Evidence linking exposure of fish primary macrophages to antibiotics activates the NF-kB pathway.

Low doses of antibiotics are ubiquitous in the marine environment and may exert negative effects on non-target aquatic organisms. Using primary macrophages of common carp, we investigated the mechanisms of action following exposure to several common antibiotics; cefotaxime, enrofloxacin, tetracycline, sulfamonomethoxine, and their mixtures, and explored the immunomodulatory effects associated with the nuclear factor-κB (NF-κB) signaling pathway. A KEGG pathway analysis was conducted using the sixty-six differentially expressed genes found in all treatments, and showed that exposure to 100 μg/L of antibiotics could affect regulation of the NF-κB signaling pathway, suggesting that activation of NF-κB is a common response in all four classes of antibiotics. In addition, the four antibiotics induced nf-κb and NF-κB-associated cytokines expression, as verified by qPCR, however, these induction responses by four antibiotics were minor when compared to the same concentration of LPS treatment (100 μg/L). Antagonists of NF-κB blocked many of the immune effects of the antibiotics, providing evidence that NF-κB pathways mediate the actions of all four antibiotics. Moreover, exposure to environmentally relevant, low levels (0.01-100 μg/L) of antibiotics induced a NF-κB-mediated immune response, including endogenous generation of ROS, activity of antioxidant enzymes, as well as expression of cytokine and apoptosis. Moreover, exposure to mixtures of antibiotics presented greater effects on most tested immunological parameters than exposure to a single antibiotic, suggesting additive effects from multiple antibiotics in the environment. This study demonstrates that exposure of fish primary macrophages to low doses of antibiotics activates the NF-kB pathway

LHPP promotes the intracellular reactive oxygen species accumulation and sensitivity of gastric cancer to cisplatin via JNK and p38 MAPK pathways

Background. Cisplatin is the first-line chemotherapy drug for the treatment of gastric cancer (GC) patients. However, GC patients who are resistant to cisplatin often do not benefit from it. Therefore, finding a key molecule that affects cisplatin sensitivity is expected to enhance the efficacy of cisplatin in GC treatment. Methods. The human GC cell lines SGC-7901 and BGC-823 were used. The protein chip array was used to screen the cisplatin-resistance genes from the complete response and non-complete response GC patients’ tissues, then, the differential gene expression analysis, GO function annotation analysis, and KEGG pathway enrichment analysis were performed. The GC tissue chip in the GEO database was analyzed to screen the target gene. Flow cytometry, Hoechst 33342 staining assay, Western Blot, MTT, tumor sphere formation, cell cycle, and apoptosis assays were performed to explore the effect of Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase (LHPP) on the apoptosis, stemness, and reactive oxygen species (ROS) accumulation of cisplatin-resistant GC cells treated with cisplatin. In vivo, the cisplatin-resistant GC cell lines transfected with pcDNA-LHPP or si-LHPP were injected subcutaneously into mice to construct GC subcutaneous xenograft GC models. Results. Based on protein chip array and bioinformatics analysis, it was found that LHPP is the core molecule in the cisplatin resistance regulatory network in GC, and its expression is down-regulated in GC cisplatin-resistant tissues and cells. In vitro and in vivo experimental results show that the up-regulated expression of LHPP is closely related to the increase in sensitivity of GC to cisplatin. Mechanically, we found that overexpression of LHPP may inhibit the activation of the JNK and p38 MAPK pathways, promote cisplatininduced ROS accumulation, suppress stemness, and enhance the sensitivity of GC to cisplatin. Conclusions. Up-regulation of LHPP may inhibit the activation of the JNK and p38 MAPK pathways, attenuate stemness, and enhance the accumulation of intracellular ROS, thereby promoting cisplatin-mediated GC cell apoptosis and enhancing cisplatin sensitivity

Enrofloxacin Induces Intestinal Microbiota-Mediated Immunosuppression in Zebrafish

