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.

Two fragments G1 and G2 of the glycoprotein G gene of bovine respiratory syncytial virus(BRSV) were selected for expression in Escherichia coli based on the analysis of glycoprotein G by DNA Star software.Then the two fragments of glycoprotein G were amplified by PCR with synthesized G gene of BRSV as the template.The amplified fragments G1 and G2 are 570bp and 308bp in length,respectively.The PCR products were cloned into pET30a vector and expressed in soluble form in E.coli after induction of cultured E.coli with IPTG.Both of the recombinant proteins G1 and G2 were purified by immobilized Ni ion affinity chromatography under native conditions.Then the purified proteins were analysed by Western blotting.The results showed that the purified recombinant protein G1 retained good antigenicity and specificity.But the purified recombinant protein G2 didn't possess biological activity.Antibodies against BRSV were detected in suspected bovine serum samples in China by using indirect ELISA and Western blotting with the purified recombinant protein G1.The purified recombinant protein G1 might be used as antigen for establishing serological methods for diagnosis of BRSV infection.And the purified recombinant protein G1 might also be used for preparing polyclonal and monoclonal antibodies for research on biological functions of glycoprotein G of BRSV.

The effects of a non-selective inhibitor of cyclo-oxygenase (COX) indomethacin, and exogenous prostaglandin E(2) (PGE(2)) on A(delta) units and C units in the saphenous nerve of diabetic hyperalgesic rats were studied. The results showed that the conduction velocity of A(delta) units and C units and their mechanical threshold in diabetic hyperalgesic rats were obviously decreased, and a small number of A(delta) units (4/24) and C units (2/18) produced increased spontaneous activities. Intraperitoneal injection of indomethacin in diabetic hyperalgesic rats significantly relieved mechanical hyperalgesia, and resulted in a decrease in spontaneous afferent activities of the A(delta) units and C units. Subcutaneous injection of exogenous PGE(2) into the diabetic hyperalgesic and control rats produced a significant decrease in mechanical threshold of the A(delta) units and C units, and elicited discharge from 3 A(delta) units (3/24) and 1 C unit (1/18) in diabetic hyperalgesic rats and from 2 A(delta) units (2/13) in control rats. The present data suggest that the synthesis and release of PGs are increased in diabetic neuropathy, PGs can sensitize and /or activate A(delta) units and C units and elicit hyperalgesia and allodynia in diabetic rats.
Afferent Pathways ; drug effects ; physiopathology ; Animals ; Diabetes Mellitus, Experimental ; physiopathology ; Femoral Nerve ; drug effects ; physiopathology ; Hyperalgesia ; physiopathology ; Indomethacin ; pharmacology ; Male ; Pain Threshold ; drug effects ; Prostaglandin Antagonists ; pharmacology ; Rats ; Rats, Sprague-Dawley

BACKGROUNDThe recurrence of pterygium after surgery is high. A variety of adjunctive treatment approaches have been developed to improve the clinical efficacy and many related articles have been published. This study aimed to determine the risk for postoperative pterygium recurrence comparing autologous conjunctival transplantation (ACT) versus mitomycin C (MMC).

METHODSRelevant literature published until December 2010 in Medline, Embase, Cochrane, Cochrane library, Science Citation Index, and Google Scholar were searched. Qualified random clinical trial (RCT) studies on the comparison of recurrence rate of pterygium after ACT and MMC treatment were included in this study.

RESULTSEight RCTs with 663 eyes entered the final analysis. The recurrent rate of pterygium was 8.7% (30/343) for ACT and 18.75% (60/320) for MMC. Using fixed-effect meta analysis, we found that the recurrence was significantly lower after ACT than MMC treatment (odds ratio (OR) = 0.40, 95% confidence index (CI), 0.25 - 0.63, P < 0.0001). In sensitivity analyses, we employed random-effects model and excluded studies of low quality or studies in which MMC was administrated after the operation. All the sensitivity analyses confirmed that ACT led to lower recurrence rates than MMC. Sub-group analysis revealed that the recurrence rate was 20.2% (20/99) and 27.65% (26/94) for conjunctival autograft (CA) and MMC respectively, and no significant difference in the recurrence rate was detected (OR = 0.65, 95%CI 0.33 - 1.28, P = 0.22). However, we found that conjunctival limbal autograft (CLA) had lower recurrence rate than MMC (OR = 0.26, 95%CI 0.14 - 0.48, P = 0.0001).

