Non-coding RNAs: The potential biomarker or therapeutic target in hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury (HIRI) is the major complication of liver surgery and liver transplantation, that may increase the postoperative morbidity, mortality, tumor progression, and metastasis. The underlying mechanisms have been extensively investigated in recent years. Among these, oxidative stress, inflammatory responses, immunoreactions, and cell death are the most studied. Non-coding RNAs (ncRNAs) are defined as the RNAs that do not encode proteins, but can regulate gene expressions. In recent years, ncRNAs have emerged as research hotspots for various diseases. During the progression of HIRI, ncRNAs are differentially expressed, while these dysregulations of ncRNAs, in turn, have been verified to be related to the above pathological processes involved in HIRI. ncRNAs mainly contain microRNAs, long ncRNAs, and circular RNAs, some of which have been reported as biomarkers for early diagnosis or assessment of liver damage severity, and as therapeutic targets to attenuate HIRI. Here, we briefly summarize the common pathophysiology of HIRI, describe the current knowledge of ncRNAs involved in HIRI in animal and human studies, and discuss the potential of ncRNA-targeted therapeutic strategies. Given the scarcity of clinical trials, there is still a long way to go from pre-clinical to clinical application, and further studies are needed to uncover their potential as therapeutic targets.

Long non-coding RNA SNHG16 promotes human placenta-derived mesenchymal stem cell proliferation capacity through the PI3K/AKT pathway under hypoxia.

BACKGROUND: The effect of hypoxia on mesenchymal stem cells (MSCs) is an emerging topic in MSC biology. Although long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) are reported to play a critical role in regulating the biological characteristics of MSCs, their specific expression and co-expression profiles in human placenta-derived MSCs (hP-MSCs) under hypoxia and the underlying mech anisms of lncRNAs in hP-MSC biology are unknown. AIM: To reveal the specific expression profiles of lncRNAs in hP-MSCs under hypoxia and initially explored the possible mechanism of lncRNAs on hP-MSC biology. METHODS: Here, we used a multigas incubator (92.5% N2, 5% CO2, and 2.5% O2) to mimic the hypoxia condition and observed that hypoxic culture significantly promoted the proliferation potential of hP-MSCs. RNA sequencing technology was applied to identify the exact expression profiles of lncRNAs and mRNAs under hypoxia. RESULTS: We identified 289 differentially expressed lncRNAs and 240 differentially expressed mRNAs between the hypoxia and normoxia groups. Among them, the lncRNA SNHG16 was upregulated under hypoxia, which was also validated by reverse transcription-polymerase chain reaction. SNHG16 was confirmed to affect hP-MSC proliferation rates using a SNHG16 knockdown model. SNHG16 overexpression could significantly enhance the proliferation capacity of hP-MSCs, activate the PI3K/AKT pathway, and upregulate the expression of cell cycle-related proteins. CONCLUSION: Our results revealed the specific expression characteristics of lncRNAs and mRNAs in hypoxia-cultured hP-MSCs and that lncRNA SNHG16 can promote hP-MSC proliferation through the PI3K/AKT pathway.

Octreotide ameliorates hepatic ischemia-reperfusion injury through SNHG12/TAF15-mediated Sirt1 stabilization and YAP1 transcription.

