bluuebunny/crossref_metadata_2025 huggingface dataset:
Ghrelin as an Anti-Sepsis Peptide: Review
Authors: Mathur Nimisha , Mehdi Syed F. , Anipindi Manasa , Aziz Monowar , Khan Sawleha A. , Kondakindi Hema , Lowell Barbara , Wang Ping , Roth Jesse
Published: January 2021

Sepsis continues to produce widespread inflammation, illness, and death, prompting intensive research aimed at uncovering causes and therapies. In this article, we focus on ghrelin, an endogenous peptide with promise as a potent anti-inflammatory agent. Ghrelin was discovered, tracked, and isolated from stomach cells based on its ability to stimulate release of growth hormone. It also stimulates appetite and is shown to be anti-inflammatory in a wide range of tissues. The anti-inflammatory effects mediated by ghrelin are a result of both the stimulation of anti-inflammatory processes and an inhibition of pro-inflammatory forces. Anti-inflammatory processes are promoted in a broad range of tissues including the hypothalamus and vagus nerve as well as in a broad range of immune cells. Aged rodents have reduced levels of growth hormone (GH) and diminished immune responses; ghrelin administration boosts GH levels and immune response. The anti-inflammatory functions of ghrelin, well displayed in preclinical animal models of sepsis, are just being charted in patients, with expectations that ghrelin and growth hormone might improve outcomes in patients with sepsis.
Cannabinoids as Key Regulators of Inflammasome Signaling: A Current Perspective
Authors: Suryavanshi Santosh V. , Kovalchuk Igor , Kovalchuk Olga
Published: January 2021

Inflammasomes are cytoplasmic inflammatory signaling protein complexes that detect microbial materials, sterile inflammatory insults, and certain host-derived elements. Inflammasomes, once activated, promote caspase-1–mediated maturation and secretion of pro-inflammatory cytokines, interleukin (IL)-1β and IL-18, leading to pyroptosis. Current advances in inflammasome research support their involvement in the development of chronic inflammatory disorders in contrast to their role in regulating innate immunity. Cannabis (marijuana) is a natural product obtained from the Cannabis sativa plant, and pharmacologically active ingredients of the plant are referred to as cannabinoids. Cannabinoids and cannabis extracts have recently emerged as promising novel drugs for chronic medical conditions. Growing evidence indicates the potent anti-inflammatory potential of cannabinoids, especially Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), and synthetic cannabinoids; however, the mechanisms remain unclear. Several attempts have been made to decipher the role of cannabinoids in modulating inflammasome signaling in the etiology of chronic inflammatory diseases. In this review, we discuss recently published evidence on the effect of cannabinoids on inflammasome signaling. We also discuss the contribution of various cannabinoids in human diseases concerning inflammasome regulation. Lastly, in the milieu of coronavirus disease-2019 (COVID-19) pandemic, we confer available evidence linking inflammasome activation to the pathophysiology of COVID-19 suggesting overall, the importance of cannabinoids as possible drugs to target inflammasome activation in or to support the treatment of a variety of human disorders including COVID-19.
Mechanisms Governing Immunotherapy Resistance in Pancreatic Ductal Adenocarcinoma
Authors: Schmiechen Zoe C. , Stromnes Ingunn M.
Published: January 2021

Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy with an overall 5-year survival rate of 10%. Disease lethality is due to late diagnosis, early metastasis and resistance to therapy, including immunotherapy. PDA creates a robust fibroinflammatory tumor microenvironment that contributes to immunotherapy resistance. While previously considered an immune privileged site, evidence demonstrates that in some cases tumor antigen-specific T cells infiltrate and preferentially accumulate in PDA and are central to tumor cell clearance and long-term remission. Nonetheless, PDA can rapidly evade an adaptive immune response using a myriad of mechanisms. Mounting evidence indicates PDA interferes with T cell differentiation into potent cytolytic effector T cells via deficiencies in naive T cell priming, inducing T cell suppression or promoting T cell exhaustion. Mechanistic research indicates that immunotherapy combinations that change the suppressive tumor microenvironment while engaging antigen-specific T cells is required for treatment of advanced disease. This review focuses on recent advances in understanding mechanisms limiting T cell function and current strategies to overcome immunotherapy resistance in PDA.
Revisiting the Hygiene Hypothesis in the Context of Autoimmunity
Authors: Bach Jean-François
Published: January 2021

Initially described for allergic diseases, the hygiene hypothesis was extended to autoimmune diseases in the early 2000s. A historical overview allows appreciation of the development of this concept over the last two decades and its discussion in the context of evolution. While the epidemiological data are convergent, with a few exceptions, the underlying mechanisms are multiple and complex. A major question is to determine what is the respective role of pathogens, bacteria, viruses, and parasites,versuscommensals. The role of the intestinal microbiota has elicited much interest, but is it a cause or a consequence of autoimmune-mediated inflammation? Our hypothesis is that both pathogens and commensals intervene. Another question is to dissect what are the underlying cellular and molecular mechanisms. The role of immunoregulatory cytokines, in particular interleukin-10 and TGF beta is probably essential. An important place should also be given to ligands of innate immunity receptors present in bacteria, viruses or parasites acting independently of their immunogenicity. The role of Toll-Like Receptor (TLR) ligands is well documented includingviaTLR ligand desensitization.
Cytokine Signature Induced by SARS-CoV-2 Spike Protein in a Mouse Model
Authors: Gu Tingxuan , Zhao Simin , Jin Guoguo , Song Mengqiu , Zhi Yafei , Zhao Ran , Ma Fayang , Zheng Yaqiu , Wang Keke , Liu Hui , Xin Mingxia , Han Wei , Li Xiang , Dong Christopher D. , Liu Kangdong , Dong Zigang
Published: January 2021

