A comparative analysis of soil physicochemical properties and microbial community structure among four shelterbelt species in the northeast China plain.

Conducting studies that focus on the alterations occurring in the soil microbiome within protection forests in the northeast plain is of utmost importance in evaluating the ecological rehabilitation of agricultural lands in the Mollisols region. Nevertheless, the presence of geographic factors contributes to substantial disparities in the microbiomes, and thus, addressing this aspect of influence becomes pivotal in ensuring the credibility of the collected data. Consequently, the objective is to compare the variations in soil physicochemical properties and microbial community structure within the understory of diverse shelterbelt species. In this study, we analyzed the understory soils of Juglans mandshurica (Jm), Fraxinus mandschurica (Fm), Acer mono (Am), and Betula platyphylla (Bp) from the same locality. We employed high-throughput sequencing technology and soil physicochemical data to investigate the impact of these different tree species on soil microbial communities, chemical properties, and enzyme activities in Mollisols areas. Significant variations in soil nutrients and enzyme activities were observed among tree species, with soil organic matter content ranging from 49.1 to 67.7 g/kg and cellulase content ranging from 5.3 to 524.0 µg/d/g. The impact of tree species on microbial diversities was found to be more pronounced in the bacterial community (Adnoism: R = 0.605) compared to the fungal community (Adnoism: R = 0.433). The linear discriminant analysis effect size (LEfSe) analysis revealed a total of 5 (Jm), 3 (Bp), and 6 (Am) bacterial biomarkers, as well as 2 (Jm), 6 (Fm), 4 (Bp), and 1 (Am) fungal biomarker at the genus level (LDA3). The presence of various tree species was observed to significantly alter the relative abundance of specific microbial community structures, specifically in Gammaproteobacteria, Ascomycota, and Basidiomycota. Furthermore, environmental factors, such as pH, total potassium, and available phosphorus were important factors influencing changes in bacterial communities. We propose that Fm be utilized as the primary tree species for establishing farmland protection forests in the northeastern region, owing to its superior impact on enhancing soil quality. IMPORTANCE: The focal point of this study lies in the implementation of a controlled experiment conducted under field conditions. In this experiment, we deliberately selected four shelterbelts within the same field, characterized by identical planting density, and planting year. This deliberate selection effectively mitigated the potential impact of extraneous factors on the three microbiomes, thereby enhancing the reliability and validity of our findings.

Glucan from Oudemansiella raphanipes suppresses breast cancer proliferation and metastasis by regulating macrophage polarization and the WNT/ß-catenin signaling pathway.

Background: The glucan extract of Oudemansiella raphanipes (Orp) has multiple biological properties, similar to extracts of other natural edible fungi. Drugs traditionally used in cancer treatment are associated with several drawbacks, such as side effects, induction of resistance, and poor prognosis, and many recent studies have focused on polysaccharides extracted from natural sources as alternatives. Our study focuses on the therapeutic role and molecular mechanism of action of Orp in breast cancer progression. Methods: MMTV-PyMT transgenic mice were used as the spontaneous breast cancer mice model. Immunoblotting, hematoxylin-eosin staining, immunohistochemistry, and immunofluorescence were used to evaluate the tumor behaviors in breast cancer. The inflammatory cell model was constructed using TNF-α. Macrophage activation and WNT/ß-catenin signaling were assayed using western blotting and immunofluorescence. Results: Orp management significantly inhibited tumor growth and promoted tumor cell apoptosis in MMTV-PyMT transgenic mice. Besides, the Orp challenge also attenuated the ability of breast tumors to metastasize into lung tissues. Mechanistically, Orp treatment restrained the polarization of M1 macrophages to M2 macrophages and suppressed WNT/ß-catenin signaling in mouse tumor tissues, which implied that Orp-mediated tumor inhibition partly occurred via regulating the inflammatory response. Findings from in vitro experiments confirmed that Orp inhibited the TNF-α-induced nuclear transportation of ß-catenin, thus preventing inflammation signaling and the expression of c-Myc in MCF-7 cells. Conclusion: Orp inhibits breast cancer growth and metastasis by regulating macrophage polarization and the WNT/ß-catenin signaling axis. The findings of this study suggest that Orp may be a promising therapeutic strategy for breast cancer.

