Search Results (11,321)

Background/Objectives: The rising global prevalence of inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, has resulted in an increase in the number of affected patients requiring dental care. The heightened risk of Clostridioides difficile infection (CDI) in IBD patients, particularly when exposed to commonly used dental antibiotics, is attributable to their altered gut microbiota and frequent immunosuppressive therapy. The objective of this review is to evaluate current antibiotic strategies for dental management in IBD and to identify safe and effective alternatives that minimise CDI risk. Methods: A narrative review was conducted in accordance with the SANRA guidelines. A comprehensive analysis of literature sourced from PubMed, Embase, Scopus, and Google Scholar was conducted. Results: The available evidence suggests that first- and second-line dental antibiotics—amoxicillin, ampicillin, and clindamycin—carry the highest risk of CDI. In contrast, metronidazole, which exhibits a comparable antimicrobial spectrum, has been shown to possess significantly reduced CDI potential and minimal disruption of gut microbiota. The utilisation of emerging local delivery systems, such as platelet-rich fibrin (PRF), has the potential to further reduce systemic antibiotic exposure. The adjunctive use of probiotics, prebiotics and synbiotics has been demonstrated to have the capacity to maintain microbial balance during therapy. Conclusions: Tailored, microbiome-conscious antibiotic strategies are essential in dental management of IBD patients. Further clinical research is needed to develop evidence-based guidelines and validate promising adjunctive approaches. Full article

Eosinophilic esophagitis (EoE) has emerged as a distinct clinicopathological entity and a major cause of upper gastrointestinal morbidity worldwide. Once misinterpreted as a variant of Gastroesophageal Reflux Disease (GERD), its unique identity as an immune-mediated inflammatory disease was solidified by foundational studies in the early 1990s. This discursive review synthesizes key findings from peer-reviewed literature to outline the evolution of EoE’s diagnosis and management. The review highlights that a definitive diagnosis is now a multidisciplinary process that integrates clinical symptoms, characteristic endoscopic findings, and, most critically, a comprehensive histopathological evaluation of esophageal biopsies. It emphasizes the limitations of relying on a single eosinophil count and underscores the value of ancillary histological features and the Histologic Scoring System, which provides a more nuanced and predictive assessment of disease activity. The review also discusses the evolving understanding of PPI-responsive esophageal eosinophilia as a subtype of EoE, streamlining the diagnostic approach. In conclusion, while EoE is a chronic condition that can lead to significant esophageal remodeling if untreated, a robust diagnostic framework and a range of effective therapies are now available to manage the disease, though a continued lack of clinical awareness remains a key challenge. Full article

Multiple Sclerosis (MS) therapies effectively modulate peripheral immune responses but largely fail to promote neural repair within the central nervous system. This review evaluates whether psychedelic compounds (PSYs), via 5-HT2A activation, can fill a critical therapeutic gap: the need for agents that simultaneously suppress neuroinflammation and promote regeneration. We dissect the evidence suggesting PSYs can reprogram the neuroimmune milieu by downregulating key pro-inflammatory cytokines (e.g., TNF-α, IL-6) in glial cells while concurrently upregulating crucial neurotrophic factors (e.g., BDNF) that promote synaptic plasticity and oligodendrocyte support. However, we argue that the current evidence, largely derived from non-specific inflammation models, is insufficient to predict clinical efficacy in an autoimmune disease like MS. We critically analyze the significant translational barriers—from cardiovascular and psychiatric risks to profound legal and ethical challenges—that temper the immediate clinical promise. Finally, we propose a forward-looking perspective, suggesting that the true value of PSYs may lie not in their direct clinical use, but in uncovering novel therapeutic pathways. The emergence of non-hallucinogenic, functionally selective 5-HT2A agonists, inspired by psychedelic pharmacology, represents a more viable strategy to harness these mechanisms for MS therapy, demanding rigorous preclinical validation in disease-relevant models. Full article

