bluuebunny/crossref_metadata_2025 huggingface dataset:
Levetiracetam and N-Cadherin Antibody Alleviate Brain Pathology Without Reducing Early Epilepsy Development After Focal Non-convulsive Status Epilepticus in Rats
Authors: Avdic Una , Ahl Matilda , Andersson My , Ekdahl Christine T.
Published: February 2021

Focal non-convulsive status epilepticus (fNCSE) is a neurological condition characterized by a prolonged seizure that may lead to the development of epilepsy. Emerging experimental evidence implicates neuronal death, microglial activation and alterations in the excitatory and inhibitory synaptic balance as key features in the pathophysiology following fNCSE. We have previously reported alterations in the excitatory adhesion molecule N-cadherin in rats with fNCSE originating from the hippocampus that subsequently also develop spontaneous seizures. In this study, fNCSE rats were treated intraperitoneally with the conventional anti-epileptic drug levetiracetam in combination with intraparenchymal infusion of N-cadherin antibodies (Ab) for 4 weeks post-fNCSE. The N-cadherin Ab was infused into the fornix and immunohistochemically N-cadherin Ab-stained neurons were detected within the dorsal hippocampal structures as well as in superjacent somatosensory cortex. Continuous levetiracetam treatment for 4 weeks post-fNCSE reduced microglia activation, including cell numbers and morphological changes, partly decreased neuronal cell loss, and excitatory post-synaptic scaffold protein PSD-95 expression in selective hippocampal structures. The additional treatment with N-cadherin Ab did not reverse neuronal loss, but moderately reduced microglial activation, and further reduced PSD-95 levels in the dentate hilus of the hippocampus. Despite the effects on brain pathology within the epileptic focus, neither monotherapy with systemic levetiracetam nor levetiracetam in combination with local N-cadherin Ab administration, reduced the amount of focal or focal evolving into bilateral convulsive seizures, seizure duration, or interictal epileptiform activity during 1 month of continuous electroenephalogram recordings within the hippocampus after fNCSE. Behavioral tests for spatial memory, anxiety, social interaction and anhedonia did not detect gross behavioral differences between fNCSE rats with or without treatment. The results reveal the refractory features of the present rodent model of temporal lobe epilepsy following fNCSE, which supports its clinical value for further therapeutic studies. We identify the persistent development of epilepsy following fNCSE, in spite of partly reduced brain pathology within the epileptic focus.
Case Report: Anti-NMDAR Encephalitis With Anti-MOG CNS Demyelination After Recurrent CNS Demyelination
Authors: Ren Bing-Yan , Guo Yi , Han Jing , Wang Qian , Li Zai-Wang
Published: February 2021

Introduction: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, a serious neurological autoimmune disorder caused by autoantibodies with diverse clinical manifestations, may simultaneously onset with antimyelin oligodendrocyte glycoprotein (MOG) demyelination after recurrent central nervous system (CNS) demyelination.

Case Report: We present a case of anti-NMDAR encephalitis combining with anti-MOG CNS demyelination following recurrent CNS demyelination. A 38-year-old man admitted to hospital developed epileptic seizures following recurrent episodes of cross-sensory disturbance and dizziness. Magnetic resonance imaging (MRI) showed a demyelinating lesion in the right brainstem initially. Despite a good response to methylprednisolone pulse therapy at the beginning, the patient still had relapses and progression after corticosteroid reduction or withdrawal. Then brain MRI discovered new serpentine lesions involving extensive cerebral cortex on his second relapse. Repeat autoantibodies test indicated cerebrospinal fluid (CSF) NMDAR antibodies coexisted with MOG-Abs simultaneously, suggesting the diagnosis of anti-NMDAR encephalitis with anti-MOG CNS demyelination.

Results: After a definite diagnosis, the patient was treated with mycophenolate mofetil (MMF) and corticosteroid. He was discharged after his symptoms ameliorated. No neurological sequels remained, and there were no effects on his activities of daily living after 6 months of immunoregulatory therapy of MMF and corticosteroid.

Conclusion: For individuals with recurrent CNS demyelination, especially combining with cortical encephalitis, repeated detection of autoantibodies against AE, and demyelination in CSF/serum can be helpful to enable a definite early diagnosis. For patients who suffer from anti-NMDAR encephalitis combining with anti-MOG CNS demyelination, second-line immunotherapy is recommended when first-line treatment such as steroids, intravenous immunoglobulin G (IVIG) and plasma exchange has been proven ineffective to prevent the relapse of disease.
The Frontal Aslant Tract: A Systematic Review for Neurosurgical Applications
Authors: La Corte Emanuele , Eldahaby Daniela , Greco Elena , Aquino Domenico , Bertolini Giacomo , Levi Vincenzo , Ottenhausen Malte , Demichelis Greta , Romito Luigi Michele , Acerbi Francesco , Broggi Morgan , Schiariti Marco Paolo , Ferroli Paolo , Bruzzone Maria Grazia , Serrao Graziano
Published: February 2021

