DCL presents a unique opportunity to examine genetic variants in the donors and recipients with regards to progression to malignancy.The long-standing debate of whether patients with acute myeloid leukemia (AML) should proceed to allogeneic hematopoietic cell transplantation (HCT) during first complete remission (CR1) remains unsettled. Although allogeneic HCT during CR1 used to be recommended for those with intermediate or poor cytogenetics if they had a matched sibling donor, the concept of indications for allogeneic HCT during CR1 has been evolving by virtue of advances in understanding of the molecular pathogenesis of AML and innovations in transplantation practice attained over the last few decades. The incorporation of molecular profiles of leukemia has been shown to contribute to further refinements of risk classification that had previously relied mostly on cytogenetics, while the progress in transplantation procedures has made it possible to perform transplantations more safely even for patients without a matched sibling donor.  https://www.selleckchem.com/products/lxs-196.html  These significant changes have underpinned the need to reappraise indications for allogeneic HCT during CR1 of AML. Improvements in clinical applications of genetic and measurable residual disease information as well as in transplantation technology are expected to further refine indications for allogeneic HCT during CR1, and thus promote an individualized approach for the treatment of AML.This longitudinal cohort study compared ocular surface indicators in forty allogeneic hematopoietic stem cell transplant (HSCT) subjects with twenty healthy controls at baseline and identified changes in ocular graft-versus-host disease (oGVHD). Outcome measures included Ocular Surface Disease Index (OSDI), tear osmolarity, Schirmer's test, Oxford corneal staining score, tear break-up time (TBUT), and tear and serum biomarkers (IFN-γ, IL-10, MMP-9, IL-12, IL-13, IL-17α, IL-1β, IL-2, IL-4, IL-6, IL-8, CXCL10, MCP-1, MIP-1α, RANTES, TNF-α). At baseline the HSCT group had higher median Oxford corneal staining score (1.7 vs. 0.0; P  less then  0.0001), higher tear TNF-α (20.0 vs. 11.2 pg/mL; P  less then  0.0001), lower tear RANTES (70.4 vs. 190.2 pg/mL; P  less then  0.0001), higher serum IL-8 (10.2 vs. 4.5 pg/mL; P = 0.0008), and higher serum TNF-α (8.7 vs. 4.2 pg/mL; P  less then  0.0001). The incidence of oGVHD was 62% and associated changes included increased Oxford corneal staining score (4.6 vs. 1.8, P = 0.0001), decreased Schirmer's test (3.0 vs. 10.0; P  less then  0.0001), and decreased TBUT (4.7 vs. 9.0 s; P = 0.0004). Baseline differences in ocular surface indicators suggest a tendency toward ocular dryness in individuals with hematologic disorders preparing for HSCT. Individuals who developed oGVHD showed changes in corneal staining score, Schirmer's test, and TBUT.Aristolochic acid I (AAI) is a well-known nephrotoxic carcinogen, which is currently reported to be also associated with hepatocellular carcinoma (HCC). Whether AAI is a direct hepatocarcinogen remains controversial. In this study we investigated the association between AAI exposure and HCC in adult rats using a sensitive rat liver bioassay with several cofactors. Formation of glutathione S-transferase placental form-positive (GST-P+) foci was used as the marker for preneoplastic lesions/clonal expansion. We first conducted a medium-term (8 weeks) study to investigate whether AAI had any tumor-initiating or -promoting activity. Then a long-term (52 weeks) study was conducted to determine whether AAI can directly induce HCC. We showed that oral administration of single dose of AAI (20, 50, or 100 mg/kg) in combination with partial hepatectomy (PH) to stimulate liver proliferation did not induce typical GST-P+ foci in liver. In the 8-week study, only high dose of AAI (10 mg · kg-1 · d-1, 5 days a week for 6 weestigation of the associations between AA and HCC.Cardiovascular safety assessment is vital for drug development, yet human cardiovascular cell models are lacking. In vitro mass-generated human pluripotent stem cell (hPSC)-derived cardiovascular cells are a suitable cell model for preclinical cardiovascular safety evaluations. In this study, we established a preclinical toxicology model using same-origin hPSC-differentiated cardiomyocytes (hPSC-CMs) and endothelial cells (hPSC-ECs). For validation of this cell model, alirocumab, a human antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), was selected as an emerging safe lipid-lowering drug; atorvastatin, a common statin (the most effective type of lipid-lowering drug), was used as a drug with reported side effects at high concentrations, while doxorubicin was chosen as a positive cardiotoxic drug. The cytotoxicity of these drugs was assessed using CCK8, ATP, and lactate dehydrogenase release assays at 24, 48, and 72 h. The influences of these drugs on cardiomyocyte electrophysiology were detected using the patch-clamp technique, while their effects on endothelial function were determined by tube formation and Dil-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake assays. We showed that alirocumab did not affect the cell viability or cardiomyocyte electrophysiology in agreement with the clinical results. Atorvastatin (5-50 μM) dose-dependently decreased cardiovascular cell viability over time, and at a high concentration (50 μM, ~100 times the normal peak serum concentration in clinic), it affected the action potentials of hPSC-CMs and damaged tube formation and Dil-Ac-LDL uptake of hPSC-ECs. The results demonstrate that the established same-origin hPSC-derived cardiovascular cell model can be used to evaluate lipid-lowering drug safety in cardiovascular cells and allow highly accurate preclinical assessment of potential drugs.Lung cancer is the leading cause of cancer death worldwide, with poor prognosis and a high rate of recurrence despite early surgical removal. Hypoxic regions within tumors represent sources of aggressiveness and resistance to therapy. Although long non-coding RNAs (lncRNAs) are increasingly recognized as major gene expression regulators, their regulation and function following hypoxic stress are still largely unexplored. Combining profiling studies on early-stage lung adenocarcinoma (LUAD) biopsies and on A549 LUAD cell lines cultured in normoxic or hypoxic conditions, we identified a subset of lncRNAs that are both correlated with the hypoxic status of tumors and regulated by hypoxia in vitro. We focused on a new transcript, Nuclear LUCAT1 (NLUCAT1), which is strongly upregulated by hypoxia in vitro and correlated with hypoxic markers and poor prognosis in LUADs. Full molecular characterization showed that NLUCAT1 is a large nuclear transcript composed of six exons and mainly regulated by NF-κB and NRF2 transcription factors.