محمد شکرزاده

L-arginine is an essential amino acid used for glutathione synthesis and as a precursor to nitric oxide, it can act as a free radical scavenger and inhibitor of lipid peroxidation. Therefore, this study aimed to investigate the protective effect of L-Arginine on cisplatin-induced cytotoxicity, genotoxicity, and oxidative stress in normal kidney cells and human blood lymphocytes.

In this experimental study, normal kidney cells (Vero cell line) and human blood lymphocytes were used. Vero cells were pre-treated with various concentrations of L-Arginine (9.35, 18.75, 37.5, 75, 150, and 300 µg/mL) and a damaging dose of cisplatin (1.7 µg/mL). Cell viability and IC50 (inhibitory concentration) were evaluated using the MTT assay. For genotoxicity assessment, 5 mL of venous blood sample was collected from a healthy, non-smoking, non-alcoholic volunteer using a heparin syringe and after isolating lymphocytes, different concentrations of L-Arginine were pre-treated with cisplatin at an optimal genotoxic dose. To evaluate micronucleus formation in cytokinesis-blocked binucleated lymphocytes, the slide was prepared and was evaluated by light microscopy. Oxidative stress tests, including ROS and MDA levels, were conducted. ROS levels were measured using a fluorimeter device and DA-DCFH reagent. To measure the amount of malondialdehyde (MDA) produced during the lipid peroxidation process Thiobarbituric acid (TBA) was used as a reagent. Data analysis was performed using one-way ANOVA with GraphPad Prism.8 software.

Cisplatin exhibited dose-dependent cytotoxicity at concentrations (0.39, 0.78, 1.56, 3.12, 6.25, 12.5, 25, and 50 μg/ml) after 48 hours incubation, with an IC50 of 1.7 μg/mL. Based on the results of this study, Pre-treatment with L-arginine at concentrations of 18.75, 37.5, 75, 150, and 300 μg/ml with 1.7 μg/ml cisplatin significantly reduced cytotoxic effects, so that with the increase of L-arginine concentration, increasing the viability of normal lung cells compared to cisplatin alone as a positive control group. On the other hand, micronucleus test results showed that L-arginine significantly inhibited the genotoxicity of cisplatin in human blood lymphocytes. So in the concentration of 18.75 µg/mL, there was a significant difference with the positive control group (P<0.05), and in concentrations 37.5 to 300 µg/ml this significant difference was evident (P<0.001). Also, L-arginine in different concentrations, reduced oxidative stress caused by cisplatin by decreasing reactive oxygen species (ROS) and malondialdehyde (MDA) production. Statistically, L-arginine had a significant difference with the positive control group in all concentrations (P<0.001).

The study demonstrated that L-Arginine, as an antioxidant compound, moderated cisplatin-induced cytotoxicity, genotoxicity, and oxidative stress in normal kidney (Vero) cells and human blood lymphocytes, showing significant protective effects. Therefore, it can be hoped for potential use as a preventive agent.

Today, despite the abundance of chemical drugs, the use of medicinal plants is increasing; Curcumin (curcumin) is a yellow pigment obtained from the turmeric plant and is considered the effective ingredient of turmeric. This crystalline and crystallized product is widely used in Indian medicine. Recently, the beneficial effects of curcumin on stomach, colon, and mouth cancers have been proven in mice. Curcumin usually plays its role through pharmacological processes such as antioxidant, anti-inflammatory, antithrombotic, apoptotic, and hepatoprotective effects. Antioxidative, antiproliferative, and antiangiogenic properties of curcumin have been noticed in recent years. However, the low solubility of curcumin and its severe degradation have made it impossible to introduce it in clinical use. In recent years, studies and reviews have been conducted to prepare and design polymeric micelles (PMMCs) on a nanoscale to improve the cellular transport of curcumin. Green tea flavonoids, including epicatechin, have recently received attention. In in vitro research, these compounds have been proposed as antioxidants by inhibiting lipid peroxidation, trapping free radicals, and chelating metal ions, and this property is mentioned due to their unique structure (therefore, the purpose of this study is to determine the effect The synergism of curcumin and epicatechin has been carried out in the investigation of apoptosis and cell proliferation of HT29 cell lines and apoptotic factors.

This study is experimental. After obtaining HT29 cells from the Pasteur Institute cell bank and completing cell passage and proliferation, the cells were distributed in triplicate wells across 7 test groups and 2 control groups (positive and negative). In test groups 1, 2, and 3, three concentrations of curcumin nanomicelles (10, 20, 50 µg/ml) were incubated in triplicate. In groups 4, 5, and 6, three concentrations of epicatechin (10, 20, 50 µg/ml) were incubated for 24 hours. Test group 7 consisted of HT29 cells treated with the IC50 concentration of nanomicelle curcumin combined with the IC50 concentration of epicatechin. Group 8, the positive control, consisted of cells treated with 5FU (100 µg/ml), while group 9, the negative control, consisted of cells exposed only to the cell culture medium. After the 24-hour incubation period, an MTT assay was performed to assess cell proliferation, and Annexin flow cytometry was used to determine the level of apoptosis.

