Design, synthesis and antidiabetic activity studies of purine derivatives / 药学学报

Based our previous work, twelve purine derivatives were designed and synthesized as dual modulators of GPR119 and DPP-4by conjugating the GPR119 activating and DPP-4 inhibiting fragments with the position 6 and 9 of purine core via an approach of merged pharmacophores. Compound 11, bearing 2-fluoro-4-methylsulphonyl anilide and cyanopyrrolidine moieties, exhibited the most potent GPR119 agonistic activities (EC50 = 0.33 μmol·L-1, IA = 71.1%) and DPP-4 inhibitory (58.4% inhibition at 10 μmol·L-1, 21.2% inhibition at 1 μmol·L-1) activities in the in vitro antidiabetic study. Subsequently, we performed studies on structure activity relationships and molecular docking to guide the further drug design.

Research progress of active probes targeting specific aminoacids / 药学学报

Activity-based protein (proteomic) profiling (ABPP) has emerged as a key component of the broad field of chemical techniques capable of directly analyzing enzyme activity in living systems. With the deepening of research on electrophilic warheads and nucleophilic amino acids, and the continuous proposal and improvement of effective development strategies, the application of amino acid-targeting active probes in various biological systems has facilitated the identification, development of new targets in various disease contexts and discovery of inhibitors. The purpose of this review is to summarize the latest progress in the design and application of active probes targeting specific amino acids, in order to provide support for the further development of amino acid-targeted covalent inhibitordrugs.

Effects of Electroacupuncture at Zhongji and Guanyuan on Urge Urinary Incontinence after Stroke / 中国康复理论与实践

Objective:To observe the effects of electroacupuncture on urge urinary incontinence after stroke. Methods:From May, 2015 to May, 2018, 40 patients with urge urinary incontinence after stroke were randomly divided into control group (n = 20) and electroacupuncture group (n = 20). Both groups accepted routine rehabilitation, while the electroacupuncture group accepted electroacupuncture at Zhongji (CV3) and Guanyuan (CV4) in addition, for four weeks. They recorded the urination log (72 hours), and were assessed with Incontinence Scale, and tested with urodynamics before and after treatment. Results:There were 17 cases in the control group and 18 in the electroacupuncture group finishing the trial. The total number of urination, the number of urge incontinence and the number of calls for urination carer at night decreased, the average volume of urine increased, and the score of Incontinence Scale decreased (|t| > 4.770, P < 0.001) in both groups, which were better in the electroacupuncture group than in the control group (|t| > 2.962, P < 0.01). The maximum cystometric bladder capacity and bladder compliance increased in both groups, while the maximum bladder pressure and maximum detrusor pressure decreased after treatment (|t| > 4.052, P < 0.001), which were better in the electroacupuncture group than in the control group (|t| > 2.716, P < 0.05). Conclusion:Electroacupuncture at Zhongji and Guanyuan is effective on urge urinary incontinence, which relates with reducing detrusor and bladder pressure, increasing bladder volume, and improving bladder compliance.

Concentration-dependent effects of nitric oxide on tumors and chemosensitivity / 药学学报

The resistance and dose limitation of tumors is a serious obstacle to cytotoxic drug therapy in the field of medical oncology. Nitric oxide (NO) is a powerful adjuvant for tumor hypersensitivity for traditional chemotherapy and radiation therapy. The concentration of NO plays an important role in affecting its anti-tumor effect. This review summarizes the mechanism of concentration-dependent effects of NO on tumor cells and the mechanism of chemotherapy sensitization. It provides evidence for rational use of NO to exert anti-tumor effects, and overcoming multidrug resistance and anti-tumor drug development.

Influence of G-protein β-Polypeptide 3 C825T Polymorphism on Antihypertensive Response to Telmisartan and Amlodipine in Chinese Patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>G-protein β-polypeptide 3 (GNB3) is a β subunit isoform of G-protein that plays important role in signal transduction of membrane G-protein coupled receptors (GPCRs). The GNB3 splice variant C825T (rs5443) is associated with risk for essential hypertension (EH) and efficacy of therapeutic drugs targeting GPCRs. It is unknown whether the polymorphism is associated with blood pressure (BP) response to telmisartan or amlodipine, two widely prescribed antihypertensive drugs.</p><p><b>METHODS</b>A total of 93 subjects initially diagnosed as EH were recruited and underwent a 4-week treatment with telmisartan (42 patients) or amlodipine (51 patients) monotherapy. Both baseline and after-treatment BP were measured. GNB3 C825T polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism.</p><p><b>RESULTS</b>Baseline systolic BP (SBP) and diastolic BP (DBP) were comparable among C825T genotypes in both telmisartan and amlodipine treatment groups. Patients with the CT or TT genotypes showed significantly lower body mass index (BMI) as compared with CC homozygotes in both groups (P < 0.05, respectively). GNB3 825TT homozygotes showed significantly higher after-treatment DBP and mean arterial pressure (MAP) than those carrying at least one 825C allele (P < 0.01) in the telmisartan treatment group. No difference in after-treatment SBP, DBP, and MAP levels among C825T genotypes was observed in the amlodipine treatment group. No significant difference in absolute changes in BP levels was observed among the genotypes in either treatment group.</p><p><b>CONCLUSION</b>The GNB3 C825T splice variant is associated with the DBP-lowering effect of telmisartan but not amlodipine in Chinese EH patients.</p>

