ABSTRACT Interleukin 6 (IL‐6), a type of cytokine, plays a role in the onset, progression, and prognosis of various diseases. IL‐6's single nucleotide polymorphisms (SNPs) markedly affect clinical conditions by influencing gene expression, including that of other cytokines. This review synthesizes existing literature to explore the relationship between IL‐6 SNPs and diseases. Current evidence indicates that these SNPs are associated with the clinicopathological features of different diseases, with these associations partly influenced by population ethnicity. Although IL‐6 SNPs could potentially serve as biomarkers for disease susceptibility and progression, larger‐scale studies across diverse regions and populations are required to confirm their clinical significance.
Glutamine cyclase, an enzyme involved in posttranslational modifications, is encoded by the glutaminyl-peptide cyclotransferase (QPCT) gene. Gene microarray analysis revealed that the QPCT gene was highly expressed in HepG2.2.15 cells compared with that in HepG2 cells. The serum expression level of the QPCT gene was detected by ELISA and was significantly greater in HBV-infected patients than in healthy controls. The mRNA and protein expression levels of the QPCT gene were markedly greater in the HBV-expressing cell lines (HepG2.2.15, and HepG2 and Huh7 cells transfected with the pBlu-HBV plasmid) than in the HepG2 and Huh7 cells. The levels of HBV pgRNA and HBV-DNA copy number, as well as the levels of HBeAg and HBsAg, also increased in the HepG2 and Huh7 cell lines cotransfected with the QPCT gene expression plasmid and the HBV 1.3-fold plasmid. Our study indicated that HBV can promote the expression of the QPCT gene, which in turn promotes the expression and replication of HBV.
Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC), pegylated-interferon-α(PEG-IFNα) and long-term nucleos(t)ide analogs (NUCs) are mainly drugs used to treat HBV infection, but the effectiveness is unsatisfactory in different populations, the exploration of novel therapeutic approaches is necessary. RAD51C is associated with DNA damage repair and plays an important role in the development and progression of tumors. Early cDNA microarray results showed that RAD51C expression was significantly increased in HBV-infected HCC cells, however, the relationship between HBV infection and abnormal expression of RAD51C has not been reported. Therefore, we conducted RT-PCR, western blot, Co-immunoprecipitation(Co-IP), and immunofluorescence(IF) to detect HBV-RAD51C interaction in RAD51C overexpression or interfering HCC cells. Our results showed that RAD51C and HBV X protein(HBX) produced a direct interaction in the nucleus, the HBV infection of HCC cells promoted RAD51C expression, and the increased expression of RAD51C promoted HBV replication. This indicated that RAD51C is closely related to the occurrence and development of HCC caused by HBV infection, and may bring a breakthrough in the the prevention and treatment study of HCC.
Objective To investigate the epidemiological features in children after the coronavirus disease 2019 (COVID-19) pandemic. Methods This study collected throat swabs and serum samples from hospitalized pediatric patients of Renmin Hospital of Wuhan University, Wuhan, Hubei province, China before and after the COVID-19 pandemic. Respiratory infected pathogens [adenovirus (ADV), influenza virus A/B (Flu A/B), parainfluenza virus 1/2/3 (PIV1/2/3), respiratory syncytial virus (RSV), Mycoplasma pneumoniae (MP), and Chlamydia pneumoniae (CP)] were detected. The pathogens, age, and gender were used to analyze the epidemiological features in children after the COVID-19 pandemic. Results The pathogen detection rate was significantly higher in females than in males ( P <0.05), and the infection of PIV1 and MP was mainly manifested. After the COVID-19 pandemic, PIV1, PIV3, RSV, and MP had statistically different detection rates among the age groups ( P <0.05), and was mainly detected in patients aged 0–6 years, 0–3 years, 0–3 years, and 1–6 years, respectively. When comparing before the COVID-19 pandemic, the total detection rate of common respiratory pathogens was lower ( P <0.05). Except for the increase in the detection rate of PIV1 and CP, the infection rate of other pathogens had almost decreased. Conclusion The prevention and control measures for the COVID-19 pandemic effectively changed the epidemiological features of common respiratory tract infectious diseases in pediatric children.
Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread across many other countries. While the majority of patients were considered mild, critically ill patients involving respiratory failure and multiple organ dysfunction syndrome are not uncommon, which could result death. We hypothesized that cytokine storm is associated with severe outcome. We enrolled 102 COVID-19 patients who were admitted to Renmin Hospital (Wuhan, China). All patients were classified into moderate, severe and critical groups according to their symptoms. 45 control samples of healthy volunteers were also included. Inflammatory cytokines and C-Reactive Protein (CRP) profiles of serum samples were analyzed by specific immunoassays. Results showed that COVID-19 patients have higher serum level of cytokines (TNF-alpha, IFN-gamma, IL-2, IL-4, IL-6 and IL-10) and CRP than control individuals. Within COVID-19 patients, serum IL-6 and IL-10 levels are significantly higher in critical group (n = 17) than in moderate (n = 42) and severe (n = 43) group. The levels of IL-10 is positively correlated with CRP amount (r = 0.41,P < 0.01). Using univariate logistic regression analysis, IL-6 and IL-10 are found to be predictive of disease severity and receiver operating curve analysis could further confirm this result (AUC = 0.841, 0.822 respectively). Our result indicated higher levels of cytokine storm is associated with more severe disease development. Among them, IL-6 and IL-10 can be used as predictors for fast diagnosis of patients with higher risk of disease deterioration. Given the high levels of cytokines induced by SARS-CoV-2, treatment to reduce inflammation-related lung damage is critical.
Lymphocyte count (LYM) of peripheral blood and some indices of general biochemical analysis had diagnostic and prognostic value for coronavirus disease 2019 (COVID‐19), and the value of other remaining indices is rare.
Cervical cancer is the fourth most common cancer among women worldwide. The treatment of cervical cancer mainly focused on surgery and radiotherapy, whereas the prognosis of invasive cervical cancer is still low. Ginkgo biloba is an ancient medicinal plant that has been used for decades to treat ischemic strokes and cognitive decline. Ginkgolide B, an active ingredient extracted from Ginkgo biloba, has multiple biological activities such as antioxidant, anti-apoptotic, and anti-inflammatory effects. Ginkgolide B has been found to have anti-tumor effects and inhibits the progression of multiple types of cancers. However, its potential role in cervical cancer is still unclear. In this study, we found that ginkgolide B suppresses the proliferation of cervical cancer cells in a dose-dependent manner. Ginkgolide B also induces cell cycle arrest and stimulates cell apoptosis by modulating the MAPK signaling pathway. We, therefore, present a novel and promising anti-tumor drug for the treatment of cervical cancer.
Background: Among patients with coronavirus disease 2019 (COVID-19), the cases of a significant proportion of patients are severe. A viral nucleic acid test is used for the diagnosis of COVID-19, and some hematological indicators have been used in the auxiliary diagnosis and identification of the severity of COVID-19. Regarding body fluid samples, except for being used for nucleic acid testing, the relationship between COVID-19 and routine body fluid parameters is not known. Our aim was to investigate the value of urine biochemical parameters in the prediction of the severity of COVID-19. Methods: A total of 119 patients with COVID-19 were enrolled at Renmin Hospital of Wuhan University. According to the severity of COVID-19, the patients were divided into three groups (moderate 67, severe 42 and critical 10), and 45 healthy persons were enrolled in the same period as healthy controls. The relationship between the results of urine biochemical parameters and the severity of COVID-19 was analyzed. Results: The positive rates of urine occult blood (BLOOD) and proteinuria (PRO) were higher in COVID-19 patients than in healthy controls (p < 0.05); the urine specific gravity (SG) value was lower in patients than in healthy controls (p < 0.05), and the urine potential of hydrogen (pH) value was higher in patients than in healthy controls (p < 0.01). The positive rates of urine glucose (GLU-U) and PRO in the severe and critical groups were higher than those in the moderate group (p < 0.01 and p < 0.05, respectively); other biochemical parameters of urine were not associated with the severity of COVID-19. Conclusions: Some urine biochemical parameters are different between patients with severe acute respiratory syndrome (SARS)-CoV-2 and healthy controls, and GLU-U and PRO may be helpful for the differentiation of COVID-19 severity.
Transit from the nuclear complex to the cytoplasm through the nuclear pore complex permits modification of mRNA, including processing such as splicing, capping, and polyadenylation, etc. At each of these events, mRNA interacts with various proteins to form mRNA-protein complex. Visualizing the mRNA is crucial for understanding the mechanisms underlying mRNA processing and elucidating its structure and recent advances in mRNA imaging allow detection of real-time mRNA localization in living cells. However, these techniques revealed only the location of mRNA but cannot visualize the conformation of mRNA-protein complex in cells. On the other hand, transmission electron microscopy has been used to visualize the structure of the Balbiani ring-derived large mRNA, but their observations were limited to the insect cells. In this study, we visualized the structure of mRNA-protein complex in human culture cells by using immuno-electron microscopy. Through immuno-detection, an mRNA exon junction binding complex Y14, and its binding protien Upf2, different gold particle patterns were imaged with transmission electron microscopy and analyzed. Characteristic linear and stacked particle orientation were observed. Across the nuclear membrane, only linear aggregation pattern was observed, whereas the stacked aggregation pattern was detected in the cytoplasm. Our method is able to visualize mRNA-conformation and applicable to many cell types, including mammalian cells, where genes can easily be manipulated.
