bluuebunny/crossref_metadata_2025 huggingface dataset:
MIR100HG Regulates CALD1 Gene Expression by Targeting miR-142-5p to Affect the Progression of Bladder Cancer Cells in vitro, as Revealed by Transcriptome Sequencing
Authors: Zhang Sheng , Wang Qin , Li Wenfeng , Chen Jinzhong
Published: January 2022

Background/Aim: The role of long non-coding RNA (lncRNA) and competing endogenous RNAs (ceRNA) networks in bladder cancer, especially the function of lncRNA-miRNA-mRNA regulatory network in bladder cancer, are still relatively poorly understood. This research mainly used transcriptome sequencing to screen key lncRNAs and ceRNAs, explore their pathogenic mechanism in bladder cancer, and search for potential diagnostic and therapeutic targets.

Methods: High-throughput transcriptome sequencing, combined with the limma package, Kaplan-Meier curve analysis, lncRNA-mRNA coexpression network, univariate Cox analysis, multivariate Cox analysis, protein-protein interaction (PPI), functional enrichment, weighed gene co-expression network analysis (WGCNA), ceRNA network and quantitative PCR (qPCR) analyses were performed to assess and screen differentially expressed lncRNAs and mRNAs. Then, the effects of MIR100HG on the proliferation, migration and invasion of the bladder cancer cell line 5,637 were evaluated using cell counting kit-8(CCK-8), wound-healing and transwell assays, respectively. A dual luciferase reporter assay was used to validate the MIR100HG/miR-142-5p and miR-142-5p/CALD1 targeting relationship, and the regulatory relationship among MIR100HG/miR-142-5p/CALD1 expression was explored using qPCR and western blot.

Results: A total of 127 differentially expressed lncRNAs and 620 differentially expressed mRNAs were screened. Based on the survival prognosis analysis, Cox analysis, lncRNA-mRNA network, PPI network and WGCNA, we obtained 3 key lncRNAs and 13 key mRNAs, as well as the MIR100HG/miR-142-5p/CALD1 key regulatory axis. qPCR results showed that compared with the adjacent tissues, the expression of MIR100HG and CALD1 was up-regulated, and the expression of miR-142-5p was down-regulated. Moreover, MIR100HG expression was positively correlated with the tumor grade and clinical grade of patients with bladder cancer. Overexpression of MIR100HG effectively promoted the proliferation, migration and invasion of 5,637 cells, inhibited the expression of miR-142-5p, and induced the expression of CALD1 in 5,637 cells. In addition, miR-142-5p inhibited CALD1 expression in bladder cancer cells through a direct association, and reversed the proliferation and CALD1 expression in 5,637 cells overexpressing of MIR100HG.

Conclusion: MIR100HG regulates CALD1 expression by targeting miR-142-5p to inhibit the proliferation, migration and invasion of bladder cancer cells. MIR100HG is an independent prognostic factor for bladder cancer, with potential as a biomarker for the diagnosis and treatment of bladder cancer.
Episodic Memory Impairment Mediates the Loss of Awareness in Mild Cognitive Impairment
Authors: Gagliardi Geoffroy , Vannini Patrizia
Published: January 2022

Introduction

Loss of awareness is a common symptom in Alzheimer's Disease (AD) and responsible for a significant loss of functional abilities. The mechanisms underlying loss of awareness in AD is unknown, although previous findings have implicated dysfunction of primary executive functioning (EF) or episodic memory (EM) to be the cause. Therefore, our main study objective was to explore the involvement of EF and EM dysfunction in amyloid-related loss of awareness across the clinical spectrum of AD.

Methods

A total of 895 participants (362 clinically normal [CN], 422 people with mild cognitive impairment [MCI] and 111 with dementia) from the Alzheimer's Disease Neuroimaging Initiative were used for the analyses. A sub-analysis was performed in 202 participants who progressed in their clinical diagnosis from CN to MCI or MCI to dementia as well as dementia patients. Mediation models were used in each clinical group with awareness (assessed with the Everyday Cognitive function questionnaire) as a dependent variable to determine whether EF and/or EM would mediate the effect of amyloid on awareness. We also ran these analyses with subjective and informant complaints as dependent variables. Direct correlations between all variables were also performed.

Results

We found evidence for a decline in awareness across the groups, with increased awareness observed in the CN group and decreased awareness observed in the MCI and dementia groups. Our results showed that EM, and not EF, partially mediated the relationship between amyloid and awareness such that greater amyloid and lower EM performance was associated with lower awareness. When analyzing each group separately, this finding was only observed in the MCI group and in the group containing progressors and dementia patients. When repeating the analyses for subjective and informant complaints separately, the results were replicated only for the informant's complaints.

Discussion

Our results demonstrate that decline in EM and, to a lesser degree, EF, mediate the effect of amyloid on awareness. In line with previous studies demonstrating the development of anosognosia in the prodromal stage, our findings suggest that decreased awareness is the result of an inability for the participant to update his/her insight into his/her cognitive performance (i.e., demonstrating a petrified self).
α9-Containing Nicotinic Receptors in Cancer
Authors: Pucci Susanna , Zoli Michele , Clementi Francesco , Gotti Cecilia
Published: January 2022

Neuronal nicotinic acetylcholine receptors containing the α9 or the α9 and α10 subunits are expressed in various extra-neuronal tissues. Moreover, most cancer cells and tissues highly express α9-containing receptors, and a number of studies have shown that they are powerful regulators of responses that stimulate cancer processes such as proliferation, inhibition of apoptosis, and metastasis. It has also emerged that their modulation is a promising target for drug development. The aim of this review is to summarize recent data showing the involvement of these receptors in controlling the downstream signaling cascades involved in the promotion of cancer.
Prognosis and Predictors of Symptomatic Intracranial Hemorrhage After Endovascular Treatment of Large Vessel Occlusion Stroke
Authors: Shen Huixin , Ma Qingfeng , Jiao Liqun , Chen Fei , Xue Sufang , Li Jingya , Li Zhengping , Song Haiqing , Huang Xiaoqin
Published: January 2022

Background

Symptomatic intracranial hemorrhage (sICH) is a devastating complication of endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) and is associated with high risk of disability and mortality. This study intended to evaluate the predictors of sICH after EVT in patients with large vessel occlusion (LVO)-induced AIS.

