bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Responses and Predictors of Low-Dose Interleukin-2 in Systemic Lupus Erythematosus
Authors: Miao Miao , Li Yimin , Xu Dan , Zhang Ruijun , He Jing , Sun Xiaolin , Li Zhanguo 
Published: January 2021

Abstract
Objective. Interleukin-2 (IL-2) is effective and well tolerated in patients with systemic lupus erythematosus (SLE). However, patient response to IL-2 therapy varies. Therefore, biomarkers are needed to efficiently identify patients who may respond well to IL-2 treatment. We investigated clinical and immunological biomarkers to predict low-dose IL-2 responses.Methods. A pooled post-hoc analysis was performed in SLE patients who received low-dose IL-2 treatment in two clinical trials. Factors predicting responses in clinical and T-cell subset changes were evaluated by logistic regression. Good response (GR) and poor response (PR) were defined according to whether patients achieved or did not achieve an SLE Responder Index-4 (SRI-4), respectively.Results. A good response at 68% of patients was achieved in the lower Treg group, compared to 0% in the higher Treg group. A good response at 68% was achieved in patients with lower Treg, compared to 0% in patients with higher Treg. In comparison to PR, GR was more strongly associated with low Treg proportions at baseline (12.85±6.07% vs. 9.43±2.82%, P<0.01). There were more patients with skin rash in the GR group than in the PR group (68.75% vs. 30.77%, P=0.042). Multivariate analysis showed that low Treg proportions and skin rash presence were both independently associated with GR to low-dose IL-2 treatment. A nomogram to identify GR probability exhibited a clear discrimination (concordance index, 0.812; 95% confidence interval, 0.64-0.97). Based on the area under the receiver operating characteristic (ROC) curve (AUC) of 0.813, the specificity of a low regulatory T cells (Tregs) proportion (≤13.35%) plus skin rash to predict GR to IL-2 therapy was 100%, with a sensitivity of 68.75%.Conclusion. A low Treg proportion and skin rash indicate GR to low-dose IL-2 treatment in SLE patients.Trial registration number ClinicalTrials.gov Registries ((NCT02465580 and NCT02084238).
Validation of the Relationship Between Coagulopathy and Localization of Hydroxyethyl Starch on the Vascular Endothelium in a Rat Hemodilution Model
Authors: Azumaguchi Ryu , Tokinaga Yasuyuki , Kazuma Satoshi , Kimizuka Motonobu , Hamada Kosuke , Sato Tomoe , Yamakage Michiaki 
Published: January 2021

Abstract
BackgroundVarious anticoagulant properties have been associated with hydroxyethyl starch (HES), including coagulation disorders measured by point-of-care devices, decreases in von Willebrand factor and coagulation factor VIII, and inhibition of the interactions between platelet-membrane glycoproteins and of coagulation factors by coating of platelets. However, the mechanism for these properties remains unclear. The aim of this study was to test the hypothesis that coagulopathy induced by HES is caused by endothelial or glycocalyx damage as a result of localization of HES on the endothelium, due to the high shear viscosity of blood, using a rat model.MethodsWe compared blood coagulability measured by Sonoclot®, levels of endothelial and glycocalyx damage markers and coagulation factors, and blood shear viscosity when hemodilution was performed with physiological saline (PS), 6% HES 130/0.4 in PS (HES130) and 10% HES 200/0.5 in PS (HES200). To precisely evaluate the basic mechanism of coagulopathy induced by HES, we performed hemodilution with an emphasis on dilutional equality by taking into consideration the intravascular residual rates of the infusion preparations. We also evaluated the localization rates of fluorescently labeled HES on endothelium in the isolated aorta. Statistical analyses were performed by one-way ANOVA followed by Tukey’s test or Kruskal–Wallis test, and then Dunn’s test for multiple comparisons.ResultsSonoclot® measurements revealed that HES130 and HES200 decreased the fibrin gel formation rate to a greater extent than PS, and HES200 decreased the rate more than HES130. Similarly, HES130 and HES200 decreased von Willebrand factor levels to a greater extent than PS. HES130 and HES200 had a more protective effect than PS, with no evidence of damage to the endothelium or glycocalyx. Shear viscosity was variable between all pairs, and was lowest for PS and highest for HES200. HES130 and HES200 demonstrated comparable degrees of localization on the endothelium.ConclusionsHES was shown to cover the endothelium, possibly due to its high shear viscosity, and this mechanism potentially acted to protect the endothelium and glycocalyx. However, this covering effect may be the cause of coagulopathy due to inhibition of von Willebrand factor secretion from the endothelium.
Effects of Humic Acid-Irrigation Coupling Techniques on Temperature, Radiation and Rice Growth in Songnen Plain China
Authors: Zheng Ennan , Zhu Yinhao , Hu Jianyu , Xu Tianyu , Zhang Zhongxue 
Published: January 2021

