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BACKGROUND: The present study aimed to dissect the cellular complexity of Crohn's disease (CD) using single-cell RNA sequencing, focusing on identifying key cell populations and their transcriptional profiles in inflamed tissue. METHODS: We applied scRNA-sequencing to compare the cellular composition of CD patients with healthy controls, utilizing Seurat for clustering and annotation. Differential gene expression analysis and protein-protein interaction networks were constructed to identify crucial genes and pathways. RESULTS: Our study identified eight distinct cell types in CD, highlighting crucial fibroblast and T cell interactions. The analysis revealed key cellular communications and identified significant genes and pathways involved in the disease's pathology. The role of fibroblasts was underscored by elevated expression in diseased samples, offering insights into disease mechanisms and potential therapeutic targets, including responses to ustekinumab treatment, thus enriching our understanding of CD at a molecular level. CONCLUSIONS: Our findings highlight the complex cellular and molecular interplay in CD, suggesting new biomarkers and therapeutic targets, offering insights into disease mechanisms and treatment implications.
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Enfermedad de Crohn , Análisis de la Célula Individual , Ustekinumab , Enfermedad de Crohn/genética , Enfermedad de Crohn/tratamiento farmacológico , Humanos , Ustekinumab/uso terapéutico , Análisis de la Célula Individual/métodos , Perfilación de la Expresión Génica/métodos , Mapas de Interacción de Proteínas , Fibroblastos/metabolismo , Biomarcadores , Femenino , Transcriptoma , Adulto , Masculino , Linfocitos T/metabolismo , Linfocitos T/inmunología , Resultado del Tratamiento , Análisis de Secuencia de ARN/métodos , Redes Reguladoras de GenesRESUMEN
Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome, is a systemic acute vasculitis belonging to autoimmune disease. Up to now, the specific pathogenesis of this disease remains unclear, and it may involve various factors such as immune response, inflammatory response, and vascular endothelial injury caused by the activation of the nuclear factor-kappa B (NF-κB) signaling pathway. In particular, children with KD and cardiac injury tend to have a poor prognosis, and researchers hope to explore the specific pathogenesis of cardiac injury in KD to provide new options for clinical diagnosis and treatment and reduce the incidence rate of this disorder. This article reviews the recent research on the role of the NF-κB signaling pathway in cardiac injury in children with KD, so as to provide a basis for future studies.
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Síndrome Mucocutáneo Linfonodular , FN-kappa B , Humanos , Niño , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/diagnóstico , Transducción de Señal , IncidenciaRESUMEN
FAM60A,a cell cycle protein,is a subunit of the SIN3 transcription regulator family member A/histone deacetylase(SIN3-HDAC)complex and plays an important role in cell cycle regulation,cell morphology change,cell proliferation,differentiation and migration,early embryogenesis and so on.Studies in recent years have shown that FAM60A plays a role in the occurrence and development of tumors including human osteosarcoma,esophageal cancer,gastric cancer,lung cancer and liver cancer,providing a new research direction for tumor diagnosis and treatment.Based on the research results in recent years at home and abroad,this paper discussed the effects of FAM60A on cellular functions.
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Proteínas de Ciclo Celular , Proteínas de Unión al ADN , Diferenciación Celular , Proliferación Celular , Humanos , Complejo Correpresor Histona Desacetilasa y Sin3RESUMEN
OBJECTIVE: To investigate the effect and molecular mechanism of interferon-α (INF-α) on the apoptosis of the mouse podocyte cell line MPC5 induced by hepatitis B virus X (HBx) protein. METHODS: MPC5 cells were transfected with the pEX plasmid carrying the HBx gene. RT-PCR was used to measure the mRNA expression of HBx at different time points. MPC5 cells were divided into 4 groups: control group (MPC5 cells cultured under normal conditions), INF-α group (MPC5 cells cultured with INF-α), HBx group (MPC5 cells induced by HBx), and HBx+INF-α group (MPC5 cells induced by HBx and cultured with INF-α). After 48 hours of intervention under different experimental conditions, flow cytometry was used to measure the apoptosis of MPC5 cells, and quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression of slit diaphragm-related proteins (nephrin, CD2AP, and synaptopodin) and the cytoskeleton-related protein transient receptor potential cation channel 6 (TRPC6). RESULTS: MPC5 cells transfected by pEX-HBx had the highest expression of HBx mRNA at 48 hours after transfection (P<0.05). Compared with the control, INF-α and HBx+INF-α groups, the HBx group had a significant increase in the apoptosis rate of MPC5 cells (P<0.05). Compared with the control and INF-α groups, the HBx group had significant reductions in the mRNA and protein expression of nephrin, synaptopodin, and CD2AP and significant increases in the mRNA and protein expression of TRPC6 (P<0.05). Compared with the HBx group, the HBx+INF-α group had significant increases in the mRNA and protein expression of nephrin, synaptopodin, and CD2AP and significant reductions in the mRNA and protein expression of TRPC6 (P<0.05). CONCLUSIONS: INF-α can inhibit the apoptosis of podocytes induced by HBx, possibly through improving the abnormal expression of slit diaphragm-related proteins (CD2AP, nephrin, and synaptopodin) and cytoskeleton-related protein (TRPC6) induced by HBx.
