Search Results (9,761)

In the human reproductive system, extracellular vesicles (EVs) have been recognized as playing a vital role in mediating cell–cell communication. They are considered critical for embryo development, implantation, gamete interaction, and fertilization. The various cargoes carried by EVs, depending on the physiological and pathological state of the cell, include proteins, lipids, nucleic acids, and mitochondrial components. EVs are recognized as critical carriers of redox-related signals and mitochondrial components, linking oxidative stress (OS) to reproductive failure and influencing gamete quality and embryo competence. Although considerable progress has been made, research remains poorly integrated, despite individual omics technologies providing valuable molecular insights. The use of multi-omics technologies, including transcriptomics, proteomics, metabolomics, and microbiome analysis, has been proposed as a global approach to understanding the complexities associated with EVs and discovering new biomarkers associated with infertility. ML and AI have been proposed to identify predictive signatures linked to ART effectiveness and reproductive outcomes, with a strong capacity to handle high-dimensional data. The review aims to provide an overview of current knowledge on EV-mediated redox–mitochondrial signaling in human reproduction, while highlighting the importance of emerging multi-omics and AI technologies for EV-mediated biomarker development. The review discusses the promise of EVs in the development of minimally invasive diagnostic approaches and therapeutic interventions, as well as the challenges in the standardization, integration, and clinical translation of EV-mediated research. In addition, the review proposes integrating computational approaches to better understand molecular pathways involved in the development of next-generation precision medicine in human reproduction. Full article

This study investigated the association between serum hypoxia-inducible factor 1-alpha (HIF-1α) levels and clinical severity in patients with coronavirus disease 2019 (COVID-19). This prospective case–control study included 91 patients with confirmed COVID-19, of whom 51 had severe-critical disease with pneumonia and 40 had mild disease without pneumonia, as well as 39 healthy controls. Vital signs, including body temperature, pulse rate, respiratory rate, oxygen saturation, and blood pressure, were recorded. Biochemical parameters such as complete blood count, D-dimer, ferritin, creatinine, urea, and high-sensitivity cardiac troponin T were analyzed. Serum HIF-1α levels were measured using ELISA. Median HIF-1α levels were 132.9 pg/mL (IQR: 131.7–138.0) in the severe-critical disease group, 137.35 pg/mL (IQR: 131.65–152.75) in the mild disease group, and 136.6 pg/mL (IQR: 132.2–162.2) in controls. Significant differences were observed between groups (p = 0.012). ROC analysis showed a discriminatory performance for HIF-1α, with a sensitivity of 89.01% and specificity of 35.90% at a cut-off value of ≤154 pg/mL for distinguishing mild disease from controls, and a sensitivity of 86.3% and specificity of 42.5% at a cut-off value of ≤141.1 pg/mL for distinguishing severe-critical disease from mild disease. HIF-1α levels decreased with increasing disease severity. HIF-1α levels were found to be associated with disease severity; however, the low AUC values indicate that this parameter has limited discriminative ability for clinical use when used alone. Full article

Plant-derived bioactive metabolites have emerged as promising modulators of oxidative stress and inflammation, two interconnected processes involved in the pathogenesis of numerous chronic diseases. Arid ecosystems, particularly the Sonoran Desert, constitute an underexplored source of structurally diverse phytochemicals with significant pharmacological potential. This review provides a comprehensive overview of major classes of plant-derived bioactives, including polyphenols, flavonoids, terpenoids, and alkaloids, with emphasis on their molecular mechanisms of antioxidant and anti-inflammatory action. These compounds exert cytoprotective effects through direct reactive oxygen species (ROS) scavenging and indirect regulation of endogenous defense systems, primarily via activation of the Nrf2/Keap1 pathway and suppression of NF-κB signaling. Additional pathways, including MAPK, PI3K/Akt, AMPK, and mitochondrial regulatory networks, are discussed as critical mediators of redox balance and inflammatory control. Particular attention is given to Sonoran Desert plant species such as Bucida buceras, Phoradendron californicum, Larrea tridentata, Opuntia spp., and Agave deserti, all of which demonstrate promising biological activities associated with enhanced adaptation to environmental stress. Experimental approaches used to evaluate phytochemical bioactivity, including chemical assays, cellular models, omics technologies, and translational strategies, are also examined. Furthermore, this review discusses current limitations related to bioavailability, phytochemical variability, and clinical validation, highlighting emerging nanodelivery systems and precision medicine approaches as potential solutions. Collectively, the evidence supports the therapeutic relevance of Sonoran Desert plant bioactives as multi-target agents for modulating oxidative stress, inflammation, and chronic disease progression Full article

