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1.
Bioorg Med Chem Lett ; 52: 128405, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34624489

RESUMO

Vidarabine (ARA) was one of the earliest marine-related compounds to be used clinically for antiviral therapy, however, its fast metabolism is the main defect of this drug. To overcome this, we designed and synthesized a group of phosphamide-modified ARA compounds using ProTide technology. With a phosphamide modification, these compounds could become the substrate of specific phospholipase enzymes expressed in the liver. Among all 16 synthesized compounds, most showed stronger activity against herpes simplex virus type 1 (HSV-1) than ARA (EC50 of approximately 10 µM). The top three compounds were compound 2 (EC50 = 0.52 ± 0.04 µM), compound 6 (EC50 = 1.05 ± 0.09 µM) and compound 15 (EC50 = 1.18 ± 0.08 µM) (about 2 times higher than Sp type compound 2). This study provides evidence for use of the phosphamide modification, which could give ARA higher activity and liver cell targeting.


Assuntos
Antivirais/farmacologia , Dimetoato/farmacologia , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 1/efeitos dos fármacos , Vidarabina/farmacologia , Antivirais/síntese química , Antivirais/química , Dimetoato/química , Relação Dose-Resposta a Droga , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Vidarabina/síntese química , Vidarabina/química
2.
BMC Womens Health ; 20(1): 126, 2020 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-32552719

RESUMO

BACKGROUND: Nearly all uterine cervical cancer (UCC) cases result from human papillomavirus (HPV) infection. After high-risk HPV infection, most HPV infections are naturally cleared by humoral and cell-mediated immune responses. Thus, cervical lesions of only few patients progress into cervical cancer via cervical intraepithelial neoplasia (CIN) and lead to persistent oncogenic HPV infection. This suggests that immunoregulation plays an instrumental role in the carcinogenesis. However, there was a few studies on the relation between the immunologic dissonance and clinical characteristics of UCC patients. METHOD: We examined the related immune cells (Th1, Th2, Th17, and Treg cells) by flow cytometric analysis and analyzed their relations with UCC stages, tumor size, differentiation, histology type, lymph node metastases, and vasoinvasion. Next, we quantified the Th1, Th2, Th17, and Treg cells before and after the operation both in UCC and CIN patients. RESULTS: When compared with stage I patients, decreased levels of circulating Th1 cells and elevated levels of Th2, Th17, and Treg cells were detected in stage II patients. In addition, the imbalance of Th1/Th2 and Th17/Treg cells was related to the tumor size, lymph node metastases, and vasoinvasion. We found that immunological cell levels normalized after the operations. In general, immunological cell levels in CIN patients normalized sooner than in UCC patients. CONCLUSIONS: Our findings suggested that peripheral immunological cell levels reflect the patient's condition.


Assuntos
Linfócitos T Reguladores/metabolismo , Células Th1/metabolismo , Células Th17/metabolismo , Células Th2/metabolismo , Displasia do Colo do Útero/imunologia , Neoplasias do Colo do Útero/imunologia , Adulto , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Carga Tumoral , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/metabolismo , Displasia do Colo do Útero/sangue
3.
Future Oncol ; 15(6): 653-662, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30648886

RESUMO

The receptor tyrosine kinase Axl and its ligand Gas6 regulate fundamental biological processes, including cell proliferation, survival and motility, through multiple downstream signaling pathways. Evidence to date suggests that aberrant Axl expression frequently occurs in many malignancies, including hepatocellular carcinoma, and that this is critical for promoting cell proliferation, migration, angiogenesis and metastasis. Moreover, deregulated Axl expression or activation is reportedly associated with resistance to cancer drugs and targeted cancer therapies. Thus, Axl inhibitors may represent a novel therapeutic approach for cancer treatment. This Review summarizes the latest advances concerning the biological role of Axl in hepatocellular carcinoma and its potential clinical relevance.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Animais , Biomarcadores Tumorais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Suscetibilidade a Doenças , Regulação Neoplásica da Expressão Gênica , Humanos , Ligantes , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Terapia de Alvo Molecular , Prognóstico , Ligação Proteica , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas/química , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/química , Receptores Proteína Tirosina Quinases/genética , Relação Estrutura-Atividade , Receptor Tirosina Quinase Axl
4.
Appl Microbiol Biotechnol ; 103(19): 8191-8202, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31478060

