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1.
Braz. j. biol ; 83: e244977, 2023. tab, graf
Artigo em Inglês | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1285621

RESUMO

Abstract Hepatitis C virus (HCV) is the serious global public health burden of liver disease. Approximately 170 million people in the world are infected with (HCV). In Pakistan, where the disease has high occurrence rate. The present study envisages an up-to-date prevalence of HCV and genotypic distribution in the general population of Mardan District, Khyber Pakhtunkhwa (KP), Pakistan. The blood samples from 6,538 individuals including 3,263 males and 3,275 females were analyzed for hepatitis C surface antigen by Immuno-chromatographic test (ICT), Enzyme-linked immunosorbent assay (ELISA), and reverse transcription-polymerase chain reaction (PCR). It was found that 396 (12.13%) out of 3263 individuals contained antibodies in their blood against HCV, while among the different age groups, the highest incidences of HCV antibodies were found in the 31-40 age group (11.01%). The ICT positive samples were further screened by nested PCR to determine the existence of active HCV-RNA. It was identified that 7.11% (3263) of the total population (6538) tested was positive, among which the 461 (14.07%) females possessed antibodies in their blood against HCV. Our data showed total HCV infection in the investigated population was 5.78%. Higher percentage of HCV prevalence was detected in males than females in the age group 31-40 and 41-50. To compare the prevalence of HCV genotypes age-wise in male and female genotype 3a was found most prevalent genotype followed by 1a, 2a and 3b, respectively.


Resumo O vírus da hepatite C (HCV) é o grave problema de saúde pública das doenças hepáticas. Aproximadamente 170 milhões de pessoas no mundo estão infectadas com HCV; no Paquistão, a doença tem alto índice de ocorrência. O presente estudo prevê uma prevalência atualizada do HCV e distribuição genotípica na população geral do distrito de Mardan, Khyber Pakhtunkhwa (KP), Paquistão. As amostras de sangue de 6.538 indivíduos, incluindo 3.263 homens e 3.275 mulheres, foram analisadas para o antígeno de superfície da hepatite C por teste imunocromatográfico (ICT), ensaio imunoenzimático (ELISA) e reação em cadeia da polimerase de transcrição reversa (PCR). Verificou-se que 396 (12,13%) de 3.263 indivíduos continham anticorpos no sangue contra o HCV, enquanto entre as diferentes faixas etárias as maiores incidências de anticorpos anti-HCV foram encontradas na faixa etária de 31 a 40 anos (11,01%). As amostras positivas para ICT foram posteriormente rastreadas por nested PCR para determinar a existência de HCV-RNA ativo. Identificou-se que 7,11% (3.263) do total da população (6.538) testada foram positivos, dentre os quais 461 (14,07%) mulheres possuíam anticorpos no sangue contra o HCV. Nossos dados mostraram que a infecção total pelo HCV na população investigada foi de 5,78%. Maior porcentagem de prevalência de HCV foi detectada em homens do que em mulheres nas faixas etárias de 31-40 e 41-50. Para comparar a prevalência de genótipos de HCV com relação à idade no genótipo masculino e feminino 3a foi encontrado o genótipo mais prevalente seguido por 1a, 2a e 3b, respectivamente.

2.
Braz. j. biol ; 82: e245813, 2022. tab, graf
Artigo em Inglês | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1285592

RESUMO

Abstract Hepatitis B virus infection is perilous among the five types of Hepatitis, as it remains clinically asymptomatic. The present study draws up-to-date prevalence of Hepatitis B virus (HBV) in the general population of Mardan, Khyber Pakhtunkhwa Pakistan. The blood samples from 4803 individuals including 2399 male and 2404 females were investigated. All the suspected samples were analyzed for hepatitis B surface antigen using Immuno-chromatographic test (ICT), Enzyme-linked immunosorbent assay (ELISA), and followed by Reverse transcription-polymerase chain reaction (RT-PCR). Results showed that 312 (13.00%) out of 2399 individuals contained antibodies in their blood against HBV, while among the different age groups, the highest incidences of HBV antibodies were found in the age of 21-30 groups (10.73%). Furthermore, the ICT positive samples were screened by nested polymerase chain reaction to detect the existence of active HBV-DNA. It was observed that 169 (7.04%) out of (2399) male of the total population (4803) tested was positive. On the other hand, the female 463 (19.25%) possessed antibodies in their blood against HBV. Accumulatively, our results showed a higher percentage of HBV prevalence in males than females in the age group 21-30 years. The total HCV infected in Mardan general population was recorded at 5.7% comprising both male and female.


