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Colorectal cancer (CRC) is the third most revalent type of cancer in the world and the second most common cause of cancer death (about 1 million per year). Historically, natural compounds and their structural analogues have contributed to the development of new drugs useful in the treatment of various diseases, including cancer. Essential oils are natural odorous products made up of a complex mixture of low molecular weight compounds with recognized biological and pharmacological properties investigated also for the prevention and treatment of cancer. The aim of this paper is to highlight the possible role of essential oils in CRC, their composition and the preclinical studies involving them. It has been reviewed the preclinical pharmacological studies to determine the experimental models used and the anticancer potential mechanisms of action of natural essential oils in CRC. Searches were performed in the following databases PubMed/Medline, Web of science, TRIP database, Scopus, Google Scholar using appropriate MeSH terms. The results of analyzed studies showed that EOs exhibited a wide range of bioactive effects like cytotoxicity, antiproliferative, and antimetastatic effects on cancer cells through various mechanisms of action. This updated review provides a better quality of scientific evidence for the efficacy of EOs as chemotherapeutic/chemopreventive agents in CRC. Future translational clinical studies are needed to establish the effective dose in humans as well as the most suitable route of administration for maximum bioavailability and efficacy. Given the positive anticancer results obtained from preclinical pharmacological studies, EOs can be considered efficient complementary therapies in chemotherapy in CRC., (© 2022. The Author(s).)

Injury from the severe burn is exacerbated by a persistent inflammatory response. This response is mediated by cytokines and chemokines, which are released from various immune cells, including mast cells. In this study, the ability of the acellular ovine small intestine submucosa (AOSIS) to load and release of Mineral Pitch (MP) was first investigated, and it was found that the preparation of the scaffold by a modified method enables it to load and release water-soluble drugs. Then, 32 male Wistar rats were divided into four groups, a third-degree burn was created, and except for the control group, the others were treated with: AOSIS, WJ-MSCs seeded AOSIS, or AOSIS loaded with WJ-MSCs and MP. Wound sampling on the 5th day after treatment showed that the number of intact and degranulated mast cells in the treatment groups was associated with a decrease compared to the control group. In the last group, this decrease was the largest (and statically significant (p < 0.05)). Also, by measuring the level of inflammatory factors in blood serum, it was found that in the treatment groups compared to the control group, IL-10 was associated with an increase, and TNF-α was associated with a decrease. The changes in inflammatory factors were more significant (p < 0.05) in the last group. So, our results indicate that AOSIS loaded with WJ-MSCs and MP could be used as an innovative tissue-engineered device to control inflammatory condition during burn wound healing., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Exosomes are small bilayer-lipid membrane vesicles secreted by living cells that are able to transfer regulatory molecules and genetic information from one cell to another. These vesicles are enriched with several nucleic acids including mRNAs, microRNAs (miRNAs), other non-coding RNAs, as well as proteins and lipids. Alterations in the exosomal content and functions are observed in numerous reproductive diseases in both animals and human cases. MicroRNAs, a class of small endogenous RNA molecules, can negatively regulate gene expression at the post-transcription level. Aberrant microRNA expression has been reported in multiple human reproductive diseases such as polycystic ovary syndrome, preeclampsia, uterine leiomyomata, ovarian cancer, endometriosis, and Asherman's syndrome. This study focuses to review recent research on alterations of microRNA expression and the role of exosomes in female reproductive diseases. It has been demonstrated that exosomes may be a potential therapeutic approach in various female reproductive diseases. In addition, changes in expression of microRNAs act as molecular biomarkers for diagnosis of several reproductive diseases in women, and regulation of their expression can potentially reduce infertility., (© 2021. Society for Reproductive Investigation.)

The roots, leaves, and seeds of Lepidium sativum L., popularly known as Garden cress in different regions, have high economic importance; although, the crop is particularly cultivated for the seeds. In traditional medicine, this plant has been reported to possess various biological activities. This review is aimed at providing updated and critical scientific information about the traditional, nutritional, phytochemical, and biological activities of L. sativum . In addition, the geographic distribution is also reviewed. The comprehensive literature search was carried out with the help of different search engines PubMed, Web of Science, and Science Direct. This review highlighted the importance of L. sativum as an edible herb that possesses a wide range of therapeutic properties along with high nutritional values. Preclinical studies (in vitro and in vivo) displayed anticancer, hepatoprotective, antidiabetic, hypoglycemic, antioxidant, antimicrobial, gastrointestinal, and fracture/bone healing activities of L. sativum and support the clinical importance of plant-derived bioactive compounds for the treatment of different diseases. Screening of literature revealed that L. sativum species and their bioactive compounds may be a significant source for new drug compounds and also could be used against malnutrition. Further clinical trials are needed to effectively assess the actual potential of the species and its bioactive compounds., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Sakshi Painuli et al.)

