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Allicin (diallyl thiosulfinate) is the best-known biologically active component in freshly crushed garlic extract. We developed a novel, simple method to isolate active allicin, which yielded a stable compound in aqueous solution amenable for use in in vitro and in vivo studies. We focused on the in vitro effects of allicin on cell proliferation of colon cancer cell lines HCT-116, LS174T, HT-29, and Caco-2 and assessed the underlying mechanisms. This allicin preparation exerted a time- and dose-dependent cytostatic effect on these cells at concentrations ranging from 6.2 to 310 μM. Treatment with allicin resulted in HCT-116 apoptotic cell death as demonstrated by enhanced hypodiploid DNA content, decreased levels of B-cell non-Hodgkin lymphoma-2 (Bcl-2), increased levels of bax and increased capability of releasing cytochrome c from mitochondria to the cytosol. Allicin also induced translocation of NF-E2-related factor-2 (Nrf2) to the nuclei of HCT-116 cells. Luciferase reporter gene assay showed that allicin induces Nrf2-mediated luciferase transactivation activity. SiRNA knock down of Nrf2 significantly affected the capacity of allicin to inhibit HCT-116 proliferation. These results suggest that Nrf2 mediates the allicin-induced apoptotic death of colon cancer cells.  相似文献   
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Objectives

Anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has demonstrated success in the treatment of advanced NSCLC. Recently, PD-1/PD-L1 blockade also has demonstrated interesting results in small trials of neoadjuvant treatment in stage IB to IIIA NSCLC. In addition, several clinical trials using anti–PD-1/PD-L1 immunotherapy as an adjuvant or neoadjuvant treatment in patients with resectable stage NSCLC are ongoing. However, few analyses of anti–PD-1/PD-L1 immunotherapy–related biomarkers in early-stage squamous cell lung carcinoma (SqCLC) have been reported. In this study, we evaluated PD-L1 protein expression, tumor mutation burden, and expression of an immune gene signature in early-stage SqCLC, providing data for identifying the potential role for patients with anti–PD-1/PD-L1 treatment in early-stage SqCLC.

Methods

A total of 255 specimens from patients with early-stage SqCLC were identified within participating centers of the Strategic Partnering to Evaluate Cancer Signatures program. PD-L1 protein expression by immunohistochemistry was evaluated by using the Dako PD-L1 22C3 pharmDx kit on the Dako Link 48 auto-stainer (Dako, Carpinteria, CA). Tumor mutation burden (TMB) was calculated on the basis of data from targeted genome sequencing. The T-effector and interferon gamma (IFN-γ) gene signature was determined from Affymetrix gene chip data (Affymetrix, Santa Clara, CA) from frozen specimens.

Results

The prevalence of PD-L1 expression was 9.8% at a tumor proportion score cutoff of at least 50%. PD-L1 mRNA and programmed cell death 1 ligand 2 mRNA positively correlated with PD-L1 protein expression on tumor cells (TCs) and tumor-infiltrating immune cells. PD-L1 protein expression on tumor-infiltrating immune cells was correlated with the T-effector and IFN-γ gene signature (p < 0.001), but not with TMB. For TCs, all of these biomarkers were independent of each other and neither PD-L1 protein expression, TMB, or T-effector and IFN-γ gene signatures were independently prognostic for patient outcomes.

Conclusions

Evaluation of PD-L1 expression, TMB, and T-effector and IFN-γ gene signatures in the cohort with early-stage SqCLC found them to be independent of each other, and none was associated with overall survival. Our results also support the hypothesis that PD-L1 expression is regulated by an intrinsic mechanism on TCs and an adaptive mechanism on immune cells.  相似文献   
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Clinical Rheumatology - Both Sjögren’s syndrome (SS) and non-autoimmune sicca syndrome (nSS) can show symptoms of dry eyes and a dry mouth, and objective reductions in tear and saliva...  相似文献   
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Fish consumption is of great importance to children’s health and is essential for neurodevelopment, which begins in pregnancy and continues throughout early childhood and into adolescence. However, fish consumption presents conflicting health outcomes associated with its nutritional benefits and its adverse contaminant risks, because both avoiding fish as well as the consumption of contaminated fish can potentially harm children. This may be challenging to communicate. The present review was performed to assess the current knowledge and recommendations around ‘smart’ fish-consumption decisions. Health Canada advises, as well as other advisories and guides, that fish should be consumed for its health benefits, while also informing consumers, especially women and children, to limit certain fish consumption. The current literature must attempt to handle the challenges inherent in communicating the dilemmas of children’s fish consumption. Incorporation of new knowledge translation strategies are proposed as a means to raise the level of knowledge about optimal fish consumption practices.  相似文献   
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Background: The first studies concerning changes in moral virtues during alcohol addiction therapy were published during the last decade. However, as all of these studies applied a variable-oriented approach, it is impossible to capture differences between starting points and changes in variables of interest. 

Method: In this study, we employed a person-oriented approach to identify trajectories of change in two moral virtues—forgiveness and gratitude—during alcohol addiction treatment. The sample consisted of 358 alcohol-dependent individuals who were receiving outpatient therapy. Measurements were taken (1) at the beginning of the basic treatment, (2) after its completion (5–7?weeks from baseline), and (3) about six months later. Three forgiveness scales and the Gratitude Questionnaire (GQ-6) were used to assess the patients’ moral virtues. 

Results: Latent class growth analysis (LCGA) revealed four trajectories for self-forgiveness and gratitude, and three trajectories for forgiveness of others and feeling forgiven by God. For patients with a low baseline level of moral virtues, the changes varied depending on the kind of moral virtue. Patients with a relatively high initial level of moral virtues maintained that level in subsequent measurements. Significant correlates of trajectory class membership were gender, education, age, religiosity, diagnosis of coexisting psychiatric disorders, and frequency of attending Alcoholics Anonymous (AA) meetings. 

Conclusions: This study highlights the clinical importance of considering differences at the baseline level and in changes of forgiveness and gratitude, as well as personal and alcohol-related correlates of trajectory group membership among people who participate in alcohol addiction therapy.  相似文献   
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