BACKGROUND: Hepatic ischemia-reperfusion (HIR) injury is a pathological condition initiated by interrupted hepatic blood supply and exaggerated after reperfusion, which is one of the most lethal risks in liver transplantation and other liver surgeries. We aimed to investigate the protective mechanism of octreotide (Oct) against HIR injury. METHODS: The function of Oct was evaluated in the in vivo mouse model of HIR injury. Histological examinations were performed to assess the pathological changes. Serum parameters including ALT and AST were measured to evaluate the liver damage. qRT-PCR and western blot analysis were employed to determine the levels of long non-coding RNA SNHG12 (SNHG12) and autophagy or apoptosis-related proteins. RNA pull-down and RIP assays were used to verify the interaction between SNHG12 and TAF15. The transcriptional regulation of TAF15 in YAP1 was validated by ChIP and luciferase reporter assays. RESULTS: In the in vivo HIR injury model, Oct efficiently alleviated HIR-caused hepatic damage by suppressing apoptosis and activating autophagy. However, silencing of SNHG12 abrogated the protective effects of Oct via inactivating autophagy. Further mechanism investigation revealed that SNHG12 promoted the stabilization of Sirt1 and increased YAP1 transcriptional activity via interacting with TAF15. Up-regulation of Sirt1 and YAP1 was essential for maintaining the protective effect of Oct against HIR injury through increasing autophagic flux and suppressing apoptosis. CONCLUSIONS: Oct-induced up-regulation of SNHG12 attenuated HIR injury via promoting Sirt1 stabilization and YAP1 transcription to activate autophagy and repress apoptosis.

[Protective effects of aqueous extracts from Sedum sarmentosum growing under different light intensity on CCl_4-induced damage in HepG2 cells].

To explore the effect of light intensity in cultivating environment on the hepetoprotective activity of Sedum sarmentosum, S. sarmentosum were planted under five water treatments for 60 days, namely 100% full sunlight(G1), 77% full sunlight(G2), 60% full sunlight(G3), 38% full sunlight(G4), and 16% full sunlight(G5) and CCl_4 drug-induced liver injury model in vitro was used. Cell viability, cell cycle, and cell apoptosis were individually detected by MTT, PI single staining, and Annexin-V FITC/PI double staining assays. Additionally, ALT, AST and antioxidant index in supernatant were determined by colorimetry. And the relationship among the protective effects, chemical composition and antioxidant activity were also analyzed. The results showed that S. sarmentosum aqueous extract could significantly improve the HepG2 cell viability. Among the five S. sarmentosum groups, the cell viability of G1(100% full sunlight) treatment was the highest, and the cell apoptosis was the least. Meanwhile, the level of ALT, AST, and MDA in G1 was the lowest, but it achieved the highest level of SOD and GSH. Moderate light shading(60% full light) also improved the effect of protecting liver and reducing the enzyme. It was found that cell viability was positively correlated with ferricion reducing capacity. ALT activity was positively correlated with isorhamnetin content. Taken together, different light intensity had great influence on hepatoprotective effect of S. sarmentosum, which may be related to its antioxidant capacity. From the perspective of hepetoprotective activity, S. sarmentosum should be planted under full light.

Application of peer education in mental health education for adolescent primary and middle school students / 中国学校卫生

Objective@#To assess the application effect of peer education in mental health education for adolescent primary and middle school students and to provide evidence for promoting the mental health of adolescent primary and middle school students in application.@*Methods@#The non-randomized controlled trial was performed, 4-5 th grade students of two primary and 7-8 th grade students of two middle schools in a district of Chongqing were chosen as peer-education experimental group, and students in the same grade of another two school were chosen as the blank control group. The Mental Health Inventory of Middle School Students scale and self-made questionnaire were used to exam in mental health status of the subjects before and after intervention.@*Results@#The detection rates after intervention of the mental health, compulsion, paranoia, hostility, interpersonal relationship, depression, anxiety, academic stress, emotional imbalance and psychological imbalance (36.8%, 46.1%, 36.6%, 33.3%, 37.2%, 38.8%, 40.9%, 45.7%, 49.2%, 30.3%) in experimental group were lower than those before intervention (39.9%, 55.3%, 38.8%, 37.9%, 43.9%, 40.5%, 42.7%, 48.0%, 52.5%, 32.1%). The detection rate after intervention of maladjustment(39.8%)was higher than that before intervention(37.7%)(P<0.05). Logistic regression analysis showed that the detection rate after intervention of the mental health, compulsion, paranoia, hostility, interpersonal relationship, depression, anxiety and academic stress status of adolescent primary and middle school students in experimental group was 0.63 times more than the rate of the control group(95%CI=0.49-0.81),0.73(95%CI=0.58-0.91),0.68(95%CI=0.54-0.86),0.71(95%CI=0.56-0.91)(P<0.05).@*Conclusion@#Peer education is an effective measure and method to improve compulsion,paranoia,hostility,interpersonal relationship,depression,anxiety and intervention effect of adolescent primary and middle school students.

