Search Results (13,599)

Background/Objectives: Catatonia is a severe transdiagnostic neuropsychiatric syndrome for which accessible biological correlates remain insufficiently characterized. This study explored whether complete blood count (CBC)-derived inflammatory indices differ between psychiatric inpatients with catatonia and matched psychiatric controls without catatonia. Methods: This retrospective matched case–control study included 46 patients with catatonia and 46 psychiatric controls selected from the same clinical setting and study period. Controls were frequency-matched by sex, age distribution, and broad psychiatric diagnosis. CBC parameters obtained within the first 24 h of admission were used to calculate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune–inflammation index (SII), and systemic inflammation response index (SIRI). Group comparisons, adjusted log–linear regression models, Spearman correlations with documented catatonic signs, and exploratory receiver operating characteristic analyses were performed. Results: SII was higher in patients with catatonia than in controls and remained significant after Bonferroni correction (median 584 [IQR 468–823] vs. 476 [IQR 339–619], Bonferroni-adjusted p = 0.032). In secondary adjusted models, catatonia was associated with higher SII and SIRI after adjustment for body mass index, smoking, antipsychotic exposure, diabetes mellitus, and arterial hypertension. No inflammatory index correlated significantly with the number of documented catatonic signs after correction. Exploratory discrimination was poor to fair, with SII showing the highest AUC (0.665, 95% CI 0.550–0.773). Conclusions: CBC-derived indices, particularly SII, may reflect systemic inflammatory or physiological stress burden in catatonia, but they should be interpreted as exploratory markers rather than diagnostic biomarkers. Full article

Background: Artemisia absinthium (A. absinthium) is a perennial plant valued for its antibacterial, antioxidant, and anti-inflammatory properties, exhibiting broader therapeutic potential. Given the need to deliver low doses of A. absinthium extract, mesoporous silica nanoparticles have attracted considerable attention as promising nanocarriers due to their distinctive physical and chemical properties. Methods: Physicochemical characterization of the materials was performed and biological assays were conducted to investigate the ROS, antibacterial and antioxidant activity of A. absinthium extract encapsulated within cerium- and calcium-doped mesoporous silica nanoparticles (MNSiCaCe) against both aerobic and anaerobic bacteria. Results: FTIR, SEM, and BET analysis confirmed successful synthesis of the MNSiCaCe. Phytochemical profiling of Artemisia absinthium extract using HPLC revealed the presence of artemisinin and a rich composition of phenolic and flavonoid constituents, with a total phenolic content of 182 ± 3.6 mg GAE/100 g dry plant material and a total flavonoid content of 42.5 ± 0.6 mg QE/100 g. Quantitative drug loading profiling demonstrated that while plain MNSi nanocarriers achieved a loading capacity of 16.96%, the MNSiCaCe enhanced this threshold to 43.11%. The in vitro controlled-release kinetics exhibited a highly prolonged and slow-release profile of the MNSiCaCe. The materials demonstrated excellent hemocompatibility and high mitochondrial activity with human periodontal ligament cells (hPDLCs). Elevated ROS generation was observed under conditions where antibacterial activity was most pronounced. While the artemisinin-doped nanoparticles showed notable antibacterial effects, the complete Artemisia absinthium-loaded nanoparticles achieved a significantly greater reduction in bacterial viability probably due to the synergistic interaction between artemisinin and the extract’s rich polyphenol profile. Conclusions: These findings highlight MNSiCaCe as a promising and safe nanocarrier system for drug delivery, with strong antibacterial potential, offering valuable applications in antibacterial therapies. Full article

