Search Results (10,858)

Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system (CNS) characterized by inflammation, demyelination, axonal degeneration, and gliosis. Its pathophysiology involves a complex interplay of genetic susceptibility, environmental triggers, and immune dysregulation, ultimately leading to progressive neurodegeneration and functional decline. Although significant advances have been made in disease-modifying therapies (DMTs), many patients continue to experience disease progression and unmet therapeutic needs. Drug repurposing—the identification of new indications for existing drugs—has emerged as a promising strategy in MS research, offering a cost-effective and time-efficient alternative to traditional drug development. Several compounds originally developed for other diseases, including immunomodulatory, anti-inflammatory, and neuroprotective agents, are currently under investigation for their efficacy in MS. Repurposed agents, such as selective sphingosine-1-phosphate (S1P) receptor modulators, kinase inhibitors, and metabolic regulators, have demonstrated potential in promoting neuroprotection, modulating immune responses, and supporting remyelination in both preclinical and clinical settings. Simultaneously, artificial intelligence (AI) is transforming drug discovery and precision medicine in MS. Machine learning and deep learning models are being employed to analyze high-dimensional biomedical data, predict drug–target interactions, streamline drug repurposing workflows, and enhance therapeutic candidate selection. By integrating multiomics and neuroimaging data, AI tools facilitate the identification of novel targets and support patient stratification for individualized treatment. This review highlights recent advances in drug repurposing and discovery for MS, with a particular emphasis on the emerging role of AI in accelerating therapeutic innovation and optimizing treatment strategies. Full article

Globally, endometriosis affects almost 10% of reproductive-aged women, leading to chronic pain and discomfort. Endocrine-disrupting compounds (EDCs) seem to play a pivotal role as a causal factor. The current manuscript aims to explain potential molecular pathways, synthesize current evidence regarding EDCs as causative agents of endometriosis, and highlight implications in the general population and clinical work. A thorough review of experimental, epidemiologic, and mechanistic research studies was conducted to explain the association between EDCs and endometriosis. Among the primary EDCs under investigation are polychlorinated biphenyls, dioxins, phthalates, and bisphenol A (BPA). Despite methodological heterogeneity and some discrepancies, epidemiologic evidence supports a positive association between some increased levels of BPA, phthalates, and dioxins in urine or in blood, and endometriosis. Experiments support some effect of EDCs on endometrial cells and causing endometriosis. EDCs function as xenoestrogens, alter immune function, induce oxidative stress, and disrupt progesterone signaling. Epigenetic reprogramming may play a role in mediating EDC-induced endometriosis. Endocrine, immunological, and epigenetic pathways link EDCs and endometriosis. Prevention techniques require deeper comprehension of those factors. Causal linkages and possible treatment targets should be based on longitudinal studies and multi-omics techniques. Restriction of EDCs could be beneficial for endometriosis prevalence limitation. Full article

Biofilms are structured communities of microorganisms encased in a self-produced extracellular matrix, and they represent one of the most widespread forms of microbial life on Earth. Their presence poses serious challenges in both environmental and clinical settings. In natural and industrial systems, biofilms contribute to water contamination, pipeline corrosion, and biofouling. Clinically, biofilm-associated infections are responsible for approximately 80% of all microbial infections, including endocarditis, osteomyelitis, cystic fibrosis, and chronic sinusitis. A particularly critical concern is their colonization of medical devices, where biofilms can lead to chronic infections, implant failure, and increased mortality. Implantable devices, such as orthopedic implants, cardiac pacemakers, cochlear implants, urinary catheters, and hernia meshes, are highly susceptible to microbial attachment and biofilm development. These infections are often recalcitrant to conventional antibiotics and frequently necessitate surgical revision. In the United States, over 500,000 biofilm-related implant infections occur annually, with prosthetic joint infections alone projected to incur revision surgery costs exceeding USD 500 million per year—a figure expected to rise to USD 1.62 billion by 2030. To address these challenges, surface modification of medical devices has emerged as a promising strategy to prevent bacterial adhesion and biofilm formation. This review focuses on recent advances in chemical surface functionalization using non-antibiotic agents, such as enzymes, chelating agents, quorum sensing quenching factors, biosurfactants, oxidizing compounds and nanoparticles, designed to enhance antifouling and mature biofilm eradication properties. These approaches aim not only to prevent device-associated infections but also to reduce dependence on antibiotics and mitigate the development of antimicrobial resistance. Full article

