bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular mechanism underlying cardioprotective effect of dehydroepiandrosterone on endoplasmic reticulum stress induced apoptosis in human vascular smooth muscle cells and human umbilical vein endothelial cells
Authors: Zhu Ye , Wei Junxiu , Yang Xin , Zhu Wei 
Published: January 2025

IntroductionThis study aimed to investigate the underlying mechanisms involved in the cardioprotective effects of dehydroepiandrosterone (DHEA) on endoplasmic reticulum stress (ERS) -mediated apoptosis in human vascular smooth muscle cells (HVSMCs) and human umbilical vein endothelial cells (HUVECs).Material and methodsVarious concentrations of Dithiothreitol (DTT) were used to induce ERS-mediated apoptosis. DHEA was utilized to inhibit the apoptotic effects of DTT, while estrogen receptor (ER) antagonists ICI 182,780 and G15, the androgen receptor (AR) antagonist flutamide and the aromatase inhibitor letrozole were used to identify the receptors activated during DHEA treatment in HVSMCs and HUVECs. Flow cytometry assessed the apoptotic rate, and Western blotting analysis evaluated the expression levels of ERS-related proteins GRP78 and PERK, and the apoptotic protein marker CHOP. Furthermore, the primary receptor signaling pathways were identified using signaling pathway blockers: LY294002 (PI3K blocker), SP600125 (JNK blocker), and U0126 (ERK1/2 blocker).ResultsIn the DTT pretreatment group (0.8 mmol/L, for 8 h), the expressions of GRP78 and CHOP were significantly up regulated, indicating that an optimal ERS model was successfully established. Additionally, 10-4 mmol/L DHEA significantly inhibited the DTT-induced upregulation of GRP78 and CHOP. The results also demonstrated that the apoptotic rate in the DTT group was increased, while DHEA significantly reduced this rate. The addition of ER antagonists ICI 182,780 and G15 to HVSMCs reversed the effects of DHEA; however, the aromatase inhibitor letrozole and the AR antagonist flutamide did not reverse this effect. Notably, the use of the JNK inhibitor SP600125, the PI3K inhibitor LY294002, and the ERK1/2 inhibitor U0126 antagonized the protective effects of DHEA, with SP600125 showing the most significant impact on both HVSMCs and HUVECs.ConclusionOur study has identified a novel mechanism underlying the cardioprotective effects of DHEA. Specifically, DHEA may mitigate ERS-induced cell apoptosis by activating estrogen receptors ERα, ERβ, and GPER via the activated JNK pathway.
Compound identification of Shuangxinfang and its potential mechanisms in the treatment of myocardial infarction with depression: insights from LC-MS/MS and bioinformatic prediction
Authors: Sun Yize , Zhao Haibin , Wang Zheyi 
Published: January 2025

BackgroundPatients with myocardial infarction (MI) have a high incidence of depression, which deteriorates the cardiac function and increases the risk of cardiovascular events. Shuangxinfang (Psycho-cardiology Formula, PCF) was proved to possess antidepressant and cardioprotective effects post MI. However, the compounds of PCF remain unidentified, and the pertinent mechanism is still not systematic. The purpose of this study is to determine the ingredients of PCF, further to probe the underlying mechanism for MI with depression.MethodsThe compounds of PCF were qualitatively identified by LC-MS/MS. The optimal dosage for lavage with the PCF solution in rats was determined to be 1 mL/100 g/day for a duration of 5 days. We also detected the PCF components migrating to blood in the control and model rats. Then the targets of PCF compounds were searched on Swiss target database, and the targets of depression and MI were predicted on TTD, OMIM, GeneCards, DrugBank and PharmGkb database. All the targets were intersected to construct the Protein-Protein Interaction (PPI) network on Metascape platform and the herb-compound-target (HCT) network on Cytoscape, to identify the hub targets. GO and KEGG pathway enrichment analysis were conducted on DAVID platform. Molecular docking was modeled on AutoDock Vina software.ResultsThere were 142 bioactive compounds from PCF acting on 270 targets in a synergistic way. And a total of seven components migrating to blood were identified, including Miltionone I, Neocryptotanshinone, Danshenxinkun A, Ferulic acid, Valerophenone, Vanillic acid and Senkyunolide D. Then SRC and MAPK3 were obtained as the hub proteins by degree value in PPI network, and P2RY12 was picked out as seed proteins ranked by scores from MCODES. Further analysis of biological process and signaling pathways also revealed the significance of ERK/MAPK. Statistical analyses (e.g., GO and KEGG pathway enrichment, PPI network analysis) demonstrated the significance of the identified targets and pathways (p &lt; 0.05). Molecular docking results showed that the binding energies were all less than −5 kcal/mol. The stability of Neocryptotanshinone possessed the lowest binding energy to MAPK3.ConclusionWe identified PCF’s bioactive compounds and predicted its therapeutic mechanism for MI with depression using LC-MS/MS and bioinformatics. Key targets SRC, MAPK3, and seed protein P2RY12 were crucial for PCF’s cardio-neuroprotective effects. Neocryptotanshinone showed the strongest binding to MAPK3, suggesting it as a pivotal active ingredient. These findings offer new insights and targets for future research on PCF.
A current review on animal models of anti-asthmatic drugs screening
Authors: Singh Shivam , Kularia Sunita , Shukla Shivakshi , Singh Mithilesh , Kumar Manish , Sharma Ashish Kumar 
Published: January 2025