Excessive gestational weight gain (EGWG) promotes adverse physiological and molecular changes in the placenta. In the present study, we examined the whole placental transcriptomic profile in women with EGWG to elucidate the molecular basis of EGWG pathogenesis. Whole transcriptome profile was analyzed in placentas from term patients with EGWG compared to controls using RNA-seq. Eight genes were found to be downregulated, and 318 genes were found to be upregulated in the placentas of the EGWG group in comparison with those of the women with adequate gestational weight gain (AGWG). Analysis of differentially expressed genes showed eight biological processes, nine cellular components, and ten molecular functions activated, and ten biological processes, ten cellular components, and ten molecular functions suppressed in the placentas from women with EGWG compared to AGWG. EGWG is characterized by significant alterations in placental gene expression, impacting various biological processes, cellular components, and molecular functions, including activation of chromatin organization and remodeling, nucleoplasm, and histone-modifying activity, and suppression of response to stimulus, organelle, and protein binding. Full article

Plant extracts in vegetable oils are foundational and eco-responsible for skin care, combining their emollient properties with other additional benefits, derived from their antioxidant, antimicrobial and UV-absorbing activity. The present research conducted a complex investigation of Usnea barbata extract in Karanja oil (KO), aiming for its further incorporation into various cosmetic formulations. The lichen extract (UBKO) was obtained through cold maceration. Phytochemical screening was performed using the Folin–Ciocalteu method and Graphite Furnace Atomic Absorption Spectrophotometry (GFAAS). Physicochemical properties were evaluated via Fourier Transform Infrared Spectroscopy (FTIR) and Atomic Force Microscopy (AFM). The rheological behavior and oxidative stability of the oil samples, UBKO and KO, were also investigated. UBKO had a slightly lower density (0.827 vs. 0.955) and pH (4.22 vs. 4.86) than KO, and a slightly higher oxidative resistance, quantified as the induction period (IP) value (6.45 vs. 6.00). The total phenolic-equivalent content (TPC, µg GAE/mL oil sample) was significantly greater in UBKO than in KO (567.16 ± 14.96 vs. 433.26 ± 22.96, p = 0.001). The values of minimum inhibitory concentration (MIC, mg/mL) indicated significantly higher antibacterial effect against S. aureus and antifungal effect against C. albicans for UBKO than KO (9.62 ± 2.87 vs. 31.25 ± 18.75, p = 0.049, and, respectively, 5.06 ± 1.68 vs. 37.50 ± 12.50, p = 0.01). Finally, our results showed that UBKO had an estimated sun-protective factor (SPF) of 30.9, slightly higher than 29.8 for the base oil formulation, KO; these findings represent baseline in vitro UV-absorbing trends. All of these results suggest that U. barbata extract in Karanja oil may exhibit complementary bioactive properties with potential applications in skincare. Full article

Endophytic fungi from Malaysian medicinal plants constitute a metabolically prolific yet underexplored reservoir for natural product discovery. This scoping review of 56 studies published between 2015 and 2025 identified a fundamental methodological divergence within the field: while phenotypic bioactivity screening dominates the literature (>87% of studies), it is weakly supported by chemical characterization (<25%) and entirely disconnected from genomic investigation (0% biosynthetic gene cluster studies). This phenotype-first paradigm has largely confined the field to descriptive reporting, limiting mechanistic understanding and translational potential. Collectively, the evidence reveals a substantial disconnect between reported bioactivities and their underlying biosynthetic foundations. To address this limitation, a practical genotype-to-phenotype workflow is proposed that integrates strain prioritisation, multi-omics-guided activation, chemical mapping, and mechanism-oriented validation. By linking genomic potential with metabolite production and biological function, this framework provides a roadmap for advancing fungal natural product discovery beyond conventional phenotype-driven screening. Adoption of such approaches may improve the identification of chemically novel and biologically relevant metabolites while supporting the sustainable development of Malaysia’s endophytic fungal resources for biotechnological and pharmaceutical applications. Full article

