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1.
Sci Total Environ ; 806(Pt 3): 151217, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34717999

RESUMO

An outdoor solar assisted large-scale cleaning system (SALSCS) was constructed to mitigate the levels of fine particulate matter (PM2.5) in urban areas of Xi'an China, providing a quasi-experimental opportunity to examine the biologic responses to the changes in pollution level. We conducted this outdoor SALSCS based real-world quasi-interventional study to examine the associations of the SALSCS intervention and changes in air pollution levels with the biomarkers of systemic inflammation and oxidative stress in healthy elders. We measured the levels of 8-hydrox-2-deoxyguanosine (8-OHdG), Interlukin-6 (IL-6), as well as tumor necrosis factor alpha (TNF-α) from urine samples, and IL-6 from saliva samples of 123 healthy retired participants from interventional/control residential areas in two sampling campaigns. We collected daily 24-h PM2.5 samples in two residential areas during the study periods using mini-volume samplers. Data on PM10, gaseous pollutants and weather factors were collected from the nearest national air quality monitoring stations. We used linear mixed-effect models to examine the percent change in each biomarker associated with the SALSCS intervention and air pollution levels, after adjusting for time trend, seasonality, weather factors and personal characteristics. Results showed that the SALSCS intervention was significantly associated with decreases in the geometric mean of biomarkers by 47.6% (95% confidence interval: 16.5-67.2%) for 8-OHdG, 66% (31.0-83.3%) for TNF-α, 41.7% (0.2-65.9%) and 43.4% (13.6-62.9%) for urinary and salivary IL-6, respectively. An inter-quartile range increase of ambient PM2.5 exposure averaged on the day of the collection of bio-samples and the day before (34.1 µg/m3) was associated, albeit non-significantly so, with 22.8%-37.9% increases in the geometric mean of these biomarkers. This study demonstrated that the SALSCS intervention and decreased ambient air pollution exposure results in lower burden of systemic inflammation and oxidative stress in older adults.

2.
Liver Int ; 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34811877

RESUMO

BACKGROUND & AIMS: Biallelic pathogenic variants in MYO5B cause microvillus inclusion disease (MVID), or familial intrahepatic cholestasis (FIC). The reported FIC patients are scarce and so the genotype-phenotype correlation has not been fully characterised. This study aimed to report more MYO5B-associated FIC patients and correlate genotypes to phenotypes in more detail. METHODS: The phenotype and genetic data of 12 newly diagnosed MYO5B-associated (including 11 FIC) patients, as well as 118 previously reported patients with available genotypes, were summarised. Only patients with biallelic MYO5B variants were enrolled. Nonsense, frameshift, canonical splice sites, initiation codon loss, and single exon or multiexon deletion were defined as null MYO5B variants. RESULTS: Phenotypically, 50 were isolated MVID, 47 involved both liver and intestine (combined), and 33 were isolated FIC (9 persistent, 15 recurrent, 3 transient, and 6 un-sub-classified) patients. The severity of intestinal manifestation was positively correlated to an increased number of null variants (ρ = 0.299, P = .001). All FIC patients carried at least one non-null variant, and the severity of cholestasis was correlated to the presence of a null variant (ρ = 0.420, P = .029). The proportion of FIC patients (16/29, 55%) harbouring missense/in-frame variants affecting the non-motor regions of MYO5B was significantly higher than that of MVID (3/25, 12%, P = .001) and combined patients (3/31, 10%, P = .000). 10 of the 29 FIC patients harboured missense/in-frame variants at the IQ motifs comparing to none in the 56 MVID and combined patients (P = .000). CONCLUSIONS: The phenotype of MYO5B deficiency was associated with MYO5B genotypes, the nullity or the domain affected.

