bluuebunny/crossref_metadata_2025_split huggingface dataset:
Putative Candidate Drug Targets for Sarcopenia-Related Traits Identified Through Mendelian Randomization Analysis of the Blood Proteome
Authors: Chen Bin-Bin , Wang Jia-Qi , Meng Xiang-He , Luo Zhe , Liu Xiao-Wen , Shen Hui , Xiao Hong-Mei , Deng Hong-Wen 
Published: July 2022

Purpose: The increasing prevalence of sarcopenia remains an ongoing challenge to health care systems worldwide. The lack of treatments encouraged the discovery of human proteomes to find potential therapeutic targets. As one of the major components of the human proteome, plasma proteins are functionally connected with various organs of the body to regulate biological processes and mediate overall homeostasis, which makes it crucial in various complex processes such as aging and chronic diseases. By performing a systematic causal analysis of the plasma proteome, we attempt to reveal the etiological mechanism and discover drug targets for sarcopenia.Methods: By using data from four genome-wide association studies for blood proteins and the UK Biobank data for sarcopenia-related traits, we applied two-sample Mendelian randomization (MR) analysis to evaluate 310 plasma proteins as possible causal mediators of sarcopenia-related traits: appendicular lean mass (ALM) and handgrip strength (right and left). Then we performed a two-sample bidirectional Mendelian randomization analysis for the identified putatively causal proteins to assess potential reverse causality that the trait values may influence protein levels. Finally, we performed phenome-wide MR analysis of the identified putatively causal proteins for 784 diseases to test the possible side effects of these proteins on other diseases.Results: Five plasma proteins were identified as putatively causal mediators of sarcopenia-related traits. Specifically, leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2), asporin (ASPN), and contactin-2 (CNTN2) had potential causal effects on appendicular lean mass, and ecto-ADP-ribosyltransferase 4 (ART4) and superoxide dismutase 2 (SOD2) had putative causal effects on the handgrip strength, respectively. None of the five putatively causal proteins had a reverse causality relationship with sarcopenia-related traits, and no side effects on other diseases were identified.Conclusion: We identified five plasma proteins that may serve as putatively potential novel drug targets for sarcopenia. Our study attested to the value of two-sample MR analysis in identifying and prioritizing putatively potential therapeutic targets for complex diseases.
Pyroptosis-Related Signature as Potential Biomarkers for Predicting Prognosis and Therapy Response in Colorectal Cancer Patients
Authors: Li Zhiyong , Liu Yang , Lin Baiqiang , Yan Wei , Yi Huijie , Wang Haoran , Wei Yunwei 
Published: July 2022

Background: Abnormal mucosal inflammation is a critical risk factor for pathogenesis and progression of colorectal cancer (CRC). As a type of proinflammatory death, pyroptosis can recast a suitable microenvironment to promote tumor growth. However, the potential role of pyroptosis in CRC remains unclear.Methods: A total of 38 pyroptosis-related gene (PRG) expression profiles and clinical information were collected from multiple public datasets. Bioinformatics methods were used to analyze the clinical significance, functional status, immune infiltration, genomic alteration, and drug sensitivity in different subgroups. Whole-genome microarray analysis was performed to analyze the regulation of gut microbiota on the expression of PRGs.Results: Two distinct molecular subtypes were identified and suggested that multilayer PRG alterations were associated with patient clinicopathological features, prognosis, and tumor microenvironment (TME) infiltrating characteristics. Furthermore, we obtained eight PRG signatures by applying differential expression analysis and univariate Cox and Lasso regression analyses. A risk prognosis model was constructed for predicting overall survival (OS) and recurrence-free survival (RFS) based on the PRG signature. There were significant differences in clinical characteristics, 22 immune cells, and immune functions between the high- and low-risk groups. In addition, the PRG signature was significantly associated with the microsatellite instability (MSI), tumor mutation burden (TMB), cancer stem cell (CSC) index, immunotherapeutic characteristics, and chemotherapeutic drug sensitivity. Moreover, the in vitro experiments had shown that Fusobacterium nucleatum (F.n) could affect the CASP6 expression, which was associated with the chemoresistance to 5-fluorouracil (5-Fu) in CRC.Conclusion: Our findings provided a foundation for future research targeting pyroptosis and a new insight into the prognosis and immune cell infiltration of CRC, and they suggested that F.n might influence CRC progression through pyroptosis.
A Pan-Cancer Analysis Reveals the Prognostic and Immunotherapeutic Value of Stanniocalcin-2 (STC2)
Authors: Jiang Zhong-Hui , Shen Xianfeng , Wei Yanhong , Chen Yongji , Chai Hongbo , Xia Lingyun , Leng Weidong 
Published: July 2022

