bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of the Molecular Mechanisms Underlying Erlong Zuoci Treatment of Age-Related Hearing Loss via Network Pharmacology-Based Analyses Combined with Experimental Validation
Authors: Liu Qing , Li Ning , Yang Yifang , Yan Xirui , Dong Yang , Peng Yinting , Shi Jianrong 
Published: November 2021

Background: The traditional Chinese medicine formula ErLong ZuoCi (ELZC) has been extensively used to treat age-related hearing loss (ARHL) in clinical practice in China for centuries. However, the underlying molecular mechanisms are still poorly understood.Objective: Combine network pharmacology with experimental validation to explore the potential molecular mechanisms underlying ELZC with a systematic viewpoint.Methods: The chemical components of ELZC were collected from the Traditional Chinese Medicine System Pharmacology database, and their possible target proteins were predicted using the SwissTargetPrediction database. The putative ARHL-related target proteins were identified from the database: GeneCards and OMIM. We constructed the drug-target network as well as drug-disease specific protein-protein interaction networks and performed clustering and topological property analyses. Functional annotation and signaling pathways were performed by gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Finally, in vitro experiments were also performed to validate ELZC’s key target proteins and treatment effects on ARHL.Results: In total, 63 chemical compounds from ELZC and 365 putative ARHL-related targets were identified, and 1860 ARHL-related targets were collected from the OMIM and GeneCards. A total of 145 shared targets of ELZC and ARHL were acquired by Venn diagram analysis. Functional enrichment analysis suggested that ELZC might exert its pharmacological effects in multiple biological processes, such as cell proliferation, apoptosis, inflammatory response, and synaptic connections, and the potential targets might be associated with AKT, ERK, and STAT3, as well as other proteins. In vitro experiments revealed that ELZC pretreatment could decrease senescence-associated β-galactosidase activity in hydrogen peroxide-induced auditory hair cells, eliminate DNA damage, and reduce cellular senescence protein p21 and p53. Finally, Western blot analysis confirmed that ELZC could upregulate the predicted target ERK phosphorylation.Conclusion: We provide an integrative network pharmacology approach, in combination with in vitro experiments to explore the underlying molecular mechanisms governing ELZC treatment of ARHL. The protective effects of ELZC against ARHL were predicted to be associated with cellular senescence, inflammatory response, and synaptic connections which might be linked to various pathways such as JNK/STAT3 and ERK cascade signaling pathways. As a prosperous possibility, our experimental data suggest phosphorylation ERK is essential for ELZC to prevent degeneration of cochlear.
Characterization of Alpelisib in Rat Plasma by a Newly Developed UPLC-MS/MS Method: Application to a Drug-Drug Interaction Study
Authors: Wang Qiong , Lan Xia , Zhao Zhuofei , Su Xiaohang , Zhang Yuji , Zhou Xiao-Yang , Xu Ren-Ai 
Published: December 2021

Alpelisib, an oral selective and small-molecule phosphoinositide 3-kinase inhibitor, was lately approved in the United States to treat breast cancer. A sensitive method to quantify alpelisib levels in rat plasma on the basis of ultra-performance liquid chromatography–tandem mass spectrometry technique was established and validated, which was successfully employed to explore the effects of CYP3A4 inhibitors on alpelisib pharmacokinetics in rats. A C18 column named Acquity UPLC BEH C18 was applied to achieve the separation of alpelisib and internal standard duvelisib after protein precipitation with acetonitrile. The mobile phase in this study had two components, namely, acetonitrile and water having 0.1% formic acid, and a program with gradient elution method was used at a flow rate of 0.40 ml/min. Mass spectrometry in a positive multiple reaction monitoring mode was operated. In the scope of 1–5,000 ng/ml, this assay had excellent linearity. Our newly developed assay was verified in all aspects of bioanalytical method validation, involving lower limit of quantification, selectivity, accuracy and precision, calibration curve, extraction recovery, matrix effect, and stability. Then, this assay was used to detect the plasma levels of alpelisib from a drug-drug interaction investigation, where ketoconazole remarkably increased the plasma concentration of alpelisib and changed alpelisib pharmacokinetics more than itraconazole. This study will help better understand the pharmacokinetic properties of alpelisib, and further clinical studies should be done to confirm this result in patients.
In Vitro Selective Antibacterial and Antiproliferative Effects of Ethanolic Extracts from Cambodian and Philippine Plants Used in Folk Medicine for Diarrhea Treatment
Authors: Kudera Tomas , Fiserova Barbora , Korytakova Marie , Doskocil Ivo , Salmonova Hana , Tulin Edgardo E. , Nguon Samnang , Bande Marlito M. , Kokoska Ladislav 
Published: December 2021