In this study, epicatechin and curcumin have been able to decrease cell viability of colon cancer cells (HT29) and increase the percent of apoptotic cells P<0.05, which was in a dose-dependent manner, also the combination of these two drugs caused a synergistic effect in high dose P<0.05. Epicatechin in concentrations of 20, 10 μg/mL, 50, and 100 has a significant difference compared to the negative control group with P<0.05, which has caused a decrease in cell viability in colon cancer cells with increasing dose. Curcumin is the group Nanomicelle with epicatechin at IC50 concentration compared to the positive control group of 5-FU in HT-29 cell line has greatly reduced cell viability of HT-29 cell line showed that curcumin and epicatechin nano micelles had a synergistic effect. The results of cell apoptosis have shown that curcumin and epicatechin nano micelle groups at IC50 concentrations had a synergistic effect.

epicatechin and curcumin have been able to increase the death rate of colon cancer cells (HT29) by increasing apoptosis, which indicates the anti-cancer effects of these compounds. So it can suggest these compounds in colon cancer therapeutics.

Among the different categories of antifungal drugs, azole antifungals have received more attention due to their broad spectrum, high potency, and acting on specific target enzyme. Fluconazole is one of these drugs that as a bis-triazole, was the first triazole drug to enter the market. New-generation antifungal drugs such as albaconazole and voriconazole have been designed by replacing one of the triazole rings of fluconazole with other heterocycles. Based on this strategy, in this research, a new derivative of fluconazole in which a triazole residue of fluconazole is replaced by 4-benzylpiperazine dithiocarbamate was synthesized and its effects were evaluated in vitro.

The desired final compound (6) was obtained from the reaction of two key intermediates, oxirane, and N-benzylpiperazine, in the presence of carbon disulfide and triethylamine in ethanol. To prepare the oxirane derivative, the reaction of a ketonic compound namely 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl) ethan-1-one with trimethylsulfoxonium iodide was used. On the other hand, for the synthesis of N-benzyl piperazine, benzyl chloride was refluxed with the excess of piperazine. It should be noted that the purification of the compounds was done with common methods of extraction and recrystallization and there is no need for chromatography. The structure of the final synthesized compound was confirmed by infrared (IR) nuclear magnetic resonance (NMR) and mass spectrometry (MS). The antifungal activity of the synthesized compound was investigated in comparison with fluconazole against several species of pathogenic fungi sensitive to fluconazole, including Candida albicans, Candida glabrata, Candida parapsilosis, Candida krusei, and Candida tropicalis, as well as fluconazole-resistant isolates, and the minimum inhibitory concentration (MIC) was determined in vitro by broth micro-dilution method. In addition, the hemolytic effect on red blood cells and cytotoxicity on HepG2 cells were investigated for this compound. The docking mode of the target compound with lanosterol 14α-demethylase (CYP51) enzyme was also studied.

Preliminary investigation of antifungal effects on ten fungi strains sensitive to fluconazole showed that the target compound with MIC values between 0.063 and 1 μg/ml has strong antifungal effects on C. albicans, C. glabrata, C. parapsilosis, C. krusei, and C. tropicalis. In general, its antifungal activity was 4-64 times more than that of fluconazole. Also, the compound showed a good anti-Candida profile against fluconazole-resistant species. While the MIC values of fluconazole against C. albicans and C. krusei isolates were equal to or greater than 64 μg/ml, compound 6 effectively inhibited the growth of C. albicans and C. krusei resistant to fluconazole at concentrations of 8 or 16 μg/ml. The MIC value of this compound against C. parapsilosis was equal to 0.5 μg/ml. The results of in vitro hemolysis and cytotoxicity tests also showed that this compound is as safe for human cells as fluconazole. The docking study showed that the designed compound can interact more tightly with the lanosterol 14α-demethylase enzyme due to the presence of a benzylpiperazine dithiocarbamate scaffold in its structure.

According to the obtained results, the compound synthesized in this study is a suitable candidate for conducting in vivo tests and other preclinical and pharmacokinetic tests to discover a new antifungal drug.

Infertility is one of the medical problems in the world today. Clomiphene citrate drug is used to treat infertility. One of the side effects of this drug is the formation of tumor tissue in the ovary. Quercetin is a flavonoid found abundantly in nature. Quercetin is found in many fruits, vegetables, leaves, seeds, and grains. Quercetin has the potential to be used in the treatment of cancer. The most well-known and common tumor suppressor gene in humans is the p53 gene. The p53 gene was discovered in 1979 and recognized as a tumor suppressor gene in 1989. This gene was recognized as the guardian of the genome in 1992 due to its role in maintaining the stability of the genome. The p53 gene is the most commonly mutated in human cancers. The purpose of this study is to evaluate the protective effect of quercetin on normal ovary cell viability induced by clomiphene citrate drug and its correlation with p53 gene expression.

