Continence and micturition involve urethral closure. Especially, insufficient strength of the pelvic floor muscles including the urethral sphincter muscles causes urinary incontinence (UI). Thus, it is most important to understand the main mechanism causing UI and the relationship of UI with the urethral sphincter. Functionally and anatomically, the urethral sphincter is made up of the internal and the external sphincter. We highlight the basic and clinical anatomy of the internal and the external sphincter and their clinical meaning. Understanding these relationships may provide a novel view in identifying the main mechanism causing UI and surgical techniques for UI.
Autonomic Nervous System ; Muscles ; Pelvic Floor ; Pudendal Nerve ; Urethra ; Urinary Incontinence ; Urination

Background and Objectives: Autophagy is known to be associated with pathogen infection. However, the expression of autophagy-related proteins has not been studied in chronic otitis media without cholesteatoma (COM) or with cholesteatoma (CholeOM). This study aimed to determine whether there is a difference between COM and CholeOM in autophagy-related gene mRNA expression. Subjects and Methods: For 47 patients with chronic otitis media, the inflammatory tissues were classified into granulation tissue (COM) or cholesteatoma (CholeOM) according to biopsy results. Results: PI3K mRNA expression (COM vs. CholeOM, mean±SD, 0.009±0.010 vs. 0.003±0.004; p=0.004) was lower, whereas Beclin-1 mRNA expression (0.089±0.107 vs. 0.176±0.163; p=0.034) was higher in the CholeOM group. Expression of PI3K mRNA in the CholeOM group was lower than that in the COM subgroups with presence of bacteria (0.022±0.019 vs. 0.001±0.001; p=0.001), otorrhea (0.049±0.068 vs. 0.003±0.004; p=0.004), and hearing loss over 40 dB (0.083±0.130 vs. 0.003±0.004; p=0.005). Conclusions The data suggested that different autophagy proteins play important roles in chronic otitis media according to the presence or absence of cholesteatoma.

Erectile dysfunction (ED) has an adverse impact on men's quality of life. Penile erection, which is regulated by nerves that are innervated into the erectile tissue, can be affected by functional or anatomical trauma of the perineal region, including specific structures of the penis, causing ED. Penile erection is neurologically controlled by the autonomic nervous system. Therefore, it is of utmost importance to understand the neurogenic structure of the erectile tissue and the types of neurotransmitters involved in the penile erection process. Here, we highlight the basic clinical anatomy and erectile function of the penis. Understanding the clinical connotation of the relationship between penile erectile structure and function may provide fresh insights for identifying the main mechanisms involved in ED and help develop surgical techniques for the treatment of ED.
Autonomic Nervous System ; Erectile Dysfunction ; Male ; Neuroanatomy* ; Neurotransmitter Agents ; Parasympathetic Nervous System ; Penile Erection* ; Penis ; Quality of Life

BACKGROUND AND OBJECTIVES: To investigate whether taste thresholds, as determined by electrogustometry (EGM) and chemical taste tests, differ by age and the severity of facial palsy in patients with Bell's palsy. SUBJECTS AND METHODS: This study included 29 patients diagnosed with Bell's palsy between January 2014 and May 2015 in our hospital. Patients were assorted into age groups and by severity of facial palsy, as determined by House-Brackmann Scale, and their taste thresholds were assessed by EGM and chemical taste tests. RESULTS: EGM showed that taste thresholds at four locations on the tongue and one location on the central soft palate, 1 cm from the palatine uvula, were significantly higher in Bell's palsy patients than in controls (p<0.05). In contrast, chemical taste tests showed no significant differences in taste thresholds between the two groups (p>0.05). The severity of facial palsy did not affect taste thresholds, as determined by both EGM and chemical taste tests (p>0.05). The overall mean electrical taste thresholds on EGM were higher in younger Bell's palsy patients than in healthy subjects, with the difference at the back-right area of the tongue differing significantly (p<0.05). In older individuals, however, no significant differences in taste thresholds were observed between Bell's palsy patients and healthy subjects (p>0.05). CONCLUSIONS: Electrical taste thresholds were higher in Bell's palsy patients than in controls. These differences were observed in younger, but not in older, individuals.
Bell Palsy* ; Facial Paralysis* ; Healthy Volunteers ; Humans ; Palate, Soft ; Taste Threshold* ; Tongue ; Uvula

