Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field

PERAN ORANG TUA DALAM MEMBINA NILAI KARAKTER ANAK DI KECAMATAN SIMPANG TIGA ACEH BESAR

ABSTRAKRahmayanti KS, Sri. 2016. Peran Orang Tua Dalam Membina Nilai Karakter Anak di Kecamatan Simpang Tiga Kabupaten Aceh Besar. Skripsi, Jurusan Pendidikan Kesejahteraan Keluarga, Fakultas Keguruan dan Ilmu Pendidikan, Universitas Syiah Kuala. Pembimbing:(1)Dr. Anizar Ahmad, M.Pd., (2). Dra. Fitriana, M.SI.Kata Kunci: Nilai Karakter Anak, Peran Orang TuaPeran orang tua adalah partisipasi atau kesadaran jiwa orang tua untuk memperdulikan anaknya, terutama dalam hal memberikan dan memenuhi kebutuhan hidup anaknya baik dari segi sosial maupun material. Penelitian ini untuk mengetahui usaha orang tua dalam membina nilai karakter anak di Kecamatan Simpang Tiga Kabupaten Aceh Besar. Penelitian ini bertujuan untuk (1) mengetahui usaha yang dilakukan orang tua dalam membina nilai karakter anak dan (2) mengetahui sistem pengawasan yang diterapkan oleh orang tua terhadap anak. Metode yang digunakan dalam penelitian ini adalah metode deskriptif kuantitatif. Data penelitian ini bersumber dari orang tua yang memiliki anak usia 4 sampai 10 tahun berjumlah 28 keluarga, pengumpulan data menggunakan kuisioner. Pengolahan data penelitian ini menggunakan rumus persentase. Simpulan penelitian ini berpengaruh pada usaha orang tua dalam membina nilai karakter anak, walau sebagian kecil yang mengetahui nilai-nilai karakter, tetapi sebagian besar sudah berusaha menanamkan nilai karakter tersebut. Lebih dari setengah responden menanamkan nilai religius kepada anak dengan tujuan agar anak mempunyai akhlak yang mulia kedepannya. Sedangkan yang berperan dalam membina nilai karakter anak adalah suami dan istri. Sistem pengawasan yang diterapkan orang tua berpengaruh terhadap pembentukkan nilai karakter anak. Seluruh anak termasuk kedalam katagori anak yang mudah bersahabat. Penanaman nilai karakter pada anak di mulai pada awal masa kanak-kanak ketika berumur 2-6 tahun. Responden juga menerapkan perilaku disiplin kepada anak karena usia awal kanak-kanak merupakan usia yang masih rentan, dan akan meniru semua yang dikerjakan oleh orang tuanya. Saran untuk orang tua agar dapat mendidik anaknya dengan baik, tidak mengedepankan emosi, dapat meluangkan waktu, adanya komunikasi yang dibina orang tua dengan anak, dan jangan bersikap apatis terhadap apa yang dikerjakan sianak

Role of SPI-1 Secreted Effectors in Acute Bovine Response to Salmonella enterica Serovar Typhimurium: A Systems Biology Analysis Approach

Salmonella enterica Serovar Typhimurium (S. Typhimurium) causes enterocolitis with diarrhea and polymorphonuclear cell (PMN) influx into the intestinal mucosa in humans and calves. The Salmonella Type III Secretion System (T3SS) encoded at Pathogenicity Island I translocates Salmonella effector proteins SipA, SopA, SopB, SopD, and SopE2 into epithelial cells and is required for induction of diarrhea. These effector proteins act together to induce intestinal fluid secretion and transcription of C-X-C chemokines, recruiting PMNs to the infection site. While individual molecular interactions of the effectors with cultured host cells have been characterized, their combined role in intestinal fluid secretion and inflammation is less understood. We hypothesized that comparison of the bovine intestinal mucosal response to wild type Salmonella and a SipA, SopABDE2 effector mutant relative to uninfected bovine ileum would reveal heretofore unidentified diarrhea-associated host cellular pathways. To determine the coordinated effects of these virulence factors, a bovine ligated ileal loop model was used to measure responses to wild type S. Typhimurium (WT) and a ΔsipA, sopABDE2 mutant (MUT) across 12 hours of infection using a bovine microarray. Data were analyzed using standard microarray analysis and a dynamic Bayesian network modeling approach (DBN). Both analytical methods confirmed increased expression of immune response genes to Salmonella infection and novel gene expression. Gene expression changes mapped to 219 molecular interaction pathways and 1620 gene ontology groups. Bayesian network modeling identified effects of infection on several interrelated signaling pathways including MAPK, Phosphatidylinositol, mTOR, Calcium, Toll-like Receptor, CCR3, Wnt, TGF-β, and Regulation of Actin Cytoskeleton and Apoptosis that were used to model of host-pathogen interactions. Comparison of WT and MUT demonstrated significantly different patterns of host response at early time points of infection (15 minutes, 30 minutes and one hour) within phosphatidylinositol, CCR3, Wnt, and TGF-β signaling pathways and the regulation of actin cytoskeleton pathway