In this research, Normal ovarian cells of the CHO cell line were used. Concentrations of 10, 50, 100, 500, and 1000 mg/ml quercetin 50 μM clomiphene citrate drug and 0.29 μg/ml cisplatin were prepared and added to the cultured cells for 24 hours. In this study, Clomiphene Citrate and Cisplatin are both positive controls. Cell viability was evaluated by MTT assay. RNA was extracted and p53 gene expression was analyzed by Real-Time PCR. In this study, the primer used for the p53 gene was designed using NCBI and primer3 sites. In this study, the internal control gene is GAPDH.

Results showed that the concentrations of 50, 100, 500, and 1000 mg/ml of quercetin reduced the toxicity of clomiphene citrate drug and cisplatin (both positive controls). So the higher quercetin concentration leads to a higher number of living cells and at 1000 mg/ml quercetin the number of living cells reached 83%. The results of Real-time PCR showed that Quercetin significantly increased the expression of the p53 gene compared to the positive control group (clomiphene citrate) and negative control (P<0.05). In the concentrations of 500 (P=0.0020) and 1000 (P<0.0001) quercetin compared to clomiphene citrate, this expression increase was more significant. Also, in the concentrations of 500 (P<0.0001) and 1000 (P<0.0001) quercetin compared to the negative control, a substantial increase in p53 gene expression was observed.

The findings of this study showed that the use of quercetin inhibits the cytotoxicity of clomiphene citrate and increases the expression of the p53 gene, and its effectiveness is dose-dependent. However, Our study may partially explain the role of quercetin in the tumorigenesis process in the development of cancer in normal ovarian cells.

after heart diseases and accidents, cancer is considered the third cause of death in Iran (1), and is a major health problem not only in Iran but also in many developed and developing countries. (2). Breast cancer is a disease in which breast cells grow out of control. This disease has different types based on the type of breast cells that become cancerous. Breast cancer accounts for about one-third of all types of cancer in the female population and is the main cause of cancer-related deaths in women worldwide (3). Estrogen receptor-α is one of the isoforms of estrogen receptor encoded by the ESR1 gene. ESR-α is a nuclear receptor that acts as a ligand-dependent transcription factor (4). After binding of estrogen, ESR-α binds to the estrogen response regions in the promoter of the target genes and causes changes in the expression of the target genes (5). The present study investigates the expression level of the estrogen receptor gene (ESR1) and long non-coding RNAs (lncRNAs) related to It investigates the allele frequency and genotype of single nucleotide polymorphism (SNP) rs2234693 in ESR1 gene in patients with breast cancer.

In this case-control study, the expression of ESR1 and related coding and non-coding RNAs were investigated by microarray (17 control samples and 104 patient samples), TCGA RNAseq (on 113 normal samples, 1102 primary tumors and seven Metastatic tumor samples) and data analysis was done by R Studio and limma, and ENCORI and GEPIA2 databases. Evaluation of microRNA interaction was done by miRWalk and lncRNA interaction finding was done by lncBase 3. Protein-protein interaction was analyzed by STRING and survival and correlation analysis by GEPIA2 and ENCORI. Pathway enrichment and gene ontology (GO) analyses were performed by KEGG and Enrichr and SNP analysis was performed by RFLP test.

ESR1 gene expression was increased in breast cancer and miR-15a-3p gene had a significant interaction with ESR1 and lncRNA OIP5-AS1. OIP5-AS1 and ESR1 had significant positive expression in patient samples. The frequency of TC, TT, and CC genotypes in healthy people was 65%, 15%, and 20%, respectively, and in the patient group it was 38.5%, 38.5% and 23%. There was a significant difference in the prevalence of ESR1 gene genotypes between patients and controls.

ESR1 polymorphism may be associated with an increased risk of breast cancer and rs2234693 T>C SNP can be considered a strong marker for breast cancer screening. OIP5-AS1 may regulate breast cancer progression by altering ESR1 expression regulation.

Biocompatibility of endodontic sealers plays an important role in the success of root canal treatment. Hence, this study was conducted to compare the cytotoxicity of bioceramic sealer ( Sure-Seal Root) and resin based sealer(Adseal), on mouse fibroblast cell line L929

In this experimental in vitro study, extraction of each sealer was obtained and incubated with dilutions of 1/2, 1/4 and 1/8 with fibroblast cell line for 48 hours in the cell culture media. MTT assay was employed to evaluate the cytotoxicity. Finally, the collected data were analyzed using One-way ANOVA and Tukey’s post-test . P<0.05 were considered statistically significant

MTT assay showed that higher dilutions of the tested materials resulted in higher viability of mouse fibroblast cell line L929. In both sealers, with increasing dilution, the survival rate of cells increased. Among two sealers, Adseal in all dilutions had lower cytotoxicity and higher cell viability percentage than sealer Sure-Seal Root ,showed that it was not significant in dilutions of 1/2and 1/8. respectively  (P=0.115) and (P=0.915), but it was significant in dilution of 1/4 .(P=0.001).

