Prospects and potentials of underutilized leafy Amaranths as vegetable use for health-promotion.

Climate change causes environmental variation worldwide, which is one of the most serious threats to global food security. In addition, more than 2 billion people in the world are reported to suffer from serious malnutrition, referred to as 'hidden hunger.' Dependence on only a few crops could lead to the loss of genetic diversity and high fragility of crop breeding in systems adapting to global scale climate change. The exploitation of underutilized species and genetic resources, referred to as orphan crops, could be a useful approach for resolving the issue of adaptability to environmental alteration, biodiversity preservation, and improvement of nutrient quality and quantity to ensure food security. Moreover, the use of these alternative crops will help to increase the human health benefits and the income of farmers in developing countries. In this review, we highlight the potential of orphan crops, especially amaranths, for use as vegetables and health-promoting nutritional components. This review highlights promising diversified sources of amaranth germplasms, their tolerance to abiotic stresses, and their nutritional, phytochemical, and antioxidant values for vegetable purposes. Betalains (betacyanins and betaxanthins), unique antioxidant components in amaranth vegetables, are also highlighted regarding their chemodiversity across amaranth germplasms and their stability and degradation. In addition, we discuss the physiological functions, antioxidant, antilipidemic, anticancer, and antimicrobial activities, as well as the biosynthesis pathway, molecular, biochemical, genetics, and genomic mechanisms of betalains in detail.

SIGLEC-3 (CD33) serves as an immune checkpoint receptor for HBV infection.

Chronic hepatitis B (CHB) infection is rarely eradicated by current antiviral nucleos(t)ide analogues. We found that α2,6-biantennary sialoglycans of HBV surface antigen (HBsAg) bound human SIGLEC-3 (CD33) by IP and ELISA, and the binding affinity between SIGLEC-3 and α2,6-biantennary sialoglycans was determined by biolayer interferometry (equilibrium dissociation constant [KD]: 1.95 × 10-10 ± 0.21 × 10-10 M). Moreover, HBV activated SIGLEC-3 on myeloid cells and induced immunosuppression by stimulating immunoreceptor tyrosine-based inhibitory motif phosphorylation and SHP-1/-2 recruitment via α2,6-biantennary sialoglycans on HBsAg. An antagonistic anti-SIGLEC-3 mAb reversed this effect and enhanced cytokine production in response to TLR-7 agonist GS-9620 in PBMCs from CHB patients. Moreover, anti-SIGLEC-3 mAb alone was able to upregulate the expression of molecules involved in antigen presentation, such as CD80, CD86, CD40, MHC-I, MHC-II, and PD-L1 in CD14+ cells. Furthermore, SIGLEC-3 SNP rs12459419 C, which expressed a higher amount of SIGLEC-3, was associated with increased risk of hepatocellular carcinoma (HCC) in CHB patients (HR: 1.256, 95% CI: 1.027-1.535, P = 0.0266). Thus, blockade of SIGLEC-3 is a promising strategy to reactivate host immunity to HBV and lower the incidence of HCC in the CHB patient population.

Somatic mutation distributions in cancer genomes vary with three-dimensional chromatin structure.

Somatic mutations in driver genes may ultimately lead to the development of cancer. Understanding how somatic mutations accumulate in cancer genomes and the underlying factors that generate somatic mutations is therefore crucial for developing novel therapeutic strategies. To understand the interplay between spatial genome organization and specific mutational processes, we studied 3,000 tumor-normal-pair whole-genome datasets from 42 different human cancer types. Our analyses reveal that the change in somatic mutational load in cancer genomes is co-localized with topologically-associating-domain boundaries. Domain boundaries constitute a better proxy to track mutational load change than replication timing measurements. We show that different mutational processes lead to distinct somatic mutation distributions where certain processes generate mutations in active domains, and others generate mutations in inactive domains. Overall, the interplay between three-dimensional genome organization and active mutational processes has a substantial influence on the large-scale mutation-rate variations observed in human cancers.

[Serumimmunological study of moxibustion on helicobacter pylori gastritis in rats].

