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Cellular Heterogeneity of Lung Adenocarcinoma is Correlated with EGFR Inhibitor Resistance 肺腺癌的细胞异质性与表皮生长因子受体抑制剂的耐药性有关
IF 0.1 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2023-11-02 DOI: 10.31901/24566330.2023/23.04.879
Ying Huang
Although EGFR inhibitors have high curative effect on lung adenocarcinoma, EGFR inhibitor resistance is still a difficult problem that must be overcome at present. By integrating bulk RNA-seq data from EGFR inhibitorsensitive and resistant lung adenocarcinoma cell lines, the researchers identified key genes associated with EGFR inhibitor resistance. By integrating single-cell RNA-seq data from 12 clinical lung adenocarcinoma samples, 22 subpopulations of lung adenocarcinoma cells were identified. This study not only confirmed that the cellular heterogeneity of lung adenocarcinoma is associated with EGFR inhibitor resistance, but also cell subpopulations with EGFR inhibitor resistance properties, such as cluster6, may be closely related to tumor malignancy, suggesting that the study focusing on EGFR inhibitor resistant subpopulations will help to find suitable strategies to overcome EGFR inhibitor resistance.
尽管表皮生长因子受体(EGFR)抑制剂对肺腺癌有很高的疗效,但EGFR抑制剂耐药仍是目前必须攻克的难题。通过整合表皮生长因子受体抑制剂敏感和耐药肺腺癌细胞系的大量RNA-seq数据,研究人员发现了与表皮生长因子受体抑制剂耐药相关的关键基因。通过整合12个临床肺腺癌样本的单细胞RNA-seq数据,确定了22个肺腺癌细胞亚群。这项研究不仅证实了肺腺癌的细胞异质性与表皮生长因子受体抑制剂耐药有关,而且具有表皮生长因子受体抑制剂耐药特性的细胞亚群(如cluster6)可能与肿瘤的恶性程度密切相关,这表明以表皮生长因子受体抑制剂耐药亚群为重点的研究将有助于找到克服表皮生长因子受体抑制剂耐药的合适策略。
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引用次数: 0
Genetic Underpinnings of Adolescent Idiopathic Scoliosis: A Review 青少年特发性脊柱侧凸的遗传基础:综述
IF 0.1 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2023-11-02 DOI: 10.31901/24566330.2024/24.01.880
Ekta Rai
Adolescent Idiopathic Scoliosis (AIS) is a three-dimensional spine deformity with lateral curvature having a Cobb angle exceeding 10° in the individual. It affects about 1-4 percent of adolescents globally and more frequently occurs in females than males. Despite the extensive research carried out on AIS, its aetiology is not known yet. However, several genetic studies suggest the contribution of various genetic variants in the possible aetiology of AIS. This review summarises the genetic association studies, including linkage, candidate as well as genome-wide association studies that were carried out globally on AIS and also categorised the associated genes in different biological pathways such as neurodevelopmental, hormone-related, cartilage and bone development pathways, based on their potential functional roles in the respective pathway, to understand the pathology of the disorder.
青少年特发性脊柱侧弯症(AIS)是一种三维脊柱畸形,患者侧弯的Cobb角超过10°。全球约有 1-4% 的青少年患有此病,女性多于男性。尽管对 AIS 进行了广泛的研究,但其病因尚不清楚。不过,一些遗传学研究表明,各种遗传变异在 AIS 的可能病因中起着重要作用。本综述总结了全球范围内针对 AIS 开展的遗传关联研究,包括关联研究、候选研究和全基因组关联研究,并根据相关基因在不同生物通路(如神经发育通路、激素相关通路、软骨和骨骼发育通路)中的潜在功能作用,对相关基因进行了分类,以了解该疾病的病理。
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引用次数: 0
Calculating the Delta Entropy of Differentiation Module in Different Paediatric Sepsis via Analysis of Gene Network 通过基因网络分析计算不同儿科败血症分化模块的德尔塔熵
IF 0.1 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2023-11-02 DOI: 10.31901/24566330.2024/24.01.823
Dan Yu
Paediatric sepsis refers to the body reaction disorder caused by the infection of blood by pathogens. In this study, the researchers aimed to differentiate the 5 types of paediatric sepsis by integrating the mRNA data and PINs analysis. Twenty-three SIRS, 24 uncomplicated sepsis, 21 severe sepsis, 33 septic shock and 28 sepsis deaths were enrolled. The potential genes related to paediatric sepsis were explored. The researchers found that the nodes of SIRS modules were 8, 7 and 4 with corresponding edges of 28, 21 and 6. The nodes of uncomplicated sepsis were 6, 3 and 5, with corresponding edges of 15, 3 and 10. The nodes of severe sepsis module and corresponding edges respectively were 3 and 3. One differentiation module of sepsis death contained 4 nodes and 6 edges. In conclusion, the genes that participate in the ribosome and cell cycle pathways probably play important roles in the development of paediatric sepsis.
