Search Results (21,334)

Mitochondria perform critical roles in cellular functions, particularly in metabolism and cell death regulation. Mutations in nuclear and mitochondrial genes can cause mitochondrial dysfunction, leading to classical mitochondrial diseases. Emerging evidence suggests that mitochondrial adaptations in cancer support the high energy demands of proliferating cells and contribute to tumor progression through anti-apoptotic mechanisms, dysregulated mitochondrial quality control (mtQC), and altered mitochondrial DNA (mtDNA) copy numbers. Interestingly, several mitochondrial pathways involved in cancer progression resemble those implicated in mitochondrial diseases. From this perspective, although cancer is not a classical mitochondrial disease, its progression involves mitochondria-associated pathways similar to those in mitochondrial disorders, suggesting that cancer may be considered a mitochondria-related disease in a broader sense. Understanding these shared mechanisms could provide new insights into precision treatment strategies. Furthermore, mitochondrial dysfunction is increasingly recognized in precancerous conditions, suggesting its potential as a target for early intervention. Oral potentially malignant disorders (OPMDs) serve as a valuable model for studying these mitochondria-associated mechanisms, offering a promising avenue for both therapeutic advancements and preventive approaches. Full article

The incorporation of probiotics into food products has gained substantial attention, primarily due to their well-documented health benefits such as modulating gut microbiota, enhancing immune responses, and providing potential therapeutic effects. This comprehensive review discusses recent advancements in the application of probiotics in the food industry, focusing on diverse food matrices, technological and regulatory challenges, and consumer acceptance. Particular emphasis is placed on fermentation-based approaches that enhance both sensory and nutritional attributes, while acting as effective delivery systems for viable probiotics. The impact of matrices such as dairy, meat, cereals, plant-based beverages (e.g., soy or almond milk), and solid plant-derived foods (e.g., fermented vegetables) on probiotic survival, sensory properties, and product acceptability is critically examined. Understanding these interactions is crucial for the development of stable, efficacious, and consumer-oriented probiotic-enriched functional foods. Full article

As the fields of plastic surgery and dermatology advance, regenerative medicine is positioned to play a transformative role in both aesthetic and reconstructive procedures. This narrative review examines current and emerging applications of biologic therapies, including exosomes, platelet-rich plasma (PRP), and adipose-derived stem cells (ASCs) with an emphasis on their mechanisms of action, clinical efficacy, and regulatory considerations. We also explore synergistic strategies, such as the combined use of biologics with laser-based technologies, which may enhance therapeutic outcomes. Looking forward, we highlight promising developments in mitochondrial-based therapies, microRNA-based therapies, synthetic exosome mimetics, and AI-assisted biologic design, offering a framework for personalized, precision-driven interventions. By synthesizing existing clinical data alongside scientific and ethical challenges, this narrative review provides a comprehensive perspective on how regenerative therapies are transforming the landscape of aesthetics. Ultimately, successful integration of these innovations will require rigorous validation, ethical responsibility, and a patient-centered approach by plastic surgeons and dermatologists to ensure both safety and accessibility in mainstream practice. Full article

Influenza A virus (IAV) infection triggers excessive activation of PANoptosis—a coordinated form of programmed cell death integrating pyroptosis, apoptosis, and necroptosis—which contributes to severe immunopathology and acute lung injury. However, the molecular regulators that drive PANoptosis during IAV infection remain poorly understood. In this study, we integrated bulk and single-cell RNA sequencing (scRNA-seq) datasets to dissect the cellular heterogeneity and transcriptional dynamics of PANoptosis in the influenza-infected lung. PANoptosis-related gene activity was quantified using the AUCell, ssGSEA, and AddModuleScore algorithms. Machine learning approaches, including Support Vector Machine (SVM), Random Forest (RF), and Least Absolute Shrinkage and Selection Operator (LASSO) regression, were employed to identify key regulatory genes. scRNA-seq analysis revealed that PANoptosis activity was primarily enriched in macrophages and neutrophils. Integration of transcriptomic and computational data identified cathepsin B (CTSB as a central regulator of PANoptosis. In vivo validation in an IAV-infected mouse model confirmed elevated expression of PANoptosis markers and upregulation of CTSB. Mechanistically, CTSB may facilitate NLRP3 inflammasome activation and promote lysosomal dysfunction-associated inflammatory cell death. These findings identify CTSB as a critical mediatoCTSBr linking lysosomal integrity to innate immune-driven lung injury and suggest that targeting CTSB could represent a promising therapeutic strategy to alleviate influenza-associated immunopathology. Full article

