Search Results (1,519)

Background: The aim of this review is to summarize and evaluate the properties of antibacterial polysaccharides for application in dental implantology to identify knowledge gaps and provide new research ideas. Methods: The electronic databases PubMed, Medline, ProQuest, and Google Scholar were used to search for peer-reviewed scientific publications published between 2018 and 2025 that provide insights to answer research questions on the role of antibacterial polysaccharides in combating pathogens in dental implantology without triggering immune reactions and inflammation. Further research questions relate to the efficacy against various dental pathogens and the understanding of the antibacterial mechanism, which may enable the development of functionalized polysaccharides with long-term antibacterial activity. Results: Biomedical implants have revolutionized medicine but also increased the risk of infections. Implant infections are a major problem in implantology and lead to implant failure and replacement. An antibacterial coating could be an excellent strategy to extend the lifespan of implants and improve the quality of the patient’s life. Bacterial resistance to antibiotics poses significant challenges for researchers, forcing them to search for new ways to prevent bacterial infections in implantology. Antibacterial natural polymers have recently received considerable research attention due to their long-term antibacterial activity. Polysaccharides from marine sources, such as chitosan and alginate, or pectin, xanthan, etc., from various plants, appear to be promising biopolymers for such applications in implantology due to their antibacterial activity, biocompatibility, and osteogenic properties. The antibacterial activity of these natural biopolymers depends on their chemical and physical properties. Nanopolysaccharides exhibit higher antibacterial activity than conventional polysaccharides, but their toxicity to human cells must be considered. Their antibacterial activity is based on the disruption of bacterial DNA or RNA synthesis, increased cell wall permeability, membrane disruption, and cytoplasmic leakage. Conclusions: Polysaccharides are a class of natural polymers with a broad spectrum of biological activities. They exhibit antioxidant, immunomodulatory, anticoagulant, anticancer, anti-inflammatory, antibacterial, and antiviral activity. Furthermore, polysaccharides are non-cytotoxic and exhibit good biocompatibility with osteogenic cells. Bactericidal polysaccharides are attractive new antibacterial materials against implant infections and open up new perspectives in implantology. Full article

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterised by hepatic steatosis in the absence of significant alcohol consumption or other specific causes of liver injury. It has become one of the leading causes of liver dysfunction worldwide. However, the precise pathophysiological mechanisms underlying NAFLD remain unclear, and effective therapeutic strategies are still under investigation. Autophagy, a vital intracellular process in eukaryotic cells, enables the degradation and recycling of cytoplasmic components through a membrane trafficking pathway. Recent studies have demonstrated a strong association between impaired or deficient autophagy and the development and progression of NAFLD. Restoring autophagic function may represent a key approach to mitigating hepatocellular injury. Nevertheless, due to the complexity of autophagy regulation and its context-dependent effects on cellular function, therapeutic strategies targeting autophagy in NAFLD remain limited. This review aims to summarise the relationship between autophagy and NAFLD, focusing on autophagy as a central mechanism. We discuss the latest research advances regarding interventions such as diet and exercise, pharmacological therapies (including modern pharmacological therapy and plant-derived compounds), and other approaches (such as hormones, nanoparticles, gut microbiota, and vitamins). Furthermore, we briefly highlight potential autophagy-related molecular targets that may offer novel therapeutic insights for NAFLD management. Full article