Methods

We conducted a retrospective review on consecutive AIS patients who underwent EVT in our University hospital between January 2019 and August 2020. The patients were classified into two groups based upon the occurrence of sICH. The main outcomes were the occurrence of sICH using the Heidelberg Bleeding Classification and functional condition at 90 days. Multivariate logistic regression analysis and receiver operating characteristics (ROC) curves were used to identify independent predictors of sICH after EVT.

Results

Three hundred and 69 patients were enrolled in the study, of which 16.8% (n = 62) developed sICH. Favorable neurological outcome was lower in patients with sICH than in patients without sICH (6.5 vs. 43.3%; P < 0.001), with the overall mortality being 112 (30.4%) at 90 days post- EVT. Results from univariate analysis showed significant differences between the two groups in the prevalence of diabetes, initial Alberta Stroke Program Early CT Score (ASPECTS) score, National Institutes of Health Stroke Scale (NIHSS) score after operation, the levels of fasting blood glucose (FBG), neutrophil to lymphocyte ratio (NLR), platelets (PLT), and thrombin time (TT) at admission. Multivariate logistic regression analysis showed that FBG ≥ 7.54 mmol/L (OR: 2.765; 95% confidence interval [CI]: 1.513–5.054), NLR ≥ 5.48 (OR: 2.711; 95% CI: 1.433–5.128), TT at admission ≥ 16.25 s (OR: 2.022; 95% CI: 1.115–3.667), and NIHSS score within 24 h after the operation ≥ 10 (OR: 3.728; 95% CI: 1.516–9.170) were independent predictors of sICH. The combination of NLR ≥ 5.48, FBG ≥ 7.54 mmol/L, TT at admission ≥ 16.25 s, and NIHSS score within 24 h after the operation ≥ 10 generated an optimal prediction model (AUC: 0.723).

Conclusion

Higher levels of FDG, NLR, TT at admission, and NIHSS score after operation were associated with sICH after EVT in patients with LVO-induced AIS.
Emotional Recognition in Patients With Mesial Temporal Epilepsy Associated With Enlarged Amygdala
Authors: Kuchukhidze Giorgi , Unterberger Iris , Schmid Elisabeth , Zamarian Laura , Siedentopf Christian Michael , Koppelstaetter Florian , Gizewski Elke , Kronbichler Martin , Luef Gerhard , Jokeit Hennric , Trinka Eugen
Published: January 2022

Background:

Amygdalae play a central role in emotional processing by interconnecting frontal cortex and other brain structures. Unilateral amygdala enlargement (AE) is associated with mesial temporal lobe epilepsy (mTLE). In a relatively large sample of patients with mTLE and AE, we aimed to evaluate functional integration of AE in emotion processing and to determine possible associations between fMRI activation patterns in amygdala and deficits in emotion recognition as assessed by neuropsychological testing.

Methods:

Twenty-two patients with drug resistant unilateral mTLE due to ipsilateral AE were prospectively recruited in a large epilepsy unit and compared with 17 healthy control subjects in terms of amygdala volume, fMRI activation patterns and performance in emotion recognition as assessed by comprehensive affect testing system (CATS) and Ekman faces. All patients underwent structural and functional 1.5 Tesla MRI, electro-clinical assessment and neuropsychological testing.

Results:

We observed BOLD signal ipsilateral to AE (n = 7; group PAT1); contralateral to AE (n = 6; group PAT2) and no activation (n = 9; group PAT3). In the region of interest (ROI) analysis, beta estimates for fearful face > landscape contrast in the left amygdala region did not differ significantly in patients with left TLE vs. patients with right TLE [T(16) = −1.481; p = 0.158]. However, beta estimates for fearful face > landscape contrast in the right amygdala region were significantly reduced in patients with right TLE vs. patients with left TLE [T(16) = −2,922; p = 0.010]. Patients showed significantly lower total scores in CATS and Ekman faces compared to healthy controls.

Conclusion:

In our cohort, patients with unilateral mesial TLE and ipsilateral AE, an amygdala could display either functional integration in emotion recognition or dysfunction as demonstrated by fMRI. Perception and recognition of emotions were impaired more in right-sided mTLE as compared to left-sided mTLE. Neuropsychological tests showed deficits in emotion recognition in patients as compared to healthy controls.
Cutaneous Allodynia in Migraine: A Narrative Review
Authors: Mínguez-Olaondo Ane , Quintas Sonia , Morollón Sánchez-Mateos Noemí , López-Bravo Alba , Vila-Pueyo Marta , Grozeva Vesselina , Belvís Robert , Santos-Lasaosa Sonia , Irimia Pablo
Published: January 2022

Objective

In the present work, we conduct a narrative review of the most relevant literature on cutaneous allodynia (CA) in migraine.

Background

CA is regarded as the perception of pain in response to non-noxious skin stimulation. The number of research studies relating to CA and migraine has increased strikingly over the last few decades. Therefore, the clinician treating migraine patients must recognize this common symptom and have up-to-date knowledge of its importance from the pathophysiological, diagnostic, prognostic and therapeutic point of view.

