ABSTRACT
OBJECTIVE@#To explore the mechanism by which estradiol modulates the immunophenotype of macrophages through the endoplasmic reticulum stress pathway.@*METHODS@#Peritoneal macrophages isolated from C57 mice were cultured in the presence of 60 ng/mL interferon-γ (IFN-γ) followed by treatment with estradiol (1.0 nmol/L) alone, estradiol with estrogen receptor antagonist (Acolbifene, 4 nmol/L), estradiol with IRE1α inhibitor (4 μ 8 C), or estradiol with IRE1α agonist. After the treatments, the expression levels of MHC-Ⅱ, iNOS and endoplasmic reticulum stress marker proteins IRE1α, eIF2α and ATF6 in the macrophages were detected with Western blotting, and the mRNA levels of TGF-β, IL-6, IL-10 and TNF-α were detected with RT-PCR.@*RESULTS@#Estrogen treatment of the macrophages significantly decreased the expressions of M1-related proteins MHC-Ⅱ (P=0.021) and iNOS (P < 0.001) and the mRNA expressions of TNF-α (P=0.003) and IL-6 (P=0.004), increased the mRNA expression of TGF-β (P=0.002) and IL-10 (P=0.008), and up-regulated the protein expressions of IRE1α (P < 0.001) and its downstream transcription factor XBP-1 (P < 0.001). Addition of the estrogen inhibitor obviously blocked the effect of estrogen. Compared with estrogen treatment alone, combined treatment of the macrophages with estrogen and the IRE1α inhibitor 4 μ 8 C significantly up-regulated the protein expressions of MHC-Ⅱ (P=0.002) and iNOS (P=0.003) and the mRNA expressions of TNF-α (P=0.003) and IL-6 (P=0.024), and obviously down-regulated the mRNA expression of TGF-β (P < 0.001) and IL-10 (P < 0.001); these changes were not observed in cells treated with estrogen and the IRE1α agonist.@*CONCLUSION@#Estrogen can inhibit the differentiation of murine macrophages into a pro-inflammatory phenotype by up-regulating the IRE1α-XBP-1 signaling axis, thereby producing an inhibitory effect on inflammatory response.
Subject(s)
Animals , Mice , Cell Differentiation/drug effects , Endoribonucleases/metabolism , Estradiol/pharmacology , Estrogens/metabolism , Interleukin-10 , Interleukin-6/metabolism , Macrophages, Peritoneal/metabolism , Phenotype , Protein Serine-Threonine Kinases/metabolism , RNA, Messenger/metabolism , Signal Transduction/drug effects , Transforming Growth Factor beta/metabolism , Tumor Necrosis Factor-alpha/metabolism , Up-Regulation/drug effects , X-Box Binding Protein 1/metabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of neuropeptide Y (NPY) Y1 receptor antagonist PD160170 in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and accelerating healing of femoral defect in rats.</p><p><b>METHODS</b>The third generation of rat BMSCs were treated with PBS (control) or 10, 10, or 10 mol/L NPY Y1 receptor antagonist PD160170. After 7 and 14 days of treatment, the cells were examined for osteogenic differentiation with alkaline phosphatase (ALP) and alizarin red staining. At 7 and 21 days of treatment, the mRNA and protein expressions of collagen type I (COLI), osteocalcin (OCN) and Runt-related transcription factor 2 (Runx2) in the cells were detected using q-PCR and Westem Blotting. In a male SD rat model (body weight 300∓20 g) of bilateral femoral condyle defects (2.5 mm in diameter), the effect of daily local injection of 0.2 mL PD160170 (10 and 10 mol/L, for 28 consecutive days) in promoting bone defect repair was evaluated with micro-CT scans.</p><p><b>RESULTS</b>ALP and alizarin red staining showed that the BMSCs treated with PD160170, at the optimal concentration of 10 mol/L, contained more intracellular cytoplasmic brown particles and mineralized nodules in extracellular matrix than PBS-treated cells. PD160170 (10 mol/L) significantly up-regulated the mRNA and protein expressions of COLI at day 7 and those of OCN and Runx2 at day 21 (P<0.05). In the rat models of femoral bone defect, the volume/tissue volume ratio, bone mineral density and the number of bone trabeculae were significantly greater in 10 mol/L PD160170 group than in the control group (P<0.05), but the bone trabecular thickness (P=0.07) and bone volume (P=0.35) were similar between the two groups.</p><p><b>CONCLUSION</b>NPY Y1 receptor antagonist PD160170 can promote osteogenic differentiation of BMSCs and healing of femoral defects in rats, suggesting the potential of therapeutic strategies targeting NPY Y1 receptor signaling in the prevention and treatment of bone fracture and osteoporosis.</p>
ABSTRACT
