Drug Target Insights最新文献_第8页

7-NI and ODQ Disturbs Memory in the Elevated Plus Maze, Morris Water Maze, and Radial Arm Maze Tests in Mice. 7-NI和ODQ对高架迷宫、Morris水迷宫和桡臂迷宫小鼠记忆的干扰

IF 2.7

Drug Target Insights Pub Date : 2015-03-04 eCollection Date: 2015-01-01 DOI: 10.4137/DTI.S23378

Oguz Mutlu, Furuzan Akar, Ipek Komsuoglu Celikyurt, Pelin Tanyeri, Guner Ulak, Faruk Erden

{"title":"7-NI and ODQ Disturbs Memory in the Elevated Plus Maze, Morris Water Maze, and Radial Arm Maze Tests in Mice.","authors":"Oguz Mutlu, Furuzan Akar, Ipek Komsuoglu Celikyurt, Pelin Tanyeri, Guner Ulak, Faruk Erden","doi":"10.4137/DTI.S23378","DOIUrl":"https://doi.org/10.4137/DTI.S23378","url":null,"abstract":"Nitric oxide (NO) is an atypical neurotransmitter that causes changes in cognition. Nitric oxide synthase (NOS) and guanylate cyclase (GC) inhibitors have been shown to exert some effects on cognition in previous studies; however, the findings have been controversial. This study was aimed at understanding the effects of an NOS inhibitor, 7-nitroindazole (7-NI), and a guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), on spatial memory in modified elevated plus maze (mEPM), Morris water maze (MWM), and radial arm maze (RAM) tests. Male Balb-c mice were treated via intraperitoneal injections with 7-NI (15 mg/kg), ODQ (3, 10 mg/kg), L-arginine (100 mg/kg) + 7-NI (15 mg/kg), or physiological saline. ODQ (3 mg/kg) and 7-NI (15 mg/kg) significantly increased the second-day latency in the mEPM test. 7-NI (15 mg/kg) and ODQ (10 mg/kg) significantly increased the escape latency in second, third, and fourth sessions, decreased the time spent in the escape platform's quadrant, and increased the mean distance to the platform in the probe trial of the MWM test. ODQ (3, 10 mg/kg) and 7-NI (15 mg/kg) significantly increased the number of errors, whereas only 7-NI increased the latency in the RAM test. The administration of L-arginine (100 mg/kg) prior to 7-NI inverted the effects of 7-NI, which supports the role of NO on cognition. Our study shows that the NO/cGMP/GS pathway can regulate spatial memory in mice. ","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"9 ","pages":"1-8"},"PeriodicalIF":2.7,"publicationDate":"2015-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/DTI.S23378","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33145207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 27

Screening Analogs of β-OG Pocket Binder as Fusion Inhibitor of Dengue Virus 2 登革病毒2型融合抑制剂β-OG口袋结合物的筛选

IF 2.7

Drug Target Insights Pub Date : 2015-01-01 DOI: 10.4137/DTI.S31566

Usman SF Tambunan, H. Zahroh, A. A. Parikesit, Syarifuddin Idrus, D. Kerami

引用次数: 19

Management of Diabetes Associated with Nephrotic Syndrome: Therapeutic Potential of Dapagliflozin for Protracted Volume Retention 糖尿病肾病综合征的管理:达格列净治疗持续性容量潴留的潜力

IF 2.7

Drug Target Insights Pub Date : 2015-01-01 DOI: 10.4137/DTI.S31710

T. Imai, T. Akimoto, C. Ito, Takahiro Masuda, D. Nagata

引用次数: 12

Genome-wide Analysis of Mycoplasma hominis for the Identification of Putative Therapeutic Targets. 人支原体基因组分析鉴定推定治疗靶点。

IF 2.7

Drug Target Insights Pub Date : 2014-12-09 eCollection Date: 2014-01-01 DOI: 10.4137/DTI.S19728

Md Masud Parvege, Monzilur Rahman, Mohammad Shahnoor Hossain

引用次数: 8

The Expression of Serum Antibodies Against Gonadotropin-releasing Hormone (GnRH1), Progonadoliberin-2, Luteinizing Hormone (LH), and Related Receptors in Patients with Gastrointestinal Dysfunction or Diabetes Mellitus. 胃肠功能紊乱或糖尿病患者血清中促性腺激素释放激素 (GnRH1)、前列腺素-2、促黄体生成素 (LH) 及相关受体抗体的表达。

IF 2.7

Drug Target Insights Pub Date : 2014-11-10 eCollection Date: 2014-01-01 DOI: 10.4137/DTI.S19352

