PURPOSE: Testosterone replacement therapy is an effective treatment for late-onset hypogonadism (LOH) despite a few contraindications and side-effects. The aim of this study was to determine whether modified Ojayeonjonghwan (KH-204, Korean herbal formula) improved LOH. KH-204 is a strong antioxidant herbal formula. We evaluated the effect of Korean herbal prescription on androgen receptor (AR) expression in an aged rat model of LOH. MATERIALS AND METHODS: Eighteen-month-old rats were used as aged LOH rat models. Eighteen Sprague-Dawley rats were randomly divided into three equal groups of six animals each and treated with one of the following: 1) normal control group (oral administration with distilled water, n=6), 2) KH-204 200 group (oral administration with 200 mg/kg of KH-204, n=6), and 3) KH-204 400 group (oral administration with 400 mg/kg of KH-204, n=6). After four weeks of treatment (once daily, distilled water or KH-204), serum testosterone levels, changes in testicular and epididymal weight, Western blotting analysis of AR expression and measurement of oxidative stress were examined. RESULTS: Treatment with the herbal formulation KH-204 200 mg/kg and 400 mg/kg (1) increased the weights of testis and epididymis; (2) increased the level of serum testosterone; (3) increased the level of superoxide dismutase and reduced the level of 8-hydroxy-20-deoxyguanosine; and (4) upregulated AR expression in testicular tissue. CONCLUSIONS: KH-204 might be an effective alternative for LOH. It improves antioxidant mechanisms and increases testicular AR expression without side-effects.
Aging* ; Animals ; Blotting, Western ; Epididymis ; Hypogonadism* ; Male ; Models, Animal* ; Oxidative Stress ; Phytotherapy ; Prescriptions ; Rats* ; Rats, Sprague-Dawley ; Receptors, Androgen* ; Superoxide Dismutase ; Testis ; Testosterone ; Water ; Weights and Measures

BACKGROUND: Both human leukocyte antigen (HLA) class I and programmed death-ligand 1 (PD-L1) molecules are known to play important roles in cancer immunity. In this study, we evaluated HLA class I expression in resected adenocarcinoma of the lung, and investigated its prognostic impact in correlation with PD-L1 expression. METHODS: HLA class I and PD-L1 expression was evaluated by immunohistochemistry in a total of 403 resected lung adenocarcinomas using tissue microarray. Correlations between the expression of HLA class I/PD-L1 and clinicopathologic features and prognostic significance were analyzed. RESULTS: HLA class I expression was reduced in 91.6% of adenocarcinoma, and more frequently reduced in patients with younger age, absence of vascular invasion, and low pathologic stage (p = .033, p = .007, and p = .012, respectively). Positive PD-L1 expression in tumor cells was 16.1% (1% cut-off), and associated with poor differentiation, presence of vascular invasion and nodal metastasis (p < .001, p = .002, and p = .032, respectively). On survival analysis, HLA class I or PD-L1 expression alone did not show any statistical significance. On the integrated analysis, HLA class I (+)/PD-L1 (+) subgroup showed a significantly shorter overall survival than other groups (p = .001). Multivariate analysis revealed that coexpression of HLA class I and PD-L1 was an independent poor prognostic factor of lung adenocarcinoma. (p < .001; hazard ratio, 6.106; 95% confidence interval, 2.260 to 16.501). CONCLUSIONS: Lung adenocarcinoma with coexpression of HLA class I and PD-L1 was associated with poor prognosis. This subgroup may evade immune attack by expressing PD-L1 protein despite HLA expression.
Adenocarcinoma ; Carcinoma, Non-Small-Cell Lung ; Humans ; Immunohistochemistry ; Leukocytes ; Lung ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis

PURPOSE: Many patients with benign prostatic hyperplasia need treatment for remaining storage symptoms after surgery. Therefore, we evaluated the effect of the phytotherapeutic agent WSY-1075 on persistent detrusor overactivity (DO) after the relief of bladder outlet obstruction (BOO). MATERIALS AND METHODS: Rats were assigned to 3 groups: control (n=6), persistent DO (n=6), and persistent DO treated with the phytotherapeutic agent WSY-1075 (n=6). Persistent DO after relief of partial BOO was generated in the rat model, and 6 of the rats with this condition were orally administered WSY-1075. After 4 weeks of administration, cystometry was performed. Additionally, 8-hydroxy-2-deoxyguanosine and superoxide dismutase were measured to evaluate oxidative stress in the bladder. Pro-inflammatory cytokines, such as interleukin-8 and tumor necrosis factor-α, were analyzed, as were the M2 and M3 muscarinic receptors of the bladder. RESULTS: Significantly increased contraction pressure and a decreased contraction interval were observed in the persistent DO group after relief of BOO. Moreover, oxidative stress, pro-inflammatory cytokines, and M3 muscarinic receptors were significantly increased. After treatment with WSY-1075, significantly reduced DO was observed by cystometry in comparison with the persistent DO group. Additionally, significantly decreased levels of oxidative stress, pro-inflammatory cytokines, and M3 muscarinic receptors in the bladder were observed after treatment with WSY-1075. CONCLUSIONS: Treatment with WSY-1075 improved persistent DO after the relief of BOO mediated by antioxidative and anti-inflammatory effects. Further studies are necessary to identify the exact mechanism of the treatment effect of WSY-1075.
Animals ; Cytokines ; Humans ; Interleukin-8 ; Lower Urinary Tract Symptoms ; Models, Animal ; Necrosis ; Oxidative Stress ; Phytotherapy ; Prostatic Hyperplasia ; Rats ; Receptors, Muscarinic ; Superoxide Dismutase ; Urinary Bladder Neck Obstruction* ; Urinary Bladder* ; Urinary Bladder, Overactive

Signal transducer and activator of transcription 3 (STAT3) has a crucial role in various autoimmune disorders including, inflammatory bowel disease (IBD). Our previous study demonstrated that STAT3 activation by IL-6 in colonic epithelial cells exacerbates experimental ulcerative colitis. Activated T lymphocytes are also found in ulcerative colitis patients with intestinal inflammation, but the role of STAT3 in T cells remains elusive. To determine the STAT3 function of T cells in intestinal inflammation, we generated T cell-specific STAT3 knockout (KO) mice and used dextran sulfate sodium (DSS) to induce colitis. In this study, we demonstrated that T cell-specific STAT3 deletion alleviated DSS-induced colitis in mice, resulting in reduced histological scores and myeloperoxidase (MPO) activity. Importantly, the population of T cells in the spleen and lymph nodes was significantly decreased in the control and DSS-induced groups of STAT3 KO mice. In addition, STAT3 deficiency in T cells markedly reduced the production of interferon (IFN)-γ, IL-6, and IL-17A, whereas IL-10 secretion was increased. Collectively, the results suggest that STAT3 in T cells may be a therapeutic target in ulcerative colitis by balancing the immune response through T cell homeostasis.
Animals ; Colitis* ; Colitis, Ulcerative ; Colon ; Cytokines ; Dextran Sulfate* ; Dextrans* ; Epithelial Cells ; Homeostasis ; Humans ; Inflammation ; Inflammatory Bowel Diseases ; Interferons ; Interleukin-10 ; Interleukin-17 ; Interleukin-6 ; Lymph Nodes ; Mice ; Peroxidase ; Spleen ; STAT3 Transcription Factor ; T-Lymphocytes

Current affiliation of Su Jin Kim has been changed, but it was not reflected in the process of publishing. The publishing office and editorial office would like to apologize for any inconvenience caused.

PURPOSE: Erectile dysfunction (ED) remains a major complication from cavernous nerve injury during radical prostatectomy. Recently, stem cell treatment for ED has been widely reported. This study was conducted to investigate the availability, differentiation into functional cells, and potential of human muscle-derived stem cells (hMDSCs) and human adipose-derived stem cells (hADSCs) for ED treatment. MATERIALS AND METHODS: We compared the neural differentiation of hMDSCs and hADSCs. Human muscle and adipose tissues were digested with collagenase, followed by filtering and centrifugation. For neural induction, isolated hMDSCs and hADSCs were incubated in neurobasal media containing forskolin, laminin, basic-fibroblast growth factor, and epidermal growth factor for 5 days. Following neural induction, hMDSCs and hADSCs were differentiated into neural cells, including neurons and glia, in vitro. RESULTS: In neural differentiated hMDSCs (d-hMDSCs) and differentiated hADSCs (d-hADSCs), neural stem cell marker (nestin) showed a significant decrease by immunocytochemistry, and neuronal marker (beta-tubulin III) and glial marker (GFAP) showed a significant increase, compared with primary hMDSCs and hADSCs. Real-time chain reaction analysis and Western blotting demonstrated significantly elevated levels of mRNA and protein of beta-tubulin III and GFAP in d-hADSCs compared with d-hMDSCs. CONCLUSIONS: We demonstrated that hMDSCs and hADSCs can be induced to undergo phenotypic and molecular changes consistent with neurons. The neural differentiation capacity of hADSCs was better than that of hMDSCs.
Adipose Tissue ; Blotting, Western ; Caves ; Cell Differentiation ; Centrifugation ; Collagenases ; Epidermal Growth Factor ; Erectile Dysfunction ; Forskolin ; Humans ; Immunohistochemistry ; Laminin ; Male ; Muscles ; Neural Stem Cells ; Neuroglia ; Neurons ; Prostatectomy ; RNA, Messenger ; Stem Cells ; Tubulin