In this study, the effects of water bath and ultrasonic bath systems on bioactive properties, phenolic components and fatty acid profiles of unroasted and roasted pumpkin seeds were investigated. It is thought that determining the bioactive components, phenolic constituents and fatty acid profiles of unroasted and roasted pumpkin seeds will lead to the establishment of usage norms according to their composition characteristics. Total phenolic quantities of the pumpkin seed extracts obtained by water bath extraction of the seeds were defined to be between 7.58 (control) and 11.55 (25 min) and 10.20 (control) and 17.18 mg GAE/100 g (50 min), respectively. Phenolic content increased by 50% after 50 min of ultrasonic extraction, indicating the efficiency of this method. Also, total flavonoid amounts increased about 55% after 25 min of ultrasonic extraction, indicating the efficiency of this method. It was observed that the catechin contents of unroasted pumpkin seeds obtained in water and ultrasonic baths decreased significantly at the 50th minute of extraction compared to the control. The antioxidant activity values (DPPH) of roasted pumpkin seeds treated in water- and ultrasonic bath systems increased by approximately 10% compared to the control at 50 min of sonication in both systems, respectively. Also, the 3,4-dihydroxybenzoic acid amounts of the extracts obtained by both extraction systems of roasted pumpkin seeds were determined between 9.85 (50 min) and 17.22 mg/100 g (control) and 11.17 (25 min) and 13.74 mg/100 g (50 min), respectively. The linoleic acid amounts of unroasted pumpkin seed oils extracted in water- and ultrasonic baths varied between 52.34 (50 min) and 53.33% (control) to 52.90 (50 min) and 53.04% (control), respectively. The linoleic acid values of the roasted pumpkin seed oils were established to be between 52.30 (50 min) and 52.84 (25 min) and 52.32 (50 min) and 53.46% (25 min), respectively. In general, the phenolic compound amounts of roasted pumpkin seeds were higher than those of unroasted ones. The fatty acid amounts of pumpkin seed oils extracted with an ultrasonic bath were generally slightly higher than those extracted with a water bath. In future studies, changes in the phytochemical and bioactive properties of pumpkin seed oils obtained by applying different roasting techniques and extraction methods will be investigated. Full article

Foodborne illness caused by bacterial pathogens is a global health concern and results in millions of infections annually. Therefore, food products typically undergo several processing stages, including sanitation steps, before being distributed in an attempt to remove pathogens. However, many sanitation methods have compounding effects on the color, texture, flavor, and nutritional quality of the product or do not effectively reduce the pathogens that food can be exposed to. Some bacterial pathogens particularly possess traits and tactics that make them even more difficult to mitigate such as biofilm formation. Non-thermal plasma sanitation techniques, including plasma-treated water (PTW), have proven to be promising methods that significantly reduce pathogenic bacteria that food is exposed to. Published work reveals that PTW can effectively mitigate both gram-positive and gram-negative bacterial biofilms. This study presents a novel analysis of the differences in antimicrobial effects of PTW treatment between biofilm-forming gram-positive bacteria, commonly associated with foodborne illness, that are sporulating (Bacillus cereus) and non-sporulating (Listeria monocytogenes). After treatment with PTW, the results suggest the following hypotheses: (1) that the non-sporulating species experiences less membrane damage but a greater reduction in metabolic activity, leading to a possible viable but non-culturable (VBNC) state, and (2) that the sporulating species undergoes spore formation, which may subsequently convert into vegetative cells over time. PTW treatment on gram-positive bacterial biofilms that persist in food processing environments proves to be effective in reducing the proliferating abilities of the bacteria. However, the variance in PTW’s effects on metabolic activity and cell vitality between sporulating and non-sporulating species suggest that other survival tactics might be induced. This analysis further informs the application of PTW in food processing as an effective sanitation method. Full article