Tissue engineering which is applied in regenerative medicine has three basic components: cells, scaffolds and growth factors. This multidisciplinary field can regulate cell behaviors in different conditions using scaffolds and growth factors. Scaffolds perform this regulation with their structural, mechanical, functional and bioinductive properties and growth factors by attaching to and activating their receptors in cells. There are various types of biological extracellular matrix (ECM) and polymeric scaffolds in tissue engineering. Recently, many researchers have turned to using biological ECM rather than polymeric scaffolds because of its safety and growth factors. Therefore, selection the right scaffold with the best properties tailored to clinical use is an ideal way to regulate cell behaviors in order to repair or improve damaged tissue functions in regenerative medicine. In this review we first divided properties of biological scaffold into intrinsic and extrinsic elements and then explain the components of each element. Finally, the types of scaffold storage methods and their advantages and disadvantages are examined.

Three dimensional (3D) printing has recently expanded in popularity and has become an effective approach for tissue engineering. Advances in tissue engineering have increased the effectiveness of cell-based therapies. Indeed, the ultimate goal of such treatment is the development of conditions similar to fetal wound regeneration. In this context, technology of 3D printing also allows researchers to more effectively compose multi-material and cell-laden scaffolds with less effort. In this study, we explored a synthetic gel scaffold derived from 3D bioprinter with or without stem cells to accelerate wound healing and skin defects. Adipose-derived stem cells (ADSCs) were isolated and seeded into 3D bioprinter derived-gel scaffold. Morphological and cell adherence properties of 3D scaffold were assessed by hemotoxylin & eosin (H&E) staining and scanning electron microscopy and cell viability was determined by methylthiazolyldiphenyl-tetrazolium bromide assay. In vivo assessment of the scaffold was done using H&E staining in the full-thickness burn rat model. The experimental groups included; (a) untreated (control), (b) 3D bioprinter derived-gel scaffold (Trial 1), and (c) 3D bioprinter derived-gel scaffold loaded with ADSC (Trial 2). Our results represented 3D bioprinter derived-gel scaffold with or without ADSCs accelerated wound contraction and healing compared to control groups. Epithelization was completed until 21 days after operation in scaffold alone. In scaffold with ADSCs group, epithelization was faster and formed a multi-layered epidermis with the onset of cornification. In conclusion, 3D bioprinter derived-gel scaffold with or without ADSCs has the potential to be used as a wound graft material in skin regenerative medicine., (© 2021 John Wiley & Sons Ltd.)

PTEN (Phosphatase and tensin homolog deleted on chromosome ten) is a tumor suppressor that is frequently mutated in most human cancers. PTEN is a lipid and protein phosphatase that antagonizes PI3K/AKT pathway through lipid phosphatase activity at the plasma membrane. More recent studies showed that, in addition to the putative role of PTEN as a PI(3,4,5)P3 3-phosphatase, it is a PI(3,4)P2 3-phosphatase during stimulation of class I PI3K signaling pathway by growth factor. Although PTEN tumor suppressor function via it's lipid phosphatase activity occurs primarily in the plasma membrane, it can also be found in the nucleus, in cytoplasmic organelles and extracellular space. PTEN has also shown phosphatase independent functions in the nucleus. PTEN can exit from the cell through exosomal export or secretion and has a tumor suppressor function in adjacent cells. PTEN has a critical role in growth, the cell cycle, protein synthesis, survival, DNA repair and migration. Understanding the regulation of PTEN function, activity, stability, localization and its dysregulation outcomes and also the intracellular and extracellular role of PTEN and paracrine role of PTEN-L in tumor cells as an exogenous therapeutic agent can help to improve clinical conceptualization and treatment of cancer.

Objectives: Three-dimensional biomimetic scaffolds have widespread applications in biomedical tissue engineering due to similarity of their nanofibrous architecture to native extracellular matrix. Co-culture system has stimulatory effect on chondrogenesis of adult mesenchymal stem cells. This work presents a co-culture strategy using human articular chondrons and adipose-derived stem cells (ASCs) from infrapatellar fat pad (IPFP) for cartilage tissue production., Materials and Methods: Isolated stem cells were characterized by flowcytometry. Electrospun and polycaprolactone (PCL) scaffolds (900 nm fiber diameter) was obtained from Bon Yakhteh (Tehran-Iran) and human infrapatellar fat pad-derived stem cells (IPFP-ASCs) were seeded on them. IPFP-ASCs on scaffolds were co-cultured with articular chondrons using transwell. After 21 day, chondrogenic differentiation of stem cell was evaluated by determining the genes expression of collagen2, aggrecan and Indian hedgehog using real-time RT-PCR., Results: Genes expression of collagen2, aggrecan by IPFP-ASCs did not alter significantly in comparison with control group. Howevers, expression of Indian hedgehog decreased significantly compared to control group (P< 0.05)., Conclusion: These findings indicate that chondrons obtained from osteoarthritic articular cartilage did not stimulate chondrogenic differentiation of IPFP-ASCs in co-culture.

