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Abstract Papaver genus, commonly known as popies, is a valuable source of alkaloids used in medicine, including papaverine, morphine, codeine, and thebaine. We isolated six endophytic fungal isolates producing morphinan alkaloids from four Papaver species growing in Kurdistan Province, Iran. To do this, a 1:1 mixture of methanol and chloroform was used to extract fungal cultures. The contents of morphinan alkaloids in the extracts were subsequently determined using phase high-performance liquid chromatography. Among the morphinan alkaloid-producing fungal isolates, IRAN 4653C had the highest yield giving 23.06 (mg/g) morphine and 2.03 (mg/g) codeine when grown in potato dextrose liquid medium. The identity of this isolate was examined and recognized as a new fungal species named as Pithoascus kurdistanesis sp. nov. based on multi-gene phylogenetic analyses of ITS, TEF-1α, and TUB2 sequences data and morphological features. The morphinan-producing endophytic fungus and the isolated Pithoascus species from Papaver are being reported for the first time. Accordingly, this fungus shows promise as a new source of valuable compounds which is illustrated and introduced here as a new Microascaceae member belonging to Pithoascus from Kurdistan Province, Iran. Moreover, the morphinan productivity of P. kurdistanesis was further validated by gas chromatography-mass spectrometry (GC–MS).

Abstract Stevia (Stevia rebaudiana Bertoni) is a natural sweetener plant that accumulates highly sweet steviol glycosides (SGs) especially in leaves. Stevia is native to humid areas and does not have a high tolerance to drought which is the most serious abiotic stress restricting its production worldwide. C2H2 zinc finger proteins (C2H2-ZFPs) are a group of well-known transcription factors that involves in various developmental, physiological and biochemical activities as well as in response to abiotic stresses. Here we analyzed C2H2-ZFP gene family in stevia and identified a total of 185 putative SrC2H2-ZF proteins from the genome sequence of S. rebaudiana. We further characterized the identified C2H2-ZF domains and their organization, additional domains and motifs and analyzed their physicochemical properties, localization and gene expression patterns. The cis-element analysis suggested multiple roles of SrC2H2-ZFPs in response to light, phytohormone, and abiotic stresses. In silico analysis revealed that the stevia C2H2-ZFP genes are interactively expressed in different tissues and developmental stages and some C2H2-ZFP genes are involved in response to drought stress. This study provides a background for future exploration of the functional, and regulatory aspects of the C2H2-ZFP gene family in S. rebaudiana.

Thyme species are a good source of thymol and carvacrol, which play a key role in controlling diseases. For the first time, the expression patterns of γ-terpinene synthase (TPS2), CYP71D178, and CYP71D180 genes and the amount of phenolics compounds were evaluated in T. migricus and T. daenensis after different methyl jasmonate (MeJA) treatments. The highest thymol and carvacrol contents were observed in T. migricus (86.27%) and T. daenensis (17.87%) at MeJA 100 µM, which was consistent with the expression patterns of the three investigated genes. All species treated showed high total phenolic and flavonoid content compared to control plants for which the highest amounts were observed in T. vulgaris treated with 100 µM and 10 µM MeJA. Furthermore, in the 100 µM MeJA treatment, the relative expression of TPS2 and CYP71D178 in T. migricus increased 7.47 and 9.86-fold compared with the control, respectively. The highest level of CYP71D180 transcripts (5.15-fold) was also observed for T. daenensis treated. This finding highlights the notion that thymol was known as the dominant component of the essential oil rather than carvacrol in diffident thyme species. This implies that MeJA at different concentrations influenced metabolic pathways and induced expression changes, resulting in a rise in essential oil levels.

The sesquiterpene costunolide has a broad range of biological activities and is the parent compound for many other biologically active sesquiterpenes such as parthenolide. Two enzymes of the pathway leading to costunolide have been previously characterized: germacrene A synthase (GAS) and germacrene A oxidase (GAO), which together catalyse the biosynthesis of germacra-1(10),4,11(13)-trien-12-oic acid. However, the gene responsible for the last step toward costunolide has not been characterized until now. Here we show that chicory costunolide synthase (CiCOS), CYP71BL3, can catalyse the oxidation of germacra-1(10),4,11(13)-trien-12-oic acid to yield costunolide. Co-expression of feverfew GAS (TpGAS), chicory GAO (CiGAO), and chicory COS (CiCOS) in yeast resulted in the biosynthesis of costunolide. The catalytic activity of TpGAS, CiGAO and CiCOS was also verified in planta by transient expression in Nicotiana benthamiana. Mitochondrial targeting of TpGAS resulted in a significant increase in the production of germacrene A compared with the native cytosolic targeting. When the N. benthamiana leaves were co-infiltrated with TpGAS and CiGAO, germacrene A almost completely disappeared as a result of the presence of CiGAO. Transient expression of TpGAS, CiGAO and CiCOS in N. benthamiana leaves resulted in costunolide production of up to 60 ng.g(-1) FW. In addition, two new compounds were formed that were identified as costunolide-glutathione and costunolide-cysteine conjugates.

