A B S T R A C T
Handicrafts and tourism are two interdependent sectors. According to today's developments, marketing and solving the challenges faced in this field are necessary to advance the development of the handicrafts sector. In this research, an attempt has been made to identify and explore the factors affecting the marketing of handicrafts in the direction of tourism development from the elite's point of view. The research method is descriptive-analytical and based on the collection of survey data. The data collection technique is a questionnaire. The statistical population of the research was made up of experts in the fields of handicrafts and tourism who, using the snowball method, identified a total of 85 experts and completed the questionnaire. The results showed that 22 factors affecting the marketing of handicrafts in the direction of Iran's tourism development are known and important. The result showed that the total effect value was 0.81, and in total, the examined factors can explain about 81% of the positive effects in improving the marketing of handicrafts and tourism. In this context, the handicrafts market development factor in the context of technology with an explanation of 0.987 and low-cost tourism services with an explanation of 0.901 are known as the two factors that have the most influence on the marketing of handicrafts in the direction of tourism development.In order to solve the handicraft sector and especially their marketing problems, some obstacles and effective factors must be solved in this field. These factors include economic, social, managerial, and political factors
Extended AbstractIntroduction
Tourism and handicrafts are two interdependent sectors, and the development of each can lead to the improvement of the other. In addition, each has independent social and economic effects at the local and national levels. Nevertheless, considering the connections between these two sectors, it is necessary to help develop them together with basic planning and formulating optimal solutions. One of the important sectors in which Iran's tourism and handicrafts are neglected is the marketing of handicrafts. Marketing can help the handicraft business to be successful in the competitive market and earn high income. Also, handicraft marketing can help the tourism industry. With proper advertising and marketing, handicrafts can be known as tourist attractions in different regions and attract tourists. As the number of tourists increases, the sale of handicrafts also increases, and this can help develop the industry and create job opportunities in different areas. Therefore, the principle of marketing is very important in both handicrafts and tourism. In this regard, examining the issue of handicraft marketing with an emphasis on tourism can be considered one of the important steps in the study and development of this sector because the lack of basic attention, even in the studies department, has been effective in the lack of development of handicrafts and tourism marketing. This research can be a step forward in the direction of the importance of the subject. Thus, considering the relationship between handicrafts and tourism, this research tried to emphasize the marketing issue. So, this research aims to identify and analyze the factors affecting the marketing of handicrafts in the direction of tourism development.
Methodology
The research method is descriptive-analytical and based on the applied goal. Also, in terms of time, except cross-sectional research and based on the way of data collection, it is quantitative research. The statistical population of the research is made up of experts on the subject of handicrafts and handicrafts. Accurate statistics regarding the number of expert statistical communities have not been available, and they cannot be used to determine them using different formulas. The sample size was determined to be 85 people using the snowball sampling. Another point is that this number of samples is available to the researcher, and the same number of people have shown their acceptance of completing the questionnaire. The data collection tool was a questionnaire whose validity was confirmed through elite society, and reliability was confirmed through Cronbach's alpha with a coefficient of 0.78. SPSS software was also used for data analysis.
Results and discussion
A sample t-test was used to investigate the factors affecting marketing. The result of the test shows that 22 investigated factors were significant at a level of less than 0.05 and equal to 0.000. Examining the direction of significance using the mean shows that the direction of significance is also evaluated as positive. In this context, the highest average was related to the localization of tourism services with an emphasis on handicrafts, which had a value of 4.458. Also, two factors of investment in the handicraft sector, with an average of 4.176, and price control of handicraft products, with an average of 4.164, are known in the second and third ranks. Therefore, the three mentioned factors are known as factors that can have a significant impact on the development of handicrafts marketing. In other words, these factors are more important compared to other factors. The overall fit of the model of the effect of various factors on the marketing of handicrafts in the direction of tourism development and the effect of independent variables on the dependent variable of the research was investigated. The result showed that the role of the mentioned indicators in marketing among the respondents is significant at the 99% confidence level. The critical ratio is higher than the value of 2.58 (a critical ratio higher than 2.58 indicates the significance of the effect) and also indicates the significance of the effect of the independent variable of the research (investigated factors) on the dependent variable (handicrafts and tourism marketing). In total, it can be said that 22 investigated factors, including low-cost tourism services, investment in the handicraft sector, information related to handicrafts, localization of tourism services with an emphasis on handicrafts, development of handicrafts market in the context of Technology, advertising and attention to handicrafts and indigenous, training of human resources, etc. can be effective in the marketing status of handicrafts and tourism. Examining the role of 22 influential factors in the marketing situation shows that the total effect value is 0.81, and in total, the investigated factors can explain about 81% of the variance, role-playing, and positive effects in improving the marketing of handicrafts and tourism. According to the results of this model, the most influential factor is related to the handicraft market development factor in the technological context with an explanation of 0.987, which actually has the most significant impact among the analyzed factors in improving handicraft marketing in the direction of tourism development. Low-cost tourism services, with an explanation of 0.901, as well as information related to handicrafts, with an explanation of 0.798, are known in the second and third ranks of the factors investigated in the field of improving the marketing of handicrafts in the direction of tourism development. In addition, the two factors of using native-local festivals with an explanation of 0.789 and advertising and paying attention to local handicrafts with an explanation of 0.788 have been placed in the next important and influential ranks. Therefore, the 22 investigated factors influence the marketing of handicrafts in the direction of tourism development, and the extent of this influence is reported separately for each factor in the table below.
Conclusion
Overall, the analysis of the results confirms that marketing is influenced by various contextual, structural, and behavioral factors, and all these factors can be effective in improving the marketing of handicrafts with a tourism approach. In order for the marketing of this sector to be placed in a proper process, emphasizing these factors and turning to new methods, especially in the technology sector, is an undeniable necessity. In line with the mentioned results, two suggestions are presented:
1.It is suggested that marketing methods be strengthened in the context of technology and technology in the handicrafts sector;
2.It is suggested that advertising and information necessary for the introduction and marketing of handicrafts be emphasized.