Anti-CTLA-4 monoclonal antibody improves efficacy of the glyceraldehyde-3-phosphate dehydrogenase protein vaccine against Schistosoma japonicum in mice.

Schistosomiasis is a devastating disease caused by Schistosoma infection. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has emerged as a candidate vaccine component against Schistosoma japonicum, but only confers partial protection. Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates T cell activation and shows negative effects on vaccine-induced immune protection; however, its potential influence on the protective effects of a GAPDH vaccine against S. japonicum and the underlying mechanism remain unclear. In this study, we established a mouse model of S. japonicum infection, and the mice were randomly divided into uninfected, infected control, anti-CTLA-4 monoclonal antibody (anti-CTLA-4 mAb), GAPDH, and GAPDH combined with anti-CTLA-4 mAb groups to compare the protective effects against infection and the consequent tissue damage. The worm reduction rate in the GAPDH-treated infected mice was 26.58%, which increased to 54.61% when combined with anti-CTLA-4 mAb. The frequency of regulatory T cells (Tregs) was significantly higher in the anti-CTLA-4 mAb group and was lower in the GAPDH group. However, both anti-CTLA-4 mAb and GAPDH elevated the levels of the cytokines IFN-γ, IL-2, IL-4, and IL-5 in the spleens of infected mice, and their combination further enhanced cytokine production. The diameter of egg granuloma in the anti-CTLA-4 mAb group and combined treatment group increased significantly compared to that of the other groups. These results suggest that anti-CTLA-4 mAb can be used as an adjuvant to enhance the immune protection of the GAPDH vaccine via inducing the Th1 immune response, although this comes at the cost of enhanced body injury.

Carvedilol blockage of delayed rectifier Kv2.1 channels and its molecular basis.

Previous studies indicated that one of the action targets of carvedilol is the voltage-gated potassium (Kv) channel, which has a fundamental role in the control of electrical properties in excitable cells. It is not clear whether this compound exerts any actions specifically on delayed rectifier Kv2.1 channels. The present study is conducted on Kv2.1 currents heterologously expressed in HEK293 cells to characterize the block by carvedilol in detail, identifying molecular determinants and providing biophysical insights of the block. Macroscopic Kv2.1 currents obtained by whole-cell recording were substantially inhibited after addition of carvedilol with an IC50 value of 5.1 µM. This drug also led to a largely hyperpolarizing shift (30 mV) of the inactivation curve, which may contribute to the blocking action due to more inactivation of Kv2.1 currents occurred in depolarization potentials. Mutations at Y380 (a putative TEA binding site) and K356 (a K+ binding site) in the outer vestibule of Kv2.1 channels significantly eliminated the inhibitory effects of carvedilol and prevented the leftward shift of inactivation. Moreover, mutations at above positions modulated the effects of carvedilol on the deactivation but not activation kinetics of Kv2.1 channels. Collected data indicate that carvedilol can exert a blocking effect on the closed-state of Kv2.1 channels, and specific residues within the S5-P and P-S6 linkers in the outer vestibule may play crucial roles in carvedilol-induced blocking for Kv2.1 channels.

[Decipherment of ancient literature about fresh use,crude use and processed use of Puerariae Lobatae Radix].

Puerariae Lobatae Radix is a traditional Chinese medicine,which was first recorded in Shennong Classic of Materia Medica,and was recorded in many ancient books. Its main effect is to relieve muscles to expel heat,produce saliva and promote eruption,invigorate splenic yang and stop diarrhea. CNKI and Wanfang Data were searched in this paper with the words " Pueraria", " puerarin usage" and " puerarin application" as the key words,and it was found that the puerarin usage characteristics were rarely reported.Therefore,the application characteristics of fresh use,crude use and processed use of Puerariae Lobatae Radix in ancient books were summarized in this paper,in order to provide a reference for the modern development of Puerariae Lobatae Radix.

