bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL6/adiponectin/HMGB1 feedback loop mediates adipocyte and macrophage crosstalk and M2 polarization after myocardial infarction
Authors: Zheng Yue , Wang Yuchao , Qi Bingcai , Lang Yuheng , Zhang Zhibin , Ma Jie , Lou Minming , Liang Xiaoyu , Chang Yun , Zhao Qiang , Gao Wenqing , Li Tong 
Published: March 2024

BackgroundDifferences in border zone contribute to different outcomes post-infarction, such as left ventricular aneurysm (LVA) and myocardial infarction (MI). LVA usually forms within 24 h of the onset of MI and may cause heart rupture; however, LVA surgery is best performed 3 months after MI. Few studies have investigated the LVA model, the differences in border zones between LVA and MI, and the mechanism in the border zone.MethodsThe LVA, MI, and SHAM mouse models were used. Echocardiography, Masson’s trichrome staining, and immunofluorescence staining were performed, and RNA sequencing of the border zone was conducted. The adipocyte-conditioned medium-treated hypoxic macrophage cell line and LVA and MI mouse models were employed to determine the effects of the hub gene, adiponectin (ADPN), on macrophages. Quantitative polymerase chain reaction (qPCR), Western blot analysis, transmission electron microscopy, and chromatin immunoprecipitation (ChIP) assays were conducted to elucidate the mechanism in the border zone. Human subepicardial adipose tissue and blood samples were collected to validate the effects of ADPN.ResultsA novel, simple, consistent, and low-cost LVA mouse model was constructed. LVA caused a greater reduction in contractile functions than MI owing to reduced wall thickness and edema in the border zone. ADPN impeded cardiac edema and promoted lymphangiogenesis by increasing macrophage infiltration post-infarction. Adipocyte-derived ADPN promoted M2 polarization and sustained mitochondrial quality via the ADPN/AdipoR2/HMGB1 axis. Mechanistically, ADPN impeded macrophage HMGB1 inflammation and decreased interleukin-6 (IL6) and HMGB1 secretion. The secretion of IL6 and HMGB1 increased ADPN expression via STAT3 and the co-transcription factor, YAP, in adipocytes. Based on ChIP and Dual-Glo luciferase experiments, STAT3 promoted ADPN transcription by binding to its promoter in adipocytes. In vivo, ADPN promoted lymphangiogenesis and decreased myocardial injury after MI. These phenotypes were rescued by macrophage depletion or HMGB1 knockdown in macrophages. Supplying adipocytes overexpressing STAT3 decreased collagen disposition, increased lymphangiogenesis, and impaired myocardial injury. However, these effects were rescued after HMGB1 knockdown in macrophages. Overall, the IL6/ADPN/HMGB1 axis was validated using human subepicardial tissue and blood samples. This axis could serve as an independent factor in overweight MI patients who need coronary artery bypass grafting (CABG) treatment.ConclusionThe IL6/ADPN/HMGB1 loop between adipocytes and macrophages in the border zone contributes to different clinical outcomes post-infarction. Thus, targeting the IL6/ADPN/HMGB1 loop may be a novel therapeutic approach for cardiac lymphatic regulation and reduction of cell senescence post-infarction.
Bioinformatics and system biology approach to identify the influences among COVID-19, influenza, and HIV on the regulation of gene expression
Authors: Zhang Zhen , Jin Hao , Zhang Xu , Bai Mei , Zheng Kexin , Tian Jing , Deng Bin , Mao Lingling , Qiu Pengcheng , Huang Bo 
Published: March 2024

