bluuebunny/crossref_metadata_2025 huggingface dataset:
Parvalbumin-Positive Interneurons Regulate Cortical Sensory Plasticity in Adulthood and Development Through Shared Mechanisms
Authors: Rupert Deborah D. , Shea Stephen D.
Published: May 2022

Parvalbumin-positive neurons are the largest class of GABAergic, inhibitory neurons in the central nervous system. In the cortex, these fast-spiking cells provide feedforward and feedback synaptic inhibition onto a diverse set of cell types, including pyramidal cells, other inhibitory interneurons, and themselves. Cortical inhibitory networks broadly, and cortical parvalbumin-expressing interneurons (cPVins) specifically, are crucial for regulating sensory plasticity during both development and adulthood. Here we review the functional properties of cPVins that enable plasticity in the cortex of adult mammals and the influence of cPVins on sensory activity at four spatiotemporal scales. First, cPVins regulate developmental critical periods and adult plasticity through molecular and structural interactions with the extracellular matrix. Second, they activate in precise sequence following feedforward excitation to enforce strict temporal limits in response to the presentation of sensory stimuli. Third, they implement gain control to normalize sensory inputs and compress the dynamic range of output. Fourth, they synchronize broad network activity patterns in response to behavioral events and state changes. Much of the evidence for the contribution of cPVins to plasticity comes from classic models that rely on sensory deprivation methods to probe experience-dependent changes in the brain. We support investigating naturally occurring, adaptive cortical plasticity to study cPVin circuits in an ethologically relevant framework, and discuss recent insights from our work on maternal experience-induced auditory cortical plasticity.
The Task Pre-Configuration Is Associated With Cognitive Performance Evidence From the Brain Synchrony
Authors: Xiang Jie , Fan Chanjuan , Wei Jing , Li Ying , Wang Bin , Niu Yan , Yang Lan , Lv Jiaqi , Cui Xiaohong
Published: May 2022

Although many resting state and task state characteristics have been studied, it is still unclear how the brain network switches from the resting state during tasks. The current theory shows that the brain is a complex dynamic system and synchrony is defined to measure brain activity. The study compared the changes of synchrony between the resting state and different task states in healthy young participants (N = 954). It also examined the ability to switch from the resting state to the task-general architecture of synchrony. We found that the synchrony increased significantly during the tasks. And the results showed that the brain has a task-general architecture of synchrony during different tasks. The main feature of task-based reasoning is that the increase in synchrony of high-order cognitive networks is significant, while the increase in synchrony of sensorimotor networks is relatively low. In addition, the high synchrony of high-order cognitive networks in the resting state can promote task switching effectively and the pre-configured participants have better cognitive performance, which shows that spontaneous brain activity and cognitive ability are closely related. These results revealed changes in the brain network configuration for switching between the resting state and task state, highlighting the consistent changes in the brain network between different tasks. Also, there was an important relationship between the switching ability and the cognitive performance.
Different Clinicoradiological Characteristics of Posterior Reversible Encephalopathy Syndrome in Pediatric Oncology and Post-Bone Marrow Transplantation Cases: A Retrospective Study
Authors: Shash Hwazen , Aldaama Saad , Omer Hala , Alafghani Sameera
Published: May 2022

Posterior reversible encephalopathy syndrome (PRES) is receiving increasing recognition in pediatrics. However, comparisons between PRES in pediatric oncology and post-bone marrow transplantation (BMT) are lacking. Therefore, we aimed to describe the risk factors and clinical and radiological features of PRES and investigate the differences between PRES in pediatric oncology and post-BMT. The PRES data of 13 patients from our center were combined with those of 217 cases from the PubMed, Scopus, and Web of Science databases. The patients were divided into either an oncology or a post-BMT group. We included 230 patients in the analysis, 26.1% of whom belonged to the post-BMT group. Oncology patients developed PRES at a younger age (p = 0.010) and were more likely to develop encephalopathy (p = 0.004). Systemic hypertension (S-HTN) preceding PRES occurred in 43.5% (66/154) of patients. Post-BMT patients were more likely to have S-HTN (p = 0.003). Cyclosporine levels were detected in 37 patients; 40.5% had supra-therapeutic levels. The radiological findings were atypical in 74.3% of patients, and delayed repeated imaging increased the occurrence of resolution (p = 0.004). Sixteen (7%) patients developed PRES recurrence after a median of 8 weeks, with the between-group difference being non-significant. Oncology patients were more likely to develop chronic epilepsy, while BMT patients were more likely to develop rare neurologic abnormalities (p < 0.001). In conclusion, atypical clinical presentation and imaging findings should not hinder the diagnosis of PRES. S-HTN is a risk factor, particularly in post-BMT patients. Supra-therapeutic levels of cyclosporine and previous exposure to immunosuppression did not increase the risk of recurrence.
Progressive Brain Structural Impairment Assessed via Network and Causal Analysis in Patients With Hepatitis B Virus-Related Cirrhosis
Authors: Lin Shiwei , Guo Zheng , Chen Shengli , Lin Xiaoshan , Ye Min , Qiu Yingwei
Published: May 2022

Objectives

This research amid to elucidate the disease stage-specific spatial patterns and the probable sequences of gray matter (GM) deterioration as well as the causal relationship among structural network components in hepatitis B virus-related cirrhosis (HBV-RC) patients.

