Effects of environmentally relevant concentration of short-chain chlorinated paraffins on BV2 microglia activation and lipid metabolism, implicating altered neurogenesis.

Short-chain chlorinated paraffins (SCCPs), a class of persistent organic pollutants, have been found to cause diverse organ and systemic toxicity. However, little is known about their neurotoxic effects. In this study, we exposed BV2, a mouse microglia cell line, to environmentally relevant concentration of SCCPs (1 µg/L, 10 µg/L, 100 µg/L) for 24 h to investigate their impacts on the nervous system. Our observations revealed that SCCPs induced the activation of BV2 microglia, as indicated by altered morphology, stimulated cell proliferation, enhanced phagocytic and migratory capabilities. Analysis at the mRNA level confirmed the activation status, with the downregulation of TMEM119 and Tgfbr1, and upregulation of Iba1 and CD11b. The upregulated expression of genes such as cenpe, mki67, Axl, APOE and LPL also validated alterations in cell functions. Moreover, BV2 microglia presented an M2 alternative phenotype upon SCCPs exposure, substantiated by the reduction of NF-κB, TNF-α, IL-1ß, and the elevation of TGF-ß. Additionally, SCCPs caused lipid metabolic changes in BV2 microglia, characterized by the upregulations of long-chain fatty acids and acylcarnitines, reflecting an enhancement of ß-oxidation. This aligns with our findings of increased ATP production upon SCCPs exposure. Intriguingly, cell activation coincided with elevated levels of omega-3 polyunsaturated fatty acids. Furthermore, activated microglial medium remarkably altered the proliferation and differentiation of mouse neural stem cells. Collectively, exposure to environmentally relevant concentrations of SCCPs resulted in activation and lipid metabolic alterations in BV2 microglia, potentially impacting neurogenesis. These findings provide valuable insights for further research on the neurotoxic effect of SCCPs.

Effect of Ulinastatin Combined with Somatostatin on Inflammatory Markers, Hemodynamics and Immune Cells in the Treatment of Severe Pancreatitis.

Objective: Severe pancreatitis presents a formidable clinical challenge, often associated with high mortality rates and compromised quality of life. This study aimed to assess the efficacy of combining ulinastatin with somatostatin in treating severe pancreatitis, with a focus on improving patient outcomes. Methods: We conducted a study on 98 severe pancreatitis patients at our hospital from January 2022 to March 2023. These patients were randomly divided into two groups: a control group (n=49) treated with somatostatin and an experimental group (n=49) treated with ulinastatin plus somatostatin. The control group received 250 micrograms per hour of somatostatin intravenously for 72 hours. The experimental group received 200 000 units of ulinastatin every 8 hours intravenously, along with the same somatostatin regimen. We compared clinical efficacy, inflammatory markers (TNF-α, CRP, IL-6), hemodynamic parameters (MAP, CVP, HR, SVR), and immune cell function between the groups. Results: Post-treatment, the experimental group showed significant improvements compared to the control group (P < .05) in various parameters. Decreases in AMS, TNF-α, CRP, IL-6, MAP, CVP, and CD8+ T-cells were more pronounced in the experimental group. Notably, AMS levels dropped from 450 U/L to 150 U/L, and TNF-α levels from 55 pg/mL to 20 pg/mL in the experimental group. Conversely, increases in HR, SVR, CD4+ T-cells, CD4+/CD8+ ratio, and NK cell counts were observed. For instance, CD4+ T-cells rose from 300 cells/µL to 500 cells/µL. The experimental group exhibited a higher clinical efficacy rate of 97.96%, compared to 85.71% in the control group. The combined treatment of ulinastatin with somatostatin demonstrated significant effectiveness in improving clinical outcomes compared to the control group. Statistical analysis robustly supported these findings, providing confidence in their reliability. Importantly, the combined therapy showed promise in reducing mortality rates and enhancing the quality of life for patients with severe pancreatitis. Conclusion: The findings of this study hold substantial clinical implications, potentially influencing treatment protocols and patient management strategies for severe pancreatitis. The integration of ulinastatin combined with somatostatin into standard care protocols could significantly improve treatment outcomes and patient prognosis.