Asthma is a chronic inflammatory respiratory condition characterised by airway constriction, smooth muscle spasm, and severe morbidity. It affects around 300 million people globally, with children being especially vulnerable. Despite its worldwide effect, the invention of innovative asthma medicines has been slow over the last 5 decades, leaving significant unmet requirements in asthma care. Although intriguing medicines have demonstrated efficacy in animal models, many fail to fulfil safety and effectiveness requirements in human trials, highlighting the critical need for more predictive models that better transfer to human results. This comprehensive review investigates the mechanisms and efficacy of anti-asthmatic drugs using both genetic and conventional animal models. Both genetic and traditional models of anti-asthmatic agents, their characteristics, and their significance are summarized as: In-Vitro Animal Models: Histamine receptor assay, Cell Culture Method, WST Assay, Spasmolytic Activity of the Lungs of Guinea Pigs, Airway and Vascular Responses to an Isolated Lung, The Isolated Perfused Guinea Pig Trachea’s Reactivity. In-Vivo Models: In vivo small animal models, Broncho Spasmolytic Activity in anaesthetized Guinea Pigs, Guinea Pigs Respiratory and Vascular Dysfunction Caused by Arachidonic Acid or platelet-activated factor (PAF), Guinea Pig Asphyxia Induced by Serotonin Aerosol and Anaphylactic Microshock, Guinea Pigs Under Anaesthesia: Histamine-Induced Bronchoconstriction, Microshock in Rabbits and Pneumotachography in Guinea Pigs, Guinea Pig Bronchial Hyperactivity, Guinea Pig Airway Microvascular Leakage, Mice With Inflammatory Airways. Conclusion: This review focusses on the benefits and limitations of current animal models in asthma research, emphasising the need for more sophisticated, predictive models to decrease translational failures. By critically evaluating these models, the review emphasises their importance in directing anti-asthmatic drug development and highlights the urgent need for innovation to bridge the gap between preclinical success and clinical efficacy.
The spectrum-efficacy correlation of Kai-Xin-San for cognition of Aβ42 transgenic Drosophila and verification of its active ingredients
Authors: Wu Jinfu , Sun Hang , Zhao Yiyang , Lian Lian , Bian Hongsheng , Guo Yong , Li Dan , Huang Lili 
Published: January 2025

