Search Results (3,983)

Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as the most transformative cellular immunotherapy modality, with its evolutionary trajectory intrinsically coupled to advances in immune receptor structure–function paradigms. Recent technological breakthroughs have yielded unprecedented mechanistic insights into immune receptors. Cryo-electron microscopy, single-cell omics, and structural biology have revealed the molecular architecture and functional dynamics of key receptors, including T-cell receptors (TCRs) and B-cell receptors (BCRs). This comprehensive review systematically integrates the latest discoveries in immune receptor structure–function relationships, emphasizing the mechanistic underpinnings of receptor diversity generation, signal transduction networks, and their direct translational impact on CAR-T therapeutic optimization. We critically examine the innovative design principles governing fourth-generation CAR-T cells, delineate breakthrough strategies for overcoming solid tumor immunoresistance, and analyze the synergistic potential of CAR-T and TCR-T technological convergence. Particular attention is devoted to elucidating how fundamental immune receptor research can be harnessed to address the tripartite challenges of safety, efficacy, and persistence that currently constrain CAR-T clinical applications. This review establishes a mechanistic framework for developing next-generation CAR-T technologies grounded in immune receptor biology and provides strategic insights for accelerating cellular immunotherapy clinical translation. Full article

Background: Endometriosis is a chronic condition associated with substantial healthcare costs, diagnostic delays and long-term impairment in quality of life. Despite the recognized economic burden, patient-reported financial distress remains insufficiently studied. The aim of this study was to adapt and validate the Polish version of the Comprehensive Score for Financial Toxicity (COST-FACIT) for use in women with endometriosis, as well as to examine demographic and clinical factors associated with financial toxicity. Methods: A cross-sectional study was conducted among Polish women with endometriosis using an online survey. The COST-FACIT was adapted following standard forward–backward translation procedures, with FACIT approval. Psychometric evaluation included internal consistency, construct validity, convergent validity with the Financial Well-Being Scale, and test–retest reliability. Exploratory and confirmatory factor analyses were performed, and multivariable models were used to identify factors associated with financial toxicity. Results: The adapted scale demonstrated good psychometric properties, with excellent internal consistency (Cronbach’s α = 0.92; McDonald’s ω = 0.92) and strong test–retest reliability (r = 0.87). Exploratory factor analysis supported a two-factor structure of the instrument. COST-FACIT scores were strongly correlated with financial well-being (r = 0.78). Higher education, stable employment and higher income were associated with better financial well-being, whereas longer symptom duration, greater distance to care and higher healthcare expenditures were associated with worse scores. Conclusions: The Polish COST-FACIT demonstrated good psychometric properties and may serve as a useful instrument for assessing financial toxicity in women with endometriosis. The results highlight the financial burden of the disease and support the use of patient-reported measures to identify individuals at risk of financial distress and reduced quality of life. This tool may facilitate clinical research and improve patient-centered care. Full article

Wound healing is a complex physiological process involving multiple stages, including hemostasis, inflammation, proliferation, and remodeling, which imposes high demands on the functionality and adaptability of wound repair materials. Hydrogels, as a class of novel materials, have become ideal wound dressings due to their excellent biocompatibility, breathability, and conformability. Sodium alginate-based composite hydrogels offer advantages such as readily available raw materials and mild preparation conditions. They can also endow materials with properties including antibacterial, anti-inflammatory, hemostatic, and pro-angiogenic effects, meeting the application requirements for multifunctional and highly efficient wound dressings. As a result, they have attracted considerable attention in the field of wound repair. This article introduces the preparation methods of physically and chemically crosslinked sodium alginate-based composite hydrogels, as well as the drug release mechanisms from these hydrogels. It elaborates on their applications in wound dressings, discusses key challenges including difficulties in large-scale preparation, high barriers to clinical translation, insufficient long-term in vivo stability, and low integration of intelligent functions, and outlines future research directions in terms of large-scale fabrication, regulatory compliance, long-term safety, and intelligent design. This review aims to provide a theoretical basis for the development of novel sodium alginate-based composite hydrogels for wound dressings and to promote their clinical translation and practical application in this field. Full article

Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation, playing a critical role in the pathogenesis of various cardiomyopathies, including hypertrophic, dilated, diabetic, ischemic, doxorubicin-induced, and septic cardiomyopathy, as well as myocardial ischemia–reperfusion injury. This article provides a comprehensive narrative review of the molecular mechanisms of ferroptosis—centered on dysregulation of the GPX4/System Xc⁻ axis, iron metabolism, and lipid metabolism—and its role in cardiovascular diseases, with a specific focus on the cardioprotective effects of Traditional Chinese Medicine (TCM). Through a systematic analysis of recent literature, we highlight active components (e.g., baicalin, ginsenoside Rg3, resveratrol, tanshinone IIA), compound formulations (e.g., Qishen Granule, Zhilong Huoxue Tongyu Capsule), and electroacupuncture therapy, which exert effects via multi-target regulation of ferroptosis-related pathways such as Nrf2/HO-1/GPX4, p53/SLC7A11, and PI3K/AKT. Evidence indicates that TCM interventions effectively alleviate cardiomyocyte ferroptosis by activating the Nrf2 antioxidant pathway to upregulate GPX4/SLC7A11, modulating iron metabolism to reduce labile iron pools, and inhibiting ACSL4/ALOX15-mediated lipid peroxidation, with these effects validated in diverse cardiovascular disease models showing improved cardiac function. Targeting ferroptosis offers a novel therapeutic strategy for cardiovascular diseases, and TCM—with its synergistic multi-component, multi-target, multi-pathway advantages—holds significant potential in this context. Future research should prioritize elucidating complex network mechanisms and advancing clinical translation via high-quality studies to provide new theoretical foundations and drug candidates for cardiovascular disease management. Full article

Major depressive disorder (MDD) and anxiety disorders are increasingly understood as conditions involving complex metabolic dysregulation across multiple biological domains. This review aimed to synthesize current clinical and translational evidence on amino acid metabolism, lipid metabolism and short-chain fatty acids (SCFAs) as potential biomarkers, and components of integrative metabolic profiling in these disorders. A structured narrative approach was applied, focusing on studies assessing metabolomic alterations, their clinical correlates and their potential role in patient stratification, and treatment response. The available evidence indicates that amino acid disturbances, particularly within the tryptophan–kynurenine pathway, represent the most consistent and clinically interpretable findings. Lipid-related alterations, especially involving long-chain polyunsaturated fatty acids, provide complementary insights into membrane function, inflammation and neuroplasticity. In contrast, SCFAs appear to function as context-dependent markers rather than robust standalone biomarkers, with their clinical relevance depending on biological matrix, metabolic context and host–microbiota interactions. Importantly, most studies assess individual metabolites rather than integrated metabolic profiles, limiting their interpretability within a metabolomic framework. Overall, current evidence supports a shift toward integrative biomarker models that combine metabolic data with selected molecular and clinical parameters. Future research should focus on standardized, reproducible profiling approaches to enable biologically informed stratification and personalized treatment strategies. Full article

Cannabidiol (CBD), a major non-psychoactive phytocannabinoid, has attracted considerable attention owing to its broad therapeutic potential. Its anti-inflammatory, antimicrobial, and antitumor properties make it a promising candidate for the treatment of mucosa-associated diseases. However, the clinical translation of CBD is significantly hindered by its unfavorable physicochemical properties, particularly high lipophilicity and poor aqueous solubility, which result in low bioavailability. To overcome these limitations, the rational selection of administration routes in combination with advanced drug delivery systems tailored to disease pathophysiology is essential. Such strategies are critical for improving the stability of CBD, enhancing mucosal permeation, and enabling controlled and targeted release at diseased sites. Nevertheless, a systematic review focusing on these aspects is still lacking. This review first summarizes the relationship between CBD and the mucosal endocannabinoid system, together with its pharmacological effects. It then discusses the therapeutic potential of CBD in mucosal disorders of the digestive and respiratory systems. In addition, current administration routes and advanced delivery systems for CBD are reviewed to provide insights for future research and clinical translation. Finally, the remaining challenges associated with the clinical application of CBD and future development directions are discussed. Full article