Background: Uterine receptivity for the implantation is a complicated process, that ovarian factors (hormonal), endometrium and embryo simultaneously are involved in this phenomenon. A successful implantation needs appropriate development of the endometrium. Furthermore, embryo must be capable of reacting with the endometrium and producing suitable adhesion molecules. This study aimed to examine one of endometrial maturation indices in mice before implantation, i.e., proliferation of stromal cells., Materials and Methods: A total of 40 adult female mice were divided into four groups: Control, gonadotropin, gonadotropin + progesterone, and gonadotropin + sildenafil citrate. The three experimental groups were first injected 7.5 IU of human chorionic gonadotropin (HCG) and then 7.5 IU of human menopausal gonadotropin (HMG). Then, every two female mice were placed in a cage with a male mouse for mating. Two groups were injected 1 mg of progesterone and 3 mg/kg of sildenafil citrate at intervals of 24, 48, and 72 h after injection of HMG. After 96 h, all the mice were killed, and their uterine samples subjected to tissue passage and prepared for analysis. Immunohistochemical method, Ki-67, and stromal mitotic cell count were used in this study., Results: Our observations in all groups showed changes in the luminal epithelium. ANOVA analysis Ki-67-positive stromal cells among all groups were not statistically significant., Conclusion: The results showed that administration of HMG and HCG following that of progesterone and sildenafil citrate could change the indices of endometrial maturation, and they were not involved in the phase immediately before implantation in stromal mitotic index.

Pistachio (Pistacia vera L.) oil has important nutritional and therapeutic properties because of its high concentration of essential fatty acids. The extraction method used to obtain natural compounds from raw material is critical for product quality, in particular to protect nutritional value. This study compared the fatty acid composition of pistachio oil extracted by two conventional procedures, Soxhlet extraction and maceration, analyzed by a gas chromatography-flame ionization detector (GC-FID). Four solvents with different polarities were tested: n-hexane (Hx), dichloromethane (DCM), ethyl acetate (EtAc) and ethanol (EtOH). The highest unsaturated fatty acid content (88.493 %) was obtained by Soxhlet extraction with EtAc. The Soxhlet method extracted the most oleic and linolenic acids (51.99 % and 0.385 %, respectively) although a higher concentration (36.32 %) of linoleic acid was extracted by maceration.

The present study investigated the chemical composition of the essential oil (EO) from aerial parts (flowering stage) of Achillea wilhelmsii C. Koch by GC-MS. In addition, the antioxidant activity of the EO as well as its antimicrobial activity against methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MRSA) strains was tested. Antioxidant activity was measured by the ability of the EO to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals while the antimicrobial activity was assessed by the disc-diffusion method. In total, 52 compounds were recognized, accounting for 97.33 % of the EO. The main compounds in the EO were carvacrol (22.49 %), dihydrocarvone (13.23 %), linalool (12 %), 1,8-cineol (11.42 %), camphene (8.31 %), thymol (5.28 %), camphor (3.71 %), pulegone (2.82 %) α-terpineol (2.11 %), bornyl acetate (1.14 %), and farganol (1.01 %). The EC 50 value of the EO was 0.01 and 0.08 mg/mL for the antioxidant and DPPH-scavenging ability, respectively. A. wilhelmsii EO affected methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA, but the impact was more effective on MSSA.

Background: Medicinal herbs such as Citrullus Colocynthis (C.C) have been used traditionally in the treatment of diabetes mellitus. However therapeutic applications and adverse effects of C.C and its natural variants are not determined well. The current work investigates the effects of pulp and seed extract of C.C on hepatocyte's glycogen stores., Materials and Methods: Thirty six male rabbits were divided into six groups (control and diabetic) randomly. Alloxan was used in order to induce diabetes mellitus in animals. Among 5 diabetic groups, one remained as control and the rest received 100 and 200 mg/kg/day of either pulp or seed extract. One month later, animals were sacrificed and their liver specimen fixed in 10% Formalin was stained with periodic acid schiff (PAS) for light microscopic scanning., Results: PAS staining of hepatocytes revealed large amounts of glycogen stores in diabetic animals treated with pulp and seed extracts of C.C, contrary with non-treated diabetic rabbits. Sites of glycogen deposition were also different in animals treated with seed extract (P < 0.0001). No hepatic congestion was seen in treated animals. Dose escalation has no effect on the obtained results., Conclusions: The anti-diabetic effects of C.C can be explained by its effects on accumulation of glycogen stores in hepatocytes. The importance of varied sites of glycogen deposition by the application of C.C needs to be determined.

