Nanocurcumin-mediated down-regulation of telomerase via stimulating TGF beta 1 signaling pathway in hepatocellular carcinoma cells

Background: Curcumin, extracted from turmeric, represents enormous potential to serve as an anticancer agent. Telomerase is viewed as a prominent molecular target of curcumin, and transforming growth factor- beta 1 [TGF beta 1] has proven to be a major inhibitory signaling pathway for telomerase activity. In the current study, we aimed to explore suppressive effects of nanocurcumin on telomerase expression through TGF beta 1 pathway in a hepatocellular carcinoma cell line [Huh7]

Methods: MTT assay was used to determine the effect of nonocurcumin on viability of Huh7 cells. RT-PCR was used to analyze the gene expression patterns

Results: MTT assay revealed that nanocurcumin acts in a dose- and time-dependent manner to diminish the cell viability. RT-PCR analysis indicated that nanocurcumin results in augmentation of TGF beta 1 72 hours post treatment and leads to the reduction of telomerase expression 48 and 72 hours post exposure. Also, up-regulation of Smad3 and E2F1 and down-regulation of Smad7 confirmed the effect of nanocurcumin on intermediate components of TGF beta 1 pathway. Furthermore, transfection of the proximal promoter of telomerase triggered a significant reduction in luciferase activity

Conclusion: The data from the present study lead us to develop a deeper understanding of the mechanisms underlying nanocurcumin-mediated regulation of telomerase expression, thereby presenting a new perspective to the landscape of using nanocurcumin as a cancer-oriented therapeutic agent

Preparation and evaluation of rifampicin and co-trimoxazoleloaded nanocarrier against brucella melitensis infection

Background: Brucellosis or Malta fever is a contagious infection common between human and domestic animals. Many antibiotics are used for brucellosis treatment, but they are not efficient and put heavy burden on society. Co-trimoxazole and rifampicin are two candidates for brucellosis treatment. In this study, we aimed to enhance the efficacy of these antibiotics using designed nanoparticles

Methods: Different concentrations of cotrimoxazole and rifampicin were used for loading onto a nanostructure of synthesized monomethoxy poly[ethylene glycol]-oleate [mPEG-OA]. The solubility, cytotoxicity, and efficacy of these nano-packed antibiotics on Brucella-infected murine phagocytic cells were examined, as compared with free antibiotics. Then the release nanoparticles was increased approximately 3.5 and 1.5fold, respectively, which is considerable in comparison with free insoluble ones

Results: Despite acceptable loading percentage, the application of co-trimoxazole-loaded nanoparticle on Brucella-infected J774A.1 murine macrophage-like cells did not lead to reduction in the number of bacteria; however, the efficacy of rifampicin on Brucella-infected murine phagocytic cells enhanced

Conclusion: In the current study, the efficacy of rifampicin on reducing the number of Brucella melitensis increased by the novel synthesized nanostructure. In contrast, since co-trimoxazole efficacy did not enhance by loading onto nanoparticles, the co-trimoxazole inefficiency is most likely not due to its low penetration or insolubility, and probably there are other factors that remain to be clarified in the future investigations

[Antimutagenicity and cytotoxic effects of Malus domestica peel extract]

Background: At present, cancer is one of the leading causes of mortality in the world. Therefore, prevention can be considered as important as treatment in the management of cancer. Diet can play a vital role in cancer prevention. Nowadays, scientists are looking for natural food which can prevent the cancer occurrence. The purpose of this research was to examine antimutagenicity and anticancer effects of apple peel extract

Materials and methods: In this experimental study, HUT-78 cell line were cultured in 90% RPMI1640, supplemented with 10% fetal calf serum, l- glutamine, peniciline, streptomycin and then incubated at 37 degree C for 2 days. The cancer cell line was treated by different apple peel extract concentrations and cellular vital capacity was determined by MTT assay. The apple peel extract was subsequently evaluated in terms of antimutagenicity and anticancer properties by a standard reverse mutation assay [Ames test]

Results: During MTT assay, T cell lymphoma cancerous cells revealed significant cell death compared with controls [p<0.01]. In Ames test, the apple peel extract prevented the reverted mutations and the hindrance percent was 81.3%

Conclusion: The results demonstrated that apple peel extract has anticancer effects in in vitro condition. So, we can persuade people to add apple peel to daily diet

Analysis of the antiproliferative effects of curcumin and nanocurcumin in MDA-MB231 as a breast cancer cell line

