1,3-Diaryl Triazenes Incorporating Disulfonamides Show Both Antiproliferative Activity and Effective Inhibition of Tumor-associated Carbonic Anhydrases IX and XII.

AIM: The aim of this study was to synthesize a library of novel di-sulfa drugs containing 1,3- diaryltriazene derivatives TS (1-13) by conjugation of diazonium salts of primary sulfonamides with sulfa drugs to investigate the cytotoxic effect of these new compounds in different cancer types and to determine their inhibitory activity against tumor-associated carbonic anhydrases IX and XII. MATERIALS AND METHODS: A carbonic anhydrase inhibitory activity of the obtained compounds was evaluated against four selected human carbonic anhydrase isoforms (hCA I, hCA II, hCA IX and hCA XII) by a stoppedflow CO2 hydrase assay. In addition, in vitro, cytotoxicity studies were applied by using A549 (lung cancer), BEAS-2B (normal lung), MCF-7 (breast cancer), MDA-MB-231 (breast cancer), CRL-4010 (normal breast epithelium), HT-29 (colon cancer), and HCT -116 (colon cancer) cell lines. RESULTS: As a result of the inhibition data, the 4-aminobenzenesulfonamide derivatives were more active than their 3-aminobenzenesulfonamide counterparts. More specifically, compounds TS-1 and TS-2, both of which have primary sulfonamides on both sides of the triazene linker, showed the best inhibitory activity against hCA IX with Ki values of 19.5 and 13.7 nM and also against hCA XII with Ki values of 6.6 and 8.3 nM, respectively. In addition, in vitro cytotoxic activity on the human breast cancer cell line MCF-7 showed that some derivatives of di-sulfa triazenes, such as TS-5 and TS-13, were more active than SLC-0111. CONCLUSION: With the aim of developing more potent and isoform-selective CA inhibitors, these novel hybrid molecules containing sulfa drugs, triazene linkers, and the classical primary sulfonamide chemotype may be considered an interesting example of effective enzyme inhibitors and important anticancer agents.

Deep brain stimulation for the abernethy malformation related tremor.

Deep brain stimulation (DBS) is introduced for the surgical treatment of movement disorders such as Parkinson's disease, tremor, dystonia, and tics. Electrostimulation of the ventral thalamus or subthalamic area has been found effective in different types of tremors that have different etiologies. Abernethy malformation is a rare congenital abnormality characterized by the presence of a congenital extrahepatic portosystemic shunt between the portal vein and systemic circulation. In this report, we present as a case of Abernethy malformation that caused hyperammonemia congenitally and presented as action and resting tremor in the hands and, treated with DBS.

Effectiveness of Mesenchymal Stem Cell Therapy for COVID-19 Patients in the Intensive Care Unit: A Case-Control Study

Objective: Many methods are used in the treatment of coronavirus disease 2019 (COVID-19), which causes acute respiratory distress syndrome (ARDS), and there are conflicting reports in the literature regarding the results of mesenchymal stem cell (MSC) therapy, which is one of those methods. The aim of our study is to evaluate the effect of MSC treatment applied together with standard treatments on survival. Materials and Methods: This retrospective case-control study evaluates the survival effect of MSC treatment administered to patients treated in intensive care after the development of ARDS due to COVID-19 between March 2020 and March 2021. The age, gender, comorbid disease status, APACHE II score, and overall and comorbidity-based survival rates were compared between patients who received standard medical treatment (SMT) and patients who received MSC treatment together with SMT. Results: There were 62 patients in the group receiving only SMT and 81 patients in the group receiving SMT and MSC. No difference was observed between the groups in terms of age, gender, presence of comorbid diseases, or APACHE II scores. There were also no differences according to Kaplan-Maier analysis for the survival statuses of the groups. There was no serious adverse effect due to MSC treatment among these patients. Conclusion: Our study presents the largest case series in the literature, and it was observed that MSC treatment may not significantly affect overall survival or comorbid disease-based survival, in contrast to many other studies in the literature.

