Search Results (1,371)

Background: The endocannabinoid system (ECS) and the Kisspeptin system (KS) play crucial roles in the central and peripheral regulation of male reproduction. The KS comprises Kisspeptins, the cleavage product of the Kiss1 protein, and its receptor Kiss1R; it is a critical central regulatory factor of the Gonadotropin Releasing Hormone (GnRH), but its role in the testis in sustaining spermatogenesis is not fully understood. Similarly, in addition to the brain, the ECS is widely expressed in the testis, where it regulates spermatogenesis, steroidogenesis, and the production of high-quality gametes. Since the possible crosstalk between KS and ECS at the gonadal level is poorly understood, this study investigates the possible mutual modulation between ECS and KS in rat testis. Methods: Experiment 1: Testis pieces collected from adult rats were treated ex vivo for 1 h with the endocannabinoid anandamide (AEA, 10⁻⁸ M) ± SR141716A (10⁻⁷ M, a cannabinoid receptor (CB) 1 antagonist), or with SR141716A alone. Experiment 2: Testis pieces were treated for 4 h with decreasing doses of Kisspeptin-10 (Kp10, 10⁻⁶–10⁻⁹ M) ± Kp234 (a Kiss1R antagonist). Proteins extracted from the treated tissues were analyzed by Western blot for Kiss1R, Kiss1, CB1, CB2, AEA-hydrolyzing enzyme Fatty Acid Amide Hydrolase (FAAH), and AEA-biosynthetic enzyme N-acylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD) proteins. Results: AEA treatment, via CB1, reduced Kiss1R protein in testis. Kp10 treatment increased the expression of CBs and NAPE-PLD at all doses and increased FAAH at 10⁻⁹ M dose only. Pre-incubation with Kp234 abolished Kp10 effects on CB1, NAPE-PLD, and FAAH, suggesting a direct Kp10-dependent modulation; on the other hand, pre-incubation with Kp234 did not abolish Kp10’s effects on CB2, suggesting an indirect action of Kp10 on CB2. Conclusions: Mutual modulation between ECS and KS exists in the testis: AEA, via CB1, suppresses Kisspeptin signaling, while Kisspeptin regulates the ECS through both Kiss1R-dependent and independent mechanisms. These local interactions identify new potential mechanisms in the intratesticular communications sustaining spermatogenesis via ECS and suggest that KS might be a new therapeutic target to rescue ECS impairment in male reproductive dysfunction. Full article

Background: Soil streptomycetes, particularly those isolated from extreme environments, are valuable sources of bioactive compounds. Their genomes encode a large number of biosynthetic gene clusters (BGCs), many of which can be simultaneously expressed. Methods: Molecular genetic methods were employed to identify Streptomyces anulatus 89 (Illumina NovaSeq 2 × 150 bp). Whole-genome phylogeny based on orthologous genes was employed using the Bacterial and Viral Bioinformatics Resource Centre services. Liquid chromatography–mass spectrometry analysis of biomass extract was carried out to identify antibiotics. Bioassays on cell lines were employed to evaluate the cytotoxicity and antitumor activity of the crude extract of the S. anulatus 89 strain. Results: Genome analysis identified 36 BGCs associated with secondary metabolites. The strain synthesized nactins, pladienolide, phenazinomycin, and 21-hydroxyoligomycin. The biomass extract demonstrated cytotoxicity against cancer cells and induced apoptosis. The A549 and A431 cell lines were the most sensitive. Changes in tumor cell morphology included rounding, shrinkage, increased granularity, and vacuolization. Conclusions: The ability of S. anulatus 89 to simultaneously synthesize different classes of anticancer antibiotics was reported. The investigated crude extract exhibited pronounced antitumor activity, making it a promising candidate for further studies. The underlying hypothesis suggested that strains with broad adaptive potential may serve as promising producers of natural products with antitumor properties. Full article

Endophytic fungi from Malaysian medicinal plants constitute a metabolically prolific yet underexplored reservoir for natural product discovery. This scoping review of 56 studies published between 2015 and 2025 identified a fundamental methodological divergence within the field: while phenotypic bioactivity screening dominates the literature (>87% of studies), it is weakly supported by chemical characterization (<25%) and entirely disconnected from genomic investigation (0% biosynthetic gene cluster studies). This phenotype-first paradigm has largely confined the field to descriptive reporting, limiting mechanistic understanding and translational potential. Collectively, the evidence reveals a substantial disconnect between reported bioactivities and their underlying biosynthetic foundations. To address this limitation, a practical genotype-to-phenotype workflow is proposed that integrates strain prioritisation, multi-omics-guided activation, chemical mapping, and mechanism-oriented validation. By linking genomic potential with metabolite production and biological function, this framework provides a roadmap for advancing fungal natural product discovery beyond conventional phenotype-driven screening. Adoption of such approaches may improve the identification of chemically novel and biologically relevant metabolites while supporting the sustainable development of Malaysia’s endophytic fungal resources for biotechnological and pharmaceutical applications. Full article

