Search Results (2,861)

Xylella fastidiosa (Xf) is a Gram-negative bacterium responsible for severe diseases in several commercially significant crops, including olive, grapevine, citrus and almond. Its management is particularly challenging due to its transmission via widespread vector insects, its ability to form biofilms, its high genetic diversity and, sometimes, latent symptoms. Current control strategies focus on integrated and preventive approaches, including the use of resistant varieties, agronomic practices, and vector control through chemical and biological methods. Direct control of the bacterium has always been a complex challenge that includes strategies to limit vector presence and activity in the field; however, several compounds have recently been evaluated that are able to inhibit biofilm formation and Xf growth. This review provides an up-to-date summary of studies investigating the efficacy of various treatments based on organic compounds, synthetic molecules and salt- or metal-based formulations. By evaluating the results of in vitro and in vivo experiments, the most promising solutions were identified that address the main challenges and limitations of chemical control strategies. These include N-acetylcysteine and zinc- and copper-based formulations, which are effective and potentially transferable to the field for crops such as citrus and olive trees. Antimicrobial peptides and nanoparticles, on the other hand, have demonstrated high efficacy in vitro, although further studies directly in the field are required. The evidence emerging from the analyzed studies offer insights to guide future research towards more effective and sustainable management approaches to mitigate the spread and impact of Xf. Full article

The emergence of multi-drug-resistant bacteria (known as superbugs) represents one of the greatest challenges for human health and modern medicine. Due to their remarkable ability to rapidly develop resistance to currently used antibiotics, new molecular targets for bacteria and substances capable of effectively combating related infections are still being sought. Lasso (known also as lariat) peptides are an unusual subclass of ribosomally synthesized and post-translationally modified peptides (RiPPs) with a structurally constrained knotted fold resembling a lasso. They are synthesized by certain groups of microorganisms as a result of complex processes involving intricate structural changes leading to the formation of the lasso structure. Reproducing these processes using known peptide synthesis methods poses a major challenge for synthetic chemistry. Lasso peptides exhibit a range of bioactivities including antibacterial activity. Due to the lasso structure, the peptides are capable of binding to new molecular targets, including atypical sides of ribosomes, in relation to currently used antibiotics. Thus, creating new mechanisms that inhibit metabolic processes leading to the death of pathogenic bacteria. This feature makes lasso peptides a potential “last chance” weapon in the fight against emerging superbugs. Full article

Background/Objectives: Diabetes mellitus (DM) is an increasingly prevalent endocrine disorder affecting humans and companion animals. Type 1 DM (T1DM) and type 2 DM (T2DM) are well characterized in humans, and canine DM most often resembles T1DM, marked by insulin dependence and β-cell destruction. Conversely, feline DM shares key features with human T2DM, including insulin resistance, obesity-related inflammation, and islet amyloidosis. This review provides a comprehensive comparative analysis of antidiabetic therapies in humans, dogs, and cats, focusing on three core areas: disease pathophysiology, pharmacological and delivery strategies, and translational implications. In human medicine, a wide array of insulin analogs, oral hypoglycemic agents, and incretin-based therapies, including glucagon-like peptide-1 receptor agonists (liraglutide) and sodium-glucose cotransporter-2 inhibitors (empagliflozin), are available. Veterinary treatments remain limited to species-adapted insulin formulations and off-label use of human drugs. Interspecies differences in gastrointestinal physiology, drug metabolism, and behavioral compliance influence therapeutic efficacy and pharmacokinetics. Recent innovations, such as microneedle patches for insulin delivery and continuous glucose monitoring systems, show promise in humans and animals. Companion animals with naturally occurring diabetes serve as valuable models for preclinical testing of novel delivery platforms and long-acting formulations under real-world settings. While these technologies show potential, challenges remain in regulatory approval and behavioral adaptation in animals. Conclusions: Future research should prioritize pharmacokinetic bridging studies, veterinary-specific formulation trials, and device validation in animal models. By highlighting shared and species-specific characteristics of DM pathogenesis and treatment, this review advocates a One Health approach toward optimized antidiabetic therapies that benefit human and veterinary medicine. Full article

