In compound [Zn(sulfasalazine)2(pyridine)] (1), each zinc atom not only coordinates to nitrogen atom of pyridine, but also is connected with four oxygen atoms from carboxylic acid groups of four sulfasalazine ligands,...In compound [Zn(sulfasalazine)2(pyridine)] (1), each zinc atom not only coordinates to nitrogen atom of pyridine, but also is connected with four oxygen atoms from carboxylic acid groups of four sulfasalazine ligands, to result in the formation of a distorted tetragonal pyramid. In addition, each sulfasalazine ligand coordinates to two zinc atoms through its two oxygen atoms of carboxylic acid group to afford a 1D chain. CCDC: 274842.展开更多
BACKGROUND Sulfasalazine has been used as a standard-of-care in ulcerative colitis for decades,however,it results in severe adverse symptoms,such as hepatotoxicity,blood disorders,male infertility,and hypospermia.Acco...BACKGROUND Sulfasalazine has been used as a standard-of-care in ulcerative colitis for decades,however,it results in severe adverse symptoms,such as hepatotoxicity,blood disorders,male infertility,and hypospermia.Accordingly,the new treatment strategy has to enhance pharmacological efficacy and stimultaneously minimize side effects.AIM To compare the anti-inflammatory action of sulfasalazine alone or in combination with herbal medicine for ulcerative colitis in a dextran sodium sulfate(DSS)-induced colitis mouse model.METHODS To induce ulcerative colitis,mice received 5%DSS in drinking water for 7 d.Animals were divided into five groups(n=9 each)for use as normal(non-DSS),DSS controls,DSS+sulfasalazine(30 mg/kg)-treatment experimentals,DSS+sulfasalazine(60 mg/kg)-treatment experimentals,DSS+sulfasalazine(30 mg/kg)+Citrus unshiu peel and Bupleuri radix mixture(30 mg/kg)(SCPB)-treatment experimentals.RESULTS The SCPB treatment showed an outstanding effectiveness in counteracting the ulcerative colitis,as evidenced by reduction in body weight,improvement in crypt morphology,increase in antioxidant defenses,down-regulation of proinflammatory proteins and cytokines,and inhibition of proteins related to apoptosis.CONCLUSIONSCPB may represent a promising alternative therapeutic against ulcerative colitis,without inducing adverse effects.展开更多
AIM: To investigate the characteristics and short-term efficacy of sulfasalazine (SASP) in patients with mildly and moderately active ulcerative colitis (UC).METHODS: Two hundred and twenty-eight patients with mildly ...AIM: To investigate the characteristics and short-term efficacy of sulfasalazine (SASP) in patients with mildly and moderately active ulcerative colitis (UC).METHODS: Two hundred and twenty-eight patients with mildly and moderately active UC were recruited, 106patients in 1993-1995, and 122 patients in 2000-2002,they were assigned as the 1990s group (n = 106) and the 2000s group (n = 122), prospectively. The general characteristics, clinical manifestations, colonoscopic and histological data were compared between the two groups.The short-term efficacy and safety of SASP 3 g per d were evaluated.RESULTS: Between 2000s and 1990s groups, the gender ratio of men to women was 1:1.18 and 1:1.04, 57.4%and 50.9% of the patients were between 30 and 49 years old. The gender ratio and age of UC patients were not significantly different. The total course of 50.0% and 37.1% of UC patients was less than 1 year (P＜0.05), 10.6% and 31.2% of the cases had a duration of more than 5 years (P＜0.05) in 2000s and 1990s groups, respectively. The most common clinical type was first episode in 2000s group and chronic relapse in 1990s group. The patients showed a higher frequency of abdominal pain and tenderness in 1990s group than in 2000s group. Erosions were found in 84.4% and 67.9% of patients in 2000s and 1990s groups (P＜0.05). Rough and granular mucosa (67.9%vs43.4%, P＜0.05)and polyps (47.2% vs 32.8%, P＜0.05)were identified in 1990s group more than in 2000s group.There were no significant differences in clinical, colonoscopic and histological classifications. After SASP (1 g thrice