scholarly journals Association of Pericyte Loss With Microthrombosis After Subarachnoid Hemorrhage in ApoE-Deficient Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Jinwei Pang ◽  
Yue Wu ◽  
Jianhua Peng ◽  
Ping Yang ◽  
Ligang Chen ◽  
...  
Keyword(s):  
Delayed Cerebral Ischemia ◽  
Early Brain Injury ◽  
Underlying Mechanism ◽  
Neurobehavioral Performance ◽  
Promising Strategy ◽  
Pathway Activation ◽  
Neurobehavioral Deficits ◽  
Pericyte Loss ◽  
The Relationship ◽  
Deficient Mice

Background: The occurrence of microthrombosis contributes to not only delayed cerebral ischemia (DCI), but also early brain injury (EBI) after SAH. However, the underlying mechanism is not completely investigated. In the current study, we explored the underlying mechanism of microthrombosis in EBI stage after SAH in ApoE-deficient mice.Methods: Experimental SAH was established by endovascular perforation in apolipoprotein E (ApoE)-deficient mice and wild type (WT) mice. Neurobehavioral, molecular biological and histopathological methods were used to assess the relationship between pericytes loss, neurobehavioral performance, and microthrombosis.Results: We found that the number of microthrombi was significantly increased and peaked 48 h after SAH in WT mice. The increased microthrombosis was related to the decreased effective microcirculation perfusion area and EBI severity. ApoE-deficient mice showed more extensive microthrombosis than that of WT mice 48 h after SAH, which was thereby associated with greater neurobehavioral deficits. Immunohistochemical staining showed that microthrombi were predominantly located in microvessels where pericytes coverage was absent. Mechanistically, ApoE deficiency caused more extensive CypA-NF-κB-MMP-9 pathway activation than that observed in WT mice, which thereby led to more degradation of N-cadherin, and subsequently more pericytes loss. Thereafter, the major adhesion molecule that promoting microthrombi formation in microvessels, P-selectin, was considerably increased in WT mice and increased to a greater extent in the ApoE-deficient mice.Conclusion: Taken together, these data suggest that pericytes loss is associated with EBI after SAH through promoting microthrombosis. Therapies that target ApoE to reduce microthrombosis may be a promising strategy for SAH treatment.

scholarly journals Augmentation of Bone Regeneration by Depletion of Stress-Induced Senescent Cells Using Catechin and Senolytics

2020 ◽  
Vol 21 (12) ◽  
pp. 4213 ◽  
Author(s):  
Yoshitomo Honda ◽  
Anqi Huang ◽  
Tomonari Tanaka ◽  
Xiaoyu Han ◽  
Beiyuan Gao ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Epigallocatechin Gallate ◽  
Underlying Mechanism ◽  
Gelatin Sponge ◽  
Cell Numbers ◽  
Promising Strategy ◽  
Stress Induced Premature Senescence ◽  
The Relationship ◽  
Hematoxylin Eosin

Despite advances in bone regenerative medicine, the relationship between stress-induced premature senescence (SIPS) in cells and bone regeneration remains largely unknown. Herein, we demonstrated that the implantation of a lipopolysaccharide (LPS) sustained-release gelatin sponge (LS-G) increases the number of SIPS cells and that the elimination of these cells promotes bone formation in critical-sized bone defects in the rat calvaria. Histological (hematoxylin–eosin and SA-β-gal) and immunohistological (p16 and p21 for analyzing cellular senescence and 4-HNE for oxidation) staining was used to identify SIPS cells and elucidate the underlying mechanism. Bone formation in defects were analyzed using microcomputed tomography, one and four weeks after surgery. Parallel to LS-G implantation, local epigallocatechin gallate (EGCG) administration, and systemic senolytic (dasatinib and quercetin: D+Q) administration were used to eliminate SIPS cells. After LS-G implantation, SA-β-gal-, p16-, and p21-positive cells (SIPS cells) accumulated in the defects. However, treatment with LS-G+EGCG and LS-G+D+Q resulted in lower numbers of SIPS cells than that with LS-G in the defects, resulting in an augmentation of newly formed bone. We demonstrated that SIPS cells induced by sustained stimulation by LPS may play a deleterious role in bone formation. Controlling these cell numbers is a promising strategy to increase bone regeneration.