Although COVID-19 has become a major challenge to global health, there are currently no efficacious agents for effective treatment. Cytokine storm syndrome (CSS) can lead to acute respiratory distress syndrome (ARDS), which contributes to most COVID-19 mortalities. Research points to interleukin 6 (IL-6) as a crucial signature of the cytokine storm, and the clinical use of the IL-6 inhibitor tocilizumab shows potential for treatment of COVID-19 patient. In this study, we challenged wild-type and adenovirus-5/human angiotensin-converting enzyme 2-expressing BALB/c mice with a combination of polyinosinic-polycytidylic acid and recombinant SARS-CoV-2 spike-extracellular domain protein. High levels of TNF-α and nearly 100 times increased IL-6 were detected at 6 h, but disappeared by 24 h in bronchoalveolar lavage fluid (BALF) following immunostimulant challenge. Lung injury observed by histopathologic changes and magnetic resonance imaging at 24 h indicated that increased TNF-α and IL-6 may initiate CSS in the lung, resulting in the continual production of inflammatory cytokines. We hypothesize that TNF-α and IL-6 may contribute to the occurrence of CSS in COVID-19. We also investigated multiple monoclonal antibodies (mAbs) and inhibitors for neutralizing the pro-inflammatory phenotype of COVID-19: mAbs against IL-1α, IL-6, TNF-α, and granulocyte-macrophage colony-stimulating factor (GM-CSF), and inhibitors of p38 and JAK partially relieved CSS; mAbs against IL-6, TNF-α, and GM-CSF, and inhibitors of p38, extracellular signal-regulated kinase, and myeloperoxidase somewhat reduced neutrophilic alveolitis in the lung. This novel murine model opens a biologically safe, time-saving avenue for clarifying the mechanism of CSS/ARDS in COVID-19 and developing new therapeutic drugs.
C-Reactive Protein Levels in Systemic Lupus Erythematosus Are Modulated by the Interferon Gene Signature and CRP Gene Polymorphism rs1205
Authors: Enocsson Helena , Gullstrand Birgitta , Eloranta Maija-Leena , Wetterö Jonas , Leonard Dag , Rönnblom Lars , Bengtsson Anders A. , Sjöwall Christopher
Published: January 2021

Objectives

Patients with systemic lupus erythematosus (SLE) often display modest elevations of C-reactive protein (CRP) despite raised disease activity and increased interleukin (IL-) 6. We asked to what extent IL-6 levels, the CRP polymorphism rs1205, and the type I interferon (IFN) gene signature affects the basal CRP levels in patients with SLE during a quiescent phase of the disease.

Methods

CRP and IL-6 were analyzed in plasma from 57 patients meeting established classification criteria for SLE. The CRP polymorphism rs1205 was assessed and gene expression analyzed including four type I IFN-regulated genes (IGS).

Results

CRP was increased in patients with detectable IL-6 levels (p=0.001) and decreased among IGS-positive subjects (p=0.033). A multiple linear regression model revealed IL-6 to have a positive association with CRP levels, whereas both IGS-positivity and CRP genotype (rs1205) AA/GA were negatively associated with CRP-levels.

Conclusion

Our data offer an explanation to the modest CRP levels seen in viral infections and IFN-α driven autoimmunity and corroborate prior observations showing an IFN-α dependent downregulation of CRP. The latter observation, together with the fact that the CRP-lowering polymorphism rs1205 is overrepresented in human SLE, could explain low basal CRP and inadequate CRP-responses among patients with active SLE.
Gut Microbiota Profiles and Microbial-Based Therapies in Post-operative Crohn's Disease: A Systematic Review
Authors: Zhuang Xiaojun , Tian Zhenyi , Li Na , Mao Ren , Li Xiaozhi , Zhao Min , Xiong Shanshan , Zeng Zhirong , Feng Rui , Chen Minhu
Published: January 2021

Background and Aims: Gut microbiota recolonization after intestinal resection had been reported to be associated with post-operative recurrence in Crohn's disease (CD). However, the results of different studies are inconsistent and even contradictory. In addition, knowledge on the efficacy of microbial-based therapies in preventing post-operative recurrence of CD is limited. Therefore, the aim of this review was to investigate gut microbiota profiles in patients with CD before and after surgery and evaluate microbial-based therapies in preventing post-operative recurrence.

Methods: Electronic databases were searched from inception to 31 June 2020 using predefined terms. Studies that investigated gut microbiota pre- and post-intestinal resection, and microbial-based therapies in preventing post-operative recurrence, were eligible. Study quality was assessed using either the Newcastle–Ottawa scale or Jadad scoring system.

Results: Twelve studies investigating gut microbiota of CD patients suffering from operation, and other 12 studies evaluating the efficacy of antibiotics and probiotics, were included in our review. The mucosa-associated microbiota in surgical biopsy of CD patients is significantly distinct from that in normal mucosa from healthy subjects. Gut microbiota recolonization following surgery might be associated with post-operative recurrence in CD patients. Furthermore, CD patients with post-operative recurrence presented a gain in pro-inflammatory pathogenic bacteria and a loss in short-chain fatty acid-producing bacteria before and after surgery. However, no consistent bacteria or metabolites were found to predict the post-operative recurrence of CD. Additionally, microbial-based therapies are deficient and present restricted widespread clinical utility due to several deficiencies.