Methods

We performed a comprehensive narrative review to analyze existing literature regarding CA in migraine, with a special focus on epidemiology, pathophysiology, assessment methods, risk for chronification, diagnosis and management. PubMed and the Cochrane databases were used for the literature search.

Results

The prevalence of CA in patients with migraine is approximately 60%. The mechanisms underlying CA in migraine are not completely clarified but include a sensitization phenomenon at different levels of the trigemino-talamo-cortical nociceptive pathway and dysfunction of brainstem and cortical areas that modulate thalamocortical inputs. The gold standard for the assessment of CA is quantitative sensory testing (QST), but the validated Allodynia 12-item questionnaire is preferred in clinical setting. The presence of CA is associated with an increased risk of migraine chronification and has therapeutic implications.

Conclusions

CA is a marker of central sensitization in patients with migraine that has been associated with an increased risk of chronification and may influence therapeutic decisions.
A Brief Overview of the Cerebrospinal Fluid System and Its Implications for Brain and Spinal Cord Diseases
Authors: Wichmann Thea Overgaard , Damkier Helle Hasager , Pedersen Michael
Published: January 2022

A comprehensive understanding of the cerebrospinal fluid (CSF) system is essential for our understanding of health and disease within the central nervous system (CNS). The system of CSF refers to all components involved in CSF production, movement, and absorption. In recent years, extensive research has resulted in vastly improved understanding of the CSF system in health and disease. Yet, several aspects remain to be fully clarified, notably along the spinal cord as the preponderance of research has focused on the brain. This review briefly summarizes the CSF system and its implications for CNS diseases and highlights the knowledge gaps that require further research.
Association of Epigenetic Differences Screened in a Few Cases of Monozygotic Twins Discordant for Attention-Deficit Hyperactivity Disorder With Brain Structures
Authors: Fujisawa Takashi X. , Nishitani Shota , Makita Kai , Yao Akiko , Takiguchi Shinichiro , Hamamura Shoko , Shimada Koji , Okazawa Hidehiko , Matsuzaki Hideo , Tomoda Akemi
Published: January 2022

The present study examined the relationship between DNA methylation differences and variations in brain structures involved in the development of attention-deficit hyperactivity disorder (ADHD). First, we used monozygotic (MZ) twins discordant (2 pairs of 4 individuals, 2 boys, mean age 12.5 years) for ADHD to identify candidate DNA methylation sites involved in the development of ADHD. Next, we tried to replicate these candidates in a case-control study (ADHD: N = 18, 15 boys, mean age 10.0 years; Controls: N = 62, 40 boys, mean age 13.9 years). Finally, we examined how methylation rates at those sites relate to the degree of local structural alterations where significant differences were observed between cases and controls. As a result, we identified 61 candidate DNA methylation sites involved in ADHD development in two pairs of discordant MZ twins, among which elevated methylation at a site in the sortilin-related Vps10p domain containing receptor 2 (SorCS2) gene was replicated in the case-control study. We also observed that the ADHD group had significantly reduced gray matter volume (GMV) in the precentral and posterior orbital gyri compared to the control group and that this volume reduction was positively associated with SorCS2 methylation. Furthermore, the reduced GMV regions in children with ADHD are involved in language processing and emotional control, while SorCS2 methylation is also negatively associated with emotional behavioral problems in children. These results indicate that SorCS2 methylation might mediate a reduced GMV in the precentral and posterior orbital gyri and therefore influence the pathology of children with ADHD.
Anxiety and Depression Assessments in a Mouse Model of Congenital Blindness
Authors: Bouguiyoud Nouhaila , Roullet Florence , Bronchti Gilles , Frasnelli Johannes , Al Aïn Syrina
Published: January 2022

Previous studies have reported that visual impairment can affect the quality of life leading to mental health disorders. This study aimed to investigate associations between vision impairment, depression and anxiety using a mouse model of congenital blindness. We phenotyped 15 anophthalmic and 17 sighted adult mice in a battery of tests for anxiety and depression-like behaviors: open field test, elevated plus maze, coated test, splash test, and forced swim test. We found that: (1) Anxiety levels of the anophthalmic mice were significantly lower when compared with sighted mice, (2) Anophthalmic mice displayed more exploratory behaviors in a new environment than the sighted one, and (3) Depression levels between those groups were similar. In conclusion, this behavioral study showed that early visual deprivation lowers anxiety levels, associated with heightened exploratory activity, but does not induce depressive symptoms in a mouse model of congenital blindness, underlying several behavioral adaptations.
Radiomics and Qualitative Features From Multiparametric MRI Predict Molecular Subtypes in Patients With Lower-Grade Glioma
Authors: Sun Chen , Fan Liyuan , Wang Wenqing , Wang Weiwei , Liu Lei , Duan Wenchao , Pei Dongling , Zhan Yunbo , Zhao Haibiao , Sun Tao , Liu Zhen , Hong Xuanke , Wang Xiangxiang , Guo Yu , Li Wencai , Cheng Jingliang , Li Zhicheng , Liu Xianzhi , Zhang Zhenyu , Yan Jing
Published: January 2022

Background

Isocitrate dehydrogenase (IDH) mutation and 1p19q codeletion status have been identified as significant markers for therapy and prognosis in lower-grade glioma (LGG). The current study aimed to construct a combined machine learning-based model for predicting the molecular subtypes of LGG, including (1) IDH wild-type astrocytoma (IDHwt), (2) IDH mutant and 1p19q non-codeleted astrocytoma (IDHmut-noncodel), and (3) IDH-mutant and 1p19q codeleted oligodendroglioma (IDHmut-codel), based on multiparametric magnetic resonance imaging (MRI) radiomics, qualitative features, and clinical factors.