Bacterial diarrhea remains a global health problem, especially in developing tropical countries. Moreover, dysbiosis caused by diarrheagenic bacteria and inappropriate antimicrobial treatment has been associated with intestinal carcinogenesis. Despite the rich tradition of the use of herbs for the treatment of gastrointestinal disorders in Cambodian and Philippine folk medicine, many of them have not yet been systematically studied for their in vitro selective inhibitory effects on intestinal bacteria and cells. In the present study, in vitro inhibitory activities of 35 ethanolic extracts derived from 32 Cambodian and Philippine medicinal plants were determined by broth microdilution method against 12 pathogenic bacteria. Furthermore, cytotoxicity against intestinal cancer cells (Caco-2 and HT-29) using thiazolyl blue tetrazolium bromide cytotoxicity assay and safety to six beneficial intestinal bacteria (bifidobacteria and lactobacilli) and intestinal normal cells (FHs 74 Int) were determined for the antimicrobially active extracts. Selectivity indices (SIs) were calculated among the averages of minimum inhibitory concentrations (MICs), half-maximal inhibitory concentrations (IC50), and 80% inhibitory concentrations of proliferation (IC80) for each type of the tested agents. The extracts of Artocarpus blancoi (Elmer) Merr. (Moraceae), Ancistrocladus tectorius (Lour.) Merr. (Ancistrocladaceae), and Pentacme siamensis (Miq.) Kurz (Dipterocarpaceae) produced significant growth-inhibitory effects (MICs = 32–512 μg/ml) against intestinal pathogenic bacteria at the concentrations nontoxic to normal intestinal cells (IC80 values &gt;512 μg/ml; SIs = 0.11–0.2). Moreover, the extract of P. siamensis (Miq.) Kurz was relatively safe to beneficial bacteria (MICs ≥512 μg/ml; SI = 0.1), and together with A. blancoi (Elmer) Merr., they selectively inhibited intestinal cancer cells (IC50 values ≥51.98 ± 19.79 μg/ml; SIs = 0.3 and 0.6). Finally, a strong selective antiproliferative effect on cancer cells (IC50 values 37.89 ± 2.68 to 130.89 ± 13.99 μg/ml; SIs = 0.5) was exerted by Ehretia microphylla Lam. (Boraginaceae), Lagerstroemia cochinchinensis Pierre ex Gagnep. (Lythraceae), and Melastoma saigonense (Kuntze) Merr. (Melastomataceae) (leaves with flower buds). The results suggest that the above-mentioned species are promising materials for the development of new selective antibacterial and antiproliferative agents for the treatment of infectious diarrhea and associated intestinal cancer diseases. However, further research is needed regarding the isolation and identification of their active constituents.
The Protective Effects of Zornia diphylla (L.) Pers. Against Acute Liver Injury Induced by Carbon Tetrachloride in Mice
Authors: Xie Su-Zhi , Zhai Xiang-Yang , Xi Sheng-Yan , Qiu Ying-Kun , Zhang Yu-Mei , Kong Xiang-Jun , Li Yun-Hong , Zhu Lin , Wang Zheng , Zhang Shan-Gang , Huang Shu-Qiong , Lu Da-Wei , Wang Zheng 
Published: November 2021