Dihydromyricetin (DHM), a naturally occurring flavanonol predominantly found in medicinal plants like Ampelopsis grossedentata, has emerged as a promising source of natural antioxidants with multi-target pharmacological activities relevant to drug discovery. DHM exhibits a strong redox-modulating capacity, effectively attenuating oxidative stress and inflammation central drivers of chronic disease pathogenesis. Beyond direct radical scavenging, DHM regulates multiple redox-sensitive and kinase-mediated signalling pathways, thereby influencing key cellular processes involved in disease initiation and progression. This review synthesizes current evidence on the therapeutic potential of DHM, critically evaluating its mechanistic basis and translational prospects, with emphasis on its dual redox-driven and kinase-mediated modes of action. We detail its roles in metabolic disorders such as diabetes, obesity, and liver diseases, neuroprotection, cardio protection, and cancer prevention, focusing on the modulation of critical networks such as AMPK, PI3K/Akt, MAPK, NF-κB, and Nrf2. The interplay between these pathways underpins DHM’s efficacy across disease models. Furthermore, we highlight structure–activity relationship (SAR) analyses and molecular modelling studies that elucidate how the flavanonol scaffold, hydroxylation pattern, and stereochemistry of DHM govern its biological activities and target engagement. Key pharmacokinetic limitations, advances in extraction techniques, bioavailability challenges, and emerging formulation strategies including advanced delivery systems are discussed to address translational hurdles. Despite compelling preclinical data, the clinical translation of DHM remains constrained by limited human studies and incomplete mechanistic resolution. This review underscores the need for integrated pharmacological studies and innovative delivery approaches to translate the multifaceted promise of DHM into viable clinical interventions. Full article

Pharmacomicrobiomics is the study of drug–microbiome interactions. It examines the dynamic relationship between the drug, the host, and the microbiome, and has become a rapidly evolving area in the realm of pharmacology and personalized medicine. Emerging evidence demonstrates that the gut microbiome can influence the pharmacodynamics and pharmacokinetics of drugs through various mechanisms, while drugs can simultaneously alter microbial composition. Treatment approaches include regular targeted pharmaceutical therapies (e.g., antibiotics, antidepressants) and alternative treatment approaches (e.g., CAM treatments such as supplements and herbs). Microbiome-based medication treatment is an alternative treatment approach that has been studied extensively in the last decade. This article reviews the current knowledge on drug–microbiome interactions across multiple therapeutic systems, including cardiovascular, central nervous system, gastrointestinal, respiratory, endocrine, oncologic, musculoskeletal, anti-infective therapies, and supplements (such as melatonin). We also highlight the various pathways by which microbes can alter the mechanisms (such as drug absorption), bioavailability, efficacy, and incidence of adverse effects, along with highlighting the clinical implications of drug-induced dysbiosis. Full article

Background: Workplace victimization is a form of repeated and systematic psychological violence that can severely affect both mental and physical health. From a psychological perspective, it impacts mood states, defense mechanisms, and personality functioning. Methods: This cross-sectional study investigated the psychological and behavioural correlates of workplace victimization in a sample of 33 workers from various professional sectors, using a multidimensional assessment including standardized measures of personality traits, mood states, and defense mechanisms. Results: The MMPI-2 profile revealed elevated scores in Hypochondriasis (Hs: 72.00), Depression (D: 70.21), Hysteria (Hy: 67.61), and Paranoia (Pa: 68.76), indicating somatic symptoms, depressive features, and suspiciousness. The POMS showed increased Tension–Anxiety (T: 65.06), Depression–Dejection (D: 68.21), Anger–Hostility (A: 68.15), and Fatigue–Inertia (F: 65.24), alongside reduced Vigor–Activity (V: 43.18). The DMI analysis highlighted a high Reversal score (REV: 65.91), suggesting a predominant use of defense mechanisms such as altruism and idealization to cope with distress. Conclusions: In this selected sample of adults referred for psychological evaluation for suspected or documented workplace victimization, participants showed a clinically relevant psychological burden, including depressive symptoms, somatic concerns, Anger–Hostility, fatigue, reduced vigor, and specific defensive patterns. Given the cross-sectional design, small sample size, and absence of a control group, these findings should be interpreted as preliminary and cannot establish causality or the specificity of this profile to workplace victimization. Full article

