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SummaryThe role of hyaluronic acid (HA) as a ‘physiologic selector’ is also well recognized in vitro: it has been demonstrated that spermatozoa that bind to immobilized HA in vitro are those having completed their plasma membrane remodelling, and cytoplasmic and meiotic maturation. Sperm selection using HA has been expected to increase the implantation rate in intracytoplasmic sperm injection (ICSI) cycles. This work was designed to evaluate an alternative product for slowing sperm motility that contains HA and measures its outcomes: fertilization rate, embryo quality, and implantation and pregnancy rates. The present study found a positive drift in embryo quality that was statistically significant in the study group (SpermSlow™-ICSI) with teratozoospermia compared with PVP-ICSI in the same group. There were differences in the pregnancy rate (statistically insignificant in normozoospermia, asthenozoospermia, oligozoospermia, and teratozoospermia) in the SpermSlow-ICSI group compared with PVP-ICSI. The HA-ICSI technique in assisted reproduction technology (ART) is an important way to improve fertilization rate, embryo quality, and pregnancy rate.

Melittin (MEL), a major peptide component of bee venom (BV), has shown chemopreventive as well as chemotherapeutic effects against many cancers in preclinical model systems. However, its applicability to humans has met with limited success due to several issues including its toxicity, nonspecificity, degradation, inefficient systemic delivery and limited bioavailability. Earlier, the concept of "nanochemoprevention" i.e. the use of nanotechnology to improve the outcome of cancer chemoprevention is introduced. Then, "non-targeted nanobees" i.e. nanoformulated mellitin is developed to exhibit excellent anti-prostate cancer efficacy in vitro and in animal models coining the concept as ‘Nanobee- Chemoprevention’. Here, we are extending this work and developed nanobees targeted with small molecular entities (A10 2′-fluoropyrimidine RNA aptamers (Apt)), able to bind to prostate specific membrane antigen (PSMA), a transmembrane protein that is overexpressed in prostate cancer (PCa) and evaluated their efficacy in preclinical studies. The Apt-Nanobees led to an enhanced anti-proliferative activity in PCa cell lines compared to the free melittin. The behavior of Apt-Nanobees in modulating apoptosis and cell-cycle, was also determined. Then, in vivo experiments, in mouse xenograft model of prostatic tumor using nanobees with a model of targeted nanosystems, were conducted. The obtained data supported our hypothesis of targeted nanobees enhanced the bioavailability and limited unwanted toxicity of melittin, thus leading to a significant potential for probable clinical outcome. Citation Format: Islam Rady, Sayed Bakry, Fatma Abou El-Azm, Hasan Mukhtar. Aptamer conjugated prostate specific membrane antigen (PSMA) targeting nanobees for prostate cancer prevention and therapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4502.

Objective (s): Assessment of fertilization rate, grading of embryos, blastocyst formation rate,arrested 2PN and clinical pregnancy outcome during intracytoplasmic sperm injection (ICSI) in fresh testicular sperm versus frozen–thawed testicular sperm in Egyptians non-obstructive azoospermia. Design: Prospective study. Setting: assisted reproduction unit at the ELITE fertility care center,Heliopolis, Cairo, Egypt between October 2017 and September 2019. Subject: evaluate testicular sperm selection technique using fresh and thawing testicular sperm extraction (TESE) in intracytoplasmic sperm injection (ICSI). The study population consisted of 97 couples. Results: The study population of 97 couples who referred to ICSI divided into 2 groups, fresh testicular sperm and frozen–thawed testicular sperm, including complete dissecting analyses, flow up and comparison between the changes between two groups during ICSI outcome. Conclusion: the present study show significant differences in fertilization rate between two groups, and no significant differences in grading of embryos, blastocyst formation rate,arrested 2PN and clinical pregnancy rate.

