bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of microRNAs in the pathogenesis, grading and treatment of hepatic fibrosis in schistosomiasis
Authors: Chen Qianglin , Zhang Jianqiang , Zheng Ting , Chen Hui , Nie Hao , Zheng Bing , Gong Quan 
Published: December 2019

AbstractSchistosomiasis is a prevalent parasitic disease worldwide. The main pathological changes of hepatosplenic schistosomiasis are hepatic granuloma and fibrosis due to worm eggs. Portal hypertension and ascites induced by hepatic fibrosis are usually the main causes of death in patients with chronic hepatosplenic schistosomiasis. Currently, no effective vaccine exists for preventing schistosome infections. For quite a long time, praziquantel (PZQ) was widely used for the treatment of schistosomiasis and has shown benefit in treating liver fibrosis. However, drug resistance and chemical toxicity from PZQ are being increasingly reported in recent years; therefore, new and effective strategies for treating schistosomiasis-induced hepatic fibrosis are urgently needed. MicroRNA (miRNA), a non-coding RNA, has been proved to be associated with the development of many human diseases, including schistosomiasis. In this review, we present a balanced and comprehensive view of the role of miRNAs in the pathogenesis, grading, and treatment of schistosomiasis-associated hepatic fibrosis. The multiple regulatory roles of miRNAs, such as promoting or inhibiting the development of liver pathology in murine schistosomiasis are also discussed in depth. Additionally, miRNAs may serve as candidate biomarkers for diagnosing liver pathology of schistosomiasis and as novel therapeutic targets for treating schistosomiasis-associated hepatic fibrosis.
Unique primed status of microglia under the systemic autoimmune condition of lupus-prone mice
Authors: Nomura Atsushi , Noto Daisuke , Murayama Goh , Chiba Asako , Miyake Sachiko 
Published: December 2019

Abstract
Background
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of various autoantibodies. This disease causes disabling neuropsychiatric symptoms even in the absence of apparent inflammation in the central nervous system (CNS), but the mechanisms involved remain unknown. Innate immune-mediated inflammation has attracted attention as a pathogenic mechanism in neuropsychiatric diseases.

Methods
We investigated the CNS of lupus-prone mice focusing on innate immunity. Three strains of lupus-prone mice, FcγRIIB−/−Yaa, an F1 hybrid of NZB and NZW (NZB/NZW) mice, and MRL/Faslpr (MRL/lpr) mice were used to analyze CNS immunopathology.

Results
Flow cytometry analysis demonstrated the numbers of brain CD45+ cells were increased compared with controls in lupus-prone mice. Upregulation of MHC class I and PDCA1 was observed in microglia and CD11b+ myeloid cells of lupus-prone mice, indicating they were activated in response to interferons (IFN). Microglial gene expression analysis of FcγRIIB−/−Yaa mice revealed the upregulation of IFN-responsive genes and inflammation-related genes including Axl, Clec7a, and Itgax, which were previously reported in neurodegenerative conditions and primed conditions. Upregulated chemokine gene expressions including Ccl5 and Cxcl10 were concurrent with increased numbers of T cells and monocytes, especially Ly6Clo monocytes in the CNS. Upregulation of Axl, Clec7a, Itgax, Ccl5, and Cxcl10 was also observed in NZB/NZW mice, indicating common lupus pathology. The primed status of microglia in FcγRIIB−/−Yaa mice was also demonstrated by morphological changes such as enlarged cell bodies with hypertrophic processes, and hyperreactivity to lipopolysaccharide. Immunohistochemistry of FcγRIIB−/−Yaa mice indicated reactive responses of astrocytes and vascular endothelium. Behavioral studies of FcγRIIB−/−Yaa mice revealed depressive-like behavior and heat hyperalgesia in the forced swim test and the tail-flick test, respectively.