The use of nanotechnology can reduce the challenges facing the use of herbal compounds in the fight against infectious agents. The aim of the present research is to produce nano niosomes containing Bunium persicum essential oil with high efficiency in the temperature and acidity of the living environment of Trichomonas vaginalis parasite and to investigate its toxicity on this parasite. First, Essential oil compounds were identified using GC-Mass. Then six niosomal formulations were made using Tween 40, 60, and 80 and cholesterol by thin film method. Three formulations that have more suitable particle size, zeta potential, and essential oil release and encapsulation efficiency were selected by MTT method to investigate the toxicity on HFF (Human foreskin fibroblasts) cell line. The formulation with lower toxicity was optimized using DSPE-mPEG(2000) polymer. Encapsulation efficiency, particle size, zeta potential, release of essential oil (in temperature and acidity similar to Trichomonas vaginalis living environment), particle morphology and toxicity of optimal formulation (on HFF and Trichomonas vaginalis) were investigated. At the end, the stability of the optimized nanoparticles was studied for 120 days. 12 chemical compounds including γ-Terpinene, Cuminic aldehyde and Para-cymene were identified Bunium persicum essential oil. The optimized formulation has a particle size of 159.73 nm, a zeta potential of −25.1 mV and an encapsulation efficiency of 63.11 %, which has a slow and continuous release at the similar temperature and acidity as Trichomonas vaginalis. Niosomal nanoparticles have a spherical shape and a smooth surface and have little toxicity on the HFF cell line. Also, the toxicity of nano niosomes containing essential oil on Trichomonas vaginalis is higher than free essential oil in all concentrations. The optimized niosomal nanoparticles have good stability because their physicochemical properties have changed very little during 120 days. In conclusion optimized Niosomal formulation containing Bunium persicum essential oil compared to free essential oil can have a higher efficiency to deal with Trichomonas parasite in laboratory conditions.

Background: Trichomonas vaginalis, a parasitic flagellated protozoan, is one of the main non-viral sexually transmitted diseases worldwide. Treatment options for trichomoniasis are limited to nitroimidazole compounds. However, resistance to these drugs has been reported, which requires the development of new anti-Trichomonas agents that confer suitable efficacy and less toxicity. Methods: In the present work, we assessed the effectiveness of the liposomal system containing essential oils of Bunium persicum and Trachyspermum ammi against T. vaginalis in vitro. The chemical composition of B. persicum and T. ammi were analyzed using gas chromatography-mass spectrometry (GC–MS). Liposomal vesicles were prepared with phosphatidylcholine) 70%) and cholesterol)30%) using the thin-film method. The essential oils of B. persicum and T. ammi were loaded into the liposomes using the inactive loading method. Liposomal vesicles were made for two plants separately. Their physicochemical features were tested using Zeta-Sizer, AFM and SEM. The anti-Trichomonas activity was determined after 12 and 24 h of parasite cultures in TYI-S-33 medium. Results: After 12 and 24 h of administration, the IC50 of the B. persicum essential oil nano-liposomes induced 14.41 μg/mL and 45.19 μg/mL, respectively. The IC50 of T. ammi essential oil nano-liposomes induced 8.08 μg/mL and 25.81 μg/mL, respectively. Conclusions: These data suggested that nano-liposomes of the essential oils of B. persicum and T. ammi may be a promising alternative to current treatments for Trichomonas infection.