Background/Objectives: Developing effective therapies for patients with triple-negative breast cancer (TNBC) remains an urgent clinical priority. Compared with other subtypes, the basal B type of TNBC exhibits a less differentiated and mesenchymal-like phenotype that models highly invasive and metastatic breast malignancies. To target metastatic TNBC, our current study sought to identify effective therapeutic drugs and the underlying mechanisms. Methods: A systematic screening of 140 FDA-approved drugs was conducted for repurposing using live-cell imaging-based wound-healing assays. Candidate efficacy was validated by in vitro transwell invasion assays, in vivo allograft/xenograft models, and ex vivo three-dimensional air–liquid interface (ALI) and patient-derived organoid (PDO) cultures. Results: Dasatinib emerged as a promising anti-cancer agent in aggressive TNBC, particularly in the basal B type, with high ETS proto-oncogene 1 (ETS1) expression. Mechanistically, dasatinib disrupts the actin cytoskeleton, impairing cell motility and migration while concurrently suppressing the expression of ETS1 and matrix metalloproteinase-3 (MMP3) to remodel the extracellular matrix (ECM) and inhibit invasion. Moreover, the combination of dasatinib with an anti-programmed cell death protein-1 (PD-1) antibody represents a potential therapeutic strategy. Conclusions: These findings highlight dasatinib as a potential therapeutic option for metastatic TNBC and suggest that selecting patients with high ETS1 expression may optimize treatment response. Full article

Osteoarthritis (OA) is a leading cause of pain, disability, and healthcare utilization worldwide, yet clinical diagnosis commonly occurs after irreversible structural damage, limiting opportunities for prevention. Advances in molecular profiling, quantitative imaging, biomechanics, and longitudinal cohort studies have identified a reproducible preclinical interval, termed pre-osteoarthritis (pre-OA), during which molecular, compositional, and biomechanical perturbations emerge long before persistent symptoms or radiographic changes. The recognition of pre-OA as a distinct pathophysiologically meaningful stage supports the possibility of earlier targeted interception. Cross-disciplinary studies have consistently reported very early cartilage matrix alterations, pro-catabolic and low-grade inflammatory signatures, and biomechanical and biochemical marker shifts, indicating a critical detection window. Building on these findings, I propose a pheno-endotype-oriented framework to align emerging detection strategies with interventions matched to underlying mechanisms, including lifestyle modification, metabolic modulation, and candidate disease-modifying therapies. These conceptual models are presented for evaluation by clinicians, researchers, and healthcare decision-makers. Translation into practice remains constrained by heterogeneous case definitions, lack of validated thresholds, variability in assays and imaging standards, and limited prospective trials addressing early disease diagnosis. Addressing these barriers will require harmonized consensus criteria, standardized analytic protocols, prospective validation cohorts enriched with high-risk populations, and adaptive biomarker-driven trial designs. Reconceptualizing OA as a continuum with an identifiable preclinical stage provides a foundation for earlier personalized interception strategies with the potential to alter the natural history of the disease and reduce its global burden. If translated successfully, early identification and targeted interception of pre-OA could transform OA from an inevitable consequence of aging into a largely preventable and manageable condition, which would be a paradigm shift with major clinical and public health implications. Full article

Sirtuin 6 (SIRT6), a (Nicotinamide adenine dinucleotide) NAD⁺-dependent deacylase and mono- (adenosine diphosphate) ADP-ribosyltransferase, is increasingly recognized as a pivotal regulator of genomic stability, metabolic reprogramming, and epigenetic remodeling. This review synthesizes current evidence on the dual roles of SIRT6 in cancer, highlighting its context-dependent functions as both a tumor suppressor and promoter across various malignancies. We detail its involvement in DNA damage sensing, repair coordination, glycolytic regulation, and chromatin modification, and discuss how these mechanisms contribute to tumor initiation, progression, and therapy resistance. Emerging therapeutic strategies targeting SIRT6, including small-molecule modulators, genetic interventions, and combination therapies, are critically evaluated. Our analysis underscores the necessity for context-specific therapeutic targeting, and pharmacological modulation of SIRT6 represents a promising avenue for precision oncology. Full article