BackgroundCoronavirus disease (COVID-19), caused by SARS-CoV-2, has emerged as a infectious disease, coexisting with widespread seasonal and sporadic influenza epidemics globally. Individuals living with HIV, characterized by compromised immune systems, face an elevated risk of severe outcomes and increased mortality when affected by COVID-19. Despite this connection, the molecular intricacies linking COVID-19, influenza, and HIV remain unclear. Our research endeavors to elucidate the shared pathways and molecular markers in individuals with HIV concurrently infected with COVID-19 and influenza. Furthermore, we aim to identify potential medications that may prove beneficial in managing these three interconnected illnesses.MethodsSequencing data for COVID-19 (GSE157103), influenza (GSE185576), and HIV (GSE195434) were retrieved from the GEO database. Commonly expressed differentially expressed genes (DEGs) were identified across the three datasets, followed by immune infiltration analysis and diagnostic ROC analysis on the DEGs. Functional enrichment analysis was performed using GO/KEGG and Gene Set Enrichment Analysis (GSEA). Hub genes were screened through a Protein-Protein Interaction networks (PPIs) analysis among DEGs. Analysis of miRNAs, transcription factors, drug chemicals, diseases, and RNA-binding proteins was conducted based on the identified hub genes. Finally, quantitative PCR (qPCR) expression verification was undertaken for selected hub genes.ResultsThe analysis of the three datasets revealed a total of 22 shared DEGs, with the majority exhibiting an area under the curve value exceeding 0.7. Functional enrichment analysis with GO/KEGG and GSEA primarily highlighted signaling pathways associated with ribosomes and tumors. The ten identified hub genes included IFI44L, IFI44, RSAD2, ISG15, IFIT3, OAS1, EIF2AK2, IFI27, OASL, and EPSTI1. Additionally, five crucial miRNAs (hsa-miR-8060, hsa-miR-6890-5p, hsa-miR-5003-3p, hsa-miR-6893-3p, and hsa-miR-6069), five essential transcription factors (CREB1, CEBPB, EGR1, EP300, and IRF1), and the top ten significant drug chemicals (estradiol, progesterone, tretinoin, calcitriol, fluorouracil, methotrexate, lipopolysaccharide, valproic acid, silicon dioxide, cyclosporine) were identified.ConclusionThis research provides valuable insights into shared molecular targets, signaling pathways, drug chemicals, and potential biomarkers for individuals facing the complex intersection of COVID-19, influenza, and HIV. These findings hold promise for enhancing the precision of diagnosis and treatment for individuals with HIV co-infected with COVID-19 and influenza.
Development of a customizable mouse backbone spectral flow cytometry panel to delineate immune cell populations in normal and tumor tissues
Authors: Longhini Ana Leda F. , Fernández-Maestre Inés , Kennedy Margaret C. , Wereski Matthew G. , Mowla Shoron , Xiao Wenbin , Lowe Scott W. , Levine Ross L. , Gardner Rui 
Published: March 2024

IntroductionIn vivo studies of cancer biology and assessment of therapeutic efficacy are critical to advancing cancer research and ultimately improving patient outcomes. Murine cancer models have proven to be an invaluable tool in pre-clinical studies. In this context, multi-parameter flow cytometry is a powerful method for elucidating the profile of immune cells within the tumor microenvironment and/or play a role in hematological diseases. However, designing an appropriate multi-parameter panel to comprehensively profile the increasing diversity of immune cells across different murine tissues can be extremely challenging.MethodsTo address this issue, we designed a panel with 13 fixed markers that define the major immune populations –referred to as the backbone panel– that can be profiled in different tissues but with the option to incorporate up to seven additional fluorochromes, including any marker specific to the study in question.ResultsThis backbone panel maintains its resolution across different spectral flow cytometers and organs, both hematopoietic and non-hematopoietic, as well as tumors with complex immune microenvironments.DiscussionHaving a robust backbone that can be easily customized with pre-validated drop-in fluorochromes saves time and resources and brings consistency and standardization, making it a versatile solution for immuno-oncology researchers. In addition, the approach presented here can serve as a guide to develop similar types of customizable backbone panels for different research questions requiring high-parameter flow cytometry panels.
Differences in ocular high order aberrations before and after small incision lenticule extraction for correction of myopia: a systematic review and meta-analysis
Authors: Du Yifan , Di Yu , Yang Shan , Mo Fei , Cui Ge , Chen Di , Li Ying 
Published: March 2024

ObjectiveTo examine the causes and factors that lead to high order aberration (HOA) during the treatment of myopia using small incision lenticule extraction (SMILE), as well as the differences between SMILE and other corneal refractive surgeries through a systematic review and meta-analysis.MethodsA systematic search was conducted from January 2015 to February 2023 in Pubmed, Embase, Web of Science, and Google Scholar databases to gather relevant studies on SMILE and HOA. Studies meeting specific criteria were chosen, and clinical data was retrieved for analysis.ResultsThis meta-analysis resulted in the inclusion of 19 studies involving 1,503 eyes. Pooled results showed significant induction of total HOA (tHOA, d = −0.21, p &lt; 0.001), spherical aberration (SA, d = −0.11, p &lt; 0.001) and coma aberration (CA, d = −0.18, p &lt; 0.001) after SMILE compared to pre-SMILE, while no significant change in trefoil aberration (TA) was observed (d = −0.00, p = 0.91). There was a significantly lower induction of tHOA after SMILE compared to femtosecond laser-assisted in situ keratomileusis (FS-LASIK, d = 0.04, p &lt; 0.001), and no significant difference was observed compared to wavefront aberration-guided (WFG) refractive surgery (d = 0.00, p = 0.75). There was also a significant association between different levels of myopia and astigmatism, duration of follow-up, lenticule thickness, and preoperative central corneal thickness (CCT) on the induction of tHOA after SMILE (p &lt; 0.05), while the higher preoperative myopia group (sphere &gt; -5D), lower preoperative astigmatism group (cylinder ≤ -1D), larger lenticule thickness group (lenticule thickness &gt; 100 μm), shorter follow-up group (follow-up 1 month postoperatively) and the thicker CCT group (CCT &gt; 550 μm) brought a significant induction of tHOA compared to the opposite comparison group (p &lt; 0.001).ConclusionWhile SMILE can induce HOA significantly, it induces less HOA than FS-LASIK. Postoperative HOA following SMILE can be affected by factors such as myopia, astigmatism, lenticule thickness, CCT, and duration of follow-up. Future research should continue to explore techniques to decrease the induction of HOA by using this methodology.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/.
Comparison of OBGYN postgraduate curricula and assessment methods between Canada and the Netherlands: an auto-ethnographic study
Authors: Paternotte Emma , Dijksterhuis Marja , Goverde Angelique , Ezzat Hanna , Scheele Fedde 
Published: March 2024

