Structural characteristics and in vitro starch digestibility of oil-modified cooked rice with varied addition manipulations.

Lipid has crucial applications in improving the quality of starchy products during heat processing. Herein, the influence of lipid modification and thermal treatment on the physicochemical properties and starch digestibility of cooked rice prepared with varied addition manipulations was investigated. Rice bran oil (RO) and medium chain triglyceride oil (MO) manipulations were performed either before (BC) or after cooking (AC). GC-MS was applied to determine the fatty acid profiles. Nutritional quality was analyzed by quantifying total phenolics, atherogenic, and thrombogenic indices. All complexes exhibited higher surface firmness, a soft core, and less adhesive. FTIR spectrum demonstrated that the guest component affected some of the dense structural attributes of V-amylose. The kinetic constant was in the range between 0.47 and 0.86 min-1 wherein before mode presented a higher value. The lowest glucose release was observed in the RO_BC sample, whereas the highest complexing index was observed in the RO_AC sample, indicating that the dense molecular configuration of complexes that could resist enzymatic digestion was more critical than the quantity of complex formation. Despite the damage caused by mass and heat transfer, physical barrier, intact granule forms, and strengthened dense structure were the central contributors affecting the digestion characteristics of lipid-starch complexes.

BCR::ABL1 kinase N-lobe mutants confer moderate to high degrees of resistance to asciminib.

ABSTRACT: Secondary kinase domain mutations in BCR::ABL1 represent the most common cause of resistance to tyrosine kinase inhibitor (TKI) therapy in patients with chronic myeloid leukemia. The first 5 approved BCR::ABL1 TKIs target the adenosine triphosphate (ATP)-binding pocket. Mutations confer resistance to these ATP-competitive TKIs and those approved for other malignancies by decreasing TKI affinity and/or increasing ATP affinity. Asciminib, the first highly active allosteric TKI approved for any malignancy, targets an allosteric regulatory pocket in the BCR::ABL1 kinase C-lobe. As a non-ATP-competitive inhibitor, the activity of asciminib is predicted to be impervious to increases in ATP affinity. Here, we report several known mutations that confer resistance to ATP-competitive TKIs in the BCR::ABL1 kinase N-lobe that are distant from the asciminib binding pocket yet unexpectedly confer in vitro resistance to asciminib. Among these is BCR::ABL1 M244V, which confers clinical resistance even to escalated asciminib doses. We demonstrate that BCR::ABL1 M244V does not impair asciminib binding, thereby invoking a novel mechanism of resistance. Molecular dynamic simulations of the M244V substitution implicate stabilization of an active kinase conformation through impact on the α-C helix as a mechanism of resistance. These N-lobe mutations may compromise the clinical activity of ongoing combination studies of asciminib with ATP-competitive TKIs.

Effects of Matrix Structure on Protein Digestibility and Antioxidant Property of Different Soybean Curds During In Vitro Digestion.

This study compared the three most common types of tofu (soybean curd), which were prepared by using magnesium chloride (MgCl2 tofu), calcium sulfate (CaSO4 tofu), and glucono-δ-lactone (GDL tofu) coagulants. The results showed that GDL tofu had a higher water holding capacity than MgCl2 tofu and CaSO4 tofu, which was attributed to its high surface hydrophobicity and disulfide bond content. GDL tofu possessed the lowest firmness, gumminess, and chewiness, along with a uniform network structure and a thin protein matrix. In contrast, MgCl2 tofu exhibited an inhomogeneous network structure with a thick protein matrix. Combining the results of protein hydrolysis degree, SDS-PAGE, and free amino acids during in vitro digestion, it was indicated that the degree of protein digestion in GDL tofu was the highest. After intestinal digestion, GDL tofu had the highest total phenolic content, ferric reducing antioxidant power, and DPPH value. These results demonstrated the superior protein digestibility and antioxidant property of GDL tofu during in vitro digestion due to its structural characteristics that facilitate enzyme diffusion in the matrix. The findings offer insight into the protein digestibility and antioxidant properties of different types of tofu during digestion from structural characteristic perspective and valuable reference information for consumer dietary nutrition.