Introduction: Cerebral palsy (CP) affects motor function development, requiring intensive rehabilitation. Virtual reality (VR) interventions show promise for improving motor learning through immersive, engaging experiences. This systematic review and meta-analysis evaluated VR effectiveness for motor function improvement in children with CP. Methods: Following PRISMA 2020 guidelines, we searched six electronic databases from inception to 15 June 2025. Included studies compared VR interventions versus control conditions in children with CP (ages 4–18 years), measuring motor function outcomes. Sixteen studies (n = 397 participants) met the inclusion criteria for qualitative synthesis. Random-effects models, subgroup analyses, and meta-regression were performed. Evidence certainty was evaluated using GRADE methodology. Results: Five randomized controlled trials with complete extractable data (N = 190 participants, 40 effect sizes) were included in the primary quantitative meta-analysis. The primary meta-analysis demonstrated moderate overall effects favoring VR interventions (standardized mean difference [SMD] = 0.41, 95% CI [0.16, 0.66], p = 0.001; I² = 74%); however, GRADE quality was rated LOW due to risk of bias and imprecision. Technology type critically moderated outcomes: robotic exoskeleton systems showed large effects (SMD = 1.00, p = 0.002), commercial gaming platforms showed small-to-moderate effects (SMD = 0.38, p = 0.013), while custom VR systems showed no significant benefit (SMD = 0.01, p = 0.905; Q = 29.00, p < 0.001). Age emerged as the strongest moderator: children (<6 years) demonstrated significant benefits (SMD = 0.98, p < 0.001), whereas school-age children (6–12 years) showed no effect (SMD = −0.01, p = 0.903; meta-regression slope = −0.236 per year, p < 0.001). Dose–response was non-linear, with optimal benefits at 30–40 intervention hours and diminishing returns beyond 50 h. VR proved superior to standard care (SMD = 0.83) but not to active intensive therapies (SMD = 0.09). The safety profile was favorable (1.3% adverse event rate, no serious events). No publication bias was detected. Conclusions: VR interventions demonstrated moderate, technology-dependent motor function improvements in children with CP, with benefits concentrated in young children using robotic systems. Evidence certainty is low, requiring further high-quality trials. Implementation should prioritize robotic VR for children with 30–40 h protocols. Full article

Nasopharyngeal carcinoma (NPC) is a head and neck malignancy strongly associated with Epstein–Barr virus (EBV) infection and characterized by high radiosensitivity but frequent therapy resistance. Despite advances in radiotherapy, chemotherapy, and immunotherapy, relapse and metastasis remain major challenges, underscoring the need for novel therapeutic approaches. This review aims to provide an integrated overview of the molecular mechanisms governing ferroptosis in NPC and to clarify how these pathways contribute to therapy resistance while revealing potential therapeutic vulnerabilities. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising target in NPC. Core regulators include the system xCT–GSH–GPX4 antioxidant axis, iron metabolism, and lipid remodeling enzymes such as ACSL4, with epigenetic modifiers (METTL3, IGF2BP2, HOXA9) and EBV-driven signaling further shaping ferroptosis responses. EBV-driven oncogenic programs substantially reshape ferroptosis sensitivity in NPC by activating the Nrf2/Keap1 antioxidant axis, stabilizing SLC7A11 and GPX4, and modulating iron and redox metabolism. These viral mechanisms suppress ferroptotic stress and contribute to both radioresistance and chemoresistance. Suppression of ferroptosis underlies both radioresistance and chemoresistance, whereas restoration of ferroptosis re-sensitizes tumors to treatment. Natural compounds including solasodine, berberine, cucurbitacin B, and celastrol-curcumin combinations, as well as pharmacologic modulators such as HO-1 inhibitors and GPX4 antagonists, have shown ferroptosis-inducing effects in preclinical models, although their translational potential remains to be clarified. Nanotechnology-based platforms (e.g., Bi₂Se₃ nanosheet hydrogels) further enhance efficacy and reduce toxicity by enabling controlled drug delivery. Biomarker discovery, encompassing ferroptosis-related gene signatures, epigenetic regulators, immune infiltration patterns, EBV DNA load, and on-treatment redox metabolites, provides a foundation for patient stratification. Integration of ferroptosis modulation with radiotherapy, chemotherapy, and immunotherapy represents a compelling strategy to overcome therapy resistance. In synthesizing these findings, this review highlights both the mechanistic basis and the translational promise of ferroptosis modulation as a strategy to overcome treatment resistance in NPC. Future directions include biomarker validation, optimization of drug delivery, early-phase clinical trial development, and multidisciplinary collaboration to balance ferroptosis induction in tumors while protecting normal tissues. Collectively, ferroptosis is emerging as both a vulnerability and a therapeutic opportunity for improving outcomes in NPC. Full article