ß-Glucan produced by Lentinus edodes suppresses breast cancer progression via the inhibition of macrophage M2 polarization by integrating autophagy and inflammatory signals.

BACKGROUND: ß-Glucan from Lentinus edodes (LNT), an edible mushroom, possesses strong anticancer activity. However, the therapeutic effects of LNT during the occurrence and progression of breast cancer and their underlying molecular mechanisms have not been elucidated. METHODS: Mouse mammary tumor virus-polyoma middle tumor-antigen (MMTV-PyMT) transgenic mice were used as a breast cancer mouse model. Hematoxylin and eosin, immunohistochemical, and immunofluorescence staining were performed for histopathological analysis. Moreover, we developed an inflammatory cell model using tumor necrosis factor-α (TNF-α). Macrophage polarization was assessed using western blot analysis and immunofluorescence. RESULTS: Orphan nuclear receptor 77 (Nur77) and sequestosome-1 (p62) were highly expressed and positively correlated with each other in breast cancer tissues. LNT significantly inhibited tumor growth, ameliorated inflammatory cell infiltration, and induced tumor cell apoptosis in PyMT transgenic mice. Moreover, LNT attenuated the ability of tumors to metastasize to lung tissue. Mechanistically, LNT treatment restrained macrophage polarization from M1 to M2 phenotype and promoted autophagic cell death by inhibiting Nur77 expression, AKT/mTOR signaling, and inflammatory signals in breast tumor cells. However, LNT did not exhibit a direct pro-autophagic effect on tumor cell death, except for its inhibitory effect on Nur77 expression. LNT-mediated autophagic tumor cell death depends on M1 macrophage polarization. In in vitro experiments, LNT inhibited the upregulation of p62, autophagy activation, and inflammatory signaling pathways in Nur77 cells. CONCLUSION: LNT inhibited macrophage M2 polarization and subsequently blocked the AKT/mTOR and inflammatory signaling axes in breast cancer cells, thereby promoting autophagic tumor cell death. Thus, LNT may be a promising therapeutic strategy for breast cancer.

Which Multivariate Multi-Scale Entropy Algorithm Is More Suitable for Analyzing the EEG Characteristics of Mild Cognitive Impairment?

So far, most articles using the multivariate multi-scale entropy algorithm mainly use algorithms to analyze the multivariable signal complexity without clearly describing what characteristics of signals these algorithms measure and what factors affect these algorithms. This paper analyzes six commonly used multivariate multi-scale entropy algorithms from a new perspective. It clarifies for the first time what characteristics of signals these algorithms measure and which factors affect them. It also studies which algorithm is more suitable for analyzing mild cognitive impairment (MCI) electroencephalograph (EEG) signals. The simulation results show that the multivariate multi-scale sample entropy (mvMSE), multivariate multi-scale fuzzy entropy (mvMFE), and refined composite multivariate multi-scale fuzzy entropy (RCmvMFE) algorithms can measure intra- and inter-channel correlation and multivariable signal complexity. In the joint analysis of coupling and complexity, they all decrease with the decrease in signal complexity and coupling strength, highlighting their advantages in processing related multi-channel signals, which is a discovery in the simulation. Among them, the RCmvMFE algorithm can better distinguish different complexity signals and correlations between channels. It also performs well in anti-noise and length analysis of multi-channel data simultaneously. Therefore, we use the RCmvMFE algorithm to analyze EEG signals from twenty subjects (eight control subjects and twelve MCI subjects). The results show that the MCI group had lower entropy than the control group on the short scale and the opposite on the long scale. Moreover, frontal entropy correlates significantly positively with the Montreal Cognitive Assessment score and Auditory Verbal Learning Test delayed recall score on the short scale.

Mic60 is essential to maintain mitochondrial integrity and to prevent encephalomyopathy.

