Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*

Objective:To investigate the prognostic value of enteroscopic grading for the prognostic assessment of patients with malignant hematological diseases who developed intestinal acute graft-versus-host disease (IT-aGVHD) after unrelated cord blood transplantation (UCBT) .Methods:Fifty patients with IT-aGVHD who developed hormone resistance after UCBT from June 2016 to June 2023 at Anhui Provincial Hospital were collected to compare the effective and survival rates of IT-aGVHD treatment in the group with milder enteroscopic mucosal injury (27 cases, enteroscopic grading of Ⅰ and Ⅱ) and the group with more severe injury (23 cases, enteroscopic grading of Ⅲ and Ⅳ) and to retrospectively analyze the factors affecting patients’ prognosis.Results:Patients in the mild and severe groups had an effective rate of 92.6% and 47.8% at 28 days after colonoscopy ( P<0.001), 81.5% and 39.1% at 56 days after colonoscopy ( P=0.002), with optimal effective rate of 92.6% and 65.2% ( P=0.040), respectively, and the differences were statistically significant. The multifactorial analysis found that enteroscopic grading was an independent risk factor affecting the effective rate of IT-aGVHD treatment. The overall survival rate at 2 years after colonoscopy was 70.4% (95% CI 52.0% -88.8% ) and 34.8% (95% CI 14.8% -54.8% ) for patients in the mild and severe groups, respectively, and the difference was statistically significant ( P=0.003). Multifactorial analysis revealed that enteroscopic grading, cytomegalovirus infection status, second-line treatment regimen, and patients’ age were independent risk factors for survival. Conclusion:The treatment efficacy and prognosis of patients in the group with less severe enteroscopic injury (grades Ⅰ and Ⅱ) were better than those in the group with more severe injury (grades Ⅲ and Ⅳ) .

Objective:To understand the effect of vitamin B1 on lymphocyte function in simulated microgravity.Methods:Splenocytes of mice were isolated,and the rotatary cell culture system was used to simulate microgravity.Lymphocytes were stimulated with mitotic agents Concanavalin A,and cells were treated with different concentrations of vitamin B1,proliferation indexes of lympho-cytes and levels of cytokines in supernatant were detected.Results:Simulated microgravity could inhibit proliferation of splenic lym-phocytes,and decrease levels of cytokines,while vitamin B1 could promote lymphocyte proliferation and cytokines production in cells cultured in simulated microgravity in a dose dependent manner.Conclusion:Vitamin B1 may attenuate the inhibitory effect of simulated microgravity on lymphocytes by regulating cell proliferation and secretion of cytokines.

Cell Nucleus ; Cellular Senescence/genetics* ; CRISPR-Cas Systems/genetics*

Gallic Acid/pharmacology* ; Humans ; Senotherapeutics ; Stem Cells

Animals ; Antlers ; Exosomes ; Mesenchymal Stem Cells ; Osteoarthritis/therapy*

OBJECTIVE To analyze the si tuation and hot spots of gabapentinoid drugs in the treatment of pain. METHODS Related researches about gabapentinoid drugs in the treatment of pain were retrieved from Web of Science core collection database during Jan. 1st，2011-Dec. 31st，2020. VOSviewer 1.6.17，CiteSpace 5.8.R1 and Excel 2018 software were used to statistically analyze the key characteristics of relevant literature ，such as the annual publications ，countries/regions，institutions，authors， journals and research hot spots. RESULTS & CONCLUSIONS A total of 3 519 literatures were retrieved ，and the annual publication outputs showed an upward trend generally. Totally 86 countries/regions had conducted relevant studies ，of which the United States ranked first （up to 1 219），and had close cooperation with the United Kingdom ，Canada，China，Germany，Japan， etc；a total of 3 996 institutions had published relevant literatures ，and the Pfizer Inc. issued the most publications ；the most studies were devoted by Professor Parsons from the University of California San Diego ，and the highest co-citations author was Professor Gilron from the Queen ’s University. Among 1 185 journals，Pain ranked first not only in the high-productive journal ，but also in the co-cited journal. The main hot topics include abuse and misuse of gabapentinoid ，off-label use of gabapentinoid ，clinical application of gabapentinoid as a component of multimodal analgesia ，and the update of guidelines for pain based on systematic evaluation and meta-analysis.

Humans ; Mechanistic Target of Rapamycin Complex 2/metabolism* ; Multiprotein Complexes/metabolism* ; Neural Stem Cells/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rapamycin-Insensitive Companion of mTOR Protein/metabolism* ; TOR Serine-Threonine Kinases/metabolism*