Physical therapy intervention for breast symptoms in lactating women: a randomized controlled trial.

BACKGROUND: Therapeutic ultrasound, education, and massage are the most common physical therapy interventions provided to mothers with breast symptoms. However, there is insufficient evidence on the effectiveness of the combination of these interventions. This study aimed to explore the effects of the combination of therapeutic ultrasound, education, and massage on breast symptoms in lactating women. METHODS: This study was a single-blind randomized controlled trial. Postpartum lactating women aged from 21 to 45 with breast symptoms were recruited and randomly allocated to one of three groups (ultrasound group, sham group, and usual care group). The severity of breast symptoms (pain, redness, lump, general malaise), breast engorgement, breast hardness, body temperature, breast temperature, and milk volume were assessed at baseline (T1), immediately post-intervention (T2), and at 3 months following baseline (T3). RESULTS: A total of 37 participants were included in the study (ultrasound group n = 12; sham group n = 12; usual care n = 13). The severity of breast symptoms (i.e., pain, lump, and general malaise) as well as breast engorgement, were significantly improved in the ultrasound group at T2 when compared to T1, and these improvements were sustained at T3. The severity of breast engorgement was significantly lower in the ultrasound group when compared to the usual care group at T2. However, no statistically significant differences were found between the ultrasound and sham groups for all outcomes at any assessment time points. CONCLUSIONS: Physical therapy interventions may be beneficial in relieving breast symptoms in lactating women. Larger randomized controlled trials are needed to confirm the findings of this study. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04569136); Date of registration: 29/09/2020.

Inhibiting NTRK2 signaling causes endometriotic lesion regression.

Endometriosis is a common gynecological disease in reproductive-age women. Although the hormone-dependent therapy is the first line treatment for endometriosis, it is not a curative regimen and associated with severe side-effects, which significantly decrease the life quality of affected individuals. To seek a target for treatment of endometriosis, we focused on plasma membrane proteins that are elevated in ectopic cells and exert beneficial effects in cell growth and survival. We performed bioinformatics analysis and identified the neurotrophic receptor tyrosine kinase 2 (NTRK2) as a potential candidate for treatment. The expression levels of NTRK2 were markedly upregulated in the lesions of clinical specimen as well as in the mouse endometriotic-like lesion. Mechanistic investigation demonstrated that upregulation of NTRK2 is induced by hypoxia in a hypoxia-inducible factor 1 alpha-dependent manner. Knockdown of NTRK2 or administration of ANA-12, a selective antagonist of NTRK2, significantly induced endometriotic stromal cells death, suggesting it may be a potential therapeutic agent. In vivo study using surgery-induced endometriosis mice model showed ANA-12 (1.5 mg/kg body weight) treatment induced apoptosis of endometriotic cells and caused the regression of ectopic lesions. Taken together, our findings suggest a possible mechanism responsible for the aberrant expression of NTRK2 in endometriotic lesions and this may be involved in the pathogenesis of endometriosis.

Targeting hypoxia-mediated YAP1 nuclear translocation ameliorates pathogenesis of endometriosis without compromising maternal fertility.

Endometriosis is a highly prevalent gynaecological disease that severely reduces women's health and quality of life. Ectopic endometriotic lesions have evolved mechanisms to survive in the hypoxic peritoneal microenvironment by regulating the expression of a significant subset of genes. However, the master regulator controlling these genes remains to be characterized. Herein, by using bioinformatics analysis and experimental verification, we identified yes-associated protein 1 (YAP1) as a master regulator of endometriosis. Nuclear localization and transcriptional activity of YAP1 were up-regulated by hypoxia via down-regulation of LATS1, a kinase that inactivates YAP1. Disruption of hypoxia-induced YAP1 signalling by siRNA knockdown or inhibitor treatment abolished critical biological processes involved in endometriosis development such as steroidogenesis, angiogenesis, inflammation, migration, innervation, and cell proliferation. Treatment with a YAP1 inhibitor caused the regression of endometriotic lesions without affecting maternal fertility or the growth rate of offspring in the mouse model of endometriosis. Taken together, we identify hypoxia/LATS1/YAP1 as a novel pathway for the pathogenesis of endometriosis and demonstrate that targeting YAP1 might be an alternative approach to treat endometriosis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Exercise training ameliorates glucosamine-induced insulin resistance in ovariectomized rats.

