Search Results (8,477)

Background: Xinshubao tablet (XSB), a traditional Chinese medicine (TCM) formula composed of five medicinal herbs, is used clinically to alleviate cardiovascular diseases. This study aimed to investigate the coronary vasodilatory effects of XSB and its individual herbs, exploring its active constituents and the underlying mechanisms. Methods: The vasorelaxant effects of XSB and its individual herbal intestinal absorption solutions (IASs) were evaluated by ex vivo coronary artery ring assays. The chemical constituents of the best active herbal IAS were qualitatively identified using ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC–Q-TOF-MS). Molecular docking and ex vivo assays were used to predict and validate the bioactive constituents and mechanisms responsible for coronary vasorelaxation. Results: Vasodilation experiments revealed that XSB-IAS and its individual herb IAS exhibited varying degrees of vasodilatory effects, in the range of 0.8–18 g raw materials/mL. At 6, 12, and 18 mg of raw materials/mL, Crataegus pinnatifida Bge (Shanzha) exhibited vasodilation rates of 26.45% ± 1.8%, 36.57% ± 3.5%, and 45.16% ± 6.3%, which were obviously higher than those of the other individual herbs. Fifty constituents in Shanzha IAS were identified by UPLC-Q-TOF-MS. Vasodilation-related protein–protein interaction (PPI) network revealed NOS3 as a core regulatory target. Molecular docking demonstrated that among the identified constituents, isochlorogenic acid B, betulin, etc., displayed binding affinity to NOS3. Isochlorogenic acid B was further validated to exhibit vasodilatory effects in the ranges of 0.05–2.5 mM. Mechanistic results showed that isochlorogenic acid B improved vasodilation by inhibiting Ca²⁺ influx through both voltage-dependent and receptor-operated Ca²⁺ channels, activating K⁺ channels, and exhibiting endothelium-dependent vasorelaxation. Conclusions: This study provides insights into the material basis and mechanisms underlying the vasorelaxant effects of XSB. Isochlorogenic acid B was firstly found to exert the coronary vasodilatory effect. This study can also contribute to the identification of efficacy-related quality markers in TCM. Full article

The advent of breast cancer molecular subtyping has transformed management, enabling treatment personalisation and de-escalation beyond traditional stage-based approaches. Established biomarkers, such as Ki-67 in luminal disease, HER2 amplification, and PD-L1 expression in triple-negative breast cancer, underpin seminal clinical trials yet remain imperfect predictors of response and long-term outcome. MicroRNAs have emerged as promising next-generation biomarkers and therapeutic tools. As master regulators of gene expression, both tumour-derived and circulating microRNAs can refine diagnosis and molecular subclassification, inform prognosis and therapeutic selection, act as treatment sensitisers, and potentially serve as direct therapeutic targets. Well-characterised miRNAs such as miR-221 have been implicated in endocrine resistance, while recent liquid-biopsy approaches have enabled the identification of circulating miR-145 and exosomal miR-155 as predictors of pathological complete response in HER2-positive disease. Their detectability in tissue, blood and other biofluids offers a minimally invasive means to dynamically monitor cancer behaviour and response, supporting more precise therapeutic decision-making. This review synthesises the current evidence for miRNA-based biomarkers across oestrogen-receptor positive, HER2-positive and triple-negative breast cancer and outlines their potential integration into biomarker-driven clinical trial designs and personalised treatment strategies. Full article

Chronic obstructive pulmonary disease (COPD) and pulmonary tuberculosis (TB) are major causes of morbidity and mortality worldwide. Epidemiologic studies indicate an increased risk of tuberculosis in patients with COPD; however, the shared molecular mechanisms underlying the pathogenesis of these two diseases remain insufficiently understood. Objective. Based on a comparative bioinformatics analysis of peripheral blood transcriptomic profiles in patients with COPD and pulmonary tuberculosis, to identify common systemic immune mechanisms associated with the pathogenesis of both diseases. Gene expression data from the NCBI GEO public database were analyzed. GSE34608 included blood samples from 8 patients with tuberculosis and 18 healthy controls. The GSE76705 dataset contained peripheral-blood samples from 364 former smokers (225 with COPD and 139 without). Functional enrichment (GO Biological Process and KEGG) was run in ShinyGO; protein–protein interaction networks were built in STRING, and the top-15 hub genes were ranked by the MCC algorithm in CytoHubba. In tuberculosis, 892 up-regulated and 1448 down-regulated genes were identified; in COPD, 520 up-regulated and 1329 down-regulated. Common upregulated DEGs are involved in toll-like receptor signaling pathways, NOD-like receptor signaling pathways, neutrophil extracellular trap (NET) formation, phagosomes, and tuberculosis. Downregulated genes in each of the diseases were associated with processes of transcriptional regulation and RNA metabolism, which may indicate common transcriptional abnormalities in COPD and tuberculosis. COPD and tuberculosis share common pathogenic mechanisms, including the activation of innate immune signaling pathways (TLR, NOD), neutrophilic inflammation, the formation of neutrophil extracellular traps (NETosis), and phagocyte dysfunction. The identified common genes and signaling pathways may serve as a basis for the development of biomarkers and therapeutic targets; however, they require further validation in independent cohorts. Full article

