Tehran University Medical Journal

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Background: The health risk associated with chronic exposure to organic solvents investigated in several epidemiologic studies indicates a significant relationship between solvent exposure and glomerulonephritis. Solvents are the most commonly used chemicals in industry. According to European statistics 43% of all solvent consumption takes place in the painting industry, 10% in metal cleansing, 6.7% in adhesives and 3.9 percent in the laundry (dry cleaning) industries. Although BUN and creatinine indicate massive loss of glomerular function, microalbumin is a sensitive urinary marker for nephrotoxins in the early detection of solvent-induced effects on the glomerulus. The purpose of our study was to use microalbumin, serum BUN and serum creatinine levels to identify occupational solvent-induced effects on the glomerulus.
Methods: Renal dysfunction was monitored by microalbumin, BUN and creatinine serum levels in a cohort study of 92 workers currently exposed to solvents (solvent group). A control group of 92 individuals were selected from parts of the same factory not exposed to solvents. All individuals in the study were men, without diabetes or hypertension. The percentage of smokers was equal between the two groups. The solvent group was selected using environmental monitoring of organic solvents in different parts of the painting room. The individuals were chosen by simple random selection. Exclusion factors included less than one year of work in the painting room, use analgesic or aminoglycoside one month before the study and medically diagnosed renal disease, such as glomerulonephritis or renal failure. Data was gathered using a questionnaire requesting demographic information, history of present and past diseases, present and past occupational history, drug history, history of illness in their colleagues and safety conditions at work (use of safety gloves, masks, clothing, goggles and general and local ventilation). The results analyzed with SPSS 11.5.
Results: Several studies showed that solvents cause renal disorder (tubular and glomerular), although glomerulonephritis is more prevalent. The mean age of the solvent group was 28.6 ±2.7 years and was 33.7 ±7 years in control group (p<0.05). The mean duration of solvent exposure was 4.8 ±1.5 years. Statistically meaningful differences were found between solvent and control groups for microalbuminuria, increased serum BUN and creatinine levels (p<0.05), although there was no significant correlation between these parameters and the duration of exposure (p>0.05).
Conclusion: The results suggest that kidney dysfunction results from chronic occupational exposure to solvents at levels found in automobile painting rooms in Iran. We recommend increased monitoring of workers using solvents and increased review and enforcement of safety regulations regarding such use of solvents.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Paraquat is an herbicide produced and used prevalently worldwide. Studies have shown that lung fibrosis induced by paraquat can be prevented or delayed by certain antioxidants, iron chelating agents, melatonin, and, recently, blood pressure lowering drugs such as captopril.
Methods: The protective effects of captopril on paraquat toxicity were studied using RT-PCR and immunohistochemistry to determine the gene and protein expression of p53 and Bcl-2 in lung tissue samples from rats treated with captopril before and after exposure to paraquat.
Results: We found no significant difference in the gene and protein expression of p53 in different tissue samples, except for mRNA levels in the lung tissue of captopril-treated rats. However, the protein expression of Bcl-2 is greater in tissue from rats exposed to paraquat alone and paraquat together with pre- and posttreatment with captopril compared to tissue from untreated control rats and from those treated with captopril alone, which can be due to inflammatory responses of lung tissue. By RT-PCR, we were unable to detect Bcl-2 in lung tissue samples.
Conclusion: These results show that paraquat does not induce significant DNA damage therefore, the gene and protein expression of p53 was not changed. Paraquat does induce lung tissue inflammation, which in turn increases Bcl-2 protein expression. Finally, captopril had no significant effect on the lung tissue toxicity induced by paraquat. Considering these results and the cellular interactions in lung tissue, we suggest that complementary assays and in-vitro cell culture experiments be performed to further elucidate the molecular events underlying paraquat lung toxicity.

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Background: There is a growing interest in understanding the biological effects of time-tested folk medicinal plants including the green leafy vegetables, which supply minerals and vitamins to the diet. Trigonella foenum-graecum L (fenugreek) is a dietary vegetable and there are reports concerning its antinociceptive effects in Iranian traditional medicine. Its seeds are also known for their carminative, tonic, antidiabetic, antineoplastic and restorative properties. These reports and the hypoglycemic effect of fenugreek leaf extract encouraged us to assay fenugreek aqueous extract for cytotoxicity on NIH3T3 mouse fibroblast cells.

