Application of PLGA in Tumor Immunotherapy.

Biodegradable polymers have been extensively researched in the field of biomedicine. Polylactic-co-glycolic acid (PLGA), a biodegradable polymer material, has been widely used in drug delivery systems and has shown great potential in various medical fields, including vaccines, tissue engineering such as bone regeneration and wound healing, and 3D printing. Cancer, a group of diseases with high mortality rates worldwide, has recently garnered significant attention in the field of immune therapy research. In recent years, there has been growing interest in the delivery function of PLGA in tumor immunotherapy. In tumor immunotherapy, PLGA can serve as a carrier to load antigens on its surface, thereby enhancing the immune system's ability to attack tumor cells. Additionally, PLGA can be used to formulate tumor vaccines and immunoadjuvants, thereby enhancing the efficacy of tumor immunotherapy. PLGA nanoparticles (NPs) can also enhance the effectiveness of tumor immunotherapy by regulating the activity and differentiation of immune cells, and by improving the expression and presentation of tumor antigens. Furthermore, due to the diverse physical properties and surface modifications of PLGA, it has a wider range of potential applications in tumor immunotherapy through the loading of various types of drugs or other innovative substances. We aim to highlight the recent advances and challenges of plga in the field of oncology therapy to stimulate further research and development of innovative PLGA-based approaches, and more effective and personalized cancer therapies.

ß-Nicotinamide Mononucleotide Alleviates Hydrogen Peroxide-Induced Cell Cycle Arrest and Death in Ovarian Granulosa Cells.

Maintaining normal functions of ovarian granulosa cells (GCs) is essential for oocyte development and maturation. The dysfunction of GCs impairs nutrition supply and estrogen secretion by follicles, thus negatively affecting the breeding capacity of farm animals. Impaired GCs is generally associated with declines in Nicotinamide adenine dinucleotide (NAD+) levels, which triggers un-controlled oxidative stress, and the oxidative stress, thus, attack the subcellular structures and cause cell damage. ß-nicotinamide mononucleotide (NMN), a NAD+ precursor, has demonstrated well-known antioxidant properties in several studies. In this study, using two types of ovarian GCs (mouse GCs (mGCs) and human granulosa cell line (KGN)) as cell models, we aimed to investigate the potential effects of NMN on gene expression patterns and antioxidant capacity of both mGCs and KGN that were exposed to hydrogen peroxide (H2O2). As shown in results of the study, mGCs that were exposed to H2O2 significantly altered the gene expression patterns, with 428 differentially expressed genes (DEGs) when compared with those of the control group. Furthermore, adding NMN to H2O2-cultured mGCs displayed 621 DEGs. The functional enrichment analysis revealed that DEGs were mainly enriched in key pathways like cell cycle, senescence, and cell death. Using RT-qPCR, CCK8, and ß-galactosidase staining, we found that H2O2 exposure on mGCs obviously reduced cell activity/mRNA expressions of antioxidant genes, inhibited cell proliferation, and induced cellular senescence. Notably, NMN supplementation partially prevented these H2O2-induced abnormalities. Moreover, these similar beneficial effects of NMN on antioxidant capacity were confirmed in the KGN cell models that were exposed to H2O2. Taken together, the present results demonstrate that NMN supplementation protects against H2O2-induced impairments in gene expression pattern, cell cycle arrest, and cell death in ovarian GCs through boosting NAD+ levels and provide potential strategies to ameliorate uncontrolled oxidative stress in ovarian GCs.

A Corrective Method for Different Hematocrit Values of Whole Blood Samples on the Detection of Procalcitonin.

BACKGROUND: We have explored that quantitative PCT detection can be conducted in different sample types (whole blood and/or plasma samples) with good correlation and consistency in clinical use. These findings reduce the sample volume and turnover time of PCT detection in clinical labs. However, different hematocrit (HCT) percentages of whole blood samples may affect the final results, especially abnormal hematocrit (HCT) percentages. To overcome this problem, we established a mathematical model to modify the whole blood test results and evaluated the effects of HCT correction. METHODS: First, we prepared a preliminary experiment - various hematocrit (HCT) percentages (15% - 65%) of whole blood samples with different PCT concentrations and established a mathematic model to correct the effects of PCT detection. Then, in this paper, we evaluated the consistency with Pearson's correlation and Kappa analysis between whole bloods detected by the i-Reader S system and plasma detected by the Biomerieux system. Besides, we prepared different HCT values about 15%, 40%, 60% of 9 samples with different PCT concentrations to evaluate the effects of HCT correction Results and Conclusions: Pearson's correlative studies and Kappa analysis indicated that PCT levels measured by i-Reader S (plasma & whole blood samples) were comparable to results from the VIDAS system, and HCT correction could improve consistency of PCT detection between whole blood and plasma. Analysis of samples with abnormal HCT values showed that the mathematical correction model could offset the influences of various HCT values.

