Protective roles of some natural and synthetic aromatase inhibitors in testicular insufficiency caused by Bisphenol A exposure.

In our study, the protective role of synthetic aromatase inhibitors anastrozole (ANS), letrozole (LTZ) and exemestane (EXM) and natural aromatase inhibitors resveratrol (RSV) and apigenin (APG) against testicular failure caused by exposure to Bisphenol A (BPA) was investigated. The epididymal sperm concentration, sperm motility and sperm morphology were determined. Oxidative stress and inflammatory response parameters were examined and histological examinations were performed in testicular tissues. Our results revealed that BPA exposure decreased serum testosterone and estrogen levels, increased FSH and LH levels (p < 0.05). BPA has been found to increase oxidative stress and inflammatory response and disrupt the histological structure. Also, BPA exposure decreased testicular weight, epididymal sperm concentration and motility, and increased abnormal sperm rate (p < 0.05). These results show that ANS, LTZ and RSV treatments reduce the BPA-induced testicular damage.

Benzimidazolium Salts Bearing Nitrile Moieties: Synthesis, Enzyme Inhibition Profiling, and Molecular Docking Analysis for Carbonic Anhydrase and Acetylcholinesterase.

This report presents the synthesis and characterization of a range of benzimidazolium salts featuring 3-cyanopropyl groups on the 1st nitrogen atom and varied alkyl groups on the 3rd nitrogen atom within the benzimidazole structure. Benzimidazolium salts were synthesized by N-alkylation of 1-alkyl benzimidazole with 3-cyanopropyl-bromide. The new salts were characterized by 1 H and 13 C-NMR, FT-IR spectroscopic and elemental analysis techniques. In this study, the enzyme inhibition abilities of seven nitrile substituted benzimidazolium salts were investigated against acetylcholinesterase (AChE) and carbonic anhydrase isoenzymes I and II (hCA I and hCA II). They showed a highly potent inhibition effect on AChE, hCA I and hCA II (Ki values are in the range of 26.71-119.09 nM for AChE, 19.77 to 133.68 nM for hCA I and 13.09 to 266.38 nM for hCA II). Reflecting the binding mode of the synthesized cyanopropyl series, the importance of the 2,3,5,6-tetramethylbenzyl, 3-methylbenzyl and 3-benzyl groups for optimal interactions with target proteins, evaluated by molecular docking studies. At the same time, the docking findings support the inhibition constants (Ki ) values of the related compounds in this study. Potential compounds were also evaluated by their pharmacokinetic properties were predicted.

Effect of imipramine on ether à-go-go potassium channel (Kv1.10) expression in DU145 prostate cancer cells.

In recent studies, it has been reported that ion channels play an important role in cancer formation. Therefore, it is possible that the use of pharmacological agents targeting ion channels will allow the development of new strategies for cancer treatment. In this study, we investigate the effect of imipramine on Eag1 channel expression in DU145 prostate cancer cells. Culture cells were divided into 4 groups as the control, 10, 50 and 75 µM imipramine. Eag1 channel currents and conductivity were determined by whole-cell patch-clamp technique and gene expression by real time-polymerase chain reaction (RT-PCR). Current records were taken before (at 0th minute, as control) and 10 min after imipramine administration to the cells. It was observed that all three doses of imipramine significantly reduced Eag1 currents and conductivity compared with the control. However, the differences between dose groups were not significant. Similarly, Eag1 channel protein expression was found to be significantly reduced for all three doses of imipramine compared with the control group, but there was no significant difference in gene expression between dose groups. Obtained results suggested that imipramine has the potential to be used as a pharmacological agent targeting the Eag1 channel in the treatment of prostate cancer.

Protective effect of myricetin, apigenin, and hesperidin pretreatments on cyclophosphamide-induced immunosuppression.

