[Staged Duckett urethroplasty and Byars reconstruction for severe hypospadias with dysplastic glans].

OBJECTIVE: To study the effects of staged Duckett urethroplasty and Byars reconstruction in the treatment of severe hypospadias with dysplastic glans. METHODS: We retrospectively analyzed the clinical data on 57 cases of severe hypospadias with dysplastic glans treated by two-stage Duckett urethroplasty or Byars reconstruction from September 2015 to May 2020. At stage-Ⅰ treatment, the patients were aged from 5 to 47 (mean 21) months, the diameter of the glans less than 1.4 cm, and the interval between the two stages from 6 to 41 (mean 14) months. The patients underwent Duckett urethroplasty, distal in stage Ⅰ and proximal in stage Ⅱ (group A, n = 25) or Byars reconstruction with the urethral plate in stage Ⅰ and Duplay urethroplasty in stage Ⅱ (group B, n = 32). Postoperative follow-up lasted 12－56 (mean 35) months. RESULTS: After stage Ⅱ surgery, penile straightening and smooth appearance of the graft were achieved in all the patients. Six cases of postoperative complications (24%) were observed in group A, including 4 cases of urinary fistula, 1 case of glans dehiscence, 1 case of urethral diverticulum and 1 case of urethral stricture, while 14 cases (43.8%) were observed in group B, including 9 cases of urinary fistula, 9 cases of glans dehiscence and 2 cases of urethral diverticulum, with a remarkably lower incidence rate of glans dehiscence in group A than in B (P = 0.043), but no statistically significant difference in the other observations between the two groups (P > 0.05). CONCLUSION: Both staged strategies of Duckett urethroplasty and Byars reconstruction can be used for the treatment of severe hypospadias with dysplastic glans, but the latter may result in a higher incidence rate of glans dehiscence postoperatively and bring more difficulties to subsequent repair.

[Prevalence of and associated factors for prostate calcification in ≥40-year-old males with benign prostatic enlargement].

OBJECTIVE: To investigate the prevalence of and risk factors for prostate calcification (PCal) in ≥40 years old males with benign prostatic enlargement (BPE) found in health checkup. METHODS: We retrospectively analyzed the data on 671 ≥40-year-old men found with BPE in health checkup and investigated the prevalence of and risk factors for PCal in BPE males aged ≥40 years by univariate and multivariate analyses. RESULTS: Among 1 582 men aged ≥40 years undergoing health checkup, 671 were found with BPE and 274 (17.3%) with both BPE and PCal. The incidence rate of PCal was 40.8% (274/671) in the BPE patients, which was increased with age (trend χ2 = 5.289, P = 0.021), with statistically significant differences in different age groups (χ2 = 9.243, P = 0.026). Significant differences were also observed in age, height, estimated glomerular filtration rate (eGFR), urine pH level and the number of cases of uneven prostatic echoes between the BPE patients with and those without PCal (P < 0.05). Logistic regression analysis showed that age (OR = 1.027, 95% CI: 1.010－1.044), urine pH (OR = 1.446, 95% CI: 1.148－1.823) and uneven prostatic echoes (OR = 2.150, 95% CI: 1.108－4.174) were the associated factors for PCal in BPE patients aged ≥40 years. CONCLUSION: The incidence rate of PCal is high and increased with age in BPE patients aged ≥40 years, and age, urine pH and uneven prostatic echoes are associated factors for PCal in this cohort.

[Infiltration of Th1 and Th17 cells into the L5－S2 spinal cord in CP/CPPS rats and its central sensitization mechanism].

OBJECTIVE: To explore the central sensitization mechanism of pain in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: We randomly divided 40 adult male SPF SD rats, aged 3－4 weeks and weighing 250－350 g, into a normal control and a CP/CPPS model group. After modeling, we analyzed the state of infiltration of CD4+T cells into the L5－S2 spinal cord and detected the expression levels of GFAP and CR3 in the spinal cord tissue using flow cytometry, real-time fluorescent quantitative PCR (RT-qPCR) and immunofluorescence staining. RESULTS: Compared with the normal controls, the CP/CPPS model rats showed dramatically increased expression of CD4+T cells in the mononuclear cells of the L5－S2 spinal cord tissue (P < 0.01), mRNA expressions of interferon-γ (IFN-γ) and tumor necrosis factor α (TNF-α) secreted from the Th1 cells, interleukin (IL)-17 and retinoic acid-associated orphan receptor (ROR) γt secreted from the Th17 cells, cytokines IL-6 and IL-1ß, and chemokines CCL2, CCL20 and CXCL10 (P < 0.01), and expressions of the molecular markers of Th1 and Th17 cells IFN-γ and IL-17 and those of astrocytes and microglias GFAP and CR3. CONCLUSIONS: CD4+T cells, specifically Th1 and Th17 cells, infiltrate L5－S2 spinal cord neurons in CP/CPPS model rats. The inflammatory factors secreted from these cells may damage the neuronal cells, affect nervous conduction, promote central sensitization and activate astrocytes and microglias, leading to the development and progression of pain.