Methods: The NIH3T3cell line was purchased from National Research Center for Genetic Engineering and Biotechnology of Iran. The cells were plated in 24-well microtiter plates with DMEM+F12 medium containing 10% fetal calf serum supplemented with 445 mg/L L-glutamine and maintained at 37^oC with 5% CO₂/95% air. Following a 24-hr incubation period, various concentrations (0.01-20 mg) of the extract to the culture wells. Cell viability was assessed using trypan blue and MTT assays after five days of incubation.

Results: The results show that the IC₅₀ of the fenugreek extract as calculated from the trypan blue and MTT assays were 1.25 and 2.5 mg/mL, respectively.

Conclusions: Our findings, therefore, suggest that the aqueous extract of fenugreek is classified as nontoxic. This observed cytotoxicity is not specific and could be due to membrane disturbances.

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Background: Adenosine receptors play an important role in the treatment of paroxysmal supraventricular tachycardia in cardiovascular system. This effect is through interaction with A1 type of G-protein-coupled adenosine receptors. The effect of N6-cyclopentyladenosine (CPA), an A1-selective adenosine agonist, was studied on ouabain-induced toxicity in spontaneously beating isolated guinea pig atria.

Methods: In the beginning the isolated guinea pig atria were mounted on the organ bath containing modified krebs and contractile responses in the four groups (shame, CPA, ouabain, CPA- ouabain) were measured.

Results: CPA (2-16nM) produced a dose-dependent decrease in the force of contractions (34%-51%) and in the rate of contractions (22%-48%). CPA significantly increased the time of onset of arrhythmia (toxicity) induced by ouabain (1.2µM) when it was administered 10 min before ouabain was added in organ bath. Ouabain (1.2µM) alone produced arrhythmia at 7 min and either asystole or standstill at 22 min. CPA (8nM) increased the time required to produce arrhythmia to 27.5 min and prolonged beating atria to more than 63 min and prevented the occurrence of asystole.

Conclusion: CPA produces direct cardiac action, probably due the inhibition of cardiac Ca²⁺ channel and membrane hyperpolarization of atrium cells in guinea pig atria. Moreover, our results suggest that CPA may reduce the membrane conduction through inhibition of ionic channels, which decrease ouabain- induced toxicity.

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Background: Tuberculosis with high prevalence in HIV/AIDS patients is the main reason for morbidity and mortality in these patients. About one-third of patients with HIV infection have concomitant tuberculosis. Lack of appropriate infection control on many social and economic communities will impose. Comprehensive study on the effects of anti-tuberculosis drugs in patients with HIV infecting less done, also due to the importance of reducing morbidity and mortality, reduce the cost of disease, identifying drug pharmacokinetics, the importance of completing treatment tuberculosis, this study was performed to evaluate the effects of anti- tuberculosis drugs on HIV infection and to identify the drug pharmacokinetics and so more complete tuberculosis treatment.
Methods: A historical cohort study was performed on patients referring to the research center for HIV/AIDS, consultation center, department of infection diseases of Imam Khomeini Hospital in Tehran, Iran. A total number of 75 cases with HIV negative versus HIV positive patients with pulmonary tuberculosis and positive sputum smear in accordance with inclusion and exclusion criteria were selected.
Results: In this study, the frequency of peripheral neuropathy 27(73%), arthralgia 31(83.8%), vomiting 18(48.6%), headache 26(70.3%), dizziness 20(54.1%), renal toxicity 4(10.8%) and of skin rash 10(27%) in patients with HIV virus infection were significantly more than HIV- negative patients. Hepatotoxicity, fever and anemia were not significantly more common in patients who infected with HIV virus.
Conclusion: The HIV patients, who have not received antiretroviral drugs during tuberculosis treatment, may show higher incidence of anti-tuberculosis drugs complications.

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Background: Regarding the immunomodulatory effects of lactobacillus bacteria, this study aimed to evaluate the effect of oral administration of Lactobacillus reuteri, as probiotic bacteria, on natural killer cell cytotoxicity and tumor-specific lymphocyte proliferation in Balb/c mice with breast adenocarcinoma.