Aim: Major side effects of cyclophosphamide administration are immunosuppression and myelosuppression. The immunomodulatory effects of plant bioactive compounds on chemotherapy drug-induced immunosuppression may have significant effects in cancer treatment. For this reason, we investigated the immunomodulatory effect of myricetin, apigenin, and hesperidin in cyclophosphamide-induced immunosuppression in rats.Methods: In our study, a total of 64 rats were used, and divided into eight equal groups. These groups were: control, cyclophosphamide, cyclophosphamide + myricetin (100 mg/kg), cyclophosphamide + myricetin (200 mg/kg), cyclophosphamide + apigenin (100 mg/kg), cyclophosphamide + apigenin (200 mg/kg), cyclophosphamide + hesperidin (100 mg/kg), and cyclophosphamide + hesperidin (200 mg/kg). Myricetin, apigenin, and hesperidin pretreatments were performed for 14 d, while cyclophosphamide application (200 mg/kg) was performed only on the 4th day of the study. Levels of humoral antibody production, quantitative hemolysis, macrophage phagocytosis, splenic lymphocyte proliferation, and natural killer cell cytotoxicity were determined. In addition, we measured pro-inflammatory cytokines, and followed lipid peroxidation and antioxidant markers and examined the histology of bone marrow, liver and spleen in all groups.Results: During cyclophosphamide treatment, all three phytochemicals increased the levels of humoral antibody production, quantitative hemolysis, macrophage phagocytosis, splenic lymphocyte proliferation, antioxidant markers, and natural killer cell cytotoxicity. Moreover, the agents decreased the levels of pro-inflammatory cytokines and mediators, reduced lipid peroxidation markers, and reduced tissue damage in liver, spleen, and bone marrow.Conclusion: Our study demonstrated that myricetin, apigenin, and hesperidin can reduce the immunosuppressive effect of cyclophosphamide by enhancing both innate and adaptive immune responses, and these compounds may be useful immunomodulatory agents during cancer chemotherapy.

The effect of 4.5 G (LTE Advanced-Pro network) mobile phone radiation on the optic nerve.

PURPOSE: Rapid development in mobile phone technologies increase the average mobile phone usage duration. This increase also triggers exposure to radiofrequency radiation (RF), which is a risk factor for the health. In this study, it was aimed to investigate the effect of mobile phone working with LTE-Advanced Pro (4.5 G) mobile network on the optic nerve, which is responsible for the transmission of visual information. MATERIAL AND METHODS: Thirty-two rats divided into two groups as control (no RF, sham exposure) and experimental (RF exposure using a mobile phone with LTE-Advanced Pro network; 2 hours/day, 6 weeks). The visual evoked potential (VEP) was recorded and determined amplitudes and latencies of VEP waves. Optic nerve malondialdehyde level, catalase and superoxide dismutase activities were determined. Furthermore, ultrastructural and morphometric changes of optic nerve were evaluated. RESULTS: In VEP recordings, the mean VEP amplitudes of experimental group were significantly lower than control group. In ultrastructural evaluation, myelinated nerve fibres and glial cells were observed in normal histologic appearance both in sham and experimental group. However, by performing morphometric analysis, in the experimental group, axonal diameter and myelin thickness were shown to be lower and the G-ratio was higher than in the sham group. In the experimental group, malondialdehyde level was significantly higher and superoxide dismutase and catalase activities were significantly lower than sham group. There was a high correlation between VEP wave amplitudes and oxidative stress markers. CONCLUSION: Findings obtained in this study support optic nerve damage. These results point out an important risk that may decrease the quality of life.

Myricetin inhibits angiotensin converting enzyme and induces nitric oxide production in HUVEC cell line.

Nitric oxide is known as relaxing factor because it acts as a vasodilator, increases blood flow, and inhibits platelet aggregation and adhesion, on the other hand nitric oxide can modulate cellular and physiological processes to limit oxidative injury, limiting processes such as leukocyte adhesion. As the complete mechanism of myricetin and its cardiovascular benefits is not completely understood, the aim of this study was to investigate the antihypertensive activity of myricetin in human umbilical vein endothelial cell (HUVEC). Angiotensin converting enzyme (ACE) activity, nitric oxide production, reactive oxygen species (ROS) scavenger activity, cellular calcium concentration, and endothelial nitric oxide synthase (eNOS) activity and protein expression was investigated in HUVEC treated with different concentration of myricetin (1-60 µM). Myricetin increased nitric oxide production in HUVEC through decreased ROS levels and increased nitric oxide production and eNOS activation. Activation of eNOS enzyme was achieved by an increase of cellular calcium concentration. At the same examined concentration of myricetin, the activity of ACE was significantly inhibited. These findings indicate that myricetin may be helpful for lowering blood pressure; this could be achieved through dietary intervention or by the production of new antihypertensive treatments from a natural product.

PAI-1 and tPA gene polymorphisms and susceptibility to chronic obstructive pulmonary disease in a sample of Turkish population.

