Search Results (4,306)

Foodborne diseases represent a major public health concern, particularly those associated with dairy products contaminated with Staphylococcus aureus, a pathogen capable of producing heat-stable enterotoxins. This study evaluated the potential of native lactic acid bacteria (LAB) isolated from artisanal kefir grains as natural biocontrol agents in fermented dairy foods. Kefir grains obtained from three artisanal producers were microbiologically characterized, revealing LAB as the dominant group and the absence of Enterobacteriaceae. Strains belonging mainly to the genera Lactobacillus sensu lato, Leuconostoc, and Pediococcus were isolated and exhibited differentiated metabolic profiles. Safety assessment showed no hemolytic activity and an overall susceptibility to clinically relevant antibiotics, although genus-dependent intrinsic resistance patterns were observed. Several strains displayed enzymatic activities related to carbohydrate digestion and high tolerance to simulated gastrointestinal conditions, with survival rates exceeding 90% during both gastric and intestinal phases. Neutralized cell-free supernatant (CFS) demonstrated differential inhibitory activity, with significant antagonism of S. aureus and E. coli, comparable to those of commercial reference strains. In a yogurt model system stored at 4 °C, selected Lactobacillus and Pediococcus strains induced a progressive and significant reduction in S. aureus populations, achieving complete elimination to undetectable levels in shorter times than commercial probiotic strains. Overall, these results demonstrate that native LAB from artisanal kefir grains exhibit an adequate safety and functional profile, together with strong antagonistic activity, supporting their potential application as natural protective cultures to improve the food hygiene of fermented dairy products. Full article

Background: Cysteinyl leukotrienes are components of slow-reacting substances of anaphylactic shock (SRS-A) and play a key role in asthma and inflammatory responses. Although chromone-2-carboxylic acids and substituted (aryloxy)alkanoic acids have the potential to be SRS-A antagonists, their comprehensive structure–activity relationships and pharmacokinetic characteristics remain understudied. Objective: This study integrated computational and experimental approaches, including QSAR modeling, molecular docking, ADMET analysis, molecular dynamics (MD) simulations, and antioxidant evaluation to identify and prioritize bifunctional compounds with anti-inflammatory and free radical-scavenging properties. Methods: A set of 68 compounds was analyzed using 2D and 3D quantitative structure–activity relationships (QSAR) (MLR, MNLR, SVR, ANN, and atom-based partial least squares). Molecular docking and 100 ns MD simulations were performed against the CysLT₁ receptor (PDB ID: 6RZ5). ADMET and drug-like properties of the compounds were predicted using ADMETlab 2.0 and SwissADME, and the in vitro antioxidant activity of the top-ranked compounds was evaluated using the DPPH method. Results: The atom-based 3D-QSAR model showed strong predictive power (R² = 0.9524, Q² = 0.5382). Compounds 25, 41, and 47 stood out with the most significant binding energies: −9.5 kcal/mol for 25, −10.0 kcal/mol for 41, and −9.4 kcal/mol for 47. MD simulations confirmed the structural stability and consistent interactions of the protein-compound 47 complex. ADMET analysis showed that compounds 25 and 41 had good pharmacokinetic properties, and in vitro antioxidant assays verified their free radical-scavenging efficacy. Conclusion: Our results highlight the utility of an integrated computational–experimental strategy for the discovery of dual-acting SRS-A antagonists. Compound 25 is highlighted as a promising lead compound for further preclinical development, which effectively combines leukotriene receptor antagonism and antioxidant activity. This framework provides an effective strategy for prioritizing lead compounds in anti-inflammatory drug development. Full article

