Nonhormone therapies for vasomotor symptom management.

Vasomotor symptoms (VMS) are associated with adverse health consequences and can cause significant morbidity for postmenopausal women. Although hormone therapy remains the gold standard of VMS treatment in menopausal women, some women have contraindications to or may choose not to take hormone therapy. This article provides an up-to-date overview of the current evidence-based nonhormone therapies available for managing VMS. Evidence supporting various treatment options is reviewed, including lifestyle interventions, mind-body therapies, procedures, pharmacologic agents, and emerging therapies, such as neurokinin-receptor antagonists. The efficacy, safety, and clinical use of these treatments are detailed, offering insights for clinicians to make informed decisions in menopausal VMS management.

Complex Extract of Polygonatum sibiricum and Nelumbinis semen Improves Menopause Symptoms via Regulation of Estrogen Receptor Beta in an Ovariectomized Rat Model.

Menopause is a hormone-deficiency state that causes facial flushing, vaginal dryness, depression, anxiety, insomnia, obesity, osteoporosis, and cardiovascular disease as ovarian function decreases. Hormone-replacement therapy is mainly used to treat menopause; however, its long-term use is accompanied by side effects such as breast cancer and endometriosis. To identify the effect of a complex extract of Polygonatum sibiricum (PS) and Nelumbinis semen (NS) on improving menopause without side effects, an ovariectomized rat model was established to analyze several menopause symptoms. Compared to single extracts, the complex extract restored vaginal epithelial cell thickness and decreased serotonin concentration by increasing the estrogen receptors ERα (ESR1) and ERß (ESR2), depending on the ratio. Although the complex extract exerted a lower weight-loss effect than the single extracts, improved blood-lipid metabolism was observed after increasing high-density lipoprotein cholesterol levels and decreasing low-density lipoprotein cholesterol and triglyceride levels, and ovariectomy-induced osteoporosis was alleviated by suppressing osteoclast production. Thus, by increasing only ERß expression without regulating ERα expression in the uterus, the complex extract of PS and NS may be a natural treatment for improving menopause symptoms without side effects, such as endometriosis.

The ethanolic extract of peanut shell attenuates the depressive-like behaviors of mice through modulation of inflammation and gut microbiota.

Peanut shell is an agricultural byproduct being wasted on a large scale, which is in urgent need to be recycled. To fully utilize its pharmacological ingredients, e.g. luteolin, eriodyctiol, and 5,7-dihydroxychromone, we evaluated the curative effect of ethanol extract deriving from peanut shell (PSE) in treating chronic unpredictable mild stress (CUMS)-induced depressive mice. The chronic stress lasted for 10 weeks, and PSE at 100-900 mg/kg/day was gavaged to mice in the last 2 weeks of modeling. The depressive behaviors were assessed by analyses of sucrose preference, tail suspension, and forced swimming. The brain injury was demonstrated by Hematoxylin and Eosin (H&E), Nissl body, and TdT-mediated dUTP nick end labeling (TUNEL) stainings in the mouse hippocampus. Biochemical indicators were analyzed, including levels of neurotrophic factors, neurotransmitters, stress hormones, and inflammatory mediators. The feces were collected for the 16S rDNA sequencing of gut microbiome. Administration of PSE improved the sucrose water consumption of depressive mice, while it decreased the immobile time in tail suspension and forced swimming tests. Meanwhile, the anti-depressive effect of PSE was supported by ameliorated histochemical staining, increased levels of neurotrophic factors and neurotransmitters, as well as down-regulated stress hormones. Furthermore, the treatment of PSE was able to mitigate the levels of inflammatory cytokines in brain, serum, and small intestine. Besides, the tight junction proteins, e.g., occludin and ZO-1, of gut showed elevated expressions, which coincided with the elevated abundance and diversity of gut microbiota upon PSE treatment. This study validated the therapeutic efficacy of PSE in fighting against depression, as well as its modulatory action on inflammation and gut microbiota, which promoted the recycling of this agricultural waste to be health supplements of added value.

Mood, hormone levels, metabolic and sleep across the menopausal transition in VCD-induced ICR mice.

