bluuebunny/crossref_metadata_2025 huggingface dataset:
DRJAMM Is Involved in the Oxidative Resistance in Deinococcus radiodurans
Authors: Cai Jianling , Pan Chaoming , Zhao Ye , Xu Hong , Tian Bing , Wang Liangyan , Hua Yuejin
Published: January 2022

Proteins containing JAB1/MPN/MOV34 metalloenzyme (JAMM/MPN+) domains that have Zn2+-dependent deubiquitinase (DUB) activity are ubiquitous across among all domains of life. Recently, a homolog in Deinococcus radiodurans, DRJAMM, was reported to possess the ability to cleave DRMoaD-MoaE. However, the detailed biochemical characteristics of DRJAMM in vitro and its biological mechanism in vivo remain unclear. Here, we show that DRJAMM has an efficient in vitro catalytic activity in the presence of Mn2+, Ca2+, Mg2+, and Ni2+ in addition to the well-reported Zn2+, and strong adaptability at a wide range of temperatures. Disruption of drJAMM led to elevated sensitivity in response to H2O2in vivo compared to the wild-type R1. In particular, the expression level of MoaE, a product of DRJAMM cleavage, was also increased under H2O2 stress, indicating that DRJAMM is needed in the antioxidant process. Moreover, DRJAMM was also demonstrated to be necessary for dimethyl sulfoxide respiratory system in D. radiodurans. These data suggest that DRJAMM plays key roles in the process of oxidative resistance in D. radiodurans with multiple-choice of metal ions and temperatures.
Validated Impacts of N6-Methyladenosine Methylated mRNAs on Apoptosis and Angiogenesis in Myocardial Infarction Based on MeRIP-Seq Analysis
Authors: Zhang Yingjie , Hua Wenjie , Dang Yini , Cheng Yihui , Wang Jiayue , Zhang Xiu , Teng Meiling , Wang Shenrui , Zhang Min , Kong Zihao , Lu Xiao , Zheng Yu
Published: January 2022

Objectives: N6-methyladenosine (m6A) is hypothesized to play a role in the regulation of pathogenesis of myocardial infarction (MI). This study was designed to compare m6A-tagged transcript profiles to identify mRNA-specific changes on pathophysiological variations after MI.

Methods: N6-methyladenosine methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were interacted to select m6A-modified mRNAs with samples collected from sham operated and MI rat models. m6A methylation regulated mRNAs were interacted with apoptosis/angiogenesis related genes in GeneCards. Afterwards, MeRIP-quantitative real-time PCR (MeRIP-qRT-PCR) was performed to measure m6A methylation level of hub mRNAs. m6A methylation variation was tested under different oxygen concentration or hypoxic duration in H9c2 cells and HUVECs. In addition, Western blot and qRT-PCR were employed to detect expression of hub mRNAs and relevant protein level. Flow cytometry and Tunel assay were conducted to assess apoptotic level. CCK-8, EdU, and tube formation assay were performed to measure cell proliferation and tube formation ability.

Results: Upregulation of Mettl3 was firstly observed in vivo and in vitro, followed by upregulation of m6A methylation level. A total of 567 significantly changed m6A methylation peaks were identified, including 276 upregulated and 291 downregulated peaks. A total of 576 mRNAs were upregulated and 78 were downregulated. According to combined analysis of MeRIP-seq and RNA-seq, we identified 26 significantly hypermethylated and downregulated mRNAs. Based on qRT-PCR and interactive analysis, Hadh, Kcnn1, and Tet1 were preliminarily identified as hub mRNAs associated with apoptosis/angiogenesis. MeRIP-qRT-PCR assay confirmed the results from MeRIP-seq. With the inhibition of Mettl3 in H9c2 cells and HUVECs, downregulated m6A methylation level of total RNA and upregulated expression of hub mRNAs were observed. Increased m6A level was verified in the gradient context in terms of prolonged hypoxic duration and decreased oxygen concentration. Under simulated hypoxia, roles of Kcnn1 and Tet1 in angiogenesis and Hadh, Tet1, and Kcnn1 in apoptosis were further confirmed with our validation experiments.

Conclusion: Roles of m6A-modified mRNA transcripts in the context of MI were preliminarily verified. In the context of m6A methylation, three hub mRNAs were validated to impact the process of apoptosis/angiogenesis. Our study provided theoretical basis and innovative targets for treatment of MI and paved the way for future investigations aiming at exploring upstream epigenetic mechanisms of pathogenesis after MI.
Cancer Occurrence as the Upcoming Complications of COVID-19
Authors: Rahimmanesh Ilnaz , Shariati Laleh , Dana Nasim , Esmaeili Yasaman , Vaseghi Golnaz , Haghjooy Javanmard Shaghayegh
Published: January 2022