Triple-negative breast cancer (TNBC) is one of the most aggressive and clinically challenging subtypes of breast cancer, defined by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. The lack of actionable molecular targets contributes to limited therapeutic options, frequent recurrence, and a high propensity for distant metastasis. Metastatic dissemination remains the principal cause of mortality in patients with TNBC and is driven by complex molecular mechanisms involving multiple interconnected signaling networks. This review summarizes current knowledge of the molecular mechanisms underlying metastatic progression in TNBC, with particular emphasis on signaling pathways that regulate tumor invasion, migration, and colonization of distant organs. We discuss the roles of key pathways, including PI3K/Akt, TGF-β, Wnt/β-catenin, NF-κB, and Rho/ROCK signaling, in the regulation of epithelial–mesenchymal transition, cytoskeletal remodeling, cancer stem cell phenotypes, and tumor–microenvironment interactions. A deeper understanding of these signaling networks may facilitate the identification of novel therapeutic targets and support the development of more effective strategies to limit metastatic disease in TNBC. Full article

Despite the wide and accepted implementation of contemporary pharmaceutical medicine, the use of medicinal plants still prevails in several regions around the world, including Mexico. According to the World Health Organization (WHO), the use of incorrect species in natural and complementary medicine is a threat to consumer safety. Therefore, there is a need to characterize properly those plant species used in traditional medicine. In this study, a medicinal plant called Calanca, which is traded in the local market of a small community within the State of Puebla (Mexico), was characterized by different approaches. Conventional and molecular taxonomy analyses showed that Calanca belonged to the Asteraceae family, genus Chrysactinia. On one hand, molecular markers (rbcL, matK and ITS) helped to identify Calanca at the species level, being identified as C. mexicana. On the other hand, although not used for molecular taxonomy, additional gene markers were amplified and submitted to the GenBank database to expand the toolkit for C. mexicana identification. In addition, soil taxonomy and quantitative chemical analyses provided insights into the relationship between growing conditions and the chemical compounds produced by C. mexicana. Chemical compounds associated with medicinal properties such as phenolic acids, flavonoids, terpenes, and anthocyanins were identified in C. mexicana extracts. Finally, greenhouse conditions for the cultivation of this species were also investigated. Overall, this comprehensive characterization provides the essential botanical and chemical foundation required for future toxicological and clinical safety assessments, while establishing a robust framework for the long-term conservation of this endangered medicinal resource. Full article

Chloroidium saccharophilum is a resilient green microalga with a broad ecological distribution and an increasing biotechnological interest due to its tolerance of extreme environmental conditions. In this study, a sample of C. saccharophilum from the Laguna Blanca aquifer (Magallanes, southern Chile) was physiologically and phylogenetically characterized. This is the first confirmed evidence of this strain in the Southern Cone. Molecular identification based on ITS rDNA sequencing and ITS2 secondary structure analysis confirmed its taxonomic location, showing high similarity with reference strains and no compensatory base changes. Growth performance was analyzed under controlled laboratory conditions and under outdoor desert cultivation in the Atacama Desert, focusing on temperature, salinity, nutrients limitation, and high solar irradiance operational conditions. The strain exhibited optimal growth at 22 °C under laboratory conditions and demonstrated a strong tolerance to high salinity (150 g L⁻¹ NaCl). Outdoor raceways cultivation revealed a negative relationship between temperatures above 25 °C and biomass accumulation, while nutrients depletion and strong irradiance caused moderate carotenoid accumulation. However, the low amount of carotenoid yields remained constant, even under combined stress conditions. In general, the results highlight the ecological adaptability and the stress tolerance of C. saccharophilum, supporting its potential application in saline bioprocesses and bioremediation. Nevertheless, the limited production of carotenoid synthesis suggests that additional or combined stress strategies will be required to enhance the production of high-value metabolites. This study expands the biogeographical knowledge of C. saccharophilum and provides a physiological baseline for future optimization studies in extreme and Mars-analog environments. Full article

