bluuebunny/crossref_metadata_2025 huggingface dataset:
Milk lactose protects against porcine group A rotavirus infection
Authors: Ren Xiaolei , Saleem Waqar , Haes Robin , Xie Jiexiong , Theuns Sebastiaan , Nauwynck Hans J.
Published: August 2022

Rotavirus A (RVA) is an important pathogen causing acute gastroenteritis in animals and humans. Attachment to the host receptor is a crucial step for virus replication. The VP8* domain is the distal terminal region of the RVA spike protein VP4 (expressed by the P gene) and is important for rotavirus binding and infectivity. Recent studies have indicated a role for non-sialylated glycans, including mucin core 2 and histo-blood group antigens (HBGAs), in the infectivity of human and animal group A rotaviruses. In the present study, we determined if porcine rotavirus-derived recombinant VP8* of the endemic strains 14R103 G5P[6], 13R054 G5P[7], 12R010 G4P[13], 12R046 G9P[23], and 12R022 G2P[27] interact with hitherto uncharacterized glycans. We successfully produced five recombinant GST-VP8* proteins of genotype P[6], P[7], P[13], P[23], and P[27]. The hemagglutination assay showed genotypes P[7] and P[23] hemagglutinate porcine and human red blood cells. In an array screen of > 300 glycans, recombinant VP8* of rotavirus genotype P[6], P[7], and P[13] showed specific binding to glycans with a Gal-β-1,4-Glc (β-lactose) motif, which forms the core structure of HBGAs. The specificity of glycan-binding was confirmed through an ELISA-based oligosaccharide binding assay. Further, 13R054 G5P[7] and 12R046 G9P[23] infectivity was significantly reduced by β-lactose in MA104 cells and primary porcine enterocytes. These data suggest that lactose, the main natural sugar in milk, plays an important role in protecting piglets from enteric viral replication and diarrhea.
Biophysical characterisation of the Bcl-x pre-mRNA and binding specificity of the ellipticine derivative GQC-05: Implication for alternative splicing regulation
Authors: Bhogadia Mohammed , Stone Beth , Del Villar Guerra Rafael , Muskett Frederick W. , Ghosh Sudipta , Taladriz-Sender Andrea , Burley Glenn A. , Eperon Ian C. , Hudson Andrew J. , Dominguez Cyril
Published: August 2022

The BCL2L1 gene expresses two isoforms of Bcl-x protein via the use of either of two alternative 5′ splice sites (5′ss) in exon 2. These proteins have antagonistic actions, Bcl-XL being anti-apoptotic and Bcl-XS pro-apoptotic. In a number of cancers the Bcl-XL isoform is over-expressed, resulting in cancer cell survival and growth, so switching splicing to the Xs isoform could have therapeutic benefits. We have previously proposed that a putative G-quadruplex (G4) exists downstream of the XS 5′ss and shown that the ellipticine derivative GQC-05, a previously identified DNA G4-specific ligand, induces an increase in the XS/XL ratio both in vitro and in cells. Here, we demonstrate that this G4 forms in vitro and that the structure is stabilised in the presence of GQC-05. We also show that GQC-05 binds RNA non-specifically in buffer conditions, but selectively to the Bcl-x G4 in the presence of nuclear extract, highlighting the limitations of biophysical measurements taken outside of a functional environment. We also demonstrate that GQC-05 is able to shift the equilibrium between competing G4 and duplex structures towards the G4 conformation, leading to an increase in accessibility of the XS 5′ss, supporting our previous model on the mechanism of action of GQC-05.
The link between ferroptosis and airway inflammatory diseases: A novel target for treatment
Authors: Lin Zhiwei , Yang Xiaojing , Guan Lili , Qin Lijie , Ding Jiabin , Zhou Luqian
Published: August 2022

Ferroptosis is an iron-dependent mode of cell death characterized by intracellular lipid peroxide accumulation and a redox reaction imbalance. Compared with other modes of cell death, ferroptosis has specific biological and morphological features. The iron-dependent lipid peroxidation accumulation is manifested explicitly in the abnormal metabolism of intracellular lipid oxides catalyzed by excessive iron ions with the production of many reactive oxygen species and over-oxidization of polyunsaturated fatty acids. Recent studies have shown that various diseases, which include intestinal diseases and cancer, are associated with ferroptosis, but few studies are related to airway inflammatory diseases. This review provides a comprehensive analysis of the primary damage mechanisms of ferroptosis and summarizes the relationship between ferroptosis and airway inflammatory diseases. In addition to common acute and chronic airway inflammatory diseases, we also focus on the progress of research on COVID-19 in relation to ferroptosis. New therapeutic approaches and current issues to be addressed in the treatment of inflammatory airway diseases using ferroptosis are further proposed.
Body mass index related to executive function and hippocampal subregion volume in subjective cognitive decline
Authors: Chen Ruilin , Cai Guiyan , Xu Shurui , Sun Qianqian , Luo Jia , Wang Yajun , Li Ming , Lin Hui , Liu Jiao
Published: August 2022

Objective

This study aims to explore whether body mass index (BMI) level affects the executive function and hippocampal subregion volume of subjective cognitive decline (SCD).

Materials and methods

A total of 111 participants were included in the analysis, including SCD (38 of normal BMI, 27 of overweight and obesity) and normal cognitive control (NC) (29 of normal BMI, 17 of overweight and obesity). All subjects underwent the Chinese version of the Stroop Color-Word Test (SCWT) to measure the executive function and a high-resolution 3D T1 structural image acquisition. Two-way ANOVA was used to examine the differences in executive function and gray matter volume in hippocampal subregions under different BMI levels between the SCD and NC.

Result

The subdimensions of executive function in which different BMI levels interact with SCD and NC include inhibition control function [SCWT C-B reaction time(s): F(1,104) = 5.732, p = 0.018], and the hippocampal subregion volume of CA1 [F(1,99) = 8.607, p = 0.004], hippocampal tail [F(1,99) = 4.077, p = 0.046], and molecular layer [F(1,99) = 6.309, p = 0.014]. After correction by Bonferroni method, the population × BMI interaction only had a significant effect on the CA1 (p = 0.004). Further analysis found that the SCWT C-B reaction time of SCD was significantly longer than NC no matter whether it is at the normal BMI level [F(1,104) = 4.325, p = 0.040] or the high BMI level [F(1,104) = 21.530, p < 0.001], and the inhibitory control function of SCD was worse than that of NC. In the normal BMI group, gray matter volume in the hippocampal subregion (CA1) of SCD was significantly smaller than that of NC [F(1,99) = 4.938, p = 0.029]. For patients with SCD, the high BMI group had worse inhibitory control function [F(1,104) = 13.499, p < 0.001] and greater CA1 volume compared with the normal BMI group [F(1,99) = 7.619, p = 0.007].

Conclusion

The BMI level is related to the inhibition control function and the gray matter volume of CA1 subregion in SCD. Overweight seems to increase the gray matter volume of CA1 in the elderly with SCD, but it is not enough to compensate for the damage to executive function caused by the disease. These data provide new insights into the relationship between BMI level and executive function of SCD from the perspective of imaging.
The roles, mechanism, and mobilization strategy of endogenous neural stem cells in brain injury
Authors: Liu Haijing , Wei Tao , Huang Qin , Liu Wei , Yang Yaopeng , Jin Yaju , Wu Danli , Yuan Kai , Zhang Pengyue
Published: August 2022

Brain injury poses a heavy disease burden in the world, resulting in chronic deficits. Therapies for brain injuries have been focused on pharmacologic, small molecule, endocrine and cell-based therapies. Endogenous neural stem cells (eNSCs) are a group of stem cells which can be activated in vivo by damage, neurotrophic factors, physical factor stimulation, and physical exercise. The activated eNSCs can proliferate, migrate and differentiate into neuron, oligodendrocyte and astrocyte, and play an important role in brain injury repair and neural plasticity. The roles of eNSCs in the repair of brain injury include but are not limited to ameliorating cognitive function, improving learning and memory function, and promoting functional gait behaviors. The activation and mobilization of eNSCs is important to the repair of injured brain. In this review we describe the current knowledge of the common character of brain injury, the roles and mechanism of eNSCs in brain injury. And then we discuss the current mobilization strategy of eNSCs following brain injury. We hope that a comprehensive awareness of the roles and mobilization strategy of eNSCs in the repair of cerebral ischemia may help to find some new therapeutic targets and strategy for treatment of stroke.
Afferent and efferent projections of the rostral anterior cingulate cortex in young and middle-aged mice
Authors: Ma Xinyi , Yu Wei , Yao Ping’an , Zhu Yichen , Dai Jiale , He Xiaofen , Liu Boyu , Xu Chi , Shao Xiaomei , Fang Jianqiao , Shen Zui
Published: August 2022

Research shows that across life, the incidence of mental illness is highest in the young. In the context of the COVID-19 pandemic, mental health issues of the young in particular have received global attention. The rostral anterior cingulate cortex (rACC) plays an important role in psychiatric disorders and chronic pain-psychiatric comorbidities. However, it remains unknown whether or how the afferent and efferent circuits of the rACC change with aging. In this study, we microinjected a retrograde tracer virus and an anterograde trans-monosynaptic virus into the rACC of young and middle-aged mice (both male and female), and systematically and quantitatively analyzed the whole-brain afferent and efferent connections of rACC at different ages and sexes. Notably, in young and middle-aged mice, afferents of the rACC belong to four groups of brain structures arising mainly from the amygdala [mainly basolateral amygdaloid nucleus (BLA)] and cerebral cortex (mainly orbital cortex), with a small part originating from the basal forebrain and thalamus. In contrast, efferents of the rACC belong to four groups of brain structures mainly projecting to the thalamus (mainly ventral anterior-lateral/ventromedial thalamic nucleus (VAL/VM)], with a very small part projecting to the amygdala, basal forebrain, and cerebral cortex. Compared with young mice, the BLA-rACC circuit in middle-aged mice (male and female) did not change significantly, while the rACC-VAL/VM circuit in middle-aged mice (male and female) decreased significantly. In conclusion, this study comprehensively analyzed the input-output neural projections of rACC in mice of different ages and sexes and provided preliminary evidence for further targeted research.
Glutamatergic pathways in the brains of turtles: A comparative perspective among reptiles, birds, and mammals
Authors: Hussan Mohammad Tufazzal , Sakai Akiko , Matsui Hideaki
Published: August 2022

