Emerging infectious diseases (EIDs) pose a significant threat to public health. Effective surveillance and early warning systems that monitor EIDs in a timely manner are crucial for their control. Given that more than half of EIDs are zoonotic, traditional integrated surveillance systems remain inadequate.
View Article and Find Full Text PDFGhrelin is a class of brain and intestinal peptides. It regulates food intake and body glucose levels and maintains cellular homeostasis. In recent years, research has revealed that ghrelin may positively impact learning and memory.
View Article and Find Full Text PDFSigma-1 receptor (Sig-1R) agonists has therapeutic effects in neurological disorders and possesses properties that can reverse cognitive dysfunction. This study investigated the therapeutic efficacy of Sig-1R activation on cognitive dysfunction in streptozotocin (STZ) combined with high fat and high sugar diet (HFD)-induced type 2 diabetic rats. By employing morris water maze (MWM) testing and computed tomography (CT) imaging, we observed that activation of Sig-1R effectively mitigated brain atrophy and cognitive impairment in diabetes-induced cognitive impairment (DCI) rats.
View Article and Find Full Text PDFDiabetic neuropathic pain (DNP) is a common complication of diabetes mellitus (DM) and is characterized by spontaneous pain and neuroinflammation. The Sigma-1 receptor (Sig-1R) has been proposed as a target for analgesic development. It is an important receptor with anti-inflammatory properties and has been found to regulate DNP.
View Article and Find Full Text PDFThis study aimed to clarify the protective effect of Glycyrrhizic acid (GL) against Diosbulbin B (DB) - induced liver injury in mice and investigate its mechanisms of action. A liver injury DB was established in mice through the oral administration of DB for 15 days. At the same time, GL was administered to the mice for treatment.
View Article and Find Full Text PDFIntroduction: Soil nutrient supply drives the ecological functions of soil micro-food webs through bottom-up and top-down mechanisms in degraded agroecosystems. Nutrient limitation responds sensitively to variations in degraded agroecosystems through restoration practices, such as legume intercropping.
Objectives: This study examined the effects of legume intercropping on trophic cascade dynamics through resource supply in degraded purple soil ecosystems.
Ethnopharmacological Relevance: Dioscorea bulbifera L. (DBL) was a traditional Chinese medicine commonly used to treat goitre and cancer. Nevertheless, its clinical application may lead to liver injury.
View Article and Find Full Text PDFAntifungal drug resistance is a critical concern, demanding innovative therapeutic solutions. The dual-targeting mechanism of action (MoA), as an effective strategy to reduce drug resistance, has been validated in the design of antibacterial agents. However, the structural similarities between mammalian and fungal cells complicate the development of such a strategy for antifungal agents as the selectivity can be compromised.
View Article and Find Full Text PDFEur J Med Chem
December 2024
Several empirical and theoretical studies suggest the presence of multiple enhancers per gene that collectively regulate gene expression, and that common sequence variation impacting on the activities of these enhancers is a major source of inter-individual gene expression variability. However, for the vast majority of genes, enhancers and the underlying regulatory variation remains unknown. Even for the genes with well-characterized enhancers, the nature of the combined effects from multiple enhancers and their variants, when known, on gene expression regulation remains unexplored.
View Article and Find Full Text PDFIn the present work, we pioneered a coordinated self-assembly approach aimed at fabricating carrier-free hybrid nanoparticles to address the inherent challenges of the anaerobic microenvironment and the oxidative resistance induced by reductive glutathione (GSH) in photodynamic therapy (PDT). In these nanoparticles, protoporphyrin IX (PP), HIF-1α inhibitor of '-(2,5-Dichlorosulfonyl) cystamine KC7F2 (KC), and the cofactor Fe present hydrogen bond and coordination interaction. The nanoparticles exhibited efficient cellular uptake by CAL-27 cells, facilitating their accumulation in tumors by enhanced permeability and retention (EPR) effect.
