Search Results (30,868)

Lavender essential oil (LEO) possesses broad therapeutic potential, yet translating empirical knowledge into evidence-based medicine is hindered by the descriptive literature that conflates isolated monoterpene mechanisms with whole-oil efficacy. Addressing these critical shortcomings, this review presents a target-centric synthesis that explicitly delineates the molecular pathways of pure constituents (e.g., linalool, linalyl acetate) versus intact LEO matrices and standardized oral preparations (Silexan™). We systematically integrate LEO’s multi-target signaling networks across neuroregulatory, analgesic, anti-inflammatory, and skin-regenerative domains, while critically examining how genetic taxonomy, environmental stress, and green extraction technologies dictate chemotype diversity. Furthermore, we candidly address current evidence limitations, including pre-clinical predominance, publication bias, and clinical trial narrowness. Finally, we outline actionable translational strategies centered on chemotype-driven standardization, smart delivery systems, and a dual pharmacological paradigm that valorizes non-volatile processing byproducts. This synthesis establishes a rigorous theoretical foundation for LEO’s clinical translation and pharmaceutical standardization. Full article

Background/Objectives: Alzheimer’s disease (AD) is a progressive, multifactorial neurodegenerative condition characterized by neurofibrillary tangles, neuronal loss, cognitive impairment, and accumulation of β-amyloid plaques. Considering the limitations of current treatments, which present adverse effects and only alleviate symptoms without modifying disease progression, there is an urgent need for new therapeutic approaches. This study aimed to investigate the neuroprotective potential of synthetic derivatives of (1E,4E)-1,5-bis[(het)aryl]penta-1,4-dien-3-ones, focusing on the inhibition of the cholinesterase enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), targets directly related to the cholinergic deficit observed in AD. Methods: The compounds were initially synthesized by aldol condensation reactions, with subsequent physicochemical characterization. They were then subjected to in silico assays that demonstrated high binding affinity to the active sites of AChE and BChE. The derivatives were evaluated in vitro for their inhibitory activity on these enzymes and in vivo in an experimental model of AD induced by streptozotocin in Wistar rats. Results: The synthesized derivatives showed favorable predicted interactions with the active sites of AChE and BChE, supporting their potential as cholinesterase inhibitors. In vitro assays demonstrated inhibitory activity against both enzymes, with selected derivatives showing improved activity compared with the parent scaffold. In the in vivo model, treatment with the selected compounds was associated with neuroprotective effects, suggesting preservation of nervous tissue integrity under AD-like conditions. Conclusions: These findings indicate that derivatives may represent promising candidates for further investigation as multitarget agents for AD. The study reinforces the relevance of integrating organic synthesis, molecular modeling, enzymatic assays, and in vivo evaluation in the search for new therapeutic strategies for neurodegenerative diseases. Full article

Next-generation sequencing (NGS) has become a cornerstone of precision oncology in colorectal cancer (CRC), although its role in routine patient stratification remains incompletely defined. This retrospective single-centre study characterised the molecular landscape of clinically selected CRC patients undergoing routine NGS and explored associations between genomic alterations and clinicopathological features. 97 eligible patients who underwent targeted NGS using two validated sequencing platforms were selected. Demographic, clinicopathological, and molecular data were integrated, and associations were evaluated using descriptive statistics, exploratory association testing, principal component analysis, and multiple correspondence analysis. At least one reportable genetic alteration was identified in 91 patients (93.8%), comprising 198 alteration events across multiple cancer-related genes. The most frequently altered genes with pathogenic or likely pathogenic variants were TP53 (55.7%), KRAS (40.2%), PIK3CA (18.6%), and BRAF (11.5%), while microsatellite instability was detected in 19.1% of evaluable tumours. Exploratory analyses identified associations between selected molecular alterations and clinicopathological characteristics. However, these were generally modest, frequently limited by small subgroup sizes, and none survived Benjamini–Hochberg correction. Principal component analysis demonstrated substantial molecular heterogeneity without defining distinct clinicopathological subgroups. Routine targeted NGS provides detailed molecular characterisation of CRC and generates information relevant to biomarker-informed clinical decision-making in real-world practice. However, targeted panels alone were insufficient to establish robust molecular subgroups in this retrospective cohort. These findings highlight the biological complexity of CRC and support larger prospective studies incorporating broader molecular profiling to improve precision patient stratification and optimise personalised therapeutic strategies. Full article

