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Background: Cervical cancer is one of the most common malignancies in women worldwide. As a RING type ubiquitin ligase, SIAH2 has been reported to promote the progression of a variety of tumors by interacting with and targeting multiple chaperones and substrates. The aim of this study was to further identify the role and the related molecular mechanisms involved of SIAH2 in cervical carcinogenesis. Methods and results: Cellular assays in vitro showed that knockdown of SIAH2 inhibited the proliferation, migration and invasion of human cervical cancer cells C33A and SiHa, induced apoptosis, and increased the sensitivity to cisplatin treatment. Knockdown of SIAH2 also inhibited the epithelial-mesenchymal transition and activation of the Akt/mTOR signaling pathway in cervical cancer cells, which were detected by Western blot. Mechanistically, SIAH2, as a ubiquitin ligase, induced the ubiquitination degradation of GSK3ß degradation by using coIP. The results of complementation experiments further demonstrated that GSK3ß overexpression rescued the increase of cell proliferation and invasion caused by SIAH2 overexpression. Specific expression of SIAH2 appeared in precancerous and cervical cancer tissues compared to inflammatory cervical lesions tissues using immunohistochemical staining. The more SIAH2 was expressed as the degree of cancer progressed. SIAH2 was significantly highly expressed in cervical cancer tissues (44/55, 80 %) compared with precancerous tissues (18/69, 26.1 %). Moreover, the expression level of SIAH2 in cervical cancer tissues was significantly correlated with the degree of cancer differentiation, and cervical cancer tissues with higher SIAH2 expression levels were less differentiated. Conclusion: Targeting SIAH2 may be beneficial to the treatment of cervical cancer.
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Since March 2020, the pandemic caused by SARS-CoV-2 has affected nearly all aspects of daily life. In this study, we investigated the age-stratified prevalence and genotype distribution of human papillomavirus (HPV) among females in Shandong province (eastern China) and aimed to provide guidance on HPV-based cervical cancer screening and vaccination. The distribution of HPV genotypes was analyzed using PCR-Reverse Dot Hybridization. The overall infection rate of HPV was 16.4%, which was dominated by high-risk genotypes. The most prevalent genotype was HPV16 (2.9%), followed by HPV52 (2.3%), HPV53 (1.8%), HPV58 (1.5%), and HPV51 (1.3%). Among the positive cases with HPV infection, single-genotype infection was significantly higher than that of multi-genotype infection. In subgroup analyses by age (≤25, 26-35, 36-45, 46-55, >55), HPV16, 52, and 53 were consistently the three most common hrHPV genotypes in all age groups. The infection rate of multi-genotypes in the ≤25 and >55 age groups was significantly higher than that in other age groups. A bimodal distribution of HPV infection rate was observed in different age groups. Among lrHPV genotypes, HPV6, HPV11, and HPV81 were the three most common types in the ≤25 age group, while in other age groups, HPV81, HPV42, and HPV43 are the three most common lrHPV genotypes. This study provides basic information on the distribution and genotypes of HPV in the female population in eastern China, which could improve the application of HPV diagnostic probes and vaccines.
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COVID-19 , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/prevención & control , Infecciones por Papillomavirus/prevención & control , Virus del Papiloma Humano , Pandemias , Prevalencia , Detección Precoz del Cáncer , COVID-19/epidemiología , SARS-CoV-2/genética , Genotipo , Papillomaviridae/genética , Papillomavirus Humano 16/genética , China/epidemiologíaRESUMEN
Background: Liquid biopsy has been receiving attention as an emerging detection technology in the clinical application of non-small-cell lung cancer (NSCLC). Methods: We quantified serum circulating free DNA (cfDNA) of syncytin-1 in 126 patients and 106 controls, analyzed the correlation of level with pathological parameters and explored diagnostic utility. Results: The cfDNA of syncytin-1 levels in NSCLC patients were higher than healthy controls (p < 0.0001). These levels were associated with smoking history (p = 0.0393). The area under the curve of cfDNA of syncytin-1 was 0.802, and combination of cfDNA of syncytin-1/cytokeratin 19 fragment antigen 21-1/carcinoembryonic antigen markers improved diagnostic efficiency. Conclusion: The cfDNA of syncytin-1 was detected in NSCLC patients and can be used as a novel molecular marker for early diagnosis.
