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1.
Chinese journal of integrative medicine ; (12): 308-315, 2023.
Article in English | WPRIM | ID: wpr-982278

ABSTRACT

OBJECTIVE@#To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine.@*METHODS@#Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients.@*RESULTS@#Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD.@*CONCLUSIONS@#Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).


Subject(s)
Humans , Male , Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Hyperuricemia , Kidney , Proteinuria , Renal Insufficiency, Chronic/complications
2.
Acta Pharmaceutica Sinica ; (12): 3354-3365, 2023.
Article in Chinese | WPRIM | ID: wpr-999082

ABSTRACT

Drug resistance of cancer cells is the main causes of chemotherapy failure, and gene mutation or function loss is key factor to induce drug resistance. Previous studies have shown that hairy and enhancer of split 1 (HES1) is up-regulated in herceptin-resistant gastric cancer cells, and inhibition of its activity can reverse its resistance while the potential mechanism has not yet been elucidated. In this study, we employed CRISPR/Cas9 to establish HES1 knock-out cell line (△HES1/NCI N87R) to investigate the functions of HES1 in herceptin resistance of NCI N87R cells and its potential mechanisms. We investigated proteomics profiling of △HES1/NCI N87R cells based on quantitative proteomics. Gene ontology analysis was conducted by GeneSet Enrichment Analysis (GSEA) and Metascape database, and pathway enrichment analysis was done using GeneAnalytics database. The selected molecules were quantified by Western blot and some pathways were verified by using inhibitors. The results showed that the resistance to herceptin of △HES1/NCI N87R cells decreased compared to NCI N87R cells. Proteomic data demonstrated that the expression of 1 263 genes changed significantly in △HES1/NCI N87R cells, among which 761 genes were up-regulated while 502 ones down-regulated comparing with NCI N87R cells. Pathway analysis showed that ferroptosis, fatty acid β-oxidation, autophagy and glutathione metabolism, etc. exhibited notable changes in △HES1/NCI N87R cells. The functional studies showed that the levels of iron ion and malondialdehyde increased, and glutathione decreased in △HES1/NCI N87R cells. It was further found that Fer-1, a ferroptosis inhibitor, could reverse the expression of pTP53, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in △HES1/NCI N87R cell, and reduce the sensitivity of △HES1/NCI N87R cells to herceptin. It is suggested that HES1 regulated the resistance of NCI N87R cells to herceptin through TP53/SLC7A11/GPX4 signaling pathway, and targeting TP53/SLC7A11/GPX4 signal axis mediated by HES1 is a potential strategy to reverse herceptin resistance in gastric cancer.

3.
Journal of Southern Medical University ; (12): 498-508, 2022.
Article in Chinese | WPRIM | ID: wpr-936341

ABSTRACT

OBJECTIVE@#To explore the role of Runt-related transcription factor 3 (RUNX3) in metabolic regulation of trastuzumab-resistant gastric cancer cells and investigate the mechanism of RUNX3 knockdown-mediated reversal of trastuzumab resistance.@*METHODS@#We performed a metabolomic analysis of trastuzumab-resistant gastric cancer cells (NCI N87R) and RUNX3 knockdown cells (NCI N87R/RUNX3) using ultra performance liquid chromatography (UPLC) coupled with Q Exactive Focus Orbitrap mass spectrometry (MS). Multivariate combined with univariate analyses and MS/MS ion spectrums were used to screen the differential variables. MetaboAnalyst 5.0 database was employed for pathway enrichment analysis. Differential metabolites-genes regulatory relationships were constructed based on OmicsNet database. The changes in GSH/GSSG and NADPH/NADP ratios in NCI N87R/RUNX3 cells were measured using detection kits.@*RESULTS@#The metabolic profile of NCI N87R cells was significantly altered after RUNX3 knockdown, with 81 differential metabolites identified to contribute significantly to the classification, among which 43 metabolites were increased and 38 were decreased (P < 0.01). In NCI N87R cells, RUNX3 knockdown resulted in noticeable alterations in 8 pathways involving glutamine metabolism, glycolysis, glycerophospholipid, nicotinate-nicotinamide and glutathione metabolism, causing also significant reduction of intracellular GSH/GSSG and NADPH/NADP ratios (P < 0.01). The differential metabolites-genes network revealed a regulatory relationship between the metabolic molecules and genes.@*CONCLUSION@#RUNX3 reverses trastuzumab resistance in gastric cancer cells by regulating energy metabolism and oxidation-reduction homeostasis and may serve as a potential therapeutic target for trastuzumab-resistant gastric cancer.


