bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Protective Effects and Mechanism of Crocetin From Saffron Against NAFLD by Network Pharmacology and Experimental Validation
Authors: Xu Zijin , Lin Susu , Gong Junjie , Feng Peishi , Cao Yifeng , Li Qiaoqiao , Jiang Yuli , You Ya , Tong Yingpeng , Wang Ping
Published: June 2021

Background: Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem but no drug has been approved for its treatment. Animal experiments and clinical trials have demonstrated the beneficial of saffron on NAFLD. However, the bioactive ingredients and therapeutic targets of saffron on NAFLD are unclear.

Purpose: This study aimed to identify the bioactive ingredients of saffron responsible for its effects on NAFLD and explore its therapy targets through network pharmacology combined with experimental tests.

Methods: Various network databases were searched to identify bioactive ingredients of saffron and identify NAFLD-related targets. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were conducted to enrich functions and molecular pathways of common targets and the STRING database was used to establish a protein-protein interaction network (PPI). The effect of crocetin (CCT) on NAFLD was evaluated in a mouse model of NAFLD by measuring the biomarkers of lipid, liver and renal function, oxidative stress, and inflammation. Liver histopathology was performed to evaluate liver injury. Nuclear factor erythroid-related factor (Nrf2) and hemeoxygenase-1 (HO-1) were examined to elucidate underlying mechanism for the protective effect of saffron against NAFLD.

Results: A total of nine bioactive ingredients of saffron, including CCT, with 206 common targets showed therapeutic effects on NAFLD. Oxidative stress and diabetes related signaling pathways were identified as the critical signaling pathways mediating the therapeutic effects of the active bioactive ingredients on NAFLD. Treatment with CCT significantly reduced the activities of aspartate aminotransferase (AST), alanine transaminase (ALT), and the levels of total cholesterol (TC), triglyceride (TG), malondialdehyde (MDA), blood urea nitrogen (BUN), creatinine (CR), and uric acid (UA). CCT significantly increased the activities of superoxide dismutase (SOD), and catalase (CAT). Histological analysis showed that CCT suppressed high-fat diet (HFD) induced fat accumulation, steatohepatitis, and renal dysfunctions. Results of ELISA assay showed that CCT decreased the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and increased the expression of HO-1 and Nrf2.

Conclusion: This study shows that CCT is a potential bioactive ingredient of saffron that treats NAFLD. Its mechanism of action involves suppressing of oxidative stress, mitigating inflammation, and upregulating Nrf2 and HO-1 expression.
Fecal Methylmercury Correlates With Gut Microbiota Taxa in Pacific Walruses (Odobenus rosmarus divergens)
Authors: Rothenberg Sarah E. , Sweitzer Danielle N. , Rackerby Bryna R. , Couch Claire E. , Cohen Lesley A. , Broughton Heather M. , Steingass Sheanna M. , Beechler Brianna R.
Published: June 2021

Objectives

Methylmercury metabolism was investigated in Pacific walruses (Odobenus rosmarus divergens) from St. Lawrence Island, Alaska, United States.

Methods

Total mercury and methylmercury concentrations were measured in fecal samples and paired colon samples (n = 16 walruses). Gut microbiota composition and diversity were determined using 16S rRNA gene sequencing. Associations between fecal and colon mercury and the 24 most prevalent gut microbiota taxa were investigated using linear models.

Results

In fecal samples, the median values for total mercury, methylmercury, and %methylmercury (of total mercury) were 200 ng/g, 4.7 ng/g, and 2.5%, respectively, while in colon samples, the median values for the same parameters were 28 ng/g, 7.8 ng/g, and 26%, respectively. In fecal samples, methylmercury was negatively correlated with one Bacteroides genus, while members of the Oscillospirales order were positively correlated with both methylmercury and %methylmercury (of total mercury). In colon samples, %methylmercury (of total mercury) was negatively correlated with members of two genera, Romboutsia and Paeniclostridium.

Conclusions

Median %methylmercury (of total mercury) was 10 times higher in the colon compared to the fecal samples, suggesting that methylmercury was able to pass through the colon into systemic circulation. Fecal total mercury and/or methylmercury concentrations in walruses were comparable to some human studies despite differences in seafood consumption rates, suggesting that walruses excreted less mercury. There are no members (at this time) of the Oscillospirales order which are known to contain the genes to methylate mercury, suggesting the source of methylmercury in the gut was from diet and not in vivo methylation.
Detection of Virus-Related Sequences Associated With Potential Etiologies of Hepatitis in Liver Tissue Samples From Rats, Mice, Shrews, and Bats
Authors: He Wenqiao , Gao Yuhan , Wen Yuqi , Ke Xuemei , Ou Zejin , Li Yongzhi , He Huan , Chen Qing
Published: June 2021

