bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in salivary biomarkers of oxidative status in calves at weaning and grouping
Authors: Rubio Camila Peres , Escribano Damián , Mainau Eva , Cerón José Joaquin , Navarro Elena , Manteca Xavier 
Published: December 2021

AbstractBackgroundSaliva is being increasingly used as a sample for measuring biomarkers in several species and shows a high potential of use to detect and monitor stress. The weaning and grouping in dairy calves are a particularly stressful time. Therefore, the objectives of this study were to evaluate a panel of antioxidant and oxidant biomarkers in the saliva of calves on the day of weaning (W0), 2 days after weaning or milk withdrawal (W + 2), and 4 days after grouping (G + 4). In addition, to verify if cortisol and oxytocin concentrations are related to the biomarkers measured.ResultsSalivary cupric reducing antioxidant capacity (CUPRAC), ferric reducing ability of saliva (FRAS), Trolox equivalent antioxidant capacity (TEAC), advanced oxidation protein products (AOPP), and ferrous oxidation-xylenol orange (FOX) were significantly higher (P < 0.02) 4 days after grouping than the day of weaning and 2 days after. The increases were 50 and 54% for CUPRAC, 93 and 116% for FRAS, 117 and 135% for TEAC, 22 and 49% for AOPP and 10 and 5% for FOX in comparison with weaning and 2 days after, respectively. In addition, oxytocin and cortisol showed significant negative and positive correlations (P < 0.05) respectively with the biomarkers of oxidative status.ConclusionsOur results showed that calves after grouping show increases in antioxidants and oxidants concentrations, indicating that a balance between these molecules has been tried to maintain during this stressful situation. The dynamic changes of biomarkers of oxidative status should be explored and characterised in other stressful conditions.
Ferulic acid ameliorates lipopolysaccharide-induced tracheal injury via cGMP/PKGII signaling pathway
Authors: Xie Xiaoyong , Yu Tong , Hou Yapeng , Han Aixin , Ding Yan , Nie Hongguang , Cui Yong 
Published: December 2021

Abstract
Background
Tracheal injury is a common clinical condition that still lacks an effective therapy at present. Stimulation of epithelial sodium channel (ENaC) increases Na+ transport, which is a driving force to keep tracheal mucosa free edema fluid during tracheal injury. Ferulic acid (FA) has been proved to be effective in many respiratory diseases through exerting anti-oxidant, anti-inflammatory, and anti-thrombotic effects. However, these studies rarely involve the level of ion transport, especially ENaC.

Methods
C57BL/J male mice were treated intraperitoneally with normal saline or FA (100 mg/kg) 12 h before, and 12 h after intratracheal administration of lipopolysaccharide (LPS, 5 mg/kg), respectively. The effects of FA on tracheal injury were not only assessed through HE staining, immunofluorescence assay, and protein/mRNA expressions of ENaC located on tracheas, but also evaluated by the function of ENaC in mouse tracheal epithelial cells (MTECs). Besides, to explore the detailed mechanism about FA involved in LPS-induced tracheal injury, the content of cyclic guanosine monophosphate (cGMP) was measured, and Rp-cGMP (cGMP inhibitor) or cGMP-dependent protein kinase II (PKGII)-siRNA (siPKGII) were applied in primary MTECs, respectively.

Results
Histological examination results demonstrated that tracheal injury was obviously attenuated by pretreatment of FA. Meanwhile, FA could reverse LPS-induced reduction of both protein/mRNA expressions and ENaC activity. ELISA assay verified cGMP content was increased by FA, and administration of Rp-cGMP or transfection of siPKGII could reverse the FA up-regulated ENaC protein expression in MTECs.

Conclusions
Ferulic acid can attenuate LPS-induced tracheal injury through up-regulation of ENaC at least partially via the cGMP/PKGII pathway, which may provide a promising new direction for preventive and therapeutic strategy in tracheal injury.
Extracellular vesicles and pasteurized cells derived from Akkermansia muciniphila protect against high-fat induced obesity in mice
Authors: Ashrafian Fatemeh , Keshavarz Azizi Raftar Shahrbanoo , Lari Arezou , Shahryari Arefeh , Abdollahiyan Sara , Moradi Hamid Reza , Masoumi Morteza , Davari Mehdi , khatami Shohreh , Omrani Mir Davood , Vaziri Farzam , Masotti Andrea , Siadat Seyed Davar 
Published: December 2021

Abstract
Background
Several studies have shown that probiotics have beneficial effects on weight control and metabolic health. In addition to probiotics, recent studies have investigated the effects of paraprobiotics and postbiotics. Therefore, we evaluated the preventive effects of live and pasteurized Akkermansia muciniphila MucT (A. muciniphila) and its extracellular vesicles (EVs) on HFD-induced obesity.

