Search Results (30,353)

The global prevalence of autoimmune diseases ranges from 3% to 8%, with women at a significantly higher risk than men. The core mechanisms underlying these diseases include impaired T-cell and B-cell immune tolerance, abnormal cytokine production, and aberrant activation of related signaling pathways. Conventional treatments primarily focus on suppressing immune responses, but their efficacy remains limited and they are often associated with substantial side effects. Nanomedicine leverages nanoscale materials to enable precise diagnosis and targeted therapy. Nanocarriers can penetrate biological barriers, enhance cellular uptake, and prolong circulation time in vivo, demonstrating considerable potential for drug delivery. Common nanoscale drug delivery platforms include nanoparticles, polymeric micelles, liposomes, dendrimers, mesoporous materials, hydrogels, and exosomes. Each carrier type possesses distinct characteristics in terms of drug-loading capacity, stability, responsiveness, and biocompatibility, thereby enabling targeted delivery and controlled release. This review summarizes recent advances in nano-delivery technologies for three representative chronic autoimmune diseases: diabetes mellitus (DM), inflammatory bowel disease (IBD), and rheumatoid arthritis (RA). Nano-delivery systems can improve therapeutic outcomes by optimizing drug delivery, targeting complications, and modulating the pathological microenvironment. They enhance drug bioavailability, reduce off-target and systemic adverse effects, and provide novel strategies for the precise and efficient treatment of chronic autoimmune diseases. Full article

Background: Baseline lymphopenia is common among advanced solid tumors and may influence the efficacy/safety of immune checkpoint inhibitors (ICIs), but large real-world evidence is limited. We evaluated the association between baseline absolute lymphocyte count (ALC) and clinical outcomes in adults with solid tumors treated with ICIs in routine practice. Methods: We performed a retrospective cohort study using TriNetX. Adults with solid tumors who received pembrolizumab, nivolumab, or atezolizumab (ICI-Naïve) between January 2015 and June 2026 were included. Baseline ALC was measured within 30 days before first treatment and was classified as lymphopenic (ALC < 1.5 × 10⁹/L) or non-lymphopenic (ALC ≥ 1.5 × 10⁹/L). Propensity score matching (1:1) yielded 5249 patients per group. The index date was the first immunotherapy date, and outcomes were assessed at 6, 12, 24, 36 months, and 5 years. The primary outcome was 24-month overall survival (OS); secondary outcomes were OS at 6 and 12 months and 6-month risks of healthcare utilization, immune-related adverse events (irAEs), and serious infections; and exploratory outcomes included OS at 36 months and 5 years. All outcomes were analyzed using Kaplan–Meier analysis, Cox proportional hazards models, and risk ratios. Subgroup analysis included OS stratified by solid tumor subtypes and prior lines of therapy. Results: After matching, patients with baseline lymphopenia had consistently worse OS. Compared with patients without lymphopenia, the lymphopenia cohort had lower OS at 6 months (HR 1.29, 95% CI 1.22–1.37), 12 months (HR 1.28, 95% CI 1.21–1.35), 24 months (HR 1.26, 95% CI 1.2–1.33), and, in exploratory analyses with substantial right censoring and limited observed follow-up, 36 months (HR 1.26, 95% CI 1.2–1.33) and 5 years (HR 1.26, 95% CI 1.2–1.33), though these estimates should be considered hypothesis-generating only. At 6 months, baseline lymphopenia was associated with a greater healthcare utilization (RR 1.05, 95% CI 1.02–1.09), a higher infection risk (RR 1.08, 95% CI 1.01–1.15), and similar rates of clinically coded irAEs (RR 1.0, 95% CI 0.93–1.09), an observation subject to competing risk from early mortality in the lymphopenic cohort. Subgroup analysis, stratified by tumor subtypes and prior lines of therapy, showed consistently lower OS in the lymphopenia group, consistent with the primary outcome results. Conclusions: In this large propensity-matched real-world analysis of 10,498 patients with diverse solid tumors, baseline lymphopenia at ICI initiation was associated with persistently inferior OS at 6, 12, and 24 months (primary and secondary endpoints), greater early healthcare utilization, and a higher serious infection risk. Critically, lymphopenic patients developed irAEs at an identical rate to non-lymphopenic patients despite worse survival, a dissociation suggesting that baseline ALC stratifies patients along mortality risk and immune activation capacity as partially independent axes. These findings could support the use of baseline ALC as a simple, universally available biomarker that informs not only survival prognosis but also the anticipated toxicity profile of ICI therapy and highlight the need for competing-risk analyses and prospective immune phenotyping to characterize this relationship fully. Full article