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Podocitos , Animales , Apoptosis , Virus de la Hepatitis B , Interferón-alfa , Ratones , Transactivadores , Proteínas Reguladoras y Accesorias ViralesRESUMEN
OBJECTIVES: To explore the relationship between normalization of tumor microvessels and CA9 for rh-Endostatin to inhibit Lewis lung cancer (LLC) and the expression level of CA9 in LLC. METHODS: Lewis cells of logarithmic growth phase were collected and made into 1×106 mL-1 cell suspensions were prepared. The transplanted tumor model of LLC was established on C57/BL6 mice by injected 0.2 mL cell suspensions/mice into 40 C57/BL6 mice. 40 LLC mice were randomly divided into control group and rh-ES group (20 mice per group). Control group experienced treatment of intraperitoneal injection (ip) for 0.2 mL NS/d, while rh-ES group was treated for 5 mg rh-ES/(kg·d) from the first to the ninth day. The samples of 5 mice were obtained from day 2, day 4, day 6 and day 9 after treatment in control group or rh-ES group, respectively. CA9 was tested by IHC in LLC and paracancerous tissues and estimated by RT-PCR and ELISA in the each time point of both rh-ES group and control group,respectively. RESULTS: The transplanted tumor model of LLC on C57/BL6 mice was established successfully. The expression of CA9 decreased on day 4 and day 6 in rh-ES group estimated by RT-PCR and ELISA, which indicated some great significance when compared with day 2, day 9 in rh-ES group and day 4, day 6 in control group (P<0.05), and the expression of CA9 in day 2, day 4, day 6, day 9 tested by IHC was higher in LLC than in paracancerous tissues in control group (P<0.05). CONCLUSIONS: The expression of CA9 was higher in LLC. Rh-ES could have positive effect on LLC model of C57/BL6 mice, in day 4-6 (a brief normalized time course) decreased the expression of CA9 and reversed the tumor hypoxia.
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Anhidrasa Carbónica IX/metabolismo , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Endostatinas/farmacología , Microvasos , Animales , Carcinoma Pulmonar de Lewis/metabolismo , Ratones , Ratones Endogámicos C57BL , Trasplante de Neoplasias , Distribución Aleatoria , Proteínas Recombinantes/farmacologíaRESUMEN
Osteolysis induced by chronic Gram-negative bacterial infection underlies many bone diseases such as osteomyelitis, septic arthritis, and periodontitis. Drugs that inhibit lipopolysaccharide (LPS)-induced osteolysis are critically needed for the prevention of bone destruction in infective bone diseases. In this study, we assessed the effect of puerarin, a natural isoflavone isolated from Pueraria lobata OHWI root, on LPS-induced osteoclastogenesis and bone loss. Our in vitro study showed that puerarin significantly inhibited LPS-induced osteoclast differentiation from osteoclast precursor RAW264.7 cells. The inhibition occurred through suppressing the production of osteoclast activating factor tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and prostaglandin E2 (PGE2), which led to down-regulating mRNA expression of osteoclastogenic genes including tartrate-resistant acid phosphatase (TRAP), cathepsin K and matrix metalloprotein 9 (MMP-9). Furthermore, LPS triggered activation of Akt in osteoclast precursor RAW264.7 cells, which was inhibited by puerarin treatment. In vivo, puerarin attenuated LPS-induced bone loss in a murine calvarial osteolysis model. Collectively, puerarin prevents LPS-induced osteoclast formation, function and bone loss, where the inhibition of Akt activation plays an important role. These findings provide evidences that puerarin might be beneficial as a promising candidate drug for the prevention and treatment of bacteria-induced bone destruction disease, and give new insights for understanding its possible mechanism.