Previous studies suggested that patients with comorbidities including cancer had a higher risk of mortality or developing more severe forms of COVID-19. The interaction of cancer and COVID-19 is unrecognized and potential long-term effects of COVID-19 on cancer outcome remain to be explored. Furthermore, whether COVID‐19 increases the risk of cancer in those without previous history of malignancies, has not yet been studied. Cancer progression, recurrence and metastasis depend on the complex interaction between the tumor and the host inflammatory response. Extreme proinflammatory cytokine release (cytokine storm) and multi‐organ failure are hallmarks of severe COVID‐19. Besides impaired T-Cell response, elevated levels of cytokines, growth factors and also chemokines in the plasma of patients in the acute phase of COVID-19 as well as tissue damage and chronic low‐grade inflammation in “long COVID‐19” syndrome may facilitate cancer progression and recurrence. Following a systemic inflammatory response syndrome, some counterbalancing compensatory anti-inflammatory mechanisms will be activated to restore immune homeostasis. On the other hand, there remains the possibility of the integration of SARS- CoV-2 into the host genome, which potentially may cause cancer. These mechanisms have also been shown to be implicated in both tumorigenesis and metastasis. In this review, we are going to focus on potential mechanisms and the molecular interplay, which connect COVID-19, inflammation, and immune-mediated tumor progression that may propose a framework to understand the possible role of COVID-19 infection in tumorgenesis and cancer progression.
Ferroptosis Regulator Modification Patterns and Tumor Microenvironment Immune Infiltration Characterization in Hepatocellular Carcinoma
Authors: Liu Dong-Li , Wu Ming-Yao , Zhang Tie-Ning , Wang Chun-Gang
Published: January 2022

Accumulating studies have highlighted the biologic significances of ferroptosis modification in tumor progression, but little is known whether ferroptosis modification patterns have potential roles in tumor microenvironment (TME) immune cell infiltration of hepatocellular carcinoma (HCC). In this study, we evaluated 51 ferroptosis regulators and performed consensus clustering algorithm to determine ferroptosis modification patterns and the ferroptosis related gene signature in HCC. Gene set variation analysis (GSVA) was employed to explore biological molecular variations in distinct ferroptosis modification patterns. Single sample gene set enrichment analysis (ssGSEA) algorithm was performed to quantify the relative infiltration levels of various immune cell subsets. Principal component analysis (PCA) algorithm was used to construct the ferroptosisSig score to quantify ferroptosis modification patterns of individual tumors with immune responses. Three distinct ferroptosis modification patterns were identified. GSVA enrichment analysis indicated that three ferroptosis modification subgroups were enriched in different metabolic pathways. ssGSEA analysis determined that 19 of 24 immune infiltrating cells had significant differences in three distinct ferroptosis patterns. A 91-ferroptosis gene signature was constructed to stratify patients into two ferroptosisSig score groups. Patients in the higher ferroptosisSig score were characterized by significantly prolonged survival time compared with patients in the lower ferroptosisSig score group (p < .0001). An immunotherapy cohort confirmed patients with higher ferroptosisSig score determined significant therapeutic advantages and clinical benefits. Receiver operating characteristic (ROC) curve analysis confirmed the predictive capacity of anti-PD/L1 immunotherapy by ferroptosisSig score. Our study indicated the ferroptosis modification played a significant role in TME heterogeneity and complexity. Evaluating the ferroptosis modification pattern of individual tumor could strengthen our cognition of TME infiltration characteristics and guide more effective clinic immunotherapy strategies.
Sleep-Wake Rhythm and Oscillatory Pattern Analysis in a Multiple Hit Schizophrenia Rat Model (Wisket)
Authors: Adlan Leatitia Gabriella , Csordás-Nagy Mátyás , Bodosi Balázs , Kalmár György , Nyúl László G. , Nagy Attila , Kekesi Gabriella , Büki Alexandra , Horvath Gyongyi
Published: January 2022

Electroencephalography studies in schizophrenia reported impairments in circadian rhythm and oscillatory activity, which may reflect the deficits in cognitive and sensory processing. The current study evaluated the circadian rhythm and the state-dependent oscillatory pattern in control Wistar and a multiple hit schizophrenia rat model (Wisket) using custom-made software for identification of the artifacts and the classification of sleep-wake stages and the active and quiet awake substages. The Wisket animals have a clear light-dark cycle similar to controls, and their sleep-wake rhythm showed only a tendency to spend more time in non-rapid eye movement (NREM) and less in rapid eye movement (REM) stages. In spite of the weak diurnal variation in oscillation in both groups, the Wisket rats had higher power in the low-frequency delta, alpha, and beta bands and lower power in the high-frequency theta and gamma bands in most stages. Furthermore, the significant differences between the two groups were pronounced in the active waking substage. These data suggest that the special changes in the oscillatory pattern of this schizophrenia rat model may have a significant role in the impaired cognitive functions observed in previous studies.
The Long and Winding Road—Vestibular Efferent Anatomy in Mice
Authors: Lorincz David , Poppi Lauren A. , Holt Joseph C. , Drury Hannah R. , Lim Rebecca , Brichta Alan M.
Published: January 2022

The precise functional role of the Efferent Vestibular System (EVS) is still unclear, but the auditory olivocochlear efferent system has served as a reasonable model on the effects of a cholinergic and peptidergic input on inner ear organs. However, it is important to appreciate the similarities and differences in the structure of the two efferent systems, especially within the same animal model. Here, we examine the anatomy of the mouse EVS, from its central origin in the Efferent Vestibular Nucleus (EVN) of the brainstem, to its peripheral terminations in the vestibular organs, and we compare these findings to known mouse olivocochlear anatomy. Using transgenic mouse lines and two different tracing strategies, we examine central and peripheral anatomical patterning, as well as the anatomical pathway of EVS axons as they leave the mouse brainstem. We separately tag the left and right efferent vestibular nuclei (EVN) using Cre-dependent, adeno-associated virus (AAV)-mediated expression of fluorescent reporters to map their central trajectory and their peripheral terminal fields. We couple this with Fluro-Gold retrograde labeling to quantify the proportion of ipsi- and contralaterally projecting cholinergic efferent neurons. As in some other mammals, the mouse EVN comprises one group of neurons located dorsal to the facial genu, close to the vestibular nuclei complex (VNC). There is an average of just 53 EVN neurons with rich dendritic arborizations towards the VNC. The majority of EVN neurons, 55%, project to the contralateral eighth nerve, crossing the midline rostral to the EVN, and 32% project to the ipsilateral eighth nerve. The vestibular organs, therefore, receive bilateral EVN innervation, but without the distinctive zonal innervation patterns suggested in gerbil. Similar to gerbil, however, our data also suggest that individual EVN neurons do not project bilaterally in mice. Taken together, these data provide a detailed map of EVN neurons from the brainstem to the periphery and strong anatomical support for a dominant contralateral efferent innervation in mammals.
Mechanical Punctate Pain Thresholds in Patients With Migraine Across Different Migraine Phases: A Narrative Review
Authors: Pan Li-Ling Hope , Treede Rolf-Detlef , Wang Shuu-Jiun
Published: January 2022