Atrial fibrillation (AF) is the most common tachyarrhythmia worldwide. Accompanying the increasing age of the general population, as well as an increase in underlying cardiovascular disease in the United States, is an explosive rise in the incidence and prevalence of this condition. We reviewed observational cohort studies, systematic reviews, meta-analyses, and randomized controlled trials (RCTs) to determine both underlying risk factors and treatment of AF, with particular focus on comorbid conditions influencing treatment success. Numerous studies have demonstrated a reciprocal relationship between maladaptive cardiac remodeling and AF, with the suggestion that aggressive management of both AF itself and resultant cardiovascular disease can lead to reversal of both conditions. Ultimately, many modifiable risk factors for AF exist, with treatment delays associated with a shift towards these conditions becoming unmodifiable. While a large area of focus for AF research has been on determining the optimal pharmacological strategy (i.e., rate versus rhythm control), results have been mixed, with emerging guidelines now pointing towards a flexible treatment strategy that allows for consideration of patient comorbid conditions, medication ease and affordability, and patient preference. Treatment of AF also includes prevention of thromboembolic events. In recent years, novel strategies for surgical or physical occlusion of the left atrial appendage (LAA) with devices such as the Watchman have arisen. Multiple large RCTs have demonstrated the safety and efficacy of these devices, but consideration must be given towards the patient’s bleeding risk, as short-term courses of blood thinners are still considered the standard of care. Finally, emerging therapies for AF include novel drug combinations, neuromodulation devices, and potentially glucagon-like peptide receptor-1 (GLP-1) agonist medications for reduction in overall metabolic disease. Full article

Probiotic lactic acid bacteria are widely recognized for their health-promoting effects. However, the use of live microorganisms may pose safety concerns and stability limitations. Consequently, postbiotics, defined as inactivated microbial cells and/or their components, have emerged as a promising alternative. This study integrates genome-guided evaluation of probiotic potential, experimental validation of in silico predictions and process optimization for the production of inactivated Lactiplantibacillus plantarum DM1 and KK1 cells as postbiotics. Genome mining identified genes and gene clusters associated with metabolic versatility, antimicrobial activity, gastrointestinal stress tolerance, adhesion and prebiotic substrate utilization. Building on these findings, to generate postbiotics, the efficiency of thermal, enzymatic, mechanical and radiation-based inactivation methods was evaluated in bacterial suspensions prepared in three dairy by-product matrices: milk permeate, sweet whey and sour whey. Complete inactivation of both strain cells was achieved by thermal treatment (3 min pasteurization), γ-irradiation (3 kGy), and combined lysozyme–pasteurization treatment, whereas other treatments showed partial and matrix-dependent effects. Matrix composition significantly influenced treatment efficacy, suggesting a protective role of food components used. These findings highlight the importance of combining genome mining for potential probiotic strain characterization with robust, matrix-adapted inactivation strategies for the development of stable postbiotic formulations. Full article