Resumo A infecção pelo vírus da hepatite B é perigosa entre os cinco tipos de hepatite, pois permanece clinicamente assintomática. O presente estudo traça a prevalência atualizada do vírus da hepatite B (HBV) na população geral de Mardan, Khyber Pakhtunkhwa, no Paquistão. Amostras de sangue de 4.803 indivíduos, incluindo 2.399 homens e 2.404 mulheres, foram investigadas. Todas as amostras suspeitas foram analisadas para o antígeno de superfície da hepatite B usando teste imunocromatográfico (ICT), enzyme-linked immunosorbent assay (ELISA), seguido por transcrição reversa-reação em cadeia da polimerase (RT-PCR). Os resultados mostraram que 312 (13,00%) de 2.399 indivíduos continham anticorpos no sangue contra o VHB, enquanto, entre as diferentes faixas etárias, as maiores incidências de anticorpos VHB foram encontradas nos grupos de 21 a 30 anos (10,73%). Além disso, amostras positivas para ICT foram rastreadas por reação em cadeia da polimerase aninhada para detectar a existência de HBV-DNA ativo. Observou-se que 169 (7,04%) de 2.399 homens do total da população (4803) testados foram positivos. Por outro lado, 463 mulheres (19,25%) possuíam anticorpos no sangue contra VHB. Acumulativamente, nossos resultados mostraram uma porcentagem maior de prevalência de HBV em homens do que em mulheres na faixa etária de 21 a 30 anos. O total de HCV infectados na população geral de Mardan foi registrado em 5,7%, incluindo homens e mulheres.

3.
Eur Rev Med Pharmacol Sci ; 25(20): 6160, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34730190

RESUMO

The article "Long noncoding RNA MIAT acts as an oncogene in Wilms' tumor through regulation of DGCR8, by X.-S. Zhao, N. Tao, C. Zhang, C.-M. Gong, C.-Y. Dong, published in Eur Rev Med Pharmacol Sci 2019; 23 (23): 10257-10263-DOI: 10.26355/eurrev_201912_19663-PMID: 31841180" has been withdrawn from the authors due to inaccuracies in the data. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19663#:~:text=CONCLUSIONS%3A%20The%20above%20results%20suggested,and%20therapy%20of%20Wilms'%20tumor.

4.
Zhonghua Bing Li Xue Za Zhi ; 50(11): 1222-1227, 2021 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-34719158

RESUMO

Objective: To study the expression of programmed death ligand-1 (PD-L1) in tumor cells and CD8+T lymphocytes in tumor infiltrating lymphocytes, and to analyze the correlation of PD-L1 expression with infiltration of CD8+T lymphocytes and clinicopathologic features in salivary gland lymphoepithelial carcinoma (LEC). Methods: Forty-two cases of primary salivary LECs and 21 cases of secondary salivary LECs were enrolled at the Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University between 2015 and 2017. The expression of Epstein-Barr (EB) virus, PD-L1 and CD8 was examined using chromogenic in situ hybridization (CISH) and immunohistochemistry (IHC) staining. The data were analyzed using SPSS 23.0 software package. Results: EB virus was detected in 61 cases (61/63, 96.8%), including 42 (42/42, 100%) primary LECs and 19 (19/21, 90.5%) secondary LECs. The PD-L1 positive rate (score ≥1) was 97.6% (41/42), and its high-expression rate (score ≥20) was 78.6% (33/42) in primary LECs. The PD-L1 positive rate (score ≥1) was 71.4% (15/21), and its high-expression rate (≥20) was 38.1% (8/21) in secondary LECs. However, the PD-L1 positive rate (score ≥1, P=0.004) and high-expression rate (score ≥20, P=0.001) in primary LECs were higher than those in secondary LECs. There was no difference in the infiltration degree of CD8+T lymphocytes between primary and secondary LECs. There was a significant correlation between the expression of PD-L1 and CD8 in primary LECs (P=0.001) and in secondary LECs (P=0.048), respectively. Conclusions: There is PD-L1 expression in primary and secondary salivary LECs, while the expression rate is higher in primary LECs than secondary LECs. The combination of PD-L1 expression and CD8+T lymphocytes' presence suggest that most LEC patients might be responsive to immunotherapy, and primary LECs might be more significantly responsive than secondary LECs.