The immunosuppressive effects of antibiotics and the potential associations with the intestinal microbiota of the host have been increasingly recognized in recent years. However, the detailed underlying mechanisms of immune interference of antibiotics in environmental organisms remain unclear, particularly at the early life stage of high sensitivity. To better understand the gut microbiome and immune function interactions, the vertebrate model, zebrafish, was treated with environmentally relevant concentrations of a frequently detected antibiotic, enrofloxacin (ENR), ranging from 0.01 to 100 μg/L. 16S ribosomal RNA sequencing indicated diminished diversity, richness, and evenness of intestinal flora following ENR treatment. Twenty-two taxa of gut bacteria including Rickettsiales, Pseudomonadales, and Flavobacteriales were significantly correlated with immunosuppressive biomarkers, including a significant decrease in the abundance of macrophages and neutrophils. To validate the immunomodulatory effects due to altered intestinal microbial populations, zebrafish reared under sterile and non-sterile husbandry conditions were compared after ENR treatment. A significant inhibitory effect was induced by ENR treatment under non-sterile conditions, while the number of macrophages and neutrophils, as well as biomarkers of immunosuppressive effects, were significantly salved in zebrafish under sterile conditions, confirming for the first time that immunosuppression by ENR was closely mediated through alterations of the intestinal microbiome in fish.publishedVersio

Toxicity study of oral vanadyl sulfate by NMR-based metabonomic

Vanadium compounds have been believed to be ideal drugs for diabetes biological therapy in future, but they suffer setback for the potential toxicity now. Toxicity study is necessary for vanadyl drugs development. This paper investigated the toxicity effects of vanadyl sulfate (VOSO4) oral administration in male Wistar rats using H-1 NMR-based metabonomic analysis and clinical biochemical analysis. Rat urine were collected and their H-1 NMR spectra were acquired, and then subjected to multi-variable statistical analysis. Compared to control groups, urinary excretion of lactate, TMAO, creatinine, taurine and hippurate increased following VOSO4 dosing, with concomitant decrease in the level of acetate and succinate. The dosed groups can be readily discriminated from the control groups by principle component analysis. The results showed that VOSO4 can affect energy metabolism process, interrupted intestinal microfloral metabolism, and induced liver and kidney injury. NMR-based metabonomic can offer additional information to traditional clinical chemistry in the sensitivity and specificity of results obtained

Biomolecule-assisted synthesis of 3D structure gold nanocrystals in the presence of cystamine dihydrochloride or cysteamine

A facile cystamine-assisted route was designed for the selectively controlled synthesis of 1D and novel, interesting 3D gold litchi-like nanostructures. By controlling reaction conditions such as the molar ratio between HAuCl(4) and cystamine dihydrochloride and the reaction time, the synthesis of various 3D architectural structures and 1D structure in large quantities can be controlled. The formation mechanism for the gold litchi-like assemblies with well-arranged nanorods was also discussed. In addition, as the control test, featheriness gold structures were obtained through using cysteamine as the assisted agent. On the basis of the results from SEM studies and our analysis, we speculate that the different morphologies obtained by cystamine dihydrochloride and cysteamine due to the Au-S interaction. These differences in hydrogen storage capacity are likely due to the size and density of space/pores as well as the morphology of different nanostructures. This facile, environmentally benign, and - solution-phase biomolecule-assisted method can be potentially extended to the preparation of other metal nanostructures

Plastics can be used more sustainably in agriculture

Plastics have become an integral component in agricultural production as mulch films, nets, storage bins and in many other applications, but their widespread use has led to the accumulation of large quantities in soils. Rational use and reduction, collection, reuse, and innovative recycling are key measures to curb plastic pollution from agriculture. Plastics that cannot be collected after use must be biodegradable in an environmentally benign manner. Harmful plastic additives must be replaced with safer alternatives to reduce toxicity burdens and included in the ongoing negotiations surrounding the United Nations Plastics Treaty. Although full substitution of plastics is currently not possible without increasing the overall environmental footprint and jeopardizing food security, alternatives with smaller environmental impacts should be used and endorsed within a clear socio-economic framework. Better monitoring and reporting, technical innovation, education and training, and social and economic incentives are imperative to promote more sustainable use of plastics in agriculture

Catestatin Enhances Neuropathic Pain Mediated by P2X4 Receptor of Dorsal Root Ganglia in a Rat Model of Chronic Constriction Injury