The frontal aslant tract (FAT) is a recently identified white matter tract connecting the supplementary motor complex and lateral superior frontal gyrus to the inferior frontal gyrus. Advancements in neuroimaging and refinements to anatomical dissection techniques of the human brain white matter contributed to the recent description of the FAT anatomical and functional connectivity and its role in the pathogenesis of several neurological, psychiatric, and neurosurgical disorders. Through the application of diffusion tractography and intraoperative electrical brain stimulation, the FAT was shown to have a role in speech and language functions (verbal fluency, initiation and inhibition of speech, sentence production, and lexical decision), working memory, visual–motor activities, orofacial movements, social community tasks, attention, and music processing. Microstructural alterations of the FAT have also been associated with neurological disorders, such as primary progressive aphasia, post-stroke aphasia, stuttering, Foix–Chavany–Marie syndrome, social communication deficit in autism spectrum disorders, and attention–deficit hyperactivity disorder. We provide a systematic review of the current literature about the FAT anatomical connectivity and functional roles. Specifically, the aim of the present study relies on providing an overview for practical neurosurgical applications for the pre-operative, intra-operative, and post-operative assessment of patients with brain tumors located around and within the FAT. Moreover, some useful tests are suggested for the neurosurgical evaluation of FAT integrity to plan a safer surgery and to reduce post-operative deficits.
Semantic Grounding of Novel Spoken Words in the Primary Visual Cortex
Authors: Garagnani Max , Kirilina Evgeniya , Pulvermüller Friedemann
Published: February 2021

Embodied theories of grounded semantics postulate that, when word meaning is first acquired, a link is established between symbol (word form) and corresponding semantic information present in modality-specific—including primary—sensorimotor cortices of the brain. Direct experimental evidence documenting the emergence of such a link (i.e., showing that presentation of a previously unknown, meaningless word sound induces, after learning, category-specific reactivation of relevant primary sensory or motor brain areas), however, is still missing. Here, we present new neuroimaging results that provide such evidence. We taught participants aspects of the referential meaning of previously unknown, senseless novel spoken words (such as “Shruba” or “Flipe”) by associating them with either a familiar action or a familiar object. After training, we used functional magnetic resonance imaging to analyze the participants’ brain responses to the new speech items. We found that hearing the newly learnt object-related word sounds selectively triggered activity in the primary visual cortex, as well as secondary and higher visual areas.These results for the first time directly document the formation of a link between the novel, previously meaningless spoken items and corresponding semantic information in primary sensory areas in a category-specific manner, providing experimental support for perceptual accounts of word-meaning acquisition in the brain.
The Epidemiological and Mechanistic Understanding of the Neurological Manifestations of COVID-19: A Comprehensive Meta-Analysis and a Network Medicine Observation
Authors: Shen Jiayu , Hou Yuan , Zhou Yadi , Mehra Reena , Jehi Lara , Cheng Feixiong
Published: February 2021

The clinical characteristics and biological effects on the nervous system of infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain poorly understood. The aim of this study is to advance epidemiological and mechanistic understanding of the neurological manifestations of coronavirus disease 2019 (COVID-19) using stroke as a case study. In this study, we performed a meta-analysis of clinical studies reporting stroke history, intensive inflammatory response, and procoagulant state C-reactive protein (CRP), Procalcitonin (PCT), and coagulation indicator (D-dimer) in patients with COVID-19. Via network-based analysis of SARS-CoV-2 host genes and stroke-associated genes in the human protein-protein interactome, we inspected the underlying inflammatory mechanisms between COVID-19 and stroke. Finally, we further verified the network-based findings using three RNA-sequencing datasets generated from SARS-CoV-2 infected populations. We found that the overall pooled prevalence of stroke history was 2.98% (95% CI, 1.89–4.68;I2=69.2%) in the COVID-19 population. Notably, the severe group had a higher prevalence of stroke (6.06%; 95% CI 3.80–9.52;I2= 42.6%) compare to the non-severe group (1.1%, 95% CI 0.72–1.71;I2= 0.0%). There were increased levels of CRP, PCT, and D-dimer in severe illness, and the pooled mean difference was 40.7 mg/L (95% CI, 24.3–57.1), 0.07 μg/L (95% CI, 0.04–0.10) and 0.63 mg/L (95% CI, 0.28–0.97), respectively. Vascular cell adhesion molecule 1 (VCAM-1), one of the leukocyte adhesion molecules, is suspected to play a vital role of SARS-CoV-2 mediated inflammatory responses. RNA-sequencing data analyses of the SARS-CoV-2 infected patients further revealed the relative importance of inflammatory responses in COVID-19-associated neurological manifestations. In summary, we identified an elevated vulnerability of those with a history of stroke to severe COVID-19 underlying inflammatory responses (i.e., VCAM-1) and procoagulant pathways, suggesting monotonic relationships, thus implicating causality.
APOE-ε4 Carrier Status and Gut Microbiota Dysbiosis in Patients With Alzheimer Disease
Authors: Hou Min , Xu Gaolian , Ran Maosheng , Luo Wei , Wang Hui
Published: February 2021

Background

Alternations in gut microbiota and a number of genes have been implicated as risk factors for the development of Alzheimer disease (AD). However, the interactions between the altered bacteria and risk genetic variants remain unclear.

Objective

We aimed to explore associations of the risk genetic variants with altered gut bacteria in the onset of AD.

Methods

We collected baseline data and stool and blood samples from 30 AD patients and 47 healthy controls in a case-control study. The rs42358/rs4512 (ApoE), rs3851179 (PICALM), rs744373 (BIN1), rs9331888 (CLU), rs670139 (MS4A4E), rs3764650 (ABCA7), rs3865444 (CD33), rs9349407 (CD2AP), rs11771145 (EPHA1), and rs3818361/rs6656401 (CR1) were sequenced, and microbiota composition was characterized using 16S rRNA gene sequencing. The associations of the altered gut bacteria with the risk genetics were analyzed.

