拟南芥RNA 加工因子的开花调控机制

开花调控是植物生长发育中很重要的过程。拟南芥分子遗传学分析表明，MADS-box 转录因
子FLC、RNA 结合蛋白（FCA、FPA 和FLK）和mRNA 3′ 端加工因子（FY）都参与了这一过程。开花因
子通过抑制FLC 表达来促使植物开花；RNA 结合蛋白通过转录后调控来调节FLC 的表达以调控拟南芥开
花。此外，microRNAs 也参与这一过程。本文通过综述上述几个相关因子的调控过程，来阐述RNA 加工
因子参与的拟南芥开花调控机理。     

Progress in roles of MNX1 antisense RNA 1 in malignant tumor

MNX1 antisense RNA 1 （MNX1-AS1） is a newly discovered long non-coding RNA （lncRNA）， which is highly dysregulated in various carcinomas and its expression level is closely related to the overall survival and prognosis of patients. MNX1-AS1 regulates the occurrence and development of carcinomas by endogenous competitive adsorption of miRNA， regulating cell cycle， inducing epithelial mesenchymal transformation and activating multiple signaling pathways. The in-depth study of the carcinogenesis of MNX1-AS1 is useful for the early diagnosis， targeted therapy and prognostic assessment of relevant carcinomas. This article reviews the roles of MNX1-AS1 in malignant tumor.     

Advances in research on mechanism of CCN proteins in prevention and treatment of obesity and non-alcoholic fatty liver

CCN protein family plays a role in regulating the formation and remodeling of extracellular matrix， inflammation regulation， injury repair and so on， which is closely related to the occurrence and development of metabolic diseases. This review focuses on the mechanism of CCN proteins in obesity and non-alcoholic fatty liver. The roles of CCN proteins in the adipocyte activation， the fibrosis and inflammatory response in non-alcoholic fatty liver， and the injury repair against non-alcoholic fatty liver and its complications are introduced， providing new ideas for the study of CCN proteins in metabolic diseases such as obesity and non-alcoholic fatty liver.     

BrVIN3.1 互作蛋白BrZAT12 在大白菜春化途径中行使功能初探

BrVIN3.1 在春化过程中通过调控BrFLC1 的表观修饰状态，进而调控其表达控制大白菜花期。本试验以BrVIN3.1 （Bra020445）为诱饵，进行酵母cDNA 文库筛选，从中筛选到它的互作蛋白BrZAT12（Bra006691）；进一步进行酵母双 杂一对一验证，证明BrZAT12 能够与BrVIN3.1 互作。采用低温处理不同花期的大白菜材料，进行表达模式分析，发现 BrZAT12 的表达模式在抽薹性状不同的大白菜材料中存在差异，在易抽薹材料中的表达量明显高于耐抽薹材料，且在耐抽薹 材料中变化幅度较小，同时BrZAT12 的表达模式与BrVIN3.1 相关。推测BrZAT12 可能在大白菜春化调控的开花途径中行使 功能。     

Interleukin-1β inhibits AKT to down-regulate eNOS Ser1177 phosphorylation in human umbilical vein endothelial cells

AIM To investigate whether interleukin-1β （IL-1β） regulates endothelial nitric oxide synthase （eNOS） phosphorylation at Ser1177 site in human umbilical vein endothelial cells （HUVECs）， and to explore its possible mechanism. METHODS The HUVECs were randomly divided into normal control group， tumor necrosis factor-α （TNF-α） group， IL-1β group， IL-6 group， SC79 ［protein kinase B （PKB/AKT） specific agonist］ group and SC79+IL-1β group. Western blot was used to determine the protein levels of eNOS， p-eNOS-Ser1177， AKT and p-AKT-Ser473 in the HUVECs. Chemical colorimetry was used to detect the nitric oxide （NO） content in the culture medium of HUVECs. RESULTS No statistically significant difference of p-eNOS-Ser1177 level in HUVECs treated with TNF-α and IL-6 was observed as compared with normal control group （P>0.05）， while the protein level of p-eNOS-Ser1177 in the HUVECs and the content of NO in the culture medium of HUVECs decreased significantly in IL-1β group （P<0.05）， and the protein level of p-AKT-Ser473 in the HUVECs was decreased as compared with normal control group （P<0.05）. The AKT agonist SC79 blocked the down-regulation effect of IL-1β on p-eNOS-Ser1177 level in the HUVECs and NO content in the culture medium of HUVECs （P<0.05）. CONCLUSION IL-1β down-regulates the protein level of p-eNOS-Ser1177 in HUVECs and affects the activity of eNOS， which may be involved in AKT/eNOS signaling pathway.     

