Atherosclerosis is a chronic inflammatory disease; unstable atherosclerotic plaque rupture, vascular stenosis, or occlusion caused by platelet aggregation and thrombosis lead to acute cardiovascular ...disease. Atherosclerosis-related inflammation is mediated by proinflammatory cytokines, inflammatory signaling pathways, bioactive lipids, and adhesion molecules. This review discusses the effects of inflammation and the systemic inflammatory signaling pathway on atherosclerosis, the role of related signaling pathways in inflammation, the formation of atherosclerosis plaques, and the prospects of treating atherosclerosis by inhibiting inflammation.
The highly enantioselective alkynylation of isatins, catalyzed by a bifunctional guanidine/CuI catalyst under mild reaction conditions, is described. The reaction is broad in scope with respect to ...alkyl/aryl‐substituted terminal alkynes and substituted isatins, thus affording bioactive propargylic alcohols in excellent yields and enantioselectivities.
Active duty: Asymmetric alkynylation of isatins was achieved by a new bifunctional chiral guanidine ligand in combination with CuI under mild reaction conditions. Good levels of reactivity and excellent enantioselectivities were achieved with diverse alkyl‐ and aryl‐substituted terminal alkynes and various substituted isatins, thus generating bioactive 3‐alkynyl‐3‐hydroxyindolin‐2‐ones.
During viral infection, the host cell synthesizes high amounts of viral proteins, which often causes stress to the endoplasmic reticulum (ER). To manage abnormal ER stress, mammalian cells trigger a ...response called the unfolded protein response (UPR). Previous studies have indicated that porcine reproductive and respiratory syndrome virus (PRRSV), an Arterivirus that has been devastating the swine industry worldwide, can induce ER stress and activate UPR, however, the activation pathways and the biological significance requires further investigation. In this study, we demonstrated that, among the three types of UPR pathways, PRRSV infection induced PERK and IRE1 pathways, but not the ATF6 pathway. Furthermore, the induction of UPR promoted PRRSV replication. We also found that PRRSV-induced UPR, particularly the PERK pathway, was involved in the induction of autophagy, a cellular degradation process that can alleviate cell stress. Besides, we also provided insights into the ER stress-mediated apoptosis in response to PRRSV infection. PRRSV infection induced the expression of the transcription factor CHOP, which activated caspase 3 and PARP led to ER stress-mediated apoptosis. Using 3-Methyladenine (3-MA) to inhibit autophagy, the increased ER stress and cell apoptosis were observed in the PRRSV infected cell. Taken together, our results revealed the associations of ER stress, autophagy, and apoptosis during PRRSV infection, helping us to further understand how PRRSV interacts with host cells.
Non-small cell lung cancer (NSCLC), which accounts for approximately 85% of all lung cancer cases, is associated with a poor outcome. Rafoxanide is an anthelmintic drug that inhibits tumor growth in ...certain malignancies. However, its impact on NSCLC remains unknown. In this study, we examined the effect of rafoxanide on NSCLC and dissected the underlying mechanism. The results showed that rafoxanide significantly inhibited the growth, invasion, and migration of NSCLC cells. Besides, rafoxanide can induce NSCLC cell apoptosis and cell cycle arrest in a dose-dependent manner. RNA-seq analysis revealed that genes associated with endoplasmic reticulum stress (ER) stress responses were activated. Mechanistically, we found Rafoxanide can induce ER stress and activate the unfolded protein response (UPR). Apoptosis was activated by excessive ER stress, and autophagy was activated to partially alleviate ER stress. In vivo, we found that rafoxanide inhibited the growth of A549 and H1299 xenograft mouse models without severe side effects. Collectively, the present study indicates that rafoxanide may be a candidate drug for the treatment of NSCLC.
Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has been devastating the swine industry worldwide since the late 1980s. To investigate the impact of cellular ...microRNAs (miRNAs) on the replication of PRRSV, we screened 10 highly conserved miRNAs implicated in innate immunity or antiviral function and identified miR-125b as an inhibitor of PRRSV replication. Virus titer and western blot assays demonstrated that miR-125b reduced PRRSV replication and viral gene expression in a dose-dependent manner in both MARC-145 cell line and primary porcine alveolar macrophages. Mechanistically, miR-125b did not target the PRRSV genome. Rather, it inhibited activation of NF-κB, which we found to be required for PRRSV replication. PRRSV, in turn, down-regulated miR-125b expression post-infection to promote viral replication. Collectively, miR-125b is an antiviral host factor against PRRSV, but it is subject to manipulation by PRRSV. Our study reveals an example of manipulation of a cellular miRNA by an arterivirus to re-orchestrate host gene expression for viral propagation and sheds new light on targeting host factors to develop effective control measures for PRRS.
The Ni-P-WS
2
composite coatings with prominent structures were constructed by composite electrodeposition by adding tungsten disulfide (WS
2
) nanoparticles to the electroplating solution. ...Modification of the Ni-P-WS
2
composite coating with hexadecyltrimethoxysilane (HDTMS) is going to achieve the superhydrophobic effect. The successful construction of the superhydrophobic surface was demonstrated by X-ray diffractometer (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and contact angle measurement (CA). Electrochemical impedance spectroscopy (EIS) was used to investigate the corrosion resistance. The finding indicates that hexadecyltrimethoxysilane (HDTMS) reduces the surface energy of the Ni-P-WS
2
composite coating, generates a film on its rough surface, blocks the corrosive medium, and improves the corrosion resistance of the composite coating. The Ni-P-WS
2
nanocomposite coating’s water contact angle is 156.8° and its sliding angle is 8° at 3 g/L of WS
2
particle concentration. And the composite plating has the highest self-corrosion potential (
E
corr
= − 0.285 V) and the lowest self-corrosion current density (
i
corr
= 3.206 μA cm
−2
), with a better corrosion resistance. In addition, the prepared superhydrophobic coating showed excellent corrosion resistance under the hydrophobic barrier and the layer barrier of WS
2
nanosheets.
Antibiotic-induced dysbiosis is a major risk factor for Clostridioides difficile infection (CDI), and fecal microbiota transplantation (FMT) is recommended for treating CDI. However, the underlying ...mechanisms remain unclear. Here, we show that Tritrichomonas musculis (T.mu), an integral member of the mouse gut commensal microbiota, reduces CDI-induced intestinal damage by inhibiting neutrophil recruitment and IL-1β secretion, while promoting Th1 cell differentiation and IFN-γ secretion, which in turn enhances goblet cell production and mucin secretion to protect the intestinal mucosa. T.mu can actively metabolize arginine, not only influencing the host's arginine-ornithine metabolic pathway, but also shaping the metabolic environment for the microbial community in the host's intestinal lumen. This leads to a relatively low ornithine state in the intestinal lumen in C. difficile-infected mice. These changes modulate C. difficile's virulence and the host intestinal immune response, and thus collectively alleviating CDI. These findings strongly suggest interactions between an intestinal commensal eukaryote, a pathogenic bacterium, and the host immune system via inter-related arginine-ornithine metabolism in the regulation of pathogenesis and provide further insights for treating CDI.
DExD-box helicase 21 (DDX21) is an essential member of the RNA helicase family. DDX21 is involved in the carcinogenesis of various malignancies, but there has been no comprehensive research on its ...involvement in different types of cancer.
This study used TCGA, CPTAC, GTEx, GEO, FANTOM5, BioGRID, TIMER2, GEPIA2, cBioPortal, STRING, and Metascape databases and Survival ROC software to evaluate DDX21 gene expression, protein expression, immunohistochemistry, gene mutation, immune infiltration, and protein phosphorylation in 33 TCGA tumor types, as well as the prognostic relationship between DDX21 and different tumors, by survival analysis and similar gene enrichment analysis. Furthermore, Cell Counting Kit-8 (CCK-8) and Transwell studies were employed to assess the effect of DDX21 expression on lung adenocarcinoma (LUAD) cell proliferation and migration.
