significant statistic differences in the subgroups of the medical history of anxiety/depression, history of physical disease, employment status and the insurance type, marriage, education (year), residing in Beijing (year), and the monthly income.Conclusion: Compared to the professional evaluation, patients had a higher self-rating, which may be related to some demographic characteristics. It suggests that screening can be conducted in patients with COVID-19 by self-rating first, and then professional evaluation should be carried out in the patients with suspicious or positive results.
Compensatory Belief in Health Behavior Management: A Concept Analysis
Authors: Zhao Kang , Xu Xinyi , Zhu Hanfei , Xu Qin 
Published: September 2021

PurposeThis study aimed to identify the exact definition of the concept of compensatory belief (CB) and to help clinicians and caregivers to distinguish patients who tend to form such beliefs.MethodsThis study is a conceptual analysis based on the strategy of Walker and Avant (2014). We retrieved studies from existing literature using databases such as PubMed, CINAHL, Wiley, and Web of Science, and extracted information from the results. No date limitations were applied.ResultsA total of 35 articles were sourced for data extraction. The identified attributes of CB were as follows: cognitive coping strategy, pleasure without guilt, compensatory behaviors, automatic motivated self-regulatory process, and implicit cognition. The observed antecedents were: failure to resist desire, reluctance, a conflicting motivational state, seeking appropriate balance, and self-image maintenance. The consequences of CB were lower health-related intentions, justification of unhealthy choices, relief from cognitive dissonance, continued existence of conflict feeling, and poor long-term health.ConclusionCompensatory belief stems from motivational dissonance or confliction. Despite causing feelings of pleasure and relief, it can negatively impact long-term health. Although CB is crucial to establish healthy behaviors, it is easily ignored in medical work.
Confirming the Reliability and Validity of the Sexual Minority Adolescent Stress Inventory in a National Sample of Sexual Minority Adolescents
Authors: Goldbach Jeremy T. , Schrager Sheree M. , Mamey Mary Rose , Rhoades Harmony 
Published: September 2021

Objective: Sexual minority adolescents (SMA) experience numerous behavioral health disparities, including depression, anxiety, substance use, non-suicidal self-injury, and suicidality. The primary framework to understand these disparities is minority stress theory, which frames this disproportionate burden as the result of discrimination, violence, and victimization in a homophobic culture. Empirical examinations of minority stress among SMA have been limited by lack of diverse samples or validated measures. This study engaged a national community sample of SMA to confirm reliability and validity of the Sexual Minority Adolescent Stress Inventory (SMASI).Method: A national sample of 2,310 SMA aged 14–17 was recruited in the United States through a hybrid social media and respondent-driven sampling approach. Item response theory and confirmatory factor analysis established the psychometric properties of the SMASI in this sample; minority stress was modeled as a latent variable in several regression models to verify criterion and divergent validity.Results: In this national sample (M age = 15.9; 64% female and 60% White), the factor structure of the SMASI and its 11 subscales was confirmed and shown to be invariant by demographic characteristics. Minority stress as measured by the SMASI was significantly associated with all mental and behavioral health outcomes.Conclusions: This study provides evidence that SMASI is a reliable, valid, and important tool for better understanding minority stress and subsequent health and mental health consequences among SMA.
Millipore xMap® Luminex (HATMAG-68K): An Accurate and Cost-Effective Method for Evaluating Alzheimer's Biomarkers in Cerebrospinal Fluid
Authors: Hansen Erika Oliveira , Dias Natalia Silva , Burgos Ivonne Carolina Bolaños , Costa Monica Vieira , Carvalho Andréa Teixeira , Teixeira Antonio Lucio , Barbosa Izabela Guimarães , Santos Lorena Aline Valu , Rosa Daniela Valadão Freitas , Ribeiro Aloisio Joaquim Freitas , Viana Bernardo Mattos , Bicalho Maria Aparecida Camargos 
Published: September 2021

