Search Results (6,398)

Platelet-rich gel (PRG) is a fibrin-based biobased biomaterial generated by activating platelet-rich plasma (PRP), yet its biological characterization has commonly relied on univariate measurements of isolated mediators. This study aimed to define the multivariate biological organization of PRG and related hemocomponents (PRP, chemically induced platelet lysate (CIPL), and plasma) in a canine model under single exposure to non-steroidal anti-inflammatory drugs (NSAIDs). In a randomized crossover design (n = 6 dogs), hemocomponents were produced at baseline (0 h) and 6 h after administration of carprofen or firocoxib. Platelet and white blood cell (WBC) counts, growth factors (platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor beta-1 (TGF-β1)), and cytokines (tumor necrosis factor alpha (TNF-α), interleukin-1 beta, and interleukin-10) were integrated using linear mixed-effects modeling, principal component analysis (PCA), and hierarchical clustering. PRG was derived from a leukocyte-poor PRP precursor with moderate platelet enrichment (~1.6-fold vs. whole blood) and a marked WBC reduction (~8–9-fold). In mixed-effects modeling, hemocomponent type significantly influenced the PDGF-BB:TNF-α log-ratio, with PRG (estimate −1.12; 95% CI −1.34 to −0.90) and plasma (−2.06; 95% CI −2.28 to −1.84) lower than PRP, while CIPL did not differ. Time and NSAID effects were not supported. PCA identified two orthogonal axes explaining 61.3% of total variance (PC1 = 43.7%, PC2 = 18.6%), separating a platelet/trophic dimension (log(PDGF-BB), log(TGF-β1), platelet count, PDGF-BB:TNF-α log-ratio) from an inflammatory dimension (log(TNF-α), log(IL-1β)). Overall, hemocomponent composition emerged as the primary determinant of mediator organization, supporting the interpretation of PRG as a structured, biomaterial defined by coordinated mediator networks. Full article

Background: Multiple evanescent white dot syndrome (MEWDS) is usually acute and self-limited, whereas multifocal choroiditis (MFC)/punctate inner choroidopathy (PIC) is relapsing; overlap can obscure early diagnosis and requires longitudinal multimodal imaging. Methods: We report a 4-year follow-up of a 31-year-old woman with fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and spectral-domain optical coherence tomography (SD-OCT), plus a systemic/neurologic/rheumatologic work-up. Treatment included intravenous methylprednisolone for presumed optic neuritis, followed by topical, periocular, intravitreal, and systemic corticosteroids, later escalated to adalimumab and an intravitreal dexamethasone implant. Because foveal granularity could not be documented, baseline was termed “MEWDS-like”. Diagnostic labelling was benchmarked against Standardization of Uveitis Nomenclature (SUN) criteria, and choroidal neovascularization (CNV) was assessed at each relapse by OCT and FA. Results: The right eye initially showed a MEWDS-like pattern with wreath-like FA lesions and disc leakage, hyperautofluorescent FAF lesions, focal ellipsoid zone disruption on SD-OCT, and multifocal ICGA hypofluorescent spots. A relapse at 6 months with peripapillary inflammatory foci and recurrent cystoid macular edema supported reclassification to a unilateral MFC/PIC-spectrum phenotype. At 2 years, the fellow eye developed mild vitritis, peripapillary hyperautofluorescence, peripapillary/arcade leakage on FA, delayed peripapillary filling on ICGA, and cystoid macular edema, establishing sequential bilateral MFC; no CNV developed and anti-vascular endothelial growth factor (anti-VEGF) therapy was not required. Complications included steroid-induced ocular hypertension and cataract surgery. Conclusions: The purpose of this report is to highlight longitudinal imaging “red flags” that supported reclassification from a MEWDS-like phenotype to a sequential bilateral MFC/PIC-spectrum disease. Full article

