Search Results (16,510)

Polycystic ovary syndrome (PCOS) is a systemic metabolic and endocrine disorder that significantly disrupts reproductive physiology and endometrial function. In this narrative review, we examine the molecular impact of metabolic and hormonal imbalances on the endometrium of women with PCOS. We investigate the specific mechanisms that delineate how hyperinsulinemia and insulin resistance, chronic low-grade inflammation, and estrogen/progesterone/androgen imbalance contribute to altered epigenetic, transcriptomic, metabolomic, and signaling profiles in a wide array of different cell types within endometrial tissues. The synergistic interplay between upregulated inflammatory cytokines (e.g., IL-1,2,6,8,17,18, and TNF-α), along with key changes in critical molecular pathways associated with hyperinsulinemia and insulin resistance (e.g., PI3K/AKT/MAPK, and Wnt/β-catenin), in addition to aberrant sex steroid hormone signaling (e.g., CYP19A1, COX-2, PGE₂, HOXA10, 11βHSD2), promotes deleterious changes within the endometrial microenvironment. These anomalies underpin a spectrum of clinical manifestations observed in women with PCOS at each stage of the life course, including abnormal uterine bleeding in reproductive-age women, impaired decidualization in pregnancy, and altered postmenopausal endometrial physiology. Clinically, these alterations are associated with abnormal uterine bleeding, subfertility, implantation failure, miscarriage, pregnancy complications, and postmenopausal endometrial hyperplasia and cancer. Overall, our review provides novel insights into the molecular mechanisms linking systemic metabolic and endocrine dysfunction with endometrial pathology in PCOS and has broader implications that apply to all women. Full article

Introduction: Renal cell carcinoma (RCC) develops metastatic disease in 30–50% of patients during their disease course, with approximately one quarter presenting with metastases at diagnosis. While the lungs, liver, bones, brain, and adrenal glands are the most frequent metastatic sites, duodenal involvement is exceptionally rare. This uncommon presentation poses diagnostic and therapeutic challenges, particularly regarding the role of surgical resection in the metastatic setting. Objective: We aim to evaluate the clinical presentation, management strategies, and outcomes of patients with duodenal metastasis from RCC, with particular emphasis on the potential role of surgery, through a systematic review of the literature. Methods: A comprehensive electronic search of Medline, Embase, and Scopus was conducted according to PRISMA guidelines. The following MeSH terms were applied: Kidney Neoplasms [MeSH] AND Duodenal Neoplasms/metastasis [MeSH]. Eligible studies included original reports or case series describing RCC with duodenal metastasis. Demographic, clinical, surgical, and survival data were extracted and synthesized. Results: Of 89 records identified, 83 underwent full-text review and 51 met inclusion criteria, representing 55 patients. The median age at diagnosis was 64 years, and 80% of primary tumors arose from the right kidney. Nearly all patients (98%) were symptomatic, most commonly with upper gastrointestinal bleeding, anemia, or obstructive features. Pancreaticoduodenectomy was the predominant surgical approach, performed with curative intent in selected cases. Patients undergoing surgery achieved a 5-year overall survival of 70%, compared with 0% among non-operated patients. Conclusions: Duodenal metastasis from RCC remains an uncommon entity, limiting the strength of available evidence. Nevertheless, our findings suggest that surgical management—when feasible and decided within a multidisciplinary framework—can provide meaningful survival benefit and should be considered as a complement to contemporary systemic therapies for metastatic RCC Full article

