Search Results (1,201)

Since the discovery of RNA interference (RNAi), small interfering RNA (siRNA) has emerged as a transformative therapeutic modality, shifting the paradigm from permanent genomic modification to the flexible interception of genetic information. Despite the delivery gap caused by biological barriers, innovations in chemical stabilization and delivery platforms have propelled siRNA from niche applications to the mainstream management of chronic conditions. This review provides a comprehensive analysis of the distinct mechanistic advantages of siRNA over antisense oligonucleotides, with particular emphasis on its catalytic turnover via the RISC and high target specificity. We further evaluate the critical transition from first-generation lipid nanoparticles to ligand-conjugated systems, specifically trivalent N-acetylgalactosamine (GalNAc). Through an examination of the clinical success of Inclisiran and the recent approval of Plozasiran, we discuss how these advances have improved patient compliance and extended dosing intervals. Furthermore, this article explores the emerging frontier of extra-hepatic delivery and the expansion toward metabolic and oncological targets. Ultimately, this review highlights the potential of siRNA to become a programmable standard of care for a broad spectrum of previously intractable diseases. Full article

Hemoptysis is a potentially life-threatening phenomenon with a wide range of underlying causes. While most episodes are linked to common conditions such as infections, malignancy, or pulmonary embolism, a proportion of cases are due to unusual and often unexpected etiologies. This narrative review summarizes published case reports, series, and observational studies describing rare causes of hemoptysis, including vascular malformations, congenital anomalies, benign tumors, systemic diseases, and unusual infections. These conditions are frequently overlooked, which may delay recognition and appropriate management. The reviewed examples highlight the variety of diagnostic challenges and the broad spectrum of therapeutic strategies that may be required, ranging from endovascular procedures and surgery to targeted medical therapy. Despite advances in diagnostic methods, a subset of patients remain classified as having idiopathic or cryptogenic hemoptysis. For this reason, clinicians should keep a broad differential diagnosis in mind and remain aware of rare but clinically important entities. Awareness of these uncommon presentations and individualized patient management are essential for improving outcomes and avoiding missed critical diagnoses. Full article

The increasing prevalence of fungal infections caused by Candida species, together with rising antifungal resistance, highlights the urgent need for novel therapeutic agents with improved efficacy and safety. In this study, a series of 3-substituted rhodanine derivatives (3–6) were synthesized and evaluated as potential multifunctional compounds combining antifungal activity and ferric reducing capacity in the FRAP assay. The compounds were characterized using FT-IR and NMR spectroscopy and assessed for their physicochemical and pharmacokinetic profiles through in silico ADME analysis. Biological evaluation revealed that compounds 3 and 5 exhibited the most promising antifungal activity against a panel of clinically relevant Candida strains, with compound 5 demonstrating broad-spectrum, predominantly fungicidal effects. In contrast, compounds bearing a bulky 4-chlorobenzoyl substituent (4 and 6) showed reduced activity, indicating the importance of structural features for antifungal efficacy. Ferric reducing capacity assessment using the FRAP assay confirmed that all compounds possess reducing activity, with compounds 3 and 6 showing the highest potential. Safety evaluation using zebrafish (Danio rerio) embryos and larvae revealed concentration-dependent toxicity for all compounds. Notably, compounds 5 and 6 exhibited significant embryotoxicity and neurobehavioral effects at low micromolar concentrations, whereas compound 3 demonstrated a more favorable safety profile, with minimal impact on development and locomotor activity. Taken together, these results indicate that compound 3 provides a balanced combination of antifungal activity and reduced toxicity, while compound 5 represents a highly active but more toxic derivative. The observed structure–activity relationships emphasize the importance of carefully tuning substituent-dependent properties to optimize both biological activity and safety, supporting the continued investigation of rhodanine-based multifunctional antifungal agents targeting fungal proliferation and ferric reducing properties. Full article

The sustained increase in bacterial resistance has driven the search for therapeutic alternatives that may help reduce antibiotic use, particularly in empirical treatments. In this context, topical ophthalmic antiseptics have emerged as effective and safe tools, suitable for both perioperative prophylaxis and the management of mild or superficial ocular diseases. Their broad spectrum of activity—encompassing bacteria, fungi, viruses, and protozoa—together with the low likelihood of inducing resistance, establishes them as valuable partners in daily clinical practice. This article reviews the current evidence on the use of antiseptics in veterinary ophthalmology, focusing on their clinical applications, therapeutic benefits, and limitations. It also highlights the need for further studies to establish species-specific, disease-specific, and context-based protocols. Full article

