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Objective To investigate the relationship between the expression of SLIT3 and SPARCL1 protein and the recurrence of cervical cancer after radical operation. Methods From October 2019 to April 2021, 107 patients who underwent radical surgery for cervical cancer in the hospital were selected as the study subjects, and 30 patients with benign uterine lesions were selected as the control group ; The patients were followed up for 1 year and were divided into relapse group (n = 25) and non relapse group (n = 82) according to the follow-up results. The expression levels of SLIT3 and SPARCL1 mRNA were detected by real-time fluorescence quantitative analysis (qPCR), and the expression levels of SLIT3 and SPARCL1 protein were detected by immunohistochemistry. The correlation between the expression of SLIT3 and SPARCL1 protein and clinicopathological characteristics was analyzed. Cox model was used to analyze the risk factors of cervical cancer recurrence after radical operation. Results The expression of SLIT3 and SPARCL1 mRNA in cervical cancer group was significantly lower than that in control group (P < 0.05) ; The levels of SLIT3 and SPARCL1 mRNA in cervical cancer tissues of patients with recurrence were significantly lower than those of patients without recurrence (P < 0.05).Among 107 patients with radical operation, 25 patients recurred, the recurrence rate was 23.36%. The postoperative recurrence rate of patients with low expression of SLIT3 (31.15%) was significantly higher than that of patients with high expression of SLIT3 (13.04%). The postoperative recurrence rate of patients with low expression of SPARCL1 (32.31%) was significantly higher than that of patients with high expression of sparcli (9.52%). The difference was statistically significant (P < 0.05). The expression of SLIT3 and SPARCL1 in cervical cancer was correlated with the degree of differentiation, clinical stage, lymph node metastasis and depth of stromal invasion (P < 0.05), but not with age, pathological type and maximum diameter of tumor (P > 0.05 ). Cox univariate analysis showed that the degree of differentiation, clinical stage, lymph node metastasis, stromal invasion depth, SLIT3 protein expression and SPARCL1 protein expression were correlated with the recurrence of cervical cancer patients after radical surgery (P < 0.05 ) ; Cox multivariate analysis showed that moderate/high differentiation, stage IIA, lymph node metastasis, stromal invasion depth > 50%, low expression of SLIT3 protein and SPARCL1 protein were independent risk factors for recurrence of cervical cancer patients after radical surgery (P < 0.05). Conclusion the expression of SLIT3 and SPARCL1 in cervical cancer tissue is lower than that in normal cervical tissue. The low expression of SLIT3 and SPARCL1 protein is an independent risk factor for the recurrence of cervical cancer after radical operation, and has certain clinical significance in predicting the recurrence of cervical cancer after operation. [ABSTRACT FROM AUTHOR]

Objectives: We analyzed the diagnostic efficiency of 68Ga-pentixafor PET/CT for functional nodules in primary aldosteronism (PA). Furthermore, we compared the correlation of CXCR4 expression with aldosterone synthase (CYP11B2) expression and PET/CT uptake in these patients. Methods: We prospectively assessed 50 patients diagnosed with PA and 10 patients with non-functional adrenal adenoma (NFA). All patients underwent 68Ga-pentixafor PET/CT before adrenalectomy. Immunohistochemistry (IHC) was performed to detect the protein expression of CYP11B2 and the G-protein-coupled receptor CXCR4. Results: CYP11B2 IHC revealed the presence of 43 functional nodules. Subsequently, 40/43 functional nodules could be detected on 68Ga-pentixafor PET/CT, while negative imaging findings were noted for 11/13 non-functional nodules (sensitivity, 93.0%; specificity, 84.6%). The optimum SUVmax cut-off for the identification of functional nodules was 8.95 (AUC 0.914 [0.828–1.000], p < 0.001). Regarding the size of functional nodules, diagnostic efficiency appeared to be much higher for nodules greater than 1 cm in size (sensitivity, up to 97.3%). Moreover, we examined the relationship between CXCR4 and CYP11B2 expression in 56 lesions. All 43 CYP11B2-positive nodules were CXCR4-positive, but one of the 13 CYP11B2-negative nodules (7.7%) showed false-positive staining for CXCR4. Moreover, the consistency between PET/CT uptake and CXCR4 staining results was 92.9% (52/56). Conclusions: At least 90% of functional nodules show positive uptake on 68Ga-pentixafor PET/CT, and the detection ability is much better for nodules with a diameter ≥ 1 cm. With its high sensitivity and specificity, 68Ga-pentixafor PET/CT can be considered a promising surgical decision-making tool for patients with PA. Key Points: •68Ga-pentixafor PET/CT could be a useful tool for the identification of functional adrenal nodules in APAs and even IHAs. • The diagnostic efficiency appears to be much higher for nodules ≥ 1 cm in size. • There is high consistency between the results of 68Ga-pentixafor PET/CT imaging and CXCR4 immunohistochemistry. [ABSTRACT FROM AUTHOR]