Purpose of the Review

We reviewed the studies of mechanical punctate pain thresholds (MPTs) in patients with migraine and summarized their findings focusing on the differences in MPT measurement and MPTs in different phases of migraine.

Methods

We searched the English-written articles that investigate the MPTs in the migraine population published in peer-reviewed journals with full-text using the PubMed, Web of Science, and Google Scholar databases. Moreover, we manually searched the references from the articles for possibly related studies.

Main Findings

We collected 276 articles and finally included twelve studies in this review. Most of the studies that included MPTs were measured with traditional von Frey filaments. The cephalic areas were always included in the assessment. Most studies compared the inter-ictal MPT in patients with migraine to controls. Among them, the majority found no significant differences; however, there were studies found either higher or lower levels of MPTs in migraine. Even though the studies provided the criteria to define the inter-ictal phase, not all of them followed up with the subjects regarding the next migraine attack. In studies that compared MPT between phases, lower MPTs were found during peri-ictal phases.

Changes to MPT in migraine patients were inconclusive. The selection of measurement methods as well as properly defined migraine phases should be considered for future studies.
Effect of Twist-Drill Craniostomy With Hollow Screws for Evacuation of Chronic Subdural Hematoma: A Meta-Analysis
Authors: Wei Zeng , Jiang Haixiao , Wang Ying , Wang Cunzu
Published: January 2022

Objective

This study systematically reviews the clinical efficacy and safety of twist-drill craniostomy with hollow screws in chronic subdural hematoma treatment.

Methods

A computerized search of PubMed, Embase, Web of Science, Cochrane Library, World Health Organization International Trial Registry platform, CBM, CNKI, and Wanfang Database was performed to retrieve randomized controlled trials or case-control trials using twist-drill craniostomy (TDC) with hollow screws for the evacuation of chronic subdural hematoma from the date of databases' inception to July 2021. Two investigators independently screened the studies and extracted data in strict accordance with pre-established inclusion and exclusion criteria. RevMan 5.3 software or STATA was used for meta-analysis after evaluating the methodological quality of the included studies.

Results

A total of 4 randomized controlled trials and 16 case-control trials with a total of 2,536 cases were included. Results of the meta-analysis showed that the surgical success rate and postoperative recurrence rate of TDC with hollow screws were slightly higher compared to the burr hole craniostomy (BHC) group, but showed no statistical significance (RR = 1.03, P = 0.05; RR = 1.13, P = 0.50). However, subgroup analysis showed that the use of YL-1 needle had a higher success rate and lower recurrence rate (RR = 1.05, P = 0.02 < 0.05; RR = 0.584, P = 0.002), and TDC with hollow screws had a lower incidence rate of postoperative complications and postoperative acute intracranial hemorrhage compared with BHC, also revealing an overall shorter hospital stay (RR = 0.57, P = 0.0002 < 0.05; RR = 0.584, P = 0.027 < 0.05; WMD = −3.752, P < 0.001). However, the postoperative mortality rate was practically the same between the two groups (OR = 1.01, P = 0.95 > 0.05).

Conclusion

Twist-drill craniostomy with hollow screws is not inferior or superior to BHC in efficacy, and this strategy is safer and minimally invasive, which is reflected in a lower incidence of acute intracranial hemorrhage, overall complication rate, and length of hospital stay.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier: CRD42021270835.
PyNeval: A Python Toolbox for Evaluating Neuron Reconstruction Performance
Authors: Zhang Han , Liu Chao , Yu Yifei , Dai Jianhua , Zhao Ting , Zheng Nenggan
Published: January 2022

Quality assessment of tree-like structures obtained from a neuron reconstruction algorithm is necessary for evaluating the performance of the algorithm. The lack of user-friendly software for calculating common metrics motivated us to develop a Python toolbox called PyNeval, which is the first open-source toolbox designed to evaluate reconstruction results conveniently as far as we know. The toolbox supports popular metrics in two major categories, geometrical metrics and topological metrics, with an easy way to configure custom parameters for each metric. We tested the toolbox on both synthetic data and real data to show its reliability and robustness. As a demonstration of the toolbox in real applications, we used the toolbox to improve the performance of a tracing algorithm successfully by integrating it into an optimization procedure.
A Compact Two-Loudspeaker Virtual Sound Reproduction System for Clinical Testing of Spatial Hearing With Hearing-Assistive Devices
Authors: Hamdan Eric C. , Fletcher Mark D.
Published: January 2022