Viral replication and related protein expression inside the host cells, and host antiviral immune responses can lead to the occurrence of diverse diseases. With the outbreak of viral infection, a large number of newly diagnosed and died patients infected with various viruses are still reported every year. Viral infection has already been one of the major global public health issues and lead to huge economic and social burdens. Studying of viral pathogenesis is a very important way to find methods for prevention, diagnosis, and cure of viral infection; more evidence has confirmed that major vault protein (MVP) is closely associated with viral infection and pathogenesis, and this review is intended to provide a broad relationship between viruses and MVP to stimulate the interest of related researchers.
Reduced expression of the Y14 gene is a cause of Thrombocytopenia-absent radius (TAR) syndrome. This gene contains a conserved RNA recognition motif (RRM) in the central region and nuclear localization/export sequences (NLS/NES) in the N-terminal. Y14 and Magoh proteins form tight heterodimers and are the core of exon junction complexes (EJCs), which mediate various processes of mRNA metabolism after transcription. In this report, we found that protein expression levels of exogenously expressed Magoh L136R and Y14 L118R (leucine-to-arginine substitution at amino acid residue 136 and 118 respectively, that results in the formation of the complex being lost) are lower than their wild-types. This reduction is likely caused by protein levels, as no difference in mRNA levels was detected. Meanwhile, a cycloheximide chase assay determined that the degradation rates of Magoh L136R and Y14 L118R were faster than their wild-types. Both Y14 L118R and Magoh L136R lost the ability to form heterodimers with corresponding wild-type proteins. However, Y14 L118R is able to still localize in the nucleus which causes the stability of Y14 L118R to be higher than Magoh L136R. These results reveal that the stability of Magoh and Y14 is not only dependent on the heterodimer structure, but also dependent on nuclear localization.
Serine/arginine-rich splicing factors (SRSFs) have one or two RNA recognition motifs in the N terminal and a serine/arginine-enriched domain in the C terminal. SRSFs are essential components of spliceosomes and are involved in alternative splicing, spliceosome assembly, mRNA export, and nonsense-mediated mRNA decay. The maintenance of cellular and tissue homeostasis relies on accurate alternative splicing, and various patterns of abnormal alternative splicing can cause different diseases. SRSF4 is associated with many physiological and pathological processes and has applications in the diagnosis and prognosis of specific diseases. In this review, we discuss knowledge of SRSF4 in physiological and pathological processes and highlight the applications of SRSF4 in the regulation of gene expression and associated diseases.
Objective To investigate the expression of STAT3 protein and SHP-2 protein in colorectal carcinoma(CRC),and to explore its relationships with clinical characteristics.Methods Immunohistochemisty was used to detect the expression of STAT3 and SHP-2 in 168 cases of CRC tissues and 40 cases of normal tissues.The expression of STAT3 and SHP-2 was compared between patients with different clinicopathological features of CRC.The expression of STAT3 and SHP-2 in 40 cases of CRC tissues and matched adja cent non-tumor tissues was detected by Western-blot.Results The results of immunohistochemisty demonstrated that the positive expression rate of STAT3 protein in 168 cases of CRC was significantly higher than that of normal tissues (P < 0.05),but the positive expression rate of SHP-2 protein in 168 cases of CRC was significantly lower than that of normal tissues (P < 0.05).Western-blot results showed that STAT3 protein in CRC was higher than that of matched adjacent non-tumor tissues (0.421 3 ± 0.112 7 vs 0.301 7 ± 0.079 9,P < 0.05),but SHP-2 protein level in CRC was lower than that of matched adjacent non-tumor tissues (0.239 6 ± 0.065 5 vs 0.766 5 ± 0.113 3,P < 0.001).The expression of STAT3 in CRC tissues was correlated with differentiation grade,lymph node metastasis,distant metastasis and TNM stage,but not related to gender,age and invasion depth.The expression of SHP-2 in CRC tissues was correlated with differentiation grade and lymph node metastasis,but not related to gender,age,invasion depth,distant metastasis and TNM stage.The expression of STAT3 protein was negatively correlated with the expression of SHP-2 in colorectal carcinoma protein (r =-0.501,P < 0.05).Conclusion The expression of STAT3 is higher but SHP-2 is lower in CRC patients,suggesting that the two proteins may be involved in the evolution and development process of CRC,which may be used as potential therapeutic targets in the treatment.