Effects of mammalian blood with different glucose levels on reproduction, growth and survival of the southern medicinal leech, Hirudo verbana Carena, 1820.

Medicinal leeches are generally fed using pure mammalian blood. In the present study reproduction, growth and survival of medicinal leeches (Hirudo spp.) fed by mammalian blood with modified glucose level were investigated for the first time. Leeches were fed by cattle blood in a final glucose level of 152 mg/dL (control group; Glucose-free), 200 mg/dL (G200 group), 300 mg/dL (G300 group), 500 mg/dL (G500 group), 750 mg/dL (G750 group), 1000 mg/dL (G1000 group), 2500 mg/dL (G2500 group) and 5000 mg/dL (G5000 group) with the addition of D-Glucose Monohydrate. Greatest growth performance was determined in the G2500 group with a specific growth rate of 2.34% (final body weight: 10.37 ± 3.86 g) (P < 0.05). A quadratic increase was observed in the body weight values of the leeches depending on the glucose dose (Plinear and Pquadratic < 0.05). The greatest survival and gravidity rates were 89% and 38%, respectively, in the G750 group (P < 0.05). The increased glucose level caused a sharp decrease in the survival and gravidity rates of leeches. The glucose level did not significantly effected the cocoon and offspring productivity (P > 0.05). According to the broken line model, optimum glucose levels based on growth, survival rate and gravidity rate were 2461 mg/dL, 750.0 mg/dL and 749.9 mg/dL, respectively. The study showed that, although the optimum growth performance was obtained in the G2500 group, blood with glucose level of 750 mg/dL should be used for profitable medicinal leech culture considering survival and gravidity rates.

Synthesis and biological evaluation of thiosemicarbazone derivatives.

In this study, firstly, 22 thiosemicarbazone derivatives (3a-y) were synthesized. Then, ADME parameters, pharmacokinetic properties, drug-like structures, and suitability for medicinal chemistry of these molecules were studied theoretically by using SwissADME and admetSAR programs. According to the results of these theoretical studies, it can be said that the bioavailability and bioactivity of these compounds may be high. In silico molecular docking between ligands (thiosemicarbazone derivatives) and targeted proteins (protein-78 (GRP78) for C6 and quinone reductase-2 (4ZVM for MCF 7) was analyzed using Hex 8.0.0 docking software. According to the docking data, almost all molecules had higher negative E values than Imatinib (already used as a drug). For this, in vitro anticancer studies of these molecules were done. The cytotoxic activities of thiosemicarbazone derivatives (3a-y) were evaluated on C6 glioma and MCF7 breast cancer cell lines at 24 h, and Imatinib was used as the positive control. According to the results of the cytotoxicity assay, it can be said that the five compounds (3b, c, f, g, and m with IC50 = 10.59-9.08 µg/mL; Imatinib IC50 = 11.68 µg/mL) showed more potent cytotoxic activity than Imatinib on C6 cell line. Together with to these results ten compounds (3b, d, f, g, I, k, l, m, n, and r with IC50 = 7.02-9.08 µg/mL; Imatinib IC50 = 9.24 µg/mL) had a more effective cytotoxic activity against MCF7 cell line than Imatinib. Compound 3 m showed the highest antiproliferative effect against C6 and MCF7 cell lines.

Antiproliferative and Antimigratory Effects of Isoeugenol-Based Polyphenolic Compounds.

