bluuebunny/crossref_metadata_2025_split huggingface dataset:
EZH2 Promotes Extracellular Matrix Degradation via Nuclear Factor-kB(NF-kB)and p38 signaling Pathways in Pulpitis.
Authors: He jie , Qin Man , Chen Yingyi , Hu Ziqi , Ye Ling , Hui Tianqian 
Published: December 2020

Abstract
Background: Pulpitis is a complicated chronic inflammatory process which in a dynamic balance between damage and repair. Extracellular matrix plays an important regulatory role in wound healing and tissue repair. The aim of this study was to explore role of the epigenetic mark, enhancer of zeste homolog 2 (EZH2) on the degradation of extracellular matrix during pulpitis. Methods : Quantitative polymerase chain reaction was used to assess the expression of matrix metalloproteinases (MMPs) and type I collagen in HDPCs upon EZH2 and EI1 stimulation. The mechanism of EZH2 affecting extracellular matrix was explored through quantitative polymerase chain reaction and Western blot. A rat model of dental pulp inflammation was established, and the expression of type I collagen in dental pulp under EZH2 stimulation was detected by immunohistochemical staining. Results :EZH2 upregulated the expression of MMP-1, MMP-3, MMP-8 and MMP-10 and decreased the production of type I collagen in HDPCs, while EI1 had the opposite effect .EZH2 activated the Nuclear Factor-kB(NF-kB)and p38 signaling Pathways in HDPCs, the inhibition of which reversed the induction of MMPs and the suppression of type I collagen .EZH2 can downregulated the type I collagen levels in an experimental model of dental pulpitis in rats. Conclusion: EZH2 promotes extracellular matrix degradation via Nuclear Factor-kB(NF-kB)and P38 signaling pathways in pulpitis.EZH2 can decrease the type I collagen levels in vivo and vitro.
MRI Contributes to Accurate and Early Diagnosis of Non-Radiographic HLA-B27 Negative Axial Spondyloarthritis
Authors: LU CHUN-CHI , Huang Guo-Shu , Lee Tony Szu-Hsien , Chao En , Chen Hsiang-Cheng , Yong-Si Guo , Shi-Jye Chu , Feng-Cheng Liu , Kao San-Yuan , Hou Tsung-Yun , Chen Chen-Hung , Chang Deh-Ming , Lyu Sin-Yi 
Published: December 2020

Abstract
BackgroundStructural changes to sacroiliac joints cannot be adopted to confirm active sacroiliitis on magnetic resonance imaging in the absence of bone marrow edema (BME). However, less than half of Asian patients with axial spondyloarthritis were characterized by BME. We aim to define the best methodology for accurate diagnosis, especially in the area with less common bone marrow edema and serum human leukocyte antigen-B27 (HLA-B27). Methods We included 103 patients with inflammatory back pain and morning stiffness in this prospective study. No radiograph met the definition of positive modified New York criteria. Inflammation and structural damage on magnetic resonance imaging were evaluated. Serum c-reactive protein and HLA-B27 levels were collected. Correlations between the various collected variables were analyzed. Results We demonstrated a positive association between inflammatory lesions and structural damage in the 58 ASAS-defined nr-axSpA subjects. BME on magnetic resonance imaging is moderately correlated with sclerosis and focal joint space widening (fJSW) (phi score of 0.372 and 0.319, p = 0.005 and 0.015, respectively). A moderately positive correlation between either the severity of BME and fJSW (p = 0.004) in 36 patients who had BME and met Assessment of Spondyloarthritis international Society criteria. There is a positive correlation between BME and fJSW across the whole cohort (phi score of 0.389; p < 0.001). We also identified a positive correlation between fJSW and BME in patients with non-radiographic axial spondyloarthritis and normal serum c-reactive protein levels (phi score of 0.362 and p = 0.001). Conclusion Severe erosions like fJSW on MRI-SIJs is positively correlated with development of BME on MRI and helps contribute to accurate diagnosis of non-radiographic axial spondyloarthritis either in the absence of HLA-B27 or normal serum inflammatory biomarkers, which might be used alternatively for early diagnosis of non-radiographic axial spondyloarthritis in Asian people who are characterized by less prevalence of BME and HLA-B27.
A new type of disordered CP12 protein in the marine diatom Thalassiosira pseudonana
Authors: Shao Hui , Huang Wenmin , Avilan Luisana , Receveur-Brechot Veronique , Puppo Carine , Puppo Rémy , Lebrun Régine , Gontero Brigitte , Launay Helene 
Published: December 2020