Assuntos
Antígeno B7-H1 , Carcinoma de Células Escamosas , Linfócitos T CD8-Positivos , China , Humanos , Linfócitos do Interstício Tumoral , Glândulas Salivares
5.
Artigo em Inglês | MEDLINE | ID: mdl-34774790

RESUMO

OBJECTIVE: One driving factor in the progression to posttraumatic osteoarthritis (PTOA) is the perpetuation of the inflammatory response to injury into chronic inflammation. Molecular imaging offers many opportunities to complement the sensitivity of current imaging modalities with molecular specificity. The goal of this study was to develop and characterize agents to image hyaluronan (HA)-mediated inflammatory signaling. DESIGN: We developed optical (Cy5.5-P15-1) and magnetic resonance contrast agents (Gd-DOTA-P15-1) based in a hyaluronan-binding peptide (P15-1) that has shown anti-inflammatory effects on human chondrocytes, and validated them in vitro and in vivo in two animal models of PTOA. RESULTS: In vitro studies with a near infrared (NIR) Cy5.5-P15-1 imaging agent showed a fast and stable localization of Cy5.5-P15-1 on chondrocytes, but not in synovial cells. In vivo NIR showed significantly higher retention of imaging agent in PTOA knees between 12 and 72 h (n = 8, Cohen's d > 2 after 24 h). NIR fluorescence accumulation correlated with histologic severity in cartilage and meniscus (ρ between 0.37 and 0.57, P < 0.001). By using in vivo magnetic resonance imaging with a Gd-DOTA-P15-1 contrast agent in 12 rats, we detected a significant decrease of T1 on injured knees in all cartilage plates at 48 h (-15%, 95%-confidence interval (CI) = [-18%,-11%] []) while no change was observed in the controls (-2%, 95%-CI = [-5%,+1%]). CONCLUSIONS: This study provides the first in vivo evidence that hyaluronan-related inflammatory response in cartilage after injury is a common finding. Beyond P15-1, we have demonstrated that molecular imaging can provide a versatile technology to investigate and phenotype PTOA pathogenesis, as well as study therapeutic interventions.

6.
Zhonghua Gan Zang Bing Za Zhi ; 29(10): 913-914, 2021 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-34814382

RESUMO

Clinically, chronic hepatitis B and C are the main common chronic liver diseases that lead to cirrhosis and liver cancer, followed by drug-induced liver injury, alcohol and metabolic-associated fatty liver disease, and autoimmune liver disease in adult, but, by contrast, some special liver diseases, including pregnancy-related liver disease, liver injury related to abnormal liver endocrine function, adult hereditary liver disease, and hepatitis caused by non-hepatotropic viruses are also gradually increasing. Early identification and diagnosis are the only accurate and timely manner treatment for these special liver diseases.

7.
Zhonghua Gan Zang Bing Za Zhi ; 29(10): 967-971, 2021 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-34814390

RESUMO

Objective: To analyze, explore and evaluate the clinical characteristics, abnormal thyroid function and follow-up of anti-hyperthyroidism treatment mode in patients with hyperthyroidism (commonly abbreviated as HT) combined with liver injury. Methods: The clinical data of patients with hyperthyroidism combined with liver injury were retrospectively analyzed, and then patients were divided into treated and untreated group according to whether they received anti-hyperthyroidism treatment before the consultation. Patients' thyroid and liver function test indicators at the time of treatment were analyzed to determine the main cause of liver injury. The characteristics of liver injury were analyzed in the treatment group. Patients with severe thyroid toxicity and hyperthyroidism combined with liver injury were followed-up with anti-hyperthyroid therapy, mainly low-dose methimazole (MMI) and radioactive iodine therapy to evaluate its efficacy and safety. The comparison between data groups was performed by t-test, rank sum test and χ( 2) test. Results: Among the 43 cases with hyperthyroidism combined with liver injury, 19 were males and 24 were females, aged 49.0 ± 14.6 years-old; 16 cases (16/43, 37.21%) aged 40 to≤60 years- old, and 15 cases (15/43, 34.88%) aged > 60 years-old. There were 22 untreated cases (untreated group, accounting for 51.16%), and 21 treated cases with anti-hyperthyroidism (treatment group, accounting for 48.84%) at the time of consultation. Thyroid function indicators (FT3, FT4, TSH) and liver function indicators (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyltransferase, total bilirubin) of the two groups were compared, and the difference was not statistically significant (P > 0.05). The order of liver injury from mild to severe in patients with different treatment options were: methimazole (MMI) < propylthiouracil < radioactive iodine

8.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(6): 1061-1066, 2021 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-34814507