Funding
There is no funding support.
Authors’ Contribution
Authors contributed equally to the conceptualization and writing of the article. All of the authors approved thecontent of the manuscript and agreed on all aspects of the work declaration of competing interest none.
Conflict of Interest
Authors declared no conflict of interest.
AcknowledgmentsWe are grateful to all the scientific consultants of this paper.
Sadeghi aliabadi, H., Sadeghi-aliabadi, H., Sadeghi, H., Sadeghi, H., Sadeghi, H., Mirian, M., Mirian, M., Mirian, M., Mirian, M., Mirian, M., Mirian, M., Alinia, S., Alinia, S., Alinia, S., Alinia, S., Alinia, S., Alinia, S., Abbasi, M., Abbasi, M., Abbasi, M., Abbasi, M., Abbasi, M., Abbasi, M.
Journal of Isfahan Medical School (10277595)(705)pp. 18-26
Background:Tetrazole compounds have various effects such as antiviral, anti-bacterial, anti-fungal, anti-inflammatory, anticonvulsant and anti-cancer effects. To introduce new therapeutic options, we examined the biological effects of several newly synthesized tetrazoles in order to address the lack of effectiveness and the incidence of drug resistance. Methods:Pre-synthesized tetrazole compounds were solubilized in appropriate solvent and then cytotoxic at concentrations of 0.1, 0.01 and 0.001 mM on HeLa and MCF-7 cell lines using MTT assay. The antimicrobial activity of these compounds was determined by the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of the compounds. Findings:Evaluation of studied compounds showed significant toxicity against HeLa and MCF-7 cell lines. On the other hand, all compounds except compounds 5 and 6 that had methyl and aldehyde groups respectively, showed good antimicrobial activity against selected microorganisms. Conclusion: Results of cytotoxic studies performed on the HeLa cell line shows that none of the compounds could reduce the percentage of living cells below 50% after 48 hours, while within 72 hours, all compounds except 1 and 2 (respectively with methoxy and hydroxyl groups) were reduced cell viability below 50. In the study of antimicrobial effects, 1, 2, 3 and 4 showed 0.04 µM and 0.1 mM for MIC and MBC, respectively, which illustrated relatively proper antibacterial effects against Staphylococcus aureus and Escherichia coli and antifungal effect against Candida albicans.
Gavanji S., Baghshahi H., Bakhtari A., Mohamadi A., Chamgordani Z.H., Khandan M., Sinaei J., Momtazi-borojeni, A., Momtazi-borojeni, A., Behbahani, M., Sadeghi, H.
Bakherad, Z., Bakherad, Z., Safavi, M., Safavi, M., Fassihi, A., Fassihi, A., Sadeghi, H., Sadeghi, H., Bakherad, M., Bakherad, M., Rastegar, H., Rastegar, H., Ghasemi, J.B., Ghasemi, J.B., Sepehri, S., Sepehri, S., Saghaei, L., Saghaei, L., Mahdavi, M., Mahdavi, M.
Research on Chemical Intermediates (09226168)(5)pp. 2827-2854
Bakherad, Z., Bakherad, Z., Safavi, M., Safavi, M., Fassihi, A., Fassihi, A., Sadeghi, H., Sadeghi, H., Bakherad, M., Bakherad, M., Rastegar, H., Rastegar, H., Saeedi, M., Saeedi, M., Ghasemi, J.B., Ghasemi, J.B., Saghaei, L., Saghaei, L., Mahdavi, M., Mahdavi, M.
Momtazi-borojeni, A., Momtazi-borojeni, A., Sadeghi, H., Sadeghi, H., Rabbani, M., Rabbani, M., Ghannadi, A., Ghannadi, A., Abdollahi, E., Abdollahi, E.
Research In Pharmaceutical Sciences (17355362)(3)pp. 257-264
The objective of the present study was to evaluate the cognitive enhancing of pineapple juice and ethanolic extract in scopolamine-induced cognitive deficit mice. The ethanolic extract of pineapple (Ananas comosus (L.) Merr.) was prepared by maceration method and its juice was obtained by a homogenizer. Object recognition task was used to evaluate the mice memory. Exploration time in the first and second trial was recorded. The differences in exploration time between a familiar and a novel object in the second trial were taken as a memory index. Animals were randomly assigned into 15 groups of 6 each including: control group (normal saline + vehicle), positive control group (scopolamine + rivastigmine), seven experimental groups (received scopolamine alone or scopolamine + ethanolic extract of pineapple in different doses), six other experimental groups were treated by ethanolic extract or juice of pineapple in different doses. Scopolamine (100 μL, 1 mg/kg, i.p.) and pineapple juice or extract (50, 75 and 100 mg/kg, i.p.) were administered 40 and 30 min before starting the second trial in the experimental groups. Object discrimination was impaired after scopolamine administration. Results showed that juice and ethanolic extract of pineapple significantly restored object recognition ability in mice treated with scopolamine. These finding suggested that pineapple had a protective role against scopolamine-induced amnesia, indicating its ability in management of cognitive disorders.
Mirian, M., Mirian, M., Khanahmad, H., Khanahmad, H., Darzi, L., Darzi, L., Salehi, M., Salehi, M., Sadeghi, H., Sadeghi, H.
Research In Pharmaceutical Sciences (17355362)(2)pp. 88-98
Viral hepatitis, as an international public health concern, seriously affects communities and health system. In recent years, great strides have been taken for development of new potential tools against viral hepatitis. Among these efforts, a valuable strategy introduced new molecules called "aptamers". Aptamers as potential alternatives for antibodies could be directed against any protein in infected cells and any components of viral particles. In this review, we will focus on recent advances in the diagnosis and treatment of viral hepatitis based on aptamer technology. In recent years, various types of aptamers including RNA and DNA were introduced against viral hepatitis. Some of these aptamers can be utilized for early and precise diagnosis of hepatitis infections and other group selected as therapeutic tools against viral targets. Designing diagnostic and therapeutic platforms based on aptamer technology is a promising approach in viral infections. The obtained aptamers in the recent years showed obvious potential for use as diagnostic and therapeutic tools against viral hepatitis. Although some modifications to increase the biostability and half-life of aptamers are underway, it seems these molecules will be a favorable substitute for monoclonal antibody in near future.