Evaluation of bevacizumab biosimilar on wound healing complications in patients with colorectal cancer undergoing endoscopic mucosal resection: A systematic review and meta-analysis in anorectal medicine.

Complications related to wound healing pose substantial obstacle in the management of colorectal cancer (CRC), specifically in the field of anorectal medicine. Biosimilars of bevacizumab have emerged as crucial therapeutic agents in the management of these complications. With the particular emphasis on effects of Bevacizumab Biosimilar Plus on wound healing among patients diagnosed with CRC, this review underscores the potential of this anorectal medication to improve patient outcomes and was aimed to assess the safety and efficacy of Bevacizumab Biosimilar Plus in relation to complications associated with wound healing in patients with CRC. The assessment centers on its therapeutic potential and safety profile within the domain of anorectal medicine. In accordance with the PRISMA guidelines, a comprehensive literature search was performed, resulting in the identification of 19 pertinent studies out of an initial 918. Priority was given to assessing the safety and adverse effects of Bevacizumab Biosimilar Plus in conjunction with its effectiveness in wound healing. The extracted data comprised the following: study design, patient demographics, comprehensive treatment regimens, wound healing-specific outcomes and adverse effects. The evaluation of study quality was conducted utilizing the instruments provided by the Cochrane Collaboration and the Newcastle-Ottawa Scale (NOS). Bevacizumab Biosimilar Plus demonstrates efficacy in the management of wound healing complications among patients with CRC, with a safety and efficacy profile similar to that of the original Bevacizumab, according to the analysis. Notably, several studies reported improved rates of wound healing in relation to the biosimilar. The safety profiles exhibited similarities to the anticipated anti-VEGF agent effects. In wound management, the biosimilar also demonstrated advantages in terms of prolonged efficacy. In addition, analyses of cost-effectiveness suggested that the use of biosimilars could result in cost reductions. Bevacizumab Biosimilar Plus exhibited potential as an anorectal medication for the effective management of wound healing complications in patients with CRC. This has substantial ramifications for improving the quality of patient care, encompassing the affordability and effectiveness of treatments.

Enhanced removal of phosphate from aqueous solutions by oxygen vacancy-rich MgO microspheres: Performance and mechanism.

The efficient removal of phosphate from water environments was extremely significant to control eutrophication of water bodies and prevent further deterioration of water quality. In this study, oxygen vacancy-rich magnesium oxide (OV-MgO) microspheres were synthesized by a simple solvothermal method coupling high-temperature calcination. The effects of adsorbent dosage, contact time, initial pH and coexisting components on phosphate adsorption performance were examined. The physicochemical properties of OV-MgO microspheres and the phosphate removal mechanisms were analyzed by various characterization techniques. The maximum adsorption capacity predicted by the Sips isotherm model was 379.7 mg P/g for OV-MgO microspheres. The phosphate adsorption in this study had a fast adsorption kinetics and a high selectivity. OV-MgO microspheres had a good acid resistance for phosphate adsorption, but their adsorption capacity decreased under alkaline conditions. The electrostatic attraction, ligand exchange, surface precipitation, inner-sphere surface complexation and oxygen vacancy capture were mainly responsible for efficient removal of phosphate from aqueous solutions. This study probably promoted the development of oxygen vacancy-rich metal (hydr)oxides with potential application prospects.

Effects of quaternization sites and crossing methods on the slow-release and antibacterial effects of hydroxypropyltrimethyl ammonium chloride chitosan/dialdehyde chitosan-based film.