In this research, the effect of synthesized polyphenolic compounds 4 and 5 at the cellular and molecular levels was examined. Within this framework, related substances effects on prostate cell (PC3) viability were evaluated by MTT analysis, and their effects on migration were examined by in vitro scratch analysis. Additionally, mRNA expression levels of gene regions known to be associated with metastasis and apoptosis were determined by real-time quantitative PCR. DNA binding researches have also been carried out to determine the DNA compound interactions. As a consequence, it was determined that 4 and 5 obstructed the PC3 cell viability in a manner that is dose- and time-dependent. The IC50 dose of 4 and 5 in PC3 cell was found to be 60.14 µM, 15.51 µM for 48 h, respectively. 4 and 5 substances showed suppressive effect on migration of PC3 cancer cells in the in vitro scratch model created at IC50 concentrations. Compared to the negative control, PC3 cancer cells treated with 4 and 5 showed 24 % and 46 % closure, respectively, at the wound site at 48 h. 4 and 5 compounds were treated at IC50 concentrations with PC3 cancer cells for 48 h, and then the effects of both compounds on the gene expression, that have been linked to metastasis and apoptosis, at the mRNA level were evaluated. It was determined that 4 decreased the expression of the HIF1-α gene 294 times and 5 decreased the expression of the said gene 30 times. In addition, both 4 and 5 were able to significantly increase the Bax/Bcl-2 mRNA expression ratio (32.65 and 10.46 fold, P<0.0001) in PC3 cells as compared to untreated cells after 48 h. Finally, when DNA binding analysis results were evaluated, it was determined that both polyphenolic compounds did not bind to DNA at the tested time and concentrations and did not cause DNA breaks.

Intravenous ibuprofen versus sodium valproate in acute migraine attacks in the emergency department: A randomized clinical trial.

OBJECTIVE: Sodium valproate and ibuprofen are drugs with known efficacy in the treatment of headache associated with acute migraine attacks. In this study, our aim was to compare the efficacy of these two drugs in the treatment of acute migraine attacks when administered as a single intravenous (IV) dose in the emergency department. MATERIALS AND METHOD: This study was designed as a prospective, randomized controlled, double-blinded study and included patients aged 18 to 65 years who presented to the emergency department with acute headache and met the criteria of 'migraine without aura' according to the International Classification of Headache Disorders. The patients were randomized into two groups and given a single dose of 800 mg sodium valproate or 800 mg ibuprofen in 150 mL of normal saline by IV infusion over five minutes. Changes in pain levels were assessed using the Numerical Rating Scale (NRS) for pain over a two-hour period. RESULTS: Ninety-nine patients (49 patients in the sodium valproate group and 50 in the ibuprofen group) completed the trial, and their data were included in the statistical analysis. The mean decrease in the post-treatment delta NRS values was statistically significantly higher in the sodium valproate group than in the ibuprofen group. The mean differences were 1.69 [confidence interval (CI): 1.02-2.37, p<0.001], the mean difference between N0 and N2 was 3.61 (CI: 2.96-4.26, p < 0.001), the mean difference between N0 and N3 was 4.11 (CI: 3.54-4.67, p < 0.001), and the mean difference between N0 and N4 was 3.92 (CI: 3.67-4.46, p < 0.001). The number of patients who achieved the primary endpoint of pain relief was significantly higher in the sodium valproate group than in the ibuprofen group (p < 0.001). According to the Kaplan-Meier analysis showing the rates of reaching the targeted endpoint, there was a significant difference in the efficacy of the two-treatment group (χ2 = 79.98, CI: 80.35-99.65; p = 0.000).

Intermittent Subcutaneous Injections of Apomorphine in Parkinson's Disease.

The intermittent subcutaneous injection of apomorphine is highly effective in the management of motor and non-motor symptoms of Parkinson's disease. Although it has been shown that apomorphine injection can be safely used in selected cases at all stages of the disease, there is no consensus regarding intermittent administration strategies. This review aimed to discuss the indications for intermittent subcutaneous apomorphine use in clinical practice, possible side effects and their management, and contraindicated cases in light of the literature and to present practical recommendations for clinical practice.

Function of the waterfowl nests as reproduction and living areas for leeches (Annelida: Hirudinea).