Effect of Eriocalyxin B on prostatic inflammation and pelvic pain in a mouse model of experimental autoimmune prostatitis.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disease in males. Eriocalyxin B (EriB), a natural diterpenoid purified from Isodon eriocalyx var. laxiflora, was previously reported to have antitumor effects via multiple immune-related pathways. In this study, we investigated the effect of EriB on CP/CPPS using a mouse model of experimental autoimmune prostatitis (EAP) and explored its potential mechanisms. METHODS: The EAP model was established in nonobese diabetic mice by intradermal injecting a mixture of prostate antigens and Complete Freund's Adjuvant on days 0 and 28. Then, EAP mice received daily intraperitoneal injections of EriB (5 or 10 mg/kg/d) for 14 days, from days 28 to 42 (EAP+EriB5 or EAP+EriB10 groups). The histopathological appearance of the prostate tissues was evaluated. Chronic pelvic pain development was assessed by cutaneous allodynia. Inflammatory cytokines were measured by enzyme-linked immunosorbent assay tests. We then explored anti-inflammatory potential mechanisms of EriB by studying the effects of PI3K inhibitor wortmannin (EAP+EriB10+Wort group) and NF-κB inhibitor SC75741 (EAP+EriB10+SC group) on prostate inflammation and pelvic pain using this model. RESULTS: Histological analyses revealed significant prostate inflammation in EAP mice compared with control mice. Significantly increased pelvic pain was detected in EAP mice (P < .05). Compared with the EAP+Veh group, chronic pain development, histological appearance, and cytokine levels demonstrated that EriB could alleviate the severity of EAP in a dose-dependent manner though upregulation of the PI3K/Akt/mTOR pathway and downregulation of the NF-κB pathway. Further mechanism research demonstrated that the PI3K/AKT/mTOR pathway could be blocked by wortmannin, but was not affected by SC75741. In addition, the NF-κB pathway could be further inhibited by SC75741 compared with the EAP+EriB10+Veh group. However, wortmannin could reactivate the NF-κB pathway, indicating that the PI3K/AKT/mTOR pathway negatively regulates the NF-κB pathway during EriB treatment. CONCLUSIONS: The results of the present study suggested that EriB could alleviate the severity of prostatic inflammation and pelvic pain in an EAP mouse model. These findings may broaden the value of EriB as a promising candidate for the treatment of CP/CPPS.

Efficient Synthesis of Polymer Prodrug by Thiol-Acrylate Michael Addition Reaction and Fabrication of pH-Responsive Prodrug Nanoparticles.

In this study, an efficient method is proposed for the synthesis of polymer prodrug with acid-liable linkage via thiol-acrylate Michael addition reaction of the camptothecin with tethering acrylate group and polymer scaffold containing multiple thiol groups. The polymer scaffold P(HEO2MA)- b-P(HEMA-DHLA) is prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization of the methacrylate of lipoic acid (HEMA-LA) using poly(2-(2-hydroethoxy) ethyl methacrylate) (PHEO2MA) as macro-RAFT agent followed by reduction of the disulfides in lipoic acid (LA) groups to give polymer scaffold with dihydrolipoic acid (DHLA) pendent groups. Acrylate-tethering camptothecin (ACPT) is connected to P(HEO2MA)- b-P(HEMA-DHLA) via Michael addition reaction between thiol and acrylate with a high coupling efficiency (95%). Amphiphilic polymer prodrug P(HEO2MA)- b-P(HEMA-DHLA-CPT) spontaneously self-assembles into nanoparticles in an aqueous solution and exhibits a CPT loading content as high as 40.1%. The prodrug nanoparticles with the acid-liable ß-thiopropionate linkages can release CPT under acidic conditions, and the prodrug nanoparticles show similar cytotoxicity to HeLa cells as free CPT. Overall, the prodrug nanoparticles with high drug loading contents and acid-liable linkages are promising for pH-responsive anticancer therapy.

[Impact of BKCa channel in prostate smooth muscle cells on the membrane potential in rats with chronic abacterial prostatitis].

OBJECTIVE: To investigate the impact of the BKCa channel in prostate smooth muscle cells (PSMCs) on the membrane potential in SD rats with chronic abacterial prostatitis (CAP). METHODS: CAP models were established in 20 SD rats by castration and injection of 17 beta-estrogen, and another 20 were taken as normal controls. PSMCs were cultured and purified in vitro, and treated with DiBAC4, followed by quantitative observations on the dynamic changes of the cell membrane potential by laser confocal microscopy. RESULTS: The extracellular calcium ion concentration ([Ca2+]o) was increased and the BKCa channel was activated, which induced the hyperpolarization of the PSMC membrane in both the CAP models and normal control rats. This effect was weakened with Iberiotoxin (IbTX), a specific blocker of the BKCa channel, but the amplitude of the hyperpolarization was obviously lower in the CAP than in the control group. The DiBAC4 fluorescence intensity induced by hyperpolarization was 18.78 +/- 2.92 in the former and 38.85 +/- 7.10 in the latter (P < 0.05), while that induced by IbTX was 1.61 +/- 0.46 and 6.12 +/- 1.32 (P < 0.05), respectively. CONCLUSION: Significant decrease of BKCa-mediated hyperpolarization in the CAP model can reduce its abilities of regulating the membrane potential and suppressing the excessive contraction of PSMCs, which may result in pelvic pain syndrome and lower urinary tract symptoms.

Stone attenuation on computer tomography helps surgeons make decisions between miniaturized percutaneous nephrolithotomy or retrograde intrarenal surgery for lower pole stones: a retrospective study.

A retrospective study was performed on 200 patients who underwent miniaturized percutaneous nephrolithotomy (mini-PCNL) or retrograde intrarenal surgery (RIRS) for 10-20 mm sized lower pole renal calculi to investigate the relationship between computed tomography (CT) attenuation of calculi and surgical outcomes. CT was used to examine the location, size, and CT attenuation values of the calculi. Additionally, the operation time, hospital stay, hemoglobin (Hb) reduction, stone-free rate (SFR), and complication rate were also meticulously documented and subjected to comparative analysis. Complications were assessed using the Clavien-Dindo grading system. We observed no significant differences in hospitalization data and follow-up outcomes, except for a longer hospital stay and higher Hb drops in patients receiving mini-PCNL. Statistical analysis revealed an association between CT attenuation and operation time. Compared with mini-PCNL, RIRS could reduce bleeding, hospital stay, surgery time, and complications for 10-20 mm sized lower pole kidney stones with CT values < 1000 HU. RIRS resulted in longer operation time and lower stone-free rates despite shorter hospital stays and less bleeding than mini-PCNL for stones with CT values > 1000 HU. Therefore, selecting an appropriate surgical method based on CT attenuation might improve outcomes. For patients with stone attenuation values < 1000 HU, RIRS is the recommended option. When stone attenuation values > 1000 HU, the surgical method should be chosen based on the patient's individual situation.

[Menopause-like symptoms among old and middle-aged males in Hefei area].

OBJECTIVE: To access the prevalence of menopause-like symptoms, and their related factors in old and middle-aged males in the area of Hefei. METHODS: This study included 1 026 males aged over 45 years that came to the clinic for health examination. We collected their personal data, and evaluated their general health status and the results of the questionnaire investigation using the Aging Males' Symptoms (AMS) scale. RESULTS: The total incidence of menopause-like symptoms was 64.7% among the old and middle-aged males in Hefei area, of which 58.1% were mild, 30.9% moderate and 11.0% severe. The average AMS score was 31.2 +/- 6.8, in which the scores on psychological, physical and sexual function symptoms were 8.3 +/- 2.1, 12.4 +/- 4.8 and 9.3 +/- 4.5, respectively. Sexual function symptoms were increased significantly with the increase of age (P < 0.05), but psychological and physical symptoms showed no obvious correlation with age (P > 0.05). The main risk factors of menopause-like symptoms included age, smoking, diabetes, cardiovascular diseases, and obesity, but physical exercise was an important protective factor against them. CONCLUSION: With the increase of age, the prevalence of male menopause-like symptoms rises and sexual function declines gradually, but psychological and physical scores are not affected significantly. Age, general health status and lifestyle are closely associated with the prevalence of menopause-like symptoms among old and middle-aged males.