OBJECTIVE: Glucosamine (GlcN), which has been reported to induce insulin resistance (IR), is a popular nutritional supplement used to treat osteoarthritis in menopausal women. We previously demonstrated that GlcN treatment caused IR in ovariectomized rats by reducing the expression of glucose transport protein subtype 4 (GLUT-4) in skeletal muscle. In the present study, we hypothesized that endurance exercise training can reverse GlcN-induced IR. METHODS: Fifty female rats were randomly divided into five groups with 10 rats in each group: (1) sham-operated group; (2) sham-operated group with GlcN treatment for 14 days; (3) ovariectomy (OVX) group; (4) OVX with GlcN treatment; and (5) OVX with GlcN treatment followed by exercise training (running program) for 8 weeks. RESULTS: Fasting plasma glucose increased in the OVX + GlcN group, and fasting plasma insulin and the homeostasis model assessment-insulin resistance (HOMA-IR) were significantly higher only in this group. After the rats received exercise training for 8 weeks, no increase in the fasting plasma glucose, insulin, or HOMA-IR was observed. In an intraperitoneal glucose tolerance test, the plasma glucose, plasma insulin, HOMA-IR, and glucose-insulin index were significantly elevated only in the OVX with GlcN treatment group. However, the plasma glucose, plasma insulin, HOMA-IR, and glucose-insulin index decreased after exercise training for 8 weeks, implying that GlcN-induced IR in OVX rats could be reversed through exercise. A histological analysis revealed that exercise training can reduce islet hypertrophy and maintain GLUT-4 in skeletal muscle. CONCLUSIONS: Exercise training can alleviate IR in OVX rats treated with GlcN. Islet hyperplasia was subsequently prevented. Preserving GLUT-4 expression may be one of the mechanisms by which exercise prevents IR.

Efficacy of Femarelle for the treatment of climacteric syndrome in postmenopausal women: An open label trial.

OBJECTIVE: To assess the effects of 2 months of treatment with Femarelle for climacteric syndrome in Taiwanese postmenopausal women. MATERIALS AND METHODS: A multi-center, open-label trial of 260 postmenopausal women, age ≥ 45 years with vasomotor symptoms. Women were enrolled after obtaining a detailed medical history and a thorough physical examination. They then received Femarelle (640 mg/d) twice daily for 8 weeks. The primary outcome was the changes in the frequency and severity of hot flushes from baseline to 4 weeks (1 month) and 8 weeks (2 months). Changes of general climacteric syndrome were assessed using a modified climacteric scale designed by Greene. RESULTS: The frequency and severity of hot flushes were significantly improved with Femarelle use (p < 0.001). After 8 weeks of treatment, the percentage of women with various climacteric syndromes was reduced (from 100% to 20.9% for hot flushes, from 97.7% to 87.9% for psychological symptoms, from 93.8% to 78.8% for somatic symptoms, and from 87.8% to 74.9% for sexual symptoms). General climacteric syndrome scores also significantly decreased, from 20.8 ± 0.7 at the time of enrollment to 12.9 ± 0.7 after 8 weeks of Femarelle treatment (p < 0.0001). Participants experienced improvement of various climacteric symptoms and signs after 8 weeks of treatment (75.1% for hot flushes, 68.7% for psychological symptoms, 70.6% for somatic symptoms, and 69.0% for sexual problems respectively). After 4 weeks and 8 weeks of treatment with Femarelle, patients showed statistically significant improvement in climacteric symptoms (p < 0.0001). Three women (1.2%) withdrew from the study after 4 weeks of treatment due to adverse effects. CONCLUSION: Femarelle significantly improved climacteric symptoms in Taiwanese postmenopausal women. However, further evaluation is needed regarding the safety of long-term consumption.