Results

Apolipoprotein ε4 allele and rs744373 were risk loci for the AD among 12 genetic variants. Phylum Proteobacteria; orders Enterobacteriales, Deltaproteobacteria, and Desulfovibrionales; families Enterobacteriaceae and Desulfovibrionaceae; and genera Escherichia–Shigella, Ruminococcaceae_UCG_002, Shuttleworthia, Anaerofustis, Morganelia, Finegoldia, and Anaerotruncus were increased in AD subjects, whereas family Enterococcaceae and genera Megamonas, Enterococcus, and Anaerostipes were more abundant in controls (P < 0.05). Among the altered microbiota, APOE ε4 allele was positively associated with pathogens: Proteobacteria.

Conclusion

The interaction of APOE ε4 gene and the AD-promoting pathogens might be an important factor requiring for the promotion of AD. Targeting to microbiota might be an effective therapeutic strategy for AD susceptible to APOE ε4 allele. This needs further investigation.
Identification of an Immune-Related Signature for Predicting Prognosis in Patients With Pancreatic Ductal Adenocarcinoma
Authors: Wang Weijia , Yan Liang , Guan Xiaoya , Dong Bin , Zhao Min , Wu Jianhui , Tian Xiuyun , Hao Chunyi
Published: February 2021

Purpose

Pancreatic ductal adenocarcinoma (PDAC) is one of the highest fatality rate cancers with poor survival rates. The tumor microenvironment (TME) is vital for tumor immune responses, leading to resistance to chemotherapy and poor prognosis of PDAC patients. This study aimed to provide a comprehensive evaluation of the immune genes and microenvironment in PDAC that might help in predicting prognosis and guiding clinical treatments.

Methods

We developed a prognosis-associated immune signature (i.e., PAIS) based on immune-associated genes to predict the overall survival of patients with PDAC. The clinical significance and immune landscapes of the signature were comprehensively analyzed.

Results

Owing to gene expression profiles from TCGA database, functional enrichment analysis revealed a significant difference in the immune response between PDAC and normal pancreas. Using transcriptome data analysis of a training set, we identified an immune signature represented by 5 genes (ESR2, IDO1, IL20RB, PPP3CA, and PLAU) related to the overall survival of patients with PDAC, significantly. This training set was well-validated in a test set. Our results indicated a clear association between a high-risk score and a very poor prognosis. Stratification analysis and multivariate Cox regression analysis revealed that PAIS was an important prognostic factor. We also found that the risk score was positively correlated with the inflammatory response, antigen-presenting process, and expression level of some immunosuppressive checkpoint molecules (e.g., CD73, PD-L1, CD80, and B7-H3). These results suggested that high-risk patients had a suppressed immune response. However, they could respond better to chemotherapy. In addition, PAIS was positively correlated with the infiltration of M2 macrophages in PDAC.

Conclusions

This study highlighted the relationship between the immune response and prognosis in PDAC and developed a clinically feasible signature that might serve as a powerful prognostic tool and help further optimize the cancer therapy paradigm.
Loss of 5-Hydroxymethylcytosine as an Epigenetic Signature That Correlates With Poor Outcomes in Patients With Medulloblastoma
Authors: Zhao Fu , Zhang Zhi-Wei , Zhang Jing , Zhang Shun , Zhang Heng , Zhao Chi , Chen Yang , Luo Lin , Tong Wei-Min , Li Chunde , Niu Yamei , Liu Pinan
Published: February 2021

Medulloblastoma, as the most common malignant brain tumor in children, exhibits highly dysregulated DNA methylation. The novel epigenetic marker—5-hydroxymethylcytosine (5hmC) plays essential role in gene regulation during brain development and in brain tumors. However, the biological and clinical implications of 5hmC in medulloblastoma are still unclear. Here, we detected global 5hmC levels in two independent medulloblastoma patient cohorts (discovery cohort: n = 81; validation cohort: n = 171) using ultra-high performance liquid chromatography-tandem mass spectrometry analysis. Immunohistochemistry was used to identify the cell proliferation and expression of Ten-eleven translocation 1 and 2 (TET1/2). The prognostic impacts of covariates on progression-free survival (PFS) and overall survival (OS) were evaluated using multivariate Cox hazards regression models. We observed that global 5hmC levels were decreased in medulloblastomas compared to normal cerebellums (P < 0.001). Multivariate analysis showed that low global 5hmC levels correlated with poor PFS and OS rates (discovery cohort: PFS: P = 0.003, OS: P = 0.002; validation cohort: PFS: P = 0.0002, OS: P = 0.001). Immunohistochemistry showed an inverse correlation between 5hmC score and Ki-67 index (r = -0.747, P < 0.0001). Moreover, 5hmC score in MB samples was associated with nuclear expression of TET1 (r = -0.419, P = 0.003) and TET2 (r = -0.399, P = 0.005) proteins. Our study demonstrates that loss of 5hmC is an epigenetic biomarker in medulloblastomas. Our results indicate that 5hmC could be a candidate prognostic indicator for improving survival prediction of risk stratification in patients with medulloblastoma.
The Outcome of Primary Hepatic Carcinoid Tumor: A Retrospective Study Based on Propensity Score Matched Survival Analysis
Authors: Jiang Shaotao , Wu Huijie , Fu Rongdang , Mai Jialuo , Yao Jiyou , Hua Xuefeng , Chen Huan , Liu Jie , Lu Minqiang , Li Ning
Published: February 2021

Background

Primary hepatic carcinoid tumor (PHCT) is rare and has unclear clinical characteristics and prognosis.