Background/Objectives: The global increase in multidrug-resistant (MDR) bacterial infections underscores the urgent need for effective and sustainable antimicrobial alternatives. This study investigates the antimicrobial activity of exometabolite-based formulations (ExAFs), derived from the cell-free supernatants (CFS) of native lactic acid bacteria (LAB) applied individually or in combination thereof, against MDR-Escherichia coli strain L1PEag1. Methods: Fourteen ExAFs were screened for inhibitory activity using time–kill assays, and structural damage to bacterial cells was assessed via scanning and transmission electron microscopy (SEM/TEM). The most potent formulation was further characterized by liquid chromatography–tandem mass spectrometry (LC–MS/MS) employing a Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectra (SWATH) approach for untargeted metabolite profiling. Results: Among the tested formulations, E10, comprising CFS from Weissella cibaria UTNGt21O, exhibited the strongest inhibitory activity (zone of inhibition: 17.12 ± 0.22 mm), followed by E1 (CFS from Lactiplantibacillus plantarum Gt28L and Lactiplantibacillus plantarum Gt2, 3:1 v/v) and E2 (Gt28L CFS + EPS from Gt2, 3:1 v/v). Time–kill assays demonstrated rapid, dose-dependent bactericidal activity: E1 and E10 achieved >98% reduction in viable counts within 2–3 h, at 1× MIC, while E2 sustained 98.24% inhibition over 18 h, at 0.25× MIC. SEM and TEM revealed pronounced ultrastructural damage, including membrane disruption, cytoplasmic condensation, and intracellular disintegration, consistent with a membrane-targeting mode of action. Metabolomic profiling of E10 identified 22 bioactive metabolites, including lincomycin, the proline-rich peptide Val–Leu–Pro–Val–Pro–Gln, multiple flavonoids, and loperamide. Several compounds shared structural similarity with ribosomally synthesized and post-translationally modified peptides (RiPPs), including lanthipeptides and lassopeptides, suggesting a multifaceted antimicrobial mechanism. Conclusions: These findings position ExAFs, particularly E10, as promising, peptide-rich, bio-based antimicrobial candidates for food safety or therapeutic applications. The co-occurrence of RiPP analogs and secondary metabolites in the formulation suggests the potential for complementary or multi-modal bactericidal effects, positioning these compounds as promising eco-friendly alternatives for combating MDR pathogens. Full article

Cathelicidins are a family of antimicrobial peptides (AMPs) with broad-spectrum activity and immunomodulatory functions. Among them, the only human cathelicidin LL-37 has garnered significant interest due to its potent antimicrobial, antiviral, antifungal, antiparasitic, and antitumor properties. However, the clinical application of LL-37 is hindered by several limitations, including low proteolytic stability, cytotoxicity, and high production costs. To overcome these challenges, a wide range of design strategies have been employed to modify LL-37 and improve its therapeutic potential. LL-37-based analogs represent promising candidates for the development of next-generation antimicrobial and immunomodulatory therapies. Despite significant progress, further research is required to optimize peptide design, ensure cost-effective production, and validate long-term safety and efficacy. Advances in computational modeling, high-throughput screening, and nanotechnology will play an important role in the translation of modified cathelicidins into clinical practice. This review summarizes key strategies of chemical and structural modifications of LL-37 aimed at enhancing its functional properties. Particular attention is given to truncated and retro-analogs, which preserve or improve biological activity while exhibiting reduced toxicity and increased proteolytic resistance. Furthermore, we highlight the use of nanoscale delivery systems, which facilitate targeted delivery, prolong peptide half-life, and mitigate cytotoxic effects. Full article

Despite significant medical advancements, two major health challenges persist: antibiotic resistance in microbial pathogens and drug resistance in cancer cells. To address these issues, research has increasingly focused on discovering novel natural compounds with dual antimicrobial and anticancer activities. Among such candidates, antimicrobial peptides (AMPs) have attracted attention due to their ability to selectively target microbial and cancer cells while exhibiting minimal toxicity toward normal cells. Although Vietnam possesses rich biodiversity, including a wide range of Anura species, studies on AMPs from these organisms remain limited. In this study, a novel AMP, brevinin-1 E8.13, was identified from the skin secretion of Sylvirana guentheri, a frog species native to Vietnam. The brevinin-1 E8.13 peptide was successfully cloned, sequenced, and chemically synthesized. Functional assays revealed that brevinin-1 E8.13 possesses strong antibacterial activity against Staphylococcus aureus and exerts significant antiproliferative effects on various human cancer cell lines, including A549 (lung), AGS (gastric), Jurkat (leukemia), HCT116 (colorectal), HL60 (leukemia), and HepG2 (liver). The peptide demonstrated moderate to potent cytotoxic activity, with IC₅₀ values ranging from 7.5 to 14.8 μM, depending on the cell type. Notably, brevinin-1 E8.13 exhibited low cytotoxicity toward normal human dermal fibroblast (HDF) cells and even promoted cell proliferation at lower concentrations. Furthermore, Chemically Activated Fluorescent Expression (CAFLUX) bioassay results confirmed that the peptide significantly downregulated Cyp1a1 gene expression in HepG2 cells. Collectively, these findings highlight the therapeutic potential of brevinin-1 E8.13 as a dual-function antimicrobial and anticancer agent derived from the skin secretion of Sylvirana guentheri. Full article

