754 research outputs found
Chemokine CXCL12 activates dual CXCR4 and CXCR7-mediated signaling pathways in pancreatic cancer cells
<p>Abstract</p> <p>Background</p> <p>Previously assumed to be a select ligand for chemokine receptor CXCR4, chemokine CXCL12 is now known to activate both CXCR4 and CXCR7. However, very little is known about the co-expression of these receptors in cancer cells.</p> <p>Methods</p> <p>We used immunohistochemistry to determine the extent of co-expression in pancreatic cancer tissue samples and immunoblotting to verify expression in pancreatic cancer cell lines. In cell culture studies, siRNA was used to knock down expression of CXCR4, CXCR7, K-Ras and β-arrestin -2 prior to stimulating the cells with CXCL12. Activation of the mitogen-activated protein kinase pathway (MAPK) was assessed using both a Raf-pull down assay and western blotting. The involvement of the receptors in CXCL12-mediated increases in cell proliferation was examined via an ATP-based proliferation assay.</p> <p>Results</p> <p>First, we discovered frequent CXCR4/CXCR7 co-expression in human pancreatic cancer tissues and cell lines. Next, we observed consistent increases in ERK1/2 phosphorylation after exposure to CXCL12 or CXCL11, a CXCR7 agonist, in pancreatic cancer cell lines co-expressing CXCR4/CXCR7. To better characterize the receptor-mediated pathway(s), we knocked down CXCR4 or CXCR7, exposed the cells to CXCL12 and examined subsequent effects on ERK1/2. We observed that CXCR7 mediates the CXCL12-driven increase in ERK1/2 phosphorylation. Knockdown of CXCR4 expression however, decreased levels of K-Ras activity. Conversely, KRAS knockdown greatly reduced CXCL12-mediated increases in ERK1/2 phosphorylation. We then evaluated the role of β-arrestin-2, a protein directly recruited by chemokine receptors. We observed that β-arrestin-2 knockdown also inhibited increases in ERK1/2 phosphorylation mediated by both CXCR4 and CXCR7. Finally, we investigated the mechanism for CXCL12-enhanced cell proliferation and found that either receptor can modulate cell proliferation.</p> <p>Conclusions</p> <p>In summary, our data demonstrate that CXCR4 and CXCR7 are frequently co-expressed in human pancreatic cancer tissues and cell lines. We show that β-arrestin-2 and K-Ras dependent pathways coordinate the transduction of CXCL12 signals. Our results suggest that the development of therapies based on inhibiting CXCL12 signaling to halt the growth of pancreatic cancer should be focused at the ligand level in order to account for the contributions of both receptors to this signaling pathway.</p
Adherence to anti-tuberculosis treatment among pulmonary tuberculosis patients: a qualitative and quantitative study
BACKGROUND: Tuberculosis (TB) patients have difficulty following a long-term treatment regimen. Efforts to improve treatment outcomes require better understanding of adherence as a complex behavioral issue and of the particular barriers to and facilitators of patient adherence. METHODS: This study was carried out in Jiangsu Province of China with both quantitative and qualitative approaches. For the quantitative study, 780 sputum-smear positive TB patients consecutively registered since 2006 in 13 counties (districts) were queried with a structured questionnaire. Patients who had missed 10% of their total prescribed doses of TB drugs were deemed as non-adherent. Risks for non-adherence were estimated by computing odds ratios (ORs) and their 95% confidence intervals (95% CIs) using a logistic regression model. We also invited 20 TB patients and 10 local health workers for in-depth interviews. We then used content analysis based on this qualitative study to explore factors associated with non-adherence. RESULTS: The proportion of non-adherence among 670 patients was 12.2%. Univariate analysis showed that patients, who were illiterate, divorced/widowed, lacked health insurance and were migrants, were more likely to be non-adherent. The crude ORs(95%CIs) were 2.38(1.37-4.13), 2.42(1.30-4.52), 1.89(1.07-3.32) and 1.98(1.03-3.83), respectively. The risk of non-adherence was lower among patients whose treatment was given under direct observation by village doctors or regular home visits by health workers, with ORs (95% CIs) of 0.19(0.10-0.36) and 0.23(0.10-0.51), respectively. In multivariate analysis, factors associated with non-adherence included illiteracy (OR: 2.42; 95% CI: 1.25-4.67) and direct observation by village doctors (OR: 0.23; 95% CI: 0.11-0.45). The in-depth interviews indicated that financial burdens and extra medical expenditures, adverse drug reactions, and social stigma were additional potential factors accounted for non-adherence. CONCLUSION: More importance should be given to treatment adherence under the current TB control program. Heavy financial burdens, lack of social support, adverse drug reactions and personal factors are associated with non-adherence. Direct observation and regular home visits by health workers appear to reduce the risk of non-adherence. More patient-centered interventions and greater attention to structural barriers are needed to improve treatment adherence
Experimental measurement of the quantum geometric tensor using coupled qubits in diamond
Geometry and topology are fundamental concepts, which underlie a wide range
of fascinating physical phenomena such as topological states of matter and
topological defects. In quantum mechanics, the geometry of quantum states is
fully captured by the quantum geometric tensor. Using a qubit formed by an NV
center in diamond, we perform the first experimental measurement of the
complete quantum geometric tensor. Our approach builds on a strong connection
between coherent Rabi oscillations upon parametric modulations and the quantum
geometry of the underlying states. We then apply our method to a system of two
interacting qubits, by exploiting the coupling between the NV center spin and a
neighboring C nuclear spin. Our results establish coherent dynamical
responses as a versatile probe for quantum geometry, and they pave the way for
the detection of novel topological phenomena in solid state
A systematic review of maggot debridement therapy for chronically infected wounds and ulcers
SummaryObjectiveThis study aimed to systematically evaluate maggot debridement therapy (MDT) in the treatment of chronically infected wounds and ulcers.MethodsWe performed a meta-analysis referring to the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We searched for published articles in the following databases: PubMed, Web of Science, Embase, Wanfang (Chinese), and the China National Knowledge Infrastructure (CNKI). The latest search was updated on March 14, 2014. For dichotomous outcomes, the effects of MDT were expressed as the relative risk (RR) and 95% confidence interval (CI). For continuous outcomes with different measurement scales, we calculated the standardized mean difference (SMD). The pooled effects were estimated using a fixed effect model or random effect model based on the heterogeneity test. Subgroup analyses were performed according to the types of wounds or ulcers.ResultsMDT had a significantly increased positive effect on wound healing compared with conventional therapies, with a pooled RR of 1.80 (95% CI 1.24–2.60). The subgroup analysis revealed that the combined RRs were 1.79 (95% CI 0.95–3.38) for patients with diabetic foot ulcers (DFU) and 1.70 (95% CI 1.28–2.27) for patients with other types of ulcers. The time to healing of the ulcers was significantly shorter among patients treated with MDT, with a pooled SMD of −0.95 (95% CI −1.24, −0.65). For patients with DFU, the SMD was −0.79 (95% CI −1.18, −0.41), and for patients with other types of ulcers, the SMD was −1.16 (95% CI −1.63, −0.69).ConclusionMDT not only shortened the healing time but also improved the healing rate of chronic ulcers. Therefore, MDT may be a feasible alternative in the treatment of chronic ulcers
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