Gestational bisphenol A exposure advances puberty onset in female offspring: Critical time window identification.

Increasing evidence shows that the early onset of puberty in female offspring may be caused by maternal prenatal exposure to bisphenol A (BPA) during pregnancy; however, the critical time window of maternal prenatal BPA exposure remains unknown. Here, we identify the critical time window of gestational BPA exposure that induces early onset of puberty in female offspring. Pregnant CD-1 mice were gavaged with BPA (8 mg/kg) daily during the early gestational stage (GD1-GD6), middle gestational stage (GD7-GD12) or late gestational stage (GD13-GD18). We show that maternal BPA exposure during the early and middle gestational stages could advance the vaginal opening time and increase the serum levels of kisspeptin-10 and GnRH in the female offspring at PND 34. Mechanistically, maternal BPA exposure during early and middle gestation could significantly increase CpG island methylation in the Eed gene promoters but reduce the mRNA expression of Eed in the hypothalamus tissues of the female offspring. In conclusion, the critical period of maternal BPA exposure-induced early onset of puberty in female offspring is early and middle gestation; this BPA-induced early onset of puberty might be partly attributed to epigenetic programming of the Eed gene in the hypothalamus. This study provides important insights regarding the relationship and the mechanisms between BPA and offspring pubertal development.

Utilization of Isoflavones in Soybeans for Women with Menopausal Syndrome: An Overview.

Based on their nutrient composition, soybeans and related foods have been considered to be nutritious and healthy for humans. Particularly, the biological activity and subsequent benefits of soy products may be associated with the presence of isoflavone in soybeans. As an alternative treatment for menopause-related symptoms, isoflavone has gained much popularity for postmenopausal women who have concerns related to undergoing hormone replacement therapy. However, current research has still not reached a consensus on the effects of isoflavone on humans. This overview is a summary of the current literature about the processing of soybeans and isoflavone types (daidzein, genistein, and S-equol) and supplements and their extraction and analysis as well as information about the utilization of isoflavones in soybeans. The processes of preparation (cleaning, drying, crushing and dehulling) and extraction of soybeans are implemented to produce refined soy oil, soy lecithin, free fatty acids, glycerol and soybean meal. The remaining components consist of inorganic constituents (minerals) and the minor components of biologically interesting small molecules. Regarding the preventive effects on diseases or cancers, a higher intake of isoflavones is associated with a moderately lower risk of developing coronary heart disease. It may also reduce the risks of breast and colorectal cancer as well as the incidence of breast cancer recurrence. Consumption of isoflavones or soy foods is associated with reduced risks of endometrial and bladder cancer. Regarding the therapeutic effects on menopausal syndrome or other diseases, isoflavones have been found to alleviate vasomotor syndromes even after considering placebo effects, reduce bone loss in the spine and ameliorate hypertension and in vitro glycemic control. They may also alleviate depressive symptoms during pregnancy. On the other hand, isoflavones have not shown definitive effects regarding improving cognition and urogenital symptoms. Because of lacking standardization in the study designs, such as the ingredients and doses of isoflavones and the durations and outcomes of trials, it currently remains difficult to draw overall conclusions for all aspects of isoflavones. These limitations warrant further investigations of isoflavone use for women's health.

In Vitro and Vivo Identification, Metabolism and Action of Xenoestrogens: An Overview.

Xenoestrogens (XEs) are substances that imitate endogenous estrogens to affect the physiologic functions of humans or other animals. As endocrine disruptors, they can be either synthetic or natural chemical compounds derived from diet, pesticides, cosmetics, plastics, plants, industrial byproducts, metals, and medications. By mimicking the chemical structure that is naturally occurring estrogen compounds, synthetic XEs, such as polychlorinated biphenyls (PCBs), bisphenol A (BPA), and diethylstilbestrol (DES), are considered the focus of a group of exogenous chemical. On the other hand, nature phytoestrogens in soybeans can also serve as XEs to exert estrogenic activities. In contrast, some XEs are not similar to estrogens in structure and can affect the physiologic functions in ways other than ER-ERE ligand routes. Studies have confirmed that even the weakly active compounds could interfere with the hormonal balance with persistency or high concentrations of XEs, thus possibly being associated with the occurrence of the reproductive tract or neuroendocrine disorders and congenital malformations. However, XEs are most likely to exert tissue-specific and non-genomic actions when estrogen concentrations are relatively low. Current research has reported that there is not only one factor affected by XEs, but opposite directions are also found on several occasions, or even different components stem from the identical endocrine pathway; thus, it is more challenging and unpredictable of the physical health. This review provides a summary of the identification, detection, metabolism, and action of XEs. However, many details of the underlying mechanisms remain unknown and warrant further investigation.