Conclusions
Our data indicated that microglia in lupus exhibit a unique primed phenotype characterized by the upregulated expressions of neurodegeneration-related genes and IFN-responsive genes. Interaction with peripheral cells and brain resident cells was presumed to orchestrate neuroinflammation. Targeting innate immune cells, such as microglia and monocytes, may be a promising therapeutic approach for neuropsychiatric SLE.
MMP-2 salivary activity in type 2 diabetes mellitus patients
Authors: Arreguin-Cano Juan Antonio , Ayerdi-Nájera Brenda , Tacuba-Saavedra Arvey , Navarro-Tito Napoleón , Dávalos-Martínez Alfonso , Emigdio-Vargas Abel , Barrera-Rodríguez Elia , Blanco-García Nubia , Gutiérrez-Venegas Gloria , Ventura-Molina Elías , León-Dorantes Gladys 
Published: December 2019

Abstract
Background
Type 2 diabetes mellitus (T2DM) and periodontitis are chronic inflammatory diseases with a bidirectional relationship. The uncontrolled levels of glucose in T2DM patients change the pathophysiology and balance of inflammatory mediators. Matrix Metalloproteinase-2 (MMP-2) is a zinc-dependent endopeptidase that is responsible for tissue remodeling and degradation of the extracellular matrix in periodontal tissue. Therefore, the uncontrolled levels of glucose in T2DM could lead to an imbalance in MMP-2 activity in saliva, favoring the development of periodontitis.

Methods
Ninety-seven T2DM patients from Hospital Dr. Donato Alarcon were included in the study. Following clinical examination, the patients were classified into four groups according to the presence and degree of periodontal disease and glycemic control. Blood and whole saliva samples (WSS) were collected from each patient. Blood samples were used for Hba1c and polymorphonuclear cells count determination, while WSS were used to determine MMP-2 activity, TIMP-1 and nitrite. MMP-2 activity was determined by zymography. TIMP-1 were determined by Western blotting, and nitric oxide (NO) levels were determined by the Griess method.

Results
Of the 97 patients with T2DM, 66 had periodontitis of different severities: 18 patients had mild periodontitis, 15 had moderate and 33 had severe. Salivary MMP-2 activity, HbA1c and TIMP-1 were positively correlated with the severity of periodontitis. On the other hand, the increase in HbA1c was negatively correlated with MMP-2 activity and quantity of TIMP-1 but was positively correlated with nitrite levels.

Conclusions
T2DM with glycemic uncontrol conditions, distinct clinical alterations in periodontal tissue were identified, including a decrease in the gingival redness, increased the clinical attachment loss and imbalance of MMP-2/TIMP-1, as the possible causes of disorders promoting the progression of periodontitis. Accelerated periodontitis development with poor glycemic uncontrol likely results from the altered response of host defenses and decreased activity of polymorphonuclear cells. Taken together, these findings identify MMP-2 as a promising molecular market for periodontitis.
Silencing or inhibition of H3K79 methyltransferase DOT1L induces cell cycle arrest by epigenetically modulating c-Myc expression in colorectal cancer
Authors: Yang Liqun , Lei Qian , Li Lin , Yang Jie , Dong Zhen , Cui Hongjuan 
Published: December 2019

Abstract
Background
Epigenetic regulations play pivotal roles in tumorigenesis and cancer development. Disruptor of telomeric silencing-1-like (DOT1L), also known as KMT4, is the only identified histone methyltransferase that catalyzes the mono-, di-, and tri-methylation of lysine 79 histone 3 (H3K79). However, little is known about the effect of H3K79 methylation on the modulation of colorectal cancer (CRC) development.

Methods
DOT1L expression profiles in different subgroups of CRC tissues and its clinical significances were analyzed from some online datasheets. DOT1L in CRC cell lines was silenced by either lentivirus-mediated knockdown or inhibited by its specific inhibitor, EPZ004777. Then cell proliferation was detected by MTT assay, BrdU assay, and soft agar assay; cell cycle was detected by cytometry; and tumorigenicity was detected by using nude mice xenograft models. Clinical co-expression was analyzed between DOT1L and c-Myc. Chromatin immunoprecipitation (ChIP) assay was used to determine whether the translation of c-Myc was epigenetically regulated by H3K79me2 induced by DOT1L. c-Myc overexpression was used to rescue the cell cycle arrest and tumor growth induced by DOT1L silencing or inhibition in CRC.