Hepatitis is a major global health concern. However, the etiology of 10–20% hepatitis cases remains unclear. Some hepatitis-associated viruses, like the hepatitis E virus, are zoonotic pathogens. Rats, shrews, and bats are reservoirs for many zoonotic pathogens. Therefore, understanding the virome in the liver of these animals is important for the investigation of the etiologies of hepatitis and monitoring the emerging zoonotic viruses. In this study, viral metagenomics and PCR methods were used to investigate viral communities in rats, mice, house shrews, and bats livers. Viral metagenomic analysis showed a diverse set of sequences in liver samples, comprising: sequences related to herpesviruses, orthomyxoviruses, anelloviruses, hepeviruses, hepadnaviruses, flaviviruses, parvoviruses, and picornaviruses. Using PCR methods, we first detected hepatovirus sequences in Hipposideros larvatus (3.85%). We also reported the first detection of Zika virus-related sequences in rats and house shrews. Sequences related to influenza A virus and herpesviruses were detected in liver. Higher detection rates of pegivirus sequences were found in liver tissue and serum samples from rats (7.85% and 15.79%, respectively) than from house shrews. Torque teno virus sequences had higher detection rates in the serum samples of rats and house shrews (52.72% and 5.26%, respectively) than in the liver. Near-full length genomes of pegivirus and torque teno virus were amplified. This study is the first to compare the viral communities in the liver of bats, rats, mice, and house shrews. Its findings expand our understanding of the virome in the liver of these animals and provide an insight into hepatitis-related viruses.
Short-Term Effect in Soil Microbial Community of Two Strategies of Recovering Degraded Area in Brazilian Savanna: A Pilot Case Study
Authors: Selari Priscila Jane Romano Gonçalves , Olchanheski Luiz Ricardo , Ferreira Almir José , Paim Tiago do Prado , Calgaro Junior Guido , Claudio Flavio Lopes , Alves Estenio Moreira , Santos Darliane de Castro , Araújo Welington Luiz , Silva Fabiano Guimarães
Published: June 2021

The Brazilian Cerrado is a highland tropical savanna considered a biodiversity hotspot with many endemic species of plants and animals. Over the years, most of the native areas of this biome became arable areas, and with inadequate management, some are nowadays at varying levels of degradation stage. Crop-livestock integrated systems (CLIS) are one option for the recovery of areas in degradation, improving the physicochemical and biological characteristics of the soil while increasing income and mitigating risks due to product diversification. Little is known about the effect of CLIS on the soil microbial community. Therefore, we perform this pilot case study to support further research on recovering degraded areas. The bacterial and fungal soil communities in the area with CLIS were compared to an area under moderate recovery (low-input recovering - LI) and native savanna (NS) area. Bacterial and fungal communities were investigated by 16S and ITS rRNA gene sequencing (deep rRNA sequencing). Ktedonobacteraceae and AD3 families were found predominantly in LI, confirming the relationship of the members of the Chloroflexi phylum in challenging environmental conditions, which can be evidenced in LI. The CLIS soil presented 63 exclusive bacterial families that were not found in LI or NS and presented a higher bacterial richness, which can be related to good land management. The NS area shared 21 and 6 families with CLIS and LI, respectively, suggesting that the intervention method used in the analyzed period brings microbial diversity closer to the conditions of the native area, demonstrating a trend of approximation between NS and CLIS even in the short term. The most abundant fungal phylum in NS treatment was Basidiomycota and Mucoromycota, whereas Ascomycota predominated in CLIS and LI. The fungal community needs more time to recover and to approximate from the native area than the bacterial community. However, according to the analysis of bacteria, the CLIS area behaved differently from the LI area, showing that this treatment induces a faster response to the increase in species richness, tending to more accelerated recovery. Results obtained herein encourage CLIS as a sustainable alternative for recovery and production in degraded areas.
Genomic Characterization of mcr-1.1-Producing Escherichia coli Recovered From Human Infections in São Paulo, Brazil
Authors: Girardello Raquel , Piroupo Carlos Morais , Martins Joaquim , Maffucci Marcia Helena , Cury Ana Paula , Franco Maria Renata Gomes , Malta Fernanda de Mello , Rocha Natália Conceição , Pinho João Renato Rebello , Rossi Flavia , Duarte Alberto José da Silva , Setubal João Carlos
Published: June 2021

Polymyxins are one of most important antibiotics available for multidrug-resistant Gram-negative infections. Diverse chromosomal resistance mechanisms have been described, but the polymyxin resistance phenotype is not yet completely understood. The objective of this study was to characterize colistin resistant mcr-1-producing strains isolated from human infections over one year in a hospital setting (Hospital das Clínicas, São Paulo, Brazil). We isolated 490 colistin-resistant Gram-negative rods, of which eight were mcr-1.1-positive Escherichia coli, the only species with this result, indicating a low incidence of the mcr-1 production mechanism among colistin-resistant isolates. All mcr-1.1 positive isolates showed similarly low MICs for colistin and were susceptible to most antibiotics tested. The isolates showed diversity of MLST classification. The eight mcr-1.1-positive E. coli genomes were sequenced. In seven of eight isolates the mcr-1.1 gene is located in a contig that is presumed to be a part of an IncX4 plasmid; in one isolate, it is located in a contig that is presumed to be part of an IncHI2A plasmid. Three different genomic contexts for mcr-1.1 were observed, including a genomic cassette mcr-1.1-pap2 disrupting a DUF2806 domain-containing gene in six isolates. In addition, an IS1-family transposase was found inserted next to the mcr-1.1 cassette in one isolate. An mcr-1.1-pap2 genomic cassette not disrupting any gene was identified in another isolate. Our results suggest that plasmid dissemination of hospital-resident strains took place during the study period and highlight the need for continued genomic surveillance.
A Comparative Analysis on the Structure and Function of the Panax notoginseng Rhizosphere Microbiome
Authors: Kui Ling , Chen Baozheng , Chen Jian , Sharifi Rouhallah , Dong Yang , Zhang Zhanjiang , Miao Jianhua
Published: June 2021

