Search Results (7,696)

Mastitis, an inflammatory disease caused by the invasion of various pathogenic microorganisms into mammary gland tissue, is a core health issue plaguing the global dairy industry. The consequences of this disease are manifold. In addition to directly compromising the health and welfare of dairy cows, it also precipitates a substantial decline in lactation function, a precipitous drop in raw milk production, and alterations in milk composition (e.g., increased somatic cell counts and imbalanced ratios of milk protein to fat). These changes result in a marked degradation of milk quality and safety, and in turn, engender significant economic losses for the livestock industry. Therefore, the establishment and implementation of a comprehensive prevention and control system is a key strategy to effectively curb the occurrence of mastitis, reduce its incidence rate, and minimise economic losses. This review systematically explores the complex etiological factors and pathogenic mechanisms of mastitis in dairy cows, and summarises various diagnostic methods, including milk apparent indicators monitoring, pathogen detection, physiological parameter monitoring, omics technologies, and emerging technologies. Furthermore, it undertakes an analysis of treatment protocols for mastitis in dairy cows, with a particular emphasis on the significance of rational antibiotic use and alternative therapies. Moreover, it delineates preventive measures encompassing both environmental and hygiene management, and dairy cow health management. The objective of this paper is to provide a comprehensive and scientific theoretical basis and practical guidance for dairy farming practices. This will help to improve the health of dairy cows, ensure a stable supply of high-quality dairy products, and promote the sustainable and healthy development of the dairy farming industry. Full article

Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease affecting approximately 1 million people in the United States. Despite extensive research into the mechanisms of disease development, many aspects of the biological changes during MS progression and the varying symptoms among patients remain unclear. In the era of high-throughput sequencing, transcriptome databases are flooded with data. However, bulk RNA sequencing (RNA-seq) data are typically used only for differential gene expression analysis. Alternative splicing, a key process that alters the transcriptome, can also be identified from bulk data. Here, we accessed 11 studies with bulk RNA-seq data of postmortem MS patients’ brain samples via NCBI’s Gene Expression Omnibus (GEO). We extracted additional information from these data by identifying exclusively alternatively spliced genes via replicate multivariate analysis of transcript splicing (rMATS) analysis. Our analyses revealed that changes in RNA splicing mediate distinct biological signals compared to those driven by differential gene expression. Gene ontology and protein do-main analyses of genes exclusively regulated by alternative splicing revealed distinct molecular differences between progressive and relapsing–remitting MS as well as among lesions from different brain regions and between white and gray matter. These findings highlight the critical role of alternative splicing and its associated pathways in MS disease development and progression. Full article

Gelatin from bovine hide, especially yak hide, is valued in the food and pharmaceutical industries; however, as the most common domestic cattle in China, gelatin made from yellow cattle hide remains unexplored. Thus, the physicochemical properties, nutritional components, and flavor characteristics of gelatin produced from yellow cattle hides and yak hides, both before and after hair removal, were analyzed. It was found that yellow cattle hide gelatin (YCHG) not only had a higher protein content (68.45–71.51%) than yak hide gelatin (YHG) (66.81–67.56%) but also had a higher Fe content (86.75 ± 1.650 mg/kg). Additionally, 17 amino acids were detected in the four bovine hide gelatin samples; among them, dehaired yellow cattle hide gelatin (DYCHG) was richer in sweet-tasting amino acids than the others. Notably, non-dehaired yellow cattle hide gelatin (NDYCHG) featured 4-methyl-3-penten-2-one (with a honey aroma), whereas non-dehaired yak hide gelatin (NDYHG) featured β-pinene, 1-nonanal, acetic acid-D, (E)-2-pentenal, and allyl sulfide. Therefore, yellow cattle hide gelatin (YCHG) exhibits prominent nutritional and flavor properties, suggesting its potential as an alternative raw material for food industry applications. Full article