RESUMO

Although the niche differentiation of anammox bacteria has been extensively observed in a lab-scale reactor, the inherent mechanism for this ecological phenomenon is still elusive. Here, we combined the long-term reactor operation, genome-centered metagenome, and metatranscriptome analyses to gain insight into the substrate competition and niche differentiation of Candidatus Jettenia and Candidatus Brocadia. After 146 days of operation, we found the anammox bacterial population shifted from Ca. Jettenia to Ca. Brocadia in the immobilization-anaerobic baffled reactor (I-ABR) with the ammonium and nitrite concentrations of 30 mg/L. Importantly, the genome and transcript comparisons of Ca. Jettenia and Ca. Brocadia showed that Ca. Brocadia harbored more complete function in cell chemotaxis, flagellar assembly, and two-component system and more redundant function in nitrite reduction, in which the genes were also highly expressed. Ca. Brocadia out-competed Ca. Jettenia at the mainstream condition. Meanwhile, though the highest biomass concentration led to the highest nitrogen removal rate (NRR) in the first compartment (C1), the competition of Ca. Jettenia and Ca. Brocadia could also affect the NRR of different compartments through affecting the bacterial activity. Substrate competition of anammox bacteria led to higher transcript activity of Ca. Jettenia and Ca. Brocadia in the second (C2) and fourth (C4) compartments, respectively. Further, high transcript activity of Ca. Brocadia led to the higher NRR in C4. A comparison of metabolic potential based on the metagenome-assembled genome adds a different dimension for understanding the discrepantly physiological characteristics and competition of anammox bacteria for wastewater treatment.


Assuntos
Amônia/metabolismo , Antibiose , Bactérias/classificação , Bactérias/metabolismo , Metagenômica/métodos , Anaerobiose , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Perfilação da Expressão Gênica/métodos , Oxirredução
5.
Environ Sci Technol ; 51(16): 9155-9164, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28737376

RESUMO

Substrate concentrations generally fluctuate in wastewaters. However, how anammox biomass behaves to overcome the stress of alternating feed loadings remains unclear. Here, we combined long-term reactor operation, batch tests, 16S rRNA transcript sequencing, and metabolomics analysis to investigate the aggregation of anammox biomass under the regulation of c-di-GMP, a key second messenger, in response to alternating feed loadings. We demonstrated that the aggregation process was significantly faster under alternating loadings and was significantly correlated with higher levels of c-di-GMP and extracellular polymeric substances (EPS) production. The increase in c-di-GMP was positively correlated with a higher relative transcript expression level in the c-di-GMP pathway-dependent community. The targeted metabolomics results indicated that the increased production of fructose 6-phosphate and UDP-N-acetyl-d-glucosamine, the precursor substances for the synthesis of exopolysaccharides, was induced by higher levels of c-di-GMP. Consequently, the granulation process was accelerated via EPS production. Higher levels of intracellular hydrophobic amino acids were also positively correlated with increased extracellular protein levels, considering the significant increase in peptides under alternating loadings. On the basis of our findings, we believe that c-di-GMP regulation and EPS production of the anammox biomass are important mechanisms to enhance its tolerance against unfavorable feed stress. These results highlight the role of c-di-GMP in anammox biomass as it works to survive in unfavorable niches.


Assuntos
GMP Cíclico/análogos & derivados , RNA Ribossômico 16S , Águas Residuárias , Acetilglucosamina
6.
J Cardiovasc Pharmacol ; 63(2): 107-12, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24126568

RESUMO

OBJECTIVE: Levosimendan is a calcium sensitizer that enhances myocardial contractility without increasing myocardial oxygen use. Limited data are available on its renal-protective effect, and no statistically significant effects have been found. A meta-analysis was conducted for randomized studies to show whether perioperative levosimendan use could reduce acute kidney injury (AKI) in patients undergoing cardiac surgery. DATA SOURCES: BioMed Central, PubMed EMBASE, and the Cochrane Central Register of Controlled Trials were searched for pertinent studies. STUDY SELECTION: Randomized trials that compared levosimendan versus placebo or any other control in cardiac surgery with data on AKI were included. Exclusion criteria were duplicate publications, nonadult studies, oral administration of levosimendan, and studies with no data on AKI. DATA EXTRACTION: Study endpoints, study design, population, clinical setting, levosimendan dosage, and treatment duration were extracted. DATA SYNTHESIS: Data from 529 patients in 5 randomized trials were analyzed. The analysis showed that levosimendan decreased postoperative incidence of AKI in the levosimendan group. CONCLUSIONS: This analysis suggests that levosimendan might reduce renal injury in adult patients undergoing cardiac surgery. More prospective randomized studies are needed to further demonstrate the benefits of levosimendan on renal protection in cardiac surgery.