Abstract
Background
CP12 is a small chloroplast protein that is widespread in various photosynthetic organisms and is often involved in the redox metabolic on/off switch of the Calvin Benson Bassham (CBB) cycle. The gene encoding this protein is conserved in many diatoms, but the protein has been overlooked in these organisms, despite their ecological predominance and their complex and still enigmatic evolutionary background.
Methods
A combination of biochemical, bioinformatics and biophysical methods including electrospray ionization-mass spectrometry, circular dichroism, nuclear magnetic resonance and small X ray scattering spectroscopy, was used to characterize a diatom CP12.
Results
Here, we demonstrate that CP12 is expressed in the marine diatom Thalassiosira pseudonana constitutively in dark-treated and in continuous light-treated cells as well as in all growth phases. This CP12 behaves abnormally under gel electrophoresis, is heat resistant and lacks a structural core, all features of intrinsically disorder family similarly to its homologues in other species. By contrast, unlike other known CP12 proteins that are monomers, this protein is a dimer as shown by native electrospray ionization-mass spectrometry and small angle X-ray scattering. In addition, small angle X-ray scattering showed that this CP12 is an elongated cylinder with kinks. Circular dichroism spectra indicated that CP12, though it has features of disordered proteins, has a high content of α-helices. Nuclear magnetic resonance spectroscopy showed that these helices are unstable and dynamic within a millisecond timescale. Together with in silico predictions, these results suggest that T. pseudonana CP12 has both coiled-coil and disordered regions.
Conclusions
These findings bring new insights into the large family of intrinsically disordered proteins increasing the diversity of known CP12 proteins. This raises questions about the role of this protein in addition to the well-established regulation of the CBB cycle.
Hsa_circ_001659 serves as a diagnostic and prognostic biomarker for colorectal cancer
Authors: He Baoyu , Chao Wei , Huang Zhizhuo , Zeng Jianchao , Yang Jie , Luo Delan , Huang Shishun , Pan Hongli , Hao Yujun 
Published: December 2020

Abstract
Background: Colorectal cancer (CRC) is prevalent worldwide and novel diagnostic and prognostic biomarkers are needed to improve precision medicine. Circulating circular RNAs (circRNAs) are currently being considered as emerging tumor biomarkers. Methods: Candidate circRNA was selected by integrating analysis of Gene Expression Omnibus (GEO) database using GEO2R program. The expression data of serum circ_001659 were obtained from the quantitative real-time polymerase chain reaction (qRT-PCR). Receiver operating characteristic curves were applied to evaluate the clinical applications of circ_001659. Finally, biological functions and potential mechanisms of circ_001659 in tumor progression were investigated in CRC progression. Results: The results showed that the diagnostic performance of serum circ_001659 were excellent for CRC detection. The predictive values and likelihood ratios were satisfactory for the diagnosis of CRC, including patients in early-stage disease or patients with carcinoembryonic antigen (CEA)-negative status. Serum levels of circ_001659 declined significantly 3 months after surgery in both preoperative CEA-positive and CEA-negative patients. Functionally, circ_001659 influenced tumor cell metastasis via regulating epithelial-mesenchymal transition (EMT) and cytoskeleton organization. Conclusion: Our findings demonstrate that circ_001659 could be a useful serum biomarker for CRC diagnosis and prognosis. Targeting circ_001659 and its pathway may be meaningful for treating patients with CRC.
Mismatch repair deficiency is associated with specific morphologic features and frequent loss of ARID1A expression in ovarian clear cell carcinoma
Authors: Ge Huijuan , Xiao Yaoxin , Qin Guangqi , Gu Yanzi , Cai Xu , Jiang Wenhua , Tu Xiaoyu , Yang Wentao , Bi Rui 
Published: December 2020