Haemonchus contortus is one of the most prevalent gastrointestinal nematodes in all ecosystems in Mexico, where sheep are raised on pasture, and it poses a significant threat. This study aimed to examine the surgical isolation of a Mexican H. contortus strain, its morphological and molecular characterization, and the maintenance of this strain for future research. Biological behavior and some phenotypic aspects of the adults were considered. Fecal samples were obtained from naturally infected sheep, larval cultures were performed, and a nematode-free lamb was infected. Once the infection was established, the donor sheep were euthanized, the adults recovered, and H. contortus females and males were selected. A surgical transfer from H. contortus adult to the abomasum of a receptor lamb was performed, and the beginning of the egg excretion was confirmed three days post-transfer; fecal cultures from the receptor lamb were conducted to verify the purity of the strain. After three lambs were infected with 3000, 5000, and 10,000 L3, the pre-patent period, prolificacy, and measurements of the adult stages of the strain were studied. The molecular characteristics were evaluated by qPCR; primers were designed based on NCBI genomic DNA sequences of H. contortus to amplify a 176 bp fragment, and the amplicon was sequenced for taxonomic identification. The results of this study describe biological characteristics and some phenotypic aspects of the adults, as well as eggs and infective larvae, and molecular characteristics of the isolated strain, and establish a successful methodology for isolating and maintaining a pure strain of H. contortus (FESC-strain); it can be used as a reference in experimental infections or anthelmintic resistance studies. Full article

Individual differences in the sensitivity and response to drugs of abuse are reliably associated with later patterns of substance use and, for some, progression to a substance use disorder diagnosis. This review synthesizes human drug challenge, longitudinal, and translational animal evidence to characterize how early or initial sensitivity to drugs, shaped by heritable and developmental factors, may relate to subsequent risk. These initial responses, through associative learning, may influence how drug-paired cues acquire motivational significance over time. Ample evidence suggests that early response variability is a biologically grounded and measurable correlate of SUD vulnerability, detectable well before chronic neuroadaptation, with potential utility for targeted prevention and intervention efforts. Full article

Stingless bees, or meliponines, are essential pollinators in Brazil, with over 300 described species. These bees produce propolis or geopropolis (characterized by the incorporation of mineral material and clay) used to protect their nests. This product has aroused increasing scientific interest due to its therapeutic potential, including antimicrobial and anti-inflammatory activities. However, there is still limited knowledge about its volatile composition, which can vary according to the bee species and the botanical origin of the resins, influencing their biological and aromatic properties. The purpose of this study was to characterize the volatile composition of (geo)propolis produced by different species of native stingless bees from the Southeastern region of Brazil (São Paulo and Minas Gerais) and to detect if this composition is influenced by the species or by the region. The samples were analyzed by headspace solid-phase microextraction (HS-SPME) coupled to gas chromatography–mass spectrometry (GC-MS). The results indicated that, despite some variations, the chemical profile for each species was mostly constant between regions. In São Paulo, about 25% of the features varied between species, whereas in Minas Gerais, only 5% showed significant differences, although one species (Melipona quadrifasciata) presented a very constant composition. Although the local vegetation determines the supply of resins for these bees, differences in the chemical composition of propolis are a result of a species’ choice of plant species. Full article

