Cell and Tissue Journal

Abstract Aim: The field of targeted drug delivery is a rapidly advancing area of pharmaceutical research that focuses on optimizing the efficacy and safety of therapeutic agents. The primary goal is to enhance the concentration of a drug at its desired site of action while minimizing its presence in non-target areas. This selective accumulation not only improves the therapeutic outcomes but also significantly reduces the adverse effects often associated with drug therapies. By employing various carriers and mechanisms, targeted delivery systems can exert precise control over the rate and duration of drug release. This is particularly beneficial in chronic treatments where maintaining therapeutic drug levels is crucial. Moreover, the reduction in systemic exposure allows for lower dosages, which inversely correlates with increased bioavailability and drug effectiveness. Consequently, this leads to decreased healthcare costs and less frequent dosing schedules, improving patient compliance and quality of life. One innovative approach in this field is the utilization of nanotopography, which involves the replication of natural surface patterns at the nanometer scale onto drug carrier systems. These nature-inspired designs are not merely aesthetic; they play a functional role in modulating the interactions between the drug delivery vehicle and the biological target. For instance, surfaces mimicking the intricate patterns found in natural environments can influence cellular behavior, enhance adhesion, or even provide antimicrobial properties. Exploring the nuances of nano-engineered surfaces, this scholarly work reviews how nature-inspired topographies impact drug delivery and efficacy in pharmaceutical applications. It discusses the various methods of fabricating nanoscale topographies and their implications for drug delivery systems. The review highlights how these microscopic landscapes can affect biological functions such as cell adhesion, tissue barrier dynamics, and drug absorption rates. Surface modification techniques at the nanoscale are diverse, ranging from simple chemical treatments to sophisticated lithography and microcasting. These methods allow for the creation of specific patterns that can be tailored to enhance the performance of drug carriers. For example, In the context of drug delivery systems, the use of virus-inspired particles has facilitated drug absorption. These bioinspired designs enhance therapeutic outcomes. The role of nanotopography in drug delivery is multifaceted. It can facilitate the formation of bioadhesive interfaces that ensure the drug remains at the site of action for extended periods. This is particularly useful in mucosal drug delivery, where rapid clearance by bodily fluids can be a challenge. Additionally, the rearrangement of cellular barriers can be induced by these topographies, allowing for more efficient drug penetration in areas like the blood-brain barrier. Antimicrobial interfaces created through nanotopography can prevent the colonization of pathogens on drug delivery devices, reducing the risk of infections. This is especially important in implantable devices where biofilm formation can lead to device failure and serious health complications. In a nutshell, the review article provides a comprehensive overview of how nature-inspired nanotopography can revolutionize the field of drug delivery. By mimicking the wisdom of natural designs, pharmaceutical scientists can develop more effective and safer drug delivery systems that promise to improve therapeutic outcomes and patient care.
 

Abstract Aim: Dates are the second most important crops in Iran after pistachios, which show different structural and textural adaptations to drought and high temperatures. Acquiring the necessary knowledge about various structural and physiological changes from flowering to fruit ripening plays a significant role in obtaining high-quality and marketable fruit. Date fruit is a berry characterized by exocarp, fleshy mesocarp and membrane endocarp around the seed. This berry is formed from a fertilized carpel present in the female flower, while the other two carpels do not grow and decay. The fruit development period is long and lasts about 7 months. The sweetness and texture of date fruit is closely related to the maturity stage of the fruit. During the growth period of date fruit, several changes in the color and chemical composition of the fruit are observed. Mozafati is one of the most important commercial varieties of dates in Iran especially in Bam city. In the present study, the morphology and histology of the date fruit (Phoenix dactylifera L.) of the Mozafati cultivar were investigated during the developmental stages.
Material and Methods: Samples were collected from a commercial garden located in Bam city. Five adult 17-year-old date palms of Mozafati cultivar derived from offshoots grown in similar environmental conditions were used as female parents. The pollen used in this experiment is the same pollen that is normally used by local gardeners for pollination. Sample collection was done in five different developmental stages including Hababouk, Kimri, Khalal, Sarkhal and Rutab (4, 12, 19, 24 and 25 weeks after pollination, respectively). In this research, the local Iranian names such as Sarkhal and Rutb were used for the last two stages. The collected fruits, after cleaning and sorting, were packed and stored at 4ºC. The hand sections prepared from the fresh samples at each developmental stage were studied with an optical microscope after staining and then photographed.