OBJECTIVES: The aim of this study was to assess the influence of plasminogen activator inhibitor-1 (PAI-1) 4G/5G or tissue plasminogen activator (tPA) I/D polymorphisms in chronic obstructive pulmonary disease (COPD) cases in a sample of Turkish population. METHODS: PAI-1 4G/5G and tPA Alu-repeat I/D genetic polymorphisms in 153 COPD subjects and 160 controls were investigated using PCR-RFLP and PCR methods, respectively. RESULTS: 4G allele frequency was 0.62 and 0.39 for COPD and control groups, respectively. 4G allele had an estimated 2.56- fold [95% CI = 1.85-3.53] increased risk of COPD. tPA I allele frequency was 0.55 and 0.50, for COPD and control groups, respectively. I allele had an estimated 1.19-fold [95% CI = 0.87-1.62] increased risk of COPD. CONCLUSIONS: PAI-1 4G/4G and 4G/5G genotypes seemed to play a key role in the pathophysiology of COPD in Turkish individuals.

Effect of Imipramine on radiosensitivity of Prostate Cancer: An In Vitro Study.

Prostate cancer is the most common cancer and leading cause of cancer death for males. Imipramine (IMI), which is a tricyclic antidepressant, has also been shown to has antineoplastic effect. This study was performed to investigate the radiosensitizing effect of IMI on DU145 prostate cancer cell. Cells were divided into 4 groups. Cell index, apoptotic activity, cell cycle arrest, oxidative stress and EAG1 channel currents were determined in all groups. Our findings showed that combined treatment with IMI and radiotherapy (RAD) did not enhance radiosensitivity of DU145 cells but as unexpected finding, treatment of IMI alone was more effective in DU145 cells.

Genotoxic action of Luna Experience-SC 400 fungicide on rat bone marrow.

Background: Fungicides describe all chemicals used to control fungi that infect plants. Luna Experience SC-400 is a new line of fungicide that consist of Fluopyram and Tebuconazole. Objective: In this study, We investigated the genotoxicty and cytotoxicty of Luna Experience-SC 400 using comet assay, micronucleus test and polychromatic erythrocytes number in rat bone marrow. The present study is the first report indicating the effects of genotoxic and cytotoxic of Luna experience SC-400 on rat bone marrow cells. Material and Methods: We used three different doses (5mg/kg, 10mg/kg, 20mg/kg) of Luna Experience SC 400 at 48 h intervals during 30 days by gavage in rats.Genotoxicity was evaluated using comet assay and micronucleus test and cytotoxicity was measured the PCE/NCE rate in rat bone marrow. Results: Based on these experimental results, we report that Luna Experience-SC 400 fungicide presents genotoxic and cytotoxic potential on rat bone marrow. There is a significant difference between negative control group and all the doses of Luna Experience-SC 400 (p < 0.05) for comet assay and micronucleus. Even moderate and high doses of fungicides seem to have reached the values of almost positive control group for Genetic Damage Index (GDI) and Damaged Cell Percentage (DCP). In this study, we also investigated the PCE/NCE rate. Fungicide caused a decrease in the level of significant in the PCE/NCE ratio (p < 0.05). Conclusion: Our in vivo study suggests that the gavage exposure to Luna experience SC 400 used in the present investigation may be genotoxic and cytotoxic in rat bone marrow in view of these findings. Because this findings is first report represented in the pesticide biology, it is important to carry out more investigations using various cytogenetic tests under different experimental conditions to definitively resolve the the possible genotoxic and cytotoxic risk associated with new generation pesticides-fungicides.

Effect of low-level 1800 MHz radiofrequency radiation on the rat sciatic nerve and the protective role of paricalcitol.

The nervous system is an important target of radiofrequency (RF) radiation exposure since it is the excitable component that is potentially able to interact with electromagnetic fields. The present study was designed to investigate the effects of 1,800 MHz RF radiation and the protective role of paricalcitol on the rat sciatic nerve. Rats were divided into four groups as control, paricalcitol, RF, and RF + paricalcitol. In RF groups, the rats were exposed to 1,800 MHz RF for 1 h per day for 4 weeks. Control and paricalcitol rats were kept under the same conditions without RF application. In paricalcitol groups, the rats were given 0.2 µg/kg/day paricalcitol, three times per week for 4 weeks. Amplitude and latency of nerve compound action potentials, catalase activities, malondialdehyde (MDA) levels, and ultrastructural changes of sciatic nerve were evaluated. In the RF group, a significant reduction in amplitude, prolongation in latency, an increase in the MDA level, and an increase in catalase activity and degeneration in the myelinated nerve fibers were observed. The electrophysiological and histological findings were consistent with neuropathy, and the neuropathic changes were partially ameliorated with paricalcitol administration. Bioelectromagnetics. 39:631-643, 2018. © 2018 Wiley Periodicals, Inc.