scholarly journals An Update on Antioxidative Stress Therapy Research for Early Brain Injury After Subarachnoid Hemorrhage

2021 ◽  
Vol 13 ◽  
Author(s):  
Fa Lin ◽  
Runting Li ◽  
Wen-Jun Tu ◽  
Yu Chen ◽  
Ke Wang ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Early Brain Injury ◽  
Research Progress ◽  
Oxidative Stresses ◽  
Antioxidative Stress ◽  
Stress Therapy ◽  
The Relationship

The main reasons for disability and death in aneurysmal subarachnoid hemorrhage (aSAH) may be early brain injury (EBI) and delayed cerebral ischemia (DCI). Despite studies reporting and progressing when DCI is well-treated clinically, the prognosis is not well-improved. According to the present situation, we regard EBI as the main target of future studies, and one of the key phenotype-oxidative stresses may be called for attention in EBI after laboratory subarachnoid hemorrhage (SAH). We summarized the research progress and updated the literature that has been published about the relationship between experimental and clinical SAH-induced EBI and oxidative stress (OS) in PubMed from January 2016 to June 2021. Many signaling pathways are related to the mechanism of OS in EBI after SAH. Several antioxidative stress drugs were studied and showed a protective response against EBI after SAH. The systematical study of antioxidative stress in EBI after laboratory and clinical SAH may supply us with new therapies about SAH.

scholarly journals Altered Expression of Peroxiredoxins in Mouse Model of Progressive Myoclonus Epilepsy upon LPS-Induced Neuroinflammation

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 357
Author(s):  
Mojca Trstenjak Prebanda ◽  
Petra Matjan-Štefin ◽  
Boris Turk ◽  
Nataša Kopitar-Jerala
Keyword(s):  
Mouse Model ◽  
Redox Homeostasis ◽  
Underlying Mechanism ◽  
Loss Of Function ◽  
Altered Expression ◽  
Lps Challenge ◽  
Progressive Myoclonus Epilepsy ◽  
Myoclonus Epilepsy ◽  
The Brain ◽  
Deficient Mice

Stefin B (cystatin B) is an inhibitor of endo-lysosomal cysteine cathepsin, and the loss-of-function mutations in the stefin B gene were reported in patients with Unverricht–Lundborg disease (EPM1), a form of progressive myoclonus epilepsy. Stefin B-deficient mice, a mouse model of the disease, display key features of EPM1, including myoclonic seizures. Although the underlying mechanism is not yet completely clear, it was reported that the impaired redox homeostasis and inflammation in the brain contribute to the progression of the disease. In the present study, we investigated if lipopolysaccharide (LPS)-triggered neuroinflammation affected the protein levels of redox-sensitive proteins: thioredoxin (Trx1), thioredoxin reductase (TrxR), peroxiredoxins (Prxs) in brain and cerebella of stefin B-deficient mice. LPS challenge was found to result in a marked elevation of Trx1 and TrxR in the brain and cerebella of stefin B deficient mice, while Prx1 was upregulated only in cerebella after LPS challenge. Mitochondrial peroxiredoxin 3 (Prx3), was upregulated also in the cerebellar tissue lysates prepared from unchallenged stefin B deficient mice, while after LPS challenge Prx3 was upregulated in stefin B deficient brain and cerebella. Our results imply the role of oxidative stress in the progression of the disease.