Gibberellic acids (GAs) are a class of tetracyclic diterpene carboxylic acid compounds produced by green plants, fungi, and bacteria, which have a wide range of applications in agricultural production and food ingredients processing. Owing to the continuously growing market demand, enhancing GA yield has become imperative. The biosynthesis of GAs is a multi-enzymatic synergistic process that can be enhanced through genetic and metabolic engineering strategies. In this review, we first summarize recent advances in GA production by Fusarium fujikuroi. We then highlight key metabolic engineering strategies, including biosynthetic pathway engineering, cluster-specific channeling of geranylgeranyl diphosphate biosynthesis, cofactor engineering, as well as regulatory mechanisms involving nitrogen modulation and histone modification. Finally, we discuss promising approaches for constructing high-efficiency microbial cell factories, such as implementation of the CRISPR/Cas9 system, the application of strong promoters, the development of target-specific technologies for small molecules, and the employment of genome-scale metabolic models. Recent metabolic engineering efforts have achieved GA3 titers of up to 3.16 g/L through multi-target nitrogen regulation strategies, highlighting the potential for further yield improvement. Full article

The vast majority of the ocean’s microbial natural product biosynthetic potential remains undescribed. To access this chemical diversity, we employed Small Molecule In Situ Resin Capture (SMIRC) across three ecologically distinct sites in San Diego, California. Using high-resolution LC-MS/MS, we detected spatial and temporal variability in the metabolomes captured. Low annotation rates and evidence of extensive halogenation supported the chemical novelty of the compounds captured. We detected rare chlorinated polyketides in the pinnaic acid class, previously known only from filter-feeding invertebrates. We also report the first detection of chlorosulfolipids in the Pacific Ocean including one that contained 11 chlorine atoms. We linked compound abundances to weekly phytoplankton counts to identify candidate producers and found evidence that different taxa produce chlorosulfolipids of different carbon chain lengths. This study provides evidence of the chemical novelty that can be captured directly from the environment and a framework for integrating environmental metabolomics with phytoplankton counts as a method to identify candidate compound producers. Full article

Melanoma remains highly lethal with frequent resistance to current therapies. Here we identify a marine-derived cyclopentapeptide, turnagainolide B, as a potent anti-melanoma agent that selectively kills B16-F10 melanoma cells (IC₅₀ = 50 μM) with low toxicity to normal skin cells. Using bioassay-guided isolation, we also obtained a new analogue, turnagainolide H, and elucidated their structures and biosynthetic pathways. Mechanistically, turnagainolide B induces a previously undescribed “dual-hit” autophagic signature: it simultaneously promotes autophagy initiation (via PI3K/mTOR suppression, evidenced by ATG5 and LC3B-II upregulation) and blocks autophagic degradation (evidenced by p62 accumulation). Co-treatment with chloroquine partially rescued cell viability and decreased LC3B levels, confirming that cell death depends on active autophagic flux disruption. Transcriptomic analysis, together with AI target prediction and docking, identified PI3K as a potential direct target, with downregulation of PI3K, mTOR, and BNIP3 supporting an imbalanced autophagic state. In a syngeneic mouse melanoma model, turnagainolide B significantly suppressed tumor growth, reduced melanin content and Ki67 expression, and enhanced CD8⁺ T cell infiltration. Collectively, this work expands the chemical diversity of the turnagainolide family, uncovers a unique “dual-hit” autophagic mechanism, and establishes turnagainolide B as a promising lead for melanoma therapy. Full article

Salt stress severely restricts plant growth and reduces crop yield. Strigolactones (SLs) are carotenoid-derived phytohormones involved in the regulation of plant salt tolerance. Salt stress can modulate the expression of SL biosynthetic and signaling genes, thereby affecting SL accumulation and signaling responses. SLs also interact with abscisic acid (ABA), reactive oxygen species (ROS), and other signaling molecules to coordinate downstream stress responses. At the physiological level, SLs alleviate salt stress by maintaining Na⁺/K⁺ homeostasis, enhancing osmotic adjustment and antioxidant defense, and reducing damage to the photosynthetic system. In addition, SLs can enhance plant resource acquisition and adaptive capacity under salt stress by regulating root architecture and promoting hyphal branching of arbuscular mycorrhizal fungi (AMF). This review focuses on SL-mediated regulation of plant salt tolerance at the molecular and physiological levels and further summarizes exogenous SL application strategies for alleviating salt stress, as well as research progress on key genes in the SL pathway for the genetic improvement of salt tolerance. Clarifying the potential of SLs in regulating plant responses to salt stress could provide new insights into sustainable crop production in saline-alkali environments. Full article

