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Neurodegenerative diseases refer to a group of neurological disorders as a consequence of various destructive illnesses, that predominantly impact neurons in the central nervous system, resulting in impairments in certain brain functions. Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and other neurodegenerative disorders represent a major risk to human health. In order to optimize structural and functional recovery, reconstructive methods integrate many approaches now, to address the complex and multivariate pathophysiology of neurodegenerative disorders. Stem cells, with their unique property of regeneration, offer new possibilities in regenerative and reconstructive medicine. Concurrently, there is an important role for natural products in controlling many health sufferings and they can delay or even prevent the onset of various diseases. In addition, due to their therapeutic properties, they have been used as neuroprotective agents to treat neurodegenerative disorders. After decades of intensive research, scientists made advances in treating these disorders so far, but current therapies are still not capable of preventing the illnesses from progressing. Therefore, in this review, we focused on a new perspective combining stem cells and natural products as an innovative therapy option in the management of neurodegenerative diseases.

PURPOSE: The aim of this investigation was to design a perfusion-based decellularization protocol to provide whole human uterine bio-scaffolds with preserved structural and componential characteristics and to investigate the in vivo properties of the decellularized tissues. METHODS: Eight human uteri, donated by brain-dead patients, were decellularized by perfusion of sodium dodecyl sulfate (SDS) through the uterine arteries using a peristaltic pump. The bio-scaffolds were evaluated and compared with native human uterus regarding histological, immunohistochemical, structural, and bio-mechanical properties, in addition to CT angiographies to examine the preservation of the vascular networks. Subsequently, we obtained acellular patches and implanted them on uterine defects of female Wistar rats to investigate the bio-compatibility and regenerative potential of the bio-scaffolds. Finally, we performed immunostaining to investigate the potential role of circulating stem cells in recellularization of the implanted bio-scaffolds. RESULTS: The outcomes of this investigation confirmed the efficacy of the proposed protocol to provide whole human uterine scaffolds with characteristics and extra-cellular matrix components similar to the native human uterus. Subsequent in vivo studies demonstrated the bio-compatibility and the regenerative potential of the scaffolds and suggested a signaling pathway as an underlying mechanism for the regenerative process. CONCLUSIONS: To the best of our knowledge, this investigation provides the first efficient perfusion-based decellularization protocol for the human uterus to obtain whole-organ scaffolds. The outcomes of this investigation could be employed in future human uterus tissue engineering studies which could ultimately result in the development of novel treatments for female infertile patients.

Background: Silkworm products were first used by physicians more than 8500 years ago, in the early Neolithic period. In Persian medicine, silkworm extract has several uses for treating and preventing neurological, cardiac, and liver diseases. Mature silkworms (Bombyx mori) and their pupae contain a variety of growth factors and proteins that can be used in many repair processes, including nerve regeneration. Objectives: The study aimed to evaluate the effects of mature silkworm (Bombyx mori), and silkworm pupae extract on Schwann cell proliferation and axon growth. Methods: Silkworm (Bombyx mori) and silkworm pupae extracts were prepared. Then, the concentration and type of amino acids and proteins in the extracts were evaluated by Bradford assay, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and liquid chromatograph-mass spectrometer (LC-MS/MS). Also, the regenerative potential of extracts for improving Schwann cell proliferation and axon growth was examined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay, electron microscopy, and NeuroFilament-200 (NF-200) immunostaining. Results: According to the results of the Bradford test, the total protein content of pupae extract was almost twice that of mature worm extract. Also, SDS-PAGE analysis revealed numerous proteins and growth factors, such as bombyrin and laminin, in extracts that are involved in the repair of the nervous system. In accordance with Bradford's results, the evaluation of extracts using LC-MS/MS revealed that the number of amino acids in pupae extract was higher than in mature silkworm extract. It was found that the proliferation of Schwann cells at a concentration of 0.25 mg/mL in both extracts was higher than the concentrations of 0.01 and 0.05 mg/mL. When using both extracts on dorsal root ganglion (DRGs), an increase in length and number was observed in axons. Conclusions: The findings of this study demonstrated that extracts obtained from silkworms, especially pupae, can play an effective role in Schwann cell proliferation and axonal growth, which can be strong evidence for nerve regeneration, and, consequently, repairing peripheral nerve damage.

Background: This study was conducted to investigate the effects of intravitreal injection of bone marrow mononuclear stem cells (BMMNC) on neurological and vascular damages in a rat model of retinopathy of prematurity (ROP). Methods: Ten newborn Wistar rats were divided randomly into the control and the oxygen-induced retinopathy (OIR) group. Animals in the OIR group were incubated in an oxygen chamber to induce retinopathy. One eye of animals in the OIR group received BMMNC suspension (treated eyes), and the contralateral eye received the same volume of saline injection. Then, all animals underwent funduscopy, electroretinography, and histopathological assessments. Results: Compared to the saline injection group, eyes treated with BMMNC had less vascular tortuosity while veins and arteries had relatively same caliber, as revealed by fundus examination. Eyes in treatment group showed significantly elevated photopic and scotopic B waves amplitude. In histopathological assessments, nuclei count in inner retinal layer in the treatment group was significantly lower compared to untreated eyes. Also, BMMNC transplantation reduced apoptosis of neural retina cells. Conclusions: Our results indicated that intravitreal injection of BMMNC reduces neural and vascular damages and results in recovered retinal function in rat model of ROP. Ease of extraction without in vitro processing, besides the therapeutic effects of BMMNCs, make this source of stem cells as a new choice of therapy for ROP or other retinal ischemic diseases in further biomedical research.