Background: The previous studies showed that herpes human virus-6 (HHV-6) and HHV-7 exist in salivary glands. One of the important areas in oral and maxillofacial pathology field is tumors of the salivary glands. In this study, to declare the major sites of persistent infection with HHV-6 and HHV-7, the existence of HHV-6 and HHV-7 genomes in formalin-fixed paraffin embedded tissue samples of salivary gland tumors., Methods: This analytical study was performed in 60 paraffin blocks samples of malignant and benign neoplasms of both major and minor salivary glands. This study performed with highly sensitive real time PCR method., Results: Among 60 paraffin blocks salivary gland tumors with equal chances of presence of the HHV-7 and HHV-6 in the samples, 34% were positive for both HHV-7 and HHV-6 while 47.2% were only positive for HHV-7, 18.9% samples were positive for HHV-6. A relationship was noticed between HHV-7 and HHV-6 genomes., Conclusion: In conclusion, this study showed no relation between virus and diseases with P=0.953. Also it could be inferred that there is a relationship between HHV-6 and 7 in salivary glands neoplasms.

Background and Purpose: The user's satisfaction with information system in fact denotes the extent the user is satisfied with the system's achievement in fulfilling his/her information requirements. This study tries to explore the users' satisfaction with hospital information systems (HISs) based on DeLone and McLean's model focusing on the medical-teaching hospitals of Isfahan city., Methodology: This study which was applied and descriptive-analytical in nature was carried out in the medical-teaching hospitals of Isfahan city in 2009. Research population consisted of the system users from which a sample was selected using random sampling method. The size of the sample was 228. Data collection instrument was a self-developed questionnaire produced based on the satisfaction criterion in the DeLone and McLean's model. Its content validity was assessed based on the opinions given by the computer sciences professionals with its estimated Cronbach's alpha found to be 92.2%. The data were analyzed using SPSS software., Findings: As the findings of the study showed, the differences among the mean scores obtained for the satisfaction with different kinds of HISs in use in the hospitals were statistically significant (p value≤0.05). Generally, Kowsar System (old version) and Pouya Samaneh Diva system gained the highest and lowest mean scores for the criterion in question, respectively. The overall mean score for the satisfaction was 54.6% for different types of systems and 55.6% among the hospitals., Conclusion: Given the findings of the study, it can be argued that based on the used model, the level of users' satisfaction with the systems in question was relatively good. However, to achieve the total optimum condition, when designing the system, the factors affecting the enhancement of the users' satisfaction and the type of hospital activity and specialty must be given special consideration.

Background: The effect of electromagnetic field (EMF) as an environmental factor on different organs including female reproductive system is of critical concern. The aim of the present study is to evaluate the effect of low-frequency (LF)-EMF on oocyte differentiation and follicular development., Materials and Methods: The experiment was carried out in animal lab of Faculty of Medicine Tabriz University of Medical Sciences. For this purpose, the BALB/c mice were divided into control and experimental group in animal lab. The pregnant mice in the experimental group were exposed to 3 mT EMF field, 4 h/day during the pregnancy period. The LF-EMF was produced by a system using 50 Hz alternative current, in the control group the pregnant mice were kept in a similar condition without exposure to EMF. The neonatal mice from both groups were sacrificed immediately after birth and their ovary was dissected apart and prepared for light and electron microscopy., Result: Microscopy revealed that in the experimental group, in comparison to control group, oocyte nests were mostly broken and irregularly arranged. The primordial follicles were less developed and nuclei of oocytes with an electron microscope appeared heterochromatic, shrunken and had vacuolated cytoplasm., Conclusion: It is concluded that exposure to EMF during the developmental period could affect both oocyte differentiation and folliculogenesis and may result in reduced fertility, by decreasing ovarian reservoir.