17ß-estradiol protects against glucosamine-induced pancreatic ß-cell dysfunction.

OBJECTIVE: Glucosamine (GlcN) is a popular supplement for osteoarthritis in postmenopausal women. Although GlcN possibly induces insulin resistance, the effects of GlcN on ß-cell dysfunction are still obscure. METHODS: In the present study, we investigated changes in insulin production and ß-cell apoptosis in pancreatic islets after GlcN treatment in rats with or without ovariectomy and used MIN-6 cells to investigate the protective effects and molecular mechanisms of 17ß-estradiol (E2) in GlcN-induced ß-cell dysfunction. The rats were divided into four groups: (1) sham operation (SHAM; n = 8); (2) SHAM with 750 mg/kg/day GlcN injected intraperitoneally for 14 days (SHAM + GlcN; n = 10); (3) ovariectomy (OVX; n = 9); and (4) OVX with 750 mg/kg/day GlcN injected intraperitoneally for 14 days (OVX + GlcN; n = 9). RESULTS: Both GlcN and ovariectomy reduced the expression of insulin, determined by the staining intensity of insulin and reverse polymerase chain reaction. GlcN alone also induced ß-cell apoptosis, and this adverse effect was aggravated after ovariectomy. In addition, we found that GlcN decreased calcium influx and insulin secretion by decreasing the protein levels of inwardly rectifying potassium in the ATP-sensitive potassium channel. GlcN decreased the protein levels of endoplasmic reticulum (ER) stress-associated proteins, including C/EBP homologous protein, phospho-protein kinase-like endoplasmic reticulum kinase, phospho-eukaryotic initiation factor 2α, and phospho-c-Jun N-terminal kinase. Finally, GlcN decreased cell viability. E2 counteracted GlcN-mediated attenuation in intracellular calcium concentration, extracellular insulin secretion, protein levels of inwardly rectifying potassium, cell viability, and protein levels of ER stress-associated proteins. ICI182.780 inhibited these beneficial effects of E2. CONCLUSIONS: GlcN impairs insulin secretion of ß-cells by inhibiting Ca influx and enhancing ß-cell apoptosis with increases in ER stress-related proteins, whereas E2 counters these adverse effects of GlcN.

Upregulation of steroidogenic enzymes and ovarian 17beta-estradiol in human granulosa-lutein cells by Cordyceps sinensis mycelium.

There is increasing evidence that 17beta-estradiol (E2) directly influences the quality of maturing oocytes and thus the outcome of assisted reproduction treatment. Although Cordyceps sinensis (CS) mycelium, a Chinese herbal medicine, is believed to enhance libido and fertility in both sexes, the mechanism of its effect in women has not been determined. The aim of the present study was to evaluate the effects of CS on steroidogenic enzyme expression and E2 biosynthesis in human granulosa-lutein cells (GLC). We found that CS induced E2 production by GLC in a dose- and time-dependent manner and that a 3-h treatment with CS induced increased levels of mRNAs coding for the P450 side chain cleavage enzyme (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), and aromatase. Western blot analysis demonstrated that, after treatment with CS for 3 h, protein levels of steroidogenic acute regulatory protein (StAR) and aromatase were upregulated while P450scc and 3beta-HSD levels showed no substantial change. New protein synthesis was required for CS-induced E2 production because it was abrogated by cycloheximide pretreatment. Addition of 22(R)-hydroxycholesterol, thus bypassing the need for StAR protein, did not induce as much E2 production as CS treatment, indicating that upregulation of StAR protein was not the only factor contributing to CS-induced steroidogenesis. Cotreatment of GLCs with CS and aminoglutethimide, an aromatase inhibitor, completely abolished CS-induced E2 production. In conclusion, treatment of GLCs with CS results in increased E2 production due, at least in part, to increased StAR and aromatase expression. These data may help in the development of treatment regimens to improve the success rate of in vitro fertilization.