Introduction: Chronic inflammation causes articular bone and cartilage degeneration in people with rheumatoid arthritis (RA). Despite recent advancements in the management of RA, adverse side effects and ineffective treatments remain a problem. Access to treatment is hampered by financial restrictions. As a result, medications that reduce inflammation and bone resorption that are both safe and less expensive are required. Mesenchymal stem cells (MSCs) have recently been identified as a potential therapy for RA. Aim of study: The aim of this study was to examine the anti-arthritic effect of rat bone marrow-MSCs, oligosaccharides and human placental extract, individually and combined on RA model, using Complete Freund's adjuvant (CFA) induced arthritis in rats. Materials and methods: In female rats, RA was induced by injecting CFA in the paw of hind limb. Rat bone marrow-MSCs, oligosaccharides, and human placental extract (HPE) were given individually and in combination via intra-peritoneal route. Complete blood picture (CBC), erythrocyte sedimentation rate (ESR), serum cortisol, urea, uric acid and other biochemical parameters were measured to determine the safety and efficacy of the different treatments. Histopathological analysis of bone sections was carried out.Result: Combining oligosaccharides and HPE with rat-bone marrow MSCs had a favorable anti-arthritic and anti-inflammatory effect in CFA-induced arthritis in rats, with no negative effects on CBC, renal functions, serum cortisol, ESR, and liver enzymes. Histopathological analysis showed healing and remodeling of osteoporotic lesions in arthritic rats. Conclusion: Combination of rat MSCs, oligosaccharides and HPE has potential to be an effective treatment for rheumatoid arthritis.

Purpose: To assess the effects passive smoking and heavy metal concentrations in the blood and follicular fluid on assisted reproductive technology outcome.Methods: A prospective study was conducted between March 2017 and January 2018 in population consisted of 75 female patients undergoing an In vitro fertilization (IVF) cycle at Dr. Faris Medical center for Infertility and Human Reproduction located on Heliopolis, Cairo, Egypt; with unexplained infertility who underwent intracytoplasmic sperm injection (ICSI) using GnRH-antagonist protocol. Concentrations of three toxic metals Cadmium (Cd), Lead (Pb) and Arsenic (As) were measured both in blood sera and follicular fluid specimens. Patients were evaluated in two groups both undergoing ICSI; the first group consisted of patients who does not smoke or exposed to smoking (n=28) and the group passive smoker females (n=47). Results: These three heavy metals were significantly higher in serum and follicular fluid of passive smoking females (P

Heavy metals and trace elements adversely affect animal health and the reproductive system and its functions through direct or indirect effects on numerous organs and systems. This study was aimed to evaluate the effect of heavy metals levels in follicular fluid on a patient undergoing Intracytoplasmic Sperm Injection (ICSI) outcomes namely Cadmium (Cd), Lead (Pb), and Arsenic (As). In comparison between the normal concentration level of Cd and the high concentration level of Cd the present study showed a significant difference in embryos quality (P=0.01611), while no statistically significant difference in pregnancy rate was observed. Although Pb showed a significant difference in embryos quality; grade I embryos in normal level concentration than high-level group (P=0.00021), and grade III embryos were significant in a high-level concentration of Pb than low-level group (P=0.0043). The present study concluded that a high level of heavy metal concentration in the follicular fluid has a harmful effect on the grading of embryos and these lead to a decrease in the chance to select the beast embryos before transferred (Cd and Pb).

Chitosan is a sugar obtained from the shellfish exoskeleton, such as oysters, shrimp, and crab. Chitosan nanoparticles (CNPs) are used in many industrial preparations, especially pharmaceuticals, as it represents its important role in delivering drugs to treat many diseases. To examine the effect of chitosan nanoparticles against Hydroxyapatite nanoparticles, 60 male rats of albino were distributed to six equal groups. For thirty days, rats were given Nano chitosan for a dose of 140 mg per kilogram of body weight per day. For month, Nano Hydroxyapatite was administered daily at doses of 200 and 400 mg/kg body weight. Via oral gavage tube along the period of the experiment. The results showed that there was a substantial rise in the TBRAS levels, as well as a major drop in SOD, GSH and catalase activates in testicular tissues was detected in treated rats with low dose of hydroxyapatite nanoparticles (Ld HAP-NPs) as compared to high dose of hydroxyapatite. Conclusion: results revealed that; administration of rats with CNPs insignificant in total motility and progressive motilitycompared to the control group. Total motility and progressive motility were a significantly decrease in low or high dose of hydroxyapatite nanoparticles. After hydroxyapatite nanoparticles treatments, in rats given CNPs, there was a substantial reduction in sperm head abnormalities.