Sulforaphane (SFN) is a bioactive compound belonging to the isothiocyanate family, known for its neuroprotective properties. While transcriptomic studies have highlighted SFN’s role in regulating gene expression, its impact on alternative splicing (AS), a key regulatory mechanism in neuronal metabolism, remains underexplored. In this study, we investigated whether SFN pre-treatment influences mRNA splicing patterns in an in vitro neuronal model using retinoic acid (RA)-differentiated SH-SY5Y cells. Using a dedicated RNA-seq-based splicing analysis pipeline, we identified 194 differential alternative splicing events (DASEs) associated with SFN treatment. Gene Ontology enrichment revealed significant over-representation of DNA repair processes. To better understand the functional implications, we integrated in silico predictions of premature stop codons, DASE/miRNA hybridizations, and DASE/RNA-binding protein (RBP) motif occurrences. Our findings suggest that SFN may modulate splicing of key DNA repair genes, contributing to protecting neurons against DNA damage. These preliminary results underscore a novel layer of SFN’s molecular effects and propose it as a valuable adjuvant in physiological conditions to enhance cellular health. Further studies are warranted to dissect the mechanistic underpinnings of SFN-mediated AS and its relevance in DNA-damage-related disorders. Full article

Worldwide, 13.3% of food was wasted in 2020. Ethylene biosynthesis, responsible for fruit ripening, regulates key processes in plant growth and aging. Aptamers are DNA or RNA molecules with the capacity to bind with high affinity and specificity to proteins due to their three-dimensional structure. Therefore, conventional aptamer selection methods are often costly, inefficient, and time-consuming. In this context, in silico molecular docking offers an efficient alternative, enabling the evaluation of binding potential prior to experimental assays. This research identified aptamers with high predicted affinity for the 1-aminocyclopropane-1-carboxylate synthase (ACC synthase) and 1-aminocyclopropane-1-carboxylate oxidase (ACC oxidase) enzymes, essential in ethylene biosynthesis. Using ZDOCK for preliminary screening and HDOCK for refined analysis, aptamer-enzyme interactions were modeled. Aptamers AB451 and ABR6P.1 showed promising binding to ACC synthase, while RO33828 and O0O6O1 were optimal for ACC oxidase. These results represent a computational foundation for the development of aptamer-based inhibitors to potentially delay ripening and reduce postharvest losses. Experimental validation will be required to confirm their inhibitory function. Full article

Precision fermentation, a highly controlled process of microbial fermentation, is emerging as a transformative tool to produce cosmetic ingredients. This technology leverages engineered micro-organisms to produce high-value compounds with applications in skincare, hair care, and other cosmetic formulations. Unlike traditional methods of ingredient sourcing, which often rely on extraction from plants or animals, precision fermentation offers a sustainable and scalable alternative, minimizing environmental impact and enhancing the consistency of ingredient supply. This paper explores the potential of precision fermentation to revolutionize the cosmetic industry by enabling the production of complex molecules, such as peptides, proteins, and other bioactive compounds, which are essential for cosmetic efficacy. Using synthetic biology, micro-organisms such as yeast, bacteria, and fungi are programmed to biosynthesize specific cosmetic ingredients, which can include antioxidants, emulsifiers, and moisturizers. This technique not only ensures high purity and ingredients safety but also allows for the production of novel compounds that may be difficult or impossible to obtain through traditional methods. Furthermore, precision fermentation can be employed to address growing consumer demand for cruelty-free, vegan, and eco-friendly products, as it eliminates the need for animal-derived ingredients and reduces resource consumption associated with conventional farming and extraction processes. This review highlights key advancements in the field, discussing the challenges faced by industry, such as regulatory framework, and presents potential solutions for overcoming these obstacles. The paper concludes by examining the prospects of precision fermentation in cosmetics, forecasting how continued innovation in this area could further drive sustainability, ethical production practices, and the development of highly functional, scientifically advanced cosmetic products. Full article