IntroductionThis study aims to establish the fingerprint spectra of Kai-Xin-San (KXS) and investigate its spectrum-effect relationship in treating Alzheimer’s disease (AD).MethodsInitially, the fingerprints of 15 batches of KXS were established and analyzed using HPLC, with the method’s precision, stability, and repeatability thoroughly evaluated. Subsequently, the effects of the 15 batches of KXS were assessed in an olfactory escape memory experiment, utilizing Aβ42 transgenic drosophila as a model. Finally, the spectrum-effect relationship between the KXS fingerprint and memory improvement was analyzed, with the active ingredients subjected to validation testing.ResultsThe results identified seventeen common peaks in the fingerprint, and eight active components were determined: polygalaxanthone III, 3-6-disinapoylsucrose, ginsenoside Rg1, ginsenoside Rb1, β-asarone, α-asarone, dehydrotumulosic acid, and dehydropachymic acid. Treatment with KXS (1%, for 4 days) significantly enhanced the performance index of Aβ42 flies in the olfactory experiment. Both spectrum-effect analysis and validation tests indicated that polygalaxanthone III, ginsenoside Rg1, ginsenoside Rb1, β-asarone, and α-asarone were positively correlated with the performance index and improved the performance index in the olfactory experiment. The HPLC fingerprint method for KXS demonstrated excellent precision, accuracy, and reproducibility, making it suitable for quality evaluation and control of KXS. Polygalaxanthone III, ginsenoside Rg1, ginsenoside Rb1, β-asarone, and α-asarone are identified as potential active ingredients of KXS for anti-AD effects.DiscussionThese findings provide an experimental basis for developing new drugs based on KXS and its active ingredient combinations.
The effects of 8 weeks of multi-directional movement training combined with balance training on the change of direction of young table tennis players
Authors: Chen Qianqian , Li Yanfei , Heng Xinchen , Zhao Lei , Wu Bin 
Published: January 2025

BackgroundChange of direction (COD) skills are crucial for athletic performance in sports such as table tennis. Improving COD can enhance overall agility and responsiveness during competition.ObjectiveTo investigate the effects of an 8-week multi-directional movement training combined with balance training on the COD performance of young table tennis players.MethodsThirty young table tennis players from the same team were randomly assigned to two groups: the multi-directional movement training combined with the balance training group (MB, n = 15) and the control group (CON, n = 15). The MB group underwent balance training on unstable surfaces, while the CON group performed the same balance exercises on stable ground. Both groups participated in the same multi-directional movement training program, which was conducted three times a week with 24–48 h of recovery between sessions for a duration of 8 weeks.ResultsSignificant group effects were observed in the modified agility test, non-dominant leg, dominant leg, and push block side lunge right test (p &lt; 0.05). No significant group effects were found for the hexagon agility test, 3 m side slide test, A-movement test, or the whole table variable speed pendulum test (p &gt; 0.05). Significant time-by-group interactions were noted for all variables (p &lt; 0.05), indicating that improvements over time differed between the MB and CON groups. In the MB group, significant improvements were observed across all tests post-intervention, with high effect sizes (Partial η2 values ranging from 0.361 to 0.815). In contrast, the CON group showed significant time effects in only a few tests, including the 3 m side slide test, A-movement test, modified agility test, and push block side lunge right test (p &lt; 0.05), with no significant time effects for other variables.ConclusionThis study aimed to explore whether multi-directional movement training, when combined with balance exercises, could improve COD skills in young table tennis players. The results will inform future training strategies for enhancing agility and movement efficiency in table tennis athletes.
Trade-off strategies between growth and defense of spring ephemeral plants in early spring
Authors: Pan Liben , Wang Tianqi , Gavrikov Vladimir L. , Guo Xiaorui , Mu Liqiang , Tang Zhonghua 
Published: January 2025

IntroductionSpring ephemeral plants represent a unique ecological category of herbaceous plants, characterized by early blooming and vivid flowers with significant ornamental value. Understanding the adaptive strategies of spring ephemerals is crucial for the introduction and cultivation of early spring plants, as well as for optimizing light energy utilization and nutrient cycling within ecosystems.MethodsWe evaluated 26 functional traits across four spring ephemerals and four spring non-ephemeral plants along an elevation gradient. By establishing a plant functional trait network, we examined the adaptation strategies of early spring plants at different elevations and compared the differences in adaptation strategies between two types of plants.ResultsSpring ephemerals exhibited higher concentrations of carbon and nitrogen, lower concentrations of carbohydrates, higher edge density and modularity in trait networks, and stronger linkages between defense traits. Plants at higher elevations demonstrated higher leaf dry matter content and leaf total flavonoid concentration, and lower nitrogen concentration, influenced by temperature, precipitation, and soil nutrients.DiscussionThese results demonstrated that spring ephemerals have a strong nutrient uptake capacity, and adopt resource competition strategies to rapidly accumulate nutrients and reproduce. The plants at higher elevations adopt more conservative strategies, with trait networks showing increased modularity, edge density, and closer correlations among traits to enhance resource utilization. This study provides new insights into the adaptive strategies of spring ephemerals by demonstrating how plants allocate resources for growth and defense through the regulation of trait variation and correlations among traits.
2-Brain Regulation for Improved Neuroprotection during Early Development (2-BRAINED): a translational hyperscanning research project
Authors: Billeci Lucia , Riva Valentina , Capelli Elena , Grumi Serena , Paola Pili Miriam , Cassa Maddalena , Siri Eleonora , Roberti Elisa , Borgatti Renato , Provenzi Livio 
Published: January 2025