The 2-μm thulium laser resection of the prostate-tangerine technique (TmLRP-TT) has been introduced as a minimally invasive treatment for benign prostatic hyperplasia (BPH). This study was undertaken to assess the clinical efficacy and safety of TmLRP-TT for the treatment of BPH patients with previously negative transrectal prostate biopsy. A prospective analysis of 51 patients with previously negative transrectal prostate biopsy who underwent surgical treatment using TmLRP-TT was performed from December 2011 to December 2013. Preoperative status, surgical details, and perioperative complications were recorded. The follow-up outcome was evaluated with subjective and objective tests at 1 and 6 months. TmLRP-TT was successfully completed in all patients. Mean prostate volume, operative duration, and catheterization time were 93.3 ± 37.9 ml, 69.5 ± 39.5 min, and 6.5 ± 1.3 days, respectively. The mean International Prostate Symptom Score, quality of life score, maximum urinary flow rate, and post-void residual urine volume changed notably at 6-month follow-up (22.5 ± 6.9 vs 6.1 ± 3.2, 4.8 ± 1.3 vs 1.1 ± 0.9, 7.3 ± 4.5 vs 18.9 ± 7.1 ml s-1 , and 148.7 ± 168.7 vs 28.4 ± 17.9 ml). Two (3.9%) patients required blood transfusion perioperatively, while 3 (5.9%) patients experienced transient hematuria postoperatively, and 2 (3.9%) patients received 3 days recatheterization due to clot retention. TmLRP-TT is a safe and effective minimally invasive technique for patients with previously negative transrectal prostate biopsy during the 6-month follow-up. This promising technology may be a feasible surgical method for previously negative transrectal prostate biopsy in the future.
ABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of purgation and detoxification therapy on gastrointestinal dysfunction of critically ill patients undergoing abdominal surgery.</p><p><b>METHODS</b>Totally 56 inpatients with severe gastrointestinal dysfunction after abdominal surgery at ICU of Guangdong Provincial Hospital of Traditional Chinese Medicine were assigned to the treatment group and the control group, 28 in each group. All patients received routine Western medical treatment. Patients in the treatment group additionally took Modified Huanglian Jiedu Decoction (MHJD) and received electroacupuncture (EA) for 7 days. The first exhaust time, defecation time, scores for gastrointestinal dysfunction, mechanical ventilation time, ICU hospitalization time, and 28-day fatality rate were observed. Furthermore, serum levels of diamine oxidase (DAO) and D-lactic acid were detected at day 1, 3, and 7 after treatment.</p><p><b>RESULTS</b>The first exhaust time and the first defecation time in the treatment group were ahead of schedule, when compared with those of the control group (P <0. 05). Scores for gastrointestinal dysfunction, mechanical ventilation time, serum levels of DAO obviously decreased in the treatment group (P <0. 05). There was no statistical difference in serum levels of D-lactic acid, ICU stay time, the incidence of pulmonary infection, and 28-day mortality between the two groups (P >0. 05). Results of Logistic analysis showed that scores for gastrointestinal dysfunction were related with the incidence of pulmonary infection (P <0. 05).</p><p><b>CONCLUSION</b>MHJD combined EA could promote the recovery of gastrointestinal function in critically ill patients after abdominal surgery via improving intestinal barrier function, which was benefit for shortening mechanical ventilation time.</p>
Subject(s)
Humans , Critical Illness , Defecation , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Electroacupuncture , Gastrointestinal Diseases , Drug Therapy , Lactic Acid , Medicine, Chinese TraditionalABSTRACT
The inhibition of 3-hydroxy-3-methylglutaryl CoA reductase [HMGCR] is considered able to decrease serum cholesterol levels and dramatically reduce the risk for cardiovascular and cerebrovascular diseases. The statins, competitive inhibitors of HMGCR, have been employed to control hypercholesterolemia. But their side effects, especially their safety of long-term administration have attracted great attention. Therefore, there is still an urgent requirement for the development of safer inhibitors of HMGCR with less serious side effects. In this study, we cloned and purified the catalytic domain of human HMGCR [delta HMGCR], and applied the method of Ultra Performance Liquid Chromatography [UPLC] to assay delta HMGCR activity and screen its inhibitors from natural products. The results indicated that EGCG can inhibit delta HMGCR in the presence of some glycerol in vitro and can decrease cellular total cholesterol in HepG2 cells. As a consequence, it is promising to put EGCG into the development of hypolipidemic health product
Subject(s)
Hydroxymethylglutaryl CoA Reductases , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Glycerol , Chromatography, High Pressure LiquidABSTRACT
