Protein regulation mechanism of cold tolerance in Haemaphysalis longicornis

Ticks are external parasitic arthropods that can transmit a variety of pathogens by sucking blood.Low-temperature tolerance is essential for ticks to survive during the cold winter.Exploring the protein regulation mechanism of low-temperature tolerance of Haemaphysalis longicornis could help to explain how ticks survive in winter.In this study,the quantitative proteomics of several tissues of H.longicornis exposed to low temperature were studied by data independent acquisition technology.Totals of 3699,3422,and 1958 proteins were identified in the salivary gland,midgut,and ovary,respectively.The proteins involved in energy metabolism,cell signal transduction,protein synthesis and repair,and cytoskeleton synthesis changed under low-temperature stress.The comprehensive analysis of the protein regulation of multiple tissues of female ticks exposed to low temperature showed that maintaining cell homeostasis,maintaining cell viability,and enhancing cell tolerance were the most important means for ticks to maintain vital signs under low temperature.The expression of proteins involved in and regulating the above cell activities was the key to the survival of ticks under low temperatures.Through the analysis of a large amount of data,we found that the expression levels of arylamine N-acetyltransferase,inositol polyphosphate multikinase,and dual-specificity phosphatase were up-regulated under low temperature.We speculated that they might have important significance in low-temperature tolerance.Then,we performed RNA interference on the mRNA of these 3 proteins,and the results showed that the ability of female ticks to tolerate low temperatures decreased significantly.

Promotion of structural plasticity in area V2 of visual cortex prevents against object recognition memory deficits in aging and Alzheimer's disease rodents

Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to produce satisfa ctory effects.Therefore,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of ORM.In this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s disease.Furthermore,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDNF).A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s disease.Therefore,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.

Effects of serum containing natural cerebrolysin on glucose-regulated protein 78 and CCAAT enhancer-binding protein homologous protein expression in neuronal PC12 cells following tunicamycin-induced endoplasmic reticulum stress

BACKGROUND： Glucose-regulated protein 78 （GRP78）, a marker of endoplasmic reticulum stress, can prolong cell survival. Alternatively, CCAAT enhancer-binding protein homologous protein （CHOP）, a transcription factor specific for endoplasmic reticulum stress, can cause cell cycle arrest and cell apoptosis. OBJECTIVE： To study the protective effects of serum containing natural cerebrolysin on endoplasmic reticulum stress in tunicamycin-induced neuronal PC12 cells, and analyze the influence on GRP78 and CHOP expressions. DESIGN, TIME AND SETTING： A parallel controlled study was performed at the Institute of Integrated Western and Traditional Chinese Medicine, Shenzhen Hospital, Southern Medical University, between March 2006 and August 2008. MATERIALS： Adult Sprague-Dawley rats were perfused with natural Cerebrolysin aqueous extract （0.185 g/kg/d） to produce serum containing natural Cerebrolysin. Physiological saline was used to produce blank serum. PC12 cell line was provided by Shanghai Institute of Cell Biology, Chinese Academy of Science. Tunicamycin was provided by Sigma （St. Louis, USA）, and natural Cerebrolysin, containing ginseng, rhizoma gastrodiae, and gingko leaf （1：2：2）, by Shengzhen Institute of Integrated Western and Traditional Chinese Medicine. METHODS： PC12 cells were treated with DMEM culture media containing 10% blank serum （normal control group）, tunicamycin （1 μg/mL; model group）, and 5%, 10%, and 15% serum containing natural cerebrolysin and tunicamycin （1 μ g/mL; low-, moderate-, and high-dose serum containing natural cerebrotysin groups）, for 2 hours. MAIN OUTCOME MEASURES： PC12 cells were treated with tunicamycin for 48 hours after which apoptosis was measured using the TUNEL method to calculate apoptotic index. GRP78 expression was detected using immunocytochemistry. After 24 hours of treatment with tunicamycin, GRP78 and CHOP mRNA expressions were measured using RT-PCR. RESULTS： The apoptotic index and CHOP mRNA expression were in the model group and three cerebrolysin groups were significantly increased when compared to the normal control group （P 〈 0.05）. In contrast, GRP78 mRNA and protein expressions were significantly decreased （P 〈 0.05）. CONCLUSION： Serum containing natural cerebrolysin significantly reduced apoptosis in neuronal PC12 cells following tunicamycin-induced endoplasmic reticulum stress. These results may be related to an up-regulation of GRP78 expression and down-regulation of CHOP expression, both of which displayed dose-dependent effects.