[Identification of Peripheral Blood GZMK + CD8 + T Cells As Biomarkers of Alzheimer's Disease Based on Single-Cell Transcriptome].

Objective: Based on single-cell RNA sequencing (scRNA-seq) to explore immune characteristics in the peripheral blood of patients with Alzheimer's disease (AD) as biomarkers. Methods: GSE168522, the scRNA-seq dataset of AD peripheral blood immune cells, was downloaded from the Gene Expression Omnibus (GEO) database and was analyzed in the RAD-Blood web server (http://www.bioinform.cn/RAD-Blood/). The changes in blood cell composition in AD patients were analyzed. The abnormal communications between different types of cells in AD patients were investigated by the CellChat R package. Results: There were two kinds of CD8 + T cells in the blood of AD patients and healthy individuals, one of which highly expressed granzyme K ( GZMK) (false discovery rate [FDR]<0.05), and the other highly expressed GZMA, GZMB, and GZMH (FDR<0.05). In the blood of AD patients, the content of GZMK + CD8 + T cells was increased by 32.9% ( P=5.15E-21), their interactions with other cell types were increased, and they might be associated with AD through the abnormal signal transduction of major histocompatibility complex class Ⅰ (MHC-Ⅰ). Erythrocyte provided the main ligands, that are, human leukocyte antigen (HLA) class Ⅰ molecules, including HLA- A, HLA- B, HLA- C, and HLA- E, for the abnormal MHC-Ⅰ signaling pathway of GZMK + CD8 + T cells. The RESISTIN signaling pathway was specifically enriched in the blood of AD patients. Conclusion: The increased content of peripheral blood GZMK + CD8 + T cells, the increased interaction between GZMK + CD8 + T cells and erythrocytes, and the enhanced RESISTIN pathway are potential blood biomarkers of AD.

GSCA: an integrated platform for gene set cancer analysis at genomic, pharmacogenomic and immunogenomic levels.

Cancer initiation and progression are likely caused by the dysregulation of biological pathways. Gene set analysis (GSA) could improve the signal-to-noise ratio and identify potential biological insights on the gene set level. However, platforms exploring cancer multi-omics data using GSA methods are lacking. In this study, we upgraded our GSCALite to GSCA (gene set cancer analysis, http://bioinfo.life.hust.edu.cn/GSCA) for cancer GSA at genomic, pharmacogenomic and immunogenomic levels. In this improved GSCA, we integrated expression, mutation, drug sensitivity and clinical data from four public data sources for 33 cancer types. We introduced useful features to GSCA, including associations between immune infiltration with gene expression and genomic variations, and associations between gene set expression/mutation and clinical outcomes. GSCA has four main functional modules for cancer GSA to explore, analyze and visualize expression, genomic variations, tumor immune infiltration, drug sensitivity and their associations with clinical outcomes. We used case studies of three gene sets: (i) seven cell cycle genes, (ii) tumor suppressor genes of PI3K pathway and (iii) oncogenes of PI3K pathway to prove the advantage of GSCA over single gene analysis. We found novel associations of gene set expression and mutation with clinical outcomes in different cancer types on gene set level, while on single gene analysis level, they are not significant associations. In conclusion, GSCA is a user-friendly web server and a useful resource for conducting hypothesis tests by using GSA methods at genomic, pharmacogenomic and immunogenomic levels.

A miR-9-5p/FOXO1/CPEB3 Feed-Forward Loop Drives the Progression of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide, but its regulatory mechanism remains unclear and potential clinical biomarkers are still lacking. Co-regulation of TFs and miRNAs in HCC and FFL module studies may help to identify more precise and critical driver modules in HCC development. Here, we performed a comprehensive gene expression and regulation analysis for HCC in vitro and in vivo. Transcription factor and miRNA co-regulatory networks for differentially expressed genes between tumors and adjacent tissues revealed the critical feed-forward loop (FFL) regulatory module miR-9-5p/FOXO1/CPEB3 in HCC. Gain- and loss-of-function studies demonstrated that miR-9-5p promotes HCC tumor proliferation, while FOXO1 and CPEB3 inhibit hepatocarcinoma growth. Furthermore, by luciferase reporter assay and ChIP-Seq data, CPEB3 was for the first time identified as a direct downstream target of FOXO1, negatively regulated by miR-9-5p. The miR-9-5p/FOXO1/CPEB3 FFL was associated with poor prognosis, and promoted cell growth and tumor progression of HCC in vitro and in vivo. Our study identified for the first time the existence of miR-9-5p/FOXO1/CPEB3 FFL and revealed its regulatory role in HCC progression, which may represent a new potential target for cancer therapy.

