Dietary supplementation of Eucommia leaf extract to growing-finishing pigs alters muscle metabolism and improves meat quality.

OBJECTIVE: The objective of this study was to investigate the influence of dietary supplementation of Eucommia ulmoides leaf extract (ELE) on muscle metabolism and meat quality of pigs with and without pre-slaughter transportation. METHODS: In a 43-day feeding experiment, a total of 160 pigs with an initial body weight 60.00±2.00 kg were randomly assigned into four groups in a completely randomized design with 10 replicates. Pigs in groups A and C were fed a basal diet and pigs in groups B and D were fed a basal diet supplemented with 0.5% ELE. Pigs were slaughtered with (group B and D) or without (group A and C) pre-slaughter transport. Muscle chemical composition, postmortem glycolysis, meat quality and muscle metabolome were analyzed. RESULTS: Dietary ELE supplementation had no effect on the proximate composition of porcine muscle, but increased free phenylalanine, proline, citruline, norvaline, and the total free amino acids in muscle. In addition, dietary ELE increased decanoic acid and eicosapentaenoic acid, but decreased heptadecanoic acid, oleic acid, trans-oleic acid, and monounsaturated fatty acids in muscle. Meat quality measurement demonstrated that ELE improved meat water holding capacity and eliminated the negative effects of pre-slaughter transport on meat cooking yield and tenderness. Dietary ELE reduced muscle glycolytic potential, inhibited glycolysis and muscle pH decline in the postmortem conversion of muscle to meat and increased the activity of citrate synthase in muscle. Metabolomics analysis by liquid chromatographic tandem mass spectrometric showed that ELE enhanced muscle energy level, regulated AMP-activated protein kinase (AMPK) signaling, modulated glycogenolysis/glycolysis, and altered the metabolism of carbohydrate, fatty acids, ketone bodies, amino acids, purine, and pyrimidine. CONCLUSION: Dietary ELE improved meat quality and alleviated the negative effect of preslaughter transport on meat quality by enhancing muscle oxidative metabolism capacity and inhibiting glycolysis in postmortem muscle, which is probably involved its regulation of AMPK.

Resection of inferior vena cava, abdominal aorta, bilateral common iliac arteries, and bilateral partial external iliac arteries with artificial vessel replacement during radical endometrial cancer surgery: a case report.

BACKGROUND: Endometrial carcinoma (EC) is a common malignant tumor of the female reproductive system, often accompanied by lymph node metastasis. Artificial vascular implantation is a common surgical treatment for mediastinal tumors and abdominal aortic aneurysms but is rarely used in gynecological surgery. CASE PRESENTATION: A 54-year-old female patient was first admitted to the hospital in January 2018 due to "irregular vaginal bleeding over 3 months". CT showed a mass in the uterine cavity, and several swollen lymph nodes in the retroperitoneum and pelvic cavity. The initial diagnosis was an endometrial malignant tumor. We performed radical endometrial cancer surgery with parallel resection of inferior vena cava, abdominal aorta, bilateral common iliac arteries, bilateral external iliac arteries, and artificial vessel replacement, which was successful, with good postoperative recovery and no lesion progression at 3 years postoperative follow-up. CONCLUSION: This is an early case of gynecological clinical use of prostheses. Through multidisciplinary cooperation, the surgical resection rate of patients with EC in radical surgery was improved without serious fatal complications and achieved a high long-term postoperative survival rate.

In leukemia, knock-down of the death inducer-obliterator gene would inhibit the proliferation of endothelial cells by inhibiting the expression of CDK6 and CCND1.