Heparan sulfate proteoglycans (HSPGs) within the neuronal niche are expressed during brain development, contributing to multiple aspects of neurogenesis, yet their roles in glial lineage commitment remain elusive. This study utilised three human cell models expanded under basal culture conditions followed by media-induced lineage induction to identify a reproducible and robust model of gliogenesis. SH-SY5Y human neuroblastoma cells (neuronal control), ReNcell CX human neural progenitor cells (astrocyte inductive) and ReNcell VM human neural progenitor (mixed neural induction) models were examined. The cultures were characterised during basal and inductive states via Q-PCR, Western Blotting, immunocytochemistry (ICC) and calcium signalling activity analyses. While the ReNcell lines did not produce fully mature or homogeneous astrocyte cultures, the ReNcell CX cultures most closely resembled an astrocytic phenotype with ReNcell VM cells treated with platelet-derived growth factor (PDGF) biased toward an oligodendrocyte lineage. The glycated variant of surface-bound glypican-2 (GPC2) was found to be associated with lineage commitment, with GPC6 and 6-O HS sulfation upregulated in astrocyte lineage cultures. Syndecan-3 (SDC3) emerged as a lineage-sensitive proteoglycan, with its cytoplasmic domain enriched in progenitor-like states and lost upon differentiation, supporting a role in maintaining neural plasticity. Conversely, the persistence of transmembrane-bound SDC3 in astrocyte cultures suggest continued involvement in extracellular signalling and proteoglycan secretion, demonstrated by increased membrane-bound HS aggregates. This data supports HSPGs and HS GAGs as human neural lineage differentiation and specification markers that may enable better isolation of human neural lineage-specific cell populations and improve our understanding of human neurogenesis. Full article

The functional role of MAPKK genes in potato (Solanum tuberosum L.) under high-temperature stress remains unexplored, despite their critical importance in stress signaling and yield protection. We characterized StMAPKK1, a novel group D MAPKK localized to plasma membrane/cytoplasm. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed cultivar-specific upregulation in potato (‘Atlantic’ and ‘Desiree’) leaves under heat stress (25 °C, 30 °C, and 35 °C). Transgenic lines overexpressing (OE) StMAPKK1 exhibited elevated antioxidant enzyme activity, including ascorbate peroxidase (APX), catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD), mitigating oxidative damage. Increased proline and chlorophyll accumulation and reduced oxidative stress markers, hydrogen peroxide (H₂O₂) and malondialdehyde (MDA), indicate improved cellular redox homeostasis. The upregulation of key antioxidant and heat stress-responsive genes (StAPX, StCAT1/2, StPOD12/47, StFeSOD2/3, StMnSOD, StCuZnSOD1/2, StHSFA3 and StHSP20/70/90) strengthened the enzymatic defense system, enhanced thermotolerance, and improved photosynthetic efficiency, with significant improvements in net photosynthetic rate (Pn), transpiration rate (E), and stomatal conductance (Gs) under heat stress (35 °C) in StMAPKK1-OE plants. Superior growth and biomass (plant height, plant and its root fresh and dry weights, and tuber yield) accumulation, confirming the positive role of StMAPKK1 in thermotolerance. Conversely, RNA interference (RNAi)-mediated suppression of StMAPKK1 led to a reduction in enzymatic activity, proline content, and chlorophyll levels, exacerbating oxidative stress. Downregulation of antioxidant-related genes impaired ROS scavenging capacity and declines in photosynthetic efficiency, growth, and biomass, accompanied by elevated H₂O₂ and MDA accumulation, highlighting the essential role of StMAPKK1 in heat stress adaptation. These findings highlight StMAPKK1’s potential as a key genetic target for breeding heat-tolerant potato varieties, offering a foundation for improving crop resilience in warming climates. Full article