Panax notoginseng, an important Chinese medicinal herb, can be mainly cultivated in two planting patterns, cropland planting (DT) and understory planting (LX). We speculate that the rhizosphere microbiome may vary in DT and LX and may play an important role in promoting the growth and health of P. notoginseng. In the present study, culture-independent Illumina HiSeq was employed to investigate the rhizosphere bacteria and fungi under DT and LX planting patterns. Predominant phyla include Proteobacteria, Acidobacteria, Actinobacteria, Gemmatimonadetes, and Ascomycota in the two planting patterns. DT has higher alpha diversity index than LX. The predominant LX-core genera include Bradyrhizobium, Streptomyces, and Actinomadura, and the predominant DT-core genera include Sphingomonas, Variovorax, and Novosphingobium. Total relative abundance of the disease-suppression phylum (Proteobacteria, Firmicutes, and Actinobacteria) and the potential plant growth-promoting rhizobacteria (PGPR) were both significantly higher in LX than in DT. We also identified over-presented microbial functional traits mediating plant–microbe and microbe–microbe interactions, nutrition acquisition, and plant growth promotion in P. notoginseng rhizosphere. Our findings provide a valuable reference for studying beneficial microbes and pathogens of P. notoginseng planted in DT and LX.
Urine Metabolomics Profiling of Lumbar Disc Herniation and its Traditional Chinese Medicine Subtypes in Patients Through Gas Chromatography Coupled With Mass Spectrometry
Authors: Shan Letian , Yang Jinying , Meng Shijie , Ruan Hongfeng , Zhou Li , Ye Fusheng , Tong Peijian , Wu Chengliang
Published: June 2021

Lumbar disc herniation (LDH) possesses complex pathogenesis, which has not been well elucidated yet. To date, specific or early diagnosis of LDH remains unavailable, resulting in missed opportunity for effective treatment. According to Traditional Chinese medicine (TCM) theory, LDH can be divided into two subtypes (reality syndrome and deficiency syndrome). The purpose of this study was to analyze the metabolic disorders of LDH and its TCM subtypes and screen out potential biomarkers for LDH diagnosis. Gas chromatography coupled with mass spectrometry (GC-MS) was applied to test the urine samples from 66 participants (30 healthy volunteers, 18 LDH patients with deficiency syndrome and 18 patients with reality syndrome). PCA analysis showed a distinct separation tendency between the healthy subjects and LDH patients but no obvious separation between the different syndromes (reality syndrome and deficiency syndrome) of LDH patients. As a result, 23 metabolites were identified significantly altered in the LDH patients, as compared with the healthy subjects. The altered metabolites belong to amino acid metabolism, nucleic acid metabolism, carbohydrate metabolism, and vitamin metabolism, which are related to osteoporosis and inflammation. Our results indicate metabolic disorders of LDH and thereby propose a group of metabolic biomarkers for potential application in early diagnosis of LDH in clinic, which provide a reasonable explanation for the pathogenesis of LDH.
Targeted Demethylation of the PLOD2 mRNA Inhibits the Proliferation and Migration of Renal Cell Carcinoma
Authors: Cao Congcong , Ma Qian , Huang Xinbo , Li Aolin , Liu Jun , Ye Jing , Gui Yaoting
Published: June 2021

N6-methyladenosine (m6A) RNA modification is the most common internal mRNA modification in mammals and has been reported to play a key role in gene expression regulation. In this study, we detected a high level of m6A methylation of the PLOD2 3′-untranslated regions (3′UTR) in renal cell carcinoma (RCC). Furthermore, we found that the high expression level of PLOD2 was a prognostic indicator for patients with RCC. A dm6ACRISPR demethylation system was performed to accurately and specifically demethylate 3′UTR of PLOD2 and caused an inactivation of PLOD2 expression. Furthermore, we also performed many in vitro experiments to confirm that PLOD2 exerted tumor promoter effects by promoting tumor proliferation and migration. In conclusion, PLOD2 mRNA demethylated by dCas13b-ALKBH5 might provide a new light on the treatment for RCC.
HINT1 Is Involved in the Chronic Mild Stress Elicited Oxidative Stress and Apoptosis Through the PKC ε/ALDH-2/4HNE Pathway in Prefrontal Cortex of Rats
Authors: Liu Fei , Dong Ying-ying , Lei Gang , Zhou Yuan , Liu Peng , Dang Yong-hui
Published: June 2021

Major depressive disorder (MDD) is a severe, highly heterogeneous, and life-threatening psychiatric disease which affects up to 21% of the population worldwide. A new hypothesis suggests that the mitochondrial dysfunction causing oxidative stress (OS) and dysregulation of apoptosis in brain might be one of the key pathophysiological factors in MDD. Histidine triad nucleotide binding protein 1 (HINT1), which was first supposed to be protein kinase C (PKC) inhibitor, has been gradually demonstrated to be involved in diverse neuropsychiatric diseases. It still remains elusive that how HINT1 involves in depression. The present study utilized a rat model exposed to chronic mild stress (CMS) to explore the involvement of HINT1 in depression. Face validity, construct validity and predictive validity of CMS model were comprehensive evaluated in this study. Behavioral tests including sucrose preference test, open field test, and elevated plus maze and forced swimming test revealed that stressed rats displayed elevated level of anxiety and depression compared with the controls. CMS rats showed a significant decrease of superoxide dismutase, and a marked increase malondialdehyde levels in prefrontal cortex (PFC). We also found the CMS rats had elevated expression of HINT1, decreased levels of phosphorylated-PKC ε and aldehyde dehydrogenase-two (ALDH-2), and accumulated 4-hydroxynonenal (4HNE) in PFC. Moreover, CMS increased the levels of cleaved caspase-3 and Bax, and decreased the level of Bcl-2 in PFC. The alterations in behavior and molecule were prevented by antidepressant venlafaxine. These results demonstrated that HINT1 was involved in the CMS elicited OS and apoptosis in PFC, probably through the PKC ε/ALDH-2/4HNE pathway. The results suggest that the suppression of HINT1 might have potential as a novel therapeutic strategy for depression.
Interaction in Assistive Robotics: A Radical Constructivist Design Framework
Authors: Bettoni Marco C. , Castellini Claudio
Published: June 2021