Under limitations of this invitro study ,results of this study showed that AD Seal showed less toxicity than Sure seal root in all dilutions.

In clinical treatment of cancer, improving the efficacy of drugs and targeted drug delivery have always been a fundamental problem requiring more focused solutions. The purpose of this study was to investigate the protective effects of copper nanoparticles in prostate normal and cancer cell lines.

In this experimental study, different concentrations of copper nanoparticles (0, 25, 50, 100, 150, 200, 250, 300, and 600 μg) were prepared. Cell growth and oxidative stress in reactive oxygen species (ROS) and reduced glutathione (GSH) were studied in prostate normal and cancer cell lines using MTT assay. 

Copper nanoparticles created toxicity in prostate normal cells due to release of ROS and reduction of glutathione reserves. Also, this mechanism inhibited the growth of cancer cells.

According to this study, copper nanoparticles induced toxicity in normal cells through oxidative stress pathway and inducing ROS and decreased the growth of normal cells. Also, copper nanoparticles inhibited the growth of cancer cells by the oxidative stress pathway. So, copper nanoparticles cannot be an effective drug in treatment of prostate cancer as they cause high toxicity in normal cells.

It is well established that valproic acid (VPA) is teratogenic associated with oxidative stress in humans and in all animal species tested. In this study, considering the chemical composition of catechins, we investigated its protective effect on the survival of PC12 nerve cells exposed to valproic acid.

The protective effects of epicatechin (EC) at different concentrations (10, 50, 100, 500, 1000 μg/ml) on survival and viability of PC12 neuronal cells exposed to valproic acid were measured by MTT assay and oxidative stress tests (GPx, SOD, ROS, and lipid peroxidation). All data were analyzed in GraphPad Prism 8.0 using one-way ANOVA and Tukey post-test.

According to findings, EC reduced the cytotoxic effects of valproic acid at 500 and 1000 µg/ml (P<0.0001). EC significantly reduced the oxidative stress induced by valproic acid via decreasing reactive oxygen species (ROS) and malondialdehyde (MDA) production (P<0.001 and P<0.0001, respectively).

The present study showed that epicatechin could increase antioxidant potential and exhibits significant cytoprotective effect against valproic acid toxicity in PC12 cells.

Pistacia atlantica tree essential oil is known as an antimicrobial compound against most microorganisms. Lutein extract also has antioxidant properties that reduce oxidation. The aim of this study was to reduce sodium nitrite consumption in meat products that have caused common cancers in the community. In this research for the formulation sausage 40% chicken without sodium nitrite, 200 ppm, 400 ppm and 600 ppm of the extract of lutein pigment were used alone or in combination with 2 ml of Pistacia atlantica essence and, qualitative properties of the samples were compared, including antioxidant, microbial and sensory tests during 1, 10, 20 and 30 days after production (in refrigerator conditions), with control (without lutein pigment, Pistacia atlantica essence). The results showed that treatments containing higher concentrations of lutein extract pigment and also Pistacia atlantica essence had higher antioxidant potency and antimicrobial properties. Finally observed the sample containing 600 ppm of lutein pigment with 2 ml of Pistacia atlantica essence in the formulation seemed to be the most favorable for the color (a * or more intense redness (12.89) and b* or lesser jaundice (13.964)) also this sample in terms of antioxidant properties (3.06 mgMalondialdehyde/kg), total count (39×105 Cfu/g), mold and yeast (7.66 Cfu/g), coliform (Clostridium perfringens (11 Cfu/g) and Staphylococcus aureus (7.66 Cfu/g) and sensory properties was no significant difference with the control sample and selected as superior treatment.

Background & Aim:

Cancer is one of the serious health problems of today's societies, and extensive efforts are being made to deal with it. Nevertheless, in many cases, cancer cells can finally deal with the provided treatment solutions and even sometimes, with the emergence of resistance to chemotherapy, they can benefit from the treatments used for faster tumor growth. Currently, there are several specific CDK4/6 inhibitors such as Palbociclib, Ribociclib, Abemaciclib, and these specific inhibitors significantly reduce tumorigenesis, growth, and tumor invasion. The aim of this study was to investigate the cytotoxicity of Abemaciclib drug on the growth rate and ROS production in two cancer cell lines, A549 and AGS.

Materials & Methods:

In this experimental study, AGS (gastric cancer) and 549A (lung cancer) cell lines were cultured. Cell viability was measured by MTT test and oxygen free radical production rate by ROS test to check the sensitivity of Abemaciclib drug in doses of 1, 2.5, 5, 10, 20 μM in specified cell lines. The data was analyzed with Graph Pad Prism v.:8 software and P<0.05 was considered as a significant level.

The findings of this study show that Abemaciclib can be used as a therapeutic agent in these two cancers, because with the increase in drug concentration, the growth of the target cancer cells decreased.

