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1.
Int J Pharm ; 642: 123190, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37391109

RESUMO

Tendon adhesion is one of the sequelae of tendon injury and can lead to disability in severe cases. Metformin is a commonly used antidiabetic drug. Some studies had shown that metformin could reduce tendon adhesion as well. Considering the characteristic of low absorption rate and short half-life, we established a sustained-release system, i.e., hydrogel-nanoparticle system to deliver metformin. In vitro, metformin could effectively suppress TGF-ß1-induced cell proliferation and accelerate cell apoptosis, according to cell counting kit-8, flow cytometry, and 5-ethynyl-2'-deoxyuridine (EdU) staining studies. In vivo, hydrogel-nanoparticle/metformin system could significantly lower adhesion scores and improve the gliding function of repaired flexor tendons, as well as decrease the expression of fibrotic proteins Col1a1, Col3a1, and α-smooth muscle actin (α-SMA). Histological staining revealed that the inflammation had subsided and that the gap between the tendon and the surrounding tissue was wider in the hydrogel-nanoparticle/metformin treatment group. Finally, we speculated that effect of metformin on reducing tendon adhesion might be achieved by regulating both Smad and MAPK-TGF-ß1 signaling pathways. In conclusion, metformin delivered through hydrogel-nanoparticle sustained-release system may be a promising strategy for coping with tendon adhesion.


Assuntos
Metformina , Nanopartículas , Traumatismos dos Tendões , Humanos , Fator de Crescimento Transformador beta1 , Metformina/farmacologia , Hidrogéis , Preparações de Ação Retardada , Traumatismos dos Tendões/tratamento farmacológico , Aderências Teciduais
2.
J Thorac Dis ; 15(2): 679-689, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36910047

RESUMO

Background: Unlike the conventional spectral analyses of spectral computed tomography (CT) that cannot fully represent the whole lesion, the volumetric quantitative analysis reveals the information of the whole lesion and is of more accurate. So this study sought to evaluate the value of volumetric quantitative analysis in the differential diagnosis of pulmonary adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). Methods: Fifty-seven patients with lung cancer confirmed by pathology, including 35 ADC and 22 SQCC patients, were retrospectively analyzed. Calcium concentration and effective-Z (Eff-Z) in plain scan (PS), iodine concentration, and water concentration in the arterial phase (AP) were measured. The Student t-test or rank-sum test was used to determine the statistically significant parameters. Receiver operating characteristic (ROC) curve was used, and the corresponding area under the curve (AUC), sensitivity and specificity was calculated to evaluate the diagnostic efficacy in differential diagnosis of ADC and SQCC. Results: In the volumetric quantitative analysis of spectral CT, the concentration of calcium [(6.97±2.83) mg/cm3], Eff-Z (7.90±0.14), and iodine [1.42 (0.84) mg/cm3] was significantly higher in ADC than SQCC [(5.14±2.39) mg/cm3, (7.80±0.10), 1.16 (0.65) mg/cm3, t=2.513, 2.860, Z=-2.246, P=0.015, 0.006, 0.025], but the concentration of water was significantly lower in ADC [995.00 (38.70) mg/cm3] than SQCC [1,007.00 (14.38) mg/cm3, Z=-2.082, P=0.037]. Moreover, whether it's ADC or SQCC, the concentrations of calcium [(8.51±4.28) mg/cm3, (5.96±2.50) mg/cm3], Eff-Z (7.97±0.20, 7.86±0.13), and water [1,007.00 (14.38) mg/cm3, 1,029.28 (10.49) mg/cm3] were lower in the volumetric spectral analysis than the conventional spectral analysis, while the concentration of iodine [1.33 (0.80) mg/cm3, 0.94 (0.63) mg/cm3] was significantly higher in the volumetric spectral analysis than the conventional spectral analysis. The ROC curve analysis showed that the areas under the curves (AUC) (0.76, 0.76, 0.75, 0.71), sensitivity (66.7%, 66.7%, 66.7%, 85.2%), and specificity (92.3%, 84.6%, 86.9%, 69.2%) of the volumetric spectral analysis parameters for the differential diagnosis of ADC and SQCC were higher than those of the conventional spectral analysis [(0.65, 0.66, 0.73, 0.63), (44.4%, 48.1%, 59.3%, 66.7%), (69.2%, 69.2%, 84.6%, 53.8%)] parameters. Conclusions: The volumetric quantitative analysis has a promising advantage in the observation range of whole lesions, it may be invaluable in the differential diagnosis of ADC and SQCC, and is worthy of clinical recommendation.

