Search Results (343)

Over the past decade, the number and diversity of identified protein post-translational modifications (PTMs) have grown significantly. However, most PTMs occur at relatively low abundance, making selective enrichment of modified peptides essential. To address this, we developed a thermodynamic model describing the free beads enrichment in suspension enrichment process and derived a theoretical relationship between material dosage and analyte recovery. The model predicts a non-linear trend, with enrichment efficiency increasing up to an optimal dosage and declining thereafter—a pattern confirmed by experimental data. We validated the model using centrifugation-based enrichment for glycosylated peptides and magnetic-based enrichment for phosphorylated peptides. In both cases, the results aligned with theoretical predictions. Additionally, the optimal dosage varied among peptides with the same modification type, highlighting the importance of tailoring enrichment strategies. This study provides a solid theoretical and experimental basis for optimizing PTMs enrichment and advancing more sensitive, accurate, and efficient mass spectrometry-based proteomic workflows. Full article

Although Hylocereus polyrhizus pulp residues polysaccharides (HPPP) have shown potential in improving metabolic disorders and intestinal barrier function, the mechanism by which they exert their effects through regulating O-glycosylation modifications in the mucus layer remains unclear. Therefore, this study established a HFD-induced obese colitis mouse model (n = 5 per group) and combined nano-capillary liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) technology to quantitatively analyze the dynamic changes in O-glycosylation. Additionally, through quantitative O-glycosylation proteomics and whole-proteome analysis, we identified 155 specifically altered O-glycosylation sites in colon tissue, with the glycosylation modification level of the MUC2 core protein increased by approximately 2.1-fold. The results indicate that HPPP alleviates colonic mucosal damage by regulating interactions between mucus O-glycosylation. Overall, we demonstrated that HPPP increases HFD-induced O-glycosylation sites, improves intestinal mucosal structure in obese mice, and provides protective effects against obesity-induced intestinal mucosal damage. Full article

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Its sustained proliferative signaling poses a major challenge for effective therapeutic intervention. Since CRC originates from aberrantly proliferating crypt cells, limiting proliferation or inducing senescence may offer a promising treatment approach. Lycium barbarum glycopeptide (LbGP), a traditional Chinese medicine component, is known for its immunomodulatory and other beneficial effects. This study aims to examine the anti-tumor effects of LbGP in CRC as well as its underlying mechanisms of action. We used CT26 CRC cells to investigate the effects of LbGP on tumor proliferation both in vitro and in an allograft mouse model. LbGP treatment significantly inhibited CT26 cell proliferation in vitro and suppressed tumor growth in CT26-implanted mice. Furthermore, LbGP treatment significantly upregulated p53/p21 levels both in vitro and in vivo, leading to CT26 cell cycle arrest in the S phase and the induction of tumor cell senescence. These findings demonstrate that LbGP effectively induces CRC cell cycle arrest and senescence via the p53/p21 pathway and may serve as a promising candidate for CRC adjuvant therapy. Full article

Background:Enterococcus spp. is the third leading cause of healthcare-associated infections in the American continent, often because of the virulence factors that protect the bacterium against host defenses and facilitate tissue attachment and genetic material exchange. In addition, vancomycin, considered a last-resort treatment, has shown reduced efficacy in Enterococcus spp. strains. However, the relationship between bacterial resistance and virulence factors remains unclear. This study intends to evaluate the prevalence of glycopeptide-resistant genotypes and virulence factors in Enterococcus spp. strains. Methods: Over six months, 159 Enterococcus spp. strains causing nosocomial infections were analyzed. Multiplex PCR was performed to identify species, glycopeptide-resistant genotypes, and 12 virulence factors. Results: The most abundant species identified were Enterococcus faecalis and E. faecium. Vancomycin resistance was observed in 10.7% of the isolates, and the vanA genotype was present in 47% of resistant samples. The main virulence factors detected were acm (54%), which is related to cell adhesion; gel E (66%), a metalloproteinase linked to tissue damage; and the sex pheromones cpd (64%) and ccf (84%), which are involved in horizontal gene transfer. A significant association was found between the prevalence of acm, ccf, and cpd in VRE isolates, indicating the potential dissemination of genes to emerging strains via horizontal gene transfer. In addition, a new E. faecium, which displayed five virulence factors and harbored the vanA sequence type, was identified and registered as ST2700. Conclusions:Enterococcus faecalis and E. faecium are clinically critical due to multidrug resistance and virulence factors like acm, which aids host colonization. Genes ccf and cpd promote resistance spread via horizontal transfer, while the emerging ST2700 strain requires urgent monitoring to curb its virulent, drug-resistant spread. Full article

