Marx for his times. Book Review of: 'Karl Marx : greatness and illusion' by Gareth Stedman Jones

Potential downstream targets for CD274. RNA-sequencing was performed with WT and CD274-null LICs, and the candidate genes related to proliferation and cell cycle was analyzed. (PDF 116 kb

Malignant B Cells Induce the Conversion of CD4+CD25− T Cells to Regulatory T Cells in B-Cell Non-Hodgkin Lymphoma

Recent evidence has demonstrated that regulatory T cells (Treg) were enriched in the tumor sites of patients with B-cell non-Hodgkin lymphoma (NHL). However, the causes of enrichment and suppressive mechanisms need to be further elucidated. Here we demonstrated that CD4+CD25+FoxP3+CD127lo Treg were markedly increased and their phenotypes were different in peripheral blood (PB) as well as bone marrow (BM) from newly diagnosed patients with B-cell NHL compared with those from healthy volunteers (HVs). Involved lymphatic tissues also showed higher frequencies of Treg than benign lymph nodes. Moreover, the frequencies of Treg were significantly higher in involved lymphatic tissues than those from PB as well as BM in the same patients. Suppression mediated by CD4+CD25+ Treg co-cultured with allogeneic CFSE-labeled CD4+CD25− responder cells was also higher in involved lymphatic tissues from B-cell NHL than that mediated by Treg from HVs. In addition, we found that malignant B cells significantly induced FoxP3 expression and regulatory function in CD4+CD25− T cells in vitro. In contrast, normal B cells could not induce the conversion of CD4+CD25− T cells to Treg. We also showed that the PD-1/B7-H1 pathway might play an important role in Treg induction. Taken together, our results suggest that malignant B cells induce the conversion of CD4+CD25− T cells to Treg, which may play a role in the pathogenesis of B-cell NHL and represent a promising therapeutic target

Does unequal economic development contribute to the inequitable distribution of healthcare resources? Evidence from China spanning 2001–2020

Abstract Background There is a dearth of research combining geographical big data on medical resource allocation and growth with various statistical data. Given the recent achievements of China in economic development and healthcare, this study takes China as an example to investigate the dynamic geographical distribution patterns of medical resources, utilizing data on healthcare resources from 290 cities in China, as well as economic and population-related data. The study aims to examine the correlation between economic growth and spatial distribution of medical resources, with the ultimate goal of providing evidence for promoting global health equity. Methods The data used in this study was sourced from the China City Statistical Yearbook from 2001 to 2020. Two indicators were employed to measure medical resources: the number of doctors per million population and the number of hospital and clinic beds per million population. We employed dynamic convergence model and fixed-effects model to examine the correlation between economic growth and the spatial distribution of medical resources. Ordinary least squares (OLS) were used to estimate the β values of the samples. Results The average GDP for all city samples across all years was 36,019.31 ± 32,029.36, with an average of 2016.31 ± 1104.16 doctors per million people, and an average of 5986.2 ± 6801.67 hospital beds per million people. In the eastern cities, the average GDP for all city samples was 47,672.71 ± 37,850.77, with an average of 2264.58 ± 1288.89 doctors per million people, and an average of 3998.92 ± 1896.49 hospital beds per million people. Cities with initially low medical resources experienced faster growth (all β  |βi|, i = 1, 2, 3, …, 9, all β doc: |βi|, i = 3, 4, 5, …, 10, P < 0.001). Economic growth significantly affected the convergence speed of medical resources, and this effect was nonlinear (doc: βi < 0, i = 1, 2, 3, …, 9, P < 0.05; bed: βi < 0, i = 1, 2, 3, …, 10, P < 0.01). The heterogeneity between provinces had a notable impact on the convergence of medical resources. Conclusions The experiences of China have provided significant insights for nations worldwide. Governments and institutions in all countries worldwide, should actively undertake measures to actively reduce health inequalities. This includes enhancing healthcare standards in impoverished regions, addressing issues of unequal distribution, and emphasizing the examination of social determinants of health within the domain of public health research

Functional analysis of induced FoxP3-expressing CD4 cells in vitro.

