Activation of STAT3 stimulates AHSP expression in K562 cells

Studies on the chaperone proteinα-hemoglobin stabilizing protein(AHSP)reveal that abundant AHSP in erythroid cells enhance the cells’tolerance to oxidative stress imposed by excessα-hemoglobin in pathological conditions.However,the potential intracellular modulation of AHSP expression itself in response to oxidative stress is still unknown.The present study examined the effect and molecular mechanism of STAT3,an oxidative regulator,on the expression of AHSP.AHSP expression increased in K562 cells upon cytokine IL-6-induced STAT3 activation and decreased in STAT3 knock-down K562 cells.Regulation of AHSP in oxidative circumstance was then examined inα-globin-overloaded K562 cells,and real-time PCR showed strengthened expression of both AHSP and STAT3.ChIP analysis showed binding of STAT3 to AHSP promoter and binding was significantly augmented with IL6 stimulation and uponα-globin overexpression.Dual luciferase reporter assays of the wildtype and mutated SB3 element,an IL-6RE site,in the AHSP promoter in K562 cells highlighted the direct regulatory effect of STAT3 on AHSP gene.Finally,direct binding of STAT3 to SB3 site of AHSP promoter was confirmed with EMSA assays.Our work reveals an adaptive AHSP regulation mediated by the redox-sensitive STAT3 signaling pathway,and provides clues to the therapeutic strategy for AHSP enhancement.     

Potentialities of induced pluripotent stem (iPS) cells for treatment of diseases

Induced pluripotent stem (iPS) cell research has been growing a new height throughout the world due to its potentialities in medical applications. We can explore several therapeutic applications through the iPS cell research. In this review, we have first discussed the development of iPS cells, reprogramming factors, and effectiveness of iPS cells. Then we have emphasized the potential applications of iPS cells in pharmaceutical and medical sectors, such as, study of cellular mechanisms for spectrum of disease entities, disease-specific iPS cell lines for drugs discovery and development, toxicological studies of drugs development, personalized medicine, and regenerative medicine.     

A strategy for fusion expression and preparation of functional glucagon-like peptide-1 (GLP-1) analogue by introducing an enterokinase cleavage site

KGLP-1, a 31-amino acid glucagon-like peptide-1 (GLP-1) analogue, has a great therapeutic potential for anti-diabetes. In this work, a strategy for expression and purification of functional KGLP-1 peptide has been established. KGLP-1 cDNA was fused with glutathione S-transferase (GST), with an enterokinase cleavage site in the fusion junction. The recombinant fusion protein GST–KGLP-1 was affinity purified via the GST-tag, and then digested with enterokinase. The resulting GST part as well as the enzymes were eliminated by ultra-filtration followed by size exclusion chromatograph. The yield of purified KGLP-1 was approximately 12.1 mg/L, with purity of 96.18 %. The recombinant KGLP-1 was shown to have similar bioactivity as native GLP-1 when evaluated in a Chinese hamster ovary cell line expressing a GLP-1 receptor-egfp reporter gene.     

Nuptial gift chemistry reveals convergent evolution correlated with antagonism in mating systems of harvestmen (Arachnida,Opiliones)

Nuptial gifts are material donations given from male to female before or during copulation and are subject to sexual selection in a wide variety of taxa. The harvestman genus Leiobunum has emerged as a model system for understanding the evolution of reproductive morphology and behavior, as transitions between solicitous and antagonistic modes of courtship have occurred multiple times within the lineage and are correlated with convergence in genital morphology. We analyzed the free amino acid content of nuptial gift secretions from five species of Leiobunum using gas chromatography–mass spectrometry. Multivariate analysis of the free amino acid profiles revealed that, rather than clustering based on phylogenetic relationships, nuptial gift chemical composition was better predicted by genital morphology and behavior, suggesting that convergent evolution has acted on the chemical composition of the nuptial gift. In addition, we found that, species with solicitous courtship produce gifts consisting of a 19% larger proportion of essential amino acids as compared to those with more antagonistic courtship interactions. This work represents the first comparative study of nuptial gift chemistry within a phylogenetic framework in any animal group and as such contributes to our understanding of the evolution of reproductive diversity and the participant role of nuptial gift chemistry in mating system transitions.     