Background: Combining natural products with conventional antidiabetic agents to inhibit α-glucosidase activity is an effective strategy for preventing postprandial hyperglycemia. Baicalein, a natural flavonoid with well-documented low toxicity, showed potential synergistic effect with acarbose in diabetic models; however, the synergistic performance and mechanisms of the two agents targeting human maltase–glucoamylase (MGAM) remain unclear. Methods: Recombinant human MGAM-C and MGAM-N were expressed in Pichia pastoris for in vitro inhibition assays. Maltose-loaded mice were used to assess the in vivo hypoglycemic activity and intestinal maltase inhibition. Inhibitor–enzyme interactions were investigated by fluorescence spectroscopy, circular dichroism (CD), multiple molecular docking, and molecular dynamics (MD) simulations. Results: Baicalein potently inhibited MGAM-C and MGAM-N with IC₅₀ values of 20.41 ± 4.80 μM and 14.04 ± 0.94 μM, respectively, and demonstrated a synergistic effect when combined with acarbose. In vivo, co-administration significantly reduced blood glucose levels and suppressed small intestinal maltase activity in maltose-loaded mice. Mechanistic studies revealed that baicalein functions as a non-competitive inhibitor by binding to the allosteric site of MGAM-C via stable hydrogen bonds with residues Ile1716 and Trp1749. This interaction induces conformational changes in the enzyme’s secondary structure and optimizes the hydrophobic microenvironment of the active site, thereby enhancing the binding affinity and hydrogen bond stability of acarbose. These molecular events collectively contribute to the synergistic inhibition of MGAM-C hydrolytic activity. Conclusions: This research revealed the synergistic inhibitory effect of baicalein and acarbose on MGAM and the underlying mechanisms, thereby providing a theoretical basis for developing pharmaceutical formulations to enhance acarbose efficacy. Full article

Caloric restriction (CR), defined as a 30–60% decrease in ad libitum food intake without malnutrition, has emerged as one of the most robust non-pharmacological interventions for promoting metabolic health and longevity in various species, including yeast, worms, flies, rodents, and perhaps non-human primates. In addition, CR has been shown to reduce the incidence of age-related disorders (for example, diabetes, cancer, and cardiovascular disorders) in mammals. Among the key organs influenced by CR, the pancreas—particularly the insulin-producing β-cells—plays a central role in maintaining glucose homeostasis and metabolic balance. A growing body of evidence suggests that CR exerts its beneficial effects, at least in part, through the modulation of nutrient-sensing pathways and epigenetic regulators. Sirtuins, a family of NAD⁺-dependent deacetylases and ADP-ribosyltransferases, have gained attention as pivotal molecular mediators of CR. By responding to changes in cellular energy status, sirtuins regulate diverse processes including gene expression, oxidative stress response, mitochondrial function, and autophagy. In the pancreas, sirtuins such as SIRT1, SIRT3, and SIRT6 have been implicated in preserving β-cell function, enhancing insulin secretion, and protecting against metabolic stress and inflammation. This review critically examines current evidence regarding the role of individual sirtuins in mediating the pancreatic response to caloric restriction, with particular emphasis on β-cell physiology, insulin secretion, mitochondrial function, autophagy, oxidative stress, and inflammatory signaling. We further discuss how these molecular mechanisms contribute to systemic metabolic homeostasis and may influence healthy longevity. Importantly, we integrate experimental findings with emerging clinical evidence demonstrating the recovery of β-cell function following dietary energy restriction and identify current controversies, limitations, and key knowledge gaps that should guide future translational research. Collectively, available evidence suggests that sirtuins represent central molecular links between caloric restriction and β-cell adaptation, highlighting their potential as therapeutic targets for preserving pancreatic function and preventing metabolic disease. Full article