Exciting developments in hearing aid and cochlear implant technology for linking signal processing across the ears have improved spatial hearing outcomes. This has resulted in an increased emphasis on clinical assessment of the spatial hearing abilities of hearing-assistive device users. Effective assessment of spatial hearing currently requires a large and costly loudspeaker array system, housed in a heavily acoustically treated testing room. This imposes economic and logistical constraints that limit proliferation of array systems, particularly in developing nations. Despite their size and cost, the ability of current clinical array systems to reproduce realistic spatial sound fields is limited, which substantially reduces the range of realistic acoustic scenes that can be used for diagnostic testing. We propose an alternative low-cost, compact virtual acoustics system with just two loudspeakers. This system uses crosstalk cancelation to reproduce pressure signals at the device microphones that match those for real-world sound sources. Furthermore, in contrast to clinical array systems, the system can adapt to different room acoustics, removing the requirement for a heavily acoustically treated testing environment. We conducted a proof-of-concept study in two stages: in the first, we evaluated the physical performance of the system for a stationary listener in anechoic conditions and in a small audiological testing booth with moderate acoustic treatment. To do this, a head and torso simulator was fitted with specially adapted hearing-assistive devices that allowed direct access to the microphone signals. These microphone signals were compared for real and virtual sound sources at numerous source locations. In the second stage, we quantified the system’s robustness to head rotations with and without the system adapting for head position. In the stationary case, the system was found to be highly effective at reproducing signals, such as speech, at all tested source locations. When head rotation was added, it performed well for rotations of up to 2°, even without adapting. However, performance improved markedly for larger rotations when the system adapted. These findings suggest that a compact, low-cost virtual acoustics system can give wider access to advanced and ecologically valid audiological testing, which could substantially improve clinical assessment of hearing-assistive device users.
SRPK2 Expression and Beta-Amyloid Accumulation Are Associated With BV2 Microglia Activation
Authors: Tian Ziqi , Zeng Wenfang , Yan Cuihuan , Li Qiang , Li Nan , Ruan Lin , Li Jie , Yao Xiaoguang , Li Si
Published: January 2022

Introduction

The extracellular deposition of β-amyloid (Aβ) is a pathological hallmark in Alzheimer's disease (AD), which induces microglial activation in the pathology of AD. The expression of serine/threonine-protein kinase 2 (SRPK2) is increased in the brain tissues of patients with AD. In this study, we examined the effect of SRPK2 in the activation of microglia.

Methods

Microglia (BV2) cells were cultured and the expression of SRPK2 was enhanced by transfection of SRPK2 recombinant vectors or knockdown by SRPK2 small interfering RNA (siRNA). The cells were stimulated by lipopolysaccharide (LPS) + interferon-γ (IFN-γ) or Aβ in vitro, generating inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)-10, and IL-6], which were investigated by real-time quantitative PCR (qPCR) and ELISA. The proliferation ability of the BV2 cells with/without SRPK2 expression was evaluated by WST-1 under pressure in the presence of Aβ. The effects of SRPK2 on microglia polarization were evaluated by investigating the expression of CD16/32 and CD206 by western blot and the expression of ionized calcium-binding adapter molecule-1 (IBA-1) and arginase-1 (Arg-1) by immunofluorescence. Hippocampal cells HT-22 were cultured with a BV2 cell (with/without SRPK2 expression)-derived medium stimulated by Aβ or LPS + IFN-γ, prior to the evaluation of HT-22 cytotoxicity by assessment of cell viability. Possible relationships between Akt and SRPK2 in the BV2 cells were investigated by western blot.

Results

The expression of SRPK2 was related to the phenotype polarization changes of microglia with increased expression of CD16/32 and IBA-1. The expression of proinflammatory cytokines IL-6 and TNF-α was increased, whereas the expression of anti-inflammatory cytokine IL-10 was decreased in the BV2 cells with SRPK2 overexpression. Moreover, with the expression enhancement of SRPK2, the BV2 cells had a higher proliferation rate. Aβ treatment can promote SRPK2 expression in BV2 cells. Aβ or LPS + IFN-γ promoted the production of cytokines IL-6 and TNF-α but decreased cytokine IL-10 in the BV2 cells. SRPK2 deficiency alleviated the cytotoxic effects of Aβ or LPS + IFN-γ exposed microglia on HT22 cells. In addition, the activated Akt pathway promoted the expression of SRPK2 in the BV2 cells.

Conclusion

Our data have found that enhanced SRPK2 expression contributed to the proinflammatory activation of microglia. Thus, SRPK2 may be a key modulating pathway of inflammatory mediators in AD pathology.
The Lonely Brain – Associations Between Social Isolation and (Cerebro-) Vascular Disease From the Perspective of Social Neuroscience
Authors: Gronewold Janine , Engels Miriam
Published: January 2022

The current COVID-19 pandemic led to a considerable reduction in in-person social contacts all over the world. In most individuals, reduced social contacts lead to the perception of social isolation causing feelings of loneliness, which are experienced as stressful. Experiencing social distress due to actual or perceived social isolation has been associated with negative health outcomes such as depression, (cerebro-) vascular disease and mortality. Concrete mechanisms behind this association are still a matter of debate. A group of researchers around Hugo Critchley with special contributions of Sarah Garfinkel and Lisa Quadt proposes a framework for the underlying brain-body interactions including elements from models of social homeostasis and interoceptive predictive processing that provides important insights and testable pathways. While in a previous publication, we reviewed literature on the observed association between social isolation and stroke and coronary heart disease, we now extent this review by presenting a comprehensive model to explain underlying pathomechanisms from the perspective of social neuroscience. Further, we discuss how neurodivergent people, e.g. autistic individuals or persons with attention deficit disorders, might differ in these pathomechanisms and why they are especially vulnerable to social isolation. Finally, we discuss clinical implications for the prevention and therapy of (cerebro-) vascular diseases.
Cerebellar Contributions to Social Cognition in ASD: A Predictive Processing Framework
Authors: Frosch Isabelle R. , Mittal Vijay A. , D’Mello Anila M.
Published: January 2022

