International Journal of Medical Sciences最新文献

Fine particulate matter (PM_2.5) can damage airway epithelial barriers. The anion transport system plays a crucial role in airway epithelial barriers. However, the detrimental effect and mechanism of PM_2.5 on the anion transport system are still unclear. In this study, airway epithelial cells and ovalbumin (OVA)-induced asthmatic mice were used. In transwell model, the adenosine triphosphate (ATP)-induced transepithelial anion short-circuit current (I_sc) and airway surface liquid (ASL) significantly decreased after PM_2.5 exposure. In addition, PM_2.5 exposure decreased the expression levels of P2Y2R, CFTR and cytoplasmic free-calcium, but ATP can increase the expressions of these proteins. PM_2.5 exposure increased the levels of Th2-related cytokines of bronchoalveolar lavage fluid, lung inflammation, collagen deposition and hyperplasisa of goblet cells. Interestingly, the administration of ATP showed an inhibitory effect on lung inflammation induced by PM_2.5. Together, our study reveals that PM_2.5 impairs the ATP-induced transepithelial anion I_sc through downregulating P2Y2R/CFTR pathway, and this process may participate in aggravating airway hyperresponsiveness and airway inflammation. These findings may provide important insights on PM_2.5-mediated airway epithelial injury.

Endothelial dysfunction may contribute to pathogenesis of Takotsubo cardiomyopathy, but mechanism underlying endothelial dysfunction in the setting of catecholamine excess has not been clarified. The study reports that D1/D5 dopamine receptor signaling and small conductance calcium-activated potassium channels contribute to high concentration catecholamine induced endothelial cell dysfunction. For mimicking catecholamine excess, 100 μM epinephrine (Epi) was used to treat human cardiac microvascular endothelial cells. Patch clamp, FACS, ELISA, PCR, western blot and immunostaining analyses were performed in the study. Epi enhanced small conductance calcium-activated potassium channel current (I_SK1-3) without influencing the channel expression and the effect was attenuated by D1/D5 receptor blocker. D1/D5 agonists mimicked the Epi effect, suggesting involvement of D1/D5 receptors in Epi effects. The enhancement of I_SK1-3 caused by D1/D5 activation involved roles of PKA, ROS and NADPH oxidases. Activation of D1/D5 and SK1-3 channels caused a hyperpolarization, reduced NO production and increased ROS production. The NO reduction was membrane potential independent, while ROS production was increased by the hyperpolarization. ROS (H2O2) suppressed NO production. The study demonstrates that high concentration catecholamine can activate D1/D5 and SK1-3 channels through NADPH-ROS and PKA signaling and reduce NO production, which may facilitate vasoconstriction in the setting of catecholamine excess.

Background: Growing evidence suggests that endometriosis (EMs) is a risk factor for endometriosis-associated ovarian cancer (EAOC). The aim was to identify and validate gene signatures associated with EMs that may serve as potential biomarkers for evaluating the prognosis of patients with EAOC. Methods: The data of EMs and control samples was obtained from GEO database. The weighted gene co-expression network analysis (WGCNA) identified modular genes significantly associated with EMs. The KEGG pathway and GO functional enrichment analyses were also performed. Univariate Cox regression analysis was conducted to screen marker genes associated with the prognosis of EAOC patients. Finally, RT-qPCR and immunohistochemical verified the expression of ADAMTS19 and TUBB in normal ovarian and EAOC tissues, and the biological functions of ADAMTS19 and TUBB were preliminarily explored by CCK8 and Transwell assays. Results: The WGCNA identified 2 co-expression modules, which in total included 615 genes, and 7642 differentially expressed genes (DEGs) were detected thorough analysis of the EAOC dataset. After taking the intersection of 615 modular genes and 7642 DEGs, 214 shared genes were obtained, and univariate COX regression analysis pointed 10 genes associated with the prognosis of EAOC. Moreover, it was demonstrated by RT-qPCR and immunohistochemical staining experiments that ADAMTS19 expression was elevated, while TUBB expression was reduced in EAOC compared with normal ovarian cells and tissues. Finally, cell experiments revealed that ADAMTS19 promoted the proliferation and invasion in EAOC cells, while overexpression of TUBB inhibited these processes. Conclusions: The present study identified and validated new EMs-associated gene markers, which could serve as potential biomarkers for assessing the prognostic risk of EAOC patients. In addition, some of these genes may have significance as novel therapeutic targets and could be used to guide clinical applications.