Some species of leeches migrate into waterfowl nests and use these both as general habitats and to deposit cocoons, but ecological associations between leeches and birds are not well understood. In the present study, characteristics of waterfowl nests both as living area for leeches (Hirudinea) and as reproduction areas for select hirudinid leeches (Hirudo verbana and Haemopis sanguisuga) was investigated in both natural and controlled laboratory conditions. A total of 48 leeches were detected in 23 of the 51 nests surveyed in natural habitats. The leeches were detected more frequently but there were less dense populations in the nests of the great crested grebe (Podiceps cristatus) (frequency: 57 %, population density: 0.71 ± 0.76 leeches/nest), and leeches were detected less frequently but there were more dense populations in the nests of coots (Fulica atra) (frequency: 36 %, population density: 0.91 ± 1.70 leeches/nest). Although the hirudinid leeches naturally reproduce between June and September, cocoons were only detected in August and September, when the nests were not actively used by the waterfowl and when water depths were less. In laboratory conditions, gravid medicinal leeches prefer moist peat rather than waterfowl nests for cocoon deposition. Results from the present study indicate leeches more frequently use the nests of coots, which have both dry and wet layers, compared to the nests of the great crested grebe, which have only a wet layer. Leeches were also found to be more prevalent in bird nests during spring months, during the reproductive periods of the waterfowl.

ADME properties, bioactivity and molecular docking studies of 4-amino-chalcone derivatives: new analogues for the treatment of Alzheimer, glaucoma and epileptic diseases.

In this study, in vitro inhibition effects of (E)-1-(4-aminophenyl)-3-(aryl) prop-2-en-1-one (4-amino-chalcones) derivatives (3a-o) on acetylcholinesterase (AChE) enzyme and human erythrocyte carbonic anhydrase I and II isoenzymes (hCA I- II) were investigated. And also, the biological activities of 4-amino-chalcone derivatives against enzymes which names are acetylcholinesterase (PDB ID: 1OCE), human Carbonic Anhydrase I (PDB ID: 2CAB), human carbonic anhydrase II (PDB ID: 3DC3), were compared. After the results obtained, ADME/T analysis was performed in order to use 4-amino-chalcone derivatives as a drug in the future. Effective inhibitors of carbonic anhydrase I and II isozymes (hCAI and II) and acetylcholinesterase (AChE) enzymes with Ki values in the range of 2.55 ± 0.35-11.75 ± 3.57 nM for hCA I, 4.31 ± 0.78-17.55 ± 5.86 nM for hCA II and 96.01 ± 25.34-1411.41 ± 32.88 nM for AChE, respectively, were the 4-amino-chalcone derivatives (3a-o) molecules. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-021-00094-x.

The correlation between carbamazepine and valproic acid monotherapy with serum adiponectin and carnitine.

Antiepileptic drugs may cause systemic and metabolic side effects. The aim of our study was to investigate the effects of valproic acid and carbamazepine monotherapy used in the treatment of epilepsy patients on serum adiponectin and carnitine levels. The study included 60 patients, of which 30 patients receiving valproic acid monotherapy and 30 patients receiving carbamazepine monotherapy, who were followed up by the epilepsy outpatient clinic with the diagnosis of idiopathic epilepsy, and 30 healthy volunteers. Patients, who used drugs for at least 6 months, were selected. Venous blood samples were collected from the patients and healthy volunteers after their consent was obtained. Serum carnitine and adiponectin levels in the collected samples were measured using the ELISA method. Serum carnitine levels were 5166.55 ng/ml (± 1954.92) in patients receiving carbamazepine, 4224.56 ng/ml (± 2055.54) in patients using valproic acid, and 5802.64 ng/ml (± 3422.57) in the control group. Serum adiponectin levels were 13,606.51 ng/ml (± 5915.92) in patients using carbamazepine, 11,986.58 ng/ml (± 5367.82) in patients receiving valproic acid, and 14,033.43 ng/ml (± 5646.34) in the control group. In both groups, both serum carnitine and serum adiponectin levels were lower than the control group. There was a negative but insignificant correlation between the duration and dose of carbamazepine and valproic acid drug use and serum adiponectin and carnitine levels. There is a need for more extensive studies with larger sample size to investigate the effect of antiepileptic drugs used on serum adiponectin and carnitine levels.

