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Psoriasis is a non-infectious chronic inflammatory skin disease. It′s acknowledged that interleukin (IL)-17 signaling pathway dominantly drives the development of psoriasis. Recently, the role of neuro-immune axis in psoriasis has attracted widespread attention. Lidocaine, a local anesthetic, has ability to block the conduction of nerve impulses, while its therapeutic efficacy on psoriasis remains to be confirmed. Here, we evaluated the therapeutic efficacy of topical application of compound lidocaine cream (LIDO) on imiquimod (IMQ)-induced mouse psoriasis model. Animal welfare and experimental procedures follow the regulations of the Ethics Committee of China Pharmaceutical University. The psoriasis area and severity index (PASI) scoring was used to evaluate the severity of psoriasis-like symptoms. Hematoxylin-eosin staining was used to examine histopathological changes and epidermal thickness was measured. Ki67 immunofluorescence staining was used to evaluate the proliferation of keratinocytes. The relative mRNA expression of inflammatory cytokines (including Il17, Il22, Il23 and Il36) in skin was measured by real-time quantitative PCR. Results show that IMQ-induced increases in the PASI score, epidermal thickness, number of Ki67+ cells and the mRNA expression of inflammatory cytokines are significantly alleviated by topical application of LIDO, whose therapeutic efficacy is also better than that of the positive control drug calcipotriol. Our study suggests that LIDO could be used for psoriasis treatment.
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Background@#It is well-established that serum testosterone in men decreases with age, yet the underlying mechanism of this change remains elusive. @*Methods@#The expression patterns of Fancd2 opposite-strand (Fancd2os) in BALB/c male mice and testicular tissue derived cell lines (GC-1, GC-2, TM3, and TM4) were assessed using real-time polymerase chain reaction (RT-PCR), Western blot and immunofluorescence. The Fancd2os-overexpressing or knockdown TM3 cells were constructed by infecting them with lentivirus particles and were used to evaluated the function of Fancd2os. The testosterone production was measured using enzyme linked immunosorbent assay (ELISA) and the steroidogenic enzymes such as steroidogenic acute regulatory protein (StAR), P450 cholesterol side-chain cleavage (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD) were analysed using RT-PCR. The apoptosis of TM3 cells induced by ultraviolet light or testicular tissues was detected using flow cytometry, Western blot or dUTP-biotin nick end labeling (TUNEL) assays. Pearson correlation analysis was used to assess the correlation between the Fancd2os expression and TUNEL-positive staining in mouse testicular Leydig cells. @*Results@#The Fancd2os protein was predominantly expressed in mouse testicular Leydig cells and its expression increased with age. Fancd2os overexpression inhibited testosterone levels in TM3 Leydig cells, whereas knockdown of Fancd2os elevated testosterone production. Fancd2os overexpression downregulated the levels of StAR, P450scc and 3β-HSD, while Fancd2os knockdown reversed this effect. Fancd2os overexpression promoted ultraviolet light-induced apoptosis of TM3 cells. In contrast, Fancd2os knockdown restrained apoptosis in TM3 cells. In vivo assays revealed that higher Fancd2os levels and mouse age were associated with increased apoptosis in Leydig cells and decreased serum testosterone levels. Pearson correlation analysis exhibited a strong positive correlation between the expression of Fancd2os and TUNEL-positive staining in mouse testicular Leydig cells. @*Conclusion@#Our findings suggest that Fancd2os regulates testosterone synthesis via both steroidogenic enzymes and the apoptotic pathway.
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Transient receptor potential vanilloid 3 (TRPV3) is a non-selective cation channel, located on cell membranes. TRPV3 is extensively expressed in various organs such as skin, brain, dorsal root ganglia, heart and colon. It's reported that TRPV3 involves in many physiological processes including sensation, skin barrier formation, hair growth and vasodilatation, and pathological processes like pruritus, cutaneous inflammatory disease and cancer. TRPV3 can respond to innoxious warm stimulation (≥ 33 ℃), endogenous substances (e.g., farnesylpyrophosphate) and exogenous small molecules (e.g., carvacrol, camphor and 2-APB). Recently, several natural or synthetic small molecules (e.g., osthole, 74a and dyclonine) have been shown to suppress TRPV3 activity, accompanying with therapeutic efficacy in animal models of diseases, which suggests the potential of TRPV3 as drug target. This paper reviews the research progress on the structure, physiological functions, related diseases and modulators of the TRPV3 channel to provide theoretical references for the future study on TRPV3 channel.
