The effect of transcutaneous application of carbon dioxide (CO₂) on skeletal muscle

Quasispecies is a remarkable characteristic of hepatitis C virus (HCV) and has profound roles in HCV biology and clinical practice. The understanding of HCV quasispecies behavior, in particular in acute HCV infection, is valuable for vaccine development and therapeutic interference. However, acute HCV infection is seldom encountered in clinic practice due to its silent onset. In the present study, we reported a unique case of de novo HCV infection associated with the transplantation of bone marrow from a HCV-positive donor. HCV quasispecies diversity was determined in both the donor and the recipient over a 4-year follow-up, accompanied with simultaneous measurement of HCV neutralizing antibody. Detailed genetic and phylogenetic analyses revealed a divergent quasispecies evolution, which was not related to dynamic changes of HCV neutralizing antibody. Instead, our data suggested an essential role of the fitness adaptation of founder viral population in driving such an evolutionary pattern.     

Do CD4+ Foxp3+ Treg cells correlate with transplant outcomes: a systematic review on recipients of solid organ transplantation

Regulatory T cells (Tregs) are considered to be critical for the induction of transplant tolerance. Tregs counts were measured in blood, biopsy and urine sample after transplantation in many studies. Although not unanimous, some studies have suggested that Tregs is associated with better outcome and can also serve as an immune marker to predict the individual risk of rejection and identify tolerant patients. In this study, we systematically reviewed the correlation between Tregs and transplant outcomes, identifying if Tregs can predict transplant rejection and tolerance. A total of 22 articles were included and assessed, the results showed that Tregs in recipients are helpful to maintain a stable graft function, reduce acute/chronic rejection rate. And the Tregs in graft and urine, rather than in PBL, may have a better diagnostic value for transplant outcomes. However, since the low quality of included studies, results may be influenced by bias. More high quality studies with bigger sample size are still needed in future.     

Analysis of lung surfactant phosphatidylcholine metabolism in transgenic mice using stable isotopes

Stable isotope labelling of lipid precursors coupled with mass spectrometry-based lipidomic analyses and determination of isotope enrichment in substrate, intermediate and product pools provide the parameters needed to determine absolute flux rates through lipid pathways in vivo. Here, as an illustration of the power of such analyses we investigated lung phosphatidylcholine (PC) synthesis in Surfactant Protein-D (SP-D) null mice. These animals develop emphysema, foamy alveolar macrophages and an alveolar lipoproteinosis with increasing age. We used the incorporation of methyl-9-[²H] choline chloride coupled with ESI-MS/MS to quantify absolute rates of lung surfactant PC synthesis and secretion in an SP-D^−/− mouse model, together with an analysis of the molecular specificity of lung PC synthesis. PC synthetic rates were comparable in control (0.52 μmol/lung/h) and SP-D^−/− (0.69 μmol/lung/h) mice, as were rates of surfactant PC secretion (29.8 and 30.6 nmol/lung/h, respectively). Increased lung PC in the SP-D^−/− mouse was due to impaired catabolism, with a rate of accumulation of 0.057 μmol/lung/h. The relatively low rates of surfactant PC secretion compared with total lung PC synthesis were compatible with a suggested ABCA1-mediated basolateral lipid efflux from alveolar type II epithelial cells. Finally, PC molecular species analysis suggested that a proportion of newly synthesised PC is secreted rapidly into the lung air spaces in both control and SP-D^−/− mice before significant PC acyl remodelling occurs.     

肠道微生态与白血病的研究进展

微生物群与人体的健康密切相关,约20%的恶性肿瘤与微生态失调有关。研究显示肠道微生物可以调节造血,其与血液系统疾病的关系逐渐得到研究者的关注,肠道微生物参与白血病的发生发展,影响白血病的治疗效果。较早的暴露于微生物群是儿童白血病的保护性因素,化疗会引起肠道微生物紊乱,肠道微生物可以改变化疗药物的疗效和毒性,其多样性和组成能够预测化疗相关的并发症,通过微生态制剂和粪菌移植可以减少化疗相关的并发症。本文从肠道微生态与白血病及其并发症的关系,以及调节肠道微生态对白血病的影响两个方面的最新进展进行综述。     

The protective and pathogenic roles of CXCL17 in human health and disease: Potential in respiratory medicine

C-X-C motif chemokine 17 (CXCL-17) is a novel chemokine that plays a functional role maintaining homeostasis at distinct mucosal barriers, including regulation of myeloid-cell recruitment, angiogenesis, and control of microorganisms. Particularly, CXCL17 is produced along the epithelium of the airways both at steady state and under inflammatory conditions. While increased CXCL17 expression is associated with disease progression in pulmonary fibrosis, asthma, and lung/hepatic cancer, it is thought to play a protective role in pancreatic cancer, autoimmune encephalomyelitis and viral infections. Thus, there is emerging evidence pointing to both a harmful and protective role for CXCL17 in human health and disease, with therapeutic potential for translational applications. In this review, we provide an overview of the discovery, characteristics and functions of CXCL17 emphasizing its clinical potential in respiratory disorders.     