Assuntos
Injúria Renal Aguda/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/métodos , Hidrazonas/uso terapêutico , Piridazinas/uso terapêutico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Adulto , Cardiotônicos/uso terapêutico , Humanos , Incidência , Assistência Perioperatória/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Simendana
7.
FEBS Open Bio ; 14(1): 127-137, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37964494

RESUMO

Sorafenib resistance greatly restricts its clinical application in patients with hepatocellular carcinoma (HCC). Numerous studies have reported that ID1 exerts a crucial effect in cancer initiation and development. Our previous research revealed an inhibitory role of ID1 in sorafenib resistance. However, the upstream regulatory mechanism of ID1 expression is unclear. Here, we discovered that ID1 expression is negatively correlated with promoter methylation, which is regulated by DNMT3B. Knockdown of DNMT3B significantly inhibited ID1 methylation status and resulted in an increase of ID1 expression. The demethylating agent 5-aza-2'-deoxycytidine (5-aza) remarkably upregulated ID1 expression. The combination of 5-aza with sorafenib showed a synergistic effect on the inhibition of cell viability.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Sorafenibe/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Linhagem Celular Tumoral , Azacitidina/farmacologia , Metilação , Proteína 1 Inibidora de Diferenciação/genética , Proteína 1 Inibidora de Diferenciação/metabolismo
8.
Sci Total Environ ; 914: 169629, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38157906

RESUMO

High level dissolved B, which poses risks to human health, has been widely observed in geothermal water. In the Guide Basin, NW China, a series of geothermal water samples along a fault show a wide range of B contents ranging from 3.14 to 8.33 mg/L, which are higher than the WHO Guideline value equaling 2.4 mg/L in drinking water. To identify the sources and fate of B, we conduct a comprehensive analysis of hydrochemistry and stable isotopes (D, 18O and 11B) of three thermal fields representing three stages of hydrogeochemical evolution (stages I, II and III). From stage I to III, there are trends of increasing mineral dissolution, which is supported by increasing mean reservoir temperature and concentrations of conservative elements (Cl, Na, K, Li and Si). Geothermal water in stage I with meteoric origin and the lowest reservoir temperature has the highest B/Na resulting from silicate dissolution and falls on the mixing line between granitoids and cold water on the plot of δ11B versus 1/B, showing the control of silicate dissolution. However, geothermal water in stage III has lower Ca, B Sr and B/Na than that in stage II. Because of the occurrence of other processes, geothermal water in stages II and III deviates from the LMWL. Compared with geothermal water in stage I, the increased Sr/Ca and decreased B/Ca show that B are removed by both coprecipitation and vapor separation. With the aid of B isotopes, we find vapor separation dominates in stage II, whereas carbonate precipitation dominates in stage III. Overall, a combined use of three isotopes (H, O and B) and three element ratios (B/Na, B/Ca and Sr/Ca) leads to a complete understanding of B cycle and hydrogeochemical evolution in hydrothermal systems.