In this study, the active food packaging film were prepared using hydroxypropyltrimethyl ammonium chloride chitosan with different substitution sites (O-HACC & N-HACC) and dialdehyde chitosan (DCS) grafted with protocatechuic acid (PA). To explore the effect of chitosan quaternization positions and crosslinking approaches on the slow-release and antibacterial properties, the double-crosslinked film were fabricated through the self-coupling reaction of PA and Schiff base reaction between amino groups on HACC and aldehyde groups on DCS. The HACC/DCS-based film exhibited stable porous three-dimensional networks with high nisin loading ratios (>90 %). With the participation of the catechol-catechol structure, the dense double-crosslinked film effectively restricted the diffusion of the water molecules, resulting in excellent slow-release properties fitting with the Korsmeyer-Peppas kinetic model. Especially, O-HACC/PA-g-DCS film, which had more reaction sites for Schiff base crosslinking than N-HACC, exhibited the equilibrium swelling ratio of 800 % at 60 h and could sustainably release nisin via non-Fickian diffusion behavior until 48 h. Moreover, the HACC/DCS-based double-crosslinked film performed good long-time antibacterial activity and preservation effects on salmon. On the 10th day of storage, the TVBN of N-HACC/PA-g-DCS and O-HACC/PA-g-DCS groups were only 28.26 ± 1.93 and 29.06 ± 1.68 mg/100 g and still lower than the thresholds.

Injectable Inflammation-Responsive Hydrogels for Microenvironmental Regulation of Intervertebral Disc Degeneration.

Chronic local inflammation and excessive cell apoptosis in nucleus pulposus (NP) tissue are the main causes of intervertebral disc degeneration (IDD). Stimuli-responsive hydrogels have great potential in the treatment of IDD by facilitating localized and controlled drug delivery. Herein, an injectable drug-loaded dual stimuli-responsive adhesive hydrogel for microenvironmental regulation of IDD, is developed. The gelatin methacryloyl is functionalized with phenylboronic acid groups to enhance drug loading capacity and enable dual stimuli-responsive behavior, while the incorporation of oxidized hyaluronic acid further improves the adhesive properties. The prepared hydrogel exhibits an enhanced drug loading capacity for diol-containing drugs, pH- and reactive oxygen species (ROS)-responsive behaviors, excellent radical scavenging efficiency, potent antibacterial activity, and favorable biocompatibility. Furthermore, the hydrogel shows a beneficial protective efficacy on NP cells within an in vitro oxidative stress microenvironment. The in vivo results demonstrate the hydrogel's excellent therapeutic effect on treating IDD by maintaining water retention, restoring disc height, and promoting NP regeneration, indicating that this hydrogel holds great potential as a promising therapeutic approach for regulating the microenvironment and alleviating the progression of IDD.

Arsenic-enhanced plant growth in As-hyperaccumulator Pteris vittata: Metabolomic investigations and molecular mechanisms.

The first-known As-hyperaccumulator Pteris vittata is efficient in As uptake and translocation, which can be used for phytoremediation of As-contaminated soils. However, the underlying mechanisms of As-enhanced plant growth are unknown. We used untargeted metabolomics to investigate the potential metabolites and associated metabolic pathways regulating As-enhanced plant growth in P. vittata. After 60 days of growth in an MS-agar medium containing 15 mg kg-1 As, P. vittata biomass was 33-34 % greater than the no-As control. Similarly, the As contents in P. vittata roots and fronds were 272 and 1300 mg kg-1, considerably greater than the no-As control. Univariate and multivariate analyses based on electrospray ionization indicate that As exposure changed the expression of 1604 and 1248 metabolites in positive and negative modes. By comparing with the no-As control, As exposure significantly changed the expression of 14 metabolites including abscisic acid, d-glucose, raffinose, stachyose, chitobiose, xylitol, gibberellic acids, castasterone, citric acid, riboflavin-5-phosphate, ubiquinone, ubiquinol, UDP-glucose, and GDP-glucose. These metabolites are involved in phytohormone synthesis, energy metabolism, and sugar metabolism and may all potentially contribute to regulating As-enhanced plant growth in P. vittata. Our data provide clues to understanding the metabolic regulations of As-enhanced plant growth in P. vittata, which helps to enhance its phytoremediation efficiency of As-contaminated soils.

Injectable pathological microenvironment-responsive anti-inflammatory hydrogels for ameliorating intervertebral disc degeneration.