Introduction: Lung cancer, characterized by uncontrolled cellular proliferation within the lung tissues, is the predominant cause of cancer-related fatalities worldwide. The traditional medicinal herb Piper longum has emerged as a significant contender in oncological research because of its documented anticancer attributes, suggesting its potential for novel therapeutic development. Methods: This study adopted network pharmacology and omics methodology to elucidate the anti-lung cancer potential of P. longum by identifying its bioactive constituents and their corresponding molecular targets. Results: Through a comprehensive literature review and the Integrated Medicinal Plant Phytochemistry and Therapeutics database (IMPPAT), we identified 33 bioactive molecules from P. longum. Subsequent analyses employing tools such as SwissTargetPrediction, SuperPred, and DIGEP-Pred facilitated the isolation of 676 potential targets, among which 72 intersected with 666 lung cancer-associated genetic markers identified through databases including the Therapeutic Target Database (TTD), Online Mendelian Inheritance in Man (OMIM), and GeneCards. Further validation through protein-protein interaction (PPI) networks, gene ontology, pathway analyses, boxplots, and overall survival metrics underscored the therapeutic potential of compounds such as 7-epi-eudesm-4(15)-ene-1β, demethoxypiplartine, methyl 3,4,5-trimethoxycinnamate, 6-alpha-diol, and aristolodione. Notably, our findings reaffirm the relevance of lung cancer genes, such as CTNNB1, STAT3, HIF1A, HSP90AA1, and ERBB2, integral to various cellular processes and pivotal in cancer genesis and advancement. Molecular docking assessments revealed pronounced affinity between 6-alpha-diol and HIF1A, underscoring their potential as therapeutic agents for lung cancer. Conclusion: This study not only highlights the bioactive compounds of P. longum but also reinforces the molecular underpinnings of its anticancer mechanism, paving the way for future lung cancer therapeutics.

Background: Both observational studies and clinical trials have demonstrated a link between the gut microbiota and the geriatric syndrome. Nevertheless, the exact nature of this relationship, particularly concerning causality, remains elusive. Mendelian randomization (MR) is a method of inference based on genetic variation to assess the causal relationship between an exposure and an outcome. In this study, we conducted a two-sample Mendelian randomization (TSMR) study to fully reveal the potential genetic causal effects of gut microbiota on geriatric syndromes. Methods: This study used data from genome wide association studies (GWAS) to investigate causal relationships between the gut microbiota and geriatric syndromes, including frailty, Parkinson's disease (PD), delirium, insomnia, and depression. The primary causal relationships were evaluated using the inverse-variance weighted method, MR Egger, simple mode, weighted mode and weighted median. To assess the robustness of the results, horizontal pleiotropy was examined through MR-Egger intercept and MR-presso methods. Heterogeneity was assessed using Cochran's Q test, and sensitivity was evaluated via the leave-one-out method. Results: We identified 41 probable causal relationships between gut microbiota and five geriatric syndrome-associated illnesses using the inverse-variance weighted method. Frailty showed five positive and two negative causal relationships, while PD revealed three positive and four negative causal connections. Delirium showed three positive and two negative causal relationships. Similarly, insomnia demonstrated nine positive and two negative causal connections, while depression presented nine positive and two negative causal relationships. Conclusions: Using the TSMR method and data from the public GWAS database and, we observed associations between specific microbiota groups and geriatric syndromes. These findings suggest a potential role of gut microbiota in the development of geriatric syndromes, providing valuable insights for further research into the causal relationship between gut microbiota and these syndromes.

Objective: The immune response initiated by SARS-CoV-2 infection in pregnancy is poorly elucidated. We aimed to access and compare the antiviral cellular responses and lymphocytes activation between healthy pregnancies and pregnant women infected with SARS-CoV-2. Methods: We detected the immunological changes of lymphocytes in peripheral blood of healthy non-pregnant women, non-pregnant women with COVID-19, healthy pregnant women, pregnant women with COVID-19 and convalescent group by flow cytometry. In vitro blockade was used to identify NKT-like cell activation through ICOS-ICOSL pathway. Results: We found that CD3⁺CD56⁺ NKT-like cells decreased significantly in COVID-19 positive pregnant women compared to healthy pregnant women. NKT-like cells of pregnant women expressed higher level of activating receptors CD69 and NKp46 after SARS-CoV-2 infection. Particularly, they also increased the expression of the co-stimulatory molecule ICOS. NKT-like cells of pregnant women with COVID-19 up-regulated the expression of IFN-γ, CD107a and Ki67. Meanwhile, we found that ICOSL expression was significantly increased on pDCs in pregnant women with COVID-19. Blocking ICOS in vitro significantly decreased the antiviral activity of NKT-like cells in COVID-19 positive pregnant women, suggesting that ICOS-ICOSL may play an important role in the virus clearance by NKT-like cells. Conclusions: During SARS-CoV-2 infection, NKT-like cells of pregnant women activated through ICOS-ICOSL pathway and played an important role in the antiviral response.