Methods

A retrospective study using data from the SEER database for patients diagnosed with PHCT used univariate and multivariate Cox models to screen for independent prognostic factors. The outcomes of patients in the surgical and nonsurgical groups were compared, and Propensity Score Matching (PSM) analysis was used to reduce confounder bias.

Results

A total of 186 PHCT patients were identified and the median survival was 65 (95% CI [43.287, 86.713]) months. Tumor size(HR = 2.493, 95% CI[1.222,5.083], p = 0.012), male(HR = 1.690, 95% CI[1.144,2.497], p = 0.008), age(HR = 2.583, 95% CI[1.697,3.930], p < 0.001), SEER stage(HR = 1.555, 95% CI[1.184,2.044], p = 0.002) and surgery(HR = 0.292, 95% CI[0.135,0.634], p = 0.002) were significantly correlated with patient prognosis. In multivariate analysis, sex(HR = 3.206, 95% CI[1.311,7.834], p = 0.011) and surgery(HR = 0.204, 95% CI[0.043,0.966], p = 0.0045) were independent predictors of patient prognosis. Females are potentially susceptible to PHCT but have a better prognosis. With consistent baseline data, surgical patients have a better prognosis.

Conclusions

PHCT is uncommon and survival time is longer than that of other primary liver cancers. We found that none-surgery was potentially independent risk factors for poor prognosis.
Glioma Stem Cells as Immunotherapeutic Targets: Advancements and Challenges
Authors: Piper Keenan , DePledge Lisa , Karsy Michael , Cobbs Charles
Published: February 2021

Glioblastoma is the most common and lethal primary brain malignancy. Despite major investments in research into glioblastoma biology and drug development, treatment remains limited and survival has not substantially improved beyond 1–2 years. Cancer stem cells (CSC) or glioma stem cells (GSC) refer to a population of tumor originating cells capable of self-renewal and differentiation. While controversial and challenging to study, evidence suggests that GCSs may result in glioblastoma tumor recurrence and resistance to treatment. Multiple treatment strategies have been suggested at targeting GCSs, including immunotherapy, posttranscriptional regulation, modulation of the tumor microenvironment, and epigenetic modulation. In this review, we discuss recent advances in glioblastoma treatment specifically focused on targeting of GCSs as well as their potential integration into current clinical pathways and trials.
Deoxypodophyllotoxin Inhibits Non-Small Cell Lung Cancer Cell Growth by Reducing HIF-1α-Mediated Glycolysis
Authors: Yang Yuping , Liu Lingling , Sun Jinghui , Wang Shu , Yang Zhongyuan , Li Honghui , Huang Na , Zhao Wei
Published: February 2021

Cancer cell proliferation is a metabolically demanding process that requires high rate of glycolysis to support anabolic growth. Deoxypodophyllotoxin (DPT) is a natural flavonolignan with various pharmacological activities, including antitumor effect. However, whether DPT affects the metabolic reprogramming of cancer cells is unknown. The purpose of this study is to investigate the role of DPT on non-small cell lung cancer (NSCLC) and to explore whether HIF-1α-mediated glycolysis is involved in its mechanism of action.The level of HIF-1α mRNA and protein in NSCLC cells following DPT treatment was detected using qRT-PCR and western blotting, respectively. Cell Counting Kit-8 (CCK-8) and caspase-3 activity assays were performed to analyze cell proliferation and apoptosis. The underlying molecular mechanism was identified by dual luciferase assay, Western blotting, qRT-PCR, glucose consumption, lactate production, and immunoprecipitation. A murine NSCLC model was used to clarify the effect of DPT treatment on tumor cell proliferation. Our findings showed that DPT treatment inhibited NSCLC cell growth in a dose- and time-dependent manner. Further analysis suggested that DPT treatment inhibited HIF-1α signaling pathway by Parkin-mediated protein degradation in NSCLC cells. DPT treatment significantly decreased glucose consumption and lactate production. In addition, DPT treatment reduced the expression of HIF-1α target genes, including GLUT1, HK2 and LDHA, resulting in reduction in glycolysis. We further revealed that DPT-induced cell growth inhibition and increased glucose and lactate levels could be reversed by overexpressing HIF-1α. Additionally, we found that DPT repressed NSCLC growth and GLUT1, HK2 and LDHA expression in vivo. Overall, this study suggested that DPT inhibited NSCLC growth by preventing HIF-1α-mediated glycolysis.
Antagonizing αvβ3 Integrin Improves Ischemia-Mediated Vascular Normalization and Blood Perfusion by Altering Macrophages
Authors: Li Yongjie , Gao Qian , Shu Xin , Xiao Lamei , Yang Yan , Pang Ningbo , Luo Yulin , He Jing , Zhang Liping , Wu Jianbo
Published: February 2021

Background: αVβ3 integrin has been implicated in the physiological processes and pathophysiology of important angiogenesis-related disorders; however, the preclinical and clinical data on integrin αVβ3 antagonists have not demonstrated improved outcomes. Our goal was to test the hypothesis that inhibition of αVβ3 integrin improves blood flow in a mouse hindlimb ischemia model.