AIMS: Menopausal transition is the transitional period before menopause in women, often accompanied by abnormal fluctuations in hormone levels that increase the risk of aging-related diseases. 4-vinylcyclohexene dioxide (VCD) is a chemical agent that induces gradual depletion of ovarian follicles, which can mimic the natural human process of transition from menopausal transition to post-menopause. Previous studies have shown that the onset of menopausal transition or menopause in VCD-injected mice is associated with a specific strain, even in inbred animals. Institute of Cancer Research (ICR) mice constitute general purpose outbred population, which has not been well-characterized in the VCD-induced model. Thus, the current study aimed to explore the characteristic features, including sleep, mood, and metabolism, of the model by examining the effect of timing of VCD injection in ICR mice to extend the applications of this model. MATERIALS AND METHODS: ICR mice were randomly divided into six groups: 20d VCD and 20d Control, 35d VCD and 35d Control, 52d VCD and 52d Control. VCD mice were intraperitoneally injected with VCD (160 mg/kg), while Control mice were injected intraperitoneally with sesame oil for 4 consecutive weeks, five times a week daily. A vaginal smear was used to observe the estrous cycle of the mice. On the 20th, 35th, and 52nd day after VCD or sesame oil injection, the ovarian morphology, the number of atretic cells, hormone levels, anxiety, depression-like behaviors, sleep phase, and energy metabolism were observed. KEY FINDINGS: The menopausal transition model was successfully replicated by injecting VCD into ICR mice. On the specific days after VCD treatment, the number of atretic follicles increased, the level of E2 decreased and FSH increased, the depressive- and anxiety-like behavior increased, the time of REM and NREM sleep time decreased, and energy metabolism was reduced. SIGNIFICANCE: These results suggested that the ICR mice model has human-like characteristics during the menopause transition. Moreover, the ICR model has a long menopausal transition duration.

Influence of Flaxseed (Linum usitatissimum) on Female Reproduction.

This review describes the chemical composition of flaxseed (Linum usitatissimum) and its general health effects, as well as the currently available knowledge concerning its action on the female reproductive state, functions on the ovary and ovarian cells and reproductive hormones, as well as possible constituents and extra- and intracellular mediators mediating its effects on female reproductive processes. Flaxseed contains a number of biologically active molecules, which, acting through multiple signalling pathways, can determine numerous physiological, protective and therapeutic effects of flaxseed. The available publications demonstrate the action of flaxseed and its constituents on the female reproductive system - ovarian growth, follicle development, the resulting puberty and reproductive cycles, ovarian cell proliferation and apoptosis, oo- and embryogenesis, hormonal regulators of reproductive processes and their dysfunctions. These effects can be determined by flaxseed lignans, alpha-linolenic acid and their products. Their actions can be mediated by changes in general metabolism, metabolic and reproductive hormones, their binding proteins, receptors and several intracellular signalling pathways, including protein kinases, transcription factors regulating cell proliferation, apoptosis, angiogenesis and malignant transformation. Flaxseed and its active molecules are found potentially useful for improving farm animal reproductive efficiency and treatment of polycystic ovarian syndrome and ovarian cancer.

Impacts of selenium nanoparticles and spirulina alga to alleviate the deleterious effects of heat stress on reproductive efficiency, oxidative capacity and immunity of doe rabbits.

Effects of dietary inclusion of spirulina platensis (SP) and selenium nanoparticles (SeNPs) combination (SP-SeNPs) on the reproductive performance in vivo and in vitro, reproductive and metabolic hormones, hemato-bichemical parameters, oxidative stress, and immunity of heat-stressed doe rabbis were evaluated. All supplements significantly increased live litter size at birth and weaning, viability rate at birth, hemoglobin and red blood cells, and plasma T3, T4, insulin, total proteins and albumin compared with control. Plasma estradiol 17-ß (pre-mating), progesterone (mid-pregnancy), and prolactin (day -7 postpartum) were significantly increased only by SeNPs (0.3, 0.4, and 0.5 mg/kg). All dietary supplements significantly reduced WBCs, cortisol, lipid profile, and improved liver and kidney functions. Immunoglobulins levels, antioxidants capacity were significantly increased, superoxide dismutase was increased by SeNPs (0.4 and 0.5 mg/kg), while malondialdehyde was reduced by 0.3, 0.4 and 0.5 SeNPs mg/kg. Sexual receptivity, pregnancy rate, viability rate at weaning, ovulation rate, and embryo quality were significantly increased by increasing SeNPs above 0.1 mg, while embryo yield was increased by >0.2 mg SeNPs/kg. A combination of SP and SeNPs, could be potentially used as a strong antioxidant to enhance heat regulation and doe rabbit reproduction via improving reproductive and metabolic hormones, antioxidant status and immunological parameters.

