Growth hormone receptor inhibition decreases the growth and metastasis of pancreatic ductal adenocarcinoma.
Abstract Pancreatic cancer is the only major cancer with very low survival rates (1%). It is the fourth leading cause of cancer-related death. Hyperactivated growth hormone receptor (GHR) levels have been shown to increase the risk of cancer in general and this pathway is a master regulator of key cellular functions like proliferation, apoptosis, differentiation, metastasis, etc. However, to date there is no available data on how GHR promotes pancreatic cancer pathogenesis. Here, we used an RNA interference approach targeted to GHR to determine whether targeting GHR is an effective method for controlling p...
Source: exp Mol Med - October 14, 2014 Category: Molecular Biology Authors: Subramani R, Lopez-Valdez R, Salcido A, Boopalan T, Arumugam A, Nandy S, Lakshmanaswamy R Tags: Exp Mol Med Source Type: research

miR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6.
Abstract Dysregulated microRNA (miRNA) expression has a critical role in tumor development and metastasis. However, the mechanism by which miRNAs control melanoma metastasis is unknown. Here, we report reduced miR-98 expression in melanoma tissues with increasing tumor stage as well as metastasis; its expression is also negatively associated with melanoma patient survival. Furthermore, we demonstrate that miR-98 inhibits melanoma cell migration in vitro as well as metastatic tumor size in vivo. We also found that IL-6 is a target gene of miR-98, and IL-6 represses miR-98 levels via the Stat3-NF-κB-lin28B ...
Source: exp Mol Med - October 9, 2014 Category: Molecular Biology Authors: Li F, Li XJ, Qiao L, Shi F, Liu W, Li Y, Dang YP, Gu WJ, Wang XG, Liu W Tags: Exp Mol Med Source Type: research

Redox proteomics: from bench to bedside.
Abstract In general protein posttranslation modifications (PTMs) involve the covalent addition of functional groups or molecules to specific amino acid residues in proteins. These modifications include phosphorylation, glycosylation, S-nitrosylation, acetylation, lipidation, among others (Angew Chem Int Ed Engl 44(45):7342-7372, 2005). Although other amino acids can undergo different kinds of oxidative posttranslational modifications (oxPTMs) (Exp Gerontol 36(9):1495-1502, 2001), in this chapter oxPTM will be considered specifically related to Cysteine oxidation, and redox proteomics here is translated as ...
Source: exp Mol Med - October 3, 2014 Category: Molecular Biology Authors: Ckless K Tags: Adv Exp Med Biol Source Type: research

Enhanced proliferation and differentiation of Oct4- and Sox2-overexpressing human adipose tissue mesenchymal stem cells.
Abstract Mesenchymal stem cells (MSCs) are attractive candidates for clinical repair or regeneration of damaged tissues. Oct4 and Sox2, which are essential transcription factors for pluripotency and self-renewal, are naturally expressed in MSCs at low levels in early passages, and their levels gradually decrease as the passage number increases. Therefore, to improve MSC proliferation and stemness, we introduced human Oct4 and Sox2 for conferring higher expansion and differentiation capabilities. The Oct4-IRES-Sox2 vector was transfected into human adipose tissue MSCs (ATMSCs) by liposomal transfection and ...
Source: exp Mol Med - September 28, 2014 Category: Molecular Biology Authors: Han SM, Han SH, Coh YR, Jang G, Chan Ra J, Kang SK, Lee HW, Youn HY Tags: Exp Mol Med Source Type: research

Inhibitory G proteins and their receptors: emerging therapeutic targets for obesity and diabetes.
Abstract The worldwide prevalence of obesity is steadily increasing, nearly doubling between 1980 and 2008. Obesity is often associated with insulin resistance, a major risk factor for type 2 diabetes mellitus (T2DM): a costly chronic disease and serious public health problem. The underlying cause of T2DM is a failure of the beta cells of the pancreas to continue to produce enough insulin to counteract insulin resistance. Most current T2DM therapeutics do not prevent continued loss of insulin secretion capacity, and those that do have the potential to preserve beta cell mass and function are not effective ...
Source: exp Mol Med - September 28, 2014 Category: Molecular Biology Authors: Kimple ME, Neuman JC, Linnemann AK, Casey PJ Tags: Exp Mol Med Source Type: research