Bioactivities of simplified adociaquinone B and naphthoquinone derivatives against Cdc25B,MKP-1, and MKP-3 phosphatases

Some simplified adociaquinone B analogs and a series of 1,4-naphthoquinone derivatives were synthesized and tested against the three enzymes Cdc25B, MKP-1, and MKP-3. Cdc25B and MKP-1 in particular are enzymes overexpressed in human cancer cells, and they represent potential molecular targets for novel cancer chemotherapeutic treatments. A number of analogs exhibited significant inhibitory activity against these enzymes, and the bioassay data in addition to structure–activity relationships of these compounds will be discussed.     

Activation characteristics of transient receptor potential ankyrin 1 and its role in nociception

Transient receptor potential (TRP) ankyrin 1 (TRPA1) is a Ca(2+)-permeant, nonselective cationic channel. It is predominantly expressed in the C afferent sensory nerve fibers of trigeminal and dorsal root ganglion neurons and is highly coexpressed with the nociceptive ion channel transient receptor potential vanilloid 1 (TRPV1). Several physical and chemical stimuli have been shown to activate the channel. In this study, we have used electrophysiological techniques and behavioral models to characterize the properties of TRPA1. Whole cell TRPA1 currents induced by brief application of lower concentrations of N-methyl maleimide (NMM) or allyl isothiocyanate (AITC) can be reversed readily by washout, whereas continuous application of higher concentrations of NMM or AITC completely desensitized the currents. The deactivation and desensitization kinetics differed between NMM and AITC. TRPA1 current amplitude increased with repeated application of lower concentrations of AITC, whereas saturating concentrations of AITC induced tachyphylaxis, which was more pronounced in the presence of extracellular Ca(2+). The outward rectification exhibited by native TRPA1-mediated whole cell and single-channel currents was minimal as compared with other TRP channels. TRPA1 currents were negatively modulated by protons and polyamines, both of which activate the heat-sensitive channel, TRPV1. Interestingly, neither protein kinase C nor protein kinase A activation sensitized AITC-induced currents, but each profoundly sensitized capsaicin-induced currents. Current-clamp experiments revealed that AITC produced a slow and sustained depolarization as compared with capsaicin. TRPA1 is also expressed at the central terminals of nociceptors at the caudal spinal trigeminal nucleus. Activation of TRPA1 in this area increases the frequency and amplitude of miniature excitatory or inhibitory postsynaptic currents. In behavioral studies, intraplantar and intrathecal administration of AITC induced more pronounced and prolonged changes in nociceptive behavior than those induced by capsaicin. In conclusion, the characteristics of TRPA1 we have delineated suggest that it might play a unique role in nociception.     

High‐fat diet‐induced dysbiosis mediates MCP‐1/CCR2 axis‐dependent M2 macrophage polarization and promotes intestinal adenoma‐adenocarcinoma sequence

High‐fat diet (HFD) is a well‐known risk factor for gut microbiota dysbiosis and colorectal cancer (CRC). However, evidence relating HFD, gut microbiota and carcinogenesis is limited. Our study aimed to demonstrate that HFD‐induced gut dysbiosis promoted intestinal adenoma‐adenocarcinoma sequence. In clinical study, we found that HFD increased the incidence of advanced colorectal neoplasia (AN). The expression of monocyte chemoattractant protein 1 (MCP‐1), CC chemokine receptor 2 (CCR2) and CD163 in CRC patients with HFD was significantly higher than that in CRC patients with normal diet. When it comes to the Apc^min/+ mice, HFD consumption could induce gut dysbiosis and promote intestinal carcinogenesis, accompanying with activation of MCP‐1/CCR2 axis that recruited and polarized M2 tumour‐associated macrophages. Interestingly, transfer of faecal microbiota from HFD‐fed mice to another batch of Apc^min/+ mice in the absence of HFD could also enhance carcinogenesis without significant body weight gain and induced MCP‐1/CCR2 axis activation. HFD‐induced dysbiosis could also be transmitted. Meanwhile, antibiotics cocktail treatment was sufficient to inhibit HFD‐induced carcinogenesis, indicating the vital role of dysbiosis in cancer development. Conclusively, these data indicated that HFD‐induced dysbiosis accelerated intestinal adenoma‐adenocarcinoma sequence through activation of MCP‐1/CCR2 axis, which would provide new insight into better understanding of the mechanisms and prevention for HFD‐related CRC.     