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Carcinoma de Pulmón de Células no Pequeñas , Ácidos Nucleicos Libres de Células , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Biomarcadores de Tumor/genética , Detección Precoz del Cáncer , ADNRESUMEN
INTRODUCTION: Syncytin-1 is a human endogenous retroviral (HERVW) envelope protein, which has been implicated in trophoblast and cancer cell fusions as well as in immunomodulatory functions. We investigated syncytin-1 expression and promoter methylation in non-small cell lung cancer (NSCLC) and the adjacent, para-carcinoma tissues. In addition, the correlation to patient survival differentiation of between 5-year survival and death group was analyzed. METHODS: Survival ratio was calculated by Kaplan-Meier survival curve. Death risk assessment was executed by Cox risk regression model. The 5'-LTR methylation level of HERVW promoter was detected by EpiTYPER method. RESULTS: Syncytin-1 expression in NSCLC tissue was found to be significantly higher than in para-carcinoma tissues. Moreover, the 5-year survival group has a lower syncytin-1 expression than the death group. Clinical stage and the percentage of syncytin-1 positive cells were top risk factors according to Cox ratio risk regression model analysis. While the methylation level of the 5'-LTR in HERVW gene promoter was relatively lower in NSCLC than para-carcinoma tissues, the methylation status of a CpG-2 site overlapping the Oct-1 binding site was found to be an important element potentially involved in the epigenetic regulation of HERVW gene expression. CONCLUSION: These findings suggest that syncytin-1 could be a biomarker for the diagnosis/prognosis of NSCLC, and further studies are required to elucidate the exact role of syncytin-1 in the development of NSCLC as well as the underlying molecular mechanism for syncytin-1 function and regulation.
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Syncytin 1 is considered as an oncogene in various malignant tumors, but its effect on non-small cell lung cancer (NSCLC) has not been reported. We investigated the specific role of Syncytin 1 on NSCLC through the transfection of Syncytin 1 knockdown or overexpression plamids in A549 cells. Our results proved that knockdown of Syncytin 1 inhibited the proliferation, and blocked the cell cycle on G1 phase by inhibiting the expression of Nusap1, Cyclin D1, CDK6, and CDK4. Cell cycle arrest also leaded to increased apoptosis in Syncytin 1 knockdown cells. Suppression of Syncytin 1 inhibited the migration and invasion, as well as the expressions of epithelial-mesenchymal transition (EMT) makers, N-cadherin, ß-catenin, and Vimentin, indicating that Syncytin 1 knockdown inhibited the metastasis via reversing the EMT process in A549 cells. The phosphorylation levels of Akt, mTOR, and Erk1/2 were all decreased in Syncytin 1 knockdown cells, suggesting the signaling pathways by which Syncytin 1 operated as an oncogene in NSCLC. Moreover, the underexpression of transcription factor SP1 downregulated the Syncytin 1 expression in A549 cells. The rescue experiment of Syncytin 1 in SP1 knockdown cells further proved that Syncytin 1 could block the inhibition of cell growth induced by SP1 knockdown. In conclusion, knockdown of SP1/Syncytin1 axis inhibited the progression of NSCLC by the reversion of tumor epithelial-mesenchymal transition process and suppression of Akt and Erk signaling pathways, suggesting that they are potential targets for targeted therapy of NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Productos del Gen env/genética , Neoplasias Pulmonares/genética , Proteínas Gestacionales/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor de Transcripción Sp1/metabolismo , Células A549 , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Ciclo Celular , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Técnicas de Inactivación de Genes , Humanos , Neoplasias Pulmonares/metabolismo , Sistema de Señalización de MAP Quinasas , FosforilaciónRESUMEN
The current study analyzed the correlation between the use of antibiotics and development of a resistant bacterial infection in 454 patients in intensive care units (ICUs), and this study also examined factors related to development of an infection in order to facilitate more rational use of antibiotics and to reduce the incidence of resistant bacterial infections. Potential subjects were patients who were admitted to the ICU in 2016, and 454 such patients were selected using cluster sampling. Patient information was documented using an original questionnaire, Patients in the ICU with a Resistant Bacterial Infection. The correlation between use of an antibiotic and development of a resistant bacterial infection was examined. The rate of infection significantly increased over time and with receipt of various antibiotics. The development of a resistant bacterial infection was found to correlate with the use of antibiotics. Antibiotics should be used more carefully to reduce the incidence of resistant bacterial infections.