Methods: In this study, we examined the effect of cilengitide, an αVβ3/αVβ5 integrin-specific RGD-mimetic cyclic peptide, on blood perfusion and angiogenesis after hindlimb ischemia. Blood flow was measured using Laser Doppler Scanner. Vascular density, and macrophages infiltration were examined by immunofluorescence. Macrophage polarization was measured by quantitative real time PCR.

Results: We found that low-dose, not high-dose, cilengitide increased blood flow perfusion, capillary formation, and pericyte coverage, accompanied by an accumulation of macrophages and increased expression of the chemokine (C-C motif) ligand 2 (CCL2) in ischemic muscles. Macrophage depletion using clodronate liposomes resulted in a reduction in low-dose cilengitide-induced blood flow perfusion, macrophage accumulation, pericyte coverage, and CCL2 expression. Finally, in vitro assays showed that low-dose, not high-dose, cilengitide increased macrophage migration.

Conclusion: These studies identified a novel role of the inhibition of αVβ3 integrin in modulating ischemia-induced angiogenesis, possibly through effects on macrophage infiltration and polarization, and revealed αVβ3 integrin inhibition to be a promising therapeutic strategy for peripheral artery disease.
Comparative Assessment of the Activity of Racemic and Dextrorotatory Forms of Thioctic (Alpha-Lipoic) Acid in Low Back Pain: Preclinical Results and Clinical Evidences From an Open Randomized Trial
Authors: Pacini Alessandra , Tomassoni Daniele , Trallori Elena , Micheli Laura , Amenta Francesco , Ghelardini Carla , Di Cesare Mannelli Lorenzo , Traini Enea
Published: February 2021

Peripheral neuropathies, characterized by altered nociceptive and muscular functions, are related to oxidative stress. Thioctic acid is a natural antioxidant existing as two optical isomers, but most clinically used as racemic mixture. The present study investigated the central nervous system’s changes which followed loose-ligation-derived compression of sciatic nerve, the putative neuroprotective role of thioctic acid and the pain-alleviating effect on low-back pain suffering patients. Loose ligation of the right sciatic nerve was performed in spontaneously hypertensive rats (SHR), a model of increased oxidative stress, and in normotensive Wistar-Kyoto rats (WKY). Animals with sciatic nerve ligation were left untreated or were treated intraperitoneally for 15 days with 250 μmol·kg−1·die−1 of (+/−)-thioctic acid; 125 μmol·kg−1·die−1 of (+/−)-thioctic acid; 125 μmol·kg−1·die−1 of (+)-thioctic acid lysine salt; 125 μmol·kg−1·die−1 of (−)-thioctic acid; 300 μmol·kg−1·die−1 pregabalin. Control SHR and WKY rats received the same amounts of vehicle. The clinical trial NESTIORADE (Sensory-Motor Neuropathies of the Sciatic Nerve: Comparative evaluation of the effect of racemic and dextro-rotatory forms of thioctic acid) examined 100 patients (49 males and 51 females aged 53 ± 11 years) dividing them into two equal-numbered groups, each treated daily for 60 days with 600 mg of (+/−)-thioctic acid or (+)-thioctic acid, respectively. The trial was registered prior to patient enrollment at EudraCT website (OSSC Number: 2011-000964-81). In the preclinical study, (+)-thioctic acid was more active than (+/−)- or (−)-enantiomers in relieving pain and protecting peripheral nerve as well as in reducing oxidative stress and astrogliosis in the spinal cord. Main findings of NESTIORADE clinical trial showed a greater influence on painful symptomatology, a quicker recovery and a better impact on quality of life of (+)-thioctic acid vs. (+/−)-thioctic acid. These data may have a pharmacological and pharmacoeconomical relevance and suggest that thioctic acid, above all (+)-enantiomer, could be considered for treatment of low-back pain involving neuropathy.
The NTCP p.Ser267Phe Variant Is Associated With a Faster Anti-HBV Effect on First-Line Nucleos(t)ide Analog Treatment
Authors: Wu Lina , Xu Wenxiong , Li Xuejun , Liu Ying , Wang Lu , Zhu Shu , Yang Fangji , Xie Chan , Peng Liang
Published: February 2021

Sodium taurocholate cotransporting polypeptide (NTCP) acts as a cellular receptor for the hepatitis B virus infection of host hepatocytes. Previously, many studies confirmed that the NTCP p.Ser267Phe variant was a protective factor against HBV-related disease progression. We therefore designed this study to investigate whether the NTCP p.Ser267Phe variant exerts an additive anti-HBV effect in chronic hepatitis B (CHB) patients on mainstream NAs treatment. After propensity score matching (PSM), a total of 136 CHB patients were included, among whom 68 were heterozygous carriers and 68 were wild-type controls. Proportions of primary nonresponse, partial virological response, virological breakthrough and hepatitis B reactivation and the HBV DNA clearance rate at each time point were compared using the chi-square test. Kaplan-Meier analysis and matched t-tests were also performed to estimate the speed of viral clearance and serum HBV DNA reduction, respectively. The proportion of primary nonresponse was significantly lower in heterozygous carriers than in wild-type controls (p < 0.001), especially in patients using entecavir (p = 0.013). Specifically, heterozygous carriers achieved HBV DNA clearance faster than wild-type controls (log-rank p = 0.0198). HBV DNA levels were reduced more in heterozygous carriers after 12 weeks (p < 0.001) and 24 weeks (p = 0.006) of treatment, especially among patients using ETV. Here, our study demonstrated that heterozygous mutations in rs2296651 enhanced the antiviral response of first-line NAs and helped to explore the possibility of combining NAs and NTCP blockers for a better anti-HBV effect.
Effects of Apigenin Treatment on Random Skin Flap Survival in Rats
Authors: Ma Xinyi , Lin Yuting , Liu yingying , Li Wenjie , He Jibing , Fang Miaojie , Lin Dingsheng
Published: February 2021

