Rapamycin-induced β-Globin Family Locus Remodeling Regulates the Gene Switching Expression / 中国生物化学与分子生物学报

β-Thalassemia caused by abnormal coding of the β-globin gene is the most common hemoglobinopathy in many Asian countries. The in-depth study of the molecular basis and epigenetic mechanism of globin gene expression is the key to explore a new treatment for thalassemia. In this study, FAIRE (formaldehyde-assisted isolation of regulatory elements), 3C (chromosome conformation capture) and ChIP (Chromatin Immunoprecipitation) were used to investigate the three-dimensional interaction network of β-globin family gene loci and the molecular mechanism of functional regulation of gene expression during rapamycin-induced chromatin remodeling in CD4+ T cells. The results showed that the opening degree of globin gene chromatin, the interaction frequency between the gene promoter region and the regulatory element LCR (Locus control regions), and the enrichment efficiency of CTCF (CCCTC-binding factor) in the gene promoter region changed differently during the change of rapamycin treatment concentration from low to high, which led to the same change trend of the gene expression pattern. At the 10 nmol/ L concentration, chromatin accessibility and gene expression decreased (P < 0. 05). At 20 nmol/ L and 50 nmol/ L concentrations, chromatin accessibility increased and gene expression was up-regulated (P < 0. 05). In this study, the molecular mechanism of gene expression regulation of the β-globin family was expounded through this dynamic change process. Our work provides a theoretical and clinical practice basis for clinical precision treatment.

Aqueous extracts of Tribulus terrestris protects against oxidized low-density lipoprotein-induced endothelial dysfunction / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the role of aqueous extracts of Tribulus terrestris (TT) against oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) dysfunction in vitro.</p><p><b>METHODS</b>HUVECs were pre-incubated for 60 min with TT (30 and 3 μg/mL respectively) or 10(-5) mol/L valsartan (as positive controls) and then the injured endothelium model was established by applying 100 μg/mL ox-LDL for 24 h. Cell viability of HUVECs was observed by real-time cell electronic sensing assay and apoptosis rate by Annexin V/PI staining. The cell migration assay was performed with a transwell insert system. Cytoskeleton remodeling was observed by immunofluorescence assay. The content of endothelial nitric oxide synthase (eNOS) was measured by enzyme-linked immunosorbent assay. Intracellular reactive oxygen species (ROS) generation was assessed by immunofluorescence and flow cytometer. Key genes associated with the metabolism of ox-LDL were chosen for quantitative real-time polymerase chain reaction to explore the possible mechanism of TT against oxidized LDL-induced endothelial dysfunction.</p><p><b>RESULTS</b>TT suppressed ox-LDL-induced HUVEC proliferation and apoptosis rates significantly (41.1% and 43.5% after treatment for 3 and 38 h, respectively; P<0.05). It also prolonged the HUVEC survival time and postponed the cell's decaying stage (from the 69th h to over 100 h). According to the immunofluorescence and transwell insert system assay, TT improved the endothelial cytoskeletal network, and vinculin expression and increased cell migration. Additionally, TT regulated of the synthesis of endothelial nitric oxide synthase and generation of intracellular reactive oxygen species (P<0.05). Both 30 and 3 μg/mL TT demonstrated similar efficacy to valsartan. TT normalized the increased mRNA expression of PI3Kα and Socs3. It also decreased mRNA expression of Akt1, AMPKα1, JAK2, LepR and STAT3 induced by ox-LDL. The most notable changes were JAK2, LepR, PI3Kα, Socs3 and STAT3.</p><p><b>CONCLUSIONS</b>TT demonstrated potential lowering lipid benefits, anti-hypertension and endothelial protective effects. It also suggested that the JAK2/STAT3 and/or PI3K/AKT pathway might be a very important pathway which was involved in the pharmacological mechanism of TT as the vascular protective agent.</p>

Y-chromosome-specific microsatellite variation in Li ethnic groups of Hainan Island, China / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>The study was conducted to reveal the distribution of genetic polymorphism of four Y chromosome specific short tandem repeat (Y-specific STR) loci in Li ethnic groups in Hainan Island, China.</p><p><b>METHODS</b>Four tetranucleotide STR loci were simultaneously amplified with fluorescently labeled primers, and genotypes were determined with an automated DNA sequencer.</p><p><b>RESULTS</b>Among 230 unrelated males, the alleles at the four Y-specific STR loci were composed of some complex repeat structure. 4,5,4,5 alleles were observed in loci DYS3891, DYS390, DYS391, DYS393 respectively. A set of human allele ladders for the typing of the four Y-specific STRs was obtained in Li ethnic population. Gene diversity index (D) and haplotype diversity data were estimated for the four Y-STRs.</p><p><b>CONCLUSION</b>The preliminary study indicates a reference population for detecting male migration events and should be useful in population genetics and forensic applications.</p>