Background: The hemoglobin-to-red-cell distribution width ratio has emerged as a novel prognostic marker in various clinical settings. However, its association with total bone mineral density in adolescents remains inadequately explored. Methods: This cross-sectional study was based on data from the 2011–2018 National Health and Nutrition Examination Survey, including adolescents aged 12–19 years with complete data on hemoglobin, red cell distribution width, and total bone mineral density. Weighted multivariable linear regression models and generalized additive models were used to evaluate the association between hemoglobin-to-red-cell distribution width and total bone mineral density. A two-piecewise linear regression model was applied to assess potential threshold effects, with log-likelihood ratio tests used to determine the significance of inflection points. Subgroup and interaction analyses were further conducted to examine whether age, sex, race, and milk product consumption modified this association. Results: A total of 3789 adolescents were included. Participants in the highest hemoglobin-to-red-blood-cell distribution width ratio quartile had significantly higher hemoglobin levels, lower red blood cell distribution width, greater total bone mineral density, higher total calcium and blood urea nitrogen levels, and lower body mass index, high-density lipoprotein cholesterol, and serum 25OHD levels compared to lower quartiles. The hemoglobin-to-red-blood-cell distribution width ratio was positively associated with total bone mineral density (fully adjusted β = 0.078, 95% CI: 0.053, 0.104, p < 0.0001). A two-piecewise linear regression model identified an inflection point at the hemoglobin-to-red-cell distribution width ratio = 1.055; the positive association became stronger above this threshold (β = 0.143 vs. β = 0.039 below the threshold, p = 0.003 for nonlinearity). Subgroup analysis revealed significant gender interactions (p < 0.0001). A higher HRR was significantly associated with greater total BMD in males (β = 0.130, 95% CI: 0.089–0.171, p < 0.0001), whereas no significant association was observed in females (β = −0.009, 95% CI: −0.043–0.025, p = 0.604). Positive associations were also observed among participants aged 12–15 years, non-Hispanic Whites, non-Hispanic Blacks, other Hispanics, Mexican Americans, and frequent milk consumers. Conclusions: Our results indicate that the hemoglobin-to-red-cell distribution width ratio shows a potential association with bone mineral density in male adolescents, which may offer supportive value for bone health assessment but requires further validation. Full article

Malignant pericardial effusion (MPE) is a life-threatening condition in patients with cancer, with common recurrences after simple pericardiocentesis. Consequently, the intrapericardial instillation of sclerosing or cytotoxic agents has been explored, with limited evidence from small studies with different methodologies. We undertook an observational, retrospective, single-centre study, including all patients diagnosed with a solid neoplasm and clinically significant and/or recurrent, cytology-confirmed MPE, treated with Intrapericardial Instillation of Cisplatin (IPIC), between 2009 and 2022. Patients with hematological malignancies were excluded. The procedure followed a multidisciplinary approach and a standardized protocol. Variables collected included baseline patient characteristics, neoplasm details, MPE impact, adverse events (AEs) from procedures (pericardiocentesis and IPIC) and outcomes (time to MPE recurrence and survival). This study adhered to the STROBE guidelines. A total of 41 patients were included, 51% female, with a median age of 61 (51–69) years. Non-small cell lung cancer (NSCLC) was the predominant primary tumour (78%) and in 44% of the cohort, MPE was identified at cancer diagnosis. Most patients (90.2%) presented symptoms related to MPE at diagnosis, and 88% had cardiac tamponade on echocardiography. IPIC was administered a median of four times. IPIC-related AEs occurred in 10 patients (24.4%), with transient atrial fibrillation (AF) being the most frequent one. Two patients (4.9%) experienced MPE recurrence within 30 days after IPIC. The median survival time from MPE diagnosis was 161 days (5.4 months; IQR 73–455 days). IPIC appears to be a feasible, effective and safe option for reducing the risk of MPE recurrence, mainly in NSCLC. Full article

Magnesium (Mg²⁺) is a key regulator of cellular biochemical processes and an essential cofactor in skeletal muscle physiology. Although Mg²⁺ deficiency has been linked to reduced muscle strength, its role in the regulation of calcium (Ca²⁺) signaling and in inflammation remains incompletely understood. In this study, we examined the effects of Mg²⁺ availability using the murine myoblast cell line C2C12. Cells were differentiated under low, normal, or high Mg²⁺ conditions, and myotube formation, intracellular Ca²⁺ fluxes, and resistance to inflammatory stimuli were assessed. Mg²⁺ deficiency impaired myotube differentiation, while Mg²⁺ supplementation preserved Ca²⁺ response during stimulation and contributed to protect myotubes against inflammation-induced damage. Collectively, these findings highlight a dual role of Mg²⁺ in sustaining functional performance under repeated stress and protecting myotubes against inflammatory injury. This study supports the importance of adequate dietary Mg²⁺ intake as a potential strategy to mitigate muscle loss associated with aging and chronic inflammation. Full article