Results
The results showed that body weight, metabolic tissues weight, food consumption, and plasma metabolic parameters were increased in the HFD group, whereas A. muciniphila preventive treatments inhibited these HFD. The effects of pasteurized A. muciniphila and its extracellular vesicles were more noticeable than its active form. The HFD led to an increase in the colonic, adipose tissue, and liver inflammations and increased the expression of genes involved in lipid metabolism and homeostasis. Nevertheless, these effects were inhibited in mice that were administered A. muciniphila and its EVs. The assessment of the gut microbiota revealed significant differences in the microbiota composition after feeding with HFD. However, all treatments restored the alterations in some bacterial genera and closely resemble the control group. Also, the correlation analysis indicated that some gut microbiota might be associated with obesity-related indices.

Conclusions
Pasteurized A. muciniphila and its EVs, as paraprobiotic and postbiotic agents, were found to play a key role in the regulation of metabolic functions to prevent obesity, probably by affecting the gut-adipose-liver axis.

Graphical Abstract
Silencing of the lncRNA H19 enhances sensitivity to X-ray and carbon-ions through the miR-130a-3p /WNK3 signaling axis in NSCLC cells
Authors: Zhao Xueshan , Jin Xiaodong , Zhang Qiuning , Liu Ruifeng , Luo Hongtao , Yang Zhen , Geng Yichao , Feng Shuangwu , Li Chengcheng , Wang Lina , Wang Xiaohu , Li Qiang 
Published: December 2021

Abstract
Background
The lncRNA H19 is believed to act as an oncogene in various types of tumors and is considered to be a therapeutic target and diagnostic marker. However, the role of the lncRNA H19 in regulating the radiosensitivity of non-small cell lung cancer (NSCLC) cells is unknown.

Methods
The expression profiles of lncRNAs in NSCLC were explored via transcriptome sequencing. CCK-8, EdU incorporation and clonogenic survival assays were conducted to evaluate the proliferation and radiosensitivity of NSCLC cells. Flow cytometry and Western blotting were conducted to measure the level of apoptosis. The binding relationship between the lncRNA H19 and miR-130a-3p was determined by a dual-luciferase reporter assay. A binding relationship was also identified between miR-130a-3p and With-No-Lysine Kinase 3 (WNK3).

Results
Expression patterns of lncRNAs revealed that the lncRNA H19 was upregulated in radioresistant NSCLC (A549-R11) cells compared with A549 cells. Knockdown of the lncRNA H19 enhanced the sensitivity of NSCLC cell lines to X-ray and carbon ion irradiation. Mechanistically, the lncRNA H19 serves as a sponge of miR-130a-3p, which downregulates WNK3 expression. The lncRNA H19–miR-130a-3p–WNK3 axis modulates radiosensitivity by regulating apoptosis in NSCLC cell lines.

Conclusion
Knockdown of the lncRNA H19 promotes the sensitivity of NSCLC cells to X-ray and carbon ion irradiation. Hence, the lncRNA H19 might function as a potential therapeutic target that enhances the antitumor effects of radiotherapy in NSCLC.
YTHDC1-mediated VPS25 regulates cell cycle by targeting JAK-STAT signaling in human glioma cells
Authors: Zhu Xiaolong , Yang Hui , Zhang Mengying , Wu Xingwei , Jiang Lan , Liu Xiaocen , Lv Kun 
Published: December 2021

