Using association rules mining to explore pattern of Chinese medicinal formulae (prescription) in treating and preventing breast cancer recurrence and metastasis.

published_or_final_versio

CLEC5A-mediated enhancement of the inflammatory response in myeloid cells contributes to influenza virus pathogenicity in vivo

Human infections with influenza viruses exhibit mild to severe clinical outcomes as a result of complex virus-host interactions. Induction of inflammatory mediators via pattern recognition receptors may dictate subsequent host responses for pathogen clearance and tissue damage. We identified that human C-type lectin domain family 5 member A (CLEC5A) interacts with the hemagglutinin protein of influenza viruses expressed on lentiviral pseudoparticles through lectin screening. Silencing CLEC5A gene expression, blocking influenza-CLEC5A interactions with anti-CLEC5A antibodies, or dampening CLEC5A-mediated signaling using a spleen tyrosine kinase inhibitor consistently reduced the levels of proinflammatory cytokines produced by human macrophages without affecting the replication of influenza A viruses of different subtypes. Infection of bone marrow-derived macrophages from CLEC5A-deficient mice showed reduced levels of tumor necrosis factor alpha (TNF-α) and IP-10 but elevated alpha interferon (IFN-α) compared to those of wild-type mice. The heightened type I IFN response in the macrophages of CLEC5A-deficient mice was associated with upregulated TLR3 mRNA after treatment with double-stranded RNA. Upon lethal challenges with a recombinant H5N1 virus, CLEC5A-deficient mice showed reduced levels of proinflammatory cytokines, decreased immune cell infiltration in the lungs, and improved survival compared to the wild-type mice, despite comparable viral loads noted throughout the course of infection. The survival difference was more prominent at a lower dose of inoculum. Our results suggest that CLEC5A-mediated enhancement of the inflammatory response in myeloid cells contributes to influenza pathogenicity in vivo and may be considered a therapeutic target in combination with effective antivirals. Well-orchestrated host responses together with effective viral clearance are critical for optimal clinical outcome after influenza infections.published_or_final_versio

Contribution of the cyclic nucleotide gated channel subunit, CNG-3, to olfactory plasticity in Caenorhabditis elegans.

In Caenorhabditis elegans, the AWC neurons are thought to deploy a cGMP signaling cascade in the detection of and response to AWC sensed odors. Prolonged exposure to an AWC sensed odor in the absence of food leads to reversible decreases in the animal's attraction to that odor. This adaptation exhibits two stages referred to as short-term and long-term adaptation. Previously, the protein kinase G (PKG), EGL-4/PKG-1, was shown necessary for both stages of adaptation and phosphorylation of its target, the beta-type cyclic nucleotide gated (CNG) channel subunit, TAX-2, was implicated in the short term stage. Here we uncover a novel role for the CNG channel subunit, CNG-3, in short term adaptation. We demonstrate that CNG-3 is required in the AWC for adaptation to short (thirty minute) exposures of odor, and contains a candidate PKG phosphorylation site required to tune odor sensitivity. We also provide in vivo data suggesting that CNG-3 forms a complex with both TAX-2 and TAX-4 CNG channel subunits in AWC. Finally, we examine the physiology of different CNG channel subunit combinations

Language barrier and its relationship to diabetes and diabetic retinopathy

10.1186/1471-2458-12-781BMC Public Health121

Impact of Migration and Acculturation on Prevalence of Type 2 Diabetes and Related Eye Complications in Indians Living in a Newly Urbanised Society

Background: Health of migrants is a major public health challenge faced by governments and policy makers. Asian Indians are among the fastest growing migration groups across Asia and the world, but the impact of migration and acculturation on diabetes and diabetes-related eye complications among Indians living in urban Asia remains unclear. Methodologies/Principal Findings: We evaluated the influence of migration and acculturation (i.e., migration status and length of residence) on the prevalence of type-2 diabetes mellitus (T2DM) and diabetes-related eye complications (diabetic retinopathy (DR) and cataract), among first-generation (defined as participant born in India with both parents born in India, n = 781) and second-generation (participants born in Singapore with both parents born in India, n = 1,112) Indian immigrants from a population-based study of Adult Indians in Singapore. Diabetes was defined as HbA1c≥6.5%, use of diabetic medication or a physician diagnosis of diabetes. Retinal and lens photographs were graded for the presence of DR and cataract. Compared to first generation immigrants, second generation immigrants had a higher age- and gender-standardized prevalence of T2DM (34.4% versus 29.0%, p<0.001), and, in those with T2DM, higher age- and gender-standardized prevalence of DR (31.7% versus 24.8%, p<0.001), nuclear cataract (13.6% versus 11.6%, p<0.001), and posterior sub-capsular cataract (6.4% versus 4.6%, p<0.001). Among first generation migrants, longer length of residence was associated with significantly younger age of diagnosis of diabetes and greater likelihood of having T2DM and diabetes-related eye complications. Conclusion: Second generation immigrant Indians and longer length of residence are associated with higher prevalence of diabetes and diabetes-related complications (i.e., DR and cataract) among migrant Indians living in Singapore. These data highlight potential worldwide impacts of migration patterns on the risk and burden of diabetes

Prevalence of Cataract Surgery and Visual Outcomes in Indian Immigrants in Singapore: The Singapore Indian Eye Study

10.1371/journal.pone.0075584PLoS ONE810-POLN

Construction of large-volume tissue mimics with 3D functional vascular networks

We used indirect stereolithography (SL) to form inner-layered fluidic networks in a porous scaffold by introducing a hydrogel barrier on the luminal surface, then seeded the networks separately with human umbilical vein endothelial cells and human lung fibroblasts to form a tissue mimic containing vascular networks. The artificial vascular networks provided channels for oxygen transport, thus reducing the hypoxic volume and preventing cell death. The endothelium of the vascular networks significantly retarded the occlusion of channels during whole-blood circulation. The tissue mimics have the potential to be used as an in vitro platform to examine the physiologic and pathologic phenomena through vascular architecture.ope