Background: Antimicrobial stewardship in Neonatal (NICU) and Pediatric Intensive Care Units (PICUs) is complicated by rapid physiological maturation and the high vulnerability of the developing gut microbiome. Traditional metrics fails to capture the true utilization density of antibiotics in these settings. This study evaluated antimicrobial consumption patterns and alignment with the WHO AWaRe framework in two Indonesian hospitals and its impact towards patients’ length of stay. Methods: A retrospective multicenter study was conducted at a public hospital (Haji Hospital) and a private university hospital (HU Hospital) across 2024–2025. The study population includes all admitted patients (n = 315 in NICU and n = 12 in PICU) to calculate utilization density. Consumption was quantified using Defined Daily Dose (DDD)/100 bed-days, and qualitative assessment was performed using the WHO AWaRe classification. Results: Generalized linear modeling revealed that appropriate antibiotic therapy was significantly associated with a 17% reduction in hospital length of stay (β = −0.187, p = 0.035). At HU Hospital, PICU exhibited a seven-fold higher antimicrobial density (37.56 DDD/100) compared to NICU (5.22 DDD/100). At Haji Hospital, NICU density was 4.95 DDD/100 bed-days. Weight-normalized simulations revealed weight-based dosing disparity with low absolute DDD values in neonates mask a significant biological burden and intense selection pressure on the gut resistome due to immature renal clearance. While Haji Hospital maintained high “Access” category adherence (92.21%), HU Hospital’s PICU showed a high reliance on “Watch” agents (71.27%), specifically Ceftriaxone and Meropenem, which are known drivers of multidrug resistance. Conclusions: Low absolute dosing in neonates does not equate to low therapeutic density or reduced environmental pressure. The heavy use of broad-spectrum agents in the PICU acts as a primary driver for microbiome disruption. To mitigate the emergence of multidrug-resistant organisms, stewardship must transition from adult-indexed metrics (DDD) to more precise measures like Days of Therapy (DOT) and prioritize “Access” protocols to preserve microbiome integrity. Full article

Colorectal cancer (CRC) is one of the most prevalent gastrointestinal malignancies worldwide and remains a major cause of cancer-related mortality. Although current treatment strategies, including surgery, chemotherapy, radiotherapy, and targeted therapies, have improved patient outcomes, their effectiveness is frequently limited by multidrug resistance, severe adverse effects, tumour recurrence, and restricted patient applicability. Consequently, there is an urgent need to develop novel therapeutic agents with improved efficacy and reduced toxicity. Marine bioactive peptides have emerged as promising candidates for CRC therapy because of their remarkable structural diversity, unique evolutionary adaptations, and broad spectrum of biological activities. Numerous marine-derived peptides exhibit potent anti-CRC effects by inducing apoptosis, regulating cell-cycle progression, suppressing invasion and metastasis, inhibiting angiogenesis, and modulating the tumour microenvironment while generally demonstrating low toxicity toward normal cells. Despite these advantages, the clinical translation of marine peptides remains constrained by several challenges, including poor stability, rapid enzymatic degradation, limited bioavailability, difficulties in large-scale production, insufficient target characterization, and a lack of long-term safety evaluation. Recent advances in peptide engineering and pharmaceutical technology have significantly accelerated progress in this field. Strategies such as structural modification, cyclization, nanoformulation, intelligent delivery systems, and artificial intelligence-assisted peptide design have improved peptide stability, targeting efficiency, pharmacokinetic properties, and production feasibility. These technological innovations provide new opportunities to overcome the major limitations associated with marine peptide therapeutics. This review systematically summarizes the sources, structural characteristics, extraction and purification methods, molecular mechanisms, and in vitro and in vivo anti-CRC activities of marine-derived peptides. In addition, the major translational challenges and current technological solutions are critically discussed, with particular emphasis on the integration of multidisciplinary approaches for the development of next-generation marine peptide-based therapeutics for colorectal cancer. Full article