Hypophosphatasia (HPP) encompasses a group of inherited metabolic bone disorders characterized by defective skeletal mineralization and variable clinical severity in childhood. Substantial allelic heterogeneity contributes to a broad pediatric clinical spectrum, ranging from life-threatening perinatal disease to milder phenotypes characterized by chronic functional impairment. Historically, management relied primarily on supportive interventions aimed at sustaining survival, without modifying the underlying enzymatic defect. The introduction of enzyme replacement therapy (ERT) with asfotase alfa has fundamentally altered the natural history of pediatric HPP by supplementing deficient alkaline phosphatase activity at sites of active mineralization, thereby improving skeletal integrity, enhancing survival in severe forms, and supporting long-term functional gains. This therapeutic shift has redirected clinical priorities from survival alone toward sustained functional development and health-related quality of life. Nevertheless, variability in disease expression and therapeutic response persists, reflecting both diagnostic timing and the molecular heterogeneity of ALPL variants, whose phenotypic consequences cannot be predicted with complete certainty. Growing recognition of the importance of early diagnosis has prompted exploratory efforts toward systematic identification strategies, including neonatal screening initiatives reported in selected populations, which suggest the potential for earlier therapeutic intervention during active skeletal development. Together, these considerations highlight pediatric HPP as a model of precision-oriented management in rare metabolic bone disease, where timely diagnosis and targeted enzyme replacement must be aligned with long-term, multidisciplinary care to optimize outcomes. Full article

Cystic fibrosis (CF) is one of the most common rare genetic diseases. It is caused by pathogenic variants of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. More than 2200 variants have been identified in the CFTR gene that need detailed knowledge and functional characterization in order to develop specific therapeutic strategies. The traditional therapy for CF relied on addressing symptoms through mucolytic and antibiotic treatments, respiratory physiotherapy and aerosol therapy. However, in the last few years, the development of small new molecules targeting and restoring the underlying CFTR channel defect marked an important step in CF treatment. In addition, the implementation of patient-specific cellular models allowed the evaluation of pharmacological responses, leading to therapeutic advances in the direction of personalized treatment. The focus of this review is to describe and discuss the strategies for restoring the CFTR functional defects depending on the specific CFTR pathogenic variants. In particular, the review highlights the possible application of experimental and clinical drugs to CF treatment, which may allow improvements in patients’ quality of life and life expectancy. The in vitro testing of therapeutic drugs (theratyping) is performed nowadays through the use of several cellular models, especially those derived from patient-specific tissues. This topic is a hot point in CF research and the review also aims to provide an overview of the state of the art in theratyping. The novelty of this review is the integrated view of the most recent achievements in precision diagnostics and therapy of CF at the molecular, cellular and clinical level, which are able to change the natural history of this disease. Full article

Background: The increasing prevalence of antifungal resistance among Candida albicans isolates necessitates the exploration of alternative antifungal strategies and novel molecular targets. Plant-derived bioactive compounds represent a promising source of antifungal agents; however, their chemical composition and mechanisms of action remain insufficiently characterized. Methods: Ethanolic extracts of Azadirachta indica leaves and Ficus benghalensis aerial roots were subjected to qualitative phytochemical screening, gas chromatography–mass spectrometry (GC–MS), and Fourier transform infrared (FTIR) analysis to characterize their bioactive constituents. Molecular docking studies were performed to evaluate the interaction of selected phytochemicals with C. albicans N-myristoyltransferase (PDB ID: 1IYK), a validated antifungal drug target. Results: Phytochemical screening revealed the presence of alkaloids, carbohydrates, and phenolic compounds in both extracts, while saponins were detected only in A. indica. GC–MS analysis demonstrated greater chemical diversity in A. indica, including fatty acids and phenolic derivatives, compared with F. benghalensis, which was dominated by terpenoids and long-chain hydrocarbons. FTIR analysis confirmed functional groups relevant to protein–ligand interactions. Molecular docking showed favorable binding interactions between several A. indica–derived compounds and N-myristoyltransferase, whereas compounds from F. benghalensis did not exhibit detectable binding under the conditions tested. Conclusions: The integrated phytochemical and in silico analyses provide insight into the antifungal potential of A. indica, suggesting possible interactions between identified phytochemicals and the selected drug target protein. This study highlights the value of combining chemical characterization with target-based computational screening in the rational exploration of plant-derived antifungal agents. Full article