Background/Objectives: Infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa are steadily increasing, thus the discovery and development of new and effective agents are needed. Antimicrobial peptides (AMPs) are a heterogeneous group of innate defense system peptides with broad antimicrobial activity. In this study, 17 AMPs were tested, identifying CAP-18, a cathelicidin-based compound, as the most active. CAP-18 was optimized by synthesizing structural derivatives, which were selected for further studies based on their activity against a collection of MDR and colistin-resistant P. aeruginosa strains. Methods: AMPs collection was initially tested against different P. aeruginosa strains, identifying CAP-18 as the most active. CAP-18 derivatives were synthetized and assessed by the Minimum Inhibitory Concentration (MIC), time-kill kinetics, cytotoxicity against human cell lines, hemolytic activity, and therapeutic index (IC₅₀/MIC₉₀). The mechanism of action was assessed by Transmission Electron Microscopy (TEM), and in vivo efficacy was determined through a murine skin infection model. Results: CAP-18 and D-CAP-18 had a MIC₉₀ of 4 and 2 μg/mL, respectively, whereas CAP-18₃₁ and D-CAP-18₃₁ presented MIC₉₀ values of 16 mg/L. The shorter derivatives of CAP-18 showed a lower activity. Time-kill curves revealed a fast bactericidal effect. These derivatives showed low toxicity against different human cell lines and low hemolysis, resulting in a wide therapeutic index (IC₅₀/MIC₉₀), with D-CAP-18 having the best therapeutic index (137.4). TEM provided insight into the mechanism of action, revealing bacterial membrane damage. In vivo studies of both CAP-18 and D-CAP-18 showed good activity with a 3 log decrease compared to the infected control group. Conclusions: Among the investigated four peptides, D-CAP-18 is the most promising candidate to treat skin infections caused by MDR P. aeruginosa since it shows potent activity both in vitro and in vivo, and a high therapeutic index. Full article

Regular physical activity induces a dynamic crosstalk between skeletal muscle and adipose tissue, modulating the key molecular pathways that underlie metabolic flexibility, mitochondrial function, and inflammation. This review highlights the role of myokines and adipokines—particularly IL-6, irisin, leptin, and adiponectin—in orchestrating muscle–adipose tissue communication during exercise. Exercise stimulates AMPK, PGC-1α, and SIRT1 signaling, promoting mitochondrial biogenesis, fatty acid oxidation, and autophagy, while also regulating muscle hypertrophy through the PI3K/Akt/mTOR and Wnt/β-catenin pathways. Simultaneously, adipose-derived factors like leptin and adiponectin modulate skeletal muscle metabolism via JAK/STAT3 and AdipoR1-mediated AMPK activation. Additionally, emerging exercise mimetics such as the mitochondrial-derived peptide MOTS-c and myostatin inhibitors are highlighted for their roles in increasing muscle mass, the browning of white adipose tissue, and improving systemic metabolic function. The review also addresses the role of anti-inflammatory compounds, including omega-3 polyunsaturated fatty acids and low-dose aspirin, in mitigating NF-κB and IL-6 signaling to protect mitochondrial health. The resulting metabolic flexibility, defined as the ability to efficiently switch between lipid and glucose oxidation, is enhanced through repeated exercise, counteracting age- and disease-related mitochondrial and functional decline. Together, these adaptations demonstrate the importance of inter-tissue signaling in maintaining energy homeostasis and preventing sarcopenia, obesity, and insulin resistance. Finally, here we propose a stratified treatment algorithm based on common age-related comorbidities, offering a framework for precision-based interventions that may offer a promising strategy to preserve metabolic plasticity and delay the age-associated decline in cardiometabolic health. Full article