Overexpression of cathepsin K during silica-induced lung fibrosis and control by TGF-β

BACKGROUND: Lung fibrosis is characterized by tissue remodeling resulting from an imbalance between synthesis and degradation of extracellular organic matrices. To examine whether cathepsin(s) (Cat) are important in the development of pulmonary fibrosis, we assessed the expression of four Cat known for their collagenolytic activity in a model of silica-induced lung fibrosis. METHODS: Different strains of mice were transorally instilled with 2.5 mg crystalline silica or other particles. Cat expression (Cat K, S, L and B) was quantified in lung tissue and isolated pulmonary cells by quantitative RT-PCR. In vitro, we assessed the effect of different cytokines, involved in lung inflammatory and fibrotic responses, on the expression of Cat K by alveolar macrophages and fibroblasts. RESULTS: In lung tissue, Cat K transcript was the most strongly upregulated in response to silica, and this upregulation was intimately related to the fibrotic process. In mouse strains known for their differential response to silica, we showed that the level of Cat K expression following silica treatment was inversely related to the level of TGF-β expression and the susceptibility of these strains to develop fibrosis. Pulmonary macrophages and fibroblasts were identified as Cat K overproducing cells in the lung of silicotic mice. In vitro, Cat K was downregulated in mouse and human lung fibroblasts by the profibrotic growth factor TGF-β1. CONCLUSION: Altogether, these data suggest that while Cat K may contribute to control lung fibrosis, TGF-β appears to limit its overexpression in response to silica particles

The ERK and JNK pathways in the regulation of metabolic reprogramming.

Most tumor cells reprogram their glucose metabolism as a result of mutations in oncogenes and tumor suppressors, leading to the constitutive activation of signaling pathways involved in cell growth. This metabolic reprogramming, known as aerobic glycolysis or the Warburg effect, allows tumor cells to sustain their fast proliferation and evade apoptosis. Interfering with oncogenic signaling pathways that regulate the Warburg effect in cancer cells has therefore become an attractive anticancer strategy. However, evidence for the occurrence of the Warburg effect in physiological processes has also been documented. As such, close consideration of which signaling pathways are beneficial targets and the effect of their inhibition on physiological processes are essential. The MAPK/ERK and MAPK/JNK pathways, crucial for normal cellular responses to extracellular stimuli, have recently emerged as key regulators of the Warburg effect during tumorigenesis and normal cellular functions. In this review, we summarize our current understanding of the roles of the ERK and JNK pathways in controlling the Warburg effect in cancer and discuss their implication in controlling this metabolic reprogramming in physiological processes and opportunities for targeting their downstream effectors for therapeutic purposes.Brunel Research Initiative & Enterprise Fund, Brunel University of London (to CB), Kay Kendall Leukemia Fund (KKL443) (to CB), 250 Great Minds Fellowship, University of Leeds (to SP), AMMF Cholangiocarcinoma Charity (to SP and PMC), and Bloodwise (17014) (to SP and CB)

The use of autologous platelet-leukocyte gels to enhance the healing process in surgery, a review

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Meniscal Allograft Transplants and New Scaffolding Techniques

A Clinical management of meniscal injuries has changed radically in recent years. We have moved from the model of systematic tissue removal (meniscectomy) to understanding the need to preserve the tissue. Based on the increased knowledge of the basic science of meniscal functions and their role in joint homeostasis, meniscus preservation and/or repair, whenever indicated and possible, are currently the guidelines for management. However, when repair is no longer possible or when facing the fact of the previous partial, subtotal or total loss of the meniscus, meniscus replacement has proved its clinical value. Nevertheless, meniscectomy remains amongst the most frequent orthopaedic procedures. Meniscus replacement is currently possible by means of meniscal allograft transplantation (MAT) which provides replacement of the whole meniscus with or without bone plugs/slots. Partial replacement has been achieved by means of meniscal scaffolds (mainly collagen or polyurethane-based). Despite the favourable clinical outcomes, it is still debatable whether MAT is capable of preventing progression to osteoarthritis. Moreover, current scaffolds have shown some fundamental limitations, such as the fact that the newly formed tissue may be different from the native fibrocartilage of the meniscus. Regenerative tissue engineering strategies have been used in an attempt to provide a new generation of meniscal implants, either for partial or total replacement. The goal is to provide biomaterials (acellular or cell-seeded constructs) which provide the biomechanical properties but also the biological features to replace the loss of native tissue. Moreover, these approaches include possibilities for patient-specific implants of correct size and shape, as well as advanced strategies combining cells, bioactive agents, hydrogels or gene therapy. Herein, the clinical evidence and tips concerning MAT, currently available meniscus scaffolds and future perspectives are discussed.I. F. Cengiz thanks the Portuguese Foundation for Science and Technology (FCT) for the Ph.D. scholarship (SFRH/BD/99555/2014). J. M. Oliveira also thanks the FCT for the funds provided under the program Investigador FCT 2012 and 2015 (IF/00423/2012 and IF/01285/2015).info:eu-repo/semantics/publishedVersio