IntroductionAlthough the Dutch and the Canadian postgraduate Obstetrics and Gynecology (OBGYN) medical education systems are similar in their foundations [programmatic assessment, competency based, involving CanMED roles and EPAs (entrustable professional activities)] and comparable in healthcare outcome, their program structures and assessment methods considerably differ.Materials and methodsWe compared both countries' postgraduate educational blueprints and used an auto-ethnographic method to gain insight in the effects of training program structure and assessment methods on how trainees work. The research questions for this study are as follows: what are the differences in program structure and assessment program in Obstetrics and Gynecology postgraduate medical education in the Netherlands and Canada? And how does this impact the advancement to higher competency for the postgraduate trainee?ResultsWe found four main differences. The first two differences are the duration of training and the number of EPAs defined in the curricula. However, the most significant difference is the way EPAs are entrusted. In Canada, supervision is given regardless of EPA competence, whereas in the Netherlands, being competent means being entrusted, resulting in meaningful and practical independence in the workplace. Another difference is that Canadian OBGYN trainees have to pass a summative written and oral exit examination. This difference in the assessment program is largely explained by cultural and legal aspects of postgraduate training, leading to differences in licensing practice.DiscussionDespite the fact that programmatic assessment is the foundation for assessment in medical education in both Canada and the Netherlands, the significance of entrustment differs. Trainees struggle to differentiate between formative and summative assessments. The trainees experience both formative and summative forms of assessment as a judgement of their competence and progress. Based on this auto-ethnographic study, the potential for further harmonization of the OBGYN PGME in Canada and the Netherlands remains limited.
Characteristics and risk factors for invasive fungal infection in hospitalized patients with acute-on-chronic hepatitis B liver failure: a retrospective cohort study from 2010 to 2023
Authors: Wu Yin-Ping , Li Feng-Cai , Ma Hang-Yu , Yang Xue-Yan , Zuo Jing , Tian Yu-Xin , Lv Li , Wang Kai , Fan Yu-Chen 
Published: March 2024

Background and aimThe global burden of invasive fungal infections (IFIs) is emerging in immunologic deficiency status from various disease. Patients with acute-on-chronic hepatitis B liver failure (ACHBLF) are prone to IFI and their conditions are commonly exacerbated by IFI. However, little is known about the characteristics and risk factors for IFI in hospitalized ACHBLF patients.MethodsA total of 243 hospitalized ACHBLF patients were retrospectively enrolled from January 2010 to July 2023. We performed restricted cubic spline analysis to determine the non-linear associations between independent variables and IFI. The risk factors for IFI were identified using logistic regression and the extreme gradient boosting (XGBoost) algorithm. The effect values of the risk factors were determined by the SHapley Additive exPlanations (SHAP) method.ResultsThere were 24 ACHBLF patients (9.84%) who developed IFI on average 17.5 (13.50, 23.00) days after admission. The serum creatinine level showed a non-linear association with the possibility of IFI. Multiple logistic regression revealed that length of hospitalization (OR = 1.05, 95% CI: 1.02–1.08, P = 0.002) and neutrophilic granulocyte percentage (OR = 1.04, 95% CI: 1.00–1.09, P = 0.042) were independent risk factors for IFI. The XGBoost algorithm showed that the use of antibiotics (SHAP value = 0.446), length of hospitalization (SHAP value = 0.406) and log (qHBV DNA) (SHAP value = 0.206) were the top three independent risk factors for IFI. Furthermore, interaction analysis revealed no multiplicative effects between the use of antibiotics and the use of glucocorticoids (P = 0.990).ConclusionIFI is a rare complication that leads to high mortality in hospitalized ACHBLF patients, and a high neutrophilic granulocyte percentage and length of hospitalization are independent risk factors for the occurrence of IFI.
Detection of iodixanol-induced allergic reaction signals in Chinese inpatients: a multi-center retrospective database study using prescription sequence symmetry analysis
Authors: Zhang Dandan , Yang Xinchen , Yang Zhangwei , Sun Wei , Chen Shunjie , Xu Lingxiao 
Published: March 2024