BACKGROUND: Endothelial cells (ECs) are a critical component of the hematopoietic niche, and the cross-talk between ECs and leukemia was reported recently. This study aimed to determine the genes involved in the proliferation inhibition of endothelial cells in leukemia. METHODS: Human umbilical vein endothelial cells (HUVEC) were cultured alone or co-cultured with K562 cell lines. GeneChip assays were performed to identify the differentially expressed genes. The Celigo, MTT assay, and flow cytometric analysis were used to determine the effect of RNAi DIDO on cell growth and apoptosis. The differently expressed genes were verified by qRT-PCR (quantitative real-time PCR) and western-blot. RESULTS: In K562-HUVEC co-cultured cell lines, 323 down-regulated probes were identified and the extracellular signal-regulated kinase 5 (ERK5) signaling pathway was significantly inhibited. Among the down-regulated genes, the death inducer-obliterator gene (DIDO) is a part of the centrosome protein and may be involved in cell mitosis. As shown in the public data, leukemia patients with lower expression of DIDO showed a better overall survival (OS). The HUVEC cells were infected with shDIDO lentivirus, and reduced expression, inhibited proliferation, and increased apoptosis was observed in shDIDO cells. In addition, the expression of Cyclin-Dependent Kinase 6 (CDK6) and Cyclin D1 (CCND1) genes was inhibited in shDIDO cells. Finally, the public ChIP-seq data were used to analyze the regulators that bind with DIDO, and the H3K4me3 and PolII (RNA polymerase II) signals were found near the Exon1 and exon2 sites of DIDO. CONCLUSION: The knock-down of DIDO will inhibit the proliferation of endothelial cells in the leukemia environment. The expression of DIDO may be regulated by H3K4me3 and the inhibition of DIDO may lead to the down-regulation of CDK6 and CCND1. However, how DIDO interacts with CDK6 and CCND1 requires further study.

Characterization of microbiota in acute leukemia patients following successful remission induction chemotherapy without antimicrobial prophylaxis.

PURPOSE: In the present study, we characterized the microbiomes of acute leukemia (AL) patients who achieved complete remission following remission induction chemotherapy (RIC) as outpatients, but who did not receive antimicrobials to treat or prevent febrile neutropenia. METHODS: Saliva and stool samples from 9 patients with acute myeloid leukemia, 11 patients with acute lymphoblastic leukemia, and 5 healthy controls were subjected to 16S ribosomal RNA sequencing at baseline and at 3 months following RIC. Only patients who achieved remission at 3 months post-treatment were included. We excluded anyone who used antimicrobials within 2 months of enrollment or at any time during the study period. RESULTS: At baseline, the relative abundances of species of Prevotella maculosa (P=0.001), Megasphaera micronuciformis (P=0.014), Roseburia inulinivorans (P=0.021), and Bacteroides uniformis (P=0.004) in saliva and Prevotella copri (P=0.002) in the stools of controls were significantly higher than in AL patients. Following RIC, the relative abundances of Eubacterium sp. oral clone DO008 (P=0.012), Leptotrichia sp. oral clone IK040 (P=0.002), Oribacterium sp. oral taxon 108 (P=0.029), Megasphaera micronuciformis (P=0.016), TM7 phylum sp. oral clone DR034 (P<0.001), Roseburia inulinivorans (P=0.034), Actinomyces odontolyticus (P=0.014), Leptotrichia buccalis (P=0.005), and Prevotella melaninogenica (P=0.046) in saliva and Lactobacillus fermentum (P=0.046), Coprococcus catus (P=0.050), butyrate-producing bacterium SS3/4 (P=0.013), and Bacteroides coprocola (P=0.027) in the stools of AL patients were significantly greater than in controls. CONCLUSION: Following RIC, several taxa are changed in stool and salvia samples of AL patients. Our results warrant future large-scale multicenter studies to examine whether the microbiota might have an effect on clinical outcomes of AL patients.

Proteomic analysis reveals that lysine acetylation mediates the effect of antemortem stress on postmortem meat quality development.

To explore the involvement of protein lysine acetylation in the conversion of muscle to meat, a quantitative analysis of the acetylome in postmortem porcine muscle with or without antemortem stress was conducted. In total, 771 acetylpeptides containing 681 lysine acetylation sites mapping to 176 acetylproteins were identified. Acetylproteins were enriched in muscle contraction, carbohydrate metabolism, cell apoptosis and calcium signaling. Bioinformatic analysis suggests that preslaughter handling may be associated with glycolysis in postmortem muscle and the overall meat quality, via acetylation of multiple enzymes of glycogenolysis/glycolysis, regulate rigor mortis via acetylation of contractile, ATP production and calcium signaling-related proteins, and regulate stress response, cell apoptosis and meat tenderization via regulating the functions of heat shock proteins and permeability transition pore complex. This study provides the first overview of the acetylome in postmortem muscle as affected by preslaughter handling and broadens knowledge of the biochemistry regulating meat quality development.