OBJECTIVES: Factors predictive of the severity of and recovery from Bell's palsy remain unclear. This study evaluated the association between neutrophil to lymphocyte ratio (NLR) and the severity of and recovery from Bell's palsy. METHODS: This retrospective study included 51 patients who were hospitalized with Bell's palsy from 2015 to 2017. Degree of paralysis was assessed by House-Brackmann (H-B) grade. Patients with H-B grades 2–4 were classified as having mild to moderate palsy and patients with H-B grade 5 or 6 were classified as having severe palsy. Patients were evaluated for obesity, hypertension and diabetes mellitus, and blood tests were performed to determine NLR and platelet to lymphocyte ratio. Patients were treated with steroids and antiviral agents. H-B grade was assessed 1 week, 1 month, and 3 months after treatment. RESULTS: NLR was significantly higher in patients with severe than with mild to moderate palsy (P=0.048). Recovery time was significantly longer in patients with high NLR than low NLR (P=0.045). CONCLUSION: Higher NLR in patients with Bell's palsy was associated with longer recovery time. NLR may be prognostic of recovery time in patients with Bell's palsy.
Antiviral Agents ; Bell Palsy ; Blood Platelets ; Diabetes Mellitus ; Facial Paralysis ; Hematologic Tests ; Humans ; Hypertension ; Lymphocytes ; Neutrophils ; Obesity ; Paralysis ; Retrospective Studies ; Steroids

Myelinated Schwann cells in the peripheral nervous system express the p75 nerve growth factor receptor (p75NGFR) as a consequence of Schwann cell dedifferentiation during Wallerian degeneration. p75NGFR has been implicated in the remyelination of regenerating nerves. Although many studies have shown various mechanisms underlying Schwann cell dedifferentiation, the molecular mechanism contributing to the re-expression of p75NGFR in differentiated Schwann cells is largely unknown. In the present study, we found that lysosomes were transiently activated in Schwann cells after nerve injury and that the inhibition of lysosomal activation by chloroquine or lysosomal acidification inhibitors prevented p75NGFR expression at the mRNA transcriptional level in an ex vivo Wallerian degeneration model. Lysosomal acidification inhibitors suppressed demyelination, but not axonal degeneration, thereby suggesting that demyelination mediated by lysosomes may be an important signal for inducing p75NGFR expression. Tumor necrosis factor-alpha (TNF-alpha) has been suggested to be involved in regulating p75NGFR expression in Schwann cells. In this study, we found that removing TNF-alpha in vivo did not significantly suppress the induction of both lysosomes and p75NGFR. Thus, these findings suggest that lysosomal activation is tightly correlated with the induction of p75NGFR in demyelinating Schwann cells during Wallerian degeneration.
Axons ; Cell Dedifferentiation ; Chloroquine ; Demyelinating Diseases ; Lysosomes ; Myelin Sheath ; Nerve Growth Factor ; Peripheral Nervous System ; RNA, Messenger ; Schwann Cells ; Tumor Necrosis Factor-alpha ; Wallerian Degeneration

In the peripheral nerves, injury-induced cytokines and growth factors perform critical functions in the activation of both the MEK/ERK and JAK/STAT3 pathways. In this study, we determined that nerve injury-induced ERK activation was temporally correlated with STAT3 phosphorylation at the serine 727 residue. In cultured Schwann cells, we noted that ERK activation is required for the serine phosphorylation of STAT3 by neuropoietic cytokine interleukin-6 (IL-6). Serine phosphorylated STAT3 by IL-6 was transported into Schwann cell nuclei, thereby indicating that ERK may regulate the transcriptional activity of STAT3 via the induction of serine phosphorylation of STAT3. Neuregulin-1 (NRG) also induced the serine phosphorylation of STAT3 in an ERK-dependent fashion. In contrast with the IL-6 response, serine phosphorylated STAT3 induced by NRG was not detected in the nucleus, thus indicating the non-nuclear function of serine phosphorylated STAT3 in response to NRG. Finally, we determined that the inhibition of ERK prevented injury-induced serine phosphorylation of STAT3 in an ex-vivo explants culture of the sciatic nerves. Collectively, the results of this study show that ERK may be an upstream kinase for the serine phosphorylation of STAT3 induced by multiple stimuli in Schwann cells after peripheral nerve injury.
Cell Nucleus ; Cytokines ; Intercellular Signaling Peptides and Proteins ; Interleukin-6 ; Neuregulin-1 ; Peripheral Nerve Injuries ; Peripheral Nerves ; Phosphorylation ; Phosphotransferases ; Schwann Cells ; Sciatic Nerve ; Serine

Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.