Dynamic changes of key metabolites during liver fibrosis in rats.

BACKGROUND: Fibrosis is the single most important predictor of significant morbidity and mortality in patients with chronic liver disease. Established non-invasive tests for monitoring fibrosis are lacking, and new biomarkers of liver fibrosis and function are needed. AIM: To depict the process of liver fibrosis and look for novel biomarkers for diagnosis and monitoring fibrosis progression. METHODS: CCl4 was used to establish the rat liver fibrosis model. Liver fibrosis process was measured by liver chemical tests, liver histopathology, and Masson's trichrome staining. The expression levels of two fibrotic markers including α-smooth muscle actin and transforming growth factor ß1 were assessed using immunohistochemistry and real-time polymerase chain reaction. Dynamic changes in metabolic profiles and biomarker concentrations in rat serum during liver fibrosis progression were investigated using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. The discriminatory capability of potential biomarkers was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: To investigate the dynamic changes of metabolites during the process of liver fibrosis, sera from control and fibrosis model rats based on pathological results were analyzed at five different time points. We investigated the association of liver fibrosis with 21 metabolites including hydroxyethyl glycine, L-threonine, indoleacrylic acid, ß-muricholic acid (ß-MCA), cervonoyl ethanolamide (CEA), phosphatidylcholines, and lysophosphatidylcholines. Two metabolites, CEA and ß-MCA, differed significantly in the fibrosis model rats compared to controls (P < 0.05) and showed prognostic value for fibrosis. ROC curve analyses performed to calculate the area under the curve (AUC) revealed that CEA and ß-MCA differed significantly in the fibrosis group compared to controls with AUC values exceeding 0.8, and can clearly differentiate early stage from late stage fibrosis or cirrhosis. CONCLUSION: This study identified two novel biomarkers of fibrosis, CEA and ß-MCA, which were effective for diagnosing fibrosis in an animal model.

Non­canonical Wnt signaling contributes to ventilator­induced lung injury through upregulation of WISP1 expression.

Mechanical ventilation may cause ventilator­induced lung injury (VILI). Canonical Wnt signaling has been reported to serve an important role in the pathogenesis of VILI. Bioinformatics analysis revealed that canonical and non­canonical Wnt signaling pathways were activated in VILI. However, the role of non­canonical Wnt signaling in the pathogenesis of VILI remains unclear. The present study aimed to analyze the potential role of non­canonical Wnt signaling in VILI pathogenesis. Lung injury was assessed via Evans blue albumin permeability and histological scoring, as well as by inflammatory cytokine expression and total protein concentration in bronchoalveolar lavage fluid. The relative protein expression of canonical and non­canonical Wnt signaling pathway components were examined via western blotting and immunohistochemistry. The results demonstrated that 6 h of mechanical ventilation at low tidal volume (LTV; 6 ml/kg) or moderate tidal volume (MTV; 12 ml/kg) induced lung injury in sensitive A/J mice. Ventilation with MTV increased the protein levels of Wnt­induced secreted protein 1 (WISP1), Rho­associated protein kinase 1 (ROCK1), phosphorylated (p)­Ras homolog gene family, member A and p­C­Jun N­terminal kinase (JNK). Inhibition of ROCK1 by Y27632 and JNK by SP600125 attenuated MTV­induced lung injury and decreased the expression of proteins involved in non­canonical Wnt signaling, including WISP1. In conclusion, non­canonical Wnt signaling participates in VILI by modulating WISP1 expression, which has been previously noted as critical for VILI development. Therefore, the non­canonical Wnt signaling pathway may provide a preventive and therapeutic target in VILI.

[Effects of light intensity on growth, quality and antioxidant activities of Sedum sarmentosum].