Random skin flaps are often used in plastic surgery, but the complications of marginal flap ischemia and necrosis often limit their wider clinical application. Apigenin (Api) is a flavonoid found in various fruits and vegetables. Api has been shown to promote angiogenesis, as well as reduce oxidative stress, membrane damage, and inflammation. In this study, we assessed the effects of Api treatment on random skin flap survival. Dorsal McFarlane skin flaps were transplanted into rats, which were randomly divided into three groups: control (normal saline), low-dose Api (20 mg/kg), and high-dose Api (50 mg/kg). Seven days after the surgery, the activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were measured. Histological analyses were performed to determine flap survival and tissue edema. H&E staining was performed to assess the histopathological changes in skin flaps, and the levels of microvascular density (MVD) were determined. Laser doppler flowmetry was used to assess microcirculation blood flow. Flap angiography was performed by injection of lead oxide/gelatin. The expression levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interlukin-1β (IL-lβ) were evaluated by immunohistochemistry. Rats in the high-dose Api group exhibited higher average flap survival area, microcirculatory flow, increased SOD activity, and higher VEGF expression levels compared with the other two groups. Furthermore, the levels of MDA and pro-inflammatory cytokines were significantly decreased in rats treated with high-dose Api. Our findings suggest the potential usefulness of Api in preventing skin flap tissue necrosis.
Transcriptomic and Metabolomic Analyses of Diaphorina citri Kuwayama Infected and Non-infected With Candidatus Liberibacter Asiaticus
Authors: Liu Kai , He Jiawei , Guan Ziying , Zhong Mingzhao , Pang Rui , Han Qunxin
Published: February 2021

The Asian citrus psyllid Diaphorina citri is the transmission vector of Huanglongbing (HLB), a devastating disease of citrus plants. The bacterium “Candidatus Liberibacter asiaticus” (CLas) associated with HLB is transmitted between host plants by D. citri in a circulative manner. Understanding the interaction between CLas and its insect vector is key for protecting citrus cultivation from HLB damage. Here, we used RNA sequencing and liquid chromatography-mass spectrometry (LC-MS) to analyze the transcriptome and metabolome of D. citri interacting with CLas. We identified 662 upregulated and 532 downregulated genes in CLas-infected insects. These genes were enriched in pathways involving carbohydrate metabolism, the insects’ immune system, and metabolism of cofactors and vitamins. We also detected 105 differential metabolites between CLas-infected and non-infected insects, including multiple nucleosides and lipid-related molecules. The integrated analysis revealed nine pathways—including those of the glycine, serine, threonine, and purine metabolism—affected by the differentially expressed genes from both groups. The network for these pathways was subsequently constructed. Our results thus provide insights regarding the cross-talk between the transcriptomic and metabolomic changes in D. citri in response to CLas infection, as well as information on the pathways and genes/metabolites related to the CLas–D. citri interaction.
Antioxidant and Protective Effects of Artemisia campestris Essential Oil Against Chlorpyrifos-Induced Kidney and Liver Injuries in Rats
Authors: Saoudi Mongi , Badraoui Riadh , Rahmouni Fatma , Jamoussi Kamel , El Feki Abdelfattah
Published: February 2021

This study is aimed to elucidate the possible antioxidant and protective effects of Artemisia campestris essential oil (ACEO) against the deleterious effects of chlorpyrifos (CPF) in rats. The in vivo study revealed increases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) activities and the serum contents of creatinine, urea, uric acid, cholesterol, triglycerides, low density lipoproteins (LDL), and glucose in rats treated with CPF as compared to controls. Meanwhile, hepatic and renal activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in liver and kidney decreased and the content of malondialdehyde (MDA) increased. Some histopathologic features were noticed in liver and kidney of the CPF group. Interestingly, ACEO alleviated the biochemical disruptions and reduced these hepato-renal morphologic changes.
Comparative Transcriptomic and Expression Profiles Between the Foot Muscle and Mantle Tissues in the Giant Triton Snail Charonia tritonis
Authors: Zhang Gege , Xu Meng , Zhang Chenglong , Jia Huixia , Zhang Hua , He Maoxian , Liu Wenguang
Published: February 2021