Regulation of Hepatitis C Virus Replication and Gene Expression by the MAPK-ERK Pathway

The mitogen activated protein kinases-extracellular signal regulated kinases （MAPK-ERK） pathway is involved in regulation of multiple cellular processes including the cell cycle. In the present study using a Huh7 cell line Conl with an HCV replicon, we have shown that the MAPK-ERK pathway plays a significant role in the modulation of HCV replication and protein expression and might influence IFN-a signalling. Epithelial growth factor （EGF） was able to stimulate ERK activation and decreased HCV RNA load while a MAPK-ERK pathway inhibitor U0126 led to an elevated HCV RNA load and higher NS5A protein amounts in Conl cells. It could be further demonstrated that the inhibition of the MAPK-ERK pathway facilitated the translation directed by the HCV internal ribosome entry site. Consistently, a U0126 treatment enhanced activity of the HCV reporter replicon in transient transfeetion assays. Thus, the MAPK-ERK pathway plays an important role in the regulation of HCV gene expression and replication. In addition, cyclin-dependent kinases （CDKs） downstream of ERK may also be involved in the modulation of HCV replication since roscovitine, an inhibitor of CDKs had a similar effect to that of U0126. Modulation of the cell cycle progression by cell cycle inhibitor or RNAi resulted consistently in changes of HCV RNA levels. Further, the replication of HCV replicon in Conl cells was inhibited by IFN-~z. The inhibitory effect of IFN-CZ could be partly reversed by pre-incubation of Con-1 cells with inhibitors of the MAPK-ERK pathway and CDKs. It could be shown that the MAPK-ERK inhibitors are able to partially modulate the expression of interferon-stimulated genes.

Role of Extracelluar Regulated Protein Kinases in FTY720-induced Apoptosis of Leukemia Cell Lines HL-60 and U937

The effects of a novel immunosuppressive agent FTY720 on proliferation inhibition and apoptosis of acute leukemia cell lines HL 60 and U937, and the role of extracelluar regulated protein kinase (ERK) in the course of proliferation inhibition and apoptosis induced by FTY720 were studied. The proliferation inhibition rate of HL 60 and U937 cells by various concentrations of FTY720 was detected by MTT assay. Cell apoptosis was detected by DNA fragment analysis and flow cytometry. The phosphorylated ERK1/2 protein expression was observed by Western blotting. The change of intracellular distribution of ERK1/2 protein was identified by SP immunohistochemical staining. The results showed that FTY720 could inhibit the growth of HL 60 and U937 cells effectively in a dose dependent manner. After incubation with FTY720 for 24 h, apoptosis was observed in HL 60 and U937 cells. The intracellular expression of phosphorylated ERK1/2 protein was also down regulated and the distribution of ERK1/2 protein in cell nuclear was reduced during FTY720 induced apoptosis. So, that FTY720 inhibited ERK1/2 phosphorylation might mediate the role of FTY720 induced apoptosis and proliferation inhibition of leukemia cells.

The43,000Growth - associated Protein Functions as a Negative Growth Regulator in Glioma.

Previous molecular analyses of human astrocytomas have identified many genetic changes associated with astrocy-toma formation and progression.In an effort to identify novel gene expression changes associated with astrocytomaformation,which might reveal new potential targets for glioma therapeutic drug design,we used the B8-RAS-transgenic mouse astrocytoma model.Using multiplex gene expression profiling,we found that

Specific effects of c-Jun NH2-terminal kinaseinteracting protein 1 in neuronal axons

c-Jun NH2-terminal kinase（JNK）-interacting protein 3 plays an important role in brain-derived neurotrophic factor/tropomyosin-related kinase B（Trk B） anterograde axonal transport. It remains unclear whether JNK-interacting protein 1 mediates similar effects, or whether JNK-interacting protein 1 affects the regulation of Trk B anterograde axonal transport. In this study, we isolated rat embryonic hippocampus and cultured hippocampal neurons in vitro. Coimmunoprecipitation results demonstrated that JNK-interacting protein 1 formed Trk B complexes in vitro and in vivo. Immunocytochemistry results showed that when JNK-interacting protein 1 was highly expressed, the distribution of Trk B gradually increased in axon terminals. However, the distribution of Trk B reduced in axon terminals after knocking out JNK-interacting protein 1. In addition, there were differences in distribution of Trk B after JNK-interacting protein 1 was knocked out compared with not. However, knockout of JNK-interacting protein 1 did not affect the distribution of Trk B in dendrites. These findings confirm that JNK-interacting protein 1 can interact with Trk B in neuronal cells, and can regulate the transport of Trk B in axons, but not in dendrites.

