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BACKGROUND AND OBJECTIVES: Aged red blood cell (RBC) transfusions in lung cancer patients are often related to cancer recurrence and shorter lifespans. Extracellular vesicles (EVs) accumulated in stored RBC suspensions may be one of the important influential factors. This study aims to investigate how EVs derived from RBC suspensions affect the progress of lung cancer through the most enriched microRNAs (miRNAs) previously reported in our research. STUDY DESIGN AND METHODS: EVs derived from stored RBC suspensions in Weeks 1, 3 and 5 were harvested via ultracentrifugation. Lung adenocarcinoma H1975 cells were co-cultured with EVs and transfected with miR1246 and miR150-3p mimics to evaluate alterations in their proliferation, invasion and migration abilities in vitro. Proteomics and bioinformatics were performed to predict the signalling pathway related to invasion and migration of H1975, which were verified by western blotting (WB) and flow cytometry. RESULTS: EVs derived from stored RBC suspensions in Weeks 3 and 5 could significantly enhance the invasion and migration ability of H1975 cells and also increase the expression of miR1246 and miR150-3p. After transfection with miR1246 and miR150-3p mimics, invasion, migration and proliferation of H1975 cells were obviously enhanced. Proteomics analysis demonstrated that EVs co-cultivation and miRNA transfection groups were both enriched in cell adhesion molecules. WB and cytometry indicated that integrin beta-1 (ITGB1) and Rap1b were increased. CONCLUSIONS: EVs derived from stored RBC suspensions can enhance invasion and migration ability of lung cancer cells via the most accumulated miR1246 and miR150-3p, which may increase the expression of ITGB1 through Rap1 signalling pathway.
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BACKGROUND: ABO-nonidentical platelets transfusion has been frequently employed to address clinical platelets insufficiencies. The significance of ABO compatibility for platelets transfusion is not clearly defined. This study is aimed to explore the transfusion outcomes and clinical safety of ABO-nonidentical platelets transfusion. STUDY DESIGN AND METHODS: A systematic articles search was performed for eligible studies published up to November 30, 2023 through the PubMed, Embase, Cochrane library, Chinese National Knowledge Infrastructure database, Wanfang database and SinMed. Meta-analysis Of Observational Studies in Epidemiology study guidelines for observational studies and Newcastle Ottawa bias scale were implemented to assess studies. Meta-analysis was performed using Manager 5.3. This study is registered with PROSPERO, number CRD42023417824. RESULTS: A total of 11 retrospective cohort studies and 7 prospective cohort studies with a sample size of 104,359 platelets transfusions were included. There was significant difference in transfusion effectiveness between the ABO-identical and ABO-nonidentical platelets transfusions (RR 1.20, 95 % CI 1.11-1.38, P < 0.00001, I2 = 21 %), also the ABO-identical platelets transfusions showed more platelets increment than ABO-nonidentical ones, but it was not statistically significant (MD 0.34, 95 % CI - 0.01 to 0.70, P = 0.06, I2 = 0 %). Allergy and fever occurred more in ABO-nonidentical platelets transfusions in terms of adverse reactions (RR 0.63, 95 % CI 0.41-0.96, P = 0.03, I2 = 0 %; RR 0.59, 95 % CI 0.37-0.94, P = 0.03, I2 = 31 %). When it comes to the mortality, the ABO-identical platelets transfusions did not statistically improve survival in patients who received multiple platelets transfusions (RR 0.77, 95 % CI 0.72-0.83, P = 0.17, I2 = 38 %) and who only received less than 3 transfusions (RR 0.74, 95 % CI 0.52-1.06, P = 0.10, I2 = 47 %) compared with the ABO-nonidentical platelets transfusions. CONCLUSION: In comparison to ABO-identical platelets transfusions, nonidentical platelets transfusions exhibited lower transfusion efficacy. However, the clinical safety between these two groups was similar, which indicated that ABO-nonidentical transfusions are acceptable, albeit inferior to ABO-identical ones.
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BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammatory reactions and tissue damage in the joints. Long-term drug use in clinical practice is often accompanied by adverse reactions. Extracorporeal photopheresis (ECP) is an immunomodulatory therapy with few side effects, offering a potential and safe therapeutic alternative for RA through the induction of immune tolerance. This study aimed to investigate the therapeutic effects of ECP on RA using a collagen-induced arthritis (CIA) murine model, as well as to explore its immunomodulatory effects in vivo. Additionally, particular attention was given to the significant role of monocytes during the ECP process. METHODS: A murine model of rheumatoid arthritis was established by administering two injections of bovine type II collagen to DBA/1J mice. ECP, ECP-MD (mononuclear cells were depleted during the ECP), MTX, and PBS treatment were applied to the CIA mice. During the treatment process, clinical scores and body weight changes of CIA mice were closely monitored. After six treatment sessions, micro-CT images of the hind paws from live mice were captured. Ankle joints and paws of the mice were collected and processed for histological evaluation. Spleen samples were collected to measure the Th17/Treg cells ratio, and serum samples were collected to assess cytokine and anti-type II collagen IgG levels. Monocytes and dendritic cells populations before and after ECP in vitro were detected by flow cytometry. RESULT: ECP therapy significantly attenuated the progression of CIA, alleviated the severity of clinical symptoms in CIA mice and effectively suppressed synovial hyperplasia, inflammation, and cartilage damage. There was an expansion in the percentage of CD3 + CD4 + CD25 + FoxP3 + Tregs and a decrease in CD3 + CD4 + IL17A + Th17 cells in vivo. Furthermore, ECP reduced the serum levels of pro-inflammatory cytokines IL-6 (53.47 ± 7.074 pg/mL vs 5.142 ± 1.779 pg/mL, P < 0.05) and IL-17A (3.077 ± 0.401 pg/mL vs 0.238 ± 0.082 pg/mlL, P < 0.0001) compared with PBS. Interestingly, the depletion of monocytes during the ECP process did not lead to any improvement in clinical symptoms or histological scores in CIA mice. Moreover, the imbalance in the Th17/Treg cells ratio became even more pronounced, accompanied by an augmented secretion of pro-inflammatory cytokines IL-6 and IL-17A. In vitro, compared with cells without ECP treatment, the proportion of CD11b + cells were significantly reduced (P < 0.01), the proportion of CD11c + cells were significantly elevated (P < 0.001) 24 h after ECP treatment. Additionally, the expression of MHC II (P < 0.0001), CD80 (P < 0.01), and CD86 (P < 0.001) was downregulated in CD11c + cells 24 h after ECP treatment. CONCLUSION: Our study demonstrates that ECP exhibits a therapeutic effect comparable to conventional therapy in CIA mice, and the protective mechanisms of ECP against RA involve Th17/Treg cells ratio, which result in decreased IL-6 and IL-17A. Notably, monocytes derived from CIA mice are an indispensable part to the efficacy of ECP treatment, and the proportion of monocytes decreased and the proportion of tolerogenic dendritic cells increased after ECP treatment in vitro.