Background: Small cell lung cancer (SCLC) is a malignant carcinoma characterized by high proliferative rate and early metastatization with limited treatment options and poor prognosis. The approval of ICIs has established a new standard of care for extensive-stage (ES)-SCLC (5). Atezolizumab, an anti PD-L1 monoclonal antibody, has been the first immune checkpoint inhibitor (ICI) to be approved for SCLC patients. This study aims to retrospectively evaluate the real-world effectiveness and safety of atezolizumab in a cohort of patients with ES-SCLC. Methods: We conducted a monocentric retrospective analysis of SCLC patients who received atezolizumab in addition to chemotherapy, between January 2020 and December 2023. Study design endpoints included progression-free survival (PFS), overall survival (OS), and adverse events. Results: A total of 134 patients were included in this study. Out of 134 patients who began the CEA protocol, 100 continued maintenance. Currently, 25 are alive, 17 still on atezolizumab, 5 on second-line therapy, and 3 receiving best supportive care. The median age was 65 years. Patients received a median of four cycles of CEA (range 1–6 cycles), while the median number of atezolizumab maintenance cycles was eight (range 0–75). The overall median survival was 15 months, with patients who received more than 30 cycles of atezolizumab showing OS of 46.7% at 48 months. Common adverse events included skin disorders, pneumonitis, colitis, alanine, and aspartate deaminase increment, dysthyroidism, and blood disorders with only 3% of patients experiencing grade 3 or higher toxicities. Conclusions: In this real-world cohort, atezolizumab demonstrated comparable effectiveness to clinical trial results, with a manageable safety profile. These findings support the use of atezolizumab as a viable treatment option for ES-SCLC in routine clinical practice. Full article

Background: Glioblastoma multiforme (GBM) is an aggressive primary brain malignancy associated with poor prognosis and limited therapeutic options. Nanoparticle-based drug delivery systems provide a promising strategy to enhance treatment efficacy by circumventing barriers such as the blood–brain barrier. This study was conducted to synthesize, characterize, and evaluate the in vitro anticancer potential of andrographolide–iron oxide nanoparticles (AG-IONPs) against GBM cells. Methods: Iron oxide nanoparticles (IONPs) were synthesized through co-precipitation and subsequently functionalized with andrographolide. Morphology, size, and surface charge were assessed by transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis. Functionalization was confirmed by Fourier-transform infrared spectroscopy (FTIR) and UV–Vis spectroscopy. Nanoparticle stability was monitored over three months. Cytotoxicity toward DBTRG-05MG cells was evaluated using MTT assays at 24, 48, and 72 h, while anti-migratory effects were determined using scratch-wound assays. Results: TEM analysis revealed nearly spherical IONPs (7.0 ± 0.15 nm) and AG-IONPs (13.5 ± 1.25 nm). DLS indicated an increased hydrodynamic diameter following functionalization, while zeta potential values decreased from +21.22 ± 1.58 mV to +8.68 ± 0.87 mV. The successful incorporation of andrographolide was confirmed by FTIR and UV–Vis spectra. AG-IONPs demonstrated excellent colloidal stability for up to three months. Cytotoxicity assays revealed a dose- and time-dependent decrease in cell viability, with LC₅₀ values declining from 44.01 ± 3.23 μM (24 h) to 15.82 ± 2.30 μM (72 h). Scratch-wound assays further showed significant inhibition of cell migration relative to untreated controls. Conclusions: AG-IONPs exhibit favorable physicochemical properties, long-term stability, and potent anti-proliferative and anti-migratory effects against GBM cells in vitro. These findings support their potential as a multifunctional therapeutic platform, warranting further preclinical investigation. Full article