Consumers Complain More Fiercely Through Small-Screen Devices: The Role of Spatial Crowding Perception

2020 ◽  
Vol 23 (3) ◽  
pp. 353-367
Author(s):  
Yuanyuan Zhou ◽  
Bin Tian ◽  
Tingting Mo ◽  
Zhuoying Fei
Keyword(s):  
Secondary Data ◽  
Underlying Mechanism ◽  
Screen Size ◽  
Design Elements ◽  
Perception Theory ◽  
Fourth Experiment ◽  
Complaint Behavior ◽  
The Relationship ◽  
Small Screen

Previous research has mainly focused on the determinants of consumers’ complaint channel choices. Little attention has been paid to the behavioral consequences of different complaint channels, particularly different complaint devices. Drawing on spatial crowding perception theory, this study finds that in an online complaint context, consumers’ complaint intensity is shaped by complaint devices that differ in screen size. Crowding perception produced by visually restrictive tension mediates the relationship between the screen size of the complaint device and the complaint intensity. The results of secondary data confirm that consumers’ complaint intensity is higher while complaining through a small-screen device (as opposed to a large-screen one). Three scenario-based experiments are conducted to examine the role of perceived spatial crowding in producing a more intense complaint behavior when complaints are submitted through smaller screen devices (as opposed to larger screen devices). The fourth experiment reveals that crowding perception can be lessened by adjusting certain design elements of the interface, ultimately mitigating the intensity of the complaint submitted through a small-screen device. Our research identifies the specific causality and underlying mechanism of the influence of device type on consumers’ postconsumption behavior, thus contributing to clarify some ambiguities in the literature.

Mediating Effect of WhatsApp Addiction Between Social Loneliness and Preference for Online Social Interaction: A Cross-cultural Study

2021 ◽  
pp. 097215092110556
Author(s):  
Komal Nagar ◽  
Gurmeet Singh ◽  
Rabinder Singh
Keyword(s):  
Social Interaction ◽  
Underlying Mechanism ◽  
Mediating Effect ◽  
Mediating Role ◽  
Cross Cultural Study ◽  
Online Social Interaction ◽  
The Relationship ◽  
Moderating Role ◽  
Social Loneliness

The present study aims to explore the relationship between social loneliness and online interaction through WhatsApp addiction among a sample of Indian and Fijian respondents. Based on the responses of 202 Indian and 73 Fijian respondents, the present research study validated the mediating role of WhatsApp addiction, revealing that social loneliness increased the possibility of preferring to interact online through increased WhatsApp addiction. The empirical results showed that the underlying mechanism of social loneliness might indirectly influence consumers’ preference for online social interaction (POSI). The study further assessed the moderating role of culture in the association between social loneliness and POSI. Findings of the moderated mediation analysis demonstrated that, the association between loneliness and preference to socialize online differed, based on the identified cultural differences between Indian and Fijian groups.

Tapping the Power of Social Media on Innovation Performance

2021 ◽  
Vol 9 (2) ◽  
pp. 143-151
Author(s):  
Shan Shan Teh ◽  
Daisy Mui Hung Kee ◽  
Munazza Zahra ◽  
Gadi Dung Paul
Keyword(s):  
Social Media ◽  
Data Collection ◽  
Open Innovation ◽  
Underlying Mechanism ◽  
Jel Classification ◽  
Innovation Performance ◽  
Great Idea ◽  
New Evidence ◽  
The Relationship ◽  
Innovation Impact

Objective - This study investigates the relationship between social media and innovation performance among SMEs in Malaysia. This study also extends social media literature by investigating the underlying mechanism of open innovation in the relationship between social media and innovation performance. Methodology/Technique - A questionnaire was used to collect data from the respondents. A total of 173 samples from data collection were then used to test the hypotheses by using the SPSS and SmartPLS software. Finding - The result has revealed that social media has a significant effect on innovation performance. Besides, outbound innovation is also found to mediate the relationship between social media and innovation performance. Novelty - This study contributes to the literature on social media and innovation by providing new evidence regarding outbound innovation impact on performance among SMEs. It also provides a great idea of social media's importance to SME managers in improving innovation performance in an organization. Type of Paper - Empirical. Keywords: Social Media, Innovation Performance, Open Innovation, Smes, Malaysia JEL Classification: URI: http://gatrenterprise.com/GATRJournals/GJBSSR/vol9.2_4.html DOI: https://doi.org/10.35609/gjbssr.2021.9.2(4) Pages 143 – 151

scholarly journals Perinatal Hypercholesterolemia Exacerbates Atherosclerosis Lesions in Offspring by Altering Metabolism of Trimethylamine-N-Oxide and Bile Acids