Background:Zornia diphylla (L.) Pers. (ZDP) is a traditional Chinese herbal medicine that has been used for several decades to treat patients with liver diseases. Whether ZDP is best administered as a single agent or adjunctive therapy has yet to be determined as does the mechanism whereby it exerts its effects on antagonizing acute liver injury (ALI).Aim of the study: To investigate the protective effects of ZDP on ALI induced by carbon tetrachloride (CCl4) and the potential underlying mechanisms.Materials and Methods: Sixty adult mice were randomized into six study groups (n = 10/group). Three groups were treated with different concentrations of ZDP (2.5, 1.25, 0.625 g/kg), one with bifendate (0.0075 g/kg) alone (positive control) and one with physiologic saline (normal, negative control). All groups were treated for 14 days. Two hours after the last administration, the normal group received an intraperitoneal injection of peanut oil, and the other five groups received an intraperitoneal injection of an equal dose of CCl4 peanut oil solution. At 24 h, the liver index, histology and serum or tissue levels and/or protein expression of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), alkaline phosphatase (ALP), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione (GSH), Akt, phosphorylated Akt (p-Akt), nuclear factor kappa B p65 (NF-κB p65), inhibitor of NF-κB α (IκB-α), interleukin-1 β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), E-cadherin and vimentin were determined.Results: Compared to the model controls, the degree of inflammatory cell infiltration and hepatocyte injury of liver tissue was relieved in the bifendate and three ZDP groups; liver index in the ZDP (2.5, 1.25 g/kg) groups and serum liver function indices in the ZDP (2.5, 1.25 and 0.625 g/kg) groups were decreased; antioxidants SOD, CAT and GSH in liver tissue were increased but the lipid peroxidation index MDA was decreased; protein expression of inflammatory cytokines Akt, p-Akt, NF-κB p65, IκB-α, IL-1β, IL-6 and TNF-α in the liver was ameliorated, and E-cadherin expression was increased. The results of liver histopathology also showed that ZDP had a significant effect on ALI.Conclusion: ZDP has obvious protective effects on CCl4-induced ALI as a single therapy and appears to act by inhibiting oxidation, reducing the release of inflammatory factors and promoting hepatocyte repair.
Ferruginol Restores SIRT1-PGC-1α-Mediated Mitochondrial Biogenesis and Fatty Acid Oxidation for the Treatment of DOX-Induced Cardiotoxicity
Authors: Li Weili , Cao Jing , Wang Xiaoping , Zhang Yawen , Sun Qianbin , Jiang Yanyan , Yao Junkai , Li Chun , Wang Yong , Wang Wei 
Published: November 2021

Background: Doxorubicin (DOX), a broad-spectrum chemotherapy drug, has life-threatening cardiotoxicity. Therefore, searching cardioprotective drugs for DOX-induced cardiotoxicity (DIC) is urgently needed.Objectives: This study aimed to explore cardioprotective effect and specific mechanism by which Ferruginol (FGL) attenuated DIC in vivo and in vitro.Methods: We evaluated the cardioprotection of FGL and performed high-throughput RNA-Seq on a DIC mouse. Whereafter, multiple methods, including western blot, RT-qPCR, a transmission electron microscope, CO-IP, immunofluorescence, and other staining methods, and antagonist of SIRT1 and PGC-1α were utilized to confirm the cardioprotection and molecular mechanism of FGL.Results: FGL-exerted cardioprotection manifested as enhanced cardiac function and reduced structural damage and apoptosis. The transcriptome and other results revealed that FGL facilitated PGC-1α-mediated mitochondrial biogenesis and fatty acid oxidation (MB and FAO) by increasing the expression of PGC-1α and concurrently promoting the expression of SIRT1-enhancing deacetylase SIRT1 deacetylating and activating PGC-1α.Conclusions: These results documented that FGL exerted cardioprotective effects restoring MB&amp;FAO via the SIRT1–PGC-1α axis.
Entinostat Improves Motor Function and Neuronal Damage Via Downregulating NLRP3 Inflammasome Activation After Spinal Cord Injury
Authors: Dai Chen , Liu Bin , Peng Bibo , Qu Bo , Lin Jiezhi , Peng Baogan , Li Duan-Ming 
Published: December 2021