Background/Objectives: Truncating mutations in PALB2, a critical component of the BRCA1-PALB2-BRCA2 homologous recombination repair complex, are associated with increased risk and aggressiveness of breast cancer. The consequences of PALB2 truncation on the expression, localization, and functional dynamics of the scaffold protein IQGAP1 were investigated in this study based on two cases of truncated PALB2 human breast invasive ductal carcinoma (IDC), specifically, c.1240C>T (p.Arg414*) and c.2257C>T (p.Arg753*). Methods: Using confocal microscopy, we examined co-expression patterns of IQGAP1 with PALB2, PCNA, CK7, and β-tubulin in tumor tissues from both control cancer and PALB2-mutated cases. Results: In PALB2-truncated tumors, IQGAP1 exhibited enhanced peripheral and plasma membrane localization with elevated co-localization levels compared to controls, suggesting altered cytoskeletal organization. PALB2 truncation increased nuclear and cytoplasmic N-terminal PALB2 immunoreactivity, indicating the presence of truncated isoforms disrupting the homologous recombination repair system. Co-expression analyses with PCNA revealed an inverse expression pattern between IQGAP1 and proliferation markers, suggesting S-phase cell cycle-dependent heterogeneity. Furthermore, the loss of IQGAP1 dominance over CK7 and β-tubulin in mutant tumors, along with persistent intercellular spacing, implied a loss of cell–cell cohesion and the acquisition of invasive traits. Conclusions: These data support a model where PALB2 truncation triggers a reorganization of IQGAP1 that disrupts its canonical structural functions and facilitates tumor progression via enhanced motility and impaired cell–cell interaction. IQGAP1 thus serves as both a functional effector and potential biomarker in PALB2-mutated IDC, opening novel paths for diagnosis and targeted therapeutic intervention. Full article

Ovine herpesvirus 2 (OvHV-2) causes the fatal veterinary disease malignant catarrhal fever (MCF). Fusion is an essential step in the host cell entry of enveloped viruses and is an important target for vaccine development. OvHV-2 cannot be propagated in vitro, so a robust virus-free cell–cell membrane fusion assay is necessary to elucidate its entry mechanism. OvHV-2 cell–cell fusion requires three conserved herpesviral envelope glycoproteins: gB, gH, and gL. OvHV-2 fusion activity is detectable but low. We hypothesize that enhancing the cell surface expression of gB, which is the core herpesviral fusogen, will increase cell–cell fusion. We generated C-terminal truncation mutants of gB and determined their cell surface expression, subcellular distribution, and fusion activity. Two mutants, including one that lacked the entire cytoplasmic tail domain, failed to function in the cell–cell fusion assay, despite wild-type levels of surface expression. This suggests that the OvHV-2 gB cytoplasmic tail is critical for fusion. A gB mutant truncated at amino acid 847 showed increased surface expression and fusion relative to the wild type. This suggests that the robust fusion activity of gB847 is the result of increased surface expression. gB847 may be used in place of wild-type gB in an improved, more robust OvHV-2 fusion assay. Full article

Helicobacter pylori infection is the strongest known risk factor for the development of gastric cancer. The bacterium leverages several unique virulence factors to its advantage in order to colonize the human host. Among these, T4SS-delivered cytotoxin-associated gene A (CagA) has the most well-established links to severe forms of disease. To explore the effect of lactobacilli in disrupting CagA functions within host cells, we expressed HA-tagged humanized cagA in the human gastric epithelial AGS cell line and studied both the phosphorylation levels of CagA and its downstream binding partners. We found that gastric-specific Lactobacillus gasseri Kx110 A1 suppressed the phosphorylation of CagA and inhibited phosphorylation-dependent downstream signaling, resulting in the suppression of CagA-induced cell elongation of AGS cells, commonly known as the hummingbird phenotype. Surprisingly, phosphorylation-independent signaling was unaffected by L. gasseri. Furthermore, our confocal microscopy analysis revealed that CagA was mislocalized to the cytoplasm, suggesting that L. gasseri interferes with its membrane localization and thereby hinders its phosphorylation. Live L. gasseri that had direct contact with host cells was found to be necessary to suppress the hummingbird phenotype. In summary, the data suggest that a L. gasseri strain can inhibit CagA phosphorylation and suppress cell elongation. Full article