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Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Infección Hospitalaria/etiología , Farmacorresistencia Bacteriana , Antibacterianos/efectos adversos , Análisis por Conglomerados , Cuidados Críticos , Infección Hospitalaria/tratamiento farmacológico , Hospitalización , Humanos , Incidencia , Unidades de Cuidados Intensivos , Encuestas y CuestionariosRESUMEN
The expression of T-cell immunoglobulin domain, mucin domain-3 (Tim-3) in unexplained recurrent spontaneous abortion (URSA) was investigated.Tim-3 mRNA expression in peripheral blood mononuclear cells (PBMCs) of URSA and control groups was assayed by fluorescent quantitative real-time polymerase chain reaction. Tim-3 protein expression intensity and localization in placental villi and uterine decidua were determined using immunohistochemical assay. The CD4Tim-3/CD4 cell ratio in PBMCs was determined by flow cytometry.Tim-3 mRNA expression in PBMCs was significantly higher in URSA than in normal controls (1.32â±â0.25 vs 1.20â±â0.12, Pâ<â.05). Tim-3 was expressed in placental tissue from both URSA patients and normal pregnant females (controls); however, the expression intensity was higher in the URSA group (0.54â±â0.31 vs 0.35â±â0.22, Pâ<â.05). CD4Tim-3/CD4 cell ratio in PBMCs was significantly higher in the URSA group than that in the control group (4.53â±â1.66% vs 1.28â±â0.71%, Pâ<â.05).Increased Tim-3 expression in PBMCs and placental tissue of URSA might affect maternal-fetal immune tolerance. Tim-3 was involved in the pathogenesis of URSA, which was expected to serve as an indicator for the immune evaluation of URSA.
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Aborto Habitual/sangre , Receptor 2 Celular del Virus de la Hepatitis A/biosíntesis , Leucocitos Mononucleares/metabolismo , ARN Mensajero/biosíntesis , Adulto , Linfocitos T CD4-Positivos/metabolismo , Femenino , Citometría de Flujo , Humanos , Placenta/metabolismo , Embarazo , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
AIMS AND OBJECTIVES: To study the effect of quantitative assessment-based nursing intervention on the bowel function and life quality of patients with neurogenic bowel dysfunction after spinal cord injury. BACKGROUND: Neurogenic bowel dysfunction after spinal cord injury was clinically manifested by abdominal distension, intractable constipation, prolonged defecation and faecal incontinence, which seriously affected the normal life of patients. Traditional ways of nursing for these patients focused on basic care, but lacked sufficient recognition of disease severity and individual needs. DESIGN: One hundred and eighty-four patients with neurogenic bowel dysfunction after spinal cord injury were randomly allocated into observation group (n = 92) and control group (n = 92). METHODS: The patients in the control group were given regular nursing, and the patients in the observation group were given quantitative assessment-based nursing intervention. Recovery of bowel function, quality of life and satisfaction were compared between the two groups. RESULTS: Scores for bowel function including bloating, constipation, prolonged defecation, defecation drug dependence and faecal incontinence in the observation group were significantly lower than those in the control group (p < .05). The scores for the quality of life including physical function, general health, social functioning, role-motional, mental health in the observation group were significantly higher than those in the control group (p < .001). Finally, the satisfaction rate in the observation group was 95.56%, which was significantly higher than that in the control group (83.7%) (p < .01). CONCLUSION: We concluded that quantitative assessment-based nursing intervention contributed to recovery of bowel function and improvement of life quality and satisfaction. RELEVANCE TO CLINICAL PRACTICE: Our finding can increase the rational allocation of nurse-patient ratio and provide personalised nursing for severe patients to reduce complications and promote the rehabilitation of the disease. Our findings can also serve as a reference for other countries to develop the nurse practitioner role.