Background and Aims: The excessive and repeated use of antibiotics in medicine has led to the development of antibiotic-resistant microbial strains, including Staphylococcus aureus whose emergence of antibiotic-resistant strains has reduced the number of antibiotics available to treat clinical infections caused by this bacterium. In this study, antioxidant and antimicrobial activities of methanolic extract of Xanthium strumarium L. leaves were evaluated on methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MRSA) spp., Materials and Methods: Antiradical and antioxidant activities X. strumarium L. leaf extract were evaluated based on its ability to scavenge the synthetic 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical and by the paired diene method, respectively, whereas the antimicrobial activity was assayed by the disc diffusion method., Statistical Analysis: Data were subjected to analysis of variance following an entirely random design to determine the least significant difference at P < 0.05 using SPSS v. 11.5., Results and Conclusions: The IC50 values of the extract were 0.02 mg/mL and 0.09 mg/mL for the antioxidant and DPPH-scavenging capacity, respectively. X. strumarium extract affected both methicillin-sensitive Staphylococcus aureus and MRSA, though antibacterial activity was more effective on methicillin-susceptible S. aureus spp. The antibacterial and antioxidant activities exhibited by the methanol extract may justify the traditional use of this plant as a folk remedy worldwide.

Unlabelled: Endometrial epithelial pinopodes are considered as markers of endometrial receptivity and seem to be directly involved in the adhesion of the blastocysts to the endometrial surface. The aim of the study was to assess the effects of ovarian stimulation and progesterone injection on pinopode expression, and compare morphological characteristics in the preimplantation stage in mice. Adult female mice (n=30) were divided into three groups: control, superovulated and superovulated-progesterone injected. In experimental groups the mice received 7.5I.U human menopausal gonadotropin (HMG) and then after 48h 7.5I.U human chorionic gonadotropic (HCG) hormone. After that every two females were put with one male in one cage for mating. Superovulated-progesterone group were injected with progesterone (1mg/mouse) in 24, 48, 72h interval after the HMG injection. Animals were sacrificed in 96h after HMG injection, and their uterines (the middle one-third) were prepared for transmission electron microscope studies. That demonstrated that all groups differed from each other. In most of the controls and hyperstimulated-progesterone mice 4 days after HMG injection, long and short microvilli were seen, but they had no developed pinopodes, while in hyperstimulated mice, well developed pinopodes were expressed 4 days after HMG injection., In Conclusion: hyperstimulated mice without progesterone injection may be useful for the studies of pinopodes and implantation., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Electromagnetic fields with high energy same as ionizing radiation inserts their destructive effects via free radical production. Using antioxidants or herbal plants with antioxidants components could diminish hazardous effects of EMF. Polygonum aviculare has a high amount of phenolic and flavonoid and proved that has antioxidants effects. The aim of this study was to evaluate the effects of Polygonum aviculare herbal extract on sperm parameters after EMF exposure in mouse. Twenty four male mice, 8 weeks divided to 4 groups (one control and three experimental groups). Control group didn't receive EMF exposure. EMF group mice received 3 mT EMF during 2 months, 4 h daily and 5 days weekly. Polygonum aviculare group received 50 mg kg(-1) herbal extract during 2 months and poly -EMF group received 3 mT EMF during 2 months, 4 h daily and 5 days weekly and 50 mg kg(-1) herbal extract during 2 months. After 2 months the mice sacrificed with cervical dislocation and sperm obtained from tail of epididymis and motility and morphology of them were analyzed. Sperm analysis results showed that in group with Polygonum aviculare, morphology and motility of sperm developed (p < 0.05). Present results showed that EMF can reduce motility of sperm and treatment of Polygonum aviculare after EMF exposure developed sperm quality after EMF exposure.

Objective: Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that plays a key role in the pathogenesis of osteoarthritis (OA). Growth factors (GFs) capable of antagonizing the catabolic actions of cytokines may have therapeutic potential in the treatment of OA. Herein, we investigated the potential synergistic effects of insulin-like growth factor (IGF-1) and platelet-derived growth factor (PDGF-bb) on different mechanisms participating in IL-1β-induced activation of nuclear transcription factor-κB (NF-κB) and apoptosis in chondrocytes., Methods: Primary chondrocytes were treated with IL-1β to induce dedifferentiation and co-treated with either IGF-1 or/and PDGF-bb and evaluated by immunoblotting and electron microscopy., Results: Pretreatment of chondrocytes with IGF-1 or/and PDGF-bb suppressed IL-1β-induced NF-κB activation via inhibition of IκB-α kinase. Inhibition of IκB-α kinase by GFs led to the suppression of IκB-α phosphorylation and degradation, p65 nuclear translocation and NF-κB-regulated gene products involved in inflammation and cartilage degradation (COX-2, MMPs) and apoptosis (caspase-3). GFs or BMS-345541 (specific inhibitor of the IKK) reversed the IL-1β-induced down-regulation of collagen type II, cartilage specific proteoglycans, β1-integrin, Shc, activated MAPKinase, Sox-9 and up-regulation of active caspase-3. Furthermore, the inhibitory effects of IGF-1 or/and PDGF-bb on IL-1β-induced NF-κB activation were sensitive to inhibitors of Src (PP1), PI-3K (wortmannin) and Akt (SH-5), suggesting that the pathway consisting of non-receptor tyrosine kinase (Src), phosphatidylinositol 3-kinase and protein kinase B must be involved in IL-1β signaling., Conclusion: The results presented suggest that IGF-1 and PDGF-bb are potent inhibitors of IL-1β-mediated activation of NF-κB and apoptosis in chondrocytes, may be mediated in part through suppression of Src/PI-3K/AKT pathway, which may contribute to their anti-inflammatory effects.

