Determination of voiding pressure in infants with normal lower urinary tracts: Exploring the possible effect of sacral development.

OBJECTIVE: To investigate the association between sacral underdevelopment, as defined by subnormal sacral ratio (SR) measurements, with increased maximum detrusor voiding pressure (P det. Max) in infants. METHODS: In this 2007-2015 retrospective cohort study, the medical records of all infants who underwent a pyeloplasty due to congenital ureteropelvic junction obstruction were added. Their P det. Max was evaluated through the suprapubic catheter utilized for urinary drainage intraoperatively, without imposing any additional risk of urethral catheterization on the infant. SR was calculated via the plain kidney, ureter, and bladder (KUB) radiography film obtained during the voiding cystourethrogram (VCUG) evaluation before the surgery. Participants were categorized into SR < 0.74 or SR ≥ 0.74. P det. Max was subsequently compared between these two groups. RESULTS: A total of 45 patients were included in our analysis. Twenty-eight (62.2%) patients had a (SR < 0.74), while 17 (37.8%) had a (SR ≥ 0.74). P det. Max was shown to be significantly higher in the SR < 0.74 compared to the SR ≥ 0.74 group (167.5 ± 60.8 vs. 55.7 ± 17.9 cmH2O, p < 0.001). After adjusting for age and sex, SR remained a significant contributor to P det. Max (p < 0.001). Physiologic detrusor sphincter dyscoordination (PDSD) rate was significantly higher in the SR < 0.74 versus SR ≥ 0.74 group (100.0% vs. 70.6%, respectively; p = 0.005). CONCLUSION: Lumbosacral underdevelopment, as indicated by subnormal sacral ratios, is associated with sphincter-detrusor dyscoordination, which causes PDSD and can ultimately result in higher P det. Max in infants.

Non-coding RNAs in Recurrent implantation failure.

Recurrent implantation failure (RIF), defined as the inability to achieve conception following multiple consecutive in-vitro fertilization (IVF) attempts, represents a complex and multifaceted challenge in reproductive medicine. The emerging role of non-coding RNAs in RIF etiopathogenesis has only gained prominence over the last decade, illustrating a new dimension to our understanding of the intricate network underlying RIF. Successful embryo implantation demands a harmonious synchronization between an adequately decidualized endometrium, a competent blastocyst, and effective maternal-embryonic interactions. Emerging evidence has clarified the involvement of a sophisticated network of non-coding RNAs, including microRNAs, circular RNAs, and long non-coding RNAs, in orchestrating these pivotal processes. Disconcerted expression of these molecules can disrupt the delicate equilibrium required for implantation, amplifying the risk of RIF. This comprehensive review presents an in-depth investigation of the complex role played by non-coding RNAs in the pathogenesis of RIF. Furthermore, it underscores the vast potential of non-coding RNAs as diagnostic biomarkers and therapeutic targets, with the ultimate goal of enhancing implantation success rates in IVF cycles. As ongoing research continues to unravel the intercalated web of molecular interactions, exploiting the power of non-coding RNAs may offer promising avenues for mitigating the challenges posed by RIF and improving the outcomes of assisted reproduction.

Circulating levels of inflammatory biomarkers in Huntington's disease: A systematic review and meta-analysis.

BACKGROUND: Huntington's disease (HD) is an autosomal dominant disease caused by an abnormally high number of CAG repeats at the huntingtin-encoding gene, HTT. This genetic alteration results in the expression of a mutant form of the protein (mHTT) and the formation of intracellular aggregates, inducing an inflammatory state within the affected areas. This dysfunction of inflammatory response leads to elevated levels of related inflammatory markers in both CNS tissue samples and body fluids. This study aims to investigate peripheral/blood concentrations of inflammatory molecules in HD. METHODS: A search was conducted in MEDLINE, Scopus, Web of Science, and Embase databases until March 30th, 2023. Random-effect meta-analysis was used for exploring concentrations of inflammatory molecules in HD. Subgroup and sensitivity analyses were used to assess heterogeneity among the included studies. The study protocol has been registered in PROSPERO with the ID number CRD42022296078. RESULTS: Ten studies were included in the meta-analysis. Plasma levels of Interleukin 6 (IL-6) and IL-10 were higher in HD compared to controls. Other biomarkers, namely, complement component C-reactive protein (CRP), C3, interferon-γ (IFN-γ), IL-1, IL-2, IL-8, and tumor necrosis factor-α (TNF-α), did not show any significant differences between the two groups. In addition, the subgroup analysis results established no significant differences in levels of these biomarkers in body fluids among premanifest and manifest HD patients. CONCLUSION: The results of this study provide evidence for the presence of higher plasma levels of IL-6 and IL-10 in HD patients in comparison with healthy controls.