Background/Aims: Neuropathic pain (NPP) is the consequence of a number of central nervous system injuries or diseases. Previous studies have shown that NPP is mediated by P2X4 receptors that are expressed on satellite glial cells (SGCs) of dorsal root ganglia (DRG). Catestatin (CST), a neuroendocrine multifunctional peptide, may be involved in the pathogenesis of NPP. Here, we studied the mechanism through which CST affects NPP. Methods: We made rat models of chronic constriction injury (CCI) that simulate neuropathic pain. Rat behavioral changes were estimated by measuring the degree of hyperalgesia as assessed by the mechanical withdrawal threshold (MWT) and the thermal withdrawal latency (TWL). P2X4 mRNA expression was detected by quantitative real-time reverse transcription-polymerase chain reaction. P2X4 protein level and related signal pathways were assessed by western blot. Additionally, double-labeled immunofluorescence was employed to visualize the correspondence between the P2X4 receptor and glial fibrillary acidic protein. An enzyme-linked immunosorbent assay was performed to determine the concentration of CST and inflammatory factors. Results: CST led to lower MWT and TWL and increased P2X4 mRNA and protein expression on the SGCs of model rats. Further, CST upregulated the expression of phosphor-p38 and phosphor-ERK 1/2 on the SGCs of CCI rats. However, the expression level of phosphor-JNK and phosphor-p65 did not obviously change. Conclusion: Taken together, CST might boost NPP by enhancing the sensitivity of P2X4 receptors in the DRG of rats, which would provide us a novel perspective and research direction to explore new therapeutic targets for NPP

Insights into technical challenges in the field of microplastic pollution through the lens of early career researchers (ECRs) and a proposed pathway forward

Early career researchers (ECR) face a series of challenges related to the inherent difficulties of starting their careers. Microplastic (MP) research is a topical field attracting high numbers of ECRs with diverse backgrounds and expertise from a wealth of disciplines including environmental science, biology, chemistry and ecotoxicology. In this perspective the challenges that could hinder scientific, professional, or personal development are explored, as identified by an international network of ECRs, all employed in MP research, that was formed following a bilateral workshop for scientists based in the UK and China. Discussions amongst the network were grouped into four overarching themes of technical challenges: in the field, in the laboratory, in the post data collection phase, and miscellaneous. The three key areas of representativeness, access to appropriate resources, training, and clean labs, and the use of databases and comparability, as well as the overarching constraint of available time were identified as the source of the majority of challenges. A set of recommendations for pathways forward are proposed based on the principles of research openness, access to information and training, and widening collaborations. ECRs have great capacity to promote research excellence in the field of MPs and elsewhere, when provided with appropriate opportunities and suitable support

Insights into technical challenges in the field of microplastic pollution through the lens of early career researchers (ECRs) and a proposed pathway forward

Early career researchers (ECR) face a series of challenges related to the inherent difficulties of starting their careers. Microplastic (MP) research is a topical field attracting high numbers of ECRs with diverse backgrounds and expertise from a wealth of disciplines including environmental science, biology, chemistry and ecotoxicology. In this perspective the challenges that could hinder scientific, professional, or personal development are explored, as identified by an international network of ECRs, all employed in MP research, that was formed following a bilateral workshop for scientists based in the UK and China. Discussions amongst the network were grouped into four overarching themes of technical challenges: in the field, in the laboratory, in the post data collection phase, and miscellaneous. The three key areas of representativeness, access t

Correlation between musculoskeletal ultrasound signs of gouty arthritis and disease activity

717-721Gouty arthritis is an extremely painful condition that involves small joints and causes tissue stiffness and joint dysfunction in patients. Musculoskeletal ultrasound (MSUS) offers significant advantages over conventional examinations such as X-ray, computed tomography (CT) and magnetic resonance imaging (MRI) in obtaining images of bones and soft tissues. Here, we analyzed the correlation between musculoskeletal ultrasound signs of gouty arthritis and disease activity. Eighty-nine patients with gouty arthritis who were diagnosed and treated in Affiliated Nanhua Hospital, University of South China, Hengyang, China, between November 2019 and December 2021 were involved in this retrospective research. The patients were devided into Group H (DAS＞3.2, n=41) and Group L (2.6＜DAS≤3.2, n=48) according to the disease activity scores (DASs). All patients underwent musculoskeletal ultrasound and were assessed for disease activity. Pearson analysis was employed to analyze the correlation between musculoskeletal ultrasound manifestations and disease activity. Patients with moderate to high disease activity showed significantly higher musculoskeletal ultrasound scores and DAS results than those with low disease activity (P <0.05). Synovial hyperplasia score, blood flow signal score, joint effusion score, bone erosion score, and total musculoskeletal ultrasound score were all positively correlated with disease activity (r=0.811, 0.814, 0.837, 0.788, 0.976, all P <0.05). Gouty arthritis musculoskeletal ultrasound findings are positively correlated with disease activity. Thus, the manifestations of musculoskeletal ultrasound demonstrate a good potential to provide informative evidence for the assessment of disease activity in patients with gouty arthritis