This study investigates the protective effects of taurine against infertility induced by radar electromagnetic radiation (EMR) in male rats. Exposure to radar EMR led to a significant decrease in reproductive hormone levels (e.g., testosterone), sperm quality (motility and count), and a marked increase in oxidative stress markers and reactive oxygen species (ROS) production. Taurine supplementation attenuated these effects by restoring the activities of key antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH)]. The research utilized 30 male albino rats divided into a control group, an EMR-exposed group, and a taurine-treated group. EMR exposure (2.5 GHz for 4 weeks) caused an approximately 40% decrease in testosterone levels and a 30% reduction in sperm motility. Taurine supplementation (2% in drinking water) effectively restored antioxidant enzyme levels to near-control values, reduced ROS production, and prevented testicular atrophy. The results underscore taurine's potential as a therapeutic agent to combat EMR-associated infertility, particularly in occupational settings with prevalent radar exposure. This study emphasizes the need for antioxidant interventions to protect reproductive health in high-EMR environments, aligning with broader research on taurine's role in mitigating oxidative stress in tissues like the liver, heart, and testes.
BACKGROUND:The molecular pathogenesis of hepatocellular carcinoma (HCC) exhibits striking etiological heterogeneity, with non-HCV-associated cases representing an increasingly prominent clinical challenge in regions like Egypt, where environmental carcinogens significantly contribute to the disease burden. METHODS:Through integrated analysis of genomic data Egyptian cohort comprising 48 HCC cases (23 non-HCV, 25 HCV-positive) was examined and validated against TCGA/ICGC datasets using cBioPortal and Cytoscape. RESULTS:This study identifies a distinct oncogenic program in non-viral HCC characterized by recurrent alterations in receptor tyrosine kinases (RTKs) FGFR1, MET, ERBB2 and FLT3. These mutations were found to be 4.3-fold more prevalent in non-HCV HCC compared to viral counterparts (26.1% vs. 6.0%, p=0.008), demonstrating strong etiological specificity. Functional characterization revealed these alterations converge on MAPK and PI3K-AKT-mTOR signaling cascades through shared adaptor proteins, creating an interconnected signaling network that drives tumor progression. CONCLUSION:Clinically, FGFR1/MET co-alterations predicted significantly worse outcomes (HR=2.3 for recurrence, 95% CI 1.1-4.8), while maintaining 92% specificity for non-viral HCC diagnosis. These findings establish the FGFR1-MET-ERBB2 axis as both a molecular classifier and therapeutic target, providing a rationale for etiology-specific management strategies in HCC precision oncology.
BACKGROUND:Although a wide variety of medicinal interventions and lifestyles have been endeavored so far for the treatment of diabetes mellitus, it is still intractable. The current study aimed to examine the effect of mesenchymal stem cells (MSCs) and/or placental extract (PE) on streptozotocin (STZ) induced diabetic rats. METHODS:Fifty male albino rats were used. Ten of them as negative control (group I) and the remaining forty rats were subjected to diabetes induction using 50 mg/kg STZ then divided into; group II (positive controls), group III (MSCs treated), group IV (PE treated), and group V (MSCs/PE combination treated). After 4 weeks of treatment, animals were sacrificed; blood samples were collected for determination of glycated hemoglobin by HPLC, and serum was separated for determination of glucose spectrophotometrically and insulin by ELISA. Pancreatic tissues were harvested for histopathological examination and pancreatic duodenal homeobox 1 (Pdx1) gene expression by PCR. RESULTS:The three treated groups showed significant enhancement in glycemic parameters and Pdx1 gene expression compared with positive control group (P < 0.05). Histopathological examination revealed great improvement in the three treated groups where group V showed the best picture and the best glycemic control. CONCLUSIONS:This study points to the possible role of PE in DM treatment. The MSCs/PE combination had the ability to return all parameters and Pdx1 gene expression to their normal levels. This action could be attributed to MSCs homing into the pancreas and the pancreatic rejuvenation provided by PE contents of growth factors; EGF, HGF, IGF-1 and IGF-II.