Methods

Totally 30 HBV-RC patients and 38 healthy controls (HC) were recruited for this study. High-resolution T1-weighted magnetic resonance imaging and psychometric hepatic encephalopathy score (PHES) were evaluated in all participants. Voxel-based morphometry (VBM), structural covariance network (SCN), and causal SCN (CaSCN) were applied to identify the disease stage-specific GM abnormalities in morphology and network, as well as their causal relationship.

Results

Compared to HC (0.443 ± 0.073 cm3), the thalamus swelled significantly in the no minimal hepatic encephalopathy (NMHE) stage (0.607 ± 0.154 cm3, p <0.05, corrected) and further progressed and expanded to the bilateral basal ganglia, the cortices, and the cerebellum in the MHE stage (p < 0.05, corrected). Furthermore, the thalamus swelling had a causal effect on other parts of cortex-basal ganglia-thalamus circuits (p < 0.05, corrected), which was negatively correlated with cognitive performance (r = −0.422, p < 0.05). Moreover, the thalamus-related SCN also displayed progressive deterioration as the disease advanced in HBV-RC patients (p < 0.05, corrected).

Conclusion

Progressive deterioration of GM morphology and SCN exists in HBV-RC patients during advanced disease, displaying thalamus-related causal effects. These findings indicate that bilateral thalamus morphology as well as the thalamus-related network may serve as an in vivo biomarker for monitoring the progression of the disease in HBV-RC patients.
Recognition of the Effect of Indirect Revascularization for Moyamoya Disease: The Balance Between the Stage Progression and Neoangiogenesis
Authors: Bao Xiang-Yang , Wang Qian-Nan , Wang Xiao-Peng , Yang Ri-Miao , Zou Zheng-Xing , Zhang Qian , Li De-Sheng , Duan Lian
Published: May 2022

Objective

To explore the long-term progression of neoangiogenesis after indirect revascularization for moyamoya disease (MMD).

Methods

We enrolled patients who were diagnosed with MMD and treated by encephaloduroarteriosynangiosis (EDAS) surgery at our center from December 2002 through September 2009. A comparative study between short-term (6–12 months) and long-term (duration ≥ 8 years) follow-up angiographies was performed. The development of collateral circulation through EDAS was graded according to the system described by the Matsushima grade system.

Results

A total of 78 patients who received indirect EDAS were enrolled in the study. The mean age at the first operation was 26.9 ± 15.0 years. The Matsushima grades of the same hemisphere were higher at the long-term follow-up compared with the short-term follow-up. Importantly, no attenuation was observed in any hemisphere during the long-term follow-up. In total, 51 hemispheres (32.7%) and 26 hemispheres (16.6%) had progression during the short-term and the long-term follow-up, respectively. The ipsilateral Suzuki stage showed a significant negative correlation with progression pace. Furthermore, higher Suzuki stages were significantly correlated with the postsurgical Matsushima grade at both time points. A total of nine strokes (11.5%) occurred in 78 patients was reported at the long-term follow-up. The annual incidence rate of recurrent strokes was higher for the stage progression group than for the stable group.

Conclusion

For patients with MMD, postsurgical neoangiogenesis after indirect bypass continuously improved with time. The short-term progression of the internal carotid artery (ICA) might be attributed to cerebral revascularization, while the long-term progression should be attributed to the natural progression of the disease.
Altered Pain in the Brainstem and Spinal Cord of Fibromyalgia Patients During the Anticipation and Experience of Experimental Pain
Authors: Ioachim Gabriela , Warren Howard J. M. , Powers Jocelyn M. , Staud Roland , Pukall Caroline F. , Stroman Patrick W.
Published: May 2022

Chronic pain associated with fibromyalgia (FM) affects a large portion of the population but the underlying mechanisms leading to this altered pain are still poorly understood. Evidence suggests that FM involves altered neural processes in the central nervous system and neuroimaging methods such as functional magnetic resonance imaging (fMRI) are used to reveal these underlying alterations. While many fMRI studies of FM have been conducted in the brain, recent evidence shows that the changes in pain processing in FM may be linked to autonomic and homeostatic dysregulation, thus requiring further investigation in the brainstem and spinal cord. Functional magnetic resonance imaging data from 15 women with FM and 15 healthy controls were obtained in the cervical spinal cord and brainstem at 3 tesla using previously established methods. In order to investigate differences in pain processing in these groups, participants underwent trials in which they anticipated and received a predictable painful stimulus, randomly interleaved with trials with no stimulus. Differences in functional connectivity between the groups were investigated by means of structural equation modeling. The results demonstrate significant differences in brainstem/spinal cord network connectivity between the FM and control groups which also correlated with individual differences in pain responses. The regions involved in these differences in connectivity included the LC, hypothalamus, PAG, and PBN, which are known to be associated with autonomic homeostatic regulation, including fight or flight responses. This study extends our understanding of altered neural processes associated with FM and the important link between sensory and autonomic regulation systems in this disorder.
Hallucinogenic Persisting Perception Disorder: A Case Series and Review of the Literature
Authors: Ford Hannah , Fraser Clare L. , Solly Emma , Clough Meaghan , Fielding Joanne , White Owen , Van Der Walt Anneke
Published: May 2022

Background

Hallucinogen persisting perception disorder (HPPD) is characterized by the re-emergence of perceptual symptoms experienced during acute hallucinogen intoxication following drug cessation. The underlying pathophysiology is poorly understood. We report the clinical characteristics and investigation findings of a series of HPPD cases with a literature review of previous case reports. We draw parallels between the features of HPPD and Visual Snow Syndrome (VSS).