Background/Objectives: Cyclooxygenase-2 (COX-2) is a well-established target in the development of anti-inflammatory drugs due to its central role in mediating inflammation. The identification of novel COX-2 inhibitors remains a key focus in pharmaceutical research. This study aimed to develop a robust and interpretable machine learning framework to predict COX-2 inhibitory activity and support virtual screening efforts. Methods: A curated dataset of 2052 compounds was obtained from the ChEMBL database. Molecular structures were encoded using Morgan fingerprints derived from SMILES representations. Several machine learning algorithms were trained and evaluated, including ensemble-based methods. Model performance was assessed using internal validation and external test sets. Robustness was further evaluated through Y-randomization tests. Model interpretability was investigated using SHAP (SHapley Additive exPlanations) analysis to identify key structural features contributing to activity. Results: Among the evaluated models, ensemble methods demonstrated superior predictive performance, with the Random Forest algorithm providing the most consistent and reliable results across validation and external datasets. Y-randomization confirmed that the model predictions were not due to chance correlations. SHAP analysis revealed that the most influential features corresponded to chemically meaningful substructures aligned with known COX-2 pharmacophore characteristics. The final optimized model was successfully deployed as a publicly accessible web application for real-time prediction using SMILES input. Conclusions: This study demonstrates the effectiveness of explainable machine learning approaches in predicting COX-2 inhibitory activity. The developed framework provides a reliable and interpretable tool for accelerating COX-2 inhibitor discovery and facilitating virtual screening in drug development. Full article

This work focused on the identification of angiotensin I-converting enzyme (ACE) inhibitory peptides from royal jelly (RJ) proteins and elucidated their inhibition patterns and mechanisms. RJ proteins were analyzed for ACE inhibition potential using in silico tools, and suitable enzymes were selected for peptide release. Hydrolysis conditions were optimized using response surface methodology (RSM), and the resulting peptides were fractionated and purified. Mass spectrometry identified 57 peptides, with seven selected for synthesis based on scoring. IDFDF, DVNFR, and SFHRL showed the highest ACE inhibition, with IC₅₀ values of 16.9 μM, 42.5 μM, and 242.6 μM, respectively. Lineweaver–Burk plots revealed IDFDF as a competitive inhibitor, DVNFR as a non-competitive inhibitor, and SFHRL as a mixed inhibitor. Molecular docking indicated that peptide–ACE interactions were primarily mediated through hydrogen bonds and Zn(II) coordination. This work promotes the sustainable utilization of RJ and the development of ACE inhibitory peptides derived from food sources. Full article

Bloodstream infections (BSIs) are associated with substantial morbidity, mortality, and healthcare costs. Conventional diagnostics are limited by delayed results, often postponing appropriate antimicrobial therapy. This review aimed to evaluate the clinical and economic value of rapid microbiological diagnostics in BSI management. A state-of-the-art evidence synthesis was conducted using structured searches of PubMed/MEDLINE, Scopus, Web of Science, EconLit, and Google Scholar (2013–2025). Eligible studies included economic evaluations and clinical studies reporting downstream economic or resource-use outcomes. Screening and data extraction were performed by two reviewers, and findings were narratively synthesized. Fifty-nine studies were included. Rapid diagnostics consistently reduced time to pathogen identification and targeted therapy compared to conventional methods. Molecular platforms provided results within hours, while MALDI-TOF enabled identification within 30–60 min after culture positivity. Clinical benefits included earlier therapy optimization, reduced mortality, and shorter hospital stays, particularly when combined with antimicrobial stewardship programs (ASPs). Economic evaluations demonstrated improved cost-effectiveness, including reduced hospitalization, ICU utilization, and antimicrobial costs. MALDI-TOF with stewardship showed notable cost savings and improved outcomes. However, results varied depending on implementation context, infrastructure, and workflow integration. Rapid microbiological diagnostics offer significant clinical and economic benefits in BSI management, particularly when integrated with stewardship programs. Context-specific implementation is essential to maximize their value across healthcare systems. Full article