Dendritic cells fused with endothelial progenitor cells play immunosuppressive effects on angiogenesis in acute myeloid leukemia mice.

This study aimed to explore role of dendritic cells (DCs) fused with endothelial progenitor cells (EPCs) in inhibiting angiogenesis in acute myeloid leukemia (AML) mice. EPCs were isolated from human AML bone marrow mononuclear cells and fused with DCs, which were then injected back into AML mice. Changes in leukemia cells, micro-vessel density (MVD), early EPC molecular markers vascular endothelial growth factor receptor 2 (VEGFR2/KDR) and CD133 in bone marrow were measured. The results indicated that CD133 and KDR expression in EPCs was significantly higher than in epithelial cells (HUVECs). There were 46.14% ± 8.21% DCs doubly positive for VEGFR2 and CD11c, and it was 8.53% ± 1.27% in co-culture group. Fusion rate of DC/EPCs was 37.61% ± 6.94%, and 35.63% ± 6.09% in DC/ECs group. Growth rate of DC/EPCs was faster than that of EPCs (P<0.05). At 14-20 days after fused cells injection, symptoms gradually decreased. There were a greater number of micro-vessels in bone marrow biopsy sections of AML mice than in normal controls (P<0.05). There was slightly lower MVD in EC/DCs compared with EPC/DCs (P>0.05). Positive expression of CD133 and VEGFR2 in bone marrow biopsies of AML mice was significantly higher than that in control mice (P<0.05). Positive expression of CD133 and VEGFR2 in DC/EC fused cells was significantly lower than that before fusion (P<0.05). In conclusion, DC-EPCs play a certain immunosuppressive effect on angiogenesis in AML mice. Our findings provide experimental data support for the construction of a cell vaccine with anti-angiogenic effect.

Acetylome profiling reveals extensive involvement of lysine acetylation in the conversion of muscle to meat.

Protein lysine acetylation is an post-translational modification that regulates gene expression, metabolism, cell signaling, and diseases, but its implication in the postmortem (PM) meat quality development is basically unclear. In the present study, a quantitative proteomic analysis was conducted to profile acetylome in porcine muscle within 24 h PM. In total 595 acetylation sites assigned to 163 proteins were identified in porcine muscle, of which 460 sites distributing to 110 proteins significantly changed in acetylation levels in the conversion of muscle to meat. The dynamic acetylation/deacetylaion of muscle proteins was closely associated with critical chemical-biophysical changes in PM muscle. Bioinformatic analysis revealed that protein lysine acetylation likely regulated postmortem meat quality development by regulating glycolysis and muscle pH, cell stress reponse and apoptosis, muscle contraction and rigor mortis, calcium signaling and proteolysis, IMP synthesis and meat flavor development, and even the stability of pigment proteins and meat color. This study provided the first overview of protein lysine acetylation in PM muscle and revealed its significance in the conversion of muscle to meat. Future exploration of the exact role of protein lysine acetylation at specific sites will further our understanding regarding the underlying mechanisms and be helpful for meat quality control. SIGNIFICANCE: This is the first analysis of acetylome in farm animal and postmortem muscle. Our data showed that the dynamic acetylation/deacetylation of muscle proteins was closely related to the postmortem changes of muscle that affect the final quality of raw meat. Proteins related to glucose metabolism and muscle contraction were the two largest clusters of acetylproteins identified in postmortem porcine muscle. Networks of acetylproteins involved in apoptosis, calcium signaling and IMP synthesis were identified in postmortem porcine muscle at the same time. Our results revealed that protein lysine acetylation regulated the conversion of muscle to meat. It likely regulated meat quality development by regulating postmortem glycolysis, mitochondrion initiated cell apoptosis, calcium signaling, rigor mortis, meat flavor compound sysnthesis and meat tenderization. Our study broadened our understanding of the biochemistry regulating the postmortem conversion of muscle to meat and final meat quality development, which may be helpful for future meat quality control.