The present study was conducted to explore the effect of light intensity on growth, bioactivity compounds accumulation and anti-oxidative activity of Sedum sarmentosum. The growth, yield, contents of total flavonoids, total phenolic, quercetin, kaempferol and isorhamnetin, and antioxidant activities were assessed in S. sarmentosum under five light intensities, namely 100% full sunlight (G1), 77% full sunlight (G2), 60% full sunlight (G3), 38% full sunlight (G4), and 16% full sunlight (G5). The results showed that light intensity significantly affected the growth and the chemical compounds accumulation. With the decrease of light intensity, the maximum branch length and the average internode distance increased. G2 treatment greatly promoted the numbers of leaf layers and branches, and G3 treatment remarkably improved the yield. The highest total flavonoids and phenolic contents were obtained in G3 treatment. Meanwhile, the highest quercetin and isorhamnetin contents were obtained in G1 treatment. The difference of kaempferol content was not significant. In addition, based on DPPH, FTC and FRAP methods, the antioxidant activities of the aqueous extracts under G1 treatment were superior to the others. The results indicated that more than 60% full sunlight was the optimum light intensity condition to achieve high yield and quality of S. sarmentosum.

[Protective effects of Sedum sarmentosum under different soil moisture in CCl4-induced damage in HepG2 cells].

At present, there were few studies about the effects of cultivation measures on the quality and pharmacological activity of medicinal plants. To explore the hepetoprotective activity of Sedum sarmentosum aqueous extracts after different water treatments, S. sarmentosum were planted under five water treatments for 60 days, namely 15%-20% FC (field capacity, S1), 35%-40% FC (S2), 55%-60% FC (S3), 75%-80% FC(S4), and 95%-100% FC (S5) and CCl4 drug-induced liver injury model in vitro was used. Cell viability, cell cycle, and cell apoptosis were individually detected by MTT, PI single staining, and Annexin-V FITC/PI double staining assays. Additionally, ALT, AST and antioxidant index in supernatant were determined by colorimetry. The results showed that, compared with the model group, S. sarmentosum aqueous extract could significantly improve the HepG2 cell viability. Among the five S. sarmentosum groups, the cell viability of S4 (75%-80% FC) treatment was the highest, and the cell apoptosis was the least. Meanwhile, the level of ALT, AST, and MDA in S4 was the lowest, but it achieved the highest level of SOD and GSH. Taken together, different water treatments had great influence on hepatoprotective effect of S. sarmentosum, and the soil moisture of the 75%-80% FC is beneficial to the hepetoprotective activity of S. sarmentosum.

Characterization and molecular basis for the block of Kv1.3 channels induced by carvedilol in HEK293 cells.

Carvedilol is a non-selective ß-adrenoreceptor antagonist and exhibits a wide range of biological activities. The voltage-gated K+ (Kv) channel is one of the target ion channels of this compound. The rapidly activating Kv1.3 channel is expressed in several different tissues and plays an important role in the regulation of physiological functions, including cell proliferation and apoptosis. However, little is known about the possible action of carvedilol on Kv1.3 currents. Using the whole-cell configuration of the patch-clamp technique, we have revealed that exposure to carvedilol produced a concentration-dependent blocking of Kv1.3 channels heterologously expressed in HEK293 cells, with an IC50 value of 9.7 µM. This chemical decelerated the deactivation tail current of Kv1.3 currents, resulting in a tail crossover phenomenon. In addition, carvedilol generated a markedly hyperpolarizing shift (20 mV) of the inactivation curve, but failed to affect the activation curve. Mutagenesis experiments of Kv1.3 channels identified G427 and H451, two related sites of TEA block, as important residues for carvedilol-mediated blocking. The present results suggest that carvedilol acts directly on Kv1.3 currents by inducing closed- and open-channel block and helps to elucidate the mechanisms of action of this compound on Kv channels.

The effects of probiotics on total cholesterol: A meta-analysis of randomized controlled trials.