Cotton, as a globally significant economic crop, is intricately regulated in its growth and development by the key genes for SA (Salicylic acid) biosynthesis. In the present study, a systematic analysis of genes related to SA biosynthesis was conducted across four cotton species, leading to the identification of 70 genes. Specifically, the tetraploid species Gossypium hirsutum and G. barbadense were found to harbor 22 and 23 genes, respectively, representing a substantial expansion compared to the 12 and 13 genes identified in the diploid progenitors G. arboreum and G. raimondii. Comprehensive characterization of chromosomal localization, phylogeny, domain architecture, and promoter cis-elements revealed a uniform distribution of key genes involved in SA biosynthesis across A/D sub-genomes of tetraploids with extensive interspecific collinearity; whole-genome and segmental duplication act as the dominant drivers for the expansion of this gene family, while partial gene loss following polyploidization results in non-doubled gene copy numbers in tetraploids relative to diploids, which reflects the evolutionary selection for genomic dosage balance. The key genes for SA biosynthesis demonstrate a high degree of conservation in protein sequences, protein structures, and conserved motifs, which constitute the structural basis for the stable maintenance of their core functions in the SA biosynthesis pathway during plant evolution. This is closely related to their core function in the salicylic acid (SA) synthesis pathway and serves as the structural basis for the stable maintenance of gene functions during evolution. Analysis of cis-elements revealed that the expression of key genes involved in SA biosynthesis is governed by a complex interplay of phytohormones, stress signals, and transcription factors. Yeast one-hybrid (Y1H) assays confirmed the interaction between the GhPAL and GhICS gene and predicted candidate transcription factors, specifically the binding of GhWRKY21 to GhICS2-1 promoter and GhMYB12 to GhPAL1-2 promoter, thus elucidating their stage-specific regulatory mechanisms in cotton fiber development and reflecting their evolution. This study provides a fundamental basis for investigating the role of the SA signaling pathway in cotton development and offers support for cotton molecular breeding. Full article

Wild orchid populations are declining with intensified habitat fragmentation posing severe challenges to germplasm conservation. As an important ornamental Orchidaceae species, Cymbidium ensifolium has abundant germplasm resources and frequent natural and artificial hybridization. Long-term natural evolution and anthropogenic disturbance have led to complex genetic backgrounds and ambiguous phylogenetic relationships hindering accurate germplasm identification, elite resource excavation, and selective breeding. As a distinctive variety, Cymbidium ensifolium var. susin has great breeding potential. Clarifying its phenotypic and genetic characteristics is crucial for accelerating breeding progress. In this study, phenotypic determination, Hyper-seq reduced-representation genome sequencing, SNP/InDel genotyping, genetic diversity analysis, and core collection construction were used to evaluate the genetic diversity, population differentiation, and core germplasm screening of 13 Cymbidium ensifolium var. susin accessions. The results showed significant phenotypic differences and rich genetic variation among tested materials. Based on highly weighted floral traits, accessions were divided into three major phenotypic groups. At the molecular level, 963,239 SNP and 182,399 InDel loci were identified and mainly distributed in intergenic regions, followed by introns and exons. A phylogenetic tree was constructed from SNP loci combined with principal component and phenotypic clustering analyses. This study preliminarily clarified the genetic structure of pure-heart Cymbidium ensifolium var. susin, showing a distinct geographical pattern: “high consistency in Fujian and Guangdong; strong differentiation in Southwest China; and a transitional gradient in Central China”. Meanwhile, six core germplasm accessions were screened in this study, which provides a solid theoretical basis and material support for the conservation of pure-heart Cymbidium ensifolium var. susin accessions, variety improvement, hybrid parent selection, and molecular marker-assisted breeding. This is of great significance for promoting the innovation of Chinese orchid germplasm resources and the high-quality development of the industry. Full article

The global seafood industry faces persistent challenges related to product quality, safety, and authenticity, driven by complex supply chains, increasing demand, and the perishable nature of aquatic products. Traditional analytical methods often fall short in providing rapid, comprehensive, and non-destructive insights into the intricate biochemical changes occurring in seafood. ¹H Nuclear Magnetic Resonance (¹H NMR) spectroscopy has emerged as a powerful and versatile tool for metabolomics, offering a holistic view of the low-molecular-mass compounds (metabolites) present in biological samples. The present study applied ¹H NMR for chemical fingerprint identification in mullets (Mugil liza) from Brazil. Dorsal muscle samples were taken from the fish during summer, autumn, and winter. The procedure involved freeze-drying the muscle tissue, thereafter extracting polar metabolites using designated solvents (methanol, water, and chloroform), and analyzing them using a 600 MHz spectrometer. As a result, 23 metabolites related to degradation biomarkers, essential metabolites, energy expenditure, and muscle structure were identified. The statistical analysis demonstrated a distinct separation between the geographical origins (RJ vs. SC), mostly influenced by variations in the concentrations of lactate, histidine, threonine, phenylalanine, and ornithine. Factors like fish size and seasonal variations did not markedly affect the overall metabolic profile, underscoring the reliability of these chemicals as stable origin indicators. The Principal Component Analysis identified two distinct groups of metabolites, establishing a profile for each geographical origin. The developed protocol can be applied to the processes of geographical identification. Thus, the ¹H NMR tool was efficient in determining metabolites that can be considered biomarkers in analyses for seafood traceability. Full article