RESUMO

Objective: To compare the seroprevalence of hepatitis B in Guangzhou in 2008 and 2018. Methods: According to the proportion of Guangzhou population size, two-stage cluster sampling was used to select the residents aged 1-59 years in the two surveys. Results: 4 989 and 3 980 people aged 1-59 years were involved in 2008 and 2018, respectively. HBsAg prevalence was 9.50% (95%CI:7.34%-11.66%) in 2018 and 12.45% (95%CI:10.58%-14.33%) in 2008 among the people aged 1-59 years, with no significant difference statistically (χ2=18.302, P=0.075). The decrease of HBsAg prevalence was mainly in the population aged 7-16 years. For the people aged 7-16 years, the HBsAg prevalence was 0.88% (95%CI: 0.35%-1.42%) in 2018 and decreased by 80.62% as compared with the rate 4.54% (95%CI:2.71%-6.36%) in 2008, with statistically significant difference (χ2=34.144,P=0.000). Anti-HBs prevalence was 72.30% (95%CI:69.56%-75.04%) in 2018 and ascended by 11.35% as compared with the rate of 64.93% (95%CI:61.65 %-68.22%) in 2008 among the people aged 1-59 years, with statistically significant difference (χ2=51.618, P=0.001). The rise of anti-HBs prevalence was mainly in the population aged 17-59 years. For the people aged 17-59 years, the anti-HBs prevalence was 71.93% (95%CI: 68.90%-74.96%) and risen by 12.80% as compared with the rate of 63.77% (95%CI: 60.16%-67.37%) in 2008, with a statistically significant difference (χ2=28.422, P=0.001). HBV infection rate was 48.10% (95%CI: 43.20%-53.00%) in 2018 and decreased by 22.76% as compared with the rate of 62.27% (95%CI: 59.11%-65.44%) in 2008, with statistically significant difference (χ2=167.138, P=0.000). The HBV infection rates in the population aged 1-6 years, 7-16 years, and 17-59 years were 4.58%, 5.13%, and 56.56% (a decrease of 81.83%, 85.91%, and 18.47%), respectively. The infection rate of HBV was 48.87% (a decrease of 24.70%) in high epidemic areas and 28.81% (a decrease of 38.75%) in people with a history of hepatitis B immunization. Conclusion: The prevention and control of hepatitis B in Guangzhou have achieved remarkable results it already reached the national goal of reducing HBsAg prevalence to less than 1% among children under five years since 2008. However, the target goal of reducing the hepatitis B mortality rate is quite demanding. The neonatal hepatitis B vaccination and monitoring and screening in adults are still needed.

9.
J Physiol Pharmacol ; 72(3)2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34810290

RESUMO

This study aimed to investigate the effects of gastric cancer interstitial fluid (GCIF) on tumors and explore the possible mechanism of Xiaotan Sanjie decoction (XTSJ) on treatment of gastric cancer from the view of regulating microRNA-21 (miR-21) expression. The GCIF was extracted and identified by measuring the levels of interleukin-8 (IL-8), intercellular adhesion molecule 1 (ICAM-1) and miR-21. The effects of GCIF on the proliferation of SGC-7901 cells and tumor growing were assessed by cell counting kit-8 (CCK-8) assay and subcutaneously transplanted tumor-bearing nude mice model, respectively. Additionally, inhibition effect of XTSJ decoction on proliferation of SGC-7901 cells intervened by GCIF were assessed in vitro and anti-cancer effect of it was further assessed using orthotopic transplanted tumor-bearing nude mice model. The concentration of SGC-7901 gastric cancer cells were dependent on the concentration of the added GCIF. After 72 hours of continuous culture, the interstitial fluid had an obvious proliferative effect on the SGC-7901 tumor cells, which was the most significant in the high concentration group. XTSJ decoction could inhibit the growth-promoting effect (P < 0.01) of GCIF on gastric cancer cells. Intervention of the GCIF might promote the growth (P < 0.05) of the subcutaneously transplanted tumors in nude mice and decrease the net weight of the tumor-bearing nude mice (P < 0.05) after tumor removal. The GCIF was able to up-regulate the expression (P < 0.001) of miR-21 in the subcutaneously transplanted tumors. XTSJ decoction could downregulate the expression (P < 0.05) of miR-21 in SGC-7901 orthotopically transplanted tumors. XTSJ decoction can inhibit the multiplicative effect of GCIF on gastric cancer cells, growth of gastric tumor and promotion effect of GCIF on tumors, probably due to the down-regulating miR-21 expression in tumor tissues.

10.
Clin Exp Dermatol ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34798679

RESUMO

The diagnosis of the most common cutaneous T-cell lymphomas (CTCLs), mycosis fungoides (MF) and Sézary syndrome (SS) are often delayed because of unspecific clinical and histopathological findings in the early stages of the disease.1 In SS, erythroderma is considered an important diagnostic criterion; however, it is not always the presenting feature.2 Secondary SS refers to a diagnosis of SS following established MF3 ; whereas, pre-SS refers to erythroderma with a sézary cell count of less than 1000 cells/mm4 . To date, cutaneous manifestations which precede the development of confluent erythroderma include lesions suggestive of non-specific dermatitis, patches and plaques of MF, and urticaria2 which challenge the historical clinical tenet. Here, we present one patient who developed confluent erythroderma with a sézary cell count of less than 1000 cells/mm following an initial presentation of intertriginous lesions.