Abstract
In the past decades, the application of organ fertilizer in agricultural soils has attracted wide attention. However, few studies have carefully explored the effects of humic acid on soil and canopy temperature, radiation, the physiological process of plant leaves, especially coupling with the different irrigation methods. To provide a better growing environment for crops and explore the best regulation mode of humic acid and irrigation coupling techniques in the farmland soil environment in the Songnen Plain Heilongjiang Province, through field experiment, we selected rice as the test crop and applied humic acid in the soil with different irrigation methods. The temperature conditions, radiation, agronomic and fluorescence characteristics were monitored by different stages. The effects of different humic acid and irrigation coupling techniques on the temperature and radiation changes during different growth stages were discussed, and the subtle differences of agronomic and fluorescence characteristics in different growth stages of rice plants were compared. The results showed that the humic acid application with different irrigation methods was not beneficial to the maintenance of soil temperature, the differences among the different treatments, were no found significant at 5% probability statistically. However, the differences of radiation interception was obvious, and the best value was CT5 treatment, there were also similarities to plant height. The fluorescence indexes and leaf chlorophyll relative content (SPAD) had the differences with the change of humic acid application rate and irrigation methods. Over all, under the humic acid application rate of 1500 kg·ha-1 with the control irrigation method, could bring the best humic acid and irrigation effects.
High-Fat Diet Attenuates the Improvement of Hypoxia-induced Pulmonary Artery Hypertension in Mice During Reoxygenation.
Authors: Sugimoto Koichi , Yokokawa Tetsuro , Misaka Tomofumi , Kaneshiro Takashi , Yoshihisa Akiomi , Nakazato Kazuhiko , Takeishi Yasuchika 
Published: January 2021

Abstract
Background: It has been widely recognized that metabolic disorder is associated with pulmonary hypertension. It is known that elevated pulmonary artery pressure induced by hypoxia in mice returns to normal pressure under reoxygenation. However, it is still unclear how metabolic disorder affects the reverse remodeling of pulmonary arteries. In this study, we investigated the effects of a high-fat diet (HFD) on the decrease of pulmonary artery pressure and reverse remodeling of pulmonary arteries in mice with hypoxia-induced pulmonary hypertension.Methods: We used female C57/Bl6 mice aged 8 weeks. After the mice were exposed to hypoxia (10% oxygen for 4 weeks) for induction of pulmonary hypertension. Then, they were returned to normoxic conditions and randomized into a normal diet (ND) group and a HFD group. Both groups were fed their respective diets for 12 weeks.Results: The right ventricular systolic pressure measured by a micro-manometer catheter and the Fulton index were significantly higher in the HFD group than in the ND group at 12 weeks after reoxygenation. The medial smooth muscle area was larger in the HFD group. Caspase 3 activity in lung tissue of the HFD group was decreased, and an apoptosis of pulmonary smooth muscle cells was suppressed after reoxygenation. Moreover, the expression levels of peroxisome proliferator-activated receptor-γ and apelin were lower in the HFD group than in the LFD group.Conclusion: Our results suggest the metabolic disorder may suppress pulmonary artery reverse remodeling in mice with hypoxia-induced pulmonary hypertension under reoxygenation.
Difference of Binding Modes Among Three Ligands to a Receptor mSin3B Corresponding to Their Inhibitory Activities
Authors: Hayami Tomonori , Kamiya Narutoshi , Kasahara Kota , Kawabata Takeshi , Kurita Jun-ichi , Fukunishi Yoshifumi , Nishimura Yoshifumi , Nakamura Haruki , Higo Junichi 
Published: January 2021

