A complete oral regimen for induction therapy of patients with high-risk APL: An oral etoposide instead of intravenous infusion for cytoreductive chemotherapy.

There is an urgent need for an oral, efficient and safe regimen for high-risk APL under the pandemic of COVID-19. We retrospectively analysed 60 high-risk APL patients. For induction therapy (IT), in addition to all-trans retinoic acid (ATRA) and oral arsenic (RIF), 22 patients received oral etoposide (VP16) as cytotoxic chemotherapy (CC), and 38 patients received intravenous CC as historical control group. The median dose of oral VP16 was 1000 mg [interquartile rage (IQR), 650-1250]. One patient died during IT in the control group, 59 evaluable patients (100%) achieved complete haematological remission (CHR) after IT and complete molecular remission (CMR) after consolidation therapy. The median time to CHR and CMR was 36 days (33.8-44) versus 35 days (32-42; p = 0.75) and 3 months (0.8-3.5) versus 3.3 months (2.4-3.7; p = 0.58) in the oral VP16 group and in the control group. Two (9.1%) and 3 (7.9%) patients experienced molecular relapse in different group respectively. The 2-year estimated overall survival and event-free survival were 100% versus 94.7% (p = 0.37) and 90.9% versus 89.5% (p = 0.97) respectively. A completely oral, efficient and safe induction regimen including oral VP16 as cytoreductive chemotherapy combined with ATRA and RIF is more convenient to administer for patients with high-risk APL.

Melanoxylonin A-G, neoflavonoids from the heartwood of Dalbergia melanoxylon and their cardioprotective effects.

Seven undescribed neoflavonoids, named melanoxylonins A-G, were isolated from the heartwood of Dalbergia melanoxylon, and all the non-toxic isolates were evaluated for their cardioprotective effect against ischemia/reoxygenation (I/R) injury in H9c2 cells. Of these, melanoxylonin A-D containing the 8-OH group showed better potent cardioprotective effects than the other four congeners. Molecular docking studies confirmed the capacity of melanoxylonin D to interact with the myeloperoxidase (MPO) protein. These results indicated that the potential cardioprotective effects of melanoxylonin D in H9c2 cells with I/R injury may be imparted through suppression of MPO. These results may provide a new medicinal usage of D. melanoxylon.

LncRNA-SMILR modulates RhoA/ROCK signaling by targeting miR-141 to regulate vascular remodeling in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a fatal progressive disease characterized by an increased blood pressure in the pulmonary arteries. RhoA/Rho-kinase (RhoA/ROCK) signaling activation is often associated with PAH. The purpose of this study is to investigate the role and mechanisms of long noncoding RNA (lncRNA) smooth muscle-induced lncRNA (SMILR) to activate the RhoA/ROCK pathway in PAH. SMILR, microRNA-141 (miR-141), and RhoA were identified by qRT-PCR in PAH patients' serum. 3-(4,5-Dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT), wound-healing assay, cell counting kit-8 (CCK-8) assay, and flow cytometry were performed to determine cell viability, migration, proliferation, and cell cycle in human pulmonary arterial smooth muscle cells (hPASMCs) and primary PASMCs from PAH patients. We also performed bioinformatical prediction, luciferase reporter assay, and RNA-binding protein immunoprecipitation (RIP) to assess the interaction among SMILR, miR-141, and RhoA. The RhoA/ROCK pathway and proliferation-related proteins were measured by Western blotting. Finally, we introduced the small hairpin (sh)SMILR to monocrotaline-induced PAH rat model and used the hemodynamic measurement, qRT-PCR, and immunohistochemistry to examine the therapeutic effects of shSMILR. SMILR and RhoA expression were upregulated, while miR-141 expression was downregulated in PAH patients. SMILR directly interacted with miR-141 and negatively regulated its expression. Knockdown of SMILR suppressed PASMC proliferation and migration induced by hypoxia. Furthermore, overexpression of miR-141 could inhibit the RhoA/ROCK pathway by binding to RhoA, thereby repressing cell proliferation-related signals. Knockdown of SMILR significantly inhibited the Rho/ROCK activation and vascular remodeling in monocrotaline-induced rats. Knockdown of SMILR effectively elevated miR-141 expression and in turn inhibited the RhoA/ROCK pathway to regulate vascular remodeling and reduce blood pressure in PAH.NEW & NOTEWORTHY Smooth muscle enriched long noncoding RNA (SMILR), as a long noncoding RNA (lncRNA), was increased in pulmonary arterial hypertension (PAH) patients and in vitro and in vivo models. SMILR activated RhoA/ROCK signaling by targeting miR-141 to disinhibit its downstream target RhoA. SMILR knockdown or miR-141 overexpression inhibited hypoxia-induced cell proliferation and migration via repressing RhoA/ROCK signaling in pulmonary arterial smooth muscle cells (PASMCs), which was confirmed in vivo experiments that knockdown of SMILR inhibited vascular remodeling and alleviated PAH in rats. SMILR may be a promising and novel therapeutic target for the treatment and drug development of PAH.

The Usage of Separating Gel Vacuum Tube with Different IgG Concentration.

BACKGROUND: Observing serum IgG concentration on the distribution of serum, blood cells, and separation gel after centrifugation in different separation gel vacuum tubes. METHODS: 3 mL venous blood was collected in each of two separation gel procoagulant vacuum tubes: BD Vacutainer SST II(3.5ml, 75×13 mm) and BD Vacutainer SST(5ml, 100×13 mm). After complete solidifaction, both tubes were centrifuged at 2000g for 10 minutes. The distribution of serum, blood cells, and separation gel in the vacuum tube was observed. The immunoglobulin concentration was detected using the special protein analyzer Siemens BNII. RESULTS: 1. In the group of BD Vacutainer SST II where the IgG concentration exceeded 50g/L but less than 122g/L: The serum was located below the separation gel and was distributed in three layers: separation gel, serum, and blood cells. 2. In the group of BD Vacutainer SST where the IgG concentration exceeded 50g/L but less than 122g/L: The serum was located above the separating gel, and was distributed in three layers: serum, separation gel, and blood cells. 3. Increases in IgA and IgM serum concentration did not cause the separation gel inversion. CONCLUSIONS: Increases in serum IgG were positively correlated with the concentration of total protein. The rising of serum IgG caused the floating of separation gel after centrifugation. The BD Vacutainer SST was more suitable for clinical blood sample collection.