per d) treatment for 6 wk, the clinical, colonoscopic and histological remission rates were 71.8%, 21.8% and 16.4%,respectively. In 79 patients with clinical remission, 58.2%and 67.1% remained grade 1 in colonoscopic and histological findings, respectively. The overall effects in first episode type (complete remission in 10, 18.9%, partial remission in 28, 52.8%, and improvement in 9, 17.0%) were better than in chronic relapse type (complete remission in 3,7.5%; partial remission in 16, 40.0%; and improvement in 15, 37.5%) and chronic persistent type (complete remission in 1, 5.9%; partial remission in 6, 35.3%; and improvement in 6, 35.3%) respectively (P＜0.05). In 110patients treated with SASP, 18 patients (16.4%) had adverse reactions. Except for two cases of urticaria and one case of WBC decrease, none of the patients had to stop the treatment because of severe adverse reactions.CONCLUSION: Patients with mildly and moderately active UC in 2000s group had a shorter disease course, milder clinical manifestations, more first episode type and higher frequency of acute mucosal lesions in colonoscopy than in 1990s group. The patients in 1990s group had higher proportion of chronic relapse type and chronic mucosal change in colonoscopy than in 2000s group. The shortterm efficacy of SASP could be mainly remission of clinical manifestations. But more than half of the patients still had light inflammation in colonoscopy and histology. The overall effects of SASP in first episode type were better than those in other types. SASP was a safe and effective drug to treat mildly and moderately active UC.展开更多
BACKGROUND:Most pancreatic carcinomas are clinically insensitive to chemotherapeutics.The exact mechanisms of their apoptosis and multiple drug resistance are obscure at present.This study was undertaken to explore th...BACKGROUND:Most pancreatic carcinomas are clinically insensitive to chemotherapeutics.The exact mechanisms of their apoptosis and multiple drug resistance are obscure at present.This study was undertaken to explore the influence of chemotherapy on anti-proliferation,apoptosis and the cell cycle,and lay a fundamental basis for further research into the apoptotic mechanisms and prevention of multiple drug resistance in pancreatic carcinoma. METHODS:The human pancreatic carcinoma cell line BxPC-3 was cultured in vitro.The growth inhibition rate,cell cycle and apoptotic rate of cells treated with 5-fluorouracil（5-FU）,sulfasalazine alone or a combination at different concentrations were evaluated with the MTT method and flow cytometry.Phase-contrast microscopy was used to observe morphological changes in the cells treated with 5-FU,sulfasalazine or both for 24 hours. RESULTS:The growth inhibition rate of the BxPC-3 cells treated with 5-FU and sulfasalazine significantly increased in a time-and dose-dependent manner.The growth inhibition rate of the cells treated with 5-FU gradually increased,but decreased at different concentrations of sulfasalazine for a prolonged period.The apoptotic rate of the BxPC-3 cells induced by sulfasalazine（200 mg/L）, 5-FU（100 mg/L）or both for 12 hours were（2.68±0.36）%, （6.59±0.90）%,and（10.52±0.55）%,respectively,compared with the corresponding control values were（3.17±0.08）%, （1.50±0.06）%,and（4.08±0.31）%[(t=2.33（P】0.05）,9.78 and 17.56（P【0.01）].It increased to（7.63±0.68）%,（40.43± 1.79）%,and（64.69±0.82）%for 48 hours,in comparison with the control that was（29.20±2.18）%,（5.61±0.13）%,and（12.02±0.52）%[t=17.06,33.66 and 94.51（P【0.01）]. The apoptotic rate,proportion of cells in S-phase and proliferative index rose after use of 5-FU（12.5,25,50,75, and 100 mg/L）alone for 24 hours.However,the apoptotic rate at augmented concentrations of sulfasalazine for 24 hours slowly increased from（1.47±0.08）%to（3.45± 0.28）%,the proportion of cells in G0/G1-phase increased from（35.13±0.32）%to（54.32±1.45）%,the proportion of cells in S-phase decreased from（45.37±1.48）%to（16.67± 2.73）%,and the proliferative index gradually lowered.The proportion of G0/G1-phase cells