Abstract
A preceding experiment suggested that a compound, which inhibits binding of the REST/NRSF segment to the cleft of a receptor protein mSin3B, can be a potential drug candidate to ameliorate many neuropathies. We have recently developed an enhanced conformational sampling method, genetic-algorithm-guided multi-dimensional virtual-system-coupled canonical molecular dynamics, and in the present study, applied it to three systems consisting of mSin3B and one of three compounds, sertraline, YN3, and acitretin. Other preceding experiments showed that only sertraline inhibits the binding of REST/NRSF to mSin3B. The current simulation study produced the spatial distribution of the compounds around mSin3B, and showed that sertraline and YN3 bound to the cleft of mSin3B with a high propensity, although acitretin did not. Further analyses of the simulation data indicated that only the sertraline–mSin3B complex produced a hydrophobic core similar to that observed in the molecular interface of the REST/NRSF–mSin3B complex: An aromatic ring of sertraline sunk deeply in the mSin3B’s cleft forming a hydrophobic core contacting to hydrophobic amino-acid residues located at the bottom of the cleft. The present study proposes a step to design a compound that inhibits competitively the binding of a ligand to its receptor.
Modelling Deep Habits in Iranian Economy using a Markov-Switching DSGE Model
Authors: Davoudi Narmin , Heidari Hassan 
Published: January 2021

Abstract
This paper attempts to solve and estimate a Markov-Switching Dynamic Stochastic General Equilibrium (MS-DSGE) model with deep habit-adjusted consumption in both private and public sectors for Iranian data from 1991 to 2015. A comprehensive New Keynesian Philips Curve (NKPC) is also extracted, including stock of private and public habit consumption in firm's profit maximization problem as a constraint. The model is estimated both with constant parameters and regime switching in monetary reaction function, and it is concluded that the model with regime switching is able to fit the Iranian data better. The results of estimating parameters indicate that the degree of habit formation, together with the persistence of habit stock, are significant parameters. However, it is shown that deep habits do not succeed in reducing inflation in Iranian economy in reaction to a monetary shock. The results confirm that consumption increases and inflation decreases, simultaneously in response to fiscal shocks.
Morphological and Molecular Characteristics of Spheroid Formation in HT-29 and Caco-2 Colorectal Cancer Cell Lines
Authors: Gheytanchi Elmira , Naseri Marzieh , Karimi-Busheri Feridoun , Atyabi Fatemeh , Mirsharif Ensie Sadat , Bozorgmehr Mahmood , Ghods Roya , Madjd Zahra 
Published: January 2021

Abstract
Background: Relapse and metastasis in colorectal cancer (CRC) are often attributed to cancer stem-like cells (CSCs), as small sub-population of tumor cells with ability of drug resistance. Accordingly, development of appropriate models to investigate CSCs biology and establishment of effective therapeutic strategies is warranted. Hence, we aimed to assess the capability of two widely used and important colorectal cancer cell lines, HT-29 and Caco-2, in generating spheroids and their detail morphological and molecular characteristics.Methods: CRC spheroids were developed using hanging drop and forced ﬂoating in serum-free and non-attachment condition and their morphological features were evaluated by scanning electron microscopy (SEM). Then, the potential of CSCs enrichment in spheroids was compared to their adherent counterparts by analysis of serial sphere formation capacity, real-time PCR of key stemness genes (KLF4, OCT4, SOX2, NANOG, C-MYC) and the expression of potential CRC-CSCs surface markers (CD166, CD44, and CD133) by flow cytometry. Finally, the expression level of some EMT-related (Vimentin, SNAIL1, TWIST1, N-Cadherin, E-Cadherin, ZEB1) and multi-drug resistant (ABCB1, ABCC1, ABCG2) genes was evaluated.Results: Although with different morphological features, both cell lines were formed CSCs-enriched spheroids, indicated by ability to serial sphere formation, significant up-regulation of stemness genes, SOX2, C-MYC, NANOG and OCT4 in HT-29 and SOX2, C-MYC and KLF4 in Caco-2 spheroids (p-value<0.05) and increased expression of CRC-CSC markers compared to parental cells (p-value<0.05). Additionally, HT-29 spheroids exhibited a signiﬁcant higher expression of both ABCB1 and ABCG2 (p-value=0.02). The significant up-regulation of promoting EMT genes, ZEB1, Twist1, E-cadherin and SNAIL1 in HT-29 spheroids (p-value=0.03), SNAIL1 and Vimentin in Caco-2 spheroids (p-value<0.05) and N-cadherin down-regulation in both spheroids were observed.Conclusion: Based on enrichment of CSC-related features in HT-29 and Caco-2 spheroids, our findings suggest CRC spheroids culture as simple, cost-effective and efficient model to imitate the complexity of in vivo CRC tumors including self-renewal, drug resistance and invasion potential for CSC research.
Resuscitative Endovascular Balloon Occlusion of the Aorta in a Normovolemic Rabbit Model: a Pilot Study
Authors: Liu Juanfang , Zhang Jianhao , Xie Shanshan , Liu Yingxia , Zhou Xueliang , Li Zhaonan , Han Xinwei 
Published: January 2021