The results obtained from this study showed that Abemaciclib significantly reduced cell survival and proliferation in (549A) and (AGS) cell lines compared to the control at doses of 10 and 20 μM. More laboratory and animal studies are needed to investigate the exact molecular and clinical processes of Abemaciclib.

Cervical cancer is the fourth most common cancer in the world. The most important issue in cancer treatment is the destruction of cancer cells in the presence of normal cells. For this reason, it is necessary to use natural resources such as plants to treat cancer. The aim of this study is to evaluate the antibacterial effects of the ethanolic extract of Alhagi maurorum on Staphylococcus aureus and Pseudomonas aeruginosa and cytotoxicity on HeLa cervical cancer cell line.

In this experimental study, first the ethanolic extract of Alhagi maurorum was prepared, and then the two standard strains of Staphylococcus aureus (ATCC: 25923) and Pseudomonas aeruginosa (ATCC: 27853) were lyophilized by culturing in nutrient medium. In order to confirm the standard strains, biochemical tests were performed. Microdilution method was used to determine the minimum inhibitory concentration and after obtaining the minimum inhibitory concentration, the minimum bactericidal concentration was evaluated. Furthermore, the effects of the cytotoxicity of the extract at concentrations of 0.1, 10, 50, 100, 500 and 1000 μg/ml was evaluated on the HeLa cell line in a period of 48 hours using the MTT method and comparing its toxicity with the cisplatin group (positive control group).

Ethanol extract of Alhagi maurorum at a concentration of 50 μg/ml reduced the growth of cancer cells, and in the statistical comparison, 50, 500 and 1000 μg concentrations revealed significant differences (p<0.05). According to minimum inhibitory concentration results, the minimum growth inhibitory concentration of the extract on the standard strain of Staphylococcus aureus and Pseudomonas aeruginosa was reported to be 4000 and 16000 μg/ml, respectively, and according to minimum bactericidal concentration results, the minimum bactericidal concentration of the extract was found 4 times the minimum inhibitory concentration (16000 μg/ml) in Staphylococcus aureus (ATCC: 25923), but it was not lethal in Pseudomonas aeruginosa (ATCC: 27853).

The results of the study showed that the ethanolic extract of Alhagi maurorum affected HeLa cells through antioxidant activity and inhibited their growth, and according to minimum inhibitory concentration and minimum bactericidal concentration results, it was also shown that the most inhibitory effect was on the standard strain of Staphylococcus aureus while it showed no effects on the strain of Pseudomonas aeruginosa.

In today's society, chemicals have many benefits and applications. One of these chemicals is Drabkin’s solution which is used in the hematology laboratory. Drabkin’s solution is toxic and is harmful to skin health. In this study, considering the chemical composition of vitamin C and the phytochemical properties of ginger plant, we decided to investigate the effects of the hydroalcoholic solution of this plant on the survival of normal skin and gum cells in the presence of Drabkin solution.

Protective effects of ginger extract and vitamin C (doses 0.1, 10, 50, 100, 500, and 1000 μM) on the toxicity caused by Drabkin’s solution was measured by colorimetric assay (MTT) to investigate the survival and viability of normal gingival and skin cells. Prism statistical software version 8 and one-way ANOVA and Tukey tests were used for statistical analysis. A significance level of P<0.05 was considered.

The results of this study showed that high concentrations of vitamin C and ginger inhibit the toxicity of Drabkin’s solution, so that there was a significant increase in the growth of normalized cells. Drabkin’s solution in concentrations higher than 50 μM has toxicity on the studied cell lines.

The results of this study showed that the consumption of ginger extract and vitamin C in different concentrations increased the growth of normal cells of the gums and skin, and as a result, caused cell protection from the damage caused by Drabkin’s solution.

Nowadays, multi-drug regimens or combination therapy are new approaches in cancer treatment that combine two or several therapeutic agents. Combination therapy aims at improving the therapeutic efficacy of anticancer drugs while reducing toxicity and preventing drug resistance. The aim of this study was to determine the synergistic effect of combined clarithromycin and doxorubicin in lung cancer A549 cell line.

Combined cytotoxicity of doxorubicin and clarithromycin was evaluated by MTT assay in A549 cell line. The nature of the interaction observed between doxorubicin and clarithromycin was analyzed in Compusyn software based on Chou and Talalay method. In order to clarify the molecular mechanism of the drug synergism, apoptosis was measured by Annexin V/PI double staining.

Clarithromycin at 500 µM synergistically reduced the IC50 value of doxorubicin. The enhanced cytotoxicity of doxorubicin by clarithromycin was associated with increased apoptotic cell death in A549 cell line.

Clarithromycin is a suitable candidate when combined with other anticancer drugs in vitro. However, more investigations are needed to evaluate the application of clarithromycin in adjuvant cancer therapy.