Arsenicum album Induces Cell Cycle Arrest and Apoptosis, and Inhibits Epithelial-Mesenchymal Transition in Hormone-Dependent MCF7 Breast Cancer Cells.

BACKGROUND: Arsenic trioxide (As2O3) has been in therapeutic use since the 18th century for various types of cancers including skin and breast; however, it gained popularity following FDA approval for its use against acute promyelocytic leukemia. This present work was designed to evaluate the anti-cancer potential of a homeopathic potency of arsenic trioxide (Arsenicum album 6C) in hormone-dependent breast cancer. METHODS: Breast cancer cells (MCF7) were treated with Arsenicum album (Ars 6C) to evaluate its anti-proliferative and apoptotic potential. We examined the effect of Ars 6C on the cell cycle, wound healing, reactive oxygen species (ROS) generation, and modulation of expression of key genes which are aberrant in cancer. RESULTS: Treating breast cancer cells with Ars 6C halted the cell cycle at the sub-G0 and G2/M phases, which could be attributed to DNA damage induced by the generation of ROS. Apoptotic induction was associated with upregulation of Bax expression, with concurrent downregulation of the Bcl-2 gene. Ars 6C was also seen to reverse epithelial to mesenchymal transition and reduce the migration of breast cancer cells. CONCLUSION: The findings suggest that Ars has significant anti-proliferative and apoptotic potential against breast cancer cells. Further studies are required to elucidate the mechanism by which Ars exerts its effect in the in vivo setting.

Pectolinarigenin shows lipid-lowering effects by inhibiting fatty acid biosynthesis in vitro and in vivo.

Pectolinarigenin is the main flavonoid compound and presents in Linaria vulgaris and Cirsium chanroenicum. In this study, RNA sequencing (RNA-seq) was applied to dissect the effect of pectolinarigenin on the transcriptome changes in the high lipid Huh-7 cells induced by oleic acid. RNA-seq results revealed that 15 pathways enriched by downregulated genes are associated with cell metabolism including cholesterol metabolism, glycerophospholipid metabolism, steroid biosynthesis, steroid hormone biosynthesis, fatty acid biosynthesis, etc. Moreover, 13 key genes related to lipid metabolism were selected. Among them, PPARG coactivator 1 beta (PPARGC1B) and carnitine palmitoyltransferase 1A (CPT1A) were found to be upregulated, solute carrier family 27 member 1(SLC27A1), acetyl-CoA carboxylase alpha (ACACA), fatty-acid synthase (FASN), 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR), etc. were found to be downregulated. Glycolysis/gluconeogenesis, steroid hormone biosynthesis, and fatty acid biosynthesis were all significantly downregulated, according to gene set variation analysis and gene set enrichment analysis. Besides, protein levels of FASN, ACACA, and SLC27A1 were all decreased, whereas PPARγ and CPT1A were increased. Docking models showed that PPARγ may be a target for pectolinarigenin. Furthermore, pectolinarigenin reduced serum TG and hepatic TG, and improved insulin sensitivity in vivo. Our findings suggest that pectolinarigenin may target PPARγ and prevent fatty acid biosynthesis.

Anticancer Effects of Propolis Extracts Obtained with the Cold Separation Method on PC-3 and DU-145 Prostate Cancer Cell Lines.

Plant extracts are increasingly tested for their biological activity and interactions with neoplastic cells. One of such sources of biologically active substances is propolis. This product has been known for thousands of years and is widely used in alternative, folk medicine. Articles describing its effects on the metabolism and cell signaling pathways of neoplastic cells derived from different organs are also published more and more frequently. The purpose of our study was to evaluate the biological activity of propolis extract produced with the cold separation method into hormone-dependent and hormone-independent prostate cancer cell lines. In our study, the propolis extracts showed at least an inhibitory effect on the growth of PC-3 and DU-145 neoplastic cells. Our results suggest that propolis extracts obtained with the cold separation method may be considered as promising compounds for the production of health-promoting supplements.