Bodil Roth, Kerstin Berntorp, Bodil Ohlsson

{"title":"The Expression of Serum Antibodies Against Gonadotropin-releasing Hormone (GnRH1), Progonadoliberin-2, Luteinizing Hormone (LH), and Related Receptors in Patients with Gastrointestinal Dysfunction or Diabetes Mellitus.","authors":"Bodil Roth, Kerstin Berntorp, Bodil Ohlsson","doi":"10.4137/DTI.S19352","DOIUrl":"10.4137/DTI.S19352","url":null,"abstract":"Gonadotropin-releasing hormone (GnRH) 1 and 2 and luteinizing hormone (LH) receptors have been described in the gastrointestinal tract. We have previously demonstrated antibodies in serum against GnRH1 in patients with gastrointestinal dysfunction and diabetes mellitus, and antibodies against GnRH receptor, LH, and LH receptor in patients with infertility. The aim of this study was to search for the expression of serum antibodies against GnRH1 with an improved enzyme-linked immune sorbent assay (ELISA), and antibodies against progonadoliberin-2, GnRH2, GnRH receptor, LH, and LH receptor with newly developed ELISAs, in patients with gastrointestinal dysfunction or diabetes mellitus. Healthy blood donors served as controls. Medical records were scrutinized. Our conclusion was that IgM antibodies against GnRH1, progonadoliberin-2, and/or GnRH receptors were more prevalent in patients with functional gastrointestinal disorders, gastrointestinal dysmotility, and/or diabetes mellitus, whereas IgG antibodies against these peptides, and LH- and LH receptor antibodies, were expressed in the same magnitude as in controls. ","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"8 ","pages":"45-50"},"PeriodicalIF":2.7,"publicationDate":"2014-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32861958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Febuxostat for hyperuricemia in patients with advanced chronic kidney disease. 非布司他治疗晚期慢性肾病患者的高尿酸血症。

IF 2.7

Drug Target Insights Pub Date : 2014-08-13 eCollection Date: 2014-01-01 DOI: 10.4137/DTI.S16524

Tetsu Akimoto, Yoshiyuki Morishita, Chiharu Ito, Osamu Iimura, Sadao Tsunematsu, Yuko Watanabe, Eiji Kusano, Daisuke Nagata

{"title":"Febuxostat for hyperuricemia in patients with advanced chronic kidney disease.","authors":"Tetsu Akimoto, Yoshiyuki Morishita, Chiharu Ito, Osamu Iimura, Sadao Tsunematsu, Yuko Watanabe, Eiji Kusano, Daisuke Nagata","doi":"10.4137/DTI.S16524","DOIUrl":"https://doi.org/10.4137/DTI.S16524","url":null,"abstract":"Febuxostat is a nonpurine xanthine oxidase (XO) inhibitor, which recently received marketing approval. However, information regarding the experience with this agent among advanced chronic kidney disease (CKD) patients is limited. In the current study, we investigated the effects of oral febuxostat in patients with advanced CKD with asymptomatic hyperuricemia. We demonstrated, for the first time, that not only the serum levels of uric acid (UA) but also those of 8-hydroxydeoxyguanosine, an oxidative stress marker, were significantly reduced after six months of febuxostat treatment, with no adverse events. These results encouraged us to pursue further investigations regarding the clinical impact of lowering the serum UA levels with febuxostat in advanced CKD patients in terms of concomitantly reducing oxidative stress via the blockade of XO. More detailed studies with a larger number of subjects and assessments of the effects of multiple factors affecting hyperuricemia, such as age, sex, and dietary habits, would shed light on the therapeutic challenges of treating asymptomatic hyperuricemia in patients with various stages of CKD. ","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"8 ","pages":"39-43"},"PeriodicalIF":2.7,"publicationDate":"2014-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/DTI.S16524","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32659674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 30

Molecular and Kinetic Characterization of Babesia microti Gray Strain Lactate Dehydrogenase as a Potential Drug Target. 微巴贝斯虫灰色菌株乳酸脱氢酶作为潜在药物靶点的分子和动力学特性

IF 2.7

Drug Target Insights Pub Date : 2014-07-28 eCollection Date: 2014-01-01 DOI: 10.4137/DTI.S16504

Patrick Vudriko, Tatsunori Masatani, Shinuo Cao, Mohamad Alla Terkawi, Ketsarin Kamyingkird, Ahmed A Mousa, Paul F Adjou Moumouni, Yoshifumi Nishikawa, Xuenan Xuan

