Variations in Rhizospheric and Endophytic Root Fungal Communities of Scrophularia ningpoensis in Different Producing Areas.

Few studies have examined the association of factors associated with soil fertility and composition with the structure of microbial communities in the rhizosphere and endosphere. Hence, this study aimed to explore the effects of geographical differences on fungal communities in the roots of Scrophularia ningpoensis and the relationship between the fungal communities and secondary metabolic components in the host plant. We found that there was greater diversity in the fungal communities of the rhizosphere compartment than in endosphere communities. Ascomycota and Basidiomycota were dominant among the endosphere fungi, whereas Mortierellomycota was distributed in the rhizosphere. The composition of bulk soil obtained from different producing areas was significantly different, and the correlation between the rhizospheric and physicochemical compartments of the soil was higher than that observed with the endophytic compartment. Redundancy analysis and canonical correspondence analysis of the rhizospheric and endophytic samples revealed that the organic matter, total organic carbon, total nitrogen, and Hg levels were adequately correlated with the composition of rhizospheric and endophytic fungal communities. Multiple linear regression analyses facilitated the identification of potentially beneficial fungi whose abundance was correlated with levels of secondary metabolites, such as harpagide and harpagoside. These fungi could potentially provide valuable information regarding the use of S. ningpoensis in the medicinal plant industry.

[Cytomegalovirus infection after haploidentical stem cell transplantation may reduce relapse risk in leukemia].

OBJECTIVE: To analyze the relationship between cytomegalovirus (CMV) reactivation and leukemia relapse after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). METHODS: A total of 61 patients diagnosed as hematological malignancies undergoing haplo-HSCT were analyzed retrospectively in our center. RESULTS: In the cohort, 36 patients had CMV reactivation after haplo-HSCT. The 100-day cumulative incidence of CMV reactivation was 59%. Compared with that in patients without CMV reactivation after transplantation, the incidence of leukemia relapse was lower in patients with CMV reactivation (16.9% vs 40.0%, P=0.034). The correlation of CMV reactivation and decreased relapse rate was only found in patients with acute myeloid leukemia (P=0.019). In multivariate analysis, relapsed disease status before transplant was a significant negative predictor of overall survival (OS) and relapse after transplant (RR was 2.866 and 3.331 respectively). CMV reactivation after transplant had a protective effect on disease relapse (RR=0.300, P=0.047). CONCLUSIONS: The rate of CMV reactivation after haplo-HSCT is high. CMV reactivation may reduce risk of relapse in patients diagnosed as acute myeloid leukemia undergoing haplo-HSCT. However, CMV reactivation is one of the important predictors of non-relapse death after transplant, active anti-viral treatment is still needed.

CMRxRecon: A publicly available k-space dataset and benchmark to advance deep learning for cardiac MRI.

Cardiac magnetic resonance imaging (CMR) has emerged as a valuable diagnostic tool for cardiac diseases. However, a significant drawback of CMR is its slow imaging speed, resulting in low patient throughput and compromised clinical diagnostic quality. The limited temporal resolution also causes patient discomfort and introduces artifacts in the images, further diminishing their overall quality and diagnostic value. There has been growing interest in deep learning-based CMR imaging algorithms that can reconstruct high-quality images from highly under-sampled k-space data. However, the development of deep learning methods requires large training datasets, which have so far not been made publicly available for CMR. To address this gap, we released a dataset that includes multi-contrast, multi-view, multi-slice and multi-coil CMR imaging data from 300 subjects. Imaging studies include cardiac cine and mapping sequences. The 'CMRxRecon' dataset contains raw k-space data and auto-calibration lines. Our aim is to facilitate the advancement of state-of-the-art CMR image reconstruction by introducing standardized evaluation criteria and making the dataset freely accessible to the research community.

Molecular cloning, expression, and characterization of a Ca2+-dependent nuclease of Arabidopsis thaliana.