Background: Diabetes is one of the most important causes of mortality and morbidity all over the world. Renewal of functional pancreatic islets has been a goal of stem cell biologists since early 2000. Since that time, many studies have reported successful creation of glucose-responsive pancreatic beta-cells. Aim of work: This work aimed to study the effect of MSC.s alone and/or in combination with vitamin D3in Streptozotocin (STZ)- induced diabetic male albino rats to detect its potential therapeutic effect and its possible application to humans. Material and methods: Twenty-four male albino rats (150 – 170 grams) were included in this study. They were divided into four equal groups; each group have six rats: Group I (Normal: control of healthy), group II (STZ: control of diabetes), group III (diabetic group post-treated with MSC.s) and group IV (diabetic group post-treated with MSC.sin combination with vitamin D3). Diabetes was induced by intraperitoneal injection of STZ (50 mg/kg); MSC.s were injected intravenously into the rat tail vein in group III and group IV then left for sixweeks; vitamin D (cholecalciferol) was administered orally at 150 ng (500 IU/kg) each other day at three times per week for a long 6 weeks.Blood glucose leveland body weight were measured weekly for all groups at the beginning of the study at the intervalsixweeks. While, haematological parameters were measured after six weeks. Results: Diabetic group (group II) showed significant higher glucose levels while there was a significant lower body weight levels compared to control of non-diabetic group. Group IIIas well as group IV showed significant elevation of body weightand reduction of blood glucose level as well as amelioration of haematological parameters in compared to group II.Conclusion: treatment with MSC.sand/or in combination with vitamin D3 showed significant lower levels of glucose and higher body weight levels as compared to diabetic group.

Lithocholic acid (LCA) is a secondary bile acid that is selectively toxic to human neuroblastoma, breast and prostate cancer cells, whilst sparing normal cells. We previously reported that LCA inhibited cell viability and proliferation and induced apoptosis and necrosis of androgen-dependent LNCaP and androgen-independent PC-3 human prostate cancer cells. In the present study, we investigated the roles of endoplasmic reticulum (ER) stress, autophagy and mitochondrial dysfunction in the toxicity of LCA in PC-3 and autophagy deficient, androgen-independent DU-145 cells. LCA induced ER stress-related proteins, such as CCAAT-enhancer-binding protein homologous protein (CHOP), and the phosphorylation of eukaryotic initiation factor 2-alpha (p-eIF2α) and c-Jun N-terminal kinases (p-JNK) in both cancer cell-types. The p53 upregulated modulator of apoptosis (PUMA) and B cell lymphoma-like protein 11 (BIM) levels were decreased at overtly toxic LCA concentrations, although PUMA levels increased at lower LCA concentrations in both cell lines. LCA induced autophagy-related conversion of microtubule-associated proteins 1A/1B light chain 3B (LC3BI–LC3BII), and autophagy-related protein ATG5 in PC-3 cells, but not in autophagy-deficient DU-145 cells. LCA (>10 µM) increased levels of reactive oxygen species (ROS) concentration-dependently in PC-3 cells, whereas ROS levels were not affected in DU-145 cells. Salubrinal, an inhibitor of eIF2αdephosphorylation and ER stress, reduced LCA-induced CHOP levels slightly in PC-3, but not DU-145 cells. Salubrinal pre-treatment increased the cytotoxicity of LCA in PC-3 and DU-145 cells and resulted in a statistically significant loss of cell viability at normally non-toxic concentrations of LCA. The late-stage autophagy inhibitor bafilomycin A1 exacerbated LCA toxicity at subtoxic LCA concentrations in PC-3 cells. The antioxidantα-tocotrienol strongly inhibited the toxicity of LCA in PC-3 cells, but not in DU-145 cells. Collectively, although LCA induces autophagy and ER stress in PC-3 cells, these processes appear to be initially of protective nature and subsequently consequential to, but not critical for the ROS-mediated mitochondrial dysfunction and cytotoxicity of LCA. The full mechanism of LCA-induced mitochondrial dysfunction and cytotoxicity in the similarly sensitive DU-145 cells remains to be elucidated.