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Incontinencia Fecal/enfermería , Intestino Neurogénico/enfermería , Traumatismos de la Médula Espinal/enfermería , Adulto , Estreñimiento/etiología , Defecación , Incontinencia Fecal/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intestino Neurogénico/etiología , Satisfacción del Paciente , Calidad de Vida , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/rehabilitación , Resultado del TratamientoRESUMEN
OBJECTIVE: To observe the influence of RNA interference targeting against survivin gene on the biological behaviors of human adenoid cystic cancer (ACC) cells and propose the action mechanism. METHOD: Specific siRNA (small interfering RNA) was constructed and transfected into ACC-2 cells using liposomes. The expressions of survivin and Caspase-3 in the transfected ACC-2 cells were detected by Western Blot and RT-PCR. Cell apoptosis was detected by transmission electron microscopy, TUNEL method and flow cytometry; ultrastructural changes and cell cycles were observed. RESULTS: Recombinant siRNA interference plasmid specifically targeting against survivin gene was constructed successfully. Survivin protein expression in the transfected ACC-2 cells was downregulated significantly, while Caspase-3 protein and mRNA expressions were upregulated and cell proliferation was inhibited considerably. CONCLUSION: Recombinant siRNA interference plasmid inhibited survivin mRNA and protein expressions at high efficiency, thereby inhibiting the proliferation of ACC cells.
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The aim of this study was to evaluate the expression of human T cell immunoglobulin domain and mucin-3 (Tim-3) in renal tissue from patients with immunoglobulin A nephropathy (IgAN) and without IgAN and to evaluate the difference in Tim-3 expression between them. A total of 71 patients with IgAN as IgA group and 13 patients without IgAN as control group were enrolled in the present study. Patients in IgAN accepted percutaneous renal biopsy. We examined the expression of Tim-3 in renal tissue and the serological parameters in serum from all enrolled cases. The expression of Tim-3 and serological parameters were compared between the different groups. Positive staining of Tim-3 protein was seen in 94.3 % patients with IgAN (67 out of 71), but only 15.4 % (2 out of 13) in the cases without IgAN were positive staining of Tim-3. There were significant differences between two groups in almost all serological markers, which reflect IgAN activity. There was a nearly positive correlation between pathological manifestations and expression degree of Tim-3. High immuno-reactivity of Tim-3 was found to be significantly correlated with serological grade (p < 0.001) in IgA group, but there was no such phenomenon in control group. The results showed that there was the expression of Tim-3 in renal tissue from the patients with IgAN, but rarely expression in cases without IgAN. Expression of Tim-3 was associated with the diseases' activity.