Tumor Microenvironment Triggered the In Situ Synthesis of an Excellent Sonosensitizer in Tumor for Sonodynamic Therapy.

An ultrasound-triggered sonodynamic therapy has shown great promise for cancer therapy. However, its clinical applications are very limited because the traditional sonosensitizers tend to suffer from very poor efficiency combined with low retention in cancer cells and low tumor selectivity. Therefore, sonosensitizers with higher effectivity, higher tumor cell retention, and higher tumor cell specificity are highly required. Herein, we constructed a Ti2C(OH)X nanosheet, which was a poor sonosensitizer but had a long circulation in the blood system. However, it was very interesting to find that the tumor microenvironment could in situ turn Ti2C(OH)X nanosheet into a novel and excellent sonosensitizer with a nanofiber structure in tumors, exhibiting excellent ability to generate reactive oxygen species (ROS) under ultrasound. Moreover, the nanofiber structure made it very difficult to get out of cancer cells, highly enhancing the retention of the sonosensitizer in the tumor, thereby enabling it to effectively and selectively kill cancer cells in vivo. Our findings demonstrate that the strategy of the tumor microenvironment triggering the in situ synthesis of an effective sonosensitizer in tumor provided a promising means to simultaneously increase the efficiency, sonosensitizer retention in cancer cells, and cancer selectivity, thereby effectively killing cancer cells but causing little damage to healthy tissues via the sonodynamic therapy.

[Intracellular calcium ion concentration in the prostate smooth muscle cells of chronic abacterial prostatitis rat models and normal controls].

OBJECTIVE: To investigate the difference in intracellular calcium ion [Ca2+]i concentration in prostate smooth muscle cells (PSMCs) between SD rat models of chronic abacterial prostatitis (CAP) and normal controls, and to evaluate the role of [Ca2+]i concentration in CAP. METHODS: We established CAP models in SD rats using purified prostate protein and Freund's complete adjuvant, cultured in vitro and then purified the PSMCs of both the CAP models and normal controls. Continuous dynamic scanning was performed under the laser confocal scanning microscope after incubation of the cells with FLUO-3AM. RESULTS: The fluorescence intensities of [Ca2+]i in the PSMCs were 80.39 +/- 9.00 and 27.95 +/- 10.04 in the CAP models and normal controls, respectively, with statistically significant differences between the two groups (P < 0.01). CONCLUSION: The concentration of [Ca2+]i increased in the PSMCs of the CAP rat models, which might enhance the constriction of PSMCs and subsequently increase the sensibility to pain and cause lower abdominal pain.

[Quantitative expression of voltage-dependent calcium channels in prostate smooth muscle cells of rats with estradiol-induced chronic nonbacterial prostatitis].

OBJECTIVE: To construct a rat model of chronic nonbacterial prostatitis (CP) and investigate the difference in the quantitative expression of voltage-dependent calcium channels of prostate smooth muscle cells (PSMCs) between the models and controls. METHODS: We established a CP rat model by estrogen induction, cultured and purified the PSMCs in vitro, and extracted total RNA by Trizol. Then we measured the mRNA expression of the cal subunit in the calcium channel subtypes by reverse transcription and SYBR Green I real time RT-PCR, and compared it with that of the controls. RESULTS: The expressions of the L-, T- and P/Q-type calcium channels were found in both the CP and control groups, and that of the CaV1.2 L-type calcium channel was significantly increased in the former as compared with the latter (0.048 +/- 0.024 versus 0.031 +/- 0.015, t = 2.846, P = 0.007), but there were no statistically significant differences in the T- and P/Q-type calcium channels between the two groups. CONCLUSION: The number of CaV1.2 L-type calcium channels of PSMCs and calcium influx were increased in CP patients, which may be involved in the mechanism of CP.

Rhodanine-based Knoevenagel reaction and ring-opening polymerization for efficiently constructing multicyclic polymers.