Functional, structural, and cytoarchitectural differences in the cerebellum are consistently reported in Autism Spectrum Disorders (ASD). Despite this, the mechanisms governing cerebellar contributions to ASD, particularly within the sociocognitive domain, are not well understood. Recently, it has been suggested that several core features of ASD may be associated with challenges creating and using prior expectations or predictions to rapidly adapt to changing stimuli or situations, also known as adaptive prediction. Importantly, neuroimaging, clinical, and animal work find that the cerebellum supports adaptive prediction in both motor and non-motor domains. Perturbations to the cerebellum via injury or neuromodulation have been associated with impairments in predictive skills. Here, we review evidence for a cerebellar role in social cognition and adaptive prediction across individuals with and without ASD.
Mitochondrial Quality Control: A Pathophysiological Mechanism and Therapeutic Target for Stroke
Authors: Yang Miaoxian , He Yu , Deng Shuixiang , Xiao Lei , Tian Mi , Xin Yuewen , Lu Chaocheng , Zhao Feng , Gong Ye
Published: January 2022

Stroke is a devastating disease with high mortality and disability rates. Previous research has established that mitochondria, as major regulators, are both influenced by stroke, and further regulated the development of poststroke injury. Mitochondria are involved in several biological processes such as energy generation, calcium homeostasis, immune response, apoptosis regulation, and reactive oxygen species (ROS) generation. Meanwhile, mitochondria can evolve into various quality control systems, including mitochondrial dynamics (fission and fusion) and mitophagy, to maintain the homeostasis of the mitochondrial network. Various activities of mitochondrial fission and fusion are associated with mitochondrial integrity and neurological injury after stroke. Additionally, proper mitophagy seems to be neuroprotective for its effect on eliminating the damaged mitochondria, while excessive mitophagy disturbs energy generation and mitochondria-associated signal pathways. The balance between mitochondrial dynamics and mitophagy is more crucial than the absolute level of each process. A neurovascular unit (NVU) is a multidimensional system by which cells release multiple mediators and regulate diverse signaling pathways across the whole neurovascular network in a way with a high dynamic interaction. The turbulence of mitochondrial quality control (MQC) could lead to NVU dysfunctions, including neuron death, neuroglial activation, blood–brain barrier (BBB) disruption, and neuroinflammation. However, the exact changes and effects of MQC on the NVU after stroke have yet to be fully illustrated. In this review, we will discuss the updated mechanisms of MQC and the pathophysiology of mitochondrial dynamics and mitophagy after stroke. We highlight the regulation of MQC as a potential therapeutic target for both ischemic and hemorrhagic stroke.
Advancement on Milk Fat Globule Membrane: Separation, Identification, and Functional Properties
Authors: Wang Cong , Qiao Xinyu , Gao Zengli , Jiang Lianzhou , Mu Zhishen
Published: January 2022

Dairy products have become more common in people's daily diets in recent years, and numerous useful components derived from milk are widely employed in the food industry. Milk fat globule membrane (MFGM) is a kind of film that encases milk fat globules, and has been shown to have a high nutritional value. In this work, the protein, lipid, carbohydrate, and other components of MFGM are discussed, and also common separation, preparation, and analysis technologies, physicochemical properties, and functional features of MFGM are reviewed, to provide some guidance for the development and utilization of MFGM.
A Combined Proteomic and Metabolomic Strategy for Allergens Characterization in Natural and Fermented Brassica napus Bee Pollen
Authors: Yin Shuting , Tao Yuxiao , Jiang Yusuo , Meng Lifeng , Zhao Liuwei , Xue Xiaofeng , Li Qiangqiang , Wu Liming
Published: January 2022

Bee pollen is consumed for its nutritional and pharmacological benefits, but it also contains hazardous allergens which have not been identified. Here, we identified two potential allergens, glutaredoxin and oleosin-B2, in Brassica napus bee pollen using mass spectrometry-based proteomics analyses, and used bioinformatics to predict their antigenic epitopes. Comparison of fermented (by Saccharomyces cerevisiae) and unfermented bee pollen samples indicated that glutaredoxin and oleosin-B2 contents were significantly decreased following fermentation, while the contents of their major constituent oligopeptides and amino acids were significantly increased based on metabolomics analyses. Immunoblot analysis indicated that the IgE-binding affinity with extracted bee pollen proteins was also significantly decreased after fermentation, suggesting a reduction in the allergenicity of fermented bee pollen. Furthermore, fermentation apparently promoted the biosynthesis of L-valine, L-isoleucine, L-tryptophan, and L-phenylalanine, as well as their precursors or intermediates. Thus, fermentation could potentially alleviate allergenicity, while also positively affecting nutritional properties of B. napus bee pollen. Our findings might provide a scientific foundation for improving the safety of bee pollen products to facilitate its wider application.
An MRI-Based Radiomics Model for Predicting the Benignity and Malignancy of BI-RADS 4 Breast Lesions
Authors: Zhang Renzhi , Wei Wei , Li Rang , Li Jing , Zhou Zhuhuang , Ma Menghang , Zhao Rui , Zhao Xinming
Published: January 2022

Objectives

The probability of Breast Imaging Reporting and Data Systems (BI-RADS) 4 lesions being malignant is 2%–95%, which shows the difficulty to make a diagnosis. Radiomics models based on magnetic resonance imaging (MRI) can replace clinicopathological diagnosis with high performance. In the present study, we developed and tested a radiomics model based on MRI images that can predict the malignancy of BI-RADS 4 breast lesions.