BACKGROUND:Malignant liver disease is among the highest in the world, with hepatocellular carcinoma (HCC) accounting for up to 90 % of all cases. In Egypt, HCC poses a significant public-health concern, representing 47.17 % of cancer cases. The high incidence of hepatitis C virus (HCV) in the Egypt was a major predisposing factor for HCC. MATERIAL:This study included 63 Egyptian HCC patients, 55 % of whom had a history of HCV infection. METHODS:Using a paired sampling strategy, approximately 2800 COSMIC mutations from 50 oncogenes and tumor-suppressor genes were NGS sequenced. RESULTS:Total of 381 somatic mutations were identified, 91 mutations detected in the HCC group and 291 in the HCV-related HCC group. The top 10 mutated genes in the non-HCV group were TP53, ATM, EGFR, CDH1, FGFR1, MET, SMAD4, ERBB2, FLT3, and FBXW7, while in the HCV-related HCC group, genes were KIT, ATM, TP53, APC, FBXW7, KDR, RB1, SMAD4, EGFR, and PIK3CA. CONCLUSION:The present study represents the first comprehensive somatic mutation profile in HCC Egyptian patients. This finding suggests that HCV viral infection played a direct and indirect role in increasing the somatic mutation burden in HCV-related HCC patients and opens new promises of targeted therapies for those patients.
Abstract Objective Premature ovarian insufficiency (POI) is a significant reproductive health concern characterized by the depletion of primary follicles, often resulting from exposure to genotoxic agents. This study aimed to explore the therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) and/or placental extracts (PE) in ameliorating POI induced by cyclophosphamide, a widely used chemotherapeutic agent. Materials and methods Thirty-five 8–10 weeks and weight 200 ± 20 g female albino Sprague–Dawley (SD) rats were evenly distributed into five groups: negative control (Group 1), positive control cyclophosphamide (CPA) (Group 2), stem cell therapy (CPA+MSCs) (Group 3), placental extract therapy (CPA+PE) (Group 4), and combination therapy (CPA+MSCs+PE) (Group 5). Rats in the CPA group received intraperitoneal (IP) cyclophosphamide injection (50 mg/kg), followed by daily (8 mg/kg) cyclophosphamide injection (14 days). Subsequently, the rats received 1 × 106 MSCs via intravenous administration and/or 50 µL of PE, followed by sacrifice after 4 weeks. Flow cytometry was used to identify MSCs. Hormone levels (FSH, LH, E2, and progesterone) were assessed using ELISA, and primordial follicles were quantified to evaluate primordial follicle reserves. Ovarian structure was histomorphologically evaluated, and PCNA immunohistochemistry was conducted. Morphometric measurements and statistical analyses were performed. Results Hormonal measurements revealed a decrease in E2 and progesterone levels, accompanied by an increase in FSH levels following cyclophosphamide treatment. However, after BM-MSC therapy, hormonal levels nearly returned to normal. In addition to BM-MSC therapy, PE treatment was also evaluated. PE administration resulted in partial restoration of hormonal balance, showing a mild increase in E2 and progesterone levels, with a slight reduction in FSH levels compared to the cyclophosphamide-treated group. Histological examination revealed that cyclophosphamide caused significant loss of primordial follicles, stromal blood vessel damage, and substantial fibrosis. Interestingly, combination of MSCs and PE treatment showed some ameliorative effects on ovarian histology, with reduced fibrosis and slight preservation of ovarian follicles, although these changes were less pronounced than those observed with BM-MSC therapy alone. Conclusion MSCs therapy was more effective in restoring ovarian folliculogenesis, whereas combination with PE provided moderate protection against the histological and immunohistochemical alterations induced by cyclophosphamide.