{"title":"Molecular and Kinetic Characterization of Babesia microti Gray Strain Lactate Dehydrogenase as a Potential Drug Target.","authors":"Patrick Vudriko, Tatsunori Masatani, Shinuo Cao, Mohamad Alla Terkawi, Ketsarin Kamyingkird, Ahmed A Mousa, Paul F Adjou Moumouni, Yoshifumi Nishikawa, Xuenan Xuan","doi":"10.4137/DTI.S16504","DOIUrl":"https://doi.org/10.4137/DTI.S16504","url":null,"abstract":"Babesia microti is an emerging zoonotic protozoan organism that causes \"malaria-like\" symptoms that can be fatal in immunocompromised people. Owing to lack of specific therapeutic regiment against the disease, we cloned and characterized B. microti lactate dehydrogenase (BmLDH) as a potential molecular drug receptor. The in vitro kinetic properties of BmLDH enzyme was evaluated using nicotinamide adenine dinucleotide (NAD(+)) as a co-factor and lactate as a substrate. Inhibitory assay was also done using gossypol as BmLDH inhibitor to determine the inhibitory concentration 50 (IC50). The result showed that the 0.99 kbp BmLDH gene codes for a barely soluble 36 kDa protein (332 amino acids) localized in both the cytoplasm and nucleus of the parasite. In vitro enzyme kinetic studies further revealed that BmLDH is an active enzyme with a high catalytic efficiency at optimal pH of 10.2. The K m values of NAD(+) and lactate were 8.7 ± 0.57 mM and 99.9 ± 22.33 mM, respectively. The IC50 value for gossypol was 0.345 μM, while at 2.5 μM, gossypol caused 100% inhibition of BmLDH catalytic activity. These findings, therefore, provide initial evidence that BmLDH could be a potential drug target, although further in vivo studies are needed to validate the practical application of lactate dehydrogenase inhibitors against B. microti infection. ","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"8 ","pages":"31-8"},"PeriodicalIF":2.7,"publicationDate":"2014-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/DTI.S16504","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32587107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

Effects of zaprinast and rolipram on olfactory and visual memory in the social transmission of food preference and novel object recognition tests in mice. 扎普利司特和罗利普兰对食物偏好社会传递和新物体识别实验小鼠嗅觉和视觉记忆的影响。

IF 2.7

Drug Target Insights Pub Date : 2014-04-29 eCollection Date: 2014-01-01 DOI: 10.4137/DTI.S14813

Furuzan Akar, Oguz Mutlu, Ipek K Celikyurt, Emine Bektas, Mehmet H Tanyeri, Guner Ulak, Pelin Tanyeri, Faruk Erden

{"title":"Effects of zaprinast and rolipram on olfactory and visual memory in the social transmission of food preference and novel object recognition tests in mice.","authors":"Furuzan Akar, Oguz Mutlu, Ipek K Celikyurt, Emine Bektas, Mehmet H Tanyeri, Guner Ulak, Pelin Tanyeri, Faruk Erden","doi":"10.4137/DTI.S14813","DOIUrl":"10.4137/DTI.S14813","url":null,"abstract":"The role of phosphodiesterase (PDE) inhibitors in central nervous system has been investigated and shown to stimulate neuronal functions and increase neurogenesis in Alzheimer patients. The aim of this study is to investigate effect of PDE5 inhibitor zaprinast and PDE4 inhibitor rolipram on visual memory in novel object recognition (NOR) test, on olfactory memory in social transmission of food preference (STFP) test, and also on locomotion and anxiety in open field test in naive mice. Male Balb-c mice were treated intraperitoneally (i.p.) with zaprinast (3 and 10 mg/kg), rolipram (0.05 and 0.1 mg/kg), or physiological saline. Zaprinast (10 mg/kg) significantly increased cued/non-cued food eaten compared to control group, while rolipram had a partial effect on retention trial of STFP test. Zaprinast (10 mg/kg) and rolipram (0.05 and 0.1 mg/kg) significantly increased ratio index (RI) compared to control group in retention trial of NOR test. There was no significant effect of zaprinast and rolipram on total distance moved, speed, and center zone duration in open field test. Results of this study revealed that both zaprinast and rolipram enhanced visual memory in NOR test, however zaprinast exerted a significant memory-enhancing effect compared to rolipram in STFP test in mice. ","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"8 ","pages":"23-9"},"PeriodicalIF":2.7,"publicationDate":"2014-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/DTI.S14813","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32363561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

The Antidepressant Agomelatine Improves Memory Deterioration and Upregulates CREB and BDNF Gene Expression Levels in Unpredictable Chronic Mild Stress (UCMS)-Exposed Mice. 抗抑郁药阿戈美拉汀改善不可预测的慢性轻度应激(UCMS)暴露小鼠的记忆退化和上调CREB和BDNF基因表达水平。

IF 2.7

Drug Target Insights Pub Date : 2014-03-05 eCollection Date: 2014-01-01 DOI: 10.4137/DTI.S13870

