Perfluoroalkyl substances (PFAS) are widely used in various manufacturing processes. Accumulation of these chemicals has adverse effects on human health, including inflammation in multiple organs, ...yet how PFAS are sensed by host cells, and how tissue inflammation eventually incurs, is still unclear. Here, we show that the double-stranded DNA receptor AIM2 is able to recognize perfluorooctane sulfonate (PFOS), a common form of PFAS, to trigger IL-1β secretion and pyroptosis. Mechanistically, PFOS activates the AIM2 inflammasome in a process involving mitochondrial DNA release through the Ca
-PKC-NF-κB/JNK-BAX/BAK axis. Accordingly, Aim2
mice have reduced PFOS-induced inflammation, as well as tissue damage in the lungs, livers, and kidneys in both their basic condition and in an asthmatic exacerbation model. Our results thus suggest a function of AIM2 in PFOS-mediated tissue inflammation, and identify AIM2 as a major pattern recognition receptor in response to the environmental organic pollutants.
Background and Aim
Cresyl violet (CV) is a topical dye that allows simultaneous chromoendoscopy and in vivo confocal laser endomicroscopy in identification of neoplastic changes of the lower ...gastrointestinal tract without intravenous injection of fluorescein, but as yet no investigation has reported its application in the diagnosis of gastric intestinal metaplasia (GIM). This study aims to assess the feasibility as well as diagnosis accuracy of topical CV for in vivo diagnosis of GIM by using probe‐based confocal laser endomicroscopy (pCLE).
Methods
In this prospective, open‐label, feasibility study, 129 confocal videos from 22 patients with known GIM were analyzed and compared with corresponding histological images to establish the CV staining characteristics. In addition, 47 patients with known or suspected GIM were prospectively enrolled to evaluate the accuracy of this topical CV endomicroscopic imaging.
Results
Probe‐based confocal laser endomicroscopy with topical CV enabled clear visualization of the goblet cells, absorptive cells, and intestinal villi of GIM. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of pCLE diagnosis of GIM on a per‐location analysis was 93.01%, 91.95%, 93.51%, 86.96%, and 96.11%, respectively. The intraclass correlation coefficient for inter‐observer agreement and mean kappa value for intra‐observer agreement for the diagnosis of GIM was 0.82 and 0.87, respectively.
Conclusions
Topical CV enables real‐time chromoendoscopy in conjunction with pCLE examination of the stomach and warrants accurate diagnosis of GIM. It may be an acceptable and potentially alternative dye for confocal imaging in the future.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Biliary tract cancers (BTCs), including cholangiocarcinoma and gallbladder carcinoma, originate from the biliary epithelium and have a poor prognosis. Surgery is the only choice for cure in the early ...stage of disease. However, most patients are diagnosed in the advanced stage and lose the chance for surgery. Early diagnosis could significantly improve the prognosis of patients. Bile has complex components and is in direct contact with biliary tract tumors. Bile components are closely related to the occurrence and development of biliary tract tumors and may be applied as biomarkers for BTCs. Meanwhile, arising evidence has confirmed the immunoregulatory role of bile components. In this review, we aim to summarize and discuss the relationship between bile components and biliary tract cancers and their ability as biomarkers for BTCs, highlighting the role of bile components in regulating immune response, and their promising application prospects.
