Publications by authors named "Halil Ciftci"

78 Publications

In Vitro and In Silico Evaluation of Anticancer Activity of New Indole-Based 1,3,4-Oxadiazoles as EGFR and COX-2 Inhibitors.

Molecules 2020 Nov 7;25(21). Epub 2020 Nov 7.

Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Japan.

Epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) are crucial targetable enzymes in cancer management. Therefore, herein, new 2-[(5-((1-indol-3-yl)methyl)-1,3,4-oxadiazol-2-yl)thio]--(thiazol/benzothiazol-2-yl)acetamides () were designed and synthesized as EGFR and COX-2 inhibitors. The cytotoxic effects of compounds - on HCT116 human colorectal carcinoma, A549 human lung adenocarcinoma, and A375 human melanoma cell lines were determined using MTT assay. 2-[(5-((1-Indol-3-yl)methyl)-1,3,4-oxadiazol-2-yl)thio]--(6-ethoxybenzothiazol-2-yl)acetamide () exhibited the most significant anticancer activity against HCT116, A549, and A375 cell lines with IC values of 6.43 ± 0.72 μM, 9.62 ± 1.14 μM, and 8.07 ± 1.36 μM, respectively, when compared with erlotinib (IC = 17.86 ± 3.22 μM, 19.41 ± 2.38 μM, and 23.81 ± 4.17 μM, respectively). Further mechanistic assays demonstrated that compound enhanced apoptosis (28.35%) in HCT116 cells more significantly than erlotinib (7.42%) and caused notable EGFR inhibition with an IC value of 2.80 ± 0.52 μM when compared with erlotinib (IC = 0.04 ± 0.01 μM). However, compound did not cause any significant COX-2 inhibition, indicating that this compound showed COX-independent anticancer activity. The molecular docking study of compound emphasized that the benzothiazole ring of this compound occupied the allosteric pocket in the EGFR active site. In conclusion, compound is a promising EGFR inhibitor that warrants further clinical investigations.
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http://dx.doi.org/10.3390/molecules25215190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664637PMC
November 2020

Usability of shear wave elastography to predict the success of extracorporeal shock-wave lithotripsy: prospective pilot study.

Urolithiasis 2020 Oct 26. Epub 2020 Oct 26.

Department of Urology, Harran University, Şanlıurfa, Turkey.

The present study is intended to investigate the usability of shear wave elastography (SWE) in predicting the success of extracorporeal shock-wave lithotripsy (ESWL) used in kidney stone treatment. ESWL was performed on a total number of 52 patients diagnosed with kidney stones between May 2019 and July 2020. The presence of a residual stone greater than 4 mm was accepted as failure. The patients were divided into two groups as ESWL success and ESWL failure. SWE and Hounsfield unit (HU) measurements of stones were performed in all patients before ESWL. The two groups were compared in terms of age, gender, stone localisation, stone size, body mass index (BMI), skin-to-stone distance, HU, and SWE values of the stones. ESWL was successful in 30 of the 52 patients included in the study, while it failed in 22 of them. While the mean SWE value was 7.3 (7.9 ± 2.2) kPa in patients with success in ESWL, it was 14.6 (17.9 ± 10.2) kPa in those with failed ESWL. The mean HU was 883.5 (841.4 ± 191.1) in patients with success in ESWL and 1078 (1115.5 ± 183) in those with failed ESWL. Both SWE and HU values of the stones were found to be statistically significantly lower in the successful group (p < 0.05). It was seen that SWE and HU values were correlated to each other. The groups of successful and failed ESWL did not differ significantly in terms of age, gender distribution, stone size, BMI, and skin-to-stone distance (p > 0.05). With SWE, the hardness of the stone can be measured and its suitability for ESWL can be evaluated. It can be used as an alternative parameter to HU before ESWL treatment, since it has a lower cost compared to computed tomography (CT) and does not contain radiation.
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http://dx.doi.org/10.1007/s00240-020-01221-7DOI Listing
October 2020

A New Series of Antileukemic Agents: Design, Synthesis, In Vitro and In Silico Evaluation of Thiazole-Based ABL1 Kinase Inhibitors.

Anticancer Agents Med Chem 2020 Aug 23. Epub 2020 Aug 23.

Department of Drug Discovery, Science Farm Ltd., 1-7-30-805, Kuhonji, Chuo-ku, Kumamoto 862-0976. Japan.

Background: After the milestone approval of imatinib, more than 25 antitumor agents targeting kinases have been approved, and several promising candidates are in various stages of clinical evaluation.

Objectives: Due to the importance of thiazole scaffold in targeted anticancer drug discovery, the goal of this work is the design of new thiazolyl hydrazones as potent ABL1 kinase inhibitors for the management of chronic myeloid leukemia (CML).

Methods: New thiazolyl hydrazones (2a-p) were synthesized and investigated for their cytotoxic effects on K562 CML cell line. Compounds 2h, 2j and 2l showed potent anticancer activity against K562 cell line. The cytotoxic effects of these compounds on other leukemia (HL-60, MT-2 and Jurkat) and HeLa human cervical carcinoma cell lines were also investigated. Furthermore, their cytotoxic effects on mitogen-activated peripheral blood mononuclear cells (MA-PBMCs) were evaluated to determine their selectivity. Due to its selective and potent anticancer activity, compound 2j was benchmarked for its apoptosis-inducing potential on K562 cell line and inhibitory effects on eight different tyrosine kinases (TKs) including ABL1 kinase. In order to investigate the binding mode of compound 2j into the ATP binding site of ABL1 kinase (PDB: 1IEP), molecular docking study was conducted using MOE 2018.01 program. The QikProp module of Schrödinger's Molecular modelling package was used to predict the pharmacokinetic properties of compounds 2a-p.

Results: 4-(4-(Methylsulfonyl)phenyl)-2-[2-((1,3-benzodioxol-4-yl)methylene)hydrazinyl]thiazole (2j) showed antiproliferative activity against K562 cell line with an IC50 value of 8.87±1.93 µM similar to imatinib (IC50= 6.84±1.11 µM). Compound 2j was found to be more effective than imatinib on HL-60, Jurkat and MT-2 cells. Compound 2j also showed cytotoxic activity against HeLa cell line similar to imatinib. The higher selectivity index value of compound 2j than imatinib indicated that its antiproliferative activity was selective. Compound 2j also induced apoptosis in K562 cell line more than imatinib. Among eight TKs, compound 2j showed the strongest inhibitory activity against ABL1 kinase enzyme (IC50= 5.37±1.17 µM). According to molecular docking studies, compound 2j exhibited high affinity to the ATP binding site of ABL1 kinase forming significant intermolecular interactions. On the basis of in silico studies, this compound did not violate Lipinski's rule of five and Jorgensen's rule of three.