Mitochondrial encephalomyopathies (ME) are frequently associated with mutations of mitochondrial DNA, but the pathogenesis of a subset of ME (sME) remains elusive. Here we report that haploinsufficiency of a mitochondrial inner membrane protein, Mic60, causes progressive neurological abnormalities with insulted mitochondrial structure and neuronal loss in mice. In addition, haploinsufficiency of Mic60 reduces mitochondrial membrane potential and cellular ATP production, increases reactive oxygen species, and alters mitochondrial oxidative phosphorylation complexes in neurons in an age-dependent manner. Moreover, haploinsufficiency of Mic60 compromises brain glucose intake and oxygen consumption in mice, resembling human ME syndrome. We further discover that MIC60 protein expression declined significantly in human sME, implying that insufficient MIC60 may contribute for pathogenesis of human ME. Notably, systemic administration of antioxidant N-acetylcysteine largely reverses mitochondrial dysfunctions and metabolic disorders in haplo-insufficient Mic60 mice, also restores neurological abnormal symptom. These results reveal Mic60 is required in the maintenance of mitochondrial integrity and function, and likely a potential therapeutics target for mitochondrial encephalomyopathies.

The expression level of Neuronal Calcium Sensor 1 can predict the prognosis of cytogenetically normal AML.

Acute myeloid leukemia (AML) is malignant clonal expansion of myeloid blasts with high heterogeneity and numerous molecular biomarkers have been found to judge the prognosis in some specific classifications of AML. Furthermore, as for patients with cytogenetically normal acute myeloid leukemia (CN-AML), we need to find more new biomarkers to predict the patients' outcomes. Recently, the expression level of Neuronal Calcium Sensor 1 (NCS1) has been associated with the prognosis of breast cancer and hepatocellular carcinoma, but nothing related has been reported about hematological malignancies. Therefore, we make this study to explore the relationship between the NCS1 expression level and CN-AML. We analyzed the relation between survival and NCS1 RNA expression through 75 CN-AML patients from Cancer Genome Atlas (TCGA) database and 433 CN-AML patients (3 independent datasets) from Gene Expression Omnibus (GEO) database. Additionally, we compared the NCS1 RNA expression between 138 leukemia stem cells positive (LSCs+) samples and 89 leukemia stem cells negative (LSCs-) samples from 78 AML patients from GSE76004 dataset. In our study, CN-AML patients with high expression level of NCS1 have longer EFS or OS. In addition, the NCS1 expression level in leukemia stem cells was low (p = 0.00039). According to these findings, we concluded that the high expression of NCS1 can predict favorable prognosis in CN-AML patients. Furthermore, our work put forward that NCS1 expresses lower in LSCs+, which might be an important mechanism to explain the aggressiveness of AML.