Momtazi-borojeni, A., Momtazi-borojeni, A., Askari-khorasgani, O., Askari-khorasgani, O., Abdollahi, E., Abdollahi, E., Sadeghi, H., Sadeghi, H., Mortazaeinezhad, F., Mortazaeinezhad, F., Sahebkar, A., Sahebkar, A.
JAMS Journal of Acupuncture and Meridian Studies (20938152)(3)pp. 180-186
Varshosaz, J., Varshosaz, J., Khabbazian, E., Khabbazian, E., Hassanzadeh, F., Hassanzadeh, F., Sadeghi, H., Sadeghi, H., Rostami, M., Rostami, M., Taymouri, S., Taymouri, S.
Rezazadeh, M., Rezazadeh, M., Emami, J., Emami, J., Hassanzadeh, F., Hassanzadeh, F., Sadeghi, H., Sadeghi, H., Rostami, M., Rostami, M., Mohammadkhani, H., Mohammadkhani, H.
Mirian, M., Mirian, M., Taghizadeh, R., Taghizadeh, R., Khanahmad, H., Khanahmad, H., Salehi, M., Salehi, M., Jahanian-najafabadi, A., Jahanian-najafabadi, A., Sadeghi, H., Sadeghi, H., Kouhpayeh, S., Kouhpayeh, S.
Research In Pharmaceutical Sciences (17355362)(5)pp. 366-373
Hepatitis B virus (HBV) is considered as a global health concern and hepatitis B surface antigen (HBsAg) is the most immunogenic protein of HBV. The purpose of this study was to evaluate the expression of HBsAg on the cell surface of human embryonic kidney cell line (HEK293T). After transformation of expression vector pcDNA/HBsAg to E.coli TOP10F', plasmid was extracted and digested with BglII. Afterwards, the linearized vector was transfected to cells and treated with hygromycin B for 5 weeks to expand the resulted clonies. The permanent expression of HBsAg followed by flow cytometry uptill now about one year. Genomic DNA was extracted from transfected cells and the existence of HBsAg gene was assessed by PCR. Real-time RT-PCR was utilized to measure the expression at the RNA level and flow cytometery was carried out to assess protein expression. Insertion of HBsAg cDNA in HEK293T genome was confirmed by PCR. The results of real-time RT-PCR illustrated that each cell expresses 2275 copies of mRNA molecule. Flow cytometry showed that compared with negative control cells, 99.9% of transfected cells express HBsAg on their surface. In conclusion, stable expression of hepatitis B surface antigen on the membrane of HEK293T provides an accurate post-translational modification, proper structure, and native folding in contrast with purified protein from prokaryotic expression systems. Therefore, these exposing HBsAg cells are practical in therapeutic, pharmaceutical, and biological sets of research.
Rezazadeh, M., Rezazadeh, M., Emami, J., Emami, J., Hassanzadeh, F., Hassanzadeh, F., Sadeghi, H., Sadeghi, H., Minaiyan, M., Minaiyan, M., Mostafavi, A., Mostafavi, A., Rostami, M., Rostami, M., Lavasanifar, A., Lavasanifar, A.
Dormiani, K., Dormiani, K., Sadeghi, H.M.M., Sadeghi, H.M.M., Sadeghi, H., Sadeghi, H., Forouzanfar, M., Forouzanfar, M., Baharvand, H., Baharvand, H., Ghaedi, K., Ghaedi, K., Nasr-esfahani, M.H., Nasr-esfahani, M.H.
Cell Journal (Yakhteh) (22285806)(4)pp. 565-581
Objective: Induced pluripotent stem cells are generated from somatic cells by direct reprogramming. These reprogrammed pluripotent cells have different applications in biomedical fields such as regenerative medicine. Although viral vectors are widely used for efficient reprogramming, they have limited applications in the clinic due to the risk for immunogenicity and insertional mutagenesis. Accordingly, we designed and developed a small, non-integrating plasmid named pLENSO/Zeo as a 2A-mediated polycistronic expression vector. Materials and Methods: In this experimental study, we developed a single plasmid which includes a single expression cassette containing open reading frames of human LIN28, NANOG, SOX2 and OCT4 along with an EGFP reporter gene. Each reprogramming factor is separated by an intervening sequence that encodes a 2A self-processing peptide. The reprogramming cassette is located downstream of a CMV promoter. The vector is easily propagated in the E. coli GT115 strain through a CpG-depleted vector backbone. We evaluated the stability of the constructed vector bioinformatically, and its ability to stoichiometric expression of the reprogramming factors using quantitative molecular methods analysis after transient transfection into HEK293 cells. Results: In the present study, we developed a nonviral episomal vector named pLENSO/Zeo. Our results demonstrated the general structural stability of the plasmid DNA. This relatively small vector showed concomitant, high-level expression of the four reprogramming factors with similar titers, which are considered as the critical parameters for efficient and consistent reprogramming. Conclusion: According to our experimental results, this stable extrachromosomal plasmid expresses reliable amounts of four reprogramming factors simultaneously. Consequently, these promising results encouraged us to evaluate the capability of pLENSO/Zeo as a simple and feasible tool for generation of induced pluripotent stem cells from primary cells in the future.
Soleimani, M., Soleimani, M., Mahnam, K., Mahnam, K., Sadeghi, H.M.M., Sadeghi, H.M.M., Sadeghi, H., Sadeghi, H., Jahanian-najafabadi, A., Jahanian-najafabadi, A.