Methods

We retrospective enrolled a total of 216 BI-RADS 4 patients MRI and clinical information. We extracted 3,474 radiomics features from dynamic contrast-enhanced (DCE), T2-weighted images (T2WI), and diffusion-weighted imaging (DWI) MRI images. Least absolute shrinkage and selection operator (LASSO) and logistic regression were used to select features and build radiomics models based on different sequence combinations. We built eight radiomics models which were based on DCE, DWI, T2WI, DCE+DWI, DCE+T2WI, DWI+T2WI, and DCE+DWI+T2WI and a clinical predictive model built based on the visual assessment of radiologists. A nomogram was constructed with the best radiomics signature combined with patient characteristics. The calibration curves for the radiomics signature and nomogram were conducted, combined with the Hosmer-Lemeshow test.

Results

Pearson’s correlation was used to eliminate 3,329 irrelevant features, and then LASSO and logistic regression were used to screen the remaining feature coefficients for each model we built. Finally, 12 related features were obtained in the model which had the best performance. These 12 features were used to build a radiomics model in combination with the actual clinical diagnosis of benign or malignant lesion labels we have obtained. The best model built by 12 features from the 3 sequences has an AUC value of 0.939 (95% CI, 0.884-0.994) and an accuracy of 0.931 in the testing cohort. The sensitivity, specificity, precision and Matthews correlation coefficient (MCC) of testing cohort are 0.932, 0.923, 0.982, and 0.791, respectively. The nomogram has also been verified to have calibration curves with good overlap.

Conclusions

Radiomics is beneficial in the malignancy prediction of BI-RADS 4 breast lesions. The radiomics predictive model built by the combination of DCE, DWI, and T2WI sequences has great application potential.
Human Microbiota and Immunotherapy in Breast Cancer - A Review of Recent Developments
Authors: Vitorino Marina , Baptista de Almeida Susana , Alpuim Costa Diogo , Faria Ana , Calhau Conceição , Azambuja Braga Sofia
Published: January 2022

Breast cancer (BC) is the most common malignancy and the second cause of cancer-specific death in women from high-income countries. Infectious agents are the third most important risk factor for cancer incidence after tobacco and obesity. Dysbiosis emerged as a key player that may influence cancer development, treatment, and prognosis through diverse biological processes. Metastatic BC has a highly variable clinical course, and more recently, immune checkpoint inhibitors (ICIs) have become an emerging therapy in BC. Even with standardised treatment protocols, patients do not respond similarly, reflecting each individual´s heterogeneity, unique BC features, and tumour microenvironment. However, there is insufficient data regarding predictive factors of response to available treatments for BC. The microbiota could be a crucial piece of the puzzle to anticipate better individual BC risk and prognosis, pharmacokinetics, pharmacodynamics, and clinical efficacy. In recent years, it has been shown that gut microbiota may modulate cancer treatments’ efficacy and adverse effects, and it is also apparent that both cancer itself and anticancer therapies interact with gut microbiota bidirectionally. Moreover, it has been proposed that certain gut microbes may protect the host against inappropriate inflammation and modulate the immune response. Future clinical research will determine if microbiota may be a prognostic and predictive factor of response to ICI and/or its side effects. Also, modulation of microbiota can be used to improve outcomes in BC patients. In this review, we discuss the potential implications of metabolomics and pharmacomicrobiomics that might impact BC immunotherapy treatment.
Application of Intravoxel Incoherent Motion Diffusion-Weighted Imaging in Predicting and Monitoring Early Efficacy of Anti-Angiogenic Therapy in the C6 Glioma Rat Model
Authors: Hou Weishu , Xue Yangyang , Qian Yinfeng , Pan Hongli , Xu Man , Shen Yujun , Li Xiaohu , Yu Yongqiang
Published: January 2022

Objective

To investigate the feasibility of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in evaluating early effects of anti-angiogenic therapy in the C6 glioma rat model.

Methods

Twenty-six rats of the C6 glioma model were randomly divided into a treatment group (received bevacizumab) and a control group (physiological saline). IVIM-DWI was performed on days 0, 1, 3, 5, and 7 after anti-angiogenic therapy and tumor growth and IVIM-DWI parameters were dynamically observed. Hematoxylin and eosin, CD34 microvessel density (MVD), proliferation of cell nuclear antigen (PCNA), and Hif-α staining were performed on day 7. One-way ANOVA was used to compare intra-group differences and an independent-samples t-test was used to compare inter-group differences of MRI parameters. Correlations between IVIM-DWI parameters, tumor size, and pathological results were analyzed.

Results

The relative change in tumor volume (ΔVolume) in the two groups differed significantly on days 5 and 7 (p = 0.038 and p < 0.001). The perfusion-related parameters D*- and f-values decreased in the treatment group and demonstrated significant differences compared with the control group on days 3, 5, and 7 (p = 0.033, p < 0.001, and p < 0.001, respectively). The diffusion-related parameters ADC and D-values increased in the treatment group and were found to be significantly differently different from the control group on days 5 and 7 (both p < 0.001). The initial D-value showed a negative correlation with ΔVolume (γ = −0.744, p < 0.001), whereas the initial D*-value and relative change of D-value had a positive correlation with ΔVolume (γ = 0.718, p < 0.001 and γ = 0.800, p < 0.001, respectively). MVD was strongly positively correlated with D*-value (r = 0.886, p = 0.019), PCNA was negatively correlated with ADC- and D-values (r = −0.848, p = 0.033; and r = −0.928 p = 0.008, respectively), and Hif-1α was strongly negatively correlated with D*-value (r = −0.879, p = 0.010).