Results: An anatomical study of fruits in different stages of development revealed several general characteristics in their pericarp structure: 1) Pericarp differentiation starts in the early stages of development (immediately after pollination) and its development continues progressively and regularly. 2) The exocarp contains four differentiated layers in all developmental stages, from outside to inside, includes layers of the epidermis, hypodermis, skin parenchyma, and layer of stone cells. 3) The mesocarp (which is the largest region forming the pericarp) has a large number of layers consisting of parenchymal cells and is divided into two outer and inner regions, which are separated by a layer of parenchymal cells specialized to store tannins (idioblast). Vascular vessels with different sizes are distributed in the outer and inner mesocarp, which are less abundant in the inner parts. 4) The endocarp can be recognized as an unspecialized single-layered epidermis only in the early stages of development and eventually forms the seed coat together with the inner layers of the mesocarp.
Conclusion: Organized protection and defense mechanisms, including the presence of thick cuticle, stone layer, and specialized tannin layer (tannin idioblasts) in all stages of pericarp development, were among the interesting histological features of this cultivar, which showed its adaptive and evolutionary role in specific habitats

Abstract Aim: Cancer remains a global health problem, with ovarian cancer ranking fifth among cancers affecting women and the leading cause of cancer-related death in women. There are different types pf ovarian cancer, including Epithelial ovarian cancer, Stromal tumors and Germ cell tumors.  Epithelial ovarian cancer is the most common type that includes several subtypes, including serous carcinoma and mucinous carcinoma. To this end, several factors have been identified to increase your risk of ovarian cancer, including older age, inherited gene changes, family history of ovarian cancer, being overweight or obese, postmenopausal hormone replacement therapy, endometriosis, and never having been pregnant. The current strategies to treat ovarian cancer include surgery, chemotherapy, radiotherapy and targeted therapies, and hormone therapy. Scientists continue to investigate the foundational mechanisms involving cancer development, as well as to find new drugs and metabolites having the capacity to control cancer. Alpha-ketoglutarate (AKG), a critical metabolite in the Krebs cycle involved in cellular energy production and the regulation of gene expression. Recent studies have shown that AKG may have the potential to enhance the efficacy of cancer treatments, by modulating the tumor microenvironment and improving the immune response against cancer cells. This study investigates the effect of AKG on ovarian cancer cells.
Material and methods: SKOV3 cells were obtained from Tehran University and cultured in complete culture medium (RPMI, 10% Fetal bovine serum (FBS), and 1% Penicillin-Streptomycin (Pen/Strep)). To find the proper concentration of AKG, SKOV3 cells were cultures in 96-well plate, and treated with different concentration of AKG (range 20 to 220 µM). After 24 and 48 h, the viability of the cells was determined using MTT assay. Based on the results obtained from viability assay, 200 μM of AKG was selected for the next assessments. To evaluate the effect of AKG on SKOV3 cell proliferation using plotting a growth curve, cells were cultured in the presence (200 μM AKG) and absence of AKG, and counted the number of cells every 24h for one week. To determine the population doubling time (PDT), the cells were cultured in the presence (200 μM AKG) and absence of AKG for 72h, then the cell were collected and the number of living cells was counted using Neubauer Chamber. The PDT was calculated using a related standard method. To assess colony formation potential, the SKOV3 cell were cultured in the presence (200 μM AKG) and absence of AKG. After 7 days, the cells were fixed using 10% formalin solution, then the colonies were stained using crystal violet dye, and the number of colonies were counted using inverted microscope. To investigate the effect of AKG on the migration rate of SKOV3 cells, the cells were cultured in complete medium to reach 85% confluence, then treated with mitomycin (10 μM) for 3h, then Created a scratch in the cell monolayer using a sterile pipette tip. the cells were cultured in the presence (200 μM AKG) and absence of AKG for 3 days. The images of the scratch were taken at regular intervals using a microscope, and the closure of the scratch over time was analyzed. To analyze the cell cycle profile, the SKOV3 cell were cultured in the presence (200 μM AKG) and absence of AKG for 48h. Then, the cells were collected and analyzed using a flow cytometry.
