PARP7 negatively regulates the type I interferon response in cancer cells and its inhibition triggers antitumor immunity

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Protective Effects of a Hydrogen-Rich Preservation Solution in a Canine Lung Transplantation Model

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LEOPARD综合征一家系PTPN11基因突变分析

【摘要】 目的 明确1个LEOPARD综合征家系的PTPN11基因突变。方法 对中国科学院大学宁波华美医院确诊的1例LEOPARD综合征先证者的家系进行现场调查。提取家系内4例患者、2例健康成员及与该家系无关的100例健康对照外周血标本。PCR扩增PTPN11基因所有外显子，使用Sanger测序法进行突变位点分析。结果 该家系3代14人，其中6人患病（男3例，女3例），符合常染色体显性遗传。患者皮损主要分布于面部、躯干和四肢，具有特殊面容及心血管系统异常。4例患者存在PTPN11基因的错义突变c.1632G＞T（p.R558L），导致第558位由精氨酸变为亮氨酸，该突变既往未曾报道。该家系2例健康成员及100例健康对照未发现PTPN11基因突变。结论 该LEOPARD综合征家系患者PTPN11基因13号外显子发生c.1632G＞T错义突变，可能是该家系患者发病的分子基础。     

Changes in DNA Damage Repair Gene Expression and Cell Cycle Gene Expression Do Not Explain Radioresistance in Tamoxifen-Resistant Breast Cancer

Tamoxifen-induced radioresistance, reported in vitro, might pose a problem for patients who receive neoadjuvant tamoxifen treatment and subsequently receive radiotherapy after surgery. Previous studies suggested that DNA damage repair or cell cycle genes are involved, and could therefore be targeted to preclude the occurrence of cross-resistance. We aimed to characterize the observed cross-resistance by investigating gene expression of DNA damage repair genes and cell cycle genes in estrogen receptor-positive MCF-7 breast cancer cells that were cultured to tamoxifen resistance. RNA sequencing was performed, and expression of genes characteristic for several DNA damage repair pathways was investigated, as well as expression of genes involved in different phases of the cell cycle. The association of differentially expressed genes with outcome after radiotherapy was assessed in silico in a large breast cancer cohort. None of the DNA damage repair pathways showed differential gene expression in tamoxifen-resistant cells compared to wild-type cells. Two DNA damage repair genes were more than two times upregulated (NEIL1 and EME2), and three DNA damage repair genes were more than two times downregulated (PCNA, BRIP1, and BARD1). However, these were not associated with outcome after radiotherapy in the TCGA breast cancer cohort. Genes involved in G₁, G₁/S, G₂, and G₂/M phases were lower expressed in tamoxifen-resistant cells compared to wild-type cells. Individual genes that were more than two times upregulated (MAPK13) or downregulated (E2F2, CKS2, GINS2, PCNA, MCM5, and EIF5A2) were not associated with response to radiotherapy in the patient cohort investigated. We assessed the expression of DNA damage repair genes and cell cycle genes in tamoxifen-resistant breast cancer cells. Though several genes in both pathways were differentially expressed, these could not explain the cross-resistance for irradiation in these cells, since no association to response to radiotherapy in the TCGA breast cancer cohort was found.     

Nano-curcumin therapy,a promising method in modulating inflammatory cytokines in COVID-19 patients

BackgroundAs an ongoing worldwide health issue, Coronavirus disease 2019 (COVID–19) has been causing serious complications, including pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. However, there is no decisive treatment approach available for this disorder, which is primarily attributed to the large amount of inflammatory cytokine production. We aimed to identify the effects of Nano-curcumin on the modulation of inflammatory cytokines in COVID-19 patients.MethodForty COVID-19 patients and 40 healthy controls were recruited and evaluated for inflammatory cytokine expression and secretion. Subsequently, COVID-19 patients were divided into two groups: 20 patients receiving Nano-curcumin and 20 patients as the placebo group. The mRNA expression and cytokine secretion levels of IL-1β, IL-6, TNF-α and IL‐18 were assessed by Real‐time PCR and ELISA, respectively.ResultOur primary results indicated that the mRNA expression and cytokine secretion of IL-1β, IL-6, TNF-α, and IL-18 were increased significantly in COVID-19 patients compared with healthy control group. After treatment with Nano-curcumin, a significant decrease in IL-6 expression and secretion in serum and in supernatant (P = 0.0003, 0.0038, and 0.0001, respectively) and IL-1β gene expression and secretion level in serum and supernatant (P = 0.0017, 0.0082, and 0.0041, respectively) was observed. However, IL-18 mRNA expression and TNF-α concentration were not influenced by Nano-curcumin.ConclusionNano-curcumin, as an anti-inflammatory herbal based agent, may be able to modulate the increased rate of inflammatory cytokines especially IL-1β and IL-6 mRNA expression and cytokine secretion in COVID-19 patients, which may cause an improvement in clinical manifestation and overall recovery.     

克隆性造血对肿瘤体细胞突变检测的影响

克隆性造血（clonal hematopoiesis，CH）突变是造血干细胞（hematopoietic stem cell，HSC）携带的突变，是年龄和外在环境（吸烟、放化疗等）共同作用的结果。随着肿瘤基因研究的进展，基因检测已成为实体瘤患者全病程管理中一个重要的环节。目前CH在实体瘤中的价值越来越受到关注。将围绕CH的检出，详细阐述实体瘤患者组织样本及循环肿瘤DNA （circulating tumor DNA，ctDNA）样本中CH的检测方法，探讨CH对肿瘤体细胞突变检测的影响和挑战。     

16个产地地乌药材的系统鉴定及质量评价

目的:构建地乌药材基原物种系统鉴定体系,并对全国16个产地的地乌药材进行综合品质评价,为地乌药材产地选择及临床用药安全奠定基础。方法:使用传统鉴别方法结合DNA条形码核糖体DNA第二内部转录间隔区(ITS2)序列分子鉴定技术快速鉴别地乌药材真伪,并基于HPLC-UV对地乌药材中5个有效成分进行含量测定,采用Welch Ultimate XB-C18色谱柱(4.6 mm×250 mm,5μm),流动相乙腈-0.01%三氟乙酸溶液(30∶70),检测波长210 nm,柱温30℃,流速1.0 mL·min-1。结果:传统鉴别及DNA条形码快速鉴别技术均能准确鉴别地乌药材真伪。BLAST比对分析发现,16个产地地乌药材均与林荫银莲花Anemone flaccida具有最大相似度;基于多指标成分含量测定表明湖北恩施板桥镇的地乌药材中5个三萜皂苷类成分含量之和最高(10.59%),其次为贵州毕节赫章(6.28%)和湖北长阳都镇湾(5.64%)。结论:DNA条形码技术可作为地乌药材传统鉴定技术的有效补充,该鉴别体系可保障地乌药材基原准确及临床用药安全。HPLC多指标成分综合评价及聚类分析结果表明在本研究所涉及的产地中,湖北恩施、长阳、五峰,贵州毕节和重庆金佛山的地乌药材质量较优,可作为地乌药材的重要产地。