Cyclic polymers have a number of unique physical properties compared with those of their linear counterparts. However, the methods for the synthesis of cyclic polymers are very limited, and some multicyclic polymers are still not accessible now. Here, we found that the five-membered cyclic structure and electron withdrawing groups make methylene in rhodanine highly active to aldehyde via highly efficient Knoevenagel reaction. Also, rhodanine can act as an initiator for anionic ring-opening polymerization of thiirane to produce cyclic polythioethers. Therefore, rhodanine can serve as both an initiator for ring-opening polymerization and a monomer in Knoevenagel polymerization. Via rhodanine-based Knoevenagel reaction, we can easily incorporate rhodanine moieties in the backbone, side chain, branched chain, etc, and correspondingly could produce cyclic structures in the backbone, side chain, branched chain, etc, via rhodanine-based anionic ring-opening polymerization. This rhodanine chemistry would provide easy access to a wide variety of complex multicyclic polymers.

Stable Black Phosphorus Nanosheets Exhibiting High Tumor-Accumulating and Mitochondria-Targeting for Efficient Photothermal Therapy via Double Functionalization.

Black phosphorus (BP) has exhibited excellent biocompatibility and high photothermal conversion efficiency under near-infrared light, which makes it very promising for photothermal therapy. However, practical applications are highly hampered because it lacks a targeting property and rapidly degrades in cancer cells, especially in response to strong intracellular oxidative stress. Here, we reported that the mitochondrial targeting peptide functionalized black phosphorus nanosheets covered with an acid-labile polymer shell (doubly functionalized black phosphorus (DFBP) nanosheets) exhibited good stability. DFBP nanosheets not only have excellent ability of accumulating in tumor tissue via surface charge switching but also can target mitochondria. The doubly functionalized black phosphorus nanosheets resulted in robust cancer cell uptake but very poor normal cell accumulation. In vivo, the BP nanosheets could highly accumulate in a tumor and specifically target mitochondria, generating enough hyperthermia under near-infrared light, leading to cell death. This work provides a powerful way to ablate a tumor selectively with negligible side effects.

The prevalence of prostatitis-like symptoms in China.

PURPOSE: We studied the prevalence of prostatitis-like symptoms and identified their associated risk factors in a population based Chinese sample. MATERIALS AND METHODS: A volunteer group of 15,000 eligible men residing in Beijing, Anhui, Xi'an, Guangzhou and Gansu cities or provinces were invited randomly to take part in the survey to complete a questionnaire that elicited information regarding sociodemographics, Eysenck personality questionnaire, current stress and health ratings, lifestyle, medical history, expressed prostatic secretion evaluation, score of the National Institutes of Health Chronic Prostatitis Symptom Index and International Index of Erectile Function-5. RESULTS: Information on 12,743 (84.95%) men was collected. Of these men 1,071 (8.4%) reported prostatitis-like symptoms (mean National Institutes of Health Chronic Prostatitis Symptom Index pain score 7.55 +/- 3.22). The percent of chronic prostatitis was 4.5% (571) among the symptoms group according to past urological history and expressed prostatic secretion evaluation. Subjects with prostatitis-like symptoms (mean age 34.56 +/- 13.48 years) had higher mean pain and urinary symptoms scores (7.53 +/- 3.22 and 2.84 +/- 2.72, respectively) compared with subjects without prostatitis-like symptoms (1.18 +/- 2.32 and 0.72 +/- 1.66 for pain and urinary symptoms scores, respectively, mean age 30.7 +/- 10.17) (pain and symptoms scores, p <0.05). The quality of life score was 6.03 +/- 2.88 and 3.83 +/- 2.55 in groups with symptoms or nonsymptoms, respectively (p <0.05). CONCLUSIONS: Prostatitis-like symptoms are a multifactorial problem affecting men of all ages (15 to 60 years) and demographics, and the prevalence is high in China. The syndrome is closely related to alcohol consumption, cigarette smoking, frequent intercourse, as well as fatigue, pressure and too little sleep. These findings suggest that risk factors for this condition are largely modifiable and highlight potential targets for future prevention.

Treatment of chronic prostatitis in Chinese men.