3.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(10): 1027-1032, 2021 Oct 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34719418

RESUMO

OBJECTIVES: To study the molecular epidemiological characteristics of norovirus in children with acute gastroenteritis from 2017 to 2019. METHODS: A retrospective analysis was performed on the medical data of children with acute gastroenteritis who were admitted to Children's Hospital of Chongqing Medical University from January 2017 to December 2019. A total of 1 458 stool samples were collected from the children, and viral RNA was extracted. Reverse transcription polymerase chain reaction was used for gene amplification, sequencing, and genotype identification of the VP1 region of capsid protein in norovirus. RESULTS: Among the 1 458 stool samples, 158 (10.8%) were positive for norovirus. There was no significant difference in the positive detection rate of norovirus between different years (P>0.05). Boys had a norovirus detection rate of 12.2% (105/860), which was significantly higher than that in girls (8.9%, 53/598) (P=0.043). The children aged 12 to <18 months had the highest norovirus detection rate (16.9%, 51/301). August, September, and October were the epidemic peak season. A total of 23 norovirus-positive samples were also positive for rotavirus. The norovirus detected were mainly GII type (97.5%, 154/158), and only 4 cases were GI type (2.5%, 4/158). The sequencing of the VP1 region of capsid protein in the positive samples showed that GII.4 (69.6%, 110/158) was the dominant genotype, among which 99 (62.7%, 99/158) were GII.4 Sydney 2012, followed by GII.3 (15.2%, 24/158), GII.2 (10.1%, 16/158), GII.6 (1.9%, 3/158), and GII.17 (0.6%, 1/158). GI.3 (1.3%, 2/158), GI.2 (0.6%, 1/158), and GI.5 (0.6%, 1/158) were rarely detected. CONCLUSIONS: Norovirus GII.4 Sydney 2012 was the major epidemic strain in the children with norovirus gastroenteritis from 2017 to 2019. Although norovirus infection can exist throughout the year, August to October is the peak period. During this period, norovirus surveillance and key population protection are strengthened to help prevent and control norovirus diarrhea.


Assuntos
Gastroenterite , Norovirus , Criança , Fezes , Feminino , Gastroenterite/epidemiologia , Humanos , Masculino , Norovirus/genética , Filogenia , Estudos Retrospectivos
4.
Front Microbiol ; 12: 709849, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594310

RESUMO

Human parechoviruses (HPeVs) are important causes of infection in children. However, without a comprehensive and persistent surveillance, the epidemiology and clinical features of HPeV infection remain ambiguous. We performed a hospital-based surveillance study among three groups of pediatric patients with acute respiratory infection (Group 1), acute diarrhea (Group 2), and hand, foot and mouth disease (Group 3) in Chongqing, China, from 2009 to 2015. Among 10,212 tested patients, 707 (6.92%) were positive for HPeV, with the positive rates differing significantly among three groups (Group 1, 3.43%; Group 2, 14.94%; Group 3, 3.55%; P < 0.001). The co-infection with other pathogens was detected in 75.2% (531/707) of HPeV-positive patients. Significant negative interaction between HPeV and Parainfluenza virus (PIV) (P = 0.046, OR = 0.59, 95% CI = 0.34-0.98) and positive interactions between HPeV and Enterovirus (EV) (P = 0.015, OR = 2.28, 95% CI = 1.23-4.73) were identified. Among 707 HPeV-positive patients, 592 (83.73%) were successfully sequenced, and 10 genotypes were identified, with HPeV1 (n = 396), HPeV4 (n = 86), and HPeV3 (n = 46) as the most frequently seen. The proportion of genotypes differed among three groups (P < 0.001), with HPeV1 and HPeV4 overrepresented in Group 2 and HPeV6 overrepresented in Group 3. The spatial patterns of HPeV genotypes disclosed more close clustering of the currently sequenced strains than those from other countries/regions, although they were indeed mixed. Three main genotypes (HPeV1, HPeV3, and HPeV4) had shown distinct seasonal peaks, highlighting a bi-annual cycle of all HpeV and two genotypes (HPeV 1 and HPeV 4) with peaks in odd-numbered years and with peaks in even-numbered years HPeV3. Significantly higher HPeV1 viral loads were associated with severe diarrhea in Group 2 (P = 0.044), while associated with HPeV single infection than HPeV-EV coinfection among HFMD patients (P = 0.001). It's concluded that HPeV infection was correlated with wide clinical spectrum in pediatric patients with a high variety of genotypes determined. Still no clinical significance can be confirmed, which warranted more molecular surveillance in the future.