小儿败血症是指病原体感染血液后引起的机体反应失调。在这项研究中,研究人员旨在通过整合 mRNA 数据和 PINs 分析来区分 5 种类型的儿科败血症。研究人员对 23 例 SIRS、24 例无并发症败血症、21 例严重败血症、33 例脓毒性休克和 28 例败血症死亡病例进行了研究。研究人员探索了与儿科败血症相关的潜在基因。研究人员发现,SIRS 模块的节点分别为 8、7 和 4,相应的边分别为 28、21 和 6。未并发败血症的节点分别为 6、3 和 5,对应的边分别为 15、3 和 10。严重败血症模块的节点和相应的边分别为 3 和 3。败血症死亡的一个分化模块包含 4 个节点和 6 条边。总之,参与核糖体和细胞周期途径的基因可能在小儿败血症的发病过程中起着重要作用。
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引用次数: 0
Participation of MiR-145-5p in Neuronal Ischemia/Reperfusion Injury by Targeting Fibroblast Growth Factor-5 MiR-145-5p靶向成纤维细胞生长因子-5参与神经元缺血再灌注损伤
4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2023-10-17 DOI: 10.31901/24566330.2024/24.01.809
Lei Xu
The researchers made efforts in elucidating the mechanism for miR-145-5p participating in neuronal ischemia/reperfusion injury (I/R) via targeting fibroblast growth factor-5 (FGF5). OGD/R was performed to construct the neuronal injury model. After OGD/R, the oxidative stress injury of nerve cells was enhanced significantly, the levels of lactic dehydrogenase, reactive oxygen species and malondialdehyde rose, while the superoxide dismutase activity decreased. Both miR-145-5p and cell apoptosis rate increased. MiR-145-5p had a targeting relation to FGF5. After miR- 145-5p inhibitor transfection of nerve cells, inhibition of oxidative stress together with apoptosis was observed. FGF5 siRNA could reverse the impact on oxidative stress, FGF5, and apoptosis exerted by miR-145-5p-inhibitor in the OGD/ R model. Being a latent target of I/R treatment, miR-145-5p induces the oxidative stress injury as well as apoptosis of HT22 cells by targeting and binding FGF5.
研究人员通过靶向成纤维细胞生长因子-5 (FGF5)阐明了miR-145-5p参与神经元缺血再灌注损伤(I/R)的机制。采用OGD/R法构建神经元损伤模型。OGD/R后,神经细胞氧化应激损伤显著增强,乳酸脱氢酶、活性氧和丙二醛水平升高,超氧化物歧化酶活性降低。miR-145-5p和细胞凋亡率均升高。MiR-145-5p与FGF5具有靶向关系。miR- 145-5p抑制剂转染神经细胞后,观察到氧化应激和细胞凋亡的抑制作用。在OGD/ R模型中,FGF5 siRNA可以逆转mir -145-5p抑制剂对氧化应激、FGF5和细胞凋亡的影响。miR-145-5p作为I/R治疗的潜在靶点,通过靶向结合FGF5诱导HT22细胞氧化应激损伤和凋亡。
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引用次数: 0
Roles of LCN2, PDIA3 and HGF in Progression and Remission of Non-small Cell Lung Cancer LCN2、PDIA3和HGF在非小细胞肺癌进展和缓解中的作用
IF 0.1 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2023-01-15 DOI: 10.31901/24566330.2023/23.01.843
Jing Zhang
The research aimed to investigate the expressions of lipid-carrying protein 2 (LCN2), protein disulfideisomerase A3 (PDIA3) and hepatocyte growth factor (HGF) during the progression of non-small cell lung cancer (NSCLC), and their predictive values for disease remission. A total of 120 NSCLC patients admitted from January 2021 to January 2022 were enrolled. The patients with complete remission and partial remission were assigned into the remission group, while those with stable disease and progressive disease were assigned into the non-remission group. LCN2, PDIA3 and HGF had higher positive expression rates in the case of tumour diameter more than or equal to 3 cm, TNM stage 3/4, moderate and low differentiation, lymph node metastasis and deep invasion (P<0.05). The predictive efficiency of combination of LCN2, PDIA3 and HGF for disease remission was highest. There were positive correlations among LCN2, PDIA3 and HGF (P<0.05). LCN2, PDIA3 and HGF are highly expressed in NSCLC, and their expressions are elevated with disease progression.