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Resorción Ósea/tratamiento farmacológico , Isoflavonas/farmacología , Isoflavonas/uso terapéutico , Osteoclastos/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Animales , Resorción Ósea/patología , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Citocinas/metabolismo , Lipopolisacáridos/farmacología , Masculino , Ratones , Ratones Endogámicos ICR , Osteoclastos/citología , Osteoclastos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células RAW 264.7 , Cráneo/efectos de los fármacos , Cráneo/patologíaRESUMEN
The aim of this study is to investigate the association of ABCB1 polymorphisms with susceptibility to adult acute leukemia, and the influence of ABCB1 polymorphisms on the efficacy of high-dose methotrexate (HDMTX). ABCB1 polymorphisms in 178 acute leukemia patients (case group) and 150 healthy subjects (control group) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. All patients received HDMTX therapy. Correlation analysis was performed to explore the associations of ABCB1 polymorphisms with MTX concentration and efficacy of MTX therapy. All statistical analyses were conducted with SPSS 19.0 software. The frequency of TT genotype and T allele on ABCB1 3435C > T in case group were significantly higher than the control group (P < 0.05), while no statistical difference between the two groups was observed in genotypic distribution and allele frequencies of ABCB1 2677G > T/A (P > 0.05). Furthermore, 24-h MTX concentration of patients carrying TT and TA genotypes on 2677G > T/A was higher than carriers with other genotypes (P < 0.05), and 24-h MTX concentration of patients with TT and CT genotypes on 3435C > T was also apparently higher than carriers with CC genotype (P < 0.05). In addition, ABCB1 polymorphisms were connected with increased risk of liver dysfunction and infection (P < 0.05). Complete remission (CR) rate in patients carrying GG on 2677G > T/A was markedly lower than carriers with non-GG genotype (P < 0.05). ABCB1 3435C > T polymorphisms may be associated with susceptibility to acute leukemia, and ABCB1 polymorphisms might be a sensitive indicator for predicting efficacy of MTX therapy in the treatment of acute leukemia.
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Predisposición Genética a la Enfermedad/genética , Leucemia/tratamiento farmacológico , Leucemia/genética , Metotrexato/uso terapéutico , Polimorfismo de Nucleótido Simple/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Adolescente , Adulto , Alelos , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: To compare the clinical and pathological features between children with various genotypes of hepatitis B virus-associated glomerulonephritis (HBV-GN). METHODS: Forty-one children with HBV-GN concurrently undergoing liver and renal biopsy were randomly selected. Serum specimens were collected for genotyping and hepatitis B virus (HBV) cccDNA assay. The clinical, pathological, and HBV cccDNA differences between HBV-GN children of various genotypes were analyzed. RESULTS: Among the 41 HBV-GN children, 29 (71%) were genotype C, 10 (24%) were genotype B, and 2 (5%) were genotype B/C. The incidence rates of hematuria, albuminuria, complement 3 decrease, alanine transaminase increase, and renal insufficiency in the genotype C group were significantly higher than those in the genotype B group (P<0.05). Similarly, the HBV cccDNA positive rate was significantly higher in the genotype C group than that in the genotype B group. No difference was observed in the distribution of pathological types of renal tissues betwee the two geonotype groups. There were no significant differences in the degrees of hepatic inflammation and fibrosis between the two groups. CONCLUSIONS: Mainly genotypes C and B occur in children with HBV-GN and the former genotype is dominant. The clinical symptoms of patients with genotype C are more serious than those with genotype B. However, there is no difference in the pathological features between them.