5.
Pediatr Pulmonol ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34559474

RESUMO

OBJECTIVE: Few studies have explored the clinical features in children infected with SARS-CoV-2 and other common respiratory viruses, including respiratory syncytial virus (RSV), Influenza virus (IV), and adenovirus (ADV). Herein, we reported the clinical characteristics and cytokine profiling in children with COVID-19 or other acute respiratory tract infections (ARTI). METHODS: We enrolled 20 hospitalized children confirmed as COVID-19 positive, 58 patients with ARTI, and 20 age and sex-matched healthy children. The clinical information and blood test results were collected. A total of 27 cytokines and chemokines were measured and analyzed. RESULTS: The median age in the COVID-19 positive group was 14.5 years, which was higher than that of the ARTI groups. Around one-third of patients in the COVID-19 group experienced moderate fever, with a peak temperature of 38.27°C. None of the patients displayed wheezing or dyspnea. In addition, patients in the COVID-19 group had lower white blood cells, platelet counts as well as a neutrophil-lymphocyte ratio. Lower serum concentrations of 14 out of 27 cytokines were observed in the COVID-19 group than in healthy individuals. Seven cytokines (IL-1Ra, IL-1ß, IL-9, IL-10, TNF-α, MIP-1α, and VEGF) changed serum concentration in COVID-19 compared with other ARTI groups. CONCLUSION: Patients with COVID-19 were older and showed milder symptoms and a favorable prognosis than ARTI caused by RSV, IV, and ADV. There was a low grade or constrained innate immune reaction in children with mild COVID-19.

8.
Int J Gen Med ; 14: 3281-3285, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34267546

RESUMO

Objective: The aim of the present study was to investigate the predictive value of transvaginal ultrasonography measurement of cervical length (CL) during the second trimester for spontaneous preterm birth. Methods: Data from 1222 women with a single fetus pregnancy, who delivered at our hospital between March 2019 and May 2020, were retrospectively analyzed. CL was measured during the second trimester, with a length of <25 mm regarded as cervical shortening. The relationship between CL, cervical shortening, and pregnancy outcome was analyzed. Results: The incidence of spontaneous preterm birth and cervical shortening in the 1222 women was 7.3% (89/1222) and 0.33% (4/1222), respectively. The average CL during the second trimester was 37.9 ± 5.7 mm for the spontaneous preterm birth group and 39.3 ± 3.8 mm for those who gave birth at full term. Three of the four cases of cervical shortening resulted in a spontaneous preterm birth. This showed a predictive sensitivity of 3.33% and a specificity of 99.9%. Conclusion: CL measurement during the second trimester can be used as a routine test to predict spontaneous preterm birth. During the second trimester, the distribution of CL in women with single fetus pregnancies in China is different compared with other countries. Reducing the threshold of CL may improve the predictive value for preterm birth.

9.
Clin Sci (Lond) ; 135(12): 1505-1522, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34128977

RESUMO

Chronic hepatitis B virus (HBV) infection is a significant public health burden worldwide. HBV covalently closed circular DNA (cccDNA) organized as a minichromosome in nucleus is responsible for viral persistence and is the key obstacle for a cure of chronic hepatitis B (CHB). Recent studies suggest cccDNA transcription is epigenetically regulated by histone modifications, especially histone acetylation and methylation. In the present study, we identified transcriptionally active histone succinylation (H3K122succ) as a new histone modification on cccDNA minichromosome by using cccDNA ChIP-Seq approach. Silent mating type information regulation 2 homolog 7 (SIRT7), as an NAD+-dependent histone desuccinylase, could bind to cccDNA through interaction with HBV core protein where it catalyzed histone 3 lysine 122 (H3K122) desuccinylation. Moreover, SIRT7 acts cooperatively with histone methyltransferase, suppressor of variegation 3-9 homolog 1 (SUV39H1) and SET domain containing 2 (SETD2) to induce silencing of HBV transcription through modulation of chromatin structure. Our data improved the understanding of histone modifications of the cccDNA minichromosome, thus transcriptional silencing of cccDNA may represent a novel antiviral strategy for the prevention or treatment of HBV infection.