Microplastic pollution in farmland soils has emerged as a global concern due to its potential to degrade soil health, inhibit crop growth, and enter the food chain. However, effective and environmentally friendly remediation strategies remain limited, particularly regarding the use of biochar to mitigate polyethylene microplastic (PE-MP) stress in agroecosystems. This study investigates whether tobacco stalk biochar (TSB) can alleviate PE-MPs stress in rice seedlings. A two-factor pot experiment was conducted to systematically analyze the responses of soil physicochemical properties, rice growth indicators, and antioxidant enzyme activities to the combined application of varying concentrations of PE-MPs (0, 0.5%, 1%, and 2% (w/w)) and TSB (0, 3%, 6%, and 9% (w/w)). The results show that TSB significantly increased soil pH and organic matter content, effectively mitigating the decline in available nitrogen, phosphorus, and potassium caused by PE-MPs (e.g., under the M3B3 treatment, available nitrogen and phosphorus contents increased by 68.7% and 226%, respectively, compared with those under the M3B0 treatment). Under low-concentration PE-MP (0.5%) stress, an appropriate amount of TSB (3%) resulted in the highest rice germination rate, vigor index, and stress tolerance index, while significantly inducing the activities of superoxide dismutase (SOD) and catalase (CAT) to alleviate oxidative damage. However, high-concentration combinations of TSB and PE-MPs exhibited an antagonistic effect. In conclusion, tobacco stalk biochar can synergistically mitigate microplastic stress on rice through multiple pathways, with its remediation effects exhibiting significant dose dependence and interactive complexity. These findings provide a theoretical and technical basis for the ecological remediation of microplastic pollution in farmland. Full article

Scopolamine, also known as hyoscine, is a naturally occurring tropane alkaloid derived from plants of the Solanaceae family. Clinically, the compound has long been used for the prevention of motion sickness and postoperative nausea and vomiting, as well as for ophthalmological procedures requiring mydriasis and cycloplegia. However, beyond these established indications, increasing attention has been directed toward its broader neuropharmacological actions. This narrative review aims to summarise current knowledge regarding the pharmacological properties of scopolamine, with particular emphasis on its mechanisms of action and emerging implications in neuroscience and neuropsychiatric disorders. Scopolamine acts as a non-selective antagonist of muscarinic receptor subtypes M1–M5, interfering with cholinergic neurotransmission. Experimental and clinical studies demonstrate that scopolamine induces transient cognitive impairment. This property has led to its widespread use as a pharmacological model of Alzheimer’s disease, enabling investigation of cholinergic contributions to cognitive decline. More recently, several early clinical studies suggested that intravenous administration may produce rapid reductions in depressive symptoms, possibly through modulation of glutamatergic neurotransmission and activation of mTORC1-dependent synaptic plasticity pathways in the prefrontal cortex. Nevertheless, subsequent trials have yielded inconsistent results, and the therapeutic relevance of these findings remains uncertain. Current evidence indicates that scopolamine’s neuropsychiatric effects likely arise from complex interactions between cholinergic, glutamatergic, and neurotrophic signalling systems. Taken together, scopolamine represents both a valuable experimental tool for studying cholinergic function and a mechanistic framework for the development of novel therapeutics targeting rapid neuroplastic processes in neuropsychiatric disorders. Full article

Bacteria adapted to elevated temperatures are commonly associated with geothermal environments and are recognized for their functional diversity. In this study, cultivable bacteria were isolated from a geothermal spring in northern Sinaloa, Mexico, and characterized through physicochemical analysis, molecular identification, growth kinetics, and functional screening. The isolates were identified as Bacillus licheniformis (strains J1, J3, and J8) and Brevibacillus borstelensis (strains J6 and J9). Growth analyses showed that, in nutrient broth at 45 °C, the evaluated strains exhibited specific growth rates ranging from 1.25 to 1.78 h⁻¹ and short doubling times between 23 and 33 min, with B. borstelensis J6 displaying the highest rate. At 50 °C, μmax values ranged from 0.77 to 1.08 h⁻¹, indicating sustained growth at elevated temperatures. Functional assays demonstrated extracellular proteolytic, amylolytic, and cellulolytic activities, mainly associated with B. licheniformis strains, in addition to tolerance to the pesticides fluazinam and benomyl. Antagonistic tests showed that B. licheniformis J8 inhibited the phytopathogenic fungi Sclerotinia sclerotiorum and Sclerotium rolfsii, while qualitative mineral solubilization assays indicated the ability of selected isolates to mobilize phosphate and potassium. These findings highlight geothermal ecosystems as valuable reservoirs of thermotolerant bacteria with enzymatic versatility and environmental relevance, supporting further molecular and process-optimization studies. Full article