Histopathologic evaluation of the inflammatory factors and stromal cells in the endometriosis lesions: A case-control study.

Background: Endometriosis is a multifaceted gynecological disorder defined as a benign estrogen-dependent chronic inflammatory process in which endometrial glands and stroma-like tissues are located outside the uterine cavity. It affects around 2-10% of all women during their reproductive years. Objective: This study aimed to evaluate the traffic of mesenchymal stem cells and inflammatory factors toward the lesions. Materials and Methods: Ten samples of normal endometrium and eutopic endometrium were studied as a control group and 10 ectopic samples were considered as a case group. Hematoxylin and eosin staining was used to evaluate stromal cells and inflammatory cells. Immunohistochemical staining was performed to show the presence of proliferating cell nuclear antigen in the lesions. The cells were digested and cultured in the laboratory to study cell proliferation. The number of cells and vessels were counted with Image J software, and data analysis was performed with Prism software. Results: Data analysis showed that the number of stromal cells and vessels in ectopic tissue were significantly higher than the control group (p < 0.001). Also, the number of inflammatory cells, including neutrophils, monocytes, lymphocytes, and macrophages, in the ectopic group was much higher than in the control group (p < 0.005). Conclusion: By expanding the number of blood vessels, blood flow increases, and cell migration to tissues is facilitated. The accumulation of inflammatory cells, especially macrophages, stimulates the growth of stem cells and helps implant cells by creating an inflammatory process.

The potential key genes and pathways associated with Wilms tumor in quest of proper candidates for diagnostic and therapeutic purposes.

To designate the probable most important differentially expressed genes and genetic pathways in Wilms tumor and assess their expression and diagnostic potential by RT-PCR and statistical analysis. Systematic review of the literature and various bioinformatics analysis was carried out to gather and narrow down data. The expression of end-resulting genes was compared in Wilms tumor and normal tissue samples using RT-PCR. Statistical tests reported the diagnostic accuracy of genes and their correlation with clinicopathological features. Four genes including CDH1, NCAM1, EGF, and IGF2 were designated. The panel combining them has 100% sensitivity and specificity in differentiating tumors from normal tissue. Eight pathways, most involved in cell-cell and cell-basal matrix junction interactions, were found to be associated with disease pathogenesis. The suggested genes should undergo further evaluation to be validated as diagnostic biomarkers. Further research on the eight proposed pathways is recommended.

The role of spinal cord tractography in detecting lesions following selective bladder afferent and efferent fibers injury: A novel method for induction of neurogenic lower urinary tract dysfunction in rabbit.

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Whole-organ decellularization of the human uterus and in vivo application of the bio-scaffolds in animal models.

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.

Decellularization in Tissue Engineering and Regenerative Medicine: Evaluation, Modification, and Application Methods.

Reproduction of different tissues using scaffolds and materials is a major element in regenerative medicine. The regeneration of whole organs with decellularized extracellular matrix (dECM) has remained a goal despite the use of these materials for different purposes. Recently, decellularization techniques have been widely used in producing scaffolds that are appropriate for regenerating damaged organs and may be able to overcome the shortage of donor organs. Decellularized ECM offers several advantages over synthetic compounds, including the preserved natural microenvironment features. Different decellularization methods have been developed, each of which is appropriate for removing cells from specific tissues under certain conditions. A variety of methods have been advanced for evaluating the decellularization process in terms of cell removal efficiency, tissue ultrastructure preservation, toxicity, biocompatibility, biodegradability, and mechanical resistance in order to enhance the efficacy of decellularization methods. Modification techniques improve the characteristics of decellularized scaffolds, making them available for the regeneration of damaged tissues. Moreover, modification of scaffolds makes them appropriate options for drug delivery, disease modeling, and improving stem cells growth and proliferation. However, considering different challenges in the way of decellularization methods and application of decellularized scaffolds, this field is constantly developing and progressively moving forward. This review has outlined recent decellularization and sterilization strategies, evaluation tests for efficient decellularization, materials processing, application, and challenges and future outlooks of decellularization in regenerative medicine and tissue engineering.