Subject(s)
Humans , Chromatography, High Pressure Liquid , Core Binding Factor Alpha 3 Subunit/genetics , Glutathione Disulfide , Metabolomics , NADP , Stomach Neoplasms/genetics , Tandem Mass Spectrometry , Trastuzumab/pharmacology
4.
Journal of Integrative Medicine ; (12): 111-119, 2021.
Article in English | WPRIM | ID: wpr-881016

ABSTRACT

BACKGROUND@#Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.@*OBJECTIVE@#This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m@*MAIN OUTCOME MEASURES@#The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment.@*RESULTS@#A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group.@*CONCLUSION@#SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.@*TRIAL REGISTRATION NUMBER@#NCT02063100 on ClinicalTrials.gov.

5.
Acta Pharmaceutica Sinica ; (12): 1953-1964, 2021.
Article in Chinese | WPRIM | ID: wpr-887022

ABSTRACT

Resistance of tumor cells is a complex biological process involving multiple mechanisms and factors, in which anti-apoptosis is the most important cause of drug resistance. Previous studies have shown that the DNA binding activity of Runt related transcription factor 3 (RUNX3) increased prominently in Herceptin resistant gastric cancer cells (NCI N87R) while the relevance of which to drug resistance has not yet been confirmed. In this study, we employed CRISPR/Cas9 to establish RUNX3 knock-out cell line (△RUNX3/NCI N87R) to investigate the functions of RUNX3 in Herceptin resistance of NCI N87R cells and its potential mechanisms. We investigated proteomics profiling of △RUNX3/NCI N87R cells based on label free quantitative proteomics. Differentially expressed proteins were screened out according to fold change and significance level between △RUNX3/NCI N87R and NCI N87R cells. Pathway enrichment analysis was done using GeneAnalytics database, and gene ontology analysis was conducted by DAVID Bioinformatics Resources database. Protein-protein interaction networks were constructed based on STRING database. The results showed that △RUNX3/NCI N87R cells increased the sensitivity to Herceptin. Proteomic data demonstrated that the expression of 577 genes changed significantly in △RUNX3/NCI N87R cells, among which 191 genes were up-regulated while 386 ones down-regulated comparing with NCI N87R cells. Pathway analysis showed that autophagy, cell cycle, apoptosis, mitochondrial fatty acid β oxidation, neurogenic locus notch homolog protein 1 (NOTCH1), mammalian target of rapamycin (mTOR), Hedgehog and DNA damage response pathways exhibited notable changes based on pathway enrichment ratio and significance level (P < 0.05). These results indicated that RUNX3 knock-out altered multiple signaling pathways of NCI N87R cells. Western blotting manifested that the expression of autophagy regulatory molecules autophagy-related protein (ATG) 13, 7 and BECN1 increased remarkably while cell cycle molecules serine/threonine-protein kinase Chk2 (CHEK2) and apoptosis regulator Bcl-2 (BCL2) decreased prominently in △RUNX3/NCI N87R cells. The p-AKT expression decreased significantly in △RUNX3/NCI N87R cells compared with NCI N87R cells (P < 0.01) and was suppressed by Herceptin. These results indicated that RUNX3 knock-out altered cell cycle, increased inhibition to p-AKT by Herceptin, promoted autophagy and induced cell apoptosis of NCI N87R cells. These results suggested that RUNX3 may be a potential therapeutic target for reversing or reducing Herceptin resistance in gastric cancer cells.

6.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 185-190, 2021.
Article in Chinese | WPRIM | ID: wpr-906160

ABSTRACT

Traditional Chinese medicine (TCM) is a great treasure house, exhibiting unique advantages in the treatment of some difficult and critical diseases. The incidence rate of membranous nephropathy has increased year by year in recent years, and has become the first cause of primary glomerular diseases. However, its pathogenesis is not clear. Modern medicine often uses immunosuppressive therapy, but it often faces the problems of high side effects and high recurrence rate. The China Association of Chinese Medicine (CACM) invited clinical experts of TCM and western medicine to fully discuss membranous nephropathy, which was later confirmed to be one of the clinical diseases responding specifically to TCM. Apart from summarizing the pathogenesis and clinical diagnosis and treatment of membranous nephropathy in both TCM and western medicine, this paper also detailed TCM cognition, syndrome differentiation, and therapeutic schemes of membranous nephropathy, aiming to improve the clinical remission rate of membranous nephropathy and provide reference for its clinical treatment.

