Drug Target Insights最新文献

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Preliminary In Vivo Evaluation of a Hybrid Armored Vascular Graft Combining Electrospinning and Additive Manufacturing Techniques 结合静电纺丝和增材制造技术的混合装甲血管移植物的初步体内评价
IF 2.7
Drug Target Insights Pub Date : 2016-01-01 DOI: 10.4137/DTI.S35202
C. Spadaccio, F. Nappi, F. De Marco, P. Sedati, Fraser W. H. Sutherland, M. Chello, M. Trombetta, A. Rainer
{"title":"Preliminary In Vivo Evaluation of a Hybrid Armored Vascular Graft Combining Electrospinning and Additive Manufacturing Techniques","authors":"C. Spadaccio, F. Nappi, F. De Marco, P. Sedati, Fraser W. H. Sutherland, M. Chello, M. Trombetta, A. Rainer","doi":"10.4137/DTI.S35202","DOIUrl":"https://doi.org/10.4137/DTI.S35202","url":null,"abstract":"In this study, we tested in vivo effectiveness of a previously developed poly-L-lactide/poly-8-caprolactone armored vascular graft releasing heparin. This bioprosthesis was designed in order to overcome the main drawbacks of tissue-engineered vascular grafts, mainly concerning poor mechanical properties, thrombogenicity, and endothelialization. The bioprosthesis was successfully implanted in an aortic vascular reconstruction model in rabbits. All grafts implanted were patent at four weeks postoperatively and have been adequately populated by endogenous cells without signs of thrombosis or structural failure and with no need of antiplatelet therapy. The results of this preliminary study might warrant for further larger controlled in vivo studies to further confirm these findings.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"10 1","pages":"1 - 7"},"PeriodicalIF":2.7,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/DTI.S35202","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70698527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 32
Basal Plasma Levels of Copeptin are Elevated in Inactive Inflammatory Bowel Disease after Bowel Resection. 非活动性炎性肠病患者肠切除术后基础血浆Copeptin水平升高
IF 2.7
Drug Target Insights Pub Date : 2015-07-13 eCollection Date: 2015-01-01 DOI: 10.4137/DTI.S26589
Bodil Ohlsson, Olle Melander
{"title":"Basal Plasma Levels of Copeptin are Elevated in Inactive Inflammatory Bowel Disease after Bowel Resection.","authors":"Bodil Ohlsson,&nbsp;Olle Melander","doi":"10.4137/DTI.S26589","DOIUrl":"https://doi.org/10.4137/DTI.S26589","url":null,"abstract":"<p><p>Evidence of interactions between the enteric nervous system, neuropeptides, and the immune system is growing. The aim of this study was to examine basal plasma levels of a variety of peptide precursors in patients with inflammatory bowel disease (IBD). In two middle-aged cohorts, Malmö Preventive Medicine (n = 5,415) and Malmö Diet and Cost Study (n = 6,103), individuals with the diagnosis of IBD were identified. Medical records were scrutinized. Three controls were matched for each patient. Copeptin, midregional fragments of adrenomedullin, pro-atrial natriuretic peptide, and proenkephalin A, as well as N-terminal protachykinin A and proneurotensin were analyzed in the plasma. Sixty-two IBD patients were identified. The only difference between patients and controls was higher copeptin levels in the patients compared with controls (P = 0.006), with higher copeptin levels in resected than unresected patients (P = 0.020). There was no difference in any precursor levels between Crohn's disease and ulcerative colitis, between different distributions of disease lesions, or between different treatments. </p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"9 ","pages":"21-7"},"PeriodicalIF":2.7,"publicationDate":"2015-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/DTI.S26589","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33897047","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: 1
Medicinal Plants: A Potential Source of Compounds for Targeting Cell Division. 药用植物:靶向细胞分裂化合物的潜在来源。
IF 2.7
Drug Target Insights Pub Date : 2015-06-15 eCollection Date: 2015-01-01 DOI: 10.4137/DTI.S24946
Ihsan N Zulkipli, Sheba R David, Rajan Rajabalaya, Adi Idris
{"title":"Medicinal Plants: A Potential Source of Compounds for Targeting Cell Division.","authors":"Ihsan N Zulkipli,&nbsp;Sheba R David,&nbsp;Rajan Rajabalaya,&nbsp;Adi Idris","doi":"10.4137/DTI.S24946","DOIUrl":"https://doi.org/10.4137/DTI.S24946","url":null,"abstract":"<p><p>Modern medicinal plant drug discovery has provided pharmacologically active compounds targeted against a multitude of conditions and diseases, such as infection, inflammation, and cancer. To date, natural products from medicinal plants remain a solid niche as a source from which cancer therapies can be derived. Among other properties, one favorable characteristic of an anticancer drug is its ability to block the uncontrollable process of cell division, as cancer cells are notorious for their abnormal cell division. There are numerous other documented works on the potential anticancer activity of drugs derived from medicinal plants, and their effects on cell division are an attractive and growing therapeutic target. Despite this, there remains a vast number of unidentified natural products that are potentially promising sources for medical applications. This mini review aims to revise the current knowledge of the effects of natural plant products on cell division. </p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"9 ","pages":"9-19"},"PeriodicalIF":2.7,"publicationDate":"2015-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/DTI.S24946","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33413455","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: 32
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,&nbsp;Furuzan Akar,&nbsp;Ipek Komsuoglu Celikyurt,&nbsp;Pelin Tanyeri,&nbsp;Guner Ulak,&nbsp;Faruk Erden","doi":"10.4137/DTI.S23378","DOIUrl":"https://doi.org/10.4137/DTI.S23378","url":null,"abstract":"<p><p>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. </p>","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