Conclusion: Compound 2j stands out as a potential orally bioavailable ABL1 kinase inhibitor for the treatment of CML.

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http://dx.doi.org/10.2174/1871520620666200824100408DOI Listing
August 2020

Structure activity study of S-trityl-cysteamine dimethylaminopyridine derivatives as SIRT2 inhibitors: Improvement of SIRT2 binding and inhibition.

Bioorg Med Chem Lett 2020 10 2;30(19):127458. Epub 2020 Aug 2.

Department of Drug Discovery, Science Farm Ltd., 1-7-30-805 Kuhonji, Chuo-ku, Kumamoto 8620976, Japan; Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 8620973, Japan. Electronic address:

Sirtuin proteins are a highly conserved class of nicotinamide adenine dinucleotide (NAD)-dependent lysine deacylases. The pleiotropic human isoform 2 of Sirtuins (SIRT2) has been engaged in the pathogenesis of cancer in a plethora of reports around the globe. Thus, SIRT2 modulation is deemed as a promising approach for pharmaceutical intervention. Previously, we reported S-Trityl-l-Cysteine (STLC)-ornamented dimethylaminopyridine chemical entity named STC4 with a significant SIRT2 inhibitory capacity; this was separate from the conventional application of STLC scaffold as a kinesin-5 inhibitor. An interactive molecular docking study of SIRT2 and STC4 showed interaction between Asn168 of SIRT2 and the methyl ester of STC4, that appears to hinder STC4 to reach the selective pocket of the protein unlike strong SIRT2 inhibitor SirReal2. To improve its activity, herein, we utilized S-trityl cysteamine pharmacophore lacking the methyl ester. Nine compounds were synthesized and assayed affording three biopertinent SIRT2 inhibitors, and two of them, STCY1 and STCY6 showed higher inhibitory activity than STC4. These compounds have pronounced anti-proliferative activities against different cancer cell lines. A molecular docking study was executed to shed light on the supposed binding mode of the lead compound, STCY1, into the selective pocket of SIRT2 by interaction of the nitrogen of pyridine ring of the compound and Ala135 of the protein. The outcome of the study exposes that the active compounds are effective intermediates to construct more potent biological agents.
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http://dx.doi.org/10.1016/j.bmcl.2020.127458DOI Listing
October 2020

Anticancer activity of Turkish marine extracts: a purple sponge extract induces apoptosis with multitarget kinase inhibition activity.

Invest New Drugs 2020 10 15;38(5):1326-1333. Epub 2020 Feb 15.

Department of Drug Discovery, Science Farm Ltd., 1-7-30-805 Kuhonji, Chuo-ku, Kumamoto, 862-0976, Japan.

Marine natural products have drawn a great deal of attention as a vital source of new drugs for the last five decades. However, marine organisms in the seas surrounding Turkey (the Black Sea, the Aegean Sea and the Mediterranean Sea) haven't been yet extensively explored. In the present study, three marine organisms (Dysidea avara, Microcosmus sabatieri and Echinaster sepositus) were sampled from the Dardanelles (Turkish Straits System, Western Turkey) by scientific divers, transferred to the laboratory and then were extracted with 70% ethanol. The extracts were tested for their cytotoxic effect against K562, KMS-12PE, A549, and A375 cancer cell lines. The sponge extract elicited the most promising cytotoxic activity, thus it was further evaluated against H929, MCF-7, HeLa, and HCT116 cancer cells. Most of the designated cells showed a considerable sensitivity for the sponge extract particularly H929, K562, KMS-12PE and HeLa cells with IC less than 10 μg/mL. On the contrary, the other two extracts exhibited no cytotoxic activity on all cells at 100 μg/mL concentration. The sponge extract was tested for its capacity to induce apoptosis in cancer cells and to inhibit a panel of tyrosine kinases showing remarkable results. The outcome of this study represents a platform for discovery of new chemotherapeutic agents of marine natural origin.
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http://dx.doi.org/10.1007/s10637-020-00911-8DOI Listing
October 2020

A different look at genetic factors in individuals with non-obstructive azoospermia or oligospermia in our research study: To whom, which threshold, when, in what way?

Rev Int Androl 2021 Jan-Mar;19(1):41-48. Epub 2020 Feb 12.

Department of Urology, Faculty of Medicine, University of Harran, Sanliurfa, Turkey.

Introduction: In our study, we sought answers to many questions about male infertility from a different perspective. The first step in male infertility is anamnesis, physical examination and sperm count. The European Academy of Andrology recommends examination of genetic causes in individuals with fewer than 5million/ml semen counts. The American Urological Association and American Society for Reproductive Medicine have guidelines recommending performing karyotype and AZF subgroup deletion testing in azoospermia and fewer than 5 million sperm total count. Klinefelter syndrome and Y chromosome microdeletions are still very important in male infertility. Based on patients with Klinefelter syndrome or Y microdeletion, we sought answers to many questions in male infertility.

Materials And Methods: In the presented study 327 male patients with having fewer than 15millionsperm/ml detected in at least two consecutive sperm analysis were examined. Patients were divided into sub-groups according to the presence of semen count, chromosomal anomaly and Y microdeletion. In addition, FSH, LH and testosterone levels were analyzed.

Results: Numerical chromosomal anomalies were observed in 34 (10.4%) of 327 patients, and all of these anomalies were found as 47, XXY. Individuals with no AZF microdeletion constituted 95.1% (n=311) of the study group. The overall frequency of AZF microdeletions was 4.9% (16/327). No AZF microdeletions were detected for the patients who have sperm counts above 2million/ml. FSH, LH and testosterone levels were found significantly different between the groups.

Discussion: The results of our study provide another layer of evidence to demonstrate the controversial threshold value of the EAA. In light of our data and current literature, we recommend to set the threshold value at 2million/ml for semen analysis. Further studies conducted in different ethnic groups and larger patient groups would contribute to clarify what exact value should be used to apply genetic tests.
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http://dx.doi.org/10.1016/j.androl.2019.08.001DOI Listing
February 2020

A novel series of chlorinated plastoquinone analogs: Design, synthesis, and evaluation of anticancer activity.

Chem Biol Drug Des 2020 03 2;95(3):343-354. Epub 2020 Jan 2.

Department of Chemistry, Faculty of Science, Istanbul University, Istanbul, Turkey.