Phosphorus (P) stock scarcity is driving the need to develop alternatives to mineral fertilizers. The growing production of insects for high-protein feed results in significant amounts of residues (frass), which can be used as fertilizers. However, its efficiency as such a basic indicator for promoting the recycling of these residues has been rarely assessed. This work aimed to evaluate the efficiency of frass as a P fertilizer. To this end a study was conducted involving P fractionation of frass from two different species (TM: Tenebrio molitor and BSF: black soldier fly or Hermetia illucens) together with vermicompost and a 48-day pot experiment with lettuce (Lactuca sativa). In both frasses, water-soluble P and organic P accounted for more than 30% and 50% of total P, respectively. These P fractions explained the short- and long-term effects of frasses as P fertilizer, which showed a higher P use efficiency than mineral phosphate and vermicompost, with mineral fertilizer replacement values (MFRVs) of 150 and 180% for BSF and TM frass, respectively. Additionally, frass increased P bioavailability in soils more than superphosphate and boosted C and P cycling, thereby enhancing the soil P availability to plants. Therefore, frasses can be effective alternatives to mineral P fertilizers which also contribute to the enhancement of soil health indicators. Full article

Chronic, low-grade inflammation is a key contributor to the development of numerous non-communicable diseases (NCDs), including cardiovascular, metabolic, and neurodegenerative disorders. Conventional anti-inflammatory drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, often present safety concerns with prolonged use, highlighting the need for safer, multi-targeted therapeutic options. Iridoids, a class of monoterpenoid compounds abundant in several medicinal plants, have emerged as promising bioactive agents with diverse pharmacological properties. They exert anti-inflammatory and metabolic regulatory effects by modulating key signaling pathways, including nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), Janus kinase/signal transducer and activator of transcription (JAK/STAT), adenosine monophosphate-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor (PPAR) pathways. This review provides a comprehensive summary of the major iridoid metabolites derived from ten Bulgarian medicinal plant species, along with mechanistic insights from in vitro and in vivo studies. Documented biological activities include anti-inflammatory, antioxidant, immunomodulatory, antifibrotic, organoprotective, antibacterial, antiviral, analgesic, and metabolic effects. By exploring their phytochemical profiles and pharmacodynamics, we underscore the therapeutic potential of iridoid-rich Bulgarian flora in managing inflammation-related and metabolic diseases. These findings support the relevance of iridoids as complementary or alternative agents to conventional therapies and highlight the need for further translational and clinical research. Full article

Walnut anthracnose (Colletotrichum gloeosporioides and C. siamense) and brown spot (Alternaria alternata) cause severe yield losses globally. Conventional fungicides face the challenges of pathogen resistance and environmental toxicity. This study evaluates 4-propylphenol, a plant-derived phenolic compound, as an eco-friendly alternative against key fungal pathogens of walnut. In vitro assays determined EC₅₀ values against target pathogens (29.11–31.89 mg·L⁻¹) via mycelial growth inhibition and conidial germination suppression (EC₅₀ = 55.04–71.85 mg·L⁻¹). Mechanistic analyses confirmed membrane disruption through propidium iodide staining (9.5-to-14.0-fold fluorescence intensity increase), DNA leakage (77.82–85.15% at 250 mg·L⁻¹), and protein efflux (58.10–66.49%). In field trials, we implemented a phenology-driven strategy: 100 mg·L⁻¹ ground/canopy spray at flowering to reduce primary inoculum, followed by 400 mg·L⁻¹ canopy application at fruiting. This protocol achieved 86.67% control efficacy against disease complexes with negligible phytotoxicity (SPAD variation < 5%). 4-propylphenol provides a sustainable solution through membrane-targeting action, effectively overcoming fungicide resistance in woody crops. Full article