(1) Background: Ultra-early optical coherence tomography (OCT) changes following intravitreal injection may reflect transient mechanical compression rather than pharmacologic effects; however, this temporal profile has not been rigorously characterised with appropriate statistical methodology. (2) Methods: In this prospective observational study, 40 eyes of 40 consecutive patients (one per patient) with macular edema secondary to neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), or chronic central serous retinopathy (CSR) underwent intravitreal bevacizumab (n = 35) or triamcinolone acetonide (n = 5). Goldmann applanation tonometry and spectral-domain OCT were performed at baseline, 2–5 min, 15 ± 5 min, 24 h, and 48 h post-injection. Repeated-measures ANOVA with Greenhouse–Geisser correction, linear regression, and Spearman rank correlation were applied. (3) Results: Central subfield thickness (CST) decreased markedly at 15 ± 5 min (mean −24.8 ± 11.5%; 95% CI: −28.5% to −21.1%; p < 0.001; partial η² = 0.70), with near-complete rebound by 48 h (−1.0%; p = 0.400). Peak intraocular pressure (IOP) elevation correlated with CST reduction (Spearman r_s = 0.61; 95% CI: 0.39–0.77; p < 0.001), and baseline CST predicted thinning magnitude (R² = 0.52; p < 0.001). (4) Conclusions: Ultra-early OCT thinning after intravitreal injection is consistent with transient mechanical compression. Retinal thickness measurements within 48 h post-injection should be interpreted with caution when assessing treatment response, as early anatomic reduction may not reflect pharmacologic efficacy. Full article

DMG, including DIPG, is a highly aggressive pediatric brain tumor with dismal clinical outcomes. Radiotherapy remains the cornerstone of treatment, yet responses are transient and resistance is nearly universal. Emerging evidence indicates that EVs are key mediators of radiation response, facilitating intercellular communication and the propagation of radioresistant phenotypes within the tumor microenvironment. EVs carry diverse molecular cargo, including RNAs, proteins, and lipids, that can dynamically influence tumor behavior and treatment response. In this review, we focus on the role of EVs in shaping radiation response in DMG, while also examining their broader functions in tumor biology, biomarker development, and therapeutic delivery. We summarize evidence for EV-mediated regulation of tumor growth, invasion, microenvironmental interactions, and immune modulation. We further discuss the potential of EVs as minimally invasive biomarkers for liquid biopsy, highlighting both their advantages and current limitations relative to circulating tumor DNA (ctDNA) approaches. In addition, we review emerging strategies utilizing EVs as therapeutic delivery platforms capable of crossing the blood–brain barrier (BBB) and delivering small molecules and nucleic acid-based therapies. Finally, we explore the role of EVs in modulating radiation response, including their contribution to radioresistance and their potential as biomarkers of treatment efficacy. Although EV-based approaches hold significant promise in DMG, challenges related to standardization, specificity, and clinical validation remain. Continued investigation into EV biology and translational applications may provide new opportunities for improving diagnosis, monitoring, and treatment of this devastating disease. Full article

Cancer is still one of the world’s major causes of morbidity and mortality; thus, safer and more efficient treatment approaches are required. The structural variety, multitargeted mechanisms, and generally good safety profiles of plant-derived polyphenols have made them attractive anticancer medicines. Flavonoids (like quercetin), stilbenes (like resveratrol), phenolic acids and curcuminoids (like curcumin) are major classes that have shown strong anticancer action against a variety of cancers, including prostate, colorectal and breast cancers. Through targets including PI3K/Akt, MAPK, NF-κB, and p53 signaling networks, these substances influence important molecular pathways involved in tumor initiation and development, including oxidative stress, inflammation, apoptosis, cell cycle control, angiogenesis and metastasis. The clinical translation of polyphenols is still constrained by poor bioavailability, fast metabolism, low aqueous solubility and inefficient pharmacokinetic characteristics, which lead to insufficient systemic exposure and therapeutic efficacy despite strong preclinical data. Their therapeutic applicability is further complicated by variations in absorption and possible dose-related restrictions. To overcome these limitations, the anticancer efficacy of polyphenols has been enhanced via delivery technologies like polymeric nanoparticles, lipid-based carriers, nanoemulsions and phytosome complexes, which have shown improved stability, increased bioavailability and targeted delivery to tumor tissues. This review provides a comprehensive and integrative analysis of plant-derived polyphenols by linking molecular mechanisms, pharmacokinetic limitations and emerging delivery strategies within a translational framework. By bridging these interconnected domains, this review highlights the potential of polyphenols as viable candidates in next-generation cancer therapeutics and underscores the need for well-designed clinical studies to facilitate their successful integration into oncology practice. Full article

