Search Results (1,052)

Background and Objectives: The Gustave Roussy Immune (GRIm) score, reflecting systemic inflammation and nutritional status, has emerged as a simple and reproducible prognostic biomarker in various malignancies. However, its prognostic interaction with tumor microenvironmental factors remains unclear in gastric cancer. The primary aim of this study was to evaluate the prognostic value of the GRIm score in patients with resectable gastric adenocarcinoma, while the secondary aim was to determine whether integrating the GRIm score with tumor microenvironment–related pathological markers could improve prognostic stratification. Materials and Methods: This retrospective study analyzed 188 patients with resectable gastric adenocarcinoma treated at the Trakya University Faculty of Medicine between 2007 and 2018. GRIm scores were calculated from preoperative lactate dehydrogenase (LDH), albumin, and neutrophil-to-lymphocyte ratio (NLR) values. Pathologic parameters, including programmed death-ligand 1 (PD-L1) expression (combined positive score [CPS] ≥ 1 vs. <1), tumor–stroma ratio (TSR; stromal component ≥ 50% vs. <50%), and tumor-infiltrating lymphocyte (TIL) density (CD8+ ≥ 10% vs. <10%), were evaluated on surgical specimens. Survival outcomes were assessed using Kaplan–Meier and multivariate Cox analyses. Results: The study population had a mean age of 61.8 years and was predominantly male (72.3%). Patients with low GRIm scores had significantly longer disease-free survival (DFS; 24 vs. 12 months; p = 0.004) and overall survival (OS; 32 vs. 19 months; p = 0.006). In multivariate analysis, the GRIm score remained an independent predictor for both disease-free survival (p = 0.035) and overall survival (p = 0.044). Among combined models, the GRIm–TSR classification provided the most pronounced stratification (median DFS = 35 vs. 12 months; OS = 45 vs. 19 months; p = 0.014 and 0.001, respectively), retaining independent prognostic significance (hazard ratio [HR] = 1.23; p = 0.005). Integrating GRIm with PD-L1 and TIL density also improved prognostic discrimination. Conclusions: The GRIm score is a robust and cost-effective biomarker that independently predicts disease-free survival and overall survival in resectable gastric adenocarcinoma. Its combination with microenvironmental markers—PD-L1, TIL, and TSR—captures complementary biological dimensions of tumor aggressiveness, offering an integrative and clinically feasible framework for individualized risk assessment and postoperative management. Prospective multicenter validation is warranted. Full article

Hereditary ataxias are a heterogeneous group of disorders with overlapping clinical presentations but diverse genetic and molecular etiologies. Biomarkers are increasingly essential to improve diagnosis, refine prognosis, and accelerate the development of targeted therapies. Following PRISMA-ScR guidelines, we conducted a scoping review of PubMed and complementary sources (2010–2025) to map and describe the current landscape of genetic, imaging, fluid, electrophysiological, and digital biomarkers across the most prevalent hereditary ataxias, including SCA1, SCA2, SCA3, SCA6, SCA7, SCA17, SCA27B, dentatorubral–pallidoluysian atrophy (DRPLA), Friedreich’s ataxia (FRDA), RFC1-related ataxia (CANVAS), SPG7, and fragile X-associated tremor/ataxia syndrome (FXTAS). Eligible evidence encompassed observational cohorts, clinical trials, case series, and case reports providing primary biomarker data, with the objective of characterizing evidence breadth and identifying knowledge gaps rather than assessing comparative effectiveness. Across modalities, converging evidence highlights subtype-specific biomarker signatures. MRI volumetry, DTI, and FDG-PET map characteristic neurodegeneration patterns. Fluid biomarkers such as neurofilament light chain are informative across several SCAs and FRDA, while frataxin levels constitute robust endpoints in FRDA trials. Pathology-specific biomarkers such as ataxin-3 are advancing as tools for target engagement and may generalize to future gene-lowering strategies. Electrophysiological and oculographic measures show sensitivity for early disease detection, and wearable technologies are emerging as scalable tools for longitudinal monitoring. This scoping review synthesizes the heterogeneous evidence on hereditary ataxia biomarkers, highlighting multimodal frameworks that link molecular mechanisms with clinical endpoints. Mapping current approaches also reveals substantial variability and gaps across diseases and modalities, underscoring the need for harmonized validation in international multicenter cohorts and systematic integration into future clinical trials to advance precision medicine in hereditary ataxias. Full article

