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Abstract Background Though accumulated evidence has demonstrated visceral organ involvement in acute graft-versus-host disease (aGVHD), how aGVHD influences the bone marrow (BM) niche and the reconstitution of hematopoiesis post-hematopoietic stem cell transplantation remains largely unknown. Methods In the current study, the cell morphology, immunophenotype, multi-differentiation capacity, self-renewal capacity, and hematopoiesis promotion of the MSCs from aGVHD and non-aGVHD patients were investigated. Additionally, the stemness and hematopoiesis-promoting property of healthy donor-derived MSCs were evaluated in the presence of BM supernatant from aGVHD patients. Mechanistically, antibodies targeting inflammatory cytokines involved in aGVHD were added into the MSC culture. Furthermore, a recombinant human tumor necrosis factor (TNF-α) receptor-Ig fusion protein (rhTNFR:Fc) was used to protect healthy donor-derived MSCs. Moreover, mRNA sequencing was performed to explore the underlying mechanisms. Results The aGVHD MSCs exhibited morphological and immunophenotypic characteristics that were similar to those of the non-aGVHD MSCs. However, the osteogenic and adipogenic activities of the aGVHD MSCs significantly decreased. Additionally, the colony formation capacity and the expression of self-renewal-related genes remarkably decreased in aGVHD MSCs. Further, the hematopoiesis-supporting capacity of aGVHD MSCs significantly reduced. The antibody neutralization results showed that TNF-α contributed to the impairment of MSC properties. Moreover, rhTNFR:Fc exhibited notable protective effects on MSCs in the aGVHD BM supernatants. The mRNA sequencing results indicated that the TNF-α pathway and the Toll-like receptor pathway may be activated by TNF-α. Conclusions Thus, our data demonstrate MSCs as cellular targets of aGVHD and suggest a potential role of TNF-α blockage in maintaining the BM niche of aGVHD patients.

Nonalcoholic Fatty Liver Disease (NAFLD) is a serious problem endangering human health in the world. The pathogenesis of this disease is often accompanied by lipid metabolism disorder and can cause liver lipid accumulation. Highland barley Monascus purpureus Went extract (HBMPWE) can inhibit the liver lipid accumulation caused by a high-fat, high-fructose, high-cholesterol diet. However, it is not clear what changes have taken place in the process of liver lipid metabolism after HBMPWE administration. To fill this knowledge gap and to support the findings published in the companion research article entitled “Highland Barley Monascus purpureus Went Extract Ameliorates High-Fat, High-Fructose, High-Cholesterol Diet Induced Nonalcoholic Fatty Liver Disease by Regulating Lipid Metabolism in Golden Hamsters” [1], we provided important information related to the liver differential metabolites and identified twenty-one differential metabolites of liver metabolism. In the model group, the levels of lactate, linoleic acid, and malic acid increased significantly. After HBMPWE treatment, the expressions of these metabolites reduced significantly. Therefore, these liver differential metabolites could be used as biological signatures reflecting the severity of NAFLD and HBMPWE treatment outcomes.

Abstract Hematopoietic stem and progenitor cells (HSPCs) possess the remarkable ability to regenerate the whole blood system in response to ablated stress demands. Delineating the mechanisms that maintain HSPCs during regenerative stresses is increasingly important. Here, it is shown that Hemgn is significantly induced by hematopoietic stresses including irradiation and bone marrow transplantation (BMT). Hemgn deficiency does not disturb steady‐state hematopoiesis in young mice. Hemgn−/‐ HSPCs display defective engraftment activity during BMT with reduced homing and survival and increased apoptosis. Transcriptome profiling analysis reveals that upregulated genes in transplanted Hemgn−/− HSPCs are enriched for gene sets related to interferon gamma (IFN‐γ) signaling. Hemgn−/− HSPCs show enhanced responses to IFN‐γ treatment and increased aging over time. Blocking IFN‐γ signaling in irradiated recipients either pharmacologically or genetically rescues Hemgn−/‐ HSPCs engraftment defect. Mechanistical studies reveal that Hemgn deficiency sustain nuclear Stat1 tyrosine phosphorylation via suppressing T‐cell protein tyrosine phosphatase TC45 activity. Spermidine, a selective activator of TC45, rescues exacerbated phenotype of HSPCs in IFN‐γ‐treated Hemgn−/− mice. Collectively, these results identify that Hemgn is a critical regulator for successful engraftment and reconstitution of HSPCs in mice through negatively regulating IFN‐γ signaling. Targeted Hemgn may be used to improve conditioning regimens and engraftment during HSPCs transplantation.

