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Microplastics are regarded as ubiquitous pollutants in the ocean and have attracted worldwide concerns. Benzo[a]pyrene (B[a]P), one of typical polycyclic aromatic hydrocarbons (PAHs), is commonly detected in marine environment. Once coexisted, the microplastics and B[a]P may interact with each other and result in combined toxicity to organisms, and these remain to be systematically elucidated. Thus, this study aims to investigate (i) the effects of single micro-sized polystyrene (mPS), polyethylene terephthalate (mPET), and B[a]P on cell growth of Chaetoceros muelleri; and (ii) the interaction of microplastics and B[a]P, and their combined effects on C. muelleri. The results showed that both single microplastics and B[a]P at a high concentration of 150 μg/L inhibited the growth of C. muelleri. For single treatment of microplastics, stronger inhibition effects on microalgae was caused by mPET than that of mPS, with the highest IR of 25.23 and 11.17%, respectively. This may be attributed to the obvious surface roughness of mPET. By comparison, the combined effects of microplastics and B[a]P significantly inhibited the growth of C. muelleri as compared with the single treatment of B[a]P (P < 0.05). Synergistic effect was found in the combination of microplastics with B[a]P at high concentrations of 150 μg/L. Interestingly, the antagonistic effect on C. muelleri was observed in the combined treatment of microplastics and B[a]P at low concentrations of 10 μg/L. In addition, the pollutants reduced the content of photosynthetic pigments in microalgal cells. The SOD and MDA content of microalgae increased in the early stage of exposure to pollutants (e.g., Days 1 and 5), but decreased in the later stage (Day 15) compared with the control group. The decreased superoxide dismutase (SOD) and catalase (CAT) activity in single and composite systems may indicate that the antioxidative enzymatic system of microalgae has been inhibited or destroyed. This study will be helpful to further explore the ecological threats of microplastics and PAHs to the marine ecosystem.

Abstract Background Lupus nephritis (LN) is an inflammation of the kidneys and is a major cause of mortality in systemic lupus erythaematosus (SLE) patients. In addition, Th17/Treg balance is one of the most important factors that can promote the development of LN. It has been reported that vasoactive intestinal peptide (VIP) is associated with the downregulation of both inflammatory and autoimmune diseases through regulating T lymphocyte balance. Therefore, the aim of this study was to determine the role of VIP in modulating Th17/Treg balance in LN. Methods LN was induced in BALB/c female mice by injection pristane. After 3 months, mice were randomly divided into four groups: control, VIP + control, LN and VIP + LN. Autoantibody levels were tested by ELISA. The distribution of Th17/Treg cells in vivo and in vitro was detected by FC. Renal tissues were examined by PASM and DIF for pathology and Foxp3+CD3+. The mRNA and protein expression levels of pro- and anti-inflammatory cytokines were detected by qRT-PCR and western blotting. Results VIP can improve renal injury by regulating Th17/Treg imbalance in LN mice. Proteinuria, renal function defects and autoantibodies were significantly decreased, and Th17/Treg cell balance was restored in VIP compared with LN mice. In addition, VIP improved renal lesions by promoting the expression of Foxp3+CD3+ in renal tissue. Furthermore, VIP downregulated the mRNA and protein expression of IL-17, IL-6 and upregulated Foxp3, IL-10 expression. Conclusions VIP reduced LN proteinuria and renal function defects and restored the Th17/Treg cell balance. Furthermore, VIP also downregulated autoantibody and inflammatory cytokine expression and upregulated Foxp3 and IL-10 expression.

Environmental aging of ubiquitous microplastics (MP) occurs through the action of biotic and abiotic factors, and aged MP exhibit different physicochemical properties and environmental behavior from virgin MP. This study aimed to investigate the aged micro-sized polystyrene (mPS) and polyvinyl chloride (mPVC), and the heavy metals copper (Cu) and cadmium (Cd), and examine the effects of their combined toxicities on microalga Chlorella vulgaris. Results showed that the presence of MP inhibited cell growth as compared with the control, the inhibition rate (I) decreased as concentrations of MP rose and aged MP exhibited stronger inhibition of cells than did virgin MP. The largest I was achieved in each culture with the MP concentration of 0.01 g/L, in which aged mPS with the maximal of 36.84% (Iaged mPS) followed by aged mPVC (Iaged mPVC = 30.03%), virgin mPS (Ivirgin mPS = 29.10%) and virgin mPVC (Ivirgin mPVC = 16.72%). Addition of the heavy metals Cu2+ and Cd2+ significantly inhibited cell growth, and toxicity increased with concentrations in a range of 0.5–2.0 mg/L; the maximum I values were 19.50% (ICu) and 85.14% (ICd), respectively. The combined toxicity of aged MP + Cu or aged MP + Cd was less than that of individual heavy metals. In particular, as compared with the maximal ICd of 85.14% achieved by single Cd2+, the toxicity of Cd2+ was greatly reduced when combined with aged mPS and mPVC, with the I value decreased to 27.55% (Iaged mPS) and 32.51% (Iaged mPVC), respectively. Both single and combined treatments caused cell damage to the microalga, accompanied by increased superoxide dismutase (SOD) and intracellular malonaldehyde (MDA) content.

