Reduced T-cell repertoire restrictions in abatacept-treated rheumatoid arthritis patients.

BACKGROUND: CD28(neg) T cells, which display functional characteristic of oligoclonally expanded cytotoxic memory T lymphocytes, are believed to be pathologically relevant in rheumatoid arthritis manifestation. The CD28 co-stimulation blockade by abatacept can prevent the generation of CD28(neg) T-cell populations in these patients. METHODS: Samples were obtained before and after 12 months of abatacept therapy. T-cell phenotype and T-cell receptor diversity were evaluated by flow cytometry and complementarity-determining region-3 spectratyping, respectively, while telomerase reverse-transcriptase gene level was measured by real-time PCR. RESULTS: Abatacept induces a decrease of the percentage and number of CD4(+)CD28(neg) T cells and a reduction of T-cell repertoire restrictions; these features are directly correlated. Thymic output and telomerase activity are not modified by the therapy. CONCLUSIONS: Abatacept-induced decrease of peripheral T-cell repertoire restrictions can due to a reduced generation of senescent, chronically stimulated CD4(+)CD28(neg) T cells

Understanding the Roles of the Hedgehog Signaling Pathway during T-Cell Lymphopoiesis and in T-Cell Acute Lymphoblastic Leukemia (T-ALL)

: The Hedgehog (HH) signaling network is one of the main regulators of invertebrate and vertebrate embryonic development. Along with other networks, such as NOTCH and WNT, HH signaling specifies both the early patterning and the polarity events as well as the subsequent organ formation via the temporal and spatial regulation of cell proliferation and differentiation. However, aberrant activation of HH signaling has been identified in a broad range of malignant disorders, where it positively influences proliferation, survival, and therapeutic resistance of neoplastic cells. Inhibitors targeting the HH pathway have been tested in preclinical cancer models. The HH pathway is also overactive in other blood malignancies, including T-cell acute lymphoblastic leukemia (T-ALL). This review is intended to summarize our knowledge of the biological roles and pathophysiology of the HH pathway during normal T-cell lymphopoiesis and in T-ALL. In addition, we will discuss potential therapeutic strategies that might expand the clinical usefulness of drugs targeting the HH pathway in T-ALL

Apoptotic-induced effects of acacia catechu willd. Extract in human colon cancer cells

The research for innovative treatments against colon adenocarcinomas is still a great challenge. Acacia catechu Willd. heartwood extract (AC) has health-promoting qualities, especially at the gastrointestinal level. This study characterized AC for its catechins content and investigated the apoptosis-enhancing effect in human colorectal adenocarcinoma HT-29 cells, along with its ability to spare healthy tissue. MTT assay was used to describe the time course, concentration dependence and reversibility of AC-mediated cytotoxicity. Cell cycle analysis and AV-PI and DAPI-staining were performed to evaluate apoptosis, together with ROS formation, mitochondrial membrane potential (MMP) changes and caspase activities. Rat ileum and colon rings were tested for their viability and functionality to explore AC effects on healthy tissue. Quantitative analysis highlighted that AC was rich in (\ub1)-catechin (31.5 \ub1 0.82 mg/g) and ( 12)-epicatechin (12.5 \ub1 0.42 mg/g). AC irreversibly decreased cell viability in a concentration-dependent, but not time-dependent fashion. Cytotoxicity was accompanied by increases in apoptotic cells and ROS, a reduction in MMP and increases in caspase-9 and 3 activities. AC did not affect rat ileum and colon rings\u2019 viability and functionality, suggesting a safe profile toward healthy tissue. The present findings outline the potential of AC for colon cancer treatment

Effectiveness of a training course on smoking cessation knowledge and behaviour for health profession students. The SISMA project

Introduction. University students are at risk of starting smoking or continuing and increasing the consumption of tobacco products. The aim of the study was to assess the impact of the training course, Sisma Project, about smoking in healthcare degree courses, in terms of knowledge, behaviour and to evaluate the course. Methods. SISMA project was a pre- post study about an intervention delivered to healthcare profession students about smoking and smoking cessation. It had a before-after design and was an online optional course available on the eLearning platform Moodle 2. The course was structured in four lessons of sixty minutes, a debate among experts and a final test of evaluation. The McNemar test was used to measure the effectiveness of Sisma on smoking behaviour of students after the intervention. Students rated the course assigning a score from one to ten, and expressed free comments about point of strength and weakness of Sisma project. Results. The participants were 365 students, 28.5% males and 71.5% females, most were nursing 194 (53.2%) and dental hygienists students 105 (28.8%). Current smokers were 161 (44.1%) before and 142 (38.9%) after the course, there was statistical significant difference in smoking status after attending the course (p < 0.001). Students evaluated the course giving a high score with a mean of 8.13 (SD: 1.1); the main points of strength were the content (33.2%), the structure (15.6%) and knowledge given by the course (12.6%). The main point of weakness were the online structure 62 (37%), problem related to length and time 17 (10%) and the final test 15 (9%). Discussion. Given the central role health professionals play in patient care, students need to be aware and trained in tobacco cessation techniques. Our results indicate that smoking behaviour significantly changed after attending a university course for smoking cessation and students appreciated its contents and structure