7.
China Journal of Chinese Materia Medica ; (24): 3107-3115, 2019.
Article in Chinese | WPRIM | ID: wpr-773183

ABSTRACT

The aim of this paper was to investigate the effects of curcumin on the proliferation,migration,invasion and apoptosis of human gastric cancer cells and to explore the potential mechanisms. SGC7901,MKN45 and NCI N87 cells lines were cultured under different concentrations of curcumin( 2. 5,5,10,20,40,80 and 160 μmol·L~(-1)) at different time points( 12,24,48 and 72 h),and the effect of curcumin on cell proliferation was detected by CCK-8 assay. The migration and invasiveness of cells were determined by wound healing and Transwell assays,the apoptosis rate was assessed by flow cytometry,the expression of N-cadherin,E-cadherin,snail1,Wnt3 a,p-β-catenin,p-LRP6,Bcl-2 and Bax were detected by Western blot,and the enzymatic activity of caspase-3,caspase-8 and caspase-9 was evaluated via caspase kit. RESULTS:: indicated that the proliferation of MKN45 cells was significantly inhibited by curcumin in a dose-and time-dependent manner( IC50= 21. 93 μmol·L~(-1)). Moreover,curcumin could inhibit the migration and invasion of MKN45 cells,downregulate the expression of N-cadherin,snail1,Wnt3 a,p-β-catenin,p-LRP6 and Bcl-2,and upregulate the expression of E-cadherin and Bax,it could increase the activity of caspase-3,caspase-8,caspase-9 and induce apoptosis as well. The potential mechanism is through inhibiting the Wnt3 a/β-catenin/EMT pathway,regulating Bcl-2 signaling and caspase pathway,which might provide new potential strategies for gastric cancer treatment.


Subject(s)
Humans , Cell Line, Tumor , Cell Movement , Cell Proliferation , Curcumin , Pharmacology , Stomach Neoplasms , Drug Therapy , Pathology , Wnt Signaling Pathway , Wnt3A Protein , Metabolism , beta Catenin , Metabolism
8.
Acta Academiae Medicinae Sinicae ; (6): 539-542, 2018.
Article in Chinese | WPRIM | ID: wpr-690299

ABSTRACT

Objective To preliminarily validate the clinical usability of the ameliorated Kawashima Itch Scale(Xie-Kawashima Itch Scale) among adult pruritic patients on maintenance hemodialysis. Methods Xie-Kawashima Itch Scale was developed on the basis of Kawashima Itch Scale. Patients were asked to record their pruritus condition according to Xie-Kawashima Itch Scale or visual analogue scale(VAS) during daytime and night for two weeks. The record at the second week was used for analyzing the correlation between Xie-Kawashima Itch Scale and VAS. Results Totally 134 patients were enrolled in this study,among whom 128 entered the final analysis. Xie-Kawashima Itch Scale was positively correlated with VAS(r=0.832,95% CI=0.810-0.851,P<0.01 for daytime record;and r=0.848,95% CI=0.828-0.865,P<0.01 for night record). Subgroup analysis also showed similar correlations between different age groups and among different gender groups. Conclusion Xie-Kawashima Itch Scale has good correlation with VAS in patients on hemodialysis,without being affected by age or gender. Thus,it can be a useful tool for the assessment of pruritus in clinical practice and research.

9.
Acta Pharmaceutica Sinica ; (12): 1817-1824, 2018.
Article in Chinese | WPRIM | ID: wpr-780062

ABSTRACT

This study is aimed to investigate the potential mechanisms of herceptin-acquired resistance and curcumin to reverse resistance in NCI N87/R gastric cancer cells. Western blot was used to evaluate the effect of curcumin on the expression of IκBα, NF-κBp65, HER-2, caspase-3, Bcl-2 and Bax in herceptin resistant cells; Annexin V-FITC/PI was exploited to analyze the effect of curcumin on cell apoptosis; Caspase kit was used to evaluate the effect of curcumin on the enzymatic activity of caspase-3, 8 and 9. The results showed a low expression of IκBα in the cytoplasm and a high expression of NF-κBp65 in the nucleus of NCI N87/R cells. Correspondingly, inhibition of NF-κB pathway by EVP4593, a specific NF-κB inhibitor, preferentially reduced cell viability of NCI N87/R cells, indicating the activation of NF-κB pathway in NCI N87/R cells. Curcumin preferentially reduced cell proliferation and inhibited NF-κB signaling pathway of NCI N87/R cells, downregulated the expression of HER-2 and Bcl-2, upregulated the expression of Bax, increased the activity of caspase-3, 8 and 9. Taken together, our study demonstrates the correlation between herceptin resistance acquirement of NCI N87 cells and the activation of NF-κB pathway. Moreover, curcumin reverses herceptin resistance of NCI N87 cells possibly by inhibiting NF-κB pathway and inducing cell apoptosis.

10.
Acta Pharmaceutica Sinica ; (12): 553-560, 2018.
Article in Chinese | WPRIM | ID: wpr-779907

ABSTRACT

This study was designed to explore proteins differentially expressed in HER2 positive gastric cancer N87 cells and N87/R cells with an acquired resistance to herceptin based on label-free quantitative proteomics. The extracted proteins were reduced and alkylated, then digested using filter aided sample preparation (FASP); peptides were separated via small manual reversed phase column, analyzed by LC-MS/MS, and identified with protein database 2.1 search engine. Proteins were quantified by intensity based quantification (IBQ) to search for differential proteins by comparison with relatively quantified proteins. The enrichment and network construction in gene ontology (GO) terms, genes-disease and Wikipathway of differential proteins were established through Web Gestalt. A total of 8 509 proteins were detected, among them, 7 163 proteins were further analyzed by bioinformatics, of which 110 proteins were up-regulated and 70 were down-regulated in N87/R cells. The differential proteins showed a significant difference in cellular component, biological process and molecular function in GO terms, respectively. Genes-disease network analysis indicated the association of these differential proteins with neoplasm metastasis, neoplasm invasiveness and inflammation, etc. Wikipathway enrichment analysis revealed the relevance of several signaling pathways to herceptin resistance, which included IL-2, MAPK/ERK, mTOR, aurora A, Ret, NF-κB, immune-regulatory and metabolic pathway. Western blot showed a significant increase of ERK1/2 activities in N87/R cells compared with N87 cells. Correspondingly, SCH772984, a MAPK/ERK inhibitor, preferentially reduced the viability of N87/R cells. Taken together, our data suggested that the MAPK/ERK signaling pathway is one of the key pathways that mediate herceptin resistance. This study provides the basic information for exploring the mechanisms of acquired resistance to herceptin in gastric cancer cells.

11.
Chinese Medical Journal ; (24): 2785-2791, 2018.
Article in English | WPRIM | ID: wpr-772920

ABSTRACT

Background@#Automated peritoneal dialysis (APD) can cater to individual needs, provide treatment while asleep, take into account the adequacy of dialysis, and improve the quality of life. Currently, independent research and development of APD machines made in China are more conducive to patients. A randomized, multicenter, crossover study was conducted by comparing an APD machine made in China with an imported machine. The safety, effectiveness, and manipulability of the two machines were compared.@*Methods@#Two hundred and sixty patients who underwent peritoneal dialysis (PD) on a regular basis in 18 centers between August 2015 and February 2016 were included. The inclusion criteria include age ≥18 years and PD ≥30 days. The exclusion criteria were as follows: hemodialysis; exit site or tunnel infection; and peritonitis ≤30 days. The patients were randomly divided into Group A, who were first treated with a FM machine made in China, then changed to an imported machine; and Group B, who were treated using the reverse sequence. APD treatment was performed with 10 L/10 h and 5 cycles of exchange. After 72 h, the daily peritoneal Kt/V, the accuracy of the injection rate, accuracy of the injection temperature, safety, and manipulability of the machine were assessed. Noninferiority test was conducted between the two groups.@*Results@#The daily peritoneal Kt/V in the APD machine made in China and the imported APD machine were 0.17 (0.14, 0.25) and 0.16 (0.13, 0.23), respectively. There was no significant difference between the groups (Z = 0.15, P = 0.703). The lower limit of the daily Kt/V difference between the two groups was 0.0069, which was greater than the noninferiority value of -0.07 in this study. The accuracy of the injection rate and injection temperature was 89.7% and 91.5%, respectively, in the domestic APD machine, which were both slightly better than the accuracy rates of 84.0% and 86.8% in the imported APD machine (89.7% vs. 84.0%, P = 0.2466; 91.5% vs. 86.8%, P = 0.0954). Therefore, the APD machine made in China was not inferior to the imported APD machine. The fuselage of the imported APD machine was space-saving, while the APD machine made in China was superior with respect to body mobility, man-machine dialog operation, alarm control, and patient information recognition.@*Conclusions@#The FM machine made in China was not inferior to the imported APD machine. In addition, the FM machine made in China had better operability.@*Trial Registration@#Clinicaltrials.gov, NCT02525497; https://clinicaltrials.gov/ct2/results?cond=&term=NCT02525497&cntry=& state=&city=&dist=.


Subject(s)
Adult , Female , Humans , Male , Middle Aged , China , Cross-Over Studies , Multicenter Studies as Topic , Peritoneal Dialysis , Methods , Quality of Life , Temperature
12.
Chinese Medical Journal ; (24): 1894-1903, 2016.
Article in English | WPRIM | ID: wpr-251277

ABSTRACT

<p><b>BACKGROUND</b>The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy (IgAN) are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN.</p><p><b>METHODS</b>It is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan (80 mg/d) wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo (Group A), 50 mg/d clopidogrel (Group B), 20 mg/d leflunomide (Group C), or 50 mg/d clopidogrel and 20 mg/d leflunomide (Group D). The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry.</p><p><b>RESULTS</b>The effects of telmisartan combined with leflunomide on changes in proteinuria (0.36 [95% confidence interval (CI) 0.18-0.55] g/d, P < 0.001), in serum uric acid (76.96 [95% CI 57.44-96.49] μmol/L, P < 0.001), in serum creatinine (9.49 [95% CI 6.54-12.44] μmol/L, P < 0.001), and in estimated glomerular filtration rate (-6.72 [95% CI-9.46 to -3.98] ml·min-1·1.73 m-2, P < 0.001) were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight (P > 0.05). Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed.</p><p><b>CONCLUSIONS</b>Telmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients.</p><p><b>TRIAL REGISTRATION</b>chictr.org.cn, ChiCTR-TRC-10000776; http://www.chictr.org.cn/showproj.aspx?proj=8760.</p>


Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Benzimidazoles , Therapeutic Uses , Benzoates , Therapeutic Uses , Blood Pressure , China , Creatinine , Blood , Glomerular Filtration Rate , Glomerulonephritis, IGA , Blood , Drug Therapy , Isoxazoles , Therapeutic Uses , Kidney Function Tests , Prospective Studies , Ticlopidine , Therapeutic Uses , Treatment Outcome , Uric Acid , Blood
13.
Acta Pharmaceutica Sinica ; (12): 217-224, 2014.
Article in Chinese | WPRIM | ID: wpr-297990

ABSTRACT

To explore novel coumarin derivatives with more potent anti-proliferative activity, a series of novel compounds were designed and synthesized by linking Schiff base and N, N-bis (2-chloroethyl) amine pharmacophore of nitrogen mustards to the coumarin's framework. Their structures were confirmed by 1H NMR, MS and element analysis techniques. In vitro anti-proliferative activities were evaluated against HepG2, DU145 and MCF7 cell lines by the standard MTT assay. The results showed that some of the target compounds exhibited strong anti-proliferative activities against selected tumor cells, and compounds 7c, 7f, 7g, 7h and 7q were better than or equal to the activities of positive control, they deserved further development.


Subject(s)
Humans , Antineoplastic Agents , Pharmacology , Cell Line, Tumor , Cell Proliferation , Coumarins , Pharmacology , Drug Design , Drug Screening Assays, Antitumor , Nitrogen Mustard Compounds , Pharmacology , Schiff Bases , Structure-Activity Relationship
14.
Acta Pharmaceutica Sinica ; (12): 1259-1265, 2013.
Article in Chinese | WPRIM | ID: wpr-259485

ABSTRACT

Twenty-four novel benzothiazole derivatives containing arylpiperazine were designed and synthesized by bioisosterism principle. Anti-proliferative effect of these synthesized compounds against four cancer cell and two normal cell lines were evaluated in vitro by the standard MTT assay. Pharmacological test showed that most of the compounds exhibited potent antitumor activity. Some of the compounds (II2, II3, II6, II7) showed strong anti-proliferation activities against HepG2 and HeLa229 cell lines with the IC 50 values of 1.6-4.5 micromol x L(-1) and 2.5-5.3 micromol x L(-1), respectively, and compounds having cyan in p-substituted benzene ring (I4, I8, I12, II4, II8 and II12) were found to have better antitumor activities against AsPC-1 cell lines with the IC50 values of 5.2-11.3 micromol x L(-1). The structure-activity relationship of benzothiazole derivatives containing arylpiperazine was also discussed preliminarily.


Subject(s)
Humans , Antineoplastic Agents , Chemistry , Pharmacology , Benzothiazoles , Chemistry , Pharmacology , Cell Line, Tumor , Cell Proliferation , Drug Screening Assays, Antitumor , Inhibitory Concentration 50 , Molecular Structure , Piperazines , Chemistry , Structure-Activity Relationship
15.
Chinese Medical Journal ; (24): 4655-4659, 2013.
Article in English | WPRIM | ID: wpr-341763

ABSTRACT

<p><b>BACKGROUND</b>With the increase in hemodialysis (HD) patients, the blood dialysis patient's quality of life (QoL) and long-term survival are still a challenge for clinicians. Recent studies have found that most of the HD patients have sleep disorders, which have a certain correlation with long-term survival and QoL. But there are few studies of Chinese in this field. This study aimed to investigate whether increasing the dialysis dose can improve sleep quality, so we treated HD patients on long intermittent hemodialysis (LIHD).</p><p><b>METHODS</b>Forty patients who were treated by conventional HD at the Beijing Friendship Hospital Blood Purification Center were offered the option of LIHD. The patients' laboratory data, medication use, and questionnaire answers were analyzed. Conventional HD was delivered thrice weekly with 4 hours per treatment, and LIHD was delivered thrice weekly with 8 hours per treatment. The study lasted 6 months. Questionnaires included sleep quality survey and QoL SF-36; the former includes the Athens Insomnia Scale, Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS).</p><p><b>RESULTS</b>After conversion to LIHD the dialysis efficiency (Kt/V) significantly increased than before (P < 0.05) and clearance rate of urea nitrogen also increased from 67 to 78% (P < 0.01). After conversion, median values for Hb increased from 108.95 to 126.55 g/L (P < 0.01); albumin increased from 38.85 to 40.05 g/L (P < 0.01). Phosphorus decreased from 2.69 to 1.54 mmol/L (P < 0.01), but there was no alteration in blood calcium; phosphorus and calcium-phosphate product levels were under more control, but parathyroid hormone (iPTH) level did not change after conversion to LIHD. After conversion, blood pressure (BP) was better controlled than before and the mean number of antihypertensive drugs prescribed declined from 2.9 to 0.5 (P < 0.01). There was a significant reduction in the use of erythropoietin-stimulating agent of 5250 U/w (P < 0.01). Sleep quality significantly improved in the 2 months after conversion to LIHD, and the PSQI score decreased from 10.80 to 5.45 and the ESS score decreased from 12.05 to 5.30 (P < 0.01). However, sleep quality started to decline after 2 months on LIHD. QoL SF-36 score increased from 410.92 to 592.53 (P < 0.01).</p><p><b>CONCLUSION</b>LIHD offers an effective improvement in dialysis adequacy for Chinese maintenance HD patients, but it improves sleep quality only briefly which may be related to loss of serum calcium and parathyroid dysfunction.</p>


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Calcium , Blood , Kidney Failure, Chronic , Blood , Therapeutics , Phosphorus , Blood , Quality of Life , Renal Dialysis , Reference Standards
16.
Chinese Medical Journal ; (24): 3295-3300, 2013.
Article in English | WPRIM | ID: wpr-354493

