Search Results (9,126)

Trematodes of the genus Exorchis are parasites that are common in East and Southeast Asia. These parasites are known to infect fish, thus impacting aquaculture significantly. An introspection into the dynamics of infection of these parasites has revealed possible co-infection in shared hosts. But data on the dynamics of their shared host on their population structure and genetic variability is lacking. In this study, we investigate the intraspecific structure of the Exorchis species, Exorchis oviformis, and E. convictus, both of which coexist in the same definitive host. By using partial gene sequences of the mitochondrial cox1 gene (715 bp), including 30 newly obtained sequences from the southern part of the Russian Far East, we found a low level of genetic variation in both species, consistent with previous findings of other trematodes from the same region. We hypothesize that the observed low variability could be attributable to the process of host infection and transmission and abiotic factors influencing a recent decline in host variability and abundance. This is driving a strong selection pressure due to the limited number of parasites reaching the definitive host. This, among other factors, could possibly impact the long-term survival and adaptability of Exorchis and other trematodes at large in the region. However, we also believe that there may be a chance that these closely related species could exert an influence on each other’s genetic diversity, potentially limiting the variation within each species. To uncover the dynamics driving these observations, we propose the approach of expanding sampling, broader genetic marker analyses, and investigations of varied host populations that could elucidate the complexities of the Exorchis species genetic variability and evolutionary dynamics. Full article

Background/Objectives: According to the 2023 Ministry of Health and Welfare statistics, the suicide rate among adolescents aged 15 to 24 has steadily increased since 2018, from 3.7 to 5.5 per 100,000 populations, reaching a recent high. Although previous studies have pointed out that the future risk of suicide of those who had suffered from abuse was higher than that of the general population, researchers seldom focused on adolescent groups. Therefore, the aim of this study was to explore the risk of suicide after youth violence and the impact of subsequent comorbid mental illness and suicide risk. Methods: This retrospective matched cohort study analyzed data from the NHIRD, covering the period from 2000 to 2015. A total of 976 cases aged 10–18 who had experienced violence were included in this study. Controlled grouping was conducted by 1:10 matching based on gender, age, and the time of medical treatment, and a control group who had not experienced violence was selected for comparison. We used the Cox proportional hazards model to analyze the risk of suicide among adolescents after exposure to violence. Results: The suicide rate among adolescents who have experienced violence was significantly higher than that of the control group after 15 years of follow-up (1.0% vs. 0.5%). The prevalence of mental illness or disorders in adolescents exposed to violence was significantly higher than in the control group (45.2% vs. 40.1%). Among adolescents who had experienced violence, the methods of suicide included poisoning (solid and liquid) (53.6% vs. 43.2%), hanging (1.2% vs. 0.6%), firearms (2.4% vs. 0%), and cutting instruments (27.4% vs. 22.8%), all of which were significantly higher than in the control group. After adjusting for gender, age, residential area, and mental health comorbidities, the risk of suicide in those who had experienced violence was 1.475 times that of the control group (95% CI = 1.125–1.933; p = 0.005). Conclusions: In this study, female, younger age, and comorbid mental disorders were identified as risk factors for suicide among the adolescent victims of violence. Exposure to youth violence was associated with an increased prevalence of emotional disorders, including depression and social isolation, which subsequently elevated the suicide risk. These findings underscore the urgent need for governmental attention to the mental health of adolescent victims of violence. Implementing targeted psychological support and intervention programs could play a crucial role in mitigating the risk of suicide among this vulnerable population. Full article