This study investigated whether the therapeutic efficacy of Chinese yam polysaccharide (CYP) against ulcerative colitis (UC) depends on an intact gut microbiota. A dextran sulfate sodium (DSS)-induced colitis mouse model was established, and one treatment group received broad-spectrum antibiotics (ABXs) before CYP administration to deplete the intestinal microbiota. CYP markedly attenuated colonic injury, reduced disease activity, and suppressed inflammatory mediators under both microbiota-intact and microbiota-depleted conditions. CYP also enhanced intestinal barrier integrity, as evidenced by reduced serum endotoxin levels and increased expression of MUC-2, Claudin-1, Occludin, and ZO-1. In addition, CYP improved hepatic antioxidant status by increasing GSH-Px and catalase activities and decreasing malondialdehyde levels. Moreover, CYP reduced the activation of the NF-κB and MAPK signaling pathways, with similar trends observed under microbiota-depleted conditions. Microbiota profiling showed that CYP partially corrected DSS-induced dysbiosis, whereas the ABX + CYP group exhibited distinct microbial patterns with enrichment of carbohydrate-related metabolic pathways predicted by PICRUSt2. Collectively, these findings suggest that CYP retains protective efficacy after antibiotic pretreatment, indicating that its effects may not be exclusively dependent on gut microbiota modulation, possibly involving direct actions on immune and intestinal epithelial cells. Full article

Porcine β-defensin 2 (pBD2) possesses broad-spectrum antimicrobial properties and is crucial for gastrointestinal mucosal repair. Lactic acid bacteria (LAB) serve as optimal vectors for exogenous protein delivery due to their high biosafety, intestinal colonization capacity, and ability to modulate gut microecology. In this study, we engineered a recombinant Lactobacillus paracasei strain (pPG-N1-pBD2/27-2) that efficiently secretes pBD2. In vitro, this recombinant strain significantly enhanced the proliferation and migration of porcine intestinal epithelial cells (IPEC-J2). In vivo, oral administration of pPG-N1-pBD2/27-2 markedly alleviated dextran sulfate sodium (DSS)-induced colitis in mice. This protective effect was evidenced by reduced Disease Activity Index (DAI) scores, prevention of colon shortening, and decreased colonic activities of myeloperoxidase (MPO) and eosinophil peroxidase (EPO), alongside normalized N-acetyl-β-D-glucosaminidase (NAG) levels. Histopathological analysis revealed that the treatment preserved mucosal architecture, including goblet cells and crypts, and fortified the physical barrier by upregulating tight junction proteins. Mechanistically, the recombinant strain suppressed the colonic iNOS/COX-2 inflammatory axis, decreased serum pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), and elevated the anti-inflammatory cytokine IL-10. Furthermore, it restored systemic immune homeostasis by normalizing the proportions of splenic macrophages, T/B lymphocytes, and natural killer (NK) cells. In conclusion, pPG-N1-pBD2/27-2 mitigates colitis through a dual mechanism: reinforcing the intestinal physical barrier and rebalancing the innate–adaptive immune axis. These findings highlight the potential of pBD2-engineered probiotics as novel biological therapeutics for intestinal inflammatory diseases. Full article

Background/Objectives: Molecular tumor profiling has recently transformed oncologic care delivery, establishing precision medicine as an essential approach for defining cancer biology and revealing intratumoral heterogeneity. The growing accessibility of advanced nucleic acid sequencing technologies has created a demand for specialized expertise in interpreting comprehensive genomic profiling results. Academic institutions currently employ a strategy of conducting initial broad-spectrum genomic testing, followed by matching patients to investigational therapies targeting their specific genomic alterations. Consequently, molecular tumor boards (MTBs) have emerged predominantly within major cancer centers and academic medical institutions, providing the specialized knowledge necessary to translate precision oncology into routine clinical care. However, despite the substantial benefits of collaborative case review within tumor boards, clinicians frequently encounter multiple barriers to effective MTB implementation. Methods: this report examines these challenges performing an exploratory quantitative synthesis approach and explores implementation strategies and best practices derived from collective institutional experiences, with the goal of establishing a functional MTB at the local level and thereby expanding oncology patient access to cutting-edge therapeutic options. Full article