Methods

A total of 335 patients with LGG (WHO grade II/III) were retrospectively enrolled. The sum of 5,929 radiomics features were extracted from multiparametric MRI. Selected robust, non-redundant, and relevant features were used to construct a random forest model based on a training cohort (n = 269) and evaluated on a testing cohort (n = 66). Meanwhile, preoperative MRIs of all patients were scored in accordance with Visually Accessible Rembrandt Images (VASARI) annotations and T2-fluid attenuated inversion recovery (T2-FLAIR) mismatch sign. By combining radiomics features, qualitative features (VASARI annotations and T2-FLAIR mismatch signs), and clinical factors, a combined prediction model for the molecular subtypes of LGG was built.

Results

The 17-feature radiomics model achieved area under the curve (AUC) values of 0.6557, 0.6830, and 0.7579 for IDHwt, IDHmut-noncodel, and IDHmut-codel, respectively, in the testing cohort. Incorporating qualitative features and clinical factors into the radiomics model resulted in improved AUCs of 0.8623, 0.8056, and 0.8036 for IDHwt, IDHmut-noncodel, and IDHmut-codel, with balanced accuracies of 0.8924, 0.8066, and 0.8095, respectively.

Conclusion

The combined machine learning algorithm can provide a method to non-invasively predict the molecular subtypes of LGG preoperatively with excellent predictive performance.
Comprehensive Analysis of Immune-Related Prognosis of TK1 in Hepatocellular Carcinoma
Authors: Cai Qun , Zhu Mingyan , Duan Jinnan , Wang Hao , Chen Jingdan , Xiao Yixin , Wang Yangqin , Wang Jianfang , Yu Xuewen , Yang Hui
Published: January 2022

Increased expression of TK1 is associated with the progression of a variety of tumors. However, the relationship of TK1 expression with immune cell infiltration and its prognostic value in hepatocellular carcinoma (HCC) are still unknown. In this study the TCGA database was used to evaluate TK1 expression and its impact on survival in patients with HCC. Compared with normal tissue, TK1 in the liver tissue of patients with HCC was significantly up-regulated at both the mRNA and protein levels. Furthermore, TK1 expression was significantly related to pathological stage, tumor stage and lymph node metastasis, with high TK1 expression being an unfavorable prognostic factor for HCC. TK1 expression was also significantly associated with the infiltration of B cells, T cells, and dendritic cells in HCC. Single-cell sequencing analysis revealed that TK1 was associated with relatively large changes in T cells, especially gamma-delta T cells. A prognostic risk score based on TK1-related immune genes (CD40LG and TNFRSF4) was established using COX regression analysis. By integrating the immune-related risk score model with clinical features, a nomogram was constructed to predict the survival rate of HCC patients (1 year, 3-year and 5-year AUC of 0.782, 0.783 and 0.771, respectively). Knockdown of the target gene for TK1 was found to have significant anti-apoptosis and pro-proliferation effects on HepG2 cells. The level of TK1 in the serum and liver tissue of patients with HCC was significantly increased relative to healthy controls. These findings highlight the role of TK1 in the tumor immune response of HCC patients and in the proliferation and apoptosis of HepG2 cells. TK1 could therefore be a potential immunotherapy target for HCC patients, while the two immune genes related to TK1 (CD40LG And TNFRSF4) may be promising prognostic biomarkers in HCC.
Ceramide Composition in Exosomes for Characterization of Glioblastoma Stem-Like Cell Phenotypes
Authors: Melero-Fernandez de Mera Raquel M. , Villaseñor Alma , Rojo David , Carrión-Navarro Josefa , Gradillas Ana , Ayuso-Sacido Angel , Barbas Coral
Published: January 2022

Glioblastoma (GBM) is one of the most malignant central nervous system tumor types. Comparative analysis of GBM tissues has rendered four major molecular subtypes. From them, two molecular subtypes are mainly found in their glioblastoma cancer stem-like cells (GSCs) derived in vitro: proneural (PN) and mesenchymal (MES) with nodular (MES-N) and semi-nodular (MES-SN) disseminations, which exhibit different metabolic, growth, and malignancy properties. Many studies suggest that cancer cells communicate between them, and the surrounding microenvironment, via exosomes. Identifying molecular markers that allow the specific isolation of GSC-derived exosomes is key in the development of new therapies. However, the differential exosome composition produced by main GSCs remains unknown. The aim of this study was to determine ceramide (Cer) composition, one of the critical lipids in both cells and their cell-derived exosomes, from the main three GSC phenotypes using mass spectrometry-based lipidomics. GSCs from human tissue samples and their cell-derived exosomes were measured using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS) in an untargeted analysis. Complete characterization of the ceramide profile, in both cells and cell-derived exosomes from GSC phenotypes, showed differential distributions among them. Results indicate that such differences of ceramide are chain-length dependent. Significant changes for the C16 Cer and C24:1 Cer and their ratio were observed among GSC phenotypes, being different for cells and their cell-derived exosomes.
The Role of Circulating Biomarkers in Lung Cancer
Authors: Herath Sayuri , Sadeghi Rad Habib , Radfar Payar , Ladwa Rahul , Warkiani Majid , O’Byrne Ken , Kulasinghe Arutha
Published: January 2022