Glutamate acts as the main excitatory neurotransmitter in the brain and plays a vital role in physiological and pathological neuronal functions. In mammals, glutamate can cause detrimental excitotoxic effects under anoxic conditions. In contrast,Trachemys scripta, a freshwater turtle, is one of the most anoxia-tolerant animals, being able to survive up to months without oxygen. Therefore, turtles have been investigated to assess the molecular mechanisms of neuroprotective strategies used by them in anoxic conditions, such as maintaining low levels of glutamate, increasing adenosine and GABA, upregulating heat shock proteins, and downregulating KATPchannels. These mechanisms of anoxia tolerance of the turtle brain may be applied to finding therapeutics for human glutamatergic neurological disorders such as brain injury or cerebral stroke due to ischemia. Despite the importance of glutamate as a neurotransmitter and of the turtle as an ideal research model, the glutamatergic circuits in the turtle brain remain less described whereas they have been well studied in mammalian and avian brains. In reptiles, particularly in the turtle brain, glutamatergic neurons have been identified by examining the expression of vesicular glutamate transporters (VGLUTs). In certain areas of the brain, some ionotropic glutamate receptors (GluRs) have been immunohistochemically studied, implying that there are glutamatergic target areas. Based on the expression patterns of these glutamate-related molecules and fiber connection data of the turtle brain that is available in the literature, many candidate glutamatergic circuits could be clarified, such as the olfactory circuit, hippocampal–septal pathway, corticostriatal pathway, visual pathway, auditory pathway, and granule cell–Purkinje cell pathway. This review summarizes the probable glutamatergic pathways and the distribution of glutamatergic neurons in the pallium of the turtle brain and compares them with those of avian and mammalian brains. The integrated knowledge of glutamatergic pathways serves as the fundamental basis for further functional studies in the turtle brain, which would provide insights on physiological and pathological mechanisms of glutamate regulation as well as neural circuits in different species.
A 6-month trial of memantine for nystagmus and associated phenomena in oculopalatal tremor
Authors: Martins Ana Inês , Soares-dos-Reis Ricardo , Jorge André , Duque Cristina , Pereira Daniela Jardim , Fontes Ribeiro Carlos , Sargento-Freitas João , Matos Anabela , Negrão Luís , Lemos João
Published: August 2022

Introduction

Oculopalatal tremor (OPT) is a late manifestation of a Guillain-Mollaret triangle lesion. Memantine has been shown to improve nystagmus in OPT, but its long-term efficacy and putative distinct effects on each plane of nystagmus and on associated phenomena (e.g., gravity perception) are largely unknown.

Methods

We conducted a 6-month open-label study to evaluate the effect of memantine in OPT patients. Baseline (visit 1), 2 (visit 2), and 6 months (visit 3) assessments included video-oculography, best corrected visual acuity (BCVA), visual function questionnaire (VFQ25), palatal tremor frequency, and subjective visual vertical (SVV). Memantine was titrated to 20 mg per day and stopped after 6 months.

Results

We included six patients (5 females; mean age 68.5+/-9.7). At visit 2, nystagmus improved >50% only along the horizontal plane in two patients, while worsening >50% along the vertical and horizontal planes in 4 and 1 patients, respectively. At visit 3, previous improvement of nystagmus along the horizontal plane in two patients was not sustained, and it further worsened >50% along the vertical plane in 4. The mean vertical velocity and amplitude of nystagmus in the left eye significantly worsened from visit 2 to visit 3 (p = 0.028). Throughout the study, nystagmus frequency remained unchanged (p = 0.074), BCVA improved in both eyes (p = 0.047, p = 0.017), SVV progression was unpredictable (p = 0.513), and the mean VFQ-25 score (p = 0.223) and mean palatal frequency remained unchanged.

Conclusion

The long-term use of memantine 20 mg per day in OPT produced a modest and only transient improvement in nystagmus, predominantly along the horizontal plane. Visual acuity improved, albeit without relevant changes in vision-related quality of life.
Effectiveness and safety of acupuncture for post-stroke spasticity: A systematic review and meta-analysis
Authors: Xue Chen , Jiang Chengzhi , Zhu Yuanyuan , Liu Xiaobo , Zhong Dongling , Li Yuxi , Zhang Huiling , Tang Wenjing , She Jian , Xie Cheng , Li Juan , Feng Yue , Jin Rongjiang
Published: August 2022

Objective

This systematic review and meta-analysis aimed to comprehensively evaluate the effectiveness and safety of acupuncture for post-stroke spasticity.

Methods

Nine electronic databases were searched from their inception to 6 June 2022, to identify randomized-controlled trials (RCTs) that investigated the effectiveness and safety of acupuncture for post-stroke spasticity. Two reviewers independently screened the studies, extracted the data, assessed the risk of bias. The reporting quality of interventions in controlled trials of acupuncture was evaluated using Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). The RevMan 5.4 and R 4.2.0 software were used for statistical analysis.

Results

A total of 88 eligible studies were included, involving 6,431 individuals. The pooled data demonstrated that acupuncture combined with conventional rehabilitation (CR) was superior to CR in reducing the Modified Ashworth Scale (MAS) score (standardized mean difference [SMD] = −0.73; 95% CI = −0.83 to −0.63; I2 = 65%; low certainty of evidence). The favorable results were also observed in comparisons of acupuncture vs. CR (SMD = −0.22, 95% CI = −0.36 to −0.07; I2 = 49%; moderate certainty of evidence). Subgroup analysis showed that acupuncture treatment with a frequency of once or twice a day was more effective than CR. In addition, the antispasmodic effect of acupuncture treatment increased with more sessions. Four studies explicitly reported slight acupuncture-related adverse events.

