Erythrocyte membrane-associated protein inhibiting Th17 cell differentiation via IL-6 / STAT3 / ROR-γt signaling pathway in experimental autoimmune encephalomyelitis mice / 解剖学报

Objective To explore the effect of exogenous and endogenous erythrocyte membrane-associated protein (ERMAP) on helper T cell 17 (Th17) cell differentiation through interleukin 6 / signal transducers and activators of transcription 3 / retionoid-related orphan nuclear receptor-γt(IL-6 / STAT3 / ROR-γt) signal pathway in the mouse model of experimental autoimmune encephalomyelitis (EAE) . Methods Using flow cytometry to verify the function of ERMAP-Ig fusion protein at different concentrations; Agarose gel electrophoresis was performed to identify ERMAP knockout mice. Flow cytometry was performed to detect the effect of ERMAP-Ig fusion protein on Th17 cell differentiation in vitro. Forty 6-week-old normal C57BL / 6 mice were randomly divided into 2 groups to establish EAE models, control-Ig and ERMAP-Ig groups, with 20 mice in each group; Clinical scores were recorded; Flow cytometry was performed to detect Th17 cell differentiation in EAE mice in vivo. Forty 6-week-old identified wild-type and ERMAP knockout mice were divided into 2 groups to establish EAE models. Identified wild-type and ERMAP knockout mice were divided into 2 groups to establish EAE models, ERMAP

Mechanism of apoptosis induced by SR1078 activating RORα in ovarian cancer cells / 药学学报

This study was to investigate the effect of RORα activator SR1078 on ovarian cancer cells and its molecular mechanism in vitro. The survival rate of HeyA8 and Hey cells was detected by MTS assay; the apoptosis and cells cycle distribution after SR1078 treatment and the effect of p53 siRNA or PFT-α and PFT-β of p53 inhibitors on SR1078-induced apoptosis of HeyA8 or Hey cells were analyzed by flow cytometry. Western blot was used to detect the effect of SR1078 and p53 siRNA on the expression of p53 protein and the effect of p53 inhibitors alone or in combination with SR1078 on the expression of p53, p-p53 and its downstream pro-apoptotic protein Noxa. The results showed that SR1078 significantly reduced the cell viability and induced apoptosis in HeyA8 and Hey cells. In addition, SR1078 up-regulated the protein expression of p53 and Noxa, and p53 suppression led to significant inhibition of SR1078-induced apoptosis and the expression of Noxa in ovarian cancer cells. In summary, SR1078 induced apoptosis of ovarian cancer cells by activation of p53 signaling pathway.

Efficacy and safety of 13-cis retinoid acid and all trans retinoid acid in the redifferentiation therapy of poorly differentiated thyroid cancer / 中华内分泌代谢杂志

Objective To evaluate the efficacy and safety of 13-cis retinoid acid (13-CRA) and all trans retinoid acid (ATAR) redifferentiation therapy in patients with poorly differentiated thyroid cancer. Methods A single-center, randomized, double-blind, parallel controlled clinical trial was preformed. All patients were randomized into three groups. 78 cases were enrolled in each group. The patients were treated by 13-CRA in A group, by ATRA in B group, and by placebo in control group. The induced effects of retinoid acid (RA) and 131I treatment efficacies were defined as primary outcome of efficacy. Results After RA induction therapy, the effective rates in A, B, and control groups were 59.72%, 52.86% and 7.69%, respectively, with statistically significant difference among 3 groups (P<0.05). Compared with control group, A and B groups revealed significant induced efficacies (P<0.017), but there was no significant difference between A group and B group. After 131I treatment, the effective rates in A, B, and control group were 70.83%, 64.29%, and 28.21% respectively, with statistically significant difference (P<0.05). Compared with control group, the effective rates of 131I treatment in A and B groups were significantly raised (P<0.017), but there was no significant difference between A group and B group. The damage of skins and mucous membranes such as desquamation, dry skin, dry lips, dry eyes, etc occurred mostly in A group. The symptoms of nervous system such as headache, dizziness, etc occurred mostly in B group. Conclusions The induced differentiation of 13-CRA or ATRA is an effective method for the treatment of poorly differentiated thyroid carcinoma.

RORA Polymorphism Interacts with Childhood Maltreatment in Determining Anxiety Sensitivity by Sex: A Preliminary Study in Healthy Young Adults