Characterization of precipitation from citrus vinegar during ageing: chemical constituents, formation mechanism and anti-proliferative effect.

Precipitation formation commonly occurs in the ageing step of fermented citrus vinegar. Hitherto, the chemical characteristics and biological properties of precipitates remain unveiled. This study focused on investigating the chemical profile, formation mechanism and biological repurposing of precipitates. Nine principal components, two flavonoid glycosides and their aglycones along with five polymethoxyflavones (PMFs), were identified from a methanol extract of precipitates. Using hydrolysis models, we demonstrated that insoluble aglycones were generated through the breakage of glycosidic bonds in flavonoid glycosides under acidic condition. Moreover, soluble bound-PMFs were destroyed by yeast-acid hybrid catalysis to release insoluble free-PMFs to form precipitates. A methanol extract of precipitates exhibited a potent anti-proliferative effect on MCF-7 cells (IC50 = 0.032 µg µL-1) via inhibiting tubulin polymerization. This study will be helpful for the food industry to aid optimizing citrus vinegar brewing and for reutilizing precipitates for functional foods and health products. Furthermore, it also provides a green strategy of PMFs enrichment from citrus using an enzyme-acid hybrid system.

Association of Human Whole Blood NAD+ Contents With Aging.

Background: NAD+, nicotinamide adenine dinucleotide, is mostly described to associate with the aging process. We aimed to investigate the association between human whole blood NAD+ contents and aging in a relative large-scale community-based population and further to address the gender impact on this association. Methods: We recruited 1,518 participants aged over 18 years old and free of cardiovascular and any type of cancer from the Jidong community from 2019 to 2020. Whole blood NAD+ level was measured by cycling assay and LC-mass spectroscopy assay. The chronological age and clinical data were collected using standard questionnaires. The participants were divided into five groups according to their chronological age. General liner regression model was performed to analyze the association between NAD+ contents and aging. In addition, we also conducted subgroup analysis by gender. Results: The mean age of included 1,518 participants was 43.0 years, and 52.6% of them were men. The average levels of whole blood NAD+ of total participants was 33.0 ± 5.5 µmol/L. The whole blood NAD+ contents in men were significantly higher than that in women (34.5 vs. 31.3 µmol/L). There was significant difference in the meat diet among NAD+ quartile groups (p = 0.01). We observed a decline trend of NAD+ contents with aging before 50 years in total participants with significant level in 40-49 years old group (ß coefficients with 95% confidence interval (95% CI): -1.12 (-2.18, -0.06)), while this trend disappeared after the 50 years. In addition, this association was significantly altered by gender (p for interaction = 0.003). In men, as compared with ≤29 years group, adjusted ß coefficient decreased with aging but was only significant in the ≥60 year group (ß,-2.16; 95% CI, -4.16 to -0.15). In females, the level of whole blood NAD+ did not significantly differ among five age groups and without the trend as males. Conclusions: Association of whole blood NAD+ contents with aging significantly differed in males and females. The loss of blood NAD+ with aging only was observed in males, especially in the male middle-aged population. It is crucial to consider the gender difference in further NAD+ related studies in the future.

CBX2 and EZH2 cooperatively promote the growth and metastasis of lung adenocarcinoma.