Lung cancer is the leading cause of cancer morbidity and mortality worldwide and early diagnosis is crucial for the management and treatment of this disease. Non-invasive means of determining tumour information is an appealing diagnostic approach for lung cancers as often accessing and removing tumour tissue can be a limiting factor. In recent years, liquid biopsies have been developed to explore potential circulating tumour biomarkers which are considered reliable surrogates for understanding tumour biology in a non-invasive manner. Most common components assessed in liquid biopsy include circulating tumour cells (CTCs), cell-free DNA (cfDNA), circulating tumour DNA (ctDNA), microRNA and exosomes. This review explores the clinical use of circulating tumour biomarkers found in liquid biopsy for screening, early diagnosis and prognostication of lung cancer patients.
A CTCF-Binding Element and Histone Deacetylation Cooperatively Maintain Chromatin Loops, Linking to Long-Range Gene Regulation in Cancer Genomes
Authors: Tang Ran , Li Yiqun , Han Fang , Li Zhenzhi , Lin Xiaoyu , Sun Haoxiu , Zhang Xiaoqing , Jiang Qinghua , Nie Huan , Li Yu
Published: January 2022

Background

Genes spanning long chromosomal domains are coordinately regulated in human genome, which contribute to global gene dysregulation and carcinogenesis in cancer. It has been noticed that epigenetic modification and chromatin architecture may participate in the regulation process. However, the regulation patterns and functional elements of long-range gene regulation are unclear.

Methods

Based on the clinical transcriptome data from different tumor sets, a novel expressional correlation analysis pipeline was performed to classify the co-regulated regions and subsets of intercorrelated regions. The GLAM2 program was used to predict conserved DNA elements that enriched in regions. Two conserved elements were selected to delete in Ishikawa and HeLa cells by CRISPR-Cas9. SAHA treatment and HDAC knockdown were used to change the histone acetylation status. Using qPCR, MTT, and scratch healing assay, we evaluate the effect on gene expression and cancer cell phenotype. By DNA pull-down and ChIP, the element-binding proteins were testified. 3C and 3D-FISH were performed to depict the alteration in chromatin architecture.

Results

In multiple cancer genomes, we classified subsets of coordinately regulated regions (sub-CRRs) that possibly shared the same regulatory mechanisms and exhibited similar expression patterns. A new conserved DNA element (CRE30) was enriched in sub-CRRs and associated with cancer patient survival. CRE30 could restrict gene regulation in sub-CRRs and affect cancer cell phenotypes. DNA pull-down showed that multiple proteins including CTCF were recruited on the CRE30 locus, and ChIP assay confirmed the CTCF-binding signals. Subsequent results uncovered that as an essential element, CRE30 maintained chromatin loops and mediated a compact chromatin architecture. Moreover, we found that blocking global histone deacetylation induced chromatin loop disruption and CTCF dropping in the region containing CRE30, linked to promoted gene regulation. Additionally, similar effects were observed with CRE30 deletion in another locus of chromosome 8.

Conclusions

Our research clarified a new functional element that recruits CTCF and collaborates with histone deacetylation to maintain high-order chromatin organizations, linking to long-range gene regulation in cancer genomes. The findings highlight a close relationship among conserved DNA element, epigenetic modification, and chromatin architecture in long-range gene regulation process.
A Magnetic Resonance Imaging-Based Radiomic Model for the Noninvasive Preoperative Differentiation Between Transitional and Atypical Meningiomas
Authors: Zhang Jing , Zhang Guojin , Cao Yuntai , Ren Jialiang , Zhao Zhiyong , Han Tao , Chen Kuntao , Zhou Junlin
Published: January 2022

Preoperative distinction between transitional meningioma and atypical meningioma would aid the selection of appropriate surgical techniques, as well as the prognosis prediction. Here, we aimed to differentiate between these two tumors using radiomic signatures based on preoperative, contrast-enhanced T1-weighted and T2-weighted magnetic resonance imaging. A total of 141 transitional meningioma and 101 atypical meningioma cases between January 2014 and December 2018 with a histopathologically confirmed diagnosis were retrospectively reviewed. All patients underwent magnetic resonance imaging before surgery. For each patient, 1227 radiomic features were extracted from contrast-enhanced T1-weighted and T2-weighted images each. Least absolute shrinkage and selection operator regression analysis was performed to select the most informative features of different modalities. Subsequently, stepwise multivariate logistic regression was chosen to further select strongly correlated features and build classification models that can distinguish transitional from atypical meningioma. The diagnostic abilities were evaluated by receiver operating characteristic analysis. Furthermore, a nomogram was built by incorporating clinical characteristics, radiological features, and radiomic signatures, and decision curve analysis was used to validate the clinical usefulness of the nomogram. Sex, tumor shape, brain invasion, and four radiomic features differed significantly between transitional meningioma and atypical meningioma. The clinicoradiomic model derived by fusing the above features resulted in the best discrimination ability, with areas under the curves of 0.809 (95% confidence interval, 0.743-0.874) and 0.795 (95% confidence interval, 0.692-0.899) and sensitivity values of 74.0% and 71.4% in the training and validation cohorts, respectively. The clinicoradiomic model demonstrated good performance for the differentiation between transitional and atypical meningioma. It is a quantitative tool that can potentially aid the selection of surgical techniques and the prognosis prediction and can thus be applied in patients with these two meningioma subtypes.
Selection of Optimal Candidates for Cytoreductive Nephrectomy in Patients with Metastatic Clear Cell Renal Cell Carcinoma: A Predictive Model Based on SEER Database
Authors: Zhang Yishan , Hu Jintao , Yang Jingtian , Xie Yingwei , Chen Zhiliang , Shangguan Wentai , Han Jinli , He Wang , Yang Jingyin , Zheng Zaosong , Zhong Qiyu , Zhu Dingjun , Xie Wenlian
Published: January 2022

Background

Currently, the progress of targeted drugs in the treatment of metastatic clear cell renal cell carcinoma (mccRCC) is limited. Cytoreductive nephrectomy (CN), as an alternative treatment, can improve the prognosis of patients with metastatic renal cell carcinoma to some extent. However, it is unclear which patients would benefit from this tumor reduction operation. As a consequence, we developed a predictive model to identify patients who may well benefit from CN in terms of survival.