{"title":"Screening Analogs of β-OG Pocket Binder as Fusion Inhibitor of Dengue Virus 2","authors":"Usman SF Tambunan, H. Zahroh, A. A. Parikesit, Syarifuddin Idrus, D. Kerami","doi":"10.4137/DTI.S31566","DOIUrl":"https://doi.org/10.4137/DTI.S31566","url":null,"abstract":"Dengue is an infectious disease caused by dengue virus (DENV) and transmitted between human hosts by mosquitoes. Recently, Indonesia was listed as a country with the highest cases of dengue by the Association of Southeast Asian Nations. The current treatment for dengue disease is supportive therapy; there is no antiviral drug available in the market against dengue. Therefore, a research on antiviral drug against dengue is very important, especially to prevent outbreak explosion. In this research, the development of dengue antiviral is performed through the inhibition of n-octyl-β-D-glucoside (β-OG) binding pocket on envelope protein of DENV by using analogs of β-OG pocket binder. There are 828 compounds used in this study, and all of them were screened based on the analysis of molecular docking, pharmacological character prediction of the compounds, and molecular dynamics simulation. The result of these analyses revealed that the compound that can be used as an antiviral candidate against DENV is 5-(3,4-dichlorophenyl)-N-[2-(p-tolyl) benzotriazol-5-yl]furan-2-carboxamide.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"9 1","pages":"33 - 49"},"PeriodicalIF":2.7,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/DTI.S31566","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70698198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
{"title":"Management of Diabetes Associated with Nephrotic Syndrome: Therapeutic Potential of Dapagliflozin for Protracted Volume Retention","authors":"T. Imai, T. Akimoto, C. Ito, Takahiro Masuda, D. Nagata","doi":"10.4137/DTI.S31710","DOIUrl":"https://doi.org/10.4137/DTI.S31710","url":null,"abstract":"A 48-year-old female was admitted to our hospital presenting with a chief complaint of progressive swelling because of diabetic nephrotic syndrome. Dapagliflozin seemed to play a role in accelerating the patient's urinary sodium excretion as well as reducing gross fluid retention despite the fact that her nephrotic condition was resistant to furosemide. Our experience emphasizes a potential novel approach to overcoming loop diuretic resistance using this agent among some subsets of type 2 diabetic subjects complicated with severe volume accumulation. We believe that combination treatment consisting of dapagliflozin and furosemide may produce diuretic synergy via sequential nephron blockade. The accumulation of more experience with additional cases similar to ours requires continuous and careful attention.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"9 1","pages":"29 - 31"},"PeriodicalIF":2.7,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/DTI.S31710","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70698591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
{"title":"Genome-wide Analysis of Mycoplasma hominis for the Identification of Putative Therapeutic Targets.","authors":"Md Masud Parvege,&nbsp;Monzilur Rahman,&nbsp;Mohammad Shahnoor Hossain","doi":"10.4137/DTI.S19728","DOIUrl":"https://doi.org/10.4137/DTI.S19728","url":null,"abstract":"<p><p>Ever increasing propensity of antibiotic resistance among pathogenic bacteria raises the demand for the development of novel therapeutic agents to control this grave problem. Advances in the field of bioinformatics, genomics, and proteomics have greatly facilitated the discovery of alternative drugs by swift identification of new drug targets. In the present study, we employed comparative genomics and metabolic pathway analysis with an aim of identifying therapeutic targets in Mycoplasma hominis. Our study has revealed 40 annotated metabolic pathways, including five unique pathways of M. hominis. Our study also identified 179 essential proteins, including 59 proteins having no similarity with human proteins. Further filtering by molecular weight, subcellular localization, functional analysis, and protein network interaction, we identified 57 putative candidates for which new drugs can be developed. Druggability analysis for each of the identified targets has prioritized 16 proteins as suitable for potential drug development. </p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"8 ","pages":"51-62"},"PeriodicalIF":2.7,"publicationDate":"2014-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/DTI.S19728","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32962883","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 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":"<p><p>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. </p>","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,&nbsp;Yoshiyuki Morishita,&nbsp;Chiharu Ito,&nbsp;Osamu Iimura,&nbsp;Sadao Tsunematsu,&nbsp;Yuko Watanabe,&nbsp;Eiji Kusano,&nbsp;Daisuke Nagata","doi":"10.4137/DTI.S16524","DOIUrl":"https://doi.org/10.4137/DTI.S16524","url":null,"abstract":"<p><p>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. </p>","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,&nbsp;Tatsunori Masatani,&nbsp;Shinuo Cao,&nbsp;Mohamad Alla Terkawi,&nbsp;Ketsarin Kamyingkird,&nbsp;Ahmed A Mousa,&nbsp;Paul F Adjou Moumouni,&nbsp;Yoshifumi Nishikawa,&nbsp;Xuenan Xuan","doi":"10.4137/DTI.S16504","DOIUrl":"https://doi.org/10.4137/DTI.S16504","url":null,"abstract":"<p><p>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. </p>","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
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