Interleukin‐33 (IL‐33), a member of the IL1 family, has been found to be expressed in oligodendrocytes (OLGs) and released as an alarmin from injured OLGs to work on other glial cell‐types in the ...central nervous system. However, its functional role in OLGs remains unclear. Herein, we present that IL‐33 was mainly expressed in the nucleus of CC1+‐oligodendrocytes (OLGs) in mouse and rat corpus callosum, as well as NG2+‐oligodendrocyte precursor cells (OPCs). The in vitro study indicated that the amount of IL‐33 expressing in OPCs was higher when compared to that detected in OLGs. Results from the experiments using lentivirus‐mediated shRNA delivery against IL‐33 expression (IL33‐KD) in OPCs showed that IL33‐KD reduced the differentiation of OLGs into mature OLGs along with the down‐regulation of OLG differentiation‐related genes and mature OLG marker proteins, myelin basic protein (MBP) and proteolipid protein (PLP). Alternatively, we observed reduced differentiation of OLGs that were prepared from the brains of IL‐33 gene knockout (IL33‐KO) mice with anxiolytic‐like behavior. Observations were correlated with the results showing lower levels of MBP and PLP in IL33‐KO cultures than those detected in the control cultures prepared from wildtype (WT) mice. Transmission Electron Microscopy (TEM) analysis revealed that the myelin structures in the corpus callosum of the IL33‐KO mice were impaired compared to those observed in the WT mice. Overall, this study provides important evidence that declined expression of IL‐33 in OPCs suppresses the maturation of OLGs. Moreover, gene deficiency of IL‐33 can disrupt OLG maturation and interfere with myelin compaction.
Cover Image for this issue: doi: 10.1111/jnc.14522
Our study demonstrates that declined expression of IL‐33 (IL33‐KD) or IL‐33 gene ablation (IL33‐KO) in oligodendrocyte precursor cells (OPCs) reduced oligodendrocyte (OLG) maturation along with the down‐regulation of Olig2, Myrf, and Sox10, as well as OLG lineage markers (MBP, PLP, and CNPase). The findings also implicate that loss of IL‐33 function in OPCs might impair myelin integrity in the white matter.
Open Science: This manuscript was awarded with the Open Materials Badge
For more information see: https://cos.io/our-services/open-science-badges/
Cover Image for this issue: doi: 10.1111/jnc.14522
Hypothalamic inflammation including astrogliosis and microglia activation occurs after intake of high fat diet (HFD) in rodent models or in obese individuals. However, the effect of chronic HFD ...feeding on oligodendrocytes (OLGs), a myelin-producing glial population in the central nervous system (CNS), remains unclear. In this study, we used 8-week old male C57BL/6 mice fed by HFD for 3-6 months to induce chronic obesity.
The transmission electron microscopy imaging analysis showed that the integrity of hypothalamic myelin was disrupted after HFD feeding for 4 and 6 months. Moreover, the accumulation of Iba1
-microglia with an amoeboid hypertrophic form was continually observed in arcuate nucleus of HFD-fed mice during the entire feeding time period. Interleukin-33 (IL-33), a tissue alarmin upon injury to the CNS, was detected with an increased level in hypothalamus after HFD feeding for 3 and 4 months. Furthermore, the in vitro study indicated that exposure of mature OLGs to IL-33 impaired OLG cell structure along with a decline in the expression of myelin basic protein.
Altogether, our findings demonstrate that chronic HFD feeding triggers hypothalamic myelin disruption in accompany with IL-33 upregulation and prolonged microglial activation in hypothalamus. Given that the addition of exogenous IL-33 was harmful for the maturation of OLGs, an increase in IL-33 by chronic HFD feeding might contribute to the induction of hypothalamic myelin disruption.
Asthma patients may increase their susceptibility to SARS-CoV-2 infection and the poor prognosis of coronavirus disease 2019 (COVID-19). However, anti-COVID-19/asthma comorbidity approaches are ...restricted on condition. Existing evidence indicates that luteolin has antiviral, anti-inflammatory, and immune regulation capabilities. We aimed to evaluate the possibility of luteolin evolving into an ideal drug and explore the underlying molecular mechanisms of luteolin against COVID-19/asthma comorbidity. We used system pharmacology and bioinformatics analysis to assess the physicochemical properties and biological activities of luteolin and further analyze the binding activities, targets, biological functions, and mechanisms of luteolin against COVID-19/asthma comorbidity. We found that luteolin may exert ideal physicochemical properties and bioactivity, and molecular docking analysis confirmed that luteolin performed effective binding activities in COVID-19/asthma comorbidity. Furthermore, a protein-protein interaction network of 538 common targets between drug and disease was constructed and 264 hub targets were obtained. Then, the top 6 hub targets of luteolin against COVID-19/asthma comorbidity were identified, namely, TP53, AKT1, ALB, IL-6, TNF, and VEGFA. Furthermore, the enrichment analysis suggested that luteolin may exert effects on virus defense, regulation of inflammation, cell growth and cell replication, and immune responses, reducing oxidative stress and regulating blood circulation through the Toll-like receptor; MAPK, TNF, AGE/RAGE, EGFR, ErbB, HIF-1, and PI3K-AKT signaling pathways; PD-L1 expression; and PD-1 checkpoint pathway in cancer. The possible "dangerous liaison" between COVID-19 and asthma is still a potential threat to world health. This research is the first to explore whether luteolin could evolve into a drug candidate for COVID-19/asthma comorbidity. This study indicated that luteolin with superior drug likeness and bioactivity has great potential to be used for treating COVID-19/asthma comorbidity, but the predicted results still need to be rigorously verified by experiments.