Methods

We identified patients with metastatic clear cell renal cell carcinoma retrospectively from the Surveillance, Epidemiology, and End Results (SEER) database (2010–2015) and classified them into surgery and non-surgery groups. Propensity score matching (PSM) was performed to balance the baseline characteristics. Patients who survived longer than the median overall survival (OS) of no-surgery group were defined as surgical-benefit patients. Then, we developed a predictive model based on preoperative characteristics using multivariable Logistic regression. Calibration curves and the area under the receiver operating characteristic (AUC) were used to evaluate the efficiency of the predictive model. The clinical value of the nomogram was assessed utilizing decision curve analysis (DCA).

Results

Our study collected 5544 patients from the SEER database, with 2352(42.4%) receiving cytoreductive surgery. Overall survival (OS) was longer in the CN group than in the non-surgery group after 1:1 propensity scoring matching (median OS: 19 months vs 7 months; hazard ratio (HR) =0.4106, P< 0.001). In the matched surgery group, 65.7% (367) patients survived more than 7 months after the operation and they were considered to benefit from CN. The predictive model performed well on both the training group (AUC=73.4%) and the validation group (AUC=71.9%) and the calibration curves indicated a high degree of consistency. The decision curve analysis curve demonstrated the clinical utility. We classified surgical patients into the beneficial group and non-beneficial group by using the predictive model, then discovered a substantial difference in OS between the two groups.

Conclusions

We developed a nomogram to select ideal mccRCC patients who might benefit from cytoreductive nephrectomy. Clinicians could make a more precise treatment strategy for mccRCC patients.
Cationic Nanomaterials for Autoimmune Diseases Therapy
Authors: Xie Baozhao , Du Keqian , Huang Fujian , Lin Zhiming , Wu Linping
Published: January 2022

Cationic nanomaterials are defined as nanoscale structures smaller than 100 nm bearing positive charges. They have been investigated to apply to many aspects including clinical diagnosis, gene delivery, drug delivery, and tissue engineering for years. Recently, a novel concept has been made to use cationic nanomaterials as cell-free nucleic acid scavengers and inhibits the inflammatory responses in autoimmune diseases. Here, we highlighted different types of cationic materials which have the potential for autoimmune disease treatment and reviewed the strategy for autoimmune diseases therapy based on cationic nanoparticles. This review will also demonstrate the challenges and possible solutions that are encountered during the development of cationic materials-based therapeutics for autoimmune diseases.
Wenfei Buqi Tongluo Formula Against Bleomycin-Induced Pulmonary Fibrosis by Inhibiting TGF-β/Smad3 Pathway
Authors: Ding Lu , Li Yaxin , Yang Yingying , Song Siyu , Qi Hongyu , Wang Jing , Wang Ziyuan , Zhao Jiachao , Zhang Wei , Zhao Linhua , Zhao Daqing , Li Xiangyan , Wang Zeyu
Published: January 2022

Pulmonary fibrosis (PF) is the end stage of various chronic and progressive interstitial lung diseases. TGF-β, a profibrotic cytokine, can promote epithelial–mesenchymal transition (EMT), extracellular matrix (ECM) accumulation, and fibroblast proliferation, which contribute to progressive lung remodeling in PF. The Wenfei Buqi Tongluo (WBT) formula has been certified to be effective in the prevention and treatment of PF in clinical practice and has inhibitory effects on EMT, inflammation, and profibrotic factors. However, the pharmacological mechanisms of WBT against PF need to be further explored. In this study, we first analyzed the chemical components of the WBT formula using the UHPLC/Q-TOF-MS analysis. The potential targets of the identified compounds from WBT were predicted by the network pharmacology, which was confirmed by in vivo and in vitro study. After screening by the PubChem database, we first identified the 36 compounds of WBT and predicted the TGF-β signaling pathway, with ECM degradation as potential mechanism of WBT against PF by the network pharmacology. Furthermore, WBT treatment inhibited the levels of TGF-β and Smad3 phosphorylation and subsequently alleviated EMT and ECM accumulation in the bleomycin-induced mouse model and TGF-β1–induced cell model. These findings indicate that WBT can block the progressive process of PF by inhibiting EMT and promoting ECM degradation via the TGF-β/Smad3 pathway. This study may provide new insights into the molecular mechanism of WBT for the prevention and treatment of PF in the clinical application.
Specific Interleukin-1 Inhibitors, Specific Interleukin-6 Inhibitors, and GM-CSF Blockades for COVID-19 (at the Edge of Sepsis): A Systematic Review
Authors: Wang Ying , Zhu Kun , Dai Rulin , Li Rui , Li Miao , Lv Xin , Yu Qian
Published: January 2022