Multi-target drug design represents a paradigm shift in tackling the complexity and heterogeneity of diseases such as cancer. Conventional single-target therapies frequently face limitations due to network redundancy, pathway compensation, and adaptive resistance mechanisms. In contrast, deep generative models, empowered by advanced artificial intelligence algorithms, provide scalable and versatile platforms for the de novo generation and optimization of small molecules with activity across multiple therapeutic targets. This review provides a comprehensive overview of the recent landscape of AI-driven deep generative modeling for multi-target drug discovery, highlighting breakthroughs in model architectures, molecular representations, and goal-directed optimization strategies. We also examine the emergence of self-improving learning systems, closed-loop frameworks that iteratively refine molecular candidates through integrated feedback, as a transformative approach to adaptive drug design. Finally, key challenges, current limitations, and emerging trends are discussed to guide the evolution of next-generation intelligent and autonomous drug discovery pipelines for multi-target therapeutics. Full article

Background/Objectives: Chimeric antigen receptor (CAR) T cells have shown remarkable clinical success in certain blood cancers but remain largely ineffective in solid tumors. A major reason for this limitation is the hostile tumor microenvironment, which restricts oxygen and nutrients while producing toxic metabolites that suppress immune cell activity. This review aims to examine how targeted metabolic reprogramming can overcome these barriers and improve CAR T cell performance. Methods: We evaluated preclinical and translational studies that focused on engineering CAR T cells to resist hypoxia, improve nutrient utilization, reduce metabolic exhaustion, and counteract suppressive metabolites in solid tumors. Results: Emerging strategies include engineering resistance to low oxygen and high lactate, enhancing nutrient uptake through transporter overexpression, and blocking inhibitory pathways such as those driven by adenosine. These approaches improve CAR T cell persistence, memory formation, and cytotoxic function in challenging tumor environments. Conclusions: Integrating metabolic reprogramming with conventional CAR design is essential to unlock the full potential of CAR T therapy against solid tumors. Continued innovation in this area will be critical for translating laboratory advances into effective clinical treatments. Full article

The global spread of Monkeypox virus (MPXV) has emerged as a major public health concern, with the 2022 outbreak underscoring the urgent need for effective antiviral therapies. Current treatment options are limited because no drugs specifically target Mpox, and existing recommendations rely on repurposed smallpox antivirals that may cause resistance. This highlights the critical need for novel therapeutic agents targeting key viral and host factors involved in MPXV pathogenesis. Medicinal plants provide a rich reservoir of bioactive compounds with potential antiviral activity, particularly in low- and middle-income countries where they play an essential role in healthcare. To address this issue, we conducted a review exploring innovative in silico approaches for natural product-based drug discovery against MPXV. Computational studies identified phytochemicals such as curcumin, punicalagin, rosmarinic acid, and quercitrin with strong affinities for key viral proteins including DNA polymerase, TMPK, DdRp, A42R, MTase, p37, and envelope proteins and favorable pharmacokinetic profiles Despite these promising findings, fragmented biological datasets, viral mutability, and limited in vitro and in vivo validation hinder clinical translation. Our analysis highlights integrating AI-driven virtual screening with experimental validation to accelerate MPXV drug discovery, providing a scalable framework for managing emerging viral threats. Full article

Background and Objectives: Postoperative enterocutaneous fistulas, defined as abnormal communications between the intestinal lumen and the skin, represent one of the most challenging complications following abdominal surgery. Regenerative medicine, particularly through the use of adipose-derived mesenchymal stem cells (ADSCs), has recently emerged as a promising therapeutic option for chronic inflammatory and non-healing conditions. However, most studies have focused on complex perianal fistulas in Crohn’s disease. This prospective, single-center observational study aimed to evaluate the feasibility, safety, and preliminary efficacy of autologous ADSC injection in patients with complex postoperative enterocutaneous fistulas. Materials and Methods: Six patients (four males and two females) with persistent postoperative enterocutaneous fistulas were enrolled. Autologous adipose tissue was harvested via lipoaspiration from the abdominal wall or flank and processed in a GMP-certified laboratory to obtain a suspension containing 5–10 million viable ADSCs in 3–5 mL of isotonic solution. ADSCs were injected directly into the fistulous tract under ultrasound guidance, following CT image review. Clinical and radiologic follow-up was performed to assess closure and output reduction. Results: Four of the six patients (66.7%) achieved complete fistula closure, with no residual output and radiologic confirmation of healing within 4–12 weeks. One patient (16.7%) demonstrated a significant reduction in fistula output (>80%), while another (16.7%) showed minimal improvement and subsequently required surgical repair at 6 weeks. No complications related to ADSC administration were observed. Conclusions: Autologous ADSC therapy appears to be a feasible, safe, and minimally invasive option for managing complex postoperative enterocutaneous fistulas. These encouraging preliminary results—showing complete closure in two-thirds of treated patients—support further investigation through larger, controlled trials to validate these findings and optimize treatment protocols. Full article