SNX11, a sorting nexin protein localized on the endosomal membrane, is an important protein closely related to protein sorting and endosomal trafficking. Previously, through a genome-wide CRISPR screening, we identified SNX11 as a critical protein for the entry of Dabie bandavirus. SNX11 deletion significantly inhibits the replication of Dabie bandavirus. We further discovered that the loss of SNX11 alters endosomal pH, potentially affecting the release process of Dabie bandavirus from endosomes to the cytoplasm. However, the mechanism by which SNX11 modulates endosomal pH and whether SNX11 deletion similarly inhibits other viruses remain to be elucidated. This study reveals that SNX11 can interact with the V1 subunit of the endosomal proton pump V-ATPase, affecting the expression level of this subunit on the endosomal membrane and thereby disrupting the assembly of V-ATPase. Additionally, we found that SNX11 deletion significantly inhibits the replication of dengue virus, hantavirus, and influenza virus. These findings suggest that SNX11 may be a key protein in the process of viral infection and could serve as a broad-spectrum antiviral target. Full article

Caffeic acid-O-methyltransferase (COMT) is a key enzyme in lignin synthesis and secondary metabolism in plants, and it participates in the regulation of plant growth and development as well as plants’ stress response. To further investigate the function of COMT in grapevine, a total of 124 COMT family genes were identified from three Vitis species in this study, namely Pinot noir (Vitis vinifera L.), Vitis amurensis, and Vitis riparia. The amino acid sequence encoded by these genes ranged from 55 to 1422 aa, and their molecular mass ranged from 6640.82 to 77,034.43 Da. Subcellular localization prediction inferred that they were mainly located in the plasma membrane and cytoplasm. The prediction of secondary structures showed that α-helix and irregular coiled-coil were primary structural elements. These genes were unevenly distributed across 10 different chromosomes, respectively. Phylogenetic tree analysis of the amino acid sequences of VvCOMT, VaCOMT, VrCOMT, and AtCOMT proteins showed that they were closely related and were divided into four subgroups. The motif distribution was similar among the cluster genes, and the gene sequence was notably conserved. The 124 members of the COMT gene family possessed a variable number of exons, ranging from 2 to 13. The promoter region of all of these COMTs genes contained multiple cis-acting elements related to hormones (e.g., ABA, IAA, MeJA, GA, and SA), growth and development (e.g., endosperm, circadian, meristem, light response), and various stress responses (e.g., drought, low temperature, wounding, anaerobic, defense, and stress). The intraspecies collinearity analysis suggested that there were one pair, three pairs, and six pairs of collinear genes in Va, Pinot noir, and Vr, respectively, and that tandem duplication contributed more to the expansion of these gene family members. In addition, interspecific collinearity revealed that the VvCOMTs had the strongest homology with the VaCOMTs, followed by the VrCOMTs, and the weakest homology with the AtCOMTs. The expression patterns of different tissues and organs at different developmental stages indicated that the VvCOMT genes had obvious tissue expression specificity. The majority of VvCOMT genes were only expressed at higher levels in certain tissues. Furthermore, we screened 13 VvCOMT genes to conduct qRT-PCR verification according to the transcriptome data of VvCOMTs under abiotic stresses (NaCl, PEG, and cold). The results confirmed that these genes were involved in the responses to NaCl, PEG, and cold stress. This study lays a foundation for the exploration of the function of the COMT genes, and is of great importance for the genetic improvement of abiotic stress resistance in grapes. Full article

Autophagy is an essential eukaryotic catabolic process through which damaged or superfluous cellular components are degraded and recycled via the formation of double-membrane autophagosomes. In plants, autophagy-related genes (ATGs) are primarily expressed in the cytoplasm and are responsible for orchestrating distinct stages of autophagosome biogenesis. Among these, ATG8 proteins, orthologous to the mammalian LC3 family, are conserved ubiquitin-like modifiers that serve as central hubs in selective autophagy regulation. Although ATG8 proteins are localized in both the cytoplasm and nucleus, their functions within the nucleus remain largely undefined. In the present study, the ATG8-interacting motif (AIM) was identified and functionally characterized in the potato ATG8 homolog (StATG8), demonstrating its capacity for selective target recognition. StATG8 was shown to form both homodimeric and heterodimeric complexes with other ATG8 isoforms, implying a broader regulatory potential within the ATG8 family. Notably, StATG8 was found to interact with the Ralstonia solanacearum type III effector PopP2, a nuclear-localized acetyltransferase, suggesting a possible role in effector recognition within the nucleus. In addition, interactions between StATG8 and transcription factors AtWRKY40 and AtWRKY60 were detected in both cytoplasmic autophagosomes and the nuclear compartment. These observations provide novel insights into the noncanonical, nucleus-associated roles of plant ATG8 proteins. The nuclear interactions with pathogen effectors and transcriptional regulators suggest that ATG8 may function beyond autophagic degradation, contributing to the regulation of nuclear signaling and plant immunity. These findings offer a foundational basis for further investigation into the functional diversification of ATG8 in plant cellular compartments. Full article