Kushen （Radix Sophorae Flavescentis） has a long history of use for the treatment of tumors, inflammation and other diseases in traditional Chinese medicine. Compound Kushen Injection （CKI） is a ...mixture of natural compounds extracted from Kushen and Baituling （Rhizoma Smilacis Glabrae）. The main principles of CKI are matrine （MT） and oxymatrine （OMT） that exhibit a variety of pharmacological activities, including anti-inflammatory, anti-allergic, anti-viral, anti-fibrotic and cardiovascular protective effects. Recent evidence shows that these compounds also produce anti-cancer actions, such as inhibiting cancer cell proliferation, inducing cell cycle arrest, accelerating apoptosis, restraining angiogenesis, inducing cell differentiation, inhibiting cancer metastasis and invasion, reversing multidrug resistance, and preventing or reducing chemotherapy- and/or radiotherapy-induced toxicity when combined with chemotherapeutic drugs. In this review, we summarize recent progress in studying the anti-cancer activities of MT, OMT and CKI and their potential molecular targets, which provide clues and references for further study.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We carried out metagenomic shotgun sequencing and a metagenome-wide association study (MGWAS) of fecal, dental and salivary samples from a cohort of individuals with rheumatoid arthritis (RA) and ...healthy controls. Concordance was observed between the gut and oral microbiomes, suggesting overlap in the abundance and function of species at different body sites. Dysbiosis was detected in the gut and oral microbiomes of RA patients, but it was partially resolved after RA treatment. Alterations in the gut, dental or saliva microbiome distinguished individuals with RA from healthy controls, were correlated with clinical measures and could be used to stratify individuals on the basis of their response to therapy. In particular, Haemophilus spp. were depleted in individuals with RA at all three sites and negatively correlated with levels of serum autoantibodies, whereas Lactobacillus salivarius was over-represented in individuals with RA at all three sites and was present in increased amounts in cases of very active RA. Functionally, the redox environment, transport and metabolism of iron, sulfur, zinc and arginine were altered in the microbiota of individuals with RA. Molecular mimicry of human antigens related to RA was also detectable. Our results establish specific alterations in the gut and oral microbiomes in individuals with RA and suggest potential ways of using microbiome composition for prognosis and diagnosis.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
Cyclic GMP‐AMP synthase (cGAS) functions as a key sensor for microbial invasion and cellular damage by detecting emerging cytosolic DNA. Here, we report that GTPase‐activating protein‐(SH3 ...domain)–binding protein 1 (G3BP1) primes cGAS for its prompt activation by engaging cGAS in a primary liquid‐phase condensation state. Using high‐resolution microscopy, we show that in resting cells, cGAS exhibits particle‐like morphological characteristics, which are markedly weakened when G3BP1 is deleted. Upon DNA challenge, the pre‐condensed cGAS undergoes liquid–liquid phase separation (LLPS) more efficiently. Importantly, G3BP1 deficiency or its inhibition dramatically diminishes DNA‐induced LLPS and the subsequent activation of cGAS. Interestingly, RNA, previously reported to form condensates with cGAS, does not activate cGAS. Accordingly, we find that DNA – but not RNA – treatment leads to the dissociation of G3BP1 from cGAS. Taken together, our study shows that the primary condensation state of cGAS is critical for its rapid response to DNA.
Synopsis
Host cell encoded cGAS is a critical DNA sensor to detect invading pathogens. The stress‐granule protein G3BP1 engages cGAS in a primary condensation state to enable a rapid response to free DNA.
G3BP1 primes cGAS for its prompt activation.
G3BP1 engages cGAS in a primary condensation state.
DNA‐ but not RNA‐interaction leads to the dissociation of G3BP1 from cGAS.
Green tea compound epigallocatechin gallate (EGCG) inhibits G3BP1‐promoted cGAS phase condensation and activation.
Host cell encoded cGAS is a critical DNA sensor to detect invading pathogens. The stress‐granule protein G3BP1 engages cGAS in a primary condensation state to enable a rapid response to free DNA.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The nutritional components in oat and tartary buckwheat had been assessed to have cholesterollowering effects. However, The effect of oat and tartary buckwheat based-food (OF) on cholesterol-lowering ...and gut microbiota in hypercholesterole hamsters was still limited studied because they are usually consumed in whole gran as well as after being processed. In this study, normal diets, high fat diet (HFD) with/without OF were fed to hamsters for 30 days respectively and growth parameters, metabolic parameters, and gut microbiota were investigated, respectively. It was found that OF significantly decreased plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-cholesterol), lowered liver TC, cholesterol ester (CE), and triglycerides (TG) concentrations, and increased fecal weight and bile acids (BA) concentrations, compared with HFD (p < 0.05). Moreover, the concentrations of acetate, propionate, butyrate and total short-chain fatty acids (SCFAs) were significantly increased in hamsters fed with OF, compared with HFD (p < 0.05). OF changed the overall structure of gut microbiota. The relative abundances of Erysipelotrichaceae, Ruminococcaceae, and Lachnospiraceae were decreased and the relative abundance of Eubacteriaceae was increased, compared with HFD. These results suggested that OF could reduce the concentrations of plasma lipid by inhibiting cholesterol absorption in liver and promoting excretions of fecal lipid and BA. And it also increased SCFAs and modulated the gut microbiota effectively to exert the hypocholesterolemic effects.