Despite decades of research, muscle-based control of assistive devices (myocontrol) is still unreliable; for instance upper-limb prostheses, each year more and more dexterous and human-like, still provide hardly enough functionality to justify their cost and the effort required to use them. In order to try and close this gap, we propose to shift the goal of myocontrol from guessing intended movements to creating new circular reactions in the constructivist sense defined by Piaget. To this aim, the myocontrol system must be able to acquire new knowledge and forget past one, and knowledge acquisition/forgetting must happen on demand, requested either by the user or by the system itself. We propose a unifying framework based upon Radical Constructivism for the design of such a myocontrol system, including its user interface and user-device interaction strategy.
Putative Causal Variant on Vlgr1 for the Epileptic Phenotype in the Model Wistar Audiogenic Rat
Authors: Damasceno Samara , Fonseca Pablo Augusto de Souza , Rosse Izinara Cruz , Moraes Márcio Flávio Dutra , de Oliveira José Antônio Cortes , Garcia-Cairasco Norberto , Brunialti Godard Ana Lúcia
Published: June 2021

Wistar Audiogenic Rat is an epilepsy model whose animals are predisposed to develop seizures induced by acoustic stimulation. This model was developed by selective reproduction and presents a consistent genetic profile due to the several generations of inbreeding. In this study, we performed an analysis of WAR RNA-Seq data, aiming identified at genetic variants that may be involved in the epileptic phenotype. Seventeen thousand eighty-five predicted variants were identified as unique to the WAR model, of which 15,915 variants are SNPs and 1,170 INDELs. We filter the predicted variants by pre-established criteria and selected five for validation by Sanger sequencing. The genetic variant c.14198T>C in the Vlgr1 gene was confirmed in the WAR model. Vlgr1 encodes an adhesion receptor that is involved in the myelination process, in the development of stereocilia of the inner ear, and was already associated with the audiogenic seizures presented by the mice Frings. The transcriptional quantification of Vlgr1 revealed the downregulation this gene in the corpus quadrigeminum of WAR, and the protein modeling predicted that the mutated residue alters the structure of a domain of the VLGR1 receptor. We believe that Vlgr1 gene may be related to the predisposition of WAR to seizures and suggest the mutation Vlgr1/Q4695R as putative causal variant, and the first molecular marker of the WAR strain.
Chinese Cerebrovascular Neurosurgery Society and Chinese Interventional & Hybrid Operation Society, of Chinese Stroke Association Clinical Practice Guidelines for Management of Brain Arteriovenous Malformations in Eloquent Areas
Authors: Wang Mingze , Jiao Yuming , Zeng Chaofan , Zhang Chaoqi , He Qiheng , Yang Yi , Tu Wenjun , Qiu Hancheng , Shi Huaizhang , Zhang Dong , Kang Dezhi , Wang Shuo , Liu A-li , Jiang Weijian , Cao Yong , Zhao Jizong
Published: June 2021

Aim:The aim of this guideline is to present current and comprehensive recommendations for the management of brain arteriovenous malformations (bAVMs) located in eloquent areas.

Methods:An extended literature search on MEDLINE was performed between Jan 1970 and May 2020. Eloquence-related literature was further screened and interpreted in different subcategories of this guideline. The writing group discussed narrative text and recommendations through group meetings and online video conferences. Recommendations followed the Applying Classification of Recommendations and Level of Evidence proposed by the American Heart Association/American Stroke Association. Prerelease review of the draft guideline was performed by four expert peer reviewers and by the members of Chinese Stroke Association.

Results:In total, 809 out of 2,493 publications were identified to be related to eloquent structure or neurological functions of bAVMs. Three-hundred and forty-one publications were comprehensively interpreted and cited by this guideline. Evidence-based guidelines were presented for the clinical evaluation and treatment of bAVMs with eloquence involved. Topics focused on neuroanatomy of activated eloquent structure, functional neuroimaging, neurological assessment, indication, and recommendations of different therapeutic managements. Fifty-nine recommendations were summarized, including 20 in Class I, 30 in Class IIa, 9 in Class IIb, and 2 in Class III.

Conclusions:The management of eloquent bAVMs remains challenging. With the evolutionary understanding of eloquent areas, the guideline highlights the assessment of eloquent bAVMs, and a strategy for decision-making in the management of eloquent bAVMs.
From Physiology to Pathology of Cortico-Thalamo-Cortical Oscillations: Astroglia as a Target for Further Research
Authors: Gobbo Davide , Scheller Anja , Kirchhoff Frank
Published: June 2021

