Search Results (1,978)

Hypertension is a major pathogenic contributor to cardiovascular diseases, primarily mediated through activation of the angiotensin-converting enzyme (ACE) system. Food-derived ACE-inhibitory peptides represent a promising alternative to synthetic drugs due to their favorable safety profile and minimal side effects. ACE-inhibitory peptides have been extensively identified from various foods, with their antihypertensive activity and molecular mechanisms comprehensively characterized through in vitro and in vivo studies. ACE-inhibitory peptides can be prepared by methods such as natural extraction, enzymatic hydrolysis, and fermentation. The production process significantly modulates structural characteristics of the polypeptides including peptide chain length, amino acid composition, and sequence, consequently determining their functional activity. To comprehensively elucidate the gastrointestinal stability and mechanisms action of ACE-inhibitory peptides, integrated experimental approaches combining both in vitro and in vivo methodologies are essential. This review systematically examines current advances in food-derived ACE-inhibitory peptides in terms of sources, production, structure, in vivo and in vitro activities, and bioavailability. Full article

The global burden of hepatitis B virus (HBV) remains high, with ongoing concerted efforts to eliminate viral hepatitis as a public health concern by 2030. The absence of curative treatment against HBV makes it an active area of research to further study HBV pathogenesis. In vitro cell culture systems are essential in exploration of molecular mechanisms for HBV propagation and the development of therapeutic targets for antiviral agents. The lack of an efficient cell culture system is one of the challenges limiting the development and study of novel antiviral strategies for HBV infection. However, the evolution of cell culture systems to study HBV pathogenesis and treatment susceptibility in vitro has made a significant contribution to public health. The currently available cell culture systems to grow HBV have their advantages and limitations, requiring further optimization. The discovery of sodium taurocholate co-transporting polypeptide (NTCP) as a receptor for HBV was a major breakthrough for the development of a robust cell model, allowing the study of de novo HBV infection through NTCP expression in the HepG2 hepatoma cell line. This review is aimed at highlighting the evolution of cell culture systems to study HBV pathogenesis and in vitro treatment susceptibility. Full article

Recombinant protein hydrogels have emerged as transformative biomaterials that overcome the bioinertness and unpredictable degradation of traditional synthetic systems by leveraging genetically engineered backbones, such as elastin-like polypeptides, SF, and resilin-like polypeptides, to replicate extracellular matrix (ECM) dynamics and enable programmable functionality. Constructed through a hierarchical crosslinking strategy, these hydrogels integrate reversible physical interactions with covalent crosslinking approaches, collectively endowing the system with mechanical strength, environmental responsiveness, and controlled degradation behavior. Critically, molecular engineering strategies serve as the cornerstone for functional precision: domain-directed self-assembly exploits coiled-coil or β-sheet motifs to orchestrate hierarchical organization, while modular fusion of bioactive motifs through genetic encoding or site-specific conjugation enables dynamic control over cellular interactions and therapeutic release. Such engineered designs underpin advanced applications, including immunomodulatory scaffolds for diabetic wound regeneration, tumor-microenvironment-responsive drug depots, and shear-thinning bioinks for vascularized bioprinting, by synergizing material properties with biological cues. By uniting synthetic biology with materials science, recombinant hydrogels deliver unprecedented flexibility in tuning physical and biological properties. This review synthesizes emerging crosslinking paradigms and molecular strategies, offering a framework for engineering next-generation, adaptive biomaterials poised to address complex challenges in regenerative medicine and beyond. Full article

Cattle–yak, a hybrid of yak and cattle, exhibits significant heterosis but male infertility, hindering heterosis fixation. Although extensive research has been conducted on transcriptional mechanisms in the testes of cattle–yak, the understanding of their translational landscape remains limited. In this study, we characterized the translational landscape of yak and cattle–yak based on Ribo-seq technology integrated with RNA-seq data. The results revealed that gene expression was not fully concordant between transcriptional and translational levels, whereas cattle–yak testes exhibited a stronger correlation across these two regulatory layers. Notably, genes that were differentially expressed at the translational level only (MEIOB, MEI1, and SMC1B) were mainly involved in meiosis. A total of 4,236 genes with different translation efficiencies (TEs) were identified, and the TEs of most of the genes gradually decreased as the mRNA expression level increased. Further research revealed that genes with higher TE had a shorter coding sequence (CDS) length, lower GC content, and higher normalized minimum free energy in the testes of yaks, but this characteristic was not found in cattle–yaks. We also identified upstream open reading frames (uORFs) in yak and cattle–yak testes, and the sequence characteristics of translated uORFs and untranslated uORFs were markedly different. In addition, we identified several short polypeptides that may play potential roles in spermatogenesis. In summary, our study uncovers distinct translational dysregulations in cattle–yak testes, particularly affecting meiosis, which provides novel insights into the mechanisms of spermatogenesis and male infertility in hybrids. Full article