In the modern era of science, nanotechnology has the ability to circumvent numerous disadvantages of conservative healing preparations. Important progress has been made towards the use of tailored nanomaterials (NMs) to treat the cancer with efficiency, specificity, and high sensitivity. Tailored NMs are operationalized with precise ligands that can predictably target the cancer cells and deliver encapsulated payloads meritoriously. Moreover, NMs can also be deliberated to increase the drug loading, controlled release, improved half-life, and selective distribution by altering their size, surface chemistry, composition, and morphology. The conservative cancer treatments have provoked the event and applications of nanomaterials. The emerging evidence suggests that nanomedicines will provide the next-generation stages for anticancer remedies.

Neurogenic lower urinary tract dysfunction (NLUTD), a challenging disorder, is defined by lack of bladder control due to the abnormalities in neural pathways and can be classified based on the location of lesions within the nervous system, thus investigating the neural pathways can help us to know the site of the lesion and specify the class of the NLUTD. Diffusion Tensor Imaging (DTI) tractography, a noninvasive advanced imaging method, is capable of detecting central nervous system pathologies, even if routine magnetic resonance imaging shows no abnormality. Accordingly, tractography is an ideal technique to evaluate patients with NLUTD and visualize the pathology site within the spine. This study aimed to introduce a novel method of spinal cord injury (SCI) to establish NLUTD in the rabbit and to investigate the potential of tractography in tracing neural tracts of the spinal cord in an induced NLUTD animal model.An animal model of NLUTD was induced through cauterization of the spinal cord at the level T12-L1 in 12 rabbits. Then rabbits were assessed via DTI, urodynamic studies (UDS), voiding cystourethrogram (VCUG), and pathology assessments using antineurofilament 200 (NF200) antibody, anti-S100, anti-Smooth Muscle Actin, anti-Myogenin, and anti-MyoD1.The tractography visualized lesions within spinal cord fibers. DTI parameters including fractional anisotropy (FA) value and tract density were significantly decreased (FA: p-value = 0.01, Tract density: p-value = 0.05) after injury. The mean diffusivity (MD) was insignificantly increased compared to before the injury. Also, the results of UDS and pathology assessments corroborated that applying SCI and the establishment of the NLUTD model was completely successful.In the present study, we investigated the auxiliary role of tractography in detecting the spinal cord lesions in the novel established rabbit model of NLUTD. The introduced method of NLUTD induction was without the leg's neurological deficit, easily applicable, low-cost, and was accompanied by minimal surgical preparation and a satisfactory survival rate in comparison with other SCI animal models.

Neural tube defects (NTDs) are among the most common congenital defects during neurulation. Spina bifida is a type of NTD that can occur in different forms. Since myelomeningocele (MMC) is the most severe form of spina bifida, finding a satisfactory treatment for MMC is a gold standard for the treatment of spina bifida. The Management of Myelomeningocele Study (MOMS) demonstrated that intrauterine treatment of spina bifida could ameliorate the complications associated with spina bifida and would also reduce the placement of ventriculoperitoneal (VP) shunt by 50%. Recently developed tissue engineering (TE) approaches using scaffolds, stem cells, and growth factors allow treatment of the fetus with minimally invasive methods and promising outcomes. The application of novel patches with appropriate stem cells and growth factors leads to better coverage of the defect with fewer complications. These approaches with less invasive surgical procedures, even in animal models with similar characteristics as the human MMC defect, paves the way for the modern application of less invasive surgical methods. Significantly, the early detection of these problems and applying these approaches can increase the potential efficacy of MMC treatment with fewer complications. However, further studies should be conducted to find the most suitable scaffolds and stem cells, and their application should be evaluated in animal models. This review intends to discuss advanced TE methods for treating MMC and recent successes in increasing the efficacy of the treatment.

Introduction Approximately 15% of couples in the reproductive age are struggling with infertility which, in nearly half of them, is caused by male factors. Material and methods The present study comprised of two groups of sixteen C57BL/6 mice; each mouse received either an intraperitoneal injection of 30 mg/kg of an alkylating agent or the same amount of distilled water. Testes were harvested 30 days following the injection. Morphometric analysis of hematoxylin and eosin (H&E) stained slides including mean tubular area, diameter and intratubular particles were performed. Spermatogenesis rate was assessed by spermatogonial markers including promyelocytic leukemia zinc finger protein (PLZF) and neurogenin-3 (NGN3). Moreover, the expression rate of Wilms Tumor-1 (WT-1), A-Kinase Anchoring Protein 4 (AKAP4) and adenosine deaminase domain containing 1 (ADAD1) genes were evaluated via real-time polymerase chain reaction (RT-PCR). Results The body weight gradually increased in both groups after a period of 30 days, however, the increase was significantly (p-value = 0.023) lower in the chemically treated group. All the morphometric parameters were considerably decreased in the azoospermic mice. Also, promyelocytic leukemia zinc finger protein and neurogenin-3 expression dramatically declined (p-value

Context: Previous studies have noted that the incidence of inflammatory and fibrotic diseases is higher in diabetic menopausal women.Objective: In the present study, we evaluated effects of swimming training on inflammatory and fibrotic biomarkers in the lung of ovariectomized diabetic rats.Materials and methods: Forty female rats were assigned into four groups: sham; rats underwent surgery without ovariectomies, OVX: rats that underwent ovariectomies, OVX.Dia: ovariectomized rats with high-fat diet, OVX.Dia. Exe: ovariectomized diabetic rats with 8 weeks of swimming training. At the end of experiment, protein expressions were assessed with western blot. Lung sections were subjected to immunohistochemical and haematoxylin eosin staining.Results: There was a significant difference in the protein expressions between exercise and ovariectomized diabetic groups (p < .05).Conclusion: The present study showed strong potential of swimming training on oestrogen deficient diabetic lung. These data encourage further investigation into the inclusive effects of exercise in menopausal diabetic women.