Methods

Retrospective case series of 13 patients referred from neuro-ophthalmologists. Literature review with 24 HPPD case reports were identified through database search using the terms “hallucinogenic persisting perception disorder” OR “hallucinogen persisting perception disorder.”

Results

Lysergic acid diethylamide (LSD), 3,4-Methyl enedioxy methamphetamine (MDMA) and cannabinoid use was common. Cannabinoids and MDMA were mostly used in association with classical hallucinogens. The most frequent symptoms in our patients were visual snow, floaters, palinopsia, photophobia and nyctalopia. In the literature other symptoms included visual hallucinations altered motion perception, palinopsia, tracers and color enhancement. Ophthalmic and neurologic investigations were mostly normal. The majority of patients had ongoing symptoms. Two of our patients fully recovered—one after treatment with benzodiazepine and one without treatment. Twenty-five percent of cases from the literature fully recovered.

Conclusions

HPPD presents with heterogeneous visual phenomena on a background of previous classic and non-classic hallucinogen use. Ophthalmic investigations are typically normal. The symptoms of HPPD in our case series overlap with the typical features of Visual Snow Syndrome (VSS). Patients presenting with VSS should be screened for past recreational drug use. The DSM-5 description of HPPD does not include visual snow, nyctalopia, photophobia or floaters. A revision of the diagnostic criteria to include these symptoms may better reflect the typical clinical phenotype. Increased awareness of HPPD as a secondary cause of VSS can avoid extensive investigations. Controlled trials comparing primary and secondary VSS patients are needed to understand the pathophysiology better and optimize treatment for HPPD.
Distinct Patterns of Automatic and Controlled Incongruent Information Processing in the Human Brain
Authors: Du Jialin , Zhu Yu , Zhao Chengtian , Yang Dongju , Yu Tao , Zhang Xiaohua , Ren Liankun , Wang Yuping
Published: May 2022

It is a fundamental ability to discriminate incongruent information in daily activity. However, the underlying neural dynamics are still unclear. Using stereoelectroencephalography (SEEG), in this study, we investigated the fine-grained and different states of incongruent information processing in patients with refractory epilepsy who underwent intracranial electrode implantation. All patients performed a delayed match-to-sample paradigm in the sequential pairs of visual stimuli (S1 followed by S2). Participants were asked to discriminate whether the relevant feature of S2 was identical to S1 while ignoring the irrelevant feature. The spatiotemporal cortical responses evoked by different conditions were calculated and compared, respectively, in the context of brain intrinsic functional networks. In total, we obtained SEEG recordings from 241 contacts in gray matter. In the processing of irrelevant incongruent information, the activated brain areas included the superior parietal lobule, supramarginal gyrus, angular gyrus, inferior temporal gyrus, and fusiform gyrus. By comparing the relevant incongruent condition with the congruent condition, the activated brain areas included the middle frontal gyrus, superior temporal gyrus, middle temporal gyrus, posterior superior temporal sulcus, and posterior cingulate cortex. We demonstrated the dynamics of incongruent information processing with high spatiotemporal resolution and suggested that the process of automatic detection of irrelevant incongruent information requires the involvement of local regions and relatively few networks. Meanwhile, controlled discrimination of relevant incongruent information requires the participation of extensive regions and a wide range of nodes in the network. Furthermore, both the frontoparietal control network and default mode network were engaged in the incongruent information processing.
Transcranial Direct Current Stimulation Targeting the Entire Motor Network Does Not Increase Corticospinal Excitability
Authors: Van der Cruijsen Joris , Jonker Zeb D. , Andrinopoulou Eleni-Rosalina , Wijngaarden Jessica E. , Tangkau Ditte A. , Tulen Joke H. M. , Frens Maarten A. , Ribbers Gerard M. , Selles Ruud W.
Published: May 2022

Transcranial direct current stimulation (tDCS) over the contralateral primary motor cortex of the target muscle (conventional tDCS) has been described to enhance corticospinal excitability, as measured with transcranial magnetic stimulation. Recently, tDCS targeting the brain regions functionally connected to the contralateral primary motor cortex (motor network tDCS) was reported to enhance corticospinal excitability more than conventional tDCS. We compared the effects of motor network tDCS, 2 mA conventional tDCS, and sham tDCS on corticospinal excitability in 21 healthy participants in a randomized, single-blind within-subject study design. We applied tDCS for 12 min and measured corticospinal excitability with TMS before tDCS and at 0, 15, 30, 45, and 60 min after tDCS. Statistical analysis showed that neither motor network tDCS nor conventional tDCS significantly increased corticospinal excitability relative to sham stimulation. Furthermore, the results did not provide evidence for superiority of motor network tDCS over conventional tDCS. Motor network tDCS seems equally susceptible to the sources of intersubject and intrasubject variability previously observed in response to conventional tDCS.
Audience Interbrain Synchrony During Live Music Is Shaped by Both the Number of People Sharing Pleasure and the Strength of This Pleasure
Authors: Chabin Thibault , Gabriel Damien , Comte Alexandre , Pazart Lionel
Published: May 2022