Conclusion: Recurrence-associated bacteria observed pre- and post- operation might be promising in preventing the post-operative recurrence of CD. Furthermore, potential microbe biomarkers for predicting subsequent disease recurrence should be validated with larger sample sizes using more rigorous and standardized methodologies.
Stabilization of a Broadly Neutralizing Anti-Chikungunya Virus Single Domain Antibody
Authors: Liu Jinny L. , Webb Emily M. , Zabetakis Dan , Burke Crystal W. , Gardner Christina L. , Glass Pamela J. , Legler Patricia M. , Weger-Lucarelli James , Anderson George P. , Goldman Ellen R.
Published: January 2021

A single domain antibody (clone CC3) previously found to neutralize a vaccine strain of the chikungunya virus (PRNT50 = 2. 5 ng/mL) was found to be broadly neutralizing. Clone CC3 is not only able to neutralize a wild-type (WT) strain of chikungunya virus (CHIKV), but also neutralizes WT strains of Mayaro virus (MAYV) and Ross River virus (RRV); both arthralgic, Old World alphaviruses. Interestingly, CC3 also demonstrated a degree of neutralizing activity against the New World alphavirus, Venezuelan equine encephalitis virus (VEEV); albeit both the vaccine strain, TC-83, and the parental, WT Trinidad donkey strain had PRNT50 values ~1,000-fold higher than that of CHIKV. However, no neutralization activity was observed with Western equine encephalitis virus (WEEV). Ten CC3 variants designed to possess a range of isoelectric points, both higher and lower, were constructed. This approach successfully identified several lower pI mutants which possessed improved thermal stabilities by as much as 10°C over the original CC3 (Tm = 62°C), and excellent refolding abilities while maintaining their capacity to bind and neutralize CHIKV.
Hypothesis: Mechanisms That Prevent Recovery in Prolonged ICU Patients Also Underlie Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Authors: Stanculescu Dominic , Larsson Lars , Bergquist Jonas
Published: January 2021

Here the hypothesis is advanced that maladaptive mechanisms that prevent recovery in some intensive care unit (ICU) patients may also underlie Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Specifically, these mechanisms are: (a) suppression of the pituitary gland'spulsatilesecretion of tropic hormones, and (b) a “vicious circle” between inflammation, oxidative and nitrosative stress (O&NS), and low thyroid hormonefunction. This hypothesis should be investigated through collaborative research projects.
3D Bioprinting at the Frontier of Regenerative Medicine, Pharmaceutical, and Food Industries
Authors: Ramadan Qasem , Zourob Mohammed
Published: January 2021

3D printing technology has emerged as a key driver behind an ongoing paradigm shift in the production process of various industrial domains. The integration of 3D printing into tissue engineering, by utilizing life cells which are encapsulated in specific natural or synthetic biomaterials (e.g., hydrogels) as bioinks, is paving the way toward devising many innovating solutions for key biomedical and healthcare challenges and heralds' new frontiers in medicine, pharmaceutical, and food industries. Here, we present a synthesis of the available 3D bioprinting technology from what is found and what has been achieved in various applications and discussed the capabilities and limitations encountered in this technology.
Taxonomy, Ontogenesis and Evolutionary Relationships of the Algae-Bearing Ciliate Bourlandella viridis (Kahl, 1932) comb. nov., With Establishment of a New Genus and New Family (Protista, Ciliophora, Hypotrichia)
Authors: Song Wenya , Zhang Tengyue , Zhang Xue , Warren Alan , Song Weibo , Zhao Yan , Luo Xiaotian
Published: January 2021

Hypotrichs are the most complex and highly differentiated ciliate lineages and have great potential for evolutionary novelties. Problems in hypotrich systematics are mainly due to discordance between the morphological and genetic data (mainly small subunit rRNA gene). Species with morphologies that are characteristic of two or more higher rank taxa are probably a major contributing factor to these conflicts. The present study describes a Chinese population of a poorly known organism with numerous endosymbiotic zoochlorellae, the morphology of which corresponds well with the type population of Limnoholosticha viridis (Kahl, 1932) Li et al., 2017. Newly obtained information shows this species has a zigzag midventral cirral pattern that is diagnostic of urostylids, whereas the dorsal ciliature shares features (presence of dorsomarginal kinety and dorsal kinety 3 fragmentation) that are typical of oxytrichids. Molecular phylogenetic analyses reveal a close relationship with oxytrichids. An integrative approach combining morphological, morphogenetic, phylogenetic and ecological analyses indicates that L. viridis represents a new genus and new family which might be an intermediate form between uorstylids and dorsomarginalians. Thus, Bourlandellidae fam. nov. and Bourlandella gen. nov. are here established. Lastly, we speculate that phenotypic convergence and mixtrophy might confer on the new combination, Bourlandella viridis (Kahl, 1932) comb. nov., the ability to adapt to a wide range of environmental conditions.
Chemical-Assisted Microbially Mediated Chromium (Cr) (VI) Reduction Under the Influence of Various Electron Donors, Redox Mediators, and Other Additives: An Outlook on Enhanced Cr(VI) Removal
Authors: Rahman Zeeshanur , Thomas Lebin
Published: January 2021