A gene encoding a Ca(2+)-dependent nuclease (AtCaN2) consisting of 226 amino acids from Arabidopsis thaliana was isolated. The AtCaN2 gene was expressed in Escherichia coli as a His fusion protein. The His-AtCaN2 fusion protein was purified by affinity chromatography using a Ni-NTA column. Western blot analysis using an anti-His antibody showed that the His-AtCaN2 fusion protein was not degraded. The nuclease activity of the His-AtCaN2 fusion protein was highest at 37°C, required a neutral or weakly-alkaline environment, and was stimulated by Ca(2+) and Mg(2+), but inhibited by Zn(2+) and high concentration of Mn(2+).

Full-Length Transcriptome Sequencing Provides Insights into Flavonoid Biosynthesis in Fritillaria hupehensis.

One of the most commonly utilized medicinal plants in China is Fritillaria hupehensis (Hsiao et K.C. Hsia). However, due to a lack of genomic resources, little is known about the biosynthesis of relevant compounds, particularly the flavonoid biosynthesis pathway. A PacBio RS II sequencing generated a total of 342,044 reads from the bulb, leaf, root, and stem, of which 316,438 were full-length (FL) non-redundant reads with an average length of 1365 bp and a N50 of 1888 bp. There were also 38,607 long non-coding RNAs and 7914 simple sequence repeats detected. To improve our understanding of processes implicated in regulating secondary metabolite biosynthesis in F. hupehensis tissues, we evaluated potential metabolic pathways. Overall, this study provides a repertoire of FL transcripts in F. hupehensis for the first time, and it will be a valuable resource for marker-assisted breeding and research into bioactive compounds for medicinal and pharmacological applications.

Transcriptome sequencing and analysis reveals the molecular response to selenium stimuli in Pueraria lobata (willd.) Ohwi.

Pueraria lobata (willd.) Ohwi is a consumable selenium-enriched plant used for medicinal purposes. The molecular response to selenium (Se) stimuli in P. lobata is currently unknown. We used RNA-Seq to identify potential genes involved in selenite metabolism and analyzed their expression profiles. We obtained a total of 150,567 unigenes, of which 90,961 were annotated, including 16 structural genes, 14 sulfate transporters, and 13 phosphate transporters that may be involved in Se metabolism, and 33 candidate structural genes involved in isoflavone biosynthesis. The genes with a -foldchange- >2 and q value <0.05 after sodium selenite treatment were identified as differentially expressed genes (DEGs). We obtained a total of 4,246 DEGs, which were enriched in GO terms that included "response to stimulus", "response to stress", "signal transduction", "response to abiotic stimulus", and "response to chemical". Of the 4,246 DEGs, one sulfate transporter and five phosphate transporter genes involved Se metabolism, and nine structural genes involved in isoflavone biosynthesis were up-regulated. The expression patterns of 10 DEGs were selected randomly and validated using qRT-PCR. The Pearson Correlation Coefficient (r) was 0.86, indicating the reliability of RNA-Seq results. 22 Reactive Oxygen Species (ROS) scavenging DEGs were found, 11 of which were up-regulated. 436, 624 transcription factors (TFs) correlated with structural genes were identified that may be involved in Se and isoflavone biosynthesis, respectively, using r (r > 0.7 or r <  - 0.7). 556 TFs were related to at least one sulfate and phosphate transporter. Our results provided a comprehensive description of gene expression and regulation in response to Se stimuli in P. lobata.

Integrated transcriptomic and metabolomic data reveal the flavonoid biosynthesis metabolic pathway in Perilla frutescens (L.) leaves.