Fractalkine (FKN), also known as chemokine (C-X3-C motif) ligand 1, constitutes an intriguing chemokine with a documented role in the development of numerous inflammatory diseases including autoimmune disease. Specifically, it has been reported that FKN is involved in the disease progression of lupus nephritis (LN). The epithelial-mesenchymal transition (EMT) plays a significant role in the formation of tubulointerstitial lesions (TIL), which are increasingly recognized as a hallmark of tissue fibrogenesis after injury. However, the correlation between FKN and EMT or TIL in LN has not been determined. To investigate the potential role of FKN in EMT and TIL, MRL lymphoproliferation (MRL/lpr) strain mice were treated with an anti-FKN antibody, recombinant-FKN chemokine domain, or isotype antibody. Our results revealed that treatment with the anti-FKN antibody improved EMT, TIL, and renal function in MRL/lpr mice, along with inhibiting activation of the Wnt/β-catenin signaling pathway. In contrast, administration of the recombinant-FKN chemokine domain had the opposite effect. Furthermore, to further explore the roles of FKN in EMT, we assessed the levels of EMT markers in FKN-depleted or overexpressing human proximal tubule epithelial HK-2 cells. Our results provide the first evidence that the E-cadherin level was upregulated, whereas α-SMA and vimentin expression was downregulated in FKN-depleted HK-2 cells. In contrast, overexpression of FKN in HK-2 cells enhanced EMT. In addition, inhibition of the Wnt/β-catenin pathway by XAV939 negated the effect of FKN overexpression, whereas activation of the Wnt/β-catenin pathway by Ang II impaired the effect of the FKN knockout on EMT in HK-2 cells. Together, our data indicate that FKN plays essential roles in the EMT progression and development of TIL in MRL/lpr mice, most likely through activation of the Wnt/β-catenin signaling pathway.

Background. The transcriptional networks of Cyr61 and its function in cell injury are poorly understood. The present study depicted the lncRNA and mRNA profiles and the involvement in angiotensin II-induced injury after Cyr61 knockdown mediated by CRISPR/Cas9 in HEK293T cells. Methods. HEK293T cells were cultured, and Cyr61 knockdown was achieved by transfection of the CRISPR/Cas9 KO plasmid. lncRNA and mRNA microarrays were used to identify differentially expressed genes (DEGs). Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to determine biofunctions and signaling pathways. RT-PCR was used to validate the microarray results. Cells were divided into four groups: control, Cyr61 knockdown, angiotensin II (Ang II) without Cyr61 knockdown, and Ang II with Cyr61 knockdown. CCK8, western blotting, and flow cytometry analysis were carried out to dissect cellular function. Results. A total of 23184 lncRNAs and 28264 mRNAs were normalized. 26 lncRNAs and 212 mRNAs were upregulated, and 74 lncRNAs and 233 mRNAs were downregulated after Cyr61 knockdown. Analysis of cellular components, molecular functions, biological processes, and regulatory pathways associated with the differentially expressed mRNAs revealed downstream mechanisms of the Cyr61 gene. The differentially expressed genes were affected for small cell lung cancer, axon guidance, Fc gamma R-mediated phagocytosis, MAPK signaling pathway, focal adhesion, insulin resistance, and metabolic pathways. In addition, Cyr61 expression was increased in accordance with induction of cell cycle arrest and apoptosis and inhibition of cell proliferation induced by Ang II. Knockdown of Cyr61 in HEK293T cells promoted cell cycle procession, decreased apoptosis, and promoted cell proliferation. Conclusions. The Cyr61 gene is involved in Ang II-induced injury in HEK293T cells. Functional mechanisms of the differentially expressed lncRNAs and mRNAs as well as identification of metabolic pathways will provide new therapeutic targets for Cyr61-realated diseases.