CYP19 gene variant confers susceptibility to endometriosis-associated infertility in Chinese women.
Abstract An aromatase encoded by the CYP19 gene catalyzes the final step in the biosynthesis of estrogens, which is related to endometriosis development. To assess the association of CYP19 gene polymorphisms with the risks of endometriosis, chocolate cysts and endometriosis-related infertility, a case-control study was conducted in Chinese Han women by recruiting 225 healthy control females, 146 patients with endometriosis, 94 endometriosis women with chocolate cyst and 65 women with infertility resulting from endometriosis, as diagnosed by both pathological and laparoscopic findings. Individual genotypes ...
Source: exp Mol Med - September 28, 2014 Category: Molecular Biology Authors: Wang L, Lu X, Wang D, Qu W, Li W, Xu X, Huang Q, Han X, Lv J Tags: Exp Mol Med Source Type: research

An antibody reactive to the Gly63-Lys68 epitope of NT-proBNP exhibits O-glycosylation-independent binding.
In conclusion, we report that an antibody reactive to Gly63-Lys68 of NT-proBNP exhibits O-glycosylation-independent binding. PMID: 25236766 [PubMed - in process] (Source: exp Mol Med)
Source: exp Mol Med - September 28, 2014 Category: Molecular Biology Authors: Lee Y, Kim H, Chung J Tags: Exp Mol Med Source Type: research

Preeclampsia serum-induced collagen I expression and intracellular calcium levels in arterial smooth muscle cells are mediated by the PLC-γ1 pathway.
This study examined the hypothesis that PE sera may directly or indirectly, through human umbilical vein ECs (HUVECs), stimulate phospholipase C-γ1-1,4,5-trisphosphate (PLC-γ1-IP3) signaling, thereby increasing protein kinase C-α (PKC-α) activity, collagen I expression and intracellular Ca(2+) concentrations ([Ca(2+)]i) in human umbilical artery smooth muscle cells (HUASMCs). HUASMCs and HUVECs were cocultured with normal or PE sera before PLC-γ1 silencing. Increased PLC-γ1 and IP3 receptor (IP3R) phosphorylation was observed in cocultured HUASMCs stimulated with PE sera (P<0.05). In addition, PE serum significant...
Source: exp Mol Med - September 28, 2014 Category: Molecular Biology Authors: Jiang R, Teng Y, Huang Y, Gu J, Ma L, Li M, Zhou Y Tags: Exp Mol Med Source Type: research

Antitussive Activity of Withania somnifera and Opioid Receptors.
Abstract Arabinogalactan is a polysaccharide isolated from the roots of the medicinal plant Withania somnifera L. It contains 65 % arabinose and 18 % galactose. The aim of the present study was to evaluate the antitussive activity of arabinogalactan in conscious, healthy adult guinea pigs and the role of the opioid pathway in the antitussive action. A polysaccharide extract was given orally in a dose of 50 mg/kg. Cough was induced by an aerosol of citric acid in a concentration 0.3 mol/L, generated by a jet nebulizer into a plethysmographic chamber. The intensity of cough response was defined as the number...
Source: exp Mol Med - September 25, 2014 Category: Molecular Biology Authors: Nosálová G, Sivová V, Ray B, Fraňová S, Ondrejka I, Flešková D Tags: Adv Exp Med Biol Source Type: research

Thinning of dermas with the increasing age may be against by tetrahydroxystilbene glucoside in mice.
CONCLUSION: TSG and PME showed their protections to skin aging in mice challenged with control groups. It ensured the anti-thinning effect of dermas of TSG and provided two potential factors (insulin/IGF-1 signal pathway and the level of Ca(2+)) related to skin senescence of aging mice. PMID: 25232382 [PubMed] (Source: exp Mol Med)
Source: exp Mol Med - September 23, 2014 Category: Molecular Biology Authors: Zhou X, Ge L, Yang Q, Xie Y, Sun J, Cao W, Wang S Tags: Int J Clin Exp Med Source Type: research