AbstractBackgroundGlioma is a common type of malignant brain tumor with a high mortality and relapse rate. The endosomal sorting complex required for transport (ESCRT) has been reported to be involved in tumorigenesis. However, the molecular mechanisms have not been clarified.MethodsBioinformatics was used to screen the ESCRT subunits highly expressed in glioma tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The function of the ESCRT subunits in glioma cells was examined in vitro. Transcriptome sequencing analyzed the target genes and signaling pathways affected by the ESCRT subunit. Finally, the relationship between m6A (N6-methyladenosine) modification and high expression of the ESCRT subunit was studied.ResultsVPS25 was upregulated in glioma tissues, which was correlated with poor prognosis in glioma patients. Furthermore, VPS25 knockdown inhibited the proliferation, blocked the cell cycle, and promoted apoptosis in glioma cells. Meanwhile, VPS25 induced a G0/G1 phase arrest of the cell cycle in glioma cells by directly mediating p21, CDK2, and cyclin E expression, and JAK-signal transducer and activator of transcription (STAT) activation. Finally, YTHDC1 inhibited glioma proliferation by reducing the expression of VPS25.ConclusionThese results suggest that VPS25 is a promising prognostic indicator and a potential therapeutic target for glioma.
Expression profile of RNA binding protein in cervical cancer using bioinformatics approach
Authors: Huang Zhiyuan , Li Fang , Li Qinchuan 
Published: December 2021

Abstract
Background
It has been demonstrated by studies globally that RNA binding proteins (RBPs) took part in the development of cervical cancer (CC). Few studies concentrated on the correlation between RBPs and overall survival of CC patients. We retrieved significant DEGs (differently expressed genes, RNA binding proteins) correlated to the process of cervical cancer development.

Methods
Expressions level of genes in cervical cancer and normal tissue samples were obtained from GTEx and TCGA database. Differently expressed RNA binding proteins (DEGs) were retrieved by Wilcoxon sum-rank test. ClusterProfiler package worked in R software was used to perform GO and KEGG enrichment analyses. Univariate proportional hazard cox regression and multivariate proportional hazard cox regressions were applied to identify DEGs equipped with prognostic value and other clinical independent risk factors. ROC curve was drawn for comparing the survival predict feasibility of risk score with other risk factors in CC patients. Nomogram was drawn to exhibit the prediction model and validated by C-index and calibration curve. Correlations between differentially expressed RNA binding proteins (DEGs) and other clinical features were investigated by t test or Cruskal Wallis analysis. Correlation between Immune and DEGs in cervical cancer was investigated by ssGSEA.

Results
347 differentially expressed RBPs (DEGs) were retrieved from cervical cancer tissue and normal tissue samples. GO enrichment analysis showed that these DEGs involved in RNA splicing, catabolic process and metabolism. Cox regression model showed that there were ten DEGs significantly associated with overall survival of cervical cancer patients. WDR43 (HR = 0.423, P = 0.008), RBM38 (HR = 0.533, P < 0.001), RNASEH2A (HR = 0.474, P = 0.002) and HENMT1 (HR = 0.720, P = 0.071) played protective roles in survival among these ten genes. Stage (Stage IV vs Stage I HR = 3.434, P < 0.001) and risk score (HR = 1.214, P < 0.001) were sorted as independent prognostic risk factors based on multivariate cox regression. ROC curve validated that risk score was preferable to predict survival of CC patients than other risk factors. Additionally, we found some of these ten predictor DEGs were correlated significantly in statistic with tumor grade or stage, clinical T stage, clinical N stage, pathology or risk score (all P < 0.05). Part of immune cells and immune functions showed a lower activity in high risk group than low risk group which is stratified by median risk score.

Conclusion
Our discovery showed that many RNA binding proteins involved in the progress of cervical cancer, which could probably serve as prognostic biomarkers and accelerate the discovery of treatment targets for CC patients.
CCR9 initiates epithelial–mesenchymal transition by activating Wnt/β-catenin pathways to promote osteosarcoma metastasis
Authors: Kong Haoran , Yu Wenhui , Chen Zhuning , Li Haonan , Ye Guiwen , Hong Jiacong , Xie Zhongyu , Chen Keng , Wu Yanfeng , Shen Huiyong 
Published: December 2021

Abstract
Background
Osteosarcoma (OS) patients with lung metastasis have poor prognoses, and effective therapeutic strategies for delaying or inhibiting the spread of lung metastasis from the primary OS site are lacking. Hence, it is critical to elucidate the underlying mechanisms of OS metastasis and to identify additional new effective treatment strategies for patients.

Methods
Differential expression and functional analyses were performed to identify key genes and relevant signaling pathways associated with OS lung metastasis. The expression of CCR9 in OS cell lines and tissues was measured by RT-qPCR, western blotting and immunohistochemistry. Cell migration and invasion were assessed by wound healing and Transwell Matrigel invasion assays, respectively. The regulatory relationship between CCR9 and the Wnt/β-catenin signaling pathway was further evaluated by rescue experiments.