Results
We found that DOT1L was highly expressed in colorectal cancer and was negatively related to the prognosis of patients with CRC. Silencing or inhibition of DOT1L blocked cell proliferation, BrdU incorporation, self-renewal capability in vitro, and tumorigenicity in vivo. Besides, inhibition or silencing of DOT1L also induced cell cycle arrest at S phase, as well as decreased the expression of CDK2 and Cyclin A2. Furthermore, in the clinical databases of CRC, we found that the expression of DOT1L was positively correlated with that of c-Myc, a major regulator in the upstream of cell cycle–related factors. Besides, c-Myc expression was downregulated after DOT1L knockdown and c-Myc restoration rescued decrease of cell proliferation, BrdU corporation, self-renewal capability, cell cycle progression in vitro and tumorigenicity in vivo induced by DOT1L silencing. Then we found that H3K79 methylation was decreased after DOT1L knockdown. ChIP assay showed that H3K79me2 was enriched on the – 682~+ 284 region of c-Myc promoter, and the enrichment was decreased after DOT1L inhibition.

Conclusions
Our results show that DOT1L epigenetically promotes the transcription of c-Myc via H3K79me2. DOT1L silencing or inhibition induces cell cycle arrest at S phase. DOT1L is a potential marker for colorectal cancer and EPZ004777 may be a potential drug for the treatment of colorectal cancer.
APOE2 orchestrated differences in transcriptomic and lipidomic profiles of postmortem AD brain
Authors: Lefterov Iliya , Wolfe Cody M. , Fitz Nicholas F. , Nam Kyong Nyon , Letronne Florent , Biedrzycki Richard J. , Kofler Julia , Han Xianlin , Wang Jianing , Schug Jonathan , Koldamova Radosveta 
Published: December 2019

AbstractBackgroundThe application of advanced sequencing technologies and improved mass-spectrometry platforms revealed significant changes in gene expression and lipids in Alzheimer’s disease (AD) brain. The results so far have prompted further research using “multi-omics” approaches. These approaches become particularly relevant, considering the inheritance ofAPOEε4allele as a major genetic risk factor of AD, disease protective effect ofAPOEε2allele, and a major role of APOE in brain lipid metabolism.MethodsPostmortem brain samples from inferior parietal lobule genotyped asAPOEε2/c(APOEε2/carriers),APOEε3/3, andAPOEε4/c (APOEε4/carriers), age- and gender-matched, were used to revealAPOEallele-associated changes in transcriptomes and lipidomes. Differential gene expression and co-expression network analyses were applied to identify up- and downregulated Gene Ontology (GO) terms and pathways for correlation to lipidomics data.ResultsSignificantly affected GO terms and pathways were determined based on the comparisons ofAPOEε2/cdatasets to those ofAPOEε3/3andAPOEε4/cbrain samples. The analysis of lists of genes in highly correlated network modules and of those differentially expressed demonstrated significant enrichment in GO terms associated with genes involved in intracellular proteasomal and lysosomal degradation of proteins, protein aggregates and organelles, ER stress, and response to unfolded protein, as well as mitochondrial function, electron transport, and ATP synthesis. Small nucleolar RNA coding units important for posttranscriptional modification of mRNA and therefore translation and protein synthesis were upregulated inAPOEε2/cbrain samples compared to bothAPOEε3/3andAPOEε4/c. The analysis of lipidomics datasets revealed significant changes in ten major lipid classes (exclusively a decrease inAPOEε4/csamples), most notably non-bilayer-forming phosphatidylethanolamine and phosphatidic acid, as well as mitochondrial membrane-forming lipids.ConclusionsThe results of this study, despite the advanced stage of AD, point to the significant differences in postmortem brain transcriptomes and lipidomes, suggestingAPOEallele associated differences in pathogenic mechanisms. Correlations within and between lipidomes and transcriptomes indicate coordinated effects of changes in the proteasomal system and autophagy—canonical and selective, facilitating intracellular degradation, protein entry into ER, response to ER stress, nucleolar modifications of mRNA, and likely myelination inAPOEε2/cbrains. Additional research and a better knowledge of the molecular mechanisms of proteostasis in the early stages of AD are required to develop more effective diagnostic approaches and eventually efficient therapeutic strategies.
Kimura’s disease affecting multiple body parts in a 57-year-old female patient: a case report
Authors: Yu Bo , Xu Guoxing , Liu Xiaofan , Yin Wen , Chen Hao , Sun Baoqing 
Published: December 2019