目的:观察颈动脉粥样硬化(CAS)患者颈动脉内膜中层厚度(IMT)、白细胞分化抗原40及其配体(CD40/CD40L)和基质金属蛋白酶9(MMP-9)变化,探讨上述指标之间的关系。方法选择CAS患者94例,其中IMT增厚的有34例,颈动脉斑块形成的有60例;健康体检者20例(IMT正常组)。采用颈动脉超声检测实验组和对照组IMT,采用酶联免疫吸附试验(ELISA)法检测两组血清 CD40、CD40L和 MMP-9水平。结果随着IMT的增厚,血清CD40、CD40L、MMP-9水平明显升高(P<0.05);有不稳定斑块的 CAS患者 IMT及血清 CD40、CD40L、MMP-9水平较稳定斑块患者明显升高,不稳定斑块CAS患者脑梗死(CI)发病率高于斑块稳定组(P均<0.05)。结论血清 CD40、CD40L、MMP-9能促进 CAS 的形成和增厚,MMP-9能增加斑块的不稳定性,导致CI的发生,监测血清CD40、CD40L、MMP-9水平,能用来预测CAS患者的IMT、斑块的稳定性和疾病的预后。
目的:调查老年非小细胞肺肿瘤(NSCLC)患者贫血的发生率及临床输血情况,探讨老年NSCLC患者的输血现状及临床的重视程度.方法:收集232例老年NSCLC患者和肺良性病变患者50例,根据《AJCC肿瘤分期手册》标准对老年NSCLC患者进行分期(其中Ⅰ期87例、Ⅱ期45例、Ⅲ期71例、Ⅳ期29例),收集所有患者住院期间的血常规结果及输血情况.结果:老年NSCLC患者的输血比例远高于肺良性病变患者;随着老年NSCLC患者肿瘤恶性程度的增加,贫血的发生率在增加,但输血的比例没有随之增加;老年NSCLC患者的输血以红细胞输注为主,各期老年NSCLC患者之间成分输血没有差异.结论:老年NSCLC患者在输血时以输注红细胞为主,输血比例与肿瘤的分期无关,提示临床为了改善老年NSCLC患者的生存、生活质量,应更加关注Ⅲ、Ⅳ期老年NSCLC患者的输血.
目的:探讨老年内科患者的输血阈值水平,评价不同输血策略对老年患者红细胞输注效果及临床结局的影响.方法:回顾性调查2012-03-2014-03老年内科患者的临床输血资料及病历资料,统计分析老年患者的输血阈值水平;根据患者输血前血红蛋白(Hb)水平将患者分为开放性输血组(>60 g/L)和限制性输血组(<60 g/L),比较分析2组输注效果、病死率、输血不良反应的发生率,院内感染等指标.结果:老年内科患者输血Hb阈值达(63.8±15.1)g/L,限制性输血组输注显效率明显高于开放性输血组(P<0.01),无效及效果不佳的比率明显低于开放组(P<0.01);2组输血不良反应的发生率和住院期间病死率比较差异无统计学意义(P>0.05),院内感染率,住院天数的差异有统计学意义(P<0.01).结论:限制性输血策略对于提高老年患者的输注效率,减少院内感染率和住院时间有积极意义.
Objective:To investigate the relationship between the serum levels of procalcitonin(PCT),high-sensitivity C-reactive protein(hs-CRP)and bacterial pneumonia.Method:According to the pneumonia severity in-dex,127 patients with bacterial pneumonia were divided into level I (40 cases),II-III level(49 cases)and IV-V level (38 cases);PCT levels were detected by the fluorescence immunoassay technology,hs-CRP levels were detec-ted by the full automatic immune turbidimetry,the differences were analyzed by the statistical analysis among bacte-rial pneumonia,35 cases of non-bacterial pneumonia and 20 cases of healthy check-up (control group),the correla-tion of severity of bacterial pneumonia and the levels of PCT,hs-CRP were analyzed.Results:The serum levels of PCT and hs-CRP in patients with the bacterial pneumonia were significantly higher than the control group and the non-bacterial pneumonia group(P<0.01),serum PCT and hs-CRP levels were positive correlated with the increas-ing degree of pneumonia(r was 0.993,0.976 respectively,P<0.05).Conclusion:High serum levels of PCT and hs-CRP contributed to the difference between the lower respiratory tract bacterial and non-bacterial infection,also could reflect the severity of bacterial pneumonia.