The electrographic hallmark of childhood absence epilepsy (CAE) and other idiopathic forms of epilepsy are 2.5–4 Hz spike and wave discharges (SWDs) originating from abnormal electrical oscillations of the cortico-thalamo-cortical network. SWDs are generally associated with sudden and brief non-convulsive epileptic events mostly generating impairment of consciousness and correlating with attention and learning as well as cognitive deficits. To date, SWDs are known to arise from locally restricted imbalances of excitation and inhibition in the deep layers of the primary somatosensory cortex. SWDs propagate to the mostly GABAergic nucleus reticularis thalami (NRT) and the somatosensory thalamic nuclei that project back to the cortex, leading to the typical generalized spike and wave oscillations. Given their shared anatomical basis, SWDs have been originally considered the pathological transition of 11–16 Hz bursts of neural oscillatory activity (the so-called sleep spindles) occurring during Non-Rapid Eye Movement (NREM) sleep, but more recent research revealed fundamental functional differences between sleep spindles and SWDs, suggesting the latter could be more closely related to the slow (<1 Hz) oscillations alternating active (Up) and silent (Down) cortical activity and concomitantly occurring during NREM. Indeed, several lines of evidence support the fact that SWDs impair sleep architecture as well as sleep/wake cycles and sleep pressure, which, in turn, affect seizure circadian frequency and distribution. Given the accumulating evidence on the role of astroglia in the field of epilepsy in the modulation of excitation and inhibition in the brain as well as on the development of aberrant synchronous network activity, we aim at pointing at putative contributions of astrocytes to the physiology of slow-wave sleep and to the pathology of SWDs. Particularly, we will address the astroglial functions known to be involved in the control of network excitability and synchronicity and so far mainly addressed in the context of convulsive seizures, namely (i) interstitial fluid homeostasis, (ii) K+clearance and neurotransmitter uptake from the extracellular space and the synaptic cleft, (iii) gap junction mechanical and functional coupling as well as hemichannel function, (iv) gliotransmission, (v) astroglial Ca2+signaling and downstream effectors, (vi) reactive astrogliosis and cytokine release.
Case Report: Direct Visualization of the Nervus Intermedius During the Microvascular Decompression Procedure: Should We Take It Seriously?
Authors: Zheng Rui-zhe , Zhao Chang-yi , Zhao Zhi-jie , Li Xin-yuan
Published: June 2021

Background: Nervus intermedius neuralgia (NIN), known as geniculate neuralgia (GN), is an uncommon cranial nerve disease caused by an offending vessel compressing the nervus intermedius (NI). Microvascular decompression (MVD) has now become a valued treatment approach for NIN because it can resolve neurovascular conflict (NVC) at the root entry zone of the NI. In the era of continuously optimizing and improving the surgical technique of MVD, further minimization of all possible postoperative complications is not only welcome but also necessary.

Objective: The aim of this work is to assess the postoperative outcome of direct visualization of the NI during the MVD procedure.

Methods: This study retrospectively reviewed the clinical records of a group of seven consecutive patients with NIN who underwent MVD in the period of 2013–2020 in our clinic and 16 studies reported NIN patients who underwent MVD in the period of 2007–2020.

Results: In total, 91.3% of all patients experienced immediate and complete relief of cranial neuralgia after MVD. Six of 23 patients have experienced direct visualization of the NI intraoperatively, and 66.7% of those patients had complications such as facial paralysis, dysacousia, or a combination of these conditions postoperatively. Slight surgical approach-related complications such as complaints associated with excessive drainage of cerebrospinal fluid (CSF), nausea and vertigo, and delayed wound union were observed in 80% of the remaining 15 patients, and these symptoms are totally relieved in the telephone and outpatient follow-up after 6 months.

Conclusion: Our case series shows that MVD produced immediate pain relief in the majority of NIN patients. MVD carries surgical risk, especially in patients who experience direct visualization of the NI after mechanical stretch and blunt dissection in surgical procedures. Attempts to avoid mechanical stretch and blunt dissection of the compressed nerve were important for intraoperative neuroprotection, especially facial nerve protection
Structural and Functional Alterations in Visual Pathway After Optic Neuritis in MOG Antibody Disease: A Comparative Study With AQP4 Seropositive NMOSD
Authors: Gao Chenyang , Zhuo Zhizheng , Duan Yunyun , Yao Yajun , Su Lei , Zhang Xinghu , Song Tian
Published: June 2021

Background: Optic neuritis (ON) is an important clinical manifestation of neuromyelitis optic spectrum disease (NMOSD). Myelin oligodendrocyte glycoprotein (MOG) antibody-related and aquaporin 4 (AQP4) antibody-related ON show different disease patterns. The aim of this study was to explore the differences in structure and function of the visual pathway in patients with ON associated with MOG and AQP4 antibodies.

Methods: In this prospective study, we recruited 52 subjects at Beijing Tiantan Hospital, including 11 with MOG Ig+ ON (MOG-ON), 13 with AQP4 Ig+ ON (AQP4-ON), and 28 healthy controls (HCs). Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of optic radiation (OR), primary visual cortex volume (V1), brain volume, and visual acuity (VA) were compared among groups. A multiple linear regression was used to explore associations between VA and predicted factors. In addition, we used optical coherence tomography (OCT) to examine thickness of the peripapillary retinal nerve fiber layer (pRNFL) and retinal ganglion cell complex (GCC) in a separate cohort consisting of 15 patients with ON (8 MOG-ON and 7 AQP4-ON) and 28 HCs.

Results: Diffusion tensor imaging showed that the FA of OR was lower than controls in patients with AQP4-ON (p = 0.001) but not those with MOG-ON (p = 0.329) and was significantly different between the latter two groups (p = 0.005), while V1 was similar in patients with MOG-ON and AQP4-ON (p = 0.122), but was lower than controls in AQP4-ON (p = 0.002) but not those with MOG-ON (p = 0.210). The VA outcomes were better in MOG-ON than AQP4-ON, and linear regression analysis revealed that VA in MOG-ON and AQP4-ON was both predicted by the FA of OR (standard β = −0.467 and −0.521, p = 0.036 and 0.034). Both patients of MOG-ON and AQP4-ON showed neuroaxonal damage in the form of pRNFL and GCC thinning but showed no statistically significant difference (p = 0.556, 0.817).

