bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linoleic acid and linoleate diols in neonatal cord blood influence birth weight
Authors: Umeda Naoko , Hirai Takaharu , Ohto-Nakanishi Takayo , Tsuchiya Kenji J. , Matsuzaki Hideo 
Published: August 2022

BackgroundLow-birth-weight infants exhibit a high risk for postnatal morbidity. Cytochrome P450 (CYP) and epoxide hydrolase (EH) are involved in the metabolism of factors responsible for low-birth-weight in infants. Both CYPs and EHs have high substrate specificity and are involved in polyunsaturated fatty acid (PUFA) metabolism. The CYP pathway produces epoxy fatty acids (EpFAs), which are further degraded by soluble EH (sEH). Additionally, sEH inhibition enhances the action of EpFAs and suppresses inflammatory responses. During pregnancy, excessive activation of maternal inflammatory response is a significant factor associated with low-birth-weight. However, the association of EpFAs, which have potential anti-inflammatory properties, with the low-birth-weight of infants remains uninvestigated. This study aimed to clarify the association between the umbilical cord serum EpFA and low-birth-weight using data obtained from the Hamamatsu Birth Cohort for Mothers and Children (HBC Study) by analyzing the umbilical cord blood samples.MethodWe selected a subgroup of 200 infants (106 boys and 94 girls), quantified EpFA concentration in their cord blood samples collected at birth, and examined its correlation with birth weight.ResultsThe comparison between the low-birth-weight and normal-birth-weight groups revealed no significant correlation between PUFA and EpFA concentrations, but a significant correlation was observed in the linoleate diol concentrations of the two groups. Furthermore, birth weight did not significantly correlate with PUFA, EpFA, and diol concentrations in cord blood; however, multiple regression analysis showed a significant negative correlation of birth weight with the concentration of linoleic acid (LA) (r = −0.101, p = 0.016) as well as LA-derived dihydroxyoctadecenoic acid (diHOME) (r = −0.126, p = 0.007), 9,10-diHOME (r = −0.115, p = 0.014), and 12,13-diHOME (r = −0.126, p = 0.007) after adjusting for obstetric factors, including gestational age, infant’s sex, childbirth history, delivery method, and maternal height.ConclusionsBirth weight was significantly correlated with the concentration of LA and linoleate diol diHOME after adjusting for obstetric confounders. Our results show that CYP and sEH involved in PUFA metabolism may influence the birth weight of infants. Further validation is needed to provide insights regarding maternal intervention strategies required to avoid low-birth-weight in infants in the future.
Characterization of chromatin regulators in hepatocellular carcinoma to guide clinical therapy
Authors: Jia Xiangen , Zhang Guozhi 
Published: August 2022

Background: Hepatocellular carcinoma (HCC) is notorious for its high mortality and incidence. Accumulating evidence confirms that chromatin regulators (CRs) have a significant impact on cancer. Therefore, exploring the mode of action and prognostic value of CRs is imminent for the treatment of hepatocellular carcinoma.Method: Transcriptome and clinical data for this study have been downloaded from TCGA (https://portal.gdc.cancer.gov/) and ICGC (https://dcc.icgc.org/). Univariate analysis was used to screen CRs with prognostic value, and our prognostic risk score signature was developed using least absolute shrinkage along with selection operator (lasso) Cox regression analysis. The CRs-based prognostic model was constructed in the TCGA dataset, and low-risk HCC patients had a better prognosis, which was finally validated in the ICGC dataset. We used the receiver operating characteristic curve to identify the accuracy of the prediction model and establish a line chart to prove the clinical effectiveness of the model. We also discussed the differences in drug sensitivity via CellMiner database, tumor immune microenvironment via ssGSEA algorithm, and clinical characteristics among different risk groups.Results: A prognostic model consisting of seven CRs was constructed and verified in HCC patients. Furthermore, we found that this risk score prognostic signature could independently predict the prognosis of HCC patients. Functional enrichment analysis revealed that CRs are mainly associated with cancer-related signaling pathways and metabolic pathways. In addition, immune cell abundance correlates with risk score levelsConclusion: In brief, we systematically explored the mode of action of CRs in HCC patients and established a reliable prognostic prediction model.
A novel necroptosis-related lncRNA signature for predicting prognosis and immune response of colon cancer
Authors: Luo Jian , Peng Jiayu , Xiao Wanying , Huang Shujing , Cao Yanqing , Wang Ting , Wang Xicheng 
Published: August 2022