Assuntos
Catálise , DNA Circular/metabolismo , Histona Metiltransferases/genética , Histonas/metabolismo , Sirtuínas/metabolismo , DNA Viral/genética , Hepatite B/prevenção & controle , Hepatite B/terapia , Hepatite B/virologia , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/prevenção & controle , Humanos , Sirtuínas/genética , Transcrição Genética/genética , Replicação Viral/genética
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(2): 111-115, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33627202

RESUMO

OBJECTIVE: To explore the reasonable and effective enteral nutrition regimen for children with abdominal Henoch-Schönlein purpura (HSP). METHODS: A retrospective analysis was performed on the medical data of children with abdominal HSP who were hospitalized from August 2013 to August 2018. According to the starting time of enteral nutrition after abdominal pain relief, the children were divided into three groups: < 24 hours (n=68), 24-48 hours (n=64), and 48-72 hours (n=60). According to the type of enteral nutrition, they were divided into another three groups:amino acid-based formula (n=53), extensively hydrolyzed lactoprotein formula (n=67), and normal diet (n=72). The recurrence rate of clinical symptoms and degree of satisfaction among family members were compared between groups. Based on the retrospective analysis, 166 children with abdominal HSP were enrolled in a prospective study. They were given extensively hydrolyzed lactoprotein formula after abdominal pain relief. According to the feeding time after abdominal pain relief, they were divided into three groups: < 24 hours (n=52), 24-48 hours (n=59), and 48-72 hours (n=55). The three groups were compared in terms of the recurrence rates of abdominal pain, rash, and hematochezia, the rate of use of parenteral nutrition and intravenous steroids, and the incidence rate of weight loss at discharge. RESULTS: The retrospective analysis showed that the children who were given extensively hydrolyzed lactoprotein formula for enteral nutrition at 24-48 hours after abdominal pain relief had a lower recurrence rate of clinical symptoms and the highest degree of satisfaction among their family members (P < 0.0167). The prospective study showed that the children who were given extensively hydrolyzed lactoprotein formula for enteral nutrition at 24-48 hours after abdominal pain relief had lower recurrence rates of rash and abdominal pain, a lower rate of use of parenteral nutrition, and a lower incidence rate of weight loss at discharge (P < 0.05). CONCLUSIONS: It is reasonable and effective to start the feeding with extensively hydrolyzed lactoprotein formula at 24-48 hours after abdominal pain relief in children with abdominal HSP.


Assuntos
Nutrição Enteral , Púrpura de Schoenlein-Henoch , Criança , Humanos , Nutrição Parenteral , Estudos Prospectivos , Púrpura de Schoenlein-Henoch/terapia , Estudos Retrospectivos
11.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(2): 138-142, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33627207

RESUMO

OBJECTIVE: To study the effect of pertussis vaccination on the clinical manifestations of infants and young children with pertussis. METHODS: A retrospective analysis was performed to investigate the differences in clinical manifestations and peripheral blood cell levels between pertussis children with different pertussis vaccination status. RESULTS: A total of 1 083 children with pertussisat at age of < 3 years were enrolled, with 551 children in the unvaccinated group and 532 in the vaccinated group. Of all the children, 392 had an age of onset of < 3 months (372 were unvaccinated and 20 were vaccinated) and 691 children had an age of onset of ≥ 3 months (179 were unvaccinated and 512 were vaccinated). Compared with the vaccinated group, the unvaccinated group had a longer length of hospital stay and a higher incidence rate of respiratory failure (P < 0.05). Among the children ≥ 3 months of age, the incidence of severe pneumonia in the unvaccinated group was higher than that in the vaccinated group (P < 0.05), and the incidence of severe pneumonia was the highest in the unvaccinated group (10.6%) and the lowest in the 4-dose vaccination group (1.2%). Among the 101 patients with severe pneumonia, 80 (79.2%) were observed in the unvaccinated group and only 21 (20.8%) in the four different doses vaccination groups. For the children with an age of onset of ≥ 3 months, the unvaccinated group had higher white blood cell count, absolute value of lymphocytes, and platelet count than the vaccinated group (P < 0.05). CONCLUSIONS: Pertussis vaccination can reduce the incidence of severe pneumonia and respiratory failure and alleviate the severity of respiratory complications in infants and young children with pertussis.