Conclusion

Acupuncture could be recommended as adjuvant therapy for spasticity after stroke. However, due to the high risk of bias and heterogeneity of the included studies, the effectiveness of acupuncture for post-stroke spasticity remains to be confirmed.
Application of extracorporeal shock wave therapy in nervous system diseases: A review
Authors: Guo Juan , Hai Hong , Ma Yuewen
Published: August 2022

Neurological disorders are one of the leading causes of morbidity and mortality worldwide, and their therapeutic options remain limited. Recent animal and clinical studies have shown the potential of extracorporeal shock wave therapy (ESWT) as an innovative, safe, and cost-effective option to treat neurological disorders. Moreover, the cellular and molecular mechanism of ESWT has been proposed to better understand the regeneration and repairment of neurological disorders by ESWT. In this review, we discuss the principles of ESWT, the animal and clinical studies involving the use of ESWT to treat central and peripheral nervous system diseases, and the proposed cellular and molecular mechanism of ESWT. We also discuss the challenges encountered when applying ESWT to the human brain and spinal cord and the new potential applications of ESWT in treating neurological disorders.
The influence of different current-intensity transcranial alternating current stimulation on the eyes-open and eyes-closed resting-state electroencephalography
Authors: Wang Yao , Hou Peiyun , Li Wenjing , Zhang Mingxing , Zheng Hongliang , Chen Xiaogang
Published: August 2022

Transcranial alternating current stimulation (tACS) applies a sinusoidal oscillating current to modulate intrinsic oscillatory activity. Relevant studies of tACS have indicated that tACS can increase spontaneous brain activity in the occipital area. However, few studies have compared the effects of tACS with different current intensities on spontaneous brain activity in the occipital region. In this study, 10-Hz tACS was delivered to the occipital region at different current intensities (i.e., 1 and 2 mA). We investigated the effect of the tACS on both eyes-open and eyes-closed resting-state electroencephalography (EEG). A total of 20 subjects and fifteen subjects were recruited to participate in the 1-mA tACS experiment and the 2-mA tACS experiment, respectively. Ten subjects participated in both experiments. The experimental results demonstrated that both 1-mA tACS and 2-mA tACS could increase occipital resting-state EEG activities. For the eyes-open condition, alpha activity elicited by 2-mA tACS increased significantly greater than that elicited by 1-mA tACS, while 1-mA tACS could produce greater alpha activity compared to 2 mA for the eyes-closed condition. These results suggested that the optimal current intensity might be different for the eyes-open and eyes-closed resting-state conditions, laying a foundation for the subsequent study of occipital tACS on task-state EEG activities.
Sex differences in gene regulatory networks during mid-gestational brain development
Authors: Toledo Victor Hugo Calegari de , Feltrin Arthur Sant'Anna , Barbosa André Rocha , Tahira Ana Carolina , Brentani Helena
Published: August 2022

Neurodevelopmental disorders differ considerably between males and females, and fetal brain development is one of the most critical periods to determine risk for these disorders. Transcriptomic studies comparing male and female fetal brain have demonstrated that the highest difference in gene expression occurs in sex chromosomes, but several autossomal genes also demonstrate a slight difference that has not been yet explored. In order to investigate biological pathways underlying fetal brain sex differences, we applied medicine network principles using integrative methods such as co-expression networks (CEMiTool) and regulatory networks (netZoo). The pattern of gene expression from genes in the same pathway tend to reflect biologically relevant phenomena. In this study, network analysis of fetal brain expression reveals regulatory differences between males and females. Integrating two different bioinformatics tools, our results suggest that biological processes such as cell cycle, cell differentiation, energy metabolism and extracellular matrix organization are consistently sex-biased. MSET analysis demonstrates that these differences are relevant to neurodevelopmental disorders, including autism.
Temporal and spatial dynamic propagation of electroencephalogram by combining power spectral and synchronization in childhood absence epilepsy
Authors: Zhong Lisha , Wan Jiangzhong , Wu Jia , He Suling , Zhong Xuefei , Huang Zhiwei , Li Zhangyong
Published: August 2022

Objective

During the transition from normal to seizure and then to termination, electroencephalography (EEG) signals have complex changes in time-frequency-spatial characteristics. The quantitative analysis of EEG characteristics and the exploration of their dynamic propagation in this paper would help to provide new biomarkers for distinguishing between pre-ictal and inter-ictal states and to better understand the seizure mechanisms.

Methods

Thirty-three children with absence epilepsy were investigated with EEG signals. Power spectral and synchronization were combined to provide the time-frequency-spatial characteristics of EEG and analyze the spatial distribution and propagation of EEG in the brain with topographic maps. To understand the mechanism of spatial-temporal evolution, we compared inter-ictal, pre-ictal, and ictal states in EEG power spectral and synchronization network and its rhythms in each frequency band.

Results

Power, frequency, and spatial synchronization are all enhanced during the absence seizures to jointly dominate the epilepsy process. We confirmed that a rapid diffusion at the onset accompanied by the frontal region predominance exists. The EEG power rapidly bursts in 2–4 Hz through the whole brain within a few seconds after the onset. This spatiotemporal evolution is associated with spatial diffusion and brain regions interaction, with a similar pattern, increasing first and then decreasing, in both the diffusion of the EEG power and the connectivity of the brain network during the childhood absence epilepsy (CAE) seizures. Compared with the inter-ictal group, we observed increases in power of delta and theta rhythms in the pre-ictal group (P < 0.05). Meanwhile, the synchronization of delta rhythm decreased while that of alpha rhythm enhanced.