Background: Spinal cord injury (SCI), a major public health problem, has no effective treatment. A large number of studies have confirmed that histone deacetylases (HDACs) are involved in the physiologic processes that occur following SCI. We tried to uncover the potential neuroprotective role of entinostat (a class I HDAC inhibitor) in SCI.Methods: We conducted a study on a preclinical mouse model of SCI and OGD-induced neuronal damage to present the role of entinostat by the analysis of motor function, histopathologic damage, local NLRP3 inflammasome activation, and neuronal damage.Results: The results showed that entinostat suppressed HDAC activation (including HDAC1 and HDAC3 expression), improved the grip strength and BMS score, spinal edema, cell death, and local NLRP3 inflammasome activation in the spinal cord following SCI. Furthermore, entinostat significantly increased OGD-inhibited neuronal activity and decreased PI-positive cells, HDAC activation, caspase-1 activation, IL-1β and IL-18 levels, and NLRP3 expression.Conclusion: In summary, we first documented that entinostat improved the motor function, histopathologic damage, and local inflammatory response and NLRP3 inflammasome activation in the spinal cord following SCI and also presented the neuroprotective role of OGD-induced neuronal damage via the NLRP3 inflammasome. Thus, our study has the potential to reveal the interaction between the HDAC and NLRP3 inflammasome in the pathologic process as well as SCI and further promote the clinical indications of HDACi entinostat and clinical treatment for the inflammatory response after SCI.
Effects of Pre-, Post- and Intra-Exercise Hyperbaric Oxygen Therapy on Performance and Recovery: A Systematic Review and Meta-Analysis
Authors: Huang Xizhang , Wang Ran , Zhang Zheng , Wang Gang , Gao Binghong 
Published: November 2021

Background: As a World Anti-doping Agency (WADA)-approved treatment, hyperbaric oxygen (HBO2) therapy has been used to improve exercise performance in sports practice.Objective: We aimed to investigate the effect of pre-, post-, and intra-exercise HBO2 therapy on performance and recovery.Methods: A literature search was conducted using EMBASE, CENTRAL, PubMed, Web of Science, and SPORTDiscus to obtain literature published until May 2021. A total of 1,712 studies that met the following criteria were identified: (1) enrolled healthy adults who were considered physically active; (2) evaluated HBO2 therapy; (3) included a control group exposed to normobaric normoxic (NN) conditions; (4) involved physical testing (isokinetic or dynamic strength exercise, maximal incremental treadmill/cycle exercise, etc.); and (5) included at least one exercise performance/recovery index as an outcome measure. The Cochrane risk of bias assessment tool was used to evaluate the included studies, and the heterogeneity of therapy effects was assessed using the I2 statistic by Review Manager 5.3.Results: Ten studies (166 participants) were included in the qualitative analysis, and six studies (69 participants) were included in the quantitative synthesis (meta-analysis). In comparisons between participants who underwent HBO2 therapy and NN conditions, the effects of pre-exercise HBO2 therapy on exercise performance were not statistically significant (P &gt; 0.05), and the effects of post-exercise HBO2 therapy on recovery were not statistically significant either (P &gt; 0.05). Although individual studies showed positive effects of intra-exercise HBO2 therapy on exercise performance, a meta-analysis could not be performed.Conclusion: Hyperbaric oxygen therapy before or after exercise had no significant effect on performance and recovery. However, hyperbaric oxygen therapy during exercise could improve muscle endurance performance, which needs to be confirmed by further empirical studies. At present, the practical relevance of these findings should be treated with caution.
Empathy: Assessment Instruments and Psychometric Quality – A Systematic Literature Review With a Meta-Analysis of the Past Ten Years
Authors: Lima Felipe Fernandes de , Osório Flávia de Lima 
Published: November 2021

Objective: To verify the psychometric qualities and adequacy of the instruments available in the literature from 2009 to 2019 to assess empathy in the general population.Methods: The following databases were searched: PubMed, PsycInfo, Web of Science, Scielo, and LILACS using the keywords “empathy” AND “valid∗” OR “reliability” OR “psychometr∗.” A qualitative synthesis was performed with the findings, and meta-analytic measures were used for reliability and convergent validity.Results: Fifty studies were assessed, which comprised 23 assessment instruments. Of these, 13 proposed new instruments, 18 investigated the psychometric properties of instruments previously developed, and 19 reported cross-cultural adaptations. The Empathy Quotient, Interpersonal Reactivity Index, and Questionnaire of Cognitive and Affective Empathy were the instruments most frequently addressed. They presented good meta-analytic indicators of internal consistency [reliability, generalization meta-analyses (Cronbach’s alpha): 0.61 to 0.86], but weak evidence of validity [weak structural validity; low to moderate convergent validity (0.27 to 0.45)]. Few studies analyzed standardization, prediction, or responsiveness for the new and old instruments. The new instruments proposed few innovations, and their psychometric properties did not improve. In general, cross-cultural studies reported adequate adaptation processes and equivalent psychometric indicators, though there was a lack of studies addressing cultural invariance.Conclusion: Despite the diversity of instruments assessing empathy and the many associated psychometric studies, there remain limitations, especially in terms of validity. Thus far, we cannot yet nominate a gold-standard instrument.
Burnout, Anxiety, Stress, and Depression Among Iranian Nurses: Before and During the First Wave of the COVID-19 Pandemic
Authors: Zakeri Mohammad Ali , Rahiminezhad Elham , Salehi Farzaneh , Ganjeh Hamid , Dehghan Mahlagha 
Published: November 2021