<p><b>OBJECTIVE</b>To evaluate the clinical efficiency and safety of two-micron laser resection of the prostate-tangerine technique (TmLRP-TT) for the treatment of large-volume ( > 70 ml) prostate in patients with benign prostatic hyperplasia (BPH).</p><p><b>METHODS</b>This retrospective analysis included 80 BPH patients with the prostatic volume larger than 70 ml, all treated by TmLRP-TT. We comparatively analyzed the levels of hemoglobin and serum sodium before and after surgery, recorded intra- and post-operative com- plications, and followed up the patients at 6 and 12 months after operation for International Prostate Symptom Score (IPSS), quality of life (QOL), maximum flow rate (Qmax), and postvoid residual urine volume (PVR).</p><p><b>RESULTS</b>All the operations were successfully completed. The mean hemoglobin decreased (0.68 +/- 0.43) g/dl intraoperatively, but no apparent reduction was observed in serum sodium. Lower urinary tract symptoms were relieved significantly in all the cases. At 12 months after surgery, IPSS was decreased by 73.89% as compared with the baseline (20.03 +/- 6.9 vs 5.23 +/- 3.59), QOL by 64.55% (4.09 +/- 1.19 vs 1.45 +/- 1.36), and PVR by 79.30% (97.31 +/- 57.90 vs 20.14 +/- 24.20 ml), while Qmax increased by 140.42% ([8.04 +/- 3.62] vs [19.33 +/- 3.28] ml/s). The incidence of complications was low either intraoperatively or during the 12 months after operation.</p><p><b>CONCLUSION</b>TmLRP-TT is a safe and effective surgical endoscopic approach to the treatment of large-volume prostate in BPH patients.</p>
Subject(s)
Aged , Humans , Male , Middle Aged , Follow-Up Studies , Laser Therapy , Methods , Prostatic Hyperplasia , General Surgery , Retrospective Studies , Transurethral Resection of Prostate , Methods , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To study the different proportions of intermediate epithelial cells in human prostate cancer tissue and their clinical significance.</p><p><b>METHODS</b>We performed immunohistochemical staining for Cytokeratin 5 (CK5) and Cytokeratin 8 (CK8) on 60 samples of human prostate cancer, determined the proportions of intermediate epithelial cells in the cancer tissue, and classified the samples into 2 types, one with a majority of intermediate epithelial cells (CaP-INT, n = 32), and the other composed mostly of luminal epithelial cells (CaP-LUM, n = 28). Then we compared the 2 types of prostate cancer in the expression of the androgen receptor (AR), age of the patient, serum t-PSA, prostate volume, Gleason score, clinical stage, androgen resistance, and incidence of distant metastasis.</p><p><b>RESULTS</b>CaP-INT showed a significantly lower expression of AR ([24.42 +/- 11.41] %) and a higher incidence of distant metastasis (n = 14) than CaP-LUM ([77.21 +/- 10.22] % and n = 4) (P < 0.05). In the CaP-INT group, 6 of the 26 endocrinologically treated cases developed into androgen-independent prostate cancer (AIPC), while in the CaP-LUM group, only 1 out of 23 (P < 0.05). The former also showed remarkably higher clinical stages than the latter (P < 0.05), but no significant differences were found in age, serum t-PSA, prostate volume and Gleason score between the two groups (P > 0.05).</p><p><b>CONCLUSION</b>A higher proportion of intermediate epithelial cells may lead to increased invasiveness and metastasis of human prostate cancer.</p>
Subject(s)
Aged , Aged, 80 and over , Humans , Male , Middle Aged , Cell Count , Cell Differentiation , Epithelial Cells , Classification , Pathology , Prostate , Pathology , Prostatic Neoplasms , Pathology , Receptors, Androgen , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate a method for upper cicatricial ectropion correction using a rotated orbicularis oculi myocutaneous flap in the unsatisfied pre-operative construction of double eyelid.</p><p><b>METHODS</b>In construction of double eyelid, orbicularis oculi myocutaneous flap made by relaxed skin and orbicularis oculi was used to correct ectropion.</p><p><b>RESULTS</b>From Feb. 2003 to Dec. 2005, the authors performed correction of ectropion for 13 patients. All of these patients were followed up, and the period ranged from 2 weeks to 6 months. All of these patients received good results except one. It was corrected again for the flattening of the pedicle 6 months later.</p><p><b>CONCLUSIONS</b>Orbicularis oculi myocutaneous flap has a rich blood supply. The ratio of its length and width can be made to 6:1, and it can be transferred flexibly. In addition, the incision of the donor site is hidden in fold of double eyelid.</p>