treated by 5-FU（100 mg/L） and sulfasalazine（200 mg/L）increased from（43.31±1.52）% （12 hours）to（85.05±0.24）%（48 hours）compared with the corresponding controls[t=7.93（12 hours）,21.30（48 hours）,P【0.01],and the proportion of cells in S-phase decreased from（11.63±1.11）%（12 hours）to（4.47±0.68）% （48 hours）in contrast to the controls[t=37.68（12 hours）, 8.60（48 hours）,P【0.01].Most cells after the combined use of the two agents for 24 hours displayed pyknosis and oval shape by phase-contrast microscopy.The cells treated with 5-FU（100 mg/L）for 24 hours were pyknotic and oval shaped.A few of cells in the group treated with sulfasalazine（200 mg/L）were pyknotic at 24 hours. CONCLUSIONS:Sulfasalazine may enhance the inhibitory proliferation and apoptosis effect on BxPC-3 cells induced by 5-FU,which is closely related to synergistically the cell cycle arrested in G<sub>0</sub>/G<sub>1</sub>-phase.展开更多
Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the m...Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the molecular mechanisms of isoliquiritigenin analog 2',4',4-trihydroxychalcone(metochalcone;TEC)against carcinomas remain less well understood.In this study,we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner.TEC induced cell cycle arrest in the S-phase,cell migration inhibition in vitro,and reduced tumor growth in vivo.Moreover,transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways.TEC triggered the senescence-associated secretory phenotype(SASP)by repressing the JAK2/STAT3 axis.The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway,highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.展开更多
皮肤衰老是衰老研究领域的一个分支,生物标志物可用于客观评价皮肤衰老程度,包括了特定蛋白基因、信号通路的激活以及一系列细胞分泌因子。本文概述了皮肤衰老相关分泌表型(skin aging related secretion phenotype,SASP)的组成及其生...皮肤衰老是衰老研究领域的一个分支,生物标志物可用于客观评价皮肤衰老程度,包括了特定蛋白基因、信号通路的激活以及一系列细胞分泌因子。本文概述了皮肤衰老相关分泌表型(skin aging related secretion phenotype,SASP)的组成及其生理功能、SASP在皮肤衰老过程中的变化,以及针对SASP为功效靶点设计的化妆品功效测试组合方法,旨在对基于SASP靶点的相关功效化妆品研究有一个更加全面深刻的认识。展开更多
文摘In compound [Zn(sulfasalazine)2(pyridine)] (1), each zinc atom not only coordinates to nitrogen atom of pyridine, but also is connected with four oxygen atoms from carboxylic acid groups of four sulfasalazine ligands, to result in the formation of a distorted tetragonal pyramid. In addition, each sulfasalazine ligand coordinates to two zinc atoms through its two oxygen atoms of carboxylic acid group to afford a 1D chain. CCDC: 274842.
基金Traditional Korean Medicine R&D Program funded by the Ministry of Health&Welfare through the Korea Health Industry Development Institute(KHIDI),No.HI15C00255and National Research Foundation of Korea(NRF)funded by the Korean government(MSIP),No.2018R1A5A2025272.
文摘BACKGROUND Sulfasalazine has been used as a standard-of-care in ulcerative colitis for decades,however,it results in severe adverse symptoms,such as hepatotoxicity,blood disorders,male infertility,and hypospermia.Accordingly,the new treatment strategy has to enhance pharmacological efficacy and stimultaneously minimize side effects.AIM To compare the anti-inflammatory action of sulfasalazine alone or in combination with herbal medicine for ulcerative colitis in a dextran sodium sulfate(DSS)-induced colitis mouse model.METHODS To induce ulcerative colitis,mice received 5%DSS in drinking water for 7 d.Animals were divided into five groups(n=9 each)for use as normal(non-DSS),DSS controls,DSS+sulfasalazine(30 mg/kg)-treatment experimentals,DSS+sulfasalazine(60 mg/kg)-treatment experimentals,DSS+sulfasalazine(30 mg/kg)+Citrus unshiu peel and Bupleuri radix mixture(30 mg/kg)(SCPB)-treatment experimentals.RESULTS The SCPB treatment showed an outstanding effectiveness in counteracting the ulcerative colitis,as evidenced by reduction in body weight,improvement in crypt morphology,increase in antioxidant defenses,down-regulation of proinflammatory proteins and cytokines,and inhibition of proteins related to apoptosis.CONCLUSIONSCPB may represent a promising alternative therapeutic against ulcerative colitis,without inducing adverse effects.