The disruption of epigenetic regulation is common in tumors; the abnormal expression of epigenetic factors leads to cancer occurrence and development. In this study, to investigate the potential function of histone methylation regulators in lung adenocarcinoma (LUAD), we performed differential expression analysis using RNA-seq data downloaded from The Cancer Genome Atlas (TCGA) database, and identified CBX2 and EZH2 as obviously upregulated histone methylation regulators. CBX2 knockdown significantly inhibited LUAD cell growth and metastasis in vitro and in vivo. The combined high expression of CBX2 and EZH2 was an indicator of poor prognosis in LUAD. The inhibition of both CBX2 and EZH2 exerted cooperative suppressive effects on the growth and metastasis of LUAD cells. Mechanistically, we revealed that CBX2 and EZH2 downregulated several PPAR signaling pathway genes and tumor suppressor genes through binding to their promoter cooperatively or separately. Furthermore, knockdown of CBX2 improved the therapeutic efficiency of EZH2 inhibitor on A549 cells. Our study reveals the cooperative oncogenic role of CBX2 and EZH2 in promoting LUAD progression, thereby providing potential targets for LUAD diagnosis and therapy.

Blocking of EGFR Signaling Is a Latent Strategy for the Improvement of Prognosis of HPV-Induced Cancer.

Human papillomavirus (HPV) is a double-stranded DNA (dsDNA) virus, and its high-risk subtypes increase cancer risks. However, the mechanism of HPV infection and pathogenesis still remain unclear. Therefore, understanding the molecular mechanisms and the pathogenesis of HPV are crucial in the prevention of HPV-related cancers. In this study, we analyzed cervix squamous cell carcinoma (CESC) and head and neck carcinoma (HNSC) combined data to investigate various HPV-induced cancer common features. We showed that epidermal growth factor receptor (EGFR) was downregulated in HPV-positive (HPV+) cancer, and that HPV+ cancer patients exhibited better prognosis than HPV-negative (HPV-) cancer patients. Our study also showed that TP53 mutation rate is lower in HPV+ cancer than in HPV- cancer and that TP53 can be modulated by HPV E7 protein. However, there was no significant difference in the expression of wildtype TP53 in both groups. Subsequently, we constructed HPV-human interaction network and found that EGFR is a critical factor. From the network, we also noticed that EGFR is regulated by HPV E7 protein and hsa-miR-944. Moreover, while phosphorylated EGFR is associated with a worse prognosis, EGFR total express level is not significantly correlated with prognosis. This indicates that EGFR activation will induce a worse outcome in HPV+ cancer patients. Further enrichment analysis showed that EGFR downstream pathway and cancer relative pathway are diversely activated in HPV+ cancer and HPV- cancer. In summary, HPV E7 protein downregulates EGFR that downregulates phosphorylated EGFR and inhibit EGFR-related pathways which in turn and consequently induce better prognosis.

Ginsenoside Rg2 Ameliorates Brain Injury After Intracerebral Hemorrhage in a Rat Model of Preeclampsia.

The incidence of maternal hemorrhagic stroke is elevated in women with preeclampsia during pregnancy. Panax ginseng is a traditional medicinal herb with numerous applications, and ginsenosides are the key bioactive compounds in Panax ginseng. This study aims to evaluate the effects of ginsenoside Rg2 on pregnancy outcomes and brain injury after intracerebral hemorrhage (ICH) in a rat model of preeclampsia. Preeclampsia was induced in rats by N(ω)-nitro-L-arginine methyl ester. Then, an ICH model was prepared by intrastriatal injection of bacterial collagenase. Ginsenoside Rg2 markedly elevated the survival ratio of fetuses. The placental and body weights were increased in the ginsenoside Rg2 group. Compared with the preeclampsia group, the Garcia test score of ginsenoside Rg2-treated rats was significantly increased. Ginsenoside Rg2 treatment ameliorated the ICH-induced augmentation of Evans blue extravasation, inhibited the ICH-induced elevation of brain water content, and reduced the interleukin-1ß and tumor necrosis factor-α levels in the hemorrhagic hemisphere after ICH in preeclampsia model rats. Furthermore, ginsenoside Rg2 treatment not only inhibited augmentation of TLR-4, MyD88, p-IκBα, and p-NF-κB expression but also abated the reduction of occludin and claudin-5 expression in the hemorrhagic hemisphere. The findings indicated that ginsenoside Rg2 improved pregnancy outcomes in a rat model of preeclampsia without decreasing the blood pressure and urine protein level. The findings also demonstrated that ginsenoside Rg2 ameliorated ICH-induced neurological disorder and blood-brain barrier dysfunction in an animal model of preeclampsia by regulating the TLR4/NF-κB signaling pathway.

Bone morphogenetic protein-7 inhibits endothelial-to-mesenchymal transition in primary human umbilical vein endothelial cells and mouse model of systemic sclerosis via Akt/mTOR/p70S6K pathway.

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune inflammatory and vascular disorder that causes tissue fibrosis of the skin and internal organs. Endothelial-to-mesenchymal transition (EndoMT) has been considered an important mechanism in the pathogenesis of vascular remodeling in SSc. Recent studies suggested that bone morphogenic protein 7 (BMP-7) has anti-fibrotic effects in several fibrotic diseases. OBJECTIVES: To investigate the mechanism of BMP-7 in inhibiting TGF-ß-induced EndoMT in systemic sclerosis (SSc). METHODS: Skin tissues of both healthy controls and SSc patients were detected the distribution of BMP-7. TGF-ß was applied to induce the EndoMT model of human umbilical vein endothelial cells (HUVECs), and bleomycin was used to established the SSc mouse model. After treatment of BMP-7, the protein levels of endothelial specific markers, mesenchymal cell products, transcription factors and Akt signal pathway were examined by western blotting, immunofluorescence or immunohistochemistry both in vivo and in vitro. RESULTS: The expression of BMP-7 was decreased in the basal layer of epidermis and dermis of SSc patients. EndoMT in TGF-ß-treated HUVECs and skins of SSc mouse model were markedly attenuated after treatment with rh-BMP-7. Moreover, Akt/mTOR/p70S6K phosphorylation was involved in EndoMT and BMP-7 suppressed TGF-ß- or bleomycin-induced theses phosphorylation in HUVECs or SSc mouse model. CONCLUSION: BMP-7 reduced the production of TGF-ß-induced EndoMT in HUVECs and SSc mouse model through Akt/mTOR/p70S6K signaling pathway. These findings suggested that BMP-7 could be employed as a promising antifibrotic therapy for SSc.

A comprehensive survey for human transcription factors on expression, regulation, interaction, phenotype and cancer survival.

Transcription factors (TFs) act as key regulators in biological processes through controlling gene expression. Here, we conducted a systematic study for all human TFs on the expression, regulation, interaction, mutation, phenotype and cancer survival. We revealed that the average expression levels of TFs in normal tissues were lower than 50% expression of non-TFs, whereas TF expression was increased in cancers. TFs that are specifically expressed in an individual tissue or cancer may be potential marker genes. For instance, TGIF2LX/Y were preferentially expressed in testis and NEUROG1, PRDM14, SRY, ZNF705A and ZNF716 were specifically highly expressed in germ cell tumors. We found different distributions of target genes and TF co-regulations in different TF families. Some small TF families have huge protein interaction pairs, suggesting their central roles in transcriptional regulation. The bZIP family is a small family involving many signaling pathways. Survival analysis indicated that most TFs significantly affect survival of one or more cancers. Some survival-related TFs were also specifically highly expressed in the corresponding cancer types, which may be potential targets for cancer therapy. Finally, we identified 43 TFs whose mutations were closely correlated to survival, suggesting their cancer-driven roles. The systematic analysis of TFs provides useful clues for further investigation of TF regulatory mechanisms and the role of TFs in diseases.

Expression profile of immune checkpoint genes and their roles in predicting immunotherapy response.