Neurodegenerative diseases are associated with the senescence of functional neurons, which hampers brain functions. These diseases are caused by the accumulation of reactive oxygen species, reactive nitrogen species, cholinesterase malfunction, neuronal inflammation, and mitochondrial dysfunction. The incidence of neurodegenerative disease has been on the rise. Current therapeutic interventions are expensive, exhibit poor efficacy, and have numerous side effects. Several studies have explored the potential of crucial dietary substances rich in antioxidants and micronutrients in alleviating the clinical manifestations of such deadly diseases. Consumption of sufficient antioxidants, fatty acids, and polyphenols in regular diets delays the onset of neurodegenerative diseases. Several medicinal plants, such as Withania somnifera, Curcuma longa, Panax ginseng, Ginkgo biloba, aloe vera, Punica granatum, and various phytoextracts, contain such micronutrients in reasonable amounts. Specific dietary interventions, supplements, and patterns such as the Mediterranean-DASH intervention for neurodegenerative delay, ketogenic, paleolithic, and Wahls elimination diets have been beneficial in neurodegenerative conditions. These diet interventions and other functional foods can be an attractive, non-invasive, and inexpensive approach in the management and prevention of neurodegenerative conditions. This review discusses potential pharmacological bases involved in neurodegeneration, covering mitochondrial damage, impaired mitophagy, neuroinflammation, ferroptosis, glymphatic clearance dysfunction, brain–body interactions, and disruption of vagus nerve stimulation. The review further highlights clinical diet interventions and assorted functional foods, including fruits, vegetables, vitamins, specific supplements, and special diets, for neurodegenerative conditions. The discussion extends insights into clinical research and trials of these functional foods under neurodegenerative conditions. Overall, dietary interventions show promise in the prevention and management of neurodegenerative conditions. Full article

Effective treatment of ovarian cancer is limited by late-stage detection and chemotherapy resistance. There is a clinical need for the discovery of novel molecular targets to enable the development of innovative theranostic approaches. We investigated the coagulation factor II receptor/protease-activated receptor 1 (F2R/PAR1) as a potential diagnostic/prognostic biomarker and therapeutic target for ovarian cancer treatment. Public RNA sequence and DNA microarray data were used to analyze F2R gene expression in ovarian cancers, with protein expression confirmed in tumor samples by flow cytometry, immunofluorescence, and immunohistochemistry (IHC). Functional assays were conducted to study effects of F2R suppression on tumor progression. Our analysis confirmed elevated F2R mRNA and protein expression in ovarian cancers, notably in patients with metastatic and chemotherapy-resistant disease. Kaplan–Meier survival analysis demonstrated an association between high F2R protein detection and reduced progression-free survival. F2R suppression in ovarian cancer cell lines reduced tumor cell motility, invasion, spheroid formation, and metabolism and enhanced carboplatin sensitivity. F2R is a compelling diagnostic/prognostic and therapeutic target that could be used to treat chemotherapy-resistant and metastatic disease. The evaluation of novel F2R targeting strategies, using antibody-conjugated drugs or F2R ligand-decorated drug carriers, could lead to the development of effective therapeutics for patients with ovarian cancer. Full article