Background/Objectives: Magnetic resonance imaging (MRI) is a powerful, non-invasive diagnostic tool capable of capturing detailed anatomical and physiological information. MRI contrast agents enhance image contrast but, especially linear gadolinium-based compounds, have been associated with safety concerns. This has prompted interest in alternative contrast agents. Manganese-based contrast agents offer a promising substitute, owing to manganese’s favorable magnetic properties, natural biological role, and strong T1 relaxivity. This review aims to critically assess the structure, mechanisms, applications, and challenges of manganese-based contrast agents in MRI. Methods: This review synthesizes findings from preclinical and clinical studies involving various types of manganese-based contrast agents, including small-molecule chelates, nanoparticles, theranostic platforms, responsive agents, and controlled-release systems. Special attention is given to pharmacokinetics, biodistribution, and safety evaluations. Results: Mn-based agents demonstrate promising imaging capabilities, with some achieving relaxivity values comparable to gadolinium compounds. Targeted uptake mechanisms, such as hepatocyte-specific transport via organic anion-transporting polypeptides, allow for enhanced tissue contrast. However, concerns remain regarding the in vivo release of free Mn²⁺ ions, which could lead to toxicity. Preliminary toxicity assessments report low cytotoxicity, but further comprehensive long-term safety studies should be carried out. Conclusions: Manganese-based contrast agents present a potential alternative to gadolinium-based MRI agents pending further validation. Despite promising imaging performance and biocompatibility, further investigation into stability and safety is essential. Additional research is needed to facilitate the clinical translation of these agents. Full article

Proper subcellular localization is essential to exert the designated function of a protein, not only for endogenous proteins but also transgene-encoded proteins. Post-translational modification is a frequently used method to regulate the subcellular localization of a specific protein. While there are a number of tags that are widely used to direct the target protein to a specific location within a cell, these tags often fail to emulate the dynamics of protein trafficking, necessitating an alternative approach to the direct subcellular localization of transgene-encoded proteins. Here, we report the development of a new synthetic polypeptide protein tag comprised of ten amino acids, which promotes membrane localization of a target protein. This short synthetic peptide tag, named “Palmito-Tag”, induces ectopic palmitoylation on the cysteine residue within the tag, thereby promoting membrane localization of the target proteins without affecting their innate function. We show that the target proteins with the Palmito-Tag are incorporated into the membranous organelles within the cells, including the endosomes, as well as extracellular vesicles. Given the reversible nature of palmitoylation, the Palmito-Tag may allow us to shift the subcellular localization of the target protein in a context-dependent manner. With the advent of therapeutic applications of exosomes and other extracellular vesicles, we believe that the ability to reversibly modify a target protein and direct its deposition to the specific subcellular milieu will help us explore more effective venues to harness the potential of extracellular vesicle-based therapies. Full article

Disorders in glucose metabolism are well-established features of polycystic ovary syndrome (PCOS) and are linked to its clinical severity and phenotypic variability. This study aimed to assess serum concentrations of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and dipeptidyl peptidase-4 (DPP-4) and to examine their relationships with glucose and insulin levels, selected sex hormone concentrations, body weight, and exposure to tobacco smoke. Women with PCOS exhibited significantly elevated levels of fasting glucose, insulin, GIP, and GLP-1 compared to controls. Tobacco smoke exposure in women with PCOS was associated with reduced DPP-4 levels, which were approximately two-fold lower in smokers than in non-smokers. A significant negative correlation between DPP-4 and cotinine levels further supported this relationship. Comorbidities such as overweight/obesity or insulin resistance (IR) were also linked to elevated incretin hormone levels. However, no significant age-related trends in incretin levels were identified, despite the known association between age and glucose dysregulation. The notable alterations in incretin hormone profiles in PCOS, along with the consistent patterns of GIP or GLP-1 with metabolic and hormonal parameters, suggest that these hormones may play coordinated regulatory roles in the pathophysiology of PCOS. Full article