基于家族基因分析的甘蓝MLPK互作PUB蛋白的筛选

MLPK(M–位点受体激酶)是芸薹属自交不亲和正向调控关键元件,其参与自交不亲和信号传导的分子机制尚不明确,同时自交不亲和下游信号元件也有待于进一步分离。为了探索分离MLPK互作蛋白的思路和方法,构建了不含核定位信号的MLPK短截蛋白(MLPK-T),并利用酵母双杂交检测到MLPK与臂重复蛋白1(ARC1)作用,通过全基因组鉴定分别获得了96个甘蓝、101个白菜、70个琴叶拟南芥和62个拟南芥PUB蛋白,其中含有臂重复序列的PUB蛋白共为127个。通过系统进化分析,筛选到8个含臂重复序列的甘蓝BoPUB蛋白,其8个基因全部在柱头内表达,且成功利用酵母双杂交检测到MLPK与3个含臂重复序列的BoPUB蛋白Bol008579、Bol016165和Bol023511相互作用。     

Signaling transduction of noxious visceral stimuli in postsynaptic dorsal column neurons in spinal cord

The spinal postsynaptic dorsal column pathway plays a critical role in the visceral pain transmission in spinal cord. The noxious visceral stimuli might induce complex receptor expression and intracellular signaling transductions in postsynaptic dorsal column neurons. It has been demonstrated that neurokinin-1(NK-1) receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), and intracellular protein kinase C (PKC), protein kinase A (PKA), mitogen-activated protein kinases (MAPKs) and cAMP response element-binding (CREB) protein are involved in the signaling transduction of visceral stimuli. All these processes contribute to the sensitization of postsynaptic dorsal column neurons and enhance the spinal transmission of visceral pain, indicating a potential and promising way of visceral pain therapy to inhibit the sensitization of postsynaptic dorsal column neurons.     

Effect of protease inhibitor bortezomib on treatment of rheumatoid arthritis by affecting IL-33/ST2 signaling pathway

AIM To investigate the effect of bortezomib， a protease inhibitor， on the treatment of rheumatoid arthritis （RA） and it mechanism， based on interleukin-33 （IL-33）/suppression of tumorigenicity 2 （ST2） signaling pathway. METHODS A total of 40 Wistar rats were randomly divided into 4 groups： control group， model group， and low- and high-dose bortezomib groups， with 10 rats in each group. In addition to control group， the rats in other groups were used to construct RA model. Bortezomib was given intraperitoneally at 0.2 mg/kg and 0.5 mg/kg in low- and high-dose bortezomib groups， respectively， while the rats in control group and model group were injected with the same amount of saline， once a day for 21 d. The general situation of the rats in each group was observed， the swelling degree of the foot was calculated， and the inflammation score was evaluated. HE staining was used to observe the pathological changes of ankle joint. The automatic biochemical analyzer was used to detect blood hemoglobin content， the total number of platelets （PLT）， serum creatinine （SCr） level and blood urea nitrogen （BUN） level. The serum levels of IL-6， tumor necrosis factor-α （TNF-α）， IL-33 and ST2 were measured by ELISA. The protein expression of IL-33 and ST2 in ankle tissues of each group was determined by Western blot. RESULTS On the 7th， 14th and 21th days after modeling， compared with control group， the degree of paw swelling in model group was significantly increased （P<0.05）. Compared with model group， the swelling degree of paw in low- and high-dose groups was decreased （P<0.05）. At the end of administration， compared with control group， the synovial cells in model group were increased and in disorder， with a lot of inflammatory exudates in the articular cavity， and the inflammatory score， the levels of PLT， SCr and BUN， the serum levels of IL-6， TNF-α， IL-33 and ST2， and the protein expression of IL-33 and ST2 in ankle tissues were significantly increased （P<0.05）. Compared with model group， the inflammatory exudates in the articular cavity of the rats in low- and high-dose bortezomib groups were decreased， and the inflammatory score， the levels of PLT， SCr and BUN， the serum levels of IL-6， TNF-α， IL-33 and ST2， and the protein expression of IL-33 and ST2 in ankle tissues were decreased （P<0.05）. CONCLUSION Bortezomib may reduce the inflammation and swelling of the joints in RA rats by regulating the IL-33/ST2 signaling pathway.     