The continuous discharge of pharmaceutical residues into aquatic environments has raised significant environmental concerns due to their persistence and incomplete removal during wastewater treatment. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently detected pharmaceutical contaminants in industrial effluents. In this study, a sensitive and selective analytical method was developed for the simultaneous determination of ketoprofen (KTP), meloxicam (MEL), and celecoxib (CEL) in pharmaceutical wastewater using micellar electrokinetic chromatography (MEKC) combined with off-line solid-phase extraction (SPE). A high-volume SPE procedure (1000 mL sample) followed by evaporation and reconstitution provided a theoretical enrichment factor of approximately 10,000. Under optimised conditions, complete separation was achieved in less than 10 min. The method exhibited excellent linearity over a range of 0.5–20 µg/mL (r² > 0.999), with limits of detection in wastewater ranging from 14 to 18 ng/L. Accuracy and precision complied with ICH Q2(B) guidelines, and recoveries from spiked wastewater samples ranged from approximately 99% to 101%, indicating efficient extraction and minimal analyte loss. The validated method was successfully applied to real pharmaceutical wastewater samples, demonstrating its suitability for the routine monitoring of trace-level NSAIDs in complex industrial matrices. Full article

Background: There is growing interest in plant-derived compounds for managing vascular diseases. Veratramine (VRT), a steroidal alkaloid isolated from plants of the Veratrum genus, exhibits diverse biological effects such as antihypertensive, analgesic, and antitumor activities, yet its influence on hemostasis and thrombus formation has not been characterized. This investigation sought to determine whether VRT exerts anticoagulant effects using integrated in vitro and murine models. Methods: VRT’s anticoagulant profile was comprehensively evaluated using integrated biochemical, cellular, and murine models, including clotting time assays (aPTT/PT), chromogenic enzymatic assays, fibrin polymerization analysis, platelet aggregometry, and endothelial modulation of PAI-1/t-PA under inflammatory conditions. Results: VRT treatment significantly prolonged both intrinsic and extrinsic coagulation times, directly inhibited enzymatic activities of thrombin and FXa, and attenuated their generation by endothelial cells. Additionally, VRT interfered with fibrin clot formation and diminished agonist-induced platelet aggregation. Ex vivo coagulation analyses confirmed its anticoagulant action, while endothelial studies revealed a reduced PAI-1/t-PA ratio following VRT exposure. Conclusions: These data establish VRT as possessing novel direct dual inhibition of thrombin and FXa alongside suppression of fibrin polymerization, platelet reactivity, and PAI-1 expression—positioning it as a promising multifunctional anticoagulant agent. While preclinical murine models preclude direct clinical translation absent pharmacokinetic data, these findings warrant further mechanistic and translational investigation. Full article

Bacterial endophytes isolated from medicinal and wild plant species have recently gained significant attention for their medicinal properties, often closely linked to those of their plant hosts. This study identified two endophytic Bacillus isolates using 16S rRNA sequencing-based phylogeny. The impact of sublethal concentrations (0.5 mg/mL) of cadmium and hydrogen peroxide on metabolite production and bioactivity was also investigated. Phytochemical testing and antimicrobial and antioxidant assays revealed shifts in metabolite production under stress conditions. According to the phylogenetic analysis, Bacillus sp. NV35 and NV1 are respectively related to Bacillus cereus and B. mycoides. Phytochemical screening of methanolic crude extracts from both isolates tested positive for alkaloids, flavonoids, and saponins. Notably, tannins were detected only after cadmium treatment, while steroids were present following exposure to both cadmium and H₂O₂. LC-MS fingerprinting confirmed the presence of several tannins and steroids in treated samples. The untreated crude extracts exhibited an IC₅₀ of ~3 mg/mL with the DPPH assay, which decreased to ~1.5 mg/mL after treatment with cadmium or H₂O₂, demonstrating enhanced antioxidant potential under stress conditions. Additionally, extracts from both treated and untreated bacteria displayed antimicrobial activity against selected bacterial pathogens, with MIC values ranging from 62.5 μg/mL to 125 μg/mL. LC-MS analysis identified various antimicrobial and antioxidant metabolites, including phenoxymethylpenicilloyl, maculosin, (S,R,S)-alpha-tocopherol, 3-indoleacrylate, procyanidin A2, cis-11-eicosenamide, 3-hydroxy-3-phenacyloxindole, and 9-octadecenamide. Full article