We have previously reported on a novel monoclonal antibody (mAb) we designated F5, which was raised against a glycopeptide derived from the tandem repeat (TR) region of Mucin-4 (MUC4), a heavily O-glycosylated protein that is overexpressed in many pancreatic cancer cells. This mAb was highly specific for the MUC4 glycopeptide antigen in glycan microarrays, ELISA and SPR assays, selectively stained tissue derived from advanced-stage tumors, and bound MUC4⁺ tumor cells in flow cytometry assays. The mAb was also unique in that it did not cross-react with other commercial anti-MUC4 mAbs that were raised in a similar but non-glycosylated TR sequence. Here we describe the selective conjugation of a novel near-infrared dye to this mAb and in vivo biodistribution of this labeled mAb to various MUC4-expressing tumors in mice. The labeled mAb were selectively distributed to both cell-derived xenograft (CDX) flank tumors and patient-derived xenograft (PDX) tumors that expressed MUC4 compared to those that were MUC4-negative. Organ distribution analysis showed high uptake in MUC4⁺ relative to MUC4⁻ tumors. These results suggest that mAb F5 may be used to develop MUC4-targeted, passive antibody-based immunotherapies against Pancreatic Ductal Adenocarcinomas (PDACs) which are notorious for being refractory to many chemo- and radiotherapies Full article

Vancomycin, a cornerstone antibiotic against severe Gram-positive infections, is increasingly challenged by resistance in Methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin Enterococcus spp. (VRE), necessitating the development of novel therapeutic strategies. This review examines how structural modifications to vancomycin can enhance its antibacterial activity and explores the critical role of computational approaches in designing the next generation of analogs. By analyzing the existing literature, we highlight how strategic alterations, such as the introduction of lipophilic side chains, substitutions on the sugar moieties, and modifications to the aglycone core, have yielded derivatives with improved antibacterial potency. Notably, certain analogs (e.g., Vanc-83, Dipi-Van-Zn) have demonstrated expanded activity against Gram-negative bacteria and exhibited enhanced pharmacokinetic profiles, including prolonged half-lives and improved tissue penetration, crucial for effective treatment. Semisynthetic glycopeptides like telavancin, dalbavancin, and oritavancin exemplify successful translation of structural modifications, offering sustained plasma concentrations and simplified dosing regimens that improve patient compliance. Complementing these experimental efforts, computational methods, including molecular docking and molecular dynamics simulations, provide valuable insights into drug–target interactions, guiding the rational design of more effective analogs. Furthermore, physiologically based pharmacokinetic modeling aids in predicting the in vivo behavior and optimizing the pharmacokinetic properties of these novel compounds. This review highlights a critical path forward in the fight against multidrug-resistant infections. By meticulously examining the previously carried out structural refinement of vancomycin, guided by computational predictions and validated through rigorous experimental testing, we underscore its immense potential. Full article

Background: Due to the high prevalence of severe infections, antibiotics are frequently administered in anaesthesia and intensive care units. Despite their therapeutic efficacy, several antibiotics exhibit neurotoxic potential, resulting in central and peripheral neurological complications in patients. This review aims to summarise the current evidence on antibiotic-induced neurotoxicity, particularly in critical care settings. Methods: A comprehensive literature analysis was performed to assess the neurotoxic profiles, underlying mechanisms, and clinical manifestations associated with different antibiotic classes, including beta-lactams, fluoroquinolones, macrolides, aminoglycosides, and others. Results: Beta-lactam antibiotics (especially cephalosporins and carbapenems) are strongly associated with seizures, encephalopathy, and EEG abnormalities, mainly through GABAergic inhibition and mitochondrial dysfunction. Fluoroquinolones and macrolides can cause psychosis, insomnia, and neuropathy via NMDA activation and oxidative stress. Linezolid carries the risk of serotonin syndrome and optic neuropathy, while glycopeptides and aminoglycosides are primarily associated with ototoxicity. Risk factors include advanced age, renal or hepatic impairment, and high serum drug levels. Conclusions: The neurotoxic potential of antibiotics is a critical but under-recognised aspect of pharmacotherapy in intensive care. Improved awareness, pharmacovigilance, dose adjustment, and drug monitoring are crucial for mitigating adverse neurological effects. Full article