Synthesis, molecular docking, and biological activities of new cyanopyridine derivatives containing phenylurea.

A new class of cyanopyridine derivatives (10a-e and 11a-e) containing the phenylurea unit was synthesized and tested against some metabolic enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glycosidase (α-Gly). The new cyanopyridine derivatives showed Ki values in the range of 40.73 ± 6.54 to 87.05 ± 16.98 µM against AChE, 29.17 ± 4.88 to 124.03 ± 22.43 µM against BChE, and 3.66 ± 0.93 to 26.33 ± 5.05 µM against α-Gly. These inhibition effects were compared with standard enzyme inhibitors like tacrine (for AChE and BChE) and acarbose (for α-Gly). Also, these cyanopyridine derivatives with the best inhibition score were docked into the active site of the indicated metabolic enzymes. Finally, molecular docking calculations were made to compare the biological activities of the compounds against AChE (-8.81 kcal/mol for molecule 11d), BChE (-3.52 kcal/mol for molecule 11d), and α-Gly (-2.98 kcal/mol for molecule 11a). After molecular docking calculations, the ADME/T analysis was performed to examine the future drug use properties of the new cyanopyridine derivatives containing phenylurea.

Low serum Α-SYNUCLEIN and oligomer Α-SYNUCLEIN levels in multiple sclerosis patients.

INTRODUCTION: Multiple sclerosis (MS) is an autoimmune, inflammatory, demyelinating neurodegenerative disease progressing with attacks. Alpha-synuclein (α-Syn), a neuronal protein, has been previously associated with the inflammation and development of neurodegenerative diseases. Although the cause of neurodegeneration in multiple sclerosis is mainly associated with inflammation, α-Syn may play a role in the pathogenesis of MS, as in other classical neurodegenerative diseases such as synucleinopathies. In multiple sclerosis, α-Syn has been directly studied in central nervous system lesions and cerebrospinal fluid (CSF). However, there are few studies approaching variations in peripheral α-Syn in MS. The aim of our study was to investigate the correlation between disease progression and other clinical parameters by measuring serum α-Syn and oligomer α-Syn levels in MS patients. MATERIAL AND METHOD: The study included 60 MS patients aged 18 years or older who were admitted to the Department of Neurology between 01.02.2020-01.04.2020 and diagnosed with MS according to the 2010 MC Donald criteria, and 60 age- and sex-matched healthy controls. Those who were in the MS attack period and received cortisone treatment in the past three months were excluded from the study. The serum α-Syn and oligomer α-Syn levels of the individuals in both groups were measured. The correlation between the serum α-Syn, oligomer α-Syn, oligomer α-Syn/α-Syn ratio levels of the MS patients and their age, disease duration, number of attacks, annualized relapse rate (ARR), disease type, EDSS scores and immunomodulatory drug type used was investigated. Statistical analysis was performed using the SPSS 22.0 software. RESULTS: In our study, 73.3% of the MS patients were female and the mean age of the patients was 36.18 ± 9.5 years. The most common MS disease type was RRMS with 83.3%. Serum α-Syn (79.52 ± 34.81) and oligomer α-Syn (18.79 ± 10.48) levels were significantly lower in the MS patients compared to the control group (p < 0.001). Serum oligomer α-Syn/α-Syn ratio was higher in the MS patients compared to the control group and in SPMS compared to RRMS, but was not statistically significant. There was no significant correlation between the serum α-Syn, oligomer α-Syn and oligomer α-Syn/α-Syn ratio ratio of the MS patients and their age, disease duration, disease type, EDDS, ARR and immunomodulatory treatments. There was a significant positive correlation between α-Syn and oligomer α-Syn in MS patients (r: 0.29, p: 0.02). CONCLUSION: In our study, serum α-Syn and oligomer α-Syn levels were lower in the MS patients compared to the control group. Low levels of α-Syn in MS may play a role in the development of neuroinflammation and may be a result of the diffuse neuronal and synaptic loss. There is a need for further studies on this subject.