Conclusion: The structural integrity of OR in patients with MOG-ON, which is different from the imaging manifestations of AQP4-ON, may be a reason for the better visual outcomes of patients with MOG-ON.
Genome-Wide Association Study of Motor Coordination
Authors: Mountford Hayley S. , Hill Amanda , Barnett Anna L. , Newbury Dianne F.
Published: June 2021

The ability to finely control our movement is key to achieving many of the educational milestones and life-skills we develop throughout our lives. Despite the centrality of coordination to early development, there is a vast gap in our understanding of the underlying biology. Like most complex traits, both genetics and environment influence motor coordination, however, the specific genes, early environmental risk factors and molecular pathways are unknown. Previous studies have shown that about 5% of school-age children experience unexplained difficulties with motor coordination. These children are said to have Developmental Coordination Disorder (DCD). For children with DCD, these motor coordination difficulties significantly impact their everyday life and learning. DCD is associated with poorer academic achievement, reduced quality of life, it can constrain career opportunities and increase the risk of mental health issues in adulthood. Despite the high prevalence of coordination difficulties, many children remain undiagnosed by healthcare professionals. Compounding under-diagnosis in the clinic, research into the etiology of DCD is severely underrepresented in the literature. Here we present the first genome-wide association study to examine the genetic basis of early motor coordination in the context of motor difficulties. Using data from the Avon Longitudinal Study of Parents and Children we generate a derived measure of motor coordination from four components of the Movement Assessment Battery for Children, providing an overall measure of coordination across the full range of ability. We perform the first genome-wide association analysis focused on motor coordination (N = 4542). No single nucleotide polymorphisms (SNPs) met the threshold for genome-wide significance, however, 59 SNPs showed suggestive associations. Three regions contained multiple suggestively associated SNPs, within five preliminary candidate genes: IQSEC1, LRCC1, SYNJ2B2, ADAM20, and ADAM21. Association to the gene IQSEC1 suggests a potential link to axon guidance and dendritic projection processes as a potential underlying mechanism of motor coordination difficulties. This represents an interesting potential mechanism, and whilst further validation is essential, it generates a direct window into the biology of motor coordination difficulties. This research has identified potential biological drivers of DCD, a first step towards understanding this common, yet neglected neurodevelopmental disorder.
Exaggerated Exercise Blood Pressure as a Marker of Baroreflex Dysfunction in Normotensive Metabolic Syndrome Patients
Authors: Dutra-Marques Akothirene C. , Rodrigues Sara , Cepeda Felipe X. , Toschi-Dias Edgar , Rondon Eduardo , Carvalho Jefferson C. , Alves Maria Janieire N. N. , Braga Ana Maria F. W. , Rondon Maria Urbana P. B. , Trombetta Ivani C.
Published: June 2021

Introduction

Exaggerated blood pressure response to exercise (EEBP = SBP ≥ 190 mmHg for women and ≥210 mmHg for men) during cardiopulmonary exercise test (CPET) is a predictor of cardiovascular risk. Sympathetic hyperactivation and decreased baroreflex sensitivity (BRS) seem to be involved in the progression of metabolic syndrome (MetS) to cardiovascular disease.

Objective

To test the hypotheses: (1) MetS patients within normal clinical blood pressure (BP) may present EEBP response to maximal exercise and (2) increased muscle sympathetic nerve activity (MSNA) and reduced BRS are associated with this impairment.

Methods

We selected MetS (ATP III) patients with normal BP (MetS_NT, n = 27, 59.3% males, 46.1 ± 7.2 years) and a control group without MetS (C, n = 19, 48.4 ± 7.4 years). We evaluated BRS for increases (BRS+) and decreases (BRS−) in spontaneous BP and HR fluctuations, MSNA (microneurography), BP from ambulatory blood pressure monitoring (ABPM), and auscultatory BP during CPET.

Results

Normotensive MetS (MetS_NT) had higher body mass index and impairment in all MetS risk factors when compared to the C group. MetS_NT had higher peak systolic BP (SBP) (195 ± 17 vs. 177 ± 24 mmHg, P = 0.007) and diastolic BP (91 ± 11 vs. 79 ± 10 mmHg, P = 0.001) during CPET than C. Additionally, we found that MetS patients with normal BP had lower spontaneous BRS− (9.6 ± 3.3 vs. 12.2 ± 4.9 ms/mmHg, P = 0.044) and higher levels of MSNA (29 ± 6 vs. 18 ± 4 bursts/min, P < 0.001) compared to C. Interestingly, 10 out of 27 MetS_NT (37%) showed EEBP (MetS_NT+), whereas 2 out of 19 C (10.5%) presented (P = 0.044). The subgroup of MetS_NT with EEBP (MetS_NT+, n = 10) had similar MSNA (P = 0.437), but lower BRS+ (P = 0.039) and BRS− (P = 0.039) compared with the subgroup without EEBP (MetS_NT−, n = 17). Either office BP or BP from ABPM was similar between subgroups MetS_NT+ and MetS_NT−, regardless of EEBP response. In the MetS_NT+ subgroup, there was an association of peak SBP with BRS− (R = −0.70; P = 0.02), triglycerides with peak SBP during CPET (R = 0.66; P = 0.039), and of triglycerides with BRS− (R = 0.71; P = 0.022).

Conclusion

Normotensive MetS patients already presented higher peak systolic and diastolic BP during maximal exercise, in addition to sympathetic hyperactivation and decreased baroreflex sensitivity. The EEBP in MetS_NT with apparent well-controlled BP may indicate a potential depressed neural baroreflex function, predisposing these patients to increased cardiovascular risk.
The Spatial Distribution of Relative Corneal Refractive Power Shift and Axial Growth in Myopic Children: Orthokeratology Versus Multifocal Contact Lens
Authors: Jiang Fan , Huang Xiaopeng , Xia Houxue , Wang Bingqi , Lu Fan , Zhang Bin , Jiang Jun
Published: June 2021

Purpose

To determine if the spatial distribution of the relative corneal refractive power shift (RCRPS) explains the retardation of axial length (AL) elongation after treatment by either orthokeratology (OK) or multifocal soft contact lenses (MFCLs).