OBJECTIVE: Recent studies have reported associations of retinoid-related orphan receptor alpha (RORA) gene single nucleotide polymorphisms (SNPs) with depression and anxiety disorders. Based on these, we attempt to test whether RORA polymorphism is associated with anxiety sensitivity (AS), the intermediate phenotype of depression and anxiety disorders. Considering gene-environment interactions and sex differences in AS, childhood maltreatment (CM) and sex were considered as confounders. METHODS: Two-hundred and five healthy young Korean adults (female: 98, male: 107; age, 23.0±3.2 years) completed genotyping for the RORA SNP rs11071547, as well as measures for AS and CM. Generalized linear models were used to examine the main and interaction effects of RORA genotype, CM, and sex in determining AS. RESULTS: The main effect of RORA polymorphisms was not found (p=0.760) whereas the main effect of CM and interaction effects among sex, genotype, and maltreatment were significant on AS. In separate analyses by sex, the interaction effect between RORA genotype and maltreatment was significant only in males (p < 0.001). In females, the main effects of genotype and CM were significant (both were p < 0.001), in which both a history of CM and C genotype tended to be associated with higher AS. CONCLUSION: The association between RORA polymorphism and AS might differ by sex. The interaction between RORA polymorphism and CM was significant only in males whereas RORA genotype and CM independently associated with AS in females. Further studies are encouraged to confirm the relationship between RORA polymorphism and AS.

Efficacy of Garcinia mangostana L. (mangosteen rind extract) to reduce acne severity.

Background: In vitro studies showed that extract of mangosteen rind (EMR) (Garcinia mangostana L.) containing xanthones has antibacterial effect against Propionibacterium acnes and also anti-inflammatory effect. The aim of this study is to determine the efficacy of EMR in reducing acne vulgaris (AV). Methods: A randomized, double-blind, placebo controlled clinical trial was done on 94 subjects (18-30 years) with mild and moderate AV. The treatment group was given 400 mg EMR 3 times daily orally, for 3 weeks and control group was given placebo capsules. As a standard therapy, all subjects were given a topical cream of 0.025% retinoic acid applied on acne lesions during night time. Efficacy was assessed by counting the acne lesion number as well as proportion of subjects with more than 20% decrease in lesion. The decrease of plasma malondialdehyde (MDA) levels were also measured. Results: After 3 weeks of treatment, acne lesion counts was significantly reduced in both groups [from 934 to 584 lesion (37%) in treatment group, p < 0.001 and from 832 to 608 lesion (27%) in control group, p < 0.001]. Comparison between the two groups revealed a non significant difference (p > 0.55). The proportion of subjects whose acne lesion reduced ≥ 20% was 73% (33 of 45 subjects) in treatment group vs 66% (27 of 41 subjects) in control (p > 0.2). The level MDA was reduced from 1.16 to 1.02 nmol/mL in treatment group and from 1.32 become 1.02 nmol/mL in control (p > 0.48). Conclusion: Extract of mangosteen rind given orally for 3 weeks clinically reduced acne severity better than placebo, although statistically was not significant. Antioxidant effect of EMR seem to be unspecific in reducing acne severity.

Correlation between the Expression of RARα, PPARβ/δand the Effect of Retinoic Acid in Craniopharyngioma Cells / 昆明医科大学学报

Objective To investigate the molecular mechanism of retinoic acid in targeted treatment of craniopharyngioma by detecting the expression of RARαand PPARβ/δin craniopharyngioma cells and analyzing the correlation between the expression and effect of retinoic acid. Methods The expression of RARα and PPARβ/δ in craniopharyngioma cells from 31 patients cultured in vitro was quantified by reverse transcription-PCR. The inhibition rates of RA on craniopharyngioma with different expression of RARα and PPARβ/δ were detected by using MTT assay, and the correlation between the expression of RARα and PPARβ/δand the effect of RA was analyzed. Results 1. The RT-PCR results showed that the expression levels of PPARβ/δand RARα mRNA were different. Craniopharyngioma cells from 31 patients in primary culture were divided into three groups according the expression levels of nuclear receptor: PPARβ/δ>RARα group, RARα>PPARβ/δ group and RARα>>PPARβ/δ group. 2.MTT results showed that the inhibition rate of RARα>>PPARβ/δgroup was significantly higher than the other groups under same drug, the differences had statistical significance ( <0.01) . Conclusions The expression of PPARβ/δ, RARα can be used to evaluate the effect of RA in treatment of craniopharyngioma. The craniopharyngioma with low-expression of PPARβ/δ is more sensitive to RA. Targeting higher RARα or targeting lower PPARβ/δ is beneficial to the treatment of craniopharyngiomas.

All-Trans Retinoic Acid Attenuates Interleukin-23/Interleukin-17 Pathway and Promotes Skin Allograft Survival in Mice / 天津医药