Conclusion

IVIM-DWI was sensitive and accurate in predicting and monitoring the effects of early anti-angiogenesis therapy in a C6 glioma rat model.
Randomized Trial on Echocardiography-Guided Ductus Arteriosus Treatment to Reduce Necrotizing Enterocolitis
Authors: Bravo María Carmen , Sánchez-Salmador Rebeca , Moral-Pumarega María Teresa , López-Azorín Manuela , Mosqueda-Peña Rocío , Dorronsoro Izaskun , Cabañas Fernando , Pellicer Adelina
Published: January 2022

Objective

Patent ductus arteriosus (PDA) approach remains controversial. We aim to evaluate whether echocardiography-guided (EchoG) PDA closure (to reduce drug exposure) and 24-h continuous ibuprofen infusion (24 h-IB) (to reduce peak concentration), compared with EchoG PDA closure plus conventional bolus (bolus-IB), reduces severe bowel adverse event rate in preterm infants with hemodynamically significant (hs) PDA.

Study Design

The study design is a multicenter, blinded, randomized controlled trial. Infants with <28 weeks of gestation underwent routine echocardiographic assessment (18–72 h of birth); infants with 28–33 weeks were screened only in cases where PDA was clinically suspected. HsPDA was considered if ductal diameter >1.5 mm and indicators of pulmonary overflow, systemic hypoperfusion, or both were present. Pharmacodynamic effect of CYP450 genotypes was also analyzed.

Results

One hundred forty-six infants [median gestational age 26 (25–28) weeks; median birth weight 881 (704–1,100) g] were randomized to 24 h-IB (n = 70) or bolus-IB (n = 76) study group at 86 (58–140) h from birth. Groups were comparable regarding perinatal and neonatal clinical data, but higher prevalence of male sex in the bolus-IB group was found. Neither severe bowel adverse event rate [10% (24 h-IB) and 2.6% (bolus-IB), p = 0.1] nor ductal closure rate was different between the study groups. Postnatal age and peripheral SaO2 at treatment start and pulmonary hemorrhage were associated with severe bowel events, independent of treatment group allocation. CYP2C8 genetic polymorphisms were associated with ibuprofen efficacy (p = 0.03).

Conclusions

Ibuprofen intravenous continuous infusion compared with bolus infusion in preterm infants with hsPDA shows similar rates of success and does not reduce the prevalence of severe bowel events.
The Role of Forkhead Box Family in Bone Metabolism and Diseases
Authors: Xu Jianxiang , Wang Kanbin , Zhang Zengjie , Xue Deting , Li Weixu , Pan Zhijun
Published: January 2022

Forkhead box (Fox) family, an evolutionarily conserved family of transcription factors carrying the “Forkhead” motif, plays an indispensable role in human health and disease. Fox family genes are involved in cell differentiation, proliferation and apoptosis, embryonic development, aging, glucose and lipid metabolism, and immune regulation. The regulatory role of the Fox family in the context of bone metabolism and orthopedic diseases is an emerging research hotspot. In this review, we highlight the major molecular mechanisms underlying the regulatory role of Fox factors in bone metabolism, bone development, bone homeostasis, and bone diseases associated with inhibition or upregulation of Fox factors. In addition, we discuss the emerging evidence in the realm of Fox factor-based therapeutics.
Cyclooxygenase 2 Effector Genes as Potential Inflammation-Related Biomarkers for Colorectal Cancer Circulating Tumor Cells Detection by Liquid Biopsy
Authors: Stamatakis Konstantinos , Torres-Gérica Patricia , Jiménez-Segovia Alba , Ramos-Muñoz Edurne , Crespo-Toro Lorena , Fuentes Patricia , Toribio María L. , Callejas-Hernández Francisco , Carrato Alfredo , García Bermejo María Laura , Fresno Manuel
Published: January 2022

Cyclooxygenase 2 (COX2) has been implicated in cancer development and metastasis. We have identified several COX2-regulated inflammation-related genes in human colorectal cancer cells and shown that some of them play important roles in tumor progression. In this work, we have studied the COX2-regulated genes in the mouse colorectal cancer cell line CT26, to find that many are also regulated by COX2 over-expression. On the other hand, we generated a CT26 cell line expressing Gfp and Luciferase, to study tumor growth and metastasis in immunocompetent Balb/c mice. We then collected solid tissue, and blood samples, from healthy and tumor-bearing mice. Using the Parsortix® cell separation system and taking advantage of the fact that the tumor cells expressed Gfp, we were able to identify circulating tumor cells (CTCs) in some of the mice. We compared the mRNA expression levels of Ptgs2 and effector genes in the samples obtained from tumor-bearing or healthy mice, namely, tumor or healthy colon, Ficoll purified buffy coat, and Parsortix-isolated cells to find different patterns between healthy, tumor-bearing mice with or without CTCs. Although for genes like Il15 we did not observe any difference between healthy and tumor-bearing mice in Ficoll or Parsortix samples; others, such as Egr1, Zc3h12a, Klf4, or Nfat5, allowed distinguishing for cancer or CTC presence. Gene expression analysis in Ficoll or Parsortix processed samples, after liquid biopsy, may offer valuable diagnostic and prognostic information and thus should be further studied.
The Efficacy and Health Economics of Different Treatments for Type 1 Cesarean Scar Pregnancy
Authors: Hong Tingting , Chai Zeying , Liu Manman , Zheng Lingzhi , Qi Feng
Published: January 2022

Objectives: To evaluate the efficacy and health economics of four treatments for type 1 cesarean scar pregnancy (CSP).