Background/Objectives: Bitter Taste Receptors (encoded by TAS2R genes) are expressed in mucosal and bronchial epithelia, as well as in immune cells, contributing to defense against airborne pathogens such as SARS-CoV-2. Data on single-nucleotide polymorphisms (SNPs) in TAS2R genes or pseudogenes in COVID-19 are limited. This study examined the association between TAS2R SNPs and COVID-19 infection and seroconversion in European individuals participating in the Canadian Longitudinal Study on Aging. Methods: Data from the Genome-wide Genetic Data, Comprehensive Baseline (version 7.0), Follow-up 2 (version 1.1), COVID-19 Questionnaire Study (4-2020 to 12-2020), and COVID-19 Seroprevalence (Antibody) Study (11-2020 to 7-2021) datasets were accessed. Associations of TAS2R SNPS with COVID-19 infection or seroconversion were determined using logistic regression adjusted for sociodemographics, genetic principal components, smoking, vaccine doses, and chronic medical conditions (diabetes, immune-mediated inflammatory diseases (IMIDs), respiratory disease, and cardiovascular disease). Results: In the COVID-19 Questionnaire Study (N = 14,073), the rs117458236 (C) variant in TAS2R20 showed a trend toward an association with COVID-19 infection (OR = 1.95; 95% Confidence Interval (CI): 0.98, 3.51). In the COVID-19 Antibody Study (N = 8313), the rs2234235(G) variant in TAS2R1 was associated with anti-nucleocapsid (OR = 1.55; CI: 1.06, 2.20) and anti-spike response (OR = 0.74; CI: 0.57, 0.98); the rs2234010(A) variant in TAS2R5 was associated with anti-nucleocapsid (OR = 1.56; CI: 1.08, 2.19); and the rs34039200(A) variant in TAS2R62P was associated with anti-spike (OR = 0.86; CI: 0.77, 0.97). In a subgroup analysis, the rs2234235(G) variant in TAS2R1 was associated with a decreased anti-spike response to infection or vaccination in individuals with IMIDs or respiratory disease and an increased risk of SARS-CoV-2 infection. Conclusions: TAS2R variants are associated with COVID-19 infection and vaccine response. These data may inform personalized management and vaccination strategies. Full article

Silver nanoparticles (AgNPs) have attracted significant attention in recent years in diverse fields owing to their broad mechanisms of action. In particular, the wound healing process has become one of the main fields where the therapeutic potential of AgNPs is highlighted. AgNPs can be used as monotherapy or incorporated into composite structures in various formulations such as nanogels, hydrogels, powders, ointments, and sprays, for the treatment of a wide range of wound types including burns, excisional and incisional wounds, bone defects, surgical wounds, and diabetic ulcers. This widespread use is attributed to the strong antibacterial, anti-inflammatory, antioxidant, and cell proliferation-promoting biological properties of AgNPs. Moreover, AgNPs exhibit synergistic effects when combined with conventional antibiotics, enhancing their efficiency against resistant bacterial strains or even restoring the lost antibacterial activity. These biological properties enable AgNPs to reduce infection risk while simultaneously promoting high-quality healing by accelerating tissue regeneration. The therapeutic effectiveness of AgNPs is influenced by their physicochemical properties, including particle size, shape, and surface chemistry. In particular, synthesis methods play a significant role in determining both the biological activity and the safety profile of AgNPs. Among various methods, green synthesis approaches stand out for enabling the production of environmentally friendly, non-toxic, and highly biocompatible AgNPs. In this review, the mechanisms of action of AgNPs in wound healing are examined in detail, and recent scientific developments in this field are evaluated based on current in vitro, in vivo, and clinical studies. Full article

This study investigated the effects of asparagus powder supplementation on blood glucose regulation, insulin, lipid profile, and oxidative stress in overweight and obese individuals. Forty-four adults aged 18–59 years participated in a 12-week randomized controlled trial and were randomly assigned to receive either asparagus powder (40 mg/kg/day) or a placebo (maltodextrin, 40 mg/kg/day). Assessments included an oral glucose tolerance test (OGTT), fasting blood glucose (FBG), insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and β-cell function (HOMA-B), lipid profile, and oxidative stress markers (malondialdehyde [MDA], protein carbonyl, and superoxide dismutase [SOD]). In the asparagus group, OGTT at 30 min and low-density lipoprotein cholesterol (LDL-C) significantly decreased, while SOD activity significantly increased (all p < 0.05). In contrast, the placebo group showed significant increases in OGTT at 30 min, insulin, HOMA-IR, HOMA-B, triglycerides (TG), the TG/high-density lipoprotein cholesterol (HDL-C) ratio, and the total cholesterol (TC)/HDL-C ratio (all p < 0.05). Between-group comparisons indicated that FBG, area under the BG curve at 30–120 min, TG, TG/HDL-C, and MDA levels were significantly lower in the asparagus group than in the placebo group (all p < 0.05), whereas OGTT, LDL-C, SOD activity, insulin, HOMA-IR, HOMA-B, and TC/HDL-C did not differ significantly. Other indices, including TC, HDL-C, and protein carbonyl, showed no significant within- or between-group differences. In conclusion, 12 weeks of asparagus powder supplementation partially improved glycemic control, lipid profile, and oxidative stress in overweight and obese individuals. These findings suggest a potential role of asparagus as a complementary nutritional strategy to reduce the risk of diabetes and cardiovascular disease in this population. Full article