Results
The expression of CCR9 was elevated in OS cell lines and patients with lung metastasis. CCR9 promoted MG63 and HOS cell migration and invasion by activating the Wnt/β-catenin signaling pathway. Furthermore, knockdown of CCR9 repressed epithelial–mesenchymal transition (EMT) by downregulating mesenchymal markers (N-cadherin and Vimentin) and EMT-associated transcription factors (twist and snail) and upregulating an epithelial marker (E-cadherin).

Conclusions
Our findings suggest that CCR9 promotes EMT by activating Wnt/β-catenin pathways to promote OS metastasis. CCR9 may be a promising therapeutic target to inhibit lung metastasis and serve as a novel prognostic marker for OS.
The high methylation level of a novel 151-bp CpG island in the ESR1 gene promoter is associated with a poor breast cancer prognosis
Authors: Quintas-Granados Laura Itzel , Cortés Hernán , Carmen Manuel González-Del , Leyva-Gómez Gerardo , Bustamante-Montes Lilia Patricia , Rodríguez-Morales Miguel , Villegas-Vazquez Edgar Yebran , López-Reyes Israel , Alcaraz-Estrada Sofía Lizeth , Sandoval-Basilio Jorge , Soto-Reyes Ernesto , Sharifi-Rad Javad , Figueroa-González Gabriela , Reyes-Hernández Octavio Daniel 
Published: December 2021

Abstract
Background
The ESR1 gene suffers methylation changes in many types of cancers, including breast cancer (BC), the most frequently diagnosed cancer in women that is also present in men. Methylation at promoter A of ESR1 is the worse prognosis in terms of overall survival; thus, the early detection, prognostic, and prediction of therapy involve some methylation biomarkers.

Methods
Therefore, our study aimed to examine the methylation levels at the ESR1 gene in samples from Mexican BC patients and its possible association with menopausal status.

Results
We identified a novel 151-bp CpG island in the promoter A of the ESR1 gene. Interestingly, methylation levels at this CpG island in positive ERα tumors were approximately 50% less than negative ERα or control samples. Furthermore, methylation levels at ESR1 were associated with menopausal status. In postmenopausal patients, the methylation levels were 1.5-fold higher than in premenopausal patients. Finally, according to tumor malignancy, triple-negative cancer subtypes had higher ESR1 methylation levels than luminal/HER2+ or luminal A subtypes.

Conclusions
Our findings suggest that methylation at this novel CpG island might be a promising prognosis marker
Determinants of malaria testing at health facilities: the case of Uganda
Authors: Kigozi Ruth N. , Bwanika JohnBaptist , Goodwin Emily , Thomas Peter , Bukoma Patrick , Nabyonga Persis , Isabirye Fred , Oboth Paul , Kyozira Carol , Niang Mame , Belay Kassahun , Sebikaari Gloria , Tibenderana James K. , Gudoi Sam Siduda 
Published: December 2021

Abstract
Background
The World Health Organization (WHO) recommends prompt malaria diagnosis with either microscopy or malaria rapid diagnostic tests (RDTs) and treatment with an effective anti-malarial, as key interventions to control malaria. However, in sub-Saharan Africa, malaria diagnosis is still often influenced by clinical symptoms, with patients and care providers often interpreting all fevers as malaria. The Ministry of Health in Uganda defines suspected malaria cases as those with a fever. A target of conducting testing for at least 75% of those suspected to have malaria was established by the National Malaria Reduction Strategic Plan 2014–2020.

Methods
This study investigated factors that affect malaria testing at health facilities in Uganda using data collected in March/April 2017 in a cross-sectional survey of health facilities from the 52 districts that are supported by the US President’s Malaria Initiative (PMI). The study assessed health facility capacity to provide quality malaria care and treatment. Data were collected from all 1085 public and private health facilities in the 52 districts. Factors assessed included supportive supervision, availability of malaria management guidelines, laboratory infrastructure, and training health workers in the use of malaria rapid diagnostic test (RDT). Survey data were matched with routinely collected health facility malaria data obtained from the district health information system Version-2 (DHIS2). Associations between testing at least 75% of suspect malaria cases with several factors were examined using multivariate logistic regression.