Conclusion

The initiation and propagation of CAE seizures are related to the abnormal discharge diffusion and the synchronization network. During the seizures, brain activity is completely changed with the main component delta rhythm. Furthermore, this article demonstrated for the first time that alpha inhibition, which is consistent with the brain’s feedback regulation mechanism, is caused by the enhancement of the network connection. Temporal and spatial evolution of EEG is of great significance for the transmission mechanism, clinical diagnosis and automatic detection of absence epilepsy seizures.
Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging
Authors: Maharjan Surendra , Tsai Andy P. , Lin Peter B. , Ingraham Cynthia , Jewett Megan R. , Landreth Gary E. , Oblak Adrian L. , Wang Nian
Published: August 2022

Purpose

To evaluate the age-dependent microstructure changes in 5xFAD mice using high-resolution diffusion tensor imaging (DTI).

Methods

The 5xFAD mice at 4, 7.5, and 12 months and the wild-type controls at 4 months were scanned at 9.4T using a 3D echo-planar imaging (EPI) pulse sequence with the isotropic spatial resolution of 100 μm. The b-value was 3000 s/mm2 for all the diffusion MRI scans. The samples were also acquired with a gradient echo pulse sequence at 50 μm isotropic resolution. The microstructure changes were quantified with DTI metrics, including fractional anisotropy (FA) and mean diffusivity (MD). The conventional histology was performed to validate with MRI findings.

Results

The FA values (p = 0.028) showed significant differences in the cortex between wild-type (WT) and 5xFAD mice at 4 months, while hippocampus, anterior commissure, corpus callosum, and fornix showed no significant differences for either FA and MD. FA values of 5xFAD mice gradually decreased in cortex (0.140 ± 0.007 at 4 months, 0.132 ± 0.008 at 7.5 months, 0.126 ± 0.013 at 12 months) and fornix (0.140 ± 0.007 at 4 months, 0.132 ± 0.008 at 7.5 months, 0.126 ± 0.013 at 12 months) with aging. Both FA (p = 0.029) and MD (p = 0.037) demonstrated significant differences in corpus callosum between 4 and 12 months age old. FA and MD were not significantly different in the hippocampus or anterior commissure. The age-dependent microstructure alterations were better captured by FA when compared to MD.

Conclusion

FA showed higher sensitivity to monitor amyloid deposition in 5xFAD mice. DTI may be utilized as a sensitive biomarker to monitor beta-amyloid progression for preclinical studies.
Temporal-spatial dynamic functional connectivity analysis in schizophrenia classification
Authors: Pan Cong , Yu Haifei , Fei Xuan , Zheng Xingjuan , Yu Renping
Published: August 2022

With the development of resting-state functional magnetic resonance imaging (rs-fMRI) technology, the functional connectivity network (FCN) which reflects the statistical similarity of temporal activity between brain regions has shown promising results for the identification of neuropsychiatric disorders. Alteration in FCN is believed to have the potential to locate biomarkers for classifying or predicting schizophrenia (SZ) from healthy control. However, the traditional FCN analysis with stationary assumption, i.e., static functional connectivity network (SFCN) at the time only measures the simple functional connectivity among brain regions, ignoring the dynamic changes of functional connectivity and the high-order dynamic interactions. In this article, the dynamic functional connectivity network (DFCN) is constructed to delineate the characteristic of connectivity variation across time. A high-order functional connectivity network (HFCN) designed based on DFCN, could characterize more complex spatial interactions across multiple brain regions with the potential to reflect complex functional segregation and integration. Specifically, the temporal variability and the high-order network topology features, which characterize the brain FCNs from region and connectivity aspects, are extracted from DFCN and HFCN, respectively. Experiment results on SZ identification prove that our method is more effective (i.e., obtaining a significantly higher classification accuracy, 81.82%) than other competing methods.Post hocinspection of the informative features in the individualized classification task further could serve as the potential biomarkers for identifying associated aberrant connectivity in SZ.
Relative validity and reproducibility of a semi-quantitative food frequency questionnaire to assess fruit and vegetable consumption in school-aged children
Authors: Ilić Ana , Rumbak Ivana , Brečić Ružica , Colić Barić Irena , Bituh Martina
Published: August 2022

Background

Since the beneficial effects of fruit and vegetable (FV) consumption on health are well known due to the synergy of their nutrients and non-nutrients, it is crucial to have good tools to assess the FV intake. A food frequency questionnaire (FFQ) is an adequate method to estimate FV consumption, but it is necessary to relate this dietary method to the geographic and cultural environment. Therefore, this study presented the development of a semi-quantitative FFQ to estimate the FV intake in school-aged children who usually consume cooked homemade and school meals. It also aimed to evaluate the relative validity and reproducibility of the FFQ.

Methods

School-aged children (baseline age 8 years) from 14 primary schools in the city of Zagreb participated in the study during the 2019/2020 school year. Parents/caregivers, together with the children, completed the FFQs and 3-day dietary records (3DDRs). The FFQ was designed to assess the consumption of eight food categories. The FFQ was validated using the 3DDR of 141 children (51.4% of boys), whereas the reproducibility test included the FFQ of 161 children (53.4% of boys).

Results

Of the eight food categories, FFQ overestimates the consumption of three and underestimates the consumption of three food categories (p < 0.05; Wilcoxon signed rank test) compared to the 3DDR. De-attenuated correlation coefficients estimated a significant relationship (0.217–0.384) between the FFQ and 3DDR. Cross-classification analysis revealed that overall, 28–41% of children were classified in the same quartile, whereas less than 10% of children were extremely misclassified for all food categories obtained from 3DDR and FFQ1. κw values showed fair agreement for all food categories. The Bland–Altman analysis results showed a relatively small bias for all food categories (median between -11.7 and -54.8 g), with no systematic patterns between the FFQ and 3DDR. No differences were found between food categories estimated with the FFQs on both occasions, and Spearman’s correlation coefficients ranged from 0.664 to 0.712 (p < 0.01). Cronbach’s alpha values (α > 0.700) indicate good internal consistency, and ICCs (range 0.724–0.826; p < 0.01) indicate good reproducibility of the FFQ.

