Tumor microenvironment, in particular the stroma, plays an important role in breast cancer cell invasion and metastasis. Investigation of the molecular characteristics of breast cancer stroma may ...reveal targets for future study.
The transcriptome profiles of breast cancer stroma and normal breast stroma were compared to identify differentially expressed genes (DEGs). The method was analysis of GSE26910 and GSE10797 datasets. Common DEGs were identified and then analyses of enriched pathways and hub genes were performed.
A total of 146 DEGs were common to GSE26910 and GSE10797. The enriched pathways were associated with "extracellular matrix (ECM) organization", "ECM-receptor interaction" and "focal adhesion". Network analysis identified six key genes, including
,
,
,
,
and
. Notably,
and
were identified for the first time as cancer stromal key genes associated with breast cancer invasion and metastasis. Oncome analysis showed that the high expression levels of
and
correlated to an advanced stage of breast cancer and poor clinical outcomes.
We found that several conserved tumor stromal genes might regulate breast cancer invasion through ECM remodeling. The clinical outcome analyses of
and
suggest these two genes are promising targets for future studies.
Abstract
In our previous work, we reported a novel approach for increasing lipid production in an oleaginous fungus
Mucor circinelloides
by overexpression of mitochondrial malate transporter protein. ...This transporter plays a vital role in fatty acid biosynthesis during malate and citrate transport systems in oleaginous fungi. In this study, the controlling metabolic supplementation strategy was used to improve the lipid production by overexpression of malate transporter protein in
M. circinelloides
strain coded as Mc-MT-2. The effects of different metabolic intermediates on lipid production in batch fermentation by Mc-MT-2 were investigated. The optimal lipid production was obtained at 0.8% malic acid after 24 h of fermentation. Furthermore, in fed-batch bioreactors containing glucose as a carbon source supplemented with malic acid, the highest cell growth, and lipid production were achieved. The resulting strain showed the fungal dry biomass of 16 g/L, a lipid content of 32%, lipid yield of 5.12 g/L in a controlled bench-top bioreactor, with 1.60-, 1.60- and 2.56-fold improvement, respectively, compared with the batch control without supplementation of malic acid. Our findings revealed that the addition of malic acid during fermentation might play an important role in lipid accumulation in the recombinant
M. circinelloides
Mc-MT-2. This study provides valuable insights for enhanced microbial lipid production through metabolic supplementation strategy in large scale and industrial applications.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Accurate and unified information from the increasingly remote sensing (RS) scenes is important for RS applications in multi-sectoral association services of natural resource management. However, ...these applications in mountain areas are limited by the challenging issues of random geometric distortions and erroneous spatial associations. The paper introduces digital elevation model (DEM) maps as a unified geographic reference to search and match homonymy ground points (HGPs). The proposed computer-based procedure was tested with Landsat TM, ETM and HJ-1B satellite images using ASTER global DEM in the Longitudinal Rang-gorge Valley Region of Southwest China. 1322, 3551 and 694 pairs of HGPs were identified and acquired the geometric accuracies with 43 m (TM), 14 m (ETM) and 123 m (HJ), respectively. The deviations are significantly reduced and the disjoint ground objects are matched. The study satisfies the application requirement of multispectral satellite imagery with less labour and time costs.
GuHong injection is composed of safflower and
N
-acetyl-L-glutamine. It is widely used in clinical for cerebrovascular diseases, such as ischemic stroke and related diseases. The objective of this ...review is to comprehensively summarize the most recent information related to GuHong in the treatment of stroke, including chemical composition, clinical studies, potential pharmacological mechanisms and pharmacokinetics. Additionally, it examines possible scientific gaps in current study and aims to provide a reliable reference for future GuHong studies. The systematic review reveals that the chemical composition of safflower in GuHong is more than 300 chemical components in five categories. GuHong injection is primarily used in clinical applications for acute ischemic stroke and related diseases. Pharmacological investigations have indicated that GuHong acts in the early and recovery stages of ischemic stroke by anti-inflammatory, anti-oxidative stress, anti-coagulation, neuroprotective and anti-apoptotic mechanisms simultaneously. Pharmacokinetic studies found that the main exposed substances in rat plasma after GuHong administration are hydroxysafflor yellow A and
N
-acetyl-L-glutamine, and
N
-acetyl-L-glutamine could exert its pharmacological effect across the blood-brain barrier. As a combination of Chinese herb and chemical drug, GuHong injection has great value in drug research and clinical treatment, especially for ischemic stroke disease. This article represents a comprehensive and systematic review of existing studies on GuHong injection, including chemical composition, pharmacological mechanism, and pharmacokinetics, which provides reference significance for the clinical treatment of ischemic stroke with GuHong, as well as provides guidance for further study.