The administration of specific immunoglobulin G-based antivenoms is a key strategy for treating snakebite envenoming victims. However, serious adverse reactions, such as anaphylaxis or serum sickness, are frequently observed following such administration. In addition, inflammation associated with delayed wound healing considerably drives the irrational use of antibiotics or anti-inflammatory agents, which may be linked to adverse reactions following antivenom treatment. In this study, we evaluated the factors contributing to adverse effects following the administration of snake antivenom, especially pharmacological treatment and premedication intended to prevent adverse reactions. Our retrospective study was conducted by healthcare professionals in Narathiwat, the southernmost province in Thailand, and it involved 980 patients confirmed to have been snakebitten from 2016 to 2021. Of these cases, 513 were treated with antivenom. Prevalence rates and 95% confidence intervals were calculated, and univariate and multivariate analyses were performed to determine the correlation between adverse reactions and medications. Following antivenom administration, the majority of the patients exhibited no adverse reactions (86.7%). Nevertheless, skin rash, itching, wheezing, angioedema, chest tightness, and fever were observed in 13.3% of those receiving snake antivenom. After the administration of antivenom for Malayan pit viper bite, adverse reactions occurred in 11.7% of the sample, especially among referral patients (p < 0.001). Epinephrine and antihistamines were prescribed as prevention and treatment for hypersensitivity due to antivenom administration. Antibiotics, Non-steroidal Anti-inflammatory drugs (NSAIDs), and acetaminophen were not associated with antivenom-induced adverse reactions. Interestingly, tramadol and antihistamines significantly reduced the occurrence of adverse reactions after antivenom administration (p < 0.05). Well-trained staff, close monitoring alongside resuscitation equipment and medications that can minimise the severity of anaphylactic reactions must be promptly available whenever antivenom is administered. Full article

Postnatal corticosteroids are frequently administered to extremely preterm infants to support respiratory management, yet their effects on the immature cardiovascular system are complex and underexplored. As the second installment in a series on physiology-informed steroid use, this narrative review focuses on the cardiovascular consequences of systemic corticosteroid therapy in preterm neonates. We examine how corticosteroids influence key aspects of cardiovascular physiology, including ductal closure, systemic and pulmonary vascular resistance, myocardial remodeling, and autonomic regulation. Attention is given to the hemodynamic transition of early postnatal life and how steroid exposure may interact with patency of the ductus arteriosus and vascular development. The potential for corticosteroids to contribute to reactive myocardial hypertrophy, systemic hypertension, and pulmonary hypertension is also reviewed in the context of both short- and long-term outcomes. Emerging diagnostic and monitoring tools are discussed for their potential to guide individualized therapy. These include targeted neonatal echocardiography (TnECHO) to assess cardiac function and structure, electrocardiography (ECG) for rhythm and conduction abnormalities, heart rate variability analysis for autonomic function, and circulating biomarkers to evaluate myocardial stress and inflammation. Together, these tools may inform tailored steroid timing and dosing, especially in the research context, while monitoring for signs of cardiovascular side effects in real time. By synthesizing mechanistic insights with evolving clinical evidence, this review highlights the need for a more nuanced understanding of how corticosteroids affect the developing cardiovascular system. It underscores the importance of integrating cardiovascular monitoring into routine care to optimize therapeutic benefit while minimizing unintended harm. Alongside companion reviews addressing respiratory and growth impacts, this installment contributes to a broader framework for individualized, physiology-driven steroid use in extremely preterm infants. Full article