Morus alba L. (MA) is a member of the Moraceae family, known as “white mulberry”. Due to the high levels of bioactive compounds, mulberry plants can be considered a good source of nutrients and antioxidant compounds. Our study aims to analyze the effect of MA extract leaves on erythrocytes, focusing on its action on metabolism and membrane integrity. The choice of erythrocytes as a study model is based on their metabolic simplicity and their easy availability. Cell viability, following exposure of the cells to the extract, was evaluated by hemolysis, methemoglobin, caspase 3 activity and flow cytofluorimetric analysis; in addition, the effect of the pretreatment with the MA was detected after incubation of erythrocytes with different stressors. The impact on cell metabolism was evaluated by measuring anion flux kinetics, ATP levels and phosphatase activity. The results obtained show a peculiar (double) effect of the extract, which, on the one hand, probably by exploiting its component with antioxidant properties, protects the cell membrane by accumulating on the bilayer. On the other hand, the alteration of anion exchange could lead to the triggering of apoptosis and consequent cell death. The hypotheses, although excluded by our data, all point toward a beneficial and protective action of the extract on the health and vitality of RBCs. Full article

Direct copper-plated ceramic (DPC) substrates have emerged as a favored solution for power device packaging due to their unique technical advantages. AuSn, characterized by its high hermeticity and environmental adaptability, represents the optimal sealing technology for DPC substrates. Through the application of vacuum sintering techniques and adjustment of peak temperatures (325 °C, 340 °C, and 355 °C), the morphology and composition of interfacial compounds were systematically investigated, along with an analysis of their formation mechanisms. A gradient aging experiment was designed (125 °C/150 °C/175 °C × oxygen/argon dual atmosphere × 600 h) to elucidate the synergistic effects of environmental temperature and atmosphere on the growth of intermetallic compounds (IMCs). The results indicate that the primary reaction in the sealing weld seam involves Ni interacting with Au-Sn to form (Ni, Au)₃Sn₂ and Au₅Sn. However, upon completion of the sealing process, this reaction remains incomplete, leading to a coexistence state of (Ni, Au)₃Sn₂, Au₅Sn, and AuSn. Additionally, Ni diffuses into the weld seam center via dendritic fracture and locally forms secondary phases such as δ(Ni) and ζ’(Ni). These findings suggest that the weld seam interface exhibits a complex, irregular, and asymmetric microstructure comprising multiple coexisting compounds. It was determined that Tpeak = 325 °C to 340 °C represents the ideal welding temperature range, where the weld seam morphology, width, and Ni diffusion degree achieve optimal states, ensuring excellent device hermeticity. Aging studies further demonstrate that IMC growth remains within controllable limits. These findings address critical gaps in the understanding of the microstructural evolution and interface characteristics of asymmetric welded joints formed by multi-material systems. Full article