11.
Clin Exp Dermatol ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34773274

RESUMO

A 21-year-old male was referred to our clinic for his refractory and aggravated eczema. He had been suffering from repetitive generalized itchy eczema since the age of 6 months. Furthermore, he had repeated pneumonia, cutaneous eczema, tubercular meningitis and gastroenteritis successively, and was then diagnosed with agammaglobulinemia at the age of 6 years after repetitive testing results of low-level lymphocytes and gamma globulin. He received immunoglobulin replacement therapy infrequently.

12.
Artigo em Chinês | MEDLINE | ID: mdl-34624956

RESUMO

In order to solve the problem of dust hazard of vibrating screen machine and difficult treatment in catalyst production process, computational fluid dynamics software Fluent was used to carry out numerical simulation calculation of the local exhaust dust removal system for the main dust dispersing points of the vibrating screen machine, including fine/coarse particles outlet and product outlet blowing and cleaning the dust points. The optimal design scheme and key technical parameters of local ventilation and dust removal system of vibrating screen machine were proposed. The results showed that the dust diffusion could be prevented by setting up an upper suction hood without air blowing, but the exhaust air volume needed to be calculated accurately. On the premise of purge, it is necessary to control the air volume to form a wind speed band of 8 m/s with a height of 15 cm at the feed port, so as to effectively remove the dust on the surface of solid particles of catalyst products and ensure that the catalyst products will not be blown away when falling into the feed barrel. The simulated design was applied to the vibrating sieve powder machine of a catalyst company, and the maximum dust concentration in the workplace was reduced from 45.80 mg/m(3) to 5.46mg/m(3), which effectively improved the working environment in the workplace.


Assuntos
Poeira , Vento , Poeira/análise , Respiração , Local de Trabalho
13.
Artigo em Chinês | MEDLINE | ID: mdl-34666437

RESUMO

Objective: To analyse the clinical application of thoracodorsal artery perforator flaps (TDAPF) in the repair of head and neck defects. Methods: A retrospective review was conducted on 38 patients with oral and maxillofacial head and neck malignant tumors who underwent radical resection of oral and oropharyngeal carcinoma and TDAPF repair in the Department of Oral and Maxillofacial Head and Neck Oncology of the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from June 2017 to November 2018. Among them, 32 were males and 6 were females, aged 30-74 years. Flap size, vessel pedicle length, diameter and number of perforators, and flap fat thickness were recorded and counted. Elasti Meter and Skin Fibro Meter were applied to measure the skin elasticity and hardness in the donor areas of 4 kinds of skin flaps before the flap preparation. SPSS 19.0 statistical software was used for statistical analysis of the data. Results: All the flaps survived (100%). The mean elasticity of TDAPF [(41.2±12.9) N/m] was significantly lower than that of anterolateral thigh [(77.6±23.3) N/m, χ²=88.89, P<0.05], anterolateral thigh [(62.6±17.7) N/m, χ²=59.99, P<0.05] and or forearm flap [(51.7±8.6) N/m, χ²=37.82, P<0.05]. The hardness of TDAPF [(0.037±0.016) N] was also significantly lower than that of anterolateral femoral [(0.088±0.019) N, F=93.27, P<0.05], anteromedial femoral [(0.059±0.020) N, F=25.71, P<0.05] or forearm flap [(0.062±0.016) N, F=29.11, P<0.05]. Follow-up period ranged from 2 to 14 months. The 38 patients treated with TDAPF had a good recovery of the functions in the recipient areas, and the scars of the donor areas were not obvious after surgery, without serious complications. Conclusion: TDAPF is suitable for reconstruction of head and neck defect, with ductile texture and good recovery of the morphology and function of head and neck.


Assuntos
Retalho Perfurante , Procedimentos Cirúrgicos Reconstrutivos , China , Feminino , Artéria Femoral/cirurgia , Humanos , Masculino , Estudos Retrospectivos , Transplante de Pele , Coxa da Perna/cirurgia
14.
J Endocrinol Invest ; 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34676492