Sarcopenia, a significant loss of muscle mass and strength, is an important healthcare problem in the geriatric population. While age-related muscle decline represents the most common form, sarcopenia may also develop as a secondary condition associated with chronic diseases, including cancer, diabetes, chronic obstructive pulmonary disease, and autoimmune disorders. It increases frailty, disability, and fall risk among the elderly while also raising hospitalization rates and associated healthcare costs. Although no pharmaceutical agents have been specifically approved for the treatment of sarcopenia to date, elucidating its underlying molecular mechanisms of sarcopenia through systems biology approaches is essential for the development of novel therapeutic strategies and preventive interventions. This review examines the current definitions of sarcopenia, recent advancements in its management, and the emerging role of systems biology in uncovering potential biomarkers and therapeutic targets. We discuss how these approaches may contribute to the development of novel interventions aimed at enhancing muscle health and improving the quality of life in older adults and provide a summary of the current progress achieved through systems biology methodologies in sarcopenia research. Full article

Vitamin D is increasingly recognized as a key regulator of epithelial barrier integrity and mucosal immune homeostasis, with implications extending far beyond skeletal health. Through the vitamin D receptor (VDR), vitamin D regulates epithelial cohesion, innate immune responses, and tight-junction gene expression. This review explores the multifactorial role of vitamin D in modulating inflammation and preserving tissue barriers, with particular emphasis on its effects on tight junction (TJ) regulation and disease states characterized by barrier dysfunction, namely atopic dermatitis, psoriasis, inflammatory bowel disease (IBD), and celiac disease. In these settings, vitamin D/VDR signaling exerts protective actions by enhancing barrier structure, suppressing Th1/Th17-driven inflammation, modulating the gut and skin microbiome, and promoting epithelial repair. Animal studies and clinical data suggest that vitamin D supplementation can restore TJ expression, reduce disease activity, and improve clinical outcomes in both intestinal and dermatologic diseases. In the cardiovascular system, the role of vitamin D remains complex. While vitamin D influences endothelial function, insulin sensitivity, and systemic inflammation, supplementation trials yield mixed results, indicating a need for individualized approaches. Overall, this review synthesizes mechanistic, translational, and clinical data supporting vitamin D as a crucial modulator of barrier integrity and inflammation. These findings highlight its therapeutic relevance in chronic diseases characterized by immune dysregulation and epithelial disruption. Full article

Background: Epilepsy and cognitive impairment frequently coexist, yet their relationship remains complex and insufficiently understood. This study aims to explore the clinical and electrophysiological features of patients presenting with both conditions in order to identify patterns that may inform more accurate diagnosis and effective management within a personalized medicine framework. Methods: We retrospectively analyzed 14 patients with late-onset epilepsy and coexisting cognitive impairment, including mild cognitive impairment and Alzheimer’s disease. Clinical history, cognitive assessments, neuroimaging, and electroencephalographic recordings were reviewed. EEG abnormalities, seizure types, and treatment responses were systematically documented. Results: Patients were categorized into two groups: (1) those with established Alzheimer’s disease who later developed epilepsy and (2) those in whom epilepsy preceded cognitive impairment. Temporal lobe involvement was a key feature, with EEG abnormalities frequently localizing to the frontal–temporal electrodes and manifesting as background slowing, focal multiform slow waves, and epileptiform discharges. Levetiracetam was the most commonly used antiseizure medication, and it was effective across both groups. Conclusions: This case series highlights the value of EEG in characterizing patients with subclinical and overt epileptic activity and cognitive impairment comorbidity. The inclusion of a substantial number of cases with documented EEG abnormalities provides valuable insight into the interplay between epilepsy and neurodegenerative diseases. By integrating neurophysiological data with clinical and cognitive trajectories, this work aligns with the principles of precision medicine, facilitating a more comprehensive evaluation and tailored management approach. Further longitudinal studies are required to validate prognostic markers and guide optimal therapeutic strategies. Full article