Objectives: Research on the immunocastration vaccine is of great significance for animal management. In this study, the gonadotropin-releasing hormone (GnRH) ferritin nanoparticle vaccine was constructed using Spy Catcher-Spy Tag (SC-ST) as a delivery system; Methods: The Spy Catcher was constructed to fuse with the expression vector pET-30a-SF of ferritin nanoparticles. Two polypeptides, STG1: Spy Tag-GnRH I-PADRE and STG2: Spy Tag-GnRH I-GnRH II, coupled to SF in vitro to form two nanoparticles, were designed and synthesized to detect castration effects in mice. We mixed them with the adjuvant MONTANIDE ISA 206 VG to explore the adjuvant’s effect on immunogenicity; Results: All immunized groups produced anti-GnRH specific antibodies after the second immunization, which was significantly higher in the immunized group and the combined adjuvant group than in the control group, and the immune response could still be detected at the 12th week. The concentrations of testosterone, follicle-stimulating hormone, and luteinizing hormone in serum were significantly decreased. The number of sperm in the epididymis of mice in each immune group was significantly reduced, and the rate of sperm deformity was high; Conclusions: The two ferritin-based GnRH nanoparticles developed in this study can significantly cause testicular atrophy, decreased gonadal hormone concentration, decreased sperm count, and increased deformity rate in male mice. These findings provide experimental evidence supporting their potential application in animal immunocastration. Full article

Sourdough fermentation has emerged as a promising biotechnological approach to reducing gluten content and modifying gluten proteins in wheat-based products. This review assesses the current scientific literature on the enzymatic degradation and hydrolysis of gluten during lactic acid bacteria (LAB) sourdough fermentation. It explores implications for individuals with gluten-related disorders, including celiac disease, non-celiac gluten sensitivity and intolerance, as well as irritable bowel syndrome (IBS). In addition, LAB sourdough effect on fermentable oligo-, di-, monosaccharides and polyols (FODMAPs), amylase-trypsin inhibitors (ATIs), and phytate are revised. Selected homo- and heterofermentative LAB are capable of degrading gluten proteins, especially the polypeptides derived from the action of native cereal proteases. Mixed cultures of LAB degrade gluten peptides more effectively than monocultures. However, LAB sourdough is not sufficient to remove the toxic peptides to the minimal level (<20 ppm). This goal is achieved only if sourdough is combined with fungal proteases during sourdough fermentation. LAB sourdough directly contributes to lower FODMAPs but not ATIs and phytate. Phytate is reduced by the endogenous cereal phytases activated at acidic pHs (pH < 5.0), conditions generated during sourdough fermentation. ATIs are also lowered by endogenous cereal proteases instead of LAB proteases/peptidases. Despite LAB sourdough not fully degrading the gluten or directly reducing the ATIs and phytate, it participates through peptidases activity and acidic pH that trigger the action of endogenous cereal proteases and phytases. Full article

Obesity-driven inflammation disrupts gut barrier integrity and promotes inflammatory bowel disease (IBD). Emerging evidence highlights gut hormones—including glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), glucose-dependent insulinotropic polypeptide (GIP), peptide YY (PYY), cholecystokinin (CCK), and apolipoprotein A4 (APOA4)—as key regulators of metabolism and mucosal immunity. This review outlines known mechanisms and explores therapeutic prospects in IBD. GLP-1 improves glycemic control, induces weight loss, and preserves intestinal barrier function, while GLP-2 enhances epithelial repair and reduces pro-inflammatory cytokine expression in animal models of colitis. GIP facilitates lipid clearance, enhances insulin sensitivity, and limits systemic inflammation. PYY and CCK slow gastric emptying, suppress appetite, and attenuate colonic inflammation via neural pathways. APOA4 regulates lipid transport, increases energy expenditure, and exerts antioxidant and anti-inflammatory effects that alleviate experimental colitis. Synergistic interactions—such as GLP-1/PYY co-administration, PYY-stimulated APOA4 production, and APOA4-enhanced CCK activity—suggest that multi-hormone combinations may offer amplified therapeutic benefits. While preclinical data are promising, clinical evidence supporting gut hormone therapies in IBD remains limited. Dual GIP/GLP-1 receptor agonists improve metabolic and inflammatory parameters, but in clinical use, they are associated with gastrointestinal side effects that warrant further investigation. Future research should evaluate combination therapies in preclinical IBD models, elucidate shared neural and receptor-mediated pathways, and define optimal strategies for applying gut hormone synergy in human IBD. These efforts may uncover safer, metabolically tailored treatments for IBD, particularly in patients with coexisting obesity or metabolic dysfunction. Full article