RESUMO

PURPOSE: Previous studies have not fully described the relationship between high-density lipoprotein cholesterol (HDL-C) and death risks from all cause and cardiovascular disease (CVD). This study quantitatively evaluates HDL-C-mortality associations. METHODS: Embase and PubMed databases were searched for relevant articles published up to 1 June 2019. Random-effects models were used to pool relative risks (RRs) and 95% confidence intervals (CIs). We used restricted cubic splines to model the dose-response association. RESULTS: We identified 32 prospective cohort studies including 369,904 participants and 33,473 total deaths (9426 CVD deaths). Compared to the lowest HDL-C levels, all cause and CVD mortality risks were reduced by 18% (RR 0.82; 95% CI, 0.73-0.93) and 36% (0.64, 0.46-0.89), respectively, for the highest HDL-C levels. All cause and CVD mortality risks were reduced by 15% (0.85, 0.79-0.92) and 23% (0.77, 0.69-0.87), respectively, with each 1 mmol/L increment of HDL-C. We found evidence of nonlinear and negative dose-response associations of HDL-C with all cause and CVD mortality (Pnonlinearity < 0.001), and the lowest death risks from all cause and CVD were observed at approximately 1.34 and 1.55 mmol/L, respectively. CONCLUSION: HDL-C is inversely associated with all cause and CVD mortality risks under approximately 2.05 and 2.33 mmol/L, respectively. Optimal doses require investigation via clinical practice or high-quality research.

15.
Zhonghua Shao Shang Za Zhi ; 37(9): 853-859, 2021 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-34645151

RESUMO

Objective: To explore the effects and possible molecular mechanism of histone deacetylase 6 (HDAC6) inhibitor Tubastatin A on the proliferation and movement of human skin fibroblasts (HSFs). Methods: The experimental research method was used. HSFs in logarithmic growth phase were taken and divided into negative control group, 1 µmol/L Tubastatin A group, 5 µmol/L Tubastatin A group, and 10 µmol/L Tubastatin A group according to the random number table. The HSFs in negative control group were added with Dulbecco's modified eagle medium with the final volume fraction of 0.1% dimethyl sulfoxide (hereinafter referred to as the complete medium), and the other three groups were added with the complete medium with the corresponding final molarity of Tubastatin A. After 24 h of conventional culture, the cell proliferation activity was detected using cell counting kit 8 (CCK-8) method and 5-ethynyl-2'-deoxyuridine (EdU) staining; the range of motion of cells within 3 h was observed under the living cell workstation, and the curve movement velocity of the cells was calculated. The protein expressions of extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2) were detected by Western blotting, and the ratio of p-ERK1/2 to ERK1/2 was calculated to represent the activity of ERK1/2. The sample number in cell proliferation activity detection with CCK-8 method was 6, while the sample numbers in other experiments were 3. Data were statistically analyzed with one-way analysis of variance and least significant difference test. Results: After 24 h of culture, CCK-8 method and EdU staining showed that compared with negative control group, the cell proliferation activities in 1 µmol/L Tubastatin A group, 5 µmol/L Tubastatin A group, and 10 µmol/L Tubastatin A group were significantly decreased (P<0.01). After 24 h of culture, CCK-8 method showed that compared with 1 µmol/L Tubastatin A group, the cell proliferation activity in 10 µmol/L Tubastatin A group was significantly decreased (P<0.05); EdU staining showed that compared with 1 µmol/L Tubastatin A group, the cell proliferation activities in 5 µmol/L Tubastatin A group and 10 µmol/L Tubastatin A group were significantly decreased (P<0.05 or P<0.01). Within 3 h of observation, the ranges of cell motion in 1 µmol/L Tubastatin A group, 5 µmol/L Tubastatin A group, and 10 µmol/L Tubastatin A group were obviously reduced compared with that in negative control group. Within 3 h of observation, the curve movement velocity of cells in negative control group was (0.780±0.028) µm/min, which was obviously faster than (0.594±0.023), (0.469±0.028), and (0.391±0.021) µm/min of 1 µmol/L Tubastatin A group, 5 µmol/L Tubastatin A group, and 10 µmol/L Tubastatin A group (P<0.01); the curve movement velocity of cells in 1 µmol/L Tubastatin A group was obviously faster than those in 5 µmol/L Tubastatin A group and 10 µmol/L Tubastatin A group (P<0.01); the curve movement velocity of cells in 5 µmol/L Tubastatin A group was obviously faster than that in 10 µmol/L Tubastatin A group (P<0.05). After 24 h of culture, compared with negative control group, the activities of ERK1/2 of cells in 1 µmol/L Tubastatin A group, 5 µmol/L Tubastatin A group, and 10 µmol/L Tubastatin A group were decreased significantly (P<0.01); compared with 1 µmol/L Tubastatin A group, the activities of ERK1/2 of cells in 5 µmol/L Tubastatin A group and 10 µmol/L Tubastatin A group were decreased significantly (P<0.01); compared with 5 µmol/L Tubastatin A group, the activity of ERK1/2 of cells in 10 µmol/L Tubastatin A group was decreased significantly (P<0.05). Conclusions: HDAC6 inhibitor Tubastatin A may mediate the inhibitory effect on proliferation and movement of HSFs by inhibiting the activity of ERK1/2.