Abstract
Background
Ovarian clear cell carcinoma (OCCC) is the second subtype of ovarian epithelial carcinoma reported to be closely related to Lynch syndrome (LS). ARID1A mutation is an important pathogenetic mechanism in OCCC that leads to loss of ARID1A expression in approximately half of OCCCs. However, the correlation of MMR status and ARID1A deficiency is unclear. The current study aimed to identify the clinical and histopathological characteristics of OCCC associated with dMMR and to further explore the association between dMMR and ARID1A deficiency.
Methods
A cohort of 176 primary OCCC patients was enrolled and review included histological characteristics (nuclear atypia, necrosis, mitosis, stromal hyalinization, and background precursors) and host inflammatory response (tumor-infiltrating lymphocytes, peritumoral lymphocytes, intratumoral stromal inflammation and plasma cell infiltration). Immunohistochemical staining of MLH1, PMS2, MSH2, MSH6 and ARID1A was performed using tissue microarrays.
Results
dMMR was detected in 10/176 tumors (6%), followed by MSH2/MSH6 (6/176), MLH1/PMS2 (3/176), and MSH6 (1/176). The average age of patients with dMMR was younger than the patients with intact MMR (46 y vs 53 y). Tumors with diffuse intratumoral stromal inflammation remained a significant association after multivariate analysis. ARID1A expression was absent in 8 patients with dMMR (8/10), which is a significantly higher frequency than that observed in patients with intact MMR (80% vs. 43.2%).
Conclusion
Our study indicates that diffuse intratumoral stromal inflammation of OCCCs is associated with dMMR, with loss of MSH2/MSH6 expression being most frequent. dMMR is strongly associated with loss of ARID1A expression in OCCC.
Peptide barcodes in dogs with pulmonary hypertension secondary to mitral valve disease using MALDI-TOF MS and LC-MS/MS
Authors: Riengvirodkij Nattapon , Roytrakul Sittiruk , Jaresitthikunchai Janthima , Phaonakrop Narumon , Charoenlappanich Sawanya , Sakcamduang Walasinee 
Published: December 2020

Abstract
Background

Pulmonary hypertension (PH) is an important complication in dogs with cardiorespiratory diseases. The most common underlying disease of PH has been described to be mitral valve disease (MVD), which is the most frequent acquired heart disease found in dogs. Doppler echocardiography is generally used in routine practice for identifying PH; however, there are several limitations to this method in practical use. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a technique that can characterize specific patterns of peptide mass called peptide barcodes from various samples. In addition, in combination with liquid chromatography tandem mass spectrometry (LC-MS/MS), potential peptide sequences associated with specific conditions could be identified. The present study aimed to use MALDI-TOF coupled with LC-MS/MS to characterize specific peptide barcodes and potential peptide candidates in serum samples from healthy dogs (normal control), dogs with MVD stage B (MVD B) (asymptomatic stage), MVD stage C (MVD C) (symptomatic stage), MVD stage B with PH (MVD B PH) and MVD stage C with PH (MVD C PH).
Results

Discrete clusters of the 5 sample groups were identified by 3D plot analysis. Peptide barcodes also revealed differences in peptide patterns among the 5 groups. Six amino acid sequences of peptide candidates at 1,225.60, 1,363.85, 1,688.71, 1789.52, 2020.21 and 2156.42 Da were identified as part of the proteins CLCN1, CLUL1, EDNRA, PTEN, SLC39A7, and CLN6, respectively. The network interactions between these discovered proteins and common cardiovascular drugs were also investigated.
Conclusion

The present study revealed distinct clusters and different peptide barcodes for the MVD B, MVD C, MVD B PH, MVD C PH and normal control groups using MALDI-TOF MS. These results demonstrate that MALDI-TOF MS has promise as a technique for diagnosing dogs affected by asymptomatic and symptomatic stages of MVD with and without PH. Additionally, with MALDI-TOF MS in combination with LC-MS/MS, potential peptide candidates related to diseases were also identified. Further studies are required to identify peptide barcodes in dogs with other diseases to create peptide barcode databases in veterinary medicine before using this method as a novel diagnostic tool in the future.
Is Expected Substance Type Associated With Timing of Drug Checking Service Utilization?: a Cross-sectional Study
Authors: Beaulieu Tara , Wood Evan , Tobias Samuel , Lysyshyn Mark , Patel Priya , Matthews Jennifer , Ti Lianping 
Published: December 2020

Abstract
Background: Drug checking is a harm reduction intervention aiming to reduce substance use-related risks by improving drug user knowledge of the composition of unregulated drugs. With increasing fears of fentanyl adulteration in unregulated drugs, this study sought to examine whether the expected type of drug checked (stimulant vs. opioid) was associated with timing of drug checking service utilization (pre-consumption vs. post-consumption).Methods: Data were derived from drug checking sites in British Columbia between October 31, 2017 and December 31, 2019. Pearson’s Chi-square test was used to examine the relationship between expected sample type (stimulant vs. opioid) and timing of service utilization. Odds ratios (OR) were calculated to assess the strength of this relationship. The Mantel-Haenszel (MH) test was used to adjust for service location. Results: 3,561 unique stimulant and opioid samples were eligible for inclusion, including 691 (19.40%) stimulant samples; and 2,222 (62.40%) samples that were tested pre-consumption. Results indicated a positive association between testing stimulant samples and testing pre-consumption (OR = 1.45; 95% CI: 1.21 – 1.73). Regions outside of the epicenter of the province’s drug scene showed a stronger association with testing pre-consumption (ORMH = 2.33; 95% CI: 1.51 - 3.56) than inside the epicenter (ORMH = 1.33; 95% CI: 1.09 - 1.63).Conclusion: Stimulant samples were more likely to be checked pre-consumption as compared with opioid samples, and stimulant samples were more likely to be tested pre-consumption in regions outside the epicenter of the province’s drug scene. This pattern may reflect a concern for fentanyl-adulterated stimulant drugs.
Long Noncoding RNA UCA1 Promotes Glutamine-Driven Anaplerosis of Bladder Cancer by Interacting With hnRNP I/L to Upregulate GPT2 Expression
Authors: Zhao Hua , Wu Wenjing , Li Xu , Chen Wei 
Published: December 2020

