Search Results (722)

Although flaviviruses, including DENV, ZIKV and JEV, remain important causes of febrile, congenital, and neurological diseases, treatment options remain largely supportive, with limited availability of virus-specific antiviral therapies. Marine organisms and marine-derived microorganisms produce chemically distinct antiviral materials, including sulfated polysaccharides, terpenoids, alkaloids, peptides, cyclodepsipeptides, and polyketides. However, their activities range from preliminary extract-level inhibition to direct biochemical target validation, making mechanistic comparison difficult. This review critically evaluates marine-derived anti-flaviviral agents using two complementary dimensions, the infection stage implicated by experimental assays and the strength of evidence supporting that assignment. DENV evidence is dominated by sulfated algal macromolecules that interfere with adsorption or internalization, whereas ZIKV studies encompass lipophilic algal metabolites, fungal alkaloids, cyclodepsipeptides, and a few target-oriented candidates. Across the field, most reports remain stage-associated rather than target-validated. Cross-study potency comparisons are constrained by differences in virus strains, cell models, assay formats, and treatment schedules. JEV-specific evidence is particularly sparse. Based on the DENV and ZIKV evidence map, we propose concise priorities for JEV-oriented discovery: early compound-level dereplication, parallel cytotoxicity testing, orthogonal confirmation of productive infection, stage-resolved assays, and biochemical or genetic validation of conserved flaviviral targets. This evidence-based framework can help distinguish promising chemical candidate scaffolds from preliminary antiviral signals and guide mechanism-informed development of marine-derived natural products against flaviviruses. Full article

Marine-derived rare actinomycetes are a chemically prolific yet underexploited source of structurally diverse secondary metabolites. In this review, rare actinomycetes are operationally defined as marine-derived non-Streptomyces actinomycetes that remain comparatively underexplored yet possess demonstrated or predicted capacity for specialized-metabolite biosynthesis. Genome sequencing has revealed that their biosynthetic potential greatly exceeds the range of metabolites recovered under standard cultivation conditions. However, many reported compounds remain only loosely associated with the gene clusters that encode them. This review provides a biosynthesis-centered perspective on marine-derived rare actinomycetes, focusing on secondary metabolites for which biosynthetic gene clusters (BGCs) or pathways have been proposed, experimentally assessed, or functionally validated. It focuses on compounds reported after 2017, along with earlier metabolites whose biosynthetic origins were resolved only later. Representative examples are organized by genus and structural class and weighed according to the level of evidence linking each metabolite to its BGC, ranging from bioinformatic prediction and metabolomic correlation to validation by gene inactivation, heterologous expression, and enzymatic characterization. The surveyed metabolites include polyketides, nonribosomal peptides, polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrids, siderophores, angucyclines, anthracyclines, macrolides, diketopiperazine derivatives, and other unusual scaffolds. Collectively, these findings indicate how integrating genome mining, metabolomics, and molecular networking with targeted biosynthetic experiments can accelerate marine natural product discovery and unravel novel enzymatic functions and biosynthetic mechanisms in rare actinomycetes. Full article

Background/Objectives: Pseudorabies virus (PRV) variant strains have caused widespread outbreaks in China since 2011, and currently available vaccines provide suboptimal protection. Glycoprotein D (gD), the principal target of virus-neutralizing antibodies, represents a promising antigen for subunit vaccine development. However, CHO cell-based production systems suitable for large-scale manufacturing remain insufficiently explored. This study aimed to develop a potentially scalable CHO cell-derived PRV gD subunit vaccine and evaluate its immunogenicity and protective efficacy in mice. Methods: A stable Chinese hamster ovary (CHO) suspension cell line secreting the extracellular domain of PRV gD was established through signal peptide optimization and stepwise serum-free adaptation. The recombinant gD protein was purified using Ni²⁺- Sepharose High-Performance affinity chromatography and subsequently formulated with MONTANIDE ISA 206 adjuvant. Immunogenicity and protective efficacy were assessed in BALB/c mice through serological analysis, neutralization assays, lethal challenge experiments, and quantitative PCR. Results: The gD subunit vaccine induced rapid seroconversion of gD-specific IgG antibodies as early as 7 days post immunization and exhibited a strong booster effect, maintaining high antibody levels. Neutralizing antibodies were first detected at 14 days and increased significantly after booster immunization, with titers markedly exceeding those induced by a commercial inactivated PRV vaccine at 42 days (p = 0.001). Following lethal challenge with 10⁴ TCID₅₀ of the highly virulent PRV-TJ variant strain, vaccinated mice achieved 100% survival without clinical signs. Viral genome copy numbers in the brain and spinal cord were reduced by approximately 3.3 to 4.4 log₁₀ relative to the PBS control group. Conclusions: The CHO cell-derived PRV gD subunit vaccine elicits robust humoral immune responses and provides complete protection against lethal PRV variant challenge in mice. These findings support its further evaluation in the natural swine host toward the development of a safe and scalable subunit vaccine for pseudorabies control. Full article