Assuntos
Inibidores de Histona Desacetilases , Ácidos Hidroxâmicos , Fibroblastos , Desacetilase 6 de Histona , Inibidores de Histona Desacetilases/farmacologia , Humanos , Ácidos Hidroxâmicos/farmacologia , Indóis
16.
Eur Rev Med Pharmacol Sci ; 25(19): 6077-6092, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34661268

RESUMO

OBJECTIVE: Obstructive jaundice (OJ) is a common clinical pathological syndrome in hepatobiliary surgery. High incidence of multiple organ injuries during perioperative period and its associated mortality remains challenging in clinical practice. Omega-3 polyunsaturated fatty acids (ω-3 PUFA) is an important enteral immune nutrition. This study investigated the protective role of ω-3 PUFA in the regulation of inflammatory response in OJ. MATERIALS AND METHODS: Seventy-two rats were randomly divided into obstructive jaundice (OJ) group, obstructive jaundice + ω-3 PUFA group (OJPUFA) group, and sham group. OJ model was created by ligation of the bile duct. Abdominal thoracic catheter was placed to collect lymph. Body weight, liver function, serum and lymphatic levels of TNF-α, IL-1ß, IL-10, HMGB1, and nitric oxide (NO) were measured on day 3, day 7, and day 14 after operation. Hematoxylin staining and Alcian blue-periodic acid-Shiff (AB-PAS) staining were performed on the ileum tissue. Protein and mRNA expression of HMGB1, TLR4, and NF-κB p65 were measured at the aforementioned time points. RESULTS: The general condition, including body weight and liver function, were worse in the OJ and the OJPUFA group compared to that in the sham group. On day 14, the body weight recovery and liver function were significantly better in the OJPUFA group than those in the OJ group were (p<0.05 for all). No marked change in the serum and lymphatic levels of TNF-α, IL-1ß, IL-10, HMGB1 and NO was observed in the sham group after operation, while corresponding levels in the OJ and the OJPUFA groups were significantly higher. Compared with the OJPUFA group, serum and lymphatic levels of the above factors were consistently higher in the OJ group and were significantly higher on day 14 (p<0.05 for all). At the same time, ω-3 PUFA lowered the damage of intestinal villi and intestinal mucosal epithelium. It also improved the number and function of goblet cells in intestinal mucosal epithelium. The protein and mRNA expression of HMGB1, TLR4, and NF-κB p65 were significantly higher in the OJ group than those in the OJPUFA group (p<0.05 for all). CONCLUSIONS: ω-3 PUFA has protective effect in the management of obstructive jaundice. It can regulate the inflammatory response and reduce its damage to intestinal structure. Reducing the activation of HMGB1/TLR4/ NF-κB pathway might be a mechanism for its protective effect. We suggested that ω-3 PUFA and drugs targeted HMGB1/TLR4/NF-κB pathway might be potential treatment strategies in obstructive jaundice.

17.
Mater Today Bio ; 12: 100140, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34611623

RESUMO

Soft thermotropic liquid crystals (TLCs) have advantages on processability and shape memory compared to hard solids and fluids. The development of photoswitchable soft TLCs based on biomolecules would afford reworkable shape information recording biomaterials for the areas requiring biocompatibility and degradability. In recent years, anhydrous DNA TLCs composed of DNA and ammonium surfactants have been receiving continuous attention. However, the photoswitchable phase transition has not been realized for soft DNA TLCs at room temperature, owing to the absence of functional ammonium surfactant. Herein, a new type of azobenzene-containing surfactant would be applied to the fabrication of soft DNA TLCs with photoresponsive physical properties. The double-chain design of the used surfactant and the use of DOAB as a dopant guarantee the soft state of DNA TLCs at r.t., which also facilitates the azobenzene isomerization by reducing the packing density of surfactants. With the assistance of photoisomerization of azobenzene, the reported DNA TLCs achieve reversible liquid crystal-isotropic liquid transition at temperatures below clearing points even at room temperature. The repeatable shape information recording and self-erasing tests indicate these DNA TLCs would be good shape information recording biomaterials in the future. This work also provides a useful strategy for designing photoresponsive soft biomaterials based on rigid biomolecules like DNA.