Evaluation of the target dose coverage of stereotactic body radiotherapy for lung cancer using helical tomotherapy: A dynamic phantom study

AimTo evaluate the target dose coverage for lung stereotactic body radiotherapy (SBRT) using helical tomotherapy (HT) with the internal tumor volume (ITV) margin settings adjusted according to the degree of tumor motion.BackgroundLung SBRT with HT may cause a dosimetric error when the target motion is large.Materials and methodsTwo lung SBRT plans were created using a tomotherapy planning station. Using these original plans, five plans with different ITV margins (4.0–20.0 mm for superior-inferior [SI] dimension) were generated. To evaluate the effects of respiratory motion on HT, an original dynamic motion phantom was developed. The respiratory wave of a healthy volunteer was used for dynamic motion as the typical tumor respiratory motion. Five patterns of motion amplitude that corresponded to five ITV margin sizes and three breathing cycles of 7, 14, and 28 breaths per minute were used. We evaluated the target dose change between a static delivery and a dynamic delivery with each motion pattern.ResultsThe target dose difference increased as the tumor size decreased and as the tumor motion increased. Although a target dose difference of <5 % was observed at ≤10 mm of tumor motion for each condition, a maximum difference of -9.94 % ± 7.10 % was observed in cases of small tumors with 20 mm of tumor motion under slow respiration.ConclusionsMinimizing respiratory movement is recommended as much as possible for lung SBRT with HT, especially for cases involving small tumors.     

CXCR4‐SF1 bifunctional adipose‐derived stem cells benefit for the treatment of Leydig cell dysfunction‐related diseases

Stem cell transplantation is a candidate method for the treatment of Leydig cell dysfunction‐related diseases. However, there are still many problems that limit its clinical application. Here, we report the establishment of CXCR4‐SF1 bifunctional adipose‐derived stem cells (CXCR4‐SF1‐ADSCs) and their reparative effect on Leydig cell dysfunction. CD29⁺ CD44⁺ CD34^? CD45^? ADSCs were isolated from adipose tissue and purified by fluorescence‐activated cell sorting (FACS). Infection with lentiviruses carrying the CXCR4 and SF1 genes was applied to construct CXCR4‐SF1‐ADSCs. The CXCR4‐SF1‐ADSCs exhibited enhanced migration and had the ability to differentiate into Leydig‐like cells in vitro. Furthermore, the bifunctional ADSCs were injected into BPA‐mediated Leydig cell damage model mice via the tail vein. We found that the CXCR4‐SF1‐ADSCs were capable of homing to the injured testes, differentiating into Leydig‐like cells and repairing the deficiency in reproductive function caused by Leydig cell dysfunction. Moreover, we investigated the mechanism underlying SF1‐mediated differentiation and testosterone synthesis in Leydig cells, and the B‐box and SPRY Domain Containing Protein (BSPRY) gene was proposed to be involved in this process. This study provides insight into the treatment of Leydig cell dysfunction‐related diseases.     

Evidence of mesenchymal stromal cell adaptation to local microenvironment following subcutaneous transplantation

Subcutaneous transplantation of mesenchymal stromal cells (MSC) emerged as an alternative to intravenous administration because it avoids the pulmonary embolism and prolongs post‐transplantation lifetime. The goal of this study was to investigate the mechanisms by which these cells could affect remote organs. To this aim, murine bone marrow–derived MSC were subcutaneously transplanted in different anatomical regions and the survival and behaviour have been followed. The results showed that upon subcutaneous transplantation in mice, MSC formed multicellular aggregates and did not migrate significantly from the site of injection. Our data suggest an important role of hypoxia‐inducible signalling pathways in stimulating local angiogenesis and the ensuing modulation of the kinetics of circulating cytokines with putative protective effects at distant sites. These data expand the current understanding of cell behaviour after subcutaneous transplantation and contribute to the development of a non‐invasive cell‐based therapy for distant organ protection.     

A retrospective cohort study of cancer mortality in employees of a Russian chrysotile asbestos mine and mills: Study rationale and key features

Chrysotile, a serpentine asbestos fibre, is the only type of asbestos produced and consumed in the world today. It is an established human carcinogen. We have begun fieldwork on a retrospective cohort study of employees of one of the world's largest chrysotile mine and mills, situated in Asbest, Russia. The primary aim of the study is to better characterize and quantify the risk of cancer mortality in terms of (i) the dose–response relationship of exposure with risk; (ii) the range of cancer sites affected, including female-specific cancers; and (iii) effects of duration of exposure and latency periods. This information will expand our understanding of the scale of the impending cancer burden due to chrysotile, including if chrysotile use ceased worldwide forthwith. Herein we describe the scientific rationale for conducting this study and the main features of its study design.