Biofilm-associated infections caused by Gram-negative bacteria, especially multidrug-resistant strains, frequently occur in intensive care units and represent a major therapeutic challenge. The economic burden of biofilm-associated infections is considerable, making the search for new treatment approaches a focal point for policymakers and scientific funding bodies. Biofilm formation is regulated by quorum sensing (QS), a population density-dependent communication mechanism between cells mediated by small diffusible signaling molecules. QS modulates various intracellular processes, and some features of QS are common to all Gram-negative bacteria. While there are differences in the QS regulatory networks of different Gram-negative bacterial species, a common feature of most Gram-negative bacteria is the ability of N-acylhomoserine lactones (AHL) as inducers to diffuse across the bacterial membrane and interact with receptors located either in the cytoplasm or on the inner membrane. Targeting QS by inhibiting the synthesis, transport, or perception of signaling molecules using small molecules, quorum quenching enzymes, antibodies, combinatorial therapies, or nanoparticles is a promising strategy to combat virulence. In-depth knowledge of biofilm biology, antibiotic susceptibility, and penetration mechanisms, as well as a deep understanding of anti-QS agents, will contribute to the development of antimicrobial therapies to combat biofilm infections. Advancing antimicrobial therapies against biofilm infections requires a deep understanding of biofilm biology, antibiotic susceptibility, penetration mechanisms, and anti-QS strategies. This can be achieved through in vivo and clinical studies, supported by state-of-the-art tools such as machine learning and artificial intelligence. Full article

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is a common kidney cancer with limited therapeutic options. This study investigated the expression of HEAT repeat-containing protein 1 (HEATR1) and solute carrier family 27 member 2 (SLC27A2) in ccRCC and their potential as prognostic markers and therapeutic targets. Methods: Analysis of a public proteomic dataset (CPTAC) and immunohistochemistry (IHC) validation in an independent cohort of 52 ccRCC patients was performed. HEATR1 and SLC27A2 expression were correlated with survival outcomes. Reactome pathway analysis was conducted to explore the functional roles of HEATR1 and SLC27A2. Results: The analysis showed that HEATR1 is upregulated and associated with poor prognosis, while SLC27A2 is downregulated and similarly linked to shorter progression-free survival. High HEATR1 expression and low SLC27A2 expression correlated with shorter progression-free survival (PFS) and overall survival (OS) in patients with high-grade ccRCC. Reactome analysis indicated HEATR1’s involvement in RNA metabolism and SLC27A2’s role in lipid metabolism, particularly peroxisomal lipid metabolism and fatty acyl-CoA biosynthesis. HEATR1 exhibited a dual localization in both the cytoplasm and nucleus, while SLC27A2 was primarily observed at the cell membrane and the nucleus. This different subcellular distribution suggests multifaceted roles for both proteins in ccRCC pathogenesis. Conclusions: HEATR1 and SLC27A2 are potential prognostic markers in ccRCC. Further research is needed to validate these findings in larger, more diverse cohorts and elucidate their roles in ccRCC progression. Full article