Methods: A total of 30 female mice, aged 6- 8 weeks and with a weight of approximately 17- 19 g, were randomly divided into two groups of 15 mice. The case group received Lactobacillus reuteri at a dose of 2.7× 108 bacteria in half a milliliter of sterile phosphate buffer saline (PBS) and the control group only received PBS. The probiotic group received the regimen for two weeks prior to tumor transplantation, as they did for 30 days after transplantation with three-day intervals and durations of seven days. For the evaluation of natural killer cell cytotoxicity and also tumor-specific lymphocyte proliferation response, LDH and BrdU assays were performed respectively according to the manufacturers' instructions.

Results: The study showed that the mice in the case group which were receiving Lactobacillus reuteri had statistically significant differences in the replication of tumor -specific lymphocytes, natural killer cell cytotoxicity and delayed hypersensitivity responses Compared to the mice in the control group.

Conclusion: Daily consumption of probiotics seems to regulate the immune system and consequently it can be helpful in people with cancer. Moreover, consumption of probiotics in healthy individuals can also boost the efficiency of the immune system against a variety of abnormalities.

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Background: Excessive accumulation of beta-amyliod peptide (Aβ), the major component of senile plaques in Alzheimer's disease (AD), causes neuronal cell death through induction of oxidative stress. Therefore, antioxidants may be of use in the treatment of AD. The medicinal plants from the Lamiaceae family have been widely used in Iranian traditional medicine. These plants contain compounds with antioxidant activity and some species in this family have been reported to have neuroprotective properties. In the present study, methanolic extract of seven plants from salvia and satureja species were evaluated for their protective effects against beta-amyloid induced neurotoxicity.
Methods: Aerial parts of the plants were extracted with ethyl acetate and methanol, respectively, by percolation at room temperature and subsequently, methanolic extracts of the plants were prepared. PC12 cells were incubated with different concentrations of the extracts in culture medium 1h prior to incubation with Aβ. Cell toxicity was assessed 24h after addition of Aβ by MTT assay.
Results: Satureja bachtiarica, Salvia officinalis and Salvia macrosiphon methanolic extracts exhibited high protective effects against Aβ induced toxicity (P<0.001). Protective effects of Satureja bachtiarica and Salvia officinalis were dose-dependent.
Conclusion: The main constituents of these extracts are polyphenolic and flavonoid compounds such as rosmarinic acid, naringenin, apigenin and luteolin which have antioxidant properties and may have a role in neuroprotection. Based on neuroprotective effect of these plants against Aβ induced toxicity, we recommend greater attention to their use in the treatment of Alzheimer disease.

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Background: The high number of breast cancer patients who receive radiation therapy after surgery has caused many to think about a shorter period of radiotherapy, which can significantly reduce the radiotherapy machine time, labor hours, and fewer patient visits. This study was designed to evaluate the acute skin effects and cosmetic outcomes of short course radiotherapy in early-stage breast cancer in comparison with the conventional treatment method.
Methods: Fifty-two patients with operable breast cancer (pT1-3pN0M0) who underwent breast conservation surgery in Tehran Cancer Institute during January 2011 to January 2012, were randomly assigned to undergo radiotherapy by either receiving conventional treatment (dose: 50 Gy in 25 fractions) with subsequent electron boost or a short-course hypofractionated radiotherapy (dose: 42.5 Gy in 16 fractions) and a subsequent electron boost.
Results: There were no skin changes during the first or the second week of treatment in the two groups. Cutaneous complications began after the third week as grade 1 skin toxicity after termination of the short-course radiotherapy but there were no difference in complication rate after four weeks of treatment. Six months and one year after treatment, there were no differences in terms of skin complications or cosmetic outcomes between the two groups.
Conclusion: Although the use of a whole-breast irradiation with a hypofractionated schedule was associated with desirable outcomes, in term of skin toxicity and cosmetics, but longer follow-up periods with larger sample sizes are needed to confirm these results.