OBJECTIVE: To explore the immune mechanism of moxibustion on protecting gastric mucosa injury. METHODS: Forty healthy SD rats were randomly divided into four groups: a blank group, a model group, a moxibustion acupoint group and a moxibustion non-acupoint group, 10 rats in each one. Eight days before model establishment, moxibustion at "Zusanli" (ST 36), "Zhongwan" (CV 12), "Guanyuan" (CV 4), "Pishu" (BL 20) and "Weishu" (BL 21) was applied in the moxibustion acupoint group while these acupoints' controlled points were selected in the moxibustion non-acupoint group, and no treatment was given in the model group, once a day in three groups for continuous 16 days. The helicobacter pylori (Hp) model was established by intragastric administration of Hp. HE staining microscopic examination was used to observe inflammation severity in gastric mucosa, and enzyme-linked immunosorbent assay (ELISA) was adapted to measure content of heat shock protein (HSP) 72, TNF-alpha and IL-1beta, and real-time quantitative PCR was used to measure the expression of TLR2 mRNA, TLR4 mRNA, CD14 mRNA and MyD88 mRNA in peripheral blood mononuclear cells, and western blot method was used to measure content of NFkappaB and IkappaBalpha in peripheral blood mononuclear cells. RESULTS: Compared with the blank group, the expression of HP could be seen in the smear of gastric mucosa by Gram's staining in the model group; the inflammation severity score was obviously increased as well as content of serum HSP 72 and TNF-alpha and IL-1beta in gastric tissue; and expression of TLR2, 4 mRNA, CD14 mRNA, MyD88 mRNA, NFkappaB was increased (P < 0.01), but the expression of IkappaBalpha was reduced (P < 0.05). After the moxibustion, the inflammation severity score was reduced in the moxibustion acupoint group, and the content of serum HSP 72 was increased, and the expression of TNF-alpha and IL-1beta in gastric tissue and expression of TLR2 mRNA, TLR4 mRNA, CD14 mRNA, MyD88 mRNA and NFkappaB were reduced (P < 0.01), but the expression of IkappaBalpha was increased (P < 0.05). The differences between the moxibustion non-acupoint group and the model group were not significant (P > 0.05). CONCLUSION: The pretreatment of moxibustion at acupoints could induce the over expression of serum HSP 72. By combining TLR 2 and 4 receptors to trigger receptor signal transduction pathways, the releases of downstream signal substances are regulated; as a result, the releases of related immune substances are regulated to relieve the gastric mucosa injury of rats with HP gastritis.

[Effect of moxibustion on motility, absorption and content of ATP in small intestine of spleen-deficiency rats].

OBJECTIVE: To explore the mechanism of reinforcing function of moxibustion to spleen-stomach. METHODS: Forty healthy Sprague Dawley rats were randomly divided into 4 groups: group A (blank group), group B (model group), group C (moxibustion group) and group D (herbs group). The rat model of spleen-deficiency was established by intragastric administration with 200% Dahuang (Rhubarb) infusion. The rats in group A and B, and D served as the blank control, model, and Sijunzi decoction group respectively, while those in group C received moxibustion at "Zusanli" (ST 36), "Zhongwan" (CV 12), "Guanyuan" (CV 4), "Pishu" (BL 20) and "Weishu" (BL 21), etc. The common symptoms and intestinal propulsive rate were observed. The content of I-xylose in serum was detected by phloroglucinol method. Colorimetry method was used to detected content of ATP in jejunum tissues. RESULTS: Compared with group A, the symptom score in group B was increased significantly (both P < 0.01), while the intestinal propulsive rates, the content of D-xylose in serum and ATP in jejunum tissues were decreased significantly (P < 0.05, P < 0.01). Compared with group B, the symptom score in group C and D was decreased significantly (both P < 0.01), while the intestinal propulsive rates, the content of D-xylose in serum and ATP in jejunum tissues were increased significantly (P < 0.05, P < 0.01). There were no significant difference between group C and D (P > 0.05). CONCLUSION: Moxibustion at "Zusanli" (ST 36) etc. could relieve symptoms of spleen-deficiency, enhance motility and absorption functions of small intestine and improve metabolism of small intestine. The efficacy is equal to administration of Sijunzi decoction.

