Low­dose ionizing radiation attenuates high glucose­induced hepatic apoptosis and immune factor release via modulation of a miR­155­SOCS1 axis.

Diabetic liver injury (DLI) can result in several diseases of the liver, including steatohepatitis, liver fibrosis, cirrhosis, and liver cancer. Low­dose ionizing radiation (LDIR) has hormetic effects in normal/disease conditions. However, whether LDIR has a beneficial effect on DLI has not been assessed previously. MicroRNA (miR)­155 and its target gene suppressor of cytokine signaling 1 (SOCS1) play critical roles in modulating hepatic proliferation, apoptosis, and immunity. However, whether a miR­155­SOCS1 axis is involved in high glucose (HG) induced hepatic damage remains to be determined. In the present study, mouse hepatocyte AML12 cells were treated with 30 mM glucose (HG), 75 mGy X­ray (LDIR), or HG plus LDIR. The expression levels of miR­155 and SOCS1 were determined by reverse transcription­quantitative PCR and western blotting. Additionally, apoptosis was measured using flow cytometry. The release of inflammatory factors, including TNF­α, IL­1ß, IL­6, IL­10, and IFN­Î³, after HG and/or LDIR treatment was detected by ELISA. The results showed that HG may induce hepatic apoptosis by upregulating the levels of miR­155 and downregulating the levels of SOCS1. HG also stimulated the secretion of TNF­α, IL­1ß, IL­6, and IL­10. However, LDIR blocked the HG­induced activation of a miR­155­SOCS1 axis and suppressed the release of inflammatory factors. These results indicated that a miR­155­SOCS1 axis plays a role in HG­induced liver injury, and LDIR may exert a hepatoprotective effect by regulating the miR­155­SOCS1 axis.

Development of a myelodysplastic/myeloproliferative neoplasm-unclassifiable in a patient with acute myeloid leukemia: a case report and literature review.

Myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) are a heterogeneous group of hematologic malignancies characterized by dysplastic and myeloproliferative overlapping features in the bone marrow and blood. The occurrence of the disease is related to age, prior history of MPN or MDS, and recent cytotoxic or growth factor therapy, but it rarely develops after acute myeloid leukemia (AML). We report a rare case of a patient diagnosed with AML with t(8; 21)(q22; q22) who received systematic chemotherapy. After 4 years of follow-up, MDS/MPN-unclassifiable occurred without signs of primary AML recurrence.

Multiple hepatocellular adenomas associated with long-term administration of androgenic steroids for aplastic anemia: A case report and literature review.

INTRODUCTION: Anabolic steroids are widely administered to patients with aplastic anemia (AA) and are associated with numerous medical complications. To assist with future diagnoses, we report about a young boy with multiple hepatocellular adenomas (HAs) induced by long-term use of anabolic androgenic steroids (AAS) for AA and present a related literature review. PATIENT CONCERN: A 15-year-old boy who was diagnosed with AA in 2011 had been treated with stanozolol (6 mg per day) and ciclosporin A (120-150 mg per day) for almost 4 years. He presented with epigastric pain and fever, and abdominal computed tomography showed a lesion of heterogenous density measuring 13.5 × 13.0 × 8.0 cm in the left hepatic lobe, which was initially misdiagnosed as a liver abscess. DIAGNOSIS: The patient went into hemorrhagic shock twice after invasive manipulation that aimed at diagnosis and was finally diagnosed with HA using fine needle aspiration. INTERVENTIONS: The patient discontinued AAS and only reserved ciclosporin A for AA treatment. OUTCOMES: Follow-up abdominal computed tomography performed 4 years after AAS discontinuation showed obvious regression of the hepatic lesions. CONCLUSION: It is of great importance for hematologists to completely understand that the long-term use of AAS may cause HA, which carries a great risk of hemorrhage and malignant transformation.

Pegfilgrastim improves the outcomes of mobilization and engraftment in autologous hematopoietic stem cell transplantation for the treatment of multiple myeloma.