Low-molecular-weight polypeptides (<3 kDa) were prepared from Periplaneta americana via enzymatic hydrolysis and ultrafiltration, yielding 3.53 ± 0.01 mg/g of peptide-rich extract. The extract was primarily composed of peptides, proteins, polysaccharides, phenolics, and flavonoids. HPLC-MS analysis identified 1402 peptide sequences, 80.51% of which were below 1000 Da, predominantly consisting of tri-, tetra-, and octapeptides. Monosaccharide profiling detected D-(+)-galactose, and quantitative assays determined the contents of total phenolics (12.28 mg/g), flavonoids (15.50 mg/g), proteins (85.84 mg/g), and total sugars (17.62 mg/g). The biological activities of the extract were systematically evaluated. The peptide fraction inhibited hyaluronidase activity by 58% at 5 mg/mL, suggesting protection of extracellular matrix integrity. In HaCaT keratinocytes, it promoted cell proliferation by 62.6%, accelerated scratch wound closure by 54%, upregulated Wnt-10b and β-catenin expression, and reduced intracellular ROS levels under oxidative stress. In LPS-stimulated RAW 264.7 macrophages, the extract decreased TNF-α, IL-6, and IL-1β production by 30%, 25%, and 28%, respectively, reduced MDA levels by 35.2%, and enhanced CAT and SOD activities by 12.3% and 60.3%. In vivo, complete closure of full-thickness skin wounds in mice was achieved by day 14. Safety evaluations using the chick chorioallantoic membrane assay and human patch tests confirmed the extract to be non-irritating and non-toxic. These findings highlight Periplaneta americana extract as a promising multifunctional bioactive ingredient for cosmetic and dermatological applications. Further studies on its active components, mechanisms of action, and clinical efficacy are warranted to support its development in skin health and aesthetic medicine. Full article

The synthesis of novel biodegradable polymers as non-viral vectors remains one of the challenging tasks in the field of gene delivery. In this study, the synthesis of the polysaccharide-g-polypeptide copolymers, namely, hyaluronic acid-g-polylysine (HA-g-PLys), using a copper-free strain-promoted azide-alkyne cycloaddition reaction was proposed. For this purpose, hyaluronic acid was modified with dibenzocyclooctyne moieties, and poly-L-lysine with a terminal azido group was obtained using ring-opening polymerization of N-carboxyanhydride of the corresponding protected amino acid, initiated with the amino group azido-PEG₃-amine. Two HA-g-PLys samples with different degrees of grafting were synthesized, and the structures of all modified and synthesized polymers were confirmed using ¹H NMR and FTIR spectroscopy. The HA-g-PLys samples obtained were able to form nanoparticles in aqueous media due to self-assembly driven by electrostatic interactions. The binding of DNA and model siRNA by copolymers to form polyplexes was analyzed using ethidium bromide, agarose gel electrophoresis, and SybrGreen I assays. The hydrodynamic diameter of polyplexes was ˂300 nm (polydispersity index, PDI ˂ 0.3). The release of a model fluorescently-labeled oligonucleotide in the complex biological medium was significantly higher in the case of HA-g-PLys as compared to that in the case of PLys-based polyplexes. In addition, the cytotoxicity in normal and cancer cells, as well as the ability of HA-g-PLys to facilitate intracellular delivery of anti-GFP siRNA to NIH-3T3/GFP+ cells, were evaluated. Full article

Obesity is considered a global pandemic. In Mexico, 7/10 adults, 4/10 adolescents, and 1/3 children are overweight or obese, and it is estimated that 90% of cases of type 2 diabetes (T2D) are attributable to these pathologies. Visceral adipose tissue (VAT) presents increased lipolysis, lower insulin sensitivity, and greater metabolic alterations. Glucagon-like peptide-1 (GLP-1) is a polypeptide incretin hormone that stimulates insulin secretion dependent on the amount of oral glucose consumed, reduces plasma glucagon concentrations, slows gastric emptying, suppresses appetite, improves insulin synthesis and secretion, and increases the sensitivity of β cells to glucose. Liraglutide is a synthetic GLP-1 analog that reduces VAT and improves the expression of Glucose transporter receptor type 4 (GLUT 4R), Mitogen-activated protein (MAP kinases), decreases Fibroblast growth factor type β (TGF-β), reactivates the peroxisome proliferator-activated receptor type ɣ (PPAR-ɣ) pathway, and decreases chronic inflammation. Currently, there are many studies that explain the decrease in VAT with these medications, but there are no studies that compare the decrease in patients with obesity and prediabetes vs. obesity and type 2 diabetes to know which population obtains a greater benefit from treatment with this pharmacological group; this is the reason for this study. The primary objective was to compare the difference in the determination of visceral adipose tissue in people with obesity and type 2 diabetes vs. obesity and prediabetes treated with liraglutide. Methods: A quasi-experimental, analytical, prolective, non-randomized, non-blinded study was conducted over a period of 6 months in a tertiary care center. A total of 36 participants were divided into two arms; group 1 (G1: Obesity and prediabetes) and group 2 (G2: Obesity and type 2 diabetes) for 6 months. Inclusion criteria: men and women ≥18 years with type 2 diabetes, prediabetes, and obesity. Exclusion criteria: Glomerular filtration rate (GFR) < 60 mL/min/1.73 m² elevated transaminases (>5 times the upper limit of normal), and use of non-weight-modifying antidiabetic agents. Conclusions: No statistically significant difference was found in the decrease in visceral adipose tissue when comparing G1 (OB and PD) with G2 (OB and T2D). When comparing intragroup in G2 (OB and T2D), greater weight loss was found [(−3.78 kg; p = 0.012) vs. (−3.78 kg; p = 0.012)], as well differences in waist circumference [(−3.9 cm; p = 0.049) vs. (−3.09 cm; p = 0.017)], and glucose levels [(−1.75 mmol/L; p = 0.002) vs. (−0.56 mmol/L; p = 0.002)], A1c% [(−1.15%; p = 0.001) vs. (−0.5%; p = 0.000)]. Full article