Rhizoctonia solani is a necrotrophic phytopathogenic fungus that causes disease in various crops. In agriculture, many crops suffer from root or seedling rot caused by this soil-borne pathogen, whereas cabbage and rice develop lesion-like symptoms on aboveground tissues. Diseases caused by R. solani are generally controlled using chemical fungicides; however, environmentally friendly alternatives are needed for sustainable agriculture. In this study, we evaluated the efficacy of lecithin, a mixture of phospholipids previously registered in Japan as an agrochemical for controlling cucumber powdery mildew, against Rhizoctonia diseases. In cabbage, foliar spraying of 0.2–1.0% soybean lecithin effectively suppressed leaf symptoms caused by R. solani isolate RhiCa-2, which was identified as AG-1 IB. In rice and Brachypodium distachyon, 0.2–1.0% lecithin significantly suppressed leaf symptoms induced by R. solani AG-1 IA. Hyphal staining of inoculated leaves revealed reduced hyphal density on lecithin-treated leaves. Consistently, hyphal growth of R. solani on cellophane placed on water agar was retarded by lecithin treatment. However, 5.0% lecithin induced phytotoxicity in B. distachyon. Egg yolk-derived lecithin also exhibited disease-suppressive activity in cabbage and B. distachyon, with efficacy comparable to that of soybean lecithin under the conditions tested. These results suggest that lecithin suppresses foliar infection by R. solani, at least in part, through direct inhibitory effects on fungal hyphae, and may serve as a potential alternative material for disease control in sustainable crop production. Full article

Hantaviruses (HTVs) are lethal zoonotic pathogens responsible for hemorrhagic fever with renal syndrome and HTV cardiopulmonary syndrome; however, no specific antiviral treatments or vaccines have been approved. Bee products, such as propolis, honey, royal jelly, bee venom, and bee pollen, demonstrate extensive antiviral, anti-inflammatory, antioxidant, and immunomodulatory properties against various RNA and DNA viruses. No published research has directly evaluated bee products in relation to HTV infection. This review proposes a hypothesis-driven mechanistic framework suggesting that bioactive compounds from bee products may concurrently inhibit HTV replication, alleviate the cytokine storm, diminish oxidative stress, and maintain endothelial barrier integrity. We explicitly recognize the lack of direct experimental evidence regarding bee products’ efficacy against HTVs. Considering the mechanistic similarities with other enveloped viral infections and the recognized functions of NF-κB, Nrf2, and endothelial signaling pathways in HTV pathogenesis, we present a scientifically substantiated rationale for forthcoming research endeavors. The diverse bioactive compounds present in bee products including bee pollen, bee venom, honey, propolis, and royal jelly could provide a multifaceted strategy for inhibiting HTV pathology. We propose systematic in vitro, in silico, and in vivo investigations to assess the potential of bee-derived flavonoids, peptides, and fatty acids as adjunctive therapeutic strategies for HTV disease. Full article

Background: 5q spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder characterized by progressive muscle weakness. Nusinersen, the first disease-modifying therapy for SMA, has demonstrated efficacy in both clinical trials and real-world studies. However, the precise timing of therapeutic onset following Nusinersen administration remains unclear. Methods: This retrospective study analyzed clinical data from patients with genetically confirmed 5q SMA who received Nusinersen treatment for at least six months at Peking University First Hospital. Motor function was assessed using standardized scales prior to each dose. Results: In total, 74 patients were screened, of whom 62 were enrolled, including 14 with type 1, 29 with type 2, and 19 with type 3 SMA. Thirty-two patients completed motor function assessments. After six months of treatment, 62.5% achieved a primary clinically meaningful response (an increase of ≥4 points in CHOP-INTEND or ≥3 points in HFMSE). Seven patients (21.9%) attained or regained motor milestones. Median improvements were 6 points in CHOP-INTEND (p = 0.001), 4 points in HFMSE (p = 0.003), and 1.5 points in RULM (p = 0.045). Further analysis indicated that the available median time to treatment response was approximately 2 months. In patients with severe scoliosis or prior spinal surgery, ultrasound-guided lumbar puncture demonstrated a high success rate (94.9%). Regarding safety, intrathecal injection-related adverse events occurred in eight patients (12.9%), and no adverse events led to treatment discontinuation. Conclusions: During the loading phase, Nusinersen provides clinical benefit for the majority of patients, with a median time to therapeutic response for monitoring of approximately 2 months. Ultrasound-guided intrathecal administration is the preferred approach for individuals with complicated spinal conditions. These findings may help guide clinical expectations for physicians, patients, and caregivers. Full article