PURPOSE: In neurogenic bladder, both smooth muscle contraction and nerve regeneration are very important for functional improvement. Glycine-isoleucine-lysine-valine-alanine-valine (GIKVAV) is a peptide that can induce nerve regeneration in vivo. In this study, we evaluated bladder function after injection of muscle-derived stem cells (MDSCs) and GIKVAV into the cryo-injured bladder of nude mice. MATERIALS AND METHODS: Human muscle samples were obtained from the rectus abdominis muscle of 12 patients who underwent laparotomy. The purpose and entire method of the study were explained to the patients, and all subjects who participated in this study provided written informed consent. The MDSCs were isolated by a modified preplate technique, and only CD34+ human MDSC were extracted by use of Mini-MACS kits. The nude mice were subdivided into 5 groups (n=40): normal group (N, n=8), saline injection group after cryo-injury (S, n=8), GIKVAV injection group after cryo-injury (G, n=8), human MDSC injection group after cryo-injury (M, n=8), and GIKVAV and human MDSC injection group after cryo-injury (GM, n=8). At 2 weeks after injection, we compared the contractility of a bladder muscle strip of each group by organ bath and polygraph by using electronic field stimulation (EFS). Nerve regeneration was evaluated by choline acetyl transferase (ChAT) immunostaining. RESULTS: The contractile powers of the N, S, G, M, and GM groups were 3.58+/-0.27, 1.54+/-0.25, 1.54+/-0.31, 2.49+/-0.36, and 2.44+/-0.34 mN/mg, respectively, by EFS. The contractility of the bladder muscle strip in the S and G groups was lower than that in the N group. The contractile powers of the M and GM groups were lower than those of the N group but greater than those of the S and G groups. In ChAT immunohistochemical staining, nerve regeneration was increased in the G and GM groups compared with the S and M groups. CONCLUSIONS: Nerve regeneration was induced by GIKVAV injection regardless of human MDSC injection. There was no direct effect of GIKVAV on bladder muscle contractility.
Animals ; Baths ; Choline ; Contracts ; Electronics ; Electrons ; Humans ; Informed Consent ; Laparotomy ; Mice ; Mice, Nude ; Muscle, Smooth ; Muscles ; Nerve Regeneration ; Rectus Abdominis ; Stem Cells ; Transferases ; Urinary Bladder ; Urinary Bladder, Neurogenic

PURPOSE: We studied the feasibility and results of a tissue-engineered ileal conduit using a poly (epsilon-caprolactone) (PCL) nano-sheet seeded with muscle-derived stem cells to replace a conventional ileal conduit in rats. MATERIALS AND METHODS: Muscle-derived stem cells were isolated from the gastrocnemius muscle of female Sprague-Dawley rats (200-250 g, n=6) by use of a preplate technique and were cultured on a PCL nano-sheet. The PCL nano-sheet was implanted into the omentum of rats and was then made into a conical shaped conduit. Rats were sacrificed 4 and 8 weeks after implantation, and morphologic changes were assessed by H&E and immunofluorescence staining, including DAPI staining and staining for myogenin and myosin heavy chain (MyHC). RESULTS: All rats survived until the end of the experiment. A minimal inflammatory reaction was observed around the PCL nano-sheet in the 4 week specimens but was found to be reduced in the 8 week specimen. Muscle bundles were identified at week 4 as well as week 8 after implantation on H&E staining. Around the PCL sheet, immunostaining for both myogenin and MyHC were positive, indicating skeletal muscle differentiation and ingrowth into the PCL sheet. CONCLUSIONS: A PCL nano-sheet seeded with muscle-derived stem cells showed successful skeletal muscle differentiation at 4 and 8 weeks after implantation. This preliminary result supports the feasibility of a tissue-engineered ileal conduit using a PCL nano-sheet (seeded with muscle-derived stem cells) in place of conventional ileal conduits.
Animals ; Female ; Fluorescent Antibody Technique ; Humans ; Hypogonadism ; Indoles ; Mitochondrial Diseases ; Muscle, Skeletal ; Muscles ; Myogenin ; Myosin Heavy Chains ; Omentum ; Ophthalmoplegia ; Rats ; Rats, Sprague-Dawley ; Seeds ; Stem Cells ; Tissue Engineering ; Urinary Diversion