bluuebunny/crossref_metadata_2025_split huggingface dataset:
LINC01094 Upregulates LIN28B Expression by Sponging miR-577 to Promote Pancreatic Cancer Proliferation and Metastasis
Authors: Luo Chen , Lin Kang , Hu Cegui , Zhu Xiaojian , Zhu Jinfeng , Zhu Zhengming 
Published: January 2021

Abstract
Backgroud: The leading cause of death in pancreatic cancer (PC) patients is the progression of cancer metastasis. Long non-coding RNAs (lncRNAs) play an important role in regulating cancers, however its molecular basis in pancreatic cancer (PC) remains to be explored.Methods: In this study, bioinformatics methods are used to predict the potential pairs of lncRNAs in PC. The clinical significance of LINC01094 are determined by qRT-PCR and explored its correlation with clinicopathological parameters. The biological functions and potential mechanisms of LINC01094 in PC progression are studied in vivo and in vitro. Results: We observe that LINC01094 is markedly overexpressed in pancreatic tumors and is associated with poorer prognosis. Downregulation of LINC01094 decreases PC cell invasion and inhibits tumorigenesis and metastasis in mouse xenografts. LINC01094 acts as a sponge for miR-577, sequestering it and derepressing the expression of its endogenous target the RNA‐binding protein lin‐28 homolog B (LIN28B). Conclusions: Overall, LINC01094 upregulates LIN28B by sponging miR-577, thereby promoting PC proliferation and metastasis. This indicates that LINC01094 can be regarded as a new biomarker or therapeutic target for the treatment of PC.
Mitochondrial Malic Enzyme 2 Promotes Breast Cancer Metastasis via Stabilizing HIF-1α Under Hypoxia
Authors: You Duo , Du Danfeng , Zhao Xueke , Li Xinmin , Ying Minfeng , Hu Xun 
Published: January 2021

Abstract
Background: α-ketoglutarate (α-KG) is the substrate to hydoxylate collagen and hypoxia-inducible factor-1α (HIF-1α), which are important for cancer metastasis. Previous studies showed that upregulation of collagen prolyl 4-hydroxylase in breast cancer cells stabilizes HIF-1α via depleting α-KG in breast cancer cells. We propose that mitochondrial malate enzyme 2 (ME2) may also affect HIF-1α via modulating α-KG level in breast cancer cells. Methods: ME2 protein expression was evaluated by immunohistochemistry on 100 breast cancer patients and correlated with clinicopathological indicators. The effect of ME2 knockout on cancer metastasis was evaluated by an orthotopic breast cancer model. The effect of ME2 knockout or knockdown on the levels of α-KG and HIF-1α protein in breast cancer cell lines (4T1 and MDA-MB-231) was determined in vitro and in vivo.Results: The high expression of ME2 was observed in the human breast cancerous tissues compared to the matched precancerous tissues (P=0.000). The breast cancer patients with a high expression of ME2 had an inferior survival than the patients with low expression of ME2 (P=0.019). ME2 high expression in breast cancer tissues was also related with lymph node metastasis (P=0.016), pathological staging (P=0.033) and vascular cancer embolus (P=0.014). In a 4T1 orthotopic breast cancer model, ME2 knockout significantly inhibited lung metastasis. In the tumors formed by ME2 knockout 4T1 cells, α-KG level significantly increased, collagen hydroxylation level did not change significantly, but HIF-1α protein level significantly decreased, in comparison to control. In cell culture, ME2 knockout or knockdown cells demonstrated a significantly higher α-KG level but significantly lower HIF-1α protein level than control cells under hypoxia. Exogenous malate and α-KG exerted similar effect on HIF-1α in breast cancer cells to ME2 knockout or knockdown. Treatment with malate significantly decreased 4T1 breast cancer lung metastasis. ME2 expression was associated with HIF-1α level in human breast cancer samples (P=0.027).Conclusion: We provide evidence that upregulation of ME2 is associated with a poor prognosis of breast cancer patients and propose a mechanistic understanding of a link between ME2 and breast cancer metastasis.
Soluble Guanylate Cyclase Reduced the Gastrointestinal Fibrosis in Bleomycin-induced Mouse Model of Systemic Sclerosis.
Authors: Yamamoto Yuzuru , Okano Takaichi , Yamada Hirotaka , Akashi Kengo , Sendo Sho , Ueda Yo , Morinobu Akio , Saegusa Jun 
Published: January 2021