Conclusion

The results indicate reasonable relative validity and acceptable reproducibility of the FFQ for estimating FV consumption among school-aged children.
BTN3A3 inhibits the proliferation, migration and invasion of ovarian cancer cells by regulating ERK1/2 phosphorylation
Authors: Chen Sihan , Li Zhangyun , Wang Yanyan , Fan Shaohua
Published: August 2022

Butyrophilin Subfamily 3 Member A3 (BTN3A3) is a type I transmembrane protein belonging to the immunoglobulin (Ig) superfamily, which is expressed in many cancers. Clinical data show that ovarian cancer patients with high expression of BTN3A3 have a longer survival time, but the mechanism of BTN3A3 in the occurrence and progression of ovarian cancer is still unclear. Here, we found that BTN3A3 knockdown can promote the proliferation, migration and invasion of ovarian cancer cells, while overexpression of BTN3A3 can inhibit the proliferation, migration and invasion of ovarian cancer cells. We analyzed the immunoprecipitated BTN3A3 complex by mass spectrometry and found that BTN3A3 binds to FGF2, and the overexpression of BTN3A3 leads to a decrease in the protein level of FGF2, which in turn leads to a decrease in the level of phosphorylation of ERK1/2. By increasing the protein level of FGF2, it was found that the level of ERK1/2 phosphorylation also increased. Finally, the cancer promotion phenomenon caused by BTN3A3 knockdown can be improved by using ERK1/2 inhibitor SCH772984. To sum up, BTN3A3 interacts with FGF2, which inhibits FGF2/ERK1/2 axis and ultimately inhibits the proliferation, migration and invasion of ovarian cancer cells. Our results suggest that BTN3A3 may be a prognostic marker and a potential therapeutic target for ovarian cancer.
Targeting O-GlcNAcylation to overcome resistance to anti-cancer therapies
Authors: Very Ninon , El Yazidi-Belkoura Ikram
Published: August 2022

In cancer cells, metabolic reprogramming is associated with an alteration of the O-GlcNAcylation homeostasis. This post-translational modification (PTM) that attaches O-GlcNAc moiety to intracellular proteins is dynamically and finely regulated by the O-GlcNAc Transferase (OGT) and the O-GlcNAcase (OGA). It is now established that O-GlcNAcylation participates in many features of cancer cells including a high rate of cell growth, invasion, and metastasis but little is known about its impact on the response to therapies. The purpose of this review is to highlight the role of O-GlcNAc protein modification in cancer resistance to therapies. We summarize the current knowledge about the crosstalk between O-GlcNAcylation and molecular mechanisms underlying tumor sensitivity/resistance to targeted therapies, chemotherapies, immunotherapy, and radiotherapy. We also discuss potential benefits and strategies of targeting O-GlcNAcylation to overcome cancer resistance.
Ultrasound radiomics in personalized breast management: Current status and future prospects
Authors: Gu Jionghui , Jiang Tian'an
Published: August 2022

Breast cancer is the most common cancer in women worldwide. Providing accurate and efficient diagnosis, risk stratification and timely adjustment of treatment strategies are essential steps in achieving precision medicine before, during and after treatment. Radiomics provides image information that cannot be recognized by the naked eye through deep mining of medical images. Several studies have shown that radiomics, as a second reader of medical images, can assist physicians not only in the detection and diagnosis of breast lesions but also in the assessment of risk stratification and prediction of treatment response. Recently, more and more studies have focused on the application of ultrasound radiomics in breast management. We summarized recent research advances in ultrasound radiomics for the diagnosis of benign and malignant breast lesions, prediction of molecular subtype, assessment of lymph node status, prediction of neoadjuvant chemotherapy response, and prediction of survival. In addition, we discuss the current challenges and future prospects of ultrasound radiomics.
Robot-assisted esophagectomy may improve perioperative outcome in patients with esophageal cancer – a single-center experience
Authors: Betzler Johanna , Elfinger Lea , Büttner Sylvia , Weiß Christel , Rahbari Nuh , Betzler Alexander , Reißfelder Christoph , Otto Mirko , Blank Susanne , Schölch Sebastian
Published: August 2022

Background

Although the introduction of minimally invasive surgical techniques has improved surgical outcomes in recent decades, esophagectomy for esophageal cancer is still associated with severe complications and a high mortality rate. Robot-assisted surgery is already established in certain fields and robot-assisted esophagectomy may be a possible alternative to the standard minimally invasive esophagectomy. The goal of this study was to investigate whether robot assistance in esophagectomy can improve patient outcome while maintaining good oncological control.

Material and methods

Data of all patients who underwent minimally invasive esophagectomy between January 2018 and November 2021 at University Hospital Mannheim was collected retrospectively. Patients were divided into two cohorts according to operative technique (standard minimally invasive (MIE) vs. robot-assisted esophagectomy (RAMIE), and their outcomes compared. In a separate analysis, patients were propensity score matched according to age, gender and histological diagnosis, leading to 20 matching pairs.