Swimming training modulates lung injury induced by ovariectomy in diabetic rats: involvement of inflammatory and fibrotic biomarkers.

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.

Prenatal Neural Tube Anomalies: A Decade of Intrauterine Stem Cell Transplantation Using Advanced Tissue Engineering Methods.

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.

microRNAs as novel diagnostic biomarkers in endometriosis patients: a systematic review and meta-analysis.

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.

Evaluation and Comparison of the Effects of Mature Silkworm (Bombyx mori) and Silkworm Pupae Extracts on Schwann Cell Proliferation and Axon Growth: An In Vitro Study.

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.

Gene and histomorphology alteration analysis in spermatogenesis arrest mouse model: a probable novel approach for infertility.

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 <0.001 for both markers). In comparison with the negative control group, the expression rates of A-Kinase Anchoring Protein 4 and adenosine deaminase domain containing 1, two genes participating in the sperm structure, were remarkably reduced in the intervention group (p-value <0.001); however, our investigations demonstrated that the azoospermia model could induce a 5-fold upregulation in Wilms Tumor-1 gene expression. CONCLUSIONS: Development of an azoospermia model can upregulate Wilms Tumor-1 gene expression in a higher rate after 30 days; however, expression of the testis-specific genes, A-Kinase Anchoring Protein 4 and adenosine deaminase domain containing 1, decreased after the intervention. To the best of our knowledge, this upregulation could be related to spermatogenesis recovery after the follow-up period.

Exposing Mouse Oocytes to MitoQ During In Vitro Maturation Improves Maturation and Developmental Competence.

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.

Systemic Inflammation Induced by microRNAs: Endometriosis-Derived Alterations in Circulating microRNA 125b-5p and Let-7b-5p Regulate Macrophage Cytokine Production.

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-1ß 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-1ß, 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-1ß, 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-1ß, 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.

Addition of Estradiol to Cross-Sex Testosterone Therapy Reduces Atherosclerosis Plaque Formation in Female ApoE-/- Mice.

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.

Cross-sex testosterone therapy in ovariectomized mice: addition of low-dose estrogen preserves bone architecture.

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.

Evaluation of the Effects of Local Application of Thyme Honey in Open Cutaneous Wound Healing.

BACKGROUND: Clinicians have been searching for ways to obtain "super normal" wound healing. Honey is a traditional remedy for the treatment of infected wounds. We aimed to evaluate the wound contraction and antibacterial properties of locally produced Thyme honey on managing full-thickness wounds in vivo. METHODS: This experimental study was conducted in 2015, in Department of Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran on 54 adult male Wistar rats weighing 200-250 gr, and ages of 3-4 months. A square 1.5*1.5 wound was made on the back of the neck. The rats were divided into control and two experimental groups. Additionally, the control and experimental groups were separated into three subgroups corresponding to 4, 7, and 14 d of study. The control group did not receive any treatment. For histological studies, samples were taken from the wound and adjacent skin. This tissue was examined using histological staining (H&E). Wound surface and wound healing were evaluated. Data were analyzed by using one-way ANOVA with post hoc Tukey test and (P<0.05) was significant. RESULTS: The macroscopic and microscopic evaluations showed that the percentage of wound healing on different days in the control and experimental groups were significant (P< 0.05). CONCLUSION: Using honey twice a day on open wounds will accelerate the healing process.

Impacts of morphine addiction on spermatogenesis in rats.

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<0.05). Histological studies revealed that changes in different groups of opioid application might affect sperm formation. Sperm count in morphine group was (0±0) and in naloxone group, naloxone+morphine, sham and control were 235±3.77, 220±3.81, 247.12±6.10 and 250±6.54, respectively (p<0.001). CONCLUSION: Morphine could affect all spermatogenesis stages.