Results: Based on the MTT assay, 200 μM AKG was determined as the proper concentration to investigate other biological behaviors of SKOV3 cells. Colony forming assay showed a decrease in the number and size of colonies in the AKG-treated group (P<0.05). In addition, the cell doubling time increased in the treatment group, indicating slower growth rate (P<0.05). Growth curve analysis confirmed reduced cell growth in treated group. Cell cycle analysis showed a higher percentage of treated cells arrested in S and G1 phases. The scratch assay showed slow cell migration and metastasis in the cells treated with 200 µM AKG.
Conclusion: In conclusion, AKG has an inhibitory effect on the proliferation, viability, migration in SKOV3 ovarian cancer cells, highlighting its potential as an adjuvant treatment with existing therapies. More research is necessary to fully investigate the therapeutic effect of AKG in ovarian cancer.
 

Abstract Aim: The aim of this research was to investigate the effects of different plant growth regulators and MS culture medium on the characteristics of callus weight, percentage of callus formation and embryogenesis in anther culture of two cultivars of Sina and Negin cucumbers (Cucumis sativus L.).
Materials and methods: The experiment was conducted as a factorial in a completely randomized design with three replications. In this research, to determine the stage of growth and development of microspores, male flower buds in the sizes of 0.5 to 2.2 cm were taken from mother plants. For dyeing, the anthers were separated from the buds and placed in stocarman dye solution containing one gram of carmen powder and one hundred milliliters of 45% acetic acid for one day. Then the anthers were crushed on the laboratory slide and the microspores inside them were observed under a light microscope. In the callus induction test, the factors include two cucumber cultivars (Sina and Negin), the combination of different concentrations of BAP (0, 0.7, 0.9 and 1.1 mg/liter) and 2,4-D (0, 0.75, 1 and 1.25 mg/liter). 4 anthers were cultured in each petri dish. After placing the anthers in the culture medium, the lids of the petri dishes were closed and sealed with parafilm, and then they were covered with aluminum foil and placed in the growth chamber at a temperature of 25 ± 2 degrees Celsius in the dark for 2 weeks and the environments They were cultivated once every 2 or 3 weeks.
Results: Cytogenetic experiments showed that 1.5 cm buds containing anthers and microspores in the mononuclear stage are suitable for anther culture. The results of the analysis of the variance of the data showed a statistically significant difference at the level of 0.01 between the interaction effects of genotype and culture medium. Anthers cultured in MS base medium and media prepared with different concentrations of BAP did not show a response and were destroyed after one month of cultivation. The average main effect of cultivars on callus fresh weight after several weeks of cultivation showed that the highest callus fresh weight was obtained in Sina variety. The comparison of the average triple interaction effects of cultivar × BAP × 2,4-D for callus fresh weight in this research has shown that Sina cultivar in MS culture medium contains the growth regulator compound 0.7 mg/liter BAP and 1 mg/liter 2,4 -D has the highest callus fresh weight. By examining the interaction effect of cultivar, auxin and cytokinin, it was found that the highest percentage of callus formation was 100% in both cultivars in environments with the combination of BAP (0.7 and 0.9 mg/liter) with 2,4-D (0.75, 1 and 1.25 mg/L) and in Sina cultivar BAP (1.1 mg/L) with 2,4-D (0.75, 1.1 and 1.25 mg/L). However, the lowest percentage of callus formation was observed in Nagin cultivar in the presence of 2,4-D hormone with a concentration of 1 mg/liter with an average of 33.333%.
Conclusion: In general, the use of growth regulator BAP and 2,4-D in MS culture medium induced callus in anther culture of both cucumber cultivars.

Abstract Aim: The use of algae as a food additive has many positive effects such as increasing the quality, health, and greed of food and increasing the level of growth and immunity in aquatic animals. Among the algae with many uses are the members of the red algae branch, which are seen in red due to the large amounts of phycoerythrin and phycocyanin pigments. These algae belong to primary multicellular plants of the marine species, non-flowering without roots, stems, and leaves, and they reproduce sexually. The current research was conducted to replace red algae in the diet in stomach, liver histomorphology, and some growth factors of Nile tilapia, one of the most important commercial species in the world.
Material and Methods: For this purpose, after 8 weeks of preparation, fish were fed diets containing zero, 3%, 6%, and 9% of food weight with red algae with three repetitions in each treatment. After the end of the rearing period, the fishes were anesthetized and after opening the abdominal area while measuring some growth factors, a 0.5 cm tissue sample was taken from the middle part of the stomach and liver and placed in a 10% formalin buffer solution. After going through the routine steps of tissue preparation, including dehydration with alcohol, clarification with xylol, blocking with paraffin, cutting with a thickness of 4-6 microns, and staining, finally, the study was done with a light microscope. SPSS software version 21 was used for statistical analysis of data.