Proteomic identification of Hsp70 as a new Plk1 substrate in arsenic trioxide-induced mitotically arrested cells.

We previously demonstrated that when arsenic trioxide (ATO)-induced mitotically arrested HeLa S3 cells (AIMACs) were treated with staurosporine (SSP) the cells rapidly exited mitosis. To better define the cellular targets and the underlying mechanisms of AIMACs, we applied 2-D DIGE followed by LC-MS/MS analysis and showed that SSP induced a significant change in the phosphoproteome of AIMACs. Among the proteins whose phosphorylation was modulated by SSP, we identified Hsp70, Rad 23B, and eukaryotic translation initiation factor 4B as potentially new substrates of polo-like kinase 1 (Plk1), an essential serine/threonine kinase with versatile mitotic functions. Since Hsp70 is a stress protein responsible for ATO treatment, we further identified Thr(13) , Ser(362) , Ser(631) , and Ser(633) on Hsp70 intracellularly phosphorylated in AIMACs by combining TiO(2) phospho-peptides enrichment and MS/MS analysis. Using antibody specifically against phosph-Ser(631) Hsp70 and further aided by expression of kinase-dead Plk1 and pharmacological inhibition of Plk1, we concluded that Ser(631) on Hsp70 is phosphorylated by Plk1 in AIMACs. By immnuofluorescent staining, we found the colocalization of Hsp70 and Plk1 in AIMACs but not in interphase cells. In addition, Plk1-mediated phosphorylation of Hsp70 prevented AIMACs from mitotic death. Our results reveal that Hsp70 is a novel substrate of Plk1 and that its phosphorylation contributes to attenuation of ATO-induced mitotic abnormalities.

[Effect of plasma of healthy subjects undergoing moxibustion on ethanol-injured human gastric epithelial GES-1 cells in vitro and the involved mitochondrial apoptosis pathway].

OBJECTIVE: To observe the effect of plasma derived from healthy volunteers undergoing moxibustion (moxibustion plasma) on alchol-injured human gastric epithelial GES-1 cells in vitro, and expression of heat shock protein 70 (HSP 70, cell apoptosis inhibitory protein), apoptosis inducing factor (AIF), Smac (a mitochondrial protein), and Caspase 3 and Caspase 9 (the latter 3 proteins are also involved in cell apoptosis) in order to study its mechanisms underlying protecting gastric mucous membrane. METHODS: Twenty-four healthy volunteer subjects (half men and half women) were randomized into acupoint-moximustion (A-M) [Zhongwan(CV 12), Guanyuan (CV 4) and Zusanli (ST 36)] group and non-acupoint-moxibustion (NA-M, 3 cun right to CV 12 and CV 4.1 cun medial to ST 36 ) group (n = 12/group). Moxibustion was applied to the above-mentioned 3 acupoints and non-acupoints for 30 min, once daily for 10 days. Venous blood of the subjects was collected before and after moxibustion. The cultured GES-1 cells were divided into: control group. ethanol-injury group (model), A-M plasma group (A-M-P, plasma got from volunteers undergoing A-M), and NA-M plasma group (NA-M-P,plasma got from volunteers accepting NA-M). The GES-1 cells of the latter 3 groups were treated with 8% ethanol for duplicating cell injury model. Apoptosis was detected by flowcytometry. Expression of HSP 70, second mitochondria-derived activator of Caspase (Smac) and AIF proteins of GES-1 cells were assayed by western blotting, and the immunoactivity of cysteinyl aspirate-specific proteinase-3 and 9 (Caspase-3, 9) was detected by immunocytochemistry. RESULTS: In comparison with the control group, the apoptosis rate, the expression of HSP 70, Smac and AIF proteins, and the immunoactivity of Caspase-3 and Caspase-9 of the model group were increased significantly (P < 0.01). Compared with the model group, the apoptosis rate of GES-1 cells, the expression of Smac and AIF proteins, and the immunoactivity of Caspase-3 and Caspase-9 in the A-M-P group, the apoptosis rate, the expression of Smac and the immunoactivity of Caspase-3 and Caspase-9 in the NA-M-P group were all down-regulated considerably (P < 0.05, P < 0.01). In comparison with the model group, HSP 70 expression of the A-M-P group was up-regulated significantly (P < 0.01). The apoptosis rate of GES-1 cells, the expression levels of Smac, AIF, Caspase-3 and Caspase-9 were significantly lower in the A-M-P group than in the NA-M-P group (P < 0.05, P < 0.01), while the expression of HSP 70 was apparently higher in the A-M-P group than in the NA-M-P group (P < 0.01). CONCLUSION: Plasma derived from the subjects undergoing moxibustion of Zusanli (ST 36), Zhongwan (CV 12) and Guanyuan (CV 4) can inhibit apoptosis of GES-1 cells in vitro, which is closely related to its effects in up-regulating intracellular HSP 70 expression and down-regulating mitochondrial apoptosis protein expression of AIF. Smac, Caspase-3 and Caspase-9.