Results

95 patients were included in this study. Of those, 71 patients underwent robot-assisted esophagectomy and 24 patients underwent standard minimally invasive esophagectomy. Robot-assisted esophagectomy showed a lower incidence of general postoperative complications (52.1% vs. 79.2%, p=0.0198), surgical complications (42.3% vs. 75.0%, p=0.0055), a lower rate of anastomotic leakage (21.1% vs. 50.0%, p=0.0067), a lower Comprehensive Complication Index (median of 20.9 vs. 38.6, p=0.0065) as well as a shorter duration of hospital stay (median of 15 vs. 26 days, p=0.0012) and stay in the intensive care unit (median of 4 vs. 7 days, p=0.028) than standard minimally invasive surgery. After additionally matching RAMIE and MIE patients according to age, gender and diagnosis, we found significant improvement in the RAMIE group compared to the MIE group regarding the Comprehensive Complication Index (median of 20.9 vs. 38.6, p=0.0276), anastomotic leakage (20% vs. 55%, p=0.0484) and severe toxicity during neoadjuvant treatment (0 patients vs. 9 patients, p=0.005).

Conclusion

Robot-assisted surgery can significantly improve outcomes for patients with esophageal cancer. It may lead to a shorter hospital stay as well as lower rates of complications, including anastomotic leakage.
Predictive value of hematological parameters in testicular salvage: A 12-year retrospective review
Authors: Chen Pengyu , Huang Weipeng , Liu Lei , Chen Nana , Zhou Guanglun , Sun Mengkui , Li Shoulin
Published: August 2022

Purpose

This study aimed to evaluate the predictive value of preoperative hematological parameters for testicular salvage in patients with testicular torsion.

Methods

Clinical data of patients with testicular torsion treated at Shenzhen Children's Hospital from January 2010 to December 2021 were analyzed retrospectively. The data collected included age, symptom duration, degree of spermatic cord torsion, the surgical approach adopted, hematological parameters, and ultrasound results during postoperative follow-up.

Results

The study participants were classified into three groups as follows: the successful testicular salvage group (n = 43), failed testicular salvage group (n = 124), and control group (n = 100). Univariate analysis showed that testicular salvage was related to patient age, duration of symptoms, spermatic cord torsion degree, white blood cell count, lymphocyte count, monocyte count, platelet-lymphocyte ratio, and neutrophil-lymphocyte ratio. However, multivariate analysis revealed that symptom duration (OR = 0.948, P < 0.001), degree of spermatic cord torsion (OR = 0.994, P < 0.001), and monocyte count (OR = 0.020, P = 0.011) were independent risk factors for testicular torsion salvage. The monocyte count in the failed salvage group was significantly higher than in the successful salvage and control groups (P < 0.01).

Conclusion

Monocyte count is an independent predictor of testicular salvage. Therefore, clinicians can predict the success rate of testicular salvage in patients with testicular torsion based on the monocyte count.
Changes in serum metabolomics in idiopathic pulmonary fibrosis and effect of approved antifibrotic medication
Authors: Seeliger Benjamin , Carleo Alfonso , Wendel-Garcia Pedro David , Fuge Jan , Montes-Warboys Ana , Schuchardt Sven , Molina-Molina Maria , Prasse Antje
Published: August 2022

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with significant mortality and morbidity. Approval of antifibrotic therapy has ameliorated disease progression, but therapy response is heterogeneous and to date, adequate biomarkers predicting therapy response are lacking. In recent years metabolomic technology has improved and is broadly applied in cancer research thus enabling its use in other fields. Recently both aberrant metabolic and lipidomic pathways have been described to influence profibrotic responses. We thus aimed to characterize the metabolomic and lipidomic changes between IPF and healthy volunteers (HV) and analyze metabolomic changes following treatment with nintedanib and pirfenidone. We collected serial serum samples from two IPF cohorts from Germany (n = 122) and Spain (n = 21) and additionally age-matched healthy volunteers (n = 16). Metabolomic analysis of 630 metabolites covering 14 small molecule and 12 different lipid classes was carried out using flow injection analysis tandem mass spectrometry for lipids and liquid chromatography tandem mass spectrometry for small molecules. Levels were correlated with survival and disease severity. We identified 109 deregulated analytes in IPF compared to HV in cohort 1 and 112 deregulated analytes in cohort 2. Metabolites which were up-regulated in both cohorts were mainly triglycerides while the main class of down-regulated metabolites were phosphatidylcholines. Only a minority of de-regulated analytes were small molecules. Triglyceride subclasses were inversely correlated with baseline disease severity (GAP-score) and a clinical compound endpoint of lung function decline or death. No changes in the metabolic profiles were observed following treatment with pirfenidone. Nintedanib treatment induced up-regulation of triglycerides and phosphatidylcholines. Patients in whom an increase in these metabolites was observed showed a trend towards better survival using the 2-years composite endpoint (HR 2.46, p = 0.06). In conclusion, we report major changes in metabolites in two independent cohorts testing a large number of patients. Specific lipidic metabolite signatures may serve as biomarkers for disease progression or favorable treatment response to nintedanib.
New strategies for identifying and masking the bitter taste in traditional herbal medicines: The example of Huanglian Jiedu Decoction
Authors: Ke Xiumei , Ma Hongyan , Yang Junxuan , Qiu Min , Wang Jianwei , Han Li , Zhang Dingkun
Published: August 2022