本研究旨在探讨载脂蛋白2 (LCN2)、蛋白二硫异构酶A3 (PDIA3)和肝细胞生长因子(HGF)在非小细胞肺癌(NSCLC)进展过程中的表达及其对疾病缓解的预测价值。共纳入了2021年1月至2022年1月收治的120例NSCLC患者。将完全缓解和部分缓解的患者分为缓解组,病情稳定和病情进展的患者分为非缓解组。LCN2、PDIA3、HGF在肿瘤直径≥3cm、TNM分期3/4期、中低分化、淋巴结转移及深部浸润时阳性表达率较高(P<0.05)。LCN2、PDIA3和HGF联合应用对疾病缓解的预测效率最高。LCN2、PDIA3与HGF呈正相关(P<0.05)。LCN2、PDIA3和HGF在NSCLC中高表达,且随着疾病进展表达升高。
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引用次数: 0
Expressions of miR-132, miR-145 and miR-208 in Patients with Acute Myocardial Infarction and Correlations with Gensini Score 急性心肌梗死患者miR-132、miR-145、miR-208的表达及其与Gensini评分的相关性
IF 0.1 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2023-01-15 DOI: 10.31901/24566330.2023/23.01.846
Ling Lin
The researchers aimed to investigate the correlations of miR-132, miR-145 and miR-208 with the Gensini score (GS) of patients with acute myocardial infarction (AMI). Totally 120 AMI patients and 80 healthy volunteers undergoing physical examination were included into AMI group and healthy group, respectively. The AMI patients were subdivided into low GS (LGS) group (< 30 points) and high GS (HGS) group (>30 points). Independent risk factors included troponin I (TnI), creatine kinase (CK) isoenzyme, uric acid (UA), C-reactive protein (CRP), miR-132, miR-145 and miR208, which affected the severity of coronary artery lesions (CALs) (P<0.05). Compared with miR-132, miR-145, and miR208 alone, their combination had the highest diagnostic value, with the area under curve (95%CI) of 0.911 (0.869-0.978), sensitivity of 89.89 percent and specificity of 70.91 percent (P<0.001). MiR-132, miR-145, and miR-208 are abnormally expressed in AMI patients. Their combination has higher diagnostic value for the severity of CALs in AMI patients.
研究人员旨在研究miR-132、miR-145和miR-208与急性心肌梗死(AMI)患者Gensini评分(GS)的相关性。将120例AMI患者和80名健康体检志愿者分为AMI组和健康组。AMI患者分为低GS(LGS)组(<30分)和高GS(HGS)组。独立的危险因素包括肌钙蛋白I(TnI)、肌酸激酶(CK)同工酶、尿酸(UA)、C反应蛋白(CRP)、miR-132、miR-145和miR208,它们影响冠状动脉病变(CAL)的严重程度(P<0.05),敏感性为89.89%,特异性为70.91%(P<0.001)。MiR-132、MiR-145和MiR-208在AMI患者中异常表达。它们的组合对AMI患者CAL的严重程度具有较高的诊断价值。
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引用次数: 0
Effects of Casein Kinase 2 Alpha Subunit on the Proliferation, Invasion and Migration of Pancreatic Cancer PANC-1 Cells via the PI3K/Akt/GSK-3β Pathway 酪蛋白激酶2 α亚基通过PI3K/Akt/GSK-3β通路对胰腺癌PANC-1细胞增殖、侵袭和迁移的影响
IF 0.1 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2023-01-15 DOI: 10.31901/24566330.2023/23.01.844
Qiwei Hao
The researchers aimed to evaluate the functions of casein kinase 2 alpha subunit (CK2a) expression silencing in influencing pancreatic cancer (PC) PANC-1 cells from the aspects of invasion, proliferation and migration. As PC-1, PC PANC-1 and SW1990 cells exhibited significantly reduced CK2a mRNA expression level in contrast to normal pancreatic cells HPDE6-C7, while PC tissues displayed raised expression level compared with adjacent tissues (P<0.05). CK2a mRNA expression had significant correlations with nerve infiltration, lymph node metastasis, tumor differentiation degree and tumor-node-metastasis stage. After interfering with the expression of CK2a in PANC-1 cells, p-PTEN had elevated expression, while p-Akt473, p-GSK-3β, p-c-Raf, p-Akt308, p-PDK1, Snail and Vimentin, βcatenin had significantly down-regulated expressions, impeding cell growth, decreasing the number of healing wounds and invading cells. Moreover, the transplanted tumors were inhibited in terms of growth. For PC PANC-1 cells, their metastasis, proliferation and invasion were modulated by CK2a probably through regulating the PI3K/Akt/GSK-3β pathway that targeted epithelial-mesenchymal transition.