Background and Objectives: Diabetic peripheral neuropathy (DPN) is a common and debilitating complication of obesity and type 2 diabetes (T2D) affecting up to 50% of patients with long-standing disease. While chronic hyperglycemia plays a central role in its pathogenesis, intensive glycemic control provides only partial protection, suggesting the involvement of additional metabolic pathways. The primary objective of this systematic review was to evaluate the role of lipid metabolism disturbances and advanced lipidomic alterations in the development and progression of DPN in patients with obesity and T2D. Secondary objectives included identifying specific lipid species associated with DPN and exploring their potential pathophysiological and clinical implications. Methods: This systematic review included 8 studies that met the inclusion criteria and was conducted according to PRISMA guidelines and registered in PROSPERO/2026/CRD420261288920. Study quality was assessed using the Newcastle–Ottawa Scale. Results: Large population-based cohorts reported a consistent association between hypertriglyceridemia and DPN prevalence, with triglyceride levels >204 mg/dL associated with an approximately 40% increased risk. Lipidomic analysis revealed alterations in acylcarnitine, sphingolipids, and phospholipids. However, the evidence remains limited and heterogeneous, and neuropathy-specific outcomes were insufficiently evaluated in interventional studies. Conclusions: Lipid metabolism disturbances, particularly hypertriglyceridemia and specific lipidomic alterations, may contribute to DPN beyond the effects of hyperglycemia. Although not yet clinically actionable, lipidomic alterations may represent promising future biomarkers and therapeutic targets in DPN. However, the current evidence is limited by heterogeneity and predominantly observational designs. Further well-designed longitudinal and interventional studies are needed to clarify causal relationships and clinical relevance. Full article

Silver nanoparticles (AgNPs) have attracted substantial scientific interest in biomedical research owing to their unique physicochemical characteristics, broad-spectrum antimicrobial activity, plasmonic properties, and therapeutic versatility. Although conventional physicochemical synthesis methods enable controlled NPs fabrication, their dependence on hazardous reagents, elevated energy input, and environmentally detrimental processing conditions has stimulated the development of sustainable biogenic alternatives. Biological synthesis utilizing plants, microorganisms, fungi, algae, and purified biomolecules has emerged as an eco-friendly and bio-compatible strategy for AgNP fabrication, enabling simultaneous reduction, stabilization, and intrinsic biofunctionalization of NPs. However, traditional biogenic synthesis remains constrained by limited mechanistic understanding, poor batch reproducibility, inadequate control over physicochemical properties, and challenges in large-scale manufacturing. Recent advances in bioengineering have transformed this field through the integration of metabolic engineering, synthetic biology, microfluidic-assisted synthesis, artificial intelligence-guided process optimization, and continuous-flow biomanufacturing, collectively enabling precision fabrication of biogenic AgNPs with enhanced uniformity, scalability, and functional tunability. Furthermore, strategic surface engineering and functionalization have expanded the applicability of biogenic AgNPs across targeted anticancer therapy, antimicrobial intervention, wound healing, regenerative medicine, drug delivery, and theranostic imaging. Despite these advancements, critical challenges remain regarding nano–bio interactions, toxicological safety, regulatory compliance, and translational scalability. Unlike conventional reviews focused primarily on green synthesis approaches, this review critically highlights emerging bioengineering paradigms that enable programmable, scalable, and precision-controlled biogenic AgNP fabrication. This review comprehensively examines next-generation paradigms and strategies for AgNPs biosynthesis, elucidates the molecular mechanisms governing their formation, highlights emerging functionalization and biomedical application paradigms, and discusses current translational barriers. Forming biogenic composites of AgNPs and heteroatom doped carbon nanodots needs intense research in near future. Full article