BACKGROUND:Non-obstructive azoospermia (NOA) represents an infertility problem that is usually difficult to treat. Such patients usually have testicular biopsy of germ cell aplasia or spermatogenic arrest. In recent decades, mesenchymal stem cells (MSCs) had been studied thoroughly and proved safe and effective regarding their capability for trans-differentiation into different cell types. The aim of this study was to evaluate the effect of MSCs local intratesticular injection in induction of spermatogenesis.PATIENTS AND METHOD:The current study included 87 infertile non-obstructive azoospermic patients. Clinical assessment and repeated semen analysis with centrifugation were done to confirm azoospermia. Karyotyping and AZF study were done. Some of the patients had previous testicular biopsy proving a lack of sperm in the testes. Single intratesticular injection of purified MSCs suspension was done.RESULTS:20.7% of patients showed sperm in their semen after variable period of time. Hormonal profile among treated patients showed significant improvement regardless success of treatment. Also most of the treated patients appreciated the improvement of their sexual function and libido.CONCLUSIONS:Bone marrow derived MSCs could be a new hope and therapeutic modality for treatment of refractory cases of NOA.
This study investigates the therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) in treating premature ovarian failure (POF) induced by chemotherapy. Twenty-one female Albino Sprague Dawley rats were divided into three groups: a negative control group, a positive control group receiving cyclophosphamide (CPA) to induce POF, and a treatment group receiving BM-MSC therapy following POF induction. Hormonal levels of FSH, LH, E2, and progesterone were measured using ELISA, and the ovarian structure was assessed histologically. BM-MSC homing in the ovary was confirmed using PKH-26 labelled cells under a fluorescent microscope.Results showed that CPA administration increased FSH levels and decreased E2 and progesterone levels, along with significant loss of primordial follicles, stromal blood vessel damage, and fibrosis. In contrast, BM-MSC therapy facilitated near-normal restoration of hormonal levels, enhanced ovarian folliculogenesis, and mitigated histological damage. Specifically, BM-MSCs helped restore the balance of E2, progesterone, and FSH levels and repaired the ovarian structure by reducing fibrosis and blood vessel damage. The study concludes that BM-MSCs significantly regenerate follicle maturation in CPA-induced ovarian damage, highlighting their potential as a therapeutic option for mitigating chemotherapy-induced POF.
Burn injuries pose a significant healthcare burden worldwide, often leading to long-term disabilities and reduced quality of life. To explore the impacts of the transplantation of mesenchymal stem cells (MSCs) on the healing of burns and the levels of serum cytokines, 60 fully grown Sprague–Dawley rats were randomly divided into three groups ( n = 20 each): group I (control), group II (burn induction), and group III (burn induction + bone marrow (BM)-MSC transplantation). Groups II and III were further divided into four subgroups ( n = 5 each) based on euthanasia duration (7, 14, 21, and 28 days post transplant). The experiment concluded with an anesthesia overdose for rat death. After 7, 14, 21, and 28 days, the rats were assessed by clinical, laboratory, and histopathology investigations. The results revealed significant improvements in burn healing potentiality in the group treated with MSC. Furthermore, cytokine levels were measured, with significant increases in interleukin (IL)-6 and interferon alpha (IFN) observed, while IL-10 and transforming growth factor beta (TGF-β) decreased at 7 days and increased until 28 days post burn. Also, the group that underwent the experiment exhibited increased levels of pro-inflammatory cytokines and the anti-inflammatory cytokine IL-10 when compared to the control group. Histological assessments showed better re-epithelialization, neovascularization, and collagen deposition in the experimental group, suggesting that MSC transplantation in burn wounds may promote burn healing by modulating the immune response and promoting tissue regeneration.