Autologous stem cell transplantation (ASCT) is the only curable therapy for multiple myeloma (MM), while its success primarily relies on mobilization to obtain sufficient hematopoietic stem/progenitor cells (HPC). Although the role of Pegfilgrastim (PEG), a novel PEGylated form of the recombinant G-CSF filgrastim (FIL), in mobilization has been demonstrated, it remains unclear whether this approach is cost-effective in MM treatment. Here, we performed a real-world analysis to evaluate the efficacy and cost of PEG for mobilization in a cohort of MM patients, of which 53% carried high-risk cytogenetic abnormalities. A total of 91 patients who received either a single dose of PEG (6 or 12 mg, n = 42) or multiple dosing of 10 µg/kg/day FIL (n = 49) after chemotherapy for HPC mobilization were included. The yield of MNCs and CD34+ cells per milliliter of blood collected via apheresis was significantly greater in the PEG group than that in the FIL group (P = 0.014 and P = 0.038). Mobilization with PEG yielded significantly higher median number of collected CD34+ cells than FIL (5.56 vs. 4.82 × 106/kg; P = 0.038). Moreover, the average time-to-recovery of leukocytes and platelets after transplantation was markedly shorter in the PEG group than that in the FIL group (leukocyte, 11.59 ± 1.98 vs 12.93 ± 2.83 days, P = 0.019; platelet, 12.86 ± 2.62 vs 14.80 ± 5.47, P = 0.085). However, the total cost of mobilization and apheresis using PEG or FIL was comparable (P = 0.486). Of note, mobilization with 12 mg PEG further shortened time-to-recovery of leukocytes (10.64 ± 0.51 vs. 12.04 ± 2.26 days, P = 0.05) and platelets (10.60 ± 2.89 vs. 13.33 ± 2.35 days, P = 0.031) compared with 6 mg PEG. Our results support a notion that PEG (especially 12 mg) combined with chemotherapy is a cost-effective and convenient regimen of mobilization, which might improve the outcome of ASCT in MM.

Circular RNA-100290 promotes cell proliferation and inhibits apoptosis in acute myeloid leukemia cells via sponging miR-203.

Circular RNA (CirRNA) is a type of noncoding RNA that has been shown to play a unique role in tumor development and other fields in recent years. In this study, we aimed to explore the biological role of hsa_circ_100290 in acute myeloid leukemia (AML). First, we found that the expression of hsa_circ_100290 was increased in human AML samples and cell lines. Down-regulation of hsa_circ_100290 significantly suppressed cell proliferation of AML cells. Silencing hsa_circ_100290 also dramatically induced cell cycle arrest and apoptosis. Bioinformatic prediction and luciferase assay revealed that hsa_circ_100290 and Rab10 were targeted by miR-203. Validation experiments verified that hsa_circ_100290 was co-expressed with Rab10 and was negatively correlated with miR-203 expression. Moreover, rescue experiments demonstrated that miR-203 inhibitor could reverse the role of hsa_circ_100290 knockdown on proliferation and apoptosis in AML cells. Overall, the present study identifies the crucial regulation of hsa_circ_100290 in AML cell proliferation and apoptosis via targeting the miR-203/Rab10 axis.

Analysis of clinical characteristics and efficacy of chronic myeloid leukemia onset with extreme thrombocytosis in the era of tyrosine kinase inhibitors.

The aim of this study was to investigate the clinical characteristics and efficacy of chronic myeloid leukemia (CML) onset with extreme thrombocytosis. A total of 121 newly diagnosed and untreated CML patients in chronic phase with complete clinical information from the First Hospital of Jilin University, from January 2010 to December 2014 were retrospectively recruited. Based on the platelet (PLT) count, 22 patients were assigned into CML with thrombocytosis (CML-T) group (PLT >1,000×109/L) and 65 patients were classified into CML without extreme thrombocytosis (CML-N) group (PLT ≤1,000×109/L). Fifty-four point five percent of patients in the CML-T group were female, which was higher than that in the CML-N group (27.7%) (P=0.022). Except for gender, there was no significant difference for clinical information of patients between the two groups. For Sokal and Hasford scoring systems, the percentage of patients at high risk in the CML-T group were higher than those in the CML-N group, 95.5% vs 52.3% (P=0.000) and 68.2% vs 41.5% (P=0.031), respectively; however, there was no significant difference for European Treatment and Outcome Study (EUTOS) score system between the two groups (P=0.213). In terms of major molecular response (MMR) rate, the percent of patients with MMR in CML-T group was lower than that in CML-N group at 36 months after tyrosine kinase inhibitor therapy (P=0.037). Up until December 2016, the median of event-free survival was 21 months in the CML-T group, however, that was not reached in the CML-N group (P=0.027). The majority of CML patients with extreme thrombocytosis were females, and compared to patients in the CML-N group, the percentage of high risk patients based on the Sokal and Hasford scoring systems was higher in the CML-T group, and the median event-free survival of patients was shorter.

Lack of association between MTHFR A1298C polymorphism and outcome of methotrexate treatment in rheumatoid arthritis patients: evidence from a systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to evaluate the association of methylene tetrahydrofolate reductase (MTHFR) gene polymorphism A1298C and methotrexate (MTX) outcome in rheumatoid arthritis (RA) patients. METHODS: We conducted a meta-analysis of the relevant published literature through to May 2016. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed- and random-effect models. RESULTS: A total of 1325 cases (10 studies) of MTX efficacy and 2777 cases (18 studies) of MTX toxicity in RA patients were analyzed. Pooled results showed that MTHFR gene A1298C polymorphism was not significantly related to MTX toxicity or efficacy in RA patients. However, subgroup analysis indicated a significant association between MTHFR gene A1298C polymorphism and decreased MTX efficacy in the South Asian population (CCvs. CA + AA: OR = 0.45, 95% CI = 0.23-0.89, P = 0.021). Also, MTHFR gene A1298C polymorphism in the partial folate supplementation group showed a relationship with decreased MTX efficacy (CCvs. CA + AA: OR = 0.43, 95% CI = 0.20-0.92, P = 0.029) and toxicity (CCvs. CA + AA: OR = 0.40, 95% CI = 0.17-0.96, P = 0.04; CCvs. AA: OR = 0.38, 95% CI = 0.16-0.94, P = 0.035). CONCLUSIONS: Overall, our meta-analysis suggested no significant effect of MTHFR gene A1298C polymorphism on MTX outcome in RA patients. However, due to several limitations of our meta-analysis, the results should be interpreted cautiously and require further confirmation using high-quality studies.