ABSTRACT

<p><b>BACKGROUND</b>It has been suggested that glycated hemoglobin (HbA1c) underestimate the actual glycemic control levels in maintenance hemodialysis (MHD) patients, because of anemia and the using of erythropoietin (EPO); it was recommended that glycated albumin (GA) should be an alternative marker. Therefore, the assessment performances of glycemic control were compared between GA and HbA1c in this research by referring to mean plasma glucose (MPG) in diabetes mellitus (DM) patients undergoing MHD or not.</p><p><b>METHODS</b>MPG was calculated according to the data registered at enrollment and follow-up 2 months later and corresponding HbA1c, albumin (ALB), GA, etc. were measured in 280 cases. A case-control study for comparing GA and HbA1c was done among the groups of MHD patients with DM (n=88) and without DM (NDM; n=90), and non-MHD ones with DM (n=102) using MPG for an actual glycemic control standard.</p><p><b>RESULTS</b>In these 3 groups, only for DM patients' (whether undergoing MHD or not), GA and HbA1c correlated with MPG significantly (P < 0.01). Through linear regression analysis, it could be found that the regression curves of GA almost coincided in MHD and non-MHD patients with DM, because the intercepts (2.418 vs. 2.329) and slopes (0.053 vs. 0.057) were very close to each other. On the contrary, regression curves of HbA1c did not coincide in the two groups, because variance of the slopes (0.036 vs. 0.052) were relatively large. Through comparing receiver operating characteristic (ROC) areas under the curve (AUC), it could be understood that the assessment performances of GA and HbA1c in MHD patients were lower than those in non-MHD ones, and assessment performance of HbA1c in MHD patients was better than GA (P < 0.05). In addition, the effects of Hb and EPO dose on HbA1c, or that of ALB on GA were unobvious in our study.</p><p><b>CONCLUSIONS</b>Actual glycemic control level in MHD patients with DM may be underestimated by HbA1c, and it could be avoided by GA; however, glycemic evaluating performance of HbA1c may be still better than that of GA. Therefore, HbA1c should not be replaced completely although GA can be used as a choice to monitor glycemic level.</p>


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Biomarkers , Metabolism , Case-Control Studies , Diabetes Mellitus, Type 2 , Metabolism , Therapeutics , Glycated Hemoglobin , Metabolism , Renal Dialysis , Serum Albumin , Metabolism
17.
Acta Pharmaceutica Sinica ; (12): 83-88, 2013.
Article in Chinese | WPRIM | ID: wpr-235700

ABSTRACT

Fifteen novel 5-substituted-2-(pyridyl)benzothiazole compounds were designed and synthesized by simple hydrolization and condensation reaction of the 2-amino-5-substituent benzothiazole. Activities of these synthesized compounds were evaluated on Bcap-37, HCT-15 and HepG2 tumor cells in vitro by standard MTT assay. 5-Fluorouracil (5-FU) was used as the positive control. The results revealed that most of the new compounds had potent effects on Bcap-37, HCT-15 and HepG2 tumor cells, and had no or less effect on 293T and L02 normal cells. Particularly, compounds 1c and 2e exhibited better activities on HCT-15 and HepG2 cells with IC50 values of 41.59 and 38.65 micromol x L(-1), and 1i showed excellent activities on Bcap-37 and HepG2 cells with IC50 values of 46.63 and 23.51 micromol x L(-1), respectively. The structure-activity relationship of 5-substituted-2-(pyridyl)benzothiazole compounds were also discussed preliminarily.


Subject(s)
Humans , Antineoplastic Agents , Chemistry , Pharmacology , Benzothiazoles , Chemistry , Pharmacology , Cell Line, Tumor , Cell Proliferation , Drug Screening Assays, Antitumor , Molecular Structure , Structure-Activity Relationship
18.
Chinese Medical Journal ; (24): 4204-4209, 2013.
Article in English | WPRIM | ID: wpr-327602