Research In Pharmaceutical Sciences (17355362)(3)pp. 187-199
p28 and NRC peptides are two anticancer peptides with various mechanisms have shown to be effective against breast cancer. Therefore, it seems that construction of a chimeric protein containing the two peptides might cause synergistic cytotoxic effects. However, since the two peptides bear opposite charges, production of a chimeric protein in which the two moieties do not intervene each other is difficult. In this study, our goal was to find a suitable peptide linker for the new chimeric protein in a manner that none of the peptides intervene the other's function. We selected some linkers with different characteristics and lengths and created a small library of the chimeric proteins harboring these linkers. Homology modeling and molecular dynamic simulation revealed that (PA)5 P and (EAAAK)3 linkers can separate the p28 and NRC peptides effectively. Thus, the chimeric protein linked with (PA)5 P or (EAAAK)3 linkers might show synergistic and stronger anticancer effects than the separate peptide moieties because they could exert their cytotoxic effects freely which is not influenced by the other part.
Rezazadeh, M., Rezazadeh, M., Emami, J., Emami, J., Mostafavi, A., Mostafavi, A., Rostami, M., Rostami, M., Hassanzadeh, F., Hassanzadeh, F., Sadeghi, H., Sadeghi, H., Minaiyan, M., Minaiyan, M., Lavasanifar, A., Lavasanifar, A.
Journal Of Pharmacy And Pharmaceutical Sciences (14821826)(5)pp. 647-660
Emami, J., Emami, J., Rezazadeh, M., Rezazadeh, M., Rostami, M., Rostami, M., Hassanzadeh, F., Hassanzadeh, F., Sadeghi, H., Sadeghi, H., Mostafavi, A., Mostafavi, A., Minaiyan, M., Minaiyan, M., Lavasanifar, A., Lavasanifar, A.
Drug Development and Industrial Pharmacy (03639045)(7)pp. 1137-1147
Mirian, M., Mirian, M., Behrooeian m., , Behrooeian m., , Ghanadian, M., Ghanadian, M., Dana, N., Dana, N., Sadeghi, H., Sadeghi, H.
Research In Pharmaceutical Sciences (17355362)(3)pp. 233-240
Angiogenesis, formation of new blood vessels, play an important role in some diseases such as cancer and its metastasis. Using angiogenesis inhibitors, therefore, is one of the ways for cancer treatment and prevention of metastasis. Medicinal plants have been shown to play a major role in the treatment of a variety of cancers. In this direction, cytotoxic and angiogenic effects of oleo gum resin extracts of Rhus coriaria, Pistacia vera and Pistacia khinjuk from Anacardiaceae family were studied. For IC50 values, cytotoxic effects of the plant extracts were evaluated at different concentrations (1, 10, 20, 40, 80,100 μg/ml) against human umbilical vein endothelial normal cell (HUVEC) and Y79 cell lines using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. In vitro tube formation on matrigel base was used to evaluate angiogenic effects in the presence of increasing concentrations (50, 100, 250 μg/ml) of the extracts. Vascular endothelium growth factor was used as angiogenesis stimulator. Gas chromatography results showed that α-pinene and β-pinene were the major essential oils constituents of all plant extracts. According to the MTT assay results, the R. coriaria resin extract was more cytotoxic than those of P. vera and P. khinjuk extracts (IC50, 9.1 ± 1.6 vs 9.8 ± 2.1 and 12.0 ± 1.9, respectively;P<0.05). Cytotoxic effects of all extracts against Y79 cell line was significantly higher than those of HUVEC used as a normal cell line (P<0.05). Tube formation assay also showed that extract of R. coriaria resin inhibited angiogenesis more significantly than other tested extracts (P<0.05). It could be concluded that R. coriaria resin extract possess cytotoxic effect and antiangiogenesis against cancer cells and as an anticancer natural product has a good potential for future studies.
Emami, J., Emami, J., Rezazadeh, M., Rezazadeh, M., Hassanzadeh, F., Hassanzadeh, F., Sadeghi, H., Sadeghi, H., Mostafavi, A., Mostafavi, A., Minaiyan, M., Minaiyan, M., Rostami, M., Rostami, M., Davies, N., Davies, N.
International Journal of Biological Macromolecules (01418130)pp. 29-40
Research In Pharmaceutical Sciences (17355362)(2)pp. 134-142
Multipotent mesenchymal stem cells (MSCs) are recently found to alter the tumor condition. However their exact role in tumor development is not yet fully unraveled. MSCs were established to perform many of their actions through paracrine effect. Thus investigation of MSC secretome interaction with tumor cells may provide important information for scientists who are attempting to apply stem cells in the treatment of the disease. In this study we investigated the effect of human Wharton's jelly derived MSC (WJ-MSCs) secretome on proliferation, apoptotic potential of A549 lung cancer cells, and their response to the chemotherapeutic agent doxorubicin. WJ-MSCs were isolated from human umbilical cord and then characterized according to the International Society for Cellular Therapy criteria and WJ-MSC secretome was collected. BrdU cell proliferation assay and Annexin V-PI staining were used for the evaluation of cytotoxic and proapoptotic effects of WJ-MSC secretome on A549 cells. WJ-MSC secretome neither induced proliferation of lung cancer cells nor affected the apoptotic potential of the tumor cells. We also studied the combinatorial effect of WJ-MSC secretome and the anticancer drug doxorubicinwhich showed no induction of drug resistance when A549 cells was treated with combination of WJ-MSC secretome and doxorubicin. Although MSCs did not show antitumor properties, our in vitro results showed that MSC secretome was not tumorigenic and also did not make lung cancer cells resistant to doxorubicin. Thus MSC secretome could be considered safe for other medical purposes such as cardiovascular, neurodegenerative, and autoimmune diseases which may exist or occur in cancer patients.
Dormiani, K., Dormiani, K., Sadeghi, H.M.M., Sadeghi, H.M.M., Sadeghi, H., Sadeghi, H., Ghaedi, K., Ghaedi, K., Forouzanfar, M., Forouzanfar, M., Baharvand, H., Baharvand, H., Nasr-esfahani, M.H., Nasr-esfahani, M.H.
Fattahi, A., Fattahi, A., Asgarshamsi, M., Asgarshamsi, M., Hassanzadeh, F., Hassanzadeh, F., Varshosaz, J., Varshosaz, J., Rostami, M., Rostami, M., Mirian, M., Mirian, M., Sadeghi, H., Sadeghi, H.