Background/Objectives: Catheter ablation for atrial fibrillation (AF) is a well-established therapeutic approach for maintaining sinus rhythm, though its efficacy remains suboptimal in certain patients. The left atrium (LA) volume, commonly assessed through transthoracic echocardiography (TTE), is a recognized predictor of AF recurrence after pulmonary vein isolation (PVI). However, the complex three-dimensional structure of the LA makes precise measurement challenging with traditional TTE techniques. Electroanatomic mapping (EAM) offers a more accurate evaluation of LA geometry and volume, which may enhance the prediction of ablation outcomes. Methods: This prospective study included 197 patients with AF who were referred for PVI to our center (Hospital Universitario Central de Asturias, Spain) between 2016 and 2020. All participants underwent pre-ablation TTE and EAM to assess the electric active volume (EAV) of the LA. Clinical follow-up included regular Holter monitoring and electrocardiograms to detect AF recurrences. Results: The mean age was 56.3 ± 9.67 years, and 34% had persistent AF. The mean LA volumes measured by TTE and the EAV by EAM were 62.86 ± 15.58 mL and 126.75 ± 43.35 mL, respectively, with a moderate positive correlation (r = 0.49, p < 0.001). AF recurrences were observed in 51.27% of patients over a 36 ± 15-month follow-up period. Cox regression analyses (univariate and multivariate), Kaplan–Meier curves and log-rank tests were used to illustrate freedom from atrial arrhythmia during follow-up. Both EAV by EAM and TTE volumes were significant predictors of AF recurrence in the univariate analysis (HR 1.002 [1.001–1.003], p = 0.033 and HR 1.001 [1.006–1.012], p < 0.01, respectively). Among clinical variables, persistent AF was significantly associated with a higher risk of recurrence (HR 1.17 [1.096–1.268], p = 0.02). Conclusions: EAV of the LA assessment by EAM demonstrates a significant correlation with TTE measurements and is a predictor of AF post-ablation recurrence. In patients selected for catheter ablation, EAV by EAM provides additional insights that could contribute to therapeutic decision-making and risk stratification of AF recurrences. Full article

Background: Previous epidemiological studies have shown that diabetes is associated with an increased risk of several cancers, including bladder cancer. However, prediction models for bladder cancer among diabetes patients remain scarce. This study aims to develop a scoring system for bladder cancer risk prediction among diabetes patients who receive routine care in general outpatient clinics using a machine learning-guided approach. Methods: A territory-wide retrospective cohort study was conducted using electronic health records of Hong Kong. Patients who received diabetes care in public general outpatient clinics between 2010 and 2019 without a history of malignancy were identified and followed up until December 2019. To develop a scoring system for bladder cancer risk prediction, random survival forest was employed to guide variable selection, and Cox regression was subsequently applied for weight assignment. Results: Of the 382,770 patients identified, 644 patients developed bladder cancer during follow-up (median: 6.2 years). The incidence rate was 0.29 per 1000 person-years. In the final time-to-event scoring system, age, serum creatinine, sex, and smoking were included as predictors. Serum creatinine ≥94 µmol/L appeared to be associated with an increased risk of developing bladder cancer. The 2-year and 5-year AUCs on test set were 0.88 (95%CI: 0.84–0.92) and 0.86 (95%CI: 0.80–0.92) respectively. Conclusions: Renal dysfunction could be a potential predictor of bladder cancer among diabetes patients. The proposed scoring system could be potentially useful for providing individualized risk prediction among diabetes patients. Full article

Purpose: The purpose of this study was to investigate a possible association between Herpes Zoster (HZ) and the subsequent diagnosis of breast cancer (BC). Methods: Utilizing the Disease Analyzer database, anonymized medical records from German office-based practices were accessed. Longitudinal data of female patients aged 18 years and above diagnosed with HZ between 2005 and 2021 were included. Individuals without HZ diagnoses were matched to HZ patients using a nearest neighbor propensity score matching (1:1) based on age, sex, index year, average yearly consultation frequency during the follow-up, and predefined co-diagnoses. The incidence of BC in the cohort with and without HZ was evaluated using Kaplan–Meier curves and compared using the log-rank test. Finally, a univariable Cox regression analysis was conducted to assess the association between HZ and BC. Results: This study included 64,255 women with HZ and an equal number without HZ, with comparable characteristics in terms of age, visit frequency, and comorbidities. Analysis revealed no significant association between HZ and subsequent BC incidence, with similar rates observed in both HZ and non-HZ cohorts across different age groups. Conclusions: In this retrospective cohort study consisting of well-matched patients, the results indicate no significant association between an HZ infection and the development of BC over a 10-year follow-up period. This is the largest study of its kind to date. Full article