Assuntos
Pneumonia , Coqueluche , Criança , Pré-Escolar , Humanos , Incidência , Lactente , Estudos Retrospectivos , Vacinação , Coqueluche/epidemiologia , Coqueluche/prevenção & controle
12.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(2): 192-197, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33627217

RESUMO

At present, effective antibiotics and comprehensive symptomatic/supportive treatment as early as possible are mainly used for the treatment of severe pertussis in clinical practice. However, some children with severe pertussis have unsatisfactory response to commonly used drugs and treatment measures in the intensive care unit and thus have a high risk of death. Studies have shown that certain treatment measures given in the early stage, such as exchange transfusion, may help reduce deaths, but there is still a lack of uniform implementation norms. How to determine the treatment regimen for severe pertussis and improve treatment ability remains a difficult issue in clinical practice. This article reviews the advances in the treatment of severe pertussis, in order to provide a reference for clinical treatment and research.


Assuntos
Coqueluche , Antibacterianos , Criança , Transfusão Total , Humanos , Coqueluche/tratamento farmacológico
13.
J Obstet Gynaecol Res ; 47(4): 1337-1343, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33590596

RESUMO

OBJECTIVE: To minimize the adverse events of uterine compression suture in controlling postpartum hemorrhage (PPH) and to search for a prophylactic approach to potential PPH. METHODS: A retrospective analysis was performed in 39 women with removable retropubic uterine compression suture (RRUCS) to stop PPH due to uterine atony during cesarean section (CS). The procedure was to suspend and compress the uterus to the retropubic abdominal wall using an absorbable suture. RESULTS: The technique was sufficient to stanch bleeding immediately in 36 patients (92.31%, 36/39). No morbidity or abnormalities occurred in women who underwent RRUCS. Subsequent pregnancies occurred in 10 cases, but the others lacked the desire for future pregnancy. CONCLUSION: RRUCS is a simple, safe, and effective technique in controlling atonic PPH; it is also used as a prophylactic application in patients with potential PPH after CS.


Assuntos
Cesárea , Hemorragia Pós-Parto , Inércia Uterina , Cesárea/efeitos adversos , Feminino , Humanos , Hemorragia Pós-Parto/prevenção & controle , Hemorragia Pós-Parto/cirurgia , Gravidez , Estudos Retrospectivos , Técnicas de Sutura , Suturas , Inércia Uterina/cirurgia , Útero/cirurgia
14.
J Hepatol ; 74(3): 522-534, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32987030

RESUMO

BACKGROUND & AIMS: Current antiviral therapies help keep HBV under control, but they are not curative, as they are unable to eliminate the intracellular viral replication intermediate termed covalently closed circular DNA (cccDNA). Therefore, there remains an urgent need to develop strategies to cure CHB. Functional silencing of cccDNA is a crucial curative strategy that may be achieved by targeting the viral protein HBx. METHODS: We screened 2,000 small-molecule compounds for their ability to inhibit HiBiT-tagged HBx (HiBiT-HBx) expression by using a HiBiT lytic detection system. The antiviral activity of a candidate compound and underlying mechanism of its effect on cccDNA transcription were evaluated in HBV-infected cells and a humanised liver mouse model. RESULTS: Dicoumarol, an inhibitor of NAD(P)H:quinone oxidoreductase 1 (NQO1), significantly reduced HBx expression. Moreover, dicoumarol showed potent antiviral activity against HBV RNAs, HBV DNA, HBsAg and HBc protein in HBV-infected cells and a humanised liver mouse model. Mechanistic studies demonstrated that endogenous NQO1 binds to and protects HBx protein from 20S proteasome-mediated degradation. NQO1 knockdown or dicoumarol treatment significantly reduced the recruitment of HBx to cccDNA and inhibited the transcriptional activity of cccDNA, which was associated with the establishment of a repressive chromatin state. The absence of HBx markedly blocked the antiviral effect induced by NQO1 knockdown or dicoumarol treatment in HBV-infected cells. CONCLUSIONS: Herein, we report on a novel small molecule that targets HBx to combat chronic HBV infection; we also reveal that NQO1 has a role in HBV replication through the regulation of HBx protein stability. LAY SUMMARY: Current antiviral therapies for hepatitis B are not curative because of their inability to eliminate covalently closed circular DNA (cccDNA), which persists in the nuclei of infected cells. HBV X (HBx) protein has an important role in regulating cccDNA transcription. Thus, targeting HBx to silence cccDNA transcription could be an important curative strategy. We identified that the small molecule dicoumarol could block cccDNA transcription by promoting HBx degradation; this is a promising therapeutic strategy for the treatment of chronic hepatitis B.

