Therapeutic Targeting of IL-11 for Chronic Lung Disease

Interleukin (IL)-11 was originally recognized as an immunomodulatory and hematopoiesis-inducing cytokine. However, although IL-11 is typically not found in healthy individuals, it is now becoming evident that IL-11 may play a role in diverse pulmonary conditions, including IPF, asthma, and lung cancer. Additionally, experimental strategies targeting IL-11, such as humanized antibodies, have recently been developed, revealing the therapeutic potential of IL-11. Thus, further insight into the underlying mechanisms of IL-11 in lung disease may lead to the ability to interfere with pathological conditions that have a clear need for disease-modifying treatments, such as IPF. In this review, we outline the effects, expression, signaling, and crosstalk of IL-11 and focus on its role in lung disease and its potential as a therapeutic target

Does the pain-protective GTP cyclohydrolase haplotype significantly alter the pattern or severity of pain in humans with chronic pancreatitis?

<p>Abstract</p> <p>Background</p> <p>Pain is often a dominant clinical feature of chronic pancreatitis but the frequency and severity is highly variable between subjects. We hypothesized that genetic polymorphisms contribute to variations in clinical pain patterns. Since genetic variations in the GTP cyclohydrolase (GCH1) gene have been reported to protect some patients from pain, we investigated the effect of the "pain protective haplotype" in well characterized patients with chronic pancreatitis (CP) or recurrent acute pancreatitis (RAP) from the North American Pancreatitis Study 2 (NAPS2).</p> <p>Results</p> <p>Subjects in the NAPS2 study were asked to rank their pain in one of 5 categories reflecting different levels of pain frequency and severity. All subjects were genotyped at rs8007267 and rs3783641 to determine the frequency of the GCH1 pain-protective haplotype. In Caucasian subjects the frequency of the pain-protective GCH1 haplotype was no different in the control group (n = 236), CP patients (n = 265), RAP patients (N = 131), or in CP patients subclassified by pain category compared to previously reported haplotype frequencies in the general Caucasian population.</p> <p>Conclusion</p> <p>The GCH1 pain-protective haplotype does not have a significant effect on pain patterns or severity in RAP or CP. These results are important for helping to define the regulators of visceral pain, and to distinguish different mechanisms of pain.</p

Immune state is associated with natural dietary variation in wild mice Mus musculus domesticus

1. The ability, propensity and need to mount an immune response vary both among individuals and within a single individual over time.2. A wide array of parameters have been found to influence immune state in carefully controlled experiments, but we understand much less about which of these parameters are important in determining immune state in wild populations.3. Diet can influence immune responses, for example when nutrient availability is limited. We therefore predict that natural dietary variation will play a role in modulating immune state, but this has never been tested.4. We measured carbon and nitrogen stable isotope ratios in an island population of house mice Mus musculus domesticus as an indication of dietary variation, and the expression of a range of immune?related genes to represent immune state.5. After accounting for potential confounding influences such as age, sex and helminth load, we found a significant association between carbon isotope ratio and levels of immune activity in the mesenteric lymph nodes, particularly in relation to the inflammatory response.6. This association demonstrates the important interplay between diet and an animal's response to immune challenges, and therefore potentially its susceptibility to disease

Researching curriculum, policy and leadership in mathematics education

This chapter reviews research regarding the official mathematics curriculum and its enactment, the educational leadership to support this enactment, and the associated influential policy, such as national testing. It explores the interrelationships between inherent issues such as the potential influence of textbooks, curriculum equity, and the complexities of implementing numeracy across disciplines. Substantial research has led to the development of robust theoretical models to inform both future research and practical developments across a range of aspects of curriculum, policy and leadership. However, the seemingly diverse research perspectives are all drawn towards the teacher in the classroom as the critical context for further research

The ACE gene I/D polymorphism does not affect the susceptibility to or prognosis of PBC

WOS: 000262761100006PubMed ID: 19119484Background/aims: Primary biliary cirrhosis is an autoimmune liver disease that is strongly influenced by poorly defined, complex genetic factors. Alterations of the renin-angiotensin. system have been implicated in the pathogenesis of various diseases. A deletion polymorphism of a 287-bp fragment of intron 16 of the angiotensin converting enzyme gene allele results in higher levels of circulating enzyme. Angiotensin converting enzyme deletion genotype has been linked to hypertension and sarcoidosis and has been reported to regulate liver fibrosis in HCV-mediated liver disease. We investigated the frequency of the Angiotensin converting enzyme gene insertion/deletion polymorphism in primary biliary cirrhosis patients. Methods: 52 biopsy-proven primary biliary cirrhosis patients and 98 healthy controls were evaluated. Angiotensin converting enzyme insertion/deletion polymorphism was detected by polymerase chain reaction amplification of a genomic DNA fragment on intron 16 of the angiotensin converting enzyme gene. Clinical phenotype of primary biliary cirrhosis was verified with positive anti-mitochondrial antibody or M2 antibody, demonstration of cholestatic liver enzymes, and staging of liver biopsy. The differences between these variables among different genotypes were noted. Results: There was no significant difference in. genotypes and allele frequency between the primary biliary cirrhosis group and controls. The D allele frequency was 54% in primary biliary cirrhosis cases and 55% in controls (p=ns). Furthermore, there was no significant difference in clinical features between patients with angiotensin converting enzyme-insertion, or insertion/deletion genotypes vs. patients with angiotensin converting enzyme-deletion genotype. Conclusions: In our limited sample, the angiotensin converting enzyme deletion genotype did not make a. significant contribution to the pathogenesis or progression of primary biliary cirrhosis