Background/Objectives: This preliminary pilot case series aims to evaluate the feasibility and temporal evolution of pain and function following an ultrasound-guided infiltration technique with hyaluronic acid and methylprednisolone in a specific patient population with Temporomandibular Disorders (TMD) characterized by MRI-confirmed retrodiscal tissue hyperemia. Given the absence of a control group, this study represents a preliminary exploration of a clinical approach utilizing individualized interocclusal devices during infiltration. Methods: Twenty-eight patients (16 females, 12 males) with TMD and MRI evidence of retrodiscal tissue hyperemia were enrolled in this prospective, uncontrolled study. A unique protocol was employed, utilizing individualized interocclusal devices to optimize joint space access during bilateral ultrasound-guided infiltration of a mixture containing low-molecular-weight hyaluronic acid, lidocaine, and methylprednisolone acetate. Pain intensity (VAS 0–100 mm) and associated symptoms (tinnitus, vertigo, headache, joint clicking) were assessed at baseline and at 30, 60, and 90 days’ follow-up. Results: A statistically significant temporal reduction in pain was observed at all follow-up points (p < 0.001), with the mean VAS score decreasing from 70.5 ± 11.4 mm at baseline to 43.0 ± 11.1 mm at 90 days. Joint clicking disappeared in 80% of patients immediately after treatment. Conclusions: The ultrasound-guided infiltration technique, combined with personalized interocclusal support, demonstrated preliminary feasibility and short-term temporal improvement in pain and joint clicking in this specific patient cohort. Due to the lack of a control group and the multimodal nature of the intervention, these findings should be considered preliminary and do not allow for causal inferences regarding the efficacy of individual components. Full article

This study presents a comprehensive computational evaluation of radiofrequency (RF) ablation efficacy and the spatial formation of thermal ablation zones within a 3D model of a liver tumor. By systematically comparing these configurations, the study aims to elucidate the physical mechanisms governing electromagnetic (EM) energy dissipation in hepatic tissue and to provide clear engineering guidelines for optimizing RF applicator selection and treatment planning in clinical practice. To reliably simulate the biophysical phenomena of the RF ablation procedure, a coupled electro-thermal model based on the finite element method and the Pennes bioheat equation was implemented. The research investigates six distinct applicator variants: conventional needle-type applicators and advanced expandable umbrella-type RF applicators equipped with four- and eight-tine electrodes, each evaluated in both monopolar and bipolar configurations. Numerical simulations were conducted for a standard 10 min ablation procedure at varying applied voltages to assess the specific absorption rate (SAR) distribution, transient heating dynamics, and the exact volumes of the resulting coagulation necrosis which were quantified using rigorous isotherms and the cumulative equivalent minutes at 43 °C (CEM₄₃) thermal dose index. Volumetric analysis of the ablation zones revealed that bipolar multi-tine electrodes induce highly localized heat concentration. Conversely, monopolar multi-tine setups strongly disperse EM energy. The results demonstrated that, for conventional needle applicators, the monopolar configuration generated significantly larger necrosis zones than the bipolar operating mode. The RF applicator geometry and its operating mode directly dictate the spatial extent of liver tissue necrosis. Moreover, advanced numerical treatment planning is essential for optimizing SAR and CEM₄₃ distributions and ensuring safe and complete hepatocellular carcinoma eradication. Full article