Background: Diabetes mellitus and hyperlipidemia are well-known risk factors for several illnesses including atherosclerosis, heart and vascular diseases and stroke. Herbal medicine is still the mainstay of about 75–80% of the world population, mainly in the developing countries, for primary health care because of better cultural acceptability, better compatibility with the human body and lesser side effects. Herbal extracts are introduced to the mankind since many centuries, several herbal extracts in different oral formulas have been recommended for diabetes mellitus and hyperlipidemia treatment all over the world. Objective: The present study was carried out to investigate the hypoglycemic, hypolipidemic and antioxidative effects of the extract of Bitter melon (Citrullus colocynthis) in young adult Sprague Dawley female rats for eight weeks. Materials and Methods: Forty female young adult Sprague Dawley female rats were divided into two sections. Section I (Normal animals) was S.C. injection with a vehicle (0.9% NaCl) and divided into two groups (10 rats / group), one of these served as control group and the second group was received extract of Bitter melon (Citrullus colocynthis) seed 50 mg/kg/day for 8 weeks and served as normal treated group. Group II was S.C. injection with Alloxan (diabetic rats) and divided into two group (10 rats each), one of these served as diabetic control group while the second group was received extract of Citrullus colocynthis (C-colocynthis) seed (50mg/kg/day) orally for 8 weeks and served as diabetic treated group. After 8-weeks experiment was terminated and animals were sacrificed, heart blood was drawn and sera were separated for assessment of blood glucose, lipid profile, and lipid peroxidation value (MDA), reduced glutathione (GSH), lactate dehydrogenase (LDH), alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) as well as total and direct bilirubin. Results: Both normal and diabetic rats showed a significant decrease in blood glucose, lipid peroxidation value (MDA), total cholesterol (TC), triglycerides (TG) as well as total and direct bilirubin. While, levels of reduced glutathione (GSH), lactate dehydrogenase (LDH), alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and total lipid were significantly increased in both normoglycemic and hyperglycaemic rats except ALT, AST and ALP in hyperglycaemic rats had no changes. Conclusions: The present study shed more of the light on the effect of Bitter melon (Citrullus colocynthis) extract and proves that this extract has antioxidant, hypoglycemic and hypolipidemic properties in the rats and may be used for treating diabetes mellitus.

Depo-Provera® is a contraceptive approved by the US Food and Drug Administration (FDA) since 1992 and used worldwide by more than 90 million women. Despite the fact that progestins are endogenous hormones that are secreted by the body, its excess might lead to detrimental health effects. Whether progestins as contraceptives are friends or foes is a questionable matter. In this manuscript, we drive the attention to both usage and side effects Depo-Provera. Depot-medroxyprogesterone acetate (DMPA) is a highly effective, convenient non-daily hormonal contraceptive option that has been available worldwide for many years. The experience with DMPA provides a large body of long-term data regarding the efficacy and safety of this contraceptive method; this long-term experience has established that the use of DMPA does not increase the risk of cardiovascular events, breast cancer, other gynecologic malignancy, or postmenopausal fracture; however, patients are often more concerned about the relatively immediate effects of contraceptives such as potential changes in menstrual cycle, body weight, and mood disturbances. Concerns about such issues may lead to reluctance to initiate therapy or premature discontinuation. Counseling and understanding of women’s concerns and experiences using Depo-Provera is important and could help health care providers redesign counseling strategies to improve contraceptive continuation and improve patient adherence.

Objectives: Freezing and in vitro culture of testicular spermatozoa or tissue are reliable approaches for the management of azoospermic patients and could all for the possibility of multiple IVF-ICSI procedures. However, the effect of cryopreservation duration on pregnancy outcome had been not fully examined. To analyze pregnancy outcome in patients underwent ICSI procedure in relation to duration of cryopreservation of the sperms. Materials: The present study included 62 couples who underwent to 255 cycles of ICSI; during the period from January 2013 to June 2014; in the International Islamic Centre for Population Studies and Researches. Couples of whom, male partner suffered from azoospermia underwent TESE for cryopreservation was included. Thawed testicular spermatozoa were used subsequently for an ICSI cycle. Women included in this study had also received routine infertility work-up. Frozen-thawed embryos were transferred on day 3–5. Clinical and ongoing pregnancy was defined as the presence of a gestational sac by transvaginal ultrasound in the 5th to 7th gestational week and the existence of a fetal heart beat at 12 weeks. Patient characteristics and pregnancy outcomes were documented.Results: The duration of cryopreservation had no effect on ICSI outcome, except significant difference between different groups as regard to cleavage rate (the higher cleavage rate was observed in second group, then fourth, fifth, first and third groups (it was 96.74±8.71, 94.50±8.82, 93.50±12.0, 92.35±12.47 and then 89.20±13.69 respectively). In addition, females in different groups were comparable as regard to personal characteristics.Conclusion: Duration of cryopreservation had no effect on pregnancy outcome.