Rapamycin and bafilomycin A1 alter autophagy and megakaryopoiesis.

Autophagy is an effective strategy for cell development by recycling cytoplasmic constituents. Genetic deletion of autophagy mediator Atg7 in hematopoietic stem cells (HSCs) can lead to failure of megakaryopoiesis and enhanced autophagy has been implicated in various hematological disorders such as immune thrombocytopenia and myelodysplastic syndrome. Here, we examined the hypothesis that optimal autophagy is essential for megakaryopoiesis and thrombopoiesis by altering autophagy using pharmacological approaches. When autophagy was induced by rapamycin or inhibited by bafilomycin A1 in fetal liver cells, we observed a significant decrease in high ploidy megakaryocytes, a reduction of CD41 and CD61 co-expressing cells, and less proplatelet or platelet formation. Additionally, reduced cell size was shown in megakaryocytes derived from rapamycin, but not bafilomycin A1-treated mouse fetal liver cells. However, when autophagy was altered in mature megakaryocytes, we observed no significant change in proplatelet formation, which was consistent with normal platelet counts, megakaryocyte numbers, and ploidy in Atg7flox/flox PF4-Cre mice with megakaryocyte- and platelet-specific deletion of autophagy-related gene Atg7. Therefore, our findings suggest that either induction or inhibition of autophagy in the early stage of megakaryopoiesis suppresses megakaryopoiesis and thrombopoiesis.

Expression and purification of soluble single-chain Fv against human fibroblast growth factor receptor 3 fused with Sumo tag in Escherichia coli

Background Overexpression or mutated activation of Fibroblast growth factor receptor 3 (FGFR3) is involved in the pathogenesis of many tumors. More and more studies focus on the potential usage of therapeutic antibodies against FGFR3. Results In this study, a novel single-chain Fv (ScFv) against FGFR3 was prepared and characterized. To achieve the soluble expression, ScFv was fused with Sumo (Small ubiquitin-related modifier) by polymerase chain reaction (PCR), and cloned into pET-20b. The recombinant bacteria were induced by 0.5 mM Isopropyl-ß-d-thiogalactopyranoside (IPTG) for 16 h at 20°C, and the supernatant liquid of Sumo-ScFv was harvested and purified by Ni-NTA chromatography. After being cleaved by the Sumo protease, the recombinant ScFv was released from the fusion protein, and further purified by Ni-NTA chromatography. The purity of ScFv was shown to be higher than 95% and their yield reached 4 mg per liter of bacterial culture. In vitro data showed that ScFv can significantly attenuate FGF9-induced phosphorylation of FGFR3. Conclusion We provide a novel method to produce soluble expression and bioactive functions of ScFv in Escherichia coli.

Analysis of the efficacy of lenalidomide in patients with intermediate-1 risk myelodysplastic syndrome without 5q deletion.

The aim of this study was to evaluate the efficacy and adverse effects of lenalidomide in the treatment of intermediate-1 risk non-5q deletion [non-del (5q)] myelodysplastic syndrome (MDS). A total of 30 patients with MDS were classified through G-banding chromosome karyotype analysis and fluorescence in situ hybridization (FISH). According to the International Prognostic Scoring System scores, among the 30 patients, 23 and seven cases had scores of 0.5 and 1.0, respectively. Lenalidomide (Revlimid®), 10 mg/day) was administered for 21 days every 28 days. All 30 cases were treated with lenalidomide for at least three cycles, including 20 cases with four cycles. The patients did not require erythropoietin, cyclosporine or iron chelation treatments. Statistical analysis was performed using SPSS statistical software version 13.0, and comparisons among groups were conducted using a t-test. The efficacy of lenalidomide was demonstrated in patients with intermediate-1 risk non-del (5q) MDS. Peripheral blood cell counts were improved following treatment, and absolute neutrophil, haemoglobin and platelet counts increased following 2-4 cycles of treatment. All patients became stable having undergone three cycles of treatment; however, 17 patients with chromosomal abnormalities had no cytogenetic response to the treatment, as confirmed through the FISH test. Patients with intermediate-1 risk non-del (5q) MDS treated with lenalidomide did not achieve complete haematological remission, although they demonstrated haematological improvement.