Background: Migraine is a neurological disorder affecting approximately 15% of the general population, and autonomic nervous system (ANS) dysfunction is a well-characterized feature of the condition. Sympathovagal imbalance during acute migraine attacks has been linked to cardiac electrical instability. This study aimed to evaluate atrial and ventricular myocardial repolarization markers in migraine patients at three serial electrocardiography (ECG) time points. Methods: A prospective observational cross-sectional study was conducted in a tertiary emergency department (ED), enrolling 70 migraine patients and 70 age- and sex-matched healthy controls. Three 12-lead ECGs were obtained per patient: during the migraine attack (within 60 min of ED admission), after analgesic treatment (verbal pain relief or Numeric Rating Scale [NRS] decrease greater than 4 points), and in the pain-free period (at least 24 h after the attack, within 7 days). Measured parameters included P-wave duration, P-wave dispersion, QT interval, QT dispersion, corrected QT (QTc) duration (Bazett formula), QTc dispersion, Tpeak–Tend (Tp-e) interval, Tp-e dispersion, and Tp-e/QTc ratio. ECGs were evaluated by two blinded emergency medicine specialists. Results: All repolarization markers were significantly higher in migraine patients than in controls (p < 0.05 for all). Comparing the first (ictal) with the second (post-treatment) measurements, all markers except P-wave dispersion decreased significantly (p < 0.05). All markers were significantly higher during the attack than in the pain-free period (p < 0.05 for all). Tp-e interval and Tp-e/QTc ratio showed a further significant reduction between the second and third measurements (p = 0.016 and p = 0.004, respectively). P-wave dispersion was significant only for the first-to-second comparison (p = 0.034) and did not differ significantly between the first and third (p = 0.137) or second and third (p = 0.725) measurements. Pulse rate was significantly higher in the migraine group than in controls (p = 0.012). Conclusions: Acute migraine attacks were associated with significant elevation of both atrial and ventricular repolarization markers, with near-normalization during pain-free periods. These findings are consistent with a proposed mechanism of ANS-mediated cardiac electrical instability during acute attacks, although direct confirmation in future studies is required. Clinicians managing acute migraine in the ED should consider ECG monitoring in patients with cardiovascular risk factors. For anesthesiologists and intensivists, the elevated Tp-e and Tp-e/QTc observed ictally indicate that preoperative ECG assessment in migraine patients may be warranted to guide anesthetic planning. Full article

Successful embryo implantation requires dynamic, bidirectional communication between a developmentally competent blastocyst and a receptive endometrium, integrating hormonal, molecular, and immunologic signals. Increasing evidence indicates that endometrial receptivity is critically dependent on a specialized immune microenvironment that supports trophoblast invasion while maintaining maternal tolerance. This review synthesizes current knowledge on the immunologic regulation of implantation, with emphasis on uterine natural killer (uNK) cells, regulatory T cells (Tregs), macrophages, dendritic cells, and cytokine networks. We further examine intracellular signaling pathways—including JAK/STAT, PI3K/AKT, NF-κB, and MAPK—that integrate immune and decidual responses. The bidirectional embryo–endometrium dialogue is explored through embryo-derived mediators such as human chorionic gonadotropin (hCG), cytokines, growth factors, and extracellular vesicles. The endometrium is increasingly recognized as a biosensor of embryo quality, selectively supporting viable embryos. Disruption of this complex communication network is implicated in recurrent implantation failure and early pregnancy loss. Despite substantial mechanistic advances, clinical translation remains limited. Emerging strategies, including immune profiling, microbiome modulation, and extracellular vesicle-based diagnostics, hold promise for precision reproductive medicine. Full article