Antimicrobial peptides (AMPs) occur naturally in living organisms and play an essential role in defense against pathogens. Consequently, these peptides are significant in public health research as alternatives in addressing microbial resistance. Here, we present the proteomic profile of Cryptococcus neoformans treated with RcAlb-PepII, an AMP derived from the 2S albumin of Ricinus communis seed cake. This research is noteworthy, as C. neoformans is an emerging fungal pathogen classified by the World Health Organization (WHO) as a critical threat. Proteomic analysis revealed depletion of proteins involved in DNA and RNA metabolism, reduced protein biosynthesis, and mitochondrial damage-associated proteins in C. neoformans following RcAlb-PepII treatment. These findings advance the understanding of the therapeutic profile of AMPs and underscore their importance in combating critical pathogens. Full article

As the prevalence of type 2 diabetes increases rapidly, the demand for natural origin dipeptidyl peptidase-IV (DPP-IV) inhibitors with fewer side effects is increasing. In this study, protein-rich Limnospira platensis was investigated as a source of bioactive peptides to enhance its value as a functional food ingredient. Hydrolysates were prepared using three food-processing proteases, individually and in two-step combinations, followed by in silico analysis and peptide identification via liquid chromatography–tandem mass spectrometry. Subsequently, the thermal stability, gastrointestinal resistance, and intestinal permeability (using Caco-2 cells) of the identified peptides were evaluated. It was revealed that the Orientase 22BF digest exhibited high DPP-IV inhibitory activity. From the digest, three novel peptides—SPSPN (IC₅₀ = 144.1 ± 2.2 μM), VPSV (IC₅₀ = 93.6 ± 5.8 μM), and IPIGG (IC₅₀ = 13.4 ± 2.3 μM)—were identified, exhibiting DPP-IV inhibitory potencies comparable to or higher than previously reported Limnospira-derived peptides. Although VPSV exhibited low epithelial permeability (P_app = 4.02 ± 0.69 × 10⁻⁸ cm/s), it remained stable under simulated gastrointestinal digestion conditions, suggesting potential local luminal inhibitory activity within the small intestine. Overall, these findings highlight Limnospira-derived VPSV as a promising functional ingredient candidate with high bioactivity and digestive stability. Full article

Background/Objectives: Antimicrobial peptides (AMPs) have emerged as promising alternatives to conventional antibiotics in response to the escalating global threat of antimicrobial resistance (AMR), owing to their potent antimicrobial activity and low propensity for resistance development. However, their clinical application remains limited by poor selectivity and undesirable toxicity toward mammalian cells. Methods: In this study, the naturally occurring frog-derived AMP Dermaseptin-A4 (A4) was selected as a template for rational design. Guided by the principle that optimising the balance between peptide hydrophobicity and cationicity could improve bacterial membrane targeting while reducing interactions with mammalian membranes, three analogues were designed through the targeted modulation of these physicochemical properties. Results: Among the designed analogues, A4-3 exhibited the best overall biological profile. A4-3 maintained a stable α-helical conformation in membrane-mimicking environments and displayed potent antimicrobial activity against tested Gram-positive and Gram-negative bacteria while exhibiting lower haemolytic and cytotoxic effects than the parent peptide. As a result, A4-3 showed improved selectivity, achieving a selectivity index of up to 34.5. A4-3 rapidly eradicated bacterial cells through a membrane-targeting mechanism, leading to membrane disruption and the loss of cellular integrity, and exhibited a low propensity for resistance development following prolonged exposure. A4-3 also retained its antimicrobial activity under physiologically relevant conditions. Conclusions: Collectively, these findings demonstrate that achieving an optimal balance between peptide hydrophobicity and cationicity is an effective strategy for enhancing antimicrobial selectivity without compromising antibacterial activity, highlighting A4-3 as a promising lead candidate for the development of novel antimicrobial therapeutics against drug-resistant bacterial infections. Full article

