Bone marrow macrophages are involved in the ineffective hematopoiesis of myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal disorders characterized by ineffective hematopoiesis. Accumulating evidence has shown that macrophages (MΦs) are important components in the regulation of tumor progression and hematopoietic stem cells (HSCs). However, the roles of bone marrow (BM) MΦs in regulating normal and malignant hematopoiesis in different clinical stages of MDS are largely unknown. Age-paired patients with lower-risk MDS (N = 15), higher-risk MDS (N = 15), de novo acute myeloid leukemia (AML) (N = 15), and healthy donors (HDs) (N = 15) were enrolled. Flow cytometry analysis showed increased pro-inflammatory monocyte subsets and a decreased classically activated (M1) MΦs/alternatively activated (M2) MΦs ratio in the BM of patients with higher-risk MDS compared to lower-risk MDS. BM MФs from patients with higher-risk MDS and AML showed impaired phagocytosis activity but increased migration compared with lower-risk MDS group. AML BM MΦs showed markedly higher S100A8/A9 levels than lower-risk MDS BM MΦs. More importantly, coculture experiments suggested that the HSC supporting abilities of BM MΦs from patients with higher-risk MDS decreased, whereas the malignant cell supporting abilities increased compared with lower-risk MDS. Gene Ontology enrichment comparing BM MΦs from lower-risk MDS and higher-risk MDS for genes was involved in hematopoiesis- and immunity-related pathways. Our results suggest that BM MΦs are involved in ineffective hematopoiesis in patients with MDS, which indicates that repairing aberrant BM MΦs may represent a promising therapeutic approach for patients with MDS.

Improved function and balance in T cell modulation by endothelial cells in young people.

Elderly individuals exhibit unbalanced bone marrow (BM) effector T cell subset differentiation, such as increased T helper type 1 (Th1) and T cytotoxic type 1 (Tc1) cell frequencies, but the underlying mechanism is still unclear. Endothelial cells (ECs), which are instructive components of the BM microenvironment, exhibit the phenotype of semi-professional antigen-presenting cells and regulate T cell recruitment and activation. Thus, we compared the frequency and function of BM ECs, especially their capacity to regulate effector T cell subsets, between young and elderly healthy individuals, and explored the underlying mechanism of this immunomodulatory discrepancy. Although the young and elderly EC percentages were comparable, young ECs showed fewer reactive oxygen species and better migratory and tube-forming abilities than elderly ECs. Notably, increased T cell activation molecules and inflammatory cytokines were found in elderly ECs which regulated T cells to differentiate into more proinflammatory T cells, including Th1 and Tc1 cells, than young ECs.

Monocyte subsets in bone marrow grafts may contribute to a low incidence of acute graft-vs-host disease for young donors.

Young donors are associated with a lower cumulative incidence of acute graft-vs-host disease (aGVHD) after allogenic haematopoietic stem cell transplantation (allo-HSCT) than old donors. Although grafts are harvested from healthy donors, it is unclear whether donor age is associated with aGVHD occurrence owing to its effect on cell compositions in grafts. Moreover, the differences in monocyte subsets in grafts between young and old donors and the association between monocyte subsets in bone marrow (BM) grafts and aGVHD remain to be elucidated. In the current study, non-classical monocytes and the CD4+ /CD8+ T cell ratio were remarkably decreased in BM grafts in donors <30 years old. Multivariate analysis further revealed that the level of non-classical monocytes in BM grafts (≥0.31 × 106 /kg) was an independent risk factor for the occurrence of II-IV aGVHD. In summary, our data indicate that non-classical monocytes in BM grafts may help identify patients at high risk for aGVHD after allo-HSCT. Although further validation is required, our results suggest that the low level of non-classical monocytes and a low ratio of CD4+ /CD8+ T cell in BM grafts may be correlated with the lower incidence of aGVHD in young donors.

Classification of Gan Dan Shi Re Pattern and Gan Shen Yin Xu Pattern in Patients with Hepatitis B Cirrhosis Using Metabonomics.

OBJECTIVE: This study aimed to analyze the differential metabolites and their metabolic pathways from the serum of patients with hepatitis B cirrhosis, with two typical patterns of Gan Dan Shi Re (GDSR) and Gan Shen Yin Xu (GSYX) based on the theory of traditional Chinese medicine (TCM). It also investigated the variation in the internal material basis for the two types of patterns and provided an objective basis for classifying TCM patterns using metabolomic techniques. METHODS: The serum samples taken from 111 qualified patients (40 GDSR cases, 41 GSYX cases, and 30 Latent Pattern (LP) cases with no obvious pattern characters) and 60 healthy volunteers were tested to identify the differential substances relevant to hepatitis B cirrhosis and the two typical TCM patterns under the gas chromatography-time-of-flight mass spectrometry platform. The relevant metabolic pathways of differential substances were analyzed using multidimensional statistical analysis. RESULTS: After excluding the influence of LP groups, six common substances were found in GDSR and GSYX patterns, which were mainly involved in the metabolic pathways of glycine, serine, threonine, and phenylalanine. Eight specific metabolites involved in the metabolic pathways of linoleic, glycine, threonine, and serine existed in the two patterns. CONCLUSIONS: The data points on the metabolic spectrum were found to be well distributed among the differential substances between the two typical TCM patterns of patients with hepatitis B cirrhosis using metabolomic techniques. The differential expression of these substances between GDSR and GSYX patterns provided an important objective basis for the scientific nature of TCM pattern classification at the metabolic level.

[Correlation between fasting C-peptide and serum uric acid in patients with type 2 diabetes mellitus].

OBJECTIVE: To explore the relationship between fasting C-peptide (F-CP) and serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 347 hospitalized patients with T2DM were stratified according to F-CP level to analyze the impact of increased F-CP levels on SUA level and the incidence of hyperuricemia (HUA). The patients with an elevated SUA level (>420 µmol/L) and a normal SUA level (≤420 µmol/L) were compared for general data, fasting C-peptide and other clinical indexes. Pearson or Spearman correlation analysis was used to analyze the correlation of SUA level with F-CP levels and other parameters. The risk factors of elevated SUA were analyzed by binary logistic regression, multiple regression analysis and hierarchical interaction analysis. The ROC curve was used to analyze the independent risk factors of elevated SUA and determine the corresponding cut-off values. RESULTS: Compared with those with a normal SUA level, patients with elevated SUA had higher body mass index (BMI), waist-to-hip ratio, F-CP, postprandial 2hC peptide (2hP-CP), triglyceride (TG), homocysteine (HCY), serum creatinine (SCr) level (P<0.05), and a greater percentage of drinking (44.8% vs 32.6%, P=0.006), but had significantly lowered levels of HbA1c, high-density lipoprotein (HDL), and estimated glomerular filtration rate (eGFR) (P<0.05). SUA was found to be positively correlated with F-CP, 2hP-CP, BMI, waist-to-hip ratio, diastolic blood pressure, TG, HCY, SCr, smoking and drinking (P<0.05), and was negatively correlated with gender, age, age of disease onset, HbA1c, HDL and eGFR (P<0.05). SUA level and the incidence of hyperuricemia increasea significantly with F-CP level (P<0.05). F-CP was identified as an independent risk factor for elevated SUA, and gender did not affect the relationship between F-CP and SUA. ROC curve analysis showed that a F-CP level >1.260 ng/mL was associated with a significantly increased risk of hyperuricemia in T2DM patients. CONCLUSION: F-CP is closely related with SUA and may be an independent risk factor of elevated SUA in patients with T2DM.