9.
Zhonghua Yi Xue Za Zhi ; 93(42): 3369-74, 2013 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-24418034

RESUMO

OBJECTIVE: To explore the expressions of S100A8 and S100A9 in gastric cancer. METHODS: A total of 176 patients with gastric cancer, including 124 males and 52 females, were recruit from 1998 to 2004, average age 57(26-80)years. The expressions of S100A8 (n = 125) , S100A9 (n = 176) and S100A8/A9 heterodimer (calprotectin) in gastric tissue samples were assessed by immunohistochemistry and immunofluorescence. The co-localization of S100A9 and its dimerization partner S100A8 and heterodimer S100A8/A9 were examined by laser confocal scanning.Receiver operator characteristic (ROC) curve was used in determining the cut-off value of S100A9 and S100A8-positive inflammatory cell counts in evaluating the pathological TNM stage. To obtain associations between S100A9 or S100A8 cell counts and clinicopathologic variables, the data were cross-tabulated and χ(2)-test was performed. Cumulative survival was estimated by the Kaplan-Meier method. RESULTS: ROC curves using the S100A9 and S100A8-positive inflammatory cell counts were 0.623 and 0.522 for pathological TNM stages respectively. The cutoff values were 200 and 65 per 200× magnification field with a sensitivity of 61.48% and 51.09% and a specificity of 64.29% and 51.52% respectively. Patients with S100A9 positive expression (n = 77) had better overall survival than negative expression(n = 99) ((35.1 ± 10.8) vs (20.3 ± 3.0) months, P = 0.021). There was no statistical significance between S100A8 positive expression(n = 62) and negative expression(n = 63) ((26.4 ± 2.8) vs (29.5 ± 2.9) months, P = 0.145).In gastric cancer tissues, both S100A9 and S100A8 proteins were detected in tumor-infiltrating inflammatory cells while no case of S100A8/A9 heterodimer was found. In addition, S100A9 and S100A8 proteins were detected in inflammatory cells in chronic gastritis. Distribution of these two proteins also partly overlapped. CONCLUSIONS: S100A9 positive expression in gastric cancer tissues is associated with an excellent prognosis. But S100A8 positive expression has no prognostic association. Calprotectin expression differs between gastric cancer and gastritis.Further explorations are warranted.


Assuntos
Calgranulina A/metabolismo , Calgranulina B/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Complexo Antígeno L1 Leucocitário/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Gástricas/patologia
10.
Artigo em Chinês | MEDLINE | ID: mdl-24064126

RESUMO

OBJECTIVE: To investigate the awareness and use of banned pesticides among vegetable greenhouse farmers in a town of Ledu County, Qinghai Province, China and to provide a basis for the management and control of banned pesticides. METHODS: Local residents who lived in a town of Ledu County for more than 5 years were selected as subjects in August 2012. A questionnaire survey was conducted in 267 vegetable greenhouse farmers who were selected from five villages of the town by cluster random sampling. RESULTS: Of the 267 subjects, 249 (93.26%) completed and returned the questionnaires. Eighty-seven (34.9%) of the 249 subjects were aware of banned pesticides, and the banned pesticide awareness rate varied significantly among the subjects with different education levels (χ(2) = 11.061, P = 0.011). Only education level entered the regression equation in non-conditional logistic regression analysis. Only five (2.0%) of the 249 subjects knew the banned pesticides as well as the details. All the 249 subjects used banned pesticides to varying degrees in the past 5 years. Only 9.0% (17/189) of the vegetable greenhouse farmers knew the time pesticides were initially banned in China. CONCLUSION: The banned pesticide awareness rate is relatively low in the town of Ledu County, and this rate is influenced by education level. It is needed to spread the knowledge and hazards of banned pesticides.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Exposição Ocupacional/prevenção & controle , Praguicidas , Agricultura , China , Feminino , Humanos , Masculino , Inquéritos e Questionários
11.
BMC Cancer ; 12: 316, 2012 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-22838504

RESUMO

BACKGROUND: S100A9 was originally discovered as a factor secreted by inflammatory cells. Recently, S100A9 was found to be associated with several human malignancies. The purpose of this study is to investigate S100A9 expression in gastric cancer and explore its role in cancer progression. METHODS: S100A9 expression in gastric tissue samples from 177 gastric cancer patients was assessed by immunohistochemistry. The expression of its dimerization partner S100A8 and the S100A8/A9 heterodimer were also assessed by the same method. The effect of exogenous S100A9 on motility of gastric cancer cells AGS and BGC-823 was then investigated. RESULTS: S100A9 was specifically expressed by inflammatory cells such as macrophages and neutrophils in human gastric cancer and gastritis tissues. Statistical analysis showed that a high S100A9 cell count (> = 200) per 200x magnification microscopic field in cancer tissues was predictive of early stage gastric cancer. High S100A9-positive cell count was negatively correlated with lymph node metastasis (P = 0.009) and tumor invasion (P = 0.011). S100A9 was identified as an independent prognostic predictor of overall survival of patients with gastric cancer (P = 0.04). Patients with high S100A9 cell count were with favorable prognosis (P = 0.021). Further investigation found that S100A8 distribution in human gastric cancer tissues was similar to S100A9. However, the number of S100A8-positive cells did not positively correlate with patient survival. The inflammatory cells infiltrating cancer were S100A8/A9 negative, while those in gastritis were positive. Furthermore, exogenous S100A9 protein inhibited migration and invasion of gastric cancer cells. CONCLUSIONS: Our results suggested S100A9-positive inflammatory cells in gastric cancer tissues are associated with early stage of gastric cancer and good prognosis.