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Glomerulonefritis/patología , Virus de la Hepatitis B/clasificación , Hepatitis B/complicaciones , Adolescente , Niño , ADN Viral/análisis , Femenino , Genotipo , Glomerulonefritis/etiología , Virus de la Hepatitis B/genética , Humanos , Riñón/patología , MasculinoRESUMEN
BACKGROUND: Serotonin receptor 2B (5-HT2B receptor) plays a critical role in many chronic pain conditions. The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea (IBS-D) was investigated in the present study. AIM: To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D. METHODS: Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls. The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores. The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint. Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1 (TRPV1) expression were examined following 5-HT2B receptor antagonist administration. Changes in visceral sensitivity after administration of the TRPV1 antagonist were recorded. RESULTS: Here, we observed greater expression of the 5-HT2B receptor in the colonic mucosa of patients with IBS-D than in that of controls, which was correlated with abdominal pain scores. Intracolonic instillation of acetic acid and wrap restraint induced obvious chronic visceral hypersensitivity and increased fecal weight and fecal water content. Exogenous 5-HT2B receptor agonist administration increased visceral hypersensitivity, which was alleviated by successive administration of a TRPV1 antagonist. IBS-D rats receiving the 5-HT2B receptor antagonist exhibited inhibited visceral hyperalgesia.Moreover, the percentage of 5-HT2B receptor-immunoreactive (IR) cells surrounded by TRPV1-positive cells (5-HT2B receptor I+) and total 5-HT2B receptor IR cells (5-HT2B receptor IT) in IBS-D rats was significantly reduced by the administration of a 5-HT2B receptor antagonist. CONCLUSION: Our finding that increased expression of the 5-HT2B receptor contributes to visceral hyperalgesia by inducing TRPV1 expression in IBS-D patients provides important insights into the potential mechanisms underlying IBS-D-associated visceral hyperalgesia.
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Síndrome del Colon Irritable , Humanos , Ratas , Animales , Síndrome del Colon Irritable/patología , Receptor de Serotonina 5-HT2B , Hiperalgesia/etiología , Hiperalgesia/metabolismo , Serotonina/metabolismo , Diarrea/etiología , Receptores de Serotonina , Dolor Abdominal/etiología , Dolor Abdominal/metabolismo , AcetatosRESUMEN
Following the publication of this paper, it was drawn to the Editor's attention by concerned readers that the western blotting data shown in Figs. 4C and 7B and D, the scratchwound assay images shown in Figs. 5A and 6A, and certain of the cell migration and invasion assay data shown in Figs. 5B and 6B were strikingly similar to data that had previously appeared in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 38: 17341742, 2016; DOI: 10.3892/ijmm.2016.2774].
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Di(2-ethylhexyl)phthalate (DEHP) has proven characteristics of an endocrine-disrupting compound (EDC), which can threaten the reproductive health of humans and other animals. In mammals, a series of chromosomal events occur during the meiotic stage of oocytes. External toxins may enter the body and cause infertility and other related diseases. Therefore, it is crucial to explore the influence of DEHP exposure on the molecular mechanism of germ cell meiosis. We used single-cell RNA sequencing (scRNA-seq) to analyse the ovaries of foetal mice at embryonic day 12.5 (E12.5) and E14.5 after maternal DEHP exposure. DEHP exposure further activated the pathways related to DNA repair in germ cells, increased the expression of genes related to DNA damage and changed the developmental trajectory of germ cells. DEHP exposure may affect the proliferation of pregranulosa (PG) cells. Moreover, DEHP exposure altered the signal transduction between PG cells and germ cells. We showed that DEHP affects meiosis by causing DNA damage in oocytes and disrupting the signal transduction between PG cells and germ cells. These results provide a strong theoretical basis for the prevention and treatment of DEHP-mediated female reproductive health problems.