The aim of this study is to assess the status of treatment of chronic prostatitis (CP) in Chinese men. A population-based cross-sectional survey was performed, in which 15 000 men aged between 15 and 60 years were randomly selected to receive a questionnaire designed to assess National Institutes of Health Chronic Prostatitis Symptoms Index (NIH-CPSI) status, therapeutic efficacy and 28 other items. A total of 12 743 men (84.95%) completed the questionnaire, of whom 1 071 (8.4%) were identified as having prostatitis-like symptoms and 517 (4.5%) were diagnosed with CP according to NIH-CPSI criteria and prostatitis-like symptomatology. Of the CP patients, 372 (65%) underwent long-term routine treatment 12 times per year. Additionally, 217 (72.8%) patients received antibiotic therapy and 215 (79.3%) men showed therapeutic effects. The treatment cost USD 1 151 (8 059 yuan) per person per year on average. Most CP patients received routine treatment, in most cases with antibiotics. Treatment was costly and most CP patients were not satisfied with its effectiveness. Antibacterial treatment might have been effective primarily in patients with bacterial disease.

MicroRNA expression profile in chronic nonbacterial prostatitis revealed by next-generation small RNA sequencing.

MicroRNAs (miRNAs) are considered to be involved in the pathogenic initiation and progression of chronic nonbacterial prostatitis (CNP); however, the comprehensive expression profile of dysregulated miRNAs, relevant signaling pathways, and core machineries in CNP have not been fully elucidated. In the current research, CNP rat models were established through the intraprostatic injection of carrageenan into the prostate. Then, next-generation sequencing was performed to explore the miRNA expression profile in CNP. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) bioinformatical analyses were conducted to reveal the enriched biological processes, molecular functions, and cellular components and signaling pathways. As a result, 1224, 1039, and 1029 known miRNAs were annotated in prostate tissues from the blank control (BC), normal saline injection (NS), and carrageenan injection (CAR) groups (n = 3 for each group), respectively. Among them, 84 miRNAs (CAR vs BC) and 70 miRNAs (CAR vs NS) with significantly different expression levels were identified. Compared with previously reported miRNAs with altered expression in various inflammatory diseases, the majority of deregulated miRNAs in CNP, such as miR-146b-5p, miR-155-5p, miR-150-5p, and miR-139-5p, showed similar expression patterns. Moreover, bioinformatics analyses have enriched mitogen-activated protein kinase (MAPK), cyclic adenosine monophosphate (cAMP), endocytosis, mammalian target of rapamycin (mTOR), and forkhead box O (FoxO) signaling pathways. These pathways were all involved in immune response, which indicates the critical regulatory role of the immune system in CNP initiation and progression. Our investigation has presented a global view of the differentially expressed miRNAs and potential regulatory networks containing their target genes, which may be helpful for identifying the novel mechanisms of miRNAs in immune regulation and effective target-specific theragnosis for CNP.

MnFe2O4 nanoparticles accelerate the clearance of mutant huntingtin selectively through ubiquitin-proteasome system.

Neurodegenerative disorders such as Huntington's disease (HD) are fundamentally caused by accumulation of misfolded aggregate-prone proteins. Previous investigations have shown that these toxic protein aggregates could be degraded through autophagy induced by small molecules as well as by nanomaterials. However, whether engineered nanomaterials have the capacity to degrade these protein aggregates via the ubiquitin-proteasome system (UPS), the other major pathway for intracellular protein turnover, was unknown. Herein, we have synthesized biocompatible MnFe2O4 nanoparticles (NPs) and demonstrated their unique effect in accelerating the clearance of mutant huntingtin (Htt) protein exhibiting 74 glutamine repeats [Htt(Q74)]. UPS, rather than autophagy, was responsible for the efficient Htt(Q74) degradation facilitated by MnFe2O4 NPs. Meanwhile, we demonstrated that MnFe2O4 NPs enhanced K48-linked ubiquitination of GFP-Htt(Q74). Moreover, ubiqinlin-1, but not p62/SQSTM1, served as the ubiquitin receptor that mediated the enhanced degradation of Htt(Q74) by MnFe2O4 NPs. Our findings may have implications for developing novel nanomedicine for the therapy of HD and other polyglutamine expansion diseases.

ASIC1a contributes to the symptom of pain in a rat model of chronic prostatitis.