Identification of genetic bases of vibrio fluvialis species-specific biochemical pathways and potential virulence factors by comparative genomic analysis.

Vibrio fluvialis is an important food-borne pathogen that causes diarrheal illness and sometimes extraintestinal infections in humans. In this study, we sequenced the genome of a clinical V. fluvialis strain and determined its phylogenetic relationships with other Vibrio species by comparative genomic analysis. We found that the closest relationship was between V. fluvialis and V. furnissii, followed by those with V. cholerae and V. mimicus. Moreover, based on genome comparisons and gene complementation experiments, we revealed genetic mechanisms of the biochemical tests that differentiate V. fluvialis from closely related species. Importantly, we identified a variety of genes encoding potential virulence factors, including multiple hemolysins, transcriptional regulators, and environmental survival and adaptation apparatuses, and the type VI secretion system, which is indicative of complex regulatory pathways modulating pathogenesis in this organism. The availability of V. fluvialis genome sequences may promote our understanding of pathogenic mechanisms for this emerging pathogen.

Quorum sensing regulatory cascades control Vibrio fluvialis pathogenesis.

Quorum sensing (QS) is a process by which individual bacteria are able to communicate with one another, thereby enabling the population as a whole to coordinate gene regulation and subsequent phenotypic outcomes. Communication is accomplished through production and detection of small molecules in the extracellular milieu. In many bacteria, particularly Vibrio species, multiple QS systems result in multiple signals, as well as cross talk between systems. In this study, we identify two QS systems in the halophilic enteric pathogen Vibrio fluvialis: one acyl-homoserine lactone (AHL) based and one CAI-1/AI-2 based. We show that a LuxI homolog, VfqI, primarily produces 3-oxo-C10-HSL, which is sensed by a LuxR homolog, VfqR. VfqR-AHL is required to activate vfqI expression and autorepress vfqR expression. In addition, we have shown that similar to that in V. cholerae and V. harveyi, V. fluvialis produces CAI-1 and AI-2 signal molecules to activate the expression of a V. cholerae HapR homolog through LuxO. Although VfqR-AHL does not regulate hapR expression, HapR can repress vfqR transcription. Furthermore, we found that QS in V. fluvialis positively regulates production of two potential virulence factors, an extracellular protease and hemolysin. QS also affects cytotoxic activity against epithelial tissue cultures. These data suggest that V. fluvialis integrates QS regulatory pathways to play important physiological roles in pathogenesis.

The Prevalence of Functional Quorum-Sensing Systems in Recently Emerged Vibrio cholerae Toxigenic Strains.

Vibrio cholerae live in aquatic environments and cause cholera disease. Like many other bacteria, V. cholerae use quorum-sensing (QS) systems to control various cellular functions, such as pathogenesis and biofilm formation. However, some V. cholerae strains are naturally QS-defective, including defective mutations in the quorum sensing master regulator HapR. Here we examined the QS functionality of 602 V. cholerae clinical and environmental strains isolated in China from 1960-2007, by measuring QS-regulated gene expression. We found that a greater percentage of the toxigenic strains (ctxAB(+)) had functional QS as compared to the non-toxigenic strains (ctxAB(-)), and that this trend increased significantly over time. We hypothesize that QS provides adaptive value in V. cholerae pathogenic settings.

[Isolation of phenol-degrading bacteria from natural soil and their phylogenetic analysis].

Five bacterial strains capable of utilizing phenol as sole carbon source for growth were isolated from non-contaminated natural soil sample after enrichment in the presence of phenol. They were preliminarily identified according to their phylogenetic analysis and physiological and biochemical characteristics. Strain PHD-2, PHD-4 and PHD-5 belonged to the genera of Ralstonia, Acinetobacter and Microbacterium respectively; strain PHD-1 and PHD-3 were from the genus of Pseudomonas. Homology comparing of their 16S rRNA gene sequences and phylogenetic analysis displayed the high biodiversity of phenol-degrading microorganisms in the natural soil.