Gastroesophageal cancer (GEC) represents a global health burden, with rising incidence and high mortality. Despite advancements in early detection and systemic therapies, outcomes remain poor, especially in advanced stages. Management requires a multidisciplinary, multimodal approach that integrates surgery, chemotherapy, radiotherapy, targeted agents, and immunotherapy, tailored by tumor histology, location, and molecular profile. For localized disease, perioperative chemotherapy or chemoradiotherapy is standard, with adjuvant immunotherapy now emerging in selected high-risk cases. In metastatic or unresectable settings, systemic therapy forms the backbone of treatment, with biomarker-driven regimens targeting HER2, PD-L1, MSI-H/dMMR, and CLDN18.2, offering improved outcomes. Novel agents and combinations, including bispecific antibodies, FGFR2 inhibitors, and immunotherapy-based strategies, are actively being explored in clinical trials. This review provides a comprehensive overview of the evolving therapeutic landscape of GEC. It emphasizes the growing role of precision medicine and the integration of emerging clinical data into practice. Full article

Artificial Intelligence (AI) is reshaping pharmacy practice by enhancing decision-making, personalizing therapy, and improving medication safety. AI applications now span drug discovery, clinical decision support, and adherence monitoring. This narrative review explores key innovations, practical applications, and the implications of AI integration in pharmacy practice, with a focus on emerging tools, pharmacist roles, and ethical considerations. The review was conducted using literature from PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Thematic synthesis included AI-based drug interaction checkers, Clinical Decision Support Systems (CDSS), telepharmacy, pharmacogenomics, and predictive analytics. AI enhances clinical decision-making, reduces medication errors, and supports precision medicine. AI tools support pharmacists and healthcare professionals in optimizing care. However, data privacy, algorithmic bias, and workflow integration continue to pose challenges. AI holds transformative potential in pharmacy, though its integration requires overcoming ethical and workflow-related challenges. Ethical and regulatory vigilance, coupled with pharmacist training and interdisciplinary collaboration, is essential to realize the full potential of AI. Full article

Alzheimer’s disease (AD) is the most prevalent cause of dementia, characterized by progressive cognitive decline, amyloid-β (Aβ) plaques, and neurofibrillary tangles composed of hyperphosphorylated tau protein. Other tauopathies, including frontotemporal lobar degeneration (FTLD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) share pathological hallmarks centered on abnormal tau biology. Increasing evidence highlights the role of post-translational modifications in modulating these pathogenic processes. Among these, glycosylation, the enzymatic attachment of glycans to proteins or lipids, has emerged as a critical regulator of protein folding, trafficking, aggregation, and clearance. Both N-linked glycosylation (N-glycosylation) and O-linked glycosylation (O-glycosylation) influence tau stability, Aβ processing, receptor signaling, synaptic integrity, and neuroinflammation. Dysregulated glycosylation patterns have been documented in brains and cerebrospinal fluid (CSF) of AD patients, suggesting biomarker potential and novel therapeutic targets. Moreover, glycosyltransferases and glycosidases show altered expression in neurodegeneration, linking metabolic and inflammatory pathways to tauopathy progression. This review synthesizes current evidence on the implications and consequences of glycosylation in AD and other tauopathies, integrating mechanistic, pathological, and clinical findings. We also discuss advances in glycoproteomics, the interplay between glycosylation and phosphorylation, and the translational potential of targeting glycosylation pathways for diagnosis and therapy. Full article