Methods: From January 2009 to December 2018, 326 patients diagnosed with type 1 CSP were examined, among whom 31 received ultrasound-guided local injection of methotrexate (local injection group), 160 patients received uterine artery embolization combined with suction aspiration (UAE group), 25 patients received ultrasound-guided suction aspiration (aspiration group) and 90 received ultrasound-guided local injection of lauromacrogol combined with suction aspiration (lauromacrogol group). Clinical data and outcomes were analyzed. The decision tree model was used to compare the economics of four treatments.

Results: The success rate of the local injection group was 71.0% (22/31), which was significantly different from 98.8% (158/160) of the UAE group and 100.0% (90/90) of the lauromacrogol group. The success rate of the aspiration group was 92.0% (23/25), which was significantly lower than that of the lauromacrogol group. The cost-effectiveness ratio was 1,876.53 yuan for the aspiration group, 2,164.63 yuan for the lauromacrogol group, 4,383.56 yuan for the local injection group, and 7,850.81 yuan for the UAE group. The Incremental cost effectiveness ratio (ICER) of the lauromacrogol group to the aspiration group was 5,477.75 yuan, indicating that if the willing to pay of patients was higher than 5,477.75 yuan, the lauromacrogol group had a cost-effectiveness advantage in treating type 1 CSP, compared to aspiration group. On the contrary, aspiration group has a higher cost-effectiveness advantage. The ICER of the lauromacrogol group to the local injection group or the UAE group were both less than 0, indicating that local injection group and UAE group was not cost-effective in the treatment of type 1 CSP.

Conclusion: For type 1 CSP, the ultrasound-guided local injection of lauromacrogol combined with suction aspiration and ultrasound-guided suction aspiration, are effective and economical, and the choice between the two can be based on the patient’s willing to pay.
Applications and Biocompatibility of Mesoporous Silica Nanocarriers in the Field of Medicine
Authors: Zhang Chengcheng , Xie Hongyi , Zhang Zhengyan , Wen Bingjian , Cao Hua , Bai Yan , Che Qishi , Guo Jiao , Su Zhengquan
Published: January 2022

Mesoporous silica nanocarrier (MSN) preparations have a wide range of medical applications. Studying the biocompatibility of MSN is an important part of clinical transformation. Scientists have developed different types of mesoporous silica nanocarriers (MSNs) for different applications to realize the great potential of MSNs in the field of biomedicine, especially in tumor treatment. MSNs have achieved good results in diagnostic bioimaging, tissue engineering, cancer treatment, vaccine development, biomaterial application and diagnostics. MSNs can improve the therapeutic efficiency of drugs, introduce new drug delivery strategies, and provide advantages that traditional drugs lack. It is necessary not only to innovate MSNs but also to comprehensively understand their biological distribution. In this review, we summarize the various medical uses of MSN preparations and explore the factors that affect their distribution and biocompatibility in the body based on metabolism. Designing more reasonable therapeutic nanomedicine is an important task for the further development of the potential clinical applications of MSNs.
Ethanol- and Cigarette Smoke-Related Alternations in Oral Redox Homeostasis
Authors: Zięba Sara , Maciejczyk Mateusz , Zalewska Anna
Published: January 2022

Alcohol abuse as well as smoking cigarettes has been proven to negatively affect the oral environment. The aim of this work was to provide a systematic review of the literature on the influence of ethanol and cigarette smoking on oral redox homeostasis. A search was performed for scientific articles indexed in the PubMed, Medline and Web of Science databases. We identified 32,300 articles, of which 54 were used for the final review, including the results from 2000 to 2021. Among the publications used to write this article, n = 14 were related to the influence of alcohol consumption (clinical studies n = 6, experimental studies n = 8) and n = 40 were related to the influence of smoking (clinical studies n = 33, experimental studies n = 7) on oral redox homeostasis. The reviewed literature indicates that alcohol abusers and smokers are more likely to suffer from salivary gland dysfunction, as well as develop precancerous lesions due to DNA damage. Compared to alcohol abstainers and non-smokers, alcohol drinkers and smokers are also characterized by a deterioration in periodontal health measured by various indicators of periodontal status. In summary, alcohol abuse and smoking are associated with disrupted oral redox homeostasis, which may lead not only to tooth loss, but also contribute to various adverse effects related to mental health, digestive processes and chronic inflammation throughout the human body.
Predictive Roles of Thinking Styles in Coping Strategies Among Mainland Postgraduate Students in Hong Kong
Authors: Chen Siyao
Published: January 2022

The primary objective of the present research was to explore the statistical predictive power of thinking styles in coping strategies beyond demographic factors. One hundred and forty-eight mainland postgraduate students were administered to the Thinking Styles Inventory-Revised II (TSI-R2) and the Coping Orientation to Problems Experienced (COPE) Revised. Results indicated that Type I thinking styles primarily predicted adaptive coping strategies, while Type II thinking styles positively contributed to maladaptive coping strategies. Results in the present research were largely in the expected directions beyond the influence of demographic factors. Furthermore, thinking styles varied as a function of age, gender, gender-role orientation, and marital status. Implications for postgraduate students, academics, university administrators, and the limitations of the research, are discussed.