Background/Objectives: Autism Spectrum Disorder (ASD) is a lifelong neurodevelopmental disorder characterized by social, communication, and behavioral challenges. complementary and alternative medicine (CAM) is widely used by parents worldwide, yet research exploring parents’ experiences, particularly in Arab countries, is limited. This study explored mothers’ perceptions and experiences of CAM use for children with ASD, information-seeking behaviors and challenges encountered. Methods: A qualitative study using semi-structured interviews was conducted among twenty mothers at Autism Academy of Jordan in 2024. Inclusion criteria were mothers with children diagnosed with ASD for at least six months and those who had used at least one CAM therapy. Interviews were conducted via Skype, transcribed verbatim, and analyzed using NVivo 12 with inductive thematic analysis. Results: Three major themes emerged in this qualitative study: (1) mothers’ experiences with CAM and perceptions of benefit; (2) sources of information and decision-making processes; and (3) main challenges in selecting and implementing CAM. Mothers reported using therapies such as honey, black seed, camel milk, Hujama, olive oil, supplements, and region-specific programs like Andalosiah. Faith, cultural beliefs, and the desire for natural, safe interventions strongly influenced CAM selection. Internet searches and social media groups were primary information sources. Challenges included financial, logistical, emotional burdens, and lack of trustworthy, Arabic-language information sources. Conclusions: Mothers in Arab countries navigate CAM use for their children with ASD through culturally and religiously informed practices. Interventions should focus on developing evidence-based guidance, culturally sensitive counseling, and accessible information to support families in safe, informed CAM use. Full article

Mental health disorders, particularly anxiety and insomnia, are increasingly prevalent worldwide, prompting interest in herbal-based complementary therapies. This study surveyed 168 Hungarian healthcare professionals to evaluate their knowledge and recommendations regarding herbal sedatives and analyzed seven commonly suggested OTC products available in Hungary, using thin-layer chromatography (TLC) and UV–Vis spectrophotometry according to the European Pharmacopoeia. The survey revealed that 86.9% of respondents recommend herbal products for nervous system complaints, with Valeriana officinalis and Melissa officinalis being the preferred ingredients. Herbal teas and traditional herbal medicines were the most frequently suggested product categories. Laboratory analysis confirmed the presence of marker compounds in all tested products; however, significant variability in active ingredient concentrations was observed. One homeopathic product contained an unidentified alkaloid-like compound, raising safety concerns. Essential oil yields from tea mixtures also varied markedly, and some products did not meet pharmacopoeial standards for hypericin content. These findings highlight the popularity of phytotherapy among healthcare professionals and the need for stricter quality control of OTC herbal sedatives. Future research should include multi-batch analyses and clinical trials to establish robust evidence for efficacy and safety. Full article

Type 2 diabetes mellitus (T2DM) can be traditionally treated by edible and medicinal species rich in flavonoids and triterpenoids known for their metabolic benefits. Cucumis prophetarum L. has shown antioxidant and antidiabetic properties in decoction extracts. Since solvent polarity strongly influences the extraction of secondary metabolites, this study investigated the hydroalcoholic extracts of C. prophetarum L. to explore their chemical composition and insulin-sensitizing potential. Hydroalcoholic extracts from the leaf, stem, and root of C. prophetarum L. were analyzed by UV-Vis spectroscopy, ATR-FTIR, and UHPLC-ESI-QqTOF–MS/MS to profile their secondary metabolites. The insulin-sensitizing potential of each extract was assessed using an in vitro model of palmitic-acid-induced insulin resistance in L6 skeletal muscle cells, followed by Western blot analysis of key insulin-signaling proteins. Flavonoid glycosides such as apigenin-C,O-dihexoside, apigenin-malonylhexoside, and luteolin-C,O-dihexoside were abundant in leaf and stem extracts, while cucurbitacins predominated in the root. MTT assay confirmed that hydroalcoholic stem and root extracts of C. prophetarum L. were non-cytotoxic to L6 myotubes, whereas the leaf extract reduced viability only at higher concentrations. Oil Red O staining revealed a pronounced decrease in lipid accumulation following stem and root extract treatment. Consistently, the stem extract enhanced insulin signaling through the activation of the IRS-1/PI3K/Akt pathway, while the root extract primarily modulated the AMPK–mTOR pathway. Importantly, both extracts promoted GLUT4 translocation to the plasma membrane, highlighting their complementary mechanisms in restoring insulin sensitivity. Hydroalcoholic extracts of C. prophetarum L. alleviate insulin resistance through multiple molecular mechanisms, with bioactivity and composition differing markedly from previously reported in the decoctions, which highlight a promising source of insulin-sensitizing phytochemicals and underscore the importance of solvent selection in maximizing therapeutic potential. Full article