Cancer is one of the main cause of mortality in the world which appears by the effect of enviromental physico-chemical mutagen and carcinogen agents. The identification of new cytotoxic drug with low side effects on immune system has developed as important area in new studies of immunopharmacology. Curcumin is a natural polyphenol with anti-oxidative, anti-inflammatory and anti-cancer properties. Its therapeutic potential is substantially hindered by the rather low water solubility and bioavailability, hence the need for suitable carriers. In this report we employed nanogel-based nanoparticle approach to improve upon its effectiveness. Myristic acid-chitosan [MA-chitosan] nanogels were prepared by the technique of self-assembly. Curcumin was loaded into the nanogels. The surface morphology of the prepared nanoparticles was determined using SEM and TEM. The other objective of this study was to examine the in vitro cytotoxic activity of cell death of curcumin and nanocurcumin on human breast adenocarcinoma cell line [MDA-MB231]. Cytotoxicity and viability of curcumin and nanocurcumin were assessed by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide [MTT] and dye exclusion assay. Transmission electron microscopy confirmed the particle diameter was between 150 to 200 nm. Proliferation of MDA-MB231 cells was significantly inhibited by curcumin and nanocurcumin in a concentration-dependent manner in defined times. There were significant differences in IC[50] curcumin and nanocurcumin. curcumin -loaded nanoparticles proved more effective compared to TQ solution. The high drug-targeting potential and efficiency demonstrates the significant role of the anticancer properties of curcumin -loaded nanoparticles

Anticancer activity of curcumin on human breast adenocarcinoma: role of Mcl-1 gene

Breast cancer is the second leading cause of cancer-related death among females in the world. To date, chemotherapy has been the most frequently used treatment for breast cancer and other cancers. However, some natural products have been used, as alternative treatments for cancers including breast cancer, due to their wide range of biological activities and low toxicity in animal models. The present study examined the anti-proliferative activity of curcumin and its effect[s] on the apoptosis of breast cancer cells. This study was performed by an in vitro assay and the anticancer effects of curcumin were determined by MTT [3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide]. We used quantitative real time Polymerase Chain Reaction [PCR] for detection of Mcl-1 gene expression in treated groups and then compared them to control samples. In the treatment group, there were higher levels of cell death changes than the control group. The results also showed that the Mcl-1 gene expression declined in the tested group as compared to the control group. Our present findings indicated that curcumin significantly inhibited the growth of human breast cancer cell MCF-7 by inducing apoptosis in a dose- and time- dependent manner, accompanied by a decrease in MCF-7 cell viability. Furthermore, our results showed that quantitative real-time PCR could be used as a direct method for detection Mcl-1 gene expression in tested samples and normal samples

comparison of anticancer activity of thymoquinone and nanothymoquinone on human breast adenocarcinoma

Cancer is one of the main causes of mortality in the world which is created by the effect of enviromental physico-chemical mutagen and carcinogen agents. The identification of new cytotoxic drugs with low side effects on immune system has developed as important area in new studies of pharmacology. Thymoquinone [TQ], derived from the medicinal spice Nigella sativa [also calledt black cumin] exhibit anti-inflammatory and anti-cancer activities. In this study we employed nanogel-based nanoparticle approach to improve upon its effectiveness. Myristic acid-chitosan [MA-chitosan] nanogels were prepared by the technique of selfassembly. Thymoquinone was loaded into the nanogels. The surface morphology of the prepared nanoparticles was determined using SEM and TEM. The other objective of this study was to examine the in-vitro cytotoxic activity of cell death of Thymoquinone and nanothymoquinone on human breast adenocarcinoma cell line [MCF7]. Cytotoxicity and viability of Thymoquinone and nanothymoquinone were assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide [MTT] and dye exclusion assay. Transmission electron microscopy confirmed the particle diameter was between 150 to 200 nm. Proliferation of MCF7 cells was significantly inhibited by Thymoquinone and nanothymoquinone in a concentration-dependent manner in defined times. There were significant differences in IC50 Thymoquinone and nanothymoquinone. TQ-loaded nanoparticles proved more effective compared to TQ solution. The high drug-targeting potential and efficiency demonstrates the significant role of the anticancer properties of TQ-loaded nanoparticles

Antimutagenicity effect of Citrus nobilis

Currently cancer is considered as one of the main factors of mortality globally. Many chemicals in our environment can cause genetic mutations and are potentially responsible for millions of cancer-related deaths. Nowadays the scientists are looking for food materials which can potenthially prevent the cancer occurrence. The purpose of this research is to examine antimutagenicity and anticancer effect of Citrus nobilis .The Citrus nobilis was subsequenthy evaluated in terms of antimutagenicity properties by a standard reverse mutation assay [Ames Test]. This was performed with histidine auxotroph strain of Salmonella typhimurium[TA100] .Thus, it requires histidine from a foreign supply to ensure its growth.The aforementioned strain gives rise to reverted colonies when expose to carcinogen substance [Sodium Azide] . In Ames Test the Citrus nobilis prevented the reverted mutations and the hindrance percent of Citrus nobilis was 72.46% . This is the first study that have revealed antimutagenicity effect of Citrus nobilis