AbstractBackgroundKimura’s disease (KD) is a rare chronic inflammatory disease with unknown etiology. It usually manifests as a painless soft tissue mass or subcutaneous nodule on one side of the patient’s head and/or neck and rarely affects multiple parts of the body. The disease is more common among young Asian males.Case presentationA 57-year-old Chinese woman complained of multiple masses on her body surface. Ultrasonography was used to examine the retroperitoneal, bilateral neck, bilateral supraclavicular, bilateral axillary, and bilateral inguinal superficial lymph nodes. Enlargement of multiple lymph nodes was found in all areas. Many solid nodules were also found in the right parotid gland and right posterior neck area, respectively. Numerous solid nodules were seen on the left chest wall. Laboratory tests showed that the percentage of eosinophils in the whole blood was 39.40%, total immunoglobulin E (IgE) level was > 5000 kU/L, and serum special IgE to Phadiatop (inhaled allergens) and fx5 (food allergens) were 1.01 and 1.04 kUA/L, respectively. After a complete examination, the masses located in the right neck, retroauricular and left axillary regions, and left chest wall were resected directly. Postoperative pathological findings revealed KD.ConclusionsThe case discussed in this study is extremely rare and did not meet the common affected areas and age characteristics of KD. This presentation can be used to improve disease awareness among physicians.
Cellular and molecular characterization of multiplex autism in human induced pluripotent stem cell-derived neurons
Authors: Lewis Emily M. A. , Meganathan Kesavan , Baldridge Dustin , Gontarz Paul , Zhang Bo , Bonni Azad , Constantino John N. , Kroll Kristen L. 
Published: December 2019

AbstractBackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder with pronounced heritability in the general population. This is largely attributable to the effects of polygenic susceptibility, with inherited liability exhibiting distinct sex differences in phenotypic expression. Attempts to model ASD in human cellular systems have principally involved rare de novo mutations associated with ASD phenocopies. However, by definition, these models are not representative of polygenic liability, which accounts for the vast share of population-attributable risk.MethodsHere, we performed what is, to our knowledge, the first attempt to model multiplex autism using patient-derived induced pluripotent stem cells (iPSCs) in a family manifesting incremental degrees of phenotypic expression of inherited liability (absent, intermediate, severe). The family members share an inherited variant of uncertain significance (VUS) inGPD2, a gene that was previously associated with developmental disability but here is insufficient by itself to cause ASD. iPSCs from three first-degree relatives and an unrelated control were differentiated into both cortical excitatory (cExN) and cortical inhibitory (cIN) neurons, and cellular phenotyping and transcriptomic analysis were conducted.ResultscExN neurospheres from the two affected individuals were reduced in size, compared to those derived from unaffected related and unrelated individuals. This reduction was, at least in part, due to increased apoptosis of cells from affected individuals upon initiation of cExN neural induction. Likewise, cIN neural progenitor cells from affected individuals exhibited increased apoptosis, compared to both unaffected individuals. Transcriptomic analysis of both cExN and cIN neural progenitor cells revealed distinct molecular signatures associated with affectation, including the misregulation of suites of genes associated with neural development, neuronal function, and behavior, as well as altered expression of ASD risk-associated genes.ConclusionsWe have provided evidence of morphological, physiological, and transcriptomic signatures of polygenic liability to ASD from an analysis of cellular models derived from a multiplex autism family. ASD is commonly inherited on the basis of additive genetic liability. Therefore, identifying convergent cellular and molecular phenotypes resulting from polygenic and monogenic susceptibility may provide a critical bridge for determining which of the disparate effects of rare highly deleterious mutations might also apply to common autistic syndromes.
Circ_0001667 promotes breast cancer cell proliferation and survival via Hippo signal pathway by regulating TAZ
Authors: Geng Zhongli , Wang Wei , Chen Hui , Mao Jianya , Li Zhenguo , Zhou Jing 
Published: December 2019

Abstract
Background
Breast cancer is a most common type of cancer in women. Circular RNAs (circRNAs) are involved in cancer development and progression, but their roles and regulatory mechanisms are unclear in breast cancer. Our previous study indicated that has_circ_0001667 (circ_0001667) was up-regulated in breast cancer from the array and might play an oncogenic role, however, the roles of circ_0001667 were not known. This study was aimed to investigate the role and the underlying molecular mechanism of circ_0001667 in breast cancer.

