Immunotoxicity of microplastics and polychlorinated biphenyls alone or in combination to Crassostrea gigas.

Microplastics (MPs) and polychlorinated biphenyls (PCBs) are pervasive pollutants in the marine environment, exerting adverse effects on marine organisms. While it is suggested that their exposure may compromise the immune responses of marine organisms, the cumulative immunotoxic effects remain uncertain. Additionally, the intricate mechanisms underlying the immunotoxicity of PCBs and MPs in marine organisms are not yet fully comprehended. To illuminate their combined biological impacts, Crassostrea gigas were exposed to 50 µg/L MPs (30-µm porous) alone, as well as 10 or 100 ng/L PCBs individually or in combination with 50 µg/L of MPs for 28 days. Our data demonstrated that oysters treated with the pollutants examined led to decreased total haemocyte count, inhibited phagocytosis of haemocytes, enhanced the intracellular contents of reactive oxygen species, lipid peroxidation and DNA damage, reduced lysozyme concentration and activity, gave rise to superoxide dismutase. Catalaseand glutathione S-transferaseactivity. The expression of three immune-related genes (NF-κB, TNF-α, TLR-6) was drastically suppressed by the PCBs and MPs treatment, while the apoptosis pathway-related genes (BAX and Caspase-3) showed a significant increase. In addition, compared to oysters treated with a single type of pollutant, coexposure to MPs and PCBs exerted more severe adverse impacts on all the parameters investigated, indicating a significant synergistic effect. Therefore, the risk of MPs and PCBs chemicals on marine organisms should be paid more attention.

Identification of a functional polymorphism within the 3'-untranslated region of denticleless E3 ubiquitin protein ligase homolog associated with survival in acral melanoma.

BACKGROUND: High expression of denticleless E3 ubiquitin protein ligase homologue (DTL) correlates with poor disease-free survival and overall survival in cutaneous melanoma, but the molecular features and clinical significance of this gene in acral melanoma (AM) remain unclear. METHODS: The expression levels of DTL were compared between AM and benign melanocytic nevi using existing Gene Expression Omnibus data and validated in fresh frozen tissues. Two candidate tag single-nucleotide polymorphisms (SNPs) in the 3'-untranslated region (3'UTR) of DTL in patients with AM were sequenced and analysed for their association with survival in a discovery cohort (n = 570), and the significant SNP was subjected to a replication cohort (n = 201). The expression of DTL was evaluated by immunohistochemistry. The microRNA interacting with rs11275300:C > G was predicted using in silico target prediction tools and validated by in vitro analysis. RESULTS: DTL was overexpressed in AM compared with benign melanocytic nevi. rs11275300:C > G was found to be significantly associated with progression-free survival and overall survival of patients with AM in both cohorts and the combined cohort. Furthermore, the DTL expression level in the patients with the rs11275300:G allele was higher than that in patients with the CC genotype. In vitro analysis demonstrated that DTL was a direct target of hsa-miR-4672, and the rs11275300:G allele interfered with the binding affinity of hsa-miR-4672 with the 3'UTR of DTL and thereby increased DTL expression. CONCLUSION: The rs11275300:G allele in the 3'UTR of DTL may lead to a poor prognosis and allele-specific increase in the expression of DTL by post-transcriptional regulation in AM.

Hepatitis C virus-related heat-insoluble cryoglobulinemia and thrombotic microangiopathy.

Heat-insoluble cryoglobulinemia is rare, and its pathogenesis and comorbidities remain poorly understood. Here, the authors report a case of hepatitis C virus (HCV)-related heat-insoluble cryoglobulinemia associated with thrombotic microangiopathy and cryoglobulin-occlusive membranoproliferative glomerulonephritis. The patient, a 57-year-old woman, presented with acute kidney injury, thrombocytopenia, anemia with schistocytes, high levels of serum HCV RNA of HCV genotype 2a, rheumatoid factor positivity and high levels of serum immunoglobulin (Ig) M and Igκ. The patient's serum was positive for cryoglobulin at 4°C, and the precipitate required heating to 47°C for dissolution. Cryoglobulin immunofixation was positive for monoclonal IgM and Igκ and polyclonal IgG. However, immunofixation of the cryoglobulin supernatant was negative. Histological examination of renal biopsy revealed a membranoproliferative type I glomerulonephritis. The patient was treated with plasmapheresis, corticosteroids and antiviral therapy of peginterferon plus ribavirin, but symptoms only partially resolved.