Background/Objectives: Sinonasal anatomical variations, particularly Haller cells (HCs) and the accessory maxillary ostium (AMO), are critical structural factors that may increase surgical risks in dental and otorhinolaryngological (ENT) procedures and predispose individuals to chronic sinusitis. This study aimed to investigate the relationship between HCs, AMO dimensions, maxillary sinus ostium, and sinus pathologies using cone-beam computed tomography (CBCT). Methods: In this cross-sectional retrospective study, CBCT images of 443 patients (226 males, mean age 48.4 ± 15.4 years; 217 females, mean age 46.1 ± 15.2 years) were analyzed. The presence of HCs, AMO, ostium narrowing, and ostium obstruction were recorded, along with ostium dimensions. Relationships between these variations and sinus pathologies were statistically evaluated, with a p-value < 0.05 considered significant. Results: HC prevalence was 34.5% on the right and 39.5% on the left, while AMO was present in 39.5% on the right and 34.5% on the left. Bilateral AMO was significantly associated with localized mucosal thickening, and partial opacification was more common in cases with ostium obstruction. Significant relationships were observed between HC presence and ostium narrowing. While HCs and ostium narrowing did not significantly influence maxillary sinus pathologies, sex (right OR = 0.335; left OR = 0.384; p < 0.001) and the AMO (right OR = 1.698, p = 0.018; left OR = 1.713, p = 0.014) were found to have a significant impact. Conclusions: It was concluded that (i) HCs may contribute to ostium narrowing and impaired sinus drainage, thereby increasing the risk of chronic sinusitis; (ii) the presence of a bilateral AMO is strongly associated with localized mucosal thickening; (iii) sex and the presence of an AMO emerge as independent predictors of maxillary sinus pathologies; and (iv) the careful evaluation of these anatomical variations using CBCT can support multidisciplinary treatment planning in both dental and ENT practice, enhance surgical safety, and help minimize postoperative complications. Full article

As life expectancy continues to increase, age-related disorders are becoming more prevalent. Among these, vascular complications resulting from chronic inflammation are particularly concerning, as they impair angiogenesis and hinder tissue repair, both processes that heavily rely on a well-structured extracellular matrix (ECM). In this context, MicroMatrix^® UBM Particulate, a skin substitute composed of collagen, laminin, and proteoglycans, appears to offer properties conducive to tissue regeneration. The aim of this study was to evaluate the regenerative potential of MicroMatrix^® combined with the Secretome of human Dental Pulp Stem Cells (hDPSC-S), using the medicinal leech Hirudo verbana, a well-established model for studying wound healing, angiogenesis, and tissue regeneration. Adult leeches were injected with MicroMatrix^® either suspended in FBS-free medium (CTRL) or supplemented with hDPSC-S. 1-week post-treatment, the animals were sacrificed and subjected to morphological and immunohistochemical analyses. Our findings revealed that MicroMatrix^® successfully integrated into the leech body wall. Notably, when supplemented with hDPSC-S, there was a marked increase in cell infiltration, including telocytes and Hematopoietic Precursor Stem Cells, along with a significantly higher vessel density compared to CTRL. These results support the effectiveness of the cell-free device composed of MicroMatrix^® and hDPSC-S, highlighting its potential as a promising strategy for regenerative therapies aimed at treating complex wounds with poor vascularization. Full article