Background: Metastatic melanoma is a highly aggressive malignancy with poor prognoses and frequent resistance to conventional chemotherapy. Approximately 40% of melanoma cases carry the BRAF^V600E mutation, for which vemurafenib, a selective BRAF^V600E inhibitor, is approved. Despite initial clinical benefits, vemurafenib often leads to drug resistance and relapse, highlighting the need for improved therapeutic strategies. Objectives, methods: In this study, we designed, synthesized, and characterized five novel vemurafenib analogs—RF-86A, RF-87A, RF-94A, RF-94B, and RF-96B—with the aim of enhancing anti-proliferative and anti-metastatic effects against human melanoma cells. Results: All compounds induced apoptosis in BRAF^V600E-mutated A375 cells, with RF-86A displaying the lowest IC₅₀ value among the series, comparable to that of vemurafenib. Moreover, RF-86A exhibited the highest selectivity index, as determined using HEK293T cells as a non-tumorigenic control. Additionally, migration assays and gelatin zymography demonstrated that the analogs, unlike vemurafenib, significantly inhibited matrix metalloproteinases MMP-2 and MMP-9, key enzymes involved in tumor invasion and metastasis. Conclusions: These findings suggest that structural modifications to the vemurafenib scaffold may improve therapeutic efficacy and offer a promising strategy to overcome acquired resistance. Full article

Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive liver disorder associated with metabolic risk factors such as obesity, type 2 diabetes, and cardiovascular disease. If left untreated, the accumulation of excess hepatic fat can lead to inflammation, fibrosis, cirrhosis, hepatocellular carcinoma, and ultimately liver failure. Capsaicin (CAP), the primary pungent compound in chili peppers, has previously been shown to prevent weight gain in high-fat diet (HFD)-induced obesity models. In this study, we investigated the potential of dietary CAP to prevent HFD-induced MASLD. Methods: C57BL/6 mice were fed an HFD (60% kcal from fat) with or without 0.01% CAP supplementation for 26 weeks. We evaluated CAP’s effects on hepatic fat accumulation, inflammation, and mitochondrial function to determine its role in preventing MASLD. Results: CAP acts as a potent and selective agonist of the transient receptor potential vanilloid 1 (TRPV1) channel. We confirmed TRPV1 expression in the liver and demonstrated that CAP activates hepatic TRPV1, thereby preventing steatosis, improving insulin sensitivity, reducing inflammation, and enhancing fatty acid oxidation. These beneficial effects were observed in wild-type but not in TRPV1 knockout mice. Mechanistically, CAP-induced TRPV1 activation promotes calcium influx and activates AMPK, which leads to SIRT1-dependent upregulation of PPARα and PGC-1α, enhancing mitochondrial biogenesis and lipid metabolism. Conclusions: Our findings suggest that dietary CAP prevents MASLD through TRPV1 activation. TRPV1 signaling represents a promising therapeutic target for the prevention and management of MASLD in individuals with metabolic disorders. Full article

The formation and evolution of haze layers in planetary atmospheres play a critical role in shaping their chemical composition, radiative balance, and optical properties. In the outer solar system, the atmospheres of Titan and the giant planets exhibit a wide range of compositional and seasonal variability, creating environments favorable for the production of complex organic molecules under low-temperature conditions. Among them, Uranus—the smallest of the ice giants—has, since Voyager 2, emerged as a compelling target for future exploration due to unanswered questions regarding the composition and structure of its atmosphere, as well as its ring system and diverse icy moon population (which includes four possible ocean worlds). Titan, as the only moon to harbor a dense atmosphere, presents some of the most complex and unique organics found in the solar system. Central to the production of these organics are chemical processes driven by low-energy photons and electrons (<50 eV), which initiate reaction pathways leading to the formation of organic species and gas phase precursors to high-molecular-weight compounds, including aerosols. These aerosols, in turn, remain susceptible to further processing by low-energy UV radiation as they are transported from the upper atmosphere to the lower stratosphere and troposphere where condensation occurs. In this review, I aim to summarize the current understanding of low-energy (<50 eV) photon- and electron-induced chemistry, drawing on decades of insights from studies of Titan, with the objective of evaluating the relevance and extent of these processes on Uranus in anticipation of future observational and in situ exploration. Full article