Sepsis is a syndrome with high mortality, which seriously threatens human health. During the pandemic of coronavirus disease 2019 (COVID-19), some severe and critically ill COVID-19 patients with multiple organ dysfunction developed characteristics typical of sepsis and met the diagnostic criteria for sepsis. Timely detection of cytokine storm and appropriate regulation of inflammatory response may be significant in the prevention and treatment of sepsis. This study evaluated the efficacy and safety of specific interleukin (IL)-1 inhibitors, specific IL-6 inhibitors, and GM-CSF blockades in the treatment of COVID-19 (at the edge of sepsis) patients through systematic review and meta-analysis. Methodology: A literature search was conducted on PubMed, EMBASE, Clinical Key, Cochrane Library, CNKI, and Wanfang Database using proper keywords such as “SARS-CoV-2,” “Corona Virus Disease 2019,” “COVID-19,” “anakinra,” “tocilizumab,” “siltuximab,” “sarilumab,” “mavrilimumab,” “lenzilumab,” and related words for publications released until August 22, 2021. Other available resources were also used to identify relevant articles. The present systematic review was performed based on PRISMA protocol. Results: Based on the inclusion and exclusion criteria, 43 articles were included in the final review. The meta-analysis results showed that tocilizumab could reduce the mortality of patients with COVID-19 (at the edge of sepsis) [randomized controlled trials, RCTs: odds ratio (OR) 0.71, 95%CI: 0.52–0.97, low-certainty evidence; non-RCTs: risk ratio (RR) 0.68, 95%CI: 0.55–0.84, very low-certainty evidence) as was anakinra (non-RCTs: RR 0.47, 95%CI: 0.34–0.66, very low-certainty evidence). Sarilumab might reduce the mortality of patients with COVID-19 (at the edge of sepsis), but there was no statistical significance (OR 0.65, 95%CI: 0.36–1.2, low-certainty evidence). For safety outcomes, whether tocilizumab had an impact on serious adverse events (SAEs) was very uncertain (RCTs: OR 0.87, 95%CI: 0.38–2.0, low-certainty evidence; non-RCTs 1.18, 95%CI: 0.83–1.68, very low-certainty evidence) as was on secondary infections (RCTs: OR 0.71, 95%CI: 0.06–8.75, low-certainty evidence; non-RCTs: RR 1.15, 95%CI: 0.89–1.49, very low-certainty evidence). Conclusions: This systematic review showed that tocilizumab, sarilumab, and anakinra could reduce the mortality of people with COVID-19 (at the edge of sepsis), and tocilizumab did not significantly affect SAEs and secondary infections. The current evidence of the studies on patients treated with siltuximab, mavrilimumab, and lenzilumab is insufficient. In order to establish evidence with stronger quality, high-quality studies are needed.

Systematic Review Registration: PROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42020226545
Elucidation of Cellular Contributions to Heparin-Induced Thrombocytopenia Using Omic Approaches
Authors: Giles Jason B. , Miller Elise C. , Steiner Heidi E. , Karnes Jason H.
Published: January 2022

Heparin-induced thrombocytopenia (HIT) is an unpredictable, complex, immune-mediated adverse drug reaction associated with a high mortality. Despite decades of research into HIT, fundamental knowledge gaps persist regarding HIT likely due to the complex and unusual nature of the HIT immune response. Such knowledge gaps include the identity of a HIT immunogen, the intrinsic roles of various cell types and their interactions, and the molecular basis that distinguishes pathogenic and non-pathogenic PF4/heparin antibodies. While a key feature of HIT, thrombocytopenia, implicates platelets as a seminal cell fragment in HIT pathogenesis, strong evidence exists for critical roles of multiple cell types. The rise in omic technologies over the last decade has resulted in a number of agnostic, whole system approaches for biological research that may be especially informative for complex phenotypes. Applying multi-omics techniques to HIT has the potential to bring new insights into HIT pathophysiology and identify biomarkers with clinical utility. In this review, we review the clinical, immunological, and molecular features of HIT with emphasis on key cell types and their roles. We then address the applicability of several omic techniques underutilized in HIT, which have the potential to fill knowledge gaps related to HIT biology.
Cross-Adversarial Learning for Molecular Generation in Drug Design
Authors: Wu Banghua , Li Linjie , Cui Yue , Zheng Kai
Published: January 2022

Molecular generation is an important but challenging task in drug design, as it requires optimization of chemical compound structures as well as many complex properties. Most of the existing methods use deep learning models to generate molecular representations. However, these methods are faced with the problems of generation validity and semantic information of labels. Considering these challenges, we propose a cross-adversarial learning method for molecular generation, CRAG for short, which integrates both the facticity of VAE-based methods and the diversity of GAN-based methods to further exploit the complex properties of Molecules. To be specific, an adversarially regularized encoder-decoder is used to transform molecules from simplified molecular input linear entry specification (SMILES) into discrete variables. Then, the discrete variables are trained to predict property and generate adversarial samples through projected gradient descent with corresponding labels. Our CRAG is trained using an adversarial pattern. Extensive experiments on two widely used benchmarks have demonstrated the effectiveness of our proposed method on a wide spectrum of metrics. We also utilize a novel metric named Novel/Sample to measure the overall generation effectiveness of models. Therefore, CRAG is promising for AI-based molecular design in various chemical applications.
Effects of Different Intensities and Durations of Aerobic Exercise on Vascular Endothelial Function in Middle-Aged and Elderly People: A Meta-analysis
Authors: You Qiuping , Yu Laikang , Li Gen , He Hui , Lv Yuanyuan
Published: January 2022

Background

Previous studies have found that aerobic exercise was more effective in improving vascular endothelial function than resistance training, high-intensity interval training (HIIT), and other types of exercise, while the effects between different intensities and durations of aerobic exercise were unclear. Therefore, we performed this meta-analysis to investigate the effects of different intensities and durations of aerobic exercise on the vascular endothelial function of middle-aged and elderly people.

Methods:

Databases were searched up to April 2021 for studies evaluating the influences of different intensities and durations of aerobic exercise on endothelial function assessed by flow-mediated dilation (FMD) among healthy middle-aged and elderly people. Data were pooled using random-effects models to obtain the weighted mean difference (WMD) and 95% confidence intervals (CIs).