Proximity biotinylation, which utilizes various biotin ligating enzymes (BioID, TurboID, etc.), is widely used as a powerful tool for identifying novel protein–protein interactions. However, this method has a significant limitation: the use of streptavidin on beads for enriching biotinylated proteins often results in a high background of peptides from streptavidin itself, which interferes with identification by peptide mass fingerprinting. This limitation makes it practically impossible to study samples containing a small amount of material, such as individual insect tissues. In this study, we compared different precipitation and elution conditions for the purification of biotinylated proteins from protein extracts of Drosophila melanogaster S2 cells. We found that biotinylated proteins can be purified using anti-biotin antibodies, although with lower efficiency than streptavidin-based resin. We also demonstrated that protease-resistant streptavidin (prS), previously tested in mammalian cells, can be used effectively to purify biotinylated proteins from tissues of D. melanogaster. In our experiments, prS showed precipitation efficiency comparable to regular streptavidin but generated a lower background in peptide fingerprinting. To further demonstrate the applicability of prS for studying protein–protein interactions in D. melanogaster tissues, we carried out experiments to identify interaction partners of the ecdysone receptor (EcR) in D. melanogaster ovarian tissue using TurboID-based proximity biotinylation. As a result, EcR was found to interact with both previously described and novel protein partners in Drosophila ovaries. Full article

Conventional immediate and high-temperature immediate acid treatment are crucial techniques for breaking the diapause state of silkworm eggs, but their molecular mechanisms remain unclear. This study prepared diapause eggs (CK), conventional immediate acid-treated eggs (46 °C, 5 min, and CG), and high-temperature immediate acid-treated eggs (47.5 °C, 7 min, and GW) and analyzed the transcriptome and metabolome to screen for key expressed genes and key metabolites. Transcriptome results showed that 688, 823, and 222 differentially expressed genes (DEGs) were obtained from CK vs. CG, CK vs. GW, and CG vs. GW, respectively, and 12 DEGs significantly upregulated in all three comparisons (CK vs. CG, CK vs. GW, and CG vs. GW), including glycine-N-methyltransferase, choline dehydrogenase, Hsp68, and Hsp70. The LC-MS analysis results showed that 854, 711, and 506 differential metabolites (DMs) were obtained from CK vs. CG, CK vs. GW, and CG vs. GW, respectively. A total of seven DMs upregulated in all three comparisons and with |log₂Fold Change| ≥ 0.5 in CG vs. GW, including tyrosine-isoleucine-histidine, phenylalanyl-tyrosine, tyrosine-phenylalanine-glutamate-lysine, and histidylleucine, as well as 12 downregulated DMs, were identified. Additionally, it was found that γ-linolenic acid and triglycerides were upregulated in CG vs. GW. The conjoint analysis results revealed that four small peptides, including tyrosine-isoleucine-histidine, phenylalanyl-tyrosine, tyrosine-phenylalanine-glutamate-lysine, and histidylleucine, exhibited a highly significant positive correlation with Hsp70 family genes such as Hsp68 and Hsp70. This suggests that these small peptides, along with γ-linolenic acid and triglycerides, may play a crucial role in the resistance of silkworm eggs to high-temperature stress and the associated oxidative stress. Full article

The discovery of penicillin led to remarkable progress in the treatment of diseases and far-reaching advancements in novel antibiotics’ development and use. However, the uncontrolled use and abuse of antibiotics in subsequent years have led to the emergence of the antimicrobial resistance (AMR) crisis, which now threatens modern medicine. There is an increasing number of emerging and reemerging infectious diseases, which have worsened the state of AMR and pose a serious threat to global health. The World Health Organization (WHO) reports the inadequacy of the drug development pipeline to meet the needs of the pharmaceutical sector in the face of AMR, and this poses a significant challenge in the treatment of diseases. Natural products (NPs) represent a promising group of antibiotic alternatives that can potentially mitigate AMR, as they bypass the pharmacodynamics of traditional antibiotics, thereby making them immune to the mechanisms of AMR. NPs, including plant derivatives, bacteriophages, metals, antimicrobial peptides, enzymes, and immune modulators, as monotherapies or in synergism with existing antibiotics, are gaining attention in a bid to reconstruct the antibiotic pipeline. Harnessing these as antimicrobial agents to curb AMR can help to provide sufficient defence against these infectious pathogens. The current review provides a comprehensive overview of the state of AMR and the potential of the above-mentioned antibiotic alternatives. Additionally, we discuss progress made and research breakthroughs in the application of these alternative therapies in humans, exploring findings from clinical trials and experimental models. The review further evaluates the advancement in technology, interdisciplinary approaches to the formulation and utilisation of NPs, and collaborations in alternative drug development. The research gaps present in this ever-evolving field are highlighted and evaluated together with regulatory issues, safety concerns, and technical difficulties in implementation. Full article