3.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-986011

RESUMO

Objective: To understand the social security situation of current cases of pneumoconiosis in non-coal mine industries in Jiangsu Province, and to provide reference for the treatment and security work of pneumoconiosis patients. Methods: From January to October 2020, a follow-up survey was conducted on 4038 cases of pneumoconiosis in non-coal mine industries of the province from October 1949 to December 2019. The age, type of pneumoconiosis, industry type, and social security status of the patients were collected. Namely, work-related injury insurance, employer compensation, basic medical insurance for urban and rural residents, major illness insurance, etc. SPSS 19.0 was used for statistical description and analysis. Results: The cases of pneumoconiosis in non-coal mine industries in Jiangsu Province ranged in age from 36 to 105 (70.78±8.43) years old, and had been exposed to dust for 1 to 55 (19.27±9.29) years. Silicosis was the main form (3875 cases, 95.96%), and non-metallic mining and dressing industry was the main form (2618 cases, 64.83%). A total of 3991 cases (98.84%) of pneumoconiosis patients enjoyed social security, most of them were urban and rural residents with basic medical insurance (3624 cases, 89.75%), but there were still 47 patients without any social security. 15 cases (0.37%) enjoyed the subsistence allowance, with the monthly allowance amount ranging from 104 to 3960 yuan, with the average amount of 954.87 yuan/month. Conclusion: In Jiangsu Province, the proportion of pneumoconiosis patients in non-coal mine industries enjoying social security is relatively high, but there are still patients who do not enjoy any social security, and the difference in the amount of subsistence allowance is slightly larger. It is necessary to further improve the medical security of pneumoconiosis patients and improve their quality of life.


Assuntos
Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Previdência Social , Prevalência , Qualidade de Vida , Pneumoconiose/epidemiologia , Silicose/epidemiologia , Etoposídeo , Ifosfamida , Mesna , Minas de Carvão , China/epidemiologia
4.
Acta Anatomica Sinica ; (6): 607-612, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1015282

RESUMO

Objective To investigate the effects of microRNA( miR)-29a-3p on the proliferation and invasion of gastric cancer cells and analyze its related molecular mechanism. Methods The expression level of miR-29a-3p in gastric cancer cells was detected, and the role of miR-29a-3p in the proliferation, migration, and invasion of gastric cancer cells was evaluated. Western blotting and luciferase analysis showed that miR-29a-3p was directly bound to Serpinhl 3 ' -untranslated region(3' UTR). In addition, the effects of the miR-29a-3p/Serpinhl axis on the proliferation, migration, and invasion of gastric cancer cells were detected by MTT assay, colony formation assay, and Transwell assay in vitro. Results After transfection, the expression of miR-29a-3p in the miR-29a-3p mimic group was significantly higher than that in the miR-29a-3p negative control and blank group. After transfection, the proliferation of BGC823 cells decreased significantly. Luciferase analysis showed that miR-29a-3p inhibited the expression of Serpinhl by targeting the 3 ' UTR of Serpinhl. In addition, overexpression of miR-29a-3p significantly inhibited the proliferation, invasion, and migration of gastric cancer cells by targeting Serpinhl. Conclusion MiR-29a-3p can target Serpinhl and regulate the proliferation and invasion of gastric cancer cells.