[Effects of moxibustion on gastric mucosal EGF and TGF-alpha contents and epidermal growth factor receptor expression in rats with gastric mucosal lesion].

OBJECTIVE: To observe the effects of moxibustion on contents of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) expression in the gastric mucosa tissue in rats with gastric mucosal lesion. METHODS: Thirty-six SD rats were randomly and equally divided into control, model and moxibustion groups. Gastric mucosal lesion model was duplicated by restraint and cool water immersion stress. Pre-moxibustion was applied to "Zusanli" (ST 36) and "Zhongwan" (CV 12), "Pishu" (BL 20) and "Weishu" (BL 21) alternately, once everyday for 8 days before modeling. The contents of EGF and TGF-alpha in gastric mucosa were detected by enzyme-linked immunosorbent assay (ELISA) and the expression of EGFR determined by immunohistochemistry. RESULTS: Compared with the control group, only TGF-alpha content in the gastric mucosa in the model group was increased significantly (P < 0.05). Compared with the model group, the EGF and TGF-alpha contents and EGFR immunoactivity in the gastric mucosa were increased significantly in the moxibustion group (P < 0.05, P < 0.01). CONCLUSION: Pre-moxibustion at ST 36, CV 12, BL 20 and BL 21 can up-regulate gastric mucosal EGF and TGF-alpha contents and EGFR protein expression in gastric mucosa lesion rats, which may contribute to its effect in relieving stress-induced gastric mucosal injury.

S-nitrosoproteome in endothelial cells revealed by a modified biotin switch approach coupled with Western blot-based two-dimensional gel electrophoresis.

NO-mediated S-nitrosation of cysteine residues has been recognized as a fundamental post-translational modification. S-Nitrosation of endothelial cell (EC) proteins can alter function and affect vascular homeostasis. Trace amounts of S-nitrosoproteins in endothelial cells (ECs) in vivo coupled with lability of the S-nitroso bond have hindered a comprehensive characterization. We demonstrate a convenient and reliable method, requiring minimal sample, for the screening and identification of S-nitrosoproteins. ECs treated with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) were subjected to the biotin switch method of labeling, then detected by analytical Western blot-based two-dimensional gel electrophoresis (2-DE). More than 89 SNAP-increased S-nitrosoproteins were detected and 28 of these were successfully excised from preparative 2-DE gel and identified by LC-MS/MS. Moreover, the nitrosocysteine residue for each protein (HSPA9/368, beta-actin/16, TMP3/170, vimentin/328) was also determined, and the relative ratio of S-nitrosation/non-S-nitrosation for Cys328 of vimentin was estimated using MASIC software. By the combination of the biotin switch method with 2-DE and Western blot analysis, S-nitrosoproteins can be screened and characterized by MS, providing a basis for further study of the physiological significance of each S-nitrosoproteins.

Sox2 plays a role in the induction of amacrine and Müller glial cells in mouse retinal progenitor cells.