Assuntos
Calgranulina B/imunologia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Calgranulina A/imunologia , Calgranulina A/metabolismo , Calgranulina B/genética , Calgranulina B/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Feminino , Humanos , Inflamação/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neutrófilos/imunologia , Neutrófilos/metabolismo , Prognóstico , Multimerização Proteica , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade
12.
Zhonghua Xin Xue Guan Bing Za Zhi ; 40(10): 825-9, 2012 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-23302668

RESUMO

OBJECTIVE: To investigate the related factors and pathogens of ventilator-associated pneumonia (VAP) after heart surgery. METHODS: VAP was diagnosed in 105 patients out of 1688 cases (6.2%) who underwent heart surgery in our department between January 2004 and January 2011. Clinical data, pathogens and treatments were analyzed. RESULTS: Incidence of VAP was 6.2% (105/1688), and 53.0% (105/198) in patients who required more than 48 hours of mechanical ventilation. One hundred and ninety-eight pathogen strains were isolated by bacterial culture, in which Gram negative bacteria accounted for 69.2% (137/198), Gram positive bacteria 27.8% (55/198), and fungi for 3.0% (6/198). Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, and Staphylococcus aureus were the main pathogens of VAP. The independent risk factors for VAP were: age > 70 years, emergent surgery, perioperative transfusions, reintubation and days of mechanical ventilation (all P < 0.01). Median length of stay in the ICU for patients who developed VAP or not was (24.7 ± 4.5) days versus (3.2 ± 1.5) days, respectively (P < 0.05) and in-hospital mortality was 25.7% (27/105) versus 2.9% (46/1583) respectively (P < 0.05). CONCLUSIONS: Patients undergoing heart surgery have a high frequency of developing VAP, especially in patients that require more than 48 hours of mechanical ventilation. VAP is associated with high in-hospital mortality. Age > 70 years, emergent surgery, perioperative transfusions, reintubation and prolonged mechanical ventilation use are independent risk factors for VAP in patients following cardiac surgery. Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, and Staphylococcus aureus are the main pathogens of VAP.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Pneumonia Bacteriana/microbiologia , Pneumonia Associada à Ventilação Mecânica/microbiologia , Acinetobacter baumannii , Adulto , Idoso , Feminino , Humanos , Klebsiella pneumoniae , Masculino , Pessoa de Meia-Idade , Pseudomonas aeruginosa , Estudos Retrospectivos , Fatores de Risco
13.
World J Gastrointest Oncol ; 14(6): 1067-1085, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35949213

RESUMO

Circular RNAs (circRNAs) have covalently closed loop structures at both ends, exhibiting characteristics dissimilar to those of linear RNAs. Emerging evidence suggests that aberrantly expressed circRNAs play crucial roles in hepatocellular carcinoma (HCC) by affecting the proliferation, apoptosis and invasive capacity of HCC cells. Certain circRNAs may be used as biomarkers to diagnose and predict the prognosis of HCC. Therefore, circRNAs are expected to become novel biomarkers and therapeutic targets for HCC. Herein, we briefly review the characteristics and biological functions of circRNAs, focusing on their roles in HCC to provide new insights for the early diagnosis and targeted therapy of HCC.