Cancer prevention through dietary intervention utilizing bioactive natural compounds has garnered significant attention due to the therapeutic limitations of conventional cancer treatments. These plant-derived active compounds, including polyphenols, terpenoids, organosulfur compounds, bioactive peptides, and alkaloids, possess potent anticancer properties. This systemic review addresses a critical gap in the scientific literature by elucidating the precise multitargeted oncogenic regulatory mechanisms of these molecules. A comprehensive methodology was employed, involving a systematic literature search across major electronic databases (including PubMed, Web of Science, Embase, and SCOPUS) to identify relevant original peer-reviewed studies. The evidence gathered demonstrates that these active compounds deliver significant health benefits and protect cells by modulating crucial molecular targets involved in cell cycle regulation, apoptosis, oncogenic signaling, epigenetic control, angiogenesis, oxidative stress, and inflammation. Specifically, they operate via multi-targeted cascades, such as inhibiting the PI3K/Akt, NF-κB, and STAT3 pathways. To provide a clear structural overview, these active compounds are categorized comprehensively based on their botanical and structural origins, including spices, fruits, and rhizomes. However, despite their promising bioactivities, these compounds have not yet been fully translated into clinical therapy due to challenges such as low bioavailability, rapid metabolism, limited systematic exposure, and a lack of convincing evidence from large-scale clinical trials. Although most current evidence remains rooted in in vitro and experimental animal models, clinical validation through high-quality trials is still required. Ultimately, this review underscores the potential of these active compounds and highlights how advances in formulation and nano delivery strategies offer promising solutions for effective cancer prevention. Full article

Feline infectious peritonitis virus (FIPV) causes a fatal and immune-mediated disease in cats with limited treatment options. Natural products offer promising antiviral candidates, but animal-derived peptides remain underexplored. Here, we identified PI-8, a Periplaneta americana (P. americana)-derived peptide with validated binding to ISG15, and evaluated its anti-FIPV effect and mechanism. PI-8 showed low cytotoxicity (CC₅₀ > 40 μM) and inhibited FIPV replication with an IC₅₀ of 12.9 μM, acting primarily at the post-entry stage. PI-8 significantly upregulated IFNA1, IFNB, ISG15, and MX1 in infected CRFK cells. In FIPV-infected cats, PI-8 reduced RNA levels in blood, saliva, and anal swabs, and lowered tissue viral burden in liver, spleen, lung, kidney, and intestine. It also alleviated gross and histopathological lesions and decreased inflammatory cytokine expression. These findings suggest that PI-8 is an P. americana-derived peptide with dual anti-FIPV and immunomodulatory activity associated with an IFN-ISG15-related antiviral response. PI-8 represents a potential host-directed therapeutic candidate for FIPV infection. Full article

Wound healing is a multifaceted biological process comprising the phases of hemostasis, inflammation, proliferation, and remodeling, all of which require supportive microenvironment for optimal tissue regeneration. Biopolymer-based hydrogels, derived from materials such as cellulose and its derivatives, chitosan, alginate, and hyaluronic acid, have emerged as promising wound dressing materials due to their excellent biocompatibility, biodegradability, moisture-retention capacity, and potential to mimic the native extracellular matrix. The structural characteristics, wound healing functions, and underlying mechanisms of these biopolymers are critically examined and summarized in tabular form. The review further highlights the incorporation of natural and synthetic therapeutic agents, growth factors, stem-cell-derived products, and peptides into biopolymer matrices to enhance therapeutic efficacy. The examined research findings indicate significant increases in fluid intake, moisture retention, antibacterial activity, angiogenesis, collagen deposition, tissue regeneration, and wound healing rates. Translational difficulties, regulatory issues, clinical research, and new patent activity pertaining to advanced wound healing biomaterials are also covered in the review. Despite tremendous improvements, issues still exist in bulk manufacturing, long-term safety, reproducibility, mechanical stability, and clinical validation. Future innovations are anticipated to concentrate on smart, multipurpose, and customized hydrogel systems that can integrate drug delivery, biosensing, and regenerative capabilities while reacting dynamically to wound microenvironments. Overall, biopolymer-based hydrogels are a flexible, rapidly developing platform with significant promise to improve next-generation skin tissue engineering and change the treatment of both acute and chronic wounds. Full article