Intron retention (IR) is one of the cellular mechanisms to perform alternative splicing and thus control gene expression in several mammalian cellular pathways. IR in PI-PLC γ1 mRNA was observed in some primary synoviocyte samples from osteoarthritis (OA) patients, likely due to inter-patient variability. The aim of the present manuscript was to explore the PI-PLC γ1 IR molecular mechanism as a consequence of nutraceutical treatment of synoviocytes and the molecular basis of individual response. To evaluate the gene expression modulation of molecules involved in mRNA splicing, an RNA-seq analysis was performed, and the transcription modulation of six differentially expressed genes was validated by RT-PCR. Moreover, through a silencing experiment, the relationship between PI-PLC γ1 IR and the six modulated genes was explored. Finally, two of them, the RNA-binding proteins CELF1 and PTBP3, whose mRNA levels were elevated in samples exhibiting IR, were analyzed in detail. CELF1 and PTBP3 were overexpressed in synoviocytes lacking PI-PLC γ1 IR, and we found that CELF1 was responsible for IR, whereas PTBP3 did not seem to be involved. In conclusion, in our experimental model, the role of CELF1 protein in PI-PLC γ1 IR was explored, opening new scenarios for understanding the molecular mechanisms underlying the IR phenomenon present in several kinds of diseases. Full article

Background: Despite advances in prostate cancer treatment, castration-resistant prostate cancer (CRPC) remains clinically challenging due to inherent therapy resistance and a lack of durable alternatives. Although traditional Chinese medicine offers untapped potential, the therapeutic role of paeoniflorin (Pae), a bioactive compound derived from Paeonia lactiflora, in prostate cancer has yet to be investigated. Methods: Using an integrative approach (network pharmacology, molecular docking, and experimental validation), we identified Pae key targets, constructed protein–protein interaction networks, and performed GO/KEGG pathway analyses. A Pae-target-based prognostic model was developed and validated. In vitro and in vivo assays assessed Pae effects on proliferation, migration, invasion, apoptosis, and tumor growth. Results: Pae exhibited potent anti-CRPC activity, inhibiting cell proliferation by 60% and impairing cell migration by 65% compared to controls. Mechanistically, Pae downregulated SRC proto-oncogene, non-receptor tyrosine kinase (SRC) mRNA expression by 68%. The Pae-target-based prognostic model stratified patients into high- and low-risk groups with distinct survival outcomes. Organoid and xenograft studies confirmed Pae-mediated tumor growth inhibition and SRC downregulation. Conclusions: Pae overcomes CRPC resistance by targeting SRC-mediated pathways, presenting a promising therapeutic strategy. Our findings underscore the utility of network pharmacology-guided drug discovery and advocate for further clinical exploration of Pae in precision oncology. Full article

Currently, there is an increasing demand for plant-based and low-fat snacks. Non-conventional starch and grains are alternative ingredients. Environmentally friendly processing, such as liquid nitrogen and microwaves, can be used to obtain modified starch, as well as hot air frying to cook snacks. The aim of this work was to evaluate the impact of eco-friendly physical modification of starch from Oxalis tuberosa in a low-fat snack processed by hot air frying. First, native starch (NS) was treated with liquid nitrogen (LNS) and liquid nitrogen/microwaves (LNMS), and the amylose/amylopectin content and functional properties were determined. The snacks were formulated with NS or modified starches, amaranth flour, quinoa flour, corn, onion powder, salt, and water; the ingredients were mixed and placed in an electric pasta maker and cooked by hot air frying. The hardness, hedonic test, colorimetric parameters, acrylamide, proximal composition, and fatty acid profile were analyzed. All starches showed similar values of amylose and amylopectin content. LNMS starch had the lowest water solubility index as compared to NS and LNS. The snacks with the starch modified with liquid nitrogen showed the highest values of hardness as well as the highest score for the texture from a hedonic test. The snacks with modified starches showed a lower browning index than the snack formulated with NS. Acrylamide was not detected in any snacks. The lipid value of the snacks with modified starch was 1.9–2.70 g/100 g of sample, providing ω-9, ω-6, and ω-3 fatty acids. All snacks contained 7.7 g of protein/100 g of sample. These low-fat and plant-based snacks are a healthy option made by environmentally friendly technologies. Full article