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Background: Amphotericin B Deoxycholate (ABD) has been the best therapeutic agent for treatment of most systemic fungal infections. However, untoward adverse effects like nephrotoxicity may limit its appropriate therapeutic use. We studied administration of fat emulsion early after infusion of ABD to evaluate its effects on ABD-associated nephrotoxicity.
Methods: This study was a randomized clinical trial. Patients with fungal infections admitted in Amir-Alam and Imam-Khomeini University Hospitals, Tehran, Iran, entered the study during 1390- 1391. The patients were randomized to intervention and control groups. In both groups, patients received 1mg/kg/day ABD in dextrose 5%. In intervention arm, the patients additionally received intralipid 10% daily that was started as soon as possible within one hour after infusion of ABD. ABD-associated nephrotoxicity (a minimum 50% increase in baseline serum creatinine to a minimum of 2mg/dl), daily serum creatinine changes during first two weeks of treatment and some other relevant indices of renal function were compared between groups. ABD-related hypokalemia was also compared as an additional target.
Results: Thirty one patients entered the study. ABD-associated nephrotoxicity and values of other relevant indices of renal function were not different between intervention and control groups (P>0.05). Daily changes in serum creatinine level within first two weeks of treatment in both groups were not also statistically different (P=0.62). Furthermore, ABD-related hypokalemia was not significantly different between groups (P=0.47).
Conclusion: Administration of intralipid 10% early after infusion of ABD in dextrose 5% does not have any effect in decreasing ABD-associated nephrotoxicity. Moreover, it does not have any significant effect on ABD-related hypokalemia.

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Background: Salen metal complexes are used successfully in a wide range of asymmet-ric reactions and important in the pharmaceutical and industry. On the toxicity of salen vanadium oxide (VOsalen) on embryo and cell cultures, little information is available. In the present study, the toxic and teratogenic effects of VOsalen was evaluated against chicken embryos as a animal model and liver and fibroblast cell cultures which was derived from the embryo.
Methods: The VOsalen compound was synthesized. The compound solution was inject-ed in triplicate examination, in the air sac of the eggs, at third day of incubation. Treat-ed and control eggs, on day 19 of incubation opened and embryos were weighted, then mortality rate was recorded. The liver and fibroblast cell culture were treated by this and survival fraction was recorded.
Results: The survived fraction of the embryos depends on the compound concentration. In concentration of 300μM/egg, 36/32% of the embryos survived and the Lethal dose 50% (LD50) was 226/37 μM/egg. Morphological study of the treated embryos showed retarded growth, and skeletal staining showed the deletion of caudal vertebrate. The compound was inhibited liver and fibroblast cells growth with IC50 1047/25 and 1036/82μM respectively. The cytoplasm of treated cells became dense and their interco-nnections were loosed.
Conclusion: The VOsalen compound had low toxic effects against the embryos and the cultured cells at the concentrations. Significant cytotoxic effect was not observed in the treated cells. However the proliferative cells were affected significantly in comparison with the cells which their growth was stopped. The effect of VOsalen compound against replication of liver cells were lower than fibroblast cells.

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Background: Biosynthesis of nanoparticles has attracted the attention of the scientific community in nanotechnology and biotechnology due to their extensive application in the area of material sciences and medicine. Nowadays, despite a various application of nanomaterial’s, there is a little information about their impact on human health. In this study, we investigated the comparative study on cytotoxicity effect of biological and commercial synthesized nanosilver on human gastric carcinoma (AGS) and normal lung fibroblast (MRC-5) cell lines. Methods: The current experimental study was carried out in Islamic Azad University, East Tehran Branch, from April to November 2014. The biological synthesis of nanosilver was obtained from Eucalyptus plant extract as a reducing agent. Further to more analysis, morphological study on size and shape of developed biological nanosilver was characterized by performing scanning electron microscopy and dynamic light scattering. AGS and MCR-5 cell lines were treated with various concentration of nanosilver for 24, 48 and 72 hours. Finally, the cell viability was evaluated by using MTT assay. Results: The results show that the nanosilver exerts a dose-dependent inhibitory effect on viability of cells. At 100µg/mL of commercial and biological synthesized nanosilver, the viability of AGS was reduced to 7.47±0.002% (P=0.002) and 3.65±0.01% (P=0.003) after 72 hours, respectively. In addition, the viability of MRC-5 at the same condition was reduced to 10.27±0.19% (P=0.001) and 9.16±1.53% (P=0.002), respectively. Conclusion: Based on a thorough literature surveys, the present study is the first research about biosynthesis of nanosilver using Eucalyptus plant extract. This eco-friendly and cost effective method can be used for large scale production of silver nanoparticle. In addition, based on the current obtained data, commercial and biological synthesized nanosilver can more inhibitory effect on cancer cells compared to the normal cells. Hence, silver nanoparticles might be used as a new strategy for treating many human cancers. However, further studies are necessary to ascertain their potential as anticancer agents.