The Utilization of Dehydroepiandrosterone as a Sexual Hormone Precursor in Premenopausal and Postmenopausal Women: An Overview.

Dehydroepiandrosterone (DHEA), and its metabolite, dehydroepiandrosterone sulfate ester (DHEAS), are the most abundant circulating steroid hormones, and are synthesized in the zona reticularis of the adrenal cortex, in the gonads, and in the brain. The precise physiological role of DHEA and DHEAS is not yet fully understood, but these steroid hormones can act as androgens, estrogens, and neurosteroids, and perform many roles in the human body. Since both levels decline with age, use of DHEA supplements have gained more attention due to being advertised as an antidote to aging in postmenopausal women, who may have concerns on age-related diseases and overall well-being. However, current research has not reached an overall consensus on the effects of DHEA on postmenopausal women. This overview is a summary of the current literature, addressing the metabolic pathway for DHEA synthesis and utilization, as well as the effects of DHEA on premenopausal and postmenopausal women with disease states and other factors. As for the therapeutic effects on menopausal syndrome and other age-related diseases, several studies have found that DHEA supplementations can alleviate vasomotor symptoms, preserve the integrity of the immune system, reduce bone loss, and increase muscle mass. Intravaginal DHEA has shown significant beneficial effects in menopausal women with severe vulvovaginal symptoms. On the other hand, DHEA supplements have not shown definitive effects in cardiovascular disease, adrenal insufficiency, insulin sensitivity, and cognition. Due to inadequate sample sizes and treatment durations of current studies, it is difficult to assess the safety and efficacy of DHEA and draw reliable conclusions for the physiological role, the optimal dosage, and the effects on premenopausal and postmenopausal women; therefore, the study of DHEA warrants future investigation. Further research into the roles of these steroid hormones may bring us closer to a therapeutic option in the future.

Osteoporosis in Patients with Chronic Kidney Diseases: A Systemic Review.

Chronic kidney disease (CKD) is associated with the development of mineral bone disorder (MBD), osteoporosis, and fragility fractures. Among CKD patients, adynamic bone disease or low bone turnover is the most common type of renal osteodystrophy. The consequences of CKD-MBD include increased fracture risk, greater morbidity, and mortality. Thus, the goal is to prevent the occurrences of fractures by means of alleviating CKD-induced MBD and treating subsequent osteoporosis. Changes in mineral and humoral metabolism as well as bone structure develop early in the course of CKD. CKD-MBD includes abnormalities of calcium, phosphorus, PTH, and/or vitamin D; abnormalities in bone turnover, mineralization, volume, linear growth, or strength; and/or vascular or other soft tissue calcification. In patients with CKD-MBD, using either DXA or FRAX to screen fracture risk should be considered. Biomarkers such as bALP and iPTH may assist to assess bone turnover. Before initiating an antiresorptive or anabolic agent to treat osteoporosis in CKD patients, lifestyle modifications, such as exercise, calcium, and vitamin D supplementation, smoking cessation, and avoidance of excessive alcohol intake are important. Managing hyperphosphatemia and SHPT are also crucial. Understanding the complex pathogenesis of CKD-MBD is crucial in improving one's short- and long-term outcomes. Treatment strategies for CKD-associated osteoporosis should be patient-centered to determine the type of renal osteodystrophy. This review focuses on the mechanism, evaluation and management of patients with CKD-MBD. However, further studies are needed to explore more details regarding the underlying pathophysiology and to assess the safety and efficacy of agents for treating CKD-MBD.

Isoflavone Supplements for Menopausal Women: A Systematic Review.

