Search Results (24,680)

Anxiety and depression are common comorbidities in patients with chronic obstructive pulmonary disease (COPD), which can contribute to increased morbidity, reduced quality of life, and worse clinical outcomes. Nevertheless, these psychological conditions remain largely overlooked. This narrative review includes studies published between 1983 and 2025 to synthesise the current evidence on the risk factors, clinical impacts, and therapeutic strategies for these comorbidities. While the exact mechanisms leading to their increased prevalence are not fully understood, growing evidence implicates a combination of biological (e.g., systemic inflammation), social (e.g., isolation and stigma), and behavioural (e.g., smoking and inactivity) factors. Despite current guidelines recommending the identification and management of these comorbidities in COPD, they are not currently included in COPD assessments. Undetected and unmanaged anxiety and depression have serious consequences, including poor self-management, non-adherence to medications, increased risk of exacerbation and hospitalisations, and even mortality; thus, there is a need to incorporate screening as part of COPD assessments. There is robust evidence showing that pulmonary rehabilitation, a core non-pharmacological intervention, can improve mood symptoms, enhance functional capacity, and foster psychosocial resilience. Psychological therapies such as cognitive behavioural therapy (CBT), mindfulness-based approaches, and supportive counselling have also demonstrated value in reducing emotional distress and improving coping mechanisms. Pharmacological therapies, particularly selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs), are commonly prescribed in moderate to severe cases or when non-pharmacological approaches prove inadequate. However, the evidence for their efficacy in COPD populations is mixed, with concerns about adverse respiratory outcomes and high discontinuation rates due to side effects. There are also barriers to optimal care, including underdiagnosis, a lack of screening protocols, limited provider training, stigma, and fragmented multidisciplinary coordination. A multidisciplinary, biopsychosocial approach is essential to ensure early identification, integrated care, and improved outcomes for patients with COPD. Full article

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), is strongly associated with metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD). IH exacerbates MASLD progression through oxidative stress, inflammation, and lipid accumulation. This study aims to investigate the impact of oxygen normalization on metabolic dysfunction in OSA patients using continuous positive airway pressure (CPAP) therapy, and in mice exposed to IH followed by a reoxygenation period. In the clinical study, 76 participants (44 OSA patients and 32 controls) were analyzed. OSA patients had higher insulin resistance, triglycerides, very low density lipoprotein (VLDL) content, and liver enzyme levels, along with a higher prevalence of liver steatosis. After 18 months of CPAP therapy, OSA patients showed significant improvements in insulin resistance, lipid profiles (total cholesterol and VLDL), liver function markers (AST and albumin), and steatosis risk scores (Fatty Liver Index and OWLiver test). In the experimental study, IH induced hepatic lipid accumulation, oxidative stress, and inflammation, and reoxygenation reversed these deleterious effects in mice. At the molecular level, IH downregulated fatty acid oxidation (FAO)-related genes, thus impairing the FAO process. Reoxygenation maintained elevated levels of lipogenic genes but restored FAO gene expression and activity, suggesting enhanced lipid clearance despite ongoing lipogenesis. Indeed, serum β hydroxybutyrate, a key marker of hepatic FAO in patients, was impaired in OSA patients but normalized after CPAP therapy, supporting improved FAO function. CPAP therapy improves lipid profiles, liver function, and MASLD progression in OSA patients. Experimental findings highlight the therapeutic potential of oxygen normalization in reversing IH-induced liver damage by FAO pathway restoration, indicating a metabolic reprogramming in the liver. Full article

Obstructive sleep apnea syndrome (OSAS) is a prevalent disorder with significant systemic and oral health consequences. This narrative review synthesizes the current knowledge on the interplay between dental health and sleep apnea, highlighting the expanding role of dentists in the screening, early detection, and management of OSAS. Validated questionnaires, anatomical assessments, and anthropometric measurements have enhanced dentists’ capacity for early screening. However, knowledge and training gaps remain, particularly in low- and middle-income countries. Dentists are uniquely positioned to identify anatomical and oral risk factors, facilitate referrals for diagnosis, and provide therapeutic interventions such as oral appliance therapy. Interdisciplinary collaboration between dental and medical professionals is essential to improve early detection, treatment outcomes, and patient quality of life. Enhancing education, standardizing protocols, and integrating dentists into multidisciplinary care pathways are critical steps for advancing the management of sleep apnea. Full article