18.
ESMO Open ; 6(6): 100275, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34653800

RESUMO

BACKGROUND: Biliary tract cancers (BTCs) are rare and highly heterogenous malignant neoplasms. Because obtaining BTC tissues is challenging, the purpose of this study was to explore the potential roles of bile as a liquid biopsy medium in patients with BTC. PATIENTS AND METHODS: Sixty-nine consecutive patients with suspected BTC were prospectively enrolled in this study. Capture-based targeted sequencing was performed on tumor tissues, whole blood cells, plasma, and bile samples using a large panel consisting of 520 cancer-related genes. RESULTS: Of the 28 patients enrolled in this cohort, tumor tissues were available in eight patients, and plasma and bile were available in 28 patients. Somatic mutations were detected in 100% (8/8), 71.4% (20/28), and 53.6% (15/28) of samples comprising tumor tissue DNA, bile cell-free DNA (cfDNA), and plasma cfDNA, respectively. Bile cfDNA showed a significantly higher maximum allele frequency than plasma cfDNA (P = 0.0032). There were 56.2% of somatic single-nucleotide variant (SNVs)/insertions and deletions (indels) shared between bile and plasma cfDNA. When considering the genetic profiles of tumor tissues as the gold standard, the by-variant sensitivity and positive predictive value for SNVs/indels in bile cfDNA positive for somatic mutations were both 95.5%. The overall concordance for SNVs/indels in bile was significantly higher than that in plasma (99.1% versus 78.3%, P < 0.0001). Moreover, the sensitivity of CA 19-9 combined with bile cfDNA achieved 96.4% in BTC diagnosis. CONCLUSION: We demonstrated that bile cfDNA was superior to plasma cfDNA in the detection of tumor-related genomic alterations. Bile cfDNA as a minimally invasive liquid biopsy medium might be a supplemental approach to confirm BTC diagnosis.

20.
Int J Radiat Oncol Biol Phys ; 111(3S): e399, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701362

RESUMO

PURPOSE/OBJECTIVE(S): Surveillance after definitive radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC) is critical to confirm clinical complete response, as a subset of patients develop locoregional recurrences (LRR). The Hopkins Criteria are a standardized qualitative system for assessing response using post-treatment PET/CT and are validated for overall (OS) and progression-free survival (PFS). We hypothesized that the Hopkins Criteria score is independently prognostic for LRR. MATERIALS/METHODS: We conducted an institutional retrospective study of adult patients with newly-diagnosed node-positive non-metastatic OPSCC treated with definitive (chemo)radiotherapy. Patients were eligible if they completed a pre- and post-radiotherapy PET/CT within 24 weeks after treatment. The primary outcome was the cumulative incidence of locoregional recurrence/persistence. A single board-certified nuclear medicine physician assigned Hopkins scores, which were considered either positive (scores 4-5) or negative (scores 1-3). RESULTS: Between 2004-2018, 259 patients were included in this analysis, while an additional 221 were excluded, most commonly due to lack of post-treatment PET/CT [37%] or N0 disease [22%]. Most patients were men (90%), 47% had never smoked, 86% had p16+/HPV+ tumors, and 39% had T3-4 tumors. Nearly all (98%) received concurrent chemotherapy, while 11% received induction chemotherapy. Median clinical follow-up was 40 months. Following radiotherapy, the first post-treatment PET/CT was positive (score 4-5) at the primary site in 32 patients (12%), cervical lymph nodes in 26 patients (10%), and either the primary site or neck in 50 patients (19%). This PET/CT was performed at a median of 3.3 months [range, 1.6-6.0] after radiotherapy. Thirty-four (13%) LRRs were observed. The sensitivity, specificity, negative predictive value, and overall accuracy of the Hopkins score for LRR were 68%, 88%, 95%, and 85%. The 36-month cumulative incidence of LRR was greater among patients with Hopkins scores 4-5 (45% vs. 5%, multivariable-adjusted HR 14.16, P < 0.001). Positive scores were similarly prognostic for 36-month OS (69% vs. 94%) and PFS (55% vs. 87%). LRR was similar among patients with scores of 3 relative to scores of 1-2. Performance was reduced when PET/CTs were obtained within 2.5 months of radiotherapy (accuracy: ≤2.5 months: 73%; 2.5-3.5 months: 85%; 3.5-6.0 months: 87%). Twenty-two negative biopsies or surgeries were performed among patients without LRR; negative biopsies/surgeries were more common after early PET/CT (≤2.5 months: 36%; 2.5-3.5 months: 9%; 3.5-6.0 months: 9%, P = 0.03). CONCLUSION: There is a lack of consensus reporting standards for response assessment after definitive radiotherapy for OPSCC. The Hopkins Criteria are an easily-implemented standard that appear to offer high accuracy for recurrence and death. These data support an initial PET/CT at least three months after radiotherapy to limit unnecessary diagnostic procedures.

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