Role of the transforming growth factor-β signaling pathway in the pathogenesis of colorectal cancer

The transforming growth factor-β (TGF-β) signaling pathway plays an important role in cancer cell proliferation, growth, metastasis, and apoptosis. It has been shown that TGF-β acts as a tumor suppressor in the early stages of the disease, and as a tumor promoter in its late stages. Mutations in the TGF-β signaling components, the TGF-β receptors and cytoplasmic signaling transducers, are frequently observed in colorectal carcinomas. Exploiting specific TGF-β receptor agonist and antagonist with antitumor properties may be a way of controlling cancer progression. This review summarizes the regulatory role of TGF-β signaling in the pathogenesis of colorectal cancer.     

Mutational landscape of phenylketonuria in Iran

To date more than 1000 different variants in the PAH gene have been identified in patients with phenylketonuria (PKU). In Iran, several studies have been performed to investigate the genetics bases of the PKU in different parts of the country. In this study, we have analysed and present an update of the mutational landscape of the PAH gene as well as the population genetics and frequencies of detected variants for each cohort. Published articles on PKU mutations in Iran were identified through a comprehensive PubMed, Google Scholar, Web of Science (ISI), SCOPUS, Elsevier, Wiley Online Library and SID literature search using the terms: “phenylketonuria”, “hyperphenylalaninemia”, and “PKU” in combination with “Iran”, “Iranian population”, “mutation analysis”, and “Molecular genetics”. Among the literature-related to genetics of PKU, 18 studies were on the PKU mutations. According to these studies, in different populations of Iran 1497 patients were included for mutation detection that resulted in detection of 129 different mutations. Results of genetic analysis of the different cohorts of Iranian PKU patients show that the most prevalent mutation in Iran is the pathogenic splice variant c.1066-11G > A, occurring in 19.54% of alleles in the cohort. Four other common mutations were p.Arg261Gln, p.Pro281Leu, c.168 + 5G > C and p.Arg243Ter (8.18%, 6.45%, 5.88% and 3.7%, respectively). One notable feature of the studied populations is its high rate of consanguineous marriages. Considering this feature, determining the prevalent PKU mutations could be advantageous for designing screening and diagnostic panels in Iran.     

Downregulated in adenoma and putative anion transporter are regulated by CFTR in cultured pancreatic duct cells

The mechanism of the pancreatic ductal HCO secretion defect in cystic fibrosis (CF) is not well defined. However, a lack of apical Cl(-)/HCO exchange may exist in CF. To test this hypothesis, we examined the expression of Cl(-)/HCO exchangers in cultured pancreatic duct epithelial cells with physiological features prototypical of CF [CFPAC-1 cells lacking a functional CF transmembrane conductance regulator (CFTR)] or normal duct cells (CFPAC-1 cells transfected with functional wild-type CFTR, CFPAC-WT). Cl(-)/HCO exchange activity, assayed with the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein in cells grown on coverslips, increased about twofold in cells transfected with functional CFTR. This correlated with increased apical (36)Cl influx in cells expressing functional CFTR and grown on permeable support. Northern hybridizations indicated the induction of downregulated in adenoma (DRA) in cells expressing functional CFTR. The expression of putative anion transporter PAT1 also increased significantly in cells expressing functional CFTR. DRA was detected at high levels in native mouse pancreas by Northern hybridization and localized to the apical domain of the duct cells by immunohistochemical studies. In conclusion, CFTR upregulates DRA and PAT1 expression in cultured pancreatic duct cells. We propose that the pancreatic HCO secretion defect in CF patients is partly due to the downregulation of apical Cl(-)/HCO exchange activity mediated by DRA (and possibly PAT1).     

Investigation of the role of quercetin as a heat shock protein inhibitor on apoptosis in human breast cancer cells

Molecular Biology Reports - High expression of heat shock proteins (Hsp) in breast cancer has been closely associated with tumor cell proliferation and thus a poor clinical outcome. Quercetin, a...     

Gold@Silver@Gold Core Double-Shell Nanoparticles: Synthesis and Aggregation-Enhanced Two-Photon Photoluminescence Evaluation

A facile, straightforward, and low-cost method is proposed to synthesize gold@silver@gold core double-shell nanoparticles. The technique is a seed-mediated growth protocol that contains four steps of (1) gold seed synthesis, (2) gold seed growth, (3) silver layer coating through silver salt reduction, and (4) gold layer deposition via gold precursor reduction. The prepared nanoparticles had a narrow size distribution and the average particle size of 28 ± 1 nm. Cysteine was introduced to the nanoparticles solution as a coupling agent to assemble nanoparticles. Aggregation-induced two-photon photoluminescence enhancement of three types assembled nanoparticles, i.e., gold@silver@gold, gold@silver, and gold nanoparticles, was studied. It was observed that the assembled core double-shell nanoparticles presented huge enhancement in two-photon photoluminescence signal in comparison with two other nanoparticles. Moreover, the gold@silver@gold nanoparticle is a stable and biocompatible plasmonic nanosystem. This paper provides a novel candidate for two-photon photoluminescence excitation sensing and imaging for biomedical applications.

