Efficacy and safety of Chinese patent medicine (Kang-ai injection) as an adjuvant in the treatment of patients with hepatocellular carcinoma: a meta-analysis.

CONTEXT: Kang-ai injection (KAI) is an authorized herbal medicine used in cancer treatment. However, its clinical efficacy in hepatocellular carcinoma (HCC) has not been investigated thoroughly. OBJECTIVE: To systematically evaluate the efficacy and safety of KAI in patients with HCC. MATERIALS AND METHODS: The Web of Science, PubMed, Cochrane Library, EMBASE, CBM, CNKI, VIP and Wanfang databases were systematically searched (date range: inception to December 2020) using the key terms 'Kang-ai injection' and 'hepatocellular carcinoma'. The current analysis included controlled clinical trials that compared the efficacy and safety of the combination of KAI and conventional treatment (CT) with CT alone for HCC. The current study estimated the pooled risk ratio (RR) with 95% confidence intervals (CI). RESULTS: Data pertaining to 35 trials with 2501 HCC patients were analysed. The results revealed that the combination of KAI and CT was associated with significantly superior objective response rate (RR = 1.57, 95% CI = 1.43-1.73), disease control rate (RR = 1.18, 95% CI = 1.10-1.26), and quality of life (RR = 2.40, 95% CI = 1.79-3.23), compared to CT alone. The administration of KAI significantly alleviated most of the adverse effects caused by CT, including nausea and vomiting, liver damage, peripheral neurotoxicity, fever, abdominal pain, alopecia, increased bilirubin levels, leukopoenia, and reduction in haemoglobin levels (p < 0.05, for all). CONCLUSIONS: The current meta-analysis indicates that a combination of CT and KAI could be more effective in improving the clinical efficacy of the treatment of HCC, compared to CT alone.

Silencing of long non­coding RNA NEAT1 inhibits hepatocellular carcinoma progression by downregulating SMO by sponging microRNA­503.

Hepatocellular carcinoma (HCC) poses an increasing threat to humans, due to its poor prognosis. Nuclear­enriched abundant transcript 1 (NEAT1), a type of long non­coding (lnc)RNA, has been found to function in a variety of cancer types. However, the role of NEAT1 in HCC is poorly understood. Reverse transcription­quantitative PCR was used to detect the expression levels of NEAT1, microRNA (miR)­503 and Smoothened (SMO) mRNA in HCC tissues and cells. MTT and flow cytometry assays were used to investigate cell viability and apoptosis, respectively, while Transwell assays were performed to investigate cell invasion and migration. StarBase and TargetScan were utilized to predict the target sequence between miR­503 and NEAT1 or SMO, the results of which were verified using a dual­luciferase reporter assay. The protein expression level of SMO was measured using western blot. The RNA expression level of NEAT1 and SMO was significantly elevated in HCC tissues and cells compared with that in the corresponding healthy tissues and cells, which was contrary to miR­503 expression level. NEAT1 silencing was found to restrict the viability, migration and invasion of the cells, while simultaneously induced apoptosis in the HCC cell line. Further studies found that miR­503 expression was negatively correlated with NEAT1 or SMO. It was also confirmed that NEAT1 directly interacted with miR­503 and miR­503 could bind to the 3'­untranslated region of SMO. Furthermore, overexpression of NEAT1 or SMO could reverse the effects of miR­503­mediated inhibition on cell viability, invasion, migration and promotion of apoptosis in the HCC cell lines. These results demonstrated that downregulation of NEAT1 impeded the viability, migration, invasion and induced apoptosis through the NEAT1/miR­503/SMO axis in the HCC cell line.

lncRNA NEAT1 mediates sepsis progression by regulating Irak2 via sponging miR-370-3p.

Sepsis is a life-threatening condition and often associated with multiple organ failure. Nuclear-enriched abundant transcript 1 (NEAT1), a member of the long non-coding RNAs (lncRNAs), was reported to be involved in the regulation of sepsis progression. However, its precise regulatory mechanism needs to be further explored. In this study, the cell-counting kit-8 assay was used to check cell viability. The quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the expression levels of NEAT1, miR-370-3p and Interleukin 1 receptor associated kinase 2 (Irak2). Flow cytometry assay and ELISA were used to check cell apoptosis and the concentrations of inflammatory cytokines, respectively. The starBase was used to predict binding sites between miR-370-3p and NEAT1 or Irak2 and the dual-luciferase reporter assay was performed to verify the interaction. The protein level of Irak2 in samples was measured by western blot. The high concentration of lipopolysaccharide (LPS) led to the high death ratio of RAW 264.7 and HL-1 cells. NEAT1 and Irak2 were upregulated in sepsis tissues and LPS-induced RAW 264.7 and HL-1 cells, opposite to the expression of miR-370-3p. In addition, knockdown of NEAT1 promoted viability, suppressed apoptosis and reduced the expression of inflammatory cytokines in LPS-induced RAW 264.7 and HL-1 cells. Moreover, we found that miR-370-3p interacted with NEAT1 and targeted the 3'UTR of Irak2. Further research indicated that downregulation of miR-370-3p or upregulation of Irak2 rescued NEAT1 silencing-mediated inhibitory effect on sepsis progression. Knockdown of NEAT1 hampered sepsis progression by downregulating Irak2 via interacting with miR-370-3p in LPS-induced RAW 264.7 and HL-1 cells.