Background: Adult-acquired flatfoot deformity (AAFD) is characterized by partial or complete flattening of the longitudinal medial arch, which develops after maturity. AAFD secondary to posterior tibialis tendon dysfunction (PTTD) is one of professional athletes' most common foot and ankle pathologies. Different modalities and procedures can be used to establish the diagnosis of AAFD and PTTD. However, imaging measurements such as the calcaneal inclination index and ultrasonography (US) of the posterior tibialis tendon (PTT) in professional athletes with medial ankle and focal pain along the PTT have yet to be widely studied. This study investigates the correlation of PTT ultrasound for evaluating PTTD with calcaneal inclination angle (CIA) for evaluating AAFD in professional athletes with medial ankle and focal pain along the PTT. Through this study, clinicians and radiologists may benefit from considering AAFD in athletes with PTTD. Methods: 112 Indonesian professional athletes with medial ankle or foot pain and focal pain along the direction of the PTT underwent foot radiography using the CIA and ankle ultrasound to observe PTT abnormalities. Results: A negative correlation between fluid thickness surrounding the PTT and the CIA (p<0.001; 95% CI - 0.945, - 0.885), as well as a negative correlation between PTT thickness and CIA (p<0.001, 95% CI - 0.926, - 0.845), with a correlation coefficient (r) of - 0.921 and - 0.892, respectively. No significant correlation was found between PTT tear and CIA (p = 0.728; 95% CI -0.223, - 0.159; r - 0.033). Conclusion: This study showed a negative correlation between PTTD and AAFD via ultrasound and CIA in professional athletes with medial ankle and focal pain along the PTT. A better understanding of PTTD and AAFD imaging will lead to more effective management and prompt treatment.

Introduction: Gallstones are one of the most common digestive diseases globally, with an estimated affected population of 15% in the United States. Our aim is to assess the current association between oral health and gallstones, exploring potential mediation factors. Methods: Self-reported gallstones were determined based on medical condition questionnaires. Dental status was assessed by dental professionals and oral health questionnaire. Mediation analysis was conducted for body mass index, blood glucose, triglycerides, and cholesterol, and the percentage of mediation effects was calculated. Results: We included 444 patients with gallstones and 3565 non-gallstone participants from National Health and Nutrition Examination Survey. After fully adjusting for all covariates, the prevalence of gallstones is higher when the number of missing teeth is at T3 compared to T1 (odds ratio [OR]: 1.93, confidence interval [CI]: 1.14 - 3.26, p = 0.02, p-trend = 0.01), and there was an inverted L-shaped association between missing teeth and gallstones, with an inflection point of 17. Bone loss around mouth was also associated with gallstones (OR: 1.78, 95% CI: 1.27 - 2.48, p = 0.002), but not root caries and gum disease. Mediation analysis identified blood glucose as a crucial mediator, with a mediation effect ratio of 4.91%. Conclusions: Appropriate lifestyle interventions for patients with missing teeth may help delay the onset of gallstones, such as healthy dietary habits, trace elements supplementing, and managing weight and blood sugar levels. Further exploration of the relationship between oral health and overall health contributes to disease prevention and comprehensive medical management.

Background: Triggering receptor expressed in myeloid cells 2 (TREM2), a transmembrane receptor, has garnered extensive research attention due to its pivotal role in the diagnosis and treatment of various diseases. Despite the abundance of studies on its function, there is a gap in comprehensive analysis and summarization of the current state of this research field. Methods: Articles and reviews related to TREM2 were retrieved from the Web of Science Core Collection (WOSCC) on October 1, 2023. A bibliometric analysis of TREM2 was conducted using CiteSpace, VOSviewer and Bibliometrix (R package). Results: A total of 1,502 articles, spanning from 2001 to 2022, met the search criteria. The number of publications and citations has increased steadily over the years. The United States and China are the most active countries in TREM2 research, with the University of Washington as the leading research institution. The most influential journal in the field is Neurology of Aging. The predominant research areas include molecular, biology and immunology. Alzheimer's disease, microglia, variants, and inflammation are significant keywords. Emerging directions such as metabolism and tumor microenvironment have recently gained attention in numerous studies. Conclusion: The current study utilizes bibliometric analysis software and visual graphics to intuitively highlight TREM2-related hotspots, trends, and prospects in human disease. Such insights are valuable for scholars seeking a deeper understanding of TREM2-related research progress, enabling a focused approach to its application in human disease.

Background: Celiac Disease (CD) is characterized by small intestine involvement. However, cardiac manifestations may also be seen in the clinical course. The significance of the QRS prolongation and the presence of QRS fragmentation (fQRS) has been previously studied in many chronic inflammatory disorders as an independent predictor of cardiac manifestations. The study aimed to evaluate the QRS duration and presence of fQRS in patients with CD. Methods: 164 patients with CD and 162 healthy controls were included in the present study. QRS duration and presence of fQRS were calculated from the 12-lead electrocardiogram and compared between groups. The association between these parameters and disease duration was also evaluated. Results: QRS duration was found to be higher in the CD group compared to the control group (83 (76.8-93) vs. 91 (84-94), p<0.001). The presence of fQRS was demonstrated to be higher in the CD group (n=68 (41.5%) vs n=42 (25.9%), p=0.003). Notably, QRS duration was positively correlated with disease duration (Spearman's Rho= 0.47, p<0.001). In addition, disease duration was significantly higher in the fQRS (+) group (60 (23,5-144) vs. 28,5 (15-71,5), p=0.002). Conclusion: This study revealed that QRS prolongation and the presence of fQRS were higher in patients with CD. The presence of these findings may be an indicator of early subclinical cardiac involvement, especially in those with long disease duration. Thus, patients with these ECG findings can be considered for further cardiac evaluation.