The genome of Geobacillus sp. G4, a thermophilic bacterium isolated from a geothermal field in Peru, was sequenced and analyzed to evaluate its taxonomic and biotechnological potential. This strain exhibits optimal growth at temperatures between 50 and 70 °C and at a pH range of 6.0–7.5. Phenotypic assays demonstrated extracellular enzymatic activities, including amylases, cellulases, pectinases, and xylanases, highlighting its potential for efficient polysaccharide degradation. The assembled genome comprises approximately 3.4 Mb with a G+C content of 52.59%, containing 3,490 genes, including coding sequences, rRNAs, and tRNAs. Functional annotation revealed genes associated with key metabolic pathways such as glycogen and trehalose biosynthesis, indicating adaptation to carbohydrate-rich environments. Phylogenetic analyses based on ANI and dDDH values identified Geobacillus thermoleovorans KCTC3570 as its closest relative, suggesting a strong evolutionary relationship. Additionally, the genome harbors gene clusters for secondary metabolites such as betalactone and fengycin, suggesting potential industrial and pharmaceutical applications, including bioremediation. The identification of antibiotic resistance genes, specifically those conferring glycopeptide resistance, underscores their relevance for antimicrobial resistance studies. The presence of enzymes like amylases and pullulanase further emphasizes its biotechnological potential, particularly in starch hydrolysis and biofuel production. Overall, this research highlights the significant potential of Geobacillus species as valuable sources of thermostable enzymes and biosynthetic pathways for industrial applications. Full article

Antibiotic pressure exerts profound effects on bacterial physiology, not limited to classical genetic resistance mechanisms. Increasing evidence highlights the ability of pathogens to undergo metabolic rewiring—an adaptive, reversible reorganization of core metabolic pathways that promotes survival under antimicrobial stress. This review provides a comprehensive analysis of antibiotic-induced metabolic adaptations, encompassing glycolysis, the tricarboxylic acid cycle, fermentation, redox balance, amino acid catabolism, and membrane biosynthesis. We critically examine how diverse antibiotic classes—including β-lactams, aminoglycosides, quinolones, glycopeptides, polymyxins, and antimetabolites—interact with bacterial metabolism to induce tolerance and persistence, often preceding stable resistance mutations. In parallel, we explore the ecological and host-derived signals—such as immunometabolites and quorum sensing—that modulate these metabolic responses. Therapeutically, targeting metabolic pathways offers promising strategies to potentiate antibiotic efficacy, including enzyme inhibition, metabolic adjuvants, and precision-guided therapy based on pathogen metabolic profiling. By framing metabolic plasticity as a dynamic and evolutionarily relevant phenomenon, this review proposes a unifying model linking transient tolerance to stable resistance. Integrating metabolic rewiring into antimicrobial research, clinical diagnostics, and therapeutic design represents a necessary paradigm shift in combating bacterial persistence and resistance. Full article