Simple Summary: Our aim was to elucidate the molecular mechanisms of how tyrosine kinase inhibitors, including sunitinib, contribute to vasculogenic mimicry (VM) formation and progression in renal cell carcinoma. We demonstrated that sunitinib and axitinib could induce ERβ expression in RCC cell lines and ERβ transcriptionally up-regulated the circular RNA of DGKD (circDGKD, hsa_circ_0058763) expression. The circDGKD could sponge tumor suppressor miR-125-5p family members and consequently led to increased VE-cadherin, the key adhesion molecule in the VM formation process, which is targeted by miR-125-5p at the 3′ UTR, providing novel targets for combination therapy in clinical metastatic RCC patients. Vasculogenic mimicry (VM) has been reported as an alternative channel to increase tumor nutrient supplies and accelerate tumor progression, and is associated with poor survival prognosis in multiple cancers, including renal cell carcinoma (RCC). The currently used anti-angiogenic treatment for metastatic RCC, sunitinib, a tyrosine kinase inhibitor (TKI), has been reported to induce VM formation. Previously we identified that the estrogen receptor β (ERβ) functions as an oncogenic factor to promote RCC progression, supported by the analytic results from The Cancer Genome Atlas (TCGA) database. We have also found evidence that sunitinib induces RCC VM formation by up-regulating ERβ expression. In this study, we further demonstrated that treatment with sunitinib, as well as axitinib, another TKI, could induce ERβ expression in RCC cell lines. Clinical clear cell RCC (ccRCC) patients with higher ERβ expression are more likely to be found VE-cadherin positive and VM positive. Mechanism dissection showed that TKI- induced ERβ transcriptionally up-regulates the circular RNA of DGKD (circDGKD, hsa_circ_0058763), which enhances VE-cadherin expression by sponging the microRNA miR-125-5p family. Targeting circDGKD intercepts sunitinib-pretreatment-induced RCC VM formation, reduces metastases and improves survival in an experimental orthotopic animal model. Targeting ERβ/circDGKD signals may improve the TKI efficacy and provide novel combination therapies for metastatic RCC. [ABSTRACT FROM AUTHOR]

Hypertrophic scars (HTS) develop from an excessive synthesis of structural proteins like collagen and a decreased expression of proteoglycans such as decorin. Previous research has demonstrated that decorin expression is significantly down‐regulated in HTS, deep dermal tissue, and thermally injured tissue, reducing its ability to regulate pro‐fibrotic transforming growth factor‐beta 1 (TGF‐β1) and normal fibrillogenesis. However, treatment of HTS fibroblasts with interferon‐alpha 2b (IFN‐α2b) has been shown to reduce excessive collagen synthesis and improve HTS by reducing serum TGF‐β1 levels. The expression of decorin isoforms in HTS is currently unknown and the effects of TGF‐β1 and IFN‐α2b on decorin, decorin isoform expression and type 1 collagen are of great interest to our group. Dermal fibroblasts were treated with TGF‐β1 and/or IFN‐α2b, for 48 h. The expression and secretion of decorin, decorin isoforms and type 1 collagen were quantified with reverse transcription‐quantitative polymerase chain reaction, immunofluorescence staining and enzyme‐linked immunosorbent assays. The mRNA expression of decorin and each isoform was significantly reduced in HTS fibroblasts relative to normal skin. TGF‐β1 decreased the mRNA expression of decorin and decorin isoforms, whereas IFN‐α2b showed the opposite effect. IFN‐α2b significantly inhibited TGF‐β1's effect on the mRNA expression of type I collagen alpha 1 in papillary dermal fibroblasts and overall showed relative effects of inhibiting TGF‐β1. These data support that a further investigation into the structural and functional roles of decorin isoforms in HTS pathogenesis is warranted and that IFN‐α2b is an important agent in reducing fibrotic outcomes. [ABSTRACT FROM AUTHOR]