Atrial fibrillation is the most frequent arrhythmia in elderly subjects. Cancer currently represents one of the most important causes of mortality and morbidity in the world. Often, the two pathologies coexist. Several pathophysiological mechanisms can lead to an increased risk of atrial fibrillation and cancer. Additionally, the same therapies used for cancer can increase the risk of developing atrial fibrillation. Our review aims to describe the pathophysiological mechanisms that promote the development of atrial fibrillation in cancer patients and explain the therapeutic opportunities and challenges of treating atrial fibrillation in patients with cancer. Full article

Background: Relapsed/refractory acute myeloid leukemia (R/R AML) remains a therapeutic challenge due to disease heterogeneity, resistance mechanisms, and poor tolerability to intensive regimens. Venetoclax (VEN), a BCL-2 inhibitor, has shown promise in combination with hypomethylating agents (HMAs), but data on response timing in the R/R setting are limited. The aim of this study was to assess the efficacy, safety, and kinetics of response to HMA-VEN therapy in a real-world cohort of R/R AML patients, with particular focus on early versus late responders. Methods: This prospective single-center study included 33 adult patients with R/R AML treated with VEN plus either azacitidine (AZA) or decitabine (DEC) from 2018 to 2021. The primary endpoint was the composite complete remission (cCR) rate and the rate of early and late response, respectively, occurring within two cycles of therapy or later; secondary endpoints included overall survival (OS), relapse-free survival (RFS), time to relapse (TTR), and safety. Results: The cCR was 58%, with complete remission (CR) or CR with incomplete recovery (CRi) achieved in 52% of patients. Median OS was 9 months. No significant differences in OS or TTR were observed between early (≤2 cycles) and late (>2 cycles) responders. Eight responders (42%) underwent allogeneic hematopoietic stem cell transplantation (HSCT), with comparable transplant rates in both groups of responders. Toxicity was manageable. Grade 3–4 neutropenia occurred in all patients, and febrile neutropenia occurred in 44% of patients. An Eastern Cooperative Oncology Group (ECOG) score >2 was associated with inferior response and shorter treatment duration. Conclusions: HMA-VEN therapy is effective and safe in R/R AML, including for patients with delayed responses. The absence of a prognostic disadvantage for late responders supports flexible treatment schedules and suggests that the continuation of therapy may be beneficial even without early blast clearance. Tailored approaches based on performance status and comorbidities are warranted, and future studies should incorporate minimal residual disease (MRD)-based monitoring to refine response assessment. Full article

Background: This systematic review evaluates the efficacy of rehabilitation-focused exercise interventions for lumbar degenerative disc disease (DDD), a leading cause of chronic low back pain. Methods: Following PRISMA guidelines, a comprehensive search was conducted across international and regional databases (PubMed, Scopus, Web of Science, Magiran, SID, and Noormags) covering the period from January 2010 to January 2025. The review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420251088811. Using keywords such as “lumbar DDD,” “exercise therapy,” and “rehabilitation,” a total of 2495 records were identified. After screening, 20 studies—including clinical trials, quasi-experimental, and experimental designs—met the inclusion criteria and were assessed using the McMaster Critical Review Form for Quantitative Studies. Results: Interventions such as hydrotherapy, core stability training, Pilates, and suspension exercises were found to significantly reduce pain and improve functional outcomes. While multimodal approaches (e.g., aquatic exercise combined with acupuncture) showed positive effects, the comparative studies revealed no significant differences between modalities. Suspension training demonstrated superior efficacy in pain reduction compared to isolated core stability exercises. The methodological quality of included studies ranged from good to excellent, with the majority rated as very good or excellent (McMaster scores: 8 “excellent,” 7 “very good,” and 5 “good”). Common limitations among the studies included methodological heterogeneity, small sample sizes (n = 14–30), and insufficient long-term follow-up. Conclusions: Exercise-based rehabilitation is an effective strategy for managing lumbar DDD. Evidence particularly supports the use of suspension training and aquatic therapy for superior improvements in pain and functional outcomes. Future research should aim to adopt standardized protocols, recruit larger sample sizes, and include extended follow-up periods to produce more robust and generalizable findings. Full article