Chronic local inflammation and resulting cellular dysfunction of nucleus pulposus (NP) cells are important pathogenic factors of intervertebral disc degeneration (IDD). Injectable pathological microenvironment-responsive hydrogels hold significant potential for treating IDD by adapting to dynamic microenvironment of IDD. Herein, we proposed an injectable gelatin-based hydrogel drug delivery system that could respond to the pathological microenvironment of IDD for controlled release of anti-inflammatory drug to promote degenerative NP repair. The hydrogel system was prepared by conjugating phenylboronic acid-modified gelatin methacryloyl (GP) with the naturally extracted anti-inflammatory drug epigallocatechin-3-gallate (EGCG) through dynamic boronic esters. The hydrogel exhibited excellent degradability, injectability, antioxidant properties, anti-inflammatory effects, and biocompatibility. It also displayed responsive-release of EGCG under high reactive oxygen species (ROS) levels and acidic conditions. The hydrogel demonstrated remarkable cytoprotective effects on NP cells in both hyperactive ROS environments and inflammatory cytokine-overexpressed environments in vitro. In vivo studies revealed that the hydrogel injected in situ could effectively ameliorate the intervertebral disc degeneration by maintaining the disc height and NP tissue structure in a rat IDD model. The hydrogel system exhibited excellent biocompatibility and responsive-release of diol-containing drugs in pathological microenvironments, indicating its potential application as a drug delivery platform.

Unraveling paraquat-induced toxicity on mouse neural stem cells: Dose-response metabolomics insights and identification of sensitive biomarkers for risk assessment.

Exposure to pesticide could contribute to neurodevelopmental and neurodegenerative disorders. Notably, research suggests that prenatal or early postnatal exposure to paraquat (PQ), an herbicide, might trigger neurodevelopmental toxicity in neural stem cells (NSCs) via oxidative stress. However, the molecular mechanisms of PQ-induced perturbations in NSCs, particularly at the metabolite level, are not fully understood. Using a dose-response metabolomics approach, we examined metabolic changes in murine NSCs exposed to different PQ doses (0, 10, 20, 40 µM) for 24h. At 20 µM, PQ treatment led to significant metabolic alterations, highlighting unique toxic mechanisms. Metabolic perturbations, mainly affecting amino acid metabolism pathways (e.g., phenylalanine, tyrosine, arginine, tryptophan, and pyrimidine metabolism), were associated with oxidative stress, mitochondrial dysfunction, and cell cycle dysregulation. Dose-response models were used to identify potential biomarkers (e.g., Putrescine, L-arginine, ornithine, L-histidine, N-acetyl-L-phenylalanine, thymidine) reflecting early damage from low-dose PQ exposure. These biomarkers could be used as points of departure (PoD) for characterizing PQ exposure hazard in risk assessment. Our study offers insights into mechanisms and risk assessment related to PQ-induced neurotoxicity in NSCs.

Genome-wide characterization of extrachromosomal circular DNA in SLE and functional analysis reveal their association with apoptosis.

Extrachromosomal circular DNA (eccDNA) derived from linear chromosomes, are showed typical nucleosomal ladder pattern in agarose gel which as a known feature of apoptosis and demonstrated to be immunogenicity. In systemic lupus erythematosus (SLE) patients, elevated levels of cell-free DNA (cfDNA) can be found in either linear forms or circular forms, while circular ones are much less common and harder to detect. The molecular characteristics and function of circular forms in plasma SLE patients remains elusive. Herein, we characterized the hallmarks of plasma eccDNA in SLE patients, including the lower normalized number and GC content of eccDNA in SLE plasma than in the healthy, and SLE eccDNA number positively correlated with C3 and negatively with anti-dsDNA antibodies. The differential eccGenes (eccDNAs carrying the protein coding gene sequence) of SLE was significantly enriched in apoptosis-related pathways. The artificially synthesized eccDNA with sequences of the PRF1 exon region could promote transcriptional expression of PRF1, IFNA and IFIT3 and inhibit early-stage apoptosis. Plasma eccDNA can serve as a novel autoantigen in the pathogenesis of SLE.