研究人员旨在从侵袭、增殖和迁移等方面评价酪蛋白激酶2α亚基(CK2a)表达沉默对胰腺癌症PANC-1细胞的影响。与正常胰腺细胞HPDE6-C7相比,PC PANC-1和SW1990细胞的CK2a mRNA表达水平显著降低,而PC组织的CK2a表达水平与邻近组织相比升高(P<0.05)。CK2a mRNA的表达与神经浸润、淋巴结转移、肿瘤分化程度和肿瘤结转移分期显著相关。在干扰PANC-1细胞中CK2a的表达后,p-PTEN的表达升高,而p-Akt473、p-GSK-3β、p-c-Raf、p-Akt308、p-PDK1、Snail和Vimentin、β连环蛋白的表达显著下调,阻碍细胞生长,减少愈合伤口和侵袭细胞的数量。此外,移植的肿瘤在生长方面受到抑制。对于PC PANC-1细胞,CK2a可能通过调节靶向上皮-间质转化的PI3K/Akt/GSK-3β途径来调节其转移、增殖和侵袭。
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引用次数: 0
Assessment of Association of ITLN1 SNPs rs2274907A>T and rs2274908 G>A with Coronary Artery Disease in People from Punjab 旁遮普人ITLN1 SNPs rs2274907A>T和rs2274908G>A与冠心病相关性的评估
IF 0.1 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2023-01-15 DOI: 10.31901/24566330.2023/23.01.861
N. Kaur
The objectives of the present study were to determine the genotype and allele frequency distributions of rs2274907 and rs2274908 SNPs of the ITLN1 gene in CAD cases (n=206) and controls (n=206) inhabiting the state of Punjab in northwest India and to seek association, if any, of these SNPs with CAD. Age, lifestyle patterns, dietary habits and various biochemical traits (CHOL, TG, HDL, LDL and VLDL) were examined for possible association with the studied SNP genotypes in CAD cases. Statistically significant differences were found between CAD cases and controls in physical activity (OR=0.27, p<0.0001), alcohol intake (OR=0.67, p=0.04), smoking (OR=1.93, p=0.001), diet type (OR=1.76, p=0.011) and fruit intake (OR=2.62, p<0.0001). All biochemical trait differences were also found to be highly statistically significant (p<0.0001). The present case-control study revealed that both the SNPs at ITLN1 locus were statistically significantly associated with the occurrence of CAD in the people of Punjab.
本研究的目的是确定居住在印度西北部旁遮普邦的CAD病例(n=206)和对照组(n=206)中ITLN1基因的rs2274907和rs2274908 SNPs的基因型和等位基因频率分布,并寻求这些SNPs与CAD的联系(如果有的话)。研究了年龄、生活方式、饮食习惯和各种生化特征(CHOL、TG、HDL、LDL和VLDL)与CAD病例中所研究的SNP基因型的可能关联。CAD病例与对照组在体力活动(OR=0.27,p<0.0001)、酒精摄入(OR=0.67,p=0.04)、吸烟(OR=1.93,p=0.001)、,饮食类型(OR=1.76,p=0.011)和水果摄入量(OR=2.62,p<0.0001)。所有生化特征差异也被发现具有高度统计学意义(p<0.0001),本病例对照研究表明,ITLN1基因座的两个SNPs与旁遮普人CAD的发生具有统计学意义。
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引用次数: 0
ATF1 Regulating Signaling Pathways between Nasopharyngeal Carcinoma Cells and Immortalized Epithelial Cells ATF1调节鼻咽癌细胞与永生上皮细胞之间的信号通路
IF 0.1 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2022-12-15 DOI: 10.31901/24566330.2022/22.04.831
Fangfang Wang
This study aims to provide a comprehensive pathway regulated by ATF1 and screen for differences between cancer and normal cells. Genome-wide mRNA expression microarrays were performed using RNA isolated from ATF1 over-expressing CNE1 and NP69 cells. The ATF1 regulating expression pattern and signaling was investigated by GO annotation, KEGG pathway and PPI network. A total of 1651 genes were found to be expressed differentially between CNE1-ATF1 and CNE1-control cells, 4304 genes were shown to be expressed differentially between NP69-ATF1 and NP69-control cells. In the GO annotation, KEGG analysis and PPI networks, pathways associated with cancer, apoptosis and cell proliferation exhibited the most significant correlation with ATF1 modulation in both cells. Different pathways were suggested as immune response in CNE1 cells and metabolism in NP69 cells. Taken together, the data of this study provides a comprehensive signaling pathway regulated by ATF1 and figure out the differences between cancer and normal cells.