The prognostic value of RASGEF1A RNA expression and DNA methylation in cytogenetically normal acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a significantly heterogeneous malignancy of the blood. Cytogenetic abnormalities are crucial for the prognosis of AML. However, since more than half of patients with AML are cytogenetically normal AML (CN-AML), predictive prognostic indicators need to be further refined. In recent years, gene abnormalities are considered to be strong prognostic factors of CN-AML, already having clinical significance for treatment. In addition, the relationship of methylation in some genes and AML prognosis predicting has been discovered. RASGEF1A is a guanine nucleotide exchange factors of Ras and widely expressed in brain tissue, bone marrow and 17 other tissues. RASGEF1A has been reported to be associated with a variety of malignant tumors, examples include Hirschsprung disease, renal cell carcinoma, breast cancer, diffuse large B cell lymphoma, intrahepatic cholangiocarcinoma and so on [1, 2]. However, the relationship between the RASGEF1A gene and CN-AML has not been reported. METHODS: By integrating the Cancer Genome Atlas (TCGA) database 75 patients with CN-AML and 240 Gene Expression Omnibus (GEO) database CN-AML samples, we examined the association between RASGEF1A's RNA expression level and DNA methylation of and AML patients' prognosis. Then, we investigated the RASGEF1A RNA expression and DNA methylation's prognostic value in 77 patients with AML after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) as well as 101 AML patients after chemotherapy respectively. We investigated the association between sensitivity to Crenolanib and expression level of RASGED1A in patients by integrating 191 CN-AML patients from BeatAML dadataset. We integrated the expression and methylation of RASGEF1A to predict the CN-AML patients' prognosis and investigated the relationship between prognostic of AML patients with different risk classification and expression levels or methylation levels of RASGEF1A. RESULTS: We found that RASGEF1A gene high expression group predicted poorer event-free survival (EFS) (P< 0.0001) as well as overall survival (OS) (P< 0.0001) in CN-AML samples, and the identical results were found in AML patients receiving chemotherapy (P< 0.0001) and Allo-HSCT (P< 0.0001). RASGEF1A RNA expression level is an CN-AML patients' independent prognostic factor (EFS: HR = 5.5534, 95% CI: 1.2982-23.756, P= 0.0208; OS: HR = 5.3615, 95% CI: 1.1014-26.099, P= 0.0376). The IC50 (half maximal inhibitory concentration) of Crenolanib of CN-AML samples with RASGEF1A high expression level is lower. In addition, patients with high RASGEF1A methylation level had significant favorable prognosis (EPS: P< 0.0001, OS: P< 0.0001). Furthermore, the integrative analysis of expression and methylation of RASGEF1A could classify CN-AML patients into subgroups with different prognosis (EFS: P= 0.034, OS: P= 0.0024). Expression levels or methylation levels of RASGEF1A help to improve risk classification of 2010 European Leukemia Net. CONCLUSION: Higher RASGEF1A RNA expression and lower DNA methylation predicts CN-AML patients' poorer prognosis. The RASGEF1A high expression level from patients with CN-AML have better sensitivity to Crenolanib. The integrative analysis of RASGEF1A RNA expression and DNA methylation can provide a more accurate classification for prognosis. Lower RASGEF1A expression is a favorable prognostic factor for AML patients receiving chemotherapy or Allo-HSCT. 2010 European Leukemia Net's risk classification can be improved by RASGEF1A expression levels or methylation levels.

The Emerging Role of Extracellular Vesicles from Mesenchymal Stem Cells and Macrophages in Pulmonary Fibrosis: Insights into miRNA Delivery.

Pulmonary fibrosis is a type of chronic, progressive, fibrotic lung disease of unclear cause with few treatment options. Cell therapy is emerging as a promising novel modality for facilitating lung repair. Mesenchymal stem cell (MSC)-based and macrophage-based cell therapies are regarded as promising strategies to promote lung repair, due to incredible regenerative potential and typical immunomodulatory function, respectively. Extracellular vesicles (EVs), including exosomes and microvesicles, are cell-derived lipid-bilayer membrane vesicles that are secreted from virtually every cell and are involved in intercellular communication by delivering expansive biological cargos to recipients. This review provides a deep insight into the recent research progress concerning the effects of MSC and macrophage-associated EVs on the pathogenesis of pulmonary fibrosis. In addition to discussing their respective vital roles, we summarize the importance of cross-talk, as macrophages are vital for MSCs to exert their protective effects through two major patterns, including attenuating macrophage activation and M1 phenotype macrophage polarization. Moreover, miRNAs are selectively enriched into EVs as essential components, and consideration is given to the particular effects of EV-associated miRNAs.

Global characterization of megakaryocytes in bone marrow, peripheral blood, and cord blood by single-cell RNA sequencing.

Megakaryocytes (MK) are mainly derived from bone marrow and are mainly involved in platelet production. Studies have shown that MK derived from bone marrow may have immune function, and that MK from peripheral blood are associated with prostate cancer. Single-cell transcriptome sequencing can help us better understand the heterogeneity and potential function of MK cell populations in bone marrow (BM), peripheral Blood (PB), and cord blood (CB) of healthy and diseased people.We integrated more than 1.2 million single-cell transcriptome data from 132 samples of PB, BM, and CB from healthy individuals and patients from different dataset. We examined the MK (including MK and product of MK) by single-cell RNA sequencing data analysis methods and identification of MK-related protein expression by the Human Protein atlas. We investigate the relationship between the MK subtype and Non-Small Cell Lung Cancer (NSCLC) in 77 non-cancer and 402 NSCLC. We found that MK were widely distributed and the amount of MK in peripheral blood was more than that in bone marrow and there were specificity MK subtypes in peripheral blood. We found classical MK1 with typical MK characteristics and non-classical MK2 closely related to immunity which was the most common subtype in bone marrow and cord blood. Classical MK1 was closely related to Non-Small Cell Lung Cancer (NSCLC) and can be used as a diagnostic marker. MK2 may have potential adaptive immune function and play a role in tumor NSCLC and autoimmune diseases Systemic Lupus Erythematosus. MK have 14 subtypes and are widely distributed in PB, CB, and BM. MK subtypes are closely related to immunity and have potential to be a diagnostic indicator of NSCLC.

Application of antibody-conjugated small intestine submucosa to capture urine-derived stem cells for bladder repair in a rabbit model.

The need for bladder reconstruction and side effects of cystoplasty have spawned the demand for the development of alternative material substitutes. Biomaterials such as submucosa of small intestine (SIS) have been widely used as patches for bladder repair, but the outcomes are not fully satisfactory. To capture stem cells in situ has been considered as a promising strategy to speed up the process of re-cellularization and functionalization. In this study, we have developed an anti-CD29 antibody-conjugated SIS scaffold (AC-SIS) which is capable of specifically capturing urine-derived stem cells (USCs) in situ for tissue repair and regeneration. The scaffold has exhibited effective capture capacity and sound biocompatibility. In vivo experiment proved that the AC-SIS scaffold could promote rapid endothelium healing and smooth muscle regeneration. The endogenous stem cell capturing scaffolds has thereby provided a new revenue for developing effective and safer bladder patches.

Noncanonical protease-activated receptor 1 regulates lymphatic differentiation in zebrafish.

The differentiation of lymphatic progenitors is a crucial step in lymphangiogenesis. However, its underlying mechanism remains unclear. Here, we found that noncanonical protease-activated receptor 1 (par1) regulates the differentiation of lymphatic progenitors in zebrafish embryos. Loss of par1 function impaired lymphatic differentiation by downregulating prox1a expression in parachordal lymphangioblasts and caused compromised thoracic duct formation in zebrafish. Meanwhile, the G protein gnai2a, a par1 downstream effector, was selectively required for lymphatic development in zebrafish, and its mutation mimicked the lymphatic phenotype observed in par1 mutants. Interestingly, mmp13, but not thrombin, was required for lymphatic development in zebrafish. Furthermore, analyses of genetic interactions confirmed that mmp13b serves as a par1 upstream protease to regulate lymphatic development in zebrafish embryos. Mechanistically, par1 promotes flt4 expression and phospho-Erk1/2 activity in the posterior cardinal vein. Taken together, our findings highlight a function of par1 in the regulation of lymphatic differentiation in zebrafish embryos.

ESPL1 Is a Novel Prognostic Biomarker Associated With the Malignant Features of Glioma.

Research has confirmed that extra spindle pole bodies-like 1 (ESPL1), an etiological factor, promotes the malignant progression of cancers. However, the relationship between ESPL1 and glioma has not yet been demonstrated. The purpose of this study was to reveal the potential mechanisms of ESPL1-mediated malignant glioma progression. Gene expression data and detailed clinical information of glioma cases were obtained from multiple public databases. Subsequently, a series of bioinformatics analyses were used to elucidate the effects of ESPL1 on glioma. The results demonstrated that the mRNA and protein levels of ESPL1 in glioma were higher than those in normal brain tissues. In addition, ESPL1 expression was considerably associated with the clinical and pathological features of gliomas, such as World Health Organization grade, histology, and 1p19q co-deletion status. Importantly, ESPL1 reduced the overall survival (OS) of glioma patients and had prognostic value for gliomas. Gene set enrichment analysis (GSEA) indirectly revealed that ESPL1 regulates the activation of cancer-related pathways, such as the cell cycle and base excision repair pathways. In addition, we used the Connectivity Map (CMap) database to screen three molecular drugs that inhibit ESPL1: thioguanosine, antimycin A, and zidovudine. Finally, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of ESPL1 in glioma cell lines. This study plays an important role in revealing the etiology of glioma by revealing the function of ESPL1, providing a potential molecular marker for the diagnosis and treatment of glioma, especially low-grade glioma.

