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Abstract Matrix stiffness is a mechanical characteristic of the extracellular matrix (ECM) that increases from the tumor core to the tumor periphery in a gradient pattern in a variety of solid tumors and can promote proliferation, invasion, metastasis, drug resistance, and recurrence. Cancer stem cells (CSCs) are a rare subpopulation of tumor cells with self-renewal, asymmetric cell division, and differentiation capabilities. CSCs are thought to be responsible for metastasis, tumor recurrence, chemotherapy resistance, and consequently poor clinical outcomes. Evidence suggests that matrix stiffness can activate receptors and mechanosensor/mechanoregulator proteins such as integrin, FAK, and YAP, modulating the characteristics of tumor cells as well as CSCs through different molecular signaling pathways. A deeper understanding of the effect of matrix stiffness on CSCs characteristics could lead to development of innovative cancer therapies. In this review, we discuss how the stiffness of the ECM is sensed by the cells and how the cells respond to this environmental change as well as the effect of matrix stiffness on CSCs characteristics and also the key malignant processes such as proliferation and EMT. Then, we specifically focus on how increased matrix stiffness affects CSCs in breast, lung, liver, pancreatic, and colorectal cancers. We also discuss how the molecules responsible for increased matrix stiffness and the signaling pathways activated by the enhanced stiffness can be manipulated as a therapeutic strategy for cancer.

Abstract Periostin (POSTN), a member of the matricellular protein family, is a secreted adhesion-related protein produced in the periosteum and periodontal ligaments. Matricellular proteins are a nonstructural family of extracellular matrix (ECM) proteins that regulate a wide range of biological processes in both normal and pathological conditions. Recent studies have demonstrated the key roles of these ECM proteins in the tumor microenvironment. Furthermore, periostin is an essential regulator of bone and tooth formation and maintenance, as well as cardiac development. Also, periostin interacts with multiple cell-surface receptors, especially integrins, and triggers signals that promote tumor growth. According to recent studies, these signals are implicated in cancer cell survival, epithelial-mesenchymal transition (EMT), invasion, and metastasis. In this review, we will summarize the most current data regarding periostin, its structure and isoforms, expressions, functions, and regulation in normal and cancerous tissues. Emphasis is placed on its association with cancer progression, and also future potential for periostin-targeted therapeutic approaches will be explored.

Background & Objective: In order to enhance the expression of soluble proteins and facilitate their purification and development of multi-functional polypeptide , chimerical recombinant proteins have been invented . The purpose of this study was to construct ctxB-gfp-stxB gene cassette to measure the uptake and excretion of chimerical antigen in future studies. Materials & Methods: After preparation of primers for gfp gene as a reporter gene , ctxB and stxB, attempts were made to amplify the genes via the PCR techniques . The amplified genes were clone d in the pGEM vector; and after confirmation of the gene fragments, they were fused as ctxB-gfp-stxB. The gene cassette was thereafter sub-cloned in the pET28a(+) expression vector. E. coli Bl21 (DE3) was transformed by the recombinant vector pET28a(+), and the expression of the recombinant protein was investigated by IPTG induction and SDS-PAGEelectrophoresis. Results: The amplified genes were cloned in the pGEM vector, and were confirmed via PCR, restriction enzymes, and sequence analyzing system. The confirmed gene fragments were mixed together as ctxB-gfp-stxB . The existence of the gene cassette was confirmed after sub-cloning. The expression was not observed for this gene cassette in E . coli. Conclusion: The presence of a large number of E. coli rare codons in ctxB and stxB gene sequences precluded the expression of the gene cassette in E. coli; it, therefore, requires the discovery of a suitable host cell for its expression and optimization. Given the gene cassette structure and position of restriction enzymes on the constructed fragment, this gene can be replaced with different genes and can produce a variety of gene fragments.

Background and Objective: Shiga toxin (STx) is the main virulence factor in Shigella Dysenteriae type I and is composed of an enzymatic subunit STxA monomer and a receptor-binding STxB homopentamer. Shigella toxin B subunit (STxB) is a non-toxic homopentameric protein responsible for toxin binding and internalization into target cells by interacting with glycolipid (Gb3). Cholera toxin B subunit (CTB) has been known as a mucosal adjuvant for vaccines and genetic fusions of CTB with several hetroantigens such as stxB and can increase humoral and mucosal immunity response.Materials and Methods: In this study, after primer designing, the ctxB and stxB genes were amplified by PCR and cloned into the pGEM-T vector. The stxB gene with a nonfurin linker was fused to the ctB gene in the pGEM vector via the restriction enzyme method and thereafter the fused genes of ctB-stxB were subcloned in the pET28a(+) as an expression vector. The expressed chimeric protein was induced with IPTG and evaluated via the SDS.PAGE and Western blot techniques. Result: The pET28a (+)/ctxB-stxB expression vector was confirmed by endonuclease digestion, PCR, and sequence analysis. The CTB-STB fusion protein was confirmed by the SDS-PAGE and Western-blot. Conclusion: The CTB-STB recombinant protein can be used as a new and desirable mucosal vaccine for Shigella Dysenteriae type I.

Background: In order to analyze the cecum-colon ecosystem and the treatment of the cecal impaction and hindgut acidosis, cecal cannulation is needed. It is essential to select a simple, fast and inexpensive cecal cannulation method. Because of different complications in general anesthesia, the standing surgery is known as a better option for the horse emergency surgery. Objective: The objective of the present study was to design a simple, fast and inexpensive cecal cannulation method in standing horses.For the standing surgery, a new approach was designed and experimented on four horses. Materials and Methods: For this purpose, at first a cannula with approximately 7cm, 2cm and 2.6cm in length, internal and external diameters, respectively was designed. Immediately before the standing surgery, the horses were sedated with xylazine (1mg/kg) and morphine (0.3 mg/kg). After incising the subcutaneous tissue, the external abdominal oblique, internal abdominal oblique and transverse abdominis muscles were opened by grid incision. The peritoneum was bluntly perforated and the abdomen was exposed. The muscles were separated only enough to permit one hand to enter the abdomen. The cecum was readily identified by palpation of the cecal base and the dorsoventrally oriented tenia. At this stage, a purse string was secured on the serosal surface of the cecum by nylon and a stab incision was made. Then the cannula was inserted into the cecum and the suture was tightened. Results: The surgery was successfully performed for all horses, however, some complications such as increasing body temperature, transient signs of colic, ileus, pneumoperitoneum, subcutaneous emphysema and necrosis of the borders of the skin in the sutural places were detected. All complications were alleviated by proper nursing management. Conclusion: The surgical method was successfully terminated. Therefore, the method is recommended as a simple and inexpensive emergency surgical method for cecum in order to conduct different investigation, diagnosis and treatment techniques.