Perilla frutescens (L.) is an important medicinal and edible plant in China with nutritional and medical uses. The extract from leaves of Perilla frutescens contains flavonoids and volatile oils, which are mainly used in traditional Chinese medicine. In this study, we analyzed the transcriptomic and metabolomic data of the leaves of two Perilla frutescens varieties: JIZI 1 and JIZI 2. A total of 9277 differentially expressed genes and 223 flavonoid metabolites were identified in these varieties. Chrysoeriol, apigenin, malvidin, cyanidin, kaempferol, and their derivatives were abundant in the leaves of Perilla frutescens, which were more than 70% of total flavonoid contents. A total of 77 unigenes encoding 15 enzymes were identified as candidate genes involved in flavonoid biosynthesis in the leaves of Perilla frutescens. High expression of the CHS gene enhances the accumulation of flavonoids in the leaves of Perilla frutescens. Our results provide valuable information on the flavonoid metabolites and candidate genes involved in the flavonoid biosynthesis pathways in the leaves of Perilla frutescens.

Terpenes isolated from Polyalthia simiarum and their cytotoxic activities.

Two new C31 triterpenes, polysimiaric acid A (1) and B (2) as well as one new clerodane diterpenoid, 16,16-dimethoxy-cleroda-3,13Z-dien-15-oic acid (3), together with six known compounds were isolated from Polyalthia simiarum. Their structures were determined by analysis of 1D and 2D NMR data. Three new compounds were tested for their cytotoxicity against five human tumour cell lines. Compound 3 showed cytotoxic activities against SMMC-7721 with the IC50 value of 22.43 µM.

[The effects of mesenchymal stem cells on the aging kidneys in rats].

OBJECTIVE: To study the effect of mesenchymal stem cells on the aging rat kidney and to explore the underlying mechanism. METHODS: Rat models of senile kidney were built with hypodermic injection of D-galactose daily. Injections of MSCs of 3 x 10(6) were given to each rat through vena caudalis and CFSE was used as a tracing label to detect the distribution of MSCs in vivo. After 24 h, rats were dissected and their kidneys were frozen for section. MSCs were observed with Fluophot and quantitative analysis of the various parameters of kidney was performed under a light microscope with BI2000 image analysis system. The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and kidney were measured wtih hydroxylamine and chromatometry. The expression of VEGF and P16 mRNA in kidney tissue was detected with real-time PCR and Western blotting. RESULTS: MSCs was found homing in the rat kidney, and the glomerular size, sclerosis-rate and the average cell count of glomerulus in the treated group were different from those of the model group (P < 0.05). In the treated group, the activity of SOD was significantly higher and the content of MDA was lower in serum and kidney than that in the model control group (P < 0.05). The expression of VEGF mRNA and protein in the kidneys of MSCs group increased significantly as compared with the model group (P < 0.05). The expression of P16 mRNA and protein in the kidney of MSCs group decreased significantly compared with the model group (P < 0.05). CONCLUSION: MSCs can increase the expression of VEGF while decrease the expression of P16, so as to play a key role in the anti-aging on rat kidney.

Arabidopsis Ca2+-dependent nuclease AtCaN2 plays a negative role in plant responses to salt stress.

Eukaryotic nucleases are involved in processes such as DNA restriction digestion, repair, recombination, transposition, and programmed cell death (PCD). Studies on the role of nucleases have mostly focused on PCD during plant development, while the information on nucleases involved in responses to different abiotic stress conditions remains limited. Here, we identified a Ca2+-dependent nuclease, AtCaN2, in Arabidopsis thaliana and characterized its activity, expression patterns, and involvement in plant responses to salt stress. AtCaN2 showed a dual endonuclease and exonuclease activity, being able to degrade circular plasmids, RNA, single-stranded DNA, and double-stranded DNA. Expression analysis showed that AtCaN2 was strongly induced in senescent siliques and by salt stress. Overexpression of AtCaN2 decreased the plant tolerance to salt stress conditions, leading to an excessive H2O2 accumulation. However, an atcan2 mutant showed better tolerance to salt stress and a lower level of H2O2 accumulation. Moreover, the expression of several genes (AtAPX1, AtGPX8, and AtSOD1), encoding reactive oxygen species-scavenging enzymes (ascorbate peroxidase 1, glutathione peroxidase 8, and superoxide dismutase 1, respectively), was highly induced in the atcan2 mutant under salt stress conditions. In addition, salt-stress-induced cell death was increased in the AtCaN2-overexpressing transgenic plant but decreased in the atcan2 mutant. On the basis of these findings, we conclude that AtCaN2 plays a negative role in plant tolerance to salt stress. A AtCaN2 knock out could reduce ROS accumulation, decrease ROS-induced PCD, and improve overall plant tolerance.