Immune checkpoint genes (ICGs) play critical roles in circumventing self-reactivity and represent a novel target to develop treatments for cancers. However, a comprehensive analysis for the expression profile of ICGs at a pan-cancer level and their correlation with patient response to immune checkpoint blockade (ICB) based therapy is still lacking. In this study, we defined three expression patterns of ICGs using a comprehensive survey of RNA-seq data of tumor and immune cells from the functional annotation of the mammalian genome (FANTOM5) project. The correlation between the expression patterns of ICGs and patients survival and response to ICB therapy was investigated. The expression patterns of ICGs were robust across cancers, and upregulation of ICGs was positively correlated with high lymphocyte infiltration and good prognosis. Furthermore, we built a model (ICGe) to predict the response of patients to ICB therapy using five features of ICG expression. A validation scenario of six independent datasets containing data of 261 patients with CTLA-4 and PD-1 blockade immunotherapies demonstrated that ICGe achieved area under the curves of 0.64-0.82 and showed a robust performance and outperformed other mRNA-based predictors. In conclusion, this work revealed expression patterns of ICGs and underlying correlations between ICGs and response to ICB, which helps to understand the mechanisms of ICGs in ICB signal pathways and other anticancer treatments.

Chlorogenic acid alleviates acetaminophen-induced liver injury in mice via regulating Nrf2-mediated HSP60-initiated liver inflammation.

Acetaminophen (APAP)-induced acute liver failure is a serious clinic issue. Our previous study showed that chlorogenic acid (CGA) alleviated APAP-induced liver inflammatory injury, but its concrete mechanism is still not clear. This study aims to elucidate the engaged mechanism involved in the CGA-provided alleviation on APAP-induced liver inflammation. CGA reduced the increased hepatic infiltration of immune cells and the elevated serum contents of high mobility group box 1 (HMGB1) and heat shock protein 60 (HSP60) in mice treated with APAP. CGA decreased the enhanced hepatic mRNA expression of some pro-inflammatory molecules in mice treated with APAP and in RAW264.7 cells stimulated with HMGB1 or HSP60. CGA attenuated liver mitochondrial injury, rescued the decreased lon protease homolog (Lon) protein expression, and reduced mitochondrial HSP60 release in mice treated with APAP. Moreover, the CGA-provided alleviation on APAP-induced liver inflammatory injury was diminished in mice treated with anti-HSP60 antibody. Further results showed that the CGA-provided alleviation on APAP-induced liver inflammation was also diminished in nuclear factor erythroid 2-related factor 2 (Nrf2) knock-out mice. Meanwhile, the CGA-provided reduce on serum HSP60 content and restore of mitochondrial Lon protein expression were all diminished in Nrf2 knock-out mice treated with APAP. In conclusion, our study revealed that CGA alleviated APAP-induced liver inflammatory injury initiated by HSP60 or HMGB1, and Nrf2 was critical for regulating the mitochondrial HSP60 release via rescuing the reduced mitochondrial Lon protein expression.

The expression and regulation of HOX genes and membrane proteins among different cytogenetic groups of acute myeloid leukemia.

BACKGROUND: The cytogenetic aberrations were considered as markers for diagnosis and prognosis in acute myeloid leukemia (AML), while the expression and regulation under different cytogenetic groups remain to be fully elucidated. METHODS: In this paper, for favorable, poor, and cytogenetically normal groups of AML patients, we performed comprehensive bioinformatics analyses including identifying differentially expressed genes (DEGs) and microRNAs (miRNAs) among them, functional enrichment and regulatory networks. RESULTS: We found that DEGs were enriched in membrane-related processes. Eleven genes and two miRNAs were significantly differentially expressed among these three AML groups. In survival analysis, membrane-related genes and several miRNAs were significant on prognostic outcome. Notably, six HOXA and three HOXB genes were significantly in low expression and high methylation in AML with favorable cytogenetics. Meanwhile, the miRNA-HOX gene co-regulatory networks revealed that HOXA5 was a hub node and regulated an AML oncogene SPARC. CONCLUSION: Our work may provide novel insights to the molecular characteristics and classification between AML with different cytogenetics.

The MicroRNA MiR-29c Alleviates Renal Fibrosis via TPM1-Mediated Suppression of the Wnt/ß-Catenin Pathway.