Objective. To study the biological characteristics of paclitaxel resistant endometrial carcinoma cells and its mechanism of drug resistance. Method. The paclitaxel resistant cell lines were established by high-dose paclitaxel (TAX) injection. The IC50 of paclitaxel was determined by CCK-8 assay in Ishikawa and Ishikawa-TAX. The cell cycle and apoptosis rate were detected by flow cytometry. Western blot was used to detect the expression of p-AKT and p-p70S6K. The expression of drug resistance-related genes Pgp and MDR1 was determined by RT-PCR. Cell viability was determined by soft agarose assay and invasive ability in vitro by transwell assay. Results. Paclitaxel and NVP-BEZ235 cotreatment group can further inhibit the clonogenicity and invasion of Ishikawa and Ishikawa-TAX cells compared with paclitaxel alone and NVP-BEZ235 treatment group. Paclitaxel and NVP-BEZ235 cotreated groups increased the apoptosis rate of Ishikawa and increased G0/G1 phase arrest in both cells. Paclitaxel alone significantly inhibited p-AK and p-p70 S6K protein expression in Ishikawa and Ishikawa-TAX cells and the inhibition was enhanced by NVP-BEZ235 when cotreated with paclitaxel. Conclusion. Paclitaxel can inhibit Ishikawa and Ishikawa-TAX cell via PI3K/Akt/mTOR signaling pathway. Paclitaxel and NVP-BEZ235 cotreatment can enhance the inhibitory effect. [ABSTRACT FROM AUTHOR]

Dermal wound healing, in which transforming growth factor beta 1 (TGFβ1) plays an important role, is a complex process. Previous studies suggest that vitamin D has a potential regulatory role in TGFβ1 induced activation in bone formation, and there is cross-talk between their signaling pathways, but research on their effects in other types of wound healing is limited. The authors therefore wanted to explore the role of vitamin D and its interaction with low concentration of TGFβ1 in dermal fibroblast-mediated wound healing through an in vitro study. Human dermal fibroblasts were treated with vitamin D, TGFβ1, both, or vehicle, and then the wound healing functions of dermal fibroblasts were measured. To further explore possible mechanisms explaining the synergistic effect of vitamin D and TGFβ1, targeted gene silencing of the vitamin D receptor was performed. Compared to either factor alone, treatment of fibroblasts with both vitamin D and low concentration of TGFβ1 increased gene expression of TGFβ1, connective tissue growth factor, and fibronectin 1, and enhanced fibroblast migration, myofibroblast formation, and collagen production. Vitamin D receptor gene silencing blocked this synergistic effect of vitamin D and TGFβ1 on both collagen production and myofibroblast differentiation. Thus a synergistic effect of vitamin D and low TGFβ1 concentration was found in dermal fibroblast-mediated wound healing in vitro. This study suggests that supplementation of vitamin D may be an important step to improve wound healing and regeneration in patients with a vitamin D deficiency. [ABSTRACT FROM AUTHOR]

Despite its wide-ranging benefits, whole-transcriptome or RNA exome profiling is challenging to implement in a clinical diagnostic setting. The Unified Assay is a comprehensive workflow wherein exome-enriched RNA-sequencing (RNA-Seq) assays are performed on clinical samples and analyzed by a series of advanced machine learning-based classifiers. Gene expression signatures and rare and/or novel genomic events, including fusions, mitochondrial variants, and loss of heterozygosity were assessed using RNA-Seq data generated from 120,313 clinical samples across three clinical indications (thyroid cancer, lung cancer, and interstitial lung disease). Since its implementation, the data derived from the Unified Assay have allowed significantly more patients to avoid unnecessary diagnostic surgery and have played an important role in guiding follow-up decisions regarding treatment. Collectively, data from the Unified Assay show the utility of RNA-Seq and RNA expression signatures in the clinical laboratory, and their importance to the future of precision medicine. [ABSTRACT FROM AUTHOR]