Abstract
Background: Systemic sclerosis (SSc) is a chronic autoimmune-mediated connective tissue disorder. Although the etiology of the disease remains undermined, SSc is characterized by fibrosis and proliferative vascular lesions of the skin and internal organs. SSc involves the gastrointestinal tract in more than 90% of patients. Soluble guanylate cyclase (sGC) is used to treat pulmonary artery hypertension (PAH), and has been shown to inhibit experimental skin fibrosis.Methods: Female C57BL/6J mice were treated with BLM or normal saline by subcutaneous implantation of osmotic minipump. These mice were sacrificed on day 28 or day 42. Gastrointestinal pathologies were examined by Masson Trichrome staining. The expression of fibrosis-related genes in gastrointestinal tract were analyzed by real-time PCR, and the levels of collagen in the tissue was measured by Sircol collagen assay. To evaluate peristaltic movement, the small intestinal transport (ITR%) was calculated as [Dyeing distance×(Duodenum- Appendix)] -1 ×100 (%). We treated BLM-treated mice with soluble guanylate cyclase (sGC) or DMSO orally and analyzed them on day 42.Results: Histological examination revealed that fibrosis from lamina propria to muscularis mucosa in the esophagus was significantly increased in BLM-treated mice, suggesting that BLM induces esophageal fibrosis in C57BL/6J mice. In addition, the levels of Col3a1 and CTGF were significantly increased in BLM-treated mice. More severe fibrosis was observed in the mice sacrificed on day 42 than the mice sacrificed on day 28. The ITR% was found to be significantly lower in BLM-treated mice, suggesting that gastrointestinal peristaltic movement was reduced in BLM-treated mice. Furthermore, we demonstrated that sGC treatment significantly reduced fibrosis of esophagus and intestine in BLM-treated mice, by histological examination and Sircol collagen assay. Conclusions: These findings suggest that BLM induces gastrointestinal fibrosis in C57BL/6J mice, and treatment with sGC improves the BLM-induced gastrointestinal lesion.
Effects of WeChat-based Educational Intervention on Depression and Quality of Life in Patients with Ankylosing Spondylitis: A Randomized Controlled Trail
Authors: Song Yuqing , Xie Xia , Chen Yanlin , Wang Ying , Yang Hui , Nie Anliu , Chen Hong 
Published: January 2021

Abstract
Background: Ankylosing spondylitis(AS), as a common inflammatory rheumatic disease, often cause depression and impaired health-related quality of life(QoL). Although positive effects of patient education have been demonstrated, limited studies explored the benefits of education via mobile applications for AS patients. This study aimed to evaluate the effects of the WeChat-based educational intervention on depression and health-related QoL in AS patients.Methods: We conducted a single-blind randomized controlled trial from March to December 2017. Potential patients were recruited and randomized into the intervention group who received a 12-week WeChat-based educational intervention (consisting of four individual online educational sessions, online health information) or the control group receiving standard care. Data was collected at baseline and 12 weeks after the intervention. Outcomes were measured by Beck Depression Inventory-Ⅱ, the Medical Outcomes Study Short Form 36-item Health Survey, Bath Ankylosing Spondylitis Patient Global Score, visual analogue scales. Results: A total of 118 patients with AS were included and analysed. Measures at baseline were comparable between groups. After the intervention, the intervention group reported significant higher scores of all dimensions of QoL except for physical function and validity, compared with the control group. Additionally, patients in the intervention group had lower depressive symptom than the control group. No significant difference in other outcomes was observed at 12 weeks. Conclusions: This study found that the 12-week educational intervention via WeChat had positive effects on reducing depressive symptom and improving health related QoL in Chinese patients with AS. We suggest that this intervention can be integrated into current routine care of AS patients. Trial registration: Chinese Clinical Trail Registry (registry number: ChiCTR-IPR-16009293). Registered September 29, 2016.
Unmet Needs for Informal Care Among People With Type 2 Diabetes in Rural Communities in Vietnam.
Authors: Meyrowitsch Dan Wolf , Nielsen Jannie , Bygbjerg Ib Christian , Søndergaard Jens , Thi Diep Khong , Huyen Dieu Bui Thi , Gammeltoft Tine M. , Duc Thanh Nguyen 
Published: January 2021