Silk worm (Bombyx Mori) protein, have been considered as potential materials for a variety of advanced engineering and biomedical applications for decades. Recently, silkworm silk has gained significant importance in research attention mainly because of its remarkable and exceptional mechanical properties. Silk has already been shown to have unique interactions with cells in tissues through bio-recognition units. The natural silk contains fibroin and sericin and has been used in various tissues of the human body (skin, bone, nerve, and so on). Besides, silk also still has anti-cancer, anti-tyrosinase, anti-coagulant, anti-oxidant, anti-bacterial, and anti-diabetic properties. This article is supposed to describe the diverse biomedical capabilities of Bombyx Mori silk as the appropriate biomaterial among the assorted natural and artificial polymers that are presently accessible, and ideal for usage in regenerative medicine fields. This article is protected by copyright. All rights reserved.

The extracellular matrix (ECM) of mammalian organs and tissues has been applied as a substitute scaffold to simplify the restoration and reconstruction of several tissues. Such scaffolds are prepared in various arrangements including sheets, powders, and hydrogels. One of the more applicable processes is using natural scaffolds, for this purpose discarded tissues or organs are naturally derived by processes that comprised decellularization of following tissues or organs. Protection of the complex structure and 3D (three dimensional) ultrastructure of the ECM is extremely necessary but it is predictable that all protocols of decellularization end in disruption of the architecture and potential loss of surface organization and configuration. Tissue decellularization with conservation of ECM bioactivity and integrity can be improved by providing well-designed protocols regarding the agents and decellularization techniques operated during processing. An overview of the characterization of decellularized scaffolds and the role of reagnets can validate the applied methods' efficacy.

Lung transplantation may be considered as a final treatment option for diseases such as chronic lung disease, pulmonary hypertension, bronchopulmonary dysplasia, pulmonary fibrosis, and end-stage lung disease. The five-year survival rate of lung transplants is nearly 50%. Unfortunately, many patients will die before a suitable lung donor can be found. Importantly, the shortage of donor organs has been a significant problem in lung transplantation. The tissue engineering approach uses de- and recellularization of lung tissue to create functional lung substitutes to overcome donor lung limitations. Decellularization is hope for generating an intact ECM in the development of the engineered lung. The goal of decellularization is to prepare a suitable scaffold of lung tissue that contains an appropriate framework for the functionality of regenerated lung tissue. In this chapter, we aim to describe the decellularization protocols for lung tissue regenerative purposes.

Objective: To investigate whether miRNAs have a remarkable pooled diagnostic accuracy, sensitivity, and specificity as noninvasive biomarkers to distinguish endometriosis patients from non-endometriosis women.Methods: A comprehensive literature search of PubMed, Embase, and ProQuest was performed through February 21, 2021 to find relevant studies. Two reviewers independently screened each article, and discrepancies were resolved by consensus. Deeks' funnel plot asymmetry test was performed to assess the publication bias of included studies. The STATA software and RevMan 5.4 were used for data analysis and quality assessment, respectively.Results: The overall quality of the studies was moderate to high. In total 87 datasets were assessed miRNAs' performance which results in sensitivity: 0.82, specificity: 0.79, DOR: 18, NPV: 0.80, PPV: 0.78, PLR: 3.97, and NLR: 022. We conducted subgroup analyses, which showed panels of miRNAs (DOR: 54) and serum (DOR: 43) as a target tissue was more reliable to utilize as biomarkers. Deeks' funnel plot showed that there is no publication bias (P-value = 0.25).Conclusions: Panels of miRNAs differentiate endometriosis patients from non-endometriosis women with high sensitivity and specificity; therefore, it has the potential to use as a noninvasive biomarker.

Objectives: In the present study, a new engineered bulking agent called lyophilized micronized prepuce was examined as a natural scaffold to compare its safety and efficacy with the Urodex®. Methods: For an in vivo study, 12 rabbits were divided into two groups. In the first group (n = 6), 0.2 cc of lyophilized and micronized prepuce, and in the second group, 0.2 cc of Urodex® was injected into the seromuscular wall of the bladder. The biopsy was provided from all animals for histological evaluation in 3 and 6 months’ post-surgery and for each timeline 12 animals were assigned. The biopsies were stained with H&E and trichrome Masson. IHC staining was also performed with anti-LCA+, anti-CD34+, and anti-CD68+ antibodies. Resluts: Microscopic examination of acellular prepuce compared with normal tissue demonstrated the success of this process, and ECM and collagen fibers were preserved with no evidence of cellular remnants in the acellular tissue, Immunohistochemistry staining with CD68 and LCA revealed a higher inflammation grade in Urodex as compared with Prepuce. However, no significant difference was detected in CD34 staining between Prepuce and Urodex experimental groups SEM analysis detected the micronized particle size varying between 2-5 µm. MTT assay revealed that cell proliferation was similar in the presence of control group and acellular prepuce. Conclusion: The results of this study disclosed that lyophilized and micronized prepuce could be an operative alternative to Urodex® as a natural and non-synthetic bulking agent in the treatment of children with vesicoureteral reflux (VUR).