The aim of the present study was to investigate the protective effects of Shenfu injection (SFI) against myocardial ischemia–reperfusion injury (MIRI) in model rats and to explore its mechanism of ...action. Sprague–Dawley (SD) rats were pretreated with SFI and NG-nitro-L-arginine methyl ester (L-NAME) via tail vein injection and then rats were subjected to ischemia by occlusion of the left anterior descending coronary artery for 30 min followed by reperfusion for 120 min. Left ventricular function was evaluated by echocardiography. Hemodynamic was measured by the Millar pressure–volume system; serum creatine kinase (CK), lactate dehydrogenase (LDH) and serum troponin (TNNI3) levels were determined. Myocardial infarct size was observed by 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) staining; p-Akt/Akt, and p-endothelial nitric oxide synthase (p-eNOS)/eNOS levels were assessed by Western blotting; nitric oxide (NO) content in serum was determined by the Griess reaction. SFI significantly decreased serum CK, LDH and TNNI3 levels in MIRI rats, while it significantly increased the level of left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), maximal rate of the increase of left ventricular pressure (+dp/dtmax), maximal rate of the decrease of left ventricular pressure (−dp/dtmax), left ventricle ejection fraction percentage (EF), and stroke volume (SV). In addition, SFI significantly reduced myocardial infarction area and activated the phosphorylation of eNOS via Akt. The phosphorylation of eNOS and the concurrent increase of NO production contributed significantly to the protective effects of SFI. These results demonstrate that SFI protects the rat heart against MIRI and that this effect is mediated in part by Akt/eNOS signaling.
The long-term pulmonary function and related physiological characteristics of COVID-19 survivors have not been studied in depth, thus many aspects are not understood.
COVID-19 survivors were ...recruited for high resolution computed tomography (HRCT) of the thorax, lung function and serum levels of SARS-CoV-2 IgG antibody tests 3 months after discharge. The relationship between the clinical characteristics and the pulmonary function or CT scores were investigated.
Fifty-five recovered patients participated in this study. SARS-CoV-2 infection related symptoms were detected in 35 of them and different degrees of radiological abnormalities were detected in 39 patients. Urea nitrogen concentration at admission was associated with the presence of CT abnormalities (P = 0.046, OR 7.149, 95% CI 1.038 to 49.216). Lung function abnormalities were detected in 14 patients and the measurement of D-dimer levels at admission may be useful for prediction of impaired diffusion defect (P = 0.031, OR 1.066, 95% CI 1.006 to 1.129). Of all the subjects, 47 of 55 patients tested positive for SARS-CoV-2 IgG in serum, among which the generation of Immunoglobulin G (IgG) antibody in female patients was stronger than male patients in infection rehabilitation phase.
Radiological and physiological abnormalities were still found in a considerable proportion of COVID-19 survivors without critical cases 3 months after discharge. Higher level of D-dimer on admission could effectively predict impaired DLCO after 3 months discharge. It is necessary to follow up the COVID-19 patients to appropriately manage any persistent or emerging long-term sequelae.
Key Scientific Research Projects of Henan Higher Education Institutions
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Self‐assembled nanomaterials show potential high efficiency as theranostics for high‐performance bioimaging and disease treatment. However, the superstructures of pre‐assembled nanomaterials may ...change in the complicated physiological conditions, resulting in compromised properties and/or biofunctions. Taking advantage of chemical self‐assembly and biomedicine, a new strategy of “in vivo self‐assembly” is proposed to in situ construct functional nanomaterials in living subjects to explore new biological effects. Herein, recent advances on peptide‐based nanomaterials constructed by the in vivo self‐assembly strategy are summarized. Modular peptide building blocks with various functions, such as targeting, self‐assembly, tailoring, and biofunctional motifs, are employed for the construction of nanomaterials. Then, self‐assembly of these building blocks in living systems to construct various morphologies of nanostructures and corresponding unique biological effects, such as assembly/aggregation‐induced retention (AIR), are introduced, followed by their applications in high‐performance drug delivery and bioimaging. Finally, an outlook and perspective toward future developments of in vivo self‐assembled peptide‐based nanomaterials for translational medicine are concluded.
Taking inspiration from self‐assembly systems in nature, a new strategy of “in vivo self‐assembly” is proposed to in situ construct functional nanomaterials in living subjects. This concept, from the modular molecular design, assembly driving forces, morphology control, and biological effects to biomedical applications, is discussed.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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