High glucose and palmitic acid induces neuronal senescence by NRSF/REST elevation and the subsequent mTOR-related autophagy suppression.

Cell senescence is a basic aging mechanism. Previous studies have found that the cellular senescence in adipose tissue and other tissues, such as the pancreas, muscle and liver, is associated with the pathogenesis and progression of type 2 diabetes; however, strong evidence of whether diabetes directly causes neuronal senescence in the brain is still lacking. In this study, we constructed a high glucose and palmitic acid (HGP) environment on PC12 neuronal cells and primary mouse cortical neurons to simulate diabetes. Our results showed that after HGP exposure, neurons exhibited obvious senescence-like phenotypes, including increased NRSF/REST level, mTOR activation and cell autophagy suppression. Downregulation of NRSF/REST could remarkably alleviate p16, p21 and γH2A.X upregulations induced by HGP treatment, and enhance mTOR-autophagy of neurons. Our results suggested that the diabetic condition could directly induce neuronal senescence, which is mediated by the upregulation of NRSF/REST and subsequent reduction of mTOR-autophagy.

Combined treatment with dihydrotestosterone and lipopolysaccharide modulates prostate homeostasis by upregulating TNF-α from M1 macrophages and promotes proliferation of prostate stromal cells.

Androgens and chronic inflammation, which play essential roles in the development of benign prostatic hyperplasia (BPH), are considered to be important factors in disorders of prostate homeostasis. These two factors may lead to pathological hyperplasia in the prostate transition zone of patients with BPH. However, few studies have examined the mechanism of how dihydrotestosterone (DHT) affects chronic inflammation in prostate tissue during the progression of BPH. This study examined the performance of DHT in lipopolysaccharide-treated M1 macrophages and the subsequent effects on the proliferation of prostate stromal and epithelial cells. We found that DHT increased secretion of the pro-inflammatory factor tumor necrosis factor (TNF)-α from M1 macrophages differentiated from THP-1 cells. The supernatant of M1 macrophages promoted the proliferation of WPMY-1 prostate stromal cells by upregulating B-cell lymphoma-extra large (Bcl-xL) and cellular Myc (c-Myc) levels by activating TNF-α-mediated nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Moreover, this supernatant increased the expression of androgen receptor in WPMY-1 cells, which was TNF-α-independent. Additionally, TNF-α protein expression was significantly higher in patients with BPH and a large prostate volume than that in those with a small prostate volume. Further analysis showed that higher serum testosterone combined with prostate-specific androgen concentrations was related to TNF-α expression. This study suggests that DHT modulates the inflammatory environment of BPH by increasing TNF-α expression from lipopolysaccharide-treated M1 macrophages and promotes the proliferation of prostate stromal cells. Targeting TNF-α, but not DHT, may be a promising strategy for patients with BPH.

Review of the Roles and Interaction of Androgen and Inflammation in Benign Prostatic Hyperplasia.

The lower urinary tract symptoms (LUTSs) and acute urinary retention (AUR) caused by benign prostatic hyperplasia (BPH) can seriously affect the quality of life of elderly men. Studies suggest that both androgens and inflammation greatly influence the occurrence and development of BPH in most patients. These two factors combined can also affect each other, leading to pathological changes in the stromal and epithelial tissue of the prostate transition zone in BPH patients. DHT in the prostate tissue of BPH patients may activate a chronic inflammatory response in the prostate, amplifying the expression of inflammatory factors and upregulating the proliferation ability of prostate tissue.

Neuroprotection of dihydrotestosterone via suppression of the toll-like receptor 4/nuclear factor-kappa B signaling pathway in high glucose-induced BV-2 microglia inflammatory responses.

Hyperglycemia is considered to induce neuronal apoptosis via activating microglia inflammatory responses, thus involving in the development and progression of diabetic encephalopathy and neurodegenerative disorders. Increasing evidences suggest that androgen exerts neuroprotective functions including antiapoptosis, anti-inflammation and antioxidative stress. In this study, we investigate the anti-inflammatory role of dihydrotestosterone (DHT) in high glucose (HG)-induced neuroinflammatory response in BV-2 microglia. Our results revealed that DHT significantly inhibited HG-induced production of nitric oxide and prostaglandin E2 through suppressing the expression of corresponding regulatory enzymes - inducible NO synthase and cyclooxygenase-2. Also, DHT inhibited HG-induced expression of TNF-α and IL-1ß. Moreover, DHT suppressed the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. Furthermore, when SH-SY5Y neurons were cultured in HG-treated BV-2 microglial supernatant, DHT pretreatment significantly increased neuronal survival, indicating the neuroprotective role of DHT. Collectively, these results suggest that DHT could protect SH-SY5Y neurons from HG-mediated BV-2 microglia inflammatory damage through inhibiting TLR4/NF-κB signaling, suggesting that maintenance of androgen level in brain might have potential benefit in neurodegenerative diseases, especially in diabetes patients combined with cognitive disorders.

Urinary incontinence following deep brain stimulation of the globus pallidus internus: case report.