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Aim To investigate the protective effect of paeoniflorin on TNF-α induced intestinal epithelial barrier dysfunction and its mechanisms.Methods The Caco-2 cells were cultured and the MTF assay was used to determine the effects of the paeoniflorin on Caco-2 cell activity.The Caco-2 cell intestinal epithelial barrier dysfunciton model was established through incubation of cells with TNF-α.The effects of paeoniflorin on intestinal epithelial barrier dysfunciton were studied.Results The transmembrane resistance in Caco-2 epithelial barrier was significantly reduced by TNF-α incubation;MLCK significantly increased,while tight junction protein occludin and ZO-1 significantly decreased by TNF-α.These changes were significantly reversed by paeoniflorin,which reduced MLCK expression and enhanced expression of occludin and ZO-1.The protective effects against epithelial barrier dysfunction could be abrogated by small interfering RNA(siRNA) of MLCK.Conclusions Paeoniflorin alleviates the epithelial barrier dysfunction induced by TNF-αthrough down-regulation of MLCK and enhancement of tight junction protein occludin and ZO-1.This study supplies a potential candidate drug for the clinical treatment of inflammatory bowel diseases.
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BACKGROUND: Open reduction and internal fixation have been used to treat thoracolumbar fractures, which possesses good efficacy, but causes large trauma and many complications. Minimally invasive treatment like Wiltse operative approach and Sextant, Zina system also has many defects such as large incision, insufficient fixed strength, limited orthopedic forces. OBJECTIVE: To access the effect of vertebral fixation with HXN pedicle screw system in the treatment of thoracolumbar fractures. METHODS: Totally 68 cases of thoracolumbar fractures admitted in the Department of Orthopedics, the First Affiliated Hospital of Xinxiang Medical University from October 2014 to December 2016 were randomly divided into two groups: the patients in group A received minimally invasive pedicle screw fixation with HXN system and those in group B were subjected to open reduction and internal fixation. The perioperative indexes (blood loss), Visual Analogue Scale scores, Oswestry Disability Index, anterior vertebral height, and Cobb angle were detected to compare the curative efficacy between two RESULTS AND CONCLUSION: (1) All patients were followed up for 3-24 months. (2) There were no significant differences in the operation time, intraoperative fluoroscopy times between two groups (P > 0.05), and the blood loss in the group B was significantly more than that in the group A (P < 0.05). (3) The preoperative Visual Analogue Scale and Oswestry Disability Index scores showed no significant differences between two groups (P > 0.05), and the postoperative and last follow-up scores were significantly decreased (P < 0.05), but the group A had lower scores than those in the group B (P < 0.05). (4) The anterior vertebral height and Cobb angle were significantly improved postoperatively (P <0.05); at the last follow-up, both indexes had no obvious loss and showed no significant difference between two groups (P > 0.05). (5) The incision healed well in the group A, while there were two cases of incision infection in the group B. No screw loosening, displacement or rupture occurred during follow-up. (6) These results suggest that the minimally invasive HXN pedicle screw system for thoracolumbar fracture not only has the advantages of fewer traumas, less blood loss, low incidence of incision infection, pain relief, but also is safe and easy to operate, which obtains good fixation stability and can achieve the same curative effect with the open surgery.
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Objective To identify the differential proteomic expressions between the liver tissues of male and female mice, and investigate the mechanisms underlying gender differences in liver diseases. Methods Two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry ( MALDI-TOF-MS) were used to identify the differentially expressed proteins in the liver tissues of male and female C57BL/6J mice. The differentially expressed proteins were validated by Western blot and further analyzed by bioinformatics, including Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results Among the auto-detected 1767 protein spots by 2D-DIGE, 325 protein spots were differentially expressed (|ratio|≥1. 5, P< 0. 05) between the liver tissues of male and female mice, in which 78 spots were randomly selected for MALDI-TOF-MS identification and finally 48 distinct proteins were obtained. Compared with females, 14 and 34 proteins were up-or down-regulated in males, respectively. Among them, 6 differentially expressed proteins were validated by Western blot which confirmed the reliability of 2D-DIGE results. GO analysis showed that the differentially expressed proteins in the liver tissues of male and female mice are associated to various cellular component, molecular function and biological process. 6 pathways were significantly different between the liver tissues of males and females depending on KEGG analysis. Conclusions The proteomic data and related analysis of the liver tissues of C57BL/6J mice offer crucial clues for elucidating the underlying mechanisms of different gender effects on liver diseases.
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Objective To identify the differential proteomic expressions between the liver tissues of male and female mice, and investigate the mechanisms underlying gender differences in liver diseases. Methods Two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry ( MALDI-TOF-MS) were used to identify the differentially expressed proteins in the liver tissues of male and female C57BL/6J mice. The differentially expressed proteins were validated by Western blot and further analyzed by bioinformatics, including Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results Among the auto-detected 1767 protein spots by 2D-DIGE, 325 protein spots were differentially expressed (|ratio|≥1. 5, P< 0. 05) between the liver tissues of male and female mice, in which 78 spots were randomly selected for MALDI-TOF-MS identification and finally 48 distinct proteins were obtained. Compared with females, 14 and 34 proteins were up-or down-regulated in males, respectively. Among them, 6 differentially expressed proteins were validated by Western blot which confirmed the reliability of 2D-DIGE results. GO analysis showed that the differentially expressed proteins in the liver tissues of male and female mice are associated to various cellular component, molecular function and biological process. 6 pathways were significantly different between the liver tissues of males and females depending on KEGG analysis. Conclusions The proteomic data and related analysis of the liver tissues of C57BL/6J mice offer crucial clues for elucidating the underlying mechanisms of different gender effects on liver diseases.