Effects of silica nanoparticles on isolated rat uterine smooth muscle.

In spite of their widespread use, toxicity of silica nanoparticles (SiO2 NPs) to mammalian has not been extensively investigated. In the present study, it is aimed to investigate the effects and the mechanism of action of 20 nm sized SiO2 NPs on isolated uterine smooth muscle. A total number of 84 preparations of uterine strips were used in the experiments. Study was designed as four groups: group I (control), group II (0.2 mM SiO2 NPs), group III (0.4 mM SiO2 NPs) and group IV (0.8 mM SiO2 NPs). Spontaneous contractions were recorded using mechanical activity recording system. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and malondialdehyde (MDA) levels were measured using the spectrophotometric methods. Apoptosis of the cells was detected using immunofluorescence staining assay. SiO2 NP distribution and ultrastructural changes were determined by transmission electron microscopy. In groups II-IV, the frequency of contraction was significantly lower than that of the group I, whereas the contraction energy significantly decreased only in group IV. SOD and GSH-Px activities were significantly lower in experimental groups compared to the control group. MDA level and apoptotic cells were significantly higher in all SiO2 groups compared to the control group. Numerous SiO2 NPs in cytoplasm and connective tissue were observed in all dose groups. These findings showed that 20 nm sized SiO2 NPs enter the connective tissue and cytoplasm of uterine muscle cells and cause oxidative stress and apoptosis leading to impaired uterine contractile activity.

[Investigation of the association between chronic hepatitis B and C infections and TNF-α (-308) gene polymorphism]. / Kronik hepatit B ve C enfeksiyonlari ile TNF-α (-308) gen polimorfi zmi arasindaki iliskinin arastirilmasi.

Cytokines and genetic factors play important roles in the pathogenesis of chronic hepatitis B (CHB) and chronic hepatitis C (CHC) infections. Variations in cytokine genes may effect the gene expression and may lead to changes in the clinical manifestations of diseases. One of the single nucleotide polymorphisms in the promoter region of tumor necrosis factor-alpha (TNF-α) gene is the polymorphism at -308. position which was investigated in many studies by means of its relationship between CHB and CHC infections, however their results are incompatible. Furthermore, there is no sufficient data on this subject in our country. This study was aimed to determine the relationship between TNF-α(-308) gene polymorphism with CHB and CHC infections. A total of 271 patients with chronic hepatitis and 181 healthy subjects were included in the study. Of them 167 were CHB cases (67 female, 100 male; age range 18-74 years, mean age: 40.23 ± 13.09) and 95 controls for CHB group (46 female, 49 male; mean age: 36.41 ± 15.0 years), while 104 were CHC cases (63 female, 41 male; age range: 25-79 years, mean age: 52.8 ± 12.6) and 86 controls for CHC group (41 female, 45 male; mean age: 36.4 ± 14.9 years). After the isolation of genomic DNA from blood samples of the patient and control groups, TNF-α(-308)G/A (rs 1800629) polymorphism was investigated by using the real-time polymerase chain reaction from the obtained DNAs. Among CHB group, TNF-α(-308) GG, GA, AA genotypes were detected in 126 (75.4%), 38 (22.8%) and 3 (1.8%) of the patients, respectively, while these numbers were 84 (88.4%), 11 (11.6%) and 0 (0%) in control group, respectively. Among CHC group, TNF-α(-308) GG, GA, AA genotypes were detected in 37 (35.6%), 28 (26.9%) and 39 (37.5%) of the patients, respectively, while these numbers were 38 (44.2%), 8 (9.3%) and 40 (46.5%) in control group, respectively. The frequency of GA genotype was significantly higher in both patient groups compared to the control groups (p=0.024 for CHB and p= 0.006 for CHC). When the distribution of allele frequencies of TNF-α(-308)G/A polymorphism was evaluated in the patients and control groups, it was noted that G allele was found to be high in CHB patients comparing with controls (94.2% vs 86.8%), however A allele was identified to be lower than controls (5.8% vs 13.2%) (p= 0.008). In contrast, there was no significant difference in terms of allele frequency compared with CHC patients and the control group (p= 0.969). In conclusion, our data in accordance with the results of many studies in literature, determined that TNF-α(-308) polymorphisms can influence the chronicity of hepatitis B and C infections. Further studies on this subject would contribute to the elucidation of the molecular mechanisms of chronic hepatitis B and C diseases.