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Background: Standard treatment of Gestational Trophoblastic Disease (GTD) is chemotherapy. Single-agent chemotherapy regime including Methotrexate (MTX) or Actinomycin. Single-agent is widely used in treatment of persistent trophoblastic disease. We reported an uncommon toxicity of low-dose single-agent methotrexate in a patient. Case Presentation: A 20-year-old woman, primary gravid after two months missed period and spotting with diagnosis of incomplete abortion with uterine size equivalent of ten weeks pregnancy (8-10 cm) underwent evacuation curettage. In serial follow-up, based on rise of beta-hCG titer and absence of metastatic disease, it was categorized as low-risk persistent trophoblastic disease. She was referred to gynecology oncology center of Ghaem Hospital, Mashhad University of Medical Sciences in May 2014. Because of rise of beta-hCG titer, after complete metastatic work-up and lack of disease in other sites, persistent disease was diagnosed and candidate for chemotherapy (single agent low-dose). The patient received first course of therapy with MTX (50 mg/m², intra muscular). Unfortunately, after two days of treatment she developed uncommon severe toxicity, fever, severe nausea and vomiting, tachycardia, and generalized weakness. Also, we found hematologic abnormality (WBC: -14000-15000 µI, platelet- 540 µI and sever neutropenia), and abnormal rising in liver function test (SGOT, SGPT) (three to four times) and renal function test (BUN and Creatinine) (two times). In addition, she had disseminated erosive lesion in all of body especially in face. Due to the fatal side effects of chemotherapy, she was admitted to intensive care unit (ICU). Fortunately, after two to three weeks, she was improved by conservative management. After few weeks beta-hCG titer was in normal limit. However she had normal serial beta-hCG in one year of follow-up. Conclusion: It is important to emphasis unpredictable side effects of chemotherapy with low-dose methotrexate.

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Background: Aloysia citrodora belongs to the Verbenaceae family of plants, a well-known herbal medicine in Iran. The aim of the present study was to investigate the chemical composition, antioxidant, antibacterial, cytotoxic and apoptotic effect of A. citrodora extract against human colon cancer (HT29) cells by using real-time polymerase chain reaction and flow-cytometry methods.

Methods: This experimental study was carried out in Islamic Azad University, East Tehran Branch, from March to September of 2014. At first, the A. citrodora chemical constituents were analyzed by gas chromatography-mass spectrometry (GC-MS) technique. In addition, antioxidant assay, antibacterial and anti-cancer effect was performed using 1,1-diphenyl-2-picrylhydrazyl (DPPH), disk diffusion and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) methods, respectively. The half maximal inhibitory concentration (IC50) value was calculated. We extracted total RNA molecules by using RNX solution, after which cDNA was synthesized. Finally, the pro-apoptotic (Bax) and anti-apoptotic (Bcl2) gene expression was performed by real-time polymerase chain reaction and apoptotic effects were analyzed using Flow-cytometry method.

Results: GC-MS analysis of Aloysia citrodora extract was shown 37 major components and the most frequent component was belonged to Spathulenol (17.57%) and Caryophyllene oxide (15.15%) The antioxidant activity of the extract was IC50= 0.6±0.03 mg/ml. The maximum and minimum antibacterial effects of extract were belonged to gram-negative and gram-positive bacteria, respectively. Cytotoxic results revealed that the A.citrodora extract have IC50= 20.1±0.78 mg/ml against colon cancer (HT29) cell line and real-time polymerase chain reaction results showed the expression level of Bax and Bcl2 was increased and decreased respectively in colon cancer cell line (3.470±0.72 (P< 0.05), 0.43±0.35 (P< 0.05)). In addition, the flow-cytometry results indicated the 38.66% apoptosis in colon cancer cell line.

Conclusion: According to the results, it seems that A. citrodora extract has potential antioxidant, antibacterial and anticancer effects and it suggested that further studies were performed for A. citrodora pharmaceutical importance.