Signaling pathways involved in mediating mitochondrial damage in diabetic kidney disease

Diabetic kidney disease （DKD） is one of the most common and serious chronic complications of diabetes and has gradually become the main cause of end-stage renal disease （ESRD）. As the center of energy and metabolism in cells， mitochondria have become the focus of the research on the pathogenesis of DKD in recent years. Current studies find that damage to mitochondria， such as DNA mutations， structural damage， oxidative stress imbalance， etc， leads to apoptosis of kidney cells， thus causing the loss of kidney function. In the process of mitochondrial damage， a series of important signaling pathways are involved， and exploring these signaling pathways would help us better understand the pathogenesis of DKD and find new therapeutic targets. In this article， the important signaling pathways associated with mitochondrial damage are reviewed.     

Advance in biological properties of IL-38 and its role in pulmonary diseases

Interleukin-38 （IL-38） is the most recently discovered cytokine of the IL-1 family and is an IL-36 receptor inhibitor. IL-38 is mainly expressed in human immune organs and associated with a variety of diseases. In the process of apoptosis and necrosis caused by injury or inflammation， researchers have studied quiet a lot about the kinase， cleavage sites， activity regulatory mechanism， signal transduction ligand， transduction mode and potential receptors of IL-38， but many mechanisms are still unknown. This article reviews the role of IL-38 in the pathogenesis and progression of lung tumors， asthma and interstitial lung disease. We also discussed the role of IL-38 in the treatment of these diseases， the possible relationship between IL-38 and tuberculosis， and the direction of future studies on the mechanism of IL-38 action.     

Effect of chronic atrial fibrillation on Ca2+/calmodulin dependent protein kinase Ⅱ expression in human atrial myocytes

AIM: To investigate the effect of chronic atrial fibrillation (AF) on free calcium concentration and expression of Ca2+/calmodulin dependent protein kinase Ⅱ (CaMKⅡ) in human atrial myocytes. METHODS: The intracellular free calcium concentration in acute isolated atrial myocytes and the expression of CaMKⅡ in atrial tissue of rheumatic heart disease patients with atrial fibrillation (AF) and with normal sinus rhythm were measured by laser scanning cofocal microscopy technique and Western blotting, respectively. RESULTS: The intracellular Ca2+ concentration in patients with atrial fibrillation was significantly higher than that in patients with normal sinus rhythm ［(276.38±38.12） nmol/L vs （122.28±45.63) nmol/L, P<0.05］. Western blotting analysis of atrial samples showed that CaMKⅡ expression was enhanced during chronic atrial fibrillation (10.14±0.31 vs 6.86±0.89，P<0.05). CONCLUSION: Chronic AF leads to intracellular calcium overload in human atrial myocytes. Ca2+/calmodulin dependent protein kinase signaling cascades may play an important role in maintenance of chronic AF.     

PPARs and TLR-NF-κB signaling pathway

Peroxisome proliferator-activated receptors(PPARs) influence Toll-like receptors(TLRs)-nuclear receptor-κB(NF-κB) signaling pathway through diverse mechanisms to negatively regulate TLR-NF-κB signaling-mediated inflammation and immune responses under para-inflammation condition. However, in pathological states, the balance between inhibition and promotion of inflammation, which is regulated by PPARs and TLR-NF-κB signaling pathway, respectively, has been broken down, resulting in inflammatory cascade and eventually causing chronic non-infectious inflammatory diseases, such as atherosclerosis, ulcerative colitis and rheumatoid arthritis. This review mainly focuses on the interaction between PPARs and TLR-NF-κB signaling pathway either in para-inflammatory status or pathological state, which highlights the importance of PPARs in the process of inflammation and immune responses and provides new interfering targets for the treatment of the diseases like coronary atherosclerotic heart disease.     

