Genome expression analysis by suppression subtractive hybridization identified overexpression of Humanin, a target gene in gastric cancer chemoresistance

Background: In cancer cells, apoptosis is an important mechanism that influences the outcome of chemotherapy and the development of chemoresistance. To find the genes involved in chemoresistance and the development of gastric cancer, we used the suppression subtractive hybridization method to identify the genes that are overexpressed in gastric cancer tissues compared to normal gastric tissues. Results: In the suppression subtractive hybridization library we constructed, the most highly overexpressed genes were humanin isoforms. Humanin is a recently identified endogenous peptide that has anti-apoptotic activity and has been selected for further study due to its potential role in the chemoresistance of gastric cancer. Upregulation of humanin isoforms was also observed in clinical samples by using quantitative real-time PCR. Among the studied isoforms, humanin isoform 3, with an expression level of 4.166 ± 1.44 fold, was the most overexpressed isoform in GC. Conclusions: The overexpression of humanin in gastric cancer suggests a role for chemoresistance and provides new insight into the biology of gastric cancer. We propose that humanin isoforms are novel targets for combating chemoresistance in gastric cancer. © 2014 Mottaghi-Dastjerdi et al.; licensee BioMed Central Ltd

Identification of novel genes involved in gastric carcinogenesis by suppression subtractive hybridization

Gastric cancer (GC) is one of the most common and life-threatening types of malignancies. Identification of the differentially expressed genes in GC is one of the best approaches for establishing new diagnostic and therapeutic targets. Furthermore, these investigations could advance our knowledge about molecular biology and the carcinogenesis of this cancer. To screen for the overexpressed genes in gastric adenocarcinoma, we performed suppression subtractive hybridization (SSH) on gastric adenocarcinoma tissue and the corresponding normal gastric tissue, and eight genes were found to be overexpressed in the tumor compared with those of the normal tissue. The genes were ribosomal protein L18A, RNase H2 subunit B, SEC13, eukaryotic translation initiation factor 4A1, tetraspanin 8, cytochrome c oxidase subunit 2, NADH dehydrogenase subunit 4, and mitochondrially encoded ATP synthase 6. The common functions among the identified genes include involvement in protein synthesis, involvement in genomic stability maintenance, metastasis, metabolic improvement, cell signaling pathways, and chemoresistance. Our results provide new insights into the molecular biology of GC and drug discovery: each of the identified genes could be further investigated as targets for prognosis evaluation, diagnosis, treatment, evaluation of the response to new anticancer drugs, and determination of the molecular pathogenesis of GC. © The Author(s) 2014

Brain changes due to hypoxia during light anaesthesia can be prevented by deepening anaesthesia:a study in rats

In anaesthetic practice the risk of cerebral ischemic/hypoxic damage is thought to be attenuated by deep anaesthesia. The rationale is that deeper anaesthesia reduces cerebral oxygen demand more than light anaesthesia, thereby increasing the tolerance to ischemia or hypoxia. However, evidence to support this is scarce. We thus investigated the influence of light versus deep anaesthesia on the responses of rat brains to a period of hypoxia. In the first experiment we exposed adult male Wistar rats to deep or light propofol anaesthesia and then performed [18F]- Fludeoxyglucose (FDG) Positron Emission Tomography (PET) scans to verify the extent of cerebral metabolic suppression. In subsequent experiments, rats were subjected to light/deep propofol anaesthesia and then exposed to a period of hypoxia or ongoing normoxia (n = 9-11 per group). A further 5 rats, not exposed to anaesthesia or hypoxia, served as controls. Four days later a Novel Object Recognition (NOR) test was performed to assess mood and cognition. After another 4 days, the animals were sacrificed for later immunohistochemical analyses of neurogenesis/neuroplasticity (Doublecortin; DCX), Brain Derived Neurotrophic Factor (BDNF) expression and neuroinflammation (Ionized calcium-binding adaptor protein-1; Iba-1) in hippocampal and piriform cortex slices. The hippocampi of rats subjected to hypoxia during light anaesthesia showed lower DCX positivity, and therefore lower neurogenesis, but higher BDNF levels and microglia hyper-ramification. Exploration was reduced, but no significant effect on NOR was observed. In the piriform cortex, higher DCX positivity was observed, associated with neuroplasticity. All these effects were attenuated by deep anaesthesia. Deepening anaesthesia attenuated the brain changes associated with hypoxia. Hypoxia during light anaesthesia had a prolonged effect on the brain, but no impairment in cognitive function was observed. Although reduced hippocampal neurogenesis may be considered unfavourable, higher BDNF expression, associated with microglia hyper-ramification may suggest activation of repair mechanisms. Increased neuroplasticity observed in the piriform cortex supports this, and might reflect a prolonged state of alertness rather than damage

Organic complementary-like inverters employing methanofullerene-based ambipolar field-effect transistors

Published versio

EGFR is required for Wnt9a-Fzd9b signalling specificity in haematopoietic stem cells.