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Background: Hydroxyapatite nanoparticles have a more surface contact and solubility than conventional hydroxyapatite. Hydroxynanoparticles enhances the biological and mechanical properties of new regenerated tissues. The hydroxyapatite nanoparticles have received attention as a new and effective osseous graft for using as scaffolds in bone regeneration. The reports on hydroxyapatite nanoparticles biocompatibility are controversial. It has been shown that hydroxyapatite nanoparticles induces inflammatory reaction and apoptosis. The aim of the present study was to evaluate the cytotoxicity of nano-hydroxyapatite on the human epithelial cells.

Methods: The study was experimental and completed in vitro. The study was carried out in department of Immonulogy, Faculty of Medicine, Shahid Beheshti University of Medical Sciences in November 2014. The human-derived oral epithelium cell line (KB) obtained from Pasteur Institute, Tehran, Iran were exposed to hydroxyapatite nanoparticles at 0.01, 0.05, 0.1, 0.5, 0.75, 1, 2.5 and 5 mg/ml concentrations in 24, 48 and 72 hours. Rod-shaped hydroxyapatite nanoparticles with 99% purity and maximum 100 nm sized particles were used. Methylthiazol tetrazolium bromide (MTT) method was employed for cell vitality evaluation. Enzyme-linked immunosorbent assay (ELISA) was used for assessing the viability of cells. Distilled water and fetal bovine serum (FBS) were positive and negative controls. ANOVA and Duncan tests were used for statistical analysis.

Results: The cytotoxicity of different concentrations of hydroxyapatite nanoparticles on human-derived oral epithelium cell line in 24 (P< 0.001), 48 (P< 0.001) and 72 hours (P< 0.001) was significantly different. The nano-hydroxyapatite particles at 0.5 to 1 mg/ml had the highest cytotoxicity effect on human-derived oral epithelium cells in 24, 48 and 72 hours. Lower concentrations than 0.05 mg/ml had the best biocompatibility properties in 24, 48 and 72 hours.

Conclusion: Hydroxyapatite nanoparticles had a good biocompatibility. The biocompatibility of hydroxyapatite nanoparticles were dose and time dependent. The lower concentrations than 0.05 mg/ml of nano-hydroxyapatite had the best biocompatibility over time.

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Background: The modern science of nanotechnology is an interdisciplinary science that has contributed to advances in cancer treatment. This study was performed to evaluate the therapeutic effects of biosynthesized silver nanoparticles on breast cancer cell of line MCF-7 in vitro. Methods: This analytical study was performed in Kerman and Bam University of Medical Sciences, Bam City, Kerman Province, Iran from March 2015 to March 2016. Silver nanoparticles suspension was synthesized using palm kernel extract. The resulting silver nanoparticles were studied and characterized. The ultraviolet-visible spectroscopy and transmission electron microscopy used for screening of physicochemical properties. The average particle size of the biosynthesized silver nanoparticles was determined by transmission electron microscopy. The properties of different concentrations of synthesized silver nanoparticles (1 to 3 μg/ml) and palm kernel extract (containing the same concentration of the extract was used for the synthesis of silver nanoparticles) against MCF-7 human breast cancer cells were determined by MTT assay. MTT is used to assess cell viability as a function of redox potential. Actively respiring cells convert the water-soluble MTT to an insoluble purple formazan. Results: The ultraviolet-visible spectroscopy showed strong absorption peak at 429 nm. The X-ray diffraction (XRD) and transmission electron microscopy (TEM) images revealed the formation of silver nanoparticles with spherical and octagon shape and sizes in the range between 1-40 nm, with an average size approximately 17 nm. The anti-cancer effect of silver nanoparticles on cell viability was strongly depends on the concentration of silver nanoparticles and greatly decrease with increasing the concentration of silver nanoparticles. The IC50 amount of silver nanoparticle was 2 μg/ml. Conclusion: The biosynthesized silver nanoparticles showed a dose-dependent toxicity against MCF-7 human breast cancer cells.