Is mycophenolate mofetil an alternative agent to corticosteroids in traumatic nerve paralysis?

OBJECTIVE: The effects of an immunosuppressive agent, mycophenolate mofetil (MM), were investigated and compared with those of methylprednisolone (MP) and dexamethasone (DXM) on the traumatic nerve function. STUDY DESIGN: This is a randomized controlled animal study. MATERIALS AND METHODS: This experimental study was performed on 84 male Wistar albino rats. The rats were assigned to 12 groups each consisting of 7 animals. The groups were formed according to application of normal-dose DXM (group 1A-B), high-dose MP (group 2A-B), normal-dose MP (group 3A-B), MM (group 4A-B), and MM with high-dose MP combination therapies (group VA-B). Right sciatic nerve dissection was performed, and compound muscle action potential thresholds were recorded. The nerve was traumatized with the compression of a Jeweller forceps for 20 seconds. Posttraumatic thresholds were also recorded. The compound muscle action potential thresholds were recorded in the first and fourth weeks for the assigned groups. Then, the nerve was transected and prepared for electron microscopic and histopathologic examinations. Nitric oxide and malondialdehyde assessments were performed on both tissue and blood samples. RESULTS: Only the MM and MP+MM groups had satisfactory electron microscopic findings and were about to reach the tissue characteristics of the control animals. Despite the electrophysiologic recovery, the DXM group was found to have poor electron microscopic scoring. CONCLUSIONS: Mycophenolate mofetil has been found to be beneficial in the treatment of traumatic nerve paralysis. Although a complementary investigation is needed, this immunosuppressive agent may be an alternative to corticosteroids for the selected cases where steroid therapy is contraindicated.

Effects of dietary selenium of organic form against lead toxicity on the antioxidant system in Cyprinus carpio.

In this study was evaluated potential protective effect of organic selenium (Se) on heavy metal stress induced by lead (Pb) in Cyprinus carpio. For this reason, C. carpio was exposed to sublethal concentration of Pb (1.5 mg/L Pb(NO3)2) for 14 days. The fish were fed a basal (control; measured 0.55 mg/kg Se) diet or a basal diet supplemented with 2.50 mg/kg (measured 2.92 mg/kg Se) organic Se (Sel-Plex(®)) during the experiment period. The variations in glutathione peroxidase (GSH-Px), glutathione S-transferase (GST) activities, and levels of reduced glutathione (GSH) with malondialdehyde (MDA) in liver and brain tissues of C. carpio were investigated in experimental groups. GSH levels in liver and brain tissues were significantly decreased by exposure to Pb. GST activity was significantly increased (p < 0.05) in liver tissue, but decreased in brain of treated fish by exposure to Pb. Also, GSH-Px activity was significantly increased in liver tissue, but decreased in brain of Pb-treated fish. Levels of MDA were increased in liver and brain of Pb-treated fish. The organic Se treatment for Pb-intoxicated animals improved activities of GSH-Px, GST and levels of MDA within normal limits. Supplemented Se could be able to improve Pb-induced oxidative stress by decreasing lipid peroxidation and regulating antioxidant defense system in tissues.

[Investigation of IL-1 beta, IL-1 receptor antagonist and IL-8 gene polymorphisms in patients with chronic hepatitis B and C]. / Kronik hepatit B ve C hastalarinda IL-1 beta, IL-1 reseptör antagonisti ve IL-8 gen polimorfizmlerinin arastirilmasi