Ononis spinosa L. (Fabaceae), commonly known as spiny restharrow, is a widely distributed medicinal plant traditionally used in European and Middle Eastern phytotherapy, particularly for the management of urological and inflammatory conditions. Despite its long-standing ethnomedicinal relevance, comprehensive syntheses of its phytochemical profile and biological activities remain limited. This review aimed to summarize current evidence regarding the chemical constituents and pharmacological effects of O. spinosa. Four electronic databases (PubMed, Scopus, Web of Science, and SpringerLink) were searched for studies published between 1997 and 2024. The search yielded 308 records; after duplicate removal and eligibility screening, 34 studies met the inclusion criteria. The phytochemical profile of O. spinosa is characterized predominantly by isoflavonoids (e.g., ononin and other formononetin derivatives), triterpenes, phenolic acids, and additional polyphenolic compounds. Although the phytochemical profile of O. spinosa includes multiple classes of secondary metabolites, this review places particular emphasis on phenolic compounds, given their prevalence and well-documented biological activities. Experimental evidence indicates a broad spectrum of biological activities, including anti-inflammatory effects (associated with cPLA2α inhibition and cytokine modulation), antibacterial and antifungal activity, antioxidant capacity, wound-healing and dermatological benefits, as well as diuretic and anti-adhesive effects in urinary models. Additional reported properties include antiproliferative, anti-adipogenic, analgesic, and neurotrophic activities. Proposed mechanisms of action involve enzyme inhibition (e.g., Hyal-1 and COX-2), modulation of transient receptor potential (TRP) channels, redox regulation, and interference with microbial adhesion and inflammatory signaling pathways. Overall, O. spinosa contains bioactive compounds exhibiting a wide range of pharmacological activities supported by in vitro and in vivo studies. Among the investigated effects, anti-inflammatory, urological, and wound-healing activities appear to be the most promising targets for future research. These findings highlight its therapeutic potential while emphasizing the need for well-designed clinical studies to further validate its medicinal applications. Full article

Wild mushroom poisoning remains a major medical and toxicological challenge worldwide because of the diversity of toxic compounds, the broad spectrum of clinical manifestations, and the risk of severe hepatic or renal injury. Early differentiation between self-limiting gastrointestinal syndromes and potentially fatal intoxications with progressive organ failure remain a central clinical challenge. This review examines recent advances in the diagnosis, risk stratification, and therapeutic management of wild mushroom poisoning, with amatoxin intoxication serving as the principal clinical focus. Selected evidence from other mushroom toxic syndromes is also included to support differential diagnosis, highlight syndrome-specific variability, and provide comparative clinical and methodological context. The recent literature indicates a shift from predominantly symptom-based diagnosis toward integrated models combining clinical evaluation, laboratory biomarkers, toxicological testing, and analytical and molecular methods. Liquid chromatography, mass spectrometry, immunoassays, and the molecular identification of fungal species have improved diagnostic precision, particularly in cases with uncertain exposure history or delayed presentation. Current management relies on early multimodal strategies including intensive supportive care, targeted pharmacological interventions, extracorporeal detoxification, and, in selected severe cases, liver transplantation. Overall, clinical outcome depends not only on toxin profile, but also on timely diagnosis, accurate early risk stratification, and prompt coordinated treatment. Future research should prioritize standardized diagnostic pathways, validated prognostic models, and clinically applicable treatment algorithms that support earlier escalation of care in severe mushroom intoxication. Full article

Astaxanthin (AST) is a potent carotenoid renowned for its exceptional antioxidant properties, which has attracted considerable scientific interest due to its broad spectrum of health benefits. This review comprehensively evaluates the therapeutic potential of AST in counteracting age-related decline, oxidative stress, and immune dysfunction, while also examining its beneficial effects on gut and skin health. Current evidence demonstrates that AST effectively mitigates oxidative stress and supports cellular health and longevity by neutralizing free radicals and upregulating endogenous antioxidant systems. In addition, AST modulates immune responses under conditions of immune dysfunction, thereby enhancing resilience against inflammatory disorders and infections. Emerging studies further indicate that AST promotes gut health by improving intestinal barrier integrity and maintaining a balanced gut microbiota, both of which are essential for systemic well-being. Moreover, its capacity to enhance skin elasticity and protect against ultraviolet-induced damage underscores its promising applications in cosmetic and dermatological products. This review highlights the urgent need for additional well-designed clinical trials to fully elucidate the underlying mechanisms, optimal bioavailability, dosage regimens, and long-term safety of AST. By integrating findings across multiple research domains, the present work provides a concise yet comprehensive overview of AST as a promising nutraceutical for promoting health, healthy aging, and the management of chronic diseases. Full article