ß-glucan from Lentinus edodes inhibits breast cancer progression via the Nur77/HIF-1α axis.

BACKGROUND: ß-glucan from Lentinus edodes (LNT) is a plant-derived medicinal fungus possessing significant bioactivities on anti-tumor. Both hypoxia-induced factor-1α (HIF)-1α and Nur77 have been shown to be involved in the development of breast cancer. However, there is yet no proof of Nur77/HIF-1α involvement in the process of LNT-mediated tumor-inhibition effect. METHODS: Immunohistochemistry, immunofluorescence and Hematoxylin-Eosin staining were used to investigate tumor growth and metastasis in MMTV-PyMT transgenic mice. Proliferation and metastasis-associated molecules were determined by Western blotting and reverse transcription-quantitative PCR. Hypoxic cellular model was established under the exposure of CoCl2. Small interference RNA was transfected using Lipofectamine reagent. The ubiquitin proteasome pathway was blunted by adding the proteasome inhibitor MG132. RESULTS: LNT inhibited the growth of breast tumors and the development of lung metastases from breast cancer, accompanied by a decreased expression of HIF-1α in the tumor tissues. In in vitro experiments, hypoxia induced the expression of HIF-1α and Nur77 in breast cancer cells, while LNT addition down-regulated HIF-1α expression in an oxygen-free environment, and this process was in a manner of Nur77 dependent. Mechanistically, LNT evoked the down-regulation of HIF-1α involved the Nur77-mediated ubiquitin proteasome pathway. A strong positive correlation between Nur77 and HIF-1α expression in human breast cancer specimens was also confirmed. CONCLUSION: Therefore, LNT appears to inhibit the progression of breast cancer partly through the Nur77/HIF-1α signaling axis. The findings of the present study may provide a theoretical basis for targeting HIFs in the treatment of breast cancer.

Prognostic role of ACTL10 in Cytogenetic Normal Acute Myeloid Leukemia.

ACTL10 is a member of the actin family; however, despite previous studies suggesting that certain proteins in this family may be related to the pathogenesis of leukemia, to the best of our knowledge, no studies to date have demonstrated any association between ACTAL10 and leukemia. Thus, the present study aimed to determine the association between ACTL10 expression levels, DNA methylation levels and the clinical prognosis in cytogenic normal acute myeloid leukemia (CN-AML). Data from seventy-five patients with CN-AML and patients with AML treated with chemotherapy or allogeneic hematopoietic stem cell transplantation were obtained from The Cancer Genome Atlas (TCGA) dataset and were used to analyze the clinical prognosis of ACTL10 RNA expression levels and DNA methylation levels. In addition, the study also investigated the combined clinical prognosis of ACTL10 RNA expression levels and ACTL10 DNA methylation levels in 74 patients with CN-AML from the TCGA dataset. ACTL10 RNA expression levels were observed to be highly expressed in patients with CD34+/CD38+ AML (P<0.01). Both ACTL10 RNA expression levels and DNA methylation were found to be independent prognostic factors for patients with CN-AML; patients with CN-AML in the ACTL10 RNA-high expression group had an increased EFS (P=0.0016) and OS (P=0.014) and patients in ACTL10 DNA methylation-low group also demonstrated a long EFS (P<0.0001) and OS (P=0.004). Notably, integrating ACTL10 RNA expression levels and ACTL10 DNA methylation levels could more accurately predict the prognosis of patients with CN-AML (EFS and OS, P<0.0001). In conclusion, the findings of the present study suggested that the high RNA expression levels and low DNA methylation levels of ACTL10 may predict a good prognosis in patients with CN-AML.