Background: Breast cancer (BC) survivors frequently experience depression, which is associated with poorer quality of life (QoL), increased healthcare utilization, and worse prognosis. Although traditional Chinese medicine (TCM) is commonly used as an adjunctive therapy among Chinese populations for cancer-related symptom relief and supportive care, population-based evidence remains limited regarding whether integrated Chinese and Western medicine (ICWM) confers measurable benefits over Western medicine (WM) alone in terms of healthcare utilization and survival. Taiwan’s National Health Insurance (NHI) system offers a unique nationwide setting to address this gap because it reimburses patients for both WM and TCM services and captures care from a large number of TCM clinics across Taiwan, allowing evaluation of adjunctive TCM use in routine clinical practice at a scale rarely possible in prior studies. We used emergency department visits, hospitalization, and length of stay as pragmatic proxy indicators of patients’ daily functioning and disease burden. Leveraging a 10-year enrollment window (2004–2013) and up to 17 years of follow-up, we hypothesized that ICWM would be associated with a reduced risk of acute care events and lower healthcare expenditures compared with WM alone. This hypothesis was examined in a large cohort of breast cancer patients treated across nearly 4000 medical facilities nationwide, encompassing the entire Taiwanese population. Methods: A retrospective cohort study was performed to analyze Taiwan’s National Health Insurance Research Database and Cancer Registry. Women newly diagnosed with breast cancer between 2004 and 2013 who subsequently developed depression (≥3 outpatient diagnoses or 1 hospitalization) were followed until death or 31 December 2021. Patients receiving ≥30 cumulative days of TCM after diagnosis were classified as the ICWM group, whereas those receiving <30 days were classified as the WM group. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for all-cause mortality. Healthcare utilization, including emergency department visits, hospitalization, and medical expenditures, was analyzed on a per-person-year basis. Results: A total of 1193 patients were included, with 488 in the WM group and 705 in the ICWM group. Compared with WM users, ICWM users were younger, had lower body mass index, and were more likely to have stage 0–II disease. ICWM was associated with lower total, inpatient, and emergency healthcare expenditures per person-year, as well as fewer emergency visits per person-year, although outpatient and overall visits were higher. In stage-stratified multivariable analyses, ICWM was associated with lower all-cause mortality in both stage 0–II disease (aHR = 0.61, 95% CI: 0.39–0.94) and stage III–IV disease (aHR = 0.38, 95% CI: 0.21–0.67). Kaplan–Meier analyses likewise showed significantly better overall survival in the ICWM group in both early-stage and advanced-stage disease. Conclusions: In this nationwide retrospective cohort of breast cancer patients with depression, adjunctive ICWM was associated with better survival, lower acute care utilization, and lower healthcare expenditures compared with WM alone. However, because quality of life was not directly measured and the study was based on observational data, QoL-related interpretations should be made cautiously, with healthcare utilization outcomes viewed as indirect proxy indicators rather than direct evidence of improved daily QoL. Full article

Introduction: Delirium is associated with worse outcomes in critically ill patients. Factors that could reduce delirium are patients’ environment and maintaining circadian cycles, but whether certain room characteristics improve the incidence of delirium is unclear. Our objective was to investigate whether the presence of windows or doors in patients’ rooms is associated with lower rates of delirium. Methods: In this retrospective, cohort study, adult, medical patients admitted to the Intensive Care Unit (ICU) between 1 January 2024 and 1 July 2024 were identified. Clinical and room characteristics were collected. The primary outcome was the development of Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) positive status. Secondary outcomes included ICU and hospital length of stay (LOS) and mortality. Results: Four hundred fifty-eight (458) patients met inclusion criteria (mean age 61.7 +/− 16.4 years; 51.3% male). In the adjusted multivariate analysis, neither the presence of windows (aOR 2.2; 95% CI 0.7–6.2; p = 0.155) nor closed-format rooms (aOR 0.1; 95% CI 0.0–1.2; p = 0.077) were significantly associated with CAM-ICU positivity. Although an initial association was observed between the presence of windows and increased hospital LOS (aMR 1.4; 95% CI 1.1–1.8; p = 0.008), this did not maintain statistical significance after False Discovery Rate (FDR) correction (q > 0.05). No significant associations were found for other secondary outcomes, including ICU mortality or ICU LOS. Conclusion: Room characteristics were not significantly associated with delirium or secondary outcomes after FDR correction. However, given the study’s limited power to detect moderate differences, these findings do not definitively rule out an architectural influence on delirium and warrant further investigation in larger cohorts. Studies with more discrete measurement of room characteristics are needed to investigate these associations further. Full article