Chromium (Cr) (VI) is a well-known toxin to all types of biological organisms. Over the past few decades, many investigators have employed numerous bioprocesses to neutralize the toxic effects of Cr(VI). One of the main process for its treatment is bioreduction into Cr(III). Key to this process is the ability of microbial enzymes, which facilitate the transfer of electrons into the high valence state of the metal that acts as an electron acceptor. Many underlying previous efforts have stressed on the use of different external organic and inorganic substances as electron donors to promote Cr(VI) reduction process by different microorganisms. The use of various redox mediators enabled electron transport facility for extracellular Cr(VI) reduction and accelerated the reaction. Also, many chemicals have employed diverse roles to improve the Cr(VI) reduction process in different microorganisms. The application of aforementioned materials at the contaminated systems has offered a variety of influence on Cr(VI) bioremediation by altering microbial community structures and functions and redox environment. The collective insights suggest that the knowledge of appropriate implementation of suitable nutrients can strongly inspire the Cr(VI) reduction rate and efficiency. However, a comprehensive information on such substances and their roles and biochemical pathways in different microorganisms remains elusive. In this regard, our review sheds light on the contributions of various chemicals as electron donors, redox mediators, cofactors, etc., on microbial Cr(VI) reduction for enhanced treatment practices.
Antimicrobial Activity and Proposed Action Mechanism of Linalool Against Pseudomonas fluorescens
Authors: Guo Fengyu , Chen Qianping , Liang Qiong , Zhang Ming , Chen Wenxue , Chen Haiming , Yun Yonghuan , Zhong Qiuping , Chen Weijun
Published: January 2021

In this study, linalool, one of the principal components of essential oils, was used as an antibacterial agent to investigate the antibacterial activity and mechanism of linalool against Pseudomonas fluorescens. The reduction in membrane potential (MP), leakage of alkaline phosphatase (AKP) and the release of macromolecules, including DNA, RNA and protein confirmed that damage to cell wall membrane structure and leakage of cytoplasmic contents were due to the linalool treatment. Furthermore, the decrease of enzyme activity, including the succinate dehydrogenase (SDH), malate dehydrogenase (MDH), pyruvate kinase (PK), and ATPase indicated that linalool could lead to metabolic dysfunction and inhibit energy synthesis. In addition, the activity of respiratory chain dehydrogenase and metabolic activity of respiration indicated that linalool inhibits cellular respiration. These results revealed that linalool had strong antibacterial activity against P. fluorescens via membrane damage, bacterial metabolic and oxidative respiratory perturbations, interfering in cellular functions and even causing cell death. It was suggested that linalool may be a new potential source as food antiseptics in food systems.
A Virulence Associated Siderophore Importer Reduces Antimicrobial Susceptibility of Klebsiella pneumoniae
Authors: Farzand Robeena , Rajakumar Kumar , Barer Michael R. , Freestone Primrose P. E. , Mukamolova Galina V. , Oggioni Marco R. , O’Hare Helen M.
Published: January 2021

The accessory genomes of many pathogenic bacteria include ABC transporters that scavenge metal by siderophore uptake and ABC transporters that contribute to antimicrobial resistance by multidrug efflux. There are mechanistic and recently recognized structural similarities between siderophore importer proteins and efflux pumps. Here we investigated the influence of siderophore importer YbtPQ on antimicrobial resistance of Klebsiella pneumoniae. YbtPQ is encoded in the yersiniabactin cluster in a prevalent mobile genetic element ICEKp, and is also common in pathogenicity islands of Escherichia coli and Yersinia species, where yersiniabactin enhances virulence. Deletion of ICEKp increased the susceptibility of K. pneumoniae to all antimicrobials tested. The mechanism was dependent on the yersiniabactin importer YbtPQ and may involve antimicrobial efflux, since it was affected by the inhibitor reserpine. The element ICEKp is naturally highly mobile, indeed the accessory genome of K. pneumoniae is recognized as a reservoir of genes for the emergence of hospital outbreak strains and for transfer to other Gram-negative pathogens. Introduction of ICEKp, or a plasmid encoding YbtPQ, to E. coli decreased its susceptibility to a broad range of antimicrobials. Thus a confirmed siderophore importer, on a rapidly evolving and highly mobile element capable of interspecies transfer, may have a secondary function exporting antimicrobials.
Cytotoxic, Antimitotic, DNA Binding, Photocatalytic, H2O2 Sensing, and Antioxidant Properties of Biofabricated Silver Nanoparticles Using Leaf Extract of Bryophyllum pinnatum (Lam.) Oken
Authors: Chandraker Sandip Kumar , Lal Mishri , Dhruve Preeti , Singh Rana P. , Shukla Ravindra
Published: January 2021