Isoflavones have gained popularity as an alternative treatment for menopausal symptoms for people who cannot or are unwilling to take hormone replacement therapy. However, there is still no consensus on the effects of isoflavones despite over two decades of vigorous research. This systematic review aims to summarize the current literature on isoflavone supplements, focusing on the active ingredients daidzein, genistein, and S-equol, and provide a framework to guide future research. We performed a literature search in Ovid Medline using the search terms "isoflavone" and "menopause", which yielded 95 abstracts and 68 full-text articles. We found that isoflavones reduce hot flashes even accounting for placebo effect, attenuate lumbar spine bone mineral density (BMD) loss, show beneficial effects on systolic blood pressure during early menopause, and improve glycemic control in vitro. There are currently no conclusive benefits of isoflavones on urogenital symptoms and cognition. Due to the lack of standardized research protocols including isoflavone component and dosage, outcomes, and trial duration, it is difficult to reach a conclusion at this point in time. Despite these limitations, the evidence thus far favors the use of isoflavones due to their safety profile and benefit to overall health.

Nutritional Support and Physical Modalities for People with Osteoporosis: Current Opinion.

Osteoporosis is a vital healthcare issue among elderly people. During the aging process, a gradual loss of bone mass results in osteopenia and osteoporosis. Heritable factors account for 60%-80% of optimal bone mineralization, whereas modifiable factors such as nutrition, weight-bearing exercise, body mass, and hormonal milieu affect the development of osteopenia and osteoporosis in adulthood. Osteoporosis substantially increases the risk of skeletal fractures and further morbidity and mortality. The effective prevention of fractures by reducing the loss of bone mass is the primary goal for physicians treating people with osteoporosis. Other than pharmacologic agents, lifestyle adjustment, nutritional support, fall prevention strategies, exercise, and physical modalities can be used to treat osteoporosis or prevent further osteoporotic fracture. Each of these factors, alone or in combination, can be of benefit to people with osteoporosis and should be implemented following a detailed discussion with patients. This review comprises a systematic survey of the current literature on osteoporosis and its nonpharmacologic and nonsurgical treatment. It provides clinicians and healthcare workers with evidence-based information on the assessment and management of osteoporosis. However, numerous issues regarding osteoporosis and its treatment remain unexplored and warrant future investigation.

Evaluation of leap motion control for hand rehabilitation in burn patients: An experience in the dust explosion disaster in Formosa Fun Coast.

Hand burns cause functional impairment. Leap motion control (LMC), a kind of virtual reality games, employs a novel system that provides biofeedback and training of fine motor function and functional skills. In this study, we hypothesized that LMC would improve burned hand function. Sixteen participants were allocated to either the LMC group or the control group. The LMC group played 20min identical leap motion video games after 40min traditional occupational therapy (OT). The control group received traditional OT for 60min. Both groups received interventions 2 days a week for 4 months. A series of questionnaires were administered, including BSHS-B, QuickDASH, iADL, and Barthel index. Data on baseline characteristics including joint range of motion (ROM), grip and pinch strength, and scar thickness were obtained. Furthermore, we used the Mann-Whitney U test and Wilcoxon signed-rank test for comparison, as appropriate. We found improvements in BSHS-B, QuickDASH, and iADL in the LMC group (all p<0.05) compared to those in the control group. In the LMC-trained hand, the ROM of the thumb IP joint and pinch strength increased, whereas the scar thickness over the first dorsal interossei muscle decreased (p<0.05). In conclusion, leap motion training could help patients with hand burns to increase finger ROM, decrease scar thickness, and improve hand function.

Additional Vitamin and Mineral Support for Patients with Severe Burns: A Nationwide Experience from a Catastrophic Color-Dust Explosion Event in Taiwan.

Major burn injuries, which encompass ≥20% of the total body surface area (TBSA), are the most severe form of trauma because of the stress response they provoke, which includes hypermetabolism, muscle wasting, and stress-induced diabetes. In 2015, a color-dust explosion disaster occurred in the Formosa Fun Coast of Taiwan and injured 499 people, who were transferred via a nationwide emergency delivery system. Some recommendations are currently available regarding vitamin and mineral support for wound healing and recovery in severe burns, but there is a lack of evidence to confirm the benefits. Thus, the current study aimed to investigate the effects of additional vitamin and mineral support for patients with severe burn injuries. Sixty-one hospitalized individuals with major burns (full thickness and ≥20% TBSA) were classified into the supplement (n = 30) and control (n = 31) groups, according to whether they received supplementation with additional vitamins, calcium, and magnesium. There were significant differences between the supplement and control groups in the incidence of wound infection (30.0% vs. 77.4%, p < 0.001), sepsis (13.3% vs. 41.9%, p = 0.021), and hospitalization days (51.80 vs. 76.81, p = 0.025). After adjustment, logistic regression analysis revealed that, compared to those in the control group, patients in the supplement group had a lower risk for wound infection (OR 0.11; 95% CI 0.03⁻0.43; p = 0.002) and sepsis (OR 0.09; 95% CI 0.01⁻0.61; p = 0.014). Supplementation of multiple vitamins, calcium, and magnesium reduced the risk of wound infection and sepsis, shortened the time of hospitalization, and can be considered for use in major burns.