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Dietilhexil Ftalato , Animales , Dietilhexil Ftalato/metabolismo , Dietilhexil Ftalato/toxicidad , Femenino , Células Germinativas , Humanos , Mamíferos , Meiosis , Ratones , Oocitos/metabolismo , TranscriptomaRESUMEN
OBJECTIVE: To explore the damages of paraquat to the learning and memory ability of developing mice and explore the possible mechanism involving oxidative stress. METHODS: Eighty healthy Kunming mice in aged 21 days were divided into 4 groups randomly: a control group (distilled water) and three paraquat treatment groups. The doses of paraquat were 0.89, 2.67 and 8mg/kg body weight, respectively. Paraquat was administered orally in doses of 0.1 ml/10 g body weight, respectively, once a day and for 28 consecutive days. The Morris water maze test and the shuttling and avoid dark box test were used to detect the learning and memory abilities of mice. The levels of MDA and the activities of SOD and GSH-PX were detected according to the commercial kits manual using a microplate reader. RESULTS: Morris water maze test showed that the escape latency of mice after paraquat treatment (57.98 +/- 2.78, 62.35 +/- 3.18, 85.57 +/- 5.10) were significantly increase compared with the control (21.74 +/- 1.36), respectively (P < 0.05). There were good dose-response relationship (R = 0.8629, P < 0.05). The shuttling and avoid dark box test showed that initiative avoidance latency of mice after paraquat treatment (5.56 +/- 0.29, 6.08 +/- 0.22, 8.32 +/- 0.38) were significantly increase compared with the control (3.50 +/- 0.13), respectively (P < 0.05). There were good dose-response relationship (R = 0.9579, P < 0.05). The levels of MDA in serum of mice in paraquat treatment groups (2.67 and 8 mg/kg) (24.76 +/- 1.76, 31.10 +/- 4.57) and in hippocampus of mice in each paraquat treatment groups were significantly increase compared with the control (serum: 16.38 +/- 6.26, hippocampus: 1.93 +/- 0.39) (P < 0.05, respectively). The activities of SOD in serum and hippocampus of mice in each paraquat treatment groups were significantly decrease compared with the control (serum: 213.25 +/- 6.78, hippocampus: 197.36 +/- 6.37) (P < 0.05, respectively). The activities of GSH-PX in serum and hippocampus of mice in each paraquat treatment groups were significantly decrease compared with the control (serum: 583.47 +/- 11.23, hippocampus: 412.38 +/- 13.16) (P < 0.05, respectively). CONCLUSION: Paraquat can induce the oxidative damage in hippocampus, and then influence the learning and memory abilities of developing mice.
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Hipocampo/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Estrés Oxidativo , Paraquat/toxicidad , Animales , Femenino , Hipocampo/metabolismo , Masculino , Ratones , Ratones Endogámicos , Paraquat/administración & dosificación , Superóxido Dismutasa/metabolismoRESUMEN
OBJECTIVE: To study the relationship between the polymorphisms of GST M1 and GST T1 genes and anti-tuberculous drug induced hepatic injury (ADIH). METHODS: A 1:1 matched case-control study was carried out. One hundred and six patients [age (49 +/- 19) years, 73 men and 33 women] fulfilling the criteria of ADIH during the 3 month follow-up after the initiation of anti-tuberculous therapy were included, while 106 cases [age (49 +/- 19) years, 73 men and 33 women] without any hepatic injury served as the controls. The genotypes of GST M1 and GST T1 genetic polymorphisms were detected by polymerase chain reaction (PCR) in patients who received anti-tuberculosis therapy. Using SPSS 11.5 for windows software, univariate and multivariate conditional logistic analyses were conducted for studying the relationship between the polymorphisms and ADIH. RESULTS: Univariate analysis demonstrated that the "null" genotype of GST M1 gene occurred in 50 (47.2%) of the cases, more frequent than in the controls [25 (23.6%)], with a crude OR (95%CI) 2.786 (1.513 - 5.130). No significant association was observed between ADIH and GST T1 polymorphism. Among the risk factors analyzed, body mass index and alcohol drinking were significantly associated with ADIH. In the multivariate analysis, a significant association between ADIH and the "null" genotype of GST M1 existed, after adjusting for body mass index and drinking status, adjusted OR (95%CI) being 3.022 (1.540 - 5.926). Again, no significant association was observed between GST T1 polymorphism and ADIH. CONCLUSION: This study demonstrated that patients carrying GST M1-"null" genotype may be susceptible to ADIH.
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Antituberculosos/efectos adversos , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/genética , Glutatión Transferasa/genética , Polimorfismo Genético , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Hígado/patología , Masculino , Persona de Mediana Edad , Mutación , Adulto JovenRESUMEN
The gene for hepatitis B virus X protein (HBx) comprises the smallest open reading frame in the HBV genome, and the protein product can activate various cell signaling pathways and regulate apoptosis, among other effects. However, in different cell types and under different external conditions, its mechanism of action differs. In the present study, the effect of HBx on the viability and apoptosis of mouse podocyte clone 5 (MPC5) cells was investigated. The cells were transfected with the HBx gene using pEX plasmid, and real-time quantitative PCR and western blot analysis were used to test the transfection efficiency and assess related protein expression. The highest expression of HBx occurred at 48 h after MPC5 cells were transfected with HBx. The expression of nephrin protein in the HBx transfection group was lower than that in blank and negative control groups. Following transfection of the HBx gene, podocyte viability was suppressed, while the rate of cell apoptosis was increased; moreover, the expression of signal transducer and activator of transcription 3 (STAT3) and phospho-STAT3 was increased compared with in the control groups. The present study suggests that STAT3 activation may be involved in the pathogenic mechanism of renal injuries caused by HBV injection. Thus STAT3 is a potential molecular target in the treatment of HBV-GN.