苹果糖转运蛋白基因MdSWEET1在番茄中异源表达提高其耐盐性

克隆得到苹果糖转运蛋白SWEET(sugars will eventually be exported transporters)基因MdSWEET1(MDP0000237435),组织表达分析发现该基因主要在苹果的茎和花中表达,相对定量分析发现其对NaCl、PEG、H_2O_2和ABA等均有响应。在番茄中异位表达MdSWEET1可提高植株耐盐性,并且可溶性糖含量,特别是蔗糖和果糖含量提高。     

Dihydroartemisinin enhances radiotherapy efficiency in H22 cell tumor-bearing mice by regulating PI3K/AKT signaling pathway

AIM To study the effect of dihydroartemisinin （DHA） on the radiotherapy efficiency in hepatocellular carcinoma H22 cell tumor-bearing mice and the role of phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT） signaling pathway in this process. METHODS A model of H22 cell tumor-bearing mice was established. The mice was divided into model group， single radiotherapy group， 5-fluorouracil （5-FU） group， and low-， medium- and high-dose DHA groups. The body weight and tumor volume in each group were measured every other day. At the end of administration， blood was collected from the tail of the mice and the animals were killed by neck removal immediately. The synergistic effect of DHA on radiotherapy was determined， and tumor growth inhibitory rate was calculated. The degree of lymphocyte transformation and natural killer （NK） cell activity were measured by MTT， the serum levels of interleukin-2 （IL-2） and IL-4 were measured by ELISA， and the protein levels of PI3K， AKT and p-AKT were determined by Western blot. RESULTS The H22 cell tumor-bearing mouse model was successfully constructed. Compared with model group， the TGT₃ （tumor growth time to reach 3 times of volume） of single radiotherapy group was remarkably increased （P<0.05）， while tumor weight， lymphocyte transformation degree， NK cell activity， IL-2 and IL-4 levels， PI3K protein level and AKT phosphorylation level were remarkably decreased （P<0.05）. Compared with single radiotherapy group， TGT₃， EF （enhancement factor）， tumor inhibitory rate， lymphocyte transformation degree， NK cell activity， IL-2 level and IL-4 level were increased with the increase in DHA dose （P<0.05）， and the PI3K protein level and AKT phosphorylation level were decreased （P<0.05）. CONCLUSION DHA may enhance the immunity of tumor-bearing mice by inhibiting the activity of PI3K/AKT signaling pathway， thereby enhancing the efficacy of radiotherapy.     

Progress in ClC-3 chloride channel phosphorylation and functions

ClC-3 channel is one of voltage-gated chloride channels for chloride ion transmembrane, and participates in a variety of physiological and pathological processes, such as cell volume regulation, proliferation, migration, apoptosis, organic release and acidification of synaptic vesicle. The ClC-3 channel is controlled by many factors, including phosphorylation and dephosphorylation, to regulate the opening and closing. PKA(protein kinase A), PKB, PKC and calcium calmodulin kinaseⅡ are the key kinases in cell signal transduction pathway, which take part in the processes of ClC-3 channel phosphorylation and regulate their functions. The study of ClC-3 phosphorylation and functions are helpful to understand the importance of ClC-3 in physiological and pathological processes and are premise to exploit the channel drugs for clinical therapy.     

Role of ERK on proliferation of airway smooth muscle cells in chronic asthmatic rats

AIM: To investigate the roles of extracellular signal-regulated kinase(ERK) signaling pathway on regulating proliferation of airway smooth muscle by observing the expression of ERK in airway smooth muscle(ASM) in chronic asthmatic rats.METHODS: Airway remodeling was detected in chronic asthmatic rats by using image analysis system. The expressions of ERK and proliferating cell nuclear antigen(PCNA) in lung tissue from chronic asthmatic rats were observed by immuocytochemistry staining. The expressions of ERK1/2, p ERK1/2 and PCNA were detected in airway smooth muscle (ASM) by immunofluorescence double staining with confocal microscopy, and the expressions of protein or mRNA of ERK and PCNA in ASM were also detected by immunoblotting and hybridization in situ,respectively.RESULTS: The thickening of smooth muscle and structural remodeling in airway were observed in chronic asthmatic rats by image analysis. The enhanced expressions of ERK and PCNA appeared obviously increased in same lung tissue and the expressions of protein or mRNA of ERK and PCNA were significantly increased in ASM.CONCLUSION: ERK signal pathway might be an important pathway on regulating cell proliferation of ASM resulting in asthmatic airway remodeling.     