Plutella xylostella (Linnaeus) (Lepidoptera: Plutellidae) is a major cruciferous crop pest worldwide with resistance to multiple insecticide classes, highlighting the need for sustainable alternatives. Entomopathogenic fungi (EPF) are promising biocontrol agents, but their efficacy is limited by slow pathogenicity, environmental sensitivity, and low persistence on insect cuticles. This study evaluated integrated formulation strategies to enhance the virulence of Beauveria namnaoensis PM-02 against P. xylostella under laboratory and greenhouse conditions. Putative copper and zinc nanoparticle preparations were generated using fungal biomass extracts, with nanoparticle formation inferred from visual changes in the reaction mixtures. Oil-emulsified fungal formulations and combinations with emamectin benzoate were also evaluated. Larval mortality increased significantly with concentration, indicating a clear dose-dependent response. The combined treatment of oil-emulsified fungus and emamectin benzoate, along with emamectin benzoate alone, resulted in the highest larval mortality (100%), whereas fungus alone caused the lowest mortality (43.3%). Lethal concentration (LC₅₀₎ analysis indicated high toxicity of the combined treatment, while lethal time (LT₅₀) values demonstrated more rapid mortality for emamectin benzoate (0.176 days) and the combined treatment (0.830 days) compared with fungus alone (6.25 days). Under greenhouse conditions, the combined treatment showed the highest efficacy, reducing larval survival to 30% and demonstrating enhanced insecticidal activity. Overall, integrated formulation strategies significantly improved fungal efficacy against P. xylostella. Full article

Neuroinflammation plays a central role in the onset and progression of neurodegenerative disorders. Several disease-modifying therapies have been developed to target neuroinflammatory pathways in specific disorders. However, their ability to stop disease progression or restore neuronal and mitochondrial homeostasis remains limited. This is still a major unmet clinical need. In this context, mesenchymal stromal cell (MSC)-derived Extracellular Vesicles (EVs) have emerged as a promising cell-free therapeutic strategy due to their ability to modulate immune responses and promote neuroprotection through the delivery of bioactive cargo. Recent evidence has identified a distinct subset of EVs, known as mitochondrial EVs (mito-EVs), which carry mitochondrial DNA, proteins, and functional components. These vesicles may uniquely influence cellular bioenergetics, redox balance, and neuroinflammatory signaling, offering additional therapeutic potential compared to conventional MSC-EVs. This review summarizes the role of MSC-derived EVs in neuroinflammatory disorders, with a particular focus on mito-EVs. It also discusses preconditioning strategies to enhance EV efficacy, including hypoxic, inflammatory, pharmacological priming and genetic engineering approaches. Finally, we critically evaluate current preclinical evidence regarding the treatment of major neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, Multiple Sclerosis, and Amyotrophic Lateral Sclerosis, as well as Traumatic Injury, highlighting the key challenges for clinical translation. Full article

B-cell maturation antigen (BCMA)-directed therapies (BDTs) have transformed relapsed/refractory multiple myeloma treatment, but optimal post-failure sequencing remains undefined. We evaluated real-world outcomes from three retrospective, multicenter analyses. Study 1 compared BCMA CAR-T and BCMA T-cell engagers (TCEs) in BDT-exposed patients (n = 95). Study 2 evaluated teclistamab in BDT-exposed versus BDT-naïve patients (n = 164). Study 3 examined talquetamab (GPRC5D-targeting TCE) in heavily pretreated patients (n = 68). CAR-T therapy achieved superior outcomes versus TCE (overall response rate [ORR] 79% vs. 51%, p < 0.001; median overall survival [OS] 30 vs. 12 months, p = 0.008). Teclistamab-treated BDT-exposed patients had lower ORR (53% vs. 68%, p = 0.02) and shorter median progression-free survival (PFS; 2.5 vs. 9.7 months, p = 0.01) compared with BDT-naïve patients. Administration < 6 months post-BDT showed inferior outcomes (hazard ratio [HR] 2.5 for PFS; HR 2.9 for OS). Talquetamab achieved an ORR of 68.3% among BDT-exposed patients, with significantly lower response rates when administered < 6 months post-BDT or when BDT was the immediate preceding treatment (56.8% vs. 84.6% and 48% vs. 80.6%, respectively). Treatment-free intervals of ≥6 months between T-cell-redirecting therapies improved efficacy and survival. Post-BDT sequencing should prioritize CAR-T therapy when feasible, allow >6-month intervals before BDT re-challenge, and utilize non-BCMA targets for early relapse or BDT-refractory disease. Full article