The giant triton snail (Charonia tritonis), an endangered gastropod species of ecological and economic importance, is widely distributed in coral reef ecosystems of the Indo-West Pacific region and the tropical waters of the South China Sea. Limited research on molecular mechanisms can be conducted because the complete genomic information on this species is unavailable. Hence, we performed transcriptome sequencing of theC. tritonisfoot muscle and mantle using the Illumina HiSeq sequencing platform. In 109,722 unigenes, we detected 7,994 (3,196 up-regulated and 4,798 down-regulated) differentially expressed genes (DEGs) from theC. tritonisfoot muscle and mantle transcriptomes. These DEGs will provide valuable resources to improve the understanding of molecular mechanisms involved in biomineralization ofC. tritonis.In the Gene Ontology (GO) database, DEGs were clustered into three main categories (biological processes, molecular functions, and cellular components) and were involved in 50 functional subcategories. The top 20 GO terms in the molecular function category included sulfotransferase activity, transferring sulfur-containing groups, and calcium ion binding, which are terms considered to be related to biomineralization. In KEGG classifications, transcriptomic DEGs were mainly enriched in glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate, and sulfur metabolism pathway, which may be related to biomineralization. The results of qPCR showed that three of the eight genes examined were significantly up-regulated in the mantle. The phylogenetic tree of BMP1 suggested a significant divergence between homologous genes inC. tritonis. Our results improve the understanding of biomineralization inC. tritonisand provide fundamental transcriptome information to study other molecular mechanisms such as reproduction.
The Role of Epoxyeicosatrienoic Acids in Cardiac Remodeling
Authors: Lai Jinsheng , Chen Chen
Published: February 2021

Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid by cytochrome P450 (CYP) epoxygenases, which include four regioisomers: 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET. Each of them possesses beneficial effects against inflammation, fibrosis, and apoptosis, which could combat cardiovascular diseases. Numerous studies have demonstrated that elevation of EETs by overexpression of CYP2J2, inhibition of sEH, or treatment with EET analogs showed protective effects in various cardiovascular diseases, including hypertension, myocardial infarction, and heart failure. As is known to all, cardiac remodeling is the major pathogenesis of cardiovascular diseases. This review will begin with the introduction of EETs and their protective effects in cardiovascular diseases. In the following, the roles of EETs in cardiac remodeling, with a particular emphasis on myocardial hypertrophy, apoptosis, fibrosis, inflammation, and angiogenesis, will be summarized. Finally, it is suggested that upregulation of EETs is a potential therapeutic strategy for cardiovascular diseases. The EET-related drug development against cardiac remodeling is also discussed, including the overexpression of CYP2J2, inhibition of sEH, and the analogs of EET.
QTL-Seq and Transcriptome Analysis Disclose Major QTL and Candidate Genes Controlling Leaf Size in Sesame (Sesamum indicum L.)
Authors: Sheng Chen , Song Shengnan , Zhou Rong , Li Donghua , Gao Yuan , Cui Xianghua , Tang Xuehui , Zhang Yanxin , Tu Jinxing , Zhang Xiurong , Wang Linhai
Published: February 2021

Leaf size is a crucial component of sesame (Sesamum indicumL.) plant architecture and further influences yield potential. Despite that it is well known that leaf size traits are quantitative traits controlled by large numbers of genes, quantitative trait loci (QTL) and candidate genes for sesame leaf size remain poorly understood. In the present study, we combined the QTL-seq approach and SSR marker mapping to identify the candidate genomic regions harboring QTL controlling leaf size traits in an RIL population derived from a cross between sesame varieties Zhongzhi No. 13 (with big leaves) and ZZM2289 (with small leaves). The QTL mapping revealed 56 QTL with phenotypic variation explained (PVE) from 1.87 to 27.50% for the length and width of leaves at the 1/3 and 1/2 positions of plant height.qLS15-1, a major and environmentally stable pleiotropic locus for both leaf length and width explaining 5.81 to 27.50% phenotypic variation, was located on LG15 within a 408-Kb physical genomic region flanked by the markers ZMM6185 and ZMM6206. In this region, a combination of transcriptome analysis with gene annotations revealed three candidate genesSIN_1004875,SIN_1004882, andSIN_1004883associated with leaf growth and development in sesame. These findings provided insight into the genetic characteristics and variability for sesame leaf and set up the foundation for future genomic studies on sesame leaves and will serve as gene resources for improvement of sesame plant architecture.
How Mixed Relay Teams in Swimming Should Be Organized for International Championship Success
Authors: Veiga Santiago , del Cerro Jesús Santos , Rodriguez Luis , Trinidad Alfonso , González-Ravé José María
Published: February 2021

The primary goal of the present research was to determine the order of swimmers on a mixed relay team that would ensure the best performance in the Fédération Internationale de Natation (FINA) World Championships held in Kazan (Russia, 2015), Budapest (Hungary, 2017), and Gwangju (South Korea, 2019). The data were obtained from database websites for the 4 × 100 m freestyle and 4 × 100 m medley official results,1 including 660 records from 188 entries of finals and 472 preliminary events. The results showed that the fastest swimmers (according to their best season times) were located primarily in the first or second positions of the freestyle relay. The most successful gender strategy for the 4 × 100 m freestyle (57 out of 82 observations) and for the 4 × 100 m medley (29 out of 83) relays was the order male-male-female-female, although no statistical differences were found (p = 0.79) for the medley relays. In the 4 × 100 m freestyle, the second (p = 0.002; β = 1.62) and third (p =0.003; β = 1.41) relay legs had a statistical effect on the total relay time, whereas in the 4 × 100 m medley, all four relay legs had a statistical effect (p < 0.001) on the final performance, the weight of the four strokes being different in heats with respect to the final round. Also, a later position of the first female swimmer or the consecutive position of two female swimmers in the team order significantly affected the relay performance in specific events. Mixed relay events appeared to present specific strategies in comparison to traditional male- or female-only relay lineups.
Meaning in Life: A Major Predictive Factor for Loneliness Comparable to Health Status and Social Connectedness
Authors: Macià Dídac , Cattaneo Gabriele , Solana Javier , Tormos José M. , Pascual-Leone Alvaro , Bartrés-Faz David
Published: February 2021

Objective: Loneliness is the subjective distress of feeling alone and has a strong impact on wellbeing and health. In addition to well-known predictors like isolation and poor health, a better understanding of the psychological determinants of loneliness would offer effective targets for future complementary interventions.