Journal of Materials Science: Materials in Medicine (15734838)(2)
Sadeghi, H., Sadeghi, H., Mohammadi, F., Mohammadi, F., Fazeli, H., Fazeli, H., Mirlohi, M., Mirlohi, M.
Iranian Journal Of Basic Medical Sciences (20083874)(10)pp. 815-819
Objective(s): Several beneficial effects have been attributed to the probiotic lactic acid bacteria. It was determined that lactobacilli can exert antiproliferative effects on the various cancer cell lines including colon cancer. Effects of lactic acid bacteria on colon cancer may vary from strain to strain and there is a need to find the new probiotic strains with tumor suppressing properties through in vitro studies.
Pilehrood, M., Pilehrood, M., Dilamian, M., Dilamian, M., Mirian, M., Mirian, M., Sadeghi, H., Sadeghi, H., Maleknia, L., Maleknia, L., Nousiainen, P., Nousiainen, P., Harlin, A., Harlin, A.
Varshosaz, J., Varshosaz, J., Hassanzadeh, F., Hassanzadeh, F., Sadeghi, H., Sadeghi, H., Banitalebi m., , Banitalebi m., , Rostami, M., Rostami, M., Nayebsadrian m., , Nayebsadrian m.,
Colloid and Polymer Science (0303402X)(10)pp. 2647-2662
Iranian Journal Of Basic Medical Sciences (20083874)16(11)pp. 1203-1208
Objective(s): Regarding the presence of many active biological constituents in Avicennia marina, the present investigation was carried out to study cytotoxic activity of crude methanol leave extract and column chromatographic fractions of A. marina against MDA-MB 231 cell line (human breast cancer cell) and HEK (Human embryonic kidney cell) line. Materials and Methods: The anticancer activity of crude methanol extract and sub-fractions were evaluated, using MTT assay. The induction of apoptosis was determined by analyzing DNA fragmentation in breast cancer cells treated with active fraction of crude methanol extract using agarose gel electrophoresis. To investigate molecular mechanism of apoptosis, gene expression levels of p53 and Bcl-2 were measured using quantitative real time PCR. Results: Fraction 10 was the most active fraction and was detected with HPLC as luteolin. The 50% cell cytotoxic concentration (CC50) of crude methanol extract and luteolin was 250 and 28 μg/ml, respectively. This fraction was found to be an apoptotic agent against MDA-MB 231 cells, which leads to causing DNA fragmentation. The mRNA expression level of Bcl-2 and p53 was significantly decreased and increased respectively in cancer cells treated by luteolin. Conclusion: The results suggested that Luteolin isolated from Avicennia marina could probably induce apoptosis on breast cancer cell line by the regulation of p53 and Bcl-2 pathways.
Sadeghi, H., Sadeghi, H., Karimimanesh, A., Karimimanesh, A., Varshosaz, J., Varshosaz, J.
Journal of Isfahan Medical School (10277595)(217)pp. 2169-2177
Background: Aromatase inhibitors such as letrozole inhibit the synthesis of estrogens and help in the treatment of estrogen-dependent breast cancer. Using letrozole-loaded lipid nanocapsules (LNCs) as site directed drugs may help in the treatment of these tumors. Methods: LNCs were prepared by triglycerides, lecithin and polyethylene glycol in water phase inversion method. Prepared LNCs had particle size of less than 100 nm and were characterized with their particle size, zeta potential, and polydispersity index by Malvern Zeta-Sizer. LNCs were tested against MCF-7 cells (human breast adenocarcinoma cell line). They were compared with free letrozole in terms of cytotoxicity using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Findings: S17O20L1.5W3.5, with particle size of 100 ± 3.4 nm, zeta potential of -3.6 ± 0.4, polydispersity of 0.283 ± 0.08, and loading efficiency of 96.6 ± 1.5, was the optimum formulation. Cytotoxicity of the prepared LNCs was 80% of that of free letrozole. This effect was concentrationdependent, i.e. cell survivals in stock solutions of 50 μg/ml, 10 μg/ml, and 5 μg/ml were 20%, 40%, and 60%, respectively. Conclusion: LNCS can be used as a selective formulation against cancer cells. Their cytotoxic effect is comparable to free letrozole.
Varshosaz, J., Varshosaz, J., Hassanzadeh, F., Hassanzadeh, F., Sadeghi, H., Sadeghi, H., Ghelich khan, Z., Ghelich khan, Z.
Journal of Isfahan Medical School (10277595)(218)pp. 2206-2216
Background: Anthracyclines are used to treat different types of cancer including hepatocellular carcinoma. However, they have various side effects such as cardiotoxicity. Designing a drug delivery system which targets retinoic acid receptors in hepatocellular carcinoma can reduce these side effects. Methods: Chitosan/retinoic acid/albumin nanoparticles were prepared using a coacervation method. Nanoparticles which were optimized according to their particle size, zeta potential, polydispersity index, loading efficiency and release of doxorubicin, were used for further tests of cytotoxicity on HepG2 cells [by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] and cellular uptake tests (by fluorescent microscopy). Findings: The optimum targeted nanoparticles (with particle size of 286 ± 50.0 nm, zeta potential of 30.5 ± 3.6 mv, polydispersity index of 0.50 ± 0.06, loading efficiency of 43.6 ± 13.5%, and drug release of 56.17 ± 6.00%) in a concentration of 0.5 mg/ml were two to three times more cytotoxic than non-targeted nanoparticles and free drug. Their cellular uptake was also more. Conclusion: Chitosan/retinoic acid/albumin targeted nanoparticles loaded with doxorubicin could affect HepG2 cells more effectively than non-targeted nanoparticles and free drug.
Sadeghi, H., Sadeghi, H., Alavi, M., Alavi, M., Asghari, G., Asghari, G., Mirian, M., Mirian, M.