Abstract
BACKGROUND From a diabetes management perspective, informal care has proven at least as important as care from health professionals when targeting poorly controlled diabetes. The objective of this study was to identify determinants associated with unmet needs for informal support among people with type-2 diabetes in rural communities of Vietnam. METHODS A cross-sectional survey was conducted from December 2018 to February 2019 in a rural area of northern Vietnam. From 2 districts in Thai Binh Province, Vietnam, 806 people with type-2 diabetes participated in a survey designed to assess who were their most important informal caregivers (ICGs) and to measure the association between demographic and socio-economic predictors and unmet needs of informal support of relevance for diabetes self-care using bivariate and multivariate analyses. RESULTS The spouse was reported as the most important ICG (62.9%) followed by a daughter or son (28.4%). 32.0% of the people with type-2 diabetes reported at least one type of unmet need for informal support. The most commonly reported unmet needs of informal care were: transport to health facilities and company when seeking formal care (20.5%), financial support related to costs of diabetes self-management (18.5%), and reminders to engage in physical exercise (14.5%). People living alone reported the highest odds ratio (OR) for unmet need of informal care (OR=4.41; CI95%: 2.19-8.88), followed by those being poor as compared to being wealthy (OR=3.79; CI95%: 1.25-11.52) and those being unemployed as compared to being retired (OR=2.85; CI95%: 1.61-5.05). CONCLUSIONS Almost one-third of people with type-2 diabetes reported at least one type of unmet need for informal care. These findings provide a basis for development of new modalities for strengthening support provided by ICGs in rural communities in Vietnam and in other low- and middle-income countries.
Research on mechanism of the effect of charred hawthorn on digestive by SCF /c-kit pathway
Authors: He Qian , Liu Cui , Wang Ting , Sun Jingying , Zhou Xia , Wang Yun , Ma Li , Wan Jun 
Published: January 2021

Abstract
Background

Hawthorn is the dry ripe fruit of Crataegus pinnatifida Bge in rose family which is a traditional Chinese medicine(TCM) for High-calorie-diet-induced dyspepsia (HC-DID). This study aimed to investigate whether the charred hawthorn coupled with its odor could alleviate HC-DID by brain-gut interaction and stem cell factor(SCF) /c-kit pathway.
Methods

Rats were randomly divided into 7 groups: control group, model group, cisapride group, hawthorn group (HT), charred hawthorn group (CHT), odor of charred hawthorn (OCHT), CHT + OCHT group. HC-DID rat model was established by high calorie diet for 10 days, hawthorn decoction was administered by gavage, and the self-developed solid drug odor delivery device was used for odor administration. The body weight, food intake, gastrointestinal motility, gastric fluid and gastric acid flow index were determined. HE staining was used to observe the pathological changes of rats. Electrophysiology was used to evaluate the effect of hawthorn combined with its charred odor therapy on electroencephalogram and Electrogastrogram. The SCF and c-kit levels or expressions by immunohistochemistry(IHC), enzyme linked immunosorbent assay (ELISA).
Results

We found that the odor of charred hawthorn (OCHT) affects the brain (central nervous system) of rats, and hawthorn decoction (raw hawthorn and charred hawthorn) coupled with the odor of charred hawthorn alleviated the symptoms of diet-induced dyspepsia in rats by modulating SCF/c-Kit pathway.
Conclusion

Thus, we concluded that odor of charred hawthorn has therapeutic effect on dyspepsia and hawthorn may alleviate dyspepsia related symptoms by affecting SCF/c-Kit signal pathway.
Deficiency and absence of endogenous isoprene in adults, disqualified its putative origin
Authors: Sukul Pritam , Richter Anna , Schubert Jochen K , Miekisch Wolfram 
Published: January 2021