本研究旨在提供ATF1调控的综合途径,并筛选癌症细胞与正常细胞之间的差异。使用从过表达CNE1和NP69细胞的ATF1分离的RNA进行全基因组mRNA表达微阵列。通过GO注释、KEGG通路和PPI网络研究ATF1调节表达模式和信号传导。共发现1651个基因在CNE1-ATF1和CNE1对照细胞之间差异表达,4304个基因在NP69-ATF1与NP69对照细胞之间差别表达。在GO注释、KEGG分析和PPI网络中,与癌症、细胞凋亡和细胞增殖相关的途径与两种细胞中的ATF1调节表现出最显著的相关性。CNE1细胞的免疫反应和NP69细胞的代谢途径不同。总之,本研究的数据提供了ATF1调节的综合信号通路,并找出了癌症与正常细胞之间的差异。
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引用次数: 0
Laccase Domain-Containing Protein 1 Promoted Inflammation of Osteoporosis Model via NOD2 Ubiquitination by RIP2 漆酶结构域蛋白1通过RIP2介导NOD2泛素化促进骨质疏松模型炎症反应
IF 0.1 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2022-12-15 DOI: 10.31901/24566330.2022/22.04.834
Jun Zhang
The purpose of this experiment was to elucidate the latent influence of Laccase Domain-Containing Protein 1 (LACC1) regulatory loop in the progression of osteoporosis. Serum samples of volunteers were obtained from the researchers’ hospital. Mice were induced by an osteoporosis model using ovariectomy. LACC1 mRNA expression levels were up-regulated in patients with osteoporosis. LACC1 protein and mRNA expression levels in mice with osteoporosis were measured. LACC1 promoted inflammation of osteoporosis in the in vitro model. LACC1 promoted osteoporosis in the mice model. LACC1 protein interlinked nucleotide-binding oligomerisation domain 2 (NOD2)/ receptor interacting protein 2 (RIP2) protein to reduce ubiquitination of NOD2. NOD2/RIP2 participated in the effects of LACC1 in the model of osteoporosis. These findings suggest that LACC1 promoted inflammation of the osteoporosis model via the induction of NOD2-RIP2 signalling by the inhibition of NOD2 ubiquitination. The inhibition of LACC1 regulatory loop provides new targets for treatment of osteoporosis.
本实验旨在阐明漆酶结构域蛋白1 (LACC1)调控环在骨质疏松症进展中的潜在影响。志愿者的血清样本来自研究人员所在的医院。采用卵巢切除法建立小鼠骨质疏松模型。骨质疏松患者LACC1 mRNA表达水平上调。测定骨质疏松小鼠LACC1蛋白及mRNA表达水平。LACC1在体外模型中促进骨质疏松的炎症反应。LACC1促进小鼠骨质疏松。LACC1蛋白互联核苷酸结合寡聚结构域2 (NOD2)/受体相互作用蛋白2 (RIP2)蛋白减少NOD2泛素化。NOD2/RIP2参与了LACC1在骨质疏松模型中的作用。这些发现表明,LACC1通过抑制NOD2泛素化,诱导NOD2- rip2信号传导,从而促进骨质疏松模型的炎症。抑制LACC1调控环为骨质疏松症的治疗提供了新的靶点。
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引用次数: 0
期刊
International Journal of Human Genetics
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