Background: Stanniocalcin-2 (STC2) is a secreted glycoprotein which plays an important role in regulating the homeostasis of calcium, glucose homeostasis, and phosphorus metastasis. Accumulating evidence suggests that STC2 is implicated in cancer mechanisms. However, the effects of STC2 on cancer development and progression across pan-cancer are not yet completely known.Methods: Data were downloaded from The Cancer Genome Atlas database to obtain differentially expressed genes significantly associated with prognosis (key genes). A gene was selected for subsequent correlation studies by integrating the significance of prognosis and the time-dependent ROC curve. Gene expression of different tumor types was analyzed based on the UCSC XENA website. Furthermore, our study investigated the correlation of STC2 expression between prognosis, immune cell infiltration, immune checkpoint genes (ICGs), mismatch repair genes (MMRs), tumor mutation burden (TMB), microsatellite instability (MSI), and drug sensitivity in various malignant tumors. Gene set enrichment analysis (GSEA) was conducted for correlated genes of STC2 to explore potential mechanisms.Results: A total of 3,429 differentially expressed genes and 397 prognosis-related genes were identified from the TCGA database. Twenty-six key genes were found by crossing the former and the latter, and the highest risk gene, STC2, was selected for subsequent correlation studies. STC2 had good diagnostic performance for HNSCC, and was closely related to the survival status and clinicopathological stage of HNSCC patients. In pan-cancer analysis, STC2 was upregulated in 20 cancers and downregulated in seven cancers. STC2 overexpression was overall negatively correlated with overall survival, disease-free survival, disease-specific survival, and progress-free survival. STC2 was profoundly correlated with the tumor immune microenvironment, including immune cell infiltration, ICGs, MMRs, TMB, and MSI. Moreover, STC2 was significantly negatively correlated with the sensitivity or resistance of multiple drugs.Conclusion: STC2 was a potential prognostic biomarker for pan-cancer and a new immunotherapy target.
The association of MTHFR (rs1801133) with hypertension in an indigenous south African population
Authors: Mabhida Sihle E. , Sharma Jyoti R. , Apalata Teke , Masilela Charity , Nomatshila Sibusiso , Mabasa Lawrence , Fokkens Hannah , Benjeddou Mongi , Muhamed Babu , Shabalala Samukelisiwe , Johnson Rabia 
Published: July 2022

Aims: The current study sought to investigate the association between the methylenetetrahydrofolate reductase (MTHFR) variant (rs1801133) and the risk of developing hypertension (HTN) in an indigenous South African population.Methods: A total of 442 participants (hypertensive, n = 279 and non-hypertensive, n = 163) from the indigenous tribe residing in Mthatha, Eastern Cape (South Africa) were recruited. HTN was defined as a systolic (SBP) and diastolic blood pressure (DBP) of ≥130/80 mmHg following American Heart Association guidelines. The genotyping of MTHFR (rs1801133) was assessed using MassARRAY® System. Thereafter, the association between rs1801133 in various genetic models and HTN was determined by logistic regression model analysis. Furthermore, the interaction between rs1801133 and selected risk factors on HTN was performed using the open-source multifactor dimensionality reduction (MDR).Results: The low frequency of the T allele (5%) was also observed when compared with the C allele (95%) in both cases and controls. After adjusting for confounding factors (gender, smoking status, BMI, and blood glucose levels), there were no significant associations were observed between rs1801133 and the risk of HTN in all genetic models: genotypic (OR 0.75, 95% CI 0.29–1.95, p = 0.56), dominant (OR 0.86, 95% CI 0.35–2.16, p = 0.75), co-dominant (OR 1.33, 95% CI 0.51–3.48, p = 0.55) and allelic (OR 0.80, 95% CI 0.49–1.62, p = 0.70) in logistic regression analysis. However, a significant interaction was reported among rs1801133, age, and gender (p &lt; 0.0001) with the risk of HTN.Conclusion: The present study reports on the lack of association between MTHFR (rs1801133) and the risk of HTN in an indigenous South African tribe. However, an interaction between gender, age, and rs1801133 was observed. Thus, future studies with a large sample size are required to further validate these findings.
N7-methylguanosine-related lncRNAs: Predicting the prognosis and diagnosis of colorectal cancer in the cold and hot tumors
Authors: Wu Jing-Yu , Song Qing-Yu , Huang Chang-Zhi , Shao Yu , Wang Zhen-Ling , Zhang Hong-Qiang , Fu Zan 
Published: July 2022