Abstract
Background: Isoprene (C5H8) is a clinically important breath metabolite. Although, hundreds of studies have reported differential expressions in isoprene exhalation as breath biomarker for diverse diseases, the substance couldn’t enter to clinical practice as diagnostic marker. Moreover, many experimental/basic observations upon breath isoprene remained unrelated to the corresponding pathophysiological effects on its putative metabolic origin (i.e. mevalonate pathway). Here, we investigated the fundamental reason that hindered the rational interpretation and translation of this marker from basic to clinical science.Methods: Via high-resolution mass-spectrometry based breathomics in 1026 human subjects, we discovered adults with significant deficiency (order of magnitude lower than the normal) and complete absence of breath isoprene. We prospectively applied real-time breathomics, quantitative gene expression analysis of the mevalonate pathway enzymes, lipid-profiling and hemodynamic monitoring on those isoprene deficient subjects and controls. Additionally, the subject with absence of isoprene was followed up throughout different phases of her womanhood.Results: In contrast to convention, we witnessed that adults can live healthy without exhaling isoprene or with significant deficiency. This rare phenotype represents a recessive inheritance. Despite physio-metabolic changes during menstrual cycle (that is known to profoundly affect isoprene exhalation) and profoundly increased plasma cholesterol during pregnancy and after childbirth, isoprene remained absent. All genes of mevalonate pathway enzymes were normally expressed in all participants, without any down-regulation or compensatory up-regulation.Conclusions: Absence/deficiency of isoprene despite normal lipid profiles and no mevalonate pathway malfunction disqualifies the long-believed metabolic origin of isoprene from cholesterol biosynthesis. Thus, clinical translation of breath isoprene expressions should not be generally attributed to corresponding pathophysiological effects onto mevalonate/cholesterol pathway. Our finding has refined and optimized the clinical interpretation of isoprene as biomarker in volatile metabolomics and breathomics. Future studies will address the correct metabolic origin of isoprene to imply this important marker to routine practice.
LncRNA LINC00240 suppresses invasion and migration in non-small cell lung cancer by sponging miR-7-5p
Authors: Ku Gwan Woo , Kang Yujin , Yu Seong-Lan , Park Joonghoon , Park Sejin , Jeong In Beom , Kang Min Woong , Son Ji Woong , Kang Jaeku 
Published: January 2021

Abstract
Background lncRNAs have important roles in regulating cancer biology. Accumulating evidence has established a link between the dysregulation of lncRNAs and microRNA in cancer progression. In previous studies, miR-7-5p has been found to be significantly down-regulated in mesenchymal-like lung cancer cell lines and directly regulated EGFR. In this work, we investigated the lncRNA partner of miR-7-5p in the progression of lung cancer.Methods We investigated the expression of miR-7-5p and the lncRNA after transfection with an miR-7-5p mimics using a microarray. The microarray results were validated using quantitative real time-polymerase Chain Reaction (qRT-PCR). The regulatory effects of lncRNA on miR-7-5p and its target were evaluated by changes in the expression of miR-7-5p after transfection with siRNAs for lncRNA and the synthesis of full-length lncRNA. The effect of miR-7-5p on lncRNA and the miRNA target was evaluated after transfection with miRNA mimic and inhibitor. The role of lncRNA in cancer progression was determined using invasion and migration assays. The level of lncRNA and EGFR in lung cancer and normal lung tissue was analyzed using TCGA data.Results We found that LINC00240 was downregulated in lung cancer cell line after miR-7-5p transfection with an miR-7-5p mimic. Further investigations revealed that the knockdown of LINC00240 induced the overexpression of miR-7-5p. The overexpression of miR-7-5p diminished cancer invasion and migration. The EGFR expression was down regulated after siRNA treatment for LINC00240. Silencing LINC00240 suppressed the invasion and migration of lung cancer cells, whereas LINC00240 overexpression exerted the opposite effect. The lower expression of LINC00240 in squamous lung cancer was analyzed using TCGA data.Conclusions Taken together, LINC00240 acted as a sponge for miR-7-5p and induced the overexpression of EGFR. LINC00240 may represent a potential target for the treatment of lung cancer.
Auto-diagnosis of COVID-19 using Lung CT Images with Semi-supervised Shallow Learning Network
Authors: Konar Debanjan , Panigrahi Bijaya Ketan , Bhattacharyya Siddhartha , Dey Nilanjan , Jiang Richard 
Published: January 2021

Abstract
Infection of Novel Coronavirus 2019 (COVID-19) on lung cells and human respiratory systems have raised real concern to the human lives during the current pandemic spread across the world. Recent observations on CT images of human lungs infected by COVID-19 is a challenging task for the researchers in finding suitable image patterns for automatic diagnosis. In this paper, a novel semi-supervised shallow learning network model comprising Parallel Quantum-Inspired Self-supervised Network (PQIS-Net) with Fully Connected (FC) layers is proposed for automatic segmentation followed by patch-based classifications on segmented lung CT images for the diagnosis of COVID-19 disease. The PQIS-Net model is incorporated for fully automated segmentation of lung CT scan images obviating pre-trained convolutional neural network models for feature learning. The PQIS-Net model comprises a trinity of layered structures of quantum bits inter-connected through rotation gates using an 8-connected second-order neighborhood topology for the segmentation of wide variation of local intensities of the CT images. Intensive experiments have been carried out on two publicly available lung CT image data sets thereby achieving promising segmentation outcome and diagnosis efficiency (F1-score and AUC) while compared with the state of the art pre-trained convolutional based models.
Improved Effect of a Mitochondria-Targeted Antioxidant on Hydrogen Peroxide-Induced Oxidative Stress in Human Retinal Pigment Epithelium Cells
Authors: KIM MYUNG HEE , Kim Do Hun , Yang Su Geun , Kim Dae Yu 
Published: January 2021