Background: Twist, a basic helix-loop-helix transcription factor, has been reported to play a key role in the metastatic progression of several types of cancer. Aims: To investigate the expression and clinical significance of Twist, E-cadherin, and N-cadherin in gastrointestinal stromal tumors (GISTs). Methods: The expression of Twist, E-cadherin, and N-cadherin in GISTs was determined by immunohistochemistry, and their relationship with clinicopathological characteristics was analyzed. Results: The positive rates of Twist, E-cadherin, and N-cadherin in GISTs were 66.7 % (52/78), 35.9 % (28/78), and 75.6 % (59/78), respectively. Twist was expressed significantly more in GISTs with distant metastasis or local invasion ( p < 0.05). Although E-cadherin was expressed significantly less in cases of GISTs with distant metastasis ( p < 0.05), expression of N-cadherin did not differ significantly according to clinical and pathological characteristics ( p > 0.05). Expression of Twist was correlated positively with E-cadherin ( rs = −0.253, p = 0.026) and negatively with N-cadherin ( rs = 0.245, p = 0.030). Conclusions: Twist was expressed significantly more and E-cadherin significantly less in GISTs with metastasis, and expression of both was closely related to metastasis of GISTs. [ABSTRACT FROM AUTHOR]

The neuroendocrine system of fish responds to low temperature via regulating hormones. To explore the adaptability of Larimichthys crocea to low temperature, the levels of the plasma cortisol, thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), total cholesterol (TC), and glucose were determined after exposure to low temperature and during subsequent rewarming. Furthermore, the mRNA expression of the glucocorticoid receptor (GR) gene was analyzed under the stress. We found that the levels of the plasma cortisol, TSH, T3, glucose, and TC increased under the low temperature stress, suggesting that elevated hormones may be conducive to promoting the mobilization of the glucose and lipid in L. crocea exposed to low temperature. During the rewarming period, the plasma cortisol level decreased, whereas the T3 level was still significantly higher than that in the control group. Notably, the plasma T4 level was unaffected by the temperature changes. Furthermore, the sequence alignment and phylogenetic tree analysis revealed that the GR protein of L. crocea had high homology and a similar protein structure with those from other teleosts. Under the low temperature stress, the GR mRNA expression increased in the brain and head kidney, whereas it basically returned to the control level following rewarming. These findings revealed the changes of the hormones and the potential function of the GR gene in L. crocea following exposure to low temperature, providing some insights into breeding low temperature-resistant varieties of L. crocea. • Multiple hormones released by the endocrine system stimulate energy mobilization at low temperature. • T3 may play a leading role in the metabolic recovery in Larimichthys crocea. • GR gene is considered an important candidate gene for low temperature resistance in L. crocea. • L. crocea may have the self-repair functions of the metabolism during the rewarming. [ABSTRACT FROM AUTHOR]

Background: Ethanol-type fermentation, one of the fermentation types in mixed cultures of acidogenesis with obvious advantages such as low pH tolerance and high efficiency of H2 production, has attracted widespread attentions. pH level greatly influences the establishment of the fermentation of carbohydrate acidogenesis by shaping community assembly and the metabolic activity of keystone populations. To explore the adaptation mechanisms of ethanol-type fermentation to low pH, we report the effects of initial pH on the physiological metabolism and transcriptomes of Ethanoligenens harbinense—a representative species of ethanol-type fermentation. Results: Different initial pH levels significantly changed the cell growth and fermentation products of E. harbinense. Using transcriptomic analysis, we identified and functionally categorized 1753 differentially expressed genes (DEGs). By mining information on metabolic pathways, we probed the transcriptional regulation of ethanol–H2 metabolism relating to pH responses. Multiple pathways of E. harbinense were co-regulated by changing gene expression patterns. Low initial pH down-regulated the expression of cell growth- and acidogenesis-related genes but did not affect the expression of H2 evolution-related hydrogenase and ferredoxin genes. High pH down-regulated the expression of H2 evolution- and acidogenesis-related genes. Multiple resistance mechanisms, including chemotaxis, the phosphotransferase system (PTS), and the antioxidant system, were regulated at the transcriptional level under pH stress. Conclusions: Ethanoligenens adapted to low pH by regulating the gene expression networks of cell growth, basic metabolism, chemotaxis and resistance but not H2 evolution-related genes. Regulation based on pH shifts can represent an important approach to establish and enhance ethanol-type fermentation. The complete gene expression network of ethanol fermentative bacteria for pH response provides valuable insights into the acidogenic fermentation, and offers an effective regulation strategy for the sustainable energy recovery from wastewater and solid waste. [ABSTRACT FROM AUTHOR]

