Interaction between ω-6 fatty acids intake and blood cadmium on the risk of low cognitive performance in older adults from National Health and Nutrition Examination Survey (NHANES) 2011-2014.

BACKGROUND: Identifying preventable diets and environmental exposure is essential to ensuring the health of the aging population. This study evaluated the interaction effect between blood cadmium and ω-6 fatty acids intake on low cognitive performance in Americans. METHOD: The data of this cross-sectional study were obtained from the 2011-2012 and 2013-2014 National Health and Nutritional Examination Survey (NHANES). Cognitive performance was measured by the Consortium to Establish a Registry for Alzheimer's Disease test, Animal Fluency Test, and Digit Symbol Substitution Test. Multivariate logistic regression models were used. RESULTS: A total of 1,918 individuals were included, with 467 (24.35%) low cognitive performance. Compared with participants with normal-level blood cadmium, those with high-level blood cadmium had a higher risk of low cognitive performance [odds ratio (OR) was 1.558 with 95% confidence interval (CI): 1.144-2.123]. Low-level ω-6 fatty acids intake was positively associated with low cognitive performance [OR = 1.633 (95%CI: 1.094-2.436)] compared with normal-level intake. Moreover, there was a significant interaction between low-level ω-6 fatty acids intake and high-level blood cadmium on the risk of low cognitive performance (relative excess risk due to interaction: 0.570, 95%CI: 0.208-0.932; the attributable proportion of interaction: 0.219, 95%CI: 0.102-0.336; synergy index: 1.552, 95%CI: 1.189-2.027). CONCLUSIONS: There was a synergistic interaction between low-level ω-6 fatty acids intake and high-level blood cadmium on low cognitive performance. Low-level ω-6 fatty acids intake may amplify the adverse effects of long-term exposure to cadmium on cognitive performance. This may have a certain significance for the prevention of cognitive decline in the elderly.

Withaferin A protects against spinal cord injury by inhibiting apoptosis and inflammation in mice.

CONTEXT: Withaferin A (WFA) exhibits diverse pharmaceutical applications on human diseases, including rheumatoid arthritis, cancers and microbial infection. OBJECTIVE: We evaluated the neuroprotective role of WFA using a mouse model of spinal cord injury (SCI). MATERIALS AND METHODS: BALB/c mice were administrated 10 mg/kg of WFA. Gene expression was measured by real-time PCR, western blot and immunohistochemistry. Cell morphology and apoptosis were determined by H&E staining and TUNEL assay. Motor function was evaluated by the BBB functional scale for continuous 7 weeks. RESULTS: WFA significantly improved neurobehavioural function and alleviated histological alteration of spinal cord tissues in traumatized mice. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) significantly increased in WFA-treated mice. Meanwhile, the expression of Nogo-A and RhoA remarkably decreased in the presence of WFA. Furthermore, the apoptotic cell death was attenuated in mice treated with WFA (31.48 ± 2.50% vs. 50.08 ± 2.08%) accompanied by decreased bax and increased bcl-2. In addition, WFA decreased the expression of pro-inflammatory mediators such as IL-1ß (11.20 ± 1.96 ng/mL vs. 17.59 ± 1.42 ng/mL) and TNF-α (57.38 ± 3.57 pg/mL vs. 95.06 ± 9.13 pg/mL). The anti-inflammatory cytokines including TGF-ß1 (14.32 ± 1.04 pg/mL vs. 9.37 ± 1.17 pg/mL) and IL-10 (116.80 ± 6.91 pg/mL vs. 72.33 ± 9.35 pg/mL) were elevated after WFA administration. DISCUSSION AND CONCLUSION: This study demonstrated that WFA has a neuroprotective role by inhibition of apoptosis and inflammation after SCI in mice.

Antigen-induced chimeric antigen receptor multimerization amplifies on-tumor cytotoxicity.

Ligand-induced receptor dimerization or oligomerization is a widespread mechanism for ensuring communication specificity, safeguarding receptor activation, and facilitating amplification of signal transduction across the cellular membrane. However, cell-surface antigen-induced multimerization (dubbed AIM herein) has not yet been consciously leveraged in chimeric antigen receptor (CAR) engineering for enriching T cell-based therapies. We co-developed ciltacabtagene autoleucel (cilta-cel), whose CAR incorporates two B-cell maturation antigen (BCMA)-targeted nanobodies in tandem, for treating multiple myeloma. Here we elucidated a structural and functional model in which BCMA-induced cilta-cel CAR multimerization amplifies myeloma-targeted T cell-mediated cytotoxicity. Crystallographic analysis of BCMA-nanobody complexes revealed atomic details of antigen-antibody hetero-multimerization whilst analytical ultracentrifugation and small-angle X-ray scattering characterized interdependent BCMA apposition and CAR juxtaposition in solution. BCMA-induced nanobody CAR multimerization enhanced cytotoxicity, alongside elevated immune synapse formation and cytotoxicity-mediating cytokine release, towards myeloma-derived cells. Our results provide a framework for contemplating the AIM approach in designing next-generation CARs.

[Repair and reconstruction of femoral pseudoaneurysm caused by drug injection].

OBJECTIVE: To evaluate repair and reconstruction of the femoral pseudoaneurysm caused by drug injection. METHODS: From May 2000 to May 2005, 15 cases of femoral pseudoaneurysm caused by drug injection underwent operation treatment. All patients were male, aging 20-36 years. The disease course was 18-52 days (mean 35 days) and the course of drug injection was 3-17 months. The locations were the left side in 5 cases and the right side in 10 cases. After having been bandaged with pressure and supported with nutrition, they had been all operated. One case received fistula repair, and 14 cases received vascular grafting with ePTFE man-made blood vessel. RESULTS: The wounds healed by the first intention in 14 cases. All limbs survived. The complexion, temperature and response of involved leg were in gear. The postoperative color ultrasound Doppler detection showed that all the vascular grafts were of patency. The function of the involved limbs restored to normal. CONCLUSION: Complete debridement, vascular reconstruction and better microsurgery skill were the key factors of treating successfully the femoral pseudoaneurysm caused by drug injection.

[Repair the infra-orbital defect with a rotation flap after basal cell carcinoma resection].

OBJECTIVE: To explore the method repairing the infra-orbital defect after basal cell carcinoma resection. METHOD: A facial rotation flap was applied to repair the infra-orbital defects from tumor resection in 28 cases. RESULT: All defects were repaired by this one-stage method, which avoided skin graft, shortened the operation time and minimized the operation trauma. The incision sears are inconspicuous. The facial contours are more satisfactory. CONCLUSION: This technique is simple and effective in repairing the infra-orbital defects, worthy of extensive application.