Background: 7-Methylguanosine(m7G) contributes greatly to its pathogenesis and progression in colorectal cancer. We proposed building a prognostic model of m7G-related LncRNAs. Our prognostic model was used to identify differences between hot and cold tumors.Methods: The study included 647 colorectal cancer patients (51 cancer-free patients and 647 cancer patients) from The Cancer Genome Atlas (TCGA). We identified m7G-related prognostic lncRNAs by employing the univariate Cox regression method. Assessments were conducted using univariate Cox regression, multivariate Cox regression, receiver operating characteristics (ROC), nomogram, calibration curves, and Kaplan-Meier analysis. All of these procedures were used with the aim of confirming the validity and stability of the model. Besides these two analyses, we also conducted half-maximal inhibitory concentration (IC50), immune analysis, principal component analysis (PCA), and gene set enrichment analysis (GSEA). The entire set of m7G-related (lncRNAs) with respect to cold and hot tumors has been divided into two clusters for further discussion of immunotherapy.Results: The risk model was constructed with 17 m7G-related lncRNAs. A good correlation was found between the calibration plots and the prognosis prediction in the model. By assessing IC50 in a significant way across risk groups, systemic treatment can be guided. By using clusters, it may be possible to distinguish hot and cold tumors effectively and to aid in specific therapeutic interventions. Cluster 1 was identified as having the highest response to immunotherapy drugs and thus was identified as the hot tumor.Conclusion: This study shows that 17 m7G-related lncRNA can be used in clinical settings to predict prognosis and use them to determine whether a tumor is cold or hot in colorectal cancer and improve the individualization of treatment.
Local and Systemic Immunity Are Impaired in End-Stage-Renal-Disease Patients Treated With Hemodialysis, Peritoneal Dialysis and Kidney Transplant Recipients Immunized With BNT162b2 Pfizer-BioNTech SARS-CoV-2 Vaccine
Authors: Piotrowska Magdalena , Zieliński Maciej , Tylicki Leszek , Biedunkiewicz Bogdan , Kubanek Alicja , Ślizień Zuzanna , Polewska Karolina , Tylicki Piotr , Muchlado Marta , Sakowska Justyna , Renke Marcin , Sudoł Adam , Dąbrowska Małgorzata , Lichodziejewska-Niemierko Monika , Smiatacz Tomasz , Dębska-Ślizień Alicja , Trzonkowski Piotr 
Published: July 2022

Vaccination against COVID-19 in patients with end-stage renal disease (ESRD) on replacement therapy and kidney transplant recipients (KTRs) is particularly important due to the high mortality rate. Here, we tested the local and systemic immunity to the novel Pfizer BioNTech (BNT162b2) messenger RNA (mRNA) in ESRD, KTR patients, and healthy individuals (150 subjects). The ESRD group was divided into: hemodialysis (HD) and peritoneal dialysis (PD). We investigated the local and systemic immunity based on anti-N (nucleoprotein) and anti-S (spike1/2) Immunoglobulin A (IgA) and Immunoglobulin G (IgG) antibodies, respectively. Additionally, we performed an Interferon gamma (IFN-γ) release test Interferon-gamma release assay (IGRA) to monitor the cellular component of vaccine response. The control group had the highest level of anti-S IgG antibodies (153/2,080 binding antibody units (BAU)/ml) among all analyzed patients after the 1st and 2nd dose, respectively. The HD group (48/926 BAU/ml) had a diminished antibody level compared to PD (93/1,607 BAU/ml). Moreover, the seroconversion rate after the 1st dose was lower in HD than PD (56% vs. 86%). KTRs had extremely low seroconversion (33%). IgA-mediated immunity was the most effective in the control group, while other patients had diminished IgA production. We observed a lower percentage of vaccine responders based on the IFN-γ level in all research participants (100% vs. 85% in control, 100% vs. 80% in PD, 97% vs. 64% in HD). 63% of seropositive KTRs had a positive IGRA, while 28% of seronegative patients produced IFN-γ. Collectively, PD patients had the strongest response among ESRD patients. Two doses of the Pfizer vaccine are ineffective, especially in HD and KTRs. A closer investigation of ESRD and KTRs is required to set the COVID-19 vaccine clinical guidance.Clinical Trial Registration Numberwww.ClinicalTrials.gov, identifier: NCT04 905 862
Gene-Based Variant Analysis of Whole-Exome Sequencing in Relation to Eosinophil Count
Authors: Höglund Julia , Hadizadeh Fatemeh , Ek Weronica E. , Karlsson Torgny , Johansson Åsa 
Published: July 2022

Eosinophils play important roles in the release of cytokine mediators in response to inflammation. Many associations between common genetic variants and eosinophils have already been reported, using single nucleotide polymorphism (SNP) array data. Here, we have analyzed 200,000 whole-exome sequences (WES) from the UK Biobank cohort and performed gene-based analyses of eosinophil count. We defined five different variant weighting schemes to incorporate information on both deleteriousness and frequency. A total of 220 genes in 55 distinct (&gt;10 Mb apart) genomic regions were found to be associated with eosinophil count, of which seven genes (ALOX15, CSF2RB, IL17RA, IL33, JAK2, S1PR4, and SH2B3) are driven by rare variants, independent of common variants identified in genome-wide association studies. Two additional genes, NPAT and RMI1, have not been associated with eosinophil count before and are considered novel eosinophil loci. These results increase our knowledge about the effect of rare variants on eosinophil count, which can be of great value for further identification of therapeutic targets.
Efficacy and Safety of Curcumin and Curcuma longa Extract in the Treatment of Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trial
Authors: Zeng Liuting , Yang Tiejun , Yang Kailin , Yu Ganpeng , Li Jun , Xiang Wang , Chen Hua 
Published: July 2022

BackgroundModern pharmacological research found that the chemical components of Curcuma longa L. are mainly curcumin and turmeric volatile oil. Several recent randomized controlled trials (RCT) have shown that curcumin improves symptoms and inflammation in patients with arthritis.MethodsPubmed, Cochran Library, CNKI, and other databases were searched to collect the randomized controlled trials (RCTs). Then, the risk of bias of RCTs were assessed and data of RCTs were extracted. Finally, RevMan 5.3 was utilized for meta-analysis.ResultsTwenty-nine (29) RCTs involving 2396 participants and 5 types of arthritis were included. The arthritis included Ankylosing Spondylitis (AS), Rheumatoid Arthritis (RA), Osteoarthritis (OA), Juvenile idiopathic arthritis (JIA) and gout/hyperuricemia. Curcumin and Curcuma longa Extract were administered in doses ranging from 120 mg to 1500 mg for a duration of 4-36 weeks. In general, Curcumin and Curcuma longa Extract showed safety in all studies and improved the severity of inflammation and pain levels in these arthritis patients. However, more RCTs are needed in the future to elucidate the effect of Curcumin and Curcuma longa Extract supplementation in patients with arthritis, including RA, OA, AS and JIA.ConclusionCurcumin and Curcuma longa Extract may improve symptoms and inflammation levels in people with arthritis. However, due to the low quality and small quantity of RCTs, the conclusions need to be interpreted carefully.
Nano-silica particles synergistically IgE-mediated mast cell activation exacerbating allergic inflammation in mice
Authors: Yang Yong-Shi , Cao Meng-Da , Wang An , Liu Qing-Mei , Zhu Dan-Xuan , Zou Ying , Ma Ling-Ling , Luo Min , Shao Yang , Xu Dian-Dou , Wei Ji-Fu , Sun Jin-Lyu 
Published: July 2022