Bladder outlet obstruction is a common disease, which always evokes urinary bladder wall remodeling significantly. It has been suggested that bladder outlet obstruction can make the bladder progression from inflammation to fibrosis, and hypoxia may play a vital role. It has been found the expression of microRNA‐101 varied in bladder after BOO. But what role microRNA‐101 and hypoxia play in bladder is not well known. This study is to investigate the mechanism of microRNA‐101 and hypoxia in fibrosis of bladder after BOO. We found the expression of microRNA‐101 and hif‐1α increased in bladder after BOO. Hypoxia could promote the expression of extracellular matrix subtypes and microRNA‐101 in BSMCs. When microRNA‐101b was translated into BSMCs, the smad2/3 signaling pathway was found to repress. Dual luciferase reporter detected that microRNA‐101b attenuated the TGF‐β signaling pathway by inhibiting the expression of TGFβR1. Then, we conclude microRNA‐101b is induced by hypoxia and represses fibrosis of BSMCs by inhibiting the expression of TGFβR1 through TGF‐β signaling pathway, and it may be an anti‐fibrotic miRNA for therapy. © 2018 IUBMB Life, 71(1):235–243, 2019 [ABSTRACT FROM AUTHOR]

Pregnant women and animals have increased susceptibility to a variety of intracellular pathogens including Listeria monocytogenes (LM), which has been associated with significantly increased level of sex hormones such as progesterone. CD8 T memory(Tm) cell-mediated antigen-non-specific IFN-γ responses are critically required in the host defense against LM. However, whether and how increased progesterone during pregnancy modulates CD8 Tm cell-mediated antigen-non-specific IFN-γ production and immune protection against LM remain poorly understood. Here we show in pregnant women that increased serum progesterone levels are associated with DNA hypermethylation of IFN-γ gene promoter region and decreased IFN-γ production in CD8 Tm cells upon antigen-non-specific stimulation ex vivo. Moreover, IFN-γ gene hypermethylation and significantly reduced IFN-γ production post LM infection in antigen-non-specific CD8 Tm cells are also observed in pregnant mice or progesterone treated non-pregnant female mice, which is a reversible phenotype following demethylation treatment. Importantly, antigen-non-specific CD8 Tm cells from progesterone treated mice have impaired anti-LM protection when adoptive transferred in either pregnant wild type mice or IFN-γ-deficient mice, and demethylation treatment rescues the adoptive protection of such CD8 Tm cells. These data demonstrate that increased progesterone impairs immune protective functions of antigen-non-specific CD8 Tm cells via inducing IFN-γ gene hypermethylation. Our findings thus provide insights into a new mechanism through which increased female sex hormone regulate CD8 Tm cell functions during pregnancy. [ABSTRACT FROM AUTHOR]

OsRab7, a gene responsible for vesicle traffic, was down-regulated in the anther of the CMS line (SJA) compared to the maintainer line (SJB). The rab7 mutant showes defects in tapetum degeneration and microspores development, resulting in significantly reduced pollen fertility. Over-expression of OsRab7 in the SJA (Trans A) increases pollen fertility, while OsRab7 knockdown in the SJB (Trans B) reduces polled fertility. Genes related to auxin biosynthesis (YUCCAs), auxin transport (PINs), auxin response factor (ARFs), and IAA family members (IAAs) are down-regulated in the rab7 line. Therefore, the rab7 mutant showes the reduced auxin signal. These findings highlights the role of OsRab7, in pollen development and provides valuable insights for the CMS pathway in BT-rice. [Display omitted] • OsRab7 , a gene responsible for vesicle traffic, was down-regulated in anther of CMS line (SJA) compared to the maintainer line (SJB). • The rab7 mutant showed defects in tapetum degeneration and microspores development, resulting in significantly reduced pollen fertility. • Over-expression of OsRab7 in SJA increased pollen fertility, while OsRab7 knockdown in SJB reduced polled fertility. • Reduced auxin signal was observed in the rab7 line. • These findings highlighted OsRab7 ′s impact on pollen development and provided potential links to CMS rice. Rice cytoplasmic male sterility (CMS) provides an exceptional model for studying genetic interaction within plant nuclei given its inheritable trait of non-functional male gametophyte. Gaining a comprehensive understanding of the genes and pathways associated with the CMS mechanism is imperative for improving the vigor of hybrid rice agronomically, such as its productivity. Here, we observed a significant decrease in the expression of a gene named OsRab7 in the anther of the CMS line (SJA) compared to the maintainer line (SJB). OsRab7 is responsible for vesicle trafficking and loss function of OsRab7 significantly reduced pollen fertility and setting rate relative to the wild type. Meanwhile, over-expression of OsRab7 enhanced pollen fertility in the SJA line while a decrease in its expression in the SJB line led to the reduced pollen fertility. Premature tapetum and abnormal development of microspores were observed in the rab7 mutant. The expression of critical genes involved in tapetum development (OsMYB103, OsPTC1, OsEAT1 and OsAP25) and pollen development (OsMSP1 , OsDTM1 and OsC4) decreased significantly in the anther of rab7 mutant. Reduced activities of the pDR5 :: GUS marker in the young panicle and anther of the rab7 mutant were also observed. Furthermore, the mRNA levels of genes involved in auxin biosynthesis (YUCCAs), auxin transport (PINs), auxin response factors (ARFs), and members of the IAA family (IAAs) were all downregulated in the rab7 mutant, indicating its impact on auxin signaling and distribution. In summary, these findings underscore the importance of OsRab7 in rice pollen development and its potential link to cytoplasmic male sterility. [ABSTRACT FROM AUTHOR]