Wax gourd (Benincasa hispida (Thunb.) Cogn.), a monotypic member of the Cucurbitaceae family, is a globally significant vegetable crop distinguished by its versatile nutritional and therapeutic properties. This review systematically synthesizes current knowledge on the phytochemical composition and pharmacological potential of various botanical parts, thereby bridging ethnobotanical history with modern molecular insights. Recent advancements in multi-omics technologies, particularly metabolomics and chromatography–mass spectrometry, have significantly deepened the characterization of its bioactive constituents, including specific proteins, enzymes, peptides, flavonoids, triterpenes, sterols, and polysaccharides. Special emphasis is placed on the molecular mechanisms and biosynthetic pathways underlying its pharmacological activities-ranging from antioxidant, anti-inflammatory, and immunomodulatory effects to metabolic regulation involving anti-ulcer, nephroprotective, and hypotensive properties. Recent investigations have identified over 60 bioactive compounds, including cucurbitacins, flavonoids, polysaccharides, and phenolic acids in wax gourd, and elucidated their anti-diabetic, anti-cancer, and organ-protective effects through multiple signaling pathways. By integrating traditional medicinal applications with emerging genomic insights-including recent whole-genome sequencing and QTL mapping studies-this review highlights the current understanding of the genetic basis underlying fruit quality and discusses the potential for molecular breeding approaches and the development of functional nutraceuticals. Ultimately, wax gourd represents a valuable candidate for leveraging horticultural science to enhance human health and disease management. Full article

Clonal hematopoiesis of indeterminate potential (CHIP) and the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) are both linked to NLRP3-mediated cardiovascular inflammation, but their interaction has not previously been explored. This work proposes the CHIDT axis (clonal hematopoiesis–dysbiosis–TMAO), a feed-forward mechanism in which TET2 loss-of-function CHIP- and TMAO-generating Gram-negative gut dysbiosis mutually enhance cardiovascular risk. The model proceeds in three nodes. CHIP-associated intestinal immune dysregulation promotes luminal expansion of Gammaproteobacteria, which produce both trimethylamine via CntA/CntB-mediated L-carnitine oxidation and ADP-heptose as an obligate LPS biosynthetic intermediate. TMAO amplifies NLRP3 inflammasome activation through the SIRT3 → SOD2 → mtROS pathway. The evidence base of the CHIDT model is strongest for TET2-CHIP; the proposed extension to DNMT3A-CHIP rests on indirect, associative data and requires dedicated experimental confirmation before it can be considered established. TXNIP cascade, with predicted disproportionate potency in macrophages epigenetically primed by TET2 haploinsufficiency. High concentrations of TMAO have also been shown to suppress TET2 expression in endothelial cells through CYTB promoter hypermethylation, inducing NLRP3–GSDMD-dependent pyroptosis, although it remains unclear whether physiological TMAO levels can trigger this effect. Concurrently, ADP-heptose activates the ALPK1–TIFA–NF-κB pathway in bone marrow progenitors, favoring the expansion of mutant hematopoietic stem and progenitor cells. The model identifies three potential therapeutic strategies: NLRP3 inhibition, microbial TMA lyase inhibition, and microbiome-targeted reduction in Gram-negative bacteria. None has been tested in CHIP carriers stratified by plasma TMAO. Further studies in preclinical models and human cohorts integrating CHIP genotyping and TMAO quantification are needed to validate the CHIDT axis as a target for precision cardiovascular prevention. Full article