The study of interbrain coupling in a group of people attending a concert together is a favorable framework to estimate group emotions and more precisely emotional connection between people sharing situations in the same environment. It offers the advantage of studying interactions at the group level. By recording the cerebral activity of people from an audience during a concert using electroencephalography, we previously demonstrated that the higher the emotions and the physically closer the people were, the more the interbrain synchrony (IBS) was enhanced. To further investigate the parameters that shaped inter-brain synchronization in this context, we now focus on the emotional dynamics of the group as a whole by identifying specific moments in the concert that evoked strong or weak emotions, as well as strong or weak emotional cohesion between individuals. We demonstrated that audience interbrain synchrony is mainly associated with experiencing high musical pleasure and that the group emotional cohesion can enhance IBS, but alone is not the major parameter that shapes it in this context.
Improved Brain–Computer Interface Signal Recognition Algorithm Based on Few-Channel Motor Imagery
Authors: Wang Fan , Liu Huadong , Zhao Lei , Su Lei , Zhou Jianhua , Gong Anmin , Fu Yunfa
Published: May 2022

Common spatial pattern (CSP) is an effective algorithm for extracting electroencephalogram (EEG) features of motor imagery (MI); however, CSP mainly aims at multichannel EEG signals, and its effect in extracting EEG features with fewer channels is poor—even worse than before using CSP. To solve the above problem, a new combined feature extraction method has been proposed in this study. For EEG signals from fewer channels (three channels), wavelet packet transform, fast ensemble empirical mode decomposition, and local mean decomposition were used to decompose the band-pass filtered EEG into multiple time–frequency components, and the corresponding components were selected according to the frequency characteristics of MI or the correlation coefficient between its time–frequency components and the original EEG signal. Furthermore, phase space reconstruction (PSR) was performed on the selected components after the three time-frequency decompositions, the maximum Lyapunov index was calculated, and the features were reconstructed; then, CSP projection mapping was used for the reconstructed features. The support vector machine probability output model was trained by the obtained three mappings. Probability outputs by three different support vector machines were then obtained. Finally, the classification of test samples was determined by the fusion of the Dempster–Shafer evidence theory at the decision level. The results showed that the accuracy of the proposed method was 95.71% on data set III of BCI competition II (left- and right-hand MI), which was 2.88% higher than the existing methods. On data set IIb of BCI competition IV, the average accuracy was 86.60%, which was 2.3% higher than the existing methods. This study verified the effectiveness of the proposed method and provided an approach for the research and development of the MI-BCI system based on fewer channels.
Impaired Glymphatic System Actions in Obstructive Sleep Apnea Adults
Authors: Roy Bhaswati , Nunez Alba , Aysola Ravi S. , Kang Daniel W. , Vacas Susana , Kumar Rajesh
Published: May 2022

Study Objectives

Obstructive sleep apnea (OSA) is accompanied by sleep fragmentation and altered sleep architecture, which can potentially hinder the glymphatic system, increasing risks for Alzheimer’s disease (AD), but the status is unclear in OSA. Our aim was to investigate the glymphatic system in OSA subjects and examine the relationships between OSA disease severity, sleep symptoms, and glymphatic system indices in OSA using diffusion tensor imaging (DTI).

Methods

We acquired DTI data from 59 OSA and 62 controls using a 3.0-Tesla MRI and examined OSA disease severity and sleep symptoms with the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Diffusivity maps in the x-axis (Dxx), y-axis (Dyy), and z-axis (Dzz), as well as in x-y axis (Dxy), y-z axis (Dyz), and x-z axis (Dxz) were calculated, diffusion values for the projection and association fibers extracted, and the DTI analyses along the perivascular space (DTI-ALPS index) were performed. The glymphatic system indices were compared between groups and correlated with disease severity and sleep symptoms in OSA subjects.

Results

Dzz values, derived from projection fiber areas, Dyy and Dzz values from association fiber areas, as well as ALPS and Dyzmean values were significantly reduced in OSA over controls. Significant correlations emerged between disease severity, sleep symptoms, and Dxy, Dxx, and Dzz values in OSA subjects.

Conclusion

OSA patients show abnormal glymphatic system function that may contribute to increased risks for AD. The findings suggest that the APLS method can be used to assess the glymphatic system in OSA patients.
The Altered Pattern of the Functional Connectome Related to Pathological Biomarkers in Individuals for Autism Spectrum Disorder Identification
Authors: Peng Liling , Liu Xiao , Ma Di , Chen Xiaofeng , Xu Xiaowen , Gao Xin
Published: May 2022

Objective

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by the development of multiple symptoms, with incidences rapidly increasing worldwide. An important step in the early diagnosis of ASD is to identify informative biomarkers. Currently, the use of functional brain network (FBN) is deemed important for extracting data on brain imaging biomarkers. Unfortunately, most existing studies have reported the utilization of the information from the connection to train the classifier; such an approach ignores the topological information and, in turn, limits its performance. Thus, effective utilization of the FBN provides insights for improving the diagnostic performance.

Methods

We propose the combination of the information derived from both FBN and its corresponding graph theory measurements to identify and distinguish ASD from normal controls (NCs). Specifically, a multi-kernel support vector machine (MK-SVM) was used to combine multiple types of information.

Results

The experimental results illustrate that the combination of information from multiple connectome features (i.e., functional connections and graph measurements) can provide a superior identification performance with an area under the receiver operating characteristic curve (ROC) of 0.9191 and an accuracy of 82.60%. Furthermore, the graph theoretical analysis illustrates that the significant nodal graph measurements and consensus connections exists mostly in the salience network (SN), default mode network (DMN), attention network, frontoparietal network, and social network.