西双版纳热带雨林中两种生态型蕨类植物的光合特性比较研究

通过比较分布于西双版纳热带雨林林下生境中的附生鸟巢蕨（Neottopteris nidus）和地生网脉铁角蕨（Asplenium finlaysonianum）的光合特征和光合诱导特性,来研究不同生态型蕨类植物的光斑利用策略。研究结果表明,2种蕨类植物的最大净光合速率、暗呼吸速率、表观量子效率、光饱和点和光补偿点没有显著差异,但网脉铁角蕨的最大气孔导度远远高于鸟巢蕨,表明后者具有更强的光合水分利用效率。在暗处理3／J＇,时接着光照（光强为20I~mol-m-2,s。‘）30分钟后,网脉铁角蕨的初始气孔导度显著高于鸟巢蕨。连续照射饱和强光后,网脉铁角蕨达到最大净光合速率50％（T50％）和90％的时间（T90%）比鸟巢蕨短：网脉铁角蕨和鸟巢蕨的T50%分别为0．57和5．31分钟,T90％分别为5．85和26．33分钟。诱导过程中,气孔导度对强光的响应明显滞后于净光合速率。鸟巢蕨达到最大气孔导度的时间明显比网脉铁角蕨慢,但在光合诱导消失过程中2种蕨类植物的光合诱导维持能力却没有显著差异。上述结果表明,与大多数地生林下植物（如网脉铁角蕨）相比,附生鸟巢蕨的水分保护比碳获得更重要,但却限制了附生蕨对光斑的利用。     

两种热带木质藤本幼苗形态、生长和光合能力对光强和养分的响应

比较了两种不同攀援习性,卷须缠绕种薄叶羊蹄甲（Bauhinia tenuiflora）和茎缠绕种刺果藤（Byttneria aspera）,木质藤本植物的形态、生长及光合特性对不同光强（4％、35％和全光照）和土壤养分（高和低）的响应。两种藤本植物大部分表型特征主要受光照的影响,而受土壤养分的影响较小。弱光促进地上部分生长,弱光下两种植物均具有较大的比叶面积（specific leaf area,SLA）、茎生物量比（stem mass ratio,SMR）和平均叶面积比（mean leaf area ratio,LARm）。高光强下,两种植物的总生物量和投入到地下部分的比重增加,具有更大的根生物量比（root mass ratio,RMR）、更多的分枝数、更高的光合能力（maximum photosynthetic rate,Pmax）和净同化速率（net assimilation rate,NAR）,综合表现为相对生长速率（relative growth rate,RGR）增加。两种藤本植物的Pmax与叶片含氮量的相关性均未达显著水平,但刺果藤的Pmax与SU志间呈显著的正相关,而薄叶羊蹄甲的Pmax与SLA之间相关性不显著。在相同光照强度和土壤养分条件下,卷须缠绕种薄叶羊蹄甲的RGR显著高于茎缠绕种刺果藤。薄叶羊蹄甲的RGR与NAR呈显著正相关,其RGR与SLA、平均叶面积比（EARm）及Pmax之间相关性不显著。刺果藤的RGR与NAR呈显著的正相关,而与SLA存在显著的负相关。上述结果表明,与土壤养分相比,光照强度可能是决定木质藤本分布更为重要的生态因子。卷须缠绕种薄叶羊蹄甲由于具有特化的攀援器官,在形态上和生理上具有更大的可塑性,这使得卷须缠绕种木质藤本在与其它植物的竞争中更具优势。