Results
Key malaria commodities were widely available; 92% and 85% of the health facilities reported availability of RDTs and artemether–lumefantrine, respectively. Overall, 933 (86%) of the facilities tested over 75% of patients suspected to have malaria. Predictors of meeting the testing target were: supervision in the last 6 months (OR: 1.72, 95% CI 1.04–2.85) and a health facility having at least one health worker trained in the use of RDTs (OR: 1.62, 95% CI 1.04–2.55).

Conclusion
The study findings underscore the need for malaria control programmes to provide regular supportive supervision to health facilities and train health workers in the use of RDTs.
Engineered CRISPR-Cas systems for the detection and control of antibiotic-resistant infections
Authors: Wu Yuye , Battalapalli Dheerendranath , Hakeem Mohammed J. , Selamneni Venkatarao , Zhang Pengfei , Draz Mohamed S. , Ruan Zhi 
Published: December 2021

AbstractAntibiotic resistance is spreading rapidly around the world and seriously impeding efforts to control microbial infections. Although nucleic acid testing is widely deployed for the detection of antibiotic resistant bacteria, the current techniques—mainly based on polymerase chain reaction (PCR)—are time-consuming and laborious. There is an urgent need to develop new strategies to control bacterial infections and the spread of antimicrobial resistance (AMR). The CRISPR-Cas system is an adaptive immune system found in many prokaryotes that presents attractive opportunities to target and edit nucleic acids with high precision and reliability. Engineered CRISPR-Cas systems are reported to effectively kill bacteria or even revert bacterial resistance to antibiotics (resensitizing bacterial cells to antibiotics). Strategies for combating antimicrobial resistance using CRISPR (i.e., Cas9, Cas12, Cas13, and Cas14) can be of great significance in detecting bacteria and their resistance to antibiotics. This review discusses the structures, mechanisms, and detection methods of CRISPR-Cas systems and how these systems can be engineered for the rapid and reliable detection of bacteria using various approaches, with a particular focus on nanoparticles. In addition, we summarize the most recent advances in applying the CRISPR-Cas system for virulence modulation of bacterial infections and combating antimicrobial resistance.
Graphical Abstract
Ultrasound triggered topical delivery of Bmp7 mRNA for white fat browning induction via engineered smart exosomes
Authors: Guo Yitong , Wan Zhuo , Zhao Ping , Wei Mengying , Liu Yunnan , Bu Te , Sun Wenqi , Li Zhelong , Yuan Lijun 
Published: December 2021

Abstract
Background
Efficient and topical delivery of drugs is essential for maximized efficacy and minimized toxicity. In this study, we aimed to design an exosome-based drug delivery platform endowed with the ability of escaping from phagocytosis at non-target organs and controllably releasing drugs at targeted location.

Results
The swtichable stealth coat CP05-TK-mPEG was synthesized and anchored onto exosomes through the interaction between peptide CP05 and exosomal surface marker CD63. Chlorin e6 (Ce6) was loaded into exosomes by direct incubation. Controllable removal of PEG could be achieved by breaking thioketal (TK) through reactive oxygen species (ROS), which was produced by Ce6 under ultrasound irradiation. The whole platform was called SmartExo. The stealth effects were analyzed in RAW264.7 cells and C57BL/6 mice via tracing the exosomes. To confirm the efficacy of the engineered smart exosomes, Bone morphogenetic protein 7 (Bmp7) mRNA was encapsulated into exosomes by transfection of overexpressing plasmid, followed by stealth coating, with the exosomes designated as SmartExo@Bmp7. Therapeutic advantages of SmartExo@Bmp7 were proved by targeted delivering Bmp7 mRNA to omental adipose tissue (OAT) of obese C57BL/6 mice for browning induction. SmartExo platform was successfully constructed without changing the basic characteristics of exosomes. The engineered exosomes effectively escaped from the phagocytosis by RAW264.7 and non-target organs. In addition, the SmartExo could be uptaken locally on-demand by ultrasound mediated removal of the stealth coat. Compared with control exosomes, SmartExo@Bmp7 effectively delivered Bmp7 mRNA into OAT upon ultrasound irradiation, and induced OAT browning, as evidenced by the histology of OAT and increased expression of uncoupling protein 1 (Ucp1).

Conclusions
The proposed SmartExo-based delivery platform, which minimizes side effects and maximizing drug efficacy, offers a novel safe and efficient approach for targeted drug delivery. As a proof, the SmartExo@Bmp7 induced local white adipose tissue browning, and it would be a promising strategy for anti-obesity therapy.

Graphical Abstract