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Both open and closed loop self-expandable stents were used in carotid artery stenting (CAS) for carotid bifurcation stenosis. We sought to compare the efficacy of two types of stents in CAS. The data of 212 patients treated with CAS (42 and 170 cases implanted with closed and open loop stents, respectively) for carotid bifurcation stenosis and distal filtration protection devices were retrospectively analyzed. Between closed and open loop stents, there were no significant differences in hospitalization duration, NIHSS score before and after the treatment, stenosis at 12th month, and cumulative incidence of primary endpoint events within 30 days or from the 31st day to the 12th month; while there were significant differences in hemodynamic changes and rate of difficulty in recycling distal filtration protection devices. Use of open vs. closed loop stents for carotid bifurcation stenosis seems to be associated with similar incidence of complications, except for greater rate of hemodynamic changes and lower rate of difficulty in recycling the distal filtration protection devices.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Carotid Arteries , General Surgery , Carotid Stenosis , General Surgery , Endovascular Procedures , Methods , Hemodynamics , Postoperative Complications , Self Expandable Metallic StentsABSTRACT
Both open and closed loop self-expandable stents were used in carotid artery stenting (CAS) for carotid bifurcation stenosis. We sought to compare the efficacy of two types of stents in CAS. The data of 212 patients treated with CAS (42 and 170 cases implanted with closed and open loop stents, respectively) for carotid bifurcation stenosis and distal filtration protection devices were retrospectively analyzed. Between closed and open loop stents, there were no significant differences in hospitalization duration, NIHSS score before and after the treatment, stenosis at 12th month, and cumulative incidence of primary endpoint events within 30 days or from the 31st day to the 12th month; while there were significant differences in hemodynamic changes and rate of difficulty in recycling distal filtration protection devices. Use of open vs. closed loop stents for carotid bifurcation stenosis seems to be associated with similar incidence of complications, except for greater rate of hemodynamic changes and lower rate of difficulty in recycling the distal filtration protection devices.
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<p><b>OBJECTIVE</b>To investigate the characteristics of circulatory disturbance and treatment of severe hand-foot-and-mouth disease (HFMD).</p><p><b>METHOD</b>The clinical characteristics, laboratory findings, therapy and outcome of 22 severe HFMD patients were retrospectively analyzed.</p><p><b>RESULT</b>All the 22 severe HFMD patients came from the countryside. All these patients had encephalitis. Fifteen cases had myocardial injury. All had symptoms of sympathetic excitation and 17 cases had hypertension [(128 ± 16)/(81 ± 14) mm Hg (1 mm Hg = 0.133 kPa)]. Fourteen cases had exacerbation with rapid decline of blood pressure [(61 ± 12)/(33 ± 12) mm Hg]. In cardiorespiratory failure stage, 13 patients had neurogenic pulmonary edema accompanied by circulatory failure and 12 cases had a lower glasgow scores (less than 7). Myocardial injury and ECG change were found in some cases. Inotropic and pressor drugs were given in patients with circulatory collapse. Five cases received fluid resuscitation due to refractoriness to inotropic drugs. Nine patients received blood purification. Seventeen survived and 5 cases died due to circulatory failure.</p><p><b>CONCLUSION</b>Circulation failure of severe HFMD is the main cause of death. Early and appropriate circulation support is very important to reduce mortality.</p>
Subject(s)
Child, Preschool , Female , Humans , Infant , Male , China , Epidemiology , Combined Modality Therapy , Hand, Foot and Mouth Disease , Mortality , Therapeutics , Immunoglobulins, Intravenous , Therapeutic Uses , Intensive Care Units, Pediatric , Milrinone , Therapeutic Uses , Multiple Organ Failure , Mortality , Pulmonary Edema , Mortality , Respiration, Artificial , Retrospective Studies , Shock , Mortality , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To detect the expression of important proteins associated with transforming growth factor-beta (TGF-beta)/Smad signaling pathway in Peutz-Jeghers syndrome (PJS) and investigate the correlation of these proteins to LKB1 gene expression.</p><p><b>METHODS</b>The expression and localization of LKB1, TGFbeta1 and pSmad2 proteins in 20 PJS polyp samples and normal intestinal mucosal tissues were detected with immunohistochemical staining.</p><p><b>RESULTS</b>The expressions of LKB1, TGFbeta1 and pSmad2 were lower in PJS polyps than in normal mucosa, and the differences in LKB1 and TGFbeta1 proteins were significantly different between them (P<0.05). In PJS polyps, positive correlations were found between LKB1 and TGFbeta1 and between TGFbeta1 and pSmad2 expressions.</p><p><b>CONCLUSION</b>TGFbeta/Smad pathway is probably subjected to the regulation by LKB1 and may play a role in the occurrence of PJS.</p>