Bladder Exstrophy (BE) has been considered as a rare congenital malformation of the genitourinary system, with an estimated incidence of approximately 1 per 50,000 live births [1]. The management of this anomaly is complex, involving several surgical reconstructions with numerous challenges to achieve anatomically, functionally, and cosmetically satisfactory outcomes [2]. Furthermore, the management must be early in the first months of life for better functional and cosmetic results [3,4]. Wound dehiscence, urethral outlet obstruction, bladder prolapsed, renal and bladder calculi are among the main complications following failed primary BE closure [5]. Urinary stone formation is estimated to be around 15% following bladder closure, in repaired BE patients, especially in cases living in poor or rural regions [6]. Bladder stone formation may occur following infra-vesical obstruction, neurogenic voiding dysfunction, urinary tract infection, foreign bodies, and metabolic risk factors years after reconstructive surgery [7]. Here, we report a 6-yearold boy with failed BE repair at an early age that was complicated by late surgery outcomes and secondary stone formation on missed sutured surgical sponge post-operatively.

Background and Purpose: Mitochondrion is the main indicator of oocyte quality and one of the components of oocyte, which is sensitive to oxidative damage during the maturation process. Mitoquinone mesylate (MitoQ) is a strong antioxidant targeting mitochondria as well as anti-apoptotic agent. However, the effect of MitoQ on the quality of oocytes during in vitro maturation (IVM) is still unknown. Objectives: This study investigated the possible effects of MitoQ on maturation and developmental competency in mice oocytes. Materials and Methods: The oocytes were collected at germinal vesicle stage from 6-8-week old female NMRI mice and then cultured in TCM-199 medium supplemented with 0, 0.01, 0.02 and 0.04 µM MitoQ. The sham group was treated with DMSO (0.01% v.v). Then intracellular Glutathione (GSH), reactive oxygen species (ROS) levels, mitochondria membrane potential (ΔΨm), as well as in vitro fertilization (IVF) rate in the 18-20 h matured oocytes and metaphase II (MII) oocytes (in vivo-control), were assessed. Results: The results showed that between three dose of MitoQ, the 0.02 µM significantly increased nuclear maturation rate, GSH level, fertilization rate and blastulation (92.6, 231.7, 90.19 and 81.66%, respectively) than the in vitro-control (71.14, 152, 78.84 and 73.50%, respectively) and more comparable to that of the in vivo matured oocytes (100, 243.5, 92.10 and 83%, respectively). Also, the mitochondria membrane potential in the 0.02 µM MitoQ was significantly higher compared with those in the other groups (4.4). However, the intracellular ROS level in 0.02 µM MitoQ was significantly decreased (38.72%) compared to in vitro-control (82.2%) and was similar to the in vivo-control (33.5%). Conclusion: The results indicated that supplementation of IVM medium with MitoQ (specially 0.02 µM) enhance maturation and fertilization rate. In conclusion, MitoQ might be considered as a novel component that could be added to IVM media.

Background Phytoestrogens are suggested to have estrogenic effects in the pulmonary system and have been revealed with a few adverse side effects. In this study, we tried to investigate the effect of genistein treatment on estrogen deficiency-induced lung injury and demonstrating whether genistein supplementation could replace estrogen hormone in postmenopausal women. Methods Forty adult female rats were divided into four groups; sham: rats that underwent surgery without ovariectomy, OVX: rats that underwent ovariectomies, OVX.E: ovariectomized rats with eight weeks period of estrogen treatment (20µg/kg/day), OVX.Gen: ovariectomized rats with eight week period of genistein treatment (1mg/kg/day). At the end of the experiment, lung tissue was removed and inflammatory and fibrotic biomarkers were evaluated with western blotting technique. Hematoxylin-eosin and immunohistochemical staining were used to evaluate histomorphological changes in the lung tissue. Results Genistein treatment restored ERK1/2, TGFβ1, MMP2, and IL1β, Bcl-2, and caspase3 expression levels, implying the effectiveness of genistein supplementation in targeting estrogen deficiency symptoms. Conclusions Genistein supplementation exerted protective effects against ovariectomy-induced lung injury with reducing inflammation and fibrosis, moreover, it can be recommended as a natural alternative to postmenopausal hormone therapy.

The endometrium has stem cell niches that contribute to the regeneration of the endometrial tissue following menstruation. These cells potentially could serve as a foundation of adult stem cells aimed at autologous stem cell-based therapies. A mechanistic understanding of these cells and their role in endometrial regeneration may aid to the intentional stimulation of a patient’s endometrial stem cell niche for regenerative therapies. The first evidence reporting their presence described endometrial stem cell as a clonogenic cell population in the human epithelial and stromal endometrium. Clonogenicity of epithelial cells was well supported by transforming growth factor-α (TGFα), epidermal growth factor (EGF), and platelet-derived growth factor-BB (PDGF-BB). Leukemia-inhibitory factor, hepatocyte growth factor (HGF), stem-cell factor (SCF), and insulin-like growth factor-I (IFG-I) were inadequately supportive and basic fibroblast growth factor (bFGF) did not affect clonogenicity of epithelial cells. About 3% of epithelial and 6% of stromal cells in mouse endometrium are label-retaining cells (LRCs). Moreover, CD146+ PDGF-Rβ+ human endometrial stem cell shows MSCs-like properties. Stromal cells are abundant in colony-forming cells that undergo differentiation into mesenchymal lineages and express MSC-specific surface markers CD29, CD44, CD73, CD90, and CD105. Further investigations have corroborated the evidence for MSC presence in endometrial stroma. The book chapter will provide an in-depth insight into the importance of uterine stem cell and their role in the pathogenesis of female reproductive tract diseases.