Effect of BNP- mediated cAMP-PKA signaling pathway on bFGF expression in rats with spleen-qi deficiency syndrome

AIM: To explore the changes and the mechanism of heart functions in the rats with spleen-qi deficiency syndrome. METHODS: The rats were randomly divided into blank control group and spleen-qi deficiency model group. The changes of cardiac functions in the rats were determined by ultrasonic imaging with a high-resolution in vivo imaging system. HE staining was used to observe the pathological changes. The protein expression of brain natriuretic peptide (BNP) in the myocardium was assessed by Western blotting. The contents of BNP and cAMP in the serum and myocardium were measured by ELISA. The mRNA expression of basic fibroblast growth factor (bFGF) and protein kinase A (PKA) was detected by real-time PCR. RESULTS: Compared with blank control group, the myocardial cells in the model group had different degrees of necrosis and degeneration. Stroke volume and ejection fraction were decreased. The contents of cAMP and BNP in the serum and myocardium were increased in model group. The protein expression of BNP and the mRNA expression of bFGF and PKA were also increased.CONCLUSION: Spleen-qi deficiency syndrome causes heart function decline in rats. The expression of BNP, cAMP, PKA and bFGF is all increased.     

PPARγ affects epithelial-mesenchymal transition in renal tubular epithelial cells under high glucose by regulating AKT/FAK signaling pathway through PTEN

AIM To investigate the role of peroxisome proliferator-activited receptor γ （PPARγ） in the regulation of PTEN/AKT/FAK signaling pathway and epithelial-mesenchymal transition （EMT） in renal tubular epithelial cells grown in high-glucose environment. METHODS Renal tubular epithelial cells （NRK52E cells） cultured in high glucose were used as an in vitro model system. PPARγ was over-expressed or knocked down in these cells， and its effect on PTEN expression was determined by RT-qPCR， immunofluorescence and Western blot. The changes of EMT-related proteins were also measured. The PPARγ inhibitor GW9662 and the PPARγ agonist rosiglitazone were used along with PTEN over-expression or knockdown to determine whether the effects of PPARγ were mediated through PTEN. RESULTS PPARγ over-expression resulted in the increased expression of PTEN at mRNA and protein levels， the up-regulation of E-cadherin， and the down-regulation of vimentin and α-SMA. Knockdown of PPARγ expression reduced the mRNA and protein levels of PTEN， down-regulated E-cadherin， and up-regulated vimentin and α-SMA （P<0.05）. Treatment of the NRK-52E cells with GW9662 decreased PTEN expression and increased the protein levels of p-AKT （Thr308）， FAK and p-FAK （Tyr397）. These effects were rescued by PTEN over-expression. Treatment of the NRK-52E cells with rosiglitazone increased PTEN expression and decreased the protein levels of p-AKT （Thr308）， FAK and p-FAK （Tyr397）. These effects were rescued by PTEN knockdown. These changes were all statistically significant （P<0.05）. CONCLUSION PPARγ regulates the mRNA and protein expression of PTEN in renal tubular epithelial NRK52E cells， and affects EMT in renal tubular epithelial cells. The regulation of AKT/FAK signaling pathway by PPARγ is primarily mediated by PTEN.     