The Potential Role of Apigenin in Cancer Prevention and Treatment.

Cancer is the leading cause of death worldwide. In spite of advances in the treatment of cancer, currently used treatment modules including chemotherapy, hormone therapy, radiation therapy and targeted therapy causes adverse effects and kills the normal cells. Therefore, the goal of more effective and less side effects-based cancer treatment approaches is still at the primary position of present research. Medicinal plants or their bioactive ingredients act as dynamic sources of drugs due to their having less side effects and also shows the role in reduction of resistance against cancer therapy. Apigenin is an edible plant-derived flavonoid that has received significant scientific consideration for its health-promoting potential through modulation of inflammation, oxidative stress and various other biological activities. Moreover, the anti-cancer potential of apigenin is confirmed through its ability to modulate various cell signalling pathways, including tumor suppressor genes, angiogenesis, apoptosis, cell cycle, inflammation, apoptosis, PI3K/AKT, NF-κB, MAPK/ERK and STAT3 pathways. The current review mainly emphases the potential role of apigenin in different types of cancer through the modulation of various cell signaling pathways. Further studies based on clinical trials are needed to explore the role of apigenin in cancer management and explain the possible potential mechanisms of action in this vista.

Chloroxylon swietenia (Roxb.) DC induces cell death and apoptosis by down-regulating the NF-κB pathway in MCF-7 breast cancer cells: In vitro and in vivo investigations.

BACKGROUND: Natural products with targeted bioactivity have gained major attention in the field of cancer research owing to emerging anti-cancer drug resistance and off target toxicities. Chloroxylon swietenia (Roxb.) DC is recognized as a folklore medicinal plant and has numerous therapeutic benefits in the folklore medicine system, however the anti-cancer potential of this plant and its mechanism of action is poorly understood. AIMS: The aim of the study was to investigate the anti-breast cancer efficacy of C. swietenia leaves methanol extract (CSLME) against MCF-7 hormone dependent human breast cancer cell line with possible mechanism of action. METHODS AND RESULTS: The anti-breast cancer activity of CSLME against MCF-7 cells was assessed by evaluating its efficacy toward cytotoxicity, cell migration, colony formation, DNA fragmentation, apoptosis, cytoskeleton, angiogenesis, cell cycle regulation, and animal toxicity. The preliminary screening of CSLME against MCF-7 cells revealed the cytotoxicity (IC50 20 µg/ml), inhibited cell migration, colony formation, and angiogenesis. It was observed that CSLME induces apoptosis by nuclear fragmentation and disruption of cytoskeleton by actin derangement. The results of Annexin V-FITC assay and cell cycle analysis by flow cytometry clearly pointed out the sizable fraction of apoptotic cells, and arrested the cells at G2/M phase of cell cycle. The results of the immunoblotting experiments showed that CSLME activates intrinsic pathway of apoptosis with down regulation of anti-apoptotic marker like Bcl2, up regulation of pro-apoptotic markers like Bax & Bad, along with successful cleavage of Caspase-9 and PARP-1. Further, western blot analysis revealed the possible down regulation of NF-κB pathway by CSLME, which may be responsible for anti-cancer activity in MCF-7 cells. In vivo animal model studies using NOD-SCID mice demonstrated impressive anti-tumor activity with significant reduction in tumor volume of MCF-7 tumor xenograft. Of note, in-vivo acute oral toxicity study as per Organization for Economic Cooperation and Development 423 revealed the nontoxic nature of CSLME. CONCLUSION: The in vitro and in vivo findings clearly outline the potential of CSLME as inhibitor of growth and proliferation of MCF-7 cells. Mechanistically, CSLME seems to activate intrinsic pathway of apoptosis, arrest cell cycle, target actin cytoskeleton, inhibit growth, colony formation, migration, and angiogenesis, with down regulation of NF-κB pathway leading to cell death.

The efficacy of a comprehensive bone health program in maintaining bone mineral density in postmenopausal women with early-stage breast cancer treated with endocrine therapy: real-world data.