Introdution: Common cancer treatment methods have many side effects. Therefore, the use of new methods for drug delivery to cancer cells is necessary. In the present study, nano formulations of lipid carriers containing doxorubicin have been synthesized and its physicochemical properties have been investigated. Methods: The present study was an experimental study. The liposomal systems were synthesized by the method of thin-film hydration and using Tween-20, cholesterol and soybean phosphatidylcholine. After loading Doxorubicin drug into the liposomes, physiochemical properties of nano-carriers were determined from the perspective of encapsulation efficiency, drug release profile under healthy and cancerous cells condition, hydrodynamic diameter, zeta potential, morphology and IR spectra. Results: The liposomal system had 132.9 nm in diameter, the encapsulation 93.74% and -38.73±0.18mV zeta potential. The maximum release of drug from the nano-carrier under conditions 37°C, pH=7.4 and 42°C, pH=5.4 and 37°C, pH=5.4 after 72 hours was 36.54% and 74.18% and 55.9% respectively. SEM and IR assessments revealed spherical morphology and the absence of chemical interaction between nano-carrier and drug. Conclusion: The result of this research indicates that the liposomal system, having the appropriate physiochemical properties, has not changed the chemical nature of drug and thus can be a suitable and semi-targeted carrier for doxorubicin.

Introdution: Doxorubicin is one of the most commonly used drugs in chemotherapy with many side effects; this fact has limited its use. In the present study, based on the knowledge of pharmaceutical nanocarriers, various formulations of the niosomal form of this drug were synthesized and surface optimizations were applied to the final selected formulation. Methods: The present study was an experimental study. Various formulations of niosomal systems were synthesized by the method of thin-film hydration and using Tween60 and cholesterol. Doxorubicin was encapsulated through niosome inactively. In the following, optimizations were made based on choosing two formulas out of six experimentally, then the effects of adding Tween20, DSPE-mPEG(2000) polymer and cationic phospholipid of DOTAP (respectively) was investigated. Then, physiochemical properties of nanocarriers were determined from the perspective of encapsulation efficiency, drug release profile under healthy and cancerous cells condition, hydrodynamic diameter, Poly Dispersity Index, zeta potential, morphology and Infrared spectroscopy(IR) spectrum. To plot the graphs and express the data Origin and Excel software were used, respectively. Results: The optimized final niosome formula had 98.59 nm in diameter, 91.8±0.43, -3.5mV zeta potential and 0.196 PDI. The maximum release of drug from the nanocarrier under conditions of healthy and cancerous cells (37°C, pH=7.4 and 42°C, pH=5.4) after 48 hours was 62.3% and 76.5% respectively. Field Emission Scanning Electron Microscope and IR assessments revealed spherical morphology and the absence of chemical interaction between nanocarrier and drug. Conclusion: The findings of this study prove this drug carrier to be semi-targeting. It also shows that niosome by specializing the drug delivery increases the effectiveness of drug and the life quality of patient while reducing the side effects, all without any change in the chemical nature of the drug.

Backgrounds and Aim: One of the effective strategies for targeting chemotherapy in the treatment of cancer is the use of lipid nano-carriers. In this study, an optimal formulation of niosomal drug containing doxorubicin has been developed to better fight cancer cells. Material and Methods: Niosomal vesicles were prepared using phosphatidylcholine (22%), span60 (52/5%), cholesterol (22/5%) and DSPE-PEG2000 (5%) by thin-film method. Doxorubicin were loaded into the niosomes using inactive loading method. Their physico-chemical features were assayed using Zeta-Sizer, FTIR and SEM, and drug release amount was calculated at 37° C and 44° C. At the end, the toxicity of the nano drug carrier system was measured on the KG-1 cell line of the bone marrow cancer by MTT method. Results: Niosomal vesicles containing Doxorubicin showed the size of 160.37±65.2 nm, 94.18% drug encapsulation efficiency -58.11± 1.24 mV of zeta potential and polydispersity index (PDI) of 0.234±0.02 The prepared niosomal system presented drug controlled release and FTIR investigation showed almost no interaction between nano-carrier containing drug and the drug itself. As well, morphological examination of nano-carriers using SEM microscopy revealed that they have spherical structures. Also, cellular studies showed that drug toxicity was higher in encapsulated conditions compared to non-encapsulated conditions. Conclusion:The results of this study, meanwhile confirming the proper physicochemical characteristics of the system and being Slow-release system indicate that this nano-carrier anionic increases the toxicity of the drug for the KG-1 cell line of the bone marrow, thus, this niosomal nano-carrier can be a suitable carrier for drug delivery to cancer cells.