Wnt signalling drives many processes in development, homeostasis and disease; however, the role and mechanism of individual ligand-receptor (Wnt-Frizzled (Fzd)) interactions in specific biological processes remain poorly understood. Wnt9a is specifically required for the amplification of blood progenitor cells during development. Using genetic studies in zebrafish and human embryonic stem cells, paired with in vitro cell biology and biochemistry, we determined that Wnt9a signals specifically through Fzd9b to elicit β-catenin-dependent Wnt signalling that regulates haematopoietic stem and progenitor cell emergence. We demonstrate that the epidermal growth factor receptor (EGFR) is required as a cofactor for Wnt9a-Fzd9b signalling. EGFR-mediated phosphorylation of one tyrosine residue on the Fzd9b intracellular tail in response to Wnt9a promotes internalization of the Wnt9a-Fzd9b-LRP signalosome and subsequent signal transduction. These findings provide mechanistic insights for specific Wnt-Fzd signals, which will be crucial for specific therapeutic targeting and regenerative medicine

Ambipolar charge transport in organic field-effect transistors

Published versio

Architecture of next generation of e-commerce with fuzzy-GA-based negotiator agents

For a multi-agent electronic negotiating environment to be successful, intelligent agents should be capable of adapting their negotiation strategies and tactics to achieve an agreement with optimized profit. This paper aims to present some findings from which negotiating intelligent agents in electronic commerce start negotiating using a simplified standard protocol in conjunction with a combined negotiation. Taking advantage of a new developed evolutionary algorithm, agents configure their negotiation strategies somehow they can get more profit. They can use fuzzy fairness function to have behavior with fairness or without fairness. © 2007 IEEE

Shaping mathematics identity: An exploratory study on specifications grading in Calculus I at a Hispanic-Serving institution

Calculus I courses play a pivotal role in shaping students\u27 STEM pathways, making it essential to adopt pedagogies that foster both achievement and mathematics identity development, particularly among underserved groups such as Hispanic students. This study explores the impact of Specifications Grading, an alternative assessment method where students meet specific course learning objectives through multiple attempts, on students’ mathematics identity development. Through a comparative case study of two Calculus I students at a Hispanic-Serving Institution, one enrolled in a specification graded course and the other in a traditionally-graded course, we examine shifts in their self-perceptions of competence, interest, recognition in mathematics, and overall mathematics identity. Our findings suggest that specifications grading can enhance students\u27 mathematics identity by encouraging perseverance and a sense of competence. This study contributes to the field of mathematics education by providing empirical evidence that alternative assessment structures, like specifications grading, can serve as powerful tools for creating more equitable and identity-affirming learning environments in foundational STEM courses

Green Synthesis, Characterization, and Biological Evaluation of Hydroxyl-Capped Tellurium Nanoparticles

In this study, we used a simple green method for preparing tellurium nanoparticles and mainly evaluated their toxicological effects. The nanoparticles were synthesized using lactose and characterized with different instrumentation methods. The in vitro and in vivo cytotoxicity of tellurium nanoparticles and its effect on lipid profile were also evaluated. Hydroxyl-capped tellurium nanoparticles were successfully fabricated by lactose. The results showed spherical tellurium nanoparticles with a mean size of 89 nm. The toxicological study showed that the tellurium nanoparticles did not exhibit any toxicity on the primary cells. The LD50 values for the nanoparticles were 327 and 295 mg/kg for oral and intraperitoneal administrations, respectively. Also, the results showed a significant reduction in liver enzymes at the 16, 24, and 40 mg/kg doses. Hematological parameters indicated no significant suppressive changes between the animals that were administered tellurium nanoparticles and the control group. In addition, the effects of tellurium nanoparticles on hypercholesterolemic risk factors in mice fed with cholesterol demonstrated the depletion of triglyceride, cholesterol, and low-density lipoprotein. This study showed that the toxicity of tellurium nanoparticles was lower than tellurium ions. Furthermore, tellurium nanoparticles decreased the cholesterol and triglyceride levels in the animal model

Characterization of the serum levels of Meteorin-like in patients with inflammatory bowel disease and its association with inflammatory cytokines

Background: Meteorin-like (Metrnl) is an adipokine with insulin sensitizing and anti-inflammatory properties that has been discovered recently. The relation among Metrnl, Inflammatory Bowel Disease (IBD), and obesity has been unexplored yet. Methods: The present study was conducted on 54 healthy control, 42 Ulcerative Colitis (UC), and 43 Crohn�s disease (CD) patients who were diagnosed by pathological examination. In all participants, serum levels of adiponectin, Metrnl, interleukin (IL)-6, and Tumor necrosis factor (TNF-α) were measured using ELISA kits. Results: Metrnl concentration was considerably lower in both UC (85.25 ± 36.55 pg/mL) and CD (76.93 ± 27.92 pg/mL) patients in comparison to control (107.52 ± 35.33 pg/mL). In addition, it was seen that both patient groups have a decreased level of adiponectin compared to the controls. Besides that, the level of IL-6 and TNF-α were significantly greater in the patient groups. Moreover, the result showed that the level of Metrnl is inversely correlated with body mass index (BMI) in the controls and the patients. Metrnl levels are also inversely associated with IL-6, and TNF-α in both of the patient groups. Conclusions: The current study is the first one reporting the decreased levels of Metrnl in serum among patients with IBD, which is inversely related with BMI, TNF-α, and IL-6. These results suggested a possible relation of Metrnl with the pathogenesis of IBD, particularly through inflammatory process, although further studies are warranted to dissect the possible mechanism. © 2020, The Author(s)