BACKGROUND: Aromatase inhibitors (AI) are the gold standard treatment option for hormone-sensitive postmenopausal women with breast cancer. Several studies had documented the accelerated bone loss associated with AI. AIMS: In this study, we present real-world data describing the efficacy of implementing a comprehensive bone health program to maintain bone mineral density (BMD) in postmenopausal patients with early-stage breast cancer treated with AI. METHODS: A comprehensive bone health program that includes counseling, exercise, nutritional advice, vitamin D supplements and, when needed, intravenous bisphosphonate infusion was implemented following the initiation of endocrine therapy with AI. Postmenopausal women with hormone-sensitive, early-stage breast cancer treated with endocrine therapy using AI were retrospectively identified. All patients had BMD measurements before and at least 1 year after ET initiation. RESULTS: A total of 210 patients were included, median (range) age 67 (43-86) years. At baseline, osteoporosis was documented in 38 (18.1%) and osteopenia in 101 (48.1%) patients. Despite the known negative effect of AI, 32 (84.2%) patients with baseline osteoporosis and 69 (68.3%) of those with osteopenia, had a stable or better BMD. On the other hand, 41 (57.7%) of those with normal baseline BMD had a drop in their follow up BMD, p < 0.001. Vertebral fractures were reported in 3 (11.1%) patients with osteoporosis compared to none in patients with normal BMD, p = 0.021. CONCLUSIONS: Despite the known negative effect of ET on bone health of breast cancer patients, implementing a comprehensive bone health program stabilized or improved BMD.

Inhibitory Effect of Elaeagnus umbellata Fractions on Melanogenesis in α-MSH-Stimulated B16-F10 Melanoma Cells.

When skin is exposed to UV radiation, melanocytes produce melanin. Excessive melanin production leads to skin pigmentation, which causes various cosmetic and health problems. Therefore, the development of safe, natural therapeutics that inhibit the production of melanin is necessary. Elaeagnus umbellata (EU) has long been widely used as a folk medicinal plant because of pharmacological properties that include anti-ulcer, antioxidant, and anti-inflammatory properties. In this study, we investigated the antioxidant activity and melanogenesis inhibitory effects of EU fractions in B16-F10 melanoma cells. EU fractions showed a dose-dependent increase in antioxidant activity in radical scavenging activity. In addition, we evaluated the effect of EU fractions on tyrosinase activity and melanogenesis in α-melanocyte-stimulating hormone-induced B16-F10 melanoma cells. EU was noncytotoxic at 12.5-50 µg/mL. EU fractions effectively inhibited tyrosinase activity and melanogenesis, suppressed the phosphorylation of CREB and ERK involved in the melanogenesis pathway, and down-regulated expression of melanogenesis-related proteins. Interestingly, the anti-melanogenesis effect was most effective at a concentration of 50 µg/mL EU, and the effects of the fractions were superior to those of the extract. Therefore, our study suggests that EU has potential as a safe treatment for excessive pigmentation or as a natural ingredient in cosmetics.

Pharmacological Acromegaly Treatment: Cost-Utility and Value of Information Analysis.

OBJECTIVES: To conduct a cost-utility analysis comparing drug strategies involving octreotide, lanreotide, pasireotide, and pegvisomant for the treatment of patients with acromegaly who have failed surgery, from a Brazilian public payer perspective. METHODS: A probabilistic cohort Markov model was developed. One-year cycles were employed. The patients started at 45 years of age and were followed lifelong. Costs, efficacy, and quality of life parameters were retrieved from the literature. A discount rate (5%) was applied to both costs and efficacy. The results were reported as costs per quality-adjusted life year (QALY), and incremental cost-effectiveness ratios (ICERs) were calculated when applicable. Scenario analyses considered alternative dosages, discount rate, tax exemption, and continued use of treatment despite lack of response. Value of information (VOI) analysis was conducted to explore uncertainty and to estimate the costs to be spent in future research. RESULTS: Only lanreotide showed an ICER reasonable for having its use considered in clinical practice (R$ 112,138/US$ 28,389 per QALY compared to no treatment). Scenario analyses corroborated the base-case result. VOI analysis showed that much uncertainty surrounds the parameters, and future clinical research should cost less than R$ 43,230,000/US$ 10,944,304 per year. VOI also showed that almost all uncertainty that precludes an optimal strategy choice involves quality of life. CONCLUSIONS: With current information, the only strategy that can be considered cost-effective in Brazil is lanreotide treatment. No second-line treatment is recommended. Significant uncertainty of parameters impairs optimal decision-making, and this conclusion can be generalized to other countries. Future research should focus on acquiring utility data.