Polysaccharides are major bioactive constituents and quality-related components of Anoectochilus roxburghii. However, how polysaccharide accumulation varies among cultivars and tissues remains poorly understood. Here, crude polysaccharide content was quantified in leaves and stems of three cultivars, Yuanye (YY), Hongxia (HX), and Jianye (JY), and the underlying molecular basis was investigated using transcriptomics, targeted sugar metabolomics, and integrated transcriptome–metabolome analysis. Stems accumulated significantly higher levels of crude polysaccharides than leaves, whereas cultivar-dependent differences were most pronounced in stems. JY stems showed the highest crude polysaccharide content, reaching 357.81 mg g⁻¹ dry weight. Transcriptomic and metabolomic profiles clearly differentiated the cultivars and tissues. Metabolic differences were concentrated at a limited number of sugar-metabolic nodes, whereas the transcriptome showed extensive transcriptional reprogramming. Integrative analyses consistently implicated starch and sucrose metabolism, precursor-sugar interconversion, nucleotide-sugar biosynthesis, and sugar transport, partitioning, and intracellular allocation in differential polysaccharide accumulation. Glucose and D-fructose emerged as key hub metabolites linking transcriptional variation to sugar-metabolic remodeling. These results suggest that tissue- and cultivar-dependent polysaccharide accumulation is associated with coordinated changes in sucrose turnover, precursor sugar supply, nucleotide-sugar formation, and sugar partitioning, particularly in stems. This study provides molecular evidence for the selection of high-polysaccharide germplasm and quality evaluation of A. roxburghii. Full article

Background: Chronic psychological stress drives metastasis in triple-negative breast cancer (TNBC), yet the underlying mechanisms remain poorly understood and effective interventions are lacking. Stress-induced expansion of myeloid-derived suppressor cells (MDSCs) and subsequent immune remodeling play critical roles, with aberrant myeloid differentiation of hematopoietic stem and progenitor cells (HSPCs) serving as a major source of MDSCs. This study investigates whether epicatechin gallate (ECG) suppresses stress-driven TNBC growth and lung metastasis by regulating HSPC myeloid differentiation. Methods: A mouse model of chronic unpredictable mild stress (CUMS) followed by 4T1 tumor implantation was used to evaluate the anti-tumor effects of ECG. CETSA-WB, molecular docking, HSPC differentiation assays, and MDSC functional validation assays, along with immunohistochemistry, immunofluorescence, and flow cytometry, were performed to elucidate how ECG modulates glucocorticoid (GC)/glucocorticoid receptor (GR) signaling and HSPC differentiation. Results: ECG dose-dependently alleviated depressive-like behaviors, reduced serum corticosterone (Cort), and inhibited tumor growth and lung metastasis. Notably, ECG decreased lung metastatic foci by 76.9% relative to the CUMS group. Mechanistically, chronic stress activated GR and induced its nuclear translocation in HSPCs, promoting aberrant HSPC-to-MDSC differentiation. ECG directly bound GR, blocked its nuclear translocation, and suppressed the myeloid differentiation of HSPCs into MDSCs, which was accompanied by downregulation of S100A8/A9, fibronectin, and MMP-2, as well as increased CD8⁺ T cell infiltration. Supernatants from ECG-pretreated and differentiated HSPCs reversed Cort-induced epithelial–mesenchymal transition (EMT) in 4T1 cells. Conclusions: ECG acts as a natural GR signaling blocker that directly targets GR to block chronic stress-driven abnormal myeloid differentiation of HSPCs, thereby remodeling the pulmonary immune microenvironment, suppressing EMT, and reducing breast cancer lung metastasis. These findings identify ECG as a promising GR signaling blocker and a potential adjuvant therapy for cancer patients under high-stress conditions. Full article