Determination of the inhibition profiles of pyrazolyl-thiazole derivatives against aldose reductase and α-glycosidase and molecular docking studies.

Aldose reductase (AR) is the first and rate-limiting enzyme of the polyol pathway, which converts glucose to sorbitol in an NADPH-dependent reaction. α-Glycosidase breaks down starch and disaccharides to glucose. Hence, inhibition of these enzymes can be regarded a considerable approach in the treatment of diabetic complications. AR was purified from sheep liver using simple chromatographic methods. The inhibitory effects of pyrazolyl-thiazoles ((3aR,4S,7R,7aS)-2-(4-{1-[4-(4-bromophenyl)thiazol-2-yl]-5-(aryl)-4,5-dihydro-1H-pyrazol-3-yl}phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives; 3a-i) on AR and α-glycosidase enzymes were investigated. All compounds showed a good inhibitory action against AR and α-glycosidase. Among these compounds, compound 3d exhibited the best inhibition profiles against AR, with a Ki value of 7.09 ± 0.19 µM, whereas compound 3e showed the lowest inhibition effects, with a Ki value of 21.89 ± 1.87 µM. Also, all compounds showed efficient inhibition profiles against α-glycosidase, with Ki values in the range of 0.43 ± 0.06 to 2.30 ± 0.48 µM, whereas the Ki value of acarbose was 12.60 ± 0.78 µM. Lastly, molecular modeling approaches were implemented to predict the binding affinities of compounds against AR and α-glycosidase. In addition, the ADME analysis of the molecules was performed.

Effects of maternal age on reproductive performance of the southern medicinal leech, Hirudo verbana Carena, 1820.

Medicinal leeches can be used to address important needs in medicine and veterinary medicine, as well as pharmaceutical and cosmetic industries. These leeches, however, are among the endangered species. The reproductive processes of the medicinal leeches are not well-known. The aim of the present study was to elucidate effects of maternal age on reproductive performance of medicinal leeches (Hirudo sp.). This study was conducted on Hirudo verbana which were 1, 2 and 3 years of age. The results from the study indicate the youngest maternal leeches have greater reproductive performance. Cocoon production was 4.30 ± 0.72, 3.00 ± 0.71 and 2.80 ± 0.65 cocoons/leech at 1-, 2- and 3-years of age, respectively. Offspring production was greater in younger leeches with there being 11.16 ± 0.63, 10.60 ± 0.96 and 7.14 ± 1.20 offspring produced per cocoon when the cocoon was produced by leeches that were 1, 2, and 3 years of age, respectively. With increasing age of leeches producing the cocoon, the number of cocoons from which there are no offspring produced and the rate of abnormalities of cocoons and morphological abnormalities of offspring increased. The mortality rate of offspring was 10% and 40% in offspring from cocoons produced by 1- and 3-year-old leeches, respectively, being greater when from cocoons produced by 3-year old leeches. Consistent with these findings, younger maternal leeches during their first reproductive phase after hatching from a cocoon have the greatest reproductive performance and should be utilized in leech aquaculture enterprises.

The role of Orexin-A levels in epileptic seizure.

BACKGROUND: The aim of this study is to determine the usefulness of Orexin-A levels in differentiating between epileptic seizures and psychogenic non-epileptic seizures in patients presenting to the emergency service with epileptic seizure-type symptoms. METHODS: A total of 80 individuals were included in this study, including 59 who presented to the emergency service within the first four hours of having been diagnosed with generalized tonic-clonic seizures (39 with epileptic seizures (ES) and 20 with pseudoseizures (PNES) and 21 controls. Orexin-A levels were measured in venous blood samples. RESULTS: The mean Orexin-A levels were 5.16 ng/mL in the control group, 7.17 ng/mL in the PNES group, and 11.08 ng/mL in the ES group (Table 1). The mean Orexin-A level of the ES group was significantly different from both the control group and the PNES group (Table 1, p < 0.001); the difference between the control group and the PNES group was not significant (p > 0.05). CONCLUSIONS: Results of this study suggest that blood Orexin-A may be an effective biomarker in the differential diagnosis of epileptic seizures/psychogenic non-epileptic seizures in patients presenting to the emergency service with an epileptic seizure-type clinical picture.