Canine ehrlichiosis, caused by Ehrlichia canis, represents a relevant challenge in veterinary medicine, particularly in resource-limited settings where access to laboratory-based diagnostics may be constrained. This pilot and exploratory study aimed to evaluate the feasibility of a portable electronic olfactometer as a non-invasive screening approach, based on the analysis of volatile organic compounds (VOCs) present in breath, saliva, and hair samples from dogs. Signals were acquired using an array of eight metal-oxide (MOX) gas sensors (MQ and TGS series). After preprocessing, principal component analysis (PCA) was applied for dimensionality reduction, and the resulting features were analyzed using supervised machine-learning classifiers, including AdaBoost, support vector machines (SVM), k-nearest neighbors (k-NN), and Random Forests (RF). A total of 38 dogs (19 PCR-confirmed infected cases and 19 controls) were analyzed, generating 114 samples evenly distributed across the three biological matrices. Among the evaluated models, SVM showed the most consistent performance, particularly for saliva samples, achieving an accuracy, sensitivity, and precision of 94.7% (AUC = 0.964). In contrast, breath and hair samples showed lower discriminative performance. Given the limited sample size and the exploratory nature of the study, these results should be interpreted as preliminary; nevertheless, they suggest that electronic olfactometry may represent a complementary, low-cost, non-invasive screening tool for future research on canine ehrlichiosis, rather than a standalone diagnostic method. Full article

As age progresses and the population increases, the prevalence of dementia also increases. Pharmacological interventions are used to treat cognitive decline. Alternative approaches to traditional pharmacology, such as dietary interventions, may help combat cognitive decline in aging populations. This review summarizes existing investigations using complementary and alternative approaches as mitigating interventions. We also briefly note other important modifiable factors to decrease the risk of cognitive decline, and Alzheimer’s disease and related dementias. Such approaches include nutrition and dietary interventions that show promising results for mitigating cognitive decline, as well as additional lifestyle modifying factors that are important to note (e.g., sleep, cardiovascular diseases, environmental factors, physical, social and leisure activities, cognitive stimulation, psychosocial factors, and sensory functioning) for their impact on cognition in aging. Despite the limited findings and support for complementary and alternative approaches in combating existing cognitive decline, findings suggest that such approaches may be most beneficial prior to the onset of cognitive impairment. Specific nutrition components, including flavonoids and omega fatty acids, may mitigate cognitive decline, and emerging evidence suggests that these nutrients may promote a healthy gut microbiota. Of the complementary and alternative approaches, adhering to specific diets, generally, has the most consistent support to combat cognitive decline. It is important to note that other non-nutritional or non-dietary modifiable lifestyle factors also show promising benefits in mitigating further cognitive decline. Future investigations and clinical trials with replication studies are needed to elucidate these complementary and alternative approaches as effective treatment options for clinicians. Full article