Pharmacokinetics of Maxing Shigan decoction in normal rats and RSV pneumonia model rats by HPLC-MS/MS / 中国中药杂志

To establish a LC-MS/MS method to determine the concentrations of liquiritin, glycyrrhizin, glycyrrhetinic acid, amygdalin, amygdalin prunasin, ephedrine, pseudoephedrine and methylephedrine of Maxing Shigan decoction in rat plasma, and study the differences on their pharmacokinetic process in normal rats and RSV pneumonia model rats. After normal rats and RSV pneumonia model rats were orally administered with Maxing Shigan decoction, the blood was collected from retinal vein plexus of different time points. Specifically, tetrahydropalmatine was taken as internal standard for determining ephedrine, while chloramphenicol was taken as internal standard for determining other components. After plasma samples were pre-treated as the above, the supernatant was dried with nitrogen blowing concentrator and then redissolved with methylalcohol. The chromatography was eluted with mobile phase consisted of acetonitrile and 0.1% formic acid solution in a gradient manner. ESI sources were adopted to scan ingredients in ephedra in a positive ion scanning mode and other ingredientsin a negative ion scanning mode. The multiple-reaction monitoring (MRM) method was developed the plasma concentration of each active component. The pharmacokinetic parameters of each group were calculated by using Win-Nonlin 4.1 software and put into the statistical analysis. The result showed the plasma concentration of the eight active ingredients, i.e., liquiritin, glycyrrhizin, glycyrrhetinic acid, amygdalin, amygdalin prunasin, ephedrine, pseudoephedrine and methylephedrine within the ranges of 1.04-1040, 1.04-1040, 0.89-445, 1.05-4200, 1.25-2490, 0.3-480, 0.3-480, 0.3-480 microg x L(-1), with a good linearity and satisfactory precision, recovery and stability in the above ingredients. After modeling, except for glycyrrhetinic acid whose pharmacokinetic parameters were lacked due to the data missing, all of the rest components showed significant higher Cmax, AUC(0-1) and lower clearance rate (CL) than that of the normal group, indicating the increase in absorption in rats in the pathological state by reducing the clearance rate. The method is accurate and sensitive and so can be used to determine the plasma concentrations of the eight active ingredients in Maxing Shigan decoction. RSV pneumonia-infected rats absorbed more ingredients in Maxing Shigan decoction.

Effect of fluoride on oxidative stress and Mn-SOD expression in rats with endemic fluorosis of coal burning / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the effect of fluoride on the oxidative stress of the rats in endemic fluorosis of coal burning and Mn-SOD expression at mRNA and protein levels.</p><p><b>METHODS</b>SD rats were divided into 2 groups (the number of female and male in each group was the same): control group and fluorosis group. All rats of the fluorosis group were fed corn dried by burning coal from endemic fluorosis areas with high fluoride content (fluoride 17 mg/kg in feed) to establish an animal model of fluorosis. In these rats, dental fluorosis was evaluated. The fluoride content in the urine was measured by fluorine ion-elective electrode method. The hepatic tissue and serum level of malonaldehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathion reductase (GR) were measured by biochemical methods. The index signs of liver function were also measured from the serum. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were performed to detect the alterations of Mn-SOD expression in the liver at mRNA and protein levels.</p><p><b>RESULTS</b>The dental fluorosis was observed in the fluorosis group, and the incidence was 11/11. The fluoride contents [(3.50 ± 2.58) mg/L] in the urine of fluorosis rats were increased as compared with the control [(1.42 ± 0.38) mg/L] (P < 0.05). AST [(223.74 ± 71.51) U/L] and total protein [(72.43 ± 5.59) g/L] of the hepatic function index in fluorosis rats showed obviously abnormal as compared with the control [(169.28 ± 53.74) U/L and (82.36 ± 7.31) g/L], respectively (P < 0.05). In the liver the content of MDA [(10.41 ± 0.59) µmol/g protein] increased as compared to the control [(5.80 ± 1.31) µmol/g protein, P < 0.01], and the activities of SOD [(62.60 ± 8.65) U/mg protein] and GR [ (1.17 ± 0.66) U/g protein] markedly decreased in the fluorosis group compared to the control [SOD (117.28 ± 8.64) U/mg protein and GR [(8.80 ± 1.59) U/g protein; P < 0.05, P < 0.01]. The level of Mn-SOD in the liver was markedly decreased in the fluorosis group [(14.83 ± 2.50) U/mg protein] as compared with the control [(34.05 ± 5.22) U/mg protein, P < 0.01]. The levels of mRNA (0.64 ± 0.15) and protein (0.84 ± 0.13) of Mn-SOD were markedly decreased in the fluorosis group as compared with the control [(0.86 ± 0.21) and (1.04 ± 0.14)], respectively (P < 0.05, P < 0.01).</p><p><b>CONCLUSIONS</b>Fluorosis can decrease the activities of Mn-SOD, which is associated with decreased levels of mRNA and protein of Mn-SOD. Down-regulation of Mn-SOD expression may play an important role in the aggravation of oxidative stress in endemic fluorosis.</p>