     

The role of catecholamines in mesenchymal stem cell fate

Mesenchymal stem cells (MSCs) are multipotent stem cells found in many adult tissues, especially bone marrow (BM) and are capable of differentiation into various lineage cells such as osteoblasts, adipocytes, chondrocytes and myocytes. Moreover, MSCs can be mobilized from connective tissue into circulation and from there to damaged sites to contribute to regeneration processes. MSCs commitment and differentiation are controlled by complex activities involving signal transduction through cytokines and catecholamines. There has been an increasing interest in recent years in the neural system, functioning in the support of stem cells like MSCs. Recent efforts have indicated that the catecholamine released from neural and not neural cells could be affected characteristics of MSCs. However, there have not been review studies of most aspects involved in catecholamines-mediated functions of MSCs. Thus, in this review paper, we will try to describe the current state of catecholamines in MSCs destination and discuss strategies being used for catecholamines for migration of these cells to damaged tissues. Then, the role of the nervous system in the induction of osteogenesis, adipogenesis, chondrogenesis and myogenesis from MSCs is discussed. Recent progress in studies of signaling transduction of catecholamines in determination of the final fate of MSCs is highlighted. Hence, the knowledge of interaction between MSCs with the neural system could be applied towards the development of new diagnostic and treatment alternatives for human diseases.     

Na+:HCO(3-) cotransporters (NBC): cloning and characterization

The sodium bicarbonate cotransporter (NBC1) is essential for bicarbonate transport across plasma membranes in epithelial and nonepithelial cells. The direction of the NaHCO₃ movement in secretory epithelia is opposite to that in reabsorptive epithelia. In secretory epithelia (such as pancreatic duct cells) NBC is responsible for the transport of bicarbonate from blood to the cell for eventual secretion at the apical membrane. In reabsorptive epithelia (such as kidney proximal tubule cells) NBC is responsible for the reabsorption of bicarbonate from cell to the blood. In nonepithelial cells this transporter is mainly involved with cell pH regulation. Recent molecular cloning experiments have identified the existence of four NBC isoforms (NBC1, 2, 3 and 4) and two NBC-related proteins AE4 and NCBE (Anion Exchanger 4 and Na-dependent Chloride-Bicarbonate Exchanger). All but AE4 are presumed to mediate the cotransport of Na⁺ and HCO₃ ⁻ under normal conditions and may be functionally altered in certain pathologic states. NBC1 shows a limited tissue expression pattern, is electrogenic and plays an important role in bicarbonate reabsorption in kidney proximal tubule. In addition to the kidney, NBC1 is expressed in pancreatic duct cells, is activated by cystic fibrosis transmembrane conductance regulator (CFTR) and plays an important role in HCO₃ ⁻ secretion. NBC2 and NBC3 have a wider tissue distribution than NBC1, are electroneutral, and are involved with cell pH regulation. The characterization of NBC4 is incomplete. The NBC-related protein called NCBE mediates Na-dependent, Cl⁻/Bicarbonate Exchange. The purpose of this review is to summarize recent advances on the cloning of NBC isoforms and related proteins and their role and regulation in physiologic and pathologic states. Received: 26 February 2001/Revised: 14 May 2001     

A potent peroxidase from solid cell culture of Ocimum basilicum with high sensitivity for blood glucose determination

Extensive applications of peroxidase (POX) have raised the global market demand at a considerable rate during the forecast period of 2020–2025. Nonetheless, the large-scale POX preparation still relies on the extraction from agricultural products, while there is an accumulative driving force toward employing biotechnological processes with agricultural hassle free identity. Consequently, a novel heme peroxidase was purified to homogeneity (MW of 40 kD) from the callus culture of basil in darkness on Murashige-Skoog medium supplemented by 2,4-dichlorophenoxyacetic acid (10^–6 M) and kinetin (10^–5 M). The highest activity of the purified peroxidase (ObPOX) was observed in Tris-base buffer at pH 7.5 and 80 °C. ObPOX showed high stability over pH(s) 5 to 7.5 and temperatures of 15 to 60 °C. ObPOX specific activity was 1245.142 AU mg^?1 in the presence of phenol, 4 times higher than that of HRP. ObPOX showed moderate affinity for guaiacol (K_m?=?21.5 mM), but obtained an exceptionally high specificity constant (k_cat/K_m?=?66,743.7 s^?1 M^?1) for GASA (4-[(4-Hydroxy-3-methoxyphenyl) azo]-benzenesulfonic acid), the introduced substrate for determination of blood sugar. Applying ObPOX instead of HRP in glucose measurements of the real samples improved the regression constant of the correlation diagram between the tests and the lab results from 0.958 to 0.981. Physicochemical properties of ObPOX as well as the growth rate of basil callus (5.04 g L^?1 per day) and the yield of ObPOX production (35 mg per 100 g dry biomass per subculture) designates O. basilicum cell culture for large-scale production of a robust peroxidase.