Methods

Children (8–14 years) were enrolled in the OK (n = 35) or MFCL (n = 36) groups. RCRPS maps were derived by computing the difference between baseline and 12-month corneal topography maps and then subtracting the apex values. Values at the same radius were averaged to obtain the RCRPS profile, from which four parameters were extracted: (1) Half_x and (2) Half_y, i.e., the x- and y-coordinates where each profile first reached the half peak; (3) Sum4 and (4) Sum7, i.e., the summation of powers within a corneal area of 4- and 7-mm diameters. Correlations between AL elongation and these parameters were analyzed by multiple linear regression.

Results

AL elongation in the OK group was significantly smaller than that in the MFCL group (p = 0.040). Half_x and Half_y were also smaller in the OK group than the MFCL group (p < 0.001 each). Half_x was correlated with AL elongation in the OK group (p = 0.005), but not in the MFCL group (p = 0.600). In an analysis that combined eyes of both groups, Half_x was correlated with AL elongation (β = 0.161, p < 0.001).

Conclusions

The OK-induced AL elongation and associated RCRPS Half_x were smaller than for the MFCL. Contact lenses that induce RCRPS closer to the corneal center may exert better myopia control.
The Role of Neurod Genes in Brain Development, Function, and Disease
Authors: Tutukova Svetlana , Tarabykin Victor , Hernandez-Miranda Luis R.
Published: June 2021

Transcriptional regulation is essential for the correct functioning of cells during development and in postnatal life. The basic Helix-loop-Helix (bHLH) superfamily of transcription factors is well conserved throughout evolution and plays critical roles in tissue development and tissue maintenance. A subgroup of this family, called neural lineage bHLH factors, is critical in the development and function of the central nervous system. In this review, we will focus on the function of one subgroup of neural lineage bHLH factors, the Neurod family. The Neurod family has four members: Neurod1, Neurod2, Neurod4, and Neurod6. Available evidence shows that these four factors are key during the development of the cerebral cortex but also in other regions of the central nervous system, such as the cerebellum, the brainstem, and the spinal cord. We will also discuss recent reports that link the dysfunction of these transcription factors to neurological disorders in humans.
A Muscle-Centric Perspective on Intermittent Fasting: A Suboptimal Dietary Strategy for Supporting Muscle Protein Remodeling and Muscle Mass?
Authors: Williamson Eric , Moore Daniel R.
Published: June 2021

Muscle protein is constantly “turning over” through the breakdown of old/damaged proteins and the resynthesis of new functional proteins, the algebraic difference determining net muscle gain, maintenance, or loss. This turnover, which is sensitive to the nutritional environment, ultimately determines the mass, quality, and health of skeletal muscle over time. Intermittent fasting has become a topic of interest in the health community as an avenue to improve health and body composition primarily via caloric deficiency as well as enhanced lipolysis and fat oxidation secondary to attenuated daily insulin response. However, this approach belies the established anti-catabolic effect of insulin on skeletal muscle. More importantly, muscle protein synthesis, which is the primary regulated turnover variable in healthy humans, is stimulated by the consumption of dietary amino acids, a process that is saturated at a moderate protein intake. While limited research has explored the effect of intermittent fasting on muscle-related outcomes, we propose that infrequent meal feeding and periods of prolonged fasting characteristic of models of intermittent fasting may be counter-productive to optimizing muscle protein turnover and net muscle protein balance. The present commentary will discuss the regulation of muscle protein turnover across fasted and fed cycles and contrast it with studies exploring how dietary manipulation alters the partitioning of fat and lean body mass. It is our position that intermittent fasting likely represents a suboptimal dietary approach to remodel skeletal muscle, which could impact the ability to maintain or enhance muscle mass and quality, especially during periods of reduced energy availability.
Comparison of the Nutritional Quality of Branded and Private-Label Food Products Sold in Italy: Focus on the Cereal-Based Products Collected From the Food Labeling of Italian Products Study
Authors: Angelino Donato , Del Bo' Cristian , Pellegrini Nicoletta , Martini Daniela ,   SINU Young Working Group
Published: June 2021

The packaged foods sold in food stores may be “private-label” products (PL), when branded by the supermarket, and “branded” products (BR). PL products are generally cheaper than the BR counterparts, and this can be perceived as a sign of general low quality by consumers, when items are compared with their branded counterparts. Thus, the aim of the present study was to compare the nutrient content of BR and PL cereal-based foods, by evaluating the nutritional declaration reported on the food pack of products on the home-shopping website of major retailers present on the Italian market. A total of 3,775 items (~58% BR and ~42% PL), collected in the period from July 2018 to March 2019 and updated in March 2020, were included in the final analysis. Data were analyzed by means of the Mann–Whitney nonparametric test for two independent samples for differences between BR and PL categories and types. Overall, BR products showed higher contents of total and saturates than PL items. When products were grouped for categories and types, items only differed for the content of total fats, saturates, total carbohydrates, proteins, and salt. No differences were instead found for energy and sugar contents among any of the categories. However, we did not find any consistency in the direction of results. These results could be useful for future education activities aimed to help consumers in making informed food choices.
QTL Mapping for Grain Zinc and Iron Concentrations in Bread Wheat
Authors: Wang Yue , Xu Xiaoting , Hao Yuanfeng , Zhang Yelun , Liu Yuping , Pu Zongjun , Tian Yubing , Xu Dengan , Xia Xianchun , He Zhonghu , Zhang Yong
Published: June 2021

