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Liver cancer is a prevalent malignant tumor with high mortality worldwide, making it urgent to explore new targets for liver cancer therapy. N-terminal EF-hand calcium binding protein 3 (NECAB3) is a new recognized regulator of cancer, while its role in liver cancer remained elusive. Thus, the study clarified the action of NECAB3 on liver cancer development and explored the detailed mechanism. We found that NECAB3 was enhanced in liver cancer. Knockdown of NECAB3 restrained liver cancer cell migration and invasion. Besides, knockdown of NECAB3 suppressed the activation of the hypoxia-inducible factor 1-alpha (HIF-1α)/Ras like without CAAX 1 (RIT1) pathway. Furthermore, NECAB3 regulated liver cancer migration and invasion through modulating RIT1 expression. Moreover, downregulation of NECAB3 suppressed liver cancer tumor growth in vivo. In conclusion, NECAB3 was upregulated in liver cancer. Knockdown of NECAB3 suppressed aggressive phenotype of liver cancer via modulating the HIF-1α/RIT1 axis, providing a possible target for liver cancer therapy.

Objective: To compare similarities and differences in expression changes of cytotoxic T-lymphocyte antigen-4 (CT-LA-4) and programmed death receptor 1 (PD-1) in immunosuppressed rabbits under different moxibustion interventions. Methods: Twenty large-eared white rabbits were randomly divided into normal group, model group, moxa stick moxibustion (MSM) group and herbal cake-partitioned moxibustion (HPM) group, with five rabbits in each group. CTX-induced immunosuppressed models were prepared by intraperitoneal injection for 7 consecutive days. After successful modeling, MSM and HPM were performed on alternate days for 10 treatments. Rabbits were anesthetized after treatment, and serum, liver and spleen were collected. Serum PD-1 and PD-L1 contents were detected by ELISA. PD-1 in liver tissue was detected by immunohistochemistry, and CTLA-4 mRNA in liver and spleen tissues were detected by RT-qPCR. Results: Both HPM and MSM could reduce PD-1 and PD-L1 levels due to immunosuppression, and could effectively suppress elevated levels of CTLA-4 in spleen and PD-1 and CTLA-4 in liver, which were statistically different compared with immunosuppression model group (P<0.05). Pearson correlation test showed that CTLA-4 and PD-1 in liver tissue had significant positive correlation (r=0.780 7, P<0.001). Conclusion: HPM can improve body immune function by regulating multiple immunosuppressive sites. [ABSTRACT FROM AUTHOR]

Context:The nuclear factor of activated T-cells (NFAT) is a family of transcription factors, essential for T-cell activation. Norisoboldine (NOR), an isoquinoline alkaloid fromRadix linderae, has been demonstrated to possess anti-inflammatory activity. Objective:This study examines NOR’s effect on NFAT activation and its therapeutic potential for atopic dermatitis (AD). Materials and methods:The transcriptional activity of NFAT was examined with luciferase reporter assay, using K562-luc cells, stimulated with 20 ng/mL PMA plus 1 μM ionomycin. NFAT dephosphorylation was examined by immuno-blotting in K562-luc cells and Jurkat cells. Interleukin-2 (IL-2) expression in Jurkat cells was examined by real-time PCR. A mouse model of dermatitis, induced by 2,4-dinitrochlorobenzene (DNCB), was used to test NOR’s therapeutic potential for AD. Results:NOR, dose-dependently, inhibited PMA and ionomycin-induced NFAT reporter gene expression in K562-luc cells in the range of 2–50 μM. NOR also inhibited PMA and ionomycin-induced NFAT dephosphorylation in K562-luc cells and Jurkat cells. Consequently, NOR suppressed PMA plus ionomycin-induced IL-2 expression in Jurkat cells. The administration of NOR (10 mg/kg, i.p.), alleviated DNCB-induced dermatitis in mice, by the reduction of ear swelling and attenuation of inflammatory infiltration into ear tissue. Moreover, mRNA levels of INF-γ, TNF-α, IL-4 and IL-6 in ears of NOR-treated mice were reduced by 78.4, 77.8, 72.3 and 73.9%, respectively, compared with untreated controls. Discussion and conclusion:This study demonstrates that NOR inhibits NFAT activation in T-cells and alleviates AD-like inflammatory reaction in a DNCB-induced dermatitis model, highlighting NOR as a potential therapeutic agent for AD. [ABSTRACT FROM AUTHOR]