Vemurafenib induces senescence in acute myeloid leukemia and myelodysplastic syndrome by activating the HIPPO signaling pathway: implications for potential targeted therapy.

BACKGROUND: The outcome of Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remain dismal despite the development of treatment. Targeted therapy is gaining more and more attention in improving prognosis. METHODS: Expression of BRAF was analyzed by RT-qPCR in AML and MDS patients. Cells viability treated by drugs was measured by CCK-8 assay. Network pharmacology and RNA-sequence were used to analyze the mechanism of drugs and verified in vitro and xenograft tumor model. RESULTS: Here we showed that BRAF was overexpressed in AML and MDS patients, and correlated with poor prognosis. The BRAF inhibitor-Vemurafenib (VEM) could significantly induce senescence, proliferation inhibition and apoptosis in AML cells, which can be enhanced by Bortezomib (BOR). This inhibitory effect was also verified in CD34 + cells derived from AML patients. Mechanistically, we showed that VEM combined with BOR could turn on HIPPO signaling pathway, thereby inducing cellular senescence in AML cells and xenograft mouse. CONCLUSIONS: Taken together, our findings demonstrate a significant upregulation of BRAF expression in AML and MDS patients, which is associated with unfavorable clinical outcomes. We also discovered that the BRAF inhibitor Vemurafenib induces cellular senescence through activation of the HIPPO signaling pathway. Analysis of BRAF expression holds promise as a prognostic indicator and potential therapeutic target for individuals with AML and MDS.

Acupuncture for the Treatment of Alzheimer's Disease: An Overview of Systematic Reviews.

Background: Acupuncture may be an effective complementary treatment for Alzheimer's disease (AD). The aim of this study was to summarize the evidence provided by systematic reviews (SRs)/meta-analyses (MAs) on the effect of acupuncture on AD. Methods: Eight electronic databases were searched from their inception until October 19, 2020. The methodological quality, reporting quality, and risk of bias of the included SRs were assessed by the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic Reviews (ROBIS) tool, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Moreover, the evidence quality of the outcome measures was assessed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Results: Eleven SRs/MAs met all inclusion criteria. According to the results of the AMSTAR-2, all included reviews were rated critically as being of low quality. With PRISMA, the reporting checklist was relatively complete, but some reporting weaknesses remained in the topics of the protocol and registration, search strategy, risk of bias, additional analyses, and funding. Based on the ROBIS tool, only two SRs/MAs had a low risk of bias. With the GRADE system, no high-quality evidence was found, and only seven outcomes provided moderate-quality evidence. Among the downgraded factors, the risk of bias within the original trials was ranked first, followed by inconsistency, imprecision, and publication bias. Conclusions: Acupuncture is a promising complementary treatment for AD. However, due to the low quality of the SRs/MAs supporting these results, high-quality studies with rigorous study designs and larger samples are needed before widespread recommendations can be made.

A Critical Overview of Systematic Reviews and Meta-Analyses on Acupuncture for Poststroke Insomnia.

OBJECTIVES: Acupuncture has increasingly been used for insomnia relief after stroke. We aimed to evaluate the methodological quality and summarize the evidence regarding the effectiveness of acupuncture for poststroke insomnia (PSI) from systematic reviews/meta-analyses (SRs/MAs). METHODS: Eight databases were searched from inception through August 23, 2020. SRs/MAs on acupuncture treatment for PSI were included. Methodological quality assessment was performed using Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), and evidence quality assessment was performed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). RESULTS: Six SRs/MAs on acupuncture treatment for PSI were included. The AMSTAR-2 showed that the methodological quality of all included SRs/MAs was rated as critically low. According to the evaluation results of GRADE, 38.9% (7/18) of outcomes were rated as very low-quality evidence, 22.2% (4/18) were low-quality evidence, and 8.9% (7/18) were moderate-quality evidence. Descriptive analysis results showed that acupuncture was an effective treatment modality for PSI. CONCLUSIONS: All included reviews indicated that acupuncture was more effective than the control group for the treatment of PSI, but the credibility of the results is limited owing to the generally low methodological and evidence quality of the included SRs/MAs. More high-quality evidence is needed to determine whether acupuncture is more effective than other treatments.