15.
Genes Dis ; 7(4): 535-541, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32363222

RESUMO

In December 2019, the corona virus disease 2019 (COVID-19) caused by novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and rapidly spread worldwide. Few information on clinical features and immunological profile of COVID-19 in paediatrics. The clinical features and treatment outcomes of twelve paediatric patients confirmed as COVID-19 were analyzed. The immunological features of children patients was investigated and compared with twenty adult patients. The median age was 14.5-years (range from 0.64 to 17), and six of the patients were male. The average incubation period was 8 days. Clinically, cough (9/12, 75%) and fever (7/12, 58.3%) were the most common symptoms. Four patients (33.3%) had diarrhea during the disease. As to the immune profile, children had higher amount of total T cell, CD8+ T cell and B cell but lower CRP levels than adults (P < 0.05). Ground-glass opacity (GGO) and local patchy shadowing were the typical radiological findings on chest CT scan. All patients received antiviral and symptomatic treatment and the symptom relieved in 3-4 days after admitted to hospital. The paediatric patients showed mild symptom but with longer incubation period. Children infected with SARS-CoV-2 had different immune profile with higher T cell amount and low inflammatory factors level, which might ascribed to the mild clinical symptom. We advise that nucleic acid test or examination of serum IgM/IgG antibodies against SARS-CoV-2 should be taken for children with exposure history regardless of clinical symptom.

16.
Cancer Lett ; 481: 1-14, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32268166

RESUMO

UBE2L3 is a ubiquitin-conjugating protein belonging to the E2 family that consists of 153 amino acid residues. In this study, we found that UBE2L3 was generally upregulated in clinical HCC samples compared to non-tumour samples and that there was a strong association between high UBE2L3 expression and tumour size, clinical grade and prognosis in HCC patients. UBE2L3 depletion inhibited the proliferation and induced the apoptosis of HCC cells. At the molecular level, we observed that UBE2L3 depletion enhanced the protein stability of GSK3ß, thus promoting the expression and activation of GSK3ß. Subsequently, activated GSK3ß phosphorylated p65 and promoted its nuclear translocation to increase the expression of target genes, including PUMA, Bax, Bim, Bad, and Bid. In vivo, knockout of UBE2L3 in HCC cells inhibited tumour growth in orthotopic liver injection nude mouse models. Moreover, inhibition of p65 or GSK3ß significantly restored the effects induced by UBE2L3 knockout in HCC. Together, this study reveals the stimulatory effect of UBE2L3 on HCC cell proliferation, suggesting that UBE2L3 may be an important pro-tumorigenic factor in liver carcinogenesis and a potential therapeutic target of HCC.


Assuntos
Apoptose/genética , Carcinoma Hepatocelular/genética , Glicogênio Sintase Quinase 3 beta/genética , Neoplasias Hepáticas/genética , Transdução de Sinais/genética , Fator de Transcrição RelA/genética , Enzimas de Conjugação de Ubiquitina/genética , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosforilação/genética , Regulação para Cima/genética
17.
Pathol Oncol Res ; 26(2): 1279-1285, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31267364