Background/Objectives: The clinical forms of coronavirus disease 2019 (COVID-19) vary widely in severity, ranging from asymptomatic or moderate cases to severe pneumonia that can lead to acute respiratory failure, acute respiratory distress syndrome, multiple organ dysfunction syndrome, and death. Our main objective was to determine the prevalence of bacterial and fungal secondary infections in an intensive care unit (ICU). Secondary objectives included analyzing the impact of these infections on mortality and medical resource utilization, as well as assessing antimicrobial resistance in this context. Methods: We conducted a retrospective cohort study that included critically ill severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients treated in an ICU and analyzed the prevalence of co-infections and superinfections. Results: A multivariate analysis of mortality found that the presence of superinfections increased the odds of death by more than 15-fold, while the Sequential Organ Failure Assessment (SOFA) score and C-reactive protein (adjusted for confounders) increased the odds of mortality by 51% and 13%, respectively. The antibiotic resistance profile of microorganisms indicated a high prevalence of resistant strains. Carbapenems, glycopeptides, and oxazolidinones were the most frequently used classes of antibiotics. Among patients, 27.9% received a single antibiotic, 47.5% received two from different classes, and 24.4% were treated with three or more. Conclusions: The incidence and spectrum of bacterial and fungal superinfections are higher in critically ill ICU patients, leading to worse outcomes in COVID-19 cases. Multidrug-resistant pathogens present significant challenges for ICU and public health settings. Early screening, accurate diagnosis, and minimal use of invasive devices are essential to reduce risks and improve patient outcomes. Full article

Objectives: This study aimed to characterize the basic structure of sialylated glycopeptide (SCP) from edible bird’s nest, and to explore the intervention effect and mechanism of SCP based on a mouse lung inflammation model induced by lipopolysaccharide (LPS). Methods: C57BL/6 mice were randomly divided into the control group (CON), model group (LPS), EBN group, SCP group, and SA group. Results: The results showed that SCP had the typical structures of polypeptides and carbohydrates. SCP effectively intervened in the lung inflammation response. The number of neutrophils (Neu) in BALF decreased by 41.3%, the level of tumor necrosis factor-α (TNF-α) decreased by 36.4%, and the W/D ratio of lung tissues decreased by 27.2%, effectively preventing pathological changes in lung tissues. A total of 40 differential metabolites such as choline, linolenic acid, and xanthine were screened between the SCP group and the LPS group. These differential metabolites were mainly enriched in the metabolic pathways of glycerophospholipids, alpha-linolenic acid, and purines. Conclusions: The research results support that SCP, as the active substance of edible bird’s nest, can effectively improve lung inflammation, providing theoretical guidance for the development of functional edible bird’s nest products. Full article

Ganoderma capense, a member of the Ganoderma genus within the Polyporaceae family, has long been recognized for its high nutritional value and extensive use in traditional medicine. Its primary distribution is in China and South Africa, with the type locality being South Africa. This species is rich in a diverse array of bioactive compounds, including various polysaccharides, glycopeptide macromolecules, and various small-molecule compounds, such as sesquiterpenes, triterpenes, steroids, and alkaloids. Research indicates that these chemical constituents exhibit numerous pharmacological properties, including antioxidant, anti-inflammatory, and anti-tumor activities, as well as inhibition of acetylcholinesterase, reduction in blood lipids, and promotion of neural synapse growth. Apart from its use in traditional Chinese medicine, the components of G. capense are utilized globally for the treatment of a wide range of diseases, including Alzheimer’s disease, febrile convulsions, HIV, and diabetes. This underscores the extensive medical applications of G. capense, emphasizing its significance in contemporary and traditional healthcare. This review summarizes the latest research findings on the bioactive compounds and pharmacological effects of G. capense, compiled from databases such as PubMed, Web of Science, and Elsevier. This study aimed at providing researchers in this field with in-depth scientific insights and guidance, promoting further application and development in the pharmaceutical and food industries, and serving as a reference for subsequent exploration of active substances and the development of new disease treatments. Full article