Methods: In this cross-sectional observational study (N = 2,240), we compared the explanatory power of several important risk factors of loneliness with the affective, motivational, and cognitive aspects of the Meaning in Life (MiL) construct. Different nested linear models were compared including socio-demographic, lifestyles, social-connectedness, and self-rated health variables, to assess the overlapping and non-overlapping explanatory power of each of them.

Results: Health status and MiL were found to be the most important predictors of loneliness, followed by social connectedness and, with a much lower weight, lifestyles, and socio-demographic factors. Within the MiL factor, the most cognitive component, sense of coherence, had a greater explanatory power than the more affective and motivational ones.

Conclusion: Reduced MiL, the capacity of an individual to attach “value and significance” to life, is a crucial predictor to the feeling of loneliness. These results suggest that programs aiming to combat loneliness should go well beyond situational interventions and include more cognitive, value-centered interventions that enable individuals to define and pursue a meaningful vital plan.
Dancing With Health: Quality of Life and Physical Improvements From an EU Collaborative Dance Programme With Women Following Breast Cancer Treatment
Authors: Karkou Vicky , Dudley-Swarbrick Irene , Starkey Jennifer , Parsons Ailsa , Aithal Supritha , Omylinska-Thurston Joanna , Verkooijen Helena M. , van den Boogaard Rosalie , Dochevska Yoanna , Djobova Stefka , Zdravkov Ivaylo , Dimitrova Ivelina , Moceviciene Aldona , Bonifacino Adriana , Asumi Alexis Matua , Forgione Dolores , Ferrari Andrea , Grazioli Elisa , Cerulli Claudia , Tranchita Eliana , Sacchetti Massimo , Parisi Attilio
Published: February 2021

Background:Women's health has received renewed attention in the last few years including health rehabilitation options for women affected by breast cancer. Dancing has often been regarded as one attractive option for supporting women's well-being and health, but research with women recovering from breast cancer is still in its infancy. Dancing with Health is multi-site pilot study that aimed to evaluate a dance programme for women in recovery from breast cancer across five European countries.

Methods:A standardized 32 h dance protocol introduced a range of Latin American dances presented within a sports and exercise framework with influences from dance movement therapy. Fifty-four women (M age 53.51; SD 7.99) participated in the study who had a breast cancer diagnosis <3 years, chemotherapy >6 weeks, no indication of metastasis, or scheduled surgery/chemotherapy/radiation treatment for the duration of the intervention. Primary outcome data was collected for anthropometric and fitness measures next to cancer-related quality of life.T-tests and Wilcoxon signed ranked tests were used to establish differences pre and post intervention. Cohen's d was also calculated to determine the effect size of the intervention.

Results:Statistically significant changes were found for: (i) weight, right and left forearm circumference and hip; (ii) 6 min walking, right and left handgrip, sit-to-stand and sit-and-reach; (iii) the EORTC-QLQ C30 summary score as well as the subscales of emotional and social functioning and symptoms. In all cases the direction of change was positive, while Cohen's d calculated showed that the effect of the intervention for these parameters ranged from intermediate to large.

Conclusion:Changes on the above anthropometric, fitness and quality of life measures suggest that the intervention was of value to the participating women recovering from breast cancer. Results also advocate collaborative efforts across countries to further research.
Early Detection of Ultra High Risk for Psychosis in a Norwegian Catchment Area: The Two Year Follow-Up of the Prevention of Psychosis Study
Authors: Joa Inge , Bjornestad Jone , Johannessen Jan Olav , Langeveld Johannes , Stain Helen J. , Weibell Melissa , Hegelstad Wenche ten Velden
Published: February 2021

Objectives: Most individuals experience a relatively long period of sub-clinical psychotic like symptoms, known as the ultra high risk (UHR) or at risk mental states (ARMS), prior to a first episode of psychosis. Approximately 95% of individuals who will later develop psychosis are not referred to specialized clinical services and assessed during the UHR phase. The study aimed to investigate whether a systematic early detection program, modeled after the successful early detection of psychosis program TIPS, would improve the detection of help-seeking UHR individuals. The secondary aim was to examine the rates and predictors of conversion to psychosis after 2 years.

Method: The overall study design was a prospective (2012–2018), follow- up study of individuals fulfilling UHR inclusion criteria as assessed by the structural interview for prodromal syndromes (SIPS). Help-seeking UHR individuals were recruited through systematic early detection strategies in a Norwegian catchment area and treated in the public mental health services.

Results: In the study period 141 UHR help-seeking individuals were identified. This averages an incidence of 7 per 100,000 people per year. The baseline assessment was completed by 99 of these and the 2 year psychosis conversion rate was 20%. A linear mixed-model regression analysis found that the significant predictors of conversion were the course of positive (0.038) and negative symptoms (0.017). Age was also a significant predictor and showed an interaction with female gender (<0.000).

Conclusion: We managed to detect a proportion of UHR individuals in the upper range of the expected prediction by the population statistics and further case enrichment would improve this rate. Negative symptoms were significant predictors. As a risk factor for adverse functional outcomes and social marginalization, this could offer opportunities for earlier psychosocial intervention.