Esen Gumuslu, Oguz Mutlu, Deniz Sunnetci, Guner Ulak, Ipek K Celikyurt, Naci Cine, Furuzan Akar, Hakan Savlı, Faruk Erden

{"title":"The Antidepressant Agomelatine Improves Memory Deterioration and Upregulates CREB and BDNF Gene Expression Levels in Unpredictable Chronic Mild Stress (UCMS)-Exposed Mice.","authors":"Esen Gumuslu, Oguz Mutlu, Deniz Sunnetci, Guner Ulak, Ipek K Celikyurt, Naci Cine, Furuzan Akar, Hakan Savlı, Faruk Erden","doi":"10.4137/DTI.S13870","DOIUrl":"https://doi.org/10.4137/DTI.S13870","url":null,"abstract":"Agomelatine, a novel antidepressant with established clinical efficacy, acts as an agonist of melatonergic MT1 and MT2 receptors and as an antagonist of 5-HT2C receptors. The present study was undertaken to investigate whether chronic treatment with agomelatine would block unpredictable chronic mild stress (UCMS)-induced cognitive deterioration in mice in passive avoidance (PA), modified elevated plus maze (mEPM), novel object recognition (NOR), and Morris water maze (MWM) tests. Moreover, the effects of stress and agomelatine on brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) messenger ribonucleic acid (mRNA) levels in the hippocampus was also determined using quantitative real-time polymerase chain reaction (RT-PCR). Male inbred BALB/c mice were treated with agomelatine (10 mg/kg, i.p.), melatonin (10 mg/kg), or vehicle daily for five weeks. The results of this study revealed that UCMS-exposed animals exhibited memory deterioration in the PA, mEPM, NOR, and MWM tests. The chronic administration of melatonin had a positive effect in the PA and +mEPM tests, whereas agomelatine had a partial effect. Both agomelatine and melatonin blocked stress-induced impairment in visual memory in the NOR test and reversed spatial learning and memory impairment in the stressed group in the MWM test. Quantitative RT-PCR revealed that CREB and BDNF gene expression levels were downregulated in UCMS-exposed mice, and these alterations were reversed by chronic agomelatine or melatonin treatment. Thus, agomelatine plays an important role in blocking stress-induced hippocampal memory deterioration and activates molecular mechanisms of memory storage in response to a learning experience. ","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"8 ","pages":"11-21"},"PeriodicalIF":2.7,"publicationDate":"2014-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/DTI.S13870","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32181751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 47

In Silico Molecular Characterization of Cysteine Protease YopT from Yersinia pestis by Homology Modeling and Binding Site Identification. 鼠疫耶尔森菌半胱氨酸蛋白酶YopT的同源性建模和结合位点鉴定

IF 2.7

Drug Target Insights Pub Date : 2014-01-13 eCollection Date: 2014-01-01 DOI: 10.4137/DTI.S13529

Md Anayet Hasan, S M Alauddin, Mohammad Al Amin, Suza Mohammad Nur, Adnan Mannan

{"title":"In Silico Molecular Characterization of Cysteine Protease YopT from Yersinia pestis by Homology Modeling and Binding Site Identification.","authors":"Md Anayet Hasan, S M Alauddin, Mohammad Al Amin, Suza Mohammad Nur, Adnan Mannan","doi":"10.4137/DTI.S13529","DOIUrl":"https://doi.org/10.4137/DTI.S13529","url":null,"abstract":"Plague is a major health concern and Yersinia pestis plays the central causal role in this disease. Yersinia pestis has developed resistance against the commonly available drugs. So, it is now a key concern to find a new drug target. Cysteine protease YopT enzyme is an important factor used by Yersinia pestis for pathogenesis in its host and it has the anti-phagocytic function of removal of C-termini lipid modification. The 3D structure of cysteine protease YopT of Yersinia pestis was determined by means of homology modeling through multiple alignments followed by intensive optimization and validation. The modeling was done by Phyre 2 and refined by ModRefiner. The obtained model was verified with structure validation programs such as PROCHECK, verify 3D and ERRAT for reliability. Interacting partners and active sites were also determined. PROCHECK analysis showed that 93% of the residues are in the most favored region, 5.9% are in the additional allowed region and 1.1% are in the generously allowed region of the Ramachandran plot. The verify 3D value of 0.78 indicates that the environmental profile of the model is good. SOPMA is employed for calculation of the secondary structural features of cysteine protease YopT. Active site determination through CASTp proposes that this protein can be utilized as a potential drug target. However, these findings should further be confirmed by wet lab studies for a targeted therapeutic agent design against Yersinia pestis. ","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"8 ","pages":"1-9"},"PeriodicalIF":2.7,"publicationDate":"2014-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/DTI.S13529","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32117668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 19