Protein post-translational modifications in auxin signaling

Protein post-translational modifications(PTMs),such as ubiquitination,phosphorylation,and small ubiquitin-like modifier(SUMO)ylation,are crucial for regulating protein stability,activity,subcellular localization,and binding with cofactors.Such modifications remarkably increase the variety and complexity of proteomes,which are essential for regulating numerous cellular and physiological processes.The regulation of auxin signaling is finely tuned in time and space to guide various plant growth and development.Accumulating evidence indicates that PTMs play critical roles in auxin signaling regulations.Thus,a thorough and systematic review of the functions of PTMs in auxin signal transduction will improve our profound comprehension of the regulation mechanism of auxin signaling and auxin-mediated various processes.This review discusses the progress of protein ubiquitination,phosphorylation,histone acetylation and methylation,SUMOylation,and S-nitrosylation in the regulation of auxin signaling.

Molecular cloning of promoter in human fibrinogenlike protein 2 (hfgl2) gene and functional analysis of its sequence

The aim of this study is to investigate the important regulative elements region which plays an important role on the activation of transcription exerted by the 5' noncoding region of hfgl2 gene in response to HBc and HBx. A series of promoter luciferase report plasmids, in which the hfgl2 gene has been deleted of the 5' and retained the common 3', were constructed. All the plasmids constructed were subjected to electrophoretic analysis and DNA sequencing. A eukaryotic construct expressing HBc or HBx, a luciferase reporter construct containing hfgl2 promoter and aβ-galactosidase (β-gal) plasmid were co-transfected into Chinese hamster ovary (CHO) cells and hepG2 cells, respectively. Luciferase report plasmids containing hfgl2 promoter were successfully constructed, and a serial assays of deletion of hfgl2 gene promoter showed that a strong regulatory region from -817 to -467 (relative to the transcription start site) was responsible for transcription and expression regulation of hfgl2 gene. The important regulative elements region in the promoter of hfgl2 gene was in response to HBc and HBx. which contributes to further pursuit of cis-acting elements and transcriptional factors involved in the transcription of hfgl2 gene.

Optimized new Shengmai powder(优化新生脉散方) inhibits myocardial fibrosis in heart failure by regulating the rat sarcoma/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular regulated protein kinases signaling pathway

OBJECTIVE: Exploring the effect of Optimized New Shengmai powder(优化新生脉散方, ONSMP) on myocardial fibrosis in heart failure(HF) based on rat sarcoma(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase kinase(MEK)/extracellular regulated protein kinases(ERK) signaling pathway. METHODS: Randomized 70 Sprague-Dawley rats into sham(n = 10) and operation(n = 60) groups, then established the HF rat by ligating the left anterior descending branch of the coronary artery. We randomly divided the operation group rats into the model, ONSMP [including low(L), medium(M), and high(H) dose], and enalapril groups. After the 4-week drug intervention, echocardiography examines the cardiac function and calculates the ratios of the whole/left heart to the rat's body weight. Finally, we observed the degree of myocardial fibrosis by pathological sections, determined myocardium collagen(COL) Ⅰ and COL Ⅲ content by enzyme-linked immunosorbent assay, detected the m RNA levels of COL Ⅰ, COL Ⅲ, α-smooth muscle actin(α-SMA), and c-Fos proto-oncogene(c-Fos) by universal real-time, and detected the protein expression of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ETS-like-1 transcription factor(p-ELK1), p-c-Fos, α-SMA, COL Ⅰ, and COL Ⅲ by Western blot. RESULTS: ONSMP can effectively improve HF rat's cardiac function, decrease cardiac organ coefficient, COL volume fraction, and COL Ⅰ/Ⅲ content, down-regulate the m RNA of COL Ⅰ/Ⅲ, α-SMA and c-Fos, and the protein of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ELK1, c-Fos, COL Ⅰ/Ⅲ, and α-SMA. CONCLUSIONS: ONSMP can effectively reduce myocardial fibrosis in HF rats, and the mechanism may be related to the inhibition of the RAS/RAF/MEK/ERK signaling pathway.