Journal of Isfahan Medical School (10277595)(253)pp. 1508-1517
Background: Taxus baccata is known as a source of anticancer drug called taxol. This study was performed to confirm the consistency of results obtained by extraction of Taxanes by optimal solvent system using biological assessment. Methods: Three cell lines including MDA-MB-468, Hela and K562 were cultured in PRMI-1640 medium with 10% fetal bovine serum. Powder of aerial parts of Taxus baccata was extracted using 8 different solvent by maceration method. High performance thin layer chromatography (HPTLC) was used to standardize the extracts according to taxol content. Cytotoxicity of different concentrations of extracts (acetone 20, 50 and 100%, ethanol 20, 50 and 100%, acetone dichloromethane (1-1), and pure methanol) was evaluated against cultured cells, using MTT assay. Findings: Acetone-dichloromrthane (1-1) then pure acetone extract were the most cytotoxic extracts. Meanwhile, between the three cell lines tested, the highest cytotoxic effect of the extracts was observed on K562 cells. Conclusion: The results of this study showed that among evaluated extracts, more cytotoxic effect wsa in acetone-dichloromethane (1-1) followed by pure acetone extract. Analysis of extracts showed that the highest amount of taxans has been extracted by acetone-dichloromethane or pure acetone solvent system. We can conclude that there is a direct correlation between the cytotoxic effect and amount of taxans.
Sadeghi, H., Sadeghi, H., Aliasgharluo m., , Aliasgharluo m., , Fattahi, A., Fattahi, A., Mirian, M., Mirian, M., Ghanadian, M., Ghanadian, M.
Research In Pharmaceutical Sciences (17355362)(4)pp. 299-304
Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) developed as a selective inhibitor of cyclooxygenase-2 (COX-2) for the treatment of rheumatoid arthritis disease. Recently some other mechanisms have been identified for anti cancer activity of these agents including induction of apoptosis, inhibition of tumor vascularization, stimulation of antitumor immune responses and inhibition of cellular protein synthesis. The cytotoxic effects of four synthesisized analogues of celecoxib (coded as D, E, F and G) were evaluated against Hela , MDA-MB-231, A-2780-s and HT-29 cancer cells, using MTT assay; Also their induction of apoptosis using DNA fragmentation analysis were studied. MTT assay showed that cell survival percent of COX-2 positive cell lines (HT-29, MDA-MB-231 and Hela; p≤0.05) were decreased significantly after exposure to the tested COX-2 inhibitors while little effect was observed on the COX-2 negative cell line (A-2780-s). Results also showed that A-2780-s and Hela were the most resistant and the most sensitive cell lines to these compounds, respectively. Moreover, in DNA fragmentation assay, induction of apoptosis was confirmed by electrophoretic pattern of separated DNA fragments in Hela cell line. Compounds E and G in comparison with D and F exerted more cytotoxic effect on COX-2 positive cell lines (Hela, HT-29 and MDA-MB-231). This could be due to the hydrophobic substituent (Cl, CH3) located at the para position of phenyl ring leading to more lipophilicity and cell uptake. In addition, these COX-2 inhibitors induced apoptosis on Hela cell-line, which could be considered as one of the cytotoxic mechanisms of these compounds as potential anti cancer agents.
Research In Pharmaceutical Sciences (17355362)(3)pp. 185-195
range of iron bidentae ligands containing the chelating moiety 3-hydroxypyridin-4-ones (HPOs) have been synthesized via a single or a three-step synthetic pathway. In the single-step reaction, maltol was directly reacted by suitable primary amine and in the second synthetic method; benzylated maltol was reacted with related amines to give 1-substuted-2-methyl-3- benzyloxypyridin-4-one derivatives. Finally, removal of the benzyl group under acidic conditions was performed by catalytic hydrogenation to yield the favored bidentate chelators as HCl salt. The partition coefficient of the free ligands and their iron (III) complexes between an aqueous phase buffered at pH 7.4 and 1-octanol were also determined. The cytotoxic effects of these iron chelators against HeLa and K562 cell lines were evaluated using MTT assay and the results showed that cytotoxicity was closely related to the lipophilicity of compounds so that the most lipophilic compound (4g) revealed the highest activity and compound 4e as a more hydrophilic agent (Kpart; 0.05) showed the lowest cytotoxic effect.
The aim of this study was to prepare stealth solid lipid nanoparticles (SLN S) of risperidone, for controlled delivery through the intravenous (i.v.) route to reduce the frequency of administration, dose and adverse effects during the short-term management of manifestation of psychotic disorders. Stealth SLNs were prepared by emulsification-solvent diffusion and sonication method by adding acetone/ethanol containing drug, lipid and stabilizer to aqueous phase, containing surfactant, under homogenization. The effect of lipid type, lipid percentage, stabilizer type and stabilizer percentage were evaluated on the particle size, zeta potential, drug loading efficiency and drug release for optimization of SLNs. Dialysis bag membrane was used to determine drug release, the Rose Bengal binding constant for surface hydrophobicity and serum protein adsorption. The cytotoxicity of SLNs on macrophages and red blood cells were also assessed in order to evaluate the impact of surface modifications on toxicity of the different formulations. The optimized formulation was composed of 0.05% stearyl alcohol (relative to the total volume of dispersion) and 25% PEG 40 stearate (relative to the weight of lipid) using a homogenization speed of 1000 rpm and 4 minutes sonication. The results showed that the in vitro specifications of stealth SLN S of risperidone are suitable for i.v. administration.
Asghari, G., Asghari, G., Mostajeran a., A., Mostajeran a., A., Sadeghi, H., Sadeghi, H., Nakhai a., , Nakhai a.,
Journal Of Medicinal Plants (27172058)(SUPPL. 8)pp. 74-82
Background: Taxol is an effective anticancer drug used widely in the treatment of a variety of cancers, including carcinomas of the ovary and breast. Taxol was originally isolated from the bark of Pacific yew tree Taxus bervifolia L.. Increasing demand for taxol and resource paucity of Pacific yew trees has driven several research groups to advance the taxol production methodologies, including using elicitors in suspension cultures of Taxus spp. cells. Elicitors are often used to improve taxol production incultured cells. Objectives: The aim of this work is to inject the Taxus baccata tree a single and combination of salaicylic acid and silver nitrate to improve taxol production. Methods: Salicylic acid and silver nitrate solution in different concentration were prepared and injected to tree. After 30 days of elicitors' injection the leave for aerial parts of the tree was collected. The dried powder of the leave was extracted by maceration with ethanol 96%. To detect taxol, a high-performance liquid chromatography (HPLC) system was employed. Results: The treated cells with salaicylic acid and silver nitrate displayed a significant decrease in taxol. Increasing concentration of elicitors resulted lower content of taxol. Conclusion: The injection of single and combine of salaicylic acid and silver nitrate on the Taxus baccata tree showed negative effect on taxol production. It seems that more researchs need to be done in order to understand the acting mechanisms of used elicitors.
