RNA sequencing profiles reveal dynamic signaling and glucose metabolic features during bone marrow mesenchymal stem cell senescence.

BACKGROUND: Stem cell senescence is considered as a significant driver of organismal aging. As individuals age, the number of stem cells is declined, and the ability to proliferate and survive is also weakened. It has been reported that metabolism plays an important role in stem cell self-renewal, multilineage differentiation, senescence and fate determination, which has aroused widespread concerns. However, whether metabolism-related genes or signalling pathways are involved in physiological aging remain largely undetermined. RESULTS: In the current study, we showed 868 up-regulated and 2006 down-regulated differentially expressed genes (DEGs) in bone marrow mesenchymal stem cells (MSCs) from old rats in comparison with that from young rats by performing RNA sequence. And DEGs functions and pathways were further selected by function enrichment analysis. The results indicated that the high expression of DEGs might participate in cell differentiation, growth factor binding and etc., while the down-regulated DEGs were majorly enriched in metabolism process, such as the cellular metabolic process and mitochondria. Then, we screened and verified DEGs related to glucose metabolism and investigated the glycolysis levels. We identified that glucose uptake, lactate secretion, ATP production and relative extracellular acidification rates (ECAR) were all diminished in MSCs from old rats. More importantly, we conducted microRNA prediction on the key DEGs of glycolysis to elucidate the potential molecular mechanisms of glucose metabolism affecting MSC senescence. CONCLUSIONS: Our study unravelled the profiles of DEGs in age-associated MSC senescence and their functions and pathways. We also clarified DEGs related to glucose metabolism and down-regulated glycolysis level in age-associated MSC senescence. This study will uncover the metabolic effects on regulating stem cell senescence, and provide novel therapeutic targets for ameliorating age-associated phenotypes.

Prognostic Performance of SOFA, qSOFA, and SIRS in Kidney Transplant Recipients Suffering from Infection: A Retrospective Observational Study.

INTRODUCTION: The prognostic performance of scoring systems for illness severity in infectious kidney transplant recipients (KTRs) is rarely reported. We investigated the ability of the scores for the quick Sequential Organ Failure Assessment (qSOFA), Sequential Organ Failure Assessment (SOFA) and Systemic Inflammatory Response Syndrome (SIRS) to predict in-hospital mortality, intensive care unit (ICU) admission and mechanical ventilation (MV) requirement. METHODS: This was a second analysis of a retrospective observational study. Scores for SIRS, SOFA and qSOFA were calculated upon hospitalization (infection onset was before hospitalization) or on the day of infection onset (infection episodes were during hospitalization). The primary outcome was in-hospital mortality. The secondary outcomes were ICU admission and MV requirement. Binary logistic regression and area under the receiver operating characteristic curve (AUC) were employed to assess prognostic performance. RESULTS: A total of 161 infectious episodes occurred in 97 KTRs. Forty patients (41%) experienced more than one episode. The SOFA score was available in 161 infections, and scores for qSOFA and SIRS were available in 160 infections. The SIRS score was not different between KTRs with opposite outcomes. The qSOFA score was higher in infections necessitating MV. The SOFA score was significantly higher in the deceased, those needing ICU admission, MV, and for those with positive etiology results. The SOFA score was the only independent predictor of in-hospital mortality, ICU admission, and MV requirement, and the AUCs were 0.879, 0.815, and 0.784, respectively. The optimum cutoff value of predicting the three outcomes was SOFA score ≥ 3. CONCLUSIONS: The SOFA score (but not those for SIRS and qSOFA) independently predicted in-hospital mortality, ICU admission, and MV requirement in infectious KTRs.

Risk factors and etiology of repeat infection in kidney transplant recipients.

Kidney transplantation (KT) is the best therapy available for patients with end-stage renal disease, but postoperative infections are a significant cause of mortality.In this retrospective study the frequency, risk factors, causative pathogens, and clinical manifestations of infection in KT recipients from Beijing Chao-Yang Hospital, Capital Medical University were investigated. Ninety-seven KT recipients who were hospitalized with infection between January 2010 and December 2016 were included. Clinical characteristics, surgery details, laboratory results, and etiology were compared in patients who developed single infection and patients who developed repeated infection (2 or more) after KT.A total of 161 infections were adequately documented in a total of 97 patients, of which 57 patients (58.8%) had 1 infection, 24 (24.7%) had 2, 11 (11.3%) had 3; 3 (3.1%) had 4, and 2 (2.1%) had 5 or more. The most common infection site was the urinary tract (90 infections; 56%), both overall and in the repeated infection group. The most frequently isolated pathogen was Pseudomonas aeruginosa. In the repeated infection patients, in most cases of P. aeruginosa infection (54%) it was cultured from urine. For first infections, a time between KT and infection of ≤ 21 days (area under receiver operating characteristic curve [AUC] 0.636) and a tacrolimus level ≥ 8 ng/mL (AUC 0.663) independently predicted repeat infection. The combination of these two predictive factors yielded an AUC of 0.716, which did not differ statistically significantly from either predictor alone.With regard to first infections after KT, a time between KT and infection of ≤ 21 days, and a tacrolimus level ≥ 8 ng/mL each independently predicted repeated infection in KT recipients.

A novel method for preparing quantum dot nanospheres with narrow size distribution.

Differently colored quantum dot (QD) nanoparticles are incorporated into bovine serum albumin (BSA) nanospheres by spray-drying followed by thermal denaturization, which is a rapid, highly efficient, large scale, and low cost method. Because the spray-dryer is equipped with an ultrasonic atomizer, most of the nanospheres are no more than 550 nm in diameter and a have narrow size distribution. Ultrathin sections (70 nm) of nanospheres are first prepared using a technique which is normally applied to cell sectioning. The section images show that the QD-BSA nanospheres are solid, and that the QDs are successfully dispersed inside the BSA nanospheres. The nanospheres emit bright fluorescence, and their fluorescence stabilities are not obviously changed compared with that of the QDs. This work provides a novel and simple method for preparing nanoscale spheres encapsulating differently colored QDs. We also present an ultrathin sectioning method for investigating the interior details of nanomaterials.

Transfer of quantum dots from pregnant mice to pups across the placental barrier.

Fluorescent quantum dots (QDs) have great potential for in vivo biomedical imaging and diagnostic applications. However, these nanoparticles are composed of heavy metals and are very small in diameter, and their possible toxicity must therefore be considered. As yet, no studies have reported the transfer of QDs between mother and fetus. The transfer of CdTe/CdS QDs of different sizes and dosages, and with different outer capping materials, from pregnant mice to fetuses is investigated. It is shown that QDs may be transferred from female mice to their fetuses across the placental barrier. Smaller QDs are more easily transferred than larger QDs and the number of QDs transferred increases with increasing dosage. Capping with an inorganic silica shell or organic polyethylene glycol reduces QD transfer but does not eliminate it. These results suggest that the clinical utility of QDs could be limited in pregnant women.