Objective:This study aimed to explore the signal detection method for allergic reactions induced by inpatient iodixanol injection.Methods:A database of 3,719,217 hospitalized patients from 20 large Chinese general hospitals was processed and analyzed using the prescription sequence symmetry analysis (PSSA) method.Results:126,680 inpatients who used iodixanol and were concurrently treated with anti-allergic drugs were analyzed. In the medical records of these patients, only 32 had documented iodixanol allergies. Statistical analysis identified 22 drugs in 4 categories—calcium preparations, adrenergic/dopaminergic agents, glucocorticoids, and antihistamines—as marker drugs. With time intervals of 3, 7, and 28 days, the adjusted sequence ratios (aSRs) for all anti-allergics and the 4 categories were greater than 1. The 7-day aSRs were 2.12 (95% CI: 2.08–2.15), 1.70 (95% CI: 1.68–1.73), 3.85 (95% confidence interval [CI]: 3.75–2.30), 2.30 (95% CI: 2.26–2.35), and 1.95 (95% CI: 1.89–2.02), respectively. The proportions of adverse drug events indicated by each signal were as follows: all anti-allergics (2.92%–3%), calcium gluconate (0.19%–0.52%), adrenergic/dopaminergic agents (2.20%–3.37%), glucocorticoids (3.13%–3.76%), and antihistamines (1.05%–1.32%).Conclusion:This first multi-center Chinese inpatient database study detected iodixanol-induced allergy signals, revealing that reactions may be much higher than those in collected spontaneous reports. Iodixanol risk exposure was closer to actual pharmaceutical care findings. PSSA application with ≤7-day intervals appears better suited for monitoring late allergic reaction signals with these drugs.
Comparison of the therapeutic effects of mesenchymal stem cells derived from human dental pulp (DP), adipose tissue (AD), placental amniotic membrane (PM), and umbilical cord (UC) on postmenopausal osteoporosis
Authors: Li Chuncai , Liu Yincong , Deng Mingxing , Li Jun , Li Shengqi , Li Xiaoyu , Zuo Yuling , Shen Chongyang , Wang Yichao 
Published: March 2024

Background: Osteoporosis is a systemic bone disease characterized by bone loss and microstructural degeneration. Recent preclinical and clinical trials have further demonstrated that the transplantation of mesenchymal stem cells (MSCs) derived from human adipose tissue (AD), dental pulp (DP), placental amniotic membrane (AM), and umbilical cord (UC) tissues can serve as an effective form of cell therapy for osteoporosis. However, MSC-mediated osteoimmunology and the ability of these cells to regulate osteoclast-osteoblast differentiation varies markedly among different types of MSCs.Methods: In this study, we investigated whether transplanted allogeneic MSCs derived from AD, DP, AM, and UC tissues were able to prevent osteoporosis in an ovariectomy (OVX)-induced mouse model of osteoporosis. The homing and immunomodulatory ability of these cells as well as their effects on osteoblastogenesis and the maintenance of bone formation were compared for four types of MSCs to determine the ideal source of MSCs for the cell therapy-based treatment of OVX-induced osteoporosis. The bone formation and bone resorption ability of these four types of MSCs were analyzed using micro-computed tomography analyses and histological staining. In addition, cytokine array-based analyses of serological markers and bioluminescence imaging assays were employed to evaluate cell survival and homing efficiency. Immune regulation was determined by flow cytometer assay to reflect the mechanisms of osteoporosis treatment.Conclusion: These analyses demonstrated that MSCs isolated from different tissues have the capacity to treat osteoporosis when transplanted in vivo. Importantly, DP-MSCs infusion was able to maintain trabecular bone mass more efficiently with corresponding improvements in trabecular bone volume, mineral density, number, and separation. Among the tested MSC types, DP-MSCs were also found to exhibit greater immunoregulatory capabilities, regulating the Th17/Treg and M1/M2 ratios. These data thus suggest that DP-MSCs may represent an effective tool for the treatment of osteoporosis.
Effect of long-term inorganic nitrate administration on myocardial ischemia-reperfusion injury in ovariectomized rats
Authors: Jeddi Sajad , Yousefzadeh Nasibeh , Zarkesh Maryam , Kashfi Khosrow , Ghasemi Asghar 
Published: March 2024