Background: Mutations in the KRAS oncogene occur in approximately 40% of colorectal cancers, predominantly within exon 2. Non-exon 2 mutations are less common and remain poorly characterized in terms of their clinical and biological significance. Systemic inflammatory markers are well-established prognostic indicators in colorectal cancer, yet whether their prognostic value differs across KRAS mutation subtypes has yet to be defined. We aimed to characterize and compare the clinicopathological and inflammatory profiles of patients with exon 2 versus non-exon 2 KRAS-mutated colorectal cancer and evaluate their prognostic implications. Methods: This retrospective cohort study analyzed 272 patients with microsatellite stable metastatic colorectal cancer with KRAS mutations, comprising 236 exon 2 and 36 non-exon 2 cases. Clinical, molecular, and laboratory data, including baseline systemic inflammatory markers, were extracted from electronic medical records. Survival outcomes and the prognostic impact of these variables were evaluated with Kaplan-Meier curves and univariable and multivariable Cox proportional hazards regression analyses. Results: Non-exon 2 mutations were significantly more frequent in female patients (64% vs. 45%, p = 0.048) and in left-sided primary tumors (83% vs. 64%, p = 0.035). Median overall survival was 45.7 months for the non-exon 2 group compared to 32.4 months for the exon 2 cohort; KRAS mutation subtype was not significantly associated with overall survival on univariable or multivariable analysis (univariable HR 1.36, 95% CI 0.85–2.16, p = 0.2; multivariable HR 1.376, 95% CI 0.794–2.383, p = 0.255). Systemic inflammation demonstrated distinct prognostic value, with elevated white blood cells, absolute neutrophil count, platelets, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and low albumin levels demonstrating association with worse overall survival in the exon 2 cohort. Conversely, only an elevated neutrophil-to-lymphocyte ratio predicted worse survival in the non-exon 2 group. Conclusions: KRAS exon 2 and non-exon 2 mutated metastatic colorectal cancers exhibit distinct clinical and inflammatory characteristics. Systemic inflammation exerts a significantly greater prognostic impact in exon 2 disease. As the therapeutic landscape for KRAS-mutated CRC continues to evolve, these findings hold promise for informing KRAS mutation-specific approaches to patient stratification and treatment planning. Full article

Background/Objectives: Drug repurposing has emerged as a promising strategy for identifying novel anticancer agents among clinically established drugs. Fexofenadine, a second-generation H1 antihistamine, has been proposed as a candidate for repurposing in oncology; however, the molecular mechanisms underlying its biological activity remain insufficiently characterized. This study investigated the effects of fexofenadine on oxidative stress, mitochondrial function, apoptosis, and pro-survival signaling pathways in cervical and lung cancer cells. Methods: HeLa and A549 cancer cells, as well as non-tumorigenic Beas-2B epithelial cells, were exposed to fexofenadine under in vitro conditions. Cell viability, apoptosis, reactive oxygen species generation, mitochondrial membrane potential, DNA damage, autophagy-associated responses, and PI3K/AKT and MAPK/ERK pathway activation were assessed using flow cytometry, fluorescence microscopy, electron microscopy, and biochemical assays. Three-dimensional spheroid cultures and N-acetyl-L-cysteine rescue experiments were additionally employed to evaluate biological relevance and the contribution of oxidative stress. Results: Fexofenadine induced concentration-dependent accumulation of reactive oxygen species, mitochondrial membrane depolarization, Bcl-2 inactivation, caspase-3/7 activation, DNA damage, and apoptotic cell death in HeLa and A549 cells. Antioxidant pretreatment with N-acetyl-L-cysteine significantly reduced oxidative stress, attenuated mitochondrial dysfunction, and partially suppressed apoptosis. Fexofenadine was associated with reduced PI3K/AKT and MAPK/ERK pathway activation and promoted autophagy-associated responses. In three-dimensional spheroid cultures, treatment disrupted spheroid integrity and increased apoptotic cell death. Non-tumorigenic Beas-2B cells exhibited lower sensitivity to treatment than malignant cells. Conclusions: Fexofenadine disrupts redox homeostasis and is associated with reduced activation of pro-survival signaling pathways, resulting in oxidative stress-associated mitochondrial dysfunction and apoptosis in cancer cells. These findings provide mechanistic support for further evaluation of fexofenadine as a candidate for anticancer drug repurposing, while additional pharmacokinetic and in vivo studies are required to determine its translational relevance. Full article