Breast cancer affects women at an increasingly younger age, with genetic predispositions and other factors contributing to its second-highest cancer mortality rate. The diversity of pharmacological treatment stems from its heterogeneity, which favors a more precise approach to each subtype. Despite the extensive advances in medicine in recent decades, the problem of treating cancer patients remains significant. The problem with modern therapeutic methods is low effectiveness, emerging side effects, difficulty in eliminating all cancer cells, and the quite common use of monotherapy and the associated drug resistance, which may lead to disease progression. The aim of this review is to present the latest therapeutic strategies (combination therapies) used in the treatment of breast cancer. PubMed databases and clinical data from ClinicalTrials.gov were used for this purpose. The review included characteristics of the latest clinical trials from the last year (2024–2025), which present currently recruiting studies of breast cancer treatment with immunotherapy. The review also presented characteristics of clinical trials from the last 5 years (2020–2025) using nanoparticles as an adjunct to breast cancer treatment. Articles published between 2016 and August 2025 (excluding articles that describe the first use of a given drug) were included in the review. The review analyzed drugs targeting molecular targets, including intracellular pathways responsible for cell cycle regulation, as well as new directions such as nanotechnology in treatment breast cancer. Full article

Background/Objectives: Bladder cancer (BC) carries a substantial global burden. Although lead (Pb) exposure has been linked to cancer, its molecular impact on bladder tumors remains unclear. We asked whether Pb-responsive transcriptional programs are present and clinically relevant in BC by integrating toxicogenomic resources with tumor transcriptomes and whether a composite lead-response score has prognostic value. Methods: Differential expression was performed on TCGA bladder urothelial carcinoma (BLCA) RNA-seq data (tumor vs. normal). Lead-associated genes were curated from the Comparative Toxicogenomics Database (CTD) and tested for over-representation among BLCA differentially expressed genes (DEGs) using a hypergeometric framework, with a stricter |log₂FC| ≥ 1 sensitivity. A tumor-level lead-response score was derived from the Pb–DEG overlap. Associations with overall survival (OS) were assessed using Cox models adjusted for age, sex, and pathological stage; secondary endpoints included PFI/DFI/DSS. Results: Lead-associated genes were significantly enriched among BLCA DEGs (background M = 20,530; K = 2618; n = 11,436; k = 1595; p = 4.21 × 10⁻⁹), and enrichment persisted under |log₂FC| ≥ 1 (n = 4275; k = 698; p = 9.86 × 10⁻¹⁵). Pathway over-representation highlighted synaptic/neuronal-like adhesion and transmission, MAPK-centered signaling, and cell-cycle control. Among top candidates, AQP12B was independently prognostic for OS (HR per 1 SD increase = 0.76; 95% CI 0.63–0.92; p = 0.0038; N = 404). The composite lead-response score showed a directionally protective but non-significant association in multivariable OS models (HR per 1 SD = 0.93; 95% CI 0.81–1.05; p = 0.244), while median-split Kaplan–Meier (KM) curves separated (p = 0.045). Conclusions: Lead-responsive transcriptional programs are detectable in BLCA and intersect adhesion, MAPK signaling, and cell-cycle pathways. AQP12B emerges as a plausible prognostic marker, and a composite lead-response score warrants external validation for risk stratification and clinical translation. Full article

The BCL2 family of proteins plays a pivotal role in regulating apoptosis and cellular homeostasis, making them critical therapeutic targets in cancer and other diseases characterized by pathological cell survival. BH3 mimetics, small molecules that selectively inhibit anti-apoptotic BCL2 family members, have achieved significant clinical success, particularly in hematologic malignancies. However, several challenges remain, including resistance mechanisms, toxicity (such as MCL1 inhibitor-associated cardiotoxicity), and the intricate balance between apoptotic and non-apoptotic functions. This review provides a comprehensive overview of BCL2 family biology, the development and clinical application and outcomes of BH3 mimetics, and the emerging resistance mechanism known as double-bolt locking. We also examine strategies to overcome resistance, including combination therapies and immunomodulatory approaches. Beyond oncology, we highlight the expanding therapeutic potential of BH3 mimetics in autoimmune, fibrotic, and infectious diseases, as well as regenerative and anti-aging medicine. Finally, we discuss predictive biomarkers and tissue-specific responses that inform precision therapy. Together, these insights underscore the promise of BH3 mimetics and the need for continued multidisciplinary research to optimize their clinical impact. Full article