Hypertrophic scar (HTS), a fibroproliferative disorder (FPD), complicates burn wound healing. Although the pathogenesis is not understood, prolonged inflammation is a known contributing factor. Emerging evidence suggests that fibroblasts regulate immune/inflammatory responses through toll-like receptor 4 (TLR4) activated by lipopolysaccharide (LPS) through adaptor molecules, leading to nuclear factor kappa-light-chain-enhancer of activated B cells and mitogen-activated protein kinases activation, cytokine gene transcription and co-stimulatory molecule expression resulting in inflammation. This study explored the possible role of TLR4 in HTS formation. Paired normal and HTS tissue from burn patients was collected and dermal fibroblasts isolated and cultured. Immunohistochemical analysis of tissues demonstrated increased TLR4 staining in HTS tissue. Quantitative RT-PCR of three pairs of fibroblasts demonstrated mRNA levels for TLR4 and its legend myeloid differentiation factor 88 (MyD88) in HTS fibroblasts were increased significantly compared with normal fibroblasts. Flow cytometry showed increased TLR4 expression in HTS fibroblasts compared with normal. ELISA demonstrated protein levels for prostaglandin E2, interleukin (IL)-6, IL-8 and monocyte chemotactic protein-1 (MCP-1) were significantly increased in HTS fibroblasts compared to normal. When paired normal and HTS fibroblasts were stimulated with LPS, significant increases in mRNA and protein levels for MyD88, IL-6, IL-8, and MCP-1 were detected. However, when transfected with MyD88 small interfering RNA (siRNA), then stimulated with LPS, a significant decrease in mRNA and protein levels for these molecules compared to only LPS-stimulated fibroblasts was detected. In comparison, a scramble siRNA transfection did not affect mRNA or protein levels for these molecules. Results demonstrate LPS stimulates proinflammatory cytokine expression in dermal fibroblasts and MyD88 siRNA eliminates the expression. Therefore, controlling inflammation and manipulating TLR signaling in skin cells may result in novel treatment strategies for HTS and other FPD. J. Cell. Physiol. 226: 1265-1273, 2011. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background: The genomics data analysis has been widely used to study disease genes and drug targets. However, the existence of missing values in genomics datasets poses a significant problem, which severely hinders the use of genomics data. Current imputation methods based on a single learner often explores less known genomic data information for imputation and thus causes the imputation performance loss. Results: In this study, multiple single imputation methods are combined into an imputation method by ensemble learning. In the ensemble method, the bootstrap sampling is applied for predictions of missing values by each component method, and these predictions are weighted and summed to produce the final prediction. The optimal weights are learned from known gene data in the sense of minimizing a cost function about the imputation error. And the expression of the optimal weights is derived in closed form. Additionally, the performance of the ensemble method is analytically investigated, in terms of the sum of squared regression errors. The proposed method is simulated on several typical genomic datasets and compared with the state-of-the-art imputation methods at different noise levels, sample sizes and data missing rates. Experimental results show that the proposed method achieves the improved imputation performance in terms of the imputation accuracy, robustness and generalization. Conclusion: The ensemble method possesses the superior imputation performance since it can make use of known data information more efficiently for missing data imputation by integrating diverse imputation methods and learning the integration weights in a data-driven way. [ABSTRACT FROM AUTHOR]