Background/Objective: Vancomycin, a hydrophilic glycopeptide antibiotic with bactericidal activity against Gram-positive microorganisms, is one of the most commonly used antibiotics un the intensive care unit (ICU). Different efforts have been made to achieve a therapeutically effective plasma concentration of vancomycin by using loading and subsequent maintenance doses on an individual basis, but this remains subject to debate. Our objective was to individualize a dosage regimen in a Chilean ICU to optimize the pharmacological treatment of vancomycin by using a population pharmacokinetic model. Methods: A quantitative descriptive study was carried out in 51 patients at the adult ICU, San Borja Arriarán Clinical Hospital in Santiago, Chile. The dose of vancomycin was calculated by using a population pharmacokinetic software, the Antibiotic Kinetics^®, and was subsequently validated with plasma trough levels of the drug through a patient sample. Results: The most commonly prescribed loading dose was 1500 mg and the most commonly used maintenance dose was 1000 mg, three times a day. The measured blood plasma concentrations of each patient (16.98 ± 5.423 μg/mL) were compared with the concentrations calculated through the population pharmacokinetic model (14.33 ± 4.630 μg/mL, p < 0.05). In addition, a correlation was found between the software-calculated trough concentration versus the measured trough concentration for vancomycin, with a positive correlation between both variables established (R² = 0.65; p < 0.0001). No renal side effects were observed in the treated patient group. Conclusions: In the present study, a vancomycin dosing model for critically ill patients, based on a population pharmacokinetic model, was successfully implemented for routine clinical practice. Full article

Background: In Staphylococcus aureus, antimicrobial resistance (AMR) imposes significant fitness costs (FCs), including reduced growth rate, interbacterial competitiveness, and virulence. However, the FC molecular basis remains poorly understood. This study investigated the FC omic basis and compensatory adaptations in high-risk HA-, LA-, and CA-MRSA, acquiring mono- or cross-resistance to second-line daptomycin (DAP) and dalbavancin (DAL), as well as reduced susceptibility (RS) to first-line glycopeptides, i.e., vancomycin and teicoplanin (GLYs, i.e., VAN, TEC), related to the specific mechanism of action (MOA)-related AMR-mechanisms and genomic backgrounds, paying increasing FCs. Methods: The FC omic basis associated with mono- or cross- DAP-/DAL-R and GLY-RS were investigated by integrated omics. This study focused on core-genome essential (EG) and accessory virulence gene (VG) SNPomics and transcriptomics by Illumina MiSeq whole-genome sequencing, RNA-seq, and bioinformatic analysis. Results: Moderate impact nsSNPs were identified in EGs related to vital cellular functions and VGs. Comparative EG transcriptomics revealed differential expressions and key dysregulations—via asRNAs—prevalently affecting the protein synthesis and cell-envelope EG clusters, as well as the VG cluster. Conclusions: Our data, firstly, underlined the EG and VG mutation- and transcription-driven omic-based FC burden and the compensatory adaptations associated with the emergence of mono-DAP-R, cross-DAP-R/hGISA, and DAP-R/DAL-R/GISA, linked to specific MOA-related AMR-mechanisms and genomic backgrounds in high-risk HA-, LA-, and CA-MRSA. Full article

This study deals with the extraction of active compounds for a formula (Angelica gigas, Cornus officinalis, Ganoderma lucidum, Thymus vulgaris, and Asparagus cochinchinensis) and the evaluation of its skin anti-aging properties. This formulation was inspired by the oriental medicine Gongjin-dan (Angelica gigas, Cornus officinalis, deer antler, and musk), which has been used as a restorative drug for longevity. Enzyme-based extraction and chemical purification were used to obtain a mixed fraction (GEF) enriched in glycopeptides and glycoproteins from the five herbal materials. The chemical characteristics of GEF, including the carbohydrate groups attached to the peptides and proteins, the total carbohydrate and protein contents, and the composition of monosaccharides and amino acids were determined. The chemical characteristics that were significantly different from those of the extract, generally prepared in the same ratio, were the abundance of glycopeptides and glycoproteins and the high proportions of conditionally essential amino acids (51.0%) and acidic/basic amino acids (67.7%). These are necessary components for strengthening the skin layers against aging. The in vitro skin anti-aging properties of GEF on human fibroblasts (HS68), keratinocytes (HaCaT), and adipose-derived mesenchymal stem cells (ADMSCs) were evaluated. It was found that MMP-1 gene expression was inhibited (18–28%) and fibrillin-1 protein (23–37%) was restored contrary to the effect of UV irradiation. COL1A1 and COL4A1 gene expression (25–35%), HAS2 gene expression (22–213%), and adipogenesis (15%) were facilitated. These results demonstrate the potential of GEF as a raw material for skin anti-aging and reinforce the scientific evidence supporting a traditional medicine with a long history. Full article