Aim: Primary germ cells after migration to the developing ovary differentiate to oogonia and oocytes. The formation and number of primordial follicles in early fetal life are determining factors in the fertility state of adult life. Tamoxifen is used both to stimulate ovulation and as an anticancer drug. The aim of the present study was to evaluate the effect of tamoxifen on oocyte and follicular development and differentiation in mice., Methods: Thirty adult female and 15 adult male mice were used in the present study. The female mice were divided into two groups: control and experimental. Two female mice at their sterous cycle were placed with one male mouse in a cage for mating. The observation of a vaginal plug was considered the 1st day of pregnancy. On the 13th day of pregnancy the mice received 100 microg tamoxifen by i.p. injection. At the end of pregnancy 2-, 3-, 6- and 7-day-old newborns were killed and their ovaries were fixed and prepared for light and electron microscopic studies. The number of follicular nests and diameter of primordial and primary follicles were determined using Motic software (Motic Incorporation Ltd, Canada) and compared with control values using t-test., Results: Microscopy and morphometry showed that oocyte nests are formed on the 2nd and 3rd days and follicles are distinguished on the 6th and 7th days. Morphometric studies revealed that the number and diameters of oocyte nests were significantly (P < 0.001) reduced in the experimental groups compared to the control group. However, the numbers and diameters of primordial and primary follicles in experiential and controls were not significantly different. Electron microscopic studies revealed that in the control group, oocytes were separated from each other and were at primordial follicle stage. However, in the experimental group, the oocytes were in clusters as oocyte nests., Conclusion: The results indicate that tamoxifen suppresses follicular differentiation at early stages but does not affect the development of already differentiated follicles.

The aim of the study is to determine the effect of Celecoxib administration, dietary or topical, on expression of Ki-67, c-erb-B2, bcl-2 and bax genes in rat tongue by the immunohistochemistry methods and also tdt-mediated dupt-biotin nick end labeling assay in order to explore their role in malignant transformation and the proliferation rate, apoptosis rate in tongue squamous cell carcinoma. Effects of celecoxib on tongue carcinogenesis were investigated in 40 adult male Sprague Dawley 3-3.5 months rats initiated with 30 ppm 4-nitroquinoline-1-oxide. The immunohistochemical expression of Ki-67, bcl2, bax and c-erb-B2 were also examined for analysis of the effects of Celecoxib on tongue carcinogenesis. Differences among groups were statistically analyzed with one-way analysis of variance (SPSS-13, p < 0.05). At week 8, the incidence of tongue precancer lesions was reduced by Celecoxib and there were significant differences in the average expression of Ki-67 (p = 0.00), c-erb-B2 (p = 0.01), bax (p = 0.02), bcl2 (p = 0.02) and also in TUNEL assay (p = 0.00). The results suggest probably that the level of c-erb-B2, bcl-2 and bax expression could show behavior of squamous cell carcinoma in initiation phase of developing carcinoma.

The present study was designed to explore the spermatogenic effect of intraperitoneal administration of thiotepa in mice. It is known the chemotherapy could affect testicular function and result in infertility. There are few reports on the side effect of thiotepa on spermatogenesis when are used as anticancer drug. Therefore, in the present study the effect of thiotepa on spermatogenesis was evaluated by electron microscopy. A total of 20 balb/c mice were used in this study. They were divided into control and thiotepa treated groups. Thiotepa was administrated as 2.5 mg kg(-1) for 5 days. The mice were sacrificed after 5 weeks and testicular specimens were removed, fixed in boueins fixative and 2.5% Glutaraldehide then prepared for light and electron microscopic study. Light microscopy showed that the thickness of germinal epithelium was decreased in thiotepa treated group and many seminiferous tubules have lost germinal cells. Electron microscopy revealed that in experimental group several intercellular spaces appeared between spermatogonial and sertoli cells. The basement membrane became irregular and intercellular vacuoles were present in sertoli and spermatogonial cells. Nuclear chromatin was condensed and there were several vacuolated mitochondria. It was indicated that thiotepa affected testicular germinal epithelium by both cytotoxic effect and induction of apoptosis.