Introduction: Menopause is associated with reduced nitric oxide (NO) bioavailability and lower tolerance against myocardial ischemia-reperfusion (IR) injury. This study investigated whether long-term nitrate administration provides resistance against myocardial IR injury in ovariectomized (OVX) rats.Method: After ovariectomy, female rats were assigned to the OVX and the OVX + nitrate groups (n = 14/group); the latter group consumed nitrate (100 mg/L) for 9 months. At month 9, each group was divided into two subgroups (n = 7/subgroup), of which one subgroup was exposed to myocardial IR (IR+ hearts) and the other was not exposed (IR− hearts). The hearts of rats were isolated, and NO metabolite (NOx), oxidative stress indices, and mRNA expressions of endothelial (eNOS), inducible (iNOS), and neuronal (nNOS) NO synthases, as well as markers of apoptosis, were measured in the IR− and IR+ hearts. In the IR+ hearts, cardiac function indices (CFI) and the infarct size were also measured.Results: Nitrate increased catalase activity (97%) and eNOS expression (2.94-fold) in the IR− hearts. In the IR+ hearts, nitrate reduced left ventricular (LV) end-diastolic pressure (11.6%) and infarct size (26.2%) and increased recovery of LV developed pressure (44.0%) and peak rate of positive (28.9%) and negative (15.4%) changes in LV pressure. In addition, in the IR+ hearts, nitrate increased eNOS and B-cell lymphoma-2 (Bcl-2) as well as decreased iNOS, Bcl-2 associated X protein (Bax), caspase-3, caspase-8, caspase-9, and tumor necrosis factor-α (TNF-α) expression. Nitrate increased total antioxidant capacity (TAC) and catalase (CAT) activity and decreased malondialdehyde (MDA) levels at month nine in serum and IR+ hearts.Conclusion: The favorable effects of nitrate against IR injury were associated with higher eNOS and Bcl-2 expression, CAT activity, TAC, and lower iNOS, Bax, caspase-3, caspase-8, caspase-9 and TNF-α expression, and MDA in the heart tissue. Nitrate preconditioning alleviated IR-induced myocardial injury in OVX rats; this effect was associated with eNOS upregulation before IR and the blunting of OVX-induced eNOS downregulation, iNOS upregulation, apoptosis, and oxidative stress in heart tissue after IR.
Phloretic acid requires the insulin/IGF-1 pathway and autophagy to enhance stress resistance and extend the lifespan of Caenorhabditis elegans
Authors: Li Bo , Dong Li , Meng Wei , Xiong Shi-Ying , Wu Gui-Sheng , Ma Wen-Zhe , Luo Huai-Rong 
Published: March 2024

Objective: In humans, aging is associated with increased susceptibility to most age-related diseases. Phloretic acid (PA), a naturally occurring compound found in Ginkgo biloba and Asparagus, exhibits has potential as an anti-aging agent and possesses antioxidant, anti-inflammatory, and immunomodulatory properties. This study aimed to investigate the effects of PA on longevity and stress resistance in Caenorhabditis elegans (C.elegans) and the mechanisms that underlie its effects.Methods: First, we examined the effects of PA on lifespan and healthspan assay, stress resistance and oxidative analysis, lipofuscin levels. Second, we examined the insulin/insulin-like pathway, mitochondria, autophagy-related proteins, and gene expression to explain the possible mechanism of PA prolonging lifespan.Results: Our findings demonstrated that PA dose-dependently extended the C.elegans lifespan, with 200 μM PA showing the greatest effect and increased the C.elegans lifespan by approximately 16.7%. PA enhanced motility and the pharyngeal pumping rate in senescent C.elegans while reducing the accumulation of aging pigments. Further investigations revealed that daf-16, skn-1, and hsf-1 were required for mediating the lifespan extension effect of PA in C.elegans since its impact was suppressed in mutant strains lacking these genes. This suggests that PA activates these genes, leading to the upregulation of downstream genes involved in stress response and senescence regulation pathways. Furthermore, PA did not extend the lifespan of the RNAi atg-18 and RNAi bec-1 but it attenuated SQST-1 accumulation, augmented autophagosome expression, upregulated autophagy-related gene expression, and downregulated S6K protein levels. These findings suggest that the potential life-extending effect of PA also involves the modulation of the autophagy pathway.Conclusion: These findings results highlight the promising anti-aging effects of PA and warrant further investigation into its pharmacological mechanism and medicinal development prospects.