Recently, essential rose oils and rose products have gained increasing importance in both the cosmetic and food industries, as well as in the composition of medicinal products. We investigated the in vitro antiviral activity of essential oil and floral water from Rosa damascena Mill against herpes simplex virus type 1 (HSV-1) infection in rabbit retinal cells (RRCs). The composition of the main chemical components in the rose essential oil was determined by means of gas chromatographic analysis. The effect on the viral replication cycle was determined using the cytopathic effect (CPE) inhibition assay. The virucidal activity, the effect on the adsorption stage of the virus to the host cell, and the protective effect on healthy cells were evaluated using the endpoint dilution method. The effects were determined as deviation in the viral titer, Δlg, for the treated cells from the one for the untreated viral control. The identified main active components of rose oil are geraniol (28.73%), citronellol (21.50%), nonadecane (13.13%), nerol (5.51%), heneicosane (4.87%), nonadecene (3.93), heptadecane (2.29), farnesol (2.11%), tricosane (1.29%), eicosane (1.01%), and eugenol (0.85%). The results demonstrated that both rose products do not have a significant effect on the virus replication but directly affect the viral particles and reduce the viral titer by Δlg = 3.25 for floral water and by Δlg = 3.0 for essential oil. Significant inhibition of the viral adsorption stage was also observed, leading to a decrease in the viral titers by Δlg = 2.25 for floral water and by Δlg = 2.0 for essential oil. When pretreating healthy cells with rose products, both samples significantly protected them from subsequent infection with HSV-1. This protective effect was more pronounced for the oil (Δlg = 2.5) compared to the one for the floral water (Δlg = 2.0). We used the in silico molecular docking method to gain insight into the mechanism of hindrance of viral adsorption by the main rose oil compounds (geraniol, citronellol, nerol). These components targeted the HSV-1 gD interaction surface with nectin-1 and HVEM (Herpesvirus Entry Mediator) host cell receptors, at N-, C-ends, and N-end, respectively. These findings could provide a structural framework for further development of anti-HSV-1 therapeutics. Full article

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterised by hepatic steatosis in the absence of significant alcohol consumption or other specific causes of liver injury. It has become one of the leading causes of liver dysfunction worldwide. However, the precise pathophysiological mechanisms underlying NAFLD remain unclear, and effective therapeutic strategies are still under investigation. Autophagy, a vital intracellular process in eukaryotic cells, enables the degradation and recycling of cytoplasmic components through a membrane trafficking pathway. Recent studies have demonstrated a strong association between impaired or deficient autophagy and the development and progression of NAFLD. Restoring autophagic function may represent a key approach to mitigating hepatocellular injury. Nevertheless, due to the complexity of autophagy regulation and its context-dependent effects on cellular function, therapeutic strategies targeting autophagy in NAFLD remain limited. This review aims to summarise the relationship between autophagy and NAFLD, focusing on autophagy as a central mechanism. We discuss the latest research advances regarding interventions such as diet and exercise, pharmacological therapies (including modern pharmacological therapy and plant-derived compounds), and other approaches (such as hormones, nanoparticles, gut microbiota, and vitamins). Furthermore, we briefly highlight potential autophagy-related molecular targets that may offer novel therapeutic insights for NAFLD management. Full article

The Maillard reaction refers to the reaction between carbonyl compounds with reducing properties and amino-containing compounds that undergo condensation and polymerization to produce melanoidins. In flour product processing, the Maillard reaction is a critical chemical reaction influencing color, flavor, nutrition, and safety. A moderate Maillard reaction contributes to desirable color and flavor profiles in flour products, whereas an excessive reaction leads to amino acid loss and the formation of harmful substances, posing potential health risks. This review summarizes the substrate sources, reaction stages, influencing factors, impact on quality, and mitigation strategies of harmful products, aiming to provide a reference for regulating the Maillard reaction in flour product processing. Currently, most existing mitigation strategies focus on inhibiting harmful products, while research on the synergistic optimization of color and flavor remains insufficient. Future research should focus on elucidating the molecular mechanisms of reaction pathways, understanding multi-factor synergistic effects, and developing composite regulation technologies to balance the sensory quality and safety of flour products. Full article