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Glomerulonefritis por IGA/inmunología , Riñón/inmunología , Proteínas de la Membrana/inmunología , Adulto , Sedimentación Sanguínea , Proteína C-Reactiva , Femenino , Glomerulonefritis por IGA/sangre , Receptor 2 Celular del Virus de la Hepatitis A , Humanos , Inmunoglobulina A/sangre , Masculino , Proteinuria/sangre , Proteinuria/inmunologíaRESUMEN
Syncytin-1 is a protein coded by a human endogenous retrovirus (HERV) gene of the HERV-W family (HERVWE1). Syncytin- 1 mediates formation of syncytiotrophoblasts through fusion of cytotrophoblasts, a hallmark of terminal differentiation of placental trophoblast linage. Syncytin-1 also possesses nonfusogenic functions and regulates cell cycle progression. While decreased syncytin-1 expression and syncytium deficiency are considered important pathological changes in preeclampsia, the molecular mechanism(s) underlying syncytin-1 downregulation remains unclear. In this study, we confirmed that expression levels of syncytin-1 mRNA and protein were significantly lower in preeclamptic placentas compared to normal controls. Human chorionic somatomammotropin expression, a marker for syncytium function, was also decreased in preeclamptic placentas. The mRNA levels of ASCT2, the syncytin-1 receptor involved in cell fusion process, and GCMa, a transcriptional factor known to regulate syncytin-1 expression, were not significantly altered. Methylation in the 5'LTR of syncytin-1 promoter was quantified by COBRA, methylation-specific PCR, and DNA sequencing. Results from all three assays indicated significantly hypermethylated syncytin-1 promoter in preeclamptic placentas compared to normal controls. Methylation levels were inversely correlated with syncytin-1 mRNA levels, suggesting that hypermethylation may lead to syncytin-1 downregulation. Further experiments indicated that DNMT1 and DNMT3B3 mRNA and protein levels were increased in preeclamptic placentas, suggesting that higher DNA methyltransferase activity may contribute to the hypermethylation of syncytin-1 in preeclamptic placentas. These results indicated that aberrant hypermethylation is involved in downregulation of syncytin-1, and epigenetic alterations may play a significant role in the development of preeclampsia.
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Metilación de ADN , Productos del Gen env/genética , Placenta/metabolismo , Preeclampsia/genética , Proteínas Gestacionales/genética , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Regulación hacia Abajo , Retrovirus Endógenos/genética , Epigénesis Genética , Femenino , Humanos , Embarazo , Regiones Promotoras Genéticas/efectos de los fármacos , ARN Mensajero/metabolismo , Análisis de Secuencia de ADN , Trofoblastos/metabolismoRESUMEN
T-cell immunoglobulin- and mucin domain-3-containing molecule 3 (TIM-3) is a membrane protein expressed in various kinds of immune cells and plays a pivotal role in immune regulation. Recently, TIM-3 was reported to be expressed aberrantly in melanoma cells, contributing to the low adhesion ability of tumor cells and promoting the survival of melanoma cells. We investigated TIM-3 expression in non-small cell lung cancers (NSCLCs), and further analyzed whether the aberrant expression of TIM-3 is related to the prognosis for patients with lung cancer. Tumor tissue samples from 30 patients with NSCLC were involved. Results of immunohistochemical analysis showed that TIM-3 stained positive on tumor cells in 86.7% (26/30) patients with primary NSCLC. The TIM-3 expression in NSCLC tumor cells was correlated with histologic type and pathologic T classification of the disease (P < .05). More importantly, patients with TIM-3-positive tumor cells had a significantly shorter survival time than those with TIM-3-negative tumors. Multivariate analysis demonstrated the significant role of TIM-3 expression in tumor cells as an independent prognostic factor for patients with NSCLC (relative risk, 4.481; 95% confidence interval, 1.790-11.22; P = .0005). Our results suggest that the ectopic expression of TIM-3 in tumor cells may be a potential, independent prognostic factor for patients with NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Proteínas de la Membrana/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Femenino , Receptor 2 Celular del Virus de la Hepatitis A , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Linfocitos/metabolismo , Macrófagos/metabolismo , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Factores de TiempoRESUMEN
We investigated the number of intratumoral tumor-infiltrating lymphocytes (TILs), including CD4(+), CD8(+), and CD25(+) T cells, in nonsmall cell lung cancers (NSCLC) and their correlation with patient survival time. Tumor specimens from 30 NSCLC patients were consecutively obtained during surgery. Patient survival status was monitored. Based on survival time, patients were divided into 2 groups: 5-year survival group and 5-year nonsurvival group. CD4(+), CD8(+), and CD25(+) T cells that infiltrated tumors were detected and counted by immunohistochemistry. Patients with a lower number of TILs and CD8(+) T cells showed significantly shorter survival time compared with those with a higher number (P < 0.05). However, the number of CD4(+) and CD25(+) T cells in tumors was not correlated with survival time in patients with NSCLC (P > 0.05). These data demonstrate that high numbers of CD8(+) T cells among TILs is a strong indicator for a favorable clinical outcome.