5.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-935810

RESUMO

Objective: To understand the incidence of pneumoconiosis in the non-coal mining industry in Jiangsu Province, and provide reference for the prevention and control of pneumoconiosis in the non-coal mining industry. Methods: The data of 7019 newly diagnosed pneumoconiosis patients in non-coal mining industry in Jiangsu Province from January 1956 to December 2019 were collected through the Jiangsu Province Pneumoconiosis Follow-up Network Report System, including the gender of the pneumoconiosis patients, the name of the employer and the location, the industry classification of the employer, the duration of dust exposure in dust exposure, the name of occupational pneumoconiosis disease, the date of diagnosis of pneumoconiosis, etc. The collected case data of patients with pneumoconiosis were entered into the statistical software, and the characteristics of the patients' diagnosis time, region and industry were analyzed. Results: The number of confirmed pneumoconiosis patients in the non-coal mining industry in Jiangsu Province was mostly in 2007 (395 cases) , concentrated in Wuxi City (40.96%, 2875/7019) and Suzhou City (27.72%, 1946/7019) . The industries to which the patients belonged were mainly non-metallic mining and dressing (60.95%, 4278/7019) , and the most common type of pneumoconiosis was silicosis (96.40%, 6766/7019) . The patients were mainly stageⅠpneumoconiosis (61.33%, 4305/7019) . There were statistically significant differences in the mean age of diagnosis and the average duration of dust exposure among patients with different pneumoconiosis stages (P<0.01) . The differences in the average diagnosis age and the average duration of dust exposure of patients with different types of pneumoconiosis were statistically significant (P<0.05) , the mean age of diagnosis and the average duration of dust exposure of electric welders were the smallest, which were (44.92±7.74) years old and (17.38±10.15) years, respectively. Conclusion: The regional and industry distribution characteristics of new pneumoconiosis patients in the non-coal mining industry in Jiangsu Province are obvious, and attention should be paid to the treatment of pneumoconiosis patients with young diagnosed age and short duration of dust exposure, as well as the personal protection and health protection of front-line workers such as electric welders who are exposed to productive dust in a short period of time.


Assuntos
Adulto , Humanos , Pessoa de Meia-Idade , Minas de Carvão , Poeira , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Pneumoconiose/epidemiologia , Silicose/epidemiologia
6.
Int Immunopharmacol ; 87: 106757, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32769067

RESUMO

BACKGROUND: Multiple molecular subtypes with distinct clinical outcomes in colon cancer have been identified in recent years. Nonetheless, the autophagy-related molecular subtypes as well as its mediated tumor microenvironment (TME) cell infiltration characteristics have not been fully understood. METHODS: Based on the seven colon cancer cohorts with 1580 samples, we performed a comprehensive genomic analysis to explore the molecular subtypes mediated by autophagy-related genes. The single-sample gene-set enrichment analysis (ssGSEA) was used to quantify the relative abundance of each cell infiltration in the TME. Unsupervised methods were used to perform autophagy subtype clustering. Least absolute shrinkage and selection operator regression (LASSO) was used to construct autophagy characterization score (APCS) signature. RESULTS: We determined three distinct autophagy-related molecular subtypes in colon cancer. The three autophagy subtypes presented significant survival differences. Microenvironment analyses revealed the heterogeneous TME immune cell infiltration characterization between three subtypes. Cluster 1 autophagy subtype was characterized by abundant innate and adaptive immune cell infiltration. This subtype exhibited an enhanced stromal activity including activated pathways of epithelial-mesenchymal transition, TGF-ß and angiogenesis, and an increased infiltration of fibroblasts and endothelial cells. The expression of immune checkpoint molecules was also significantly up-regulated, which may mediate immune escape in Cluster 1 subtype. Cluster 2 subtype was characterized by relatively lower TME immune cell infiltration and enhanced DNA damage repair pathways. Cluster 3 subtype was characterized by the suppression of immunity. Patients with high APCS, with poorer survival, presented a significantly positive correlation with TME stromal activity. Low APCS, relevant to activated damage repair pathways, showed enhanced responses to anti-PD-1/PD-L1 immunotherapy. Two immunotherapy cohorts confirmed patients with low APCS exhibited prominently enhanced clinical response and treatment advantages. CONCLUSIONS: This study may help understand the molecular characterization of autophagy-related subtypes. We demonstrated the autophagy genes in colon cancer could drive the heterogeneity of TME immune cell infiltration. Our study represented a step toward personalized immunotherapy in colon cancer.