Herein, we report the synthesis and cytotoxic effects of novel chlorinated plastoquinone analogs (ABQ1-17) against different leukemic cells. Compounds ABQ3, ABQ11, and ABQ12 demonstrated a pronounced antiproliferative effect against chronic myelogenous leukemia (CML) K562 cell line with IC values of 0.82 ± 0.07, 0.28 ± 0.03, and 0.98 ± 0.22 μM, respectively. Among them, ABQ11 showed approximately three times higher selectivity than imatinib on CML. ABQ11-treated CML cells induced significant apoptosis at low concentration. Inhibitory effect of ABQ11 against eight different tyrosine kinases, including ABL1, was investigated. ABQ11 inhibited ABL1 with IC value of 13.12 ± 1.71 μM, indicating that the moderate inhibition of ABL1 kinase is just an in-part mechanism of its outstanding cellular activity. Molecular docking of ABQ11 into ABL1 kinase ATP-binding pocket revealed the formation of some key interactions. Furthermore, DNA cleavage assay showed that ABQ11 strongly disintegrated DNA at 1 μM concentration in the presence of iron (II) complex system, assuming that the major mechanism for the anticancer effects of ABQ11 is DNA cleavage. In silico ADMET prediction revealed that ABQ11 is a drug-like small molecule with a favorable safety profile. Taken together, ABQ11 is a potential antiproliferative hit compound that exhibits unique cytotoxic activity distinct from imatinib.
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http://dx.doi.org/10.1111/cbdd.13651DOI Listing
March 2020

Antileukemic Activity of Twig Components of Caucasian Beech in Turkey.

Molecules 2019 Oct 25;24(21). Epub 2019 Oct 25.

Department of Medicinal Plant, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.

Despite the development of a range of anti-cancer agents, cancer diagnoses are still increasing in number, remaining a leading cause of death. Anticancer drug treatment is particularly important for leukemia. We screened Turkish plants and found the unique antileukemic activity of twig components in Turkish Caucasian beech, selectively inducing apoptosis in leukemia cells. This effect is unique among some kinds of beeches, presumably related to oxidative stress. This study would lead to effective use of discarded material, i.e., twig of beech, and a new anti-leukemic drug based on large tree.
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http://dx.doi.org/10.3390/molecules24213850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864984PMC
October 2019

Discovery and structure-activity relationship of plastoquinone analogs as anticancer agents against chronic myelogenous leukemia cells.

Arch Pharm (Weinheim) 2019 Dec 11;352(12):e1900170. Epub 2019 Oct 11.

Department of Engineering Sciences, Engineering Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey.

Two series of amino-1,4-benzoquinones (AQ1-18) based on the structural analogs of plastoquinones were synthesized and the structure-activity relationship against chronic myelogenous leukemia activity was examined. All of the synthesized compounds were tested for their cytotoxic effects on different leukemic cell lines. Of interest, AQ15 exhibited a better selectivity than the reference drug imatinib on cancer cells. Owing to this, AQ15 was selected for a further apoptosis/necrosis evaluation where AQ15-treated K562 cells demonstrated similar apoptotic effects like imatinib-treated cells at their IC values. The inhibitory effects of AQ15 and the other three compounds with various activities against eight tyrosine kinases, including ABL1, were investigated. AQ15 showed weak activity against ABL1, and a correlation was observed between the anti-K562 and anti-ABL1 activities. The binding mode of AQ15 into the ATP binding pocket of ABL1 kinase was predicted in silico, showing the formation of some key interactions. In addition, AQ15 was shown to suppress the downstream signaling of BCR-ABL in K562 cells. Finally, AQ15 obviously cleaved DNA in the presence of an iron(II) complex system, indicating that this can be the major mechanism of its antiproliferative action, whereas the mild inhibition of ABL kinase is just in-part mechanism of its overall outstanding cellular activity.
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http://dx.doi.org/10.1002/ardp.201900170DOI Listing
December 2019

Design, synthesis, and biological activity of Plastoquinone analogs as a new class of anticancer agents.

Bioorg Chem 2019 11 7;92:103255. Epub 2019 Sep 7.

Department of Drug Discovery, Science Farm Ltd., Kumamoto 860-0802, Japan; Department of Bioorganic Medicinal Chemistry, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Japan. Electronic address:

In this paper, based on Plastoquinone (PQ) analogs possessing substituted aniline containing alkoxy group(s), new 2,3-dimethyl-5-amino-1,4-benzoquinones (PQ1-15) were designed and synthesized in either two steps or one-pot reaction. Specifically, the substituted amino moiety containing mono or poly alkoxy group(s) with various positions and groups were mainly explored to understand the structure-activity relationships for the cytotoxic activity against three human cancer cell lines (K562, Jurkat, and MT-2) and human peripheral blood mononuclear cells (PBMC). PQ2 was found to be most effective anticancer compound on K562 and Jurkat cell lines with IC values of 6.40 ± 1.73 μM and 7.72 ± 1.49 μM, respectively. Interestingly, the compound was non-cytotoxic to normal PBMC and also MT-2 cancer cells. PQ2 which showed significant selectivity in MTT assay was chosen for apoptotic/necrotic evaluation and results exhibited that it induced apoptosis in K562 cell line after 6 h of treatment. PQ2 showed anti-Abelson kinase 1 (Abl1) activity with different inhibitory profile than Imatinib in the panel of eight kinases. The binding mode of PQ2 into Abl ATP binding pocket was predicted in silico showing the formation of some key interactions. In addition, PQ2 induced Bcr-Abl1 mediated ERK pathway in human chronic myelogenous leukemia (CML) cells. Furthermore, DNA-cleaving capability of PQ2 was clearly enhanced by iron (II) complex system. Afterward, a further in silico ADMET prediction revealed that PQ2 possesses desirable drug-like properties and favorable safety profile. These results indicated that PQ2 has multiple mechanism of action and two of them are anti-Bcr-Abl1 and DNA-cleaving activity. This study suggests that Plastoquinone analogs could be potential candidates for multi-target anticancer therapy.
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http://dx.doi.org/10.1016/j.bioorg.2019.103255DOI Listing
November 2019

Antiproliferative -Trityl-l-Cysteine -Derived Compounds as SIRT2 Inhibitors: Repurposing and Solubility Enhancement.

Molecules 2019 Sep 10;24(18). Epub 2019 Sep 10.

Department of Drug Discovery, Science Farm Ltd., 1-7-30-805 Kuhonji, Chuo-Ku, Kumamoto 8620976, Japan.

-trityl-l-cysteine () is a well-recognized lead compound known for its anticancer activity owing to its potent inhibitory effect on human mitotic kinesin Eg5. contains two free terminal amino and carboxyl groups that play pivotal roles in binding to the Eg5 pocket. On the other hand, such a zwitterion structure complicates the clinical development of because of the solubility issues. Masking either of these radicals reduces or abolishes activity against Eg5. We recently identified and characterized a new class of nicotinamide adenine dinucleotide-dependent deacetylase isoform 2 of sirtuin protein (SIRT2) inhibitors that can be utilized as cytotoxic agents based on an -trityl-l-histidine scaffold. Herein, we propose new -derived compounds that possess pronounced SIRT2 inhibition effects. These derivatives contain modified amino and carboxyl groups, which conferred with bioactivity, representing an explicit repurposing approach. Compounds and exhibited half maximal inhibitory concentration values of 10.8 ± 1.9 and 9.5 ± 1.2 μM, respectively, against SIRT2. Additionally, introduction of the derivatizations in this study addressed the solubility limitations of free , presumably due to interruption of the zwitterion structure. Therefore, we could obtain drug-like derivatives that work by a new mechanism of action. The new derivatives were designed, synthesized, and their structure was confirmed using different spectroscopic approaches. In vitro and cellular bioassays with various cancer cell lines and in silico molecular docking and solubility calculations of the synthesized compounds demonstrated that they warrant attention for further refinement of their bioactivity.
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http://dx.doi.org/10.3390/molecules24183295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766826PMC
September 2019

Design, synthesis and biological evaluation of a new series of thiazolyl-pyrazolines as dual EGFR and HER2 inhibitors.

Eur J Med Chem 2019 Nov 28;182:111648. Epub 2019 Aug 28.

Department of Drug Discovery, Science Farm Ltd., Kumamoto, 862-0976, Japan; Medicinal and Biological Chemistry Science Farm Joint Research Labarotary, Faculty of Life Sciences, Kumamoto University, Kumamoto, 862-0973, Japan; Stanford PULSE Institute, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA. Electronic address:

Epidermal growth factor receptor (EGFR, also known as HER1) and HER2, prominent members of receptor tyrosine kinase (RTK) superfamily, have been reported as diagnostic or prognostic markers in tumor progression. Based on the importance of molecular hybridization of pyrazoline and thiazole scaffolds in the discovery of potent anticancer agents, new thiazolyl-pyrazoline derivatives (3a-v) were synthesized and screened for their cytotoxic effects on A549 human lung adenocarcinoma, MCF-7 human breast adenocarcinoma and A375 human melanoma cell lines. 1-(4-(4-Fluorophenyl)thiazol-2-yl)-3-(4-morpholinophenyl)-5-(4-chlorophenyl)-2-pyrazoline (3c),1-(4-(4-cyanophenyl)thiazol-2-yl)-3-(4-morpholinophenyl)-5-(4-chlorophenyl)-2-pyrazoline (3f) and 1-(4-(4-cyanophenyl)thiazol-2-yl)-3-(4-piperidinophenyl)-5-(4-chlorophenyl)-2-pyrazoline (3q) were found as the most potent anticancer agents against A549 and MCF-7 cell lines compared to erlotinib. Compound 3q also showed moderate cytotoxic activity against A375 cell line. Moreover, these compounds exert a cancer cell-selective action against Jurkat cell line posing no toxicity on peripheral blood mononuclear cells (PBMCs). In order to enlighten the mechanism of action underlying anticancer activity, compounds 3c, 3f and 3q were investigated for their apoptotic effects on A549 and MCF-7 cell lines and inhibitory potencies against eight different RTKs including EGFR and HER2 compared to erlotinib. The results indicated that compounds 3f and 3q induced apoptosis in both cell lines and showed significant EGFR inhibitory activity with IC values of 4.34 ± 0.66 μM and 4.71 ± 0.84 μM, respectively when compared with erlotinib (IC = 0.05 ± 0.01 μM). Besides, compound 3f also inhibited HER2 notably with an IC value of 2.28 ± 0.53 μM making it a dual EGFR and HER2 inhibitor. Molecular docking studies, which were conducted to support the in vitro assays, pointed out that compound 3f showed high affinity into the ATP binding sites of EGFR and HER2.
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http://dx.doi.org/10.1016/j.ejmech.2019.111648DOI Listing
November 2019

Penile fracture and investigation of early surgical repair effects on erectile dysfunction.

Urologia 2019 Nov 22;86(4):207-210. Epub 2019 Apr 22.

Department of Urology, Faculty of Medicine, Harran University, Sanliurfa, Turkey.

Objectives: Penile fracture is one of the urological emergencies caused by direct trauma to an erect penis during sexual intercourse, which results in a tear in the tunica albuginea within the corpus cavernosum. Serious complications such as penile curvature and erectile dysfunction may develop due to inappropriate and/or late surgical repair. This study aims to evaluate patients with penile fracture and to describe their demographics, surgical repairs, and long-term outcomes.

Materials And Methods: A total of 56 patients who were diagnosed with penile fracture between January 2012 and June 2017 were reviewed. Clinical features, pre-operative assessment, time from injury to surgery, tunica defect properties, and presence of urethral injury were assessed. Early surgical management was performed. Outcomes, including International Index of Erectile Function 5 pre-operation and after 6 months, were evaluated.

Results: The mean age was 30.2 (18-57) years. In etiological questionnaires, 32 (57.2%) patients reported direct trauma to an erect penis during intercourse. The mean size of tunica defects was 1.61 ± 0.42 (0.3-3.6) cm of the nine (16%) patients, and penile fracture was associated with urethral injury. There was no significant difference in International Index of Erectile Function 5 scores before the surgery and 6 months after surgery. Penile skin necrosis developed in one patient 10 days post-operation.

Conclusion: Early surgical repair could be an effective method of achieving post-operative erection success in patients with penile fracture due to direct trauma during intercourse.
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http://dx.doi.org/10.1177/0391560319844657DOI Listing
November 2019

New SIRT2 inhibitors: Histidine-based bleomycin spin-off.

Bioorg Med Chem 2019 05 2;27(9):1767-1775. Epub 2019 Mar 2.

Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan. Electronic address:

Bleomycin is considered to exert its antitumor activity via DNA cleavage mediated by activated oxygen generated from the iron complex in its chelator moiety. Spin-offs from this moiety, HPH-1Trt and HPH-2Trt, with anti-cancer activities were recently synthesized. In this paper, we developed inhibitors of nicotinamide adenine dinucleotide-dependent deacetylase isoform 2 of Sirtuin protein (SIRT2), based on HPH-1Trt/HPH-2Trt, and aimed to generate new anti-cancer drugs. HPH-1Trt and HPH-2Trt had in vitro anti-SIRT2 inhibitory activity with 50% inhibitory concentration (IC) values of 5.5 and 8.8 μM, respectively. A structural portion of HPH-1Trt/HPH-2Trt, a tritylhistidine derivative TH-1, had stronger activity (IC = 1.7 μM), and thus, fourteen derivatives of TH-1 were synthesized. Among them, TH-3 had the strongest activity (IC = 1.3 μM). Selective binding of TH-3 in the pocket of SIRT2 protein was confirmed with a molecular docking study. Furthermore, TH-3 strongly lowered viability of the breast cancer cell line MCF7 with an IC of 0.71 μM. A structure-activity relationship study using cell lines suggested that the mechanism of TH-3 to suppress MCF7 cells involves not only SIRT2 inhibition, but also another function. This compound may be a new candidate anti-cancer drug.
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http://dx.doi.org/10.1016/j.bmc.2019.03.003DOI Listing
May 2019

Carotid artery intima-media thickness can predict the response of patients with erectile dysfunction to phosphodiesterase 5 inhibitors.

Int J Impot Res 2019 Mar 29;31(2):139-144. Epub 2019 Jan 29.

Harran University Faculty of Medicine, Department of Urology, Sanliurfa, Turkey.

This study investigated the role of carotid artery intima-media thickness (IMT) as a morphological marker of the response of vasculogenic erectile dysfunction (ED) patients to tadalafil, one of the phosphodiesterase 5 inhibitor (PDE5-I). Through March-December 2016, 51 men with vasculogenic ED aged over 30 years were enrolled in this prospective study. Vasculogenic ED was accepted as a normal testosterone level, with penile colour Doppler ultrasonography showing arteriogenic ED, venogenic ED or mixed arteriogenic and venogenic ED. All patients underwent biochemical and hormonal blood tests, ultrasonographic evaluation of the common carotid artery (CCA) IMT and penile colour Doppler ultrasonography. On-demand tadalafil (10 mg or 20 mg in cases of a non-response to 10 mg) was administered to each patient for 2 months. ED was assessed using the short form of International Index of Erectile Function (IIEF-5) before and after the drug therapy. According to the patients' responses to the medication, they were grouped as non-responders or responders. Thirty-one of the 51 patients responded to tadalafil. The mean CCA IMT of the non-responders and responders was 0.9 ± 0.2 mm and 0.6 ± 0.2 mm, respectively (P = 0.000). The IMT of 90% of the non-responders was >0.67 mm, whereas it was >0.67 mm in 40% of the responders. The data were analysed using the Kolmogorov-Smirnov test, Chi-square test, t-test, Mann-Whitney U test and receiver operator characteristic (ROC) curves. Measurement of CCA IMT may offer an alternative and simple method to predict the response of vasculogenic ED patients to PDE5-Is.
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http://dx.doi.org/10.1038/s41443-018-0103-xDOI Listing
March 2019

Which factors affecting the success of iatrogenic obstetric vesical fistulas?

Ann Ital Chir 2018 ;89:534-539

Aim: In developing countries, surgery, birth traumas, and especially gynecological procedures are the most common cause of vesicovaginal fistulas (VVFs). We retrospectively evaluated our treatment modalities for VVF repair caused by obstetric causes and compared with the current literature.

Materials And Methods: We compared the surgical approach preferences and their results with patient characteristics as well as fistula size and location for the management of VVFs. We retrospectively reviewed and prospectively collected data on 63 women who had uterovesical fistulae or VVF surgical repair between October 2004 and November 2017 at our university hospital in southeastern Turkey.

Results: A total of 63 patients with a diagnosis of obstetric fistula were primaries. Most of the patients had a total abdominal hysterectomy in 37 cases. After the cause of VVF, the mean time to the operation was 28±11 (range: 15-96) days. The average fistula tract size was 15.2±7.7 (range: 3-33) mm. Patients were followed up for a mean of 12 (range: 6-20) months. The patient who received antibiotic treatment due to urinary tract infection before surgery was 16 (25.3%). In seven (12.9%) patients whose fistula diameter was greater than 2 cm, a recurrence was observed. The overall success rate was 87.1%. The average operative time was 94,5±24,3 (range: 50-150) minutes for a layered closure, 75 (range: 50-80) minutes for an omental flap and 120 minutes (range: 100-150) for a martius flap. There were no intraoperative complications.

Conclusion: Obstetric VVFs are highly successful with surgical repair. Surgical success rates are especially high in fistula tract sizes of less than 20 mm and in patients with no history of urinary infection.

Key Words: Abdominal fistula repair, Transvaginal fistula repair, Vesicovaginal fistula.
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August 2019

Do dental calculi predict the presence of renal stones?

Arch Ital Urol Androl 2018 Sep 30;90(3):159-162. Epub 2018 Sep 30.

Department of Urology, Harran University Faculty of Medicine, Sanliurfa.

Objective: Pathological calcifications that occur in various parts of the body may cause stone formation over time. The structure of these stones is similar in many regions of the body. We have studied the relationship between dental calculi and kidney stones.

Material And Methods: A total of 183 patients with dental stone complaints or dental calculi were included between April and August 2016 in the Cagri Dental Hospital, Elazig, Turkey. Patients were evaluated with regard to a urinary tract ultrasonography, urinalysis, oral hygiene, and stone and surgical disease history. All information was statistically investigated.

Results: The age of the patients in the kidney stones group was significantly higher than the non-kidney stone patients (p < 0.05). In the group with kidney stones, the percentage of dental calculus formation was significantly higher than the group without stones (p < 0.05). In the groups with and without kidney stones, dental stone recurrence rates did not differ significantly (p < 0.05). Urinary pH was significantly lower in the group with stones than the group without stones (p < 0.05).

Conclusions: During a physical examination, the formation of a visible stone, such as a dental calculus, may be an indicator of other types of stones, such as kidney stones, and this should be further investigated.
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http://dx.doi.org/10.4081/aiua.2018.3.159DOI Listing
September 2018

Percutaneous Nephrolithotomy with Different Temperature Irrigation and Effects on Surgical Complications and Anesthesiology Applications.

J Endourol 2018 11;32(11):1050-1053

1 Department of Urology, Faculty of Medicine, Harran University , Sanliurfa, Turkey .

Objective: Percutaneous nephrolithotomy (PCNL) is a widely accepted and frequently performed operation for large kidney stones. However, there is not much information about the effects of irrigation fluid temperature as well as many other factors that affect success and complications during the operation. In this study, we aimed to investigate the surgical and anesthesiological effects of irrigation fluid used in body temperature and room temperature during and after PCNL.