BACKGROUND: Probiotics supplements provide a new nonpharmacological alternative to reduce cardiovascular risk factors. The impact of probiotics on the reduction of total cholesterol (TC) remains controversial. We conducted a meta-analysis to showcase the most updated and comprehensive evaluation of the studies. METHODS: Randomized controlled trials (RCTs) were searched from electronic databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang database dating from January 2007 to January 2017. The curative effects of probiotics on the reduction of TC were assessed using mean difference (MD), as well as their 95% confidence interval (CI). RevMan software (version 5.3) was used to carry out this meta-analysis. RESULTS: Thirty-two RCTs including 1971 patients met the inclusion criteria. Results of this analysis showed that compared with the control group serum TC was significantly reduced in probiotics group [MD = -13.27, 95% CI (-16.74 to 9.80), P < .05]. In addition, specific strains also significantly reduced serum TC, L acidophilus and B lactis [MD = -8.30, 95% CI (-10.44, -6.15), P < .05]; VSL#3 [MD = -11.04, 95% CI (-19.61, -2.48), P < .05]; L plantarum t ≤ 6 weeks: [MD = -1.56, 95% CI (-6.97, -3.86), P < .05] or t > 6 weeks: [MD = -22.18, 95% CI (-28.73, -15.63), P < .05]. Subgroup analysis indicated that the difference of baseline TC, probiotics forms and intervention duration might have a significant impact on the results. However, strains and doses of probiotics had no significant influence on curative effects. CONCLUSION: Available evidence indicates that probiotics supplements can significantly reduce serum TC. Furthermore, higher baseline TC, longer intervention time, and probiotics in capsules form might contribute to a better curative effect.

Knockdown of Upregulated Gene 11 (URG11) Inhibits Proliferation, Invasion, and ß-Catenin Expression in Non-Small Cell Lung Cancer Cells.

Upregulated gene 11 (URG11), a new gene upregulated by hepatitis B virus X protein, was found to be involved in the development and progression of several tumors. However, the role of URG11 in human non-small cell lung cancer (NSCLC) has not yet been determined. Therefore, the aim of the present study was to explore the role of URG11 in human NSCLC. Our results found that URG11 was highly expressed in human NSCLC tissues compared with matched normal lung tissues, and higher levels were found in NSCLC cell lines in comparison to the normal lung cell line. Moreover, we also found that knockdown of URG11 significantly inhibited proliferation, migration/invasion of NSCLC cells, as well as suppressed tumor growth in vivo. Furthermore, knockdown of URG11 suppressed the expression of ß-catenin, c-Myc, and cyclin D1 in NSCLC cells. Taken together, the study reported here provided evidence that URG11 downregulation suppresses proliferation, invasion, and ß-catenin expression in NSCLC cells. Thus, URG11 may be a novel potential therapeutic target for NSCLC.

Mesenchymal stem cells from the human umbilical cord ameliorate fulminant hepatic failure and increase survival in mice.

BACKGROUND: Cell therapy has been promising for various diseases. We investigated whether transplantation of human umbilical cord mesenchymal stem cells (hUCMSCs) has any therapeutic effects on D-galactosamine/lipopolysaccharide (GalN/LPS)-induced fulminant hepatic failure in mice. METHODS: hUCMSCs isolated from human umbilical cord were cultured and transplanted via the tail vein into severe combined immune deficiency mice with GalN/LPS-induced fulminant hepatic failure. After transplantation, the localization and differentiation of hUCMSCs in the injured livers were investigated by immunohistochemical and genetic analyses. The recovery of the injured livers was evaluated histologically. The survival rate of experimental animals was analyzed by the Kaplan-Meier method and log-rank test. RESULTS: hUCMSCs expressed high levels of CD29, CD73, CD13, CD105 and CD90, but did not express CD31, CD79b, CD133, CD34, and CD45. Cultured hUCMSCs displayed adipogenic and osteogenic differentiation potential. Hematoxylin and eosin staining revealed that transplantation of hUCMSCs reduced hepatic necrosis and promoted liver regeneration. Transplantation of hUCMSCs prolonged the survival rate of mice with fulminant hepatic failure. Polymerase chain reaction for human alu sequences showed the presence of human cells in mouse livers. Positive staining for human albumin, human alpha-fetoprotein and human cytokeratin 18 suggested the formation of hUCMSCs-derived hepatocyte-like cells in vivo. CONCLUSIONS: hUCMSC was a potential candidate for stem cell based therapies. After transplantation, hUCMSCs partially repaired hepatic damage induced by GalN/LPS in mice. hUCMSCs engrafted into the injured liver and differentiated into hepatocyte-like cells.