Methicillin-resistant Staphylococcus aureus (MRSA), characterized by high-level β-lactam resistance and increasing multi-drug resistance, poses a severe and growing global threat to human health and public safety. This review examines MRSA’s complex resistance mechanisms, including mecA/mecC-mediated expression of low-affinity PBP2a, regulatory roles of auxiliary genes like fem and vanA, enzymatic inactivation by β-lactamases and modifying enzymes, efflux pump activity, and biofilm formation. We also systematically review novel therapeutic strategies, such as combination therapies, phage-derived biofilm disruptors, membrane-targeting silver nanoparticles, cell-penetrating antimicrobial peptides, colonization-competitive probiotics, and antibiotic-synergizing phytochemicals. These advances provide critical insights for developing effective countermeasures against MRSA, while highlighting the urgent need for global collaboration, antibiotic stewardship, and innovative drug development to combat antimicrobial resistance. Full article

The growing problem of antimicrobial resistance in aquaculture, caused by the excessive and unregulated use of antibiotics, highlights the critical necessity for developing new anti-infective solutions. Based on the characteristics of glycine-rich antimicrobial peptides (AMPs) and transcriptomic data, an antimicrobial peptide, namely AfRgly1, was discovered in this study. Subsequently, the peptide was obtained through heterologous expression in E. coli, and its antibacterial spectrum was determined. Molecular dynamics simulation and molecular biology experiments were conducted to explore the antibacterial target of AfRgly1. Results showed that the mRNA expression level of AfRgly1 was significantly upregulated after Vibrio alginolyticus infection. AfRgly1 has broad-spectrum antibacterial activity targeting on bacterial cell membrane, and it may also interact with bacterial DNA. AfRgly1 displayed low selectivity for fish red blood cells. These results indicate that AfRgly1 is an antimicrobial peptide with considerable potential for application in the development of therapeutic agents. Full article

Phycobiliproteins have gained increasing attention for their antidiabetic potential, yet the specific bioactive peptides and their targets and molecular mechanisms have remained unclear. In this study, four peptides with potential hypoglycemic activity were identified through virtual screening. Network pharmacology was employed to elucidate their hypoglycemic mechanism in the treatment of T2DM. A subsequent in vitro assay confirmed that the synthesized peptides, GR-5, SA-6, VF-6, and IR-7, exhibited significant inhibitory activity against α-glucosidase and DPP-IV. In insulin-resistant HepG2 models, all four peptides exhibited no cytotoxicity. Among them, GR-5 demonstrated the most promising therapeutic potential by remarkably enhancing cellular glucose consumption capacity. Furthermore, GR-5 administration substantially increased glycogen synthesis and enzymatic activities of hexokinase and pyruvate kinase with statistically significant improvements compared to the control groups. This study provides novel peptide candidates for T2DM treatment and validates an integrative strategy for targeted bioactive peptide discovery, advancing the development of algal protein-based therapeutics. Full article

Nowadays, members of the genus Enterobacter have been documented as human and aquaculture pathogens. To date, no reports have described Enterobacter bugandensis infecting Hippocampus abdominalis. In the present study, an isolate of E. bugandensis, designated H4, was identified as a causative pathogen in cultured H. abdominalis following Koch’s postulate, and its virulence properties were further described. The isolate’s genome consisted of a single circular chromosome and harbored several virulence and resistance genes, including, but not limited to, csgG, acrB, hcp, gndA, galF, rpoS, fur, rcsB, and phoP involved in adherence, antimicrobial activity, effector delivery systems, immune modulation, and regulation, as well as baeR, blaACT-49, ramA, hns, ftsI, acrA, gyrA, fabI, crp, oqxB, parE, gyrB, phoP, rpoB, tuf, ptsI, and fosA2 functioning against aminoglycoside, cephamycin, disinfecting agent and antiseptic, fluoroquinolone, macrolide, peptide, and other antimicrobials. Additionally, the isolate exhibited multiple resistance to cephalosporins, penicillins, and tetracyclines and demonstrated a median lethal dose (LD₅₀) of 4.47 × 10⁵ CFU/mL in H. abdominalis. To our knowledge, this is the first study to describe E. bugandensis infecting H. abdominalis. These findings highlight the zoonotic potential of E. bugandensis and underscore the need for targeted health management in seahorse farming. Full article