Material And Methods: A total of 108 PCNL patients were performed between June 2016 and April 2018. The half of these patients (54) were performed with body temperature (37°C) irrigation fluid, hence known as body temperature group (BTG), and the other half with room temperature (22°C) irrigation fluid, called as room temperature group (RTG). For the study, we recorded the body temperature of the patients during and after the operation, the amount of irrigation fluid used, the size and location of the kidney stones, the duration of the operation, postoperative shivering time during the patient's wake-up period, pre- and postoperative hemoglobin value, additional blood requirements, postoperative analgesic requirements, and postoperative urinary tract infections.

Results: The age of patients, gender distribution, height, weight, body mass index, stone size, and postoperative analgesic requirement showed no significant differences in two groups. The postoperative body heat was significantly higher in the BTG than the RTG. The duration of waking was significantly higher in the RTG than the BTG. The amount of hemorrhage was significantly less in the patients who were irrigated in the RTG.

Conclusion: The temperature of the irrigation fluid can affect many parameters in the PCNL. We recommend using irrigation in room temperature especially with patients having bleeding risks and irrigation fluid in body temperature especially with patients having anesthetic risks for easier waking process.
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http://dx.doi.org/10.1089/end.2018.0581DOI Listing
November 2018

Mini-laparoscopic pyeloplasty in adults: Functional and cosmetic results.

Urol J 2018 11 17;15(6):339-343. Epub 2018 Nov 17.

Harran University Faculty of Medicine, Department of Urology.

Purpose: The study objective was to evaluate the safety and efficacy of mini-laparoscopic pyeloplasty (mLP) in an adult population and to demonstrate the functional and cosmetic results.

Methods: Data for 29 patients (19 men and 10 women) undergoing mLP for ureteropelvic junction obstruction (UPJO) from May 2014 to December 2016 in Turkey were collected in this prospective study. Inclusion criteria were age ? 18 years, body mass index (BMI) ? 30 kg/m2 and primary UPJO, and no previous surgery on the affected kidney or previous abdominal surgery. Postoperative Visual Analogue Scale scores and the Patient Scar Assessment Questionnaire (PSAQ) were used. Demographic data, perioperative parameters, complications, and postoperative functional and cosmetic results were recorded. All statistical analyses were done by SPSS software. P value of <05 was considered statistically significant.

Results: Twenty-nine adults with a mean age of 29.4 ± 10.2 years (19-38 years) were included. The patients' mean BMI was 22.4 ± 4.3 kg/m2 (a range of 16-29 kg/m2). The procedures were performed using three ports (one 5 mm port for the camera and two 3 mm ports). Mean operative time was 119 ± 28.5 minutes (85-144 minutes). Major complications were not observed, as per the Clavien-Dindo classification of surgical complications (grades IV-V). The mean VAS score was 1.2 ± 0.2 points. Functional obstruction was reported in one patient on renal scintigraphy at 12 months postoperatively. The success rate of mLP was 97%. The minimum and maximum PSAQ scores at month 3 postoperatively were 24 and 86, respectively. All the patients were satisfied with the intervention and with their cosmetic results.

Conclusion: mLP is a safe, effective and feasible treatment method for UPJO in adult patients. This treatment modality offers excellent cosmetic and functional results following treatment for UPJO.
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http://dx.doi.org/10.22037/uj.v0i0.4307DOI Listing
November 2018

Effects of Psychological Status on The Oxidation Parameters of Semen and Blood in Azoospermic Men.

Urol J 2019 06 17;16(3):295-299. Epub 2019 Jun 17.

Yildirim Beyazit University, Faculty of Medicine, Department of Clinical Biochemistry, Ankara, TURKEY.

Purpose: In limited number of studies performed concerning the psychological moods of female, and male with the diagnosis of infertility, data related to increased incidence of depression, and anxiety have been reported. The objective of this study is to determine whether azoospermia has any psychological effects on men, and investigate the potential effects of psychological mood on seminal, and plasma oxidative parametres.

Materials And Methods: Twenty-seven patients whose two consecutive semen analyses were reported as pellet -negative azoospermia constituted the azoospermic group, and 30 healthy individuals who applied to the infertility polyclinic with normal seminal parametres comprised the normozoospermic group.

Results: BECK Anxiety scores were significantly higher in the azoospermic group (P = 0.009). When compared with the normozoospermic group, higher levels of oxidative parametres, but lower levels of the antioxidative parametre were detected in the azoospermic group (P < 0.05). In the azoospermic group, a positive correlation was detected between BECK Anxiety and total oxidant status. Anxiety may increase oxidative parametres in both plasma, and seminal fluid (r = 473, p = 0.026).

Conclusion: Anxiety may increase oxidative parametres in both plasma, and seminal fluid. Oxidative milieu may impair sperm quality, and affect the success rates of assisted reproductive treatments. The determination of oxida-tive potential in infertile men, thiol, and prolidase may be used as biomarkers.
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http://dx.doi.org/10.22037/uj.v0i0.4540DOI Listing
June 2019

Structure of the 30S ribosomal decoding complex at ambient temperature.

RNA 2018 12 23;24(12):1667-1676. Epub 2018 Aug 23.

Stanford PULSE Institute, SLAC National Laboratory, Menlo Park, California 94025, USA.

The ribosome translates nucleotide sequences of messenger RNA to proteins through selection of cognate transfer RNA according to the genetic code. To date, structural studies of ribosomal decoding complexes yielding high-resolution data have predominantly relied on experiments performed at cryogenic temperatures. New light sources like the X-ray free electron laser (XFEL) have enabled data collection from macromolecular crystals at ambient temperature. Here, we report an X-ray crystal structure of the 30S ribosomal subunit decoding complex to 3.45 Å resolution using data obtained at ambient temperature at the Linac Coherent Light Source (LCLS). We find that this ambient-temperature structure is largely consistent with existing cryogenic-temperature crystal structures, with key residues of the decoding complex exhibiting similar conformations, including adenosine residues 1492 and 1493. Minor variations were observed, namely an alternate conformation of cytosine 1397 near the mRNA channel and the A-site. Our serial crystallography experiment illustrates the amenability of ribosomal microcrystals to routine structural studies at ambient temperature, thus overcoming a long-standing experimental limitation to structural studies of RNA and RNA-protein complexes at near-physiological temperatures.
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http://dx.doi.org/10.1261/rna.067660.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6239188PMC
December 2018

Is urotherapy alone as effective as a combination of urotherapy and biofeedback in children with dysfunctional voiding?

Int Braz J Urol 2018 Sep-Oct;44(5):987-995

Department of Urology, Ankara Numune Teaching and Research Hospital, University of Healthy Sciences, Ankara, Turkey.

Objective: To compare standard urotherapy with a combination of urotherapy and biofeedback sessions and to determine the changes that these therapies promote in children with dysfunctional voiding.