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OBJECTIVE: To explore the effect of ambient particle matter 2.5 (PM2.5) collected in the urban center of Hangzhou on the lung injury of rats and on the activating of endoplasmic reticulum pathway. METHODS: PM2.5 samples were collected on quartz fiber filters using a PM2.5 high-volume air sampler in the urban area of Hangzhou. The collected PM2.5 particles were extracted in ultrapure water and concentrated by vacuum freeze-drying. Twenty-four male Sprague-Dawly (SD) rats were randomly divided into 3 groups:saline control group, low dose PM2.5 exposure group (5 mg/kg BW) and high dose PM2.5 exposure groups (25 mg/kg BW). Each group received intratracheal instillation of PM2.5, once a week for 4 weeks. Twenty-four hours after the last exposure, the rats were narcotized and sacrificed, left lung was isolated and fixed with 4% paraformaldehyde for histopathological detection. The bronchoalveolar lavage fluid (BALF) was collected from the right lung. The total antioxidant capacity (T-AOC) level, the activities of superoxide dismutase (SOD) and lactic dehydrogenase (LDH) in BALF were detected by chemical colorimetry. The level of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6) cytokines in BALF was measured by enzyme linked immunosorbent assay (ELISA). And the protein expressions of glucose-regulated protein 78 (GRP78), phosphorylated protein kinase receptor-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic translation initiation factor (p-eIF2α), transcription factors C/EBP homologue protein (CHOP), inositol-requiring enzyme 1α (IRE1α) and X-box binding protein 1 (XBP1) in lung tissue were determined by Western blotting. RESULTS: Compared with control group, rats in both low dose (5 mg/kg) and high dose (25 mg/kg) PM2.5-treated groups showed obviously dose-dependent pulmonary toxicity including thickening of alveolar walls, narrowing of alveolar space, interstitial hyperplasia and inflammatory cell infiltration. Compared with control group, T-AOC level and the SOD activity in BALF in both PM2.5-treated groups were decreased dose-dependently (P<0.05), whereas the LDH activity in BALF were increased in a dose-dependent manner (P<0.05). Exposure to PM2.5 resulted in a increasing of the release of proinflammatory cytokines including TNF-α, IL-1ß and IL-6 in rat lung in a dose-dependent manner (P<0.05). The levels of GRP78, p-PERK, p-eIF2α, CHOP, IRE1α and spliced XBP1 (XBP1-S) were significantly up-regulated, whereas the level of unspliced XBP1 (XBP1-U) was down-regulated in the rat lung tissue of high-dose PM2.5 treated group. CONCLUSIONS: The PM2.5 in the urban area of Hangzhou can significantly cause lung inflammatory injury in rats. Both oxidative stress and activation of ER stress pathways may be related to such PM2.5 inhalation-induced lung inflammatory injury.
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Lesión Pulmonar , Material Particulado , Animales , Líquido del Lavado Bronquioalveolar , Interleucina-6 , Pulmón , Masculino , RatasRESUMEN
BACKGROUND AND OBJECTIVE: The glucagon-like peptide-1 (GLP-1) analog, ROSE-010, plays a critical role in alleviating abdominal pain in patients with irritable bowel syndrome (IBS); however, the underling mechanism is unclear. In the present study, we determined the serum GLP-1 level in patients with constipation-predominant IBS (IBS-C). The relationship between GLP-1 and abdominal pain was investigated. In addition, the expression of the GLP-1 receptor in the colon was determined. METHODS: Rectosigmoid biopsies were gathered from 38 patients with IBS-C who met the Rome III criteria, and 22 healthy controls. Abdominal pain was quantified by a validated questionnaire. Serum GLP-1 was measured by ELISA and correlated with abdominal pain scores. The presence of the GLP-1 receptor in the colonic mucosa was assessed by immunohistochemistry. RESULTS: Serum GLP-1 was substantially decreased in patients with IBS-C. Decreased serum GLP-1 had a negative correlation with the abdominal pain scores. Biopsies from patients with IBS-C revealed a significant down-regulation of the GLP-1 receptor in colonic mucosa compared with control subjects. CONCLUSIONS: Decreased serum GLP-1 correlates with abdominal pain in patients with IBS-C. Decreased expression of GLP-1 and GLP-1 receptor may be the basis for alleviation of abdominal pain in patients with IBS-C by ROSE-010.