This study aimed to evaluate the incidence of total knee arthroplasty (TKA), a marker of severe knee osteoarthritis (OA), among older females with concurrent knee OA and osteoporosis (OP) who were treated with denosumab or bisphosphonates. By analyzing a large population-based cohort, we sought to clarify how these treatments influence the progression of knee OA to the point of requiring surgical intervention. We used data from the Taiwan National Health Insurance Research Database, including data from females aged ≥ 50 years diagnosed with knee OA and OP who initiated treatment between 2012 and 2019. Propensity score matching (1:1) resulted in the selection of 13,774 patients (6897 per group). The TKA incidence was analyzed using Cox proportional hazards models. Patients treated with denosumab had a lower TKA incidence than those treated with bisphosphonates (6.9 vs. 8.5 per 1000 person-years). The adjusted hazard ratio (aHR) for TKA in the denosumab group was 0.77 (95% CI: 0.62–0.97; p = 0.024), with the most pronounced effect observed in patients aged ≥ 80 years (aHR = 0.39, 95% CI: 0.20–0.77; p = 0.007). These findings suggest that denosumab reduces TKA risk more effectively than bisphosphonates and may serve as a superior treatment option for mitigating severe knee OA progression, especially in older adults. Full article

Background: Although the Spinal Instability Neoplastic Score (SINS) is widely utilized to evaluate spinal instability, its prognostic value for survival in patients with cervical spinal metastases remains unclear. This study investigated the association between the SINS and survival outcomes in patients with metastatic cervical spine cancer. Methods: This retrospective cohort study included 106 patients who underwent surgery for metastatic cervical spine cancer at a single institution between 1995 and 2023. Patients were divided into two groups: high SINS (≥13) and low-to-moderate SINS (0–12). Overall survival (OS) was the primary outcome and was analyzed using Kaplan–Meier estimates and Cox regression. Secondary outcomes included changes in Eastern Cooperative Oncology Group Performance Status (ECOG-PS), operation time, estimated blood loss, and postoperative complications. Results: The median OS was significantly shorter in the high SINS group compared to the low-to-moderate SINS group (5.3 months versus 8.6 months; p = 0.023). A high SINS was independently associated with increased mortality risk (hazard ratio [HR], 1.959; 95% CI, 1.221–3.143; p = 0.005). Lung cancer (HR, 4.004; 95% CI, 1.878–8.535; p < 0.001) and rectal cancer (HR, 3.293; 95% CI, 1.126–9.632; p = 0.029) were predictive of worse survival, whereas postoperative chemotherapy (HR, 0.591; 95% CI, 0.381–0.917; p = 0.019) and radiotherapy (HR, 0.531; 95% CI, 0.340–0.827; p = 0.005) were associated with improved survival. Changes in the ECOG-PS and postoperative complication rates were not significantly different between the groups. Conclusions: A high SINS was associated with significantly shorter survival in patients with metastatic cervical spine cancer, reflecting both mechanical instability and tumor aggressiveness. Full article