CONCLUSIONCLA has better therapy efficacy against the recurrence of pterygium than MMC.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Conjunctiva ; transplantation ; Humans ; Middle Aged ; Mitomycin ; therapeutic use ; Pterygium ; therapy ; Randomized Controlled Trials as Topic ; Transplantation, Autologous

OBJECTIVETo investigate the molecular genetic mechanism of a Chinese patient with mucopolysaccharidosis type I (MPS I).

METHODSPCR-sequencing analysis was applied to detect the mutations in exons in alpha-L-iduronidase gene (IDUA) of the patient. Restriction fragment length polymorphism (RFLP) and allele-specific oligonucleotide hybridization (ASO) were used to confirm the identified mutations. PCR amplified DNA samples from 50 normal individuals were sequenced to demonstrate that the newly identified mutation was not polymorphism.

RESULTSThe patient was compound heterozygous for a previously reported nonsense mutation Q60X (178C > T) in exon 2, inherited from the mother, and a newly detected missense mutation D203N (607G > A) in exon 6 from the father. The newly identified mutation D203N was not found in PCR amplified products from 50 normal individuals, indicating that it was not polymorphism.

CONCLUSIONThe two identified mutations may be the cause resulting in patient's clinical phenotype.

Adolescent ; Base Sequence ; Codon, Nonsense ; DNA Mutational Analysis ; Exons ; genetics ; Female ; Humans ; Iduronidase ; genetics ; Male ; Mucopolysaccharidosis I ; genetics ; Mutation ; Mutation, Missense ; Pedigree ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length

Depression is a widespread psychiatric disorder with complex pathogenesis and unsatisfactory therapeutic effects. As a native flavonoid, Isorhamnetin (ISO) has been deemed to exert neuroprotective effects by antioxidation and regulation of immunity. However, no reports of anti-depressed effect of ISO have yet been found. The present study was conducted to clarify the mechanism basis of anti-depressed effect of ISO utilizing behavioral, biochemical, molecular approaches in vitro and in vivo and bio-informatics analysis. The effects of ISO on depressed mice was investigated through the SPT and FST, and the lesions were examined by H&E staining. Besides, the inflammatory factor and indicator in kynurenine pathway were assessed through detection kits, and the microbiota were checked by 16sRNA. Molecular docking study was performed to investigate the target of ISO. Additionally, Western blot was used to test the activation of PI3K/AKT signaling pathway. The results indicated that ISO could enhance the sugar water preference of mice in SPT and reduce immobility time in FST. Further more, ISO suppressed peripheral and central inflammation, regulated the changes in kynurenine pathway and gut microbiota, inhibited activation of PI3K/AKT pathway, and presented good binding patterns with target proteins on PI3K/AKT signaling pathway. Collectively, these findings demonstrate that ISO alleviated depression-like behaviour by normalizing inflammation-induced dysregulation of the crosstalk between KP and gut microbiota disorder through regulated PI3K/AKT/NF-κB pathway.

Depression is a widespread psychiatric disorder with complex pathogenesis and unsatisfactory therapeutic effects. As a native flavonoid, Isorhamnetin (ISO) has been deemed to exert neuroprotective effects by antioxidation and regulation of immunity. However, no reports of anti-depressed effect of ISO have yet been found. The present study was conducted to clarify the mechanism basis of anti-depressed effect of ISO utilizing behavioral, biochemical, molecular approaches in vitro and in vivo and bio-informatics analysis. The effects of ISO on depressed mice was investigated through the SPT and FST, and the lesions were examined by H&E staining. Besides, the inflammatory factor and indicator in kynurenine pathway were assessed through detection kits, and the microbiota were checked by 16sRNA. Molecular docking study was performed to investigate the target of ISO. Additionally, Western blot was used to test the activation of PI3K/AKT signaling pathway. The results indicated that ISO could enhance the sugar water preference of mice in SPT and reduce immobility time in FST. Further more, ISO suppressed peripheral and central inflammation, regulated the changes in kynurenine pathway and gut microbiota, inhibited activation of PI3K/AKT pathway, and presented good binding patterns with target proteins on PI3K/AKT signaling pathway. Collectively, these findings demonstrate that ISO alleviated depression-like behaviour by normalizing inflammation-induced dysregulation of the crosstalk between KP and gut microbiota disorder through regulated PI3K/AKT/NF-κB pathway.