Ascorbic acid (vitamin C) is a critical antioxidant influencing the nutritional quality of fruits. This study integrates metabolomic and transcriptomic analyses to investigate high-ascorbic-acid (HAA), medium-ascorbic-acid (MAA), and low-ascorbic-acid (LAA) jujube cultivars. Metabolomic profiling revealed significant enrichment of ascorbic acid and its precursors in HAA cultivars, whereas MAA and LAA cultivars showed lower levels. Transcriptomic analysis identified 107 differentially expressed genes (DEGs) across the three groups. Compared with LAA, 139 differentially accumulated metabolites (DAMs) were identified in HAA, with more down-accumulated (77) than up-accumulated (62); compared with MAA, 235 DAMs were found in HAA, with significantly more up-accumulated (180) than down-accumulated (55); 250 DAMs with different accumulation patterns between LAA and MAA included 199 up-accumulated and 51 down-accumulated; and 16 DAMs were common in all three comparison combinations. Potential key regulatory genes such as GDP-mannose-3′,5′-epimerase (GME) and L-galactose-1-phosphate phosphatase (GPP) were highlighted. Weighted Gene Co-expression Network Analysis (WGCNA) detected possible core genes participating in ascorbic acid biosynthesis pathways. This study provides novel insights into the genetic and metabolic basis of ascorbic acid accumulation, potentially providing valuable targets for molecular breeding. Full article

Once regarded as a benign, clinically overlooked organism, Theileria orientalis has undergone a paradigm shift in its perceived status and is now recognised as a tick-borne haemoparasite of clinical and economic importance. Severe outbreaks characterised by haemolytic anaemia, reproductive losses, and mortality, primarily associated with the Ikeda and Chitose genotypes, have been increasingly reported in Australasia, Asia, and North America. In Europe and parts of Africa, however, the epidemiological status of T. orientalis remains poorly defined, despite increasing molecular evidence of circulation and reports of predominantly subclinical infections. The parasite is transmitted transstadially in ixodid ticks, with Haemaphysalis longicornis as the principal confirmed biological vector, although vector competence remains unverified for most suspected tick species. This narrative review was based on a comprehensive PubMed search from database inception up to the date of initial manuscript submission, supplemented by reference-list screening and targeted searches. This review synthesises current knowledge on taxonomy, life cycle, transmission, genetic diversity based on the major piroplasm surface protein gene, global epidemiology, pathogenesis, clinical manifestations, co-infections, production losses, diagnostics, and control strategies. Key gaps include limited understanding of the mechanisms driving erythrocyte destruction, insufficient experimental confirmation of vector competence, absence of licensed vaccines, and incomplete epidemiological data in several regions. Future research priorities are discussed in the context of climate change and the expanding geographic distribution of tick vectors. Full article

To address the challenges of insufficient selectivity, environmentally induced signal instability, and limited quantitative reliability in the on-site rapid detection of tetracycline antibiotics (TCs) in food samples, this study developed a portable quantitative detection method for oxytetracycline (OTC) based on a molecularly imprinted fluorescent test strip. The proposed platform integrates a molecularly imprinted polymer–quantum dot (MIP–QD) recognition system with digital signal processing strategies. CdTe quantum dot-functionalized OTC-imprinted fluorescent test strips were fabricated to enable specific target recognition and fluorescence response. Digital filtering, characteristic peak identification, virtual baseline correction, and peak area integration were employed to improve the stability and accuracy of fluorescence signal extraction. A quantitative model for OTC determination was established based on the fluorescence intensity ratio between the test line and control line (T/C fluorescence ratio). The developed assay exhibited high selectivity toward OTC, with a limit of detection (LOD) of 0.01 μmol/L and a linear detection range of 0.02–0.24 μmol/L. In spiked milk and honey samples, the recoveries of OTC ranged from 96.1% to 100.9% and from 96.9% to 102.4%, respectively, with relative standard deviations (RSDs) below 5%. By integrating molecular imprinting recognition, quantum dot-based fluorescence signaling, and portable digital signal analysis, the proposed method demonstrated reliable quantitative performance in complex food matrices and provides a feasible approach for the on-site rapid screening of tetracycline antibiotics. Full article