Background: Numerous lncRNAs have been shown to affect colon cancer (CC) progression, and tumor necroptosis is regulated by several of them. However, the prognostic value of necroptosis-related lncRNA in CC has rarely been reported. In this study, a necroptosis-related lncRNA prognostic model was constructed, which can provide a reference for clinical diagnosis and treatment.Methods: The Cancer Genome Atlas (TCGA) database provided gene expression and lncRNA sequencing data for CC patients, and GSEA provided necroptosis gene data. Differentially expressed necroptosis-related lncRNAs related to prognosis were identified by differential expression analysis, Pearson correlation analysis, and least absolute shrinkage and selection operator (LASSO) regression. Based on the results of the multivariate COX regression analysis, a risk scoring model was constructed, A Kaplan-Meier analysis was performed to compare overall survival (OS) between low-risk and high-risk groups. A nomogram was then developed and validated based on the clinical data and risk scores of CC patients. In addition, Gene Set Enrichment Analysis (GSEA) and immune correlation analysis were conducted to explore the possible pathways and immune regulatory effects of these necroptosis-related lncRNAs.Results: In total, we identified 326 differentially expressed necroptosis-related lncRNAs in the TCGA database. Survival analysis showed that the OS of patients in the low-risk group was significantly better than that in the high-risk group (p &lt; 0.05). Finally, 10 prognostic necroptosis-related lncRNAs were used to construct the nomogram. The composite nomogram prediction model evaluated and validated with good prediction performance (3-year AUC = 0.85, 5-years AUC = 0.82, C-index = 0.78). The GSEA and immune correlation analyses indicated that these lncRNAs may participate in multiple pathways involved in CC pathogenesis and progression.Conclusion: We established a novel necroptosis-related lncRNA CC prognosis prediction model, which can provide a reference for clinicians to formulate personalized treatment and review plans for CC patients. In addition, we also found that these necroptosis-related lncRNAs may affect the pathogenesis and progression of colon cancer through multiple pathways, including altering the activity of various immune cells.
The effects of nutrition bio-shield superfood powder on immune system function: A clinical trial study among patients with COVID-19
Authors: Azizi Jalilian Farid , Keshavarz Gheisar , Khazaei Salman , Nezamdoost Manije , Hashemi Seyed Hamid , Mamani Mojgan , Ansari Nastaran , Amini Razieh , Khalkhali Aref , Keshavarz Arghavan , Ayubi Erfan , Fazeli Maryam , Heidari Moghadam Rashid , Alizadeh Saeid , Pourhossein Behzad , Teimouri Ali , Keramat Fariba , Karampour Sajad , Khakzad Mohammadreza 
Published: August 2022

The present study aimed to evaluate the effects of Nutrition Bio-shield Superfood (NBS) powder on the immune system function and clinical manifestations in patients with COVID-19. We compare the effects of NBS powder on the immune system function and clinical manifestations among two different groups: 1) intervention group receiving standard treatment scheduled according to treatment guidelines plus NBS powder, and 2) control group receiving only the same standard treatment. The serum levels of IL-2, IL-6, IL-17, IFNγ, and TNFα were determined after four weeks of treatment by specific ELISA kits according to the manufacturer’s instructions. Finally, the level of immune system stimulation and inflammatory markers were compared at baseline and after intervention in both groups. Data were analyzed using SPSS (version 22). A p-value of ≤ 0.05 was set as significant. A total of 47 patients with COVID-19 (24 patients in the intervention group and 23 patients in the control group) were included in this study. Results showed that the differences in the mean decrease of IL-2, IL-6, and TNF-α in the intervention group in comparison to the control group were 0.93, 10.28, and 8.11 pg/ml, respectively (P&lt;0.001). On the other hand, there was no difference in IL-17, IFNγ, monocytes, eosinophil, and other inflammatory indices between the intervention and control groups. Although NBS powder was able to significantly decrease the levels of some proinflammatory cytokines in patients with COVID-19, however, it is noteworthy that the course of the disease was to large part unaffected by NBS power and there was a reduction independent of treatment. The present study indicates that NBS powder could provide a beneficial anti-inflammatory effect in patients with COVID-19. Hence, NBS in treating patients with COVID-19 shows promise as an adjuvant to the current standard antiviral treatment of such patients.Clinical Trial Registrationhttps://www.irct.ir, identifier IRCT20200426047206N1.
Blockade of Mbd2 by siRNA-loaded liposomes protects mice against OVA-induced allergic airway inflammation via repressing M2 macrophage production
Authors: Wu Guo-Rao , Zhou Min , Wang Yi , Zhou Qing , Zhang Lei , He Long , Zhang Shu , Yu Qilin , Xu Yongjian , Zhao Jianping , Xiong Weining , Wang Cong-Yi 
Published: August 2022