Advances on hormone-like activity of Panax ginseng and ginsenosides.

Traditional Chinese medicine (TCM) has been paid much attentions due to the prevention and treatment of steroid hormone disorders. Ginseng, the root of Panax ginseng C. A. Meyer (Araliaceae), is one of the most valuable herbs in complementary and alternative medicines around the world. A series of dammarane triterpenoid saponins, also known as phytosteroids, were reported as the primary ingredients of Ginseng, and indicated broad spectral pharmacological actions, including anti-cancer, anti-inflammation and anti-fatigue. The skeletons of the dammarane triterpenoid aglycone are structurally similar to the steroid hormones. Both in vitro and in vivo studies showed that Ginseng and its active ingredients have beneficial hormone-like role in hormonal disorders. This review thus summarizes the structural similarities between hormones and dammarane ginsenosides and integrates the analogous effect of Ginseng and ginsenosides on prevention and treatment of hormonal disorders published in recent twenty years (1998-2018). The review may provide convenience for anticipate structure-function relationship between saponins structure and hormone-like effect.

The Role of Hormones and Trophic Factors as Components of Preservation Solutions in Protection of Renal Function before Transplantation: A Review of the Literature.

Transplantation is currently a routine method for treating end-stage organ failure. In recent years, there has been some progress in the development of an optimal composition of organ preservation solutions, improving the vital functions of the organ and allowing to extend its storage period until implantation into the recipient. Optimizations are mostly based on commercial solutions, routinely used to store grafts intended for transplantation. The paper reviews hormones with a potential nephroprotective effect, which were used to modify the composition of renal perfusion and preservation solutions. Their effectiveness as ingredients of preservation solutions was analysed based on a literature review. Hormones and trophic factors are innovative preservation solution supplements. They have a pleiotropic effect and affect normal renal function. The expression of receptors for melatonin, prolactin, thyrotropin, corticotropin, prostaglandin E1 and trophic factors was confirmed in the kidneys, which suggests that they are a promising therapeutic target for renal IR (ischemia-reperfusion) injury. They can have anti-inflammatory, antioxidant and anti-apoptotic effects, limiting IR injury.

The bone hormones and their potential effects on glucose and energy metabolism.

The bones form the framework of our body. We know that bones protect our vital organs, regulate calcium and phosphorous homeostasis, and function as a site of erythropoiesis. More recently, however, the identification of bone hormones has allowed us to envision bones as endocrine organs too. Within the last few years, the bone hormones osteocalcin and lipocalin 2 have been implicated with glucose and energy metabolism. We systematically reviewed articles surrounding this subject and found a clear relationship between the osteocalcin levels and glucose tolerance and insulin sensitivity. We also found that many journals have shown the detrimental effects of an absences of lipocalin 2 from adipocytes. As osteocalcin administration to mice showed decreased blood glucose levels and promoted glucose tolerance and insulin sensitivity. Future studies could perhaps explore the use of osteocalcin as a supplement for type 2 diabetes.

Beneficial and Deleterious Effects of Female Sex Hormones, Oral Contraceptives, and Phytoestrogens by Immunomodulation on the Liver.

The liver is considered the laboratory of the human body because of its many metabolic processes. It accomplishes diverse activities as a mixed gland and is in continuous cross-talk with the endocrine system. Not only do hormones from the gastrointestinal tract that participate in digestion regulate the liver functions, but the sex hormones also exert a strong influence on this sexually dimorphic organ, via their receptors expressed in liver, in both health and disease. Besides, the liver modifies the actions of sex hormones through their metabolism and transport proteins. Given the anatomical position and physiological importance of liver, this organ is evidenced as an immune vigilante that mediates the systemic immune response, and, in turn, the immune system regulates the hepatic functions. Such feedback is performed by cytokines. Pro-inflammatory and anti-inflammatory cytokines are strongly involved in hepatic homeostasis and in pathological states; indeed, female sex hormones, oral contraceptives, and phytoestrogens have immunomodulatory effects in the liver and the whole organism. To analyze the complex and interesting beneficial or deleterious effects of these drugs by their immunomodulatory actions in the liver can provide the basis for either their pharmacological use in therapeutic treatments or to avoid their intake in some diseases.