Introdution: Chemotherapy is one of most effective methods to fight metastatic tumors. Its non- targeting has many side effects. The aim of this study was to investigate various formulations of Lipo-Niosomal hybrid system to achieve an optimized and targeted formulation to provide proper function as a complementary drug in cancer chemotherapy. Methods: The present study was an experimental study. Five Lipo-Niosome systems with different formulations containing DPPC, Cholesterol, and Span60 were synthesized using thin-film method. Three formulations were chosen based on the entrapped efficiency of curcumin and their release profile was investigated in order to choose the final formula. In the following, the final formula was optimized by DSPE-mPEG(2000) and after calculating, the curcumin release profile in simulated environment of healthy and cancerous cells; physiochemical characteristics of the final formula determined by ZetaSizer, FTIR and SEM instruments. Results: Final formulation of curcumin PEGylated lipo-niosome had 147.5 nm size, 98.12%±1.85 entrapment, -8.90 mV zeta potential, and 0.176 of PDI. The maximum release of the drug for this nanosystem in an environment similar to healthy cells was 19.02% and 24.88% in cancerous cells. FTIR and SEM investigations show drug and nanocarrier had no chemical interaction leading to change the functional groups and its particles have a spherical morphology. Conclusion: The findings of this study along with confirming the system to be semi-targeting, shows that carrier released entrapped drug with continuous and controlled rate without any change in chemical nature of the drug. It appears the nanoscale size and the low anionic charge of the system is an indication of its high cellular uptake.

Introduction: Herbal Compound and their essential oils possess high antimicrobial, antioxidant, and anti-tumor properties, but conventional prescribing of them faces serious challenges. Liposomal nano-carrier is one of the common pharmaceutical strategies to overcome these challenges. In this study, slow-released liposomal system containing Mentha piperita’s essential oil was prepared in order to improve its antimicrobial, antioxidant and antitumor properties. Methods: Liposomal vesicles were prepared using phosphatidylcholine (80%) and cholesterol (20%) by thin-film method. Mentha piperita’s essential oil were loaded into the liposomes using inactive loading method. Their physico-chemical features were assayed using Zeta-Sizer, FTIR and SEM, and at the end, the essential oil release amount was calculated at 37° C. Results: Liposomal vesicles containing Mentha piperita’s essential oil showed the size of 247 13.39 nm, 61.38% ± 2.7 essential oil encapsulation efficiency, -34.54 0.74 mV of zeta potential and polydispersity index (PDI) of 0.32 .01. The prepared liposomal system presented essential oil controlled release and FTIR and SEM investigation showed no interaction between nanocarrier and the essential oil and the carriers have spherical structures. Conclusion: In the present study, Mentha piperita’s essential oil encapsulated in liposomal carriers and its physicochemical properties investigated. The results confrimed the slow-releasing ability of system and also showed that the anionic nanosystem increased the essential oil’s stability without any change in its chemical nature. Taken together, liposomal nanocarrier could be a potent and suitable carrier for the essential oil.

"n Objective: The study focuses on psychosocial variables related to suicide ideation in young soldiers . "n Method:1329 Soldiers were randomly selected from the Infantry Forces in different egions. All the soldiers were requested to complete the Beck Scale for Suicide Ideation (BSSI) as well as General Health Questionnaire (GHQ-28). Data were analyzed using correlation tests. "nResults:The results revealed that psychological factors, negative family ackground, environmental and task-related problems, and sociodemographic problems were significantly associated with suicide ideation. "nDiscussion:Overall, suicide ideation could be prevented if soldiers with sychosocial problems were identified and the Army officials applied appropriate methods to solve these psychological problems.

Objective: The study focuses on psychosocial variables related to suicide ideation in young soldiers. Method: 1329 Soldiers were randomly selected from the Infantry Forces in different regions. All the soldiers were requested to complete the Beck Scale for Suicide Ideation (BSSI) as well as General Health Questionnaire (GHQ-28). Data were analyzed using correlation tests. Results: The results revealed that psychological factors, negative family background, environmental and task-related problems, and sociodemographic problems were significantly associated with suicide ideation. Discussion: Overall, suicide ideation could be prevented if soldiers with psychosocial problems were identified and the Army officials applied appropriate methods to solve these psychological problems.

Low-pressure powder injection molding (LPIM) is a cost-effective technology for producing intricate small metal parts at high, medium, and low production volumes in applications which, to date, have involved ceramics or spherical metal powders. Since the use of irregular metal powders represents a promising way to reduce overall production costs, this study aims to investigate the potential of manufacturing powder injection molded parts from irregular commercial iron powders using the LPIM approach. To this end, a low viscosity feedstock was injected into a rectangular mold cavity, thermally wick-debound using three different pre-sintering temperatures, and finally sintered using an identical sintering cycle. During debinding, an increase in pre-sintering temperature from 600 to 850 °C decreased the number of fine particles. This decreased the sintered density from 6.2 to 5.1 g/cm3, increased the average pore size from 9 to 14 μm, and decreased pore circularity from 67 to 59%.