Fusarium wilt, caused by Fusarium oxysporum f. sp. niveum (Fon), severely restricts the sustainable development of the global watermelon industry. While conventional chemical fungicides of this disease have triggered prominent ecological issues, Bacillus-based microbial biocontrol, which combines inherent environmental compatibility with stable control efficacy, has emerged as a key green alternative to chemical management. However, the biocontrol potential of Bacillus sonorensis against this disease has not yet been fully investigated. In this study, we isolated 56 bacterial strains from healthy watermelon rhizosphere soil, and obtained a Fon-antagonistic strain A-5 with the strongest activity (70.15% mycelial inhibition rate), which was identified as B. sonorensis via polyphasic taxonomic analysis. In vitro assays showed that the sterile fermentation filtrate of strain A-5 had a maximum 81.05% inhibition rate against Fon, and its volatile organic compounds also significantly suppressed Fon growth, with broad-spectrum antifungal activity against four common phytopathogenic fungi. Functional tests confirmed that strain A-5 could secrete cell wall-degrading enzymes, produce siderophores and synthesize indole-3-acetic acid, and 17 antimicrobial secondary metabolite biosynthetic gene clusters were identified in its genome. Pot experiments verified that strain A-5 had a 78.04% relative control efficacy against watermelon Fusarium wilt, which significantly reduced seedling disease incidence and upregulated defense-related antioxidant enzyme activities in watermelon leaves. In general, B. sonorensis A-5 is a promising novel biocontrol agent for green management of watermelon Fusarium wilt. Full article

Suramin is a century-old polysulfonated naphthylurea that remains a first-line treatment for early-stage human African trypanosomiasis (HAT). Remarkably, despite its age, suramin continues to draw attention because of its unusually broad spectrum of biological activities. Historically known as an antagonist of purinergic (P2) receptors and an inhibitor of extracellular enzymes, suramin has more recently been shown to interact with a range of intracellular and mitochondrial proteins. These include succinate dehydrogenase, the ADP/ATP carrier (AAC), the aspartate/glutamate carriers AGC1 and AGC2, carnitine O-acetyltransferase (CRAT), and the ATP-Mg/Pi carrier (APC2). Across these targets, suramin displays sub-micromolar to low-micromolar potencies, largely driven by electrostatic complementarity between its highly anionic sulfonate groups and basic nucleotide- or anion-binding regions of proteins. This extensive polypharmacology helps explain the diverse biological effects reported for suramin and supports its use as a valuable pharmacological probe of mitochondrial transport and metabolism. At the same time, its largeness and high negative charge limit oral bioavailability and brain penetration, prompting efforts to develop simplified analogues. This review brings together chemical, biological, and structural perspectives on suramin, highlighting opportunities for drug repurposing, transporter-focused drug design, and a better understanding of mitochondrial toxicity. Full article

In emphysema, the alveolar septal structure is progressively destroyed, which is believed to be irreversible. However, as it has recently been linked to vascular endothelial growth factor (VEGF) deficiency, we hypothesized that VEGF stimulation can promote lung cell proliferation/migration to reverse emphysema. Our sulfated caffeic acid dehydropolymer, CDSO3, was thus examined in vitro and in vivo, given its VEGF-stimulating activity via ferrous ion (Fe²⁺) chelation-mediated stabilization of hypoxia-inducible factor-1α (HIF-1α). In lung epithelial/endothelial cells, CDSO3 promoted proliferation and wound closure by 1.6–3.0-fold at 10 μM; however, these effects were negated by excess FeSO₄ or an HIF-1α inhibitor, indicating an Fe²⁺- and HIF-1α-dependent mechanism. In rat models of established emphysema induced by cigarette smoke extract or the VEGF receptor antagonist SU5416, two-week lung administration of CDSO3 at 60 μg/kg from day 21 enabled: 68–79% recovery of exercise endurance and airspace enlargement/destruction; a 1.8-fold increase in proliferating cell nuclear antigen above healthy levels; normalization of cleaved caspase-3; restoration of HIF-1α; and a 1.3-fold increase in VEGF above healthy levels. In contrast, CDSO3 pre-chelated with Fe²⁺ was ineffective. In conclusion, Fe²⁺ chelation-mediated HIF-1α stabilization and VEGF stimulation via local lung delivery of CDSO3 can reverse established emphysema by promoting cell growth and survival. Full article

