Biomedicines最新文献

Background: Elevated estrogen has been found to contribute to the pathological development of endometrial cancer (EC), potentially through alterations in the tumor inflammatory immune microenvironment. However, the exact mechanisms underlying this process remain unclear. Methods: Bioinformatics was used to identify differentially expressed genes, analyze pathway enrichment, and assess their correlation with immune cell infiltration. Ishikawa cells and ECC-1 cells were stimulated with estradiol (E2) or the selective estrogen receptor modulator Arzoxifene, and qPCR was performed to measure gene expression changes. CCK8 and FACS assays were used to analyze cell cycle alterations, while Western blotting (WB) was used to evaluate apoptosis. Results: ZNF626 and SLK were highly expressed in EC tissues, whereas RFWD3 expression was downregulated. Immune cell infiltration analysis revealed a positive correlation between ZNF626 and M2 macrophages, while SLK was negatively correlated with M1 macrophages, memory B cells, and plasma cells. RFWD3 showed more complex correlations with multiple immune cell phenotypes, including T cells. E2 stimulation resulted in the increased expression of ZNF626 and SLK, while RFWD3 expression decreased. This was accompanied by enhanced cell proliferation and suppressed apoptosis. In contrast, Arzoxifene stimulation produced the opposite effects. Conclusions: Estrogen promotes cell proliferation and inhibits apoptosis by upregulating ZNF626 and SLK, while downregulating RFWD3. Furthermore, estrogen induces a shift in the tumor microenvironment, characterized by a reduction in memory CD4+ T cells and a transition from M1 to M2 macrophage phenotypes, thus facilitating the onset and progression of EC.

Background/Objectives: The use of direct oral anticoagulants (DOACs) in obese patients is scarcely studied despite having many advantages over warfarin. Consequently, this study aims to assess the real-world safety and effectiveness of apixaban compared to warfarin in treating atrial fibrillation (AF) in obese patients. Methods: A retrospective cohort study examined consecutive AF patients with a BMI of ≥ 30 kg/m² treated with apixaban or warfarin. Patients were started on these medications between January 2015 and December 2021. Efficacy outcomes included ischemic stroke and venous thromboembolism (VTE) occurrences, while safety outcomes encompassed bleeding incidents and mortality rates. Outcomes were assessed following propensity score matching. Results: We identified 876 patients treated with either apixaban (414) or warfarin (462). Their mean age was 76.9, with a mean CHA₂DS₂VASc score of 4.9 ± 1.97. After matching and compared to warfarin, apixaban was correlated with a lower incidence of all-cause mortality (19.7% vs. 33.7%, p < 0.001). The incidences of stroke, venous thromboembolism (VTE), and bleeding events were (4.7% vs. 4.7%, p = 1.000), (1.0% vs. 2.6%, p = 0.107), and (3.9% vs. 6.2%, p = 0.139), respectively. Using Cox-regression model, apixaban was associated with lower mortality risk (HR = 0.728, 95% CI: 0.55-0.97; p = 0.030) which remained significant after adjusting for the conventional cardiovascular risk factors and BMI values. Conclusions: Apixaban is associated with a trend of reduced incidence of thromboembolism among obese patients with atrial fibrillation and significantly lowers all-cause mortality. Despite earlier concerns, the use of apixaban is an effective and safe alternative to warfarin among obese patients with AF.

Dopamine, a key neurotransmitter in the central nervous system, is essential for regulating a wide range of physiological processes, including motor control, reward processing, mood regulation, and decision-making [...].

Background/Objectives: The translation of in vitro biomaterial evaluations into successful clinical applications often fails due to discrepancies with in vivo results. Previously, we demonstrated that differences in culture medium conditions influence the bone formation process. This study aimed to investigate the influence of culture media on gene expression during calcification induction in osteoblasts. Methods: Using MC3T3-E1 cells cultured in α Minimum Essential Medium without L-ascorbic acid (αMEM(-)) and Dulbecco's Modified Eagle Medium (DMEM), we screened gene expression profiles through microarray analysis and validated key findings with quantitative PCR. Additionally, we compared these gene expression patterns with those in primary osteoblasts (POBs) cultured under the same medium conditions. Results: The results revealed distinct gene expression profiles in MC3T3-E1 cells depending on the culture medium, while POBs exhibited minimal differences between media, except for the gene Alpl. In αMEM(-), Alpl expression in POBs was significantly increased approximately 4-fold via calcification stimulation (p < 0.0001). POBs cultured in DMEM showed calcification appearance differing from the αMEM(-) condition, even though no significant increase in Alpl expression via calcification stimulation was observed. Conclusions: Differences in media appear to remarkably impact osteoblast gene expression and mineralization. These findings may help improve biomaterial evaluation when transitioning from in vitro assessments to in vivo evaluations. Moreover, our results suggest the possibility that gene expression differences observed in MC3T3-E1 cells reflect the diverse bone formation processes in vivo. Focusing on these genes could facilitate the development of screening methods for bone formation, supporting future clinical applications in orthopedics.