文摘AIM: To investigate the characteristics and short-term efficacy of sulfasalazine (SASP) in patients with mildly and moderately active ulcerative colitis (UC).METHODS: Two hundred and twenty-eight patients with mildly and moderately active UC were recruited, 106patients in 1993-1995, and 122 patients in 2000-2002,they were assigned as the 1990s group (n = 106) and the 2000s group (n = 122), prospectively. The general characteristics, clinical manifestations, colonoscopic and histological data were compared between the two groups.The short-term efficacy and safety of SASP 3 g per d were evaluated.RESULTS: Between 2000s and 1990s groups, the gender ratio of men to women was 1:1.18 and 1:1.04, 57.4%and 50.9% of the patients were between 30 and 49 years old. The gender ratio and age of UC patients were not significantly different. The total course of 50.0% and 37.1% of UC patients was less than 1 year (P＜0.05), 10.6% and 31.2% of the cases had a duration of more than 5 years (P＜0.05) in 2000s and 1990s groups, respectively. The most common clinical type was first episode in 2000s group and chronic relapse in 1990s group. The patients showed a higher frequency of abdominal pain and tenderness in 1990s group than in 2000s group. Erosions were found in 84.4% and 67.9% of patients in 2000s and 1990s groups (P＜0.05). Rough and granular mucosa (67.9%vs43.4%, P＜0.05)and polyps (47.2% vs 32.8%, P＜0.05)were identified in 1990s group more than in 2000s group.There were no significant differences in clinical, colonoscopic and histological classifications. After SASP (1 g thrice per d) treatment for 6 wk, the clinical, colonoscopic and histological remission rates were 71.8%, 21.8% and 16.4%,respectively. In 79 patients with clinical remission, 58.2%and 67.1% remained grade 1 in colonoscopic and histological findings, respectively. The overall effects in first episode type (complete remission in 10, 18.9%, partial remission in 28, 52.8%, and improvement in 9, 17.0%) were better than in chronic relapse type (complete remission in 3,7.5%; partial remission in 16, 40.0%; and improvement in 15, 37.5%) and chronic persistent type (complete remission in 1, 5.9%; partial remission in 6, 35.3%; and improvement in 6, 35.3%) respectively (P＜0.05). In 110patients treated with SASP, 18 patients (16.4%) had adverse reactions. Except for two cases of urticaria and one case of WBC decrease, none of the patients had to stop the treatment because of severe adverse reactions.CONCLUSION: Patients with mildly and moderately active UC in 2000s group had a shorter disease course, milder clinical manifestations, more first episode type and higher frequency of acute mucosal lesions in colonoscopy than in 1990s group. The patients in 1990s group had higher proportion of chronic relapse type and chronic mucosal change in colonoscopy than in 2000s group. The shortterm efficacy of SASP could be mainly remission of clinical manifestations. But more than half of the patients still had light inflammation in colonoscopy and histology. The overall effects of SASP in first episode type were better than those in other types. SASP was a safe and effective drug to treat mildly and moderately active UC.