Novel pharmacological approaches advocate developing multitarget drugs, that is, molecules capable of simultaneously acting on two or more pharmacological targets to produce synergistic effects from a single compound in each disease. This strategy may help reduce required doses and prevent drug–drug interactions typically associated with polypharmacy. Coumarins are natural products with diverse pharmacological activities, including antioxidant, anti-inflammatory, anticancer, neuroprotective, cardioprotective, and antithrombotic effects. The pleiotropic actions of these molecules suggest that modifying the coumarin structure could yield new multi-target antiplatelet agents with greater efficacy and safety than those currently available in clinical practice. In this work, we began with a theoretical approach using molecular docking and designed three coumarins that simultaneously inhibited platelet aggregation induced by epinephrine, collagen, and ADP. Experimentally, we evaluated the structure activity relationship of three coumarins: (A) 6,7-dimethoxy-3-(1H-pyrrol-1-yl)-2H-chromen-2-one, (B) 7,8-dimethoxy-3-(1H-pyrrol-1-yl)-2H-chromen-2-one, and (C) 3-(1H-imidazol-1-yl)-6,7-dimethoxy-2H-chromen-2-one. In silico studies suggest that compounds B and C may exhibit antagonistic interactions at the α₂-adrenergic, GPVI collagen, and P₂Y₁₂ ADP receptors. Additionally, molecular docking indicates essential interactions between the compounds and the GPIIb/IIIa fibrinogen receptor. Full article

Wheat common bunt, caused by Tilletia foetida Liro, is a devastating disease in wheat production. In this study, the antagonistic endophytic bacteria 29-Y2 were screened based on the germination rate of teliospore and the control effect of wheat common bunt. During primary screening, 29-Y2 had the best performance, with a 96.73% inhibition on TFL spore germination. In the deep screening, the control effect of 29-Y2 on wheat common bunt was 66.12% in pots. Based on morphological, physiological, and biochemical characteristics and molecular biological identification, the antagonist 29-Y2 was identified as Paenibacillus polymyxa. The antagonist 29-Y2 promoted the germination rate of wheat seeds and the growth of wheat seedlings at a solution dilution of 10⁻⁵ cfu/mL. In different field trials, the antagonists 29-Y2 both had better control efficiencies of 62.31% and 67.62% for wheat common bunt. In order to further promote the inhibition activities of 29-Y2, the optimal culture condition was 11.1 g/L of glucose, 20 g/L of yeast extract powder, 3.8 g/L of soybean pepyone and 10 g/L of NaCl based on the response surface methodology; the liquid loading volume was 15 mL, of which the inoculant amount accounted for 2%, the pH was 6.8, the temperature was 30 °C and the rotation speed was 186 r/min for 26 h. When the fermentation broth obtained under these cultivation conditions was diluted 10,000 times, the inhibition rate of TFL teliospore germination could reach 80.32%. The fermentation broth control effect in pots improved from 57.77% to 84.17%. It was a promising endophytic bacterium for the prevention and control of wheat common bunt. Full article