Phosphodiesterase 4 inhibitor rolipram prevents depression- and anxiety-like behaviors in rats exposed to chronic restraint stress

AIM: To discuss the impact of phosphodiesterase 4 (PDE4) inhibitor rolipram on chronic restraint stress-induced depression- and anxiety-like behaviors in rats. METHODS: (1)Forty SD rats were randomly divided into 4 weight-matched groups: unstressed animals injected with vehicle of lithium chloride (LiCl) and rolipram, restraint-stressed animals injected daily with vehicle prior to stress, restraint stress plus 100 mg/kg LiCl group and restraint stress plus 1 mg/kg rolipram group. The open field test was conducted 24 h before the first stress and drug administration,and then the rats received drugs daily 1 h prior to restraint stress (6 h/d) for 25 d. Daily body weight recording, forced swimming test, elevated plus-maze and open field test were conducted to determine the changes of depression- and anxiety-like behaviors. The expression of phosphorylated cAMP response element-binding protein (p-CREB), brain-derived Reurotrophic factor (BDNF), p-Ser21-glycogen synthase kinase (GSK) 3α, p-Ser9-GSK3β, p-Tyr279-GSK3α, p-Tyr216-GSK3β, total GSK3α and total GSK3β was measured by Western blotting. (2)Thirty SD rats were randomly divided into 6 groups and the cannula was surgically placed above the CA1 region in the hippocampus. Seven days after the surgery, the restraint stress was conducted for 21 d after microinjection of protein kinase A (PKA) antagonist H89 and intraperitoneal injection of LiCl and rolipram everyday. The expression of PDE4D, PKA, p-CREB and p-Ser9-GSK3β was measured by Western blotting. RESULTS: (1)No difference of the locomotor activity among all groups before stress was observed. After repeated stress, the body weight,and the crossing, rearing and grooming in open field test were lower than those in control group, and LiCl and rolipram reversed these effects significantly. In addition, in comparison with control group, the immobility in forced swimming test was increased, the climbing in forced swimmming test and the open-arm exploration in elevated plus-maze were decreased and the expression of p-CREB, BDNF, p-Ser21-GSK3α and p-Ser9-GSK3β was down-regulated. Stress induced depression- and anxiety-like behaviors, and rolipram reversed these changes. The LiCl showed similar effects as rolipram except for the expression of p-CREB and BDNF. No significant difference of the expression of p-Tyr279-GSK3α, p-Tyr216-GSK3β, total GSK3α and total GSK3β among all groups was found. (2)The expression of PDE4D was increased, the expression of PKA, p-CREB and p-Ser9-GSK3β was decreased in the hippocampus induce by restraint stress. However, the effect of rolipram on the expression of PKA, p-CREB and p-Ser9-GSK3β was blocked by PKA inhibitor H89. CONCLUSION: Rolipram significantly reduces the depression- and anxiety-like behaviors, possibly through CREB/BDNF signaling and inhibitory serine-phosphorylation of GSK3-mediated signaling. Importantly, the CREB/BDNF signaling also plays a key role in the down-regulation of serine-phosphorylation of GSK3.     

Effect of Shaofu-Zhuyu decoction on MAPK/ERK signaling pathway in rats with endometriosis

AIM: To observe the effects of Shaofu-Zhuyu decoction (SFZY) on mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway in the rats with endometriosis (EM), and to explore the mechanism of SFZY for treatment of EM.METHODS: Healthy female SD rats were used to establish the EM model. The rats were randomly divided into blank control group, model group, positive control group, and low dose, middle dose and high dose of SFZY groups. The pathological changes of the endometriotic tissue were observed by HE staining. The levels of tumor necrosis factor-α (TNF-α), interleukin-6(IL-6) and IL-8 in the uterine tissue were detected by ELISA. The mRNA expression of ERK, vascular endothelial growh factor (VEGF) and matrix metalloprotein-9 (MMP-9) was detected by RT-qPCR. The protein expression of nuclear factor-κB (NF-κB), MAPK and MAPK-ERK kinase (MEK) was determined by Western blot.RESULTS: Compared with model group, the levels of TNF-α, IL-6 and IL-8 in the uterine tissue of the rats in middle dose and high dose of SFZY groups were significantly decreased (P<0.05), the mRNA expression of ERK, VEGF and MMP-9 was significantly reduced, and the protein expression of NF-κB, MEK and MAPK was decreased significantly in the rat endometriotic tissues (P<0.05).CONCLUSION: SFZY may play a key role in the treatment of EM by regulating MAPK/ERK signaling pathway.