Agri-food processing generates large quantities of residues that are increasingly recognized as sustainable sources of bioactive ingredients for high-value applications. This narrative review examines agri-food by-products as sources of antioxidant compounds and provides an integrated mechanistic perspective on their applications in skin, oral, and hair care. By highlighting the shared antioxidant mechanisms of action underlying these applications, the review offers a comprehensive framework for understanding the cosmeceutical potential of agri-food-derived bioactive compounds. Peer-reviewed studies published mainly between 2015 and 2026 were considered, focusing on the chemical composition of by-products, green recovery strategies, biological mechanisms, and evidence from in vitro, ex vivo, in vivo, and clinical studies. Fruit and vegetable peels, seeds, skins, pomaces, and other agro-industrial residues contain polyphenols, flavonoids, phenolic acids, tannins, carotenoids, vitamins, lipids, peptides, and polysaccharides with antioxidant, anti-inflammatory, antimicrobial, photoprotective, anti-aging, moisturizing, and pigmentation-modulating properties. These compounds can reduce oxidative stress, support endogenous antioxidant defences, modulate redox-sensitive signaling pathways, attenuate inflammation, preserve extracellular matrix integrity, and improve skin barrier-related outcomes. Green extraction technologies, including ultrasound-assisted extraction, microwave-assisted extraction, supercritical fluid extraction, pressurized liquid extraction, and natural deep eutectic solvents, enhance their sustainable recovery. Overall, agri-food by-products represent promising resources for circular cosmeceutical innovation, although extract standardization, safety, stability, skin bioavailability, formulation performance, and controlled clinical validation remain essential for translation. Full article

Rare actinomycetes have emerged as important yet underexplored reservoirs for the discovery of novel bioactive compounds. Microbispora, a genus of rare actinomycetes, is widely distributed across diverse ecological niches, including terrestrial soils, marine-associated environments, plant-associated ecosystems, and insect-derived environments. To date, 81 secondary metabolites have been reported from this genus, encompassing quinones, chromones and chromanones, macrolides, other polyketides, alkaloids, peptides and diketopiperazines, and miscellaneous structural classes. These metabolites display antimicrobial, anticancer, neuroprotective, antiviral, plant growth-promoting, and enzyme inhibitory activities. Beyond systematically cataloging these compounds, this review provides an integrated analysis of their structure–activity relationships (SAR), biosynthetic origins, and biological significance. In addition, the biosynthetic potential of Microbispora is discussed based on reported genomic studies, highlighting the presence of numerous predicted and poorly characterized biosynthetic gene clusters. This review provides an integrative perspective on Microbispora as an underexplored but promising source of structurally diverse and bioactive natural products for drug discovery. Full article

Background: Metabolic dysfunction-associated steatohepatitis (MASH), the progressive stage of metabolic dysfunction-associated steatotic liver disease (MASLD), is characterized by hepatic steatosis, inflammation, and fibrosis, yet no specific therapy has been established. This study evaluated the therapeutic potential of Andrias davidianus liver-derived peptides (ALPs) in a mouse model of MASH. Methods: ALPs were prepared by enzymatic hydrolysis of fresh Andrias davidianus liver. A MASH model was induced in mice using a methionine- and choline-deficient diet (MRCD). ALP was administered via oral gavage, and its effects were assessed through histological staining (H&E, Oil Red O, and Sirius Red), immunofluorescence (Ki67), apoptosis detection (TUNEL), serum biochemistry, and RNA-sequencing of liver tissues. Gut microbiota composition was also analyzed. Results: ALP treatment significantly alleviated hepatic histopathological features, including steatosis, inflammation, and fibrosis. It reduced aberrant proliferation and apoptosis of hepatocyte-like cells, and markedly improved serum biochemical markers of liver function. RNA-seq analysis revealed that ALP modulated the expression of lipid metabolism-related genes, an effect associated with suppression of the PPARγ signaling pathway. Furthermore, ALP selectively modulated MRCD-induced gut microbiota dysbiosis, particularly by reducing the Firmicutes-to-Bacteroidota (F/B) ratio and enriching Akkermansia. No overt toxicity was observed in other organs. Conclusions: Our findings demonstrate that ALP exerts protective effects against MASH by improving lipid metabolism, partially through suppression of the PPARγ signaling pathway, and by selectively modulating specific gut microbial taxa. ALP represents a promising natural therapeutic candidate for MASH. Full article

Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus, and a leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide. It is characterized by proteinuria, mesangial expansion, glomerulosclerosis and progressive loss of renal function. Current therapeutic strategies of DN, including renin–angiotensin–aldosterone system (RAAS) blockade, glucagon-like peptide-1 receptor agonists, non-steroidal mineralocorticoid receptor, and sodium-glucose cotransporter-2 (SGLT2) inhibitors, only slow the progression of the disease rather than reversing the pathology. Therefore, there is a growing interest in identifying alternative or complementary therapeutic agents, particularly those derived from natural products with multi-targeted activities. Psoralea corylifolia Linn (PCL) is a medicinal herb commonly used in traditional Asian medicine. It has known pharmacological properties on oxidative stress, inflammation, fibrosis and metabolic disorders. Accumulating recent studies indicated that PCL and its bioactive compounds, such as psoralen, bakuchiol, and corylin, mitigate pathological conditions in various diseases. Here, the current review will provide our current knowledge of major identified and characterized PCL focusing on their biological activity and function, particularly in DN. Full article

Small ruminant lentivirus (SRLV) infects goats and sheep of all breeds and ages worldwide. There are no current records regarding the three-dimensional structure or antigenic capacity of the nucleocapsid protein p14 of FESC-752 Mexican strain. The antigenic structure of p14 protein of a B1 genotype was predicted. cDNA from FESC-752 was used to overexpress the recombinant SRLV-rp14 protein. Then, its antigenicity was verified in vitro by evaluating plasma samples from goats and sheep naturally infected with SRLV. Antigenicity prediction showed a “horseshoe”-type structure shared by different lentiviruses and five epitopes distributed throughout the p14 surface regions where they coincide suggesting conserved epitopes in the zinc-finger structures of the nucleoproteins of the SRLV, Human Immunodeficiency Virus (HIV-1), and Feline Immunodeficiency virus (FIV) retroviruses. Multi-species molecular docking showed a notable structural convergence where caprine, bovine, murine, and human immunoglobulins target a predictive 23 amino acid epitope (residues 41–64) within the core zinc-finger region. Furthermore, CABS docking simulations predicted that p14-derived peptides preferentially bind within the antigen-presenting cleft of both caprine and bovine major histocompatibility complex class I (MHC-I) molecules. The stability of these immunological complexes is mediated by dense networks of hydrophobic interactions and highly conserved aromatic anchoring residues. Antigenicity analysis revealed that 78.7% of samples from naturally infected goats showed immunoreactivity toward SRLV-rp14 and the predictive evidence that p14 can simultaneously stimulate both humoral and cellular pathways makes it a strategic candidate for the design of next-generation vaccines aimed at controlling lentiviruses in small ruminants. Full article

Bioactive peptides derived from whey proteins have attracted increasing interest as natural dietary modulators of angiotensin-converting enzyme (ACE) activity and potential contributors to cardiovascular health. In this study, bioactive whey hydrolysate (BWH) was obtained by controlled enzymatic hydrolysis with plant-derived proteases and characterized in terms of physicochemical properties, peptide profile, ACE-inhibitory activity, stability, and performance in food matrices. RP-HPLC and LC–MS/MS analysis revealed a complex, reproducible peptidome across production batches, including a conserved set of antihypertensive peptide sequences. BWH exhibited high ACE-inhibitory activity (>90%) with low intra-batch variability, and dose–response analysis yielded an estimated IC₅₀ of 3.20% BWH under the assay conditions. Its bioactivity and peptide profile remained stable during storage at room temperature and under refrigeration, as well as after mild thermal treatment (pasteurization), although partial activity loss was observed after baking at high temperatures. Incorporation trials showed that BWH retained strong ACE-inhibitory functionality when incorporated at 7% into yogurt and orange juice, with minimal effects of pasteurization in the beverage matrix. These findings support the potential use of BWH as a functional ingredient for developing antihypertensive foods and beverages. Full article