N2L,a novel lipoic acid-niacin dimer,attenu⁃ates ferroptosis and decreases lipid peroxida⁃tion in HT22 cells

OBJECTIVE N2L is a novel lipoic acid-niacin dimer regulating lipid metabolism with multifunction,including antioxidant effect.We investigated the protective effect of N2L and the underlying mechanisms under the ferroptosis inducer RAS-selective lethality 3(RSL3)treat⁃ment in HT22 cells.METHODS HT22 cells were pretreated with N2L and then were treated with RSL3 to establish a ferroptosis cell model.MTT assay was used to detect the cell survival rate.Free radical probe(dihydroethidium,DHE)and ferrous probe FerroOrange were used to detect the contents of free radicals and ferrous ions in cells.The ultrastructure of mitochondria of treat⁃ed cells was observed by transmission electron microscope.The expression of ferroptosis-relat⁃ed proteins acyl-CoA synthetase long-chain family member 4(ACSL4),glutathione peroxidase 4(GPX4),cyclooxygenase-2(COX-2),ferritin Heavy Chain 1(FTH1),nuclear factor E2-related factor 2/heme oxygenase-1,and phosphoryla⁃tion levels of the c-Jun N-terminal kinase(JNK)/extracellular regulated protein kinases(ERK)pathway were detected by Western blotting.RE⁃SULTS RSL3 decreased the cell viability and induced excessive accumulation of(reactive oxy⁃gen species)ROS in HT22 cells.N2L pretreat⁃ment effectively protected HT22 cells against lipid peroxidation.What′s more,N2L recovered GPX4 protein expression and blocked the increase of COX-2 and ACSL4 expressions.Moreover,N2L also significantly prevented FTH1 from downregulation and maintained iron homeo⁃stasis.Finally,N2L pretreatment could decrease JNK/ERK activation induced by RSL3.CON⁃CLUSION N2L is an excellent ferroptosis inhibi⁃tor,and its anti-ferroptosis mechanism may be related to the reduction of lipid peroxidation and the regulation of iron homeostasis.

SIGNAL MECHANISM OF INHIBITION OF BIFIDOBACTERIA ON GROWTH OF COLON CANCER

Objective: To explore the antitumor mechanisms of bifidobacteria adolescence in vivo. Methods: The content of extracellular signal regulated proteins (ERK)1/2, C-Jun N-terminal kinase (JNK), p38, c-fos and c-jun in nude mouse transplanted large bowel carcinoma was detected by using laser confocal microscopy. The expression of NF-κB was determined by immunohistochemistry. Results: After the nude mouse transplanted tumor was treated with bifidobacteria, the average fluorescent strength of ERK1/2, JNK, c-fos and c-jun was significantly lower than that in tumor control group (P<0.01). The average fluorescent strength of p38 was not obvious difference in the two groups (P>0.05). The positive cell density of NF-κB in large bowel carcinoma transplantation tumors in Bifidobacterium injection group was markedly lower than that in tumor group(P<0.01). Conclusion: bifidobacteria adolescence could markedly decrease the activity of ERK1/2 and JNK, the expression c-fos and c-jun, and the activity of NF-κB.

TRAIL-induced apoptosis of hepatocellular carcinoma cells is augmented by targeted therapies

AIM:To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors,in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand(TRAIL),on overcoming TRAIL resistance in hepatocellular carcinoma(HCC)and to study the efficacy of agonistic TRAIL antibodies,as well as the commitment of antiapoptotic BCL-2 proteins, in TRAIL-induced apoptosis. METHODS:Surface expression of TRAIL receptors (TRAIL-R1-4)and expression levels of the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL were analyzed by flow cytometry and Western blotting,respectively. Knock-down of MCL-1 and BCL-xL was performed by transfecting specific small interfering RNAs.HCC cellswere treated with kinase inhibitors and chemotherapeutic drugs.Apoptosis induction and cell viability were analyzed via flow cytometry and 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS:TRAIL-R1 and-R2 were profoundly expressed on the HCC cell lines Huh7 and Hep-G2. However,treatment of Huh7 and Hep-G2 with TRAIL and agonistic antibodies only induced minor apoptosis rates.Apoptosis resistance towards TRAIL could be considerably reduced by adding the chemotherapeutic drugs 5-fluorouracil and doxorubicin as well as the kinase inhibitors LY294002[inhibition of phosphoinositol- 3-kinase(PI3K)],AG1478(epidermal growth factor receptor kinase),PD98059(MEK1),rapamycin(mam- malian target of rapamycin)and the multi-kinase inhibitor Sorafenib.Furthermore,the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL play a major role in TRAIL resistance:knock-down by RNA interference increased TRAIL-induced apoptosis of HCC cells.Additionally, knock-down of MCL-1 and BCL-xL led to a significant sensitization of HCC cells towards inhibition of both c-Jun N-terminal kinase and PI3K.CONCLUSION:Our data identify the blockage of survival kinases,combination with chemotherapeutic drugs and targeting of antiapoptotic BCL-2 proteins as promising ways to overcome TRAIL resistance in HCC.