Maca (Lepidium meyenii Walp.), a Brassicaceae species native to the high Andes of Peru, has gained global attention as a functional food and herbal medicinal product due to its endocrine-modulating, fertility-enhancing, and neuroprotective properties. Although numerous studies have addressed its biological effects, a systematic and up-to-date summary of its chemical constituents and analytical methodologies is lacking. This review aims to provide a critical overview of the chemical constituents of L. meyenii and to evaluate analytical studies published between 2000 and 2025, focusing on recent advances in extraction strategies and qualitative and quantitative analytical techniques for quality control. Major compound classes include macamides, macaenes, glucosinolates, and alkaloids, each contributing to maca’s multifaceted activity. Ultra-(high-)performance liquid chromatography (U(H)PLC), often coupled with ultraviolet, diode array, or mass spectrometric detection, is the primary and most robust analytical platform due to its sensitivity, selectivity, and throughput, while ultrasound-assisted extraction improves efficiency and reproducibility. Emerging techniques such as metabolomics and chemometric approaches enhance quality control by enabling holistic, multivariate assessment of complex systems and early detection of variations not captured by traditional univariate methods. As such, they provide complementary, predictive, and more representative insights into maca’s phytochemical complexity. The novelty of this review lies in its integration of conventional targeted analysis with emerging approaches, comprehensive comparison of analytical workflows, and critical discussion of variability related to phenotype, geographic origin, and post-harvest processing. By emphasizing analytical standardization and quality assessment rather than biological activity alone, this review provides a framework for quality control, authentication, and safety evaluation of L. meyenii as a functional food and dietary supplement. Full article

Omics research is changing the way medicine develops new strategies for diagnosis, prevention, and treatment. With the surge of advanced machine learning models tailored for omicss analysis, recent research has shown improved results and pushed the progress towards personalized medicine. The dissection of multiple layers of genetic information has provided new insights into precision medicine, at the same time raising issues related to data abundance. Studies focusing on single-cell scale have upgraded the knowledge about gene expression, revealing the heterogeneity that governs the functioning of multicellular organisms. The amount of information gathered through such sequencing techniques often exceeds the human capacity for analysis. Understanding the underlying network of gene expression regulation requires advanced computational tools that can deal with the complex analytical data provided. The recent emergence of artificial intelligence-based frameworks, together with advances in quantum algorithms, has the potential to enhance multiomicsc analyses, increasing the efficiency and reliability of the gene expression profile prediction. The development of more accurate computational models will significantly reduce the error rates in interpreting large datasets. By making analytical workflows faster and more precise, these innovations make it easier to integrate and interrogate multi-omics data at scale. Deep learning (DL) networks perform well in terms of recognizing complex patterns and modeling non-linear relationships that enable the inference of gene expression profiles. Applications range from direct prediction of DNA sequence-informed predictive modeling to transcriptomic and epigenetic analysis. Quantum computing, particularly through quantum machine learning methods, is being explored as a complementary approach for predictive modeling, with potential applications to complex gene interactions in increasingly large and high-dimensional biological datasets. Together, these tools are reshaping the study of complex biological data, while ongoing innovation in this field is driving progress towards personalized medicine. Overall, the combination of high-resolution omics and advanced computational tools marks an important shift toward more precise and data-driven clinical decision-making. Full article

Prostate cancer (PCa) remains one of the most prevalent malignancies in men and a leading cause of cancer-related mortality worldwide. Over the last century, PCa modelling has evolved from basic cell-based to more complex systems. Despite this, the clinical translation of research findings is limited by the constraints of current preclinical models. In this review, rat and zebrafish models are highlighted due to their long-standing and emerging translational relevance, respectively. Rat models have played a pivotal role in understanding carcinogenesis and supporting the preclinical evaluation of drugs currently approved for clinical use, such as antiandrogens and androgen-deprivation agents. In parallel, zebrafish models are increasingly recognized as powerful complementary tools for studying tumor biology, metastasis, and drug response, offering unique advantages for high-throughput and personalized medicine approaches. We summarize historical milestones, current advances, and translational perspectives, emphasizing how combining multiple model systems can bridge the gap between molecular research and clinical application. Collectively, the development and refinement of these models represent essential steps toward more predictive and ethically responsible PCa research. Full article

