CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis

CTGF is a secreted matricellular protein with very complex biology. It has been shown to modulate many signaling pathways leading to cell adhesion and migration, angiogenesis, myofibroblast activation, and extracellular matrix deposition and remodeling, which together lead to tissue remodeling and fibrosis. It has been reported in the literature that inhibition of CTGF expression by siRNA prevents CCl4-induced liver fibrosis and can reverse fibrosis when administered after significant collagen deposition is observed. A monoclonal antibody to CTGF that is currently in clinical development (FG-3019) has demonstrated the ability to reverse vascular stiffening and improve cardiac function in a rat model of diabetic complications. FG-3019 has also exhibited activity in a murine radiation-induced pulmonary fibrosis model. When FG-3019 was administered to mice after a significant radiation-induced increase in lung density could be observed by CT imaging, the density of the lungs was observed to decrease over the period during which the antibody was administered and to remain stable after therapy had ceased. When considered together, these data indicate that inhibition of CTGF can prevent and reverse the process of fibrosis

Dairy products and total calcium intake at 13 years of age and its association with obesity at 21 years of age

Background/objectives: Dairy products and specifically calcium have been suggested to play a role in obesity development but more longitudinal evidence is still needed. The objective of this study was to assess the association between dairy products and total calcium intake at age 13 and body mass index at age 21. Subjects/methods: This longitudinal study included 2159 individuals from the Epidemiological Health Investigation of Teenagers cohort (EPITeen), Porto, Portugal, evaluated at ages 13 and 21. Assessment consisted of anthropometrics measurements and structured questionnaires namely a semi-quantitative food frequency questionnaire to appraise food consumption in the past 12 months. Linear regression models were run in 941 individuals with complete information of confounders: gender, follow-up period, parents’ education, physical activity, energy, and total calcium intake. Results: Negative association was found on total calcium intake at age 13 with BMI at age 21 (model 0: β = −0.059 (95% CI: −0.113, −0.004) and model 1: −0.057 (95% CI: −0.113, −0.002)), however, no statistically significant association was found when adjusting for energy intake (model 2: β = −0.031 (95% CI: −0.110, 0.047). There were no associations between milk, yogurt, and cheese consumption at age 13 and BMI at age 21 when adjusting for confounders. Conclusions: This study did not support an independent effect of dairy products or total calcium intake in adolescence on later early adulthood adiposity.This study was funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education) (POCI-01-0145-FEDER-016829), under the project MetHyOS (Ref. FCT PTDC/DTP-EPI/6506/2014) and the Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013). Also this study was developed with the support of the research teams of the Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine of Porto University; the EPIUnit—Public Health Institute of Porto University; and the EPITeen Cohort Study

Year in review in Intensive Care Medicine 2011: III. ARDS and ECMO, weaning, mechanical ventilation, noninvasive ventilation, pediatrics and miscellanea

SCOPUS: re.jinfo:eu-repo/semantics/publishe

Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates

The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-κB as central player, whereas expression of type I interferon (IFN)-β is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI