Efficacy and safety of an HDACi- and HMA-based protocol in adults with acute myeloid leukemia of intermediate- and adverse-risk categories: a retrospective study.

OBJECTIVE: Anthracyclines and cytarabine have comprised standard induction therapy for acute myeloid leukemia (AML) for decades. Low overall survival of AML is due to non-remission or relapse after remission. Hypomethylating agent (HMA) decitabine combined with low-dose chemotherapy or other targeted agents has shown promising effect for AML in clinical trials, especially in t(8;21) acute myeloid leukemia. We previously investigated histone deacetylase inhibitor (HDACi) chidamide could regulate Wnt/ß-catenin signaling pathway in leukemia cell lines. METHODS: Adult patients with de novo or relapsed/refractory AML who were treated with chidamide and decitabine in combination with chemotherapy (chidamide group, n = 23) or only decitabine combination with chemotherapy (decitabine group, n = 17) were analyzed. RESULTS: Chidamide group represented higher complete response rate (82.6% and 52.9%, p = 0.0430, vs. decitabine group), progression-free survival and overall survival rates (p = 0.0088 and p = 0.0139, respectively), especially for patients with de novo AML. Hematological toxicity and infections were the most common adverse events (AEs) in both groups, and they were manageable by supportive treatments. CONCLUSIONS: This HDACi- and HMA-based protocol is an effective and tolerable therapy for patients with AML. The comprehensive mechanism and effects of chidamide in combination with decitabine are worth to be further explored in AML.

miR-103a-3p Silencing Ameliorates Calcium Oxalate Deposition in Rat Kidney by Activating the UMOD/TRPV5 Axis.

Maintaining the balance of calcium (Ca2+) metabolism in the kidney is crucial in preventing the formation of kidney stones. Functionally, the microRNA (miRNA) participating in this process needs to be unveiled. We induced NRK-52E cell injury by oxalate treatment. The role of transient receptor potential cation channel subfamily V member 5 (TRPV5) in oxalate-induced cells was studied by TRPV5 overexpression transfection, qRT-PCR, Western blot, MTT, and crystal adhesion detection. After identifying uromodulin (UMOD) expression in injured cells, we confirmed the interaction between TRPV5 and UMOD by coimmunoprecipitation (CoIP) and cell-surface biotinylation assays. The validation of UMOD-regulating TRPV5 in viability, crystal adhesion, and Ca2+ concentration of oxalate-induced cells was performed. Bioinformatics analysis and luciferase assay were used to identify the miRNA-targeting UMOD. The role of the miR-103a-3p-regulating UMOD/TRPV5 axis was detected by rescue experiments. We constructed a rat model with treatment of ethylene glycol (EG) to investigate the miR-103a-3p/UMOD/TRPV5 axis in vivo by hematoxylin-eosin (H&E) staining, Western blot, and immunohistochemistry (IHC). Upregulation of TRPV5 protected NRK-52E cells from oxalate-induced injury by enhancing cell viability and inhibiting CaOx adhesion. UMOD was depleted in oxalate-induced cells and positively interacted with TRPV5. UMOD silencing reversed the effect of TRPV overexpression on oxalate-induced cells. miR-103a-3p targeted UMOD and was mediated in the regulation of the UMOD/TRPV5 axis in oxalate-induced cells. Downregulating miR-103a-3p mitigated EG-induced CaOx deposition in kidney tissues in vivo by activating the UMOD/TRPV5 axis. miR-103a-3p silencing ameliorated CaOx deposition in the rat kidney by activating the UMOD/TRPV5 axis.

H-PDLC based waveform controllable optical choppers for FDMF microscopy.

An electrically waveform controllable optical chopper based on holographic polymer dispersed liquid crystal grating (H-PDLC) is presented in this paper. The theoretical analyses and experimental results show that the proposed optical chopper has following merits: (1) controllable waveform, (2) no mechanical motion induced vibrational noise, and (3) multiple-channel integration capability. The application of this unique electrically controllable optical chopper to frequency division multiplexed fluorescent microscopy is also addressed in this paper, which has the potential to increase the channel capacity, the stability and the reliability. This will be beneficial to the parallel detection, especially for dynamic studies of living biological samples.