The extracellular matrix (ECM) of mammalian organs and tissues has been applied as a substitute scaffold to simplify the restoration and reconstruction of several tissues. Such scaffolds are prepared in various arrangements including sheets, powders, and hydrogels. One of the more applicable processes is using natural scaffolds, for this purpose discarded tissues or organs are naturally derived by processes that comprised decellularization of following tissues or organs. Protection of the complex structure and 3D (three dimensional) ultrastructure of the ECM is extremely necessary but it is predictable that all protocols of decellularization end in disruption of the architecture and potential loss of surface organization and configuration. Tissue decellularization with conservation of ECM bioactivity and integrity can be improved by providing well-designed protocols regarding the agents and decellularization techniques operated during processing. An overview of the characterization of decellularized scaffolds and the role of reagnets can validate the applied methods' efficacy.

The existence of ovarian germline stem cells (GSCs) has been challenged by various research groups. The hypothesis that mammalian ovaries contain germ cells with regenerative potential continues to be tested. Recent advancements in stem cell science have led to new information in the area, leaving the question open. Anatomically, cells purported to be undifferentiated ovarian GSCs are located near the surface epithelium and express the markers for undifferentiated stem cells. Various studies have proposed the presence of specific immunological markers for ovarian GSCs but this topic is highly contentious. The mainstay of the studies performed on ovarian GSCs has demonstrated that their transplantation into otherwise sterile postnatal mice facilitated the mice to produce embryos and offspring. In another study, ovarian GCSs were identified in reproductive-age women, which put to test the established dogma of a fixed reserve pool of oocytes before birth in humans as well. If proliferative ovarian GSCs are indeed present, their impact upon the timing of menopause needs to be better understood. Last, ovarian GSCs have also been implicated in ovarian cancers. Several studies have explored a relationship between cancer stem cells (CSCs) and putative ovarian GSCs. All of these intriguing accomplishments and open questions about the prospects of using ovarian GSCs in this field are discussed in detail in this chapter.

Lung transplantation may be considered as a final treatment option for diseases such as chronic lung disease, pulmonary hypertension, bronchopulmonary dysplasia, pulmonary fibrosis, and end-stage lung disease. The five-year survival rate of lung transplants is nearly 50%. Unfortunately, many patients will die before a suitable lung donor can be found. Importantly, the shortage of donor organs has been a significant problem in lung transplantation. The tissue engineering approach uses de- and recellularization of lung tissue to create functional lung substitutes to overcome donor lung limitations. Decellularization is hope for generating an intact ECM in the development of the engineered lung. The goal of decellularization is to prepare a suitable scaffold of lung tissue that contains an appropriate framework for the functionality of regenerated lung tissue. In this chapter, we aim to describe the decellularization protocols for lung tissue regenerative purposes.

We tried to investigate the role of Schwann and satellite cells in the treatment of neurogenic bladder and bowel dysfunction; following spinal cord injury in the rabbit model. Twelve male New Zealand rabbits underwent induction of neurogenic bladder by spinal cord injury. Rabbits underwent the fiber tractography analysis to confirm the induction of spinal cord injury. Then, animals were randomly divided into two groups. In group I (n = 4), Schwann cells were obtained from autologous peroneal nerve. In group II (n = 4), the co-culture of nerve-muscle cells was obtained from autologous peroneal nerve and quadriceps muscle. Animals in the control group (n = 4) did not undergo any rehabilitation therapy. One and 4 months after injection of cells into the external anal sphincter, electromyography, urethral pressure profiles, urodynamic studies, voiding cystourethrogram, and manometry was performed to confirm the efficacy of treatment in short- (1 month) and long-term (4 months) follow-ups. The investigations validated that no statistically significant difference was detected between the two experimental groups in a short-term follow-up (p-value > 0.05). However, the functional features were improved in group II in long-term follow-up. In both groups, the external anal sphincter contracted in response to electrical signals delivered to the muscle. However, more signals were detected in group II in electromyography evaluation. The immunohistochemical staining demonstrated that the histological features of the bladder and spinal cord were more satisfactory in group II in all follow-ups compared to group I, in terms of less edema, inflammation, presence of progenitor cells, and expression of muscle and nerve markes. Our results suggested that the injection of nerve-muscle co-culture cells into the external anal sphincter may be a helpful tactic for ameliorating the urological complications; following spinal cord injury induction in the rabbit model.

Background In today’s world, coronavirus disease 2019 (COVID-19) is the most critical health problem and research is continued on studying the associated factors. But it is not clear whether endometriosis increases the risk of COVID-19. Methods Women who referred to the gynecology clinic were evaluated and 507 women with endometriosis (case group) were compared with 520 women without endometriosis (control group). COVID-19 infection, symptoms, exposure, hospitalization, isolation, H1N1 infection and vaccination, and past medical history of the participants were recorded and compared between the groups using IBM SPSS Statistics for Windows version 21. Results Comparison between the groups represent COVID-19 infection in 3.2% of the case group and 3% of the control group (P = 0.942). The control group had a higher frequency of asymptomatic infection (95.7% vs. 94.5%; P P = 0.004), while the frequency of rare symptoms was more common in the case group (P P = 0.694). COVID-19 infection was correlated with close contact (r = 0.331; P P P > 0.05). Conclusion Endometriosis does not increase the susceptibility to COVID-19 infections, but alters the manifestation of the disease. The prevalence of the disease may depend on the interaction between the virus and the individual’s immune system but further studies are required in this regard.