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Results: The phytochemical analyses of T. cherleri extract showed the 20 major components and the most frequent component was belonged to hexadecanoic acid, ethyl ester (20.7%) and 2-Pentadecanone, 6,10,14-trimethyl (19.9%). The extract had maximum antibacterial effects against Staphylococcus aureus and Streptococcus pyogenes. There was a dose dependent increase in the cytotoxicity effect of extract against A549 cancer cell. Moreover, the Real-Time PCR results indicated that the caspase 3 and caspase 9 gene expression was significantly up-regulated 2.57±0.27 (P<0.05), and 3.3±0.46 (P<0.05), respectively.

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Methods: In the present study, which was conducted experimentally from May to September 2018 in bacteriology and Cellular and Developmental Research Centers of Islamic Azad University, Shahrekord branch, the antimicrobial activity of supernatant of Lactobacillus sakei was assessed by Well Diffusion Agar (WDA) method against some pathogenic bacteria. HT-29 Colorectal adenocarcinoma cancer cells were cultured in DMEM medium with 10% bovine serum. The cells were treated in 5, 15, 10 and 20 mg/ml concentrations of sakei metabolites and incubated at 24, 48 and 72 hours. Cell growth was analyzed by celltiter 96® aqueous one solution cell proliferation assay kit to the manufacturer's protocol in all three incubation times. Results: The results of this study indicate that sakei was able to produce antimicrobial metabolites against pathogenic bacteria. Besides, the results of the celltiter 96® aqueous one solution cell proliferation assay showed that the bioavailability of HT-29 cell lines decreased at all concentrations of sakei metabolites in a dose and time-dependent manner. Conclusion: Since lactic acid probiotic bacteria can alter the metabolic activities of the intestinal microflora, attach to carcinogens and destroy them, prevent carcinogenesis such as ammonia and secondary bile acids, producing anti-cancer substances and creating an acidic state to inhibit the growth and proliferation of carcinogenic bacteria, It seems that there is a good research field for the use of bioactive compounds produced by Lactobacillus sakei in the control of bacterial pathogens and treatment of human colorectal adenocarcinoma (HT-29).

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Cancer is the second leading cause of death in the United States and has become a health problem worldwide. The reported incidence of new cancer cases is estimated at 19.3 million, with a mortality rate of 10 million in the world in 2020. There are several therapeutic approaches for cancer, including chemotherapy. Chemotherapy is consuming anti-neoplastic drugs, alone or in combination. However, it causes damages to the normal cells and has many side effects. Cardiac complications are common side effects of some chemotherapy agents. Cardiac myocytes are potentially more susceptible to the long-term adverse effects of chemotherapy agents due to the less regeneration ability in cardiac cells. Moreover, heart muscle dysfunction (cardiomyopathy) and cardiovascular complications may occur in cancer survivors even a year after chemotherapy or radiation therapy and influence their quality of life. Anthracyclines are commonly used in chemotherapy; especially doxorubicin is the most widely used drug of this family. Doxorubicin is an effective anti-malignant agent prescribed for the treatment of some solid tumors (e.g. ovary, breast, and gastrointestinal cancers). Doxorubicin can cause several side effects, ranging from cancer treatment’s common side effects such as fever, nausea, and vomiting to lethal cardiac side effects. Assumed that doxorubicin has many therapeutic and cytotoxic mechanisms, cardiotoxicity induced by doxorubicin is very common and there is no reliable treatment for this problem. The cardiac side effects of doxorubicin during a chemotherapy regimen can be acute, chronic, or even gradually progressive and persistent after the termination of doxorubicin therapy. In patients undergoing doxorubicin therapy, reported symptoms are cardiac rhythm and blood pressure changes, pericarditis, myocarditis, cardiomyopathy, and congestive heart failure. The pathophysiology of doxorubicin-induced cardiotoxicity is very wide. Disruption of normal mitochondrial function, decreased amount of antioxidant factors, production of reactive oxygen species (ROS), an imbalance in calcium hemostasis, activation of inflammatory cytokines, targeting topoisomerase-IIβ (Top2b), and induced DNA damage are associated with doxorubicin-induced cardiotoxicity. Increased doxorubicin in mitochondria activates the redox cycle that ultimately leads to the production of reactive oxygen species in both normal and tumor cells. The present review aims to investigate the cardiotoxic mechanisms of doxorubicin and explain different types of doxorubicin-induced cardiotoxicity.