All-trans-retinoic acid ameliorates experimental allergic encephalomyelitis by affecting dendritic cell and monocyte development.

Experimental allergic encephalomyelitis (EAE) can be induced in animal models by injecting the MOG35-55 peptide subcutaneously. Dendritic cells (DCs) that are located at the immunization site phagocytose the MOG35-55 peptide. These DCs mature and migrate into the nearest draining lymph nodes (dLNs), then present antigen, resulting in the activation of naive T cells. T helper type 1 (Th1) and Th17 cells are the primary cells involved in EAE progression. All-trans-retinoic acid (AT-RA) has been shown to have beneficial effects on EAE progression; however, whether AT-RA influences DC maturation or mediates other functions is unclear. In the present study, we showed that AT-RA led to the down-regulation of MHC class II, CD80 (B7-1) and CD86 (B7-2) expressed on the surface of DCs that were isolated from dLNs or spleen 3 days post-immunization in an EAE model. Changes to DC function influenced Th1/Th17 subset polarization. Furthermore, the number of CD44(+) monocytes (which might trigger EAE progression) was also significantly decreased in dLNs, spleen, subarachnoid space and the spinal cord parenchyma after AT-RA treatment. These findings are the first to demonstrate that AT-RA impairs the antigen-presenting capacity of DCs, leading to down-regulation of pathogenic Th1 and Th17 inflammatory cell responses and reducing EAE severity.

[Molecular cloning and expression analysis of an Aux/IAA gene (RgIAA1) from Rehmannia glutinosa].

To clone and analyze a member of the Auxin/indole-3-acetic acid (Aux/IAA) gene family, RgIAA1, from Rehmannia glutinosa. The transcriptional EST database of R. glutinosa was used to clone the new Aux/IAA gene by cDNA probe of AtIAA14. Bioinformatics was applied to analyze the sequence characteristics of RgIAA1 protein and construct phylogenetiC trees. Quantitative RT-PCR has been applied to detect the transcription level of RgIAA1 in seven tissues as well as in leaves under three stresses. The results showed that, the cDNA sequence of RgIAA1 contains 903 bp was obtained. The open reading frame (ORF) of RgIAA1 was 681 bp encoding 226 amino acids, which has typical structural domains and characteristic sequence of Aux/IAA family proteins. RgIAA1 showed the highest expression level in unfolded leaf, followed by the stem. And the expression of RglAA1 was quickly decreased with leaf growing up. The transcription level increased under continuous cropping conditions while it reduced both in salinity and waterlogging stresses. RgIAA1, an Aux/IAA gene from R. glutinosa has been obtained for the first time, which can lay the foundation for further studies about its molecular function in development and responses to stress.

[Epstein-Barr virus infection and p16(INK4a) overexpression in gastric adenocarcinoma].

OBJECTIVE: To study Epstein-Barr virus infection and p16 protein abnormal expresson in carcinogenesis and progression of gastric adenocarcinomas (GAC). METHODS: Immunohistochemical staining SP method was used to detect the expression of LMP-1 and p16 in 97 cases of GAC. RESULTS: EBV LMP-1 and p16 protein were detected in 30.9% (30/97) and in 63.91% (62/97) cases of gastric adenocarcinomas respectively. There was no significant difference between EBV-positive and EBV-negative gastric carcinomas in sex, histologic type, depth of tumor invision, lymph node metastasis and clinical stages (P > 0.05); overexpression of p16 was associated with lymph node metastasis and clinical stages; no correlation was found between the expression of EBV LMP-1 and p16 protein. CONCLUSION: 1. EBV play a role in carcinogensis of GAC. 2. P16 gene abnormality is frequently involved in GAC and might be one of the important prognostic factors. 3. EBV infection and p16 alteration are two independent roles in GAC carcinogenesis.