Results: Microscopic and anatomical studies of the stomach and some growth factors of the digestive system showed an increase in the measured factors as percentage of weight gain, especially in the group receiving the diet containing 9% red algae. The results of microscopic studies on the stomach showed that the mucosal lining of the stomach is of a simple type with nuclei near the base. This tissue is stretched from the surface of the mucous membrane to the inner part, so that at the beginning of the stomach, short but deep folds were also observed at different intervals. In the lamina propria of gastric mucosa, simple tubular glands were observed, whose tissue consists of a row of short cubic to cylindrical cells, which have spherical to elongated nuclei and basophils attached to the base of the cells. These cells had strong acidophilic color and covered all the lamina propria. Also liver was completely lobulated and the pancreas was located in the form of an appendix gland inside.
Conclusion: The results of this research showed that in terms of the structural characteristics of the stomach and liver tissue such as mucous glands, epithelium thickness, thickness, mucus height, and anatomical growth of the digestive system, red seaweed powder can be a suitable substitute for fish meal in the diet. Tilapia, along with possible substitutes in other animal and vegetable proteins, can be used to feed this fish, which will eventually reduce the cost and reduce the dependence on fish powder to supply the protein needed by Nile tilapia.

Abstract Aim:: The renin-angiotensin system (RAS) is an endocrine system essential for regulating blood pressure and fluid balance. Components of this system are expressed not only in various body cells but also in breast cancer cells. Angiotensin-converting enzyme (ACE) inhibitors, which are widely used as antihypertensive agents, have been proposed to have an additional benefit in reducing the risk of certain cancers. Doxorubicin is a commonly used chemotherapy drug, also employed in the treatment of breast cancer. One of the side effects of doxorubicin is its toxicity to cardiac cells. This research aims to investigate the effect of cytotoxicity of four RAS antagonists (enalapril, captopril, valsartan, and losartan) in the presence and absence of doxorubicin against two breast cancer cell lines including MCF-7 and MDA-MB-231. The study’s objective is to determine whether these RAS inhibitors can modulate the cytotoxicity of doxorubicin and their potential impact on breast cancer cell survival.Material and methods:  MTT is one of the colorimetric methods to investigate cell survival. This assay is based on the conversion of the MTT reagent to a formazan product by metabolically active cells, providing a quantitative measure of cell viability. The effect of RAS inhibitors in the presence and absence of doxorubicin on the survival of cancer cells was measured using the MTT test. Chemotherapy drugs, such as doxorubicin, typically reduce cell survival by inducing apoptosis. One of the markers of apoptosis induction in cells is the evaluation of caspase-3/7 activity. The induction of apoptosis in MDA-MB-231 cells treated with the RAS inhibitors was investigated using a caspase-3/7 activity assay kit, which quantifies the enzymatic activity in cell lysates. Results: Enalapril had no significant cytotoxic effect on breast cancer cells at concentrations up to 500 μg/mL. Captopril and losartan were toxic to breast cancer cells. Valsartan had no cytotoxic effect on breast cancer cells and increased cell proliferation over time. The cytotoxic effects of captopril and losartan on breast cancer cells may be attributed to their inhibitory effects on the RAS. The RAS plays a crucial role in regulating blood pressure and fluid balance, but it also has inhibitory effects on tumor growth and progression. By blocking the activity of the RAS with captopril and losartan, the cells may experience reduced proliferation and ultimately cytotoxicity. Enalapril, captopril, valsartan, and losartan protected breast cancer cells from doxorubicin cytotoxicity in a concentration- and time-dependent manner. Captopril and losartan treatment increased caspase-7/3 activity in MDA-MB-231 cells. The increase in caspase-7/3 activity in MDA-MB-231 cells suggests that captopril and losartan-induced cytotoxicity may be accompanied by apoptosis. Apoptosis is a desirable outcome in cancer treatment as it allows for the elimination of cancer cells while preserving normal tissue function.
Conclusion: RAS inhibitors can interfere with the cytotoxic effects of doxorubicin on breast cancer cells, depending on the concentration and duration of exposure. Further research is required to understand the optimal use and dosage of RAS system inhibitors in this context to ensure a balance between protecting the heart from doxorubicin-induced cardiotoxicity and maintaining the efficacy of cancer treatment.