PURPOSE: The transcription factor Sox2 plays important roles in both human and mouse retinal development. Although loss-of-function mutations in Sox2 have been studied in mice, gain-of-function experiments in the neural retina have been lacking. METHODS: The detailed expression pattern of Sox2 in the developing mouse retina was examined by immunohistochemistry. Then, Sox2 was expressed in a retinal explant culture prepared from E17 mouse embryos by retrovirus-mediated gene transfer to examine its role in retinal development. In addition, shRNA was used to suppress Sox2 in a retinal explant using a retrovirus-mediated system. RESULTS: Sox2 was expressed throughout the neuroblastic layer in the embryonic retina, but only in the inner nuclear layer in the mature retina. Double immunostaining revealed that Sox2 was expressed in Müller glial cells and in a subset of amacrine cells. Forced expression of Sox2 in a mouse retinal explant culture resulted in the dramatic accumulation of amacrine cells in the inner nuclear layer; in addition, cells expressing amacrine cell markers were also found on the innermost side of the outer nuclear layer. The expression of Pax6, which plays an important role in amacrine cell differentiation, was observed in the Sox2-expressing cells, and Sox2 activated the Pax6 promoter to drive luciferase expression in Y79 cells. A decrease in retinal progenitor cell proliferation accompanied these effects. The suppression of Sox2 expression by shRNA resulted in a decreased number of cells in the inner nuclear layer. CONCLUSIONS: Therefore, ectopic Sox2 expression can induce amacrine cells in the mouse retina from stage E17 onward, possibly by facilitating cell cycle exit.

[Effect of electroacupuncture of "Neiguan" (PC 6) on Na+-K+-ATPase activity and its gene expression in cardiocyte membrane in rats with myocardial ischemia-reperfusion injury].

OBJECTIVE: To compare the effects of electroacupuncture (EA) of "Neiguan" and other acupoints on Na+ -K+ -ATPase activity and its gene expression in ischemic myocrardial cell membrane in rats. METHODS: A total of 50 Wistar rats were randomly divided into pseudo-operation (control), model, Neiguan (PC6), Shenmen (HT7) and Hegu (LI4) groups, with 10 rats in each group. Myocardial ischemia-reperfusion (I/R) model was duplicated by occlusion of the descending anterior branch of the left coronary artery and reperfusion. EA (30/100 Hz, 2-4 mA) was applied to the above-mentioned acupoints for 20 min respectively. Na+ -K+ -ATPase activity was determined by inorganic phosphorus colorimetry, and Na+ -K+ -ATPase gene expression was detected using reverse transcription polymerase chain reaction (RT-PCR) technique. RESULTS: Compared with control group, the activity of Na+ -K+ -ATPase in model, PC6, HT7 and LI4 groups decreased significantly after myocardial I/R (P<0.05, 0.01); while in comparison with model, the activity of Na+ -K+ -ATPase in PC6 group increased considerably (P<0.01). Regarding the expression of Na+ -K+ -ATPase mRNA, compared with control group, it was down-regulated significantly in model, HT7 and LI4 groups (P<0.01); while in PC6 group, Na+ -K+ -ATPase mRNA expression was up-regulated markedly compared with model group (P<0.05); The activity of Na+ -K+ -ATPase and the expression of Na+ -K+ -ATPase mRNA in HT7 and LI4 groups were significantly lower than those in PC6 group (P<0.01, 0.05). No significant differences were found between HT7 and LI4 groups in the activity of Na+ -K+ -ATPase and the expression of Na+ -K+ -ATPase mRNA (P>0.05). CONCLUSION: EA of "Neiguan" (PC6) may potentiate the activity of Na+ -K+ -ATPase and up-regulate Na+ -K+ -ATPase mRNA expression, which may contribute to its protective effect on ischemic cardiocytes.