Patients And Methods: The data of 45 patients who participated in the study from January 2010 to March 2013 were evaluated. All patients underwent urinary system ultrasonography to determine post-void residual urine volumes and urinary system anomalies. All patients were diagnosed using uroflowmetry - electromyography (EMG). The flow pattern, maximum flow rate, and urethral sphincter activity were evaluated in all patients using uroflowmetry - EMG. Each patient underwent standard urotherapy, and the results were recorded. Subsequently, biofeedback sessions were added for all patients, and the changes in the results were recorded and statistically compared.

Results: A total of forty - five patients were included, of which 34 were female and 11 were male and the average age of the patients was 8.4 ± 2.44 years (range: 5 - 15 years). After the standard urotherapy plus biofeedback sessions, the post-void residual urine volumes, incontinence rates and infection rates of patients were significantly lower than those with the standard urotherapy (p < 0.05). A statistically significant improvement in voiding symptoms was observed after the addition of biofeedback sessions to the standard urotherapy compared with the standard urotherapy alone (p < 0.05).

Conclusions: Our study showed that a combination of urotherapy and biofeedback was more effective in decreasing urinary incontinence rates, infection rates and post - void residual urine volumes in children with dysfunctional voiding than standard urotherapy alone, and it also showed that this combination therapy corrected voiding patterns significantly and objectively.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2018.0194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237517PMC
December 2018

Evaluation of apoptosis indexes in currently used oral alpha-blockers in prostate: a pilot study.

Int Braz J Urol 2018 May-Jun;44(3):600-607

Department of Urology, Harran University School of Medicine, Sanliurfa, Turkey.

Objectives: Apoptosis effect of oral alpha-blockers is known in the prostate. Apoptosis index of silodosin has not been proved, yet. Aims are to present apoptosis index of silodosin in prostate and to compare this with other currently used alpha-blocker's apoptosis indexes together with their clinical effects.

Materials And Methods: Benign prostatic hyperplasia (BPH) patients were enrolled among those admitted to urology outpatient clinic between June 2014 and June 2015. Study groups were created according to randomly prescribed oral alpha-blocker drugs as silodosin 8mg (Group 1; n=24), tamsulosin 0.4mg (Group 2; n=30), alfuzosin 10mg (Group 3; n=25), doxazosin 8mg (Group 4; n=22), terazosin 5mg (Group 5; n=15). Patients who refused to use any alpha-blocker drug were included into Group 6 as control group (n=16). We investigated apoptosis indexes of the drugs in prostatic tissues that were taken from patient's surgery (transurethral resection of prostate) and/or prostate biopsies. Immunochemical dyeing, light microscope, and Image Processing and Analysis in Java were used for evaluations. Statistical significant p was p<0.05.

Results: There were 132 patients with mean follow-up of 4.2±2.1 months. Pathologist researched randomly selected 10 areas in each microscope set. Group 1 showed statistical significant difference apoptosis index in immunochemical TUNEL dyeing and image software (p<0.001). Moreover, we determined superior significant development in parameters as uroflowmetry, quality of life scores, and international prostate symptom score in Group 1.

Conclusions: Silodosin has higher apoptosis effect than other alpha-blockers in prostate. Thus, clinic improvement with silodosin was proved by histologic studies. Besides, static factor of BPH may be overcome with creating apoptosis.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2017.0668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996798PMC
July 2018

The First Pentacyclic Triterpenoid Gypsogenin Derivative Exhibiting Anti-ABL1 Kinase and Anti-chronic Myelogenous Leukemia Activities.

Biol Pharm Bull 2018 Apr 30;41(4):570-574. Epub 2018 Jan 30.

Research Institute for Drug Discovery, School of Pharmacy, Kumamoto University.

The discovery of the chimeric tyrosine kinase breakpoint cluster region kinase-Abelson kinase (BCR-ABL)-targeted drug imatinib conceptually changed the treatment of chronic myelogenous leukemia (CML). However, some CML patients show drug resistance to imatinib. To address this issue, some artificial heterocyclic compounds have been identified as BCR-ABL inhibitors. Here we examined whether plant-derived pentacyclic triterpenoid gypsogenin and/or their derivatives show inhibitory activity against BCR-ABL. Among the three derivatives, benzyl 3-hydroxy-23-oxoolean-12-en-28-oate (1c) was found to be the most effective anticancer agent on the CML cell line K562, with an IC value of 9.3 µM. In contrast, the IC against normal peripheral blood mononuclear cells was 276.0 µM, showing better selectivity than imatinib. Compound 1c had in vitro inhibitory activity against Abelson kinase 1 (ABL1) (IC=8.7 µM), the kinase component of BCR-ABL. In addition, compound 1c showed a different inhibitory profile against eight kinases compared with imatinib. The interaction between ATP binding site of ABL and 1c was examined by molecular docking study, and the binding mode was different from imatinib and newer generation inhibitors. Furthermore, 1c suppressed signaling downstream of BCR-ABL. This study suggests the possibility that plant extracts may be a source for CML treatment and offer a strategy to overcome drug resistance to known BCR-ABL inhibitors.
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http://dx.doi.org/10.1248/bpb.b17-00902DOI Listing
April 2018

Introduction of H2C2-type zinc-binding residues into HIV-2 Vpr increases its expression level.

FEBS Open Bio 2018 01 19;8(1):146-153. Epub 2017 Dec 19.

Research Institute for Drug Discovery School of Pharmacy Kumamoto University Japan.

Human immunodeficiency virus type 2 has two structurally similar proteins, Vpx and Vpr. Vpx degrades the host anti-viral protein SAMHD1 and is expressed at high levels, while Vpr is responsible for cell cycle arrest and is expressed at much lower levels. We constructed a Vpr mutant with a high level of expression by replacing the amino acids HHCR/HHCH with a putative H2C2-type zinc-binding site that is carried by Vpx. Our finding suggests that during the evolution of Vpr and Vpx, zinc-binding likely became a mechanism for regulating their expression levels.
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http://dx.doi.org/10.1002/2211-5463.12358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5757179PMC
January 2018

Design, Synthesis, and Biological Evaluation of Novel 1,3,4-Thiadiazole Derivatives as Potential Antitumor Agents against Chronic Myelogenous Leukemia: Striking Effect of Nitrothiazole Moiety.

Molecules 2017 Dec 27;23(1). Epub 2017 Dec 27.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.