文摘BACKGROUND:Most pancreatic carcinomas are clinically insensitive to chemotherapeutics.The exact mechanisms of their apoptosis and multiple drug resistance are obscure at present.This study was undertaken to explore the influence of chemotherapy on anti-proliferation,apoptosis and the cell cycle,and lay a fundamental basis for further research into the apoptotic mechanisms and prevention of multiple drug resistance in pancreatic carcinoma. METHODS:The human pancreatic carcinoma cell line BxPC-3 was cultured in vitro.The growth inhibition rate,cell cycle and apoptotic rate of cells treated with 5-fluorouracil（5-FU）,sulfasalazine alone or a combination at different concentrations were evaluated with the MTT method and flow cytometry.Phase-contrast microscopy was used to observe morphological changes in the cells treated with 5-FU,sulfasalazine or both for 24 hours. RESULTS:The growth inhibition rate of the BxPC-3 cells treated with 5-FU and sulfasalazine significantly increased in a time-and dose-dependent manner.The growth inhibition rate of the cells treated with 5-FU gradually increased,but decreased at different concentrations of sulfasalazine for a prolonged period.The apoptotic rate of the BxPC-3 cells induced by sulfasalazine（200 mg/L）, 5-FU（100 mg/L）or both for 12 hours were（2.68±0.36）%, （6.59±0.90）%,and（10.52±0.55）%,respectively,compared with the corresponding control values were（3.17±0.08）%, （1.50±0.06）%,and（4.08±0.31）%[(t=2.33（P】0.05）,9.78 and 17.56（P【0.01）].It increased to（7.63±0.68）%,（40.43± 1.79）%,and（64.69±0.82）%for 48 hours,in comparison with the control that was（29.20±2.18）%,（5.61±0.13）%,and（12.02±0.52）%[t=17.06,33.66 and 94.51（P【0.01）]. The apoptotic rate,proportion of cells in S-phase and proliferative index rose after use of 5-FU（12.5,25,50,75, and 100 mg/L）alone for 24 hours.However,the apoptotic rate at augmented concentrations of sulfasalazine for 24 hours slowly increased from（1.47±0.08）%to（3.45± 0.28）%,the proportion of cells in G0/G1-phase increased from（35.13±0.32）%to（54.32±1.45）%,the proportion of cells in S-phase decreased from（45.37±1.48）%to（16.67± 2.73）%,and the proliferative index gradually lowered.The proportion of G0/G1-phase cells treated by 5-FU（100 mg/L） and sulfasalazine（200 mg/L）increased from（43.31±1.52）% （12 hours）to（85.05±0.24）%（48 hours）compared with the corresponding controls[t=7.93（12 hours）,21.30（48 hours）,P【0.01],and the proportion of cells in S-phase decreased from（11.63±1.11）%（12 hours）to（4.47±0.68）% （48 hours）in contrast to the controls[t=37.68（12 hours）, 8.60（48 hours）,P【0.01].Most cells after the combined use of the two agents for 24 hours displayed pyknosis and oval shape by phase-contrast microscopy.The cells treated with 5-FU（100 mg/L）for 24 hours were pyknotic and oval shaped.A few of cells in the group treated with sulfasalazine（200 mg/L）were pyknotic at 24 hours. CONCLUSIONS:Sulfasalazine may enhance the inhibitory proliferation and apoptosis effect on BxPC-3 cells induced by 5-FU,which is closely related to synergistically the cell cycle arrested in G<sub>0</sub>/G<sub>1</sub>-phase.
基金funded by the National Natural Science Foundation of China(82003879)Project of Science and Technology Department of Sichuan Province(2023NSFSC1928,2023NSFSC1992)+3 种基金Young Elite Scientists Sponsorship Program China Association for Science and Technology(CACM-2020-QNRC1-01)Project of State Administration of Traditional Chinese Medicine of China(ZYYCXTD-D-202209)Project of Undergraduate Training Programs for Innovation and Entrepreneurship(S202310610637)the Open Research Fund of State Key Laboratory of Southwestern Chinese Medicine Resources(SKLTCM202205).
文摘Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the molecular mechanisms of isoliquiritigenin analog 2',4',4-trihydroxychalcone(metochalcone;TEC)against carcinomas remain less well understood.In this study,we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner.TEC induced cell cycle arrest in the S-phase,cell migration inhibition in vitro,and reduced tumor growth in vivo.Moreover,transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways.TEC triggered the senescence-associated secretory phenotype(SASP)by repressing the JAK2/STAT3 axis.The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway,highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.
文摘皮肤衰老是衰老研究领域的一个分支,生物标志物可用于客观评价皮肤衰老程度,包括了特定蛋白基因、信号通路的激活以及一系列细胞分泌因子。本文概述了皮肤衰老相关分泌表型(skin aging related secretion phenotype,SASP)的组成及其生理功能、SASP在皮肤衰老过程中的变化,以及针对SASP为功效靶点设计的化妆品功效测试组合方法,旨在对基于SASP靶点的相关功效化妆品研究有一个更加全面深刻的认识。