Risk of gestational hypertension-preeclampsia in women with preceding endometriosis: A nationwide population-based study.

OBJECTIVE: To investigate the association between preceding endometriosis and gestational hypertension-preeclampsia (GH-PE). METHODS: In this nationwide population-based longitudinal study, data from 1998-2012 Taiwan National Health Insurance Research Database were used. We used ICD9-CM codes 617.X and 642.X respectively for the diagnoses of endometriosis and GH-PE, which were further confirmed by examining medical records of surgeries, blood pressure and urine protein to ensure the accuracy of the diagnoses. The study excluded women diagnosed with endometriosis at < 15 or > 45 years of age, chronic hypertension, and GH-PE prior to endometriosis. Each pregnant woman with a prior diagnosis of endometriosis was matched to 4 pregnant women without endometriosis by age. Logistic regression analysis was used to calculate odds ratios (ORs) for the risk of GH-PE with adjustment for age, occupation, urbanization, economic status and comorbidities. RESULTS: Among 6,300 women with a prior endometriosis diagnosis who were retrieved from a population of 1,000,000 residents, 2,578 (40.92%) had subsequent pregnancies that were eligible for further analysis and were compared with 10,312 pregnant women without previous endometriosis. GH-PE occurred more in women with prior endometriosis as compared to those without endometriosis (3.88% vs. 1.63%, p<0.0001). Further analysis revealed prior endometriosis was associated with GH-PE (adjusted OR = 2.27; 95% CI:1.76-2.93). For danazol-treated and non-danazol-treated subgroups, the incidences of GH-PE were 3.13% (15/480) and 4.05% (85/2,098), respectively. Although the risk for subsequent GH-PE was lower (adjusted OR = 1.49; 95% CI:0.86-2.56) after receiving danazol treatment than average (adjusted OR = 2.27; 95% CI:1.76-2.93) for women with preceding endometriosis, the reduction of risk was not statistically remarkable for danazol-treated (adjusted OR = 1.49) vs. non-danazol-treated (adjusted OR = 2.48) subgroups (p heterogeneity = 0.12). CONCLUSIONS: Preceding endometriosis is an independent and significant risk factor for the occurrence of GH-PE.

Iron Deficiency Anemia as a Risk Factor for Osteoporosis in Taiwan: A Nationwide Population-Based Study.

The cause-effect relationship between iron deficiency anemia (IDA) and osteoporosis has not been established in the general population. Thus, the current longitudinal study determined the role of IDA as a risk factor for osteoporosis by analyzing a large nationwide population-based sample. In a sample of 1,000,000 randomly sampled individuals from the 1998-2012. Taiwan National Health Insurance Research Database, patients with IDA (case group (n = 35,751)) and individuals without IDA (control group (n = 178,755)) were compared. Patients who were <20 years of age and who had pre-existing osteoporosis prior to the diagnosis of IDA were excluded. Each patient with IDA was age- and gender-matched to five individuals without IDA. The diagnoses of IDA and osteoporosis (coded using ICD-9CM) were further confirmed with blood test results and X-ray bone densitometry to ensure the accuracy of the diagnoses. Osteoporosis occurred more often among patients with IDA compared to individuals without IDA (2.27% vs. 1.32%, p < 0.001). Cox proportional hazard analysis revealed that the risk for osteoporosis was significantly higher in the case than the control group (hazard ratio (HR) = 1.74; 95% CI = 1.61-1.88) and remained similar after adjustment for covariates (adjusted HR = 1.81; 95% CI = 1.67-1.97). Compared with individuals without IDA, the risk for osteoporosis was even higher for patients with IDA who received intravenous ferrum therapy (adjusted HR = 2.21; 95% CI = 1.85-2.63). In contrast, the risk for osteoporosis was reduced for patients with IDA who received a blood transfusion (adjusted HR = 1.47; 95% CI = 1.20-1.80). As a predictor, prior IDA is a significant and independent risk factor for development of osteoporosis.