Ferroptosis is a form of regulated cell death driven by iron-dependent phospholipid peroxidation and has emerged as a key mechanism of neuronal injury across a broad spectrum of neurological disorders. MicroRNAs (miRNAs), which function primarily as post-transcriptional regulators of gene expression, are increasingly recognized as important modulators of the regulatory networks governing ferroptosis and as potential therapeutic targets in these conditions. In this review, we synthesize current advances in miRNA-mediated regulation of ferroptosis in neurological disorders. We first outline the core molecular pathways governing ferroptosis, with particular emphasis on antioxidant defense, lipid peroxidation, and iron metabolism. We then integrate evidence from ischemic stroke, intracerebral hemorrhage, epilepsy, toxic encephalopathy, spinal cord injury, Parkinson’s disease, and Alzheimer’s disease, to illustrate how disease-specific miRNA regulatory axes shape ferroptotic vulnerability and its pathological consequences in distinct neurological settings. Importantly, we highlight exosome-based strategies targeting ferroptosis-related miRNA networks as a promising therapeutic approach for neurological disorders, with demonstrated neuroprotective and functional benefits in preclinical studies. Collectively, current evidence supports miRNA-mediated regulation of ferroptosis as an important mechanistic framework and a promising therapeutic target in neurological disorders. Full article

Background: Tectoridin is a prominent isoflavone glycoside found in herbs such as Belamcanda chinensis (L.) DC and Iris tectorum Maxim. It has drawn increasing research interest due to its promising pharmacological activities. However, no critical review to date has determined whether its broad pharmacological activity stems from binding to specific targets or from the non-specific, broad-spectrum activity commonly associated with flavonoids. This paper provides a comprehensive review of tectoridin, covering its plant sources, pharmacological effects, pharmacokinetics, and toxicity, alongside an in-depth analysis of the mechanisms underlying its pharmacological effects and strategic recommendations for advancing its clinical translation. Methods: A systematic literature search was conducted in PubMed, Web of Science, Google Scholar, SciFinder, and CNKI for publications from 1968 to 2025 using keywords including tectoridin, tectorigenin 7-O-glucoside, traditional uses, ethnopharmacology, pharmacology, bioactive compounds, biological activity, pharmacokinetics and toxicity. Results: Tectoridin exhibits a broad spectrum of pharmacological activities, including anticancer, anti-inflammatory, hepatoprotective, antidiabetic, antioxidant, cardiovascular, and estrogenic effects. Pharmacokinetic studies have shown rapid tissue distribution and slow elimination; the aglycone metabolite tectorigenin often displays enhanced bioactivity, and chemical modifications may further improve efficacy. Toxicity data suggest relative safety in medicinal food contexts, but comprehensive in vivo studies remain limited. Tectoridin shows promise for treating cancer and inflammatory diseases; however, further research is needed to elucidate its molecular mechanisms, clarify toxicity, and optimize bioactivity. Conclusions: This review bridges natural products and modern therapeutics by focusing on tectoridin, highlighting its therapeutic potential, addressing challenges, and offering new perspectives for treating various diseases. Full article

The genus Serjania (family Sapindaceae) comprises more than 240 species, primarily distributed in Brazil and Mexico, and it exhibits considerable ethnobotanical and therapeutic potential. Ethnobotanical evidence documents the widespread use of decoctions prepared from the leaves, stems, and roots of Serjania species for the treatment of gastrointestinal disorders, renal pain, inflammatory conditions, and infections. Among the most extensively studied species are S. marginata, S. erecta, S. lethalis, S. caracasana, S. goniocarpa, S. schiedeana, S. yucatenensis, S. triquetra, and S. racemose. Phytochemical research has identified a diverse array of bioactive secondary metabolites, including saponins, flavonoids, phenolic acids, tannins, and terpenoids. Significant experimental evidence supports the broad spectrum of biological activities of these Serjania species, including antimicrobial, anti-inflammatory, antioxidant, gastroprotective, antihypertensive, analgesic, antivenom, cytotoxic, antimutagenic, anti-ulcer, photoprotective, antiparasitic, and vasorelaxant effects, as demonstrated in both in vitro and in vivo models. Although preliminary toxicity assessments of extracts from some Serjania species in murine models, Oreochromis niloticus (Nile tilapia), and Artemia salina suggest a favorable safety profile, significant research gaps remain. Additionally, several Serjania species have shown potential as natural pesticides and bioherbicides, highlighting their relevance in agricultural applications. Future studies should prioritize the isolation and structural characterization of individual bioactive compounds, as well as the elucidation of their molecular mechanisms of action, moving beyond crude extract-based screening approaches. Overall, this review summarizes current knowledge on traditional uses, phytochemical composition, biological activities, and biotechnological applications of Serjania species. Full article