Progress in DNA Aptamers as Recognition Components for Protein Functional Regulation

Proteins play a central role in all domains of life,and precise regulation of their activity is essential for understanding the related biological processes and therapeutic functions.Nucleic acid aptamers,the molecular recognition components derived from systematic evolution of ligands by exponential enrichment(SELEX),can specifically identify proteins with antibody-like recognition characteristics and help to regulate their activity.This minireview covers the SELEX-based selection of protein-binding aptamers,membrane protein analytical techniques based on aptamer-mediated target recognition,aptamer-mediated functional regulation of proteins,including membrane receptors and non-membrane proteins(thrombin as a model),as well as the potential challenges and prospects regarding aptamer-mediated protein manipulation,aiming to supply some useful information for researchers in this field.

Sphingosine-1-Phosphate Protects Against the Development of Cardiac Remodeling via Sphingosine Kinase 2 and the S1PR2/ERK Pathway

Objective:Cardiac remodeling is a common pathological change in various cardiovascular diseases and can ultimately result in heart failure.Thus,there is an urgent need for more effective strategies to aid in cardiac protection.Our previous work found that sphingosine-1-phosphate(S1P)could ameliorate cardiac hypertrophy.In this study,we aimed to investigate whether S1P could prevent cardiac fibrosis and the associated mechanisms in cardiac remodeling.Methods:Eight-week-old male C57BL/6 mice were randomly divided into a sham,transverse aortic constriction(TAC)or a TAC+S1P treatment group.Results:We found that S1P treatment improved cardiac function in TAC mice and that the cardiac fibrosis ratio in the TAC+S1P group was significantly lower and was accompanied by a decrease inα-smooth muscle actin(α-SMA)and collagen type I(COL I)expression compared with the TAC group.We also found that one of the key S1P enzymes,sphingosine kinase 2(SphK2),which was mainly distributed in cytoblasts,was downregulated in the cardiac remodeling case and recovered after S1P treatment in vivo and in vitro.In addition,our in vitro results showed that S1P treatment activated extracellular regulated protein kinases(ERK)phosphorylation mainly through the S1P receptor 2(S1PR2)and spurred p-ERK transposition from the cytoplasm to cytoblast in H9c2 cells exposed to phenylephrine.Conclusion:These findings suggest that SphK2 and the S1PR2/ERK pathway may participate in the anti-remodeling effect of S1P on the heart.This work therefore uncovers a novel potential therapy for the prevention of cardiac remodeling.

Effect of Artemisia decoction on liver function and pERK/eIF2a signaling pathway in rats with alcoholic liver fibrosis