Abstract
Background: Oxidative damage to retinal pigment epithelial (RPE) cells contributes to the development of age-related macular degeneration, which is among the leading causes of visual loss in elderly people. In the present study, we evaluated the protective role of triphenylphosphonium (TPP)-Niacin against hydrogen peroxide (H2O2)-induced oxidative stress in RPE cells.Methods: The cellular viability, lactate dehydrogenase release, reactive oxygen species (ROS) generation, and mitochondrial function of retinal ARPE-19 cells were determined under treatment with H2O2 or pre-treatment with TPP-Niacin. The expression level of mitochondrial related genes and some transcription factors were assessed using real-time polymerase chain reaction (RT-qPCR). Results: TPP-Niacin significantly improved cell viability, reduced ROS generation, and increased the antioxidant enzymes in H2O2-treated ARPE-19 cells. Mitochondrial dysfunction from the H2O2-induced oxidative stress was also considerably diminished by TPP-Niacin treatment, along with reduction of the mitochondrial membrane potential (MMP) and upregulation of the mitochondrial-associated gene. In addition, TPP-Niacin markedly enhanced the expression of transcription factors (PGC-1α and NRF2) and antioxidant-associated genes (especially HO-1 and NQO-1).Conclusion: We verified the protective effect of TPP-Niacin against H2O2-induced oxidative stress in RPE cells. TPP-Niacin is believed to protect against mitochondrial dysfunction by upregulating antioxidant-related genes, such as PGC-1α, NRF2, HO-1, and NQO-1, in RPE cells.
De novo transcriptome analysis and comparative expression profiling of genes associated with the taste-modifying protein neoculin in Curculigo latifolia and Curculigo capitulata fruits
Authors: Okubo Satoshi , Terauchi Kaede , Okada Shinji , Yamaura Takao , Misaka Takumi , Nakajima Ken-ichiro , Abe Keiko , Asakura Tomiko 
Published: January 2021

Abstract
Background Curculigo latifolia is a perennial plant endogenous to Southeast Asia whose fruits contain the taste-modifying protein neoculin, which binds to sweet receptors and makes sour fruits taste sweet. Although similar to snowdrop (Galanthus nivalis) agglutinin (GNA), which contains mannose-binding sites in its sequence and 3D structure, neoculin lacks such sites and has no lectin activity. Whether the fruits of C. latifolia and other Curculigo plants contain neoculin and/or GNA family members was unclear. Results Through de novo RNA-seq assembly of the fruits of C. latifolia and the related C. capitulata and detailed analysis of the expression patterns of neoculin and neoculin-like genes in both species, we assembled 85,697 transcripts from C. latifolia and 76,775 from C. capitulata using Trinity and annotated them using public databases. We identified 70,371 unigenes in C. latifolia and 63,704 in C. capitulata. In total, 38.6% of unigenes from C. latifolia and 42.6% from C. capitulata shared high similarity between the two species. We identified ten neoculin-related transcripts in C. latifolia and 15 in C. capitulata, encoding both the basic and acidic subunits of neoculin in both plants. We aligned these 25 transcripts and generated a phylogenetic tree. Many orthologs in the two species shared high similarity, despite the low number of common genes, suggesting that these genes likely existed before the two species diverged. The relative expression levels of these genes differed considerably between the two species: the transcripts per million (TPM) values of neoculin genes were 60 times higher in C. latifolia than in C. capitulata, whereas those of GNA family members were 15,000 times lower in C. latifolia than in C. capitulata. Conclusions The genetic diversity of neoculin-related genes strongly suggests that neoculin genes underwent duplication during evolution. The marked differences in their expression profiles between C. latifolia and C. capitulata may be due to mutations in regions involved in transcriptional regulation. Comprehensive analysis of the genes expressed in the fruits of these two Curculigo species helped elucidate the origin of neoculin at the molecular level.