Venlafaxine is an antidepressant that belongs to the family of selective serotonin and norepinephrine reuptake inhibitor (SNRIs) drugs. Recent studies have indicated that prolonged use of antidepressants leads to a state where increased formation of reactive oxygen species (ROS) overwhelms body antioxidant protection and subsequently induces DNA damage, lipid peroxidation, protein modification and cytotoxicity. This study attempts to examine the protective effect of simvastatin against venlafaxine induced cytotoxicity and oxidative stress in human gingival fibroblasts (HGF) cells.

In this experimental study, the intracellular ROS generation and IC50 were measured in cells treated with venlafaxine and simvastatin at different concentrations (50, 100, 150, and 200 μM) in pre-treatment in vitro condition.

According to findings, HGF cell viability was significantly different in 150, and 200 μM of simvastatin compared with venlafaxine (P<0.01). Also, simvastatin significantly decreased the effects of venlafaxine by reducing the level of ROS at 150 and 200 μM (P<0.01).

This study suggests that simvastatin attenuates venlafaxine-induced cytotoxicity in HGF cells through scavenging excessive ROS.

Induction of cellular senescence is indicative of new strategy to prevent abnormal proliferation of cancer cells. Doxorubicin (DOX) is gaining attention for its neoplasia suppressive and inhibitory properties, but its clinical utility is limited due to irreversible effects on non-target cells/tissues. In this way, nanoliposomal structures were developed in drug delivery systems with minimal systemic side effects. The biological role of doxorubicin-loaded nanoliposome (NLDX) in inflammation, a prerequisite for the onset of senescence, is unclear. This study was designed to evaluate the function of P53 and senescence-associated inflammatory markers during NLDX clearance in normal tissue of the liver.

This experimental study included three groups of Wistar rats; DOX (0.75, 0.5, and 0.1 mg/kg/BW) and LDOX (0.1, 0.05, 0.025 mg/kg/BW) groups, and a control group. Liver tissues were studied for inflammatory markers evaluation and Real-Time PCR was performed to investigate the level of P53 expression.

Data showed that NLDX at 0.1 mg/kg/BW could significantly induce senescence in rat liver tissue by remarkable increase in expression level of P53 (P<0.05) and senescence-related inflammatory markers, including TNF-α, NF-κB, interleukin -1, and interleukin-6 compared with a similar dose of DX (P<0.01).

This research provides sufficient evidence of increased senescence in rat liver tissue caused by NLDX compared with DOX during liver excretion.

Tramadol poisoning is a serious medical emergency and one of the most common causes of drug poisoning. The present study aims to determine the epidemiological features of patients who were served by Qaemshahr pre-hospital emergency care due to tramadol toxicity in 2016.

In this descriptive cross-sectional study, medical records of patients with toxicity that received pre-hospital emergency care in Qaemshahr, Iran (2016-2017) were studied and relevant information were extracted.  Data analysis was done in SPSS V22.

Tramadol toxicity included 29.6% of the total poisonings and 50% of drug toxicity cases. There were 118 cases with tramadol poisoning, including 94.9% men and 5.1% women. The average age of patients was 26.61 years and the majority (66.1%) aged 21-30 years old. All patients took tramadol orally and the main cause of toxicity was drug abuse (94.1%). Among the patients, 65.3% had no medical history and 29.7% had the history of narcotic abuse.

In this study, tramadol toxicity was the most prevalent cause of drug poisoning especially in young people due to drug abuse. Therefore, informing young people and their families about the consequences of tramadol abuse, extra precautions in its distribution, and lower prescription rates are effective in preventing and reducing tramadol toxicity.

The use of metal alloys is an integral part of orthodontic treatment. In order to complete the treatment period, these metal alloys are used for a long time in orthodontic patients and Direct contact with saliva and food causes corrosion of metals and release of ions. Since the increase in the amount of ions released causes a cytotoxic state for the body, the present review study briefly examined the release of cytotoxic ions from fixed orthodontic wires in vitro. In this review study, articles related to Persian keywords (Orthodontic appliances, Chromium Ions, Nickel Ions, Metal Ions Release, Saliva, Orthodontic Treatment) in the Persian Data bases of Magiran, noormags, Irandoc, Scientific Information Database (SID) and English Keywords (Orthodontic appliances, Chromium Ions, Nickel Ions, Metal Ions Release, Saliva, Orthodontic Treatment) External databases were searched by Pubmed, Google Scholar, Scopus, ISI during the years 2001 to 2019 and 21 related articles in this field were reviewed. Findings from studies showed that during orthodontic treatment, metal ions such as nickel, chromium and cobalt are released from components such as brackets, wires and orthodontic bands and They are important because they can cause hypersensitivity and cytotoxic conditions. Therefore, more studies are needed to investigate the effects of various laboratory dimensions, including the effects of temperature, variable times, and types of mouthwash brands, to help more accurately identify and detect the release of toxic ions.