HLA-B*1502-bound peptides: implications for the pathogenesis of carbamazepine-induced Stevens-Johnson syndrome.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) can involve MHC-restricted presentation of a drug or its metabolites for T-cell activation. HLA-B(*)1502 tightly associated with carbamazepine (CBZ) induced these conditions in a Han Chinese population. OBJECTIVE: We sought to identify HLA-B(*)1502-bound peptides that might be involved in CBZ-induced SJS/TEN. METHODS: Soluble HLA-B(*)1502 was used to identify bound peptides in the presence and absence of CBZ by using liquid chromatography-tandem mass spectrometry. Peptide-binding assays were performed to detect the specific interaction between the HLA molecule and the identified peptides. Mass spectra were compared to detect CBZ-modified peptides. RESULTS: We identified more than 145 peptides bound to HLA-B(*)1502. In 13 of 15 peptides examined, we functionally confirmed their specificity with binding assays. Preferable uses of these peptides at the anchoring residues P2 and P9 were similar to those observed in other HLA-B alleles in the Han Chinese population. However, the preferable use of serine residues at the nonanchoring position (P) 5, P6, P7, and P8 appeared to be unique for the B(*)1502 peptides. No specific CBZ-modified peptides were detected when we compared the mass spectra of peptides detected in the presence or absence of the drug. CONCLUSION: Noncovalent interaction between a drug and an HLA complex might contribute to cytotoxic T cell-mediated cell death in patients with SJS/TEN. CLINICAL IMPLICATIONS: An understanding of pharmacologic interaction of drugs with an HLA complex might lead to safer drugs that avoid SJS/TEN.

[Expressions of epidermal growth factor receptor signaling substances in gastric mucosal cells influenced by serum derived from rats treated with electroacupuncture at stomach meridian acupoints].

OBJECTIVE: To study the effects of serum derived from rats treated with electroacupuncture at stomach meridian acupoints on the expressions of epidermal growth factor receptor (EGFR) signaling substances phospholipase C gamma-1 (PLC gamma-1), protein kinase C (PKC) and c-myc in gastric mucosal cells. METHODS: Sixty rats were randomly divided into normal group, stomach meridian group, gallbladder meridian group, stomach meridian plus PD153035 group and gallbladder meridian plus PD153035 group. Water-immersion and restrained stress methods were adopted for inducing gastric mucosal injury in the rats. Gastric mucosal cells were separated by using pronase digestion method, and incubated by PD153035, a EGFR inhibitor, and 100 ml/L serum. The expression of PLC gamma-1 in the gastric mucosal cells was tested by enzyme linked-immunosorbent assay (ELISA), while the expression of PKC by isotope incorporate assay and the expression of c-myc by reverse transcription polymerase chain reaction assay (RT-PCR). RESULTS: In gastric mucosal cells, weak expressions of PLC gamma-1, PKC and c-myc were seen in the normal group, and relatively strong expressions of PLC gamma-1, PKC and c-myc were seen in the stomach meridian group and the gallbladder meridian group, among which, the expressions of PLC gamma-1, PKC and c-myc in the stomach meridian group were the strongest, and there was a significant difference between the stomach meridian group and the gallbladder meridian group (P<0.01). Relative weak expressions of PLC gamma-1, PKC and c-myc were seen in the stomach meridian plus PD153035 group and the gallbladder meridian plus PD153035 group, and there was a significant difference between the stomach meridian group and the stomach meridian plus PD153035 group (P<0.01). CONCLUSIONS: The serum derived from the rats treated with electroacupuncture at stomach meridian acupoints can activate the EGFR singling pathway, and this provides an evidence for the theory of "relative particularity between meridians and viscera" in traditional Chinese medicine.

[Optimization of formulation matrix proportion and preparation technology of realgar floating tablets for gastric retention by uniform design and correlation analysis].

OBJECTIVE: To optimize the different components proportions of the Realgar floating tablets for gastric retention by uniform design and correlation analysis. METHOD: With the different dosage of hydroxypropyl methyl cellulose (HPMC) as the tablets frame matrix, uniform design and correlation analysis were used to optimize the best component proportions of formula, and to measure the dissolution of the tablets in vitro. RESULT: Dissolution of the tablets in vitro was conformed to the expectation of experiment. The drug-release mechanism was by diffusion and corrosion at the same time. CONCLUSION: The Realgar floating tablets for gastric retention achieved the goal of design, which demand sustained release and safety.

Prohibitin in the pathogenesis of transitional cell bladder cancer.