This study integrated an in vivo feeding trial (0.00–1.00% choline chloride) with in vitro primary hepatocyte experiments to elucidate the molecular mechanisms by which choline chloride alleviates hepatic lipid deposition in bighead carp. The results showed that dietary supplementation with 0.80–1.00% choline chloride significantly reduced hepatic triglyceride (TG) content and lipid droplet accumulation. At the molecular level, choline markedly downregulated lipogenic genes (g6pd, accα, fas) while upregulating genes involved in lipolysis (cpt1α, acox1) and lipid transport (apob-100, mttp). Non-targeted lipidomics revealed that choline maintains lipid homeostasis primarily via the glycerophospholipid metabolism pathway, significantly increasing levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS). Furthermore, choline intervention enhanced the expression of its own metabolism-related genes (slc44a2, chdh, ck, chpt1), accelerating choline transport and phosphorylation. Overall, based on the results of this experiment, 0.80% is the recommended supplemental level of choline chloride in diets, which can effectively alleviate lipid deposition in bighead carp. The mechanism involves inhibiting lipogenesis and promoting lipid decomposition and transport through glycerophospholipid pathways, while simultaneously enhancing PC synthesis to accelerate hepatic lipid export. These findings provide a theoretical basis for precise feed formulation in bighead carp. Full article

Background: Dangguibuxue decoction (DD), containing Angelica sinensis (Oliv.) Diels (AS) and Astragalus membranaceus (Fisch.) Bge. (AM) (1:5), is a well-known traditional Chinese medicine (TCM) used for strengthening qi and nourishing the blood. DD has shown therapeutic effects in nephropathy patients. However, the underlying mechanisms based on the traditional efficacy are still not fully elucidated. Methods: The chemical constituents in DD were identified using UPLC-MS/MS. Network pharmacology analysis was applied to predict the potential target genes and associated signaling pathways. A renal fibrosis mouse model was induced by the intraperitoneal injection of aristolochic acid I (AA I) at 3.0 mg/kg. Mice were treated with AM, AS, and DD at two dosages by oral gavage for 30 days. Body weights, serum biochemistry, hematology, and histopathology observations were assessed. The key targets predicted were validated using qRT-PCR and Western blotting. The active constituents were screened by molecular docking, and their anti-fibrotic effects were evaluated through in vitro assays. Results: DD effectively improved renal functions and alleviated AA I-induced renal fibrosis. DD alleviated anemia and upregulated the expression of Erythropoietin (EPO). Network pharmacology analysis indicated the involvement of signaling pathways, including the PI3K/Akt, hypoxia-inducible factor-1α (HIF-1α) and transforming growth factor-β (TGF-β) signaling pathways. Experimental validation further demonstrated that DD reduced the protein expression of HIF-1α, collagen I, and TGF-β, and the ratios of phosphorylated Smad2/3 to total Smad2/3. Molecular docking and in vitro assays suggested that rutin may be a potential bioactive compound in DD. Conclusions: This research indicated that DD ameliorated AA I-induced renal fibrosis in mice, which may be associated with the modulation of HIF-1α and TGF-β/Smad signaling pathways. Rutin may be a potential bioactive compound in DD with anti-fibrotic activity, but further studies are still needed to clarify the content of rutin in DD, the amount of its exposure in the body, and its contribution to the effects of DD. Full article