[Blocking Two Signals of Immuno-Activated T Cells from Antigen Presenting Cells Can Prevent Chronic GVHD of Murine].

OBJECTIVE: To explore the effects of blocking TCR-CD3 and B7-CD28 signals on immune function of mice with chronic GVHD by using TJU103 and CTLA4-Ig. METHODS: On the basis of foregoing murine model of chronic GVHD, according to interference modes after infusion 6×107 spleen cells of donor mice, the recipients were divided into 5 groups: blank control, cGVHD, TJU103 interference, CTLA4-Ig interference and TJU103+CTLA4-Ig interference groups. The score of clinical manifestation and tissue histopathology were used to evaluate the effects of all the interferences on chronic GVHD. RESULTS: TJU103 and CTLA4-Ig could not influence the formation of the mouse chimera. The analysis of Kaplan survival curve of mice with chronic GVHD showed that the CTLA4-Ig and TJU103+CTLA4-Ig reduced the incidence of chronic GVHD, the TJU103 could delay the occurrence of chronic GVHD, but all the interference factors could not change the severity of chronic GVHD. CONCLUSION: TJU103 can delay the onset time of chronic GVHD, and the CTLA4-Ig can reduce the incidences of cGVHD, the combining use of TJU103 and CTLA4-Ig can significantly reduce the incidence of chronic GVHD, but can not change the severity of chronic GVHD.

Sunitinib Induces NK-κB-dependent NKG2D Ligand Expression in Nasopharyngeal Carcinoma and Hepatoma Cells.

Multitargeted tyrosine kinase inhibitors (MTKIs) have been shown to combine with natural killer (NK) cell adoptive transfer for the treatment in various cancers. MTKIs sensitize cancer cells to NK cell therapy through upregulation of nature killer group 2 member D ligands (NKG2DLs) on tumor cells. However, the molecular mechanism of MTKIs-mediated upregulation of NKG2DLs is still unknown. In this study, we confirmed sunitinib induced downregulation of its targets, such as vascular endothelial growth factor, platelet-derived growth factor, and c-kit in multiple-drug-resistant nasopharyngeal carcinoma cell line CNE2/DDP and hepatoma cell line HepG2. Then, we further showed sunitinib induced cell proliferation inhibition, apoptosis, and DNA damage in CNE2/DDP and HepG2 cells. Coculture experiments showed that sunitinib-treated CNE2/DDP and HepG2 cells were able to increase the activation and cytotoxicity of NK cells. Quantitative polymerase chain reaction results showed that sunitinib upregulated NKG2DLs, apoptotic genes, DNA damage repair genes, and nuclear factor (NF)-κß family genes. Silencing of NF-κß1, NF-κß2, or RelB (NF-κß pathway) inhibited sunitinib-induced upregulation of NKG2DLs. Taken together, we concluded that sunitinib upregulated NKG2DLs through NF-κß signaling noncanonical pathway which might mediate higher cytotoxic sensitivity of CNE2/DDP and HepG2 cells to NK cells.

[Synergistic Killing Effects of Arsenic Trioxide Combined with Itraconazole on KG1a Cells].

