Hepatocellular carcinoma-derived exosomal miRNA-761 regulates the tumor microenvironment by targeting the SOCS2/JAK2/STAT3 pathway.

BACKGROUND: Exosomes and exosomal microRNAs have been implicated in tumor occurrence and metastasis. Our previous study showed that microRNA-761 (miR-761) is overexpressed in hepatocellular carcinoma (HCC) tissues and that its inhibition affects mitochondrial function and inhibits HCC metastasis. The mechanism by which exosomal miR-761 modulates the tumor microenvironment has not been elucidated. METHODS: Exosomal miR-761 was detected in six cell lines. Cell counting kit-8 (CCK-8) and transwell migration assays were performed to determine the function of exosomal miR-761 in HCC cells. The luciferase reporter assay was used to analyze miR-761 target genes in normal fibroblasts (NFs). The inhibitors AZD1480 and C188-9 were employed to determine the role of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in the transformation of cancer-associated fibroblasts (CAFs). RESULTS: In this study, we characterized the mechanism by which miR-761 reprogrammed the tumor microenvironment. We found that HCC-derived exosomal miR-761 was taken up by NFs. Moreover, HCC exosomes affected the tumor microenvironment by activating NFs via suppressor of cytokine signaling 2 (SOCS2) and the JAK2/STAT3 signaling pathway. CONCLUSIONS: These results demonstrated that exosomal miR-761 modulated the tumor microenvironment via SOCS2/JAK2/STAT3 pathway-dependent activation of CAFs. Our findings may inspire new strategies for HCC prevention and therapy.

Prevalence, diagnosis, and treatment of primary hepatic gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GIST), which is the most common mesenchymal tumor of the digestive tract, account for 1%-3% of gastrointestinal tumors. Primary stromal tumors outside the gastrointestinal tract are collectively referred to as extra GISTs, and stromal tumors in different regions often have different prognoses. A primary hepatic GIST is a rare tumor with an unknown origin, which may be related to interstitial Cajal-like cells. Although primary hepatic GIST has certain characteristics on imaging, it lacks specific symptoms and signs; thus, the final diagnosis depends on pathological and genetic evidence. This review summarizes all cases of primary hepatic GIST described in the literature and comprehensively analyzes the detailed clinical data of all patients. In terms of treatment, local resection alone or with adjuvant therapy was the prioritized choice to obtain better disease-free survival and longer survival time. For advanced unresectable cases, imatinib mesylate was applied as the first-line chemotherapy agent. Moreover, transcatheter arterial chemoembolization, radiofrequency ablation, and microwave ablation were shown to improve overall survival for selected patients. Liver transplantation was a final treatment option after resistance to chemotherapy developed.

Effects of salicylic acid on alternative pathway respiration and alternative oxidase expression in tobacco calli.

The alternative pathway (AP) respiration of plants is a cyanide-resistant and non-phosphorylating electron transport pathway in mitochondria. Alternative oxidase (AOX) is the terminal oxidase of the AP and exists in plant mitochondria as two states: the reduced, noncovalently linked state or the oxidized, covalently cross-linked state. In the present study, the effects of 20 microM exogenous salicylic acid (SA) on both AP activity and AOX expression in mitochondria of tobacco (Nicotiana rustica L. cv. yellow flower) calli were investigated. The results showed that SA treatment enhanced the AP activity. During the process of SA treatment, the AP activity increased dramatically and achieved the peak value after 8 h of treatment. Then it declined until 16 h, and maintained a steady level between 16 and 24 h. Changes in both the total AOX protein level and the reduced state were in accordance with the AP activity, but the oxidized state changed differently. The aox1 gene transcript level also showed a similar change as the AP activity and AOX protein level. The induction of AOX expression by low concentrations of SA was inferred through a reactive oxygen species (ROS)-independent pathway. These results indicate that the enhancement of AP activity in response to SA is correlated to the expression of AOX, and the reduced, non-covalently linked state of AOX plays an important role during this process.

Study on the distribution and correlation of trace elements in whole blood of children in Beijing / 中华流行病学杂志

Objective To study the distribution and correlation of trace elements in peripheral blood of children in Beijing so as to offer scientific evidence for the supplementation of trace elements and to prevent lead intoxication. Methods Contents of trace elements in whole blood of 13 929 children in Beijing region were detected by Atomic Absorption Spectrometer. According to developmental condition, children were divided into young infancy group, infancy group, toddler's age group, preschool age group, school age group and adolescence group. Every group was divided into males and females. Distribution and correlation of trace elements in different age groups and in different sex sets were then analyzed and compared. Results The level of copper, calcium and magnesium were stable in different age groups and in different sex sets.There were no obvious significant differences in age groups and sex sets and there were no deficiency of copper, calcium and magnesium discovered. The level of zinc increased gradually following the growth of age and the level of zinc was (81.71±15.91)μmol/L. There were significant differences in different age groups noticed as well in sex sets of infancy group, toddler's age group and preschool age group. The rate of deficiency of zinc decreased gradually following the growth of age. The rate of zinc deficiency was 13.7% and there were obvious differences noticed in sex sets of toddler, preschool and school age groups. The level of iron increased gradually following the growth of age with the level of iron as (8.28±0.78)mmol/L.There were significant differences noticed in different age groups, after infancy stage. There was significant difference noticed also in sex sets after school age group. The rate of iron deficiency decreased obviously following the growth of age. The iron deficiency rate was 12.9%, and significantly different in sex sets of young infancy, school age and adolescence groups. The level of lead increased gradually following the growth of age, with the overall level as (59.97±26.52)μg/L; There was an obvious significant differences noticed in different age groups with significant differences noticed in sex sets after toddler's age group. The rate of lead intoxication increased gradually following the growth of age. The rate of lead intoxication was 8.2%. There were significant differences noticed in sex sets after toddler's age group.However, there were negative correlations noticed among the levels of lead and copper, zinc, calcium,magnesium and iron. There were no correlations between the level of calcium and iron found but showed positive correlation among other trace elements. Conclusion The deficiency of calcium was basically corrected but the deficiency of zinc and iron were still obvious. There was a high level of lead noticed in these children. It is important to advocate on healthy feeding program, on culture good hygienic habit and on away from the lead pollution sites.