The host immune response is closely related to the prognosis of disease and viral persistence in hepatitis B (HBV) and hepatitis C virus (HCV) infections. Although it is well known that cytokines and genetic factors play important roles in the pathogenesis of chronic HBV and HCV infections, the underlying mechanisms are not fully understood. This study was conducted to determine the role of interleukin (IL)-1ß, IL-1 receptor antagonist (IL-1RA) and IL-8 gene polymorphisms in chronic hepatitis B and C infections. A total of 361 subjects, 171 with chronic hepatitis B (62 female, 109 male; age range: 18-74 yrs) and 104 with chronic hepatitis C (63 female, 41 male; age range: 25-79 yrs), and a control group of 86 healthy subjects (41 female, 45 male; age range: 18-72 yrs) were included in the study. Following the DNA extractions from peripheral blood leukocytes of the study groups, single nucleotide polymorphisms of IL-1ß -31, -511, +3954; IL-1RA and IL-8 -251, -353, -738, -845 gene regions were investigated by using specific primers with real-time PCR method. It was found that the genotype frequency of IL-8 -251 AT (OR: 7.895, p= 0.003) and IL-8 -738 TA (OR: 6.317, p= 0.007) in patients with chronic hepatitis B and the genotype frequency of IL-1ß-31 CT (OR: 6.757, p= 0.001), IL-1ß -511 CT (OR: 4.060, p= 0.004), IL-8 -251 AT, (OR: 13.622, p= 0.001), IL-8 -738 TA (OR: 14.058, p= 0.001), and IL-8 -845 TC (OR: 2.539, p= 0.004) in patients with chronic hepatitis C was significantly higher than the control group. When the allelic frequency was compared between chronic hepatitis B patients and the control group, it was determined that IL-1ß +3954 T allel increased the disease risk 1.5 times (p< 0.05), however, no statistically significant difference was detected for the other allels. It was also determined that IL-8 -845 C allel increased the disease risk 0.6 times in chronic hepatitis C (p< 0.05) and no statistically significant difference was detected for the other allels (p> 0.05). In conclusion, IL-1ß -31, -511 and IL-8 -251, -738, -845 gene polymorphisms may play a role in the chronicity of hepatitis B and C infection. In order to determine the importance of this cytokine polymorphisms in hepatitis B and hepatitis C virus infections, large-scale studies with different patient groups such as carriers, chronic hepatitis, cirrhosis, and hepatocellular carcinoma should be conducted to elucidate the molecular mechanisms underlying the disease process.

Long noncoding RNAs and their possible roles in tumorigenesis and drug resistance in cancer chemotherapy.

Cancer is still one of the most important diseases that have a high mortality rate around the world. The management of cancer involves many procedures, which include surgery, radiotherapy, and chemotherapy. Drug resistance in cancer chemotherapy is considered one of the most important problems in clinical oncology. A good understanding of the tumorigenesis process and the mechanisms of developing chemotherapy resistance in cancer cells will help achieve significant advances in cancer treatment protocols. In recent years, there has been an increasing interest in long noncoding RNAs (lncRNAs). LncRNAs are no longer just a transcriptional noise, and many investigations proved their possible roles in regulating mandatory cellular functions. A lot of newly published studies confirmed the implication of lncRNAs in the tumor formation process and the multiple drug resistance in cancer chemotherapy. The main aim of this review is to focus on the lncRNAs' functions in the cell, their possible roles in the tumor formation process, and their roles in the development of chemotherapy resistance in different cancer cells.

Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes.

Diabetes mellitus (DM) is still one of the most common diseases worldwide, and its prevalence is still increasing globally. According to the American and European recommendations, metformin is considered a first-line oral hypo-glycemic drug for controlling type 2 DM (T2DM) patients. Metformin is the ninth most often prescribed drug in the world, and at least 120 million diabetic people are estimated to receive the drug. In the last 20 years, there has been increasing evidence of vitamin B12 deficiency among metformin-treated diabetic patients. Many studies have reported that vitamin B12 deficiency is related to the ma-labsorption of vitamin B12 among metformin-treated T2DM patients. Vitamin B12 deficiency may have a very bad complication for the T2DM patient. In this review, we will focus on the effect of metformin on the absorption of vitamin B12 and on its proposed mechanisms in hindering vitamin B12 absorption. In addition, the review will describe the clinical outcomes of vitamin B12 deficiency in metformin-treated T2DM.

Investigation of antiviral substances in Covid 19 by Molecular Docking: In Silico Study.