Background: Visceral pain is the primary symptom of functional gastrointestinal disorders, yet its spinal molecular mechanisms remain poorly defined. Methods: Using a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced chronic inflammatory visceral pain model, the role of the spinal CXCL10/CXCR3/ERK signaling axis and the analgesic effect of docosahexaenoic acid (DHA) were investigated. Results: TNBS significantly upregulated CXCL10 and CXCR3 in spinal dorsal horn neurons and increased ERK phosphorylation. Intrathecal CXCL10-neutralizing antibody or CXCR3 antagonist NBI-74330 reduced visceral hypersensitivity and suppressed spinal ERK activation in TNBS mice. Exogenous CXCL10 induced CXCR3-dependent hyperalgesia and ERK phosphorylation in the spinal cord. Intrathecal DHA attenuated TNBS-induced visceral pain, downregulated spinal CXCL10/CXCR3 expression, and inhibited ERK signaling. In Neuro-2a cells, DHA also blocked LPS-induced activation of the same pathway. Conclusions: This study suggests that the analgesic effect of DHA may involve the inhibition of the spinal CXCL10/CXCR3/ERK signaling pathway. Full article

Obesity is a chronic, highly prevalent disease affecting nearly one-third of the global population and represents a major independent risk factor for heart failure (HF), particularly heart failure with preserved ejection fraction (HFpEF). Excess adiposity—especially visceral and epicardial adipose tissue (EAT)—acts as an active endocrine and immune organ, promoting chronic low-grade inflammation, oxidative stress, endothelial dysfunction, and adverse myocardial remodeling. Expanded EAT exerts both paracrine inflammatory effects and mechanical constraint on the myocardium, contributing to diastolic dysfunction, microvascular impairment, atrial arrhythmogenesis, and elevated filling pressures despite preserved systolic function. Evidence demonstrates a dose–response relationship between increasing body mass index and incident HF. Clinically, obesity-related HFpEF is characterized by concentric left ventricular hypertrophy, impaired relaxation, increased plasma volume, reduced exercise tolerance, and relatively low natriuretic peptide levels, complicating diagnosis. HF management includes traditional treatment with diuretics, renin-angiotensin system inhibitors, β-blockers, mineralocorticoid receptor antagonists, and angiotensin receptor-neprilysin inhibitors. These agents widely remain foundational as they primarily target hemodynamic and neurohormonal pathways in HF. In contrast, sodium–glucose cotransporter 2 inhibitors consistently reduce HF hospitalizations across the ejection fraction spectrum, while glucagon-like peptide-1 receptor agonists and dual incretin therapies (e.g., tirzepatide) promote substantial weight loss, improve symptoms, and demonstrate promising anti-remodeling effects in obesity-related HFpEF. Recognizing obesity-driven HF as a distinct cardiometabolic entity supports an integrated therapeutic strategy combining structured weight reduction with guideline-directed HF polypharmacotherapy to address both hemodynamic burden and upstream adiposity-related mechanisms. Full article

Breast cancer (BC), a multifactorial condition, remains one of the most common malignancies in women, in which the majority of BCs are hormone-sensitive and are activated by estrogens, especially 17β-estradiol (E2). Whereas aromatization of androgens to estrogens is achieved by the aromatase enzyme, the steroidogenic acute regulatory (StAR) protein, by mobilizing the transport of intra-mitochondrial cholesterol, plays an indispensable role in E2 biosynthesis. Accumulating evidence indicates that aromatase expression is aberrantly high and analogous in normal and malignant breast tissues, even though endocrine therapy, based on aromatase inhibitors (AIs), has been the mainstay of BC treatment in post-menopausal women. Despite the beneficial effects of AIs, their long-term usage has been associated with undesirable long-term side effects, including endocrine resistance, which is the leading cause of cancer death, warranting an improved therapy for mitigating this devastating disease. Along these lines, we reported that StAR is differentially expressed, along with E2 biosynthesis, in human and mouse cancerous and non-cancerous breast cells and tissues, in which we discovered that StAR is an acetylated protein, in addition to the identification of a number of lysine residues, undergoing acetylation and deacetylation, suggesting the importance of this newly uncovered StAR modification in E2 regulation in mammary tissue. One of the current therapeutic approaches for BC is targeting with histone deacetylase inhibitors (HDACIs), as these epigenetic enzymes control multiple cellular processes, including chromatin remodeling and genomic stability through the dynamic process of acetylation and deacetylation of core histones. Concomitantly, we have demonstrated that several HDACIs, including FDA-approved HDACIs, at therapeutically and clinically relevant doses, alter StAR acetylation patterns and suppress E2 accumulation in both hormone-sensitive human BC and mouse primary cultures of breast tumor epithelial cells. This review provides the molecular insights into breast pathogenesis and its therapeutics, and proposes that a combination therapy involving AI and HDACI, targeting aromatase and StAR, respectively, suppresses intra-tumoral E2 accumulation and limits antagonistic side effects, and these measures are beneficial for the prevention and/or management of hormone-sensitive BC. Full article

