Human placenta-derived mesenchymal stem cells (hPMSCs) reside in a physiologically low-oxygen microenvironment. Hypoxia influences a variety of stem cell cellular activities, frequently involving hypoxia-inducible factor-2 alpha (HIF-2α). This research showed that hPMSCs cultured in hypoxic conditions (5% O2) exhibited a more naïve morphology and had a higher proliferative capability and higher HIF-2α expression than hPMSCs cultured in normoxic conditions (21% O2). Similar to the hypoxic cultures, hPMSCs over-expressing HIF-2α showed higher proliferative potential and higher expression of CCND1 (CyclinD1), MYC (c-Myc), POU5F1 (Oct4) and the components of the MAPK/ERK pathway. In contrast, these genes were down-regulated in the HIF-2α-silenced hPMSCs. After adding the MAPK/ERK inhibitor PD0325901, cell growth and the expression of CCND1 and MYC were inhibited. Furthermore, the chromatin immunoprecipitation (ChIP) assay and electrophoretic mobility shift assay (EMSA) showed that HIF-2α bound to the MAPK3 (ERK1) promoter, indicative of its direct regulation of MAPK/ERK components at the transcriptional level during hPMSC expansion. Taken together, our results suggest that HIF-2α facilitated the preservation of hPMSC stemness and promoted their proliferation by regulating CCND1 and MYC through the MAPK/ERK signaling pathway.

Background: Stem cell-based therapy in liver diseases has received increasing interest over the past decade, but direct evidence of the homing and implantation of transplanted cells is conflicting. Reliable labeling and tracking techniques are essential but lacking. The purpose of this study was to establish human placenta-derived mesenchymal stem cells (hPMSCs) expressing green fluorescent protein (GFP) and to assay their hepatic functional differentiation in vitro. Methods: The GFP gene was transduced into hPMSCs using a lentivirus to establish GFP⁺ hPMSCs. GFP⁺ hPMSCs were analyzed for their phenotypic profile, viability and adipogenic, osteogenic and hepatic differentiation. The derived GFP⁺ hepatocyte-like cells were evaluated for their metabolic, synthetic and secretory functions, respectively. Results: GFP⁺ hPMSCs expressed high levels of HLA I, CD13, CD105, CD73, CD90, CD44 and CD29, but were negative for HLA II, CD45, CD31, CD34, CD133, CD271 and CD79. They possessed adipogenic, osteogenic and hepatic differentiation potential. Hepatocyte-like cells derived from GFP⁺ hPMSCs showed typical hepatic phenotypes. Conclusions: GFP gene transduction has no adverse influences on the cellular or biochemical properties of hPMSCs or markers. GFP gene transduction using lentiviral vectors is a reliable labeling and tracking method. GFP⁺ hPMSCs can therefore serve as a tool to investigate the mechanisms of MSC-based therapy, including hepatic disease therapy.

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BackgroundThe complete blood count (CBC) is the most common examination used to monitor overall health in clinical practice. Whether there is a relationship between CBC indexes and alanine transaminase (ALT) and aspartate aminotransferase (AST) has been unclear.Material/MethodsIn this study, 572 normal-weight and 346 overweight Chinese subjects were recruited. The relationship between CBC indexes with ALT and AST were analyzed by Pearson and Spearman correlations according to their sex, then we conducted colinearity diagnostics and multiple linear regression (MLR) analysis. A prediction model was developed by a back-propagation artificial neural network (BP-ANN).ResultsALT was related to 4 CBC indexes in the male normal-weight group and 3 CBC indexes in the female group. In the overweight group, ALT had a similar relationship with the normal group, but there was only 1 index related with AST in the normal-weight group and male overweight groups. The ALT regression models were developed in normal-weight and overweight people, which had better correlation coefficient (R>0.3). After training 1000 epochs, the BP-ANN models of ALT achieved higher correlations than MLR models in normal-weight and overweight people.ConclusionsALT is a more suitable index than AST for developing a regression model. ALT can be predicted by CBC indexes in normal-weight and overweight individuals based on a BP-ANN model, which was better than MLR analysis.

BackgroundLow-dose computed tomographic (LDCT) screening has been proven to be powerful in detecting lung cancers in early stage. However, it’s hard to carry out in less-developed regions in lacking of facilities and professionals. The feasibility and efficacy of mobile LDCT scanning combined with remote reading by experienced radiologists from superior hospital for lung cancer screening in deprived areas was explored in this study.MethodsA prospective cohort was conducted in rural areas of western China. Residents over 40 years old were invited for lung cancer screening by mobile LDCT scanning combined with remote image reading or local hospital-based LDCT screening. Rates of positive pulmonary nodules and detected lung cancers in the baseline were compared between the two groups.ResultsAmong 8073 candidates with preliminary response, 7251 eligibilities were assigned to the mobile LDCT with remote reading (n = 4527) and local hospital-based LDCT screening (n = 2724) for lung cancer. Basic characteristics of the subjects were almost similar in the two cohorts except that the mean age of participants in mobile group was relatively older than control (61.18 vs. 59.84 years old, P < 0.001). 1778 participants with mobile LDCT scans with remote reading (39.3%) revealed 2570 pulmonary nodules or mass, and 352 subjects in the control group (13.0%) were detected 472 ones (P < 0.001). Proportions of nodules less than 8 mm or subsolid were both more frequent in the mobile LDCT group (83.3% vs. 76.1%, 32.9% vs. 29.8%, respectively; both P < 0.05). In the baseline screening, 26 cases of lung cancer were identified in the mobile LDCT scanning with remote reading cohort, with a lung cancer detection rate of 0.57% (26/4527), which was significantly higher than control (4/2724 = 0.15%, P = 0.006). Moreover, 80.8% (21/26) of lung cancer patients detected by mobile CT with remote reading were in stage I, remarkedly higher than that of 25.0% in control (1/4, P = 0.020).ConclusionMobile LDCT combined with remote reading is probably a potential mode for lung cancer screening in rural areas.Trial registrationNo. of registration trial was ChiCTR-DDD-15007586 (http://www.chictr.org).