Background: Reliable preoperative identification of carotid plaque instability remains challenging. Although duplex ultrasound allows early detection of carotid stenosis, it does not consistently predict plaque biological behavior. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and have been implicated in atherosclerotic progression and plaque destabilization. The tissue-level expression of miRNAs in carotid plaques and their relationship with histological vulnerability remain incompletely defined. Methods: This exploratory, pilot, hypothesis-generating study included patients undergoing carotid endarterectomy for asymptomatic high-grade carotid stenosis (>75% NASCET). Plaque vulnerability was assessed using a multiparametric approach combining preoperative duplex ultrasound features (including Gray Scale Median, GSM), intraoperative macroscopic evaluation, and a validated histological scoring system; only plaques with concordant classification across all three modalities were retained for molecular analysis. Total RNA including small RNA was extracted from plaque tissue and miRNA expression was measured by qRT-PCR on a panel of 47 candidate miRNAs. Data were analyzed descriptively. Results: Twenty-eight patients were initially enrolled; after application of strict vulnerability criteria, five plaques (three unstable, two stable) were selected for miRNA profiling. Among the 47 miRNAs assayed, miR-122 and miR-197 showed a consistent descriptive trend toward higher expression in plaques classified as unstable; these plaques also displayed histological features of vulnerability (lipid-rich necrotic cores and inflammatory infiltrates). Given the extremely limited sample size, no inferential statistical comparisons or multiple-testing corrections were performed. Conclusions: In this small, tissue-based exploratory analysis, miR-122 and miR-197 were more highly expressed in plaques with histological features of instability. Due to the small sample size, the effect estimates are unstable, and the findings should be used solely to inform the design and power calculations of future studies. We outline the need of a clear, pragmatic validation pathway based on replication in independent, larger cohorts with standardized tissue handling and blinded assessment and parallel evaluation of circulating miRNA levels to assess noninvasive biomarker potential. Indeed, these findings are preliminary and strictly hypothesis-generating; validation in larger, prospectively collected cohorts and integration with circulating biomarkers and imaging data are required before clinical application. Full article

Background: Piper is one of the largest genera in the family Piperaceae, with approximately 2100 species. Most Piper species are used as spices or as medicinal plants. Piper methysticum G. Forst., popularly known as kava-kava (or kava), is widely used to treat anxiety disorders. Due to similar morphological features, P. auritum Kunth (known as “false kava”) is sometimes mistakenly or intentionally used as an alternative botanical source for “kava” extracts. The false kava extracts do not contain active kavalactones but contain safrole, which is hepatotoxic. It is important to verify the component botanical materials in order to evaluate the quality and safety attributes of a potential botanical drug. Some studies have evaluated genetic variation in Piper sp. using the chloroplast regions matK, rbcL, rpoC1 and trnH-psbA and the nuclear ITS2 markers. However, none has focused on the identification of P. methysticum using DNA barcodes. In the present investigation, the ITS2 DNA barcode region from the nuclear genome was tested to confirm the identification and authentication of kava-kava samples. Methods: Seven P. methysticum samples were collected from three different geographic lo-cations and two P. auritum samples were collected and the ITS2 region from the nuclear genome, was amplified, sequenced and aligned to determine their genetic distances. Results: The ITS2 locus showed high amplification and sequence output with a discriminating barcode gap. A distance-based phylogenetic tree and BLAST confirmation (using blastn) revealed the ITS2 locus as a diagnostic DNA barcode for the accurate identification of kava-kava species. Discussion: In conclusion, the ITS2 region proves to be an effective and reliable DNA barcode for distinguishing P. methysticum from closely related species such as P. auritum. Its application can significantly improve the safety, quality, and traceability of kava-containing products, addressing a critical need in the standardization of botanical drugs. Full article

Nitrogen is a critical macronutrient for plants, playing a central role in the synthesis of proteins, amino acids, and nucleic acids. To enhance nitrogen use efficiency (NUE) and ensure sustainable agricultural production, identification of nitrogen-efficient genes and application of molecular breeding techniques are crucial for developing high-NUE rice germplasm. The nitrogen signaling pathway exhibits close crosstalk with phytohormones, including auxins (IAA), gibberellins (GAs), abscisic acid (ABA), cytokinins (CTKs), brassinosteroids (BRs), and strigolactones (SLs). This review systematically summarizes the molecular mechanisms underlying crosstalk between nitrogen and phytohormones, focusing on the physiological and molecular basis underlying their synergistic regulation of root development and NUE in rice, and outlines challenges for the complicated research field and prospective directions in future. Full article