Atractylodes lancea (AL) has been shown to be a promising candidate for the treatment of cholangiocarcinoma (CCA). The study explored the potential of atractylodin (AT) and β-eudesmol (BE) to chemosensitize the effects of standard chemotherapeutics in CCA. The cytotoxicities of AT and BE on CL6, HuCCT1, and HuH28 when used in combination with 5-fluorouracil (5FU), gemcitabine (GEM), and cisplatin (Cis) were assessed by MTT assay. The modulatory effects of both compounds on mRNA expression of the reuptake and efflux transporters were determined by real-time PCR. The FIC (Fractional Inhibitory Concentration) indices indicated synergistic interactions (AT-5FU in all cell lines and BE-5FU in HuH28) and antagonistic interactions (BE-Cis in all cell lines and AT-Cis or AT-GEM in HuCCT1). The synergistic interactions observed with the AT-5FU and BE-5FU combinations were well correlated with the significant upregulation of the mRNA expression of the reuptake transporter genes hENT1 (2.64-fold) and hOCT3 (5.02-fold) and the significant downregulation of the mRNA expression of the efflux transporter gene ABCC2 (0.33-fold). AT and BE, when purified or present as significant components in AL, may benefit CCA treatment when used as adjunct therapy to standard chemotherapeutic drugs, particularly 5FU. The mechanism of synergistic activity may, at least in part, involve modulation of transporter gene expression and activity. Full article

Background/Objectives: Salidroside, a bioactive phenylethanol glycoside primarily derived from Rhodiola rosea, and its major in vivo metabolite tyrosol exhibit diverse pharmacological activities. However, their direct molecular targets remain poorly defined. Methods: In the present study, an integrated strategy combining transcriptomic profiling, Connectivity Map (CMap) analysis, and multi-level experimental validation was employed. Transcriptomic signatures derived from A549 cells treated with salidroside or tyrosol were queried against the CMap database. Molecular docking, surface plasmon resonance (SPR), and cellular thermal shift assays (CETSA) were performed to predict and validate binding interactions. Functional validation was performed in SH-SY5Y cells. The phosphorylation level of extracellular signal-regulated kinase (ERK), a downstream signaling event of dopamine D2 receptor (DRD2), was detected after salidroside and tyrosol treatment. DRD2 antagonist sulpiride pre-intervention and small interfering RNA (siRNA)-mediated DRD2 knockdown were conducted to verify the receptor dependence of the compounds’ effects. Results: CMap analysis revealed that the transcriptomic signatures of salidroside and tyrosol showed significant similarity to known DRD2 modulators. Molecular docking predicted potential binding interactions between the two compounds and DRD2, which was confirmed by SPR and CETSA to be direct physical binding. Functional studies showed that both compounds rapidly induced DRD2 downstream ERK phosphorylation in SH-SY5Y cells; this effect was abrogated by sulpiride or DRD2 knockdown, indicating DRD2-dependent signaling activation. Conclusions: These findings identify DRD2 as a direct molecular target of salidroside and tyrosol and provide mechanistic insight into their dopaminergic regulatory effects. This study highlights the utility of CMap-guided target discovery combined with rigorous experimental validation for elucidating the molecular mechanisms of natural products. Full article