Attenuation of airway inflammation by simvastatin and the implications for asthma treatment: is the jury still out?
This study not only evaluated the therapeutic potential and inhibitory mechanism of simvastatin in an ovalbumin (OVA)-specific asthma model in mice but also sought to clarify the future directions indicated by previous studies through a thorough review of the literature. BALB/c mice were sensitized to OVA and then administered three OVA challenges. On each challenge day, 40 mg kg(-1) simvastatin was injected before the challenge. The airway responsiveness, inflammatory cell composition, and cytokine levels in bronchoalveolar lavage (BAL) fluid were assessed after the final challenge, and the T cell composition and adhe...
Source: exp Mol Med - September 18, 2014 Category: Molecular Biology Authors: Liu JN, Suh DH, Yang EM, Lee SI, Park HS, Shin YS Tags: Exp Mol Med Source Type: research

MiR-152 suppresses the proliferation and invasion of NSCLC cells by inhibiting FGF2.
Abstract MicroRNAs (miRNAs) regulate the proliferation and metastasis of cancer cells. Here, we showed that miR-152 was downregulated in non-small-cell lung cancer (NSCLC) tissues and cell lines. Overexpression of miR-152 suppressed cell proliferation and colony formation and also limited migration and invasion. Fibroblast growth factor 2 (FGF2) was confirmed as a direct target of miR-152. FGF2 knockdown suppressed cell proliferation, colony formation, migration and invasion, whereas FGF2 overexpression partially reversed the suppressive effect of miR-152. Furthermore, the presence of miR-152 was inversely...
Source: exp Mol Med - September 7, 2014 Category: Molecular Biology Authors: Cheng Z, Ma R, Tan W, Zhang L Tags: Exp Mol Med Source Type: research

Diet control to achieve euglycemia induces significant loss of heart and liver weight via increased autophagy compared with ad libitum diet in diabetic rats.
In conclusion, glycemic control achieved by diet control can prevent hyperglycemia-induced renal hyperplasia in diabetes but may be deleterious even at isocaloric rate when insulin is deficient because of significant loss of heart and liver mass via increased autophagy. PMID: 25168310 [PubMed - as supplied by publisher] (Source: exp Mol Med)
Source: exp Mol Med - September 1, 2014 Category: Molecular Biology Authors: Lee JH, Lee JH, Jin M, Han SD, Chon GR, Kim IH, Kim S, Kim SY, Choi SB, Noh YH Tags: Exp Mol Med Source Type: research

Therapeutic effect of hepatocyte growth factor-secreting mesenchymal stem cells in a rat model of liver fibrosis.
In conclusion, therapy with MSCs/HGF resulted in an improved therapeutic effect compared with MSCs alone, probably because of the anti-fibrotic activity of HGF. Thus, MSC/HGF represents a promising approach toward a cell therapy for liver fibrosis. PMID: 25145391 [PubMed - in process] (Source: exp Mol Med)
Source: exp Mol Med - August 28, 2014 Category: Molecular Biology Authors: Kim MD, Kim SS, Cha HY, Jang SH, Chang DY, Kim W, Suh-Kim H, Lee JH Tags: Exp Mol Med Source Type: research

SPA0355 attenuates ischemia/reperfusion-induced liver injury in mice.
Abstract Hepatic ischemia/reperfusion (I/R) injury leads to oxidative stress and acute inflammatory responses that cause liver damage and have a considerable impact on the postoperative outcome. Much research has been performed to develop possible protective techniques. We aimed to investigate the efficacy of SPA0355, a synthetic thiourea analog, in an animal model of hepatic I/R injury. Male C57BL/6 mice underwent normothermic partial liver ischemia for 45 min followed by varying periods of reperfusion. The animals were divided into three groups: sham operated, I/R and SPA0355 pretreated. Pretreatment w...
Source: exp Mol Med - August 17, 2014 Category: Molecular Biology Authors: Bae UJ, Yang JD, Ka SO, Koo JH, Woo SJ, Lee YR, Yu HC, Cho BH, Zhao HY, Ryu JH, Lee SM, Jeon R, Park BH Tags: Exp Mol Med Source Type: research