Anxiety has been a common mental state during the epidemic of Coronavirus Disease 2019 (COVID-19) and is usually closely related to somatization. However, no study on somatization in anxiety and its ...relationship with insomnia has been conducted. Therefore, this study aimed to identify the prevalence of anxiety, somatization and insomnia and explore the relationships between different psychological states in the general population during the COVID-19 outbreak.
A total of 1,172 respondents were recruited from 125 cities in mainland China by an online questionnaire survey. All subjects were evaluated with the 7-item Generalized Anxiety Disorder (GAD-7) scale, the somatization subscale of the Symptom Checklist 90-Revised (SCL-90-R), and the 7-item Insomnia Severity Index (ISI).
The percentages of anxiety, somatization, and insomnia were 33.02%, 7.59%, and 24.66%, respectively. The prevalence of somatization was 19.38% in participants with anxiety. Compared to the anxiety without somatization group, the anxiety with somatization group had a significantly higher percentage of patients with a history of physical disease and insomnia, as well as higher GAD-7 scores and SCL-90 somatization subscores (all p < 0.001). The SCL-90 somatization subscores were positively correlated with age, history of physical disease, GAD-7 scores, and ISI scores (all p < 0.001). Furthermore, multivariate logistic regression showed that GAD-7 score, ISI score, and age were risk factors for somatization in the anxious population.
Somatic and psychological symptoms were common in the general population during the COVID-19 outbreak. Somatic symptoms, anxiety, and insomnia are closely related, and improving anxiety and sleep quality may help relieve somatic symptoms.
The domestication of wild rice occurred together with genomic variation, including the synonymous nucleotide substitutions that result in synonymous codon usage bias (SCUB). SCUB mirrors the ...evolutionary specialization of plants, but its characteristics during domestication were not yet addressed. Here, we found cytosine- and guanidine-ending (NNC and NNG) synonymous codons (SCs) were more pronounced than adenosine- and thymine-ending SCs (NNA and NNT) in both wild and cultivated species of Asian and African rice. The ratios of NNC/G to NNA/T codons gradually decreased following the rise in the number of introns, and the preference for NNA/T codons became more obvious in genes with more introns in cultivated rice when compared with those in wild rice. SCUB frequencies were heterogeneous across the exons, with a higher preference for NNA/T in internal exons than in terminal exons. The preference for NNA/T in internal but not terminal exons was more predominant in cultivated rice than in wild rice, with the difference between wild and cultivated rice becoming more remarkable with the rise in exon numbers. The difference in the ratios of codon combinations representing DNA methylation-mediated conversion from cytosine to thymine between wild and cultivated rice coincided with their difference in SCUB frequencies, suggesting that SCUB reveals the possible association between genetic and epigenetic variation during the domestication of rice. Similar patterns of SCUB shift in Asian and African rice indicate that genomic variation occurs in the same non-random manner. SCUB representing non-neutral synonymous mutations can provide insight into the mechanism of genomic variation in domestication and can be used for the genetic dissection of agricultural traits in rice and other crops.