Nayebsadrian m., , Nayebsadrian m., , Varshosaz, J., Varshosaz, J., Hassanzadeh, F., Hassanzadeh, F., Sadeghi, H., Sadeghi, H., Banitalebi m., , Banitalebi m., , Rostami, M., Rostami, M.
Fassihi, A., Fassihi, A., Mahnam, K., Mahnam, K., Moeinifard, B., Moeinifard, B., Bahmanziari, M., Bahmanziari, M., Sadeghi, H., Sadeghi, H., Zarghi, A., Zarghi, A., Sabet, R., Sabet, R., Salimi, M., Salimi, M., Mansourian, M., Mansourian, M.
Medicinal Chemistry Research (10542523)(10)pp. 2749-2761
Objectives: The medicinal plant of Avicennia marina has been used widely in traditional medicine for treatment of skin disease and rheumatoid in Iran. The present investigation was carried out to study the anticancer effects of different crude extracts of A. marina's leaves against breast cancer cell line (MDA-MB 231). Methods: MDA-MB 231 and L929 healthy cells were separately cultured in RPMI-1640 medium completed with 10% fetal calf serum and penicillin / streptomycin (50 IU/ml and 50 μg/ ml respectively). Collected leaves were dried and powdered, then were soaked in five solvents with different lipophilicity. The cytotoxic effects of different concentration of crude extracts on cultured cells were measured using the MTT assay. Chromosomal DNA was extracted, isolated and resolved using agarose gel electrophoresis. Result: Methanolic extract exerted higher anti-cancer activity on human breast cancer cells compared with other extracts. IC50 of the methanolic extract was measured at 480 μg/ml. Furthermore, the methanol extract induced a significant growth inhibition and apoptosis in a dose-dependent manner on MDA-MB 231 as human cancer cells but there was no significant effect against L929 as normal cells. Methanolic extract showed time dependent growth inhibition effect so that, after 24, 48, and 72 h treatment cell growth was inhibited by 40%, 44%, and 59%, respectively. Conclusion: The present results suggest that valuable cytotoxic components could be isolated from this plant by partitioning methanol crude extract. Further investigations are underway in this regard.
A series of 3-hydroxypyridin-4-one derivatives (HPOs) were synthesized and their partition coefficient values (Kpart) were determined. The cytotoxic effects of these iron chelators against Hela cancer cells were also evaluated. The IC50 of HPOs was determined using MTT assay. Among these ligands, compound 4e (Kpart=5.02) with an IC50 of 30 μM and 4f (Kpart=0.1) with an IC50 of 700 μM showed the lowest and highest IC50s, respectively. In conclusion, the introduction of a more hydrophobic functional group (such as butyl in compound 4e) on the nitrogen of pyridinone ring resulted in higher cytotoxic activity of ligands.
Mirian, M., Mirian, M., Zarghi, A., Zarghi, A., Sadeghi, S., Sadeghi, S., Tabaraki, P., Tabaraki, P., Tavallaee, M., Tavallaee, M., Dadrass, O., Dadrass, O., Sadeghi, H., Sadeghi, H.
Iranian Journal Of Pharmaceutical Research (17350328)(4)pp. 741-748
Panjehpour m., , Panjehpour m., , Movahedian a., A., Movahedian a., A., Sadeghi, H., Sadeghi, H., Eghbali b., , Eghbali b., , Yegdaneh, A., Yegdaneh, A.
(3)pp. 111-116
The metabolically active tumor cells may be characterized by a pronounced adenosine release that regulates the growth and development of the tumor. Consequently, the expression pattern of defined receptor subtypes will be an important determinant for specific effects of adenosine on the control of tumor cell growth. In recent studies, the expression profile, signal transduction, molecular function and cell growth modulation of adenosine receptors in the human breast cancer cell lines has been reported. To investigate the possible roles of adenosine receptors in other types of human cancers, in this study, we characterized the expression profile of adenosine receptors in two different human cancer cell lines: prostate carcinoma cell line (Du-145) and lung adenocarcinoma cell line (Calu-6). Our purpose is to test the hypothesis that diverse human cancer cell lines, according to their adenosine receptor subclass status, would show differential growth modulation. Methods: RNA was extracted and reverse transcribed to cDNA. PCR primers were synthesized from human adenosine receptor cDNA sequences. PCR was performed under optimized condition for each receptor subtype. The PCR products were separated on agarose gels. Results: All two human cancer cell lines studied contained detectable amounts of mRNA specific for adenosine receptor except A3 subtypes. Conclusion: In conclusion the differentially expressed genes identified in this study might provide new insights into the possible roles of adenosine receptors on cell growth and development.