Background: Inflammation plays a critical role in the prognosis of patients with pulmonary arterial hypertension (PAH). The lymphocyte-to-C-reactive protein ratio (LCR), as a novel inflammatory marker, has not been studied in patients with PAH. The objective of this study was to investigate the prognostic value of the LCR in patients with PAH. Methods: A retrospective cohort study was conducted on 116 patients with PAH diagnosed in Renji Hospital, School of Medicine, Shanghai Jiao Tong University, from January 2014 to December 2018. The primary outcome was a composite endpoint that included lung transplantation, rehospitalization for PAH, and all-cause death. The LCR is the ratio of the blood lymphocyte count to the C-reactive protein concentration. Results: A total of 116 patients with PAH were included in this study, with an average age of 41.53 years; 92.2% were female, and the event rate was 57.8%. Restricted cubic spline analysis confirmed a linear association between the LCR and the risk of clinical worsening events. Multivariate Cox proportional hazards analysis showed that the LCR was significantly negatively associated with clinical worsening events, with hazard ratios and 95% confidence intervals of 0.772 (0.614–0.970). The Kaplan–Meier curve showed that event-free survival decreased significantly when the LCR was less than 1.477. LASSO regression selected four potential predictors, including the LCR, to construct a nomogram. The nomogram had a high predictive strength, with an area under the ROC curve of 0.805 (0.713–0.896). The calibration curves and decision curve analysis indicated that the nomogram had good predictive performance and the ability to guide clinical management. Conclusions: The LCR is a valuable prognostic marker for predicting long-term clinical events in patients with PAH, and the nomogram incorporating the LCR could effectively stratify risk and guide clinical decision making. Full article

Background: Osteoarthritis (OA) is a chronic condition characterized by joint pain and disability, driven by excessive oxidative stress and inflammatory cytokine production in chondrocytes, resulting in cell death and cartilage matrix breakdown. Our previous study showed that in monosodium iodoacetate (MIA)-induced OA rats, oral administration of heat-killed Lactobacillus delbrueckii subsp. lactis 557 (LDL557) could significantly decrease OA progression. Methods: Accordingly, we designed an in vitro cell culture study aimed at investigating the effects of heat-killed LDL557 extracts on chondrocytes using SW1353 cells (a human chondrosarcoma cell line) challenged with 5 μM MIA to mimic OA conditions. Results: The results showed that the 10 μg/mL LDL557 extracts protected SW1353 cells from MIA-induced death and reduced extracellular matrix (ECM) loss, as evaluated by toluidine blue O staining and extracellular matrix component synthesis with RT-qPCR measurement. This was achieved by decreasing the expression of MIA-induced pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, while slightly increasing the MIA-suppressed expression of the anti-inflammatory cytokine IL-10, which were evidenced by RT-qPCR analysis. Moreover, the RT-qPCR evaluation also indicated that the LDL557 extracts slightly reduced the expression of COX-2 compared with the control, while it did not reduce the MIA-increased expression of microsomal prostaglandin E synthase-1 (mPGES-1). In addition, the LDL557 extracts influenced neither the matrix-degrading protease expressions measured via RT-qPCR nor the oxidative stress measured via fluorescence flow cytometry in the cells with or without the MIA challenge. Conclusions: This study demonstrates that LDL557 extracts may protect chondrocytes from OA damage by reducing inflammation-related factors and thus mitigating cartilage matrix loss, suggesting LDL557 extracts are attractive alternatives for OA applications. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has surged as a major cause of liver transplants in the United States. Existing studies have presented conflicting findings regarding the association between liver characteristics (specifically steatosis and fibrosis) and mortality. This study investigates the relationship between the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) via vibration-controlled transient elastography (VCTE) and all-cause mortality in MASLD patients. Methods: Using the NHANES 2017-2018 database, 3821 individuals representing the United States population with MASLD underwent VCTE for liver stiffness measurement. Exclusion criteria were applied, eliminating ineligible cases, incomplete examinations, underage individuals, and those with hepatitis B or C, along with significant alcohol consumption history. Cox proportional hazard models assessed the hazard ratio (HR) for all-cause mortality in CAP and LSM. Cox regression analysis with interaction terms was employed for deeper exploration. Results: The study unveiled a strong, independent correlation between LSM and all-cause mortality. However, the CAP failed to demonstrate a significant association with mortality in both univariate and adjusted analyses, contrary to recent findings. The analysis underscores the importance of accurately measuring liver stiffness via VCTE in predicting adverse outcomes in MASLD patients, emphasizing the pivotal role of fibrosis in assessing mortality risk. Conclusion: This study reaffirms the robust link between liver fibrosis (measured through VCTE) and mortality among MASLD individuals. The absence of a significant association between steatosis (indicated by CAP) and mortality challenges recent research, urging further comprehensive investigations with larger cohorts to delineate steatosis’ precise impact on MASLD-related mortality. Full article