OBJECTIVE: To explore the effect of arsenic trioxide combined with itraconazole on proliferation and apoptosis of KG1a cells and its potential mechanism. METHODS: The cell morphology was observed with Wrighe-Giemsa staining; cell survival rate was examined by CCK-8; and colony formation capacity was measured by methylcellulose colony formation test; the flow cytometry was used to analyse the cell apoptosis rate and cell cycle; the protein expressions of BCL-2,caspase-3,BAX,SMO,Gli1 and Gli2 were detected by Western-blot. RESULTS: The arsenic trioxide and itraconazole alone both could inhibit the KG1a cell proliferation in dose-and time-dependent manner. In comparison between single and combined drug-treatment group, both the cell survival rate and the colony number of the single drug-treatment group were significantly lower(P<0.05), and the apoptosis rate was higher in the combined drug-treatment group. In the combined-treatment group, the protein expression of Caspase-3 and BAX was upregulated, while the protein expression of BCL-2,SMO,Gli1 and Gli2 was downregulated. CONCLUSION: Arsenic trioxide combined with itraconazole can inhibit the KG1a cell proliferation and induce apoptosis, which may be related with the inhibition of Hh signaling pathway and upregulation of both Caspase-3 and BAX protein expression, and provided experimental data of arsenic trioxide combined with itraconazole for the treatment of refractory AML.

[The outcomes of the thirty patients with refractory leukemia treated with related HLA haploidentical stem cells transplantation].

OBJECTIVE: To assess the outcomes of the therapy for patients with refractory leukemia with HLA haploidentical stem cells transplantation. METHODS: To analyze the outcomes of 30 patients with refractory leukemia who underwent HLA haploidentical peripheral blood stem cells transplantation from August 1998 to August 2004. RESULTS: Thirty refractory leukemia patients including 13 cases of acute non-lymphocytic leukemia, 10 cases of acute lymphocytic leukemia (ALL), 6 cases of chronic myeloid leukemia and 1 case of phase IV non-Hodgkin's lymphoma underwent HLA haploidentical peripheral blood stem cells transplantation. The median age was 25 years old (3-52 years old). Twelve patients received stem cells from parent donors, four from daughter or son donors and the remaining from sibling donors. Three HLA loci mismatched in twelve cases, two HLA loci mismatched in thirteen cases and one HLA locus mismatched in five cases. The conditioning regime consisted of fludara (25 mg/m(2) x 5 d), busulfan (4 mg/kg x 4 d) and cyclophosphamide (60 mg/kg x 2 d). Rabbit anti-human lymphocyte globulin (5 mg/kg x 5 d) was added in some patients in the conditioning regime. A mean of 5.0 (2.9-8.0) x 10(8)/kg mononucleated cells was grafted. The number of mean CD(34)(+) cells was 5.5 (3.0-6.5) x 10(6)/kg. Twenty-seven patients were successfully grafted, one failed to graft, one died from severe fungal infection at day 2 and one died from severe veno-occlusive disease at day 28. The mean time of white cell count more than 1.0 x 10(9)/L was 14 (11-18) days and platelet count more than 20 x 10(9)/L was 15 (11-18) days. ALL the 27 successfully grafted patients got complete remission. Severe acute graft versus host disease occurred in six patients and four of them died. Seven patients suffered from chronic graft versus host disease. Seven patients relapsed and died. The median relapse time was 10 (3-24) months. Fourteen patients are still surviving, and ten have disease free survival. CONCLUSION: It is concluded from our observation that HLA haploidentical peripheral blood stem cells transplantation may be an effective therapy for refractory and relapse leukemia. Some patients with refractory and relapse leukemia treated with HLA haploidentical stem cells transplantation may have disease free survival. Graft versus leukemia effect may be strong in patients receiving HLA haploidentical blood stem cells transplantation and leukemia will probably be relapsed when the patient without complete remission was treated with this therapy.

Conditioning with Fludarabine-Busulfan versus Busulfan-Cyclophosphamide Is Associated with Lower aGVHD and Higher Survival but More Extensive and Long Standing Bone Marrow Damage.

Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and a major cause of nonrelapse mortality after allo-HSCT. A conditioning regimen plays a pivotal role in the development of aGVHD. To provide a platform for studying aGVHD and evaluating the impact of different conditioning regimens, we established a murine aGVHD model that simulates the clinical situation and can be conditioned with Busulfan-Cyclophosphamide (Bu-Cy) and Fludarabine-Busulfan (Flu-Bu). In our study, BALB/c mice were conditioned with Bu-Cy or Flu-Bu and transplanted with 2 × 107 bone marrow cells and 2 × 107 splenocytes from either allogeneic (C57BL/6) or syngeneic (BALB/c) donors. The allogeneic recipients conditioned with Bu-Cy had shorter survivals (P < 0.05), more severe clinical manifestations, and higher hepatic and intestinal pathology scores, associated with increased INF-γ expression and diminished IL-4 expression in serum, compared to allogeneic recipients conditioned with Flu-Bu. Moreover, higher donor-derived T-cell infiltration and severely impaired B-cell development were seen in the bone marrow of mice, exhibiting aGVHD and conditioned with Flu-Bu. Our study showed that the conditioning regimen with Bu-Cy resulted in more severe aGVHD while the Flu-Bu regimen was associated with more extensive and long standing bone marrow damage.

Curcumin reduces the expression of survivin, leading to enhancement of arsenic trioxide-induced apoptosis in myelodysplastic syndrome and leukemia stem-like cells.

Low response, treatment-related complications and relapse due to the low sensitivity of myelodysplastic syndrome (MDS) and leukemia stem cells (LSCs) or pre­LSCs to arsenic trioxide (ATO), represent the main problems following treatment with ATO alone in patients with MDS. To solve these problems, a chemosensitization agent can be applied to increase the susceptibility of these cells to ATO. Curcumin (CUR), which possesses a wide range of anticancer activities, is a commonly used chemosensitization agent for various types of tumors, including hematopoietic malignancies. In the present study, we investigated the cytotoxic effects and potential mechanisms in MDS-SKM-1 and leukemia stem-like KG1a cells treated with CUR and ATO alone or in combination. CUR and ATO exhibited growth inhibition detected by MTT assays and apoptosis analyzed by Annexin V/PI analyses in both SKM-1 and KG1a cells. Apoptosis of SKM-1 and KG1a cells determined by Annexin V/PI was significantly enhanced in the combination groups compared with the groups treated with either agent alone. Further evaluation was performed by western blotting for two hallmark markers of apoptosis, caspase-3 and cleaved-PARP. Co-treatment of the cells with CUR and ATO resulted in significant synergistic effects. In SKM-1 and KG1a cells, 31 and 13 proteins analyzed by protein array assays were modulated, respectively. Notably, survivin protein expression levels were downregulated in both cell lines treated with CUR alone and in combination with ATO, particularly in the latter case. Susceptibility to apoptosis was significantly increased in SKM-1 and KG1a cells treated with siRNA-survivin and ATO. These results suggested that CUR increased the sensitivity of SKM-1 and KG1a cells to ATO by downregulating the expression of survivin.

[HLA class I and II polymorphism and haplotypes in Guangdong Han population].

OBJECTIVE: To analyze the polymorphism and haplotypes of HLA class I and II in Guangdong Han population and detect the HLA-A, B, Cw and DRB1 allele frequencies. METHODS: An auto semi-quantitative PCR-sequence speacific oligonucleotide probe(PCR-SSOP) method was adopted in exploring the HLA-A, B, Cw and DRB1 genotypes of the samples from 160 bone marrow donors. RESULTS: Twelve HLA-A, 23 B, 11 Cw and 13 DRB1 alleles were obtained. A total of 9 HLA-A-B, 20 Cw-B, 7 A-Cw, and 8 A-DRB1, 9 B-DRB1, 10 Cw-DRB1 haplotypes were found. CONCLUSION: HLA class I and II alleles in Guangdong Han population have plenty of polymorphisms. The haplotype distribution possesses territory characteristic.

Curcumin Enhanced Busulfan-Induced Apoptosis through Downregulating the Expression of Survivin in Leukemia Stem-Like KG1a Cells.