Background: Estrogen depletion alters bone mineralization and oxidative stress. Antioxidants like humic acids (HA) may help mitigate bone demineralization and redox imbalances. Thus, this study evaluated the effects of HA on bone mineral composition and oxidative stress markers in an experimental menopause model. Methods: Twenty-four female C57BL/6 mice were divided into four groups (n = 6/group): Sham; Sham + HA; Ovariectomized (OVX); and OVX + HA. The menopause model was induced by bilateral ovariectomy at the beginning of the experiment. HA derived from biomass vermicompost was administered daily by gavage for 28 days. After euthanasia, femurs and fragments of the gastrocnemius muscle, liver, and kidney were collected. Bone elemental composition was analyzed using scanning electron microscopy (SEM) coupled with energy dispersive spectroscopy (EDS). Superoxide dismutase (SOD), catalase (CAT), and hydrogen peroxide (H₂O₂) activities were assessed in muscle, renal, and hepatic tissues. Data were analyzed using two-way ANOVA and Bonferroni's post hoc test. Results: Untreated OVX mice exhibited a significant reduction in femoral calcium content (p < 0.05). However, HA treatment increased calcium levels and improved the Ca/P ratio (p < 0.05). H₂O₂ activity was reduced in the liver and kidney of OVX + HA mice compared to untreated animals (p < 0.05). CAT activity in muscle increased in the OVX + HA group compared to the OVX (p < 0.05). Conclusions: HA treatment improved femoral elemental composition and modulated oxidative stress markers in an experimental menopause model.

Background/Objectives: Immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have revolutionized cancer immunotherapy, however the clinical relevance of their soluble forms (sPD-1 and sPD-L1) remains less studied. Soluble PD-1 and PD-L1 have been implicated in tumor progression, prognosis, and treatment response across various malignancies. This study aims to provide a comprehensive analysis of sPD-1 and sPD-L1 levels in serum across diverse tumor types, including rare malignancies, and to evaluate their associations with clinicopathological characteristics and prognostic significance. Methods: In this study we analyzed sPD-1 and sPD-L1 levels in serum samples from 675 cancer patients representing a range of malignancies, including ovarian cancer, breast cancer, gastric cancer, colorectal cancer, renal cell carcinoma, and bone tumors. sPD-1 and sPD-L1 concentrations were measured using ELISA. Statistical analyses were performed to evaluate associations between soluble marker concentrations and clinicopathological factors, including tumor stage, size, histological subtype, and survival outcomes. Results: Elevated sPD-L1 levels were observed in several tumor types, including ovarian cancer, renal cell carcinoma, and gastric cancer, where they were associated with features of advanced disease, such as tumor size, stage, and metastases. In contrast, sPD-1 levels showed limited associations, with significant findings solely in gastric cancer and bone tumors, where levels correlated with histological subtype and differentiation. Prognostic analyses identified sPD-L1 as a marker of poor survival outcomes in ovarian cancer and bone tumors, while sPD-1 displayed no consistent prognostic significance. Conclusions: This study identifies the potential of sPD-L1 as a biomarker for tumor progression and prognosis across multiple malignancies. In contrast, sPD-1 showed limited clinical relevance, suggesting the importance of further investigation. These findings contribute to our understanding of soluble immune checkpoint proteins and their integration into personalized oncology strategies.

Inflammatory bowel diseases (IBDs) comprise a group of chronic gastrointestinal disorders characterized by periods of relapse and remission. The mainstay of treatment is medical, involving medications such as steroids, immune modulators, monoclonal antibodies (categorized as biologics), and small molecules. These medications can provide profound therapeutic benefits, but they can also cause severe and irreversible toxicities. Clinicians may utilize laboratory tests in the diagnosis and management of IBD including assessment of disease activity, monitoring medication response or toxicity, surveillance of infectious complications, and detection of nutritional deficiencies. Routine use of laboratory tests may help clinicians avoid reactivation of life-threatening infections such as tuberculosis or hepatitis B virus upon initiation of immune suppressive therapy. They can also be used to detect vitamin deficiencies such as B12 deficiency, which has the potential to cause irreversible neurologic damage. While some laboratory tests constitute established practices, the utility of newer tests such therapeutic drug monitoring (TDM) in the era of biologics is an evolving topic. Although clinical assessment with imaging, endoscopic, and histopathological examination is standard practice, laboratory tests serve as valuable adjuncts. We aim to explore the broad range of laboratory tests available to clinicians and to summarize their application in the current management of IBD in daily clinical practice, with special attention to updates in therapeutic drug monitoring.