Microtubules play a key role in cell division and cell migration. Thus, microtubule-targeting agents (MTAs) are pivotal in cancer therapy due to their ability to disrupt cell division microtubule dynamics. Traditionally divided into stabilizers and destabilizers, MTAs are increasingly being repurposed for central nervous system (CNS) applications, including brain malignancies such as gliomas and neurodegenerative diseases like Alzheimer’s and Parkinson’s. Microtubule-stabilizing agents, such as taxanes and epothilones, promote microtubule assembly and have shown efficacy in both tumour suppression and neuronal repair, though their CNS use is hindered by blood–brain barrier (BBB) permeability and neurotoxicity. Destabilizing agents, including colchicine-site and vinca domain binders, offer potent anticancer effects but pose greater risks for neuronal toxicity. This review highlights the mapping of nine distinct tubulin binding pockets—including classical (taxane, vinca, colchicine) and emerging (tumabulin, pironetin) sites—that offer new pharmacological entry points. We summarize the recent advances in structural biology and drug design, enabling MTAs to move beyond anti-mitotic roles, unlocking applications in both cancer and neurodegeneration for next-generation MTAs with enhanced specificity and BBB penetration. We further discuss the therapeutic potential of combination strategies, including MTAs with radiation, histone deacetylase (HDAC) inhibitors, or antibody–drug conjugates, that show synergistic effects in glioblastoma models. Furthermore, innovative delivery systems like nanoparticles and liposomes are enhancing CNS drug delivery. Overall, MTAs continue to evolve as multifunctional tools with expanding applications across oncology and neurology, with future therapies focusing on optimizing efficacy, reducing toxicity, and overcoming therapeutic resistance in brain-related diseases. Full article

Atherosclerosis is a progressive, multifactorial disease driven by the interplay of lipid dysregulation, chronic inflammation, oxidative stress, and maladaptive vascular remodeling. Despite advances in systemic lipid-lowering and anti-inflammatory therapies, residual cardiovascular risk persists, highlighting the need for more precise interventions. Targeted drug delivery represents a transformative strategy, offering the potential to modulate key pathogenic processes within atherosclerotic plaques while minimizing systemic exposure and off-target effects. Recent innovations span a diverse array of platforms, including nanoparticles, liposomes, exosomes, polymeric carriers, and metal–organic frameworks (MOFs), engineered to engage distinct pathological features such as inflamed endothelium, dysfunctional macrophages, oxidative microenvironments, and aberrant lipid metabolism. Ligand-based, biomimetic, and stimuli-responsive delivery systems further enhance spatial and temporal precision. In parallel, advances in in-silico modeling and imaging-guided approaches are accelerating the rational design of multifunctional nanotherapeutics with theranostic capabilities. Beyond targeting lipids and inflammation, emerging strategies seek to modulate immune checkpoints, restore endothelial homeostasis, and reprogram plaque-resident macrophages. This review provides an integrated overview of the mechanistic underpinnings of atherogenesis and highlights state-of-the-art targeted delivery systems under preclinical and clinical investigation. By synthesizing recent advances, we aim to elucidate how precision-guided drug delivery is reshaping the therapeutic landscape of atherosclerosis and to chart future directions toward clinical translation and personalized vascular medicine. Full article

Cell-based therapies emerge as potential treatment options for various debilitating diseases. Preclinical research and clinical studies involving cells increased exponentially in the past decade. In addition to cell-based approaches, the use of extracellular vesicles (EVs), which are released by nearly all cell types, emerged as a promising cell-free alternative. Those approaches are also being explored in the field of ophthalmology. Several clinical trials involving EVs are underway to develop potential treatments for advanced ocular surface diseases, including corneal disorders, injuries, and dry eye disease. The cargo carried by EVs has been shown to include a diverse array of functional molecules such as transcription factors, cytokines, growth factors, mRNA, tRNA, rRNA, miRNA, and fragments of dsDNA. While the molecular composition of EVs is already well characterised, the specific activity of these molecules upon delivery to recipient cells remains poorly understood. In this review, we summarise recent studies investigating the bioactive molecules within EVs shown to influence or modulate cellular activity on the ocular surface. Among these, various miRNAs have most commonly been identified as therapeutic agents targeting distinct molecular pathways. The EVs studied were predominantly derived from various mesenchymal stem cells. Full article