Conclusion

This work provides insights into potential neuroimaging biomarkers that may be used for the diagnosis of ASD and offers a new perspective for the exploration of the brain pathophysiology of ASD through machine learning.
Mechanism of Electroacupuncture Against Cerebral Ischemia–Reperfusion Injury: Reducing Inflammatory Response and Cell Pyroptosis by Inhibiting NLRP3 and Caspase-1
Authors: Cai Li , Yao Zeng-Yu , Yang Lu , Xu Xiu-Hong , Luo Meng , Dong Miao-Miao , Zhou Guo-Ping
Published: May 2022

Cell pyroptosis is one of the main forms of neuronal injury after cerebral ischemia–reperfusion. It is accompanied by an inflammatory reaction and regulated by the caspase gene family. Electroacupuncture (EA) can reduce neuronal injury caused by cerebral ischemia–reperfusion, and we speculated that EA can prevent neuronal pyroptosis after cerebral ischemia–reperfusion by regulating the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/caspase-1 pathway. The cerebral ischemia–reperfusion injury model of C57 and caspase-1 gene knockout (Cas-1 ko) mice was established by Longa's method. EA was conducted at acupoints Chize (LU5), Hegu (LI4), Sanyinjiao (SP6), and Zusanli (ST36) for 1.5 h after cerebral ischemia–reperfusion injury for 20 min, and observation was carried out after 24 h. Neurological deficit scores evaluated the neurological function, cerebral infarction volume was observed by triphenyl tetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, TUNEL and caspase-1 double-labeled fluorescence staining, and NLRP3 and caspase-1 double-labeled immunofluorescence staining that were used to observe the morphology of neurons in hippocampus, and the protein expression of NLRP3, pro-caspase-1, cleaved caspase-1 p20, pro-interleukin-1β (IL-1β), cleaved IL-1β, and GSDMD was detected by Western blot assay. Results showed that EA could reduce the score of neurological deficit, reduce the volume of cerebral infarction and improve the degree of nerve cell injury, and inhibit NLRP3, pro-caspase-1, cleaved caspase-1 p20, pro-IL-1β, cleaved IL-1β, and GSDMD protein expression. In summary, EA plays a neuroprotective role by reducing the pyroptotic neurons that were caspase 1-mediated and inflammatory response after cerebral ischemia–reperfusion.
Reactive Astrocytes Derived From Human Induced Pluripotent Stem Cells Suppress Oligodendrocyte Precursor Cell Differentiation
Authors: Smith Matthew D. , Chamling Xitiz , Gill Alexander J. , Martinez Hector , Li Weifeng , Fitzgerald Kathryn C. , Sotirchos Elias S. , Moroziewicz Dorota , Bauer Lauren , Paull Daniel , Gharagozloo Marjan , Bhargava Pavan , Zack Donald J. , Fossati Valentina , Calabresi Peter A.
Published: May 2022

Astrocytes are instrumental in maintaining central nervous system (CNS) homeostasis and responding to injury. A major limitation of studying neurodegenerative diseases like multiple sclerosis (MS) is lack of human pathological specimens obtained during the acute stages, thereby relegating research to post-mortem specimens obtained years after the initiation of pathology. Rodent reactive astrocytes have been shown to be cytotoxic to neurons and oligodendrocytes but may differ from human cells, especially in diseases with genetic susceptibility. Herein, we purified human CD49f+ astrocytes from induced pluripotent stem cells derived from individual patient and control peripheral leukocytes. We compared TNF and IL1α stimulated human reactive astrocytes from seven persons with MS and six non-MS controls and show their transcriptomes are remarkably similar to those described in rodents. The functional effect of astrocyte conditioned media (ACM) was examined in a human oligodendrocyte precursor cell (OPC) line differentiation assay. ACM was not cytotoxic to the OPCs but robustly inhibited the myelin basic protein (MBP) reporter. No differences were seen between MS and control stimulated astrocytes at either the transcript level or in ACM mediated OPC suppression assays. We next used RNAseq to interrogate differentially expressed genes in the OPC lines that had suppressed differentiation from the human ACM. Remarkably, not only was OPC differentiation and myelin gene expression suppressed, but we observed induction of several immune pathways in OPCs exposed to the ACM. These data support the notion that reactive astrocytes can inhibit OPC differentiation thereby limiting their remyelination capacity, and that OPCs take on an immune profile in the context of inflammatory cues.
Honey Bee Products: Preclinical and Clinical Studies of Their Anti-inflammatory and Immunomodulatory Properties
Authors: El-Seedi Hesham R. , Eid Nehal , Abd El-Wahed Aida A. , Rateb Mostafa E. , Afifi Hanan S. , Algethami Ahmed F. , Zhao Chao , Al Naggar Yahya , Alsharif Sultan M. , Tahir Haroon Elrasheid , Xu Baojun , Wang Kai , Khalifa Shaden A. M.
Published: May 2022

Graphical Abstract

The anti-inflammatory and immunomodulatory possible mechanisms of action of bee products suggested by preclinical and clinical studies.
Network Pharmacology and Absolute Bacterial Quantification-Combined Approach to Explore the Mechanism of Tianqi Pingchan Granule Against 6-OHDA-Induced Parkinson’s Disease in Rats
Authors: Liu Zhihua , Zhao Jiahao , Yang Shuyuan , Zhang Yu , Song Lu , Wu Na , Liu Zhenguo
Published: May 2022