Characterization of microRNA expression profiles by deep sequencing of small RNA libraries in leukemia patients from Naxi ethnic.

BACKGROUND: Leukemia is a hematological malignancy characterized by the proliferation of early lymphoid precursors that replaces normal hematopoietic cells of the bone marrow. Nakhi (Naxi) ethnic minorities considered to be an area of low incidence. MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate the expression of other genes in various biological processes. The purpose of this work is to study the molecular mechanism of miRNAs in the leukemia from Naxi. METHODS: Six leukemia patients (case 2 to case 7) and one healthy person (case 1) from Nakhi (Naxi) ethnic minorities were recruited. Total RNA was extracted from these samples and small RNA deep sequencing was performed. RESULTS: A list of miRNAs (1,392 known and candidate 125 novels) expressed in leukocytes were identified, and many differentially regulated targets involved in several cellular pathways, such as cancer, Rap1 signaling pathway, Ras signaling pathway, and endocytosis. Additionally, quantitative real time-polymerase chain reaction (qRT-PCR) results show that hsa-miR-181b-5p, hsa-miR-181a-3p, hsa-miR-181a-5p, and hsa-miR-342-3p has different expression patterns in different cancer cells, hsa-miR-450a-5p, and hsa-miR-1255a were dysregulated in all leukemia cells. CONCLUSIONS: Several abnormal expressed miRNAs in leukemia patients were identified, the correlation of miRNAs dysregulation and leukemia biology demonstrates that specific miRNA can be potential therapeutic target.

Influence of pre-transplant minimal residual disease on prognosis after Allo-SCT for patients with acute lymphoblastic leukemia: systematic review and meta-analysis.

BACKGROUND: This meta-analysis was performed to explore the impact of minimal residual disease (MRD) prior to transplantation on the prognosis for patients with acute lymphoblastic leukemia (ALL). METHODS: A systematic search of PubMed, Embase, and the Cochrane Library was conducted for relevant studies from database inception to March 2016. A total of 21 studies were included. RESULTS: Patients with positive MRD prior to allogeneic stem cell transplantation (allo-SCT) had a significantly higher rate of relapse compared with those with negative MRD (HR = 3.26; P <  0.05). Pre-transplantation positive MRD was a significant negative predictor of relapse-free survival (RFS) (HR = 2.53; P <  0.05), event-free survival (EFS) (HR = 4.77; P < 0.05), and overall survival (OS) (HR = 1.98; P < 0.05). However, positive MRD prior to transplantation was not associated with a higher rate of nonrelapse mortality. CONCLUSIONS: Positive MRD before allo-SCT was a predictor of poor prognosis after transplantation in ALL. TRIAL REGISTRATION: Not applicable.

Philadelphia chromosome-negative non-Hodgkin's lymphoma occurring in Philadelphia chromosome-positive chronic myeloid leukemia: A case report and literature review.

The current study reports the case of a patient with Philadelphia chromosome-negative (Ph-) non-Hodgkin's lymphoma (NHL) and chronic phase (CP) Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) that also possessed characteristic enlarged lymph nodes. A lymph node biopsy resulted in the diagnosis of CP-CML, in addition to T-lymphoblastic cell NHL with negative break point cluster/Abelson tyrosine kinase fusion genes in the lymph node of the patient, which was diagnosed as Ph- NHL. A review of the literature was performed in the present study to investigate the genetic differences between Ph- NHL and Ph+ NHL in patients with CML. The median age of patients with NHL and CML was 41 years. The follow-up time of patients with Ph+ NHL was significantly shorter (mean, <6 months) compared to the follow-up time of patients with Ph- NHL (mean, >15 months). Therefore the present study concludes that Ph+ NHL may be more aggressive compared with Ph+ NHL. The present study suggests that additional studies are required to assess the clinical and genetic characteristics of NHL patients with CML.