Polygonatum odoratum (Mill.) Druce is a well-known traditional medicinal plant, with rhizomes as the principal medicinal tissue and polysaccharides as its key bioactive components. To conduct a systematic investigation of the polysaccharide biosynthetic pathway and screen key genes involved in the polysaccharide biosynthesis of different growth years and growth stages in P. odoratum, this study performed transcriptomic and metabolomic analyses on P. odoratum rhizomes of different growth years and growth stages. This study revealed that most saccharides, which serve as precursors for polysaccharide biosynthesis in P. odoratum rhizomes, exhibited higher levels in two-year-old P. odoratum than in three-year-old. Co-expression analysis revealed that PosacA3 showed a high positive correlation with sucrose, D-fructose, and D-glucose, while PoGT16 exhibited a high negative correlation with sucrose, D-fructose, and D-glucose. PoGT6 and PoGT32 displayed a positive correlation with D-glucose and sucrose, respectively, suggesting that these genes may be key regulators involved in polysaccharide biosynthesis in P. odoratum. Compared with two-year-old and three-year-old P. odoratum rhizomes harvested in July and September from Shaodong City, Hunan Province, China, when steroidal saponins and soluble sugars are required as medicinal components, two-year-old P. odoratum can be harvested in July or September. When alkaloids and amino acids and derivatives are the core extraction targets, both two-year-old and three-year-old P. odoratum are recommended to be harvested in September. This study furnishes a theoretical reference for the rational harvesting and utilization of P. odoratum, and lays a foundation for further elucidating its polysaccharide biosynthetic mechanism. Full article

Ketoprofen is a widely prescribed non-steroidal anti-inflammatory drug whose extensive global use, combined with limited biodegradability, has led to its increasing detection as a micropollutant in aquatic and terrestrial environments. Incomplete removal during wastewater treatment results in its continuous release into surface waters and soils, creating conditions for chronic, low-dose exposure of non-target organisms. This review synthesizes current knowledge on the physicochemical characteristics of ketoprofen, its mechanism of action, environmental occurrence, degradation pathways, and ecotoxicological effects. Particular emphasis is placed on biological and photochemical transformation processes that influence ketoprofen persistence and toxicity. While the acute toxicity of ketoprofen has been relatively well documented, data on chronic toxicity remain scarce, despite growing evidence that long-term exposure may pose significant ecological risks. Studies indicate that low environmental concentrations can induce hormetic responses in animals and plants, whereas higher levels may cause cellular damage associated with oxidative stress, affecting organisms ranging from microorganisms to vertebrates and vascular plants. By integrating available data on ketoprofen degradation and toxicity, this review highlights critical knowledge gaps regarding its chronic ecotoxicity and underscores the need for systematic environmental monitoring and the development of effective degradation strategies to mitigate risks to non-target organisms. Full article

Lasiosphaera calvatia (LC), referring to the dry fruiting bodies of certain puffball fungi, has been extensively used in traditional Chinese medicine (TCM). Documented in the Mingyi Bielu, its traditional medicinal properties encompass clearing heat, detoxification, reducing swelling, and stopping bleeding. Modern applications include promoting wound healing, anti-cancer therapy, lowering blood sugar, relieving coughs, and combating HIV, among others. This comprehensive review explores the evolving scientific understanding of LC, covering its botany, traditional use, phytochemistry, pharmacology, toxicology, and quality control. A wide range of chemical components, including steroids, phenolics, volatile compounds, amino acids, polysaccharides, and polypeptides, have been isolated and identified using diverse analytical techniques. Among these, sterols (particularly ergosterol derivatives), polysaccharides, and polypeptides are considered the major bioactive constituents. The active ingredients of LC are associated with relatively few side effects, a characteristic that supports its use in pediatric populations and underscores its significant research potential. These findings validate the traditional uses of LC and lay the groundwork for further scientific exploration. The sources utilized in this study encompass Web of Science, PubMed, CNKI site, the Chinese Pharmacopoeia, and doctoral and master’s theses. Full article