14.
World J Gastroenterol ; 28(46): 6433-6477, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36569275

RESUMO

Hepatectomy is currently considered the most effective option for treating patients with early and intermediate hepatocellular carcinoma (HCC). Unfortunately, the postoperative prognosis of patients with HCC remains unsatisfactory, predominantly because of high postoperative metastasis and recurrence rates. Therefore, research on the molecular mechanisms of postoperative HCC metastasis and recurrence will help develop effective intervention measures to prevent or delay HCC metastasis and recurrence and to improve the long-term survival of HCC patients. Herein, we review the latest research progress on the molecular mechanisms underlying postoperative HCC metastasis and recurrence to lay a foundation for improving the understanding of HCC metastasis and recurrence and for developing more precise prevention and intervention strategies.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/prevenção & controle , Prognóstico , Hepatectomia/efeitos adversos , Estudos Retrospectivos
15.
Cancer Manag Res ; 14: 1113-1124, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35300064

RESUMO

Purpose: Autologous fat grafting (AFG) is a technique that can improve the appearance of breasts in surgical patients. There are currently few studies on breast-conserving surgery (BCS) combined with immediate AFG, although we believe that it could achieve satisfactory effects. Therefore, the purpose of this study is to observe the effects of BCS combined with immediate AFG on oncologic safety, satisfaction and psychology of breast cancer patients. Patients and Methods: We retrospectively collected the data of 85 breast cancer patients from February 2018 to October 2018. After screening, 40 patients in AFG group (AG, BCS combined with immediate AFG) and 40 patients in control group (CG, BCS alone) were finally included in the study. The primary outcomes were the survival, tumor recurrence and metastasis, and BREAST-Q score of patients. The secondary outcomes were short and long-term complications, degree of depression and anxiety of patients. Results: A total of 80 patients were included in the analysis. There was no significant difference in the clinicopathological data between the two groups (P>0.05). The average follow-up time of the two groups was 40.58±2.630 and 40.28±2.679 months. In the analysis of oncologic safety, no patients died in AG and 1 patient died in CG. In addition, there was no significant difference between the two groups in terms of the overall recurrence rate and the distribution of recurrence types (P>0.05). As for satisfaction, the BREAST-Q score of AG was significantly higher than that of CG (57.85±4.833 vs 51.93±5.045, P<0.001). In the secondary outcomes, there was no short-term complication specified in the study; in the long-term complications, the incidence of calcification in AG was not significantly higher than that in CG (P=0.065). In the analysis of depression and anxiety, there was no significant difference between the two groups (P>0.05). Conclusion: BCS combined with immediate AFG can significantly improve patients' satisfaction without increasing the risk of death and tumor recurrence. However, it does not seem to play a role in improving the conditions of depression and anxiety.

16.
Front Public Health ; 10: 1047965, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36699912

RESUMO

Objective: The burden of both general and drug-resistant tuberculosis in rural areas is higher than that in urban areas in China. To characterize the genetic structure and transmission risk of Mycobacterium tuberculosis in rural China, we used whole genome sequencing to analyze clinical strains collected from patients in two counties of Yichang for three consecutive years. Methods: From 2018 to 2020, sputum samples were collected for cultures from patients with suspected tuberculosis in Yidu and Zigui county, and DNA was extracted from the positive strains for genome sequencing. The online SAM-TB platform was used to identify the genotypes and drug resistance-related mutations of each strain, establish a phylogenetic tree, and calculated the genetic distances between pairwise strains. Twelve single nucleotide polymorphisms (SNPs) were used as thresholds to identify transmission clusters. The risk of related factors was estimated by univariable and multivariable logistic regression. Results: A total of 161 out of the collected 231 positive strains were enrolled for analysis, excluding non-tuberculous mycobacterium and duplicate strains from the same patient. These strains belonged to Lineage 2 (92, 57.1%) and Lineage 4 (69, 42.9%), respectively. A total of 49 (30.4%) strains were detected with known drug resistance-related mutations, including 6 (3.7%) multidrug-resistant-TB (MDR-TB) strains and 11 (6.8%) RIF-resistant INH-susceptible TB (Rr-TB) strains. Six of the MDR/Rr-TB (35.3%) were also resistant to fluoroquinolones, which made them pre-extensively drug-resistant TB (pre-XDR-TB). There were another seven strains with mono-resistance to fluoroquinolones and one strain with resistance to both INH and fluoroquinolones, making the overall rate of fluoroquinolones resistance 8.7% (14/161). A total of 50 strains (31.1%) were identified as transmission clusters. Patients under 45 years old (adjusted odds ratio 3.46 [95% confidential intervals 1.28-9.35]), treatment-naive patients (6.14 [1.39-27.07]) and patients infected by lineage 4 strains (2.22 [1.00-4.91]) had a higher risk of transmission. Conclusion: The drug resistance of tuberculosis in rural China, especially to the second-line drug fluoroquinolones, is relatively serious. The standardized treatment for patients and the clinical use of fluoroquinolones warrant attention. At the same time, the recent transmission risk of tuberculosis is high, and rapid diagnosis and treatment management at the primary care needs to be strengthened.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Antituberculosos/uso terapêutico , Sequência de Bases , China/epidemiologia , Farmacorresistência Bacteriana Múltipla/genética , Fluoroquinolonas/uso terapêutico , Mycobacterium tuberculosis/genética , Filogenia , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Sequenciamento Completo do Genoma
17.
Am J Pathol ; 177(2): 586-97, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20581057