Effect of acupuncture on the speech and acoustics level in patients with dysarthria / 中国针灸

<p><b>OBJECTIVE</b>To observe the effect of acupuncture combined with speech therapy for dysarthria after stroke or cerebral trauma.</p><p><b>METHODS</b>Sixty-one cases were randomly divided into two groups. The observation group (30 cases) was treated with speech therapy and acupuncture at Lianquan (CV 23), Jinjin (EX-HN 12), Yuye (EX-HN 13), Fengchi (GB 20), Yifeng (TE 17) and Wangu (GB 12) as major acupoints, while the control group (31 cases) was treated with speech therapy only. The changes of speech and acoustics indices were evaluated after 9 weeks treatment.</p><p><b>RESULTS</b>The word articulation and correct rate of text of patients in two groups were both obviously improved after treatment (both P < 0.01). The total effective rate of 96.7% (29/30) in observation group was superior to that of 67.7% (21/31) in control group (P < 0.01). The maximum phonation time (MPT) of patients tested by aeromechanics analyzer were obviously prolonged in observation group (12 cases) and control group (11 cases) (both P < 0.01), and the improvement in observation group was more obvious (P < 0.01).</p><p><b>CONCLUSION</b>Acupuncture combined with speech therapy can improve the effect on language and acoustics level for dysarthria.</p>

Analysis of picture of the tongue on uroschesis patients after acute spinal cord injury / 中国康复理论与实践

@#ObjectiveTo study and find out the mechanism of uroschesis in Traditional Chinese Medicine.Methods111 cases's picture of tougue were observed and recorded.ResultsPale tongue with white and yellow coating occurred in common.Conclusions The picture of the tongue plays a role in finding out TCM mechanism of uroschesis.

Effect of scalp acupunction on children with cerebral palsy / 中国康复理论与实践

@#ObjectiveTo observe the effect of the scalp acupunction on children with cerebral palsy.Methods56 cases with cerebral palsy were divided into two groups: the treating group(scalp acupuncture and modern rehabilitation) and the control group(modern rehabilitation only) with 28 cases each. The ADL and the motion function were compared. ResultsThere is a significant defference between the two groups on the ADL, while no significant defference was observed on motor function between the two groups.Conclusions Scalp acupuncture is effective on improvment of ADL of the children with cerebral palsy.

Effect of L-dicentrine on contractility of the sprips of porcine coronary artery / 中国临床药理学与治疗学

Aim & methods The antagonism of L-dicentrine to contraction of isolated porcine coronary artery strips induced by 5-HT KCl and Ca2+ was observed with U-135 electrophsiological recorder.Results The contractions induced by 5-HT KCl and Ca2+ after high K+ depolarization in the strips of porcine coronary artery were markediy inhibited by L-dicentrine.L-dicentrine significantly depressed maximal response and caused rightward displacement of the dose -response curve. Showing a non-competitive antagonism. In Ca2+ free solution,L-dicentrine inhibited 5-HT-induced contraction of porcine coronary artery,which is dependent on Ca2+ relesed from intracellular store. After Ca2+ concentration in bath solution was restored,L-dicentrine did not influence the contraction of porcine coronary artery depending on extracellular Ca2+.Conclusion L-D have significant relaxation on porcine coronary artery ,which possibly has 5-HT receptor and histamine receptor.