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Dolor Abdominal/sangre , Estreñimiento/sangre , Péptido 1 Similar al Glucagón/sangre , Síndrome del Colon Irritable/sangre , Dolor Abdominal/etiología , Adulto , Anciano , Estreñimiento/etiología , Femenino , Humanos , Síndrome del Colon Irritable/complicaciones , Masculino , Persona de Mediana EdadRESUMEN
Prostate carcinoma is a devastating disease which is characterized by insidious early symptoms, rapid progression and a poor prognosis. Tripartite motif-containing protein 16 (TRIM16) was identified as an estrogen- and antiestrogen-regulated gene in epithelial cells stably expressing estrogen receptors. The protein encoded by this gene contains two B-box domains and a coiled-coiled region that are characteristic of the B-box zinc finger protein family. Proteins belonging to this family have been reported to be involved in a variety of biological processes including cell growth, differentiation and pathogenesis. TRIM16 expression has been detected in most tissues. However, the funtions of this gene remain to be elucidated. In the present study, immunohistochemical staining revealed that the expression of TRIM16 was decreased in prostate adenocarcinoma compared with that in normal prostate tissues. The patients with high TRIM16-expressing tumors had a significantly greater survival than those with low TRIM16-expressing tumors. Western blot analysis showed that TRIM16 was downregulated in distant metastatic cancer tissues compared with that in non-distant metastatic cancer tissues. The overexpression of TRIM16 inhibited the migration and invasion of prostate cancer cells as well as inhibiting the epithelial-to-mesenchymal transition process, whereas TRIM16 depletion enhanced these processes. Moreover, TRIM16 inhibited the Snail signaling pathway. The silencing of Snail by small interfering RNA was performed in order to determine the role of Snail in the TRIM16-mediated tumor phenotype. Taken together, these findings suggest that TRIM16 may be an important molecular target which may aid in the design of novel therapeutic agents for prostate cancer.
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Proteínas de Unión al ADN/metabolismo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Transducción de Señal , Factores de Transcripción de la Familia Snail/metabolismo , Factores de Transcripción/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Proteínas de Unión al ADN/genética , Progresión de la Enfermedad , Regulación hacia Abajo , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Pronóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/mortalidad , Factores de Transcripción/genética , Proteínas de Motivos Tripartitos , Ubiquitina-Proteína LigasasRESUMEN
BACKGROUND: Hepatitis B virus-associated glomerulonephritis (HBV-GN) is one of the extrahepatic manifestations after HBV infection, which would cause great clinical harm to people. The present study was undertaken to investigate the HBV-GN genotypes and its clinical relevance in Chinese children. METHODS: A total of 41 HBV-infected children diagnosed with HBV-GN were enrolled in the study. All patients underwent liver and kidney biopsy. The genotypes and cccDNA were detected in their serum samples to analyze the relationship between HBV genotypes and clinical characteristics, cccDNA, and pathology. RESULTS: Among the 41 children with HBV-GN, 29 (70.7%) had genotype C, 10 (24.4%) had genotype B, 2 (4.9%) had genotype B/C, and none of them had genotype non-B/C. Most children had genotypes B or C; moreover, the genotype C was the most frequent one. The incidence of hematuria and albuminuria, reduction in complement C3, increase in serum alanine aminotransferase levels and renal insufficiency in the children with genotype C were significantly higher than those in the children with genotype B (P<0.05); however, there was no statistically significant difference in hypertension and hepatomegaly (P>0.05). The frequency of HBV cccDNA positive in the genotype C group was significantly higher than that in the genotype B group (72.4% vs. 30.0%, P<0.05). No difference was observed in hepatic inflammation grades and stages of fibrosis between the two groups (P>0.05). CONCLUSIONS: Genotype C was the most frequent genotype in the described group of patients with HBV-GN, and the liver and kidney damage indicators were more likely to occur in patients with genotype C.