Deficiency of micronutrient elements, such as zinc (Zn) and iron (Fe), is called “hidden hunger,” and bio-fortification is the most effective way to overcome the problem. In this study, a high-density Affymetrix 50K single-nucleotide polymorphism (SNP) array was used to map quantitative trait loci (QTL) for grain Zn (GZn) and grain Fe (GFe) concentrations in 254 recombinant inbred lines (RILs) from a cross Jingdong 8/Bainong AK58 in nine environments. There was a wide range of variation in GZn and GFe concentrations among the RILs, with the largest effect contributed by the line × environment interaction, followed by line and environmental effects. The broad sense heritabilities of GZn and GFe were 0.36 ± 0.03 and 0.39 ± 0.03, respectively. Seven QTL for GZn on chromosomes 1DS, 2AS, 3BS, 4DS, 6AS, 6DL, and 7BL accounted for 2.2–25.1% of the phenotypic variances, and four QTL for GFe on chromosomes 3BL, 4DS, 6AS, and 7BL explained 2.3–30.4% of the phenotypic variances. QTL on chromosomes 4DS, 6AS, and 7BL might have pleiotropic effects on both GZn and GFe that were validated on a germplasm panel. Closely linked SNP markers were converted to high-throughput KASP markers, providing valuable tools for selection of improved Zn and Fe bio-fortification in breeding.
Tongue Cancer Cell-Derived CCL20 Induced by Interaction With Macrophages Promotes CD163 Expression on Macrophages
Authors: Shigeoka Manabu , Koma Yu-ichiro , Kodama Takayuki , Nishio Mari , Akashi Masaya , Yokozaki Hiroshi
Published: June 2021

Background

CD163-positive macrophages contribute to the aggressiveness of oral squamous cell carcinoma. We showed in a previous report that CD163-positive macrophages infiltrated not only to the cancer nest but also to its surrounding epithelium, depending on the presence of stromal invasion in tongue carcinogenesis. However, the role of intraepithelial macrophages in tongue carcinogenesis remains unclear. In this study, we assessed the biological behavior of intraepithelial macrophages on their interaction with cancer cells.

Materials and Methods

We established the indirect coculture system (intraepithelial neoplasia model) and direct coculture system (invasive cancer model) of human monocytic leukemia cell line THP-1-derived CD163-positive macrophages with SCC25, a tongue squamous cell carcinoma (TSCC) cell line. Conditioned media (CM) harvested from these systems were analyzed using cytokine array and enzyme-linked immunosorbent assay and extracted a specific upregulated cytokine in CM from the direct coculture system (direct CM). The correlation of both this cytokine and its receptor with various clinicopathological factors were evaluated based on immunohistochemistry using clinical samples from 59 patients with TSCC. Moreover, the effect of this cytokine in direct CM on the phenotypic alterations of THP-1 was confirmed by real-time polymerase chain reaction, western blotting, immunofluorescence, and transwell migration assay.

Results

It was shown that CCL20 was induced in the direct CM specifically. Interestingly, CCL20 was produced primarily in SCC25. The expression level of CCR6, which is a sole receptor of CCL20, was higher than the expression level of SCC25. Our immunohistochemical investigation showed that CCL20 and CCR6 expression was associated with lymphatic vessel invasion and the number of CD163-positive macrophages. Recombinant human CCL20 induced the CD163 expression and promoted migration of THP-1. We also confirmed that a neutralizing anti-CCL20 antibody blocked the induction of CD163 expression by direct CM in THP-1. Moreover, ERK1/2 phosphorylation was associated with the CCL20-driven induction of CD163 expression in THP-1.

Conclusions

Tongue cancer cell-derived CCL20 that was induced by interaction with macrophages promotes CD163 expression on macrophages.
Low Concordance Between T-Cell Densities in Matched Primary Tumors and Liver Metastases in Microsatellite Stable Colorectal Cancer
Authors: Dagenborg Vegar Johansen , Marshall Serena Elizabeth , Grzyb Krzysztof , Fretland Åsmund Avdem , Lund-Iversen Marius , Mælandsmo Gunhild Mari , Ree Anne Hansen , Edwin Bjørn , Yaqub Sheraz , Flatmark Kjersti
Published: June 2021

Background

The subtype, density and location of tumor infiltrating T-cells are being explored as prognostic and predictive biomarkers in primary colorectal cancer (pCRC) and colorectal liver metastases (CLM). Very limited data exist comparing findings in pCRC and matched CLM.

Patients and methods

Fifty-eight patients with available pCRC and matched CLM (57/58 microsatellite stable) were included in this OSLO-COMET substudy. In immunohistochemically stained sections, total (Ttot), helper (TH), cytotoxic (CTL), and regulatory (Treg) T-cells were manually counted in hotspots from the invasive margin (IM), intratumor (IT), and tumor adjacent regions to determine T-cell densities.

Results

A striking accumulation of T-cells was found in IM of both pCRC and CLM with much lower densities in the IT region, exemplified by Ttot of 2838 versus 340 cells/mm2, respectively, in CLM. The correlation at the individual level between T-cell densities in pCRC and corresponding CLM was poor for all regions and T-cell subtypes; for instance, the correlation coefficient (R2) for IM Ttot was 0.07. The IT TH : CTL and Treg : TH ratios were 2.94 and 0.44, respectively, in pCRC, and 1.84 and 0.24, respectively, in CLM.

Conclusion

The observed accumulation of T-cells in the IM regions of pCRC and CLM with low penetration to the IT regions, combined with high TH : CTL and Treg : TH ratios, point to the presence of an immune suppressive microenvironment. T-cell densities of CLM differed markedly from the matched pCRC, indicating that to evaluate T-cell biomarkers in metastasis, the commonly available pCRC cannot serve as a surrogate for the metastatic tumor.