In this paper, we propose a new sparse learning model for the classification of gene expression data, named Group K-Singular Value Decomposition (Group K-SVD). It learns the optimal dictionary and sparse representation from the training data, and then assigns the out-of-sample data to the class with the nearest centroid. Group K-SVD reduces the redundancy of over-complete dictionary by using a group update strategy during the dictionary update stage. To solve the optimization problem, we also develop a Multivariate Orthogonal Matching Pursuit (MOMP) algorithm for the sparse coefficient update stage. In the evaluation of the performance of Group K-SVD model, we implement three Group K-SVD algorithms by incorporating MOMP as well as another two popular optimization algorithms into the sparse coefficient update stage. Sufficient experimental results demonstrate that our Group K-SVD algorithms are both effective and efficient in comparison with the state-of-the-methods on real-world gene expression datasets. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) have emerged as essential players in gene regulation. An ever-increasing number of lncRNAs has been found to be associated with the biogenesis and prognosis of gastric cancer (GC). We aimed to develop an lncRNA signature with prognostic value for survival outcomes of GC. Using an lncRNA mining approach, we analyzed the lncRNA expression profiles of 492 GC patients from the Gene Expression Omnibus (GEO), which consisted of the GSE62254 set ( N = 300) and the GSE15459 set ( N = 192). The associations between the lncRNAs' expression and survival outcome were evaluated. A set of three lncRNAs ( LINC01140, TGFB2-OT1, and RP11-347C12.10) was identified to significantly correlate with overall survival. These lncRNAs were then combined to form a single prognostic signature. Based on this three-lncRNA expression signature, patients in the GSE62254 set were classified into high- and low-risk subgroups with significantly different overall survival (hazard ratio [HR] = 1.93, P < 0.001) and disease-free survival (HR = 1.91, P < 0.001). Good reproducibility for the prognostic value of this lncRNA signature was confirmed in the GSE15459 set. Further analysis showed that the prognostic value of this signature was independent of some clinical characteristics. Gene set enrichment analysis indicated that high-risk scores positively related to several molecular pathways of cancer metastasis. Our results suggest that this innovative lncRNA expression signature may be a useful biomarker for the prognosis of patients with GC based on bioinformatics analysis. [ABSTRACT FROM AUTHOR]

Backgrounds/Aims: Mitochondrial dysfunction plays an important role inthe pathogenesis of nonalcoholic steatohepatitis (NASH), where uncoupling protein (UCP) is actively involved. We previously reported the uncoupling activity of HDMCP and its role in liver steatosis. We now aim to investigate the degree and therapeutic effect of HDMCP in NASH and the regulatory role of miR-146 on HDMCP. Methods: NASH animal model was established by feeding BALB/c mice with MCD diet while L02 cell was cultured with high concentration of fatty acid (HFFA) for 72h to mimic the steatosis and inflammation of NASH in-vitro appearance. The steatosis level was assessed by H-E/oil-red staining and serum/supernatant marker detection. The inflammation activity was evaluated by levels of Hepatic activity index, transwell, apoptosis degree (TUNEL/flow cytometry) and serum/supernatant marker. HDMCP level was detected by western blot and miRNA expression was tested by qRT-PCR. NASH severity change was recorded after RNA interference while the regulatory role of miR-146 on HDMCP was confirmed by dual luciferase report system. The H2O2 and ATP levels were measured for mechanism exploration. Results: Increased HDMCP expression was identified in NASH animal model and HFFA-72h cultured L02 cell. Moreover, under regulation of miR-146, NASH alleviation was achieved after HDMCP downregulation in both in vivo and in vitro, according to the declination of steatosis and inflammation related markers. Though H2O2 and ATP levels were increased and decreased in NASH models, HDMCP down regulation both increased their levels. Conclusions: The miR-146-HDMCP-ATP/H2O2 pathway may provide novel mechanism and treatment option for NASH. [ABSTRACT FROM AUTHOR]