This study aims to validate our hypothesis that acid-sensing ion channels (ASICs) may contribute to the symptom of pain in patients with chronic prostatitis (CP). We first established a CP rat model, then isolated the L5-S2 spinal dorsal horn neurons for further studies. ASIC1a was knocked down and its effects on the expression of neurogenic inflammation-related factors in the dorsal horn neurons of rat spinal cord were evaluated. The effect of ASIC1a on the Ca2+ ion concentration in the dorsal horn neurons of rat spinal cord was measured by the intracellular calcium ([Ca2+]i) intensity. The effect of ASIC1a on the p38/mitogen-activated protein kinase (MAPK) signaling pathway was also determined. ASIC1a was significantly upregulated in the CP rat model as compared with control rats. Acid-induced ASIC1a expression increased [Ca2+]i intensity in the dorsal horn neurons of rat spinal cord. ASIC1a also increased the levels of neurogenic inflammation-related factors and p-p38 expression in the acid-treated dorsal horn neurons. Notably, ASIC1a knockdown significantly decreased the expression of pro-inflammatory cytokines. Furthermore, the levels of p-p38 and pro-inflammatory cytokines in acid-treated dorsal horn neurons were significantly decreased in the presence of PcTx-1, BAPTA-AM, or SB203580. Our results showed that ASIC1a may contribute to the symptom of pain in patients with CP, at least partially, by regulating the p38/MAPK signaling pathway.

[Changes in potassium channel currents of prostate epithelial cell of old rats and significance thereof].

OBJECTIVE: To investigate the potassium channel currents and response thereof to the blocker of potassium channel in epithelium of prostate of Sprague Dawley (SD) rats. METHODS: The dorsolateral lobes of prostates of 20 3-month-old (adult) male SD rats and 20 12-month-old (elderly) SD rats were removed, cut into small pieces of the size of 1 approximately 2 mm(3) in phosphate-buffered Ca(2+)-free Ringer's solution, and digested by collagenase IV for 25 min. Then the tissue chunks were put into fresh solution and gently agitated. These cells were cultured for one week. Pan-keratin immunocytochemistry was conducted. The potassium channel current of the prostate epithelium was recorded by whole-cell voltage clamp. Tetraethylammonium (TEA), a blocker of calcium-activated potassium channel of the concentration of 1 mmol/L, and 1 mol/L + 1 mmol/L 4-aminopyridine (4-AP), blocker of voltage-dependent potassium channel inhibitor, were sequentially added into the extra-cellular fluid and the current density was recorded. RESULTS: TEA specifically inhibited the K(Ca) current After the addition of TEA and TEA + 4-AP, the current density at the potential of +80 mv of the 12-month-old rats was (18.48 +/- 1.7) pA/pF, significantly higher than that of the 3-month-old rats [(10.84 +/- 1.54) pA/pF, P < 0.01]. The original peak current of the 3-month-old rats was (9.5 +/- 1.8) pA/pF and became (5.4 +/- 3.1) pA/pF after the addition of TEA, decreased by 44% (P < 0.01); and the peak current of the 12-month-old rats was (19.1 +/- 2.9) pA/pF and became (7.2 +/- 3.2) pA/pF after the addition of TEA, decreased by 63% (P < 0.01). CONCLUSION: Elderly rats have stronger potassium channel currents than adult rats, and their K(Ca) current is more sensitively to TEA. Aging is related to decreased prostate gland cell secretion.

[Potassium channel blocker regulates the proliferation of prostatic epithelial cells in SD rats].

OBJECTIVE: To investigate the regulatory effect of potassium channel blocker (tetraethylammonium [TEA], aminopyridine [4-AP], glibenclamide [Glib]) on the proliferation of SD rat prostatic epithelial cells in vitro. METHODS: The primary culture was prepared by collagenase dissociation of minced prostatic tissues. Cells were cultured in serum-free prostate epithelial cell growth media and identified by immunocytochemical studies. TEA and 4-AP at the concentration of 1, 5 and 10 mmol/L and Glib at the concentration of 10, 50 and 100 mol/L were added, and after 24, 48 and 72 hours of culturing, a cell column diagram was drawn and the cell number counted. The post-passage cell growth was observed by MTT assay and Hoechst33258 nucleus staining. RESULTS: The cultured cells showed the typical morphological features of epithelia, with positive stain. MTT assay and Hoechst33258 staining showed that TEA, 4-AP and Glib at the increasing concentration effected different degrees of proliferation of prostatic epithelial cells after 24, 48 and 72 h (P < 0.01). CONCLUSION: The potassium channel blocker is a direct physiological regulator of the proliferation of SD rat prostatic epithelial cells.