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Tianqi Pingchan Granule (TPG) is a clinically effective formula of traditional Chinese medicine to treat PD. However, the therapeutic effect and underlying mechanisms of TPG in PD remain unclear. Based on network pharmacology, the corresponding targets of TPG were identified using the Traditional Chinese Medicine Database and Analysis Platform Database. Differentially expressed genes in PD were obtained from the Therapeutic Target Database, Online Mendelian Inheritance in Man, GeneCards, and DrugBank databases. The protein-protein interaction (PPI) networks of intersected targets were constructed using the STRING database and visualized using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and the pathways directly related to the pathogenesis of PD were integrated manually. Furthermore, in vivo studies were carried out based on network pharmacology. The gut microbiota, peripheral inflammatory cytokines, and glia-mediated neuroinflammation in substantia nigra were evaluated. A total of 99 target genes were intersected between targets of TPG and deferentially expressed genes in PD. The PPI network analysis indicated the proinflammatory cytokine as essential targets. GO and KEGG analyses indicated that inflammatory response and its related signaling pathways were closely associated with TPG-mediated PD treatment. In vivo studies revealed that class Negativicutes and order Selenomonadales decreased, whereas class Mollicutes, order Enterobacteriales, and Mycoplasmatales increased in fecal samples of PD rats via 16S rRNA sequence analysis. Furthermore, the function prediction methods purposely revealed that TPG therapy may be involved in flavonoid biosynthesis, which have anti-inflammatory properties. In addition, in vivo studies revealed that TPG exposure was found to not only attenuate the production of peripheral inflammatory cytokines but also inhibit the activation of microglia and astrocytes in substantia nigra of PD rats. Through network pharmacology and in vivo experiment-combined approach, the mechanisms of TPG in the treatment of PD were revealed, and the role of TPG in the regulation of gut microbiota and inflammatory response was confirmed.
Protective Roles of Sodium Butyrate in Lipopolysaccharide-Induced Bovine Ruminal Epithelial Cells by Activating G Protein-Coupled Receptors 41
Authors: Yang Tianyu , Datsomor Osmond , Jiang Maocheng , Ma Xiaoyu , Zhao Guoqi , Zhan Kang
Published: May 2022

This study aimed to evaluate whether sodium butyrate (SB) attenuates the ruminal response to LPS-stimulated inflammation by activating GPR41 in bovine rumen epithelial cells (BRECs). We examined the SB regulation of GPR41 and its impact on LPS-induced inflammation using GPR41 knockdown BRECs. The LPS-induced BRECs showed increases in the expression of genes related to pro-inflammation and decreases in the expression of genes related to tight junction proteins; these were attenuated by pretreatment with SB. Compared with that in LPS-stimulated BRECs, the ratio of phosphorylated NF-κB (p65 subunit) to NF-κB (p65 subunit) and the ratio of phosphorylated IκBα to IκBα were suppressed with SB pretreatment. The LSB group abated LPS-induced apoptosis and decreased the expression of Bax, Caspase 3, and Caspase 9 mRNA relative to the LPS group. In addition, the LSB group had a lower proportion of cells in the G0–G1 phase and a higher proportion of cells in the S phase than the LPS group. The mRNA expression of ACAT1 and BDH1 genes related to volatile fatty acid (VFA) metabolism were upregulated in the LSB group compared to those in LPS-induced BRECs. In addition, pretreatment with SB promoted the gene expression of GPR41 in the LPS-induced BRECs. Interestingly, SB pretreatment protected BRECs but not GPR41KD BRECs. Our results suggest that SB pretreatment protects against the changes in BRECs LPS-induced inflammatory response by activating GPR41.
Comparison of Different Drying Methods for Asparagus [Asparagus cochinchinensis (Lour.) Merr.] Root Volatile Compounds as Revealed Using Gas Chromatography Ion Mobility Spectrometry
Authors: Chen Gan-Lin , Lin Bo , Zheng Feng-Jin , Yu Wei-Hua , Fang Xiao-Chun , Shi Qian , Hu Yi-Feng , Verma Krishan K.
Published: May 2022

Asparagus [Asparagus cochinchinensis (Lour.) Merr.] is a traditional herbal medicine plant commonly used to nourish yin, moisten dryness, and clear fire cough symptoms. Drying is an excellent option to conserve food materials, i.e., grains, fruits, vegetables, and herbs, reducing the raw materials volume and weight. This study aims to evaluate different drying approaches that could increase the value of asparagus, particularly as an ingredient in fast foods or as nutraceutical byproducts. The volatile components of asparagus roots were analyzed by using headspace-gas chromatography-ion mobility spectroscopy under different drying conditions, i.e., natural drying (ND) at ambient air temperature in the dark, well-ventilated room, temperature range 28–32°C, blast or oven drying at 50°C, heat pump or hot-air drying at temperature 50°C and air velocity at 1.5 ms–1 and vacuum freeze-drying at the temperature of −45°C and vacuum pressure of 10–30 Pa for 24 h. The findings revealed that the various drying processes had multiple effects on the color, odor index, and volatile compounds of the asparagus roots. As a result of the investigations, multiple characteristics of components, therefore, exploitation and comparison of various flavors; a total of 22 compounds were identified, such as alcohols, ketones, aldehydes, acids, esters, heterocyclic, and terpene. The present findings may help understand the flavor of the processed asparagus roots and find a better option for drying and processing.
Case Report: First Report of T-Cell Large Granular Lymphocytic Leukemia With NPL-DHX9 Gene Fusion Successfully Treated With Cladribine: Clinical Experience and Literature Review
Authors: Hu Qin , Li Yunfei , Zhang Ying , Sun Shusen , Wang Hui , Jiang Zhiping , Deng Sheng
Published: May 2022

Background

T-cell large granular lymphocytic leukemia (T-LGLL) is a rare lymphoproliferative disorder that starts in T cells and is usually indolent. Long-term use of immunosuppressants, combined with agranulocytosis, is a double-edged sword, as both can lead to serious infections, especially in patients with combined hematologic malignancies and immune defects.