Synthesis, Antiproliferative and Cytotoxic Activities, DNA Binding Features and Molecular Docking Study of Novel Enamine Derivatives.

Novel enamine derivatives were synthesized from the reaction of lactone and chalcones and their antiproliferative and cytotoxic activities against six cancer cell lines (e. g., HeLa, HT29, A549, MCF7, PC3 and Hep3B) and one normal cell lines (e. g., FL) were investigated along with their mode of interactions with CT-DNA. Most of the enamine derivatives with IC50 values of 86-168 µM demonstrated much stronger antiproliferative activity than the starting molecules against the cancer cells. While, among the enamine derivatives, four compounds displayed higher cytotoxic potency than the control drugs (5-fluorouracil and cisplatin) against the Hep3B cell lines, these compounds did not exhibit any significant toxicity against normal cells, FL. The UV/VIS spectral data suggest that eight compounds cause hypochromism with a slight bathochromic shift (∼6 nm), indicating that they bind to the DNA by way of an intercalative or minor groove binding mode. The binding constants of the compounds are in the range of 0.1×103 M-1 -2.3×104 M-1 . The antiproliferative activity of studied enamine derivatives could possibly be due to their DNA binding as well as their cytotoxic properties. In addition to these assays, the chalcones and enamine derivatives were investigated by molecular docking to calculate the synergistic effect of antiproliferative activities against six human cancer cell lines.

Antiproliferative Evaluation of Some 2-[2-(2-Phenylethenyl)-cyclopent-3-en-1-yl]-1,3-benzothiazoles: DFT and Molecular Docking Study.

The 2-[2-(2-phenylethenyl)cyclopent-3-en-1-yl]-1,3-benzothiazoles were synthesized from the reactions of 7-benzylidenebicyclo[3.2.0]hept-2-en-6-ones with 2-aminobenzenethiol. The antiproliferative activities of 2-[2-(2-phenylethenyl)cyclopent-3-en-1-yl]-1,3-benzothiazoles were determined against C6 (rat brain tumor) and HeLa (human cervical carcinoma cells) cell lines using BrdU cell proliferation ELISA assay. Cisplatin and 5-fluorouracil (5-FU) were used as standards. The most active compound was 2-{(1S,2S)-2-[(E)-2-(4-methylphenyl)ethenyl]cyclopent-3-en-1-yl}-1,3-benzothiazole against C6 cell lines with IC50 =5.89 µm value (cisplatin, IC50 =14.46 µm and 5-FU, IC50 =76.74 µm). Furthermore, the most active compound was 2-{(1S,2S)-2-[(E)-2-(2-methoxyphenyl)ethenyl]cyclopent-3-en-1-yl}-1,3-benzothiazole against HeLa cell lines with IC50 =3.98 µm (cisplatin, IC50 =37.95 µm and 5-FU, IC50 =46.32 µm). Additionally, computational studies of related molecules were performed by using B3LYP/6-31G+(d,p) level in the gas phase. Experimental IR and NMR data were compared with the calculated results and were found to be compatible with each other. Molecular electrostatic potential (MEP) maps of the most active 2-{(1S,2S)-2-[(E)-2-(2-methoxyphenyl)ethenyl]cyclopent-3-en-1-yl}-1,3-benzothiazole against HeLa and the most active 2-{(1S,2S)-2-[(E)-2-(4-methylphenyl)ethenyl]cyclopent-3-en-1-yl}-1,3-benzothiazole against C6 were investigated, aiming to determine the region that the molecule is biologically active. Biological activities of mentioned molecules were investigated with molecular docking analyses. The appropriate target protein (PDB codes: 1 M17 for the HeLa cells and 1JQH for the C6 cells) was used for 2-{(1S,2S)-2-[(E)-2-(2-methoxyphenyl)ethenyl]cyclopent-3-en-1-yl}-1,3-benzothiazole and 2-{(1S,2S)-2-[(E)-2-(4-methylphenyl)ethenyl]cyclopent-3-en-1-yl}-1,3-benzothiazole molecules exhibiting the highest biological activity against HeLa and C6 cells in the docking studies. As a result, it was determined that these molecules are the best candidates for the anticancer drug.