Diatom nanotechnology offers significant potential for the development of innovative diatom-based nanocarriers for drug delivery and bioimaging, with promising implications for the treatment and diagnosis of diverse diseases. However, clinical translation of these nanocarriers remains limited due to an incomplete understanding of their in vivo fate. Current studies on the biodistribution, intracellular behavior, biodegradation, and clearance of diatom-based nanocarriers are inadequate and often lack systematic evaluation, leaving critical knowledge gaps. A comprehensive understanding of how these nanocarriers traverse biological barriers, interact with cellular components, and are ultimately eliminated from the body is essential for their rational design and safe clinical implementation. This perspective critically examines the in vivo fate of diatom-based nanocarriers, highlighting recent advances while identifying key challenges and unresolved questions. By integrating insights into their biodistribution, intracellular interactions, toxicological profile, biodegradation, and clearance mechanisms, this article provides a framework to guide the development of more effective and clinically relevant diatom-based nanoplatforms. Furthermore, it outlines future research directions and design strategies for next-generation nanoformulations, aiming to accelerate their translation from bench to the bedside. Full article

Natural products are the fundamentals of drug discovery due to their exceptional structural diversity and biological activity’s evolutionary optimization. The review provides a critical and integrative analysis of natural products in pharmaceutical chemistry, highlighting their significance for current biomedicine and pharmacotherapy. The review is organized around a system that connects structure, function, and translation, focusing on structural analysis, scaffold design, and mechanistic understanding in major disease-relevant therapeutic areas. Investigations on representative compounds like paclitaxel, artemisinin, and curcumin are presented to explain the way molecular architecture regulates pharmacological activity, drug selectivity, and clinical performance. The review evaluates significant medicinal chemistry strategies, including semisynthetic modification, prodrug design, and scaffold optimization, and their crucial roles in enhancing potency, pharmacokinetics, and safety. We critically examine the latest advancements in drug delivery technologies, particularly those based on nanotechnology and carrier-free methods, regarding their translational potential and regulatory concern. Current challenges pertaining to pharmacokinetics and ADMET properties, as well as the standardization of analysis, are also examined, emphasizing their impact on reproducibility in research. Researchers investigate the role and limitations of emerging fields such as genome mining, synthetic biology, and network pharmacology in enhancing discovery pipelines. Thus, this review integrates chemical, pharmacological, and translational approaches and suggests an effective strategy to overcome challenges in the development of natural products as the next generation of precision medicine therapeutic agents. Full article

With colorectal cancer (CRC) accounting for over 1.9 million new cases and 930,000 deaths globally in 2020, there is a critical need for innovative indicators to forecast disease advancement and therapeutic outcomes. The gut microbiome has emerged as a fertile area for discovering such diagnostic and prognostic signals. This narrative review collected current evidence on intestinal microorganisms and their metabolic products as candidate markers for CRC control. Intestinal communities influence malignancy through diverse mechanisms, including metabolic shifts, immune modulation, inflammation, proliferation/apoptosis regulation, genotoxicity, and mucosal barrier disruption. Pathogenic species, such as Fusobacterium nucleatum and enterotoxigenic Bacteroides fragilis, facilitate tumorigenesis via FadA-mediated signaling and Th17/IL-17 responses. In contrast, beneficial taxa like Faecalibacterium prausnitzii and Akkermansia muciniphila provide protective effects through short chain fatty acid production. Macrophage phenotype physiological equilibrium is altered and inflammatory status fluctuates under the former. Metabolically, hydrogen sulfide damages mitochondrial DNA and secondary bile acids stimulate cellular proliferation. While 16S rRNA sequencing and shotgun metagenomics are established detection strategies, innovative platforms like organoids and gene arrays remain in the exploratory stage. Clinical data indicates that F. nucleatum aligns with advanced tumor stage, and its combined detection with colibactin-producing E. coli achieves high sensitivity for early-stage screening. Additionally, A. muciniphila levels can anticipate the efficacy of PD-1 blockade immunotherapy. Microbiota-derived tools represent a transformative direction in oncology. Future research must focus on standardizing protocols and validating multi-marker panels to enhance clinical translation. Full article