Background: Readout-segmented echo-planar imaging (rs-EPI) with simultaneous multislice (SMS) technology has been successfully applied to tumor research in many organs, but no feasibility study in rectal cancer has been reported, and the optimal acceleration of SMS with rs-EPI in rectal cancer has not been well determined yet. Objective: To investigate the feasibility of SMS rs-EPI of rectal cancer with different acceleration factors (AFs) and its influence on image quality, acquisition time and apparent diffusion coefficients (ADCs) in comparison to conventional sequences. Methods: All patients underwent rs-EPI and SMS rs-EPI with AFs of 2 and 3 (2 × SMS rs-EPI and 3 × SMS rs-EPI, respectively) using a 3T scanner. Acquisition times of the three rs-EPI sequences were measured. Image qualitative parameters (5-point Likert scale), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), geometric distortion, and apparent diffusion coefficient (ADC) values of the three sequences were compared. Results: A total of eighty-three patients were enrolled in our study. rs-EPI and 2 × SMS rs-EPI offered equivalently high overall image quality with a scan time reduction to nearly half (rs-EPI: 137 s, 2 × SM rs-EPI: 60 s). 3 × SMS rs-EPI showed significantly poorer image quality (p < 0.05). ADC values were significantly lower in 3 × SMS rs-EPI compared to rs-EPI in rectal tumors and normal tissue (tumor tissue: rs-EPI 1.19 ± 0.21 × 10−3 mm2/s, 3 × SMS rs-EPI 1.10 ± 0.26 × 10−3 mm2/s, p < 0.001; normal tissue: rs-EPI 1.68 ± 0.13 × 10−3 mm2/s, 3 × SMS rs-EPI 1.54 ± 0.20 × 10−3 mm2/s, p < 0.001). Conclusions: SMS rs-EPI using an AF of 2 is feasible for rectal MRI resulting in substantial reductions in acquisition time while maintaining diagnostic image quality and similar ADC values to those of rs-EPI when the slice distance and number of shots are the same among three rs-EPI sequences.

ObjectiveTo analyze changes in volume and position of target regions and organs at risk (OARs) during radiotherapy for esophageal cancer patients.MethodsOverall, 16 esophageal cancer patients who underwent radiotherapy, including 10 cases of intensity-modulated radiation therapy (IMRT) and six of three-dimensional conformal radiotherapy (3D-CRT), were enrolled. The prescription doses for the planning target volumes (PTVs) were as follows: PTV1, 64 Gy/32 fractions; and PTV2, 46 Gy/23 fractions. Repeat computed tomography (CT) was performed for patients after the 5th, 10th, 15th, 20th, and 25th fractions. Delineation of the gross tumor volume (GTV) and OAR volume was determined using five repeat CTs performed by the same physician. The target and OAR volumes and centroid positions were recorded and used to analyze volume change ratio (VCR), center displacement (ΔD), and changes in the distance from the OAR centroid positions to the planned radiotherapy isocenter (distance to isocenter, DTI) during treatment.ResultsNo patient showed significant changes in target volume (TV) after the first week of radiotherapy (five fractions). However, TV gradually decreased over the following weeks, with the rate slowing after the fourth week (40 Gy). The comparison of TV from baseline to 40 Gy (20 fractions) showed that average GTVs decreased from 130.7 ± 63.1 cc to 92.1 ± 47.2 cc, with a VCR of −29.21 ± 13.96% (p