Background: Alzheimer's disease (AD) biomarkers are of great relevance in clinical research, especially after the AT(N) framework. They enable early diagnosis, disease staging and research with new promising drugs, monitoring therapeutic response. However, the high cost and low availability of the most well-known methods limits their use in low and medium-income countries. In this context, Millipore xMap® Luminex may be a cost-effective alternative. In our study, using INNOTEST® as reference, we assess the diagnostic accuracy of Millipore xMap® and propose a cutoff point for AD.Methods: We performed lumbar puncture of seven older individuals with clinically defined AD, 17 with amnestic mild cognitive impairment (aMCI) and 11 without objective cognitive impairment-control group (CG). Cerebrospinal fluid (CSF) biomarkers concentrations for aB42, p-Tau, and t-Tau were measured by INNOTEST® and Millipore xMap®, and then the techniques were compared to assess the diagnostic accuracy of the new test and to define a cutoff.Results: INNOTEST® and Millipore xMap® measurements showed all correlations &gt;0.8 for the same biomarker, except for t-Tau that was 0.66. Millipore xMap® measurements showed a robust accuracy for all biomarkers, with AUC higher than 0.808 (t-Tau), and the best for Aβ42 (AUC = 0.952). The most accurate cutoffs were found at 1012.98 pg/ml (Aβ42), 64.54 pg/ml (p-tau), 3251.81 pg/ml (t-tau), 3.370 (t-Tau/Aβ42), and 0.059 (p-Tau/Aβ42).Conclusion: Given its good accuracy and cost-effectiveness, Milliplex xMap® tests seems a reliable and promising tool, especially for low and middle-income countries.
Effectiveness and Preparedness of Institutions' E-Learning Methods During the COVID-19 Pandemic for Residents' Medical Training in Saudi Arabia: A Pilot Study
Authors: Alsaywid Basim , Lytras Miltiadis D. , Abuzenada Maha , Lytra Hara , Sultan Lama , Badawoud Hala , Abuznadah Wesam , Alhaider Sami A. , Housawi Abdulrahman , Apostolaki Areti 
Published: September 2021

Background:Under the urgent circumstances of the COVID-19 pandemic, higher education institutions of an international scale have resorted to online education methods, exclusive or not. Among those, medical institutions are under double pressure, fighting the pandemic's effects and, at the same time providing efficient clinical training to their residents. The main aim of the study is to evaluate the preparedness of the educational institutions for the e-learning platform transition for the delivery of medical training and also to evaluate the overall satisfaction level of the participants with their e-learning experience.Methods:This is an observational cross-sectional study design. The survey's sample included 300 medical students and residents of multiple training levels and specialties, coming from more than 15 different cities of Saudi Arabia. Filling the questionnaire required specific inclusion criteria and all obtained data were secured by the Saudi Commission of Health specialty. The main objective was to evaluate the quality of e-learning methods provided by medical universities. For the collection of the data, Survey Monkey software was used and the analysis was conducted with SPSS.Results:The study found that the frequency of digital education use increased by ~61% during the coronavirus crisis, while almost 9 out of 10 residents have used some e-learning platform. It was reported that before the pandemic, participants' online training was deemed to be rather ineffective, given the rate of 3.65 out of 10. However, despite the increase in e-learning use after COVID-19, many obstacles arose duringcthe adaptation process. According to our survey: lectures and training sessions were not conducted as per the curriculum (56.33%); both students and instructors' academic behavior and attitude changed (48.33%); engagement, satisfaction, and motivation in class were rated low (5.93, 6.33, and 6.54 out of 10 accordingly), compared to the desired ones. Still, participants accredited e-learning as a potential mandatory tool (77.67%) and pinpointed the qualifications that in their opinion will maximize educational impact.Conclusion:The study concluded that innovative restructuring of online education should be based on defined critical success factors (technical support, content enhancement, pedagogy etc.) and if possible, set priority levels, so that a more permanent e-learning practice is achievable. Also our study confirmed that students were overall satisfied with the e-learning support of the training method.
The Burden of Obesity in Egypt
Authors: Aboulghate Mohamed , Elaghoury Aliaa , Elebrashy Ibrahim , Elkafrawy Nabil , Elshishiney Galal , Abul-Magd Ehab , Bassiouny Engy , Toaima Dalia , Elezbawy Baher , Fasseeh Ahmad , Abaza Sherif , Vokó Zoltán 
Published: September 2021

Objective: Estimating the burden of obesity to society is an essential step in setting priorities and raising awareness. We aimed to assess the clinical, humanistic and economic burden of obesity for adults in Egypt.Methods: We used the population attributable fraction concept to estimate the burden. A non-systematic review was conducted to estimate the prevalence of obesity and its comorbidities in addition to the obesity attributable fraction. Patient numbers, direct healthcare costs, disability adjusted life years (DALYs) and attributable mortality were estimated.Results: Obesity is a major contributor to the development of diabetes mellitus, hypertension, obstructive sleep apnea and fatty liver, in addition to several serious diseases. The estimated annual deaths due to obesity was about 115 thousand (19.08% of the total estimated deaths in 2020). DALYs attributable to obesity may have reached 4 million in 2020.The economic burden imposed by obesity is around 62 Billion Egyptian pounds annually. This value is the cost of treating diseases attributable to obesity in adults.Conclusions: Diseases attributable to obesity create a huge economic, humanistic, and clinical burden in Egypt. Reducing obesity could help dramatically decrease the catastrophic health effect of these diseases which in turn decreases mortality and DALYs lost.