Objective: To investigate the effects of Artemisia decoction on liver function and phosphorylation of extracellular regulated protein kinase/eukaryotic translation initiation factor 2α (pERK/eIF2a) signaling pathway in rats with alcoholic liver fibrosis. Methods: A total of 40 healthy Sprague-Dole (SD) rats were randomly divided into 4 groups: the normal group, the sham operation group, the model group and the Artemisia decoction group, with 10 rats in each group. Alcoholic liver fibrosis model was established by "alcohol-corn oil-pyrazole" combined with a 12-week high-fat diet. After successful modeling, the normal group was not treated, and the sham operation group was given saline. The model group and the Artemisia decoction group were given the same amount of wormwood soup at the same time. The serum hydroxyproline (HYP), hyaluronidase (HA), laminin (LN), type IV collagen (CIV), type III procollagen (PIIINP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyltranspeptidase (γ-TG), total bile acid (TBA), total bilirubin (TB), albumin (ALB), total cholesterol (CHOL), triglyceride (TG), glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured after 12 weeks of continuous treatment. The degree of liver fibrosis was observed by hematoxylin-eosin staining (HE). The expression of pERK/eIF2a signaling pathway in liver tissue was detected by enzyme-linked immunosorbent assay (ELISA). Results: Compared with the normal group, the levels of serum HYP, HA, LN, CIV, PIIINP, AST, ALT, γ-GT, ALP, TBL and TB in the sham operation group were not significantly changed (P>0.05), while these indexes in the model group were significantly elevated (P<0.01). After treatment with Artemisia decoction, the levels of serum HYP, HA, LN, CIV, PIIINP, AST, ALT, γ-GT, ALP, TBL and TB were significantly lower than those in the model group (P<0.01). The serum albumin, lipid metabolism and oxidative damage indicators showed that there was no significant change in serum ALB, CHOL, TG, GSH, SOD and MDA levels in the sham operation group compared with the normal group (P>0.01). The levels of GSH and SOD in the model group were significantly decreased (P<0.01), and the levels of CHOL, TG and MDA in the model group were significantly increased (P<0.01). Compared with the model group, the serum ALB, GSH and SOD levels were significantly increased (P<0.01), and CHOL, TG and MDA levels were significantly decreased after giving intervention with Artemisia decoction (P<0.01). The results of HE staining showed that compared with the control group, the morphology of the liver sections of the sham operation group was normal, while the liver sections of the model group showed obvious vacuolization changes. The liver sections of the rats treated with Artemisia decoction were significantly improved. The results of ELISA showed that there was no significant change in the levels of pERK and eIF2a in the liver tissue of the sham operation group compared with the normal group (P>0.05). The levels of pERK and eIF2a in the liver tissue of the model group were significantly increased (P<0.01). After treatment with Artemisia decoction, the levels of pERK and eIF2a in rat liver tissues were significantly lower than those in the model group (P<0.01). Conclusion: Artemisia decoction can effectively block the degree of liver fibrosis in rats with alcoholic liver fibrosis, reduce liver fibrosis index and improve hepatobiliary function. This effect may be related to inhibition of the pERK/eIF2a signaling pathway.

Uncoupling protein and nonalcoholic fatty liver disease

Objective To review the current advances on the role of uncoupling protein （UCP） in the pathogenesis and progress of nonalcoholic fatty liver disease （NAFLD）.Data sources A comprehensive search of the PubMed literature without restriction on the publication date was carried out using keywords such as UCP and NAFLD.Study selection Articles containing information related to NAFLD and UCP were selected and carefully analyzed.Results The typical concepts,up-to-date findings,and existing controversies of UCP2 in NAFLD were summarized.Besides,the effect of a novel subtype of UCP （hepatocellular down regulated mitochondrial carrier protein,HDMCP） in NAFLD was also analyzed.Finally,the concept that any mitochondrial inner membrane carrier protein may have,more or less,the uncoupling ability was reinforced.Conclusions Considering the importance of NAFLD in clinics and UCP in energy metabolism,we believe that this review may raise research enthusiasm on the effect of UCP in NAFLD and provide a novel mechanism and therapeutic target for NAFLD.

Arabidopsis Forkhead-Associated Domain Protein 3 negatively regulates peroxisome division

Peroxisomes are ubiquitous and dynamic eukaryotic organelles capable of altering their abun- dance in response to environmental and developmental cues, yet the regulatory mechanism of plant peroxisome division/proliferation is unclear. To identify transcriptional regulators of the peroxisome division factor gene PEX 11b, we performed a nuclear pull-clown experiment and identified Arabidopsis Forkhead- Associated Domain Protein 3 （FHA3） as a novel protein that binds to the promoter of PEX 11b. Our data supported the conclusion that, in contrast to the previously identified HY5 HOMOLOG （HYH） protein that promotes the transcription of PEX 11b, FHA3 is a negative regulator of PEX 11b expression and peroxisome division.

Autism-related protein MeCP2 regulates FGF13 expression and emotional behaviors

Methyl-CpG binding protein 2 （MeCP2） has a crucial role in transcriptional regulation and neural development （Ausi6 et al., 2014）. Loss of function mutations of MECP2 in human lead to Rett syndrome （RTT）, a severe neurodevelopmental disorders （Amir et al., 1999）, whereas individuals with the chromosomal duplications containing the MECP2 locus showed severe autism-like symptoms （Ramocki et al., 2009）.