ABSTRACT

<p><b>BACKGROUND</b>A multi-center large scale study is needed to confirm the efficacy and safety of domestic peritoneal dialysis (PD) solutions. Some researchers believe that 6 L/d is enough for adequate dialysis, but there is no multi-center prospective study on Chinese population to confirm this. In this study, we evaluated the efficacy and safety of domestic PD solution (Changfu) and its difference between 6 L and 8 L dosage.</p><p><b>METHODS</b>Adult PD patients who had taken PD therapy for at least one month were selected and divided into four groups according to two dialysis solution brands and two dialysis dosages, i.e., 6 L dose with Changfu dialysis solution, 6 L dose with Baxter dialysis solution, 8 L dose with Changfu dialysis solution, and 8 L dose with Baxter dialysis solution. After 48 weeks, the changes of primary and secondary efficacy indices were compared between different types and different dosages. We also analyzed the changes of safety indices.</p><p><b>RESULTS</b>Changes of Kt/V from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of creatinine clearance rate (Ccr). Normalized protein catabolic rate (nPCR) from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of net ultrafiltration volume (nUF) and estimated glomerular filtration rate (eGFR). Changes of nPCR from baseline to 48 weeks between 6 L and 8 L showed no statistical differences; so did those of nUF and eGFR. The decline of Kt/V from baseline to 48 weeks in 6 L group was more than that in 8 L group. Change of Ccr was similar. During the 48-week period, the mean Kt/V was above 1.7/w, and mean Ccr was above 50 L×1.73 m(-2)×w(-1). More adverse events were found in Changfu group before Changfu Corporation commenced technology optimization, and the statistical differences disappeared after that.</p><p><b>CONCLUSIONS</b>The domestic PD solution (Changfu) was proven to be as effective as Baxter dialysis solution. During 48-week period, a dosage of 6 L/d was enough for these patients to reach adequate PD. Clinical study promotes technological optimization, further helps to improve the safety indices of the medical products.</p>


Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Dialysis Solutions , Therapeutic Uses , Peritoneal Dialysis , Methods
19.
Chinese Medical Journal ; (24): 2787-2789, 2012.
Article in English | WPRIM | ID: wpr-244351

ABSTRACT

We reported a rare case of a dialysis patient coincident pituitary prolactinoma with calcification. A 55-year-old woman who had undergone hemodialysis for 8 years was admitted to the nephrology unit because of headache, blurred vision, and hypotension. Physical examination was normal; endocrinological examination demonstrated elevated serum levels of prolactin (> 4240 mIU/L), but other hormonal profiles, such as growth hormon, adrenocorticotropic hormone, thyroid stimulating hormone, free triiodothyronine, free thyroxine, follicle-stimulating hormone and luteinizing hormone, were absolutely or relatively lower. A cranial computed tomography (CT) suggested saddle area a high-density screenage with an anteroposterior diameter of 1.0 cm. A cerebral magnetic resonance scan confirmed the pituitary adenoma accompanied with calcification. Contrast-enhanced T1-weighted images revealed a less enhancing tumor, 14 mm wide round lesion with a high intensity signal. It enlarges the sella turcica, but the optic chiasma is not displaced. We suggest that in the differential diagnosis of any hemodialysis patient with severe headache, hypotension, and visual disturbances, this syndrome should be considered as prompt pituitary adenoma.


Subject(s)
Female , Humans , Middle Aged , Headache , Parasitology , Pituitary Neoplasms , Diagnosis , Prolactinoma , Diagnosis , Renal Dialysis , Vision Disorders , Pathology
20.
Acta Pharmaceutica Sinica ; (12): 194-199, 2012.
Article in Chinese | WPRIM | ID: wpr-323059

ABSTRACT

To explore new agents of gamma-aminobutyric acid (GABA) derivatives with more potent antiepileptic activity, a series of 4-(2-acetoxybenzoylamino) butyramide derivatives were designed and synthesized. All of the novel compounds (5a-51) were synthesized from GABA as starting material, and their structures were confirmed with IR, 1H NMR, EI-MS and elemental analysis. Preliminary pharmacological test in vitro showed that all target compounds displayed strong antiepileptic activities and were worth for further study. The structure-activity relationship of 4-(2-acetoxybenzoylamino) butyramide derivatives was also discussed preliminarily.


Subject(s)
Animals , Female , Male , Mice , 4-Aminopyridine , Amides , Chemistry , Therapeutic Uses , Anticonvulsants , Chemistry , Therapeutic Uses , Epilepsy , Drug Therapy , Molecular Structure , Random Allocation , Structure-Activity Relationship , gamma-Aminobutyric Acid , Chemistry
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