Abstract
Background: The purpose of this study was to verify physiological, end-organ and systemic inflammatory changes in zone II after resuscitative endovascular balloon occlusion of the aorta (REBOA) in a normovolemic rabbit model.Methods: Anaesthetized rabbits were subjected to aortic balloon occlusion for different times (15 min, 30 min, 60 min and 90 min) followed by 2 h of reperfusion. Rabbits with no balloon occlusion were set as the control group. ELISAs were used to examine the serum levels of ALT, AST, Cr, BUN, MDA, SOD, IL-8, IL-6, and TNF-α; HE staining was used to identify the morphological changes in the kidney; RT-PCR was used to detect the mRNA levels of IL-6, IL-8, TNF-α and NF-κB in the kidney and uterus; and Western blotting was used to measure the protein expression levels of IL-6, IL-8, TNF-α and NF-κB in the kidney and uterus.Results: Plasma concentrations of liver markers, kidney markers, inflammatory factors and oxidative stress indicators were significantly increased at the end of reperfusion in the 30 min, 60 min and 90 min groups. Damage to the kidney occurred in the 30 min, 60 min and 90 min groups. The mRNA and protein expression levels of IL-6, IL-8, TNF-α and NF-κB in the kidney and uterus were significantly increased at the end of reperfusion in the 30 min group, and as the time of occlusion extended, these levels continued to increase.Conclusion: Activation of systemic inflammation and ischaemia-reperfusion injury of end-organs occurred when the occlusion time reached 30 min. Therefore, 15 min should be regarded as a safe period of REBOA in zone II.
HTR7&nbsp;Promotes Laryngeal Cancer Growth Through Activating PI3K/AKT&nbsp;Pathway
Authors: Sheng Xiaoli , Liu Wenlin , Lu Zhongming , Xu Mimi , Li Rui , Zhong Rong , Li Yunxian , Liu Tao , Zhang Siyi 
Published: January 2021

Abstract
Background: Laryngeal cancer is a common malignancy of the head and neck, G protein-coupled receptors (GPCRs) are easily druggable in diseases. The 5-hydroxytryptamine receptor 7 (HTR7) belongs to the GPCR family; however, its role in laryngeal cancer remains unknown.Methods: MTT, Colony formation assay, BrdU incorporation assay, soft agar growth assay and xenograft tumor in nude mice were used to analyze the effect of HTR7 expression level on laryngeal cancer proliferation and growth.Results: We found that HTR7 was significantly upregulated in laryngeal cancer tissues and cells, and patients with high HTR7 expression had shorter survival time than those with low HTR7 expression. Univariate and multivariate Cox regression models showed HTR7 was an independent predictive factor for the prognosis of patients with laryngeal cancer. Cell proliferation assays and an animal model showed that HTR7 overexpression promoted laryngeal cancer proliferation and growth, while HTR7 knockdown inhibited laryngeal cancer proliferation and growth. Further analysis showed HTR7 activated the PI3K/AKT pathway, characterized by increased phosphorylation of AKT, luciferase reporter activity of FOXO factors and target expression. Inhibition of the PI3K/AKT pathway in HTR7-overexpressing cells suppressed proliferation and growth, suggesting HTR7 promoted laryngeal cancer proliferation and growth by activating the PI3K/AKT pathway.Conclusions: In summary, HTR7 is not only a target for laryngeal cancer therapy, but also a prognostic factor for the prognosis of patients with laryngeal cancer.
Resveratrol Protects Human Nucleus Pulposus Cells from Degeneration by Blocking IL-6/JAK/STAT3 Pathway
Authors: Wu Cenhao , Ge Jun , Yang Ming , Yan Qi , Wang Yingjie , Yu Hao , Yang Huilin , Zou Jun 
Published: January 2021