Surfactin is a lipopeptide biosurfactant with significant industrial potential, but high production costs have hindered its commercialization. In this study, we developed a sustainable and cost-effective bioprocess for surfactin biosynthesis using Bacillus subtilis 55033, utilizing kitchen waste as the primary fermentation substrate without any previous pretreatment—an advantage that simplifies the process and reduces costs compared to previous reports. To maximize productivity, the fermentation parameters were systematically optimized through single-factor and orthogonal experimental designs. The optimal conditions were as follows: a fermentation temperature of 31 °C, a duration of 48 h, a 5% v/v inoculum, a 7% w/v solid-to-liquid ratio, an initial pH of 7.5, and an agitation speed of 200 rpm. Under these conditions, the surfactin yield reached 371.67 mg/L, an increase of 100.5% from 185.4 mg/L prior to optimization. We performed a comparative analysis of the surfactin biosynthetic gene clusters between B. subtilis 55033 and the model strain B. subtilis 168. The produced surfactin exhibited potent antagonistic activity against aquatic pathogens, significantly inhibiting the growth of several species of Vibrio and the division and hatching of Cryptocaryon irritans Tomonts. These findings demonstrate that our platform not only provides a high-value valorization route for organic waste but also enables preliminary exploration of surfactin applications in aquaculture, in line with the principles of a circular bioeconomy. Full article

Natural microbial pigments offer important advantages and are widely studied for food applications. We investigated the biosynthetic pathways, characteristics, and bioactivities of the orange–red pigment produced by Bacillus velezensis YM–3, a strain isolated from the traditional Pixian Douban condiment. Whole-genome sequencing revealed complete pathways for melanin, phytoene, and heme biosynthesis. The purified extracellular pigment was characterized using ultraviolet–visible spectroscopy, Fourier-transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and ultra-performance liquid chromatography–high-resolution mass spectrometry; it was preliminarily characterized as melanin-like pigment. The pigment was highly soluble in alkaline solutions, moderately soluble in water, and insoluble in common organic solvents. It exhibited strong photostability and remained stable at low temperature, precipitated under acidic conditions, and showed high stability under alkaline environments. Furthermore, the pigment demonstrated in vitro free radical scavenging activity. Hence, this study provides a scientific foundation for exploring the potential utility of B. velezensis YM–3 and its pigment metabolites as functional agents. Full article

Amaranthin is a major red-violet betacyanin of Amaranthaceae and an increasingly relevant natural pigment for food, cosmetic, nutraceutical, and biotechnological applications. This review integrates knowledge from over 100 studies, addressing amaranthin as a chemically defined betalain, distinguishing it from other scientific uses of the term, and evaluates its natural sources, analytical methods, extraction strategies, in vitro production systems, biosynthetic regulation, and biological activity. Cultivated Amaranthus species are among the richest plant sources, with total betacyanins of 46.1–199 mg/100 g fresh weight and amaranthin comprising, on average, 80.9% of the pigment fraction. Reliable identification and quantification rely on high-performance liquid chromatography coupled with a diode array detector (HPLC-DAD), liquid chromatography-tandem mass spectrometry (LC-MS/MS), and ultraviolet–visible (UV–Vis) spectrophotometry. Microwave- and ultrasound-assisted extraction can improve pigment recovery under optimized conditions, although its stability depends strongly on pH, temperature, solvent, time and storage parameters. While plant in vitro cultures, including callus, suspension, and shoot systems, have clarified biosynthetic regulation and offer controlled production platforms, engineered yeast systems have recently expanded production options, with Yarrowia lipolytica reaching 2.97 ± 0.029 g L⁻¹ amaranthin in fed-batch fermentation. Amaranthin-rich extracts and amaranthin-type pigments show antioxidantand anti-inflammatory potential, while antimicrobial and antiviral activities have mainly been reported for mixed betacyanin fractions; direct mechanistic, bioavailability, and in vivo evidence for purified amaranthin remains limited. Standardized analytical protocols, further investigation of stable high-yield sources, physicochemical stability assessment, and structure–activity studies are identified as priorities for advancing future application-oriented research on this multipotential pigment. Full article

As the direct biosynthetic precursor of creatine, guanidinoacetic acid (GAA) exerts a pivotal regulatory role in energy homeostasis and protein metabolism. Rabbit meat has garnered increasing global recognition as a healthy food source, characterized by its outstanding high-protein and low-fat nutritional profile. Accordingly, the optimization of rabbit meat quality has attracted growing attention from both consumers and animal production practitioners. In the present study, we evaluated the impacts of dietary GAA supplementation on meat quality traits, in vivo antioxidant capacity, muscle fiber characteristics, and fatty acid metabolism in New Zealand white rabbits. A total of 960 male New Zealand white rabbits were assigned to two age groups: 40-day-old group and 60-day-old group (40 ± 2 days, 1.19 ± 0.09 kg; 60 ± 2 days, 1.82 ± 0.15 kg). Within each age group, rabbits were randomly allocated to a control diet or a diet supplemented with 100 mg/kg GAA (CON-40, GAA-40, CON-60, GAA-60). After a 45-day feeding period, two-way ANOVA revealed that GAA supplementation significantly reduced shear force (p < 0.01, diet main effect) and muscle fiber density (p < 0.01, diet main effect), with an age-dependent effect on shear force (age × diet interaction, p < 0.05). Moreover, GAA enhanced systemic antioxidant capacity, as indicated by increased serum superoxide dismutase (SOD) activity (p < 0.01) and total antioxidant capacity (T-AOC) (p < 0.05), while no significant effect on malondialdehyde (MDA) was detected under the current experimental conditions. GAA also regulated the expression of lipid metabolism-related genes (FAS, HSL, ACC) in intramuscular and perirenal fat, indicating its regulatory effect on fatty acid metabolism. In conclusion, dietary GAA supplementation improves rabbit meat tenderness and antioxidant capacity, with no negative effects on growth performance. These findings confirm that GAA has the potential to serve as a nutritional strategy to improve rabbit meat quality, supporting the development of rabbit meat as a functional food for human consumption. Full article

