Impact of sex, MHC, and age of recipients on the therapeutic effect of transferred leukocytes from cancer-resistant SR/CR mice

<p>Abstract</p> <p>Background</p> <p>Spontaneous Regression/Complete Resistant (SR/CR) mice are resistant to cancer through a mechanism that is mediated entirely by leukocytes of innate immunity. Transfer of leukocytes from SR/CR mice can confer cancer resistance in wild-type (WT) recipients in both preventative and therapeutic settings. In the current studies, we investigated factors that may impact the efficacy and functionality of SR/CR donor leukocytes in recipients.</p> <p>Results</p> <p>In sex-mismatched transfers, functionality of female donor leukocytes was not affected in male recipients. In contrast, male donor leukocytes were greatly affected in the female recipients. In MHC-mismatches, recipients of different MHC backgrounds, or mice of different strains, showed a greater negative impact on donor leukocytes than sex-mismatches. The negative effects of sex-mismatch and MHC-mismatch on donor leukocytes were additive. Old donor leukocytes performed worse than young donor leukocytes in all settings including in young recipients. Young recipients were not able to revive the declining function of old donor leukocytes. However, the function of young donor leukocytes declined gradually in old recipients, suggesting that an aged environment may contain factors that are deleterious to cellular functions. The irradiation of donor leukocytes prior to transfers had a profound suppressive effect on donor leukocyte functions, possibly as a result of impaired transcription. The cryopreserving of donor leukocytes in liquid nitrogen had no apparent effect on donor leukocyte functions, except for a small loss of cell number after revival from freezing.</p> <p>Conclusion</p> <p>Despite the functional suppression of donor leukocytes in sex- and MHC-mismatched recipients, as well as old recipients, there was a therapeutic time period during the initial few weeks during which donor leukocytes were functional before their eventual rejection or functional decline. The eventual rejection of donor leukocytes will likely prevent donor leukocyte engraftment which would help minimize the risk of transfusion-associated graft-versus-host disease. Therefore, using leukocytes from healthy donors with high anti-cancer activity may be a feasible therapeutic concept for treating malignant diseases.</p

Loss and Damage in the Rapidly Changing Arctic

Arctic climate change is happening much faster than the global average. Arctic change also has global consequences, in addition to local ones. Scientific evidence shows that meltwater of Arctic sources contributes to sea-level rise significantly while accounting for 35% of current global sea-level rise. Arctic communities have to find ways to deal with rapidly changing environmental conditions that are leading to social impacts such as outmigration, similarly to the global South. International debates on Loss and Damage have not addressed the Arctic so far. We review literature to show what impacts of climate change are already visible in the Arctic, and present local cases in order to provide empirical evidence of losses and damages in the Arctic region. This evidence is particularly well presented in the context of outmigration and relocation of which we highlight examples. The review reveals a need for new governance mechanisms and institutional frameworks to tackle Loss and Damage. Finally, we discuss what implications Arctic losses and damages have for the international debate

Cinnamomum cassia Bark in Two Herbal Formulas Increases Life Span in Caenorhabditis elegans via Insulin Signaling and Stress Response Pathways

Background: Proving the efficacy and corresponding mode of action of herbal supplements is a difficult challenge for evidence-based herbal therapy. A major hurdle is the complexity of herbal preparations, many of which combine multiple herbs, particularly when the combination is assumed to be vitally important to the effectiveness of the herbal therapy. This issue may be addressed through the use of contemporary methodology and validated animal models. Methods and Principal Findings: In this study, two commonly used traditional herbal formulas, Shi Quan Da Bu Tang (SQDB) and Huo Luo Xiao Ling Dan (HLXL) were evaluated using a survival assay and oxidative stress biomarkers in a well-established C. elegans model of aging. HLXL is an eleven herb formula modified from a top-selling traditional herbal formula for the treatment of arthritic joint pain. SQDB consists of ten herbs often used for fatigue and energy, particularly in the aged. We demonstrate here that SQDB significantly extend life span in a C. elegans model of aging. Among all individual herbs tested, two herbs Cinnamomum cassia bark (Chinese pharmaceutical name: Cinnamomi Cortex, CIN) and Panax ginseng root (Chinese pharmaceutical name: Ginseng Radix, GS) significantly extended life span in C. elegans. CIN in both SQDB and HLXL formula extended life span via modulation of multiple longevity assurance genes, including genes involved in insulin signaling and stress response pathways. All the life-span-extending herbs (SQDB, CIN and GS) also attenuated levels of H2O2 and enhanced small heat shock protein expression. Furthermore, the life spanextending herbs significantly delayed human amyloid beta (Aβ)-induced toxicity in transgenic C. elegans expressing human Aβ. Conclusion/Significance:These results validate an invertebrate model for rapid, systematic evaluation of commonly used Chinese herbal formulations and may provide insight for designing future evidence-based herbal therapy(s). Copyright: © 2010 Yu et al.published_or_final_versio

Comparison of the automated KRYPTOR chromogranin A assay with the DAKO ELISA.

Background: Currently available assays for the widely used marker for neuroendocrine tumors chromogranin A have a weak comparability, involve manual work, and require batch processing of the samples. In this study, we evaluated the automated chromogranin A KRYPTOR assay compared with the widely used DAKO ELISA. Methods: 83 samples were measured with the DAKO ELISA (EDTA plasma) and the KRYPTOR assay (serum), since different sample materials are recommended. Furthermore, different sample materials were compared. Results: The results between the two assays were highly correlated KRYPTOR serum (ng/mL) = 2.887 ELISA EDTA (U/L) + 5.028; r = 0.99). The inter-assay variation for the KRYPTOR assay was determined as 5.56% at low (95 ng/mL; n = 34) and 6.21% at high (530 ng/mL; n = 33) chromogranin A concentrations. EDTA plasma samples revealed significantly lower results than serum in the KRYPTOR assays and could not be used. Conclusions: In conclusion, the new chromogranin A KRYPTOR assay is fast, reliable, and compares well to an established test after adaptation of sample material and reported units