The contributions of estradiol and testosterone to atherosclerotic lesion progression are not entirely understood. Cross-sex hormone therapy (XHT) for transgender individuals dramatically alters estrogen and testosterone levels and consequently could have widespread consequences for cardiovascular health. Yet, no preclinical research has assessed atherosclerosis risk after XHT. We examined the effects of testosterone XHT after ovariectomy on atherosclerosis plaque formation in female mice and evaluated whether adding low-dose estradiol to cross-sex testosterone treatments after ovariectomy reduced lesion formation. Six-week-old female ApoE−/− C57BL/6 mice underwent ovariectomy and began treatments with testosterone, estradiol, testosterone with low-dose estradiol, or vehicle alone until euthanized at 23 weeks of age. Atherosclerosis lesion progression was measured by Oil Red O stain and confirmed histologically. We found reduced atherosclerosis in the estradiol- and combined testosterone/estradiol–treated mice compared with those treated with testosterone or vehicle only in the whole aorta (−75%), aortic arch (−80%), and thoracic aorta (−80%). Plaque size was similarly reduced in the aortic sinus. These reductions in lesion size after combined testosterone/estradiol treatment were comparable to those obtained with estrogen alone. Testosterone/estradiol combined therapy resulted in less atherosclerosis plaque formation than either vehicle or testosterone alone after ovariectomy. Testosterone/estradiol therapy was comparable to estradiol replacement alone, whereas mice treated with testosterone only fared no better than untreated controls after ovariectomy. Adding low-dose estrogen to cross-sex testosterone therapy after oophorectomy could improve cardiovascular outcomes for transgender patients. Additionally, these results contribute to understanding of the effects of estrogen and testosterone on atherosclerosis progression.

Objective: To determine the effect of the 3 well-known endometriosis treatments on stem cell recruitment to endometriotic lesions. Study Design: C57BL/6 mice (aged 8 weeks, n = 20) underwent bone marrow transplant following submyeloablation with 5-fluorouracil using 20 × 106 bone marrow stem cells from green fluorescent protein (GFP) mice. Two weeks after transplantation, experimental endometriosis was created in mice by suturing segments of the uterine horn into the peritoneal cavity. Mice were then randomized to receive treatment with medroxyprogesterone acetate (MPA), leuprolide acetate (Gonadotrophin-Releasing Hormone Analogue [GnRHa]), letrozole, or vehicle control (dimethyl sulfoxide). After 3 weeks of treatment, the mice were killed and the endometriosis lesions evaluated. Results: All 3 treatments resulted in a significant reduction in lesion volume and weight. Estrogen deprivation using GnRHa or letrozole resulted in greater lesion regression than the progestin MPA. The GFP+/CD45− bone marrow-derived stem cells (BMDSCs) engrafted the lesions of endometriosis. Estrogen deprivation using GnRHa or letrozole significantly reduced BMDSC engraftment in the endometriosis lesions. MPA failed to significantly reduce stem cell number in endometriosis. Conclusion: The superiority of estrogen deprivation over progestin therapy in depriving the lesions of stem cells may have implications for the long-term treatment of endometriosis. Reduced stem cell engraftment is likely to result in long-term regression of the lesions, whereas progestins may only prevent their growth acutely.

Asherman's syndrome is an acquired condition of uterine fibrosis and adhesions in response to injury that adversely affects fertility and pregnancy. We have previously demonstrated that bone marrow-derived mesenchymal stem cells (BMDSCs) contribute to uterine repair after injury and that stem cells supplementation improves fertility. Here, we demonstrate that CXCL12 is the chemokine that mediates stem cell engraftment and functional improvement using a murine model of Asherman's syndrome. After uterine injury, we demonstrate that CXCL12 augmentation increased BMDSC engraftment and that the CXCL12 receptor (CXCR4) antagonist, ADM3100, blocked stem cell recruitment. CXCL12 reduced, whereas ADM3100 increased fibrosis. CXCL12 treatment led to improved fertility and litter size, whereas ADM3100 treatment reduced fertility and litter size. ADM3100 prevented optimal spontaneous uterine repair mediated by endogenous CXCL12 production, reducing pregnancies after injury in the absence of supplemental CXCL12 administration; however, ADM3100 treatment could be partially rescued by CXCL12 augmentation. CXCL12 or other CXCR4 receptor agonists may be useful in the treatment of infertility or adverse pregnancy outcomes in Asherman's syndrome and other related uterine disorders.

Lately, stem cell approaches have provided new information on reproductive organ function and additionally recommended novel treatment possibilities. The type(s) and differentiation potential of stem cells present in the mammalian ovary are largely unknown; while oogonial stem cells have been reported, we explored the possibility that multipotent stem cells may reside in the ovary and have wide differentiation potential. In this experimental study, homogenates of whole mouse ovaries were sorted using the stem cell surface markers stem cell antigen-1 and stage specific embryonic antigen-1/CD15. Viable double-positive cells 3–10 μm in diameter were evaluated immediately after sorting and after culture using differentiation conditions. Ovarian-derived stem cells were differentiated into the three main cell types: adipocytes, chondrocytes, or osteocytes. The subsequent culture was performed in media containing bone morphogenetic protein 4 (BMP-4) and/or retinoic acid (RA). RA, BMP-4 or the two agents in combination, consistently stimulated germ cell gene expression. RA treatment strongly stimulated germline gene expression and also the development of cells that were morphologically reminiscent of oocytes. The germ cell genes Dazl, Ddx4, Figla, Gdf-9, Nobox, Prdm9, and Sycp-1 were all detected at low levels. Remarkably, treatment with BMP-4 alone significantly increased protein expression of the granulosa cell product anti-Mullerian hormone (AMH). We have shown that an inclusive isolation protocol results in the consistent derivation of multipotent stem cells from the adult ovary; these cells can be differentiated towards the germ cell fate (RA alone), somatic ovarian cell fate as indicated by AMH production (BMP-4 alone), or classical mesenchymal cell types. Taken together, these data suggest the presence of multipotent mesenchymal stem cells in the murine ovary.

Background Endometriosis is an estrogen dependent, inflammatory disorder occurring in 5–10% of reproductive-aged women. Women with endometriosis have a lower body mass index (BMI) and decreased body fat compared to those without the disease, yet few studies have focused on the metabolic abnormalities in adipose tissue in women with endometriosis. Previously, we identified microRNAs that are differentially expressed in endometriosis and altered in the serum of women with the disease. Here we explore the effect of endometriosis on fat tissue and identified a role for endometriosis-related microRNAs in fat metabolism and a reduction in adipocyte stem cell number. Methods Primary adipocyte cells cultured from 20 patients with and without endometriosis were transfected with mimics and inhibitors of microRNAs 342-3p or Let 7b-5p to model the status of these microRNAs in endometriosis. RNA was extracted for gene expression analysis by qRT-PCR. PCNA expression was used as a marker of adipocyte proliferation. Endometriosis was induced experimentally in 9-week old female C57BL/6 mice and after 10 months fat tissue was harvested from both the subcutaneous (inguinal) and visceral (mesenteric) tissue. Adipose-derived mesenchymal stem cells in fat tissue were characterized in both endometriosis and non-endometriosis mice by FACS analysis. Results Gene expression analysis showed that endometriosis altered the expression of Cebpa, Cebpb, Ppar-γ, leptin, adiponectin, IL-6, and HSL, which are involved in driving brown adipocyte differentiation, appetite, insulin sensitivity and fat metabolism. Each gene was regulated by an alteration in microRNA expression known to occur in endometriosis. Analysis of the stem cell content of adipose tissue in a mouse model of endometriosis demonstrated a reduced number of adipocyte stem cells. Conclusions We demonstrate that microRNAs Let-7b and miR-342-3p affected metabolic gene expression significantly in adipocytes of women with endometriosis. Similarly, there is a reduction in the adipose stem cell population in a mouse model of endometriosis. Taken together these data suggest that endometriosis alters BMI in part through an effect on adipocytes and fat metabolism.

Background: There are numerous investigations on wide range of issues that disrupt regulatory spermatogenesis, individuals who are exposed to drug abuse faced infertility and immature spermatogenesis. Objective: The aim of this study was to evaluate the addiction effects of morphine and its derivatives on rats spermatogenesis. Materials and Methods: 40 male Wistar rats were randomly divided into 5 equal groups, which were exposed either with intravenous morphine, naloxone, naloxone and morphine, sham (with normal saline injection) and a control group without infusion. Spermatogenesis was assessed after three months via histological sections with hematoxylin and eosin staining, using a light microscope based on measurement of spermatogonia, spermatocyte, spermatid, and spermatozoa. Results: Those rats that received opioids had changes in spermatogenesis function. The population of spermatogenesis cycle cells at spermatogonia, spermatocyte, spermatid, and spermatozoa stages was significantly decreased in those rats that received opioid in comparison to the control group (p

Objective: To evaluate whether the use of vascular endothelial growth factor (VEGF) with alginate increases oocyte maturation following in vitro maturation. Methods: This experimental study was performed on 150 immature oocytes (germinal vesicle oocytes) from females who were candidates for assisted reproductive technology. The germinal vesicle oocytes were randomly placed in the control, alginate, and VEGF plus alginate groups. The basic culture medium for oocytes culture (tissue culture medium 199, follicle-stimulating hormone 0.075 IU/mL, and fetal bovine serum 10%) was used in the control, alginate, and VEGF plus alginate groups. For the treatment groups (alginate, and VEGF plus alginate groups), alginate (8%) and VEGF (5 ng/mL) were added to the basic culture medium. After culture, immature oocytes were considered as oocytes unchanged in the nucleus whereas oocytes with a polar body were considered as mature oocytes (metaphase II stage). The mature oocytes in each group were fertilized by intracytoplasmic sperm injection and formed embryos were evaluated by reverse microscope. Results: The oocyte maturation rate (metaphase II) significantly (P < 0.05) increased in the alginate plus VEGF group as compared with the alginate alone and control groups during in vitro maturation. On day 2, the cleavage rates were significantly different in the matured oocytes between the treatment groups and the control group. The percentage of the two-cell stage, four-cell stage and eight-cell embryos was significantly higher in the treatment groups compared with the control group (P