Skin wound healing has been the subject of extensive studies and various drugs have been used in an attempt to improve wound healing. There are conflicting data regarding the effects of L-arginine, the substrate of nitric oxide, on wound healing. We examined the 1-week rate of cutaneous wound healing and collagen deposition in three groups of rats who received a (1) L-arginine (2% in drinking water)-supplemented diet from three days before until the seventh day following injury (Group 1), (2) L-arginine-supplemented diet for three days before injury (Group 2), and (3) a standard diet without L-arginine supplementation (Group 3). The wound length and width were measured each day and then the open wound area and cumulative percentage of open wound area reduction were calculated. Wound biopsy samples were examined with Trichrome-Masson stain in a subgroup of animals. Results showed that Group 1 rats had a significantly lower cumulative percentage of open wound area reduction on day 7 compared to other two groups (Mann-Whitney U test, P < 0.05). Relatively higher degrees of wound collagen deposit (day 7) were noted in groups 2 and 3. It may be concluded that L-arginine (2% in water) administered three days before until the seventh day following skin wound induction may diminish the rate of skin wound healing and collagen deposition.

The potential role of exercise in preventing the age-related spontaneous peripheral neuropathy has not been studied. We examined the effects of long-term aerobic exercise training on lipid peroxidation, Schwann cell (SC) apoptosis and ultrastructural changes in the sciatic nerve of rats during aging. Three groups of 12-week old Wistar rats ran on a treadmill for 6, 9 and 12 months (exercise trained (ET) group, n=10 each) according to an exercise training program targeted at a speed of 22 m/min (at 7 degrees incline), 60 min/day, 6 days/week. Three corresponding groups of untrained rats were used as the controls (sedentary (SED) group). At the end of each period, sciatic nerve biopsies were performed, and processed for biochemical, immunohistochemical and ultrastructural analyses. The results showed that aging was associated with an increased level of nerve malondialdehyde (MDA, marker of lipid peroxidation) and a higher number of SC apoptosis in SED group. The SED group showed irregular nerve fibers with thin myelin sheaths and areas of myelin-axon detachment. However, the ET group had significantly diminished nerve lipid peroxidation and SC apoptosis. In the ET group, nerve fibers had a thick myelin sheath with frequent folding. These findings suggest that aerobic exercise training protects peripheral nerves by attenuating oxidative reactions, and preserving SCs and myelin sheath from pathologic changes, which occur during normal aging.

Humans are continuously exposed to harmful environmental factors, including Electromagnetic Fields (EMF) produced by home appliances, diagnostic tools and industrial instruments. The present study investigates morphologically the effects of EMF on ovarian follicles. Female Wistar rats were exposed to 3 mili Tesla EMF for 4 h day(-1) for 4 months, the ovaries from both experimental and control groups were processed for Transmission Electron Microscopy (TEM) and TUNEL reaction technique. TEM revealed that in the oocytes from experimental group the nuclei were shrunken and zona pellucida appeared narrower than those in the control group. The number of microvilli were decreased significantly and in their cytoplasm there were several lipid droplets and organels were dispersed. Signs of apoptosis such as condensed nuclei, chromatin margination and nuclear membrane dilatation were common in granulosa and corona radiata cells from the EMF-exposed rats than those from the control group. Primary morphological changes in the granulosa cells from this group were retraction of granulosa cells, loss of microvilli and condensation or loss of mitochondrial cristae. The morphological changes in oocytes seem to indicate the cytotoxic effect of EMF and the changes occurred in granulosa cells coincide with initiation of apoptosis in granulosa cells. Present results suggest that EMF exposure may interfere with normal process of folliculogenesis.

Aim: The aim of the present study was to investigate the effects of long protocol ovulation induction on the ultrastructure of the human endometrial epithelium on days luteinizing hormone (LH) + 4 and LH+ 6 of the menstrual cycle., Methods: Endometrial biopsies were obtained on days LH+ 4 (n = 9) and LH+ 6 (n = 10) from infertile women who were under standard long protocol with luteal phase supplementation with IM (intramuscular) progesterone, but where the embryo had not been formed or transferred, due to the male factor problem. Biopsies were also taken on days LH+ 4 (n = 5) and LH+ 6 (n = 5) from fertile women who had not received ovulation induction drugs as control groups. After preparation and taking light and electron micrographs from samples, qualitative and quantative evaluations (morphological and morphometric) were accomplished and the data was compared using the unpaired student t-test., Results: Qualitative results showed the presence of the nuclear channel system, vacuoles of glycogen and giant mitochondria in all of the samples. Qualitative analysis showed that the volume fraction (Vv) of the euchromatin to the nucleus, the rough endoplasmic reticulum and the mitochondria to the cell, were not statistically different (P > 0.05) in samples taken on LH+ 4 in both control and test groups. The Vv of these features, however, to the cell in the test group was significantly (P < 0.05) higher than those in the control taken on LH+ 6., Conclusions: These results suggest that long protocol ovulation induction with luteal phase support with progesterone alter the normal development of the human endometrium in the mid luteal phase and could decrease the implantation success rate.