A new method in robotic-assisted laparoscopic radical prostatectomy: personalised neuroprotective surgery with neuromonitoring system-randomised controlled study.

PURPOSE: Erectile dysfunction is one of the important morbidities following the radical prostatectomy (RP) surgeries. The goal of this research is to investigate the contribution of intraoperative neuromonitorisation method (IONM) on postoperative erectile function in patients who underwent robotic-assisted laparoscopic radical prostatectomy (RALP) with the localise prostate cancer (LPCa). MATERIALS AND METHODS: In this randomised controlled study contains 88 patients with LPCa were classified based on D'Amico Risk Classification. 61 patients who met the necessary criteria were divided into two groups as neuromonitorisation group (n = 30) and control group (n = 31). All patients were operated under general anaesthesia. All patients included in the study underwent RALP by robotic-assisted system. For the neuromonitorisation, IONM electromyography electrodes were placed to the right and left cavernous bodies in neuromonitorisation group. Impulses in the corpora cavernosa were considered significant. Postoperative erectile functions were determined according to the 3th and 6th month IIEF-5 scores. Demographic data, operative procedures, Gleason scores, final pathology, surgery border, PSA, and IIEF-5 score of patients were recorded. RESULTS: No statistically difference was found between the groups in terms of demographic data, operative procedures, Gleason scores, final pathology, surgery border, and third-month PSA levels (p > 0.05). There was statistically difference between the postoperative third and 6-month IIEF-5 score in neuromonitorisation group (p < 0.05). CONCLUSION: In the IONM technique, high rate of improvement in erectile function was observed in the early period thanks to personalised neuroprotective surgery applied to patients.

Investigation of reproductive efficiency, growth performance and survival of the southern medicinal leech, Hirudo verbana Carena, 1820 fed with mammalian and poultry blood.

Medicinal leeches are one of the neglected organisms in animal reproduction studies. In this study, the effects of feeding two different types of blood, mammalian (cattle blood) and poultry (chicken blood), on the reproductive efficiency, growth performance and survival of the southern medicinal leech, Hirudo verbana, were investigated. The type of blood fed did not have a significant effect on the growth performance and survival of leeches, but the leeches fed chicken blood had a 2.5-fold greater performance compared to those fed cattle blood in terms of the gravidity process and reproductive efficiency. The final weight and survival for the cattle group was 10.79 ± 4.80 g and 87% and for the chicken group was 10.12 ± 5.26 g and 85%. Gravidity was initiated in the 7th month in both groups; however, while all gravidities in the leeches fed with chicken blood occurred in 1-month period, the gravidity of the leeches fed cattle blood occurred in a 3-month period. The cocoon efficiencies were 6.67 ± 1.50 cocoons/broodstock and 2.67 ± 3.37 cocoons/broodstock in the chicken and cattle groups, respectively. There were larger cocoons in the chicken compared to the cattle group. The offspring efficiencies were 12.59 ± 4.17 offspring/cocoon and 9.81 ± 3.67 offspring/cocoon in the chicken and cattle groups, respectively. The results of this study indicate poultry blood can be used in the management of broodstock with greater reproductive efficiency in medicinal leech aquaculture.