Background/Objectives: Heart failure (HF) remains a leading cause of hospitalization and morbidity. Arterial stiffness, measured by pulse wave velocity (PWV) and the augmentation index (AIx), has been linked to HF severity and prognosis. This study investigates the relationship between clinical parameters, biochemical indicators, and arterial stiffness in hospitalized patients with HF, aiming to identify predictors of hospitalization and improve patient management. Methods: This cross-sectional study included 98 patients admitted with HF: 53 with acutely decompensated HF (sudden worsening of symptoms) and 45 with chronic HF (stable symptoms of HF). Clinical and biochemical parameters, including ejection fraction (EF), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels, and arterial stiffness indicators (PWV and AIx), were measured at admission. During follow-up, 59 patients required re-hospitalization due to acutely decompensated HF, while 39 remained outpatients without further hospitalization. The relationship between these parameters was analyzed using Pearson correlation coefficients, and multiple Cox regression analysis was conducted to identify independent predictors of re-hospitalization. Results: A significant negative correlation between EF and PWV was found (r = −0.853, 95% CI [−0.910, −0.764]), suggesting an association between improved heart function (higher EF) and reduced arterial stiffness (lower PWV). A moderate positive correlation between EF and AIx (r = 0.626, 95% CI [0.473, 0.805]) suggests that, while higher EF is associated with increased AIx, the relationship is weaker compared to EF and PWV. This may reflect differing contributions of vascular and myocardial factors to HF severity. Hospitalized patients exhibited significantly poorer clinical and biochemical profiles, including higher NT-proBNP levels (p < 0.001) and worse blood pressure (BP) measurements (systolic and diastolic, p < 0.01). Multiple Cox regression analysis identified PWV, Aix, and NT-proBNP as independent predictors of re-hospitalization in HF patients, with significant hazard ratios: PWV (HR = 1.15, p = 0.02), AIx (HR = 1.03, p = 0.02), and NT-proBNP (HR = 1.0001, p < 0.01). Conclusions: Arterial stiffness indices (PWV and AIx), EF, and NT-proBNP were identified as significant predictors of re-hospitalization in HF patients. These findings suggest that integrating arterial stiffness measurements into routine clinical assessments may enhance the risk stratification and inform targeted interventions to reduce hospitalizations and improve outcomes. Full article

Six new sesquiterpenes, including four eremophilane derivatives fureremophilanes A–D (1–4) and two acorane analogues furacoranes A and B (5 and 6), were characterized from the culture extract of the cold-seep derived fungus Furcasterigmium furcatum CS-280 co-cultured with autoclaved Pseudomonas aeruginosa QDIO-4. All the six compounds were highly oxygenated especially 2 and 3 with infrequent epoxyethane and tetrahydrofuran ring systems. The structures of 1–6 were established on the basis of detailed interpretation of 1D and 2D NMR and MS data. Their relative and absolute configurations were assigned by a combination of NOESY and single crystal X-ray crystallographic analysis, and by time-dependent density functional (TDDFT) ECD calculations as well. All compounds were tested the anti-inflammatory activity against human COX-2 protein, among which, compounds 2 and 3 displayed activities with IC₅₀ values 123.00 µM and 93.45 µM, respectively. The interaction mechanism was interpreted by molecular docking. Full article