Oligodendrocytes (OLs), myelin-producing glia in the central nervous system (CNS), produce a myelin extension that enwraps axons to facilitate action potential propagation. An effective approach to ...induce oligodendrogenesis and myelination is important to foster CNS development and promote myelin repair in neurological diseases. Hericium (H.) erinaceus, an edible and culinary-medicinal mushroom, has been characterized as having neuroprotective activities. However, its effect on OL differentiation has not yet been uncovered. In this study using oligodendrocyte precursor cell (OPC) cultures and an ex vivo cerebellar slice system, we found that the extract from H. erinaceus mycelium (HEM) not only promoted the differentiation of OPCs to OLs in the differentiation medium, but also increased the level of myelin basic protein (MBP) on neuronal fibers. Moreover, daily oral administration of HEM into neonatal rat pups for 7 days enhanced MBP expression and OLs in the corpus callosum of the postnatal rat brain. The effect of HEM-derived bioactive compounds, the diterpenoid xylosides erinacine A (HeA) and HeC and a sesterterpene with 5 isoprene units called HeS, were further evaluated. The results showed that HeA and HeS more potently stimulated MBP expression in OLs and increased the number of OLs. Moreover, overlap between MBP immunoreactivity and neuronal fibers in cultured cerebellar tissue slices was significantly increased in the presence of HeA and HeS. In summary, our findings indicate that HEM extract and its ingredients HeA and HeS display promising functional effects and promote OL maturation, providing insights into their potential for myelination in neurodevelopmental disorders.
Consecutive peripheral immune challenges can modulate the responses of brain resident microglia to stimuli. High-fat diet (HFD) intake has been reported to stimulate the activation of astrocytes and ...microglia in the arcuate nucleus (ARC) of the hypothalamus in obese rodents and humans. However, it is unknown whether intermittent exposure to additional peripheral immune challenge can modify HFD-induced hypothalamic glial activation in obese individuals.
In this study, we administered 1 mg/kg LPS (or saline) by intraperitoneal (i.p.) injection to 8-week-old male mice after 1, 2, or 8 weeks of a regular diet (show) or HFD. The level of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) expression in the plasma and hypothalamic tissue was analyzed 24 h after each LPS injection. The behaviors of the animals in the four groups (the chow-saline, chow-LPS, HFD-saline, and HFD-LPS groups) were examined 5 months after exposure to chow or a HFD. Morphological examination of microglia in related brain regions was also conducted.
The plasma levels and hypothalamic mRNA levels of IL-1β and TNF-α were significantly upregulated 24 h after the first injection of LPS but not after the second or third injection of LPS. Chow-LPS mice displayed increased exploratory behavior 5 months after feeding. However, this LPS-induced abnormal exploratory behavior was inhibited in HFD-fed mice. Chronic HFD feeding for 5 months induced apparent increases in the number and cell body size of microglia, mainly in the ARC, and also increased the size of microglia in the nucleus accumbens (NAc) and insula. Moreover, microglial activation in the ARC, anterior cingulate cortex (ACC), insula, and basolateral amygdala (BLA) was observed in chow-LPS mice. However, microglial activation in the analyzed brain regions was suppressed in HFD-LPS mice.
Altogether, the results indicate that intermittent peripheral challenge with LPS might prime microglia in the ARC and NAc to modify their response to chronic HFD feeding. Alternatively, chronic HFD feeding might mediate microglia in LPS-affected brain regions and subsequently suppress LPS-induced atypical exploratory behavior. Our findings suggest that the interaction of intermittent acute peripheral immune challenges with chronic HFD intake can drive microglia to amend the microenvironment and further modify animal behaviors in the later life.