Background/Objectives: Radon is a significant carcinogen, particularly as a leading cause of lung cancer among non-smokers. While its carcinogenic effects are well documented, the relationship between radon exposure and inflammatory reactions remains underexplored. This systematic review investigates inflammatory biomarkers in individuals exposed to chronic radon exposure and conducts a meta-analysis on serum C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) levels. Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar using the keywords "radon" AND "inflammation biomarkers" following established guidelines. Studies reporting inflammatory biomarker levels in biological fluids of human participants exposed to residential or occupational radon were included. Statistical analyses, including pooled mean estimates, influence analysis, publication bias, and meta-regression, were performed in RStudio. Results: Ten studies involving 33,099 individuals met the inclusion criteria. Eight studies focused on residential radon exposure, and two examined occupational exposure among uranium miners. Inflammatory biomarkers were analyzed in serum, bronchoalveolar lavage fluid, and saliva. Among individuals exposed to high residential radon levels, serum CRP and TNF-α were the most frequently assessed biomarkers, with pooled mean levels of 2.11 mg/L (95% CI, 1.32-2.89) and 2.20 pg/mL (95% CI, 0.25-4.64), respectively. Conclusions: Serum CRP and TNF-α levels appear lower in adults with chronic radon exposure, suggesting potential anti-inflammatory effects despite radon's established carcinogenicity. Future longitudinal studies using standardized methods are crucial to elucidate the long-term health impacts of radon exposure.

Several etiologic factors for the development of acute leukemias have been suggested; however, none is applicable to all cases. We isolated a certain mycovirus-containing Aspergillus flavus (MCAF) from the home of a patient with acute lymphoblastic leukemia. Repeated electron microscopic evaluations proved the existence of mycovirus in this organism. According to chemical analysis, this organism does not produce any aflatoxin, possibly due to its infestation with mycoviruses. We reported that using the ELISA technique, forty pediatric patients with acute lymphoblastic leukemia (ALL) uniformly had antibodies to the products of MCAF. In contrast, three separate groups of controls, consisting of normal blood donors, individuals with solid tumors, and patients with sickle cell disease, were negative. In vitro exposure of mononuclear blood cells from patients with ALL, in full remission, to the products of MCAF induced redevelopment of cell surface phenotypes and genetic markers characteristic of ALL. The controls were negative. The incubation of normal and ALL cell lines with the products of MCAF resulted in significant cellular apoptosis, changes in the cell cycle, and the downregulation of transcription factors, including PAX-5 and Ikaros (75 and 55 kDa). Fungi are widespread in nature, and many contain mycoviruses. Normally, an individual inhales 1 to 10 fungal spores per minute, while farmers can inhale up to 75,000 spores per minute. It is known that farmers and foresters, who are more exposed to fungi, have a higher rate of acute leukemia. In contrast, asthmatics, most of whom are allergic to fungal agents, and individuals working in office settings have a lower rate. One of the theories for the development of acute leukemia suggests a genetic predisposition followed by exposure to an infectious agent. With the above findings, we propose that mycovirus-containing Aspergillus flavus may have an etiological role in leukemogenesis in immune-depressed and genetically susceptible individuals.

Neutrophils are a critical component of immunity, particularly against bacteria and other pathogens, but also in inflammation and tissue repair. As a consequence, individuals with neutropenia, defined by a reduction in absolute neutrophil counts, exhibit a strong propensity to severe infections that typically present with muted symptoms. Neutropenias encompass a heterogeneous set of disorders, comprising primary neutropenias, in which specific genes are mutated, and the more common secondary neutropenias, which have diverse non-genetic causes. These include hematological and other cancers, involving both direct effects of the cancer itself and indirect impacts via the chemotherapeutic, biological agents and cell-based approaches used for treatment. Other significant causes of secondary neutropenias are non-chemotherapeutic drugs, autoimmune and other immune diseases, infections and nutrient deficiencies. These collectively act by impacting neutrophil production in the bone marrow and/or destruction throughout the body. This review describes the biological and clinical manifestations of secondary neutropenias, detailing their underlying causes and management, with a discussion of alternative and emerging therapeutic approaches.