Steroid hormones exert diverse and tissue-specific biological effects despite sharing a conserved tetracyclic scaffold. Among these, anabolic–androgenic steroids (AAS) present a longstanding paradox: structurally related compounds can elicit markedly different anabolic, androgenic, and cardiovascular outcomes. This narrative review integrates advances in steroid structural chemistry, androgen receptor (AR) biology, and intracellular signaling to elucidate the molecular mechanisms underlying anabolic–androgenic dissociation. We summarize classical genomic and emerging non-genomic modes of steroid action, emphasizing how receptor conformation, ligand-binding domain architecture, co-regulator recruitment, and signaling bias shape downstream biological responses. Particular focus is placed on the structure–activity relationships of endogenous and synthetic androgens, with C17-substitution chemistry highlighted as a central determinant of receptor affinity, metabolic stability, pharmacokinetics, and tissue selectivity. By linking molecular structure to receptor-level mechanisms, we contextualize the physiological and pathophysiological effects of major AAS classes used clinically and non-medically, including testosterone esters, 19-nor derivatives, 17α-alkylated steroids, heterocyclic compounds, and halogenated compounds. While much of the mechanistic evidence derives from preclinical models, the integrated framework presented here provides a coherent basis for interpreting divergent anabolic, androgenic, and cardiovascular effects observed in humans. Collectively, this review bridges fundamental steroid biology with applied physiology and sports medicine, offering mechanistic insight relevant to therapeutic development, anti-doping science, and risk assessment of supraphysiological androgen exposure. Full article

Sarcopenia and glucocorticoid-induced myopathy are significant forms of muscle atrophy that pose considerable public health challenges. In this regard, preventing muscle atrophy is crucial for enhancing quality of life and increasing life expectancy. In this study, we investigated the effect of recombinant human KAI1 (rhKAI1) on myogenic differentiation and its protective effect against dexamethasone-induced muscle atrophy. rhKAI1 enhanced myogenic differentiation in both murine C2C12 myoblasts and primary human endometrial stromal cells, as evidenced by upregulation of myogenic regulatory factors and increased myotube formation. These effects were accompanied by increased phosphorylation of Akt and AMPK. In a dexamethasone (Dex)-induced atrophy model, rhKAI1 increased myotube diameter, restored MyHC expression, and reduced the expression of the E3 ligase atrogin-1, accompanied by increased phosphorylation of Akt and AMPK. In addition, rhKAI1 administration improved Dex-induced functional impairment in mice, as reflected by increased grip strength and improved rotarod performance. Molecular analyses further showed that rhKAI1 modulated Dex-induced fiber-type-related gene expression by restoring MYH7 (type I) and reducing MYH4 (type IIb) expression. Collectively, our findings demonstrate that rhKAI1 promotes myogenic differentiation and alleviates several functional and molecular features associated with glucocorticoid-induced muscle deterioration. These results support the potential of rhKAI1 as a candidate molecule for further investigation in steroid-induced muscle dysfunction. Full article