Oxidative stress identifies as the imbalance of free radicals (reactive oxygen and nitrogen species) and antioxidants defence. Cellular and tissue damage of oxidative stress causes enhances lipid peroxidation, DNA and protein damage and in finally cell death. Different exo/endogenous factors such as mycotoxins play a role in causing damage mechanism with an increase or decrease the level of the vital molecule such as malondialdehyde (MDA) and glutathione (GSH). Mycotoxins are one of the most common foods and feed contaminants in the world, which considered a serious risk factor for human and animal health. Several enzymatic and/or nonenzymatic natural compounds with antioxidant activity could be inhibiting/reducing oxidative stress damage severity due to the free radical’s imbalance via different mechanisms.The present study briefly reviews the oxidative stress of major mycotoxins as a potential pathogenic mechanism, and the protective role of some natural plant and microbial compounds with antioxidant capacity (either separately or in combination) in reducing the adverse effects of the above stress. The use of natural and indigenous compounds with antioxidant properties in each region can be considered in the strategies for discovering and producing novel medicines and processed foods that have a protective/therapeutic role as one of the goals of green government establishment in macro-management policies in the country.

Growing evidences have revealed a positive association between organophosphorus pesticides and diseases like cancer. Located in northern Iran, Mazandaran Province is a region with the overuse of agricultural pesticides. Due to the extensive use of the pesticides like diazinon in rice paddies of Mazandaran for the control of Chilo suppressalis, and high incidence rate of cancer in this province, we analysed and compared diazinon in the serum samples of the breast-cancer patients with the healthy volunteers. This cross-sectional case-control study inludes 10 breast-cancer patients and 10 healthy controls. Diazinon was extracted with a mixture of acetone and diethyl ether (1:1 v/v) in acidic medium and the residue was analyzed by GC-MS instrument. Results showed the presence of 0.151 ppm diazinon in the serum of just one healthy subject. In conclusion, despite excessive use of diazinon in Mazandaran Province, no association was found between serum level of diazinon and the incidence of breast cancer.

Abstract
Self-treatment is an important global problem. Adolescents are important groups vulnerable to self-treatment. The purpose of this study was to determine the frequency and some factors related to self-treatment in adolescents living in Gorgan.
 This cross-sectional, descriptive-analytical study was performed on 400 adolescents living in Gorgan. Data were collected through in-person interviews and checklists. SPSS software version 16 and Pearson chi-square test were used for data analysis.
Self-treatment was observed in 50% of adolescents. Most adolescents cited cold (58%) and headache (37%) as the most important causes of self-treatment. Anti-cold (58%) and non-steroidal anti-inflammatory drugs (40%) were the most important drugs used in the study. In addition, most adolescents had self-medication due to minor illness (61%) and previous drug use (42%). City pharmacies were the most important source of supply (77%). Parents and relatives were also the most important source of information for self-treatment (57%). Finally, there was a significant relationship between self-treatment and gender (P = 0.03), household dimension (P <0.001) and monthly household income (P <0.001).
Self-medication was observed in 50% of adolescents in Gorgan, which was mainly due to the use of anti-cold and non-steroidal anti-inflammatory drugs.

In this study, the effects of a mixture of deoxypodophyllotoxin/DPT and Juniperus communis L. on apoptosis and cellular inhibition were evaluated. Also, their cytotoxicity effects on prostate cancer cells (PC3 and DU145) and normal cells (HGFs), their anti-inflammatory effects, oxidation properties, and their effects on the expression of androgen receptors (AR) and clusterin (CLU) receptors were evaluated.

In this experimental study, the cells were cultured in DMEM f12 medium containing L-glutamine, penicillin, streptomycin, and 10% FBS. Morphological changes induced by reverse microscope were investigated 24, 48, 72, and 96 hrs after adding pure DPT and juniper extract at 10, 100, 500, 1000 μg/ml. Survival rate was assessed by MTT assay in all three cell lines. The rate of apoptosis in all cell lines was assessed by flow cytometric analysis. The expression levels of AR and CLU genes were evaluated by Real-Time PCR.

The 10, 100, 500, 1000 μg/ml of DPT and 500 and 1000 oncentrations of extract after 24 hours caused morphological changes in PC3 and DU145 cells and these changes intensified after 48, 72, and 96 hr. The MTT test showed significant decrease in PC3 and DU145 cell survival levels at 100, 500, and 1000 μg/ml (P<0.001). Also, the extract at 100 and 500 μg/ml significantly reduced the survival of PC3 and DU145 cancer cells (P<0.042).

Pure DPT and plant extracts have cytotoxic effects on PC3 and DU145 cells with minimal damage to normal cells.