Case Presentation

A 30-year-old female patient was admitted to the hospital because of agranulocytosis for five years, with chest tightness, fatigue, and fever for two days. Pathology and metagenomic next-generation sequencing (mNGS) detected Aspergillus. Although she received cyclosporine and methylprednisolone, the patient showed drug intolerance and progression with invasive pulmonary fungal infections. After a bone marrow aspiration biopsy and other related examinations, she was diagnosed with T-LGLL and invasive pulmonary aspergillosis (IPA). T-cell immunophenotype was CD45+CD3dim+CD5-CD4-CD8+CD7+CD57p+CD25-CD30-, TCRγδ+, transducer and activator of transcripton-3 (STAT3) Y640F mutation and fusion gene NPL-DHX9 rearrangement were confirmed, which has never been reported in hematological diseases. After voriconazole regimen adjustment during treatment based on therapeutic drug concentration monitoring (TDM) and improvement in lung infection, the patient finally treated with purine nucleoside analogues (PNA) cladribine as a single agent at 0.14 mg/kg/d for 5 days. Complete response was achieved after four-cycles cladribine treatment (WBC 2.1*109/L, HGB 117 g/L, PLT 196*109/L, ANC 1.6*109/L, and ALC 0.2*109/L).

Conclusions

To our knowledge, this is the first case of T-LGLL with a rare γδ type and fusion gene NPL-DHX9 rearrangement. The patient was successfully treated with cladribine, suggesting that this regimen could be a promising therapeutic strategy for patients with aggressive T-LGLL.
Berberine and Oligomeric Proanthocyanidins Exhibit Synergistic Efficacy Through Regulation of PI3K-Akt Signaling Pathway in Colorectal Cancer
Authors: Okuno Keisuke , Garg Rachana , Yuan Yate-Ching , Tokunaga Masanori , Kinugasa Yusuke , Goel Ajay
Published: May 2022

Background

Naturally occurring dietary botanicals offer time-tested safety and anti-cancer efficacy, and a combination of certain compounds has shown to overcome the elusive chemotherapeutic resistance, which is of great significance for improving the mortality of patients with colorectal cancer (CRC). Accordingly, herein, we hypothesized that berberine (BBR) and oligomeric proanthocyanidins (OPCs) might regulate synergistically multiple oncogenic pathways to exert a superior anti-cancer activity in CRC.

Methods

We performed a series of cell culture studies, followed by their interrogation in patient-derived organoids to evaluate the synergistic effect of BBR and OPCs against CRC. In addition, by performing whole genome transcriptomic profiling we identified the key targeted genes and pathways regulated by the combined treatment.

Results

We first demonstrated that OPCs facilitated enhanced cellular uptake of BBR in CRC cells by measuring the fluorescent signal of BBR in cells treated individually or their combination. The synergism between BBR and OPCs were investigated in terms of their anti-tumorigenic effect on cell viability, clonogenicity, migration, and invasion. Furthermore, the combination treatment potentiated the cellular apoptosis in an Annexin V binding assay. Transcriptomic profiling identified oncogene MYB in PI3K-AKT signaling pathway might be critically involved in the anti-tumorigenic properties of the combined treatment. Finally, we successfully validated these findings in patient-derived CRC tumor organoids.

Conclusions

Collectively, we for the first time demonstrate that a combined treatment of BBR and OPCs synergistically promote the anti-tumorigenic properties in CRC possibly through the regulation of cellular apoptosis and oncogene MYB in the PI3K-Akt signaling pathway.
The Importance of Metabolic Syndrome Status for the Risk of Non-Viral Hepatocellular Carcinoma: A Nationwide Population-Based Study
Authors: Cho Yuri , Cho Eun Ju , Yoo Jeong-Ju , Chang Young , Chung Goh Eun , Choi In Young , Park Sang-Hyun , Han Kyungdo , Kim Yoon Jun , Yoon Jung-Hwan , Shin Dong Wook , Yu Su Jong
Published: May 2022

The positive association between metabolic syndrome (MetS) and hepatocellular carcinoma (HCC) has been suggested. However, no studies have yet looked at how the risk of developing HCC varies with changes in MetS status. Therefore, we aimed to investigate the association between changes in MetS and subsequent HCC development. Data were obtained from the Korean National Health Insurance Service. In this study, 5,975,308 individuals who participated in health screenings both in 2009–2010 and 2011–2012 were included. Individuals with preexisting viral hepatitis, liver cirrhosis, or cancer diagnoses were excluded. Subjects were divided into four groups according to change in MetS status during the 2-year interval screening (from 2009 to 2011): sustained non-MetS, transition to MetS, transition to non-MetS, and sustained MetS. Cox regression analysis was used to examine the hazard ratios of HCC. The subjects were followed through December 31, 2018. During a median of 7.3 years of follow-up, 25,880 incident HCCs were identified. Compared to the sustained non-MetS group, age, sex, smoking, alcohol, regular exercise, and body mass index-adjusted hazard ratios (95% confidence interval) for HCC development were 1.01 (0.97–1.05) for the transition to MetS group, 1.05 (1.003–1.09) for the transition to non-MetS group, and 1.07 (1.03–1.10) for the sustained MetS group. Stratified analyses according to age, sex, smoking, alcohol intake, exercise, diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease showed similar results. A significantly increased HCC risk was observed in the sustained MetS and transition to non-MetS groups. The baseline status of MetS was associated with the risk of HCC development. Strategies to improve MetS, especially targeting insulin resistance, might prevent HCC development.
Research Advances on Anti-Cancer Natural Products
Authors: Guo Meng , Jin Jie , Zhao Dong , Rong Zheng , Cao Lu-Qi , Li Ai-Hong , Sun Xiao-Ying , Jia Li-Yi , Wang Yin-Di , Huang Ling , Li Yi-Heng , He Zhong-Jing , Li Long , Ma Rui-Kang , Lv Yi-Fan , Shao Ke-Ke , Cao Hui-Ling
Published: May 2022