Maintenance of the physiological morphologies of different types of cells and tissues is essential for the normal functioning of each system in the human body. Dynamic variations in cell and tissue morphologies depend on accurate adjustments of the cytoskeletal system. The cytoskeletal system in the glomerulus plays a key role in the normal process of kidney filtration. To enhance the understanding of the possible roles of the cytoskeleton in glomerular diseases, we constructed the Glomerular Cytoskeleton Network (GCNet), which shows the protein-protein interaction network in the glomerulus, and identified several possible key cytoskeletal components involved in glomerular diseases. In this study, genes/proteins annotated to the cytoskeleton were detected by Gene Ontology analysis, and glomerulus-enriched genes were selected from nine available glomerular expression datasets. Then, the GCNet was generated by combining these two sets of information. To predict the possible key cytoskeleton components in glomerular diseases, we then examined the common regulation of the genes in GCNet in the context of five glomerular diseases based on their transcriptomic data. As a result, twenty-one cytoskeleton components as potential candidate were highlighted for consistently down- or up-regulating in all five glomerular diseases. And then, these candidates were examined in relation to existing known glomerular diseases and genes to determine their possible functions and interactions. In addition, the mRNA levels of these candidates were also validated in a puromycin aminonucleoside(PAN) induced rat nephropathy model and were also matched with existing Diabetic Nephropathy (DN) transcriptomic data. As a result, there are 15 of 21 candidates in PAN induced nephropathy model were consistent with our predication and also 12 of 21 candidates were matched with differentially expressed genes in the DN transcriptomic data. By providing a novel interaction network and prediction, GCNet contributes to improving the understanding of normal glomerular function and will be useful for detecting target cytoskeleton molecules of interest that may be involved in glomerular diseases in future studies. [ABSTRACT FROM AUTHOR]

The calcineurin inhibitors cyclosporine A (CsA) and tacrolimus are widely used in the treatment of proteinuria diseases. As the direct target of these drugs, calcineurin has previously been demonstrated to play a role in proteinuria diseases. However, aside from its immune-related effects, the local status of calcineurin in renal inherent cells has not been fully explored in the settings of proteinuria disease and podocyte injury. In this study, calcineurin activity and protein expression in the well-known puromycin aminonucleoside (PAN)-induced podocyte injury model were examined. Interestingly, we found that calcineurin activity was abnormally increased in PAN-treated podocytes, whereas the expression of the full-length 60-kDa calcineurin protein was decreased. This result suggests that there may be another activated form of calcineurin that is independent of the full-length phosphatase. To investigate whether calpain is involved in regulating calcineurin, we exposed PAN-treated podocytes to both pharmacological inhibitors of calpain and specific siRNAs against calpain. Calpain blockade reduced the enhanced calcineurin activity and restored the down-regulated expression of 60-kDa calcineurin. In addition, purified calpain protein was incubated with podocyte extracts, and a 45-kDa fragment of calcineurin was identified; this finding was confirmed in PAN-induced podocyte injury and calpain inhibition experiments. We conclude that calcineurin activity is abnormally increased during PAN-induced podocyte injury, whereas the expression of the full-length 60-kDa calcineurin protein is down-regulated due to over-activated calpain that cleaves calcineurin to form a 45-kDa fragment. [ABSTRACT FROM AUTHOR]

The Chinese herbal preparation QiBaoMeiRan formula (QBMR) displayed estrogenic effects in ovariectomized rats after long-term administration in a previous study. The uterus and vagina are negatively influenced by estrogens in hormone therapy. While QBMR is known to be a phytoestrogen, its estrogenic effects and safety on reproductive tissues after short-term administration and its mechanism via estrogen receptor (ER) pathway haven't been studied. Here, we characterized its estrogenic effects using immature mice together with in vitro studies for further molecular characterization. Immature mice were treated with QBMR at doses of 1.125, 2.25 and 4.5 g/kg for 7 days. 1.125 and 2.25 g/kg QBMR promoted the growth and development of uterus and vagina and upregulated ERα and ERβ expression in reproductive tissues. QBMR had a stimulatory effect on proliferating cell nuclear antigen in vagina but not in uterus and was without any influence on ki-67 antigen in uterus and vagina. QBMR significantly induced luciferase expression from the ERα/β-estrogen response element (ERE) luciferase reporter and upregulated ERα and ERβ expressions in MCF-7 cells, which were significantly inhibited by estrogen antagonist ICI182,780. This study demonstrated QBMR exerts estrogenic effects on reproductive tissues without side effects and through ER-ERE-dependent pathway. [ABSTRACT FROM AUTHOR]