Sarcopenia is an age-related syndrome characterized by the progressive loss of skeletal muscle mass, strength, and function, significantly impairing older adults’ independence and quality of life. Given their anti-inflammatory, antioxidant, and metabolic regulatory properties, n-3 polyunsaturated fatty acids (n-3 PUFAs) have emerged as a promising nutritional strategy to mitigate this muscle degeneration. This review systematically synthesizes existing evidence regarding the association between n-3 PUFAs and sarcopenia. To capture the relevant literature, we searched PubMed, Web of Science, CNKI, and Wanfang Data using a combination of subject headings and free-text terms. We supplemented primary search terms—such as “n-3 polyunsaturated fatty acids,” “omega-3 fatty acids,” “sarcopenia,” and “muscle mass”—with mechanism-related keywords like “inflammation,” “muscle satellite cells,” and “oxidative stress.” We also manually screened the reference lists of the included literature. Our inclusion criteria encompassed interventional studies, observational studies, and high-quality reviews, while excluding conference abstracts, duplicate publications, and studies with incomplete data. This review first outlines the established biological mechanisms linking n-3 PUFAs to the pathological progression of sarcopenia, specifically detailing how these fatty acids improve muscle satellite cell function, suppress inflammation and oxidative stress, and ameliorate metabolic disorders. Next, we critically evaluate recent clinical studies and reviews, analyzing sources of study heterogeneity such as variations in sample size, intervention dose and duration, outcome measures, and baseline participant characteristics. We also highlight current research hotspots—including specialized pro-resolving mediators (SPMs), the gut–organ axis, combined interventions, and precision nutrition strategies—while emphasizing the functional differences between EPA and DHA to guide future intervention designs. Current evidence indicates that while n-3 PUFA supplementation can improve muscle strength and physical performance in older adults, its effects on muscle mass remain inconsistent. Addressing key research gaps, particularly the lack of standardized core outcome measures and unclear dose–response relationships, is critical. Ultimately, future research must prioritize developing high-bioavailability formulations, conducting personalized trials based on baseline n-3 PUFA status, and deepening investigations into inter-organ networks to translate these nutritional insights into effective sarcopenia prevention and management strategies. Full article

Peptide therapeutics have emerged as a versatile class of biomolecules bridging the gap between small-molecule drugs and large biologics. Advantages of such molecules include high target specificity, potent bioactivity and reduced off-target toxicity. Despite these, broader clinical translation remains constrained by inherent limitations like poor metabolic stability, rapid renal clearance, limited membrane permeability and scalable synthesis. This review aims to systematically integrate advances in peptide science across natural discovery, synthetic methodologies, structural engineering, and translational delivery systems, while identifying critical research gaps hindering clinical adoption. We highlight diverse natural sources of bioactive peptides, including plant- (lunasin), animal- (Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP)), microbial- (nisin and cyclosporine), marine- (dolastatins) and venom-derived (chlorotoxin and ω-conotoxin MVIIA (ziconotide)) agents. Advances in solid-phase peptide synthesis (SPPS), green chemistry, and catalytic strategies are discussed alongside emerging in silico approaches, including artificial intelligence-driven sequence design and molecular modeling. Structural modifications such as cyclization, hydrocarbon stapling, PEGylation, and lipidation are critically evaluated for their role in enhancing pharmacokinetic and pharmacodynamic properties. Furthermore, nanoformulation strategies, including self-assembling peptides and cell-penetrating systems, are examined for their potential to overcome biological barriers. Importantly, this review identifies key unresolved challenges, including the lack of predictive models for peptide delivery systems, safety concerns associated with long-term modifications, and limited in vivo validation of naturally derived peptides. Addressing these gaps through integrated computational and experimental approaches will be essential for advancing next-generation peptide therapeutics. Collectively, this work provides a comprehensive framework for the rational design and translation of peptide-based precision medicines. Full article

Background/Objectives: The airway epithelium plays a central role in host defense, inflammatory signaling, and disease progression across infectious, inflammatory, and genetic respiratory disorders. Human nasal epithelial organoids have emerged as accessible and patient-specific in vitro platforms with increasing translational relevance. This systematic review aimed to critically evaluate the current evidence on nasal epithelial organoid models, focusing on donor characteristics, culture methodologies, differentiation strategies, and translational applications. Methods: A systematic search of PubMed/MEDLINE, Embase, Scopus, Ovid MEDLINE, and Cochrane Library was conducted for studies published between 1990 and April 2026. The review followed PRISMA guidelines and was structured according to the PICOTS framework. Eligible studies included in vitro experimental investigations using human-derived nasal epithelial organoids in infectious, inflammatory, or precision medicine contexts. Risk of bias was assessed using the QUIN tool. Results: Seventeen studies met the inclusion criteria. Applications clustered into three principal domains: infectious disease modeling, inflammatory and epithelial remodeling research, and cystic fibrosis precision medicine. Most studies employed expandable three-dimensional Matrigel-embedded organoids or organoid-derived air–liquid interface systems. Infection-focused studies demonstrated variant-specific viral replication dynamics and epithelial immune responses, while inflammatory models reproduced disease-associated differentiation and remodeling phenotypes. Cystic fibrosis oriented studies showed that organoid swelling and electrophysiological assays correlate with CFTR functional rescue and, in selected cases, clinical response. Methodological heterogeneity across protocols and outcome reporting precluded quantitative synthesis. Conclusions: Human nasal epithelial organoids represent versatile translational platforms bridging accessible patient-derived tissue and advanced airway disease modeling. Although variability in culture protocols and functional benchmarks limits standardization, these models hold significant promise for mechanistic investigation, therapeutic stratification, and precision medicine applications. Full article