Background: Nurses are the major healthcare workforce in an epidemic and have the most contact with patients. Frontline nurses face many health challenges during the COVID-19 epidemic, are directly at risk when treating and caring for COVID-19 patients, and thus experience severe stress and problems in the workplace leading to physical, mental, and social disorders, as well as burnout, anxiety, stress, and depression. The purpose of this study was to compare burnout, anxiety, stress, and depression in nurses before and during the first wave of the COVID-19 pandemic.Methods: This was a cross sectional study. We assessed 266 frontline nurses before and 242 frontline nurses during the first wave of the COVID-19 pandemic with one year apart in 2019 and 2020 (two-stage sampling). The data were collected using demographic questionnaire, Maslach Burnout Questionnaire and Depression, Anxiety and Stress Scale (DASS-21) in public hospitals in Southern Iran.Results: There were no significant differences between groups in subscales of burnout (p &gt; 0.05). Anxiety, stress and depression scores significantly increased during the first wave of the COVID-19 pandemic compared with before the COVID-19 outbreak (p &lt; 0.05). There were significant differences between groups in level of anxiety (p &lt; 0.001) and stress (p = 0.04). Before the COVID-19 outbreak, burnout predicted 11, 15, and 13% of the variance of anxiety, stress and depression, respectively. In addition, stress, monthly working hours and shift were variables that predicted 16% of the variance of burnout before COVID-19.Conclusion: The results of the present study showed that burnout during the first wave of the COVID-19 pandemic did not change significantly compared with before COVID-19. Anxiety, stress and depression increased significantly first wave of the COVID-19 pandemic.
SPECT Functional Neuroimaging Distinguishes Adult Attention Deficit Hyperactivity Disorder From Healthy Controls in Big Data Imaging Cohorts
Authors: Amen Daniel G. , Henderson Theodore A. , Newberg Andrew 
Published: November 2021

Background: The diagnosis of attention deficit hyperactivity disorder (ADHD) relies on history and observation, as no reliable biomarkers have been identified. In this study, we compared a large single diagnosis group of patients with ADHD (combined, inattentive, and hyperactive) to healthy controls using brain perfusion single-photon emission computed tomography (SPECT) imaging to determine specific brain regions which could serve as potential biomarkers to reliably distinguish ADHD.Methods: In a retrospective analysis, subjects (n = 1,135) were obtained from a large multisite psychiatric database, where resting state (baseline) and on-task SPECT scans were obtained. Only baseline scans were analyzed in the present study. Subjects were separated into two groups – Group 1 (n = 1,006) was composed of patients who only met criteria for ADHD with no comorbid diagnoses, while a control group (n = 129) composed of individuals who did not meet criteria for any psychiatric diagnosis, brain injury, or substance use served as a non-matched control. SPECT regions of interests (ROIs) and visual readings were analyzed using binary logistic regression. Predicted probabilities from this analysis were inputted into a Receiver Operating Characteristic analysis to identify sensitivity, specificity, and accuracy.Results: The baseline ROIs and visual readings show significant separations from healthy controls. Sensitivity of the visual reads was 100% while specificity was &gt;97%. The sensitivity and specificity of the post-hoc ROI analysis were both 100%. Decreased perfusion was primarily seen in the orbitofrontal cortices, anterior cingulate gyri, areas of the prefrontal cortices, basal ganglia, and temporal lobes. In addition, ROI analysis revealed some unexpected areas with predictive value in distinguishing ADHD, such as cerebellar subregions and portions of the temporal lobes.Conclusions: Brain perfusion SPECT distinguishes adult ADHD patients without comorbidities from healthy controls. Areas which were highly significantly different from control and thus may serve as biomarkers in baseline SPECT scans included: medial anterior prefrontal cortex, left anterior temporal lobe, and right insular cortex. Future studies of these potential biomarkers in ADHD patients with comorbidities are warranted.