2017 ◽  
Vol 37 (11) ◽  
pp. 2053-2063 ◽  
Author(s):  
Charlotte Trenteseaux ◽  
Anh-thu Gaston ◽  
Audrey Aguesse ◽  
Guillaume Poupeau ◽  
Pierre de Coppet ◽  
...  
Keyword(s):  
Gene Expression ◽  
Apolipoprotein E ◽  
Bile Acids ◽  
Experimental Studies ◽  
Underlying Mechanism ◽  
Female Offspring ◽  
Promoter Regions ◽  
Maternal Hypercholesterolemia ◽  
Atherosclerosis Development ◽  
Deficient Mice

Objective— Experimental studies suggest that maternal hypercholesterolemia may be relevant for the early onset of cardiovascular disease in offspring. We investigated the effect of perinatal hypercholesterolemia on the atherosclerosis development in the offspring of apolipoprotein E–deficient mice and the underlying mechanism. Approach and Results— Atherosclerosis and related parameters were studied in adult male or female apolipoprotein E–deficient mice offspring from either normocholesterolemic or hypercholesterolemic mothers and normocholesterolemic fathers. Female born to hypercholesterolemic mothers had more aortic root lesions than female born to normocholesterolemic mothers. Lesions in whole aorta did not differ between groups. Higher trimethylamine-N-oxide levels and Fmo3 hepatic gene expression were higher in female born to hypercholesterolemic mothers offspring compared with female born to normocholesterolemic mothers and male. Trimethylamine-N-oxide levels were correlated with the size of atherosclerotic root lesions. Levels of hepatic cholesterol and gallbladder bile acid were greater in male born to hypercholesterolemic mothers compared with male born to normocholesterolemic mothers. At 18 weeks of age, female born to hypercholesterolemic mothers showed lower hepatic Scarb1 and Cyp7a1 but higher Nr1h4 gene expression compared with female born to normocholesterolemic mothers. Male born to hypercholesterolemic mothers showed an increase in Scarb1 and Ldlr gene expression compared with male born to normocholesterolemic mothers. At 25 weeks of age, female born to hypercholesterolemic mothers had lower Cyp7a1 gene expression compared with female born to normocholesterolemic mothers. DNA methylation of Fmo3, Scarb1 , and Ldlr promoter regions was slightly modified and may explain the mRNA expression modulation. Conclusions— Our findings suggest that maternal hypercholesterolemia may exacerbate the development of atherosclerosis in female offspring by affecting metabolism of trimethylamine-N-oxide and bile acids. These data could be explained by epigenetic alterations.

Moral norm is the key

2020 ◽  
Vol 32 (8) ◽  
pp. 1823-1841 ◽  
Author(s):  
Matthew Tingchi Liu ◽  
Yongdan Liu ◽  
Ziying Mo
Keyword(s):  
Purchase Intention ◽  
Structural Equation ◽  
Underlying Mechanism ◽  
Subjective Norms ◽  
Purchase Intentions ◽  
Moral Norms ◽  
Green Products ◽  
Chinese Consumers ◽  
Content Type ◽  
The Relationship

PurposeThis research extends the theory of planned behaviour (TPB) and aims to study the underlying factors that influence Chinese consumers' purchase intentions towards green products. The conceptual model encompasses four elements (subjective norms, perceived behaviour control, moral norms and attitude) and one consumer response (purchase intention).Design/methodology/approachThe current research employs a questionnaire survey and two experiments. In Study 1, the hypotheses were tested using structural equation modelling with 485 consumers in China. Study 2 employed a single-factor, two-condition (morally engaged vs control), between-subject design.FindingsThe findings reveal that the morally extended TPB framework is more applicable in predicting Chinese consumers' green purchase intentions than the original TPB model. Attitude plays the most significant role in predicting purchase intentions, and moral norms prove to be a mediator of the relationship between the original construct of subjective norms and purchase intentions. The findings further revealed that moral norms comprise the underlying mechanism of the relationship between subjective norms and attitude.Originality/valueThis study therefore expands the TPB theory by including moral norms. Moreover, it contributes to the literature by clarifying the direct, indirect and total effects of each TPB element on the purchase intentions towards green products. Finally, managerial implications are given.