Assuntos
Autofagia/genética , Neoplasias do Colo/genética , Neoplasias do Colo/imunologia , Neoplasias do Colo/mortalidade , Neoplasias do Colo/terapia , Regulação Neoplásica da Expressão Gênica , Humanos , Imunoterapia , Estimativa de Kaplan-Meier , Mutação , Microambiente Tumoral/imunologia
7.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-863887

RESUMO

Objective:To study the role of miR-155 in the differentiation of papillary thyroid carcinoma (PTC) cells, and to explore the possible mechanism.Methods:Human miR-155 analogues were constructed and transfected into PTC BCPAP cells in vitro. CCK8 test and Transwell test were used to observe the changes of cell proliferation and invasiveness. The miR-155 was transfected into BCPAP cells in vitro and the protein background and phosphorylation expression of MAPK pathway were detected by Western blot. ERK pathway inhibitor U0126 was given to observe whether it could reverse the abnormal proliferation and invasion of thyroid cancer cells caused by over-expression of miR-155.Results:The proliferation of BCPAP cells was detected by CCK8 test 48 hours after overexpression of miR-155, and the invasiveness of thyroid cancer cells was significantly enhanced by Transwell test 48 hours after overexpression of miR-155 ( P<0.05) ; Western blot method found that the expression of JNK, ERK and p38 in MAPK signal pathway was significantly up-regulated ( P<0.05) . At the same time, the expression of p-ERK protein in the cells was increased significantly ( P<0.05) . The expression of p-ERK in the cells treated with ERK pathway inhibitor U0126 and miR-155 was significantly lower than that in the miR-155 group ( P<0.05) . By detecting the proliferation and invasion of cells in each group, we found that the U0126 could reverse the proliferation and invasion promoting effect caused by miR-155. Conclusion:miR-155 can promote the proliferation and invasion of PTC BCPAP cells by activating the ERK pathway of MAPK pathway, which provides a potential target for the treatment of thyroid cancer.

8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-942048

RESUMO

OBJECTIVE@#To analyze the clinicopathological characteristics of prostate cancer patients undertaking radical prostatectomy with single positive core biopsy, and to optimize the rational choice of therapeutic strategy.@*METHODS@#In the study, 53 patients with single positive core prostate biopsy and treated by radical prostatectomy from January 2010 to December 2018, were analyzed retrospectively. The mean age was (69.7±6.9) years (54-81 years), the mean prostate specific antigen (PSA) level was (9.70±5.24) μg/L (1.69-25.69 μg/L), and the mean prostate volume was (50.70±28.39) mL (12.41-171.92 mL). Thirty-nine out of 54 (73.6%) patients presented Gleason score with 6, 11 patients (20.8%) had Gleason score of 7 and 3 patients (5.7%) showed Gleason score ≥8. For clinical stages, 6 out of the 53 patients (11.3%) had prostate cancer in cT1, 44 cases (83.0%) had prostate cancer in cT2, and 3 cases (5.7%) in cT3.The patients were divided into subgroups according to age, preoperative PSA level, Gleason score, percentage of tumor in single needle tissue and clinical stage, and the differences of their clinicopathological characteristics were compared.@*RESULTS@#Postoperative Gleason score of 6, 7 and ≥8 were found in 20 cases (37.7%), 21 cases (39.6%) and 10 cases (18.9%) respectively, another 2 cases (3.8%) were pT0 prostate cancer; pathological stages of T0, T2a, T2b, T2c and T3 were found in 2 cases (3.8%), 9 cases (17.0%), 2 cases (3.8%), 29 cases (54.7%) and 11 cases (20.8%) respectively; 11 cases (20.8%) had positive surgical margin, 10 cases (18.9%) had extracapsular invasion of prostate, and 1 case (1.9%) showed seminal vesicle invasion. Forty-two cases (79.2%) had multifocal lesions and 37 cases (69.8%) presented bilateral lesion. Compared with the biopsy Gleason score, the postoperative Gleason score was downgrated in 3 cases (5.7%), unchanged in 28 cases (52.8%), and upgraded in 20 cases (37.7%), of which 2 cases (3.8%) were pT0. Compared with the clinical stage, the postoperative pathological stage decreased in 2 cases (3.8%), unchanged in 10 cases (18.9%), and upgraded in 41 cases (77.4%). According to the postoperative pathology, the patients were divided into two groups: microfocus cancer group (n=8) and non-microfocus cancer group (n=45). The difference between the two groups in the percentage of tumor in the single-needle tissue ≤5% was statistically significant (P=0.014). Other parameter diffe-rences including age, prostate volume, and preoperative prostate special antigen density (PSAD) and Gleason scores were not statistically significant (P>0.05). The method to determine the location of cancer at the apex of prostate according to biopsy results showed 41.4% (12/29) false negative rate and 50.0% (12/24) false positive rate. There was statistically significant difference between the actual cases of lymph node dissection and reserved nerve and the cases of scheme selection in theory according to the postoperative pathology (P < 0.05).@*CONCLUSION@#The proportion of single needle cancer tissue less than or equal to 5% is a predictor of prostate microfocal cancer. 37.7% cases had pathological upgrading and 77.4% cases had pathological staging upgrading. When choosing the operation scheme, such as sexual nerve reserved, lymph node dissection and apex operation skill, it is necessary to comprehensively analyze multiple factors, such as tumor risk classification, prediction factors of nomogram, multi-parameter MRI and intraoperative situation and so on.