Oral and Maxillofacial Surgery (OMFS) is a surgical specialty with a distinctive position at the intersection of medicine and dentistry. This unique expertise enables reliable reconstructions of complex head and neck defects, with a focus on function, esthetics, and quality of life. This review examines the historical progression, current practices, and prospective directions of head and neck reconstruction, with particular emphasis on the essential contributions of Oral and Maxillofacial Surgeons (OMSs). Beginning with early reconstructive efforts in ancient civilizations and progressing through the transformative advancements of the Renaissance, the introduction of anesthesia and antiseptics, and innovations during periods of war, the specialty has evolved in response to increasing clinical complexity. The contemporary era is characterized by the integration of microvascular reconstruction, dental rehabilitation, and advanced imaging modalities, enhancing the restoration of occlusal function, facial aesthetics, and overall quality of life. Emerging innovations such as patient-specific three-dimensional printed hardware, tissue engineering, regenerative medicine, artificial intelligence, and supermicrosurgical techniques are expected to further reshape reconstructive approaches. These technological advances aim to reduce the number of surgical steps, improve biological reconstruction, and enhance diagnostic and planning capabilities. However, they also raise ethical considerations and validation challenges that warrant careful assessment. In conclusion, Oral and Maxillofacial Surgeons continue to play a central and expanding role in head and neck reconstruction and rehabilitation. Owing to comprehensive training and technological expertise, the specialty is uniquely positioned to advance value-based, multidisciplinary care while persistently striving to improve functional, aesthetic, and quality-of-life outcomes for patients with complex craniofacial defects. Full article

The emergence of vancomycin-intermediate Staphylococcus aureus (VISA) threatens the efficacy of this last-line antibiotic. The GraSR two-component system is frequently mutated in VISA strains. Here, we demonstrate that the GraS(T136I) point mutation, identified in the clinical VISA isolate XN108, is a key determinant of reduced vancomycin susceptibility. Introducing this mutation into the susceptible strain Newman increased the vancomycin MIC from 1.5 to 4 mg/L, while its reversion in XN108 decreased the MIC from 12 to 8 mg/L. The mutation conferred common phenotypes, including thickened cell wall, decreased autolysis, and reduced cell surface negative charge via upregulation of the dltABCD operon and mprF. Notably, the GraS(T136I) mutation also upregulated virulence genes (efb, hlb, sbi, hld) and enhanced hemolytic activity. Interestingly, despite this hypervirulent profile, the mutant showed impaired long-term survival within macrophages. Our study reveals that a single GraSR mutation can co-regulate vancomycin resistance and virulence, offering new insights into the adaptation of S. aureus to antibiotic pressure. Full article

Polymer-based nanoparticle systems have emerged as a versatile platform for advancing precision medicine by enabling controlled, targeted, and multifunctional drug delivery. This narrative review synthesizes recent progress in the design, functionalization, and clinical translation of polymer-based nanoparticles, with a focused scope on drug delivery, diagnostics, theranostics, nanosponges, and regenerative medicine. Specifically, it highlights three key insights: (i) surface engineering strategies, including ligand conjugation and stealth coatings, substantially enhance targeting specificity and reduce off-target toxicity; (ii) stimulus-responsive polymers enable spatiotemporally controlled drug release, improving therapeutic outcomes in complex disease microenvironments; and (iii) integration with artificial intelligence (AI) supports the rational design of personalized nanomedicines based on patient-specific molecular profiles. The innovative nature of this review lies in its comprehensive approach, which combines material design parameters with clinical outcomes and the barriers to implementation. Despite significant progress, serious challenges remain, including scalable and reproducible manufacturing, regulatory harmonization, and comprehensive long-term biosafety assessment. In the future, the priority should be to develop reliable manufacturing processes, a harmonized regulatory framework, and data-driven, clinically validated design methodologies. Overall, polymer-based nanoparticles are poised to redefine targeted therapy, but their clinical impact will depend on bridging the gap between laboratory innovation and scalable, safe, and personalized medical applications. Full article