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. Effective treatment is usually hampered by financial issues. As a result, less expensive medications that reduce both inflammation and bone resorption are required. Mesenchymal stem cells (MSCs) have recently been identified as a potential therapy for RA.Aim of the study: This study aimed to examine the anti-arthritic effect of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs), oligosaccharides (Os), and human placental extract (HPE), individually and combined, on an 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 the hind limb. Rat bone marrow-MSCs, oligosaccharides, and human placental extract (HPE) were given individually and in combination via the intraperitoneal route. A complete blood count (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.Results: Combining oligosaccharides and HPE therapy with the infusion of rat-bone marrow MSCs had beneficial antiarthritic and anti-inflammatory effects in CFA-induced arthritis in rats: overall such triple therapy significantly reduced serum levels of IL-6, IL-10, and TNF-alpha in comparison with all other combinations (all P > 0.05). Meanwhile, the triple therapy did not have negative effects on levels of CBC, serum cortisol, ESR, and liver enzymes (all NS) as well as on renal functions (NS). Also, the histopathological analysis showed significant improvements in the healing and remodelling of osteoporotic lesions in arthritic rats. As shown by counting apoptotic cells as a histopathological substitute for measuring apoptotic or regeneration markers, the lowest count was found in the group treated with a triple therapy of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs), oligosaccharides, and HPE.Conclusion: The combination of rat MSCs, oligosaccharides, and HPE has the potential to be an effective treatment for rheumatoid arthritis.
Syzygium Aromaticum (clove) and Nigella sativa (black seed), traditional medicinal herbs, display broad anticancer activity. The observations supported these oils' anti-proliferative and cytotoxic activities by MTT assay. The cold-pressed extracted oil was evaluated against cervical (HeLa), pancreatic (Panc), and colon (HCT) carcinoma cells compared to doxorubicin. Clove oil had the lowest IC50 values against HeLa, HCT, and Panc cells, which were 0.25, 0.38, and 5.26 1.1g/ml, respectively. Black seed oil was next, with IC50 values of about 5.51, 4.24, and 22.7 1.1g/ml, respectively. These oils were extra potent than the reference drug, doxorubicin, which had IC50 values of about 101, 188, and 244 1.1g/ml. According to a flow cytometry study, clove oil causes cell death in HeLa cells more than the medication doxorubicin. Clove oil has proven to possess strong inhibitory activity of the expression of anti-apoptotic protein Bcl-2 than doxorubicin. The Dip henylamine method demonstrated that clove oil causes DNA damage and increases DNA fragmentation rate more than doxorubicin. GC/MS results showed that the clove and black seed contain many valuable anticancer compounds, such as p-cymene, a-Longipinene, Idebenone, and caryophyllene for black seed and eugenol for clove. Clove oil is therefore regarded as an excellent natural anticancer agent superior to chemotherapy medications with long-term side effects.
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.
The 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.
The purpose of this study is to assess a potential association between reproductive hormone levels and testicular volumes with testicular biopsy in men with non-obstructive azoospermia (NOA) undergoing testicular sperm extraction (TESE).The complete records of 100 azoospermia men without clinical evidence of obstructive etiologies who underwent TESA.Preoperative diagnostic biopsies were not obtained and thus men with presumed NOA were defined as having no evidence of obstruction by history or physical examination.Preoperative FSH, LH and testosterone were obtained for all patients and bilateral testicular volume was determined to find the correlation between probabilities of positive sperm extraction with TESE.Two subgroups of NOA were evaluated (Group 1 TESE and Group 2 Fresh ejaculated).Results: There were significant differences in FSH, levels, in group 2 compared to group 1, and no significant differences in LH, PRL, Testosterone, and E2.Furthermore, no significant differences in right testicular volume, and left testicular volume in the two groups.The success rate of TESE was decreased when increased FSH and LH levels.In NOA cases increased FSH and LH levels, and decreased testis volumes have a negative effect on sperm retrieval but small testicular volumes only can present sperm retrieval.
Purpose: to assess safety and efficacy of autologous mesenchymal bone marrow stem cell injection in penile cavernosal tissue for erectile dysfunction therapy in diabetic men. Methods: The subjects of this study were diabetic men suffering erectile dysfunction, non-responding to maximum dose of oral PDE5I. Mesenchymal bone marrow stem cells were aspirated and injected after preparation in both corpora cavernosa at 3, 9 o’clock position. Erectile function was assessed by the International Index of Erectile Function and penile Doppler study, before and after 6 months after injection. Results: 4 patients out of 10 achieve hard erection adequate for satisfactory coitus, and 2 patients achieved penile hardness with addition of pharmacological therapy with sildenafil 100mg. Peak systolic velocity increased significantly in 4 patients (2 arteriogenic and 2 mixed erectile dysfunction), from 12∼22 cm/s to 32∼69 cm/s. Variations in end-diastolic velocity increased substantially in 2 patients with venogenic insufficiency alone at follow-up from 4∼5 cm /s to -4∼-3 cm/s. Conclusions: Despite promising stem cell treatment efficacy for patients with erectile dysfunction, more clinical studies and researches are still warranted.