Factors associated with postoperative axial symptom after expansive open-door laminoplasty: retrospective study using multivariable analysis.

PURPOSE: The aim of the present study was to investigate the factors associated with axial symptom using multivariable analysis. METHODS: The authors retrospectively assessed 249 patients treated by open-door laminoplasty. The patients were classified into two groups: axial symptom and no axial symptom group. The possible factors included demographic variables (age, sex, BMI, smoking, heart disease, diabetes, preoperative neck pain, preoperative JOA scores, preoperative NDI, course of disease and pathogenesis) and surgical and radiological variables [operation time, intraoperative blood loss, collar wear time, preoperative cervical curvature, postoperative cervical curvature, T1 slope, preoperative and postoperative C2 sagittal vertical axis (C2 SVA)]. RESULTS: The prevalence of axial symptom was 34.9% (89/249). The collar wear time, preoperative and postoperative C2 SVA were risk factors for axial symptom. A cutoff value of 22.6 mm for preoperative C2 SVA and 3.5 weeks for collar wear time predicted the development of axial symptom. CONCLUSIONS: The longer collar wear time, larger preoperative and postoperative C2 SVA were positively correlated with the higher incidence of axial symptom.

Hypoxic preconditioning of human urine-derived stem cell-laden small intestinal submucosa enhances wound healing potential.

BACKGROUND: Urine-derived stem cells (USCs) are a valuable stem cell source for tissue engineering because they can be harvested non-invasively. Small intestine submucosa (SIS) has been used as scaffolds for soft tissue repair in the clinic. However, the feasibility and efficacy of a combination of USCs and SIS for skin wound healing has not been reported. In this study, we created a tissue-engineered skin graft, termed the SIS+USC composite, and hypothesized that hypoxic preconditioning would improve its wound healing potential. METHODS: USCs were seeded on SIS membranes to fabricate the SIS+USC composites, which were then cultured in normoxia (21% O2) or preconditioned in hypoxia (1% O2) for 24 h, respectively. The viability and morphology of USCs, the expression of genes related to wound angiogenesis and reepithelialization, and the secretion of growth factors were determined in vitro. The wound healing ability of the SIS+USC composites was evaluated in a mouse full-thickness skin wound model. RESULTS: USCs showed good cell viability and morphology in both normoxia and hypoxic preconditioning groups. In vitro, hypoxic preconditioning enhanced not only the expression of genes related to wound angiogenesis (VEGF and Ang-2) and reepithelialization (bFGF and EGF) but also the secretion of growth factors (VEGF, EGF, and bFGF). In vivo, hypoxic preconditioning significantly improved the wound healing potential of the SIS+USC composites. It enhanced wound angiogenesis at the early stage of wound healing, promoted reepithelialization, and improved the deposition and remodeling of collagen fibers at the late stage of wound healing. CONCLUSIONS: Taken together, this study shows that hypoxic preconditioning provides an easy and efficient strategy to enhance the wound healing potential of the SIS+USC composite.

Clinical prognostic implications of EPB41L4A expression in multiple myeloma.

Background: Multiple myeloma (MM) is one of the most common incurable malignancies in malignant plasma cell disease. EPB41L4A is a target gene for the Wnt/ß-catenin pathway, which is closely related to the survival of multiple myeloma cells. However, there is currently no research report on the prognostic significance of the EPB41L4A gene in MM. Methods: We studied the biological significance and prognostic significance of EPB41L4A expression in MM by integrating 1956 MM samples from 7 datasets, and explored the relationship between EPB41L4A expression and MM ISS stage, molecular type, therapeutic response and survival. Results: We found that the expression level of EPB41L4A is inversely proportional to the copy number of 1q21 (P = 3.4e-13). EPB41L4A was low expressed in MAF, MMSET and proliferating molecular typing patients (P <= 0.001). High expression of EPB41L4A can predict good survival in MM (EFS: P < 0.0001; OS: P < 0.0001). We found that patients with relapsed MM had lower expression levels of EPB41L4A than those without recurrence (P = 0.0039). We also found that EPB41L4A can predict the prognosis of MM patients may be related to DNA replication. These results indicate that the initial expression level of EPB41L4A can predict the prognosis of MM patients. Conclusions: We found that the high expression of EPB41L4A predicts good survival level in MM.