Background: Due to limitations of fluoride (F) treatment as a main caries preventive measure, it is important to consider the use of other dental caries preventive measures to reduce caries prevalence, especially in its early stages. Recently, new remineralizing agents appeared on the market, with their commercial availability in a variety of oral care products. Objectives: The purposes include providing a scoping review that represents caries remineralizing efficacies of only commercially available products and their existing adverse effects (if it is presented) and ensuring that only evidence-based approved products are included. Methods: The following databases were used in searching scientific literature on 28 October 2024: PubMed, PubMed Advanced Search, MeSH database, and PubMed Clinical Queries. The study selection criteria were as follows: for laboratory, in vitro, and/or in situ—remineralization of enamel-scanning electron microscopy, spectroscopy, microhardness test, light microscopy, profilometry, transverse microhardness microradiography, integrated mineral loss, light microscopy, photothermal radiometry; if it was a randomized controlled trial—CONSORT protocol, ICDAS system (to detect dental caries), diagnostic additional devices; antibacterial ability-colony forming units, DNA-based sequencing, scanning electron microscopy, crystal violet staining, and confocal laser scanning microscopy. Results: This review includes 98 papers: 14 of them describing the current status of caries patterns in the world, 60 studies (45 laboratory studies and 15 RCTs), and 24 systematic reviews were analyzed in order to detect whether new remineralizing agents can replace fluoride in further caries prevention. Conclusions: All reviewed new remineralization agents could be used without additives to treat early caries lesions, but the combination with F promotes better remineralization. Only HAP demonstrated its potential to serve as an alternative to fluoride in oral care products. However, further clinical studies are needed to prove its role in the remineralizing process of initial caries lesions. One also needs to ensure that both the clinical trials and in vitro lab studies use the best gold standards to validate any changes in the tooth structure, both remineralization and demineralization. Full article

Background: Baicalin (BG) has been used in the treatment of many diseases. However, the effect of hepatic insufficiency on its pharmacokinetics has not been reported, and there is a lack of clinical guidance for the use of BG in patients with hepatic impairment. Methods: Carbon tetrachloride (CCl₄)-induced rat models were used to simulate hepatic failure patients to assess the effect of hepatic impairment on the pharmacokinetics and distribution of BG. In vitro metabolism and transporter studies were employed to elucidate the potential mechanisms. Results: After intragastric administration of 10 mg/kg of BG, the peak plasma concentration and exposure (AUC_0–t) of BG decreased by 64.6% and 52.6%, respectively, in CCl₄-induced rats. After intravenous administration, the AUC_0–t decreased by 73.6%, and unlike in the control group, the second absorption peak of BG was not obvious in the concentration–time curve of CCl₄-induced rats. The cumulative excretion of BG in the feces increased, but that in the bile decreased. In vivo data indicated that the absorption and enterohepatic circulation of BG were affected. In vitro studies found that the hydrolysis of BG to the aglycone baicalein decreased significantly in the intestinal tissues and contents of the CCl₄-induced rats. And BG was identified as a substrate for multiple efflux and uptake transporters, such as breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs), organic anion transporting polypeptides (OATP1B1, 1B3, 2B1), and organic anion transporters (OATs). The bile acids accumulated by liver injury inhibited the uptake of BG by OATPs, especially that by OATP2B1. Conclusions: Hepatic impairment reduced BG hydrolysis by intestinal microflora and inhibited its transporter-mediated biliary excretion, which synergistically led to the attenuation of the enterohepatic circulation of BG, which altered its pharmacokinetics. Full article