Radiotherapy for glioblastoma remains anchored to postoperative structural MRI and anatomy-based target definitions, despite marked spatial heterogeneity and dynamic biological change during chemoradiotherapy. Advanced MRI, amino-acid PET, radiomics, and habitat imaging can characterize tumor biology beyond conventional anatomy, yet their relevance to radiotherapy planning and their evidentiary maturity differ substantially. This narrative review examines the current evidence for biologically informed radiotherapy in glioblastoma and proposes an imaging-based actionability framework that organizes imaging-derived findings into five levels of evidentiary maturity, from descriptive or associative signals to intervention-ready biomarkers, to guide literature interpretation, multidisciplinary discussion, and prospective protocol design. Standard MRI-based planning remains the clinical backbone, supported by contemporary guidelines and the absence of randomized evidence demonstrating benefit from routine biologically guided target modification. Advanced MRI is discussed as the most practical serial platform for treatment-course reassessment, amino-acid PET as a selective complementary tool for metabolic clarification and recurrence assessment, and radiomics and habitat imaging as promising but not yet intervention-ready research layers. Across modalities, prospective evidence supports feasibility more consistently than clinical benefit. The proposed framework is intended to separate biologically informative findings from those sufficiently validated to justify a defined radiotherapy consequence, and to structure the translational path toward intervention-grade evidence in glioblastoma radiotherapy. Full article

Orphan enzymes are recognized and classified enzymatic activities that lack associated amino acid sequences. Since the term was coined in the mid-2000s, the proportion of orphan enzymes has substantially decreased; however, it is estimated that at least ≈900 enzymatic activities remain devoid of molecular identity to date. The putative mammalian metabolic pathway for L-fucose degradation represents a system that long consisted exclusively of orphan enzymes, with only a few recently “deorphaned” and biochemically characterized. L-Fucose is a unique monosaccharide frequently found in various glycolipids and glycoproteins synthesized by mammalian cells, such as the ABO blood group antigens in humans. While the importance of the biosynthetic pathways for its active form (GDP-L-fucose) is well established in diverse biological processes, the enzymology and physiological role of L-fucose catabolism remain largely enigmatic. In this review, we summarize the current knowledge regarding the enzymological and physiological aspects of L-fucose catabolism in mammals. Full article

Background: Gender differences in aging among people with HIV (PWH) remain poorly characterized. Women with HIV (WWH) may experience more complex aging trajectories, due to the interplay of biological, clinical, and psychosocial factors. In this context, we aimed to investigate gender-specific determinants of frailty among older people with HIV, with a particular focus on women, to better inform tailored clinical care. Methods: Cross-sectional analysis of the Over50 Cohort, including PWH aged ≥50 years from two tertiary hospitals in Spain. Participants underwent a comprehensive geriatric assessment across demographic, clinical, functional, cognitive, psychological, and social domains. Gender-stratified multivariable analyses examined frailty (by Fried criteria) and associated factors. Results: Among 588 participants, 139 (23.6%) were cisgender WWH. Despite younger age and better immune status, WWH showed higher prevalence of frailty (17% vs. 9%), musculoskeletal disease (47% vs. 28%), depressive symptoms (45% vs. 30%), sleep disturbances (10% vs. 5%), and cognitive complaints (23% vs. 11%). Men with HIV (MWH) more frequently had cardiovascular (48% vs. 35%) and renal disease (22% vs. 15%). In multivariable models, frailty in WWH was independently associated with musculoskeletal disease (OR 3.85), cognitive impairment (OR 3.21), depressive symptoms (OR 2.67), and malnutrition (OR 2.14). In MWH, frailty was associated with musculoskeletal disease, cognitive impairment, malnutrition, and older age. Conclusions: Frailty exhibits gender-specific patterns: a multidimensional phenotype in WWH versus age-driven in MWH, supporting tailored, gender-responsive care integrating geriatric, mental, and musculoskeletal health. Full article