Prognosis value of RBBP8 expression in plasma cell myeloma.

Plasma cell myeloma (PCM) secretes monoclonal immunoglobulin (Ig) by clonal plasma cells of abnormal proliferation in the bone marrow. As PCM is incurable, it is necessary to find new biomarkers to predict the prognosis and recurrence of PCM. The relationship between cancer and RBBP8 has not been fully studied. The role of RBBP8 in tumorigenesis remains inconsistent. We described the expression of RBBP8 in the gene expression profile of 1930 PCM samples (1878 PCM patients) from seven independent data sets. We analyzed the relationship between RBBP8 and survival prognosis, recurrence, and treatment response in patients with PCM, and the biological significance of RBBP8 in PCM. The gene expression level of RBBP8 was significantly related to the International staging system (ISS) grade of PCM (P = 0.0012). RBBP8 expression in different molecular subtypes was different (P < 2.2e-16). High RBBP8 expression is associated with poor survival in PCM (P < 0.0001). High expression of RBBP8 indicates that PCM patients are more likely to relapse (P = 0.0078). The biological significance of RBBP8 in PCM is related to the cell cycle (P < 0.05). High RBBP8 expression predicts poorer survival and more likely relapse in PCM. RBBP8 plays an important role in the cell cycle of PCM. RBBP8 can be considered an independent prognostic factor for PCM. RBBP8 can be used as a potential biomarker for assessing the prognosis of PCM patients.

High expression of CHML predicts poor prognosis of multiple myeloma.

Multiple myeloma is a hematological tumor with a malignant proliferation of myeloma cells. Although the survival time after treatment has improved, the recurrence rate of MM is still high. Choroideremia-like (CHML) protein is essential for the prenylation modification of various Rab proteins and it exerts biological effects on vesicle trafficking and signal transduction. However, little is identified about the relationship between CHML gene and MM. We integrated gene expression profiles of 1907 MM patients (1959 MM samples) from the 7 datasets. The relationship between CHML gene expression level and event-free survival (EFS), overall survival (OS), ISS stage, molecular subtype, relapse, therapy was analyzed. The differential gene exression profile of CHML-high MM group and CHML-low MM group and possible pathway related to CHML were conducted. Our data showed that EFS (P < 0.0001) and OS (P < 0.0001) in MM patients with high expression of CHML were lower than those with low CHML expression. The gene expression level of CHML was increased in subtypes of MM with poor prognosis, especially in proliferation subtype (P < 0.001). Cell division pathway (P < 0.01) was high enriched of the differential expressed genes of CHML-high group vs CHML-low group. CHML gene can be considered as an independent factor to evaluate the prognosis of MM. High expression of CHML is associated with poor survival, which is related to cell proliferation and cell division of myeloma cells.

The Prognostic Significance of PDE7B in Cytogenetically Normal Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a malignant hematological disease in which nearly half have normal cytogenetics. We have tried to find some significant molecular markers for this part of the cytogenetic normal AML, which hopes to provide a benefit for the diagnosis, molecular typing and prognosis prediction of AML patients. In the present study, we calculated and compared the gene expression profiles of cytogenetically normal acute myeloid leukemia (CN-AML) patients in database of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and dataset Vizome (a total of 632 CN-AML samples), and we have demonstrated a correlation between PDE7B gene and CN-AML. Then we proceeded to a survival analysis and prognostic risk analysis between the expression levels of PDE7B gene and CN-AML patients. The result showed that the event-free survival (EFS) and overall survival (OS) were significantly shorter in CN-AML patients with high PDE7B levels in each dataset. And we detected a significantly higher expression level of PDE7B in the leukemia stem cell (LSC) positive group. The Cox proportional hazards regression model showed that PDE7B is an independent risk predictor for CN-AML. All results indicate that PDE7B is an unfavorable prognostic factor for CN-AML.