Deep brain stimulation (DBS) is a well-established therapy for patients with advanced Parkinson's disease (PD), dystonia, and other movement disorders. In contrast to the strong positive effects that have been documented for motor symptoms, the effects of DBS on nonmotor symptoms have not been fully elucidated. Some reports suggest that stimulation of the subthalamic nucleus may improve lower urinary tract symptoms in patients with PD; however, reports of the effects of globus pallidus internus (GPi) DBS on urinary symptoms are limited. The authors present the case of a 49-year-old woman with PD who developed severe urinary incontinence after 27 months of GPi DBS. The urinary incontinence disappeared when stimulation was turned off, and reemerged after it was turned on again. After activation of a more dorsal contact in the left electrode, the patient's urinary dynamics returned to normal.

Identification of late-onset hypogonadism in middle-aged and elderly men from a community of China.

In this study, we investigated the essential criteria for late-onset hypogonadism (LOH) syndrome based on the presence of symptoms associated with low testosterone levels in Han Chinese men. Blood tests for total testosterone (TT) and sex hormone-binding globulin (SHBG) were performed, and the aging male symptoms (AMS) questionnaire was conducted in a randomly selected cohort composed of 944 Chinese men aged 40 to 79 years from nine urban communities. Three sexual symptoms (decreased ability/frequency of sexual activity, decreased number of morning erections, and decreased libido) were confirmed to be related to the total and free testosterone levels. The thresholds for TT were approximately 12.55 nmol l-1 for a decreased ability/frequency to perform sex, 12.55 nmol l-1 for decreased frequency of morning erections, and 14.35 nmol l-1 for decreased sexual desire. The calculated free testosterone (CFT) thresholds for these three sexual symptoms were 281.14, 264.90, and 287.21 pmol l-1 , respectively. TT <13.21 nmol l-1 (OR = 1.4, 95%CI: 1.0-1.9, P = 0.037) or CFT <268.89 pmol l-1 (OR = 1.5, 95%CI: 1.1-20, P = 0.020) was associated with an increase in the aforementioned three sexual symptoms. The prevalence of LOH was 9.1% under the criteria, including all three sexual symptoms with TT levels <13.21 nmol l-1 and CFT levels <268.89 pmol l-1 . Our results may improve the diagnostic accuracy of LOH in older men.

[Clinical trial of sexual dysfunctions in male patients with pituitary adenomas].

OBJECTIVE: To explore the clinical features and related factors of sexual dysfunctions in male patients with pituitary adenomas. METHODS: The questionnaires of sexual functions were collected from 86 male patients with pituitary adenomas. We examined the clinical features of sexual dysfunctions and analyzed the correlations between sexual behaviors and age, tumor type, invasiveness, tumor size, serum levels of prolactin (PRL) and testosterone. RESULTS: The incidence of sexual dysfunctions was 80.2% (69/86). Sexual dysfunctions were found in 84.6% (66/78) of the patients with functioning pituitary adenomas and 37.5% (3/8) of those with non-functioning pituitary adenoma respectively. In the PRL group, the incidence of erectile dysfunctions was 92.1% (35/38) and it was higher than those in the FSH (follicle-stimulating hormone) and GH (growth hormone) groups (P < 0.05). In the FSH group, the incidence of reduced sexual desire was 78.3% (18/23). In the GH group, the incidence of erectile dysfunctions was 70.6% (12/17) and the incidence of reduced sexual desire or ejaculation dysfunction was lower than that of the PRL/FSH group (P < 0.05). CONCLUSION: The incidence of sexual dysfunctions is quite high in males with pituitary adenomas, especially for those with functioning pituitary adenomas. The clinical features of sexual dysfunctions vary in different types of functioning pituitary adenoma. The incidence of erectile dysfunctions is the highest in the PRL group. Pathological type of pituitary tumors is a major risk factor of sexual dysfunctions.

[Lower urinary tract symptoms and prostatic growth pattern among old and middle-aged males in Shanghai community].

OBJECTIVE: To investigate the prevalence of lower urinary tract symptoms (LUTS) and the age-related growth pattern of the prostate among 40 -70 year-old males in Shanghai community. METHODS: Using cluster and stratified random sampling and IPSS, we investigated the prevalence of LUTS among 1000 males aged 40 -70 years in the general population of Shanghai from November 2009 to June 2010. We measured the transverse, anteroposterior and vertical diameters of the prostate and its transition zone in each volunteer by transrectal ultrasonography and established the equation for the age-related growth pattern of the prostate. RESULTS: In the 40 to 49-, 50 to 59- and 60 to 70-year groups, the incidence rates of moderate and severe LUTS (IPSS > or = 8) were 10.0%, 15.0% and 28.7%, respectively. The length, width, height and volume of the prostate and its transition zone were positively corrected with age (P < 0.05). The prostatic growth pattern equations based on the parameters of the transverse, anteroposterior and vertical diameters were Y = 1.6 x 10(-5)X3-0.002 1X2 + 0.074 6X + 0.677 2, Y = -2.4 x 10(-5)X3 + 0.003 3X2-0.1312X + 1.269, and Y = 1.6 x 10(-5)X3-0.001 8X2 + 0.073X- 0.690 9, respectively. The transverse and anteroposterior diameters of the prostate grew at a relatively similar rate, while the transverse diameter grew obviously faster than the vertical diameter before 60 years old, but the latter significantly increased and even exceeded the former after 60 years old. CONCLUSION: The prevalence of LUTS among old and middle-aged males in Shanghai community is similar to that recently reported at home and abroad. The transverse and anteroposterior diameters of the prostate grow at a relatively similar rate, but the vertical diameter increases faster after 60 years old.