Abstract
Background: Nucleus pulposus cells’ (NPCs’) degeneration is mainly responsible for the intervertebral disc degeneration (IDD), which is closely related to inflammatory response. Among the major proinflammatory factors that are related to NPCs’ degeneration, interleukin-6 (IL-6) and its downstream JAK/STAT3 pathway have received recent attention. The goal of our study is to figure out whether or how resveratrol (RSV) can protect NPCs from degeneration by affecting IL6/JAK/STAT3 pathway. Methods: Different concentrations of RSV were added to NPCs’ mediums. Cell viability was measured by MTT assay and crystal violet staining. Cell cycle and apoptosis were analyzed by flow cytometry. Protein expression level was determined by western blot. mRNA expression level was measured by qPCR.Results: Our study showed that RSV improved NPCs’ cell viability. It also inhibited cell apoptosis and cell cycle arrest, which were accompanied by the increased expression level of heat shock protein 90 (HSP90) and N-Cadherin. What’ more, RSV also improved the NPCs’ degeneration which was reflected in the increase of extracellular matrix (collagen II, Aggrecan). Moreover, RSV significantly attenuated the level of IL-6 secretion, which was accompanied by less phosphorylation of the transcription factors janus kinase 1 (JAK1) and signal transducer and activator of transcription 3 (STAT3). Conclusion: RSV exerted its protective effect on HNPCs’ degeneration by improving cell survival and function. The possible mechanism may be associated with the suppression of JAK/STAT3 phosphorylation and the decreased IL-6 production, which could be explained by a blockage of the positive feedback control loop between IL-6 and JAK/STAT3 pathway.
The pattern of gene copy number variations (CNVs) in hepatocellular carcinoma; in silico analysis
Authors: Shahrisa Arman , Tahmaseby Maryam , Ansari Hossein , Mohammadi Zahra , Carloni Vinicio , Asl Javad Mohammadi 
Published: January 2021

Abstract
Recent studies showed that genetic lost or gain in the genome can predispose cells toward malignancy. Hepatocellular carcinoma (HCC) is the most common type of liver cancer which occurs predominantly in patients with underlying chronic liver disease and cirrhosis. Prognosis of HCC is strongly connected with diagnostic delay. To date, no ideal screening modality has been developed for HCC. Recent findings demonstrated that Copy number variation (CNVs) can lead to activation of oncogenes and inactivation of tumor suppressor genes in cancers. In this study, CNV profile of 361 HCC samples was evaluated to reveal the potent - chromosomal regions involved in the disease. The obtained data showed that the chr1q and chr8p were two hotspot regions for gene amplifications and deletions in studied samples respectively. In this research, YY1AP1 (Yin Yang-1 Associated Protein 1) on chr1q22 was the most amplified gene in HCC samples and showed the positive correlation with tumor grade. Deletion of CHMP7 (Charged Multivesicular Body Protein 7) on chr8p21.3 was another frequently observed CNV among HCC patients. Both genes were interacted with variety of well-known oncogenes and tumor suppressor genes including YY1 (Yin Yang 1), CCND1 (Cyclin D1), HDAC1 (Histone deacetylase 1), VHL (von Hippel-Lindau tumor suppressor), MAD2L2 (Mitotic Arrest Deficient 2 Like 2), CEBPA (CCAAT/enhancer-binding protein alpha), CHMP4A, CHMP5, CHMP2A, CHMP3 and ENSG00000249884 (RNF103-CHMP3 gene), all of them are well-known in carcinogenesis. Although this study was based on in silico evaluations, our findings can open a new window for researchers of HCC to focus on such candidate genes during experimental assays.