ObjectiveTo address the role of methyl-CpG-binding domain 2 (MBD2) in the pathogenesis of asthma and its potential as a target for the asthmatic therapy.MethodsStudies were conducted in asthmatic patients and macrophage-specific Mbd2 knockout mice to dissect the role of MBD2 in asthma pathogenesis. Additionally, RNAi-based therapy with Mbd2 siRNA-loaded liposomes was conducted in an ovalbumin (OVA)-induced allergic airway inflammation mouse model.ResultsAsthmatic patients and mice challenged with OVA exhibited upregulated MBD2 expression in macrophages, especially in alternatively activated (M2) macrophages. In particular, macrophage-specific knockout of Mbd2 protected mice from OVA-induced allergic airway inflammation and suppressed the M2 program. Notably, intratracheal administration of liposomes carrying Mbd2 siRNA decreased the expression of Mbd2 and prevented OVA-induced allergic airway inflammation in mice, as indicated by the attenuated airway inflammation and mucus production.ConclusionsThe above data indicate that Mbd2 implicates in the pathogenesis of asthma predominantly by regulating the polarization of M2 macrophages, which supports that Mbd2 could be a viable target for treatment of asthma in clinical settings.
Comprehensive analysis of pyroptotic gene prognostic signatures associated with tumor immune microenvironment and genomic mutation in breast cancer
Authors: Zhang Hongfei , Yu Xiafei , Yang Junzhe , He Gao , Zhang Xiaoqiang , Wu Xian , Shen Li , Zhou Yi , Cheng Xuyu , Liu Xiaoan , Zhu Yanhui 
Published: August 2022

BackgroundBreast cancer is becoming a tumor with the highest morbidity rate, and inflammation-induced cell death namely pyroptosis reportedly plays dual roles in cancers. However, the specific mechanism between pyroptosis and the clinical prognosis of breast cancer patients is indistinct. Hence, novel pyroptosis-related biomarkers and their contributing factors deserve further exploration to predict the prognosis in breast cancer.MethodsPearson’s correlation analysis, and univariate and multivariate Cox regression analysis were utilized to obtain six optimal pyroptosis-related gene prognostic signatures (Pyro-GPS). The risk score of each breast cancer patient was calculated. Next, a Pyro-GPS risk model was constructed and verified in TCGA cohort (n=1,089) and GSE20711 cohort (n=88). Then analyses of immune microenvironment, genomic variation, functional enrichment, drug response and clinicopathologic feature stratification associated with the risk score of Pyro-GPS were performed. Subsequently, a nomogram based on the risk score and several significant clinicopathologic features was established. Ultimately, we further investigated the role of CCL5 in the biological behavior of MDA-MB-231 cell line.ResultsThe low-risk breast cancer patients have better survival outcomes than the high-risk patients. The low-risk patients also show higher immune cell infiltration levels and immune-oncology target expression levels. There is no significant difference in genetic variation between the two risk groups, but the frequency of gene mutations varies. Functional enrichment analysis shows that the low-risk patients are prominently correlated with immune-related pathways, whereas the high-risk patients are enriched in cell cycle, ubiquitination, mismatch repair, homologous recombination and biosynthesis-related pathways. Pyro-GPS is positively correlated with the IC50 of anti-tumor drugs. Furthermore, comprehensive analyses based on risk score and clinicopathological features were performed to predict the prognosis of breast cancer patients. Additionally, in vitro experiments confirmed that breast cancer cells with high expression of CCL5 had weaker proliferation, invasion and metastasis abilities as well as stronger apoptosis and cell cycle arrest abilities.ConclusionsThe risk score of Pyro-GPS can serve as a promising hallmark to predict the prognosis of BRCA patients. Risk score evaluation may assist to acquire relevant information of tumor immune microenvironment, genomic mutation status, functional pathways and drug sensitivity, and thus provide more effective personalized strategies.
Liver sinusoidal endothelial cell expressed vascular cell adhesion molecule 1 promotes liver fibrosis
Authors: Guo Qianqian , Furuta Kunimaro , Islam Shahidul , Caporarello Nunzia , Kostallari Enis , Dielis Kobe , Tschumperlin Daniel J. , Hirsova Petra , Ibrahim Samar H. 
Published: August 2022