A key feature that differentiates Gram-positive and Gram-negative bacteria is the outer membrane, an asymmetric membrane composed of lipopolysaccharides, phospholipids, lipoproteins and integral proteins, including the outer-membrane proteins (OMPs). By being in direct contact with the extracellular milieu, the outer membrane and OMPs participate in multiple functions in Gram-negative bacteria, including controlling nutrient and molecule access to the cytoplasm, membrane vesicle formation and resistance to environmental stresses. OMPs have a characteristic barrel shape formed by antiparallel β-strands, with or without channels that allow diffusion of substrates through the outer membrane. The marine bacterium Vibrio cholerae is responsible for non-invasive gastroenteritis and cholera disease by consumption of contaminated water or food. Its OMPs, besides having a porin function, contribute to resistance to osmotic pressure and antimicrobial agents, intracellular signaling, adhesion to host cells and biofilm formation, amongst other functions. In this review, in addition to quickly reviewing the general structure of the outer membrane, the OMPs and how they reach the outer membrane, the functions attributed to these proteins are compiled. The mechanisms used by each of the described OMP to accomplish these functions in the marine pathogenic bacterium V. cholerae are discussed. Potential clinical and bioengineering applications of OMPs, such as diagnostic tools, vaccine development, and targeted antimicrobial or anti-virulence strategies are presented. What is known about the OMPs of V. cholerae is presented below. Full article

Nowadays, healthcare systems face two global challenges: the rise of multidrug-resistant pathogens and the growing incidence of cancer. Due to their broad spectrum of activities, antimicrobial peptides emerged as potential alternatives against both threats. Our group previously described the antifungal activity of the α-helical peptide Cm-p5, a derivative of the natural peptide Cm-p1, isolated from the coastal mollusk Cenchritis muricatus; however, its anti-cancer properties remained unexplored. Analyses through calorimetry and molecular dynamics simulations suggest the relevance of phosphatidylserine for the attachment of Cm-p5 to cancer cell membranes. Cm-p5 exhibited cytotoxic activity in a dose-dependent manner against A375 melanoma cells, without toxicity against non-malignant cells or hemolytic activity. DAPI/PI and DiSC3(5) staining confirmed permeabilization, disruption, and depolarization of A375 cytoplasmic membranes by Cm-p5. Furthermore, Annexin V-FITC/PI assay revealed the induction of cellular death in melanoma cells, which can result from the cumulative membrane damage and oxidative stress due to the overproduction of reactive oxygen species (ROS). Moreover, after the treatment, the proliferation of A375 cells was dampened for several days, suggesting that Cm-p5 might inhibit the recurrence of melanomas. These findings highlight the multifunctional nature of Cm-p5 and its potential for treating malignant melanoma. Full article

The resistance of breast cancer cells to therapeutic antibodies such as anti-HER2 trastuzumab can be overcome by engaging natural killer (NK) cells for killing antibody-binding tumor cells via antibody-dependent cellular cytotoxicity (ADCC). Here, we investigated how autophagy modulation affects trastuzumab-mediated ADCC in HER2-positive JIMT1 breast cancer cells and NK cells. Autophagy inducers (rapamycin and resveratrol) had no significant impact, but the inhibitor bafilomycin nearly abolished ADCC. Protection occurred when either cancer or NK cells were pretreated, indicating dual effects. Bafilomycin reduced phosphatidylserine externalization, the loss of plasma membrane integrity, caspase-3/7 activity, and DNA fragmentation. It downregulated pro-apoptotic BAK1 and BAX without altering BCL-2. Additionally, bafilomycin decreased HER2 surface expression, impairing trastuzumab binding, and modulated immune regulators (STAT1, CD95, and PD-L1) in NK and/or in the cancer cells. Bafilomycin disrupted HER2 trafficking and induced HER2 internalization, leading to its accumulation in cytoplasmic vesicles. These findings show that autophagy inhibition by bafilomycin confers ADCC resistance by altering apoptosis, immune signaling, and HER2 dynamics. The study underscores autophagy’s role in antibody-based cancer therapy efficacy. Full article