Bryophyllum pinnatum is a perennial herb traditionally used in ethnomedicine. In the present report, silver nanoparticles (AgNPs) were synthesized using B. pinnatum leaf extract. BP-AgNPs were confirmed following UV-Vis spectroscopy with SPR peak at 412 nm and further characterized by FTIR, XRD, SEM-EDX, and TEM. Microscopic images confirmed the spherical shape and ~15 nm average size of nanostructures. BP-AgNPs were evaluated for photocatalytic degradation of hazardous dyes (methylene blue and Rhodamine-B) and showed their complete reduction within 100 and 110 min., respectively. BP-AgNPs have emerged as a unique SPR-based novel sensor for the detection of H2O2, which may deliver exciting prospects in clinical and industrial areas. DPPH and ABTS free radical scavenging activity were studied with respective IC50 values of 89 and 259 μg/mL. A strong intercalating interaction of CT-DNA with BP-AgNPs was investigated. Observed chromosomal abnormalities confirm the antimitotic potential of BP-AgNPs in the meristematic root tip. The cytotoxicity of BP-AgNPs against B16F10 (melanoma cell line) and A431 (squamous cell carcinoma cell line), was assessed with respective IC50 values of 59.5 and 96.61 μg/ml after 24 h of treatment. The presented green synthetic approach provides a novel and new door for environmental, industrial, and biomedical applications.
Age- and Sex-Specific Standard Scores for the Reading the Mind in the Eyes Test
Authors: Kynast Jana , Polyakova Maryna , Quinque Eva Maria , Hinz Andreas , Villringer Arno , Schroeter Matthias L.
Published: January 2021

The reliable, valid and economic assessment of social cognition is more relevant than ever in the field of clinical psychology. Theory of Mind is one of the most important socio-cognitive abilities but standardized assessment instruments for adults are rare. The Reading the Mind in the Eyes Test (RMET) is well-established and captures the ability to identify mental states from gaze. Here, we computed standard scores for the German version of the RMET derived from a large, community-dwelling sample of healthy adults (20–79 years). The standardization sample contains 966 healthy adult individuals of the population-based Leipzig Research Center for Civilization Diseases (LIFE) study. Before standardization, weighting factors were applied to match the current sample with distribution characteristics of the German population regarding age, sex, and education. RMET scores were translated into percentage ranks for men and women of five age groups (20–29, 30–39, 40–49, 50–59, 60+ years). Age-specific percentage ranks are provided for men and women. Independent of age, men present a larger variance in test scores compared to women. Within the specific age groups, women score higher and their scoring range is less variable. With increasing age, the scoring variance increases in both men and women. This is the first study providing age- and sex-specific RMET standard scores. Data was weighted to match German population characteristics, enabling the application of standard scores across German-speaking areas. Our results contribute to the standardized assessment of socio-cognitive abilities in clinical diagnostics.
Impact of Chaperone-Mediated Autophagy in Brain Aging: Neurodegenerative Diseases and Glioblastoma
Authors: Auzmendi-Iriarte Jaione , Matheu Ander
Published: January 2021

Brain aging is characterized by a time-dependent decline of tissue integrity and function, and it is a major risk for neurodegenerative diseases and brain cancer. Chaperone-mediated autophagy (CMA) is a selective form of autophagy specialized in protein degradation, which is based on the individual translocation of a cargo protein through the lysosomal membrane. Regulation of processes such as proteostasis, cellular energetics, or immune system activity has been associated with CMA, indicating its pivotal role in tissue homeostasis. Since first studies associating Parkinson’s disease (PD) to CMA dysfunction, increasing evidence points out that CMA is altered in both physiological and pathological brain aging. In this review article, we summarize the current knowledge regarding the impact of CMA during aging in brain physiopathology, highlighting the role of CMA in neurodegenerative diseases and glioblastoma, the most common and aggressive brain tumor in adults.
Proteomic Characterization of Human Neural Stem Cells and Their Secretome During in vitro Differentiation
Authors: Červenka Jakub , Tylečková Jiřina , Kupcová Skalníková Helena , Vodičková Kepková Kateřina , Poliakh Ievgeniia , Valeková Ivona , Pfeiferová Lucie , Kolář Michal , Vaškovičová Michaela , Pánková Tereza , Vodička Petr
Published: January 2021

Cell therapies represent a promising approach to slow down the progression of currently untreatable neurodegenerative diseases (e.g., Alzheimer's and Parkinson's disease or amyotrophic lateral sclerosis), as well as to support the reconstruction of functional neural circuits after spinal cord injuries. In such therapies, the grafted cells could either functionally integrate into the damaged tissue, partially replacing dead or damaged cells, modulate inflammatory reaction, reduce tissue damage, or support neuronal survival by secretion of cytokines, growth, and trophic factors. Comprehensive characterization of cells and their proliferative potential, differentiation status, and population purity before transplantation is crucial to preventing safety risks, e.g., a tumorous growth due to the proliferation of undifferentiated stem cells. We characterized changes in the proteome and secretome of human neural stem cells (NSCs) during their spontaneous (EGF/FGF2 withdrawal) differentiation and differentiation with trophic support by BDNF/GDNF supplementation. We used LC-MS/MS in SWATH-MS mode for global cellular proteome profiling and quantified almost three thousand cellular proteins. Our analysis identified substantial protein differences in the early stages of NSC differentiation with more than a third of all the proteins regulated (including known neuronal and NSC multipotency markers) and revealed that the BDNF/GDNF support affected more the later stages of the NSC differentiation. Among the pathways identified as activated during both spontaneous and BDNF/GDNF differentiation were the HIF-1 signaling pathway, Wnt signaling pathway, and VEGF signaling pathway. Our follow-up secretome analysis using Luminex multiplex immunoassay revealed significant changes in the secretion of VEGF and IL-6 during NSC differentiation. Our results further demonstrated an increased expression of neuropilin-1 as well as catenin β-1, both known to participate in the regulation of VEGF signaling, and showed that VEGF-A isoform 121 (VEGF121), in particular, induces proliferation and supports survival of differentiating cells.
Risk Factors for Residual Stenosis After Carotid Artery Stenting
Authors: Tao Yunlu , Hua Yang , Jia Lingyun , Jiao Liqun , Liu Beibei
Published: January 2021

Background and purpose: Stent residual stenosis is an independent risk factor for restenosis after stenting. This study aimed to analyze the factors influencing residual stenosis after carotid artery stenting (CAS).