Suppressing the bitter taste of traditional Chinese medicine (TCM) largely has been a major clinical challenge due to complex and diverse metabolites and high dispersion of bitter metabolites in liquid preparations. In this work, we developed a novel strategy for recognizing bitter substances, hiding their bitter taste, and elucidated the mechanism of flavor masking in TCM. Huanglian Jie-Du Decoction (HLJDD) with an intense bitter taste was studied as a typical case. UHPLC-MS/MS was used to analyze the chemical components in HLJDD, whereas the bitter substances were identified by pharmacophores. Additionally, the screening results of the pharmacophores were further validated by using experimental assays. The mask formula of HLJDD was effectively screened under the condition of clear bitter substances. Subsequently, computational chemistry, molecular docking, and infrared characterization (IR) techniques were then used to explicate the mechanism of flavor masking. Consequently, neotame, γ-CD, and mPEG2000-PLLA2000 significantly reduced the bitterness of HLJDD. Specifically, mPEG2000-PLLA2000 increased the colloid proportion in the decoction system and minimized the distribution of bitter components in the real solution. Sweetener neotame suppressed the perception of bitter taste and inhibited bitter taste receptor activation to eventually reduce the bitter taste. The γ-CD included in the decoction bound the hydrophobic groups of the bitter metabolites in real solution and “packed” all or part of the bitter metabolites into the “cavity”. We established a novel approach for screening bitter substances in TCM by integrating virtual screening and experimental assays. Based on this strategy, the bitter taste masking of TCM was performed from three different aspects, namely, changing the drug phase state, component distribution, and interfering with bitter taste signal transduction. Collectively, the methods achieved a significant effect on bitter taste suppression and taste masking. Our findings will provide a novel strategy for masking the taste of TCM liquid preparation/decoction, which will in return help in improving the clinical efficacy of TCM.
Exploring the pathogenesis of diabetic kidney disease by microarray data analysis
Authors: Cao Haiyan , Rao Xiaosheng , Jia Junya , Yan Tiekun , Li Dong
Published: August 2022

Diabetic kidney disease (DKD) is a major complication of diabetes mellitus, and the leading contributor of end-stage renal disease. Hence, insights into the molecular pathogenesis of DKD are urgently needed. The purpose of this article is to reveal the molecular mechanisms underlying the pathogenesis of DKD. The microarray datasets of GSE30528 and GSE30529 were downloaded from the NCBI Gene Expression Omnibus (GEO) database to identify the common differentially expressed genes (DEGs) between the glomerular DKD (GDKD) and tubular DKD (TDKD), respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to analyze the function and pathways of the common DEGs. After constructing the protein–protein interaction (PPI) network and subnetwork analysis, three types of analyses were performed, namely, identification of hub genes, analysis of the coexpressed network, and exploration of transcription factors (TFs). Totally, 348 and 463 DEGs were identified in GDKD and TDKD, respectively. Then, 66 common DEGs (63 upregulated DEGs and three downregulated DEGs) were obtained in DKD patients. GO and KEGG pathway analyses revealed the importance of inflammation response, immune-related pathways, and extracellular matrix-related pathways, especially chemokines and cytokines, in DKD. Fifteen hub genes from the 66 common DEGs, namely, IL10RA, IRF8, LY86, C1QA, C1QB, CD53, CD1C, CTSS, CCR2, CD163, CCL5, CD48, RNASE6, CD52, and CD2 were identified. In summary, through the microarray data analysis, the common functions and hub genes greatly contribute to the elucidation of the molecular pathogenesis associated with DKD.
Characterization of Nasco grape pomace-loaded nutriosomes and their neuroprotective effects in the MPTP mouse model of Parkinson’s disease
Authors: Parekh Pathik , Serra Marcello , Allaw Mohamad , Perra Matteo , Marongiu Jacopo , Tolle Giulia , Pinna Annalisa , Casu Maria Antonietta , Manconi Maria , Caboni Pierluigi , Manzoni Olivier J. J. , Morelli Micaela
Published: August 2022

Grape pomaces have recently received great attention for their richness in polyphenols, compounds known to exert anti-inflammatory and antioxidant effects. These pomaces, however, have low brain bioavailability when administered orally due to their extensive degradation in the gastrointestinal tract. To overcome this problem, Nasco pomace extract was incorporated into a novel nanovesicle system called nutriosomes, composed of phospholipids (S75) and water-soluble maltodextrin (Nutriose® FM06). Nutriosomes were small, homogeneously dispersed, had negative zeta potential, and were biocompatible with intestinal epithelial cells (Caco-2). Nasco pomace extract resulted rich in antioxidant polyphenols (gallic acid, catechin, epicatechin, procyanidin B2, and quercetin). To investigate the neuroprotective effect of Nasco pomace in the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease (PD), Nasco nutriosomes or Nasco suspension was administered intragastrically and their neuroprotective effects were evaluated. Degeneration of nigro-striatal dopaminergic neurons induced by subacute MPTP treatment, the pathological hallmark of PD, was assessed through immunohistochemical evaluation of tyrosine hydroxylase (TH) in the caudate-putamen (CPu) and substantia nigra pars compacta (SNc), and the dopamine transporter (DAT) in CPu. Immunohistochemical analysis revealed that Nasco nutriosomes significantly prevented the reduction in TH- and DAT-positive fibres in CPu, and the number of TH-positive cells in SNc following subacute MPTP treatment, while Nasco suspension counteracted MPTP toxicity exclusively in SNc. Overall, these results highlight the therapeutic effects of Nasco pomace extract when administered in a nutriosome formulation in the subacute MPTP mouse model of PD and validate the effectiveness of the nutriosome preparation over suspension as an innovative nano-drug delivery system for in vivo administration.