Assuntos
Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Biópsia por Agulha , Gradação de Tumores , Estadiamento de Neoplasias , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata , Estudos Retrospectivos
9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-828397

RESUMO

Eleven compounds were isolated and purified from Sorghum vulgare root extract, through column chromatography over silica gel, MCI gel, and preparative HPLC. Their structures were established by MS, 1 D NMR and 2 D NMR data as sorgholide A(1), β-sitosterol(2), stigmastero(3), daucosterol(4), 4-methoxycinnamic acid(5), taxiphyllin(6), chlorogenic acid(7), p-hydroxybenzaldehyde(8), succini acid(9), trans-p-hydroxycinnamic acid(10), obtusalin(11). Compounds 4,5 and 9-11 were reported from this species for the first time, and compound 1 is the first 24 ring dimeric double lactonol glycoside formed by reverse polymerization of p-hydroxyphenylacetate glucoside, named sorgholide A.


Assuntos
Glicosídeos Cardíacos , Glucosídeos , Glicosídeos , Fenóis , Sorghum
10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-804796

RESUMO

Objective@#To analyze the characteristics and patterns of occupational pneumoconiosis in Jiangsu Province, China, from 2006 to 2017, and to provide a scientific basis for government departments to develop effective interventions and preventive strategies against occupational pneumoconiosis.@*Methods@#The data of 9327 patients with occupational pneumoconiosis were retrieved from the online report of occupational pneumoconiosis in Jiangsu Province from 2006 to 2017. Excel worksheet and SPSS 20.0 software were used to organize and analyze the data, respectively. An epidemiological statistical analysis was performed on age of onset, length of dust exposure, type of work, industry category, type of pneumoconiosis, annual incidence of pneumoconiosis, regional distribution, enterprise scale, and economic category in those patients.@*Results@#A total of 9 327 patients with occupational pneumoconiosis were reported in Jiangsu Province from 2006 to 2017. In those patients, 8 559 were newly diagnosed and 768 had advanced disease. The male-female ratio was 16.34:1.Patients with stage I pneumoconiosis(6 994, 74.99%) were dominant in all the patients. The mean age of onset and length of dust exposure were 58.5±10.7 and 15.3±10.9 years, respectively. Most of the patients (6 012, 64.46%) had an age of onset between 50 and 69 years. For the length of dust exposure, the highest percentage was observed in patients exposed for no more than 5 years (2 231, 23.92%).The largest number of patients diagnosed with pneumoconiosis(1 200, 12.87%) was reported in 2010. Most of the patients(7 012, 75.18%) were from four cities, i.e, Wuxi (2 090, 22.41%), Yancheng (1 987, 21.30%), Suzhou (1 552, 16.64%), and Xuzhou (1 383, 14.83%). In all the patients, the incidence of silicosis (6791, 72.81%) was highest, followed by coal worker pneumoconiosis (1 364, 14.62%) and electric welder pneumoconiosis (563, 6.04%).Pneumoconiosis complicated by tuberculosis was found in 28 (0.3%) patients.A total of 1616 (17.33%) patients were reported in health, social security, and social welfare industries, while 1474 (15.80%) patients worked for coal mining and washing. Rock drillers (2 818, 30.21%) were dominant in those patients.State-owned economic enterprises reported the largest number of patients(5 441, 58.34%).Patients from small enterprises (4 323, 46.35%) had the highest percentage.@*Conclusion@#Pneumoconiosis is an occupational disease with a high incidence in Jiangsu Province. Pneumoconiosis patients show an industry- and job-centered distribution. The length of dust exposure is decreasing.