Medicinal plants, such as flaxseeds play an important role in the health of individuals and communities. Regarding the phytochemical properties of flaxseed, this study aimed to investigate the hydroalcoholic effects of this plant on the genetic toxicity of cyclophosphamide in peripheral blood lymphocytes. The flaxseed extract was initially prepared by maceration using ethanol solvent in two rounds. After one hour of incubation with different concentrations, the blood samples were incubated with 750µ M in a bain-marie at 37° C for 24 h. To evaluate the production of micronucleus in dual nuclear lymphocytes suppressed in cytokines, the slides were prepared and evaluated using light microscopy. The data were analyzed in SPSS software and the mean values were compared using Tukey's test and.
Ethics code: 30.96.3.1002 The incubation of blood samples with cyclophosphamide leads to induced additional genotoxicity in lymphocytes. Moreover, flaxseed extract pretreatment significantly reduced the micronucleus frequency (P<0.0001). In addition, the results showed the effective role of flaxseed extract as a protective agent in reducing the genotoxicity of the pesticide cyclophosphamide. According to the obtained results, flaxseed is a potent antigenotoxic agent against cyclophosphamide-induced DNA damage. Since the flaxseed extract does not have cytotoxic effects, it can be used as a protective agent against the toxic effects of cyclophosphamide.

Docetaxel (DTX) is one of the most potent anticancer drugs in the taxane family. The commercial formulation of DTX for clinical use consists of high concentrations of tween80, which has been caused serious patient`s difficulties. Therefore, preparation of novel drug delivery system with ability of removing tween 80 and targeting on cancer tissue can lead more effective and also decrease side effects. This study is focused on preparation, characterization and cytotoxicity evaluation of docetaxel and poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) against a tumor cell line. NPs of DTX and PLGA was prepared by a modified emulsification/solvent diffusion method. Then the obtained NPs were characterized and evaluated. For this purpose, 10000 viable cells were seeded in each well of 96-well plate and after 24 hours of incubation different concentrations of conventional and NPs were added to the wells. Then mitochondrial dehydrogenase activities in living cells were determined at 24, 48 and 72 hours by MTT assay. The average diameter of the NPs was approximately 184.3 ± 14.6 nm with poly dispersity index of 0.15. Notably, the results showed significant increase in cytotoxicity of the NPs against the A549 cell line. Inhibitory concentration (IC50) of free drug and NPs was 20.66 ± 0.22, 18.27 ± 0.45, 10.64 ± 0.38 and 0.57 ± 0.04, 0.16 ± 0.04, 0.07 ± 0.01 (µg/ml) at 24, 48 and 72 hours respectively. This study demonstrates the higher cytotoxicity of DTX-PLGA NPs on human lung cancer cell line. The present formulation can be considered for the further studies on other cell lines and in vivo evaluation.

B

Recurrent Abortion is a genetic disorder with different etiologies, as defined by the World Health Organization (WHO), three or more times consecutive pregnancy losses. Genetic anomalies are one of the main etiologies of recurrent abortion. The purpose of the study was to investigate the association between beta fibrinogen (rs1800790) gene polymorphism and recurrent abortion in Iranian women.
In this case-control study, 101 women with recurrent abortion (19-41 years) and 50 women with no history of abortion (23-57 years) (controls) were present. Five milliliters of their blood was collected in EDTA tubes in Imam Khomeini hospital, Sari, Iran, during 2017-2018. Genomic DNA was extracted using salting-out method and genotypic study of polymorphism was performed using PCR-RFLP method. Statistical analysis was performed using Medcalc software version 15.
Relative frequency of AA, GA, GG genotypes for FGB in patient group were 5.94%, 29.7% and 64.36% and in control group were 2%, 50%, 48% respectively (p= 0.040). The percentage of G and A alleles was 79% and 21% in patient and 73% and 27% in control groups, respectively (p= 0.322). Evidence indicated the AA mutant gene does not increase the risk of recurrent abortion and there is no significant association (p= 0.472). But GA heterozygote relative to GG reference genotype decrease the risk of recurrent abortion (OR= 0.44, 95%CI: 0.22-1.90, P= 0.024).
The results showed that rs1800790 FGB gene polymorphism did not increase the risk of recurrent abortion.

Type 2 diabetes mellitus is a complex heterogeneous group of metabolic conditions characterized by increased levels of blood glucose due to impairment in insulin action and/or insulin secretion. The TCF7L2 gene is considered as one of the major genes susceptible to diabetes.The single nucleotide polymorphism rs7903146 is located in intron 3 of this gene, which is significantly effective in type 2 diabetes. In this case-control study, 141 patients and 86 healthy subjects were present. 5cc peripheral blood of diabetics was collected in EDTA-containing tubes. Genomic DNA was extracted using salting-out method and polymorphism genotype was investigated using PCR-RFLP method. Genotype and allele frequencies of the rs7903146 polymorphism differed significantly between type 2 diabetic patients and non-diabetic subjects (P = 0.0468 and P = 0.0474 , respectively). The frequency of T allele was 54.5% in type 2 diabetes group and 39.5% in non-diabetic subjects, and this allele was significantly associated with type 2 diabetes risk (OR = 1.8333, 95% CI 1.0456 – 3.2144). Our results confirmed the association between the rs7903146 polymorphism of the TCF7L2 gene and the increased risk of type 2 diabetes in the west-Mazandaran, Iran.