Background: Neonatal hyperglycemia is a common metabolic complication in extremely preterm (EP) infants; however, early risk factors and associated outcomes remain incompletely defined. Objective: To evaluate the association between neonatal hyperglycemia in the first postnatal week and key neonatal morbidities including early neurodevelopmental risk in EP infants. Methods: We conducted a retrospective cohort study of EP infants born in 2018–2019 at the Women’s Wellness and Research Center. Neonatal hyperglycemia was defined as a blood glucose level > 8.3 mmol/L. Maternal factors, delivery room interventions, early physiological markers, neonatal morbidities, and follow-up outcomes were compared. Propensity score matching was applied to balance the baseline demographic and perinatal differences. Results: Among 225 EP infants, 131 (58.2%) developed neonatal hyperglycemia in the first week (mild, 21.4%; moderate, 42%; severe, 36.6%). Before matching, infants with neonatal hyperglycemia had lower gestational age and birth weight and required more delivery-room surfactant, and their mothers had lower rates of premature rupture of membranes. After matching, neonatal hyperglycemia was associated with higher rates of ventilator-associated pneumonia (1.45 vs. 0.37; IRR 6.2, 95% CI 1.4–27.6), longer duration of invasive ventilation (19.8 ± 25.3 vs. 8.9 ± 24.8 days; mean difference −10.9 days; p = 0.042), higher postnatal steroid exposure (18.2% vs. 5.5%; OR 4.6, 95% CI 1.6–14.4; p = 0.040), and severe retinopathy of prematurity (ROP) (21.6% vs. 6.4%; OR 4.0, 95% CI 1.0–15.5; p = 0.032). A trend toward moderate-to-severe bronchopulmonary dysplasia was observed (33.3% vs. 15.9%; p = 0.054). Mortality did not differ significantly between groups; however, among non-survivors, age at death was higher in the neonatal hyperglycemia group. Conclusions: In EP infants, early neonatal hyperglycemia is associated with higher respiratory morbidity and severe ROP even after propensity score matching. These findings support neonatal hyperglycemia as a clinically relevant early risk marker and justify further prospective and interventional studies. Full article

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease in children requiring long-term management, yet real-world data on treatment patterns remain limited. Objective: To evaluate treatment trends and factors associated with topical non-steroidal medication use in pediatric AD. Methods: We retrospectively analyzed 3982 children with AD treated at a tertiary referral center in Thailand between 2015 and 2024. Demographic data, healthcare coverage, and prescribed treatments were reviewed. Multivariable logistic regression was used to identify factors associated with topical non-steroidal use. Results: The median age was 7 years, with no sex difference. The most commonly prescribed treatments were antihistamines (75.0%), topical corticosteroids (47.6%), moisturizers (43.9%), systemic immunosuppressants (15.7%), topical non-steroidal agents including topical calcineurin inhibitors, phosphodiesterase-4 inhibitors, and Janus kinase (JAK) inhibitors (12.7%), and biologics (0.1%). Moderate-potency corticosteroids predominated. Adolescents were less likely to receive topical non-steroidal agents than infants (OR 0.66, 95% CI 0.50–0.87), whereas patients under the Civil Servant Medical Benefit Scheme (CSMBS) had higher access than those under the Universal Coverage Scheme (UCS) (OR 8.40, 95% CI 5.76–12.25). Conclusions: Pediatric AD management was dominated by conventional therapies, with limited access to advanced treatments. Age and healthcare coverage strongly influenced prescribing patterns, highlighting the need for more equitable access. Full article

This critical integrative review reassesses the lipid paradigm by systematically mapping 380 influential trials and cohort studies on cholesterol, saturated fats, and statins in relation to cardiovascular and cognitive outcomes. The evidence base reveals a nearly even split between studies supporting and challenging LDL-centric causality, alongside pervasive methodological flaws, including reliance on surrogate lipid markers, ecological inferences, residual confounding, and industry-related reporting biases. Trial-generation comparisons and structured risk-of-bias assessment (ROB 2, ROBINS-I) repeatedly show that substantial pharmacological LDL reductions do not consistently yield proportional reductions in myocardial infarction, stroke, or all-cause mortality. Integrating Mendelian randomization with clinical and metabolomic data, the review advances a Critical Window Hypothesis in which LDL is necessary but not sufficient for atherogenesis, exerting dominant causal influence during early and midlife plaque initiation, while inflammatory, oxidative, and hemodynamic factors become primary drivers in advanced disease. Metabolomic studies of extreme longevity and late-life cohorts demonstrate that bile acids, steroid metabolites, and low-glycemic metabolic profiles—not total cholesterol—better predict survival and cognitive preservation, and that higher LDL in the oldest-old often associates with lower mortality and dementia risk. These findings challenge universal LDL-centric policies and support lifestyle medicine strategies prioritizing systemic metabolic optimization over isolated cholesterol targets. Full article