Depo Provera®; (Medroxyprogesterone Acetate, DMPA) is a longacting, injectable progesterone derivative contraceptive that is currently used by 30 million women in 90 countries, including Egypt, United States and Canada. DMPA classified as sex hormone binding globulin (SHBG). The objective of this study was to investigate body weight and serum lipid profile following treatment of rats with the injectable contraceptive depot medroxyprogesterone acetate, (Depo Provera®; DMPA). Adult female rats (Rattus norvigcus) were treated with a single dose of DMPA that is comparable to the weightcorrected dose in humans (2.7 mg/rat or 5.4 mg/rat) and sacrificed on day ten or fifteen post treatment. Body weights were recorded and sera from both treated and control groups studied for lipid profile using a colorometric method. Treating animals with 2.7 mg/rat or 5.4 mg/rat of DMPA for 10 and 15 days led to a dose-related increase in the body weights (maximum ~ 24.77%). There was increase in total lipids (TL), triglycerides (TG), total cholesterol (TC) as well as low densitylipoprotein cholesterol (LDL-C) and very low density lipoprotein (VLDL-C). On the other hand, a marked decrease was found in high density-lipoprotein cholesterol (HDL-C) in the DMPA-treated groups. Statistical analysis indicated that these changes were significant (p 0.01) in all treated groups compared to control ones. We concluded that, this preliminary study indicates a long-term atherogenic role for DMPA. Keywords: Weight gain, Lipid Profiles; Injectable Contraceptives; Depo Provera®, LDL.

Fingolimod (FTY-720) and its non-immunosuppressive analogue (OSU2S) possess anticancer activity against hepatocellular carcinoma attributed to interference with protein kinase Cδ (PKCδ) signaling. Avascular penetration represents a major limitation for the treatment of solid tumors nonetheless colorectal cancer. Herein, we are assessing the differential antiproliferative activity of OSU2S compared to FTY720 against multicellular spheroids of HCT-116 and HT-29 colorectal cancer cell lines. In addition, we are comparing the avascular penetration properties of OSU2S to FTY720 within the avascular multicellular layers model. The IC50's of FTY720 and OSU2S were calculated in monolayer and spheroid culture models of HCT-116 and HT-29 cells using Emax model. Generally, OSU2S was found to be 1.5 to 3 folds more potent than FTY720 in both cell lines using monolayer and spheroid culture systems. The ratios between the IC50's of FTY720 in spheroid compared to monolayer cultures of HCT-116 and HT-29 cells were found to be to 5.7 and 3.4 folds, respectively. On the other hand, the ratios between the IC50's of OSU2S in spheroid compared to monolayer cultures of HCT-116 and HT-29 cells were found to be 4.5 and 3.4 folds, respectively. This might be attributed to avascular penetration problem for OSU2S and FTY720 in colorectal cancer. The pre-calculated IC50's of FTY720 and OSU2S induced significant increase in the cleaved fraction of PKCδ in both monolayer and spheroid model in HCT-116 and HT-29 cells. The influence of FTY720 and OSU2S on cell cycle analysis was studied using DNA flow cytometry analysis. Both FTY720 and OSU2S changed the cell cycle distribution of both HCT-116 and HT-29 cell lines in the monolayer culture and to a lesser extent in the spheroid culture model. The avascular penetration of OSU2S through multicellular layers of HCT-116 was 1.9 and 1.2 fold faster than FTY720 after 12 and 24 h of penetration, respectively. Also, OSU2S was faster than FTY720 in penetrating multicellular layers of HT-29 by 2.1 to 1.7 folds after 12 and 24 h of penetration, respectively. In conclusion, OSU2S possess better antiproliferative and avascular penetration profile within colorectal cancer cells compared to FTY720. Citation Format: Samir A. Zaahkouk, Serag Eldin I. Elbehairi, Aly F. El-Sayed, Sayed Bakry, Alaa Khedr, Hany A. Omar, Ahmed M. Al-Abd. Activity and avascular penetration of FTY720 (fingolimod) and its non-immune suppressant analogue (OSU2S) within three dimensional tissue culture model of colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4505. doi:10.1158/1538-7445.AM2015-4505