Background: Antibacterial resistance (ABR) poses a major challenge to global health, with methicillin-resistant Staphylococcus aureus (MRSA) being one of the prominent multidrug-resistant strains. MRSA has developed resistance through the expression of Penicillin-Binding Protein 2a (PBP2a), a key transpeptidase enzyme involved in bacterial cell wall biosynthesis. Objectives: The objective was to design and characterize a novel small-molecule inhibitor targeting PBP2a as a strategy to combat MRSA. Methods: We synthesized a new indole triazole conjugate (ITC) using eco-friendly and click chemistry approaches. In vitro antibacterial tests were performed against a panel of strains to evaluate the ITC antibacterial potential. Further, a series of in silico evaluations like molecular docking, MD simulations, free energy landscape (FEL), and principal component analysis (PCA) using the crystal structure of PBP2a (PDB ID: 4CJN), in order to predict the mechanism of action, binding mode, structural stability, and energetic profile of the 4CJN-ITC complex. Results: The compound ITC exhibited noteworthy antibacterial activity, which effectively inhibited the selected strains. Binding score and energy calculations demonstrated high affinity of ITC for the allosteric site of PBP2a and significant interactions responsible for complex stability during MD simulations. Further, FEL and PCA provided insights into the conformational behavior of ITC. These results gave the structural clues for the inhibitory action of ITC on the PBP2a. Conclusions: The integrated in vitro and in silico studies corroborate the potential of ITC as a promising developmental lead targeting PBP2a in MRSA. This study demonstrates the potential usage of rational drug design approaches in addressing therapeutic needs related to ABR. Full article

Glycyrrhiza uralensis (G. uralensis), a leguminous plant, is an important medicinal and economic plant in saline–alkaline soils of arid regions in China. Its main bioactive components include liquiritin, glycyrrhizic acid, and flavonoids, which play significant roles in maintaining human health and preventing and adjuvantly treating related diseases. However, the cultivation of G. uralensis is easily restricted by adverse soil conditions in these regions, characterized by high salinity, high alkalinity, and nutrient deficiency. This study investigated the impacts of four multistrain microbial inoculants (Pa, Pb, Pc, Pd) on the growth performance and bioactive compound accumulation of G. uralensis in moderately saline–sodic soil. The aim was to screen the most beneficial inoculant from these strains, which were isolated from the rhizosphere of plants in moderately saline–alkaline soils of the Hexi Corridor and possess native advantages with excellent adaptability to arid environments. The results showed that inoculant Pc, comprising Pseudomonas silesiensis, Arthrobacter sp. GCG3, and Rhizobium sp. DG1, exhibited superior performance: it induced a 0.86-unit reduction in lateral root number relative to the control, while promoting significant increases in single-plant dry weight (101.70%), single-plant liquiritin (177.93%), single-plant glycyrrhizic acid (106.10%), and single-plant total flavonoids (107.64%). Application of the composite microbial inoculant Pc induced no significant changes in the pH and soluble salt content of G. uralensis rhizospheric soils. However, it promoted root utilization of soil organic matter and nitrate, while significantly increasing the contents of available potassium and available phosphorus in the rhizosphere. High-throughput sequencing revealed that Pc reorganized the rhizospheric microbial communities of G. uralensis, inducing pronounced shifts in the relative abundances of rhizospheric bacteria and fungi, leading to significant enrichment of target bacterial genera (Arthrobacter, Pseudomonas, Rhizobium), concomitant suppression of pathogenic fungi, and proliferation of beneficial fungi (Mortierella, Cladosporium). Correlation analyses showed that these microbial shifts were linked to improved plant nutrition and secondary metabolite biosynthesis. This study highlights Pc as a sustainable strategy to enhance G. uralensis yield and medicinal quality in saline–alkali ecosystems by mediating microbe–plant–nutrient interactions. Full article