Objective To investigate the effects of all-trans retinoic acid (ATRA)-intragastric-administration on the survival time of mouse skin allografts and the role of interleukin (IL)-23 and IL-17 thereof. Methods The skin trans-plantation of mice was done by DBA/2 as donors and Balb/c as recipients. The recipients were divided randomly into three groups:control group, low-dose group and high-dose group. Mice of the corresponding groups were intragastrically adminis-tered corn oil, 10 mg/kg ATRA and 30 mg/kg ATRA respectively from 1 day before the transplantation to the 14th day after the transplantation. The survival time of transplanted skin was observed after the operations. Skin grafts of mice were harvested for histopathological examination in three groups. The serum levels of IL-23 and IL-17 were measured by enzyme-linked im-munosorbent assay (ELISA). The expression levels of IL-23, RORγt and IL-17 mRNA in skin allografts were detected by re-al-time fluorescent quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Results Compared with con-trol group, the average survival time of mouse skin allografts was significantly prolonged in low-dose group and high-dose group (P＜0.05). The less lymphocyte infiltration and destruction of architecture were found in the skin biopsies. The serum expression of IL-23 protein was lower (P＜0.05), but no significant difference was found in two treatment groups. The serum expression levels of IL-17 protein were reduced in turn in receptors of control group, low-dose group and high-dose group (P ＜ 0.05). The expression levels of IL-23, RORγt and IL-17 mRNA in skin grafts were significantly lower in low-dose group and high-dose group than those of control group (P＜0.05), but no significant difference was found in two treatment groups. Conclusion ATRA can effectively prolong the survival time of skin allografts, which may related with the inhibi-tion of the expression of IL-23, RORγt and IL-17 mRNA and the development of IL-23 and IL-17 protein.

Effects of all-trans retinoic acid on proliferation,iodide uptake and thyroid specific gene expression in different cell lines of human thyroid carcinoma / 中华内分泌代谢杂志

Different human thyroid carcinoma cell lines were treated with all-trans retinoic acid(RA). RA could inhibit cell growth,improve iodide uptake and increase some thyroid specific genes and retinoid acid receptor(RAR)mRNA expressions in FTC-133 cells.However,RA had no effect in C643,HTH74 and XTC. UC1 cells.These findings indicate that different thyroid carcinoma cells display diverse responses to RA.

A Case of Unilateral Keratosis Follicularis / 대한피부과학회지

Unilateral keratosis follicularis is considered a localized variant of Darier's disease and should be included in the differential diagnosis of diseases with zosteriform keratotic eruptions. It is characterized by the unilateral linear lesions in multiple locations, increased irritation by sweating, lack of solar aggravation, and negative family history. Histopathologic findings reveal acantholytic dyskeratosis similar to a generalized Darier's disease. We report a case of unilateral keratosis follicularis in a 68-year-old man, who presented with unilateral flesh-colored keratotic papules on the left axilla and inguinal area. He was effectively treated with oral 13-cis-retinoid acid (isotretinoin).

All Trans Retinoid Acid Inhibit Cell Growth in Human Retinoblastoma Cells Via Phosphorylation of JNK / 中国肿瘤生物治疗杂志

Objective: To investigate all trans retinoid Acid (ATRA) inhibition of cell growth in human retinoblastoma Y79 cells, and its mechanism. Methods: Antiproliferation effects of ATRA on Y79 cells were determined by 3 H thymidine incorporation. Cell cycle analysis was performed by flow cytometry. JNK phosphorylation was analyzed by Western blot analysis. Results: After 36 h treatment with 10 -6 mol?L -1 ATRA, 3 H thymidine incorporation decreased to 40%, under the same condition, Y79 cells were arrested in G 0 /G 1 and Sub G 1 peak appeared. Curcumin, JNK blocker, blocked the growth inhibition by ATRA. JNK was phosphorylated in 10 to 20 min. Conclusion: JNK phosphorylating mediated ATRA inhibition of apoptosis in Y79 cells. These results suggested that ATRA might have clinical application for treatment of retinoblastoma.

Function of apoptosis induced by derivatives of retinoid acid on tumor cells / 中国药理学通报

Retinoid acid and its derivatives have shown promising perspective in clinical use and lab research on the leukemia and other solid tumor cells.Some of these compounds have a stronger apoptotic potential,a lower level of cytotoxicity and a better pharmacokinetic profile than all-trans retinoic acid.The apoptosis pathways induced by these compounds are different from traditional p53-dependent pathway which recruited by many chemotherapeutics.Due to its specific molecular mechanism,these compounds could induce apoptosis in retinoic acid-resistant or multi-drug-resistant tumor cells.This paper reviews the current research on apoptosis induced by analogues of retinoid acid.

EFFECT OF ALL TRANS RETINOID ACID ON NEWBORN RAT CALVARIAL OSTEOBLASTIC CELLS IN VITRO / 营养学报

Objective: To investigate the effect of all trans retinoid acid (ATRA) on bone cell proliferation and differentiation. Methods: Newborn rat calvarial osteoblastic cells were isolated and the metabolism of the osteoblastic cells were determined by MTT, Goldens method and immunocytohistologic method. Results: 10 -5 , 10 -6 , 10 -7 , 10 -8 , 10 -9 mol/L ATRA could increase osteoblastic cells proliferation after 72 h culture; 10 -5 , 10 -6 , 10 -7 mol/L ATRA could increase ALP activity. The expression of cyclin D 1 was decreased. Conclusion: ATRA stimulates the proliferation and differentiation of rat calvarial osteoblastic cells in vitro. Cell cycle relative proteins may play an important role in control of cell proliferation and differentiation induced by retinoic acid and derivatives.