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The addition of bevacizumab to chemotherapy has prolonged overall and progression-free survival rates for metastatic colorectal cancer (mCRC). However, KRAS-mutant (KRAS-mut) CRC, lacking an ideal ...targeted agent, represents an inferior-response subgroup of patients. In the present study, we investigated a combination approach of bevacizumab + olaparib in KRAS-mut CRC in a preclinical setting. The combined therapy effectively prevented tumor growth in a KRAS-mut cancer cell-derived xenograft model, although this effect was not observed in vitro. Under bevacizumab treatment, we detected intratumor hypoxia and impaired homologous recombination repair (HRR), accompanied by vascular regression. We explored the underlying mechanism of this combined therapy by mimicking a hypoxic condition in vitro using cobalt chloride (CoCl2). The results showed that hypoxia impairs HRR and therefore sensitized KRAS-mut CRC cell lines HCT-116, SW620, and Lovo to olaparib. Furthermore, under this hypoxic condition, olaparib could arrest the cell cycle in the G2/M phase, increase DNA damage and dramatically induce cell apoptosis in KRAS-mut CRC cells. Taken together, these results indicated that the combination of bevacizumab + olaparib could be a potential therapeutic approach in a KRAS-mut CRC cohort.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
The MiRNA SNP Disease Database (MSDD, http://www.bio-bigdata.com/msdd/) is a manually curated database that provides comprehensive experimentally supported associations among microRNAs ...(miRNAs), single nucleotide polymorphisms (SNPs) and human diseases. SNPs in miRNA-related functional regions such as mature miRNAs, promoter regions, pri-miRNAs, pre-miRNAs and target gene 3′-UTRs, collectively called 'miRSNPs', represent a novel category of functional molecules. miRSNPs can lead to miRNA and its target gene dysregulation, and resulting in susceptibility to or onset of human diseases. A curated collection and summary of miRSNP-associated diseases is essential for a thorough understanding of the mechanisms and functions of miRSNPs. Here, we describe MSDD, which currently documents 525 associations among 182 human miRNAs, 197 SNPs, 153 genes and 164 human diseases through a review of more than 2000 published papers. Each association incorporates information on the miRNAs, SNPs, miRNA target genes and disease names, SNP locations and alleles, the miRNA dysfunctional pattern, experimental techniques, a brief functional description, the original reference and additional annotation. MSDD provides a user-friendly interface to conveniently browse, retrieve, download and submit novel data. MSDD will significantly improve our understanding of miRNA dysfunction in disease, and thus, MSDD has the potential to serve as a timely and valuable resource.
Hypoxic pulmonary hypertension (HPH) is a common type of pulmonary hypertension and characterized by pulmonary vascular remodeling and constriction. Alveolar epithelial cells (AECs) primarily sense ...alveolar hypoxia, but the role of AECs in HPH remains unclear. In this study, we explored whether AECs are involved in pulmonary vascular remodeling and constriction.
In the constructed rat HPH model, hemodynamic and morphological characteristics were measured. By treating AECs with hypoxia, we further detected the levels of superoxide dismutase 2 (SOD2), catalase (CAT), reactive oxygen species (ROS) and hydrogen peroxide (H
O
), respectively. To detect the effects of AECs on pulmonary vascular remodeling and constriction, AECs and pulmonary artery smooth cells (PASMCs) were co-cultured under hypoxia, and PASMCs and isolated pulmonary artery (PA) were treated with AECs hypoxic culture medium. In addition, to explore the mechanism of AECs on pulmonary vascular remodeling and constriction, ROS inhibitor N-acetylcysteine (NAC) was used.
Hypoxia caused pulmonary vascular remodeling and increased pulmonary artery pressure, but had little effect on non-pulmonary vessels in vivo. Meanwhile, in vitro, hypoxia promoted the imbalance of SOD2 and CAT in AECs, leading to increased ROS and hydrogen peroxide (H
O
) production in the AECs culture medium. In addition, AECs caused the proliferation of co-cultured PASMCs under hypoxia, and the hypoxic culture medium of AECs enhanced the constriction of isolated PA. However, treatment with ROS inhibitor NAC effectively alleviated the above effects.
The findings of present study demonstrated that AECs were involved in pulmonary vascular remodeling and constriction under hypoxia by paracrine H
O
into the pulmonary vascular microenvironment.
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► The thickness of AZ31B magnesium alloy sheet after V-bending increases. ► The neutral layer shifts to the tension zone of the sheets. ► The deformation mechanism between outer and inner region is ...asymmetric. ► The shift of neutral layer has an effect on the springback.
The evolution of springback and neutral layer for AZ31B magnesium alloy sheet was investigated by V-bending tests at temperatures from 50 to 300°C. Moreover, in order to perceive the influence of the punch radii on springback and offset of neutral layer, the tests with punch radii at 7.5, 8.1, 8.7 and 9.3mm were conducted at 100°C. The results show that the neutral layer shifts to the tension zone of the sheets. The coefficient of neutral layer (k-value) decreases with the increase of temperature and punch radii. This is mainly because of the asymmetry between the outer tension layer and inner compression layer during bending. The outer tension region is dominated by slip, while the inner compression region is dominated by twinning. With the increase of temperature, the asymmetry of tension–compression becomes weaker, and the offset of neutral layer decreases. The offset of neutral layer increases as punch radii decreases. The shift of neutral layer of AZ31B sheet results in the calculation of springback bigger than the reality.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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