Abstract
Background: Glutamine-driven anaplerosis maintains the tricarboxylic acid (TCA) cycle by replenishing its carbon source of intermediates with the glutamine-derived carbons in cancer cells. Long noncoding RNA urothelial cancer associated 1 (UCA1), initially identified in bladder cancer, is associated with multiple cellular processes, including metabolic reprogramming. However, its characteristics in the anaplerosis context of bladder cancer (BLCA) remains elusive. Methods: The mechanism of UCA1 bound to and facilitated the combination of hnRNP I/L to the promoter of GPT2 gene was investigated by RNA pulldown, qRT-PCR, western blot, dual luciferase reporter assays, immunohistochemical staining, chromatin immunoprecipitation and chromatin isolation by RNA purification. Metabolomics analysis and metabolic flux analysis were conducted to assess the effects of UCA1, hnRNP I/L, and GPT2 on metabolic reprogramming of BLCA.Results: We identified UCA1 as a binding partner of heterogeneous nuclear ribonucleoproteins (hnRNPs) I and L, RNA-binding proteins with no previously known role in metabolic reprogramming. UCA1 and hnRNP I/L profoundly affected glycolysis, TCA cycle, glutaminolysis, and viability of BLCA cells. Importantly, UCA1 specifically bound to and facilitated the combination of hnRNP I/L to the promoter of glutamic pyruvate transaminase 2 (GPT2) gene, resulting in upregulated expression of GPT2 and enhanced glutamine-derived carbons in the TCA cycle. We also systematically confirmed the influence of UCA1, hnRNP I/L, and GPT2 on metabolism and proliferation via glutamine-driven anaplerosis in BLCA cells. Conclusions: Our study reveals the critical mechanism by which UCA1 forms a functional UCA1-hnRNP I/L complex that upregulates GPT2 expression to promote glutamine-driven TCA cycle anaplerosis, providing novel evidence that lncRNA regulates metabolic reprogramming in tumor cells.
Circ-0012417/ miR-29c-5p Axis Stimulates Thyroid Cancer Growth
Authors: Zhang Fan , Luo Jing , Shi Xingyuan , Liu Jiming , Chen Guo , Chen Ting , Wang Chunchuang , Lv Huizeng , Zhou Xinke 
Published: December 2020

Abstract
Background: There is an increasing tendency of the incidence rate of thyroid cancer. Despite the advance of widespread early diagnose and good prognosis of papillary thyroid cancer (PTC), some patients still suffered from the invasiveness and metastasis of thyroid cancer. More and more evidences demonstrated that circular RNAs (circRNAs) play important roles in tumorigenesis, tumor progression and metastasis. This study aims to identify oncogenic cirRNAs and explore its underlying molecular mechanisms in thyroid cancers.Methods: With circRNA chips in GEO database, we found that circ-0012417 was over-expressed in thyroid cancer. After silencing circ-0012417 or ectopic over-expressed circ-0012417, CCK-8 was used for detecting cell proliferation and transwell is used for examining metastasis and invasion abilities. Western Blot was used to detect changes of downstream proteins. Dual luciferase reporter assay was used to verify whether miR-29c-5p is the target of circ-0012417. Tumor xenografts in nude mice were used for further in vivo verifications. Results: Circ-0012417 is overexpressed in thyroid cancer, and silencing circ-0012417 could inhibit cancer cell proliferation, metastasis and invasion. MiR-29c-5p may be the target of circ-0012417 and inhibiting miR-29c-5p could reverse this phenomenon. And further analysis of TCGA and GTEx databases showed that EGFL7 may be the target of miR-126 and a promising thyroid cancer prognosis indicator.Conclusion: Circ-0012417 promotes thyroid cancer progression through regulating miR-29c-5p /EGFL7 pathway. Our finding provided novel therapeutic targets for thyroid cancer treatment.
Multiple Targeted Self-Emulsifying Compound RGO Reveals Obvious Antitumor Potential&nbsp;in Hepatocellular Carcinoma
Authors: He Sanxiu , Tian Shaorong , Le Xin , Chen Jialin , Chen Hongyi , He Xiaoqian , Mu Junhao , Xu Ke , Xiang Qin , Wu Yue , Ning Yijiao , Chen Jiong , Xiang Tingxiu 
Published: December 2020