Background and Objectives: Eating disorders are one of the most widespread health concerns, mainly among adolescents. Children and adolescents with type 1 diabetes mellitus (T1DM) have been reported to have a high prevalence of eating disorders. The aim of our study is to evaluate the risk of diabetes-specific eating disorders in children with T1DM using continuous subcutaneous insulin infusion (CSII), with real-time glycemic data from continuous glucose monitoring (CGM). Materials and Methods: Sixty-four patients (aged 7–18 years) completed the Diabetes Eating Problem Survey-Revised (DEPS-R). The DEPS-R is a diabetes-specific self-report questionnaire to assess diabetes-specific compensatory behaviors. Auxological findings, sex, age, age at diagnosis, hemoglobin A1c (HbA1c) levels, and all CGM data were obtained from their medical records. Results: Although the median DEPS-R score was higher in children and adolescents using CSII compared to those using multiple daily injections (MDIs) (14 vs. 11), the difference was not statistically significant (p = 0.302). The risk of diabetes-specific eating disorders was identified in six patients (30%) using CSII and in nine patients (20.4%) using multiple daily injections (p = 0.403). Interestingly, in the subgroup with poor glycemic control (HbA1c > 9%), DEPS-R scores were significantly lower among those using CSII compared to the MDI group. Pearson correlation analysis demonstrated positive associations between DEPS-R scores and diabetes duration, weight SDS, body mass index (BMI), BMI SDS, HbA1c, mean glucose, Glucose Management Indicator (GMI), time above range (TAR) (very high), and coefficient of variation (CV), while a moderate negative correlation was observed with time in range (TIR). Conclusions: This study showed that the treatment of CSII had a beneficial effect on the risk of eating disorders in patients with poor glycemic control. As well, from this perspective, CSII maintains its status as a potentially beneficial therapeutic approach in diabetes management. Full article

Multilayer platforms have emerged as promising tools in the field of wound healing, offering a multifaceted approach to promote effective and accelerated tissue regeneration. This review article aims to provide a comprehensive overview of the various multilayer platforms employed in wound healing applications, highlighting their structure, fabrication methods, and potential mechanisms of action. The first section of the review focuses on the design and composition of multilayer platforms, encompassing different materials such as polymers, hydrogels, and biocompatible scaffolds. It discusses the significance of each layer in terms of its specific functionalities, including cell adhesion, drug/bioactive factor loading, antimicrobial properties, and mechanical support. The second section of the review delves into the mechanisms of action associated with multilayer platforms in wound healing. It discusses how these platforms facilitate wound closure, promote angiogenesis, modulate inflammation, and enhance tissue regeneration. The article also examines the role of multilayer platforms in providing a physical barrier against external pathogens, reducing the risk of infection, and creating a favorable microenvironment for wound healing. Overall, this review highlights the significant advancements made in the field of multilayer platforms for wound healing and underscores their potential as versatile therapeutic strategies. Full article

Oral tongue squamous cell carcinoma (OTSCC) is a common type of oral cancer influenced by genetic, epigenetic, and environmental factors like exposure to environmental toxins. These environmental toxins can decrease the effectiveness of established chemotherapy drugs, such as Irinotecan, used in OTSCC treatment. Bioinformatics, drug discovery, and machine learning techniques were employed to investigate the impact of Irinotecan on OTSCC patients by identifying targets and signaling pathways, including those that positively influence protein phosphorylation, protein tyrosine kinase activity, the PI3K-Akt (Phosphatidylinositol 3-kinase- Protein Kinase B) signaling system, cancer pathways, focal adhesion, and the HIF-1 (Hypoxia-Inducible Factor 1) signaling pathway. Later, the protein–protein interactions (PPIs) network, along with twelve cytoHubba approaches to finding the most interacting molecule, was employed to find the important proteins BCL2 and EGFR. Drugs related to BCL2 and EGFR were extracted from the DGIdb database for further molecular docking. Molecular docking revealed that Docetaxel, Paclitaxel, Imatinib, Ponatinib, Ibrutinib, Sorafenib, and Etoposide showed more binding affinity than Irinotecan (i.e., −9.8, −9.6). Of these, Paclitaxel (−10.3, −11.4) and Imatinib (−9.9, −10.4) are common in targeting BCL2 and EGFR. Using these identified candidate genes and pathways, we may be able to uncover new therapeutic targets for the treatment of OTSCC. Furthermore, molecular dynamics (MD) simulations were performed for selected ligand–receptor complexes, revealing stable binding interactions and favorable energetic profiles that supported the docking results and strengthened the reliability of the proposed drug repurposing strategy. Full article