Antibiotic resistance and biofilm-associated infections require sustainable antimicrobial platforms that combine efficacy with biocompatibility. Fermented matrices are attractive for green nanomaterial production because they provide reducing metabolites and surface-active capping compounds. Rooibos kombucha is a polyphenol-rich fermentation system with potential to serve as a biosynthetic matrix for silver nanoparticles (AgNPs). The present work aimed to develop a rooibos kombucha-enabled platform for the green biosynthesis of phytochemical-capped silver nanoparticles, AgNPs-K, and evaluate their antibacterial, antibiofilm, and in vivo activity. Rooibos kombucha was fermented for 14 days and profiled by liquid chromatography–tandem mass spectrometry (LC–MS/MS). AgNPs-K were generated using kombucha extract and AgNO₃, purified, and characterized by ultraviolet–visible spectroscopy (UV–Vis), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and nanoparticle tracking analysis. Antibacterial activity against eight Gram-positive and Gram-negative reference pathogens was assessed by EUCAST-based microdilution and time-kill assays. Biofilm inhibition was measured by the crystal violet assay. In vivo toxicity and therapeutic efficacy were evaluated in Galleria mellonella larvae. AgNP formation was confirmed by a surface plasmon resonance (SPR) peak at 415 nm. TEM showed predominantly spherical nanoparticles with a main size range of 20–30 nm, a hydrodynamic diameter of 98 nm, and a zeta potential of −14.62 ± 0.04 mV. AgNPs-K showed overlapping minimum inhibitory concentration and minimum bactericidal concentration values of 1.14 µg/mL for Gram-positive species and 1.33 µg/mL for Gram-negative species. Time-kill assays showed rapid bactericidal activity after threshold concentrations were reached, with sustained suppression at 24 h. Biofilm formation was abolished at 40 µg/mL and strongly reduced at lower concentrations. AgNPs-K were non-toxic up to 400 µg/mL and improved survival in six of seven infection models. Fermented rooibos kombucha functions as an effective biosynthetic matrix for the green production of phytochemical-capped AgNPs. The resulting nanoparticles combine low-dose antibacterial and antibiofilm activity with favorable in vivo tolerability and efficacy, supporting fermentation-enabled nanobiotechnology strategies against biofilm-associated infection. Full article

Histamine accumulation in foods poses significant public health risks, yet current control strategies present important limitations. This study assessed the in vitro antimicrobial activity of silica microparticles covalently functionalized with thymol (SiO₂-THY) and eugenol (SiO₂-EUG) against four representative histamine-producing bacterial strains: Raoultella planticola, Limosilactobacillus reuteri, Levilactobacillus hilgardii, and Pediococcus parvulus. For this purpose, functionalized particles were characterized by FESEM, zeta potential measurements, and elemental analysis, confirming successful immobilization of both compounds at comparable functionalization degrees (137–139 mg EOC/g SiO₂). Functionalized materials exhibited significant antimicrobial activity against all tested strains, with reductions exceeding 3 logarithmic cycles at the lowest concentrations tested. This effect is attributed to the functionalized particles altering bacterial membrane fluidity and disrupting membrane potential, thereby impairing cellular homeostasis, as revealed by mechanistic assays. Among the strains confirmed as histamine producers, SiO₂-THY and SiO₂-EUG substantially reduced histamine formation, with reductions reaching up to approximately 100% at bactericidal concentrations and remaining significant at sub-inhibitory levels. These findings suggest that immobilized compounds interfere not only with bacterial growth but also with histamine biosynthetic pathways. Therefore, the use of silica-immobilized essential oil constituents represents a promising strategy for mitigating histamine accumulation and enhancing food safety. Nevertheless, further validation in relevant food matrices is required. Full article