View Article and Find Full Text PDFThe branched architecture of neuronal dendrites is a key factor in how neurons form ordered networks and discoveries continue to be made identifying proteins and protein-protein interactions that direct or execute the branching and extension of dendrites. Our prior work showed that the molecular scaffold Pdlim5 and delta-catenin, in conjunction, are two proteins that help regulate the branching and elongation of dendrites in cultured hippocampal neurons and do so through a phosphorylation-dependent mechanism triggered by upstream glutamate signaling. In this report we have focused on Pdlim5's multiple scaffolding domains and how each contributes to dendrite branching.
View Article and Find Full Text PDFGlycine- and arginine-rich (GAR) motifs, commonly found in RNA-binding and -processing proteins, can be symmetrically (SDMA) or asymmetrically (ADMA) dimethylated at the arginine residue by protein arginine methyltransferases. Arginine-methylated protein motifs are usually read by Tudor domain-containing proteins. Here, using a GFP-Trap, we identify a non-Tudor domain protein, squamous cell carcinoma antigen recognized by T cells 3 (SART3), as a reader for SDMA-marked GAR motifs.
View Article and Find Full Text PDFMelasma is an acquired hypermelanotic condition characterized by the presence of irregular light-to-dark brown macules that primarily manifest on the sun-exposed areas of the skin, particularly the face. The management of melasma poses significant challenges, as it is often recalcitrant to treatment and tends to recur despite successful treatment. In this study, we explored a safe, easy, and effective melasma treatment strategy.
View Article and Find Full Text PDFPersistent inflammation and disrupted immunoregulation are critical factors in impeding diabetic wound healing. While immunoregulatory hydrogel dressings hold significant promise for clinical applications in diabetic wound healing, the current application often demands intricate interventions and high-cost treatments involving cytokines and cell therapies. The development of single component immunoregulatory hydrogels remains a complex challenge.
View Article and Find Full Text PDFSeveral empirical and theoretical studies suggest presence of multiple enhancers per gene that collectively regulate gene expression, and that common sequence variation impacting on the activities of these enhancers is a major source of inter-individual variability in gene expression. However, for vast majority of genes, enhancers and the underlying regulatory variation remains unknown. Even for the genes with well-characterized enhancers, the nature of the combined effects from multiple enhancers and their variants, when known, on gene expression regulation remains unexplored.
View Article and Find Full Text PDFWhile significant advances have been made in predicting static protein structures, the inherent dynamics of proteins, modulated by ligands, are crucial for understanding protein function and facilitating drug discovery. Traditional docking methods, frequently used in studying protein-ligand interactions, typically treat proteins as rigid. While molecular dynamics simulations can propose appropriate protein conformations, they're computationally demanding due to rare transitions between biologically relevant equilibrium states.
View Article and Find Full Text PDFHere we report on the development and comprehensive evaluations of an mRNA vaccine for chronic hepatitis B (CHB) treatment. In two different HBV carrier mouse models generated by viral vector-mediated HBV transfection (pAAV-HBV1.2 and rAAV8-HBV1.
View Article and Find Full Text PDFPhotosensitizers have been widely used to cause intratumoral generation of reactive oxygen species (ROS) for cancer therapy, but they are easily disturbed by the autophagy pathway, a self-protective mechanism by mitigating oxidative damage. Hereby, we reported a simple and effective strategy to construct a carrier-free nanodrug, Ce6@CQ namely, based on the self-assembly of the photosensitizer chlorin e6 (Ce6) and the autophagy inhibitor chloroquine (CQ). Specifically, Ce6@CQ avoided the unexpected toxicity caused by the regular nanocarrier and also ameliorated its stability in different conditions.
View Article and Find Full Text PDFHerpes zoster remains an important global health issue and mainly occurs in aged and immunocompromised individuals with an early exposure history to Varicella Zoster Virus (VZV). Although the licensed vaccine Shingrix has remarkably high efficacy, undesired reactogenicity and increasing global demand causing vaccine shortage urged the development of improved or novel VZV vaccines. In this study, we developed a novel VZV mRNA vaccine candidate (named as ZOSAL) containing sequence-optimized mRNAs encoding full-length glycoprotein E encapsulated in an ionizable lipid nanoparticle.
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