11.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-690947

RESUMO

<p><b>OBJECTIVE</b>To express and purify the mouse endothelial cell-targeted recombinant Notch ligand protein mD1R, and to investigate its effect on hematopoiesis after carbon tetrachloride damage.</p><p><b>METHODS</b>PCR was performed to clone and construct the expression vector pET22b(+)-mD1R. The mD1R successfully transformed into E. coli was induced by IPTG, and purified with Ni-beads affinity chromatography. The target protein was detected by SDS-PAGE. The fluorescence-activated cell sorting analysis (FACS), cell adhesion test, immunofluorescence staining and quantitative real-time PCR were employed to detect the endothelial cell-targeted and Notch signaling-activated biological characteristics of mD1R. The carbon tetrachloride mouse model was established to observe the effects of mD1R on the hematopoietic stem cell (HSC), myeloid cells and lymphoid cells by flow cytometry. The LinScal-1c-Kit cells were sorted by magnetic bead, FACS was performed to analyze the cell cycle, and RT-PCR was employed to observe the expression of interleukin (IL)-10.</p><p><b>RESULTS</b>The prokaryotic expression vector was successfully cloned and constructed. The purity and the activity were confirmed in mD1R recombinant protein. The purified mD1R activated the Notch signaling pathway of hematopoietic stem cells in carbon tetrachloride damaged mouse, and internally elevated the number of HSC and long-term HSC to 2.96-fold and 6.18-fold. In addition, mD1R improved the amplification of the myeloid progenitor cells and the myeloid-derived suppressor cells, particularly the granulocyte/monocyte into blood. Mechanistically, the further analyses suggested that Notch pathway could increase the proliferation of HSC and enhance expression of IL-10 after stress injury.</p><p><b>CONCLUSIONS</b>A new and activated recombinant Notch ligand protein has been obtained successfully to communicate hematopoietic stem cells and hematopoietic microenvironment. The Notch- mediated intrinsic hematopoiesis has been regulated by the anti-inflammatory factor after stress injury.</p>


Assuntos
Animais , Camundongos , Tetracloreto de Carbono , Escherichia coli , Hematopoese , Células-Tronco Hematopoéticas , Ligantes , Receptores Notch , Transdução de Sinais
12.
Bioorg Med Chem ; 23(20): 6602-11, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26404408

RESUMO

Herein we describe the synthesis and evaluation of a series of adenosine analogs for in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Out of these compounds, compound c6 has much stronger antibacterial potency against Pseudomonas aeruginosa than ciprofloxacin, and was determined to target tyrosyl-tRNA synthetase with IC50 of 0.8±0.07 µM. Structure-activity relationship analysis suggested that introduction of a fluorine atom at the 3'-position of benzene ring of the phenylacetyl moiety significantly increased affinities to the enzyme. In comparison with isopropylidene analogs, 2',3'-deprotected compounds displayed higher inhibitory activity. Molecular dockings provided an explanation for observations in biological assays.