BackgroundDuring liver injury, liver sinusoidal endothelial cells (LSECs) dysfunction and capillarization promote liver fibrosis. We have previously reported that the LSEC vascular cell adhesion molecule 1 (VCAM1) plays a key role in liver inflammation in nonalcoholic steatohepatitis (NASH) and we now aim to uncover its role in LSEC capillarization and liver fibrosis.MethodsWild-type C57BL/6J mice were fed either chow or high fat, fructose and cholesterol diet to induce NASH and treated with either anti-VCAM1 neutralizing antibody or control isotype antibody. Inducible endothelial cell-specific Vcam1 deleted mice (Vcam1Δend) and control mice (Vcam1fl/fl) were fed choline-deficient high-fat diet (CD-HFD) to induce NASH or injected with carbon tetrachloride to induce liver fibrosis. LSECs isolated from Vcam1fl/fl or Vcam1Δend and hepatic stellate cells (HSCs) isolated from wild-type mice were cocultured in a 3-D system or a μ-Slide 2 well co-culture system.ResultsImmunostaining for Lyve1 (marker of differentiated LSECs) was reduced in Vcam1fl/fl mice and restored in Vcam1Δend mice in both NASH and liver fibrosis models. Co-immunostaining showed increased α-smooth muscle actin in the livers of Vcam1fl/fl mice in areas lacking Lyve1. Furthermore, scanning electron microscopy showed reduced LSEC fenestrae in the Vcam1fl/fl mice but not Vcam1Δend mice in both injury models, suggesting that VCAM1 promotes LSEC capillarization during liver injury. HSCs profibrogenic markers were reduced when cocultured with LSECs from CD-HFD fed Vcam1Δend mice compared to Vcam1fl/fl mice. Furthermore, recombinant VCAM1 activated the Yes-associated protein 1 pathway and induced a fibrogenic phenotype in HSCs in vitro, supporting the profibrogenic role of LSEC VCAM1.ConclusionVCAM1 is not just a scaffold for leukocyte adhesion during liver injury, but also a modulator of LSEC capillarization and liver fibrosis.
Protective effects of silver nanoparticles in isoproterenol-induced myocardial infarction in rats
Authors: Arozal Wawaimuli , Monayo Edwina Rogayah , Barinda Agian Jeffilano , Perkasa Dian Pribadi , Soetikno Vivian , Nafrialdi Nafrialdi , Louisa Melva 
Published: August 2022

BackgroundSilver nanoparticles (AgNPs) are widely used in the medical field, including cardiovascular. However, limited research has investigated the effect of AgNPs on the protection of myocardial infarction (MI).ObjectivesIsoproterenol (Iso)-induced MI and the cardiac protection offered by AgNPs were investigated in the present study. Additionally, we characterized the profile of Ag in the form of nanoparticles.MethodsTwenty-four male Wistar rats were randomly divided into four groups as follows: normal, Iso, Iso + AgNO3, and Iso + AgNP groups. AgNPs and silver ion (AgNO3) were administered intraperitoneally at 2.5 mg/kg BW for 14 days. Iso induction was performed using two doses of 85 mg/kg BW given subcutaneously on days 13 and 14. Blood and cardiac tissue samples were taken 24 h after the last dose of Iso and checked for Creatine Kinase-MB (CK-MB), lactate dehydrogenase in plasma along with oxidative stress parameters, mitochondria biogenesis markers, and inflammation representative genes in cardiac tissue. Additionally, we analyzed the histopathological features in cardiac tissue.ResultsThe silver was confirmed in the form of nanoparticles by its size at intervals of 8.72–37.84 nm. Both AgNO3 and AgNPs showed similar cardioprotective effects, as shown by the decrease in biochemical markers of cardiac toxicity, namely, CK-MB. Additionally, AgNPs group have better efficacy compared with AgNO3 group in ameliorating Iso-mediated oxidative stress production, as evidenced by the significant decrease in malondialdehyde level and increased superoxide dismutase activity (P &lt; 0.0001 and P &lt; 0.01, respectively) in cardiac tissue compared with the Iso group. Mechanistically, AgNPs, but not AgNO3, enhanced the expression levels of mitochondrial transcription factor A and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha in post-MI heart and reduced the protein expression of nuclear factor-kappa B (NF-κB) assessed by western blot analysis. Furthermore, these results were confirmed with the histopathological evaluation of cardiac tissue. Nevertheless, pretreatment with either AgNO3 or AgNPs improved the aspartate aminotransferase level.ConclusionThese results suggested that AgNPs have more superior cardioprotective effect compared with AgNO3 against Iso-induced MI, at least in part through amelioration of NF-κB expression level induced by oxidative stress overproduction.
Nociception monitors vs. standard practice for titration of opioid administration in general anesthesia: A meta-analysis of randomized controlled trials
Authors: Ma Dandan , Ma Jiahui , Chen Huayong , Mu Dongliang , Kong Hao , Yu Lingzhi 
Published: August 2022