RESUMO

S100A6 has been implicated in a variety of biological functions as well as tumorigenesis. In this study, we investigated the expression status of S100A6 in relation to the clinicopathological features and prognosis of patients with gastric cancer and further explored a possible association of its expression with epigenetic regulation. S100A6 expression was remarkably increased in 67.5% of gastric cancer tissues as compared with matched noncancerous tissues. Statistical analysis demonstrated a clear correlation between high S100A6 expression and various clinicopathological features, such as depth of wall invasion, positive lymph node involvement, liver metastasis, vascular invasion, and tumor-node metastasis stage (P < 0.05 in all cases), as well as revealed that S100A6 is an independent prognostic predictor (P = 0.026) significantly related to poor prognosis (P = 0.0004). Further exploration found an inverse relationship between S100A6 expression and the methylation status of the seventh and eighth CpG sites in the promoter/first exon and the second to fifth sites in the second exon/second intron. In addition, the level of histone H3 acetylation was found to be significantly higher in S100A6-expressing cancer cells. After 5-azacytidine or trichostatin A treatment, S100A6 expression was clearly increased in S100A6 low-expressing cells. In conclusion, our results suggested that S100A6 plays an important role in the progression of gastric cancer, affecting patient prognosis, and is up-regulated by epigenetic regulation.


Assuntos
Proteínas de Ciclo Celular , Epigênese Genética , Proteínas S100 , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/farmacologia , Azacitidina/farmacologia , Sequência de Bases , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral/efeitos dos fármacos , Metilação de DNA , Feminino , Humanos , Ácidos Hidroxâmicos/farmacologia , Neoplasias Hepáticas/secundário , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas , Inibidores da Síntese de Proteínas/farmacologia , Proteína A6 Ligante de Cálcio S100 , Proteínas S100/genética , Proteínas S100/metabolismo , Neoplasias Gástricas/patologia , Regulação para Cima
18.
Histopathology ; 59(2): 198-206, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21884198

RESUMO

AIMS: The secreted phospholipase A2 type IIA (PLA2G2A) gene has been identified as a modifier of intestinal adenoma multiplicity in Apc(Min/+) mice. The aim of the present study was to analyse the clinical significance of PLA2G2A expression in human gastric cancer. METHODS AND RESULTS: Using immunohistochemistry, cytoplasmic immunoreactivity of PLA2G2A was observed in 27% (40 of 149) of gastric cancer tissues compared with negative staining in normal mucosa. The PLA2G2A expression rate in well-differentiated carcinoma was elevated significantly compared with that in poorly differentiated carcinoma (46% versus 19%, P = 0.001). Statistical analysis also revealed that PLA2G2A expression correlated negatively with depth of mural invasion, lymph node metastasis and tumour-node-metastasis (TNM) stage (P < 0.05). Patients with positive PLA2G2A expression showed higher 5-year overall survival than those with negative expression (P = 0.0004). In intestinal metaplasia, PLA2G2A was found to be abundant in Paneth cells. The coexistence of PLA2G2A and lysozyme was observed in Paneth cell-rich gastric cancer (P < 0.0001). CONCLUSIONS: PLA2G2A may predict survival and might be a potential biomarker for early detection and individualized therapy.