RESUMO

Peptidyl arginine deiminase, type II (PADI2) expression has been shown to potentiate multiple different carcinogenesis pathway including breast carcinoma and spontaneous skin neoplasia. The objective of this study was to examine the role of PADI2 in urothelial bladder cancer which has not been evaluated previously. Analysis of mutation and genome amplification of bladder cancer within The Cancer Genome Atlas (TCGA) showed that PADI2 is both mutated and amplified in a cohort of bladder cancer patients, with the largest number of mutations detected in urothelial bladder cancer. Even though PADI2 expression was not significantly correlated to survival in bladder cancer patients, it was significantly overexpressed at the mRNA and protein levels, as revealed by TCGA data and immunohistochemistry analysis, respectively. PADI2 showed wide expression pattern in bladder cancer tissues but was hardly detected in tumor adjacent normal tissue. RNAi mediated silencing of PADI2 in the bladder cancer cell line T24 did not result in a change of proliferation. Interestingly knockdown of PADI2 expression did not affect Snail1 protein, which is associated with metastatic progression, in these cells. However, PADI2 silencing remarkably attenuated both in vitro migration and invasion- in T24 cells indicating a Snail1-independent effect of PADI2 on invasive potential of urothelial bladder cancer. This was further corroborated by in vivo xenograft assays where PADI2 shRNA harboring T24 cells did not have detectable tumors by week 4 as compared to robust tumors in the control Luciferase shRNA harboring cells. PADI2 silencing did not affect proliferation rates and hence this would suggest that PADI2 knockdown is perhaps causing increased apoptosis as well as transition through the cell cycle, which needs to be confirmed in future studies. Our results reveal a yet undefined role of PADI2 as an oncogene in urothelial bladder cancer.


Assuntos
Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , Proteína-Arginina Desiminase do Tipo 2/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Animais , Carcinogênese/genética , Feminino , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Nus , Proteína-Arginina Desiminase do Tipo 2/metabolismo
19.
Brain Res ; 1724: 146464, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31536729

RESUMO

Visceral pain is a complex and common symptom of inflammatory bowel disease (IBD) patients. Developing novel efficient therapeutics is still a common interest for clinicians. Increasing evidence have shown that tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) contributes to the pathological pain state in some pain models. Resveratrol (RSV) has showed promising potential for the treatment of neuropathic pain and inflammatory pain. However, whether RSV has analgesic effect on visceral pain and the underlying mechanisms remain unclear. In this study, we established the colitis model through intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS), and found that TNBS induced colonic inflammation and visceral hypersensitivity. Meanwhile, astroglial marker glial fibrillary acidic protein (GFAP), TRAF6, phosphorylation of NF-κB (pNF-κB), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels were increased in L6-S1 spinal cord after TNBS enema. Then, intrathecal injection of TRAF6 siRNA attenuated visceral pain, blocked the upregulation of pNF-κB, TNF-α and IL-1ß levels in the spinal cord in TNBS mice. Furthermore, spinal administration of NF-κB inhibitor, BAY11-7082 reversed the pain behavior and suppressed spinal TNF-α and IL-1ß expression in TNBS mice. Finally, repeated intrathecal injection of RSV reversed TNBS-induced visceral pain hypersensitivity in a dose-dependent manner. Meanwhile, TNBS-induced enhancement of spinal GFAP, TRAF6, pNF-κB, TNF-α and IL-1ß were reduced by the same treatment of RSV. In conclusion, our results suggest that RSV exerts the effects of antinociception on colitis-induced visceral hyperalgesia through inhibition of spinal TRAF6/NF-κB signaling pathway and the production of inflammatory mediators in the spinal cord, suggesting a new application of RSV for the treatment of visceral pain.


Assuntos
Resveratrol/farmacologia , Dor Visceral/tratamento farmacológico , Dor Visceral/metabolismo , Analgésicos/farmacologia , Animais , Colite/tratamento farmacológico , Colite/fisiopatologia , Proteína Glial Fibrilar Ácida/metabolismo , Hiperalgesia/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Neuralgia/metabolismo , Resveratrol/metabolismo , Transdução de Sinais/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
20.
Chem Commun (Camb) ; 55(62): 9208-9211, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31309945

RESUMO

We report an electrochemical protocol for the direct oxidation of internal alkynes in air to provide 1,2-diketones. A variety of functional groups and heterocycle-containing substrates can be tolerated well under mild conditions.

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