Background: Endometriosis and lipedema are chronic female-predominant disorders characterized by persistent pain that is frequently disproportionate to anatomical lesion burden. Although traditionally interpreted within distinct lesion-centered frameworks, both conditions exhibit striking clinical and epidemiological parallels, including hormonally modulated symptom dynamics, overlap with central pain syndromes, weak correlation between structural disease severity and pain intensity, and symptom clustering during reproductive transitions such as puberty, pregnancy, and menopause. Methods: This study aims to synthesize clinical, molecular, neuroimmune, and endocrine evidence on the interrelationship between endometriosis and lipedema, and to propose a hypothesis-generating neuroimmune framework linking both conditions. This integrative narrative review conducted a non-systematic literature search in PubMed/MEDLINE, Scopus, and Web of Science, focusing on mechanisms related to chronic pain, mast cell biology, TRPV1 signaling, CGRP-mediated neurogenic inflammation, intracrine steroidogenesis, and peripheral and central sensitization. Results: The review identifies convergent biological characteristics between the two diseases, including mast cell activation, macrophage polarization, endothelial dysfunction, fibrosis, angiogenesis, intracrine estrogen metabolism, and persistent inflammatory signaling. In endometriosis, direct evidence demonstrates increased sensory innervation, nerve growth factor expression, TRPV1 sensitization, CGRP-positive fibers, and mast cell-nerve interactions. In lipedema, convergent upstream mechanisms, including mast cell infiltration, elevated histamine levels, adipose tissue inflammation, and local estrogen activation, support the plausibility of a functionally analogous neuroimmune organization, despite incomplete direct neural characterization. In this context, the mast cell-TRPV1-CGRP axis is proposed as a biologically plausible framework, directly supported in endometriosis and currently hypothetical in lipedema, connecting peripheral sensitization, neurogenic inflammation, hormonal chronodependence, and central nociceptive amplification. The model further conceptualizes pain crises as transient events of instability within a sensitized neuroimmune network and proposes mechanistic phenotypes that integrate gastrointestinal, inflammatory, central, and hormonal triggers. Conclusion: Endometriosis and lipedema may represent topographically distinct manifestations of a shared neuroimmune process operating within hormone-sensitive tissues. Although the evidentiary basis remains asymmetric, with stronger mechanistic support in endometriosis than in lipedema, this framework provides a biologically plausible and experimentally testable model integrating endocrine, immune, neural, and vascular contributors to chronic pain amplification. This perspective supports coordinated translational investigation across reproductive biology, endocrinology, and pain medicine and may contribute to future mechanism-based stratification and therapeutic development. This work is hypothesis-generating and is not intended to establish causality or to provide clinical recommendations; all proposed mechanistic and therapeutic inferences require prospective experimental validation. Full article

Seasonal epidemics and high variability of influenza viruses pose a severe threat to global public health security. Neuraminidase, a key functional enzyme in the life cycle of influenza viruses, represents an important target for anti-influenza drug development. Given the continuous emergence of drug-resistant strains against first-line clinical neuraminidase inhibitors (NAIs) such as oseltamivir, there is an urgent need to develop novel, broad-spectrum, and resistance-overcoming NAIs. Natural products, characterized by structural diversity and a wide range of biological activities, provide abundant resources for the discovery of new NAIs. Recent advances in computer-aided drug design, intelligent analytical platforms, and modern screening technologies have accelerated the identification of natural product-derived NAIs. In particular, biosensor-based strategies, including electrochemical, fluorescence, bioluminescence, and surface-enhanced Raman scattering biosensors, have demonstrated significant advantages in sensitivity, selectivity, rapid response, and high-throughput screening. In combination with computational methods and experimental approaches such as affinity ultrafiltration and activity-guided separation, these technologies have promoted the development of intelligent, precise, and multimodal screening platforms. Looking forward, the integration of biosensor-based high-throughput screening platforms with artificial intelligence algorithms is expected to drive the next generation of natural product screening platforms and facilitate the efficient discovery and clinical translation of novel NAIs. This paper systematically reviews the research progress of screening strategies for natural product-derived NAIs; introduces representative natural active NAIs, including phenols, terpenoids, and alkaloids; and prospects future development directions, aiming to provide a scientific reference for the efficient discovery of NAIs from natural products. Full article