PURPOSE: This study aimed to evaluate the mechanism by which miR-29c expression in fibroblasts regulates renal interstitial fibrosis. METHODS: We stimulated NRK-49F cells with TGF-ß1 to mimic the effects of fibrosis in vitro, while unilateral ureteral obstruction (UUO) was performed to obstruct the mid-ureter in mice. MiR-29c mimic or miR-29c inhibitor was used to mediate genes expressions in vitro. The recombinant adeno associated virus (rAAV) vectors carrying a FSP1 promoter that encodes miR-29c precursor or miR-29c inhibitor was used to mediate genes expressions in vivo, and a flank incision was made to expose the left kidney of each animal. RESULTS: In the present study, TGF-ß1 was demonstrated to regulate miR-29c expression through Wnt/ß-catenin signaling. In contrast, miR-29c appears to inhibit the Wnt/ß-catenin pathway by suppressing TPM1 expression. As suggested by this feedback mechanism, miR-29c may be a key fibrosis-related microRNA expressed by fibroblasts in TGF-ß1/Wnt/ß-catenin-driven renal fibrosis, and manipulation of miR-29c action may accordingly offer a potential therapeutic pathway for renal fibrosis treatment. CONCLUSION: MiR-29c expression was downregulated in UUO mouse kidneys as well as TGF-ß1-treated NRK-49F cells, which thus inhibits myofibroblast formation via targeting of TPM1. Additionally, the production of extracellular matrix (ECM) in renal fibroblasts appears to be controlled by the reciprocal regulation of miR-29c action and the Wnt/ß-catenin pathway.

A 6-Membrane Protein Gene score for prognostic prediction of cytogenetically normal acute myeloid leukemia in multiple cohorts.

Background: Cytogenetically normal acute myeloid leukemia (CN-AML) is a large proportion of AMLs with diverse prognostic outcomes. Identifying membrane protein genes as prognostic factors to stratify CN-AML patients will be critical to improve their outcomes. Purpose: This study aims to identify prognostic factors to stratify CN-AML patients to choose better treatments and improve their outcomes. Methods: CN-AML data were from TCGA cohort (n = 79) and four GEO datasets. We identified independent prognostic genes by Cox regression and Kaplan-Meier methods, and constructed linear regression model using LASSO algorithm. The prediction error curve was calculated using R package "pec". Results: Based on independent prognostic membrane genes, we constructed a regression model for CN-AML prognosis prediction: score = (0.0492 * CD52) - (0.0018 * CD96) + (0.0131 * EMP1) + (0.2058 * TSPAN2) + (0.0234 * STAB1) - (0.3658 * MBTPS1), which was named as MPG6 (6-Membrane Protein Gene) score. Tested in multiple CN-AML datasets, consistent results showed that CN-AML patients with high MPG6 score had poor survival, higher WBC count and shorter EFS. Comparing with other reported scoring models, the benchmark result of MPG6 achieved better association with survival in multiple cohorts. Moreover, by combining with other clinical indicators in CN-AML, MPG6 could improve the performance of survival prediction and serve as a robust prognostic factor. Conclusions: We identified the MPG6 score as a stable indicator with great potential for clinical application in risk stratification and outcome prediction in CN-AML.

Landscape of cancer diagnostic biomarkers from specifically expressed genes.

Although there has been great progress in cancer treatment, cancer remains a serious health threat to humans because of the lack of biomarkers for diagnosis, especially for early-stage diagnosis. In this study, we comprehensively surveyed the specifically expressed genes (SEGs) using the SEGtool based on the big data of gene expression from the The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) projects. In 15 solid tumors, we identified 233 cancer-specific SEGs (cSEGs), which were specifically expressed in only one cancer and showed great potential to be diagnostic biomarkers. Among them, three cSEGs (OGDH, MUDENG and ACO2) had a sample frequency >80% in kidney cancer, suggesting their high sensitivity. Furthermore, we identified 254 cSEGs as early-stage diagnostic biomarkers across 17 cancers. A two-gene combination strategy was applied to improve the sensitivity of diagnostic biomarkers, and hundreds of two-gene combinations were identified with high frequency. We also observed that 13 SEGs were targets of various drugs and nearly half of these drugs may be repurposed to treat cancers with SEGs as their targets. Several SEGs were regulated by specific transcription factors in the corresponding cancer, and 39 cSEGs were prognosis-related genes in 7 cancers. This work provides a survey of cancer biomarkers for diagnosis and early diagnosis and new insights to drug repurposing. These biomarkers may have great potential in cancer research and application.