Assuntos
Adenocarcinoma/enzimologia , Fosfolipases A2 do Grupo II/metabolismo , Neoplasias Gástricas/enzimologia , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , China/epidemiologia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Muramidase/metabolismo , Invasividade Neoplásica , Celulas de Paneth/enzimologia , Celulas de Paneth/patologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida
19.
Zhonghua Wai Ke Za Zhi ; 49(9): 789-94, 2011 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-22177431

RESUMO

OBJECTIVE: To investigate the effect of intensive insulin therapy on resting energy expenditure in postoperative patients underwent radical distal gastrectomy. METHODS: Sixty-four patients with gastric neoplasms in the middle or lower part of stomach from January to October 2010 were enrolled and underwent radical distal gastrectomy, then were randomized to intensive insulin therapy (IIT) group to keep glucose levels from 4.4 to 6.1 mmol/L or conventional insulin therapy (CIT) group to keep levels from 4.4 to 10.0 mmol/L. Resting energy expenditure (REE), respiratory quotient (RQ), resting energy expenditure per kilogram (REE/kg) and lipid oxidation ratio (LOR) were monitored by indirect energy metabolic system on preoperative and postoperative 1(st), 3(rd) and 7(th) day. Fasting blood glucose and insulin concentration were measured for HOMA-IR assessment. RESULTS: Compared with preoperative baseline, postoperative REE, REE/kg, LOR, Ln-HOMA-IR increased dramatically (P < 0.05, respectively). RQ decreased markedly (P < 0.05). Compared with group CIT, IIT reduced the REE/kg level [(27.2 ± 1.3) kcal/kg vs. (30.0 ± 1.5) kcal/kg, P = 0.008; (24.7 ± 1.4) vs. (25.7 ± 1.6) kcal/kg, P = 0.013]; and decreased the Ln-HOMA-IR score (P = 0.019 and 0.028) on postoperative 1(st) and 3(rd) day; IIT could decrease obviously the level of C-reaction protein level on postoperative 1(st) and 3(rd) day (P = 0.017, 0.006). The total protein and albumin concentration in IIT group were more than its levels in group CIT (P = 0.023, 0.009). CONCLUSION: There are some benefits of IIT in reducing mean energy expenditure and the consumption of proteins, decreasing postoperative insulin resistance level in this small population underwent radical distal gastrectomy.


Assuntos
Resistência à Insulina , Insulina/administração & dosagem , Neoplasias Gástricas/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Metabolismo Energético , Feminino , Gastrectomia , Humanos , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Neoplasias Gástricas/cirurgia , Adulto Jovem
20.
Water Environ Res ; 93(8): 1455-1465, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33434312

RESUMO

Substrate concentrations greatly influence bacterial growth and metabolism. However, optimal nitrogen concentrations for anammox bacteria in nitrogen-limited environments remain unclear. Here, we observed enhanced nitrogen metabolism and anabolism of anammox bacteria at low nitrogen conditions. Efficient nitrogen removal was achieved at ammonium and nitrite influent concentration of 30 mg/L under HRT of 1 hr, with an average nitrogen removal rate (NRR) of 0.73 kg N/(m3 ·day) in I-ABR composed of four compartments. The highest anammox activity of 6.25 mmol N/ (gVSS·hr) was observed in the fourth compartment (C4) with the lowest substrate levels (ammonium and nitrite of 11.6 mg/L and 7 mg/L). This could be resulted from the highest expression level of genes involved in nitrogen metabolism in C4, which was 1.49-1.67 times higher than that in other compartments. Besides, the second compartment (C2) exhibited the most active anabolism at ammonium and nitrite of 17 mg/L and 13 mg/L, respectively, which contributed to the most active amino acid synthesis and thus the highest EPS (1.35 times higher) in C2. This enhanced amino acid auxotrophy between anammox bacteria with heterotrophs, and consequently, heterotrophs thrived and competed for nitrite. These results hint at the potential application of anammox process in micro-polluted water. PRACTITIONER POINTS: High nitrogen removal and efficient biomass retention at low nitrogen concentrations under short HRT was achieved in I-ABR. Optimal concentrations for anammox nitrogen removal and anabolism were discussed under low nitrogen concentrations. More active anabolism contributed to enhanced amino acid synthesis and thus higher EPS contents. Low substrate levels led to enhanced expression of genes involved in nitrogen metabolism and thus high anammox activity.


Assuntos
Compostos de Amônio , Nitrogênio , Reatores Biológicos , Desnitrificação , Oxirredução
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