Tissue engineering is emerging as an interdisciplinary field in biomedical engineering that aims to regenerate new biological material for replacing diseased or damaged tissues or organs. So far, some research has been carried out to find medicines that may halt the advancement of these diseases. However, despite recent improvements, existing medicines are still limited by inadequate translation into practical applications. This chapter provides an up-to-date overview of the most recent advances in the applications of biodegradable polymers with high processing flexibility as the primary scaffolding materials for therapeutically relevant regenerative tissue methods. In addition, their successes, limits, and future clinical translation potential are highlighted. The possibility of applying them to treat some incurable diseases, such as osteoporosis, cardiovascular diseases, and skin wounds, is also discussed. Aside from chemical functionalization, scaffold designs that mirror the micro- and nano-characteristics of the extracellular matrix (ECM) will be described as composite and nanocomposite scaffolds.
Infertility is defined as the inability to achieve a clinical pregnancy during at least 12 months of consistent and unprotected sexual intercourse.This condition is characterized as a dysfunction of the reproductive system.Only men are thought to be involved in 45% of infertility cases, whereas 20% include both men and women.Male infertility is known to be influenced by variable lifestyle factors like smoking, radiation, or radioactive exposure that may harm biological tissue organs, such as the testis.Although there appears to be a link between increasing exposure to radiofrequency on mobile phones and decreased sperm quality, the evidence is not inconclusive.The primary lifestyle elements that contribute to a decline in male reproductive health are taken into account.These include aging, obesity, poor diet, inactivity, smoking, excessive alcohol use, stress, and low-level radio-frequency electromagnetic radiation (from mobile phones and portable computers).This work aims to study the influence of smoking and electromagnetic radiation on the efficiency of fertility in males, their effect on sperm quality and efficiency, and fertilization rate.The study population included 100 couples who were referred to Al Azhar University's International Islamic Center for Population Studies and Research's Fertility Clinic for assisted reproduction.The obtained results showed that the smoking male recorded a remarkable decline in sperm count and motility, fertilization rate, and embryo grading.The multifactor group recorded the same results, in addition to a significant increase in abnormal sperm morphology.Conclusion: Personal wrong lifestyles such as smoking and exposure to electromagnetic waves led to a decline in male reproductive health and reduced sperm count, motility, morphology, fertilization rate, and embryo quality.
Stem cell therapies hold promise for enhancing infertility treatments through improved differentiation and cytokine secretion mechanisms, particularly autologous stem cells known for safety and compatibility. Collaboration and ongoing research are essential for clinical adoption. Additionally, cell-based treatments offer potential solutions for non-obstructive azoospermia NOA, a condition characterized by absent sperm in ejaculate. Traditional therapies have limitations, prompting exploration of spermatogonial stem cells SSCs and induced pluripotent stem cells iPSCs. Animal studies demonstrate successful fertility restoration via SSC transplantation, and progress has been made in characterizing human SSCs. However, challenges persist in expanding human SSCs and optimizing iPSC differentiation. Further research is necessary to overcome technical hurdles, ensure safety, and offer a novel NOA treatment option, ultimately restoring fertility.
This work explores the revolutionary potential that arises from combining nanosensors with stem cell technologies and regenerative medicine. The objective is to revolutionize the field of medical treatments by integrating nanosensors into these advanced technologies and therapeutic approaches, offering new possibilities for a diverse array of conditions. The primary aim is to investigate and analyze the benefits, challenges, and ethical complexities that emerge when incorporating nanosensors into these cutting-edge medical practices. By conducting a thorough examination of these crucial elements, we will acquire a more profound understanding of the wide-ranging impacts of this technology, as well as the crucial decisions that need to be addressed and resolved before moving forward.