Palizaban, A., Palizaban, A., Sadeghi, H., Sadeghi, H., Abdollahpour f., , Abdollahpour f.,
Research In Pharmaceutical Sciences (17355362)(2)pp. 119-125
The anti-cancer activity of metal ions in the lanthanide group is being considered recently. It has been reported that cerium salts might stimulate the metabolism and therefore, produce anti-cancer effects. However, little is known about the effects of protein-cerium complex in controlling cancer cell growth. The aim of the present study was to elucidate the possible pathways for the cytotoxic effect of cerium in the presence of apo-transferrin on two cancer cell lines (Hela and MCF-7), that express transferrin receptors 3-4 fold higher than normal cells. The effect of different concentrations of cerium (0.1, 1, 10, 100 μM) in the presence and absence of transferrin for 48 h and 72 h incubation periods (37°C, 5% CO2 and 95 humidity) was studied using the MTT assay. The results showed that cerium has a cell-proliferation inhibitory activity which is significantly increased by transferrin protein. Compared with the direct treatment of cancer cells with cerium, the presence of transferrin assisted inhibition of cell proliferation by 20% and 40% in Hela and MCF-7 cells, respectively. Though apo-transferrin could lightly induce cell growth particularly in MCF-7 cells by itself, this phenomenon could not overcome the cerium-protein cell-proliferation inhibition activity. In conclusion, our results indicate that at a certain concentration, the cerium compounds could be possibly involved in the control of cell proliferation and inhibiting the growth of cancer cells.
Sadeghi, H., Sadeghi, H., Asghari, G., Asghari, G., Mostafavi, A., Mostafavi, A., Esmaeili a., , Esmaeili a.,
Daru Journal Of Pharmaceutical Sciences (15608115)(3)pp. 192-198
Background and the purpose of the study: Taxol, a natural antitumor agent, was first isolated from the extract of the bark of Taxus brevifolia Nutt., which is potentially a limited source for Taxol. In the search of an alternative source, optimum and cost benefit extracting solvents, various solvents with different percentage were utilized to extract Taxol from needles of Taxus baccata. Methods: One g of the dried needles of Taxus baccata, collected from Torkaman and Noor cities of Iran, was extracted with pure ethanol or acetone and 50% and 20% of ethanol or acetone in water. Solvents were evaporated to dryness and the residues were dissolved in 5 ml of methanol and filtered. To one ml of the filtrate was added 50 μl of cinamyl acetate as the internal standard and 20 μl of the resulting solution was subjected to the HPLC to determine the extraction efficiencies of tested solvents. Five μl of filtrate was also subjected to the LC-MS using water/acetonitrile (10/90) as mobile phase and applying positive electrospray ionization (ESI) to identify the authenticity of Taxol. Results: Results of this study indicated that Taxol extraction efficiency was enhanced as the percentage of ethanol or acetone was increased. HPLC analysis showed that Taxol could be quantified by UV detection using standard curve. The standard curve covering the concentration ranges of 7.8 - 500 μg/ml was linear (r2= 0.9992) and CV% ranged from 0.52 to 15.36. LC-MS analysis using ESI in positive-ion mode confirmed the authenticity of Taxol (m/z 854; M+H), as well as some adduct ions such as M+Na (m/z 876), M+K (m/z 892) and M+CH3CN+H2O (m/z 913). Conclusions: The results suggest that 100% acetone is the best solvent for the extraction of Taxol from Taxus baccata needles.
Breast cancer is the most prevalent type of cancer in pre- and postmenopausal women in most Western countries. In the treatment of metastatic breast cancer, doxorubicin has the broadest spectrum of antitumor activity of any drug currently available but produces a dose-dependent cardiomyopathy that limits its clinical usefulness. The aim of this research project was to target the affected tissues, which contain estrogen receptors (ERs). Initially, a series of estrogen derivatives with side chains linked at the 3- and 17-positions of estrone were synthesized, and then novel anticancer prodrugs were obtained from these by further linking these compounds to doxorubicin by means of various alkyl spacer groups. These estrogenic prodrugs were designed to target tumor cells containing ERs, found in human breast cancer cells, and to release the active anticancer moiety when internalized. The estrogenic prodrugs were then biologically evaluated using in vitro chemosensitivity assays against human ER-positive (MCF-7) and ER-negative (MCF-7ADR and MT-1) breast tumor cells and a leukemia (K562) cell line. The results showed that estrone derivatives with substituted aminoalcohol side chains of various lengths (2-6 carbons) linked to the 17-position of estrone were mostly inactive. Estronedoxorubicin prodrugs containing doxorubicin at the 3-position of estrone (CCRL 1042 and CCRL 1036) were relatively inactive and nonselective against all cell lines tested. However, when doxorubicin was linked to the 17-position of estrone, these prodrugs had at least an order greater activity than their 3-linked counterparts. Using a short aminoxyspacer group (2 carbons) at this position produced CCRL 1035, which had a lower activity against all cell lines tested compared to doxorubicin. In contrast, the prodrug incorporating doxorubicin at the 17-position of estrone via a long spacer group (12 carbons, CCRL 1033) was both potent and selective against ER-positive cells MCF-7. These studies have shown that linking doxorubicin to the 17-position of estrone via a long alkyl spacer group conferred selectivity of cytotoxic action against ER-positive breast cancer tumor cells.
Daru Journal Of Pharmaceutical Sciences (15608115)(3)pp. 82-87
Majority of the currently available anticancer drugs are designed to have selective toxicity to rapidly dividing cells. Among these agents the focus of many studies are compounds obtained from natural products with high therapeutic index. In this study the cytotoxicity of HESA-A, a marine compound, on cancer and normal cells was evaluated. HESA-A was prepared in normal saline as a stock solution (0.8 mg/ml, pH=7.4), sterilized and further diluted to final concentrations of 0.4, 0.2, 0.1 and 0.05 mg/ml. Cells (MDA-MB-468, Hep-2, Hela as cancer cells; L929 and McCoy as normal cells) were grown in completed RPMI 1640 and seeded in 96 well micro plates at a concentration of 1-5 × 104 cells/ml. After incubation for 24 h, different concentrations of HESA-A were added and cells were further incubated for 72 h. Using MTT assay, percent cell survival was determined by ELISA at 540 nm. Doxorubicin was used as a positive control (20 μg /ml). HESA-A (0.4 mg/ml) reduced the number of viable MDA-MB-468 and Hela cells to less than 50%. For Hep-2 cells the IC 50 was 0.8 mg/ml. In normal cells IC50 could not be obtained at any given concentrations. These results suggest that HESA-A in therapeutic doses and in a concentration dependent manner inhibits the growth of cancer cells more selectively than normal cells.