Malignant tumors seriously threaten people’s health and life worldwide. Natural products, with definite pharmacological effects and known chemical structures, present dual advantages of Chinese herbs and chemotherapeutic drug. Some of them exhibit favorable anti-cancer activity. Natural products were categorized into eight classes according to their chemical structures, including alkaloids, terpenoids and volatile oils, inorganic salts, phenylpropanoids, flavonoids and isoflavones, quinone, saponins and polysaccharides. The review focused on the latest advances in anti-cancer activity of representative natural products for every class. Additionally, anti-cancer molecular mechanism and derivatization of natural products were summarized in detail, which would provide new core structures and new insights for anti-cancer new drug development.
Comprehensive Analysis of 29,464 Cancer Cases and 35,858 Controls to Investigate the Effect of the Cytotoxic T-Lymphocyte Antigen 4 Gene rs231775 A/G Polymorphism on Cancer Risk
Authors: Wan Hongyuan , Zhou Hangsheng , Feng Yanyan , Chen Yongquan , Zhu Lijie , Mi Yuanyuan
Published: May 2022

In our previous studies, we found that the rs231775 polymorphism of cytotoxic T-lymphocyte antigen 4 (CTLA-4) is associated with risks of different cancer types; however, the association remains controversial and ambiguous, so we conducted an in-depth meta-analysis to verify the association. A complete search of the PubMed, Google Scholar, Embase, Chinese databases, and Web of Science was conducted without regard to language limitations, covering all publications since November 20, 2021. The search criteria for cancer susceptibility associated with the polymorphism in the CTLA-4 gene rs231775 resulted in 87 case-control studies with 29,464 cases and 35,858 controls. The association strength was analyzed using odds ratios and 95% confidence intervals. Overall, we found that the CTLA-4 rs231775 polymorphism may reduce cancer risk. A stratified cancer type analysis showed that CTLA-4 rs231775 polymorphism was a risk factor for colorectal cancer and thyroid cancer; on the other hand, it was a protective factor for breast cancer, liver cancer, cervical cancer, bone cancer, head and neck, and pancreatic cancer. We also classified cancer into five systems and observed an increased association with digestive tract cancer, decreased associations with orthopedic tumors, tumors of the urinary system, and gynecological tumors. In the subgroup based on race, decreased relationships were observed in both Asians and Caucasians. The same decreased association was also shown in the analysis of the source of control analysis. Our present study indicates that the CTLA-4 rs231775 polymorphism contributes to cancer development and aggression.
Cancer-Associated Fibroblasts and Squamous Epithelial Cells Constitute a Unique Microenvironment in a Mouse Model of Inflammation-Induced Colon Cancer
Authors: Vega Paige N. , Nilsson Avlant , Kumar Manu P. , Niitsu Hiroaki , Simmons Alan J. , Ro James , Wang Jiawei , Chen Zhengyi , Joughin Brian A. , Li Wei , McKinley Eliot T. , Liu Qi , Roland Joseph T. , Washington M. Kay , Coffey Robert J. , Lauffenburger Douglas A. , Lau Ken S.
Published: May 2022

The tumor microenvironment plays a key role in the pathogenesis of colorectal tumors and contains various cell types including epithelial, immune, and mesenchymal cells. Characterization of the interactions between these cell types is necessary for revealing the complex nature of tumors. In this study, we used single-cell RNA-seq (scRNA-seq) to compare the tumor microenvironments between a mouse model of sporadic colorectal adenoma (Lrig1CreERT2/+;Apc2lox14/+) and a mouse model of inflammation-driven colorectal cancer induced by azoxymethane and dextran sodium sulfate (AOM/DSS). While both models develop tumors in the distal colon, we found that the two tumor types have distinct microenvironments. AOM/DSS tumors have an increased abundance of two populations of cancer-associated fibroblasts (CAFs) compared with APC tumors, and we revealed their divergent spatial association with tumor cells using multiplex immunofluorescence (MxIF) imaging. We also identified a unique squamous cell population in AOM/DSS tumors, whose origins were distinct from anal squamous epithelial cells. These cells were in higher proportions upon administration of a chemotherapy regimen of 5-Fluorouracil/Irinotecan. We used computational inference algorithms to predict cell-cell communication mediated by ligand-receptor interactions and downstream pathway activation, and identified potential mechanistic connections between CAFs and tumor cells, as well as CAFs and squamous epithelial cells. This study provides important preclinical insight into the microenvironment of two distinct models of colorectal tumors and reveals unique roles for CAFs and squamous epithelial cells in the AOM/DSS model of inflammation-driven cancer.