Results

A total of 9 studies involving 221 participants fulfilled the inclusion criteria. Aerobic exercise improved the overall FMD of healthy middle-aged and elderly people [WMD, 1.33 (95% CI, 0.37–2.28), P < 0.05]. Specifically, vigorous-intensity exercise increased FMD significantly in healthy middle-aged and elderly people [WMD, 1.10 (95% CI, 0.27–1.93), P < 0.05], while moderate-intensity exercise had no significant association with FMD [WMD, 1.49 (95% CI, −0.62 to 3.60), P = 0.17]. In addition, long-term (8 weeks or above) aerobic exercise increased the FMD in healthy middle-aged and elderly people [WMD, 1.63 (95% CI, 0.61–2.66), P < 0.05], while one-time acute aerobic exercise had no significant association with FMD of healthy middle-aged and elderly people [WMD, 0.89 (95% CI, −1.47 to 3.24), P = 0.46]. Specifically, 8 weeks or above of vigorous-intensity exercise increased FMD significantly in healthy middle-aged and elderly people [WMD, 1.48 (95% CI, 1.06–1.90), P < 0.01], while 8 weeks or above of moderate aerobic exercise had no significant association with FMD [WMD, 1.49 (95% CI, −0.62 to 3.60), P = 0.17].

Conclusion

Aerobic exercise, especially 8 weeks or above of vigorous-intensity aerobic exercise, improved the endothelial function in healthy middle-aged and elderly people.
Alternation of the Autonomic Nervous System Is Associated With Pulmonary Sequelae in Patients With COVID-19 After Six Months of Discharge
Authors: Bai Tao , Zhou Dan , Yushanjiang Feierkaiti , Wang Dongke , Zhang Dongmei , Liu Xinghuang , Song Jun , Zhang Jianchu , Hou Xiaohua , Ma Yanling
Published: January 2022

Previous studies suggest that autonomic dysfunction is associated with disease severity in acute phase in patients with coronavirus disease 2019 (COVID-19). However, the association between autonomic dysfunction and pulmonary sequelae in patients with COVID-19 is unknown. We conducted a prospective study to investigate the association between autonomic dysfunction and pulmonary sequelae in patients with COVID-19 discharged for 6 months. We included 40 eligible participants and collected the following indicators: heart rate variability (HRV), pulmonary function tests (PFTs), lung X-ray computed tomography (CT), routine blood parameters, liver function parameters, and lymphocyte subsets. We found that at 6 months post-discharge, HRV still had a tight correlation with pulmonary fibrosis. There was a significant difference in HRV between patients with and without diffusion dysfunction, but HRV did not differ between patients with or without ventilatory dysfunction. Diffusion dysfunction and pulmonary fibrosis were tightly associated, and HRV index changes in patients with diffusion dysfunction had the same trend as that of patients with pulmonary fibrosis. They had a lower standard deviation of NN intervals (SDNN), the standard deviation of the average NN intervals (SDANN), and the triangular index, but a higher ratio between LF and HF power (LF/HF). In addition, WBC, neutrophils, and CD4/CD8 were correlated with pulmonary fibrosis and HRV. We concluded that autonomic dysfunction is closely associated with pulmonary fibrosis and diffusion dysfunction, and immune mechanisms may potentially contribute to this process.
Optimization of Tissue Culturing and Genetic Transformation Protocol for Casuarina equisetifolia
Authors: Ren Huimin , Xu Yan , Zhao Xiaohong , Zhang Yan , Hussain Jamshaid , Cui Fuqiang , Qi Guoning , Liu Shenkui
Published: January 2022

Casuarina equisetifolia is widely used in agroforestry plantations for soil stabilization, ecosystem rehabilitation, reclamation, and coastal protection. Moreover, C. equisetifolia has remarkable resistance to typhoons, desert, low soil fertility, drought, and salinity, but not cold. Therefore, it is significant to breed high-quality Casuarina varieties to improve the tolerance and adaptability to cold weather by molecular techniques. The establishment of a rapid and efficient callus induction and regeneration system via tissue culture is pre-requisite for the genetic transformation of C. equisetifolia, which is so far lacking. In this study, we reported an efficient and rapid regeneration system using stem segment explants, in which callus induction was found to be optimal in a basal medium supplemented with 0.1 mg⋅L–1 TDZ and 0.1 mg⋅L–1 NAA, and proliferation in a basal medium containing 0.1 mg⋅L–1 TDZ and 0.5 mg⋅L–1 6-BA. For bud regeneration and rooting, the preferred plant growth regulator (PGR) in basal medium was 0.5 mg⋅L–1 6-BA, and a combination of 0.02 mg⋅L–1 IBA and 0.4 mg⋅L–1 IAA, respectively. We also optimized genetic a transformation protocol using Agrobacterium tumefaciens harboring the binary vector pCAMBIA1301 with β-glucuronidase (GUS) as a reporter gene. Consequently, 5 mg L–1 hygromycin, 20 mg L–1 acetosyringone (As), and 2 days of co-cultivation duration were optimized to improve the transformation efficiency. With these optimized parameters, transgenic plants were obtained in about 4 months. Besides that, Agrobacterium rhizogenes-mediated transformation involving adventitious root induction was also optimized. Our findings will not only increase the transformation efficiency but also shorten the time for developing transgenic C. equisetifolia plants. Taken together, this pioneer study on tissue culturing and genetic transformation of C. equisetifolia will pave the way for further genetic manipulation and functional genomics of C. equisetifolia.