Asunto(s)
Complemento C3/genética , Glomerulonefritis/patología , Glomerulonefritis/virología , Virus de la Hepatitis B/genética , Hepatitis B Crónica/genética , Hepatitis B Crónica/patología , Adolescente , Biopsia con Aguja , Distribución de Chi-Cuadrado , Niño , Preescolar , China , Estudios de Cohortes , ADN Viral/análisis , Femenino , Genotipo , Glomerulonefritis/genética , Virus de la Hepatitis B/patogenicidad , Hepatitis B Crónica/sangre , Humanos , Inmunohistoquímica , Masculino , Pronóstico , Estudios Retrospectivos , Medición de RiesgoRESUMEN
Puerarin is an isoflavone extracted from Chinese plant, Pueraria lobata (Wild.) Ohwi. It has been reported to have comprehensive pharmacological action in treatment of diabetes and cardiovascular diseases. The purpose of this study was to link the scattered effects of puerarin and to find the common mechanisms underlying. We investigated the effect of puerarin on the pivotal common pathogenic factors of metabolic syndrome, which includes obesity, Type II diabetes and cardiovascular diseases. Recently, a large body of evidence indicates that there is a complicated interplay among insulin resistance, adipocytes and endothelial dysfunction that links the abnormalities of metabolic syndrome. Results of present study showed that puerarin could potentiate insulin-induced preadipocyte differentiation, promote glucose-uptake of adipocytes that have been induced insulin resistance by high glucose, and prevent TNF-a-induced apoptosis and viability loss of endothelial cells. Furthermore, we found that these effects are probably due to promote PPARgamma expression and partly through inhibiting abnormal TNF-a-induced intracellular-free Ca(2+) accumulation of endothelial cells. Overall, our synthetical study links the comprehensive pharmacological actions of puerarin to the recognized common pathogenesis of metabolic syndrome, and provides a new insight into the mechanism of puerarin effect.
Asunto(s)
Adipocitos/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Glucosa/metabolismo , Isoflavonas/farmacología , Actinas/biosíntesis , Adipocitos/citología , Adipocitos/metabolismo , Animales , Apoptosis/efectos de los fármacos , Calcio/metabolismo , Diferenciación Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Endoteliales/citología , Células Endoteliales/metabolismo , Humanos , Hipoglucemiantes/farmacología , Masculino , PPAR gamma/biosíntesis , ARN Mensajero/metabolismo , Ratas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rosiglitazona , Tiazolidinedionas/farmacología , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
A tri-block coupling-polymer composed of 4,4'-methylenediphenyl diisocyanate and poly (ethylene oxide) (PEO), abbreviated MPEO, was used as the template surface-modifying additive (SMA), based on which selected amino acids (lysine, arginine, glycin, and aspartic acid) and RGD peptide were respectively conjugated as functional endgroups of the PEO spacer-arms through sulfonyl chloride-activation routes. After the immobilization of biofunctional factors, the SMA-MPEO derivatives were noncovalently introduced onto the biomedical poly(ether urethane) (PEU) surfaces by physical blending methods. The SMA synthesis and PEU surface modification were monitored and analyzed by nuclear magnetic resonance spectroscopy, attenuated total reflection-infrared spectroscopy, and X-ray photoelectron spectroscopy. The human umbilical vein endothelial cells (HUVECs) were collected and harvested manually by collagenase digestion. The cell culture was performed respectively on the MPEO derivative-modified PEU surfaces and also on the surfaces of the commercially available polystyrene cell-culture plates (TCPS) for control. The cell adhesion rates and cell proliferation rates of the in vitro cultivated HUVEC were measured using flow cytometry. The individual cell viability rates were determined with MTT assay. The cell morphologies of the living HUVECs were investigated by optical inverted microscopy, and more detailed information was acquired from scanning electrical microscopy. The results indicated that the efficacy of SMA functional endgroups was the dominant factor for HUVEC compatibility; the proper-sized PEO spacers (M(w) 2 k) could support and mobilize the functional endgroups, optimizing the surface (interface) environment for the cell growth. As the endgroups of the SMA-MPEO derivatives and the bio-functional factors, the basic amino acids (lysine and arginine) demonstrated similar performances to that of the widely acknowledged cell growth-promoter, RGD peptide, which were superior to TCPS. Therefore, these MPEO derivative-modified PEU materials are promising to serve as novel polymeric permanent implants or interventional devices for cardiovascular biomedical applications.