A novel diterpene suppresses CWR22Rv1 tumor growth in vivo through antiproliferation and proapoptosis.

Androgen receptor (AR) is the main therapeutic target for treatment of metastatic prostate cancers (PCa). As recurrent tumors restore AR activity independent of hormones, new therapies that abolish AR activity have been sought to prevent or delay the emergence of ablation-resistant disease. Here, we report that a novel abietane diterpene, 6-hydroxy-5,6-dehydrosugiol (HDHS), isolated from the stem bark of Cryptomeria japonica, was a potent AR antagonist in PCa cells. HDHS treatment of androgen-dependent LNCaP and androgen-responsive 22Rv1 cells induced apoptosis as shown by nucleosome release, activation of caspase-3 and caspase-7, and cleavage of poly(ADP-ribose) polymerase accompanied with concomitant up-regulation of tumor suppressor p53. HDHS also decreased the protein expression of cyclins (D1 and E), cyclin-dependent kinases (CDK2, CDK4, and CDK6), and retinoblastoma phosphorylation in PCa cells, which suggest cell cycle arrest in the G(1) phase. Oral administration of HDHS at 0.5 and 2.5 mg/kg once daily for 24 days to 22Rv1 PCa xenografted mice suppressed tumor growth by 22% and 39%, respectively, in association with decreased proliferation and increased apoptosis in tumor cells, which further correlated with increased levels of HDHS in plasma and tumors. Overall, our data suggest that HDHS has potential for use in chemoprevention and chemotherapy of PCa.

Rapid authentication of Bupleurum species using an array of immobilized sequence-specific oligonucleotide probes.

Standardization and modernization of Chinese medicinal herbs are limited partially by misidentification of processed materials. Our goal was to develop an efficient method for verification of Chinese medicinal herbs, based on the variable sites of the rDNA internal transcribed spacer (ITS) region. We analyzed sequence differences in ITS of three Bupleurum species, B. kaoi Liu Chao et Chuang, B. falcatum L. and B. chinense DC., and developed a rapid detection method using a sequence-specific oligonucleotide probe (SSOP) array. The SSOP array, composed of poly-T tailed sequence-specific oligonucleotides, was hybridized to the digoxigenin (DIG)-labeled target ITS DNA of the Bupleurum species. The detected signals corresponded precisely to the specific sequences. This array provides a reliable and economical method for authenticating a large number of Chinese medicinal herbs. The short duration of the procedure (within 30 h) makes it an especially useful tool in verifying processed plant material.

Compounds from Wedelia chinensis synergistically suppress androgen activity and growth in prostate cancer cells.

Chronic inflammation can augment tumor development in various types of cancers, including prostate cancer (PCa). Reduction of inflammation is therefore an important anticancer therapeutic opportunity. Here, we report four anti-proliferative phytocompounds in Wedelia chinensis, an oriental herbal medicine, identified through their ability to modulate the androgen receptor (AR) activation of transcription from prostate-specific antigen promoter in PCa cells. The 50% inhibition concentration values of indole-3-carboxylaldehyde, wedelolactone, luteolin and apigenin, were 34.9, 0.2, 2.4 and 9.8 muM, respectively. A formula that combined the phytocompounds in the same proportions as in the herbal extract decreased the dosage of each compound required to achieve maximal AR inhibition. In correlation with the AR suppression effect, these active compounds specifically inhibited the growth of AR-dependent PCa cells and as a combination formula they also synergistically suppressed growth in AR-dependent PCa cells. Our study has identified synergistic effects of active compounds in W. chinensis and demonstrated their potential in PCa prevention and therapy. The paradigm of multiple activities and synergism is a useful framework to investigate the therapeutic effects of whole extracts from assorted medicinal plant species.

Diterpenes from Cryptomeria japonica inhibit androgen receptor transcriptional activity in prostate cancer cells.

We identified eight diterpenes from Cryptomeria japonica (Taxodiaceae), which inhibit the activity of the androgen receptor (AR) in human prostate cancer (PCa) 22Rv1-derived 103E cells. The compounds 6,12-dihydroxyabieta-5,8,11,13-tetraen-7-one ( 2), sugiol ( 3), ferruginol ( 4), and 5-epixanthoperol ( 7) have near 100 % AR inhibition efficacy at concentrations of 10, 5, 25, and 25 microM, respectively. Because these compounds have very similar structures, analysis of their differential activity may aid in the design of inhibitors for PCa treatment.