Over the past decade, numerous innovative immunotherapy strategies have transformed the treatment of cancer and improved the survival of patients unresponsive to conventional chemotherapy and radiation therapy. Immune checkpoint inhibition approaches aim to block negative regulatory pathways that limit the function of endogenous T cells, while adoptive cell therapy produces therapeutic T cells with high functionality and defined cancer specificity. While CAR engineering successfully targets cancer surface antigens, TCR engineering enables targeting of the entire cancer proteome, including mutated neo-antigens. To date, TCR engineering strategies have focused on the identification of target cancer antigens recognised by well-characterised therapeutic TCRs. In this review, we explore whether antigen-focused approaches could be complemented by TCR-focused approaches, whereby information of the TCR repertoire of individual patients provides the basis for selecting TCRs to engineer autologous T cells for adoptive cell therapy. We discuss how TCR clonality profiles, distribution in T cell subsets, and bioinformatic screening against continuously improving TCR databases can guide the selection of TCRs for therapeutic application. We further outline in vitro approaches to prioritise TCR candidates to confirm cancer reactivity and exclude recognition of healthy autologous cells, which could provide validation for their therapeutic use even when the target antigen remains unknown. Full article

Background/Objectives: Periodontitis is a chronic infectious inflammatory disorder that affects the supporting structures of the teeth. The gingival epithelium plays a crucial role as a physical and immunological barrier, producing pro-inflammatory cytokines in response to microbial pathogens. Modulation of gingival epithelial function has been proposed as a therapeutic strategy to prevent the progression of periodontal disease. Houttuynia cordata, a perennial herb traditionally used in Asian medicine, is recognized for its anti-inflammatory properties, with documented benefits in the cardiovascular, respiratory, and gastrointestinal systems. However, its potential therapeutic role in oral pathologies, such as periodontitis, remains underexplored. This study aimed to investigate the anti-inflammatory effects of H. cordata extract on interleukin (IL)-1β-stimulated primary gingival keratinocytes (PGKs) subjected to IL-1β-induced inflammatory stress, simulating the conditions encountered during orthodontic treatment. Methods: Inflammation was induced in PGKs using IL-1β, and the impact of H. cordata extract pretreatment was assessed using quantitative real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunoblotting. Results: H. cordata extract significantly downregulated the mRNA and protein expression levels of tumor necrosis factor-alpha, IL-8, and intercellular adhesion molecule-1 in IL-1β-stimulated PGKs without inducing cytotoxicity. Conclusions: These findings suggest that H. cordata holds promise as a preventive agent against periodontitis by attenuating inflammatory responses in gingival epithelial tissues. We believe that our findings will inform the development of prophylactic interventions to reduce periodontitis risk in patients undergoing orthodontic therapy. Full article

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2is), initially developed as antihyperglycemic agents, have emerged as multifunctional therapeutics with profound cardiorenal and metabolic benefits. Their unique insulin-independent mechanism, targeting renal glucose reabsorption, distinguishes them from conventional antidiabetic drugs. Mechanisms and Clinical Evidence: SGLT2is induce glycosuria, reduce hyperglycemia, and promote weight loss through increased caloric excretion. Beyond glycemic control, they modulate tubuloglomerular feedback, attenuate glomerular hyperfiltration, and exert systemic effects via natriuresis, ketone utilization, and anti-inflammatory pathways. Landmark trials (DAPA-HF, EMPEROR-Reduced, CREDENCE, DAPA-CKD) demonstrate robust reductions in heart failure (HF) hospitalizations, cardiovascular mortality, and chronic kidney disease (CKD) progression, irrespective of diabetes status. Adipose Tissue and Metabolic Effects: SGLT2is mitigate obesity-associated adiposopathy by shifting macrophage polarization (M1 to M2), reducing proinflammatory cytokines (TNF-α, IL-6), and enhancing adipose tissue browning (UCP1 upregulation) and mitochondrial biogenesis (via PGC-1α/PPARα). Modest weight loss (~2–4 kg) occurs, though compensatory hyperphagia may limit long-term effects. Emerging Applications: Potential roles in non-alcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), and neurodegenerative disorders are under investigation, driven by pleiotropic effects on metabolism and inflammation. Conclusions: SGLT2is represent a paradigm shift in managing T2DM, HF, and CKD, with expanding implications for metabolic syndrome. Future research should address interindividual variability, combination therapies, and non-glycemic indications to optimize their therapeutic potential. Full article