Transanal Irrigation (TAI) and Colon Hydrotherapy (CHT) represent emerging therapeutic options that may complement first-line interventions or serve as rescue treatments for chronic constipation and fecal incontinence. Their clinical utility depends on patient characteristics, specific therapeutic goals, device features, and probe type, as well as the procedural setting. This review presents the various pathophysiological contexts in which these techniques can be applied, analyzing their specific characteristics and potential pros and cons. Moreover, these interventions are also considered within a Psycho-Neuro-Endocrino-Immunological (PNEI) framework, given the potential influence of intestinal function and microbiota modulation on the bidirectional communication pathways linking the enteric nervous system, neuroendocrine regulation, immune activity, and global patient well-being. Since there is not yet enough scientific data on this topic, future research should prioritize randomized controlled trials comparing these techniques with other standard treatments (e.g., laxatives or dietary fiber) in defined patient populations. Longitudinal studies will also be essential to clarify long-term safety, potential effects on microbiota, and both risks and benefits. Standardization of technical procedures also remains a critical need, especially regarding professional competencies, operating parameters (e.g., instilled volumes and pressure ranges), and reproducible protocols. Moreover, future investigations should incorporate objective outcome measures, as colonic transit time, stool form and frequency, indices of inflammation or intestinal wall integrity, and changes to microbiome composition. In conclusion, TAI and CHT have the potential to serve as important interventions for the treatment and prevention of chronic constipation and intestinal dysbiosis, as well as their broader systemic correlates, in the setting of bio-integrated medicine. Full article

Ganoderma is a genus of medically significant fungi, that is used in traditional medicine and is increasingly incorporated into modern nutraceuticals and pharmaceuticals. Accurate species identification and product standardization remain major challenges due to morphological plasticity and cryptic diversity. This review articulates current advances in Ganoderma systematics, phylogenetics, and metabolomics, with an emphasis on molecular identification strategies and chemical profiling. Internal transcribed spacer (ITS) sequencing has substantially improved species delineation compared with morphology alone, but its resolving power is limited in closely related species complexes, necessitating complementary multilocus approaches. Advances in metabolomics, and LC-MS- and HPLC-based profiling of triterpenes and polysaccharides, have enhanced species discrimination, chemotaxonomic resolution, and quality control of commercial products. Integrating molecular barcoding with metabolomic fingerprints provides a more robust framework for classification, pharmacological evaluation, and standardization. This review also highlights significant geographic knowledge gaps, particularly in Africa, where molecular and metabolomic data remain scarce despite high species diversity. Full article

Despite growing interest in South African medicinal plants, advanced metabolomic workflows that integrate positive (ESI+) and negative (ESI−) ionization modes in UPLC-MS/MS remain sparsely applied to South African flora, and especially to Acorus calamus and Lippia javanica species. Herein, application of a dual-polarity (positive (ESI+) and negative (ESI−) ionization modes) using an untargeted UPLC–MS/MS workflow, integrated with HEK293T cytotoxicity screening, to map their metabolomes, and rank potential signature metabolites for targeted antiviral follow-up. SwissADME supported in silico drug-likeness. Neither plant extract was cytotoxic across the concentration range, with absorbance-based cell viability of 73.82% for L. javanica and 77.23% for A. calamus at 250 µg/mL, and fluorescence-based cell viability ≥59.87% and ≥55.89%, respectively. Dual-polarity expanded coverage with ESI− yielded 312 features, compared with 225 with ESI+, consistent with the predominance of acidic phenolics in plant species. Unsupervised and supervised models segregated the plant species (PCA PC1/PC2 variance: ESI+ 89.4%/3.0%; ESI− 93.5%/1.8%; R²X(cum) = 0.799). Differential analysis identified 118 significant features in ESI+ with 80 up-regulated, 38 down-regulated, and 139 in ESI− with 96 up-regulated, 43 down-regulated. The ESI− showed the wider dynamic range. Chemotypes enriched among significant metabolites include flavonols of 3-O-methylkaempferol, apigenin, and conjugates of Pollenin A, iridoid glycosides of oleoside, forsythoside B, and jasmonate-pathway oxylipins of 7-epi-12-hydroxyjasmonic acid and its glucoside. These also include caryoptosidic acid and catechin-7-glucoside, which are ionized in both modes, pinning the increase in biomarker robustness. In conclusion, a dual-mode UPLC–MS/MS approach, integrated with cytotoxicity exploration, delivers a complementary metabolome coverage and a safety awareness for shortlisting of potential signature metabolites from L. javanica and A. calamus. Moreover, in vitro inhibition of SARS-CoV-2 papain-like protease (PL^pro) by these plants links chemical signatures to antiviral relevance. Shortlisted significant metabolites that demonstrated favorable drug-likeness include flavonol scaffolds of 3-O-methylkaempferol, Pollenin A, and jasmonate-pathway derivatives of 7-epi-12-hydroxyjasmonic acid. Moreover, the dual ionization mode may eliminate ionization bias, broaden metabolome coverage, and yield a mechanism-ready shortlist of metabolites from South African medicinal plants for downstream antiviral investigation. Full article