BackgroundNociception monitors are being increasingly used during surgery, but their effectiveness in guiding intraoperative opioid administration is still uncertain. This meta-analysis of randomized controlled trials (RCTs) aimed to compare the effectiveness of nociception monitors vs. standard practice for opioid administration titration during general anesthesia.MethodsWe searched the electronic databases of PubMed, EMBASE, Cochrane Library, Clinical Trial, and Web of Science from inception up to August 1, 2021, to identify relevant articles, and extracted the relevant data. Intraoperative opioid administration, extubation time, postoperative pain score, postoperative opioid consumption and postoperative nausea and vomiting (PONV) were compared between patients receiving nociception monitoring guidance and patients receiving standard management. The standardized mean difference (SMD), with 95% confidence interval (CI), was used to assess the significance of differences. The risk ratio (RR), with 95% CI, was used to assess the difference in incidence of PONV. Heterogeneity among the included trials was evaluated by the I2 test. RevMan 5.3 software was used for statistical analysis.ResultsA total of 21 RCTs (with 1957 patients) were included in the meta-analysis. Intraoperative opioid administration was significantly lower in patients receiving nociception monitor-guided analgesia than in patients receiving standard management (SMD, −0.71; 95% CI, −1.07 to −0.36; P &lt; 0.001). However, pain scores and postoperative opioid consumption were not significantly higher in the former group. Considerable heterogeneity was found among the studies (92%). Extubation time was significantly shorter (SMD, −0.22; 95% CI, −0.41 to −0.03; P = 0.02) and the incidence of PONV significantly lower (RR, 0.78; 95% CI, 0.61 to 1.00; P = 0.05) in patients receiving nociception monitoring guidance.ConclusionsIntraoperative nociception monitoring guidance may reduce intraoperative opioid administration and appears to be a viable strategy for intraoperative titration of opioids.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=273619, identifier: CRD42019129776.
Cortical neuroanatomical changes related to specific language impairments in primary progressive aphasia
Authors: Kang Sung Hoon , Park Yu Hyun , Shin Jiho , Kim Hang-Rai , Yun Jihwan , Jang Hyemin , Kim Hee Jin , Koh Seong-Beom , Na Duk L. , Suh Mee Kyung , Seo Sang Won 
Published: August 2022

ObjectiveLanguage function test-specific neural substrates in Korean patients with primary progressive aphasia (PPA) might differ from those in other causes of dementia and English-speaking PPA patients. We investigated the correlation between language performance tests and cortical thickness to determine neural substrates in Korean patients with PPA.Materials and methodsNinety-six patients with PPA were recruited from the memory clinic. To acquire neural substrates, we performed linear regression using the scores of each language test as a predictor, cortical thickness as an outcome and age, sex, years of education, and intracranial volume as confounders.ResultsPoor performance in each language function test was associated with lower cortical thickness in specific cortical regions: (1) object naming and the bilateral anterior to mid-portion of the lateral temporal and basal temporal regions; (2) semantic generative naming and the bilateral anterior to mid-portion of the lateral temporal and basal temporal regions; (3) phonemic generative naming and the left prefrontal and inferior parietal regions; and (4) comprehension and the left posterior portion of the superior and middle temporal regions. In particular, the neural substrates of the semantic generative naming test in PPA patients, left anterior to mid-portion of the lateral and basal temporal regions, quite differed from those in patients with other causes of dementia.ConclusionOur findings provide a better understanding of the different pathomechanisms for language impairments among PPA patients from those with other causes of dementia.