Effects of EBN on embryo implantation, plasma concentrations of reproductive hormones, and uterine expressions of genes of PCNA, steroids, growth factors and their receptors in rats.

This study was conducted to determine the effect of edible bird's nest (EBN) supplement on uterine function and embryo-implantation rate. A total of 24 adult female rats, divided equally into four groups, were treated with different doses of EBN for 8 weeks. In the last week of treatment, intact fertile male rats were introduced into each group (three per group) for overnight for mating. On day 7 post-mating (post-implantation), blood samples were collected from the hearts of anaesthetised rats that were later sacrificed. The uteri were removed for assessment of embryo implantation rate, histological and electron microscopic examination, and immunohistochemical analyses. Results showed that as the concentration of EBN supplemented increased, the pregnancy and embryo implantation rates were also increased in the treated groups; significantly at G3 and G4. Although histological evaluation did not show much difference among the groups, scanning electron microscopic examination showed enhanced development of elongated microvilli and pinopods in G4. Results also revealed up-regulated expressions of epidermal growth factor (EGF), EGF receptor (EGFR), vascular endothelial growth factor (VEGF), proliferating cell nulear antigen (PCNA), and progesterone and estrogen receptors (P4R, E2R) in the uteri of treated groups. Moreover, plasma E2, P4, growth hormone (GH) and prolactin (P) levels were higher (p < 0.05) in G3 and G4. The EBN increased the antioxidant (AO) and total AO capacities (TAC) and reduced oxidative stress (OS) levels in pregnant rats. In conclusion, findings of this study revealed that EBN enhances fertility and embryo implantation rate via promoting proliferation and differentiation of uterine structures as evidenced by the upregulation of the expressions of steroid receptors, EGF, EGFR, VEGF, and PCNA in the uterus. Furthermore, observations of improved growth of ultrastructural pinopods that assist in embryo attachment with uterine epithelium, increased concentrations of E2, P4, GH and P levels, as well as increased AO capacities with reduced OS levels in the treated groups might reflect additional possible mechanisms by which EBN enhances embryo implantation rate and pregnancy success.

Gender dysphoria in youth: An overview for primary care providers.

BACKGROUND AND PURPOSE: Primary care providers who encounter children are often the first line of contact for individuals with gender dysphoria, which occurs when sex assigned at birth is incongruent with one's true, expressed sexual identity. Because those with untreated gender dysphoria are at risk of a variety of negative outcomes, including mood symptomatology, suicidality, substance use disorders, and other psychosocial risk factors, it is critical that health care providers are adept in the provision of holistic, patient-centered care. The purpose of this report is to provide an updated review of the current evidence from the literature pertaining to the identification, treatment, and coordination of care among children with gender dysphoria within the primary care setting or medical home. METHODS: Using PubMed and CINAHL, a literature review spanning from 2012 to the present was conducted using the following key words: gender dysphoria, transgender health, LGBT health, and hormone therapy. Reference lists of identified articles were also explored for relevance. CONCLUSIONS: Treatment may include a social transition, hormone antagonist therapy, or the administration of cross-sex hormone therapy, with a medical home needed to facilitate coordination of care. Best practice guidelines vary across pediatric and developmental groups and include both reversible and nonreversible modalities. Screening for negative psychosocial sequelae must be completed to include mood symptomatology, suicidality, substance use disorders, and risky sexual behavior, so that appropriate screening, identification, and treatment interventions can be implemented. IMPLICATIONS FOR PRACTICE: The primary care medical home must act as a foundation for the identification of gender dysphoria and/or associated comorbidities and must treat, when able, or refer, when indicated. In addition, because of structural barriers and stigmatization, public policy often fails the transgender community and can exacerbate the aforementioned psychosocial comorbidities faced by the transgender youth community. Health care providers, particularly nurse practitioners, are in a unique position to expand on the face-to-face care provided to the community and engage in advocacy efforts to dismantle structural barriers impeding transgender individuals and communities while also providing primary health care, anticipatory guidance, and care coordination.