Human beings are unavoidably exposed to ambient electromagnetic fields (EMF) generated from various electrical devices and from power transmission lines. Controversy exists about the effects of EMF on various organs. One of the critical issues is that EMF may adversely affect the reproductive system. In order to examine this 30 rat pups were exposed to 50 Hz EMF (non-ionising radiation) during in utero development (approximately 3 weeks) and postnatal life (5 weeks). Groups of exposed rats were subsequently left in an environment free of EMF in order to observe recovery, if any, from the changes induced by EMF on the boundary tissue of the seminiferous tubules. The materials were processed and observed under a light and a transmission electron microscope. In the experimental rats boundary tissue was found disrupted at various layers. This tissue showed infoldings, which were perhaps due to the loss of collagen and reticular fibrils from the inner and outer non-cellular layers. The outer non-cellular layer, which was thinner than that of the control, was stripped away from the myoid cell layer in multiple regions, giving a "blister-like" appearance. The myoid cells showed fewer polyribosomes, pinocytotic vesicles and glycogen granules. Most mitochondria were found to lack cristae. The connections between individual myoid cells were apparently lost. There were signs of recovery in the boundary tissue following withdrawal from EMF exposure. These results suggest that EMF exposure may cause profound changes in the boundary tissue of the seminiferous tubules. Therefore exposure to EMF may result in pathological changes that lead to subfertility and infertility.

Ultimobranchial bodies (UBBs) were dissected from 17-day-old chick embryos and grafted onto the chorioallantoic membrane of 8-day-old embryos. The embryos with UBB grafts as well as sham-grafted controls were injected on the 10th day of incubation with 100 ng 1,25(OH)2D3 dissolved in ethyl alcohol or with an equal volume of ethyl alcohol alone; embryos were sacrificed on the 13th day. Grafted UBBs showed ultrastructural characteristics typical of actively secreting glands. A histological study of the tibiae from all embryos showed that while the grafted embryos responded to the injection of 1,25(OH)2D3 with a peripheral rim of undermineralized bone trabeculae, sham-grafted embryos never did so. These results confirm the original hypothesis that the presence of differentiated UBBs is a precondition for the production of undermineralized bone (osteoid) by 1,25(OH)2D3. In a second series of experiments, similarly treated embryos were sacrificed on the 10th, 11th, 12th and 13th day; the levels of calcium and inorganic phosphate were determined in their blood. The injection of 1,25(OH)2D3 produced in all embryos hypercalcaemia and hypophosphataemia. However, the hypophosphataemic response was more prolonged in the embryos with UBB grafts than in sham-grafted ones. These results suggest that the grafted UBBs prolonged the hypophosphataemic response, probably by secreting calcitonin and thus reducing the rate of bone resorption. It is also probable that the prolonged hypophosphataemia produced or contributed to the undermineralization of the peripheral (subperiosteal) trabeculae.

Chick embryos were injected on the 14th day of incubation with 100 ng calcitriol. The concentration of Ca in their serum rose significantly 4 hours after the injection and the concentration of Pi started to decrease 10 hours after. When embryos of the same age were injected with a solution containing CaCl2, the concentrations of both Ca and P rose significantly 2 hours after the injection and remained high until the end of the experiment. The fact that both treatments produced hypercalcemia but had opposite effects on the concentration of Pi does not agree with the idea that the hypophosphatemic response to calcitriol might be secondary to the hypercalcemia which precedes it. The injection of a solution of NaHCO3 to embryos of the same age failed to produce hypophosphatemia. The fact that calcium salts and bicarbonate, when injected separately, fail to induce hypophosphatemia does not contradict the possibility that the hypophosphatemic response to calcitriol might result from the simultaneous increase in flux of Ca and -HCO3 from the shell. Three days after the injection of calcitriol to 14-day-old embryos, the total amount of Ca and P in the urine was significantly higher than in the controls. The concentration of Ca and P in kidney tissue was also significantly higher in the injected embryos. In addition, calcified precipitates were detected histochemically in the lumen of the kidney tubules from the treated embryos. These results are interpreted as demonstrating that an increase in the excretion of P in the urine is the main mechanism explaining calcitriol-induced hypophosphatemia in the chick embryo.(ABSTRACT TRUNCATED AT 250 WORDS)