Depression is a widespread psychiatric disorder with complex pathogenesis and unsatisfactory therapeutic effects. As a native flavonoid, Isorhamnetin (ISO) has been deemed to exert neuroprotective effects by antioxidation and regulation of immunity. However, no reports of anti-depressed effect of ISO have yet been found. The present study was conducted to clarify the mechanism basis of anti-depressed effect of ISO utilizing behavioral, biochemical, molecular approaches in vitro and in vivo and bio-informatics analysis. The effects of ISO on depressed mice was investigated through the SPT and FST, and the lesions were examined by H&E staining. Besides, the inflammatory factor and indicator in kynurenine pathway were assessed through detection kits, and the microbiota were checked by 16sRNA. Molecular docking study was performed to investigate the target of ISO. Additionally, Western blot was used to test the activation of PI3K/AKT signaling pathway. The results indicated that ISO could enhance the sugar water preference of mice in SPT and reduce immobility time in FST. Further more, ISO suppressed peripheral and central inflammation, regulated the changes in kynurenine pathway and gut microbiota, inhibited activation of PI3K/AKT pathway, and presented good binding patterns with target proteins on PI3K/AKT signaling pathway. Collectively, these findings demonstrate that ISO alleviated depression-like behaviour by normalizing inflammation-induced dysregulation of the crosstalk between KP and gut microbiota disorder through regulated PI3K/AKT/NF-κB pathway.

OBJECTIVETo investigate the effect and mechanism of blockade of STAT3 signaling pathway by JAK specific inhibitor-AG490 on invasion and metastasis of human highly metastatic pancreatic cancer line SW1990 in vitro.

METHODSAG490 was added into the culture media for SW1990 cells. The invasion ability of SW1990 cells was determined by cell invasion assay kit. Western blot was performed to detect the protein expression of the STAT3, phosphorylated STAT3 (p-STAT3), MMP-2 and VEGF. RT-PCR was performed to detect the mRNA expression of the MMP-2 and VEGF.

RESULTS20 micromol/L AG490 significantly inhibited the invasion ability of SW1990 cells and the inhibitory rate of invasion ability was (77.67 +/- 7.79) %. The use of AG490 not only markedly reduced the protein expression of p-STAT3, MMP-2 and VEGF, but also greatly reduced the mRNA expression of MMP-2 and VEGF.

CONCLUSIONBlocking STAT3 activation with AG490 can inhibit the invasion and metastasis ability of pancreatic cancer cells in vitro through down-regulation of MMP-2 and VEGF expression. Blocking STAT3 signaling pathway may provide a novel strategy in prevention of invasion and metastasis of pancreatic cancer.

Antineoplastic Agents ; pharmacology ; Blotting, Western ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Janus Kinases ; antagonists & inhibitors ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Pancreatic Neoplasms ; genetics ; metabolism ; pathology ; Phosphorylation ; drug effects ; RNA, Messenger ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; drug effects ; Tyrphostins ; pharmacology ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

Objective To investigate the effect of 1.94 μm thulium laser enucleation of benign prostatic hyperplasia (BPH) with volume >80 ml by morcellator. Methods From September 2014 to June 2016, there were 95 BPH patients with prostate volume over 80 ml treated by thulium laser were divided into two groups according to the surgical procedure: 45 cases in group A, prostate tissue were washed out of bladder after vapoenucleation by 1.94 μm thulium laser; 50 cases in group B, the enucleated prostate tissue were extracted by morcellator. The operation time, the decreasing level of hemoglobin on the first day after surgery, the hospitalization time, the gland tissue weight, catheterization duration, short-term incidence of complications, and the IPSS, PVP, Qmax, QOL in 3 months after surgeon of the two groups were observed and recorded. Results There was significant difference in operation time and gland tissue weight between the two groups. The group B have significantly short operation time compared with group A (P < 0.05), and obtained gland tissue remarkably exceed the group A (P < 0.05). No significant difference was found in hemoglobin level, hospitalization time, catheterization duration, and short-term complication between the two groups (P > 0.05). The IPSS, PVR, Qmax and QOL of 3 month, after operation were significantly improved but without any significant difference between the two groups (P < 0.05). Conclusion Vaporization cutting tissue or morcellating tissue after 1.94 μm thulium laser enucleation has high safety, good curative effect and low complication, while extraction prostate tissue by morcellator can shorten the operation time and get more tissues.