The DDX21 gene was highly expressed in most cancers, and overexpression was associated with poor overall survival (OS) and disease-free survival (DFS). DDX21 mutations were most common in uterine corpus endometrial carcinoma (UCEC; >5%), and DDX21 expression was positively correlated with the degree of infiltration of CAF and CD8
cells in several tumor types. Numerous genes were co-expressed with DDX21. Gene enrichment analysis revealed close links between DDX21, RNA metabolism, and ribosomal protein production.
analysis of LUAD cells showed that DDX21 expression was positively correlated with cell proliferation and migration capacity, consistent with prior bioinformatics studies.
DDX21 is overexpressed in a variety of cancers, and overexpression in some cancers is associated with poor prognosis. Immune infiltration and DDX21-related gene enrichment analyses indicated that DDX21 may affect cancer development through mechanisms that regulate tumor immunity, RNA metabolism, and ribosomal protein synthesis. This pan-cancer study revealed the prognostic value and the oncogenic role of DDX21.
Growth factors like insulin-like growth factor 1 (IGF-1) is reported to mediate neurogenesis in the subgranular zone (SGZ) and the subventricular zone (SVZ) of the adult mammalian brain, but its ...regulatory mechanism remains unclear. We generated transgenic mice overexpressing IGF-1 specifically in neural stem cells (NSCs) and assessed the effect of IGF-1 on neurogenesis in adult mice NSCs. Overexpression of IGF-1 could stimulate the expression of phospho-Akt and phospho-ERK1/2 while inducing proliferation and differentiation of NSCs in the SGZ and SVZ. The MEK/ERK inhibitor U0126 could inhibit ERK1/2 phosphorylation, further inhibiting the proliferation of NSCs in the SGZ and SVZ but had no effect on the phosphorylation of Akt. By contrast, The PI3K/Akt inhibitor LY294002 inhibited phosphorylation of Akt and differentiation of NSCs in the SGZ and SVZ, resulting in no change in the proliferation of NSCs and ERK1/2 phosphorylation. These results demonstrate that IGF-1 upregulates the proliferation of NSCs by triggering MEK/ERK pathway signaling in the adult mice SGZ and SVZ. Meanwhile, IGF-1 also induces differentiation of NSCs via the PI3K/Akt pathway in adult mice. However, we found no evidence of crosstalk between the PI3K/Akt and MEK/ERK pathways in adult mice NSCs. Our work provides new experimental evidence of the involvement of the PI3K/Akt and MEK/ERK pathways in the proliferation and differentiation of the NSCs of adult mice.
The intestinal bacterial community has an important role in maintaining human health. Dysbiosis is a key inducer of many chronic diseases including obesity and diabetes. Kunming mice are frequently ...used as a model of human disease and yet little is known about the bacterial microbiome resident to the gastrointestinal tract.
We undertook metagenomic sequencing of the luminal contents of the stomach, duodenum, jejunum, ileum, cecum, colon, and rectum of Kunming mice. Firmicutes was the dominant bacterial phylum of each intestinal tract and Lactobacillus the dominant genus. However, the bacterial composition differed among the seven intestinal tracts of Kunming mice. Compared with the small intestine, the large intestine bacterial community of Kunming mice is more stable and diverse.
To our knowledge, ours is the first study to systematically describe the gastrointestinal bacterial composition of Kunming mice. Our findings provide a better understanding of the bacterial composition of Kunming mice and serves as a foundation for the study of precision medicine.
How to cite: Han X, Shao H, Wang Y, et al. Composition of the bacterial community in the gastrointestinal tract of Kunming mice. Electron J Biotechnol 2020;43. https://doi.org/10.1016/j.ejbt.2019.11.003
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