Assuntos
Adenosina/análogos & derivados , Adenosina/farmacologia , Antibacterianos/farmacologia , Desenho de Fármacos , Inibidores Enzimáticos/farmacologia , Tirosina-tRNA Ligase/antagonistas & inibidores , Adenosina/química , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Simulação de Dinâmica Molecular , Estrutura Molecular , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/enzimologia , Relação Estrutura-Atividade , Tirosina-tRNA Ligase/metabolismo
13.
Bioorg Med Chem ; 23(15): 4860-4865, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-26048027

RESUMO

3-Arylfuran-2(5H)-one derivatives show good antibacterial activity and were determined as tyrosyl-tRNA synthetase (TyrRS) inhibitors. In a systematic medicinal chemistry exploration, we demonstrated chemical opportunities to treat infections caused by Helicobacter pylori. Twenty 3-arylfuran-2(5H)-ones were synthesized and evaluated for anti-H. pylori, antioxidant and anti-urease activities which are closely interconnected with H. pylori infection. The results displayed that some of the compounds show excellent antioxidant activity, and good anti-H. pylori and urease inhibitory activities. Out of these compounds, 3-(3-methylphenyl)furan-2(5H)-one (b9) showed the most potent antioxidant activity (IC50=8.2 µM) and good anti-H. pylori activity (MIC50=2.6 µg/mL), and it can be used as a good candidate for discovering novel anti-gastric ulcer agent.


Assuntos
Antibacterianos/síntese química , Antiulcerosos/síntese química , Furanos/química , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Antioxidantes/química , Sítios de Ligação , Avaliação Pré-Clínica de Medicamentos , Furanos/farmacologia , Furanos/uso terapêutico , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/enzimologia , Humanos , Simulação de Acoplamento Molecular , Estrutura Terciária de Proteína , Úlcera Gástrica/tratamento farmacológico , Tirosina-tRNA Ligase/antagonistas & inibidores , Tirosina-tRNA Ligase/metabolismo , Urease/antagonistas & inibidores , Urease/metabolismo
14.
Chinese Journal of Hepatology ; (12): 364-366, 2006.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-341364

RESUMO

<p><b>OBJECTIVES</b>To study the biological behavior of hepatocarcinoma stem cells in rats.</p><p><b>METHODS</b>Primary liver carcinomas were induced in rats using diethylnitrosamine. Tumor cells from 8 rats were separated according to rats oval cell (OVC) markers CD34, c-Kit, Thy-1, AFP, CK7, CK8, CK14, CK18, CK19 and GGT and then they were separately injected into the livers of nude mice. The tumors grown from the different subpopulation of OVC markers in the nude mice livers (10 OVC markers negative or positive cells) were weighted 1 month after the inoculations. The hepatocarcinoma cell subpopulations with higher ability in causing tumor growths were further studied in vitro. The cell cycles and DNA content of those subpopulation cells were investigated using flow cytometry.</p><p><b>RESULTS</b>(1) Subpopulation cells with CK7(-), Thy-1(+) and AFP(+) markers had a higher ability in causing tumors in nude mice; (2) Subpopulation cells, exhibiting characters of TSC, had a low growth rate in vitro.</p><p><b>CONCLUSIONS</b>(1) Different subpopulations of hepatocarcinoma cells had different abilities in causing tumors in rats. Some subpopulation cells, such as CK7(-), Thy-1(+) and AFP(+) cells, have characteristics of tumor stem cells. (2) The hepatocarcinoma stem cells may have a low growth rate in vitro.</p>


Assuntos
Animais , Masculino , Camundongos , Ratos , Ciclo Celular , Quinases Ciclina-Dependentes , Neoplasias Hepáticas Experimentais , Patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas , Patologia , Fisiologia , Ratos Sprague-Dawley , Antígenos Thy-1 , Células Tumorais Cultivadas , alfa-Fetoproteínas
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