Leukemia relapse and nonrecurrence mortality (NRM) due to leukemia stem cells (LSCs) represent major problems following hematopoietic stem cell transplantation (HSCT). To eliminate LSCs, the sensitivity of LSCs to chemotherapeutic agents used in conditioning regimens should be enhanced. Curcumin (CUR) has received considerable attention as a result of its anticancer activity in leukemia and solid tumors. In this study, we investigated the cytotoxic effects and underlying mechanisms in leukemia stem-like KG1a cells exposed to busulfan (BUS) and CUR, either alone or in combination. KG1a cells exhibiting BUS-resistance demonstrated by MTT and annexin V/propidium iodide (PI) assays, compared with HL-60 cells. CUR induced cell growth inhibition and apoptosis in KG1a cells. Apoptosis of KG1a cells was significantly enhanced by treatment with CUR+BUS, compared with either agent alone. CUR synergistically enhanced the cytotoxic effect of BUS. Seven apoptosis-related proteins were modulated in CUR- and CUR+BUS-treated cells analyzed by proteins array analysis. Importantly, the antiapoptosis protein survivin was significantly downregulated, especially in combination group. Suppression of survivin with specific inhibitor YM155 significantly increased the susceptibility of KG1a cells to BUS. These results demonstrated that CUR could increase the sensitivity of leukemia stem-like KG1a cells to BUS by downregulating the expression of survivin.

[Establishment of a mouse model of acute graft-versus-host disease by busulfan combined with cyclophosphamide].

OBJECTIVE: To develop a stable mouse model of acute graft-versus-host disease (aGVHD) by preconditioning with busulfan (BS)-cyclophospha mide (CP). METHODS: Male BALB/c (H-2kd) as recipients were conditioned with 100 mg/kg BS and 200 mg/kg CP followed by being transplanted with bone marrow cells (2×10(7)) or bone marrow cells (2×10(7))-spleen cells (2×10(7)) from female C57BL/6(H-2Kb) as donors. The general data of the transplanted mice were recorded and the manifestations of aGVHD were evaluated. Histopathological changes were observed using HE staining and chimerism in spleen and bone marrow cells was studied using flow cytometry. RESULTS: Mice transplanted with bone marrow cells-spleen cells developed classic aGVHD manifestations starting from the 7th day after transplantation with full donor chimerism. GVHD histopathological changes were seen in liver, spleen, intestine, skin and lung of these mice. The median survival time of these aGVHD mice was 10 days, and they all died within 30 days. Mice transplanted with only bone marrow cells survived over 45 days without any aGVHD signs. CONCLUSION: We developed a stable and reliable aGVHD murine model successfully, which can be used to study the pathogenesis, prevention and therapeutic effect of aGVHD.

Bone marrow mesenchymal stem cells protect against bleomycin-induced pulmonary fibrosis in rat by activating Nrf2 signaling.

Pulmonary fibrosis is a progressive and lethal disorder. Although the precise mechanisms of pulmonary fibrosis are not fully understood, oxidant/antioxidant may play an important role in many of the processes of inflammation and fibrosis. Keap1-Nrf2-ARE pathway represents one of the most important cellular defense mechanisms against oxidative stress. Mesenchymal stem cells (MSC) are in clinical trials for widespread indications including musculoskeletal, neurological, cardiac and haematological disorders. One emerging concept is that MSCs may have paracrine, rather than a functional, roles in lung injury repair and regeneration. In the present study, we investigated bone marrow mesenchymal stem cells (BMSCs) for the treatment of bleomycin-induced pulmonary fibrosis. Our results showed that BMSCs administration significantly ameliorated the bleomycin mediated histological alterations and blocked collagen deposition with parallel reduction in the hydroxyproline level. The gene expression levels of NAD(P)H: quinine oxidoreductase 1 (NQO1), gama-glutamylcysteine synthetase (γ-GCS), heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2), attenuated by bleomycin, were increased up to basal levels after BMSCs transplantation. BMSCs significantly increased superoxide dismutase (SOD) activity and inhibited malondialdehyde (MDA) production in the injured lung. The present study provides evidence that BMSCs may be a potential therapeutic reagent for the treatment of lung fibrosis.