Dermal fibroblasts, the primary stromal cells of the dermis, exhibit remarkable plasticity in response to various stimuli, playing crucial roles in tissue homeostasis, wound healing, and ECM production. This study examines the molecular mechanisms underlying fibroblast plasticity, including key signaling pathways, epigenetic regulation, and microRNA-mediated control. The impact of aging on ECM synthesis and remodeling is discussed, and the diminished production of vital components such as collagen, elastin, and glycosaminoglycans are highlighted, alongside enhanced ECM degradation through upregulated matrix metalloproteinase activity and accumulation of advanced glycation end products. The process of cellular senescence in dermal fibroblasts is explored, with its role in skin aging and its effects on tissue homeostasis and repair capacity being highlighted. The senescence-associated secretory phenotype (SASP) is examined for its contribution to chronic inflammation and ECM disruption. This review also presents therapeutic perspectives, focusing on senolytics and geroprotectors as promising strategies to combat the negative effects of fibroblast senescence. Current challenges in translating preclinical findings to human therapies are addressed, along with future directions for research in this field. This comprehensive review explores the complex interplay between dermal fibroblast plasticity, cellular senescence, and extracellular matrix (ECM) remodeling in the context of skin aging. In conclusion, understanding the complex interplay between dermal fibroblast plasticity, cellular senescence, and extracellular matrix (ECM) remodeling is essential for developing effective anti-aging interventions, which highlights the need for further research into senolytic and geroprotective therapies to enhance skin health and longevity. This approach has shown promising results in preclinical studies, demonstrating improved skin elasticity and reduced signs of aging. Full article

Obesity, a multifactorial metabolic syndrome driven by genetic–epigenetic crosstalk and environmental determinants, manifests through pathological adipocyte hyperplasia and ectopic lipid deposition. With the limitations of conventional anti-obesity therapies, which are characterized by transient efficacy and adverse pharmacological profiles, the scientific community has intensified efforts to develop plant and fungal polysaccharide therapeutic alternatives. These polysaccharide macromolecules have emerged as promising candidates because of their diverse biological activities and often act as natural prebiotics, exerting beneficial effects through multiple pathways. Plant and fungal polysaccharides can reduce blood glucose levels, alleviate inflammation and oxidative stress, modulate metabolic signaling pathways, inhibit nutrient absorption, and reshape gut microbial composition. These effects have been shown in cellular and animal models and are associated with mechanisms underlying obesity and related metabolic disorders. This review discusses the complexity of obesity and multifaceted role of plant and fungal polysaccharides in alleviating its symptoms and complications. Current knowledge on the anti-obesity properties of plant and fungal polysaccharides is also summarized. We highlight their regulatory effects, potential intervention pathways, and structure–function relationships, thereby providing novel insights into polysaccharide-based strategies for obesity management. Full article

Background: Chronic wounds are a growing clinical challenge due to their prolonged healing time and associated healthcare burden. Combined therapeutic approaches, including topical oxygen therapy (TOT) and negative-pressure wound therapy (NPWT), have shown promise in enhancing wound healing. This pilot exploratory study aimed to assess the clinical effectiveness of combined TOT and NPWT in chronic wound treatment and to explore the prognostic value of selected laboratory and thermographic markers. Methods: Eighteen patients with chronic wounds due to type 2 diabetes mellitus or chronic venous insufficiency were treated with either TOT alone (control group) or TOT combined with NPWT (intervention group). Wound characteristics, thermographic data, and laboratory parameters (NLR, MLR, PLR, CRP, and total protein) were collected at baseline and during therapy. The primary endpoints were the total treatment duration and complete wound closure. Statistical analyses were exploratory and used non-parametric tests, correlation analyses, and simple linear regression. Results: Ulcer duration was significantly associated with the wound surface area. Lower serum total protein levels correlated negatively with ulcer duration, wound size, and granulation tissue area. A significant reduction in treatment duration was observed in the intervention group compared to the controls. One strong correlation was found between MLR and peripheral wound temperature on day 7 in the control group. No significant group differences were observed in wound size or thermographic measures after one week of treatment. Conclusions: Combining TOT and NPWT may reduce treatment duration in chronic wound management. Selected laboratory and thermographic markers show promise as prognostic tools. These exploratory findings require confirmation in larger, randomized trials. Full article