Antibiotic resistance is a growing global health threat. However, its evolution cannot be fully understood without considering antibiotic tolerance and persistence. Persister cells are phenotypic variants that survive lethal antibiotic exposure without heritable resistance, primarily through growth arrest, metabolic slowdown, and stress-adaptive states. Although persistence has been viewed as a transient survival phenomenon, increasing evidence suggests that it may also have a genetic basis by preserving populations during antibiotic-induced bottlenecks and enabling regrowth, mutation, and selection under certain conditions. This review examines the molecular mechanisms underlying persister formation, including toxin–antitoxin systems, stringent-response signaling, ATP depletion, translational arrest, and stress-response networks. We discuss how persistence contributes to antibiotic tolerance in biofilms, host environments, and recurrent infections, and how repeated antibiotic exposure may promote stepwise evolution from phenotypic survival to stable resistance in specific contexts. Evidence from experimental evolution, clinical observations, and system-level analyses supports a potential but context-dependent link between persistence and resistance. We also highlight therapeutic strategies targeting persister cells, including antipersister compounds, metabolic activation, combination therapies, bacteriophages, and alternative approaches. Finally, we outline future research directions, emphasizing single-cell technologies, systems biology, longitudinal clinical studies, and evolution-informed treatment design. A comprehensive understanding of persistence and its evolutionary implications is essential for improving treatment efficacy and limiting the emergence of long-term antibiotic resistance. Full article

Background: Acute limb ischemia (ALI) is a vascular emergency characterized by abrupt limb hypoperfusion, ischemia–reperfusion injury, and a high risk of thromboinflammatory and organ complications. Complement activation has been implicated in endothelial dysfunction, glycocalyx injury, and ischemia–reperfusion damage, but the clinical relevance of ongoing terminal complement blockade in patients presenting with ALI remains unclear, highlighting a gap between mechanistic understanding and real-world clinical outcomes. Methods: A retrospective cohort study was performed using the TriNetX federated research network. Adult patients with ALI were identified and stratified according to ongoing treatment with the C5 inhibitors eculizumab or ravulizumab. Outcomes included ischemic stroke, venous thrombosis, pulmonary embolism, arterial embolism, thrombotic disorders, acute kidney injury (AKI), and the composite outcome major adverse cardiovascular events (MACE) within 31 days. Propensity score matching was performed for demographic characteristics, cardiovascular comorbidities, complement-associated diseases and medications. Results: After propensity score matching, 112 patients remained in each cohort. Compared with matched controls, patients receiving C5 inhibition had a significantly higher risk of venous thrombosis (27.9% vs. 13.7%; p < 0.001), AKI (18.9% vs. 9.4%; p = 0.001), MACE (50.0% vs. 35.1%; p = 0.001), and thrombotic disorders (46.7% vs. 31.3%; p = 0.001). Time-to-event analyses confirmed significantly lower event-free survival for venous thrombosis (HR 2.3), AKI (HR 2.1), MACE (HR 1.6), and thrombotic disorders (HR 1.7). No significant differences were observed for ischemic stroke, pulmonary embolism, or arterial embolism. Conclusions: In patients with ALI, ongoing treatment with eculizumab or ravulizumab was not associated with an apparent reduction in short-term thromboinflammatory or cardiovascular complications. Instead, the observed outcome pattern suggests persistent vulnerability in this clinically uncommon but increasingly relevant high-risk population, although substantial residual confounding by indication and disease severity remains likely. These findings support further investigation of complement-targeted therapy, endothelial injury, and short-term vascular outcomes in ALI, and emphasize the translational relevance of linking mechanistic insights with clinical data to inform risk stratification and management strategies in this population. Full article

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