Sudden cardiac death (SCD) remains a major challenge in forensic medicine, representing a leading cause of natural mortality and frequently occurring in individuals without antecedent symptoms. Although conventional autopsy and histology remain the cornerstones of investigation, up to 10–15% of cases are classified as “autopsy-negative sudden unexplained death,” underscoring the need for complementary diagnostic tools. In recent years, post-mortem biochemistry and molecular approaches have become essential to narrowing this gap. Classical protein markers of myocardial necrosis (cardiac troponins, CK-MB, H-FABP, GPBB) continue to play a fundamental role, though their interpretation is influenced by post-mortem interval and sampling site. Peptide biomarkers reflecting hemodynamic stress (BNP, NT-proBNP, copeptin, sST2) offer additional insight into cardiac dysfunction and ischemic burden, while inflammatory and immunohistochemical markers (CRP, IL-6, fibronectin, desmin, C5b-9, S100A1) assist in detecting early ischemia and myocarditis when routine histology is inconclusive. Beyond these traditional markers, molecular signatures—including cardiac-specific microRNAs, exosomal RNA, proteomic alterations, and metabolomic fingerprints—provide innovative perspectives on metabolic collapse and arrhythmic mechanisms. Molecular autopsy through next-generation sequencing has further expanded diagnostic capability by identifying pathogenic variants associated with channelopathies and cardiomyopathies, enabling both cause-of-death clarification and cascade screening in families. Emerging multi-omics and artificial intelligence frameworks promise to integrate these heterogeneous data into standardized and robust interpretive models. Pre- and post-analytical considerations, together with medico-legal implications ranging from malpractice evaluation to the management of genetic information, remain essential components of this evolving field. Overall, the incorporation of validated biomarkers into harmonized international protocols, increasingly supported by AI, represents the next frontier in forensic cardiology. Full article

Pseudomonas has been revealed as an important member of plant probiotics, with its rich species diversity implying complementary plant growth-promoting (PGP) traits. However, information on Pseudomonas species in the microecology of Angelica sinensis and medicinal plants in general remains to be further investigated. This study examined the microecological characteristics, PGP traits, and their underlying molecular mechanisms of Pseudomonas. Filling this gap will provide an important reference for microbial community design centered on dominant functional bacterial genera. In this study, we characterized the microecological traits, PGP properties, and their underlying molecular mechanisms of Pseudomonas strains. Microbiome analysis identified Pseudomonas as the dominant genus in the rhizosphere and a core endophytic genus, exerting significant influences on both (path coefficients = 0.971, 0.872). Comparative phenomics suggested potential functional complementarity among different strains. Our observations revealed significant differentiation in PGP traits: P. umsongensis X08 showed exceptional performance in IAA and siderophore production (IAA: 1.24 mg/mL, siderophore halo diameter: 2.04 cm); P. frederiksbergensis X06 exhibited advantages in ACC deaminase activity and potassium solubilization; and P. allii X32 demonstrated high organic phosphorus solubilization capability (3.98 mg/L). Finally, genomic data revealed that P. allii X32 possesses a rich repertoire of PGP-related genes and metabolic pathways, providing a basis for establishing molecular mechanistic hypotheses for these traits. In summary, Pseudomonas strains from different species, which exhibit complementary probiotic functions without antagonism in the A. sinensis microecosystem, provide valuable microbial resources for the ecological cultivation of A. sinensis. Full article