In an attempt to develop potent antitumor agents, new 1,3,4-thiadiazole derivatives were synthesized and evaluated for their cytotoxic effects on multiple human cancer cell lines, including the K562 chronic myelogenous leukemia cell line that expresses the Bcr-Abl tyrosine kinase. -(5-Nitrothiazol-2-yl)-2-((5-((4-(trifluoromethyl)phenyl)amino)-1,3,4-thiadiazol-2-yl)thio)acetamide () inhibited the Abl protein kinase with an IC value of 7.4 µM and showed selective activity against the Bcr-Abl positive K562 cell line. Furthermore, a Bcr-Abl-compound molecular modelling simulation highlighted the anchoring role of the nitrothiazole moiety in bonding and hydrophobic interaction with the key amino acid residues. These results provide promising starting points for further development of novel kinase inhibitors.
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http://dx.doi.org/10.3390/molecules23010059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017545PMC
December 2017

A Dithiol Compound Binds to the Zinc Finger Protein TRAF6 and Suppresses Its Ubiquitination.

ChemMedChem 2017 12 4;12(23):1935-1941. Epub 2017 Oct 4.

Research Institute for Drug Discovery, School of Pharmacy, Kumamoto University, Chuo-ku, 862-0973, Kumamoto, Japan.

Despite various inhibitors targeting the zinc center(s) of enzymes, drugs that target zinc fingers have not been examined in detail. We previously developed a dithiol compound named SN-1 that has an inhibitory effect on the function of zinc finger transcription factors, but its mechanism of action has not yet been elucidated. To establish a general principle for new drugs, the details of the action of SN-1 against a zinc finger protein were examined. As a zinc-finger-containing protein, we focused on TRAF6, which is related to cancer and inflammation. Binding of SN-1 to TRAF6 and its effect on TRAF6 ubiquitination were examined in vitro, and the binding mode was calculated by computational methodology. Furthermore, ubiquitination of TRAF6 and downstream signaling was examined by cell-based experiments. The results show that SN-1 binds to TRAF6, inhibiting its auto-ubiquitination and downstream NF-κB signaling. Docking studies indicate that SN-1 binds directly to the first zinc finger of TRAF6. This binding disrupts the neighboring structure, that is, the RING finger domain, to suppress the ubiquitin ligase activity of TRAF6. Taken together, this study provides a platform for developing new small molecules that target zinc finger proteins.
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http://dx.doi.org/10.1002/cmdc.201700399DOI Listing
December 2017

A clue to unprecedented strategy to HIV eradication: "Lock-in and apoptosis".

Sci Rep 2017 08 21;7(1):8957. Epub 2017 Aug 21.

Research Institute for Drug Discovery, School of Pharmacy, Kumamoto University, Kumamoto, Japan.

Despite the development of antiretroviral therapy against HIV, eradication of the virus from the body, as a means to a cure, remains in progress. A "kick and kill" strategy proposes "kick" of the latent HIV to an active HIV to eventually be "killed". Latency-reverting agents that can perform the "kick" function are under development and have shown promise. Management of the infected cells not to produce virions after the "kick" step is important to this strategy. Here we show that a newly synthesized compound, L-HIPPO, captures the HIV-1 protein Pr55 and intercepts its function to translocate the virus from the cytoplasm to the plasma membrane leading to virion budding. The infecting virus thus "locked-in" subsequently induces apoptosis of the host cells. This "lock-in and apoptosis" approach performed by our novel compound in HIV-infected cells provides a means to bridge the gap between the "kick" and "kill" steps of this eradication strategy. By building upon previous progress in latency reverting agents, our compound appears to provide a promising step toward the goal of HIV eradication from the body.
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http://dx.doi.org/10.1038/s41598-017-09129-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5567282PMC
August 2017

Outcomes of miniaturized percutaneous nephrolitotomy in infants: single centre experience.

Int Braz J Urol 2017 Sep-Oct;43(5):932-938

Department of Urology, Harran University Faculty of Medicine, Sanliurfa, Turkey.

Objectives: The present study was aim to evaluate the safety and efficacy of Mini-PNL to treat kidney stones in patients aged <3 years. This is the one of the largest series in the literature in this age group of patients.

Material And Methods: From May 2012 to April 2016, the medical records of 74 infant patients who underwent mini-PNL for renal stones were reviewed retrospectively. All infants were evaluated with the plain abdominal radiograph, urinary ultrasound, noncontrast computerized tomography and/or intravenous urogram. Pre-operative, intraoperative and post-operative data were analyzed.

Results: A total of 74 infant (42 male, 32 female) with a mean age 21.5±8.2 (10-36) months were included in this study. The mean size of the stones was 22.0±5.9 (14-45) mm. A 17 Fr rigid pediatric nephroscope with a pneumatic intracorporeal lithotripsy were used through 20-22 Fr access sheath. The stone-free rate was 84.7% at 1 month after the operation. Mean operative time was 74.0 (40-140) min. Mean fluoroscopy screening time was as 4.3(3.1-8.6) min. Average hospitalization time was 3.8 (2-9) day. Auxiliary procedures were performed to 11(15.3%) patients (7 extracorporeal shock wave lithotripsy, 3 re- percutaneous nephrolitotomy, 1 retrograde intrarenal surgery). No major complication classified as Clavien IV-V observed in study group.

Conclusions: Mini-PNL with pneumatic intracorporeal lithotripsy can be performed safely and effectively to manage kidney stones in infants with high stone free rate and low complications.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2016.0629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678527PMC
November 2017

Paraoxonase and arylesterase activity in bladder cancer.

Turk J Urol 2017 Jun 3;43(2):147-151. Epub 2017 May 3.

Department of Urology, Harran University School of Medicine, Şanlıurfa, Turkey.

Objective: Oxidative stress is the main pathogenetic mechanism in bladder cancer among many other causes. We aimed to investigate whether a potential relationship exists between bladder cancer and the activities of paraoxonase (PON1) and arylesterase (ARE) enzymes.

Material And Methods: The study included 56 patients with bladder cancer, and 57 healthy individuals. The relationships between enzyme activity and tumour grade, stage, muscular invasion and tumour size were evaluated. For statistical analysis, One-Sample Kolmogorov-Smirnov, Independent-T, ANOVA and Post-Hoc Bonferroni tests were used.

Results: Serum levels of PON1 and ARE enzymes, and total cholesterol were significantly lower in bladder cancer group. While other lipid parameters were similar in both the patient and the control groups. Levels of ARE were positively correlated with lipid parameters except for HDL cholesterol.

Conclusion: Our results showed that decreased serum PON1 and ARE enzyme activities are related with tumour load and recurrence. Further studies with larger samples are needed to confirm predictive role of enzymatic activities of PON1 and ARE in the diagnosis and prognosis of bladder cancer.
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http://dx.doi.org/10.5152/tud.2017.89411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503432PMC
June 2017