Our profiling experiment demonstrated that prohibitin 1 (PHB) was ubiquitously expressed in uroepithelial and urothelial carcinoma cell lines and exhibited a trend toward a positive relationship with tumor progression. The aim of this study was, therefore, to examine the potential role of PHB in multistage bladder carcinogenesis and predicting patient outcome. Immunohistochemical staining showed that PHB was overexpressed in 141 out of 167 cases (84.4%) of bladder cancer. This expression was positively related to met receptor overexpression (p = 0.04) and to multiple tumors (p = 0.05). Independent factors in predicting patient survival were multiple tumors (p = 0.002), muscle invasion (p = 0.003), and met overexpression (p = 0.05) in a multivariate analysis. Interestingly, patients with superficial bladder cancer overexpressing both PHB and met had a significantly lower recurrence-free survival rate than those not expressing PHB (p = 0.04). Taken together, our findings showed that PHB was activated at an early stage of carcinogenesis and that it may play a synergistic role with met in the progression of human bladder cancer. In addition, we demonstrated that genistein and justicidin A, natural chemoprevention agents, could suppress the expression of PHB in vitro. Thus, targeting PHB would be a useful approach for treating and preventing human bladder cancer.

SUMOylation of Tr2 orphan receptor involves Pml and fine-tunes Oct4 expression in stem cells.

The Tr2 orphan nuclear receptor can be SUMOylated, resulting in the replacement of coregulators recruited to the regulatory region of its endogenous target gene, Oct4. UnSUMOylated Tr2 activates Oct4, enhancing embryonal carcinoma-cell proliferation, and is localized to the promyelocytic leukemia (Pml) nuclear bodies. When its abundance is elevated, Tr2 is SUMOylated at Lys238 and seems to be released from the nuclear bodies to act as a repressor. SUMOylation of Tr2 induces an exchange of its coregulators: corepressor Rip140 replaces coactivator Pcaf, which switches Tr2 from an activator to a repressor. This involves dynamic partitioning of Tr2 into Pml-containing and Pml-free pools. These results support a model where SUMOylation-dependent partitioning and differential coregulator recruitment contribute to the maintenance of a homeostatic supply of activating, as opposed to repressive, Tr2, thus fine-tuning Oct4 expression and regulating stem-cell proliferation.

The effect of EA on the gastric mucosal histology and ITF mRNA expression in stress-induced rats.

This study focuses on the effect of electroacupuncture (EA) on the gastric mucosal histology and ITF (intestinal trefoil factor) mRNA in stress-related rat, and the relationship between the gastric protective mechanism of EA at acupoints of Stomach Meridian of Foot-Yangming (SMFY) group and Gallbladder Meridian of Foot-Shaoyang (GMFS) group. Forty rats were randomly divided into 4 groups: blank control group (BCG), model control group (MCG), SMFY group (EA at acupoints of SMFY for 7 days before model inducing), and GMFS group (EA at acupoints of GMFS for 7 days before model inducing). All rats (except normal group) were made model by water immersion and restriction (WRS) on day 7, then the gastric mucosal lesion index (GUI) was accessed, ITF mRNA expression of the tissue was detected by reverse- transcriptase-polymerase chain reaction (RT-PCR) method, and the histological change under light microscope was observed. As a result, the GUI value in SMFY/GMFS groups decreased significantly (p < 0.05 or 0.01). The level of ITF mRNA expression in SMFY group was significantly higher than that in MCG (p < 0.01), while that in GMFS group was higher than MCG but there was no statistical difference (p < 0.05). This result may be due to the intrinsic mechanism of EA's gastric mucosal protection by the upregulation of ITF mRNA expression in gastric mucosal tissue, and the expression variance indicated the classical traditional Chinese medicine (TCM) theory "Relative Particularity between SMFY and Stomach.".

Enhanced expression of epidermal growth factor receptor gene in gastric mucosal cells by the serum derived from rats treated with electroacupuncture at stomach meridian acupoints.