Methods: A total of 570 patients who underwent CAS with 159 closed-loop stents (CLS) and 411 open-loop stents (OLS) from January 2013 to January 2016 were retrospectively enrolled in this study. Carotid stenosis location in the common carotid artery or in internal carotid artery, plaque size, and features (regular or irregular morphology; with or without calcification), degree of carotid artery stenosis, and stent expansion rate were detected by carotid duplex ultrasonography. Residual stenosis was defined as a stenosis rate ≥30% after CAS, as detected by digital subtraction angiography. A logistic regression analysis was used to analyze residual stenosis risk factors.

Results: The overall incidence of residual stenosis was 22.8% (130/570 stents). The incidence of residual stenosis in the CLS group was higher than that in the OLS group (29.5 vs. 20.2%, χ2 = 5.71, P = 0.017). The logistic regression analysis showed that CLS [odds ratio (OR), 1.933; 95% confidence interval (CI), 1.009–3.702], irregular plaques (OR, 4.237; 95% CI, 2.391–7.742), and plaques with calcification (OR, 2.370; 95% CI, 1.337–4.199) were independent risk factors for residual stenosis after CAS. In addition, a high radial expansion rate of stent was a protective factor for residual stenosis (OR, 0.171; 95% CI, 0.123–0.238). The stenosis location and stent length did not impact the occurrence of residual stenosis. After 1-year follow-up, the incidence of restenosis in the residual stenosis group was higher than that in the group without residual stenosis (13.1 vs. 2.0%, χ2 = 28.05, P < 0.001).

Conclusions: The findings of this study suggest that plaque morphology, echo characteristics (with calcification), and stents type influence residual stenosis.
COVID-19 Pathophysiology Predicts That Ischemic Stroke Occurrence Is an Expectation, Not an Exception—A Systematic Review
Authors: Wijeratne Tissa , Gillard Crewther Sheila , Sales Carmela , Karimi Leila
Published: January 2021

Clinical reports of neurological manifestations associated with severe coronavirus disease 2019 (COVID-19), such as acute ischemic stroke (AIS), encephalopathy, seizures, headaches, acute necrotizing encephalitis, cerebral microbleeds, posterior reversible leukoencephalopathy syndrome, hemophagocytic lymphohistiocytosis, peripheral neuropathy, cranial nerve palsies, transverse myelitis, and demyelinating disorders, are increasing rapidly. However, there are comparatively few studies investigating the potential impact of immunological responses secondary to hypoxia, oxidative stress, and excessive platelet-induced aggregation on the brain. This scoping review has focused on the pathophysiological mechanisms associated with peripheral and consequential neural (central) inflammation leading to COVID-19-related ischemic strokes. It also highlights the common biological processes shared between AIS and COVID-19 infection and the importance of the recognition that severe respiratory dysfunction and neurological impairments associated with COVID and chronic inflammation [post-COVID-19 neurological syndrome (PCNS)] may significantly impact recovery and ability to benefit from neurorehabilitation. This study provides a comprehensive review of the pathobiology of COVID-19 and ischemic stroke. It also affirms that the immunological contribution to the pathophysiology of COVID-19 is predictive of the neurological sequelae particularly ischemic stroke, which makes it the expectation rather than the exception. This work is of fundamental significance to the neurorehabilitation community given the increasing number of COVID-related ischemic strokes, the current limited knowledge regarding the risk of reinfection, and recent reports of a PCNS. It further highlights the need for global collaboration and research into new pathobiology-based neurorehabilitation treatment strategies and more integrated evidence-based care.
To Go or Not to Go: Degrees of Dynamic Inhibitory Control Revealed by the Function of Grip Force and Early Electrophysiological Indices
Authors: Nguyen Trung Van , Hsu Che-Yi , Jaiswal Satish , Muggleton Neil G. , Liang Wei-Kuang , Juan Chi-Hung
Published: January 2021

A critical issue in executive control is how the nervous system exerts flexibility to inhibit a prepotent response and adapt to sudden changes in the environment. In this study, force measurement was used to capture “partial” unsuccessful trials that are highly relevant in extending the current understanding of motor inhibition processing. Moreover, a modified version of the stop-signal task was used to control and eliminate potential attentional capture effects from the motor inhibition index. The results illustrate that the non-canceled force and force rate increased as a function of stop-signal delay (SSD), offering new objective indices for gauging the dynamic inhibitory process. Motor response (time and force) was a function of delay in the presentation of novel/infrequent stimuli. A larger lateralized readiness potential (LRP) amplitude in go and novel stimuli indicated an influence of the novel stimuli on central motor processing. Moreover, an early N1 component reflects an index of motor inhibition in addition to the N2 component reported in previous studies. Source analysis revealed that the activation of N2 originated from inhibitory control associated areas: the right inferior frontal gyrus (rIFG), pre-motor cortex, and primary motor cortex. Regarding partial responses, LRP and error-related negativity (ERNs) were associated with error correction processes, whereas the N2 component may indicate the functional overlap between inhibition and error correction. In sum, the present study has developed reliable and objective indices of motor inhibition by introducing force, force-rate and electrophysiological measures, further elucidating our understandings of dynamic motor inhibition and error correction.
Dynamic Changes of Cytoskeleton-Related Proteins Within Reward-Related Brain Regions in Morphine-Associated Memory
Authors: Yang Xixi , Wen Yichong , Zhang Yuxiang , Gao Feifei , Yang Jingsi , Yang Zhuojin , Yan Chunxia
Published: January 2021