scholarly journals Micronized Palmitoylethanolamide Ameliorates Methionine- and Choline-Deficient Diet–Induced Nonalcoholic Steatohepatitis via Inhibiting Inflammation and Restoring Autophagy

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiaji Hu ◽  
Hanglu Ying ◽  
Jie Yao ◽  
Longhe Yang ◽  
Wenhui Jin ◽  
...  
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Hepatocellular Injury ◽  
Deficient Diet ◽  
Neuroprotective Effects ◽  
Pathway Activation ◽  
Elevated Expression ◽  
Anti Inflammatory

Nonalcoholic steatohepatitis (NASH) has become one of the serious causes of chronic liver diseases, characterized by hepatic steatosis, hepatocellular injury, inflammation and fibrosis, and lack of efficient therapeutic agents. Palmitoylethanolamide (PEA) is an endogenous bioactive lipid with various pharmacological activities, including anti-inflammatory, analgesic, and neuroprotective effects. However, the effect of PEA on nonalcoholic steatohepatitis is still unknown. Our study aims to explore the potential protective role of PEA on NASH and to reveal the underlying mechanism. In this study, the C57BL/6 mice were used to establish the NASH model through methionine- and choline-deficient (MCD) diet feeding. Here, we found that PEA treatment significantly improved liver function, alleviated hepatic pathological changes, and attenuated the lipid accumulation and hepatic fibrosis in NASH mice induced by MCD diet feeding. Mechanistically, the anti-steatosis effect of PEA may be due to the suppressed expression of ACC1 and CD36, elevated expression of PPAR-α, and the phosphorylation levels of AMPK. In addition, hepatic oxidative stress was greatly inhibited in MCD-fed mice treated with PEA via enhancing the expression and activities of antioxidant enzymes, including GSH-px and SOD. Moreover, PEA exerted a clear anti-inflammatory effect though ameliorating the expression of inflammatory mediators and suppressing the NLRP3 inflammasome pathway activation. Furthermore, the impaired autophagy in MCD-induced mice was reactivated with PEA treatment. Taken together, our research suggested that PEA protects against NASH through the inhibition of inflammation and restoration of autophagy. Thus, PEA may represent an efficient therapeutic agent to treat NASH.

scholarly journals miR-29a-5p Alleviates Traumatic Brain Injury (TBI)-Induced Permeability Disruption Via Regulating NLRP3 Pathway

2021 ◽  
Author(s):  
Aijun Zhang ◽  
Youming Lu ◽  
Lei Yuan ◽  
Pengqi Zhang ◽  
Dongdong Zou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Endothelial Cell ◽  
Brain Injury ◽  
Inflammasome Activation ◽  
Caspase 1 ◽  
Promising Strategy ◽  
Pathway Activation ◽  
Nlrp3 Expression

Abstract Blood-brain barrier (BBB) dysfunction is presented during traumatic brain injury (TBI) and is dependent upon the activation of the NLRP3/Caspase-1 inflammasome pathway. MicroRNA (miRNA) was proved to inhibit signaling pathway activation by targeting gene expression and we predicated in the database that miR-29a targets to NLRP3. Herein, this study aims to define the regulating role of miR-29a in NLRP3 expression and NLRP3/Caspase-1 inflammasome activation in TBI-induced BBB dysfunction. Our results indicated that miR-29a-5p alleviates TBI-induced the increased permeability of endothelial cell and BBB via suppressing NLRP3 expression and NLRP3/Caspase-1 inflammasome activation, providing a promising strategy for relieving TBI via inhibiting NLRP3/Caspase-1 inflammasome activation.

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