Results
The real-time PCR result showed that circ_0001667 was overexpressed in breast cancer tissues or cell lines compared to the adjacent normal tissues or normal cells. There was a negative relationship between circ_0001667 levels and the life time of breast cancer patients. Meanwhile, the inhibition of circ_0001667 suppressed the proliferation and metastasis of human breast cancer cells. Further bioinformatical analysis indicated that circ_0001667 sponged miR-125a-5p to regulate TAZ expression by Targetscan and miRanda. Dual luciferase reporter assay and western blotting experiments revealed that circ_0001667 negatively regulated miR-125a-5p expression leading to promoting TAZ expression through Hippo signal pathway in breast cancer cells.

Conclusions
This study uncovered that circ_0001667 was a potential breast cancer prognostic marker, as well as a potential therapeutic target to inhibit breast cancer metastasis by circ_0001667/miR-125a-5p/TAZ axis.
Evaluating the effectiveness of adjuvant radiotherapy in addition to surgery versus surgery alone at improving oncologic outcomes for early stage buccal carcinoma: A systematic review
Authors: Best Corliss Ann Elizabeth , Quimby Alexandra Elizabeth , Best Brittany Ann Barbara , Fergusson Dean , Alsaffar Hussain 
Published: December 2019

Objective To systematically review the evidence to evaluate oncologic outcomes for patients with early stage buccal squamous cell carcinoma treated with surgery versus surgery and adjuvant radiation therapy. Data sources Ovid MedLine, EMBASE, Google Scholar, PubMed. Review methods The primary purpose was to perform a systematic review to determine the published literature comparing oncologic outcomes of patients with early stage (Stages I&II) buccal mucosal squamous cell carcinoma, treated with surgical resection alone versus surgery plus adjuvant radiation therapy. Oncologic outcomes of interest were overall survival, locoregional recurrence, and disease specific survival. The secondary aim was to perform a meta-analysis to quantitively compare and summarize the data on oncologic outcomes between treatments. Results A total of 1457 studies were screened and five retrospective cohort studies ( n = 733 patients) were eligible for quantitative analysis. Overall study quality was moderate to high. Pooled relative risk ratios using a fixed effects model did not reveal any statistically significant difference in overall survival ( p = 0.70) or locoregional recurrence rates ( p = 0.72) in Stage I and II disease. Conclusions These results demonstrate there is sparse evidence comparing oncologic outcomes for early stage buccal squamous cell carcinoma treated with surgery alone versus surgery and adjuvant radiation therapy. Our findings based on a limited body of evidence suggest no obvious benefit in the addition of adjuvant radiation therapy, however robust randomized trials are warranted to reach firm conclusions.
Quantitative relationship between plume emission and multiple deflations after the 2014 phreatic eruption at Ontake volcano, Japan
Authors: Narita Shohei , Murakami Makoto , Tanaka Ryo 
Published: December 2019

Abstract
The phreatic eruption of Mount Ontake in 2014 caused local-scale subsidence and a mass discharge of water–vapor plumes from vents. A previous study of InSAR data analysis modeled the local subsidence as a deflation of a shallow hydrothermal reservoir (~ 500 m beneath the vents), and speculated that it was associated with plume emission continuing just after the eruption. In addition, combination of the InSAR and GNSS data implies that another, deeper deflation source (~ 3–6 km beneath the vents) contributes to the baseline contraction of the GNSS data. In this study, we estimated daily mass flux of the emitting plumes using photographed images, and compared the temporal behavior of the discharged mass with that of deflation of the two sources in order to clarify their association. The temporal profiles of the shallow deflation volume and the discharge mass both show evidence of decay, but with different characteristics; the deflation volume progress was approximated by a single exponential decay with a long relaxation time (379–641 days), whereas the discharge mass displayed a sum of a linear trend and an exponential decay with shorter relaxation time (47 days). This discrepancy, along with GNSS data, suggests the contribution of a deep deflation source with a short relaxation time (20–40 days). Estimation of mass balance between the emitting plume and fluids discharged from both shallow and deep sources revealed that more than 70% of the discharged mass came from the deep source. Based on the estimated mass balance, phase state of the shallow reservoir was estimated as a single-phase, liquid-rich reservoir. The fast decay of the deep deflation may reflect rapid depressurization due to violent fluid discharge at the onset of the eruption. In contrast, the slow decay of the shallow deflation suggests that it had a minor role in the eruption. However, such a wet reservoir has the potential to induce volcanic hazard such as snow-melting lahar for future eruptions, requiring monitoring the volcano, which will probably shift to pre-eruptive re-pressurized phase, until the future eruption.