Drug-induced memory engages complex and dynamic processes and is coordinated at multiple reward-related brain regions. The spatiotemporal molecular mechanisms underlying different addiction phases remain unknown. We investigated the role of β-actin, as well as its potential modulatory protein activity-regulated cytoskeletal-associated protein (Arc/Arg3.1) and extracellular signal-regulated kinase (ERK), in reward-related associative learning and memory using morphine-induced conditioned place preference (CPP) in mice. CPP was established by alternate morphine (10 mg/kg) injections and extinguished after a 10-day extinction training, while the withdrawal group failed to extinguish without training. In the nucleus accumbens (NAc), morphine enhanced the level of β-actin and Arc only during extinction, while p-ERK1/2 was increased during both CPP acquisition and extinction phases. In the dorsal hippocampus, morphine induced an upregulation of p-ERK only during extinction, while p-β-actin was elevated during both CPP establishment and extinction. In the dorsal hippocampus, Arc was elevated during CPP formation and suppressed during extinction. Compared with the NAc and dorsal hippocampus, dynamic changes in the medial prefrontal cortex (mPFC) and caudate putamen (CPu) were not very significant. These results suggested region-specific changes of p-β-actin, Arc/Arg3.1, and p-ERK1/2 protein during establishment and extinction phases of morphine-induced CPP. These findings unveiled a spatiotemporal molecular regulation in opiate-induced plasticity.
Multisite Autism Spectrum Disorder Classification Using Convolutional Neural Network Classifier and Individual Morphological Brain Networks
Authors: Gao Jingjing , Chen Mingren , Li Yuanyuan , Gao Yachun , Li Yanling , Cai Shimin , Wang Jiaojian
Published: January 2021

Autism spectrum disorder (ASD) is a range of neurodevelopmental disorders with behavioral and cognitive impairment and brings huge burdens to the patients’ families and the society. To accurately identify patients with ASD from typical controls is important for early detection and early intervention. However, almost all the current existing classification methods for ASD based on structural MRI (sMRI) mainly utilize the independent local morphological features and do not consider the covariance patterns of these features between regions. In this study, by combining the convolutional neural network (CNN) and individual structural covariance network, we proposed a new framework to classify ASD patients with sMRI data from the ABIDE consortium. Moreover, gradient-weighted class activation mapping (Grad-CAM) was applied to characterize the weight of features contributing to the classification. The experimental results showed that our proposed method outperforms the currently used methods for classifying ASD patients with the ABIDE data and achieves a high classification accuracy of 71.8% across different sites. Furthermore, the discriminative features were found to be mainly located in the prefrontal cortex and cerebellum, which may be the early biomarkers for the diagnosis of ASD. Our study demonstrated that CNN is an effective tool to build the framework for the diagnosis of ASD with individual structural covariance brain network.
Early Visual Processing and Perception Processes in Object Discrimination Learning
Authors: Quiñones Matías , Gómez David , Montefusco-Siegmund Rodrigo , Aylwin María de la Luz
Published: January 2021

A brief image presentation is sufficient to discriminate and individuate objects of expertise. Although perceptual expertise is acquired through extensive practice that increases the resolution of representations and reduces the latency of image decoding and coarse and fine information extraction, it is not known how the stages of visual processing impact object discrimination learning (ODL). Here, we compared object discrimination with brief (100 ms) and long (1,000 ms) perceptual encoding times to test if the early and late visual processes are required for ODL. Moreover, we evaluated whether encoding time and discrimination practice shape perception and recognition memory processes during ODL. During practice of a sequential matching task with initially unfamiliar complex stimuli, we find greater discrimination with greater encoding times regardless of the extent of practice, suggesting that the fine information extraction during late visual processing is necessary for discrimination. Interestingly, the overall discrimination learning was similar for brief and long stimuli, suggesting that early stages of visual processing are sufficient for ODL. In addition, discrimination practice enhances perceive and know for brief and long stimuli and both processes are associated with performance, suggesting that early stage information extraction is sufficient for modulating the perceptual processes, likely reflecting an increase in the resolution of the representations and an early availability of information. Conversely, practice elicited an increase of familiarity which was not associated with discrimination sensitivity, revealing the acquisition of a general recognition memory. Finally, the recall is likely enhanced by practice and is associated with discrimination sensitivity for long encoding times, suggesting the engagement of recognition memory in a practice independent manner. These findings contribute to unveiling the function of early stages of visual processing in ODL, and provide evidence on the modulation of the perception and recognition memory processes during discrimination practice and its relationship with ODL and perceptual expertise acquisition.
Identification of Slc6a19os and SOX11 as Two Novel Essential Genes in Neuropathic Pain Using Integrated Bioinformatic Analysis and Experimental Verification
Authors: Chen Peng , Wang Chen , Lin Dongsheng , Li Bing , Ye Shuai , Qu Jinglian , Wang Wenjing
Published: January 2021