[Study of antibicrobial activity of Scrophularia striata boiss]

The use of herbal medicine has a long history. In order of unveiling of the side effects of chemical drugs, human tried to use the natural resources to supply drugs. In this study, antimicrobial effect of Scrophularia striata aquatic extract on Staphylococcus aureus and Escherichia coli were studied and compared with the effects of tetracycline. In this basic- applied, the aqueous extract was prepared from the sterile and unsterile leaves and fruits of Scrophularia striata. Staphylococcus aureus and Escherichia coli after colony counting and determining dilution were cultured on known concentrations of the extract containing mediums and their effects on bacterial growth was assessed after 24 h by measurement of turbidity. Eighty percent of bacterial growth was inhibited by the extract, compared with 100% of control. The inhibitory effects of low concentrations of the extract were more than tetracycline. This study showed that the aquatic extract of Scrophularia striata could be a good candidate as an alternative or supplement to antibiotics to treat bacterial infections

Study of pentoxifylline drug effect on Bax gene expression changes in kidney after ischemic/reperfusion in rat

Ischemia Reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen. Ischemia Reperfusion induces cell death and endemic reaction that is one of the most important clinical problems with acute renal failure and renal transplantation. In this study, the effect of pentoxifylline on rat kidney function and cell injury following Ischemia Reperfusion were evaluated. In this experimental study, 20 male wistar rats with average weight of 250-300g were selected and then were accidently divided them on two tenth group of control and treatment groups. In the control group, celiotomy was performed by ventral midline incision. The left kidney was isolated, and then both the renal artery and vein were obstructed. After 60 minutes of warm ischemia, vessel obstruction resolved and the right kidney was removed. 72 hours after reperfusion, tissue samples were taken from left kidney for histopathology. All these steps in treatment group were exactly repeated after administration of 45 mg/kg/PO pentoxifylline [3 hours before operation] and in this group treatment was continued every 12h until 3 days. In this research quantitative real-time PCR is used for the detection expression Bax gene in ischemia group and PNT drug group and compared to normal sample .The results showed the gene dosage ratio of 1.24 for ischemia groups and 0.64 for drug group. The results showed the expression Bax gene in PNT group decline than to ischemia group. Therefore, quantitative real time PCR could be used as a direct method for detection of Bax gene expression in tested and normal samples

[ effects of pentoxifylline on renal apoptosis following ischemic reperfusion injury in rats]

Ischemia-reperfusion induces cell death and inflammatory reaction. It is a common clinical problem associated with acute renal failure and renal transplantation. In this study, the effects of pentoxifylline on rat kidney function and cell injury after ischemia-reperfusion were evaluated. In this experimental study, 20 male wistar rats with mean weight of 250-300g were assigned randomly into control and treatment groups [each group 10 rats]. In control group, celiotomy was performed by ventral midline incision. The left kidney was isolated, and then both the renal artery and vein were clamped. After 60 minutes of warm ischemia, the vessels were unclamped and the right kidney was removed. 72 hours after reperfusion, tissue samples from the left kidney were taken for histopathologic examination after death. The same procedures were repeated in the treatment group after administration of 45mg/kg/PO pentoxifylline, 3 hours before surgery. This treatment was continued every 12h until death. Apoptotic changes were compared between two groups by Mann-Whitney U test. Statistical significance was considered at p<0.05. The treatment group showed lower levels of cell death than the control group [P<0.05]. Pentoxifylline alone might play a role in attenuation of renal ischemia-reperfusion injury and Apoptosis

Cloning of Oct3/4 gene in embryonic stem cells

Embryonic stem cells [ESCs] are pluripotent, self-renewing cells. These cells can be used in applications such as cell therapy, drug discovery, disease modelling, and the study of cellular differentiation. In this experimental study embryonic stem cells cultured in the laboratory and were amplified. Total RNA was extracted from cells and converted to cDNA. The replication factor Oct3/4 gene was amplified by reverse transcription-polymerase chain reaction [RT-PCR] and cloned into the pTZ57R/T vector. Legated product had been transformed into susceptible bacteria and transformed bacteria were screened on a selective medium. Plasmids extracted from bacteria and enzyme digestion to confirm the sequencing was performed. Results of enzyme digestion were sequenced. Cloned gene can prepare a gene cassette to produce stem cells from somatic cell