Background. Severe asthma (SA), a heterogeneous inflammatory disease characterized by immune cell infiltration, is particularly difficult to treat and manage. The airway epithelium is an important ...tissue in regulating innate and adaptive immunity, and targeting airway epithelial cell may contribute to improving the efficacy of asthma therapy. Methods. Bioinformatics methods were utilized to identify the hub genes and signaling pathways involved in SA. Experiments were performed to determine whether these hub genes and signaling pathways were affected by the differences in immune cell infiltration. Results. The weighted gene coexpression network analysis identified 14 coexpression modules, among which the blue and salmon modules exhibited the strongest associations with SA. The blue module was mainly enriched in actomyosin structure organization and was associated with regulating stem cell pluripotency signaling pathways. The salmon module was mainly involved in cornification, skin development, and glycosphingolipid biosynthesis-lacto and neolacto series. The protein-protein interaction network and module analysis identified 11 hub genes in the key modules. The CIBERSORTx algorithm revealed statistically significant differences in CD8+ T cells (P=0.013), T follicular helper cells (P=0.002), resting mast cells (P=0.004), and neutrophils (P=0.002) between patients with SA and mild-moderate asthma patients. Pearson’s correlation analysis identified 11 genes that were significantly associated with a variety of immune cells. We further predicted the utility of some potential drugs and validated our results in external datasets. Conclusion. Our results may help provide a better understanding of the relationship between the airway epithelial transcriptome and clinical data of SA. And this study will help to guide the development of SA-targeted molecular therapy.
The 2019 novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a major challenge threatening the global healthcare system. ...Respiratory virus infection is the most common cause of asthma attacks, and thus COVID-19 may contribute to an increase in asthma exacerbations. However, the mechanisms of COVID-19/asthma comorbidity remain unclear.
The “Limma” package or “DESeq2” package was used to screen differentially expressed genes (DEGs). Alveolar lavage fluid datasets of COVID-19 and asthma were obtained from the GEO and GSV database. A series of analyses of common host factors for COVID-19 and asthma were conducted, including PPI network construction, module analysis, enrichment analysis, inference of the upstream pathway activity of host factors, tissue-specific analysis and drug candidate prediction. Finally, the key host factors were verified in the GSE152418 and GSE164805 datasets.
192 overlapping host factors were obtained by analyzing the intersection of asthma and COVID-19. FN1, UBA52, EEF1A1, ITGB1, XPO1, NPM1, EGR1, EIF4E, SRSF1, CCR5, PXN, IRF8 and DDX5 as host factors were tightly connected in the PPI network. Module analysis identified five modules with different biological functions and pathways. According to the degree values ranking in the PPI network, EEF1A1, EGR1, UBA52, DDX5 and IRF8 were considered as the key cohost factors for COVID-19 and asthma. The H2O2, VEGF, IL-1 and Wnt signaling pathways had the strongest activities in the upstream pathways. Tissue-specific enrichment analysis revealed the different expression levels of the five critical host factors. LY294002, wortmannin, PD98059 and heparin might have great potential to evolve into therapeutic drugs for COVID-19 and asthma comorbidity. Finally, the validation dataset confirmed that the expression of five key host factors were statistically significant among COVID-19 groups with different severity and healthy control subjects.
This study constructed a network of common host factors between asthma and COVID-19 and predicted several drugs with therapeutic potential. Therefore, this study is likely to provide a reference for the management and treatment for COVID-19/asthma comorbidity.
•The risk relationship between asthma and COVID-19 is controversial.•We identified 192 protein targets between asthma and COVID-19 comorbidity.•EEF1A1, EGR1, UBA52, DDX5 and IRF8 were identified as key host factors for them.•LY294002 and wortmannin might have great potential for COVID-19 and asthma.
Disease screening instruments used for secondary prevention can facilitate early determination and treatment of pathogenic factors, effectively reducing disease incidence, mortality rates, and health ...complications. Therefore, people should be encouraged to receive health examinations for discovering potential pathogenic factors before symptoms occur. Here, we used the health belief model as a foundation and integrated social psychological factors and investigated the factors influencing health examination behavioral intention among the public in Taiwan. In total, 388 effective questionnaires were analyzed through structural model analysis. Consequently, this study yielded four crucial findings: (1) The established extended health belief model could effectively predict health examination behavioral intention; (2) Self-efficacy was the factor that most strongly influenced health examination behavioral intention, followed by health knowledge; (3) Self-efficacy substantially influenced perceived benefits and perceived barriers; (4) Health knowledge and social support indirectly influenced health examination behavioral intention. The preceding results can effectively increase the acceptance and use of health examination services among the public, thereby facilitating early diagnosis and treatment and ultimately reducing disease and mortality rates.
Advocating for improving workplace safety and health has gained substantial support in recent years. The medical industry is a high-risk industry and receives considerable public attention. This ...study used an integrative approach as a starting point and combined the contextual factors of an organization: perceived organizational support, safety climate, social influence, and shared decision making. Subsequently, the effects of these factors on preventive action and safety satisfaction were investigated. This study surveyed employees of two hospitals, one in Northern Taiwan and one in Eastern Taiwan, collecting valid data from 468 respondents. Structural equation modeling (SEM) was used to verify our research framework. The finding indicates that (1) All hypotheses proposed in this study were supported. (2) The overall goodness of fit of the model was excellent, and the explained variance of the outcome variables was high. (3) Safety climate had the strongest total effects on preventive action and safety satisfaction simultaneously, whereas preventive action had the strongest direct effect on safety satisfaction. The objective of this study was to obtain empirical conclusions and make suggestions for academic theory and clinical practice. The findings may serve as a reference for future research and for scholars and practitioners, enabling the creation of healthy workplaces and, thus, a brighter future.
PDF