The aim of this study was to identify critical genes associated with neuropathic pain. We also used the competing endogenous RNA (ceRNA) hypothesis to identify related long non-coding RNAs (lncRNAs) and messenger RNAs (miRNAs) with potential regulatory roles. We downloaded GSE107180 from the Gene Expression Omnibus database, screened differentially expressed genes (DEGs) using R software, performed comprehensive bioinformatic analyses, and validated the expression of lncRNA Slc6a19os, miR-125a-5p, miR-125b-5p, miR-351-5p, and Sox11 by qRT-PCR and Western blots. We identified 620 DEGs in spared nerve injury (SNI) mice compared with sham (control) mice, including 309 mRNAs and 311 non-coding RNAs. The up-regulated mRNAs were enriched primarily in several inflammation-related GO biological processes and KEGG signaling pathways. A ceRNA network was constructed that included 82 mRNAs, 4 miRNAs, and 2 lnRNAs. An ingenuity pathway analysis (IPA)-based interaction network for mRNAs differentially expressed in the ceRNA identified several biological processes, including “cellular development, connective tissue development and function, tissue development.” Compared with sham mice, lncRNA Slc6a19os and Sox11 expression were significantly up-regulated in dorsal root ganglion (DRG) samples from SNI mice detected using qRT-PCR and Western blots (P < 0.05). MiR-125a-5p, miR-125b-5p, and miR-351-5p expression were down-regulated in DRG samples from SNI mice detected using qRT-PCR (P < 0.05). We concluded that Sox11 and lncRNA Slc6a19os were novel essential genes in the pathogenesis and progression of neuropathic pain and speculated that these two genes were regulated by miR-125a-5p, miR-125b-5p, and miR-351-5p.
The Effect of Media Professionalization on Cognitive Neurodynamics During Audiovisual Cuts
Authors: Andreu-Sánchez Celia , Martín-Pascual Miguel Ángel , Gruart Agnès , Delgado-García José María
Published: January 2021

Experts apply their experience to the proper development of their routine activities. Their acquired expertise or professionalization is expected to help in the development of those recurring tasks. Media professionals spend their daily work watching narrative contents on screens, so learning how they manage visual perception of those contents could be of interest in an increasingly audiovisual society. Media works require not only the understanding of the storytelling, but also the decoding of the formal rules and presentations. We recorded electroencephalographic (EEG) signals from 36 participants (18 media professionals and 18 non-media professionals) while they were watching audiovisual contents, and compared their eyeblink rate and their brain activity and connectivity. We found that media professionals decreased their blink rate after the cuts, suggesting that they can better manage the loss of visual information that blinks entail by sparing them when new visual information is being presented. Cuts triggered similar activation of basic brain processing in the visual cortex of the two groups, but different processing in medial and frontal cortical areas, where media professionals showed a lower activity. Effective brain connectivity occurred in a more organized way in media professionals–possibly due to a better communication between cortical areas that are coordinated for decoding new visual content after cuts.
The Relationship Between Salivary Redox, Diet, and Food Flavor Perception
Authors: Schwartz Mathieu , Neiers Fabrice , Feron Gilles , Canon Francis
Published: January 2021

The mouth is the gateway for entrance of food and microorganisms into the organism. The oral cavity is bathed by saliva, which is thus the first fluid that food and microorganisms will face after their entrance. As a result, saliva plays different functions, including lubrication, predigestion, protection, detoxification, and even transport of taste compounds to chemoreceptors located in the taste buds. To ensure its function of protection, saliva contains reactive harmful compounds such as reactive oxygen species that are controlled and neutralized by the antioxidant activity of saliva. Several antioxidant molecules control the production of molecules such as reactive oxygen compounds, neutralize them and/or repair the damage they have caused. Therefore, a balance between reactive oxidant species and antioxidant compounds exists. At the same time, food can also contain antioxidant compounds, which can participate in the equilibrium of this balance. Numerous studies have investigated the effects of different food components on the antioxidant capacity of saliva that correspond to the ability of saliva to neutralize reactive oxygen species. Contradictory results have sometimes been obtained. Moreover, some antioxidant compounds are also cofactors of enzymatic reactions that affect flavor compounds. Recent studies have considered the salivary antioxidant capacity to explain the release of flavor compoundsex vivoorin vivo. This article aims to review the effect of food on the antioxidant capacity of saliva and the impact of salivary antioxidant capacity on flavor perception after a brief presentation of the different molecules involved.
Direct Contact Ultrasound in Food Processing: Impact on Food Quality
Authors: Astráin-Redín Leire , Alejandre Marta , Raso Javier , Cebrián Guillermo , Álvarez Ignacio
Published: January 2021

Consumers' demand for “minimally processed” products that maintain the “fresh-like” characteristics has increased in recent years. Ultrasound (US) is a non-thermal technology that enhances mass and energy transfer processes resulting in improved food quality. A new method of applying US to food without using a liquid or gaseous medium for the propagation of acoustic waves has recently been under research. It is known as direct contact US, since the food is directly placed on a plate where the transducers are located. In this type of systems, the main effect is not cavitation but acoustic vibration, which encourages mass and energy transfer processes due to the “sponge effect.” Furthermore, as the product is not immersed in a liquid medium, the loss of hydrophilic nutritional compounds is reduced; systems such as these can thus be more easily implemented on an industrial level. Nevertheless, the very few studies that have been published about these systems mainly focus on dehydration and freezing. This article summarizes published research on the impact of direct contact US in nutritional and organoleptic quality of food in order to assess their potential to meet new market trends.