IntroductionVery preterm (VPT) birth is a major risk condition for child development and parental wellbeing, mainly due to multiple sources of stress (e.g., separation and pain exposure) during the neonatal intensive care unit (NICU) stay. Early video-feedback (VF) interventions proved effective in promoting VOT infants’ development and parental wellbeing. Electroencephalography (EEG) hyperscanning allows the assessment of brain-to-brain co-regulation during live interaction between infants and parents, offering promising insights into the mechanisms behind the interactive benefits of early VF interventions.GoalsThis study aimed to compare indices of brain-to-brain co-regulation between dyads of full-term (FT) and VPT infants interacting with their mothers and investigate the effect of an early post-discharge VF intervention on the brain-to-brain co-regulation indices of VPT dyads.Methods and analysisVPT and FT dyads will be enrolled at birth, and the former will be randomly allocated to one of two arms: VF intervention or care as usual. Short-term effectiveness will be assessed through ratings of mother–infant interaction videotaped before and after the VF intervention or care as usual. Mothers of VPT and FT infants will report on their mental state, parenting stress and bonding, and infant temperament and sensory profile at 3 and 6 months (corrected age, CA). At 9 months CA, all dyads will participate in a lab-based EEG-hyperscanning paradigm to assess brain-to-brain co-regulation through phase-locking value (PLV) and other explorative indices.Ethics and disseminationThis study was funded by the Italian Ministry of Health and received approval by the Ethics Committee of Pavia (Italy) and participating hospitals. Research findings will be reported in scientific publications, presented at international conferences, and disseminated to the general public.Study registration numberGR-2021-12375213 (Italian Ministry of Health registry).
Exploring neurodevelopmental concerns: insights from a public neuropediatric learning disabilities multiprofessional outpatient facility in Brazil
Authors: Augusto Janaína Aparecida de Oliveira , Ferreira Thalita Francielli Lopes , Arduini Rodrigo Genaro , Bastos Talita Meneses de Almeida , Campanha Nádia Santana Pereira , Fornasari Rita de Cássia Coutinho Vieira , Stella Patrícia Regina Flaviano , Simão Adriana Nobre de Paula , Moraes Joyce Nelly Leal de , Ciasca Sylvia Maria 
Published: January 2025

IntroductionSpecialized public services for attending children and adolescents with complaints of scholar difficulties are scarce in Brazil. It is important to recognize this target population and understand its demands, so these facilities may be able to meet their needs and offer qualified and effective services. The main objective of this study was to characterize the profile of neuropediatric patients cared for in a reference outpatient facility in Brazil.MethodData were extracted from children’s and adolescent’s records, corresponding to assessments carried out between March 2017 to March 2023.ResultsFrom 220 selected records, 70% had complaints related to learning difficulties and 79.1% to attention disorders. The most frequent diagnoses were attention-deficit/hyperactivity disorder (30%), intellectual deficiency (19.1%), and learning-specific disorder (17.7%). A significant association with scholarship was found between motor agitation [χ2(9) = 29.8; p &lt; 0.001], behavioral complaints [χ2(9) = 16.2; p = 0.050], and language difficulties [χ2(9) = 17.0; p = 0.043]. Results have indicated significant differences relating to diagnosis and gender: boys had a higher prevalence for dyslexia [χ2(1) = 4.44; p = 0.035], intellectual deficiency [χ2(1) = 8.38; p = 0.004], and autism spectrum disorder [χ2(1) = 9.29; p = 0.002], when compared to girls.ConclusionThese results corroborate international findings over complaints regarding learning difficulties and correlated disturbances, in addition to the existing comorbidities between different diagnoses related to neurodevelopment and scholar acquisitions.
Lack of sex- and gender-disaggregated data in diagnostics: findings from a scoping review of five tracer conditions
Authors: Upadhyay Vishwanath , Gangwar Rishabh , Chappuis Gabrielle Landry , Kohli Mikashmi 
Published: January 2025

