[Professor GAO Wei-bin's clinical experience of electroacupuncture with dense wave at periotic points for neurotic tinnitus].

Professor GAO Wei-bin's clinical experience of electroacupuncture (EA) with dense wave at periotic points for neurotic tinnitus is introduced. Based on the basic theory of TCM and the perspective of neuroanatomy, EA with dense wave at new periotic points (four points at mastoid process) and Ermen (TE 21), Tinggong (SI 19) could have the effects of qi reaching affected area, and play the treatment role of "where the acupoint is, where the efficacy is".

Exposure of adult mice to perfluorobutanesulfonate impacts ovarian functions through hypothyroxinemia leading to down-regulation of Akt-mTOR signaling.

Perfluorobutanesulfonate (PFBS), a short-chain perfluoroalkyl substance, is used in many industrial products. Preliminary evidence suggests that exposure to PFBS may increase the risk of infertility. The aim of this study was to investigate the influence of PFBS on ovarian function. Herein, we show that exposure of adult female mice to PFBS (200 mg/kg/day) (PFBS-mice) caused a decrease in the levels of serum total triiodothyronine and thyroxine, which depended on the activation of peroxisome proliferator-activated receptor α (PPARα). The numbers of secondary, early antral and antral follicles were reduced in PFBS-mice with an increase in the atretic follicles, and these changes were recovered by the replacement of L-thyroxinein or the treatment with PPARα antagonist GW6471. PFBS-induced hypothyroxinemia led to a decrease in the levels of Akt, mTOR and p70S6K phosphorylation in ovarian granular cells and cumulus cells, which suppressed the proliferation of these cells and enhanced autophagic death of granular cells and cumulus cells. The levels of serum estradiol and progesterone were reduced in PFBS-mice with a low expression of the steroidogenic genes Star and P450scc in ovarian tissues, which were sensitive to the replacement of L-thyroxinein or the blockade of PPARα. The results indicate that exposure to PFBS (≥200 mg/kg/day) through reducing thyroid hormones causes down-regulation of Akt-mTOR signaling in granular cells and cumulus cells, leading to the deficits in the development of follicles and the biosynthesis of ovarian hormones.

Exposure of pregnant mice to triclosan causes hyperphagic obesity of offspring via the hypermethylation of proopiomelanocortin promoter.

Triclosan (TCS), as a broad spectrum antibacterial agent, is commonly utilized in personal care and household products. Maternal urinary TCS level has been associated with changes in birth weight of infants. We in the present study investigated whether exposure of mice to 8 mg/kg TCS from gestational day (GD) 6 to GD14 alters prenatal and postnatal growth and development, and metabolic phenotypes in male and female offspring (TCS-offspring). Compared with control offspring, body weight in postnatal day (PND) 1 male or female TCS-offspring was reduced, but body weight gain was faster within postnatal 5 days. PND30 and PND60 TCS-offspring showed overweight with increases in visceral fat and adipocyte size. PND60 TCS-offspring displayed delayed glucose clearance and insulin resistance. PND30 TCS-offspring showed an increase in food intake without the changes in the oxygen consumption and respiratory exchange ratio (RER). The expression levels of proopiomelanocortin (POMC), α-melanocyte-stimulating hormone (α-MSH) and single-minded 1 (SIM1) in hypothalamus arcuate nucleus (ARC) and paraventricular nucleus (PVN), respectively, were significantly reduced in PND30 TCS-offspring compared to controls. The hypermethylation of CpG sites at the POMC promoter was observed in PND30 TCS-offspring, while the concentration of serum leptin was elevated and the level of STAT3 phosphorylation in ARC had no significant difference from control. This study demonstrates that TCS exposure during early/mid-gestation through the hypermethylation of the POMC promoter reduces the expression of anorexigenic neuropeptides to cause the postnatal hyperphagic obesity, leading to metabolic syndrome in adulthood.

Impact of Triclosan on Female Reproduction through Reducing Thyroid Hormones to Suppress Hypothalamic Kisspeptin Neurons in Mice.

Triclosan (TCS), a broad-spectrum antimicrobial agent, is widely used in clinical settings and various personal care products. The aim of this study was to evaluate the influence of TCS on reproductive endocrine and function. Here, we show that the exposure of adult female mice to 10 or 100 mg/kg/day TCS caused prolongation of diestrus, and decreases in antral follicles and corpora lutea within 2 weeks. TCS mice showed decreases in the levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and progesterone, and gonadotrophin-releasing hormone (GnRH) mRNA with the lack of LH surge and elevation of prolactin (PRL). TCS mice had lower kisspeptin immunoreactivity and kiss1 mRNA in anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). Moreover, the estrogen (E2)-enhanced AVPV-kisspeptin expression was reduced in TCS mice. In addition, the serum thyroid hormones (triiodothyronine (T3) and thyroxine (T4)) in TCS mice were reduced with increases in levels of thyroid stimulating hormone (TSH) and thyroid releasing hormone (TRH). In TCS mice, the treatment with Levothyroxine (L-T4) corrected the increases in PRL, TSH and TRH; the administration of L-T4 or type-2 dopamine receptors agonist quinpirole inhibiting PRL release could rescue the decline of kisspeptin expression in AVPV and ARC; the treatment with L-T4, quinpirole or the GPR45 agonist kisspeptin-10 recovered the levels of serum LH and FSH and progesterone, and GnRH mRNA. Furthermore, TCS mice treated with L-T4 or quinpirole resumed regular estrous cycling, follicular development and ovulation. Together, these results indicate that exposing adult female mice to TCS (≥10 mg/kg) reduces thyroid hormones causing hyperprolactinemia that then suppresses hypothalamic kisspeptin expression, leading to deficits in reproductive endocrine and function.

Exposure of Pregnant Mice to Triclosan Causes Insulin Resistance via Thyroxine Reduction.

Exposure to triclosan (TCS), an antibacterial agent, during pregnancy is associated with hypothyroxinemia and decreases in placental glucose transporter expression and activity. The objective of this study was to investigate the influence of TCS on glucose homeostasis and insulin sensitivity in gestational mice (G-mice) and nongestational female mice (Ng-mice) as a control. Herein, we show that the exposure of G-mice to TCS (8 mg/kg) from gestational day (GD) 5 to GD17 significantly increased their levels of fasting plasma glucose and serum insulin, and insulin content in pancreatic ß-cells with reduced homeostasis model assessment (HOMA)-ß index and increased HOMA-IR index. Area under curve (AUC) of glucose and insulin tolerance tests in TCS (8 mg/kg)-treated G-mice were markedly larger than controls. When compared with controls, TCS (8 mg/kg)-treated G-mice showed a significant decrease in the levels of thyroxine and triiodothyroninelevels, PPARγ and glucose transporter 4 (GLUT4) expression, and Akt phosphorylation in adipose tissue and muscle. Replacement of L-thyroxine in TCS (8 mg/kg)-treated G-mice corrected their insulin resistance and recovered the levels of insulin, PPARγ and GLUT4 expression, and Akt phosphorylation. Activation of PPARγ by administration of rosiglitazone recovered the decrease in Akt phosphorylation, but not GLUT4 expression. Although exposure to TCS (8 mg/kg) in Ng-mice reduced thyroid hormones levels, it did not cause the insulin resistance or affect PPARγ and GLUT4 expression, and Akt phosphorylation. The findings indicate that the exposure of gestational mice to TCS (≥8 mg/kg) results in insulin resistance via thyroid hormones reduction.