BackgroundAllergic respiratory diseases have increased dramatically due to air pollution over the past few decades. However, studies are limited on the effects of inorganic components and particulate matter with different particle sizes in smog on allergic diseases, and the possible molecular mechanism of inducing allergies has not been thoroughly studied.MethodsFour common mineral elements with different particle sizes in smog particles were selected, including Al2O3, TiO2, Fe2O3, and SiO2. We studied the relationship and molecular mechanism of smog particle composition, particle size, and allergic reactions using mast cells, immunoglobulin E (IgE)-mediated passive cutaneous anaphylaxis (PCA) model, and an ovalbumin (OVA)-induced asthmatic mouse model in vitro and in vivo, combined with transmission electron microscopy, scanning transmission X-ray microscopy analysis, and transcriptome sequencing.ResultsOnly 20 nm SiO2 particles significantly increased β-hexosaminidase release, based on dinitrophenol (DNP)-human serum albumin (HSA) stimulation, from IgE-sensitized mast cells, while other particles did not. Meanwhile, the PCA model showed that Evan’s blue extravasation in mice was increased after treatment with nano-SiO2 particles. Nano-SiO2 particles exposure in the asthmatic mouse model caused an enhancement of allergic airway inflammation as manifested by OVA-specific serum IgE, airway hyperresponsiveness, lung inflammation injury, mucous cell metaplasia, cytokine expression, mast cell activation, and histamine secretion, which were significantly increased. Nano-SiO2 particles exposure did not affect the expression of FcϵRI or the ability of mast cells to bind IgE but synergistically activated mast cells by enhancing the mitogen-activated protein kinase (MAPK) signaling pathway, especially the phosphorylation levels of the extracellular signal-regulated kinase (ERK)1/2. The ERK inhibitors showed a significant inhibitory effect in reducing β-hexosaminidase release.ConclusionOur results indicated that nano-SiO2 particles stimulation might synergistically activate IgE-sensitized mast cells by enhancing the MAPK signaling pathway and that nano-SiO2 particles exposure could exacerbate allergic inflammation. Our experimental results provide useful information for preventing and treating allergic diseases.
Comparative Analysis of Mutation Status and Immune Landscape for Squamous Cell Carcinomas at Different Anatomical sites
Authors: Ti Wenqi , Wei Tianhui , Wang Jianbo , Cheng Yufeng 
Published: July 2022

ObjectiveIt has been controversial whether tumor mutation burden (TMB) affects the prognosis and the efficacy of immunotherapy in different tumor types. We provided a comprehensive analysis of mutation status and immune landscape of squamous cell carcinomas (SCCs) from four sites in order to investigate the relationship of TMB with prognosis and immune cell infiltration in different SCCs.MethodsThe transcriptome profiles and somatic mutation data of SCCs downloaded from the Cancer Genome Atlas (the Cancer Genome Atlas) database were analyzed and visualized. Then, TMB was calculated to analyze its correlations with prognosis and clinical features. Differentially expressed genes (DEGs) between the high and low TMB groups were screened for functional enrichment analysis. CIBERSORT algorithm was used to compare differences of immune cell infiltration between two groups in different SCCs. In addition, immune DEGs associated with prognosis were identified and risk prediction model was constructed via Cox regression analysis.ResultsMissense mutation was the most dominant mutation type in SCCs. The difference was that the top10 mutated genes varied widely among different SCCs. High TMB group had better prognosis in lung squamous cell carcinoma (LUSC) and cervical squamous cell carcinoma (CESC), while the result was reverse in head and neck squamous cell carcinoma (HNSCC) and esophageal squamous cell carcinoma (ESCC). In addition, patients with older age, smoking history, earlier pathological stage and no lymphatic invasion had higher TMB. The identified DEGs were mainly enriched in the regulation of immune system, muscular system and the activity of epidermal cells. The proportions of CD8+T cells, CD4+ memory T cells, follicular helper T cells, macrophages were distinct between two groups. The prognosis-related hub genes (CHGB, INHBA, LCN1 and VEGFC) screened were associated with poor prognosis.ConclusionThis study reveals the mutation status and immune cell infiltration of SCCs at different anatomical sites. TMB is closely related to the prognosis of SCCs, and its effects on prognosis are diverse in different SCCs, which might result from the situation of immune cell infiltration. These findings contribute to the exploration of biomarkers for predicting the efficacy of immunotherapy in SCCs and providing innovative insights for accurate application of immunotherapy.