Poultry is a vital component of global meat production, with particular importance in Nigeria and Africa, as it promotes food security, economic growth, and rural livelihoods. Indigenous chickens, although less productive, are well adapted to local environments and provide significant socio-economic and nutritional benefits. The rising demand for animal protein and concerns over antimicrobial resistance (AMR) necessitate the development of sustainable alternatives to antibiotics in poultry production. Probiotics have emerged as effective feed additives that enhance gut health, immunity, nutrient absorption, and overall productivity. While extensively studied in commercial poultry, research on probiotics in Nigerian Indigenous Ecotype Chickens (NIECs) remains limited. Key challenges in indigenous poultry systems include low productivity, disease vulnerability, limited veterinary access, and environmental pressures. Addressing these requires improved management practices, infrastructure, veterinary support, and enabling policies. Multi-strain probiotics, particularly those containing Lactobacillus, Bifidobacterium, and Bacillus species, demonstrate promise in enhancing productivity, improving product quality, promoting environmental sustainability, and ensuring food safety. Focused research on local probiotic strains, field trials, farmer education, and policy support is crucial for harnessing the full benefits of probiotics and transforming indigenous poultry farming into a resilient and sustainable sector. Full article

Brewer’s spent grain (BSG), a byproduct of the brewing process, offers a sustainable alternative applicable to human nutrition. The nutritional composition, health advantages, and value-added uses of BSG in diverse food items, including snacks, bread, cookies, and pasta, are examined in this review. Furthermore, consumer acceptance and organoleptic attributes, including texture, taste and appearance, are discussed. BSG is composed of 60% carbohydrates (of which 50% dietary fiber), 10% lipids, and 30% proteins. BSG is also high in minerals such as calcium and phosphorous and bioactive polyphenols such as catechin, p-coumaric, and ferulic acid. BSG holds significant opportunities to be utilized in enhanced food production, biofuel generation, and other industrial applications. The reported therapeutic effects of BSG include anticarcinogenic, antiatherogenic and oxidative stress reduction. Based on sensory evaluations, the maximum amount of BSG that can be added to food products to maintain consumer acceptance is 15%. There is a need to convince manufacturers and consumers of the potential of incorporating BSG into food products, the health benefits of this, and the sustainability advantages of the use of BSG. The integration of BSG into food systems will contribute to food waste minimization and the promotion of the circular economy. Full article

Enhancing protein–protein interactions is a key therapeutic strategy to ensure effective protein function in terms of pharmacokinetics and pharmacodynamics and can be accomplished with methods like directed evolution or rationale design. Previously, two papers suggested the possible enhancement of protein–protein binding affinity via destabilizing mutations. This paper reviews the results of the previous literature and adds new data to show the generality of the strategy that destabilizing the unbound protein without significantly changing the free energy of the complex can enhance protein–protein interactions for therapeutic benefit. The first example presented is that of a variant of human growth hormone (hGHv) containing 15 mutations that improve the binding to the hGH binding protein (hGHbp) by 400-fold while retaining full biological activity. The second example is that of the YTE mutations (M252Y/S354T/T256E) in the Fc region of a monoclonal antibody (mAb). The YTE mutations improve the binding of the mAb to FcRn at pH 6.0 10-fold, resulting in elongated serum half-life of the mAb. In both cases, (i) chemical titration or differential scanning calorimetry (DSC) showed the mutations destabilize the unbound mutant proteins, (ii) isothermal titration calorimetry (ITC) showed extremely favorable enthalpy (ΔH) and unfavorable entropy (ΔS) upon binding to their respective target molecule compared with the wildtype, and (iii) hydrogen/deuterium exchange–mass spectrometry (HDX-MS) revealed that these mutations increase the free energy of unbound mutant protein without significantly affecting the free energy of the bound state, resulting in an enhancement to the binding affinities. The third example presented is that of the JAWA mutations (T437R/K248E) also located in the Fc region of a mAb. The JAWA mutations facilitate antibody multimerization upon binding to cell surface antigens, allowing for enhanced agonism and effector functions. Both DSC and HDX-MS showed that the JAWA mutations destabilize the unbound Fc, although the complex was not characterized due to weak binding. Enhancement of protein–protein interactions through incorporation of mutations that increase the free energy of a protein’s unbound state represents an alternative route to decreasing the protein–protein complex free energy through optimization of the binding interface. Full article