AIM: To investigate the effect of serum derived from rats treated with electroacupuncture at stomach meridian acupoints on the expression of epidermal growth factor receptor (EGFR) gene in gastric mucosal cells. METHODS: The stress-induced gastric mucosal injury in rat model was established by water-immersion and restrained stress methods. 52 rats were randomly divided into: normal group (n = 8), model group (n = 8), model serum group (n = 12), stomach serum group (n = 12), and gallbladder serum group (n = 12). The gastric mucosal cells were separated by pronase-EDTA digestion method and incubated with serum. The EGFR gene expression in gastric mucosal cells was detected by reverse transcription-polymerase chain reaction (RT-PCR) method. RESULTS: Compared with normal group (0.6860 +/- 0.0594), the serum derived from rats of the stomach group (1.2272 +/- 0.0813, P = 0.00 < 0.01) and gallbladder group (0.9640 +/- 0.0387, P = 0.00 < 0.01) had a tendency to enhance the EGFR gene expression in gastric mucosal cells. Such tendency existed in the model group (0.7104 +/- 0.0457) but with no significant difference (P = 0.495 > 0.05) and in model serum group (0.8516 +/- 0.0409) with an extremely obvious difference (P = 0.001 < 0.01). Furthermore, the EGFR gene expression in stomach serum group was significantly higher than that in gallbladder serum group (P = 0.00 < 0.01). CONCLUSION: The present study shows that serum derived from rats treated with electroacupuncture at stomach meridian acupoints can distinctly increase the EGFR gene expression of gastric mucosal cells. Therefore, there is certain meridian specificity in the serum, which could provide a proof for the TCM theory "particular relation between meridian and internal organ".

Effect of electroacupunture on gastric mucosal intestinal trefoil factor gene expression of stress-induced gastric mucosal injury in rats.

AIM: To investigate electroacupuncture(EA) at the acupoints of Stomach Meridian of Foot-Yangming (SMFY), Gallbladder Meridian of Foot-Yangming (SMFY) on gastric mucosal intestinal trefoil factor (ITF) gene expression detection in stress-induced rats with gastric mucosal lesion, and to explore the regulatory mechanism and significance of EA-related gastric mucosal protective effect. METHODS: Forty rats were randomly divided into 4 groups: Blank group, Model group, Model group+EA at acupoints of SMFY group ("SMFY group"), and Model group+EA at acupoints of GMFY group(GMFY group). All rats (except blank group) were made model by water immersion and restraint stress (WRS). Then the gastric mucosa tissue in each rat was taken off after assessment of gastric mucosal lesion index(GUI), and the expression of ITF mRNA of the tissues was detected by reverse transcription-polymerase chain reaction (RT-PCR) method. RESULTS: Compared with Model group(54.3+/- 1.34), the GUI value in SMFY group (31+/- 2.21) decreased significantly(P< 0.01), so did that in GMFY group (39.8+/- 1.62, P< 0.05), meanwhile GUI value in SMFY group was significantly lower than in GMFY group(P< 0.01). Compared with Model group (0.65+/- 0.01), EA had a tendency to improve the expression of gastric mucosal ITFmRNA gene: such tendency existed in GMFY group (0.66+/- 0.01) but with no significant difference(P>0.05), in SMFY group(0.76+/- 0.01) with an extremely obvious difference (P< 0.01), furthermore the expression in SMFY group was significantly higher than in GMFY group (P< 0.01). CONCLUSION: The gastric mucosal protective effect by EA at the acupoints of SMFY and GMFY was related to the expression variance of ITF, indicating certain meridian specificity exists. It could be one proof for the TCM theory "Relative particularity between SMFY and stomach".

Thyroid hormone-induced juxtaposition of regulatory elements/factors and chromatin remodeling of Crabp1 dependent on MED1/TRAP220.

The cellular retinoic acid binding protein I gene is induced by thyroid hormone (T3) through a T3 response element (TRE) approximately 1 kb upstream of the basal promoter. The upstream region is organized into a positioned nucleosomal array with the N1 nucleosome spanning the GC box region. T3 induces apparent interactions between chromatin segments containing the TRE and the GC box regions and the sliding of upstream nucleosomes toward N1 with concomitant N1 remodeling. Concurrently, the chromatin-remodeling factor BRM is replaced by BRG1 and histones are hyperacetylated. All these events are abolished in Med1/Trap220 null cells, indicating a key role for TRAP/Mediator in these processes. A MED1/TRAP220-containing Mediator complex constitutively occupies the GC box region but not the TRE, serving as a nexus for distal and proximal factors. This indicates new TRAP/Mediator functions in facilitating ultimate recruitment and function of RNA polymerase II and the general transcription machinery.