BackgroundSex and gender can affect all aspects of health-related behavior, yet there is limited information on how they influence diagnosis of any health condition. This scoping review examined the extent to which sex- and gender-disaggregated data on diagnostics are available for five tracer conditions: tuberculosis, coronavirus disease 2019 (COVID-19), diabetes, malaria, and schistosomiasis.MethodsPublications were searched between 2000 and 2022 on PubMed and Google Scholar and screened for relevance. Extracted data were analysed using descriptive quantitative and qualitative approaches.ResultsWe identified 29 relevant articles for tuberculosis, four for diabetes, six for schistosomiasis, eight for COVID-19, and three for malaria. For tuberculosis, most studies looked at gender-based barriers to diagnosis and disparities in health-seeking behaviors that predominantly affected women. For diabetes, studies noted that women had lower odds of being screened for prediabetes and potentially lower quality of care versus men. For schistosomiasis, studies suggested lower sensitivity diagnostic methods among women than men and low awareness of the disease. Studies suggest that women are less likely to be diagnosed for COVID-19 in certain settings. Studies on malaria reported that women show different health-seeking behaviors to men.ConclusionThis scoping review highlights a concerning lack of sex- and gender-disaggregated data on diagnostics. Consequently, further work is required to develop and implement an appropriate framework to assess gender and sex-related data around testing and diagnosis.
Genetic diversity and transmission pattern of multidrug-resistant tuberculosis based on whole-genome sequencing in Wuhan, China
Authors: Wei Liqing , Chen Jun , Deng Zhen , Zhang Zefang , Zhang Zhengbin , Duan Qionghong 
Published: January 2025

BackgroundInvestigating the molecular epidemiological characteristics of multidrug-resistant tuberculosis (MDR-TB) in China’s moderate-burden regions, such as Wuhan, is crucial for understanding and controlling disease transmission.Materials and methodsThis study analyzed MDR-TB isolates from pulmonary tuberculosis cases registered at Wuhan Pulmonary Hospital in 2017. Whole genome sequencing (WGS) was used to identify resistance-conferring mutations, examine their associations with specific Mycobacterium tuberculosis lineages or sublineages, and assess clustering profiles.ResultsAmong the 149 analyzed strains, the most prevalent mutations associated with resistance to 11 anti-tuberculosis drugs were identified as follows: rpoB Ser450Leu (59.73%, rifampicin), katG Ser315Thr (62.42%, isoniazid), embB Met306Val (42.86%, ethambutol), rpsL Lys43Arg (68.13%, streptomycin), pncA Trp68Arg (10.53%, pyrazinamide), gyrA Asp94Gly (22.50%, fluoroquinolones), and rrs 1401A &gt; G (50.00–100.00%, second-line injectable aminoglycosides). Additional mutations were detected in fabG1 c-15C &gt; T (42.86%, ethionamide) and thyX c-16C &gt; T (21.43%, p-aminosalicylic acid). Notably, rare mutations absent from the WHO mutation catalog, such as ahpC c-52C &gt; T and rpsL Lys43Thr, were also observed. The mutation frequency of embB Met306Ile was significantly higher in Lineage 4 (L4) strains than in Lineage 2 (L2) strains (p = 0.0150), while the rpsL Lys43Arg mutation frequency was lower in L4 compared to L2 (p = 0.0333). A total of 31 MDR MTB Mycobacterium tuberculosis isolates formed clusters, resulting in a clustering rate of 20.81% and a recent transmission rate of 11.41%. The clustering rates between L4 and L2 strains were not significantly different (χ2 = 0.0017, p &gt; 0.05).ConclusionThe genetic diversity of MDR-TB in Wuhan demonstrates unique characteristics, with evidence of localized transmission. These findings highlight the urgent need to strengthen measures to detect early cases of MDR-TB and control transmission of MDR-TB in the region.