Aims: This paper aimed to investigate the antiviral drugs against Sars-Cov-2 main protease (MPro) using in silico methods. Material and Method: A search was made for antiviral drugs in the PubChem database and antiviral drugs such as Bictegravir, Emtricitabine, Entecavir, Lamivudine, Tenofovir, Favipiravir, Hydroxychloroquine, Lopinavir, Oseltamavir, Remdevisir, Ribavirin, Ritonavir were included in our study. The protein structure of Sars-Cov-2 Mpro (PDB ID: 6LU7) was taken from the Protein Data Bank (www.rcsb. Org) system and included in our study. Molecular docking was performed using AutoDock/Vina, a computational docking program. Protein-ligand interactions were performed with the AutoDock Vina program. 3D visualizations were made with the Discovery Studio 2020 program. N3 inhibitor method was used for our validation. Results: In the present study, bictegravir, remdevisir and lopinavir compounds in the Sars-Cov-2 Mpro structure showed higher binding affinity compared to the antiviral compounds N3 inhibitor, according to our molecular insertion results. However, the favipiravir, emtricitabine and lamuvidune compounds were detected very low binding affinity. Other antiviral compounds were found close binding affinity with the N3 inhibitor. Conclusion: Bictegravir, remdevisir and lopinavir drugs showed very good results compared to the N3 inhibitor. Therefore, they could be inhibitory in the Sars Cov-2 Mpro target.

Investigation of berberine and its derivatives in Sars Cov-2 main protease structure by molecular docking, PROTOX-II and ADMET methods: in machine learning and in silico study.

Bioactive compounds found in plants also have pharmacological antiviral effects. Berberine (BBR), an alkaloid found naturally in plants, is one of the phytochemicals with a wide range of biological activities, including antiviral, anticancer, anti-inflammatory and anti-inflammatory. In this study, we firstly aimed to predict pIC50 values for selcted compounds and then extract the binding patterns of berberine and its derivatives in the Sars Cov-2 Master Protease structure via employing molecular docking approache. Our results showed that berberine and its derivatives have good binding affinities towared Sars Cov2 main protease protein. Based on docking results the pharamaccokinetic studies for berberine, berberrubine, demethylen-berberine, jatrorrhizin, and thalifendine, were conducted and showed a good pharamacokinetic properties as an oral drugs. For deep inspection, we utiilized molecular dynmaics simulation to examine the Sars Cov2 main protease-ligand stabilities. The molecular dynamics simulation and PCA investigations revealed that thalifendine have a strong willing to act as good bindinder to SARS-CoV-2 protease. Further, the network based pharamacology showed that these drugs mediate different pathways such as human T-cell leukemia virus 1 infection, viral carcinogenesis, human immunodeficiency virus 1 infection, kaposi sarcoma-associated herpesvirus infection and epstein-Barr virus infection.The findings of this study have an important recomendation for thalifendine for more in vivo and in vitro studies to work.Communicated by Ramaswamy H. Sarma.

Superior photo-induced antibacterial/antibiofilm activities of ZnPcs/TiO2 and computational simulation studies.

Bacteria can form biofilms on any surface, which causes biofilm-associated infections and bacterial resistance to antibiotics. Thus, it is important to design new-generation non-chemotherapeutic nanoagents for effective antibacterial and antibiofilm strategies. Herein, the effects of the anchoring groups, which are imidazole and carboxylic acid, of zinc phthalocyanines (ZnPcs) sensitized TiO2 on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were investigated under light-emitting diode (LED) irradiation. The photocatalytic antibacterial activities of ZnPc-1/TiO2 and ZnPc-2/TiO2 on the bacterial strains were examined by monitoring the optical density value at 600 nm (OD600 nm). Glutathione (GSH) oxidation assay was used to measure the reactive oxygen species (ROS) generation activity of the compounds. Bacterial damages were imaged by scanning electron microscopy (SEM). According to our photocatalytic antibacterial mechanism, photogenerated electrons are transferred from Pcs to TiO2 and then react with O2, thus creating ROS, which causes damage to bacterial membrane, protein and biofilm destruction as well. Further, computational simulation analysis was used to show the interaction patterns of ZnPc-1 and ZnPc-2 with penicillin binding protein 2a (PBP2a) of S. aureus and FimH lectin protein (PDB:4XO8) of E. coli to elucidate the dark molecular antibacterial mechanism of the compounds. The obtained results from computational studies showed that ZnPc-2 binds firmly through bonds with the 1MWT protein from S. aureus. On the other hand, ZnPc-1 binds firmly through bonds with the 4XO8 protein from E. coli. From combining experimental and computational results, we can conclude that this strategy can be applied to different types of bacterial infections.