Endothelial dysfunction is a hallmark of several pathological conditions, including cancer, cardiovascular disease and inflammatory disorders. In these conditions, perturbed TCA cycle and subsequent succinate accumulation have been reported. The role of succinate as a regulator of immunological responses and inflammation is increasingly being recognized. Nevertheless, how endothelial cell function and phenotype are altered by elevated intracellular succinate has not been addressed yet. Thus, we employed numerous in vitro functional assays using primary HUVECs and diethyl succinate (DES), a cell membrane-permeable succinate analogue. An MTS assay 1 h post stimulation with DES suggested reduced metabolic activity in HUVECs. Concurrently, elevated production of ROS, including mitochondrial superoxide, and a reduction in mitochondrial membrane potential were observed. These findings were corroborated by Seahorse mito-stress testing, which revealed that DES acutely lowered the OCR, maximal respiration and ATP production. Given the link between mitochondrial stress and apoptosis, we examined important survival signalling pathways. DES transiently reduced ERK1/2 phosphorylation, a response that was followed by a skewed pro-apoptotic shift in the BAX to BCL2L1 gene expression ratio, which coincided with upregulating VEGF gene expression. This indicated an induction of mixed pro-apoptotic and pro-survival signals in the cell. However, the BAX/BCL-XL protein ratio was unchanged, suggesting that the cells did not commit themselves to apoptosis. An MTS assay, caspase 3/7 activity assay and annexin V/propidium iodide staining confirmed this finding. By contrast, stimulation with DES induced acute endothelial barrier permeability, forming intercellular gaps, altering cell size and associated actin filaments without affecting cell count. Notably, during overnight DES exposure gradual recovery of the endothelial barrier and cell sprouting was observed, alongside mitochondrial membrane potential restoration, albeit with sustained ROS production. COX-2 inhibition and EP4 receptor blockade hindered barrier restoration, implicating a role of COX-2/PGE₂/EP4 signalling in this process. Interestingly, ascorbic acid pre-treatment prevented DES-induced acute barrier disruption independently from ROS modulation. In conclusion, succinate acts as a significant regulator of endothelial mitochondrial function and barrier integrity, a response that is counterbalanced by upregulated VEGF and prostaglandin production by the endothelial cells. Full article

Compounds containing the 1,2,4-triazole moiety in their structure exhibit broad biological activities. Many of these compounds demonstrate anti-inflammatory activity in vitro through various mechanisms, such as inhibiting COX-1/COX-2 and LOX, modulating pro-inflammatory cytokine levels, or having effects on other specific enzymes. Some also display activities in vivo. In many publications, the activities of new 1,2,4-triazole-based compounds exceed those of the reference drugs, suggesting their promising potential as new therapeutic agents. This review of active 1,2,4-triazole derivatives with anti-inflammatory activity is based on literature published from 2015–2024. Full article

Background: Liver cancer treatment encounters considerable therapeutic challenges, especially because hypoxic microenvironments markedly reduce sensitivity to chemotherapeutic agents. TFAM (mitochondrial transcription factor A) plays a crucial role in maintaining mitochondrial function. Oroxylin A (OA), a flavonoid with potential therapeutic properties, demonstrated prospects in cancer treatment. However, the mechanism of the sensitizing effect of OA on cancer cells has not been elucidated. Methods: MTT assays were utilized to evaluate a hypoxia-induced resistance model. Plate colony formation assays, TEM, and JC-1 staining were used to examine the effects of siTFAM on proliferation and mitochondrial damage of HepG2 cells. Cox8-EGFP-mCherry plasmid transfection, LysoTracker and MitoTracker colocalization analysis, and WB were conducted to evaluate the influence of OA on mitophagy. The effect of OA on p53 ubiquitination levels was investigated by Co-IP and the CHX chase assay. A mouse xenograft tumor model was utilized to assess the therapeutic effect of OA on HepG2 cells in vivo. Results: OA significantly improved the inhibitory effect of sorafenib by inhibiting mitophagy on HepG2 cells in in vitro and in vivo models. Notably, the molecular docking and thermal shift assays indicated a clear binding of OA and TFAM. Further research revealed that OA suppressed p53 acetylation and promoted its degradation by downregulating TFAM expression, which ultimately inhibited mitophagy in hypoxia. Conclusions: OA has demonstrated the potential to enhance the efficacy of sorafenib treatment for liver cancer, and TFAM may be one of its targets. Full article