Cross-sex hormone therapy (XHT) is widely used by transgender people to alter secondary sex characteristics to match their desired gender presentation. Here, we investigate the long-term effects of XHT on bone health using a murine model. Female mice underwent ovariectomy at either 6 or 10 wk and began weekly testosterone or vehicle injections. Dual-energy X-ray absorptiometry (DXA) was performed (20 wk) to measure bone mineral density (BMD), and microcomputed tomography was performed to compare femoral cortical and trabecular bone architecture. The 6-wk testosterone group had comparable BMD with controls by DXA but reduced bone volume fraction, trabecular number, and cortical area fraction and increased trabecular separation by microcomputed tomography. Ten-week ovariectomy/XHT maintained microarchitecture, suggesting that estrogen is critical for bone acquisition during adolescence and that late, but not early, estrogen loss can be sufficiently replaced by testosterone alone. Given these findings, we then compared effects of testosterone with effects of weekly estrogen or combined testosterone/low-dose estrogen treatment after a 6-wk ovariectomy. Estrogen treatment increased spine BMD and microarchitecture, including bone volume fraction, trabecular number, trabecular thickness, and connectivity density, and decreased trabecular separation. Combined testosterone-estrogen therapy caused similar increases in femur and spine BMD and improved architecture (increased bone volume fraction, trabecular number, trabecular thickness, and connectivity density) to estrogen therapy and were superior compared with mice treated with testosterone only. These results demonstrate estradiol is critical for bone acquisition and suggest a new cross-sex hormone therapy adding estrogens to testosterone treatments with potential future clinical implications for treating transgender youth or men with estrogen deficiency.

Context Endometriosis is characterized by aberrant inflammation. We previously reported increased levels of microRNA (miRNA) 125b-5p and decreased levels of miRNA Let-7b-5p in serum of patients with endometriosis. Objective Determine the regulatory function of miRNAs 125b-5p and Let-7b-5p on production of proinflammatory cytokines in endometriosis. Design Case-control study. Setting University hospital. Patients Women with (20) and without (26) endometriosis; human U937 macrophage cell line. Intervention Sera were collected from surgically diagnosed patients and differentiated U937 cells that were transfected with miRNAs 125b-5p and Let-7b-5p mimics and inhibitor. Main Outcome Measures Enzyme-linked immunosorbent assay for tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and IL-1β levels and quantitative real-time polymerase chain reaction for expression of miRNAs 125b-5p and Let-7b-5p in sera of patients with and without endometriosis. Transfected macrophages were evaluated for expression of inflammatory cytokines, intracellular production, and secretion of these cytokines. Results We noted substantial elevation of TNF-α, IL-1β, and IL-6, marked upregulation of miRNA 125b, and considerable downregulation of Let-7b in sera of patients with endometriosis vs control. There was a positive correlation between miRNA 125b levels and TNF-α, IL-1β, and IL-6 and a negative correlation between miRNA Let-7b levels and TNF-α in sera of patients with endometriosis. Transfection experiments showed a noteworthy upregulation of TNF-α, IL-1β, IL-6, and IL-8 in macrophages transfected with miRNA 125b mimic or Let-7b inhibitor. The secreted cytokine protein levels and intracellular imaging studies closely correlate with the messenger RNA changes. Conclusions Endometriosis-derived miRNAs regulate macrophage cytokine production that contributes to inflammation associated with this condition.

Aloe vera is a medicinal plant used to treat various skin diseases. The effects of using aloe vera gel on the healing process were investigated by microscopic methods, cell counting, and TGF-β gene expression in the wound bed. Sixty Wistar rats weighing 200–250 g were placed under anesthesia in sterile conditions. A square 1.5 cm × 1.5 cm wound was made on the back of the neck. The rats were divided into control and 2 experimental groups. Additionally, the control and experimental groups were separated into 3 subgroups corresponding to 4, 7, and 14 days of study. In the first experimental group, aloe vera was used twice on the wound. The second experimental group received aloe vera overtreatment once on the wound. The positive control group received daily application of 1% phenytoein cream following surgical wound creation. The control group did not receive any treatment. This tissue was examined using histological staining (H&E) and Masson’s Trichrome. Wound surface and wound healing were evaluated separately. TGF-β gene expression was analyzed by RT–PCR. Results showed that fibroblasts in both experimental groups were significantly increased, thereby acceleration wound healing. Application of aloe vera gel will increase TGF-β gene expression, ultimately accelerating the wound healing process.

Background: Nasal parameters are important in anthropology to distinguish race, sex and ethnic of people groups and are useful to identify unknown person. The aim of this study was to determine the anthropometric characteristics of Nose in residents of Qazvin, Iran. Materials and methods: A cross-sectional survey was performed on 300 adults from Qazvin; they were 18 to 55 years-old. There were 160 males and 140 females with a male/female ratio of 1.2:1.This group was randomly selected. Without gender prejudices their nasal parameters, nasal height, tip protrusion and alar thickness, were measured using a sliding caliper. Results: The mean nasal width/height (Nasal index -NI) was 90.7 in males and 88.2 in females. Males had a higher NI compared to females (p < 0.03). The most common type of nasal variability is type A (70.5%), Platyrrhine nose, Type B (26.7%) especially in females (mesorrhine) and Type C (leptorrhine) (2.8%). Conclusion: There is a significant correlation between sex of an individual and type of nose. Platyrrhine nose, among males and mesorrhine among females were more common, only 2.8% being leptorrhine. The nasal indices in males were higher than in females.