According to a recent WHO survey, approximately 93% of countries reported disruptions in mental healthcare provision in the post-COVID-19 era. These have had a significant impact on individuals living with bipolar disorder (BD), many of whom have encountered substantial barriers to accessing mental health services and pharmacological treatment. These factors have been associated with an increased relapse risk, heightened psychosocial stress, and impaired daily functioning. Emerging research underscores the need for interventions that address the chronic stressors experienced by individuals with BD, particularly in the wake of the global trauma induced by the pandemic. In this context, nursing-led interventions play a crucial role, not only in supporting individuals with BD, but also in engaging families and informal caregivers. These interventions emphasize proactive therapeutic engagement, education on relapse signs, and development of adaptive coping strategies. All these contribute to sustained recovery and improved quality of care. This perspective paper explored the challenges and opportunities in delivering mental healthcare to individuals with BD in the post-pandemic era and outlined targeted, nursing-driven approaches that respond to the long-term mental health burden of trauma and chronic stress. Full article

Background: Meniere’s disease (MD) is a chronic inner ear disorder affecting approximately 0.2% of the population, with 30% of patients remaining refractory to conventional treatments. The pathophysiology involves endolymphatic hydrops, suggesting that agents affecting fluid homeostasis might provide therapeutic benefit. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors, originally developed for diabetes, offer unique mechanisms including natriuresis and osmotic diuresis that may address the underlying fluid imbalance in MD. Methods: We conducted a retrospective observational study at the Korea University Anam Hospital, analyzing the medical records of patients with definite MD (Bárány Society criteria) who received off-label empagliflozin 10 mg daily between January 2023 and December 2023. Six patients (3 men, 3 women; mean age 55.8 years) with treatment-resistant MD were identified who had failed conventional therapy for at least 3 months. Primary outcomes included changes in pure tone threshold average (PTA), low-frequency threshold average (LFA), vertigo episode frequency, and vertigo severity using visual analog scale (VAS) scores, assessed at baseline and after 3 months of treatment. Results: All patients demonstrated clinically significant improvements in both auditory and vestibular symptoms. Mean PTA improved from 31.4 dB to 20.8 dB (improvement of 10.6 dB, p < 0.05). Low-frequency hearing showed more substantial recovery, with LFA improving from 37.2 dB to 15.6 dB (improvement of 21.6 dB, p < 0.01). Vertigo frequency decreased dramatically from 1.6 episodes per month to 0.1 episodes per month, with four patients experiencing a complete resolution of vertigo episodes. VAS scores for vertigo severity decreased from 5.2 to 0.5. Treatment was well-tolerated, with only minor adverse effects reported in two patients: transient polyuria in one patient and 5 kg weight loss in another, both consistent with the known pharmacological profile of SGLT-2 inhibitors. Conclusions: This preliminary study suggests a potential clinical benefit of repurposing SGLT-2 inhibitors for treatment-resistant MD. However, the retrospective design and inherent limitations prevent definitive conclusions about causality. The significant improvements observed in both hearing thresholds and vestibular symptoms warrant further investigation through randomized controlled trials with objective outcome measures to establish the true efficacy of this therapeutic approach. Full article