Abstract
Background: Currently, the treatment for advanced hepatocellular carcinoma (HCC) is extremely limited. Ginsenoside Rg3, ganoderma lucidum polysaccharide, and Oridonin have shown great potential in anti-tumor therapy in previous studies, but low bioavailability and poor solubility seriously hinder their clinical application. Hence, new strategy for liver cancer are urgently needed. Methods: Cell viability, cell proliferation, cell migration, colony formation, tubule formation, sphere formation, and flow cytometry were used to assess the effect of a new drug, RGO-SMEDDS, (self-microemulsifying drug delivery system comprising of Rg3, ganoderma lucidum polysaccharide, and Oridonin) on HCC. Specific anti-tumor mechanisms of RGO-SMEDDS were investigated by western blot, qRT-PCR, and immunohistochemistry. Xenografts and staining with hematoxylin and eosin were used to assess the effects of RGO-SMEDDS on tumorigenesis in vivo.Results: We developed a self-microemulsifying drug delivery system (RGO-SMEDDS) for these three plant monomers. Treatment with RGO-SMEDDS resulted in induction of G2/M phase arrest and apoptosis, inhibition of migration and invasion, and suppression of cell proliferation, both in vitro and in vivo. Furthermore, RGO-SMEDDS restored immune function by suppressing the production of immunosuppressive cytokine and M2-polarized macrophages, reduced angiogenesis by down-regulation of vascular endothelial growth factor and its receptor, and attenuated stemness of HCC by inhibiting EGFR/AKT/GSK-3α/β signaling pathways. In addition to excellent anti-tumor effects, RGO-SMEDDS showed considerable safety in acute toxicity tests.Conclusion: RGO-SMEDDS exerted significant anti-tumor effects by reducing angiogenesis, remodeling immune microenvironments, and promoting apoptosis, without obvious toxicities. With these attributes RGO-SMEDDS is a promising therapy for the treatment of hepatocellular carcinoma.
Application of Auriculotemporal Nerve Block and Dextrose Prolotherapy in Exercise Therapy of TMJ Closed Lock in Adolescents and Young Adults
Authors: Zhou Hongzhi , Xue Yang , Liu Ping 
Published: December 2020

Abstract
Background: Temporomandibular joint (TMJ) ‘closed lock’ is a clinical condition causing TMJ pain and limited mouth opening (painful locking). Recent studies suggest an increasing prevalence of degenerative joint disease associated with the onset of TMJ closed lock in adolescents and young adults. Early interventions are recommended, but the curative effect of standard therapies remains controversial. In this retrospective study, an alternative method of non-surgical treatment of TMJ closed lock is presented, and its long-term efficacy has been observed. Methods: Forty adolescents and young adults, aged 16 to 30 years old, with distinct combination of symptoms of TMJ closed lock, were enrolled. Patients received anesthetic blockages of the auriculotemporal nerve, then performed mandibular condylar movement exercise for 10 minutes, and subsequently received hypertonic dextrose prolotherapy in retro-discal area of TMJ. Clinical assessments at baseline and at follow-up (2 weeks, 2 months, 6 months, and 5 years) included intensity and frequency of TMJ pain, mandibular range of motion, TMJ sounds, and impairment of chewing.Results: Cone beam CT images of the TMJs revealed joint space changes in all patients and degenerative bone changes in 20% (8/40) of the patients. The patients were diagnosed as having disc displacement without reduction with limited opening. Successful reduction of displaced disc had been achieved in the treatment. And pain at rest and pain on mastication had substantially decreased in all patients and mandibular function and mouth opening had significantly improved since 2 weeks’ follow-up. The overall success rate kept at a high level of 97.5% (39/40) at 6 months and 5 years’ follow-up. Conclusions: The technique combining mandibular condylar movement exercise with auriculotemporal nerve block and dextrose prolotherapy is straightforward to perform, inexpensive and satisfactory to young patients with TMJ closed lock.