<p>(A) CD4⁺CD25⁻ cells isolated from a patient with B-cell NHL were co-cultured with purified autologous B cells for 5 days. Then, CD4⁺CD25⁺ T cells were isolated and cocultured with CFSE-labeled CD4⁺CD25⁻ T cells for 4 days in the presence of γ-irradiated (30 Gy) PBMCs, with each population 2×10⁵ cells. Histograms showed the profile of CFSE-labeled CD4⁺CD25⁻ T cells and the proliferated CD4⁺CD25⁻ T cells was measured by the percentage of CFSE^dim cells, as indicated. The converted Treg could inhibit the proliferation of allogeneic CD4⁺CD25⁻ T cells (<i>P</i><0.01). Two BM samples (patients 8 and 11) and one LN sample (patient 24) were tested, and a representative experiment of three was presented. (B) CD4⁺CD25⁻ cells isolated from a HV or patient with B-cell NHL were co-cultured with purified respective autologous B cells for 5 days. Then, the cells were stimulated with PMA plus ionomycin for 5 hours in the presence of BFA. Cells were harvested and costained with anti-CD3 and anti-CD8. Next, cells were fixed, permeabilized and stained with anti-FoxP3, anti-IL-2, anti-IFN-γ, anti-IL-4, or anti-IL-17. Dot plots were gated on CD3⁺CD4⁺(CD3⁺CD8⁻) T cells, and the numbers within each quadrant represent the percentages of CD4⁺ T cells. Two BM samples (patients 8 and 11) and one LN sample (patient 24) were tested, and the results were representatives of three independent experiments.</p

Malignant B cells induce FoxP3 expression and Treg conversion from CD4⁺CD25⁻ T cells, which partly depends on the interaction of between PD-1 and B7-H1.

<p>(A,B) Malignant B cells, but not normal B cells, were able to induce FoxP3 expression in autologous conventional T cells. CD4⁺CD25⁻ T cells were cultured for 5 days with X-ViVO™ 15 medium alone or purified autologous B cells in the presence of 100 IU/ml IL-2. The cells were then harvested, stained, and analyzed for the percentage of CD4⁺FoxP3⁺ cells. The number in the dot plot represents the percentage of gated cells expressing the relevant marker. Each open circle represents a single individual and numbers on the left of horizontal bars represent the group means. The results were representative of seven independent experiments. (C,D) Malignant B cells, but not tumor-infiltrating T cells, were able to induce the conversion of Treg from conventional T cells. CD4⁺CD25⁻ T cells isolated from involved lymphatic tissues of B-cell NHL were co-cultured with normal B cells for 5 days. CD4⁺CD25⁻ T cells isolated from PB of HVs were co-cultured with malignant B cells for 5 days. (E) The expression of B7-H1 was higher in lymphoma B cells than normal B cells. Cells were costained with anti-CD19-FITC and anti-B7-H1-PE, and then were analyzed the expression of B7-H1 on CD19⁺ B cells using flow cytometry. (F,G) Histograms showed the effect of the interaction between PD-1 and B7-H1 on the conversion of Treg from conventional T cells. CD4⁺CD25⁻ T cells were cocultured with autologous B cells purified from patients with B-cell NHL for 5 days. Cells were treated with PD-1 fusion protein or anti-B7-H1 antibody as well as their corresponding controls in the coculture system. A CD4⁺FoxP3⁺ gate was drawn based on their isotype controls. The results were representative of seven independent experiments.</p

Additional file 3: Figure S2. of CD274 promotes cell cycle entry of leukemia-initiating cells through JNK/Cyclin D2 signaling

CD274 is inversely correlated to the overall survival of AML patients. (A) In silico analysis of the expression of CD274 in human AML samples from the curated databases (the HemaExplorer, http://servers.binf.ku.dk/hemaexplorer/ ). (B) In silico analysis of the relationship between CD274 expression level and overall survival in AML patients from the databases of Leukemia Gene Atlas (LGA) ( http://www.leukemia-gene-atlas.org/LGAtlas/ ). (*, p < 0.05). (PDF 176 kb