Pulmonary fibrosis is closely associated with the recruitment of fibroblasts from capillary vessels with damaged endothelial cells, the epithelial mesenchymal transition (EMT) of type II alveolar ...epithelial cells, and the transformation of fibroblasts to myofibroblasts. Recent studies suggest that EMT is a key factor in the pathogenesis of pulmonary fibrosis, as the disruption of EMT-related effector molecules can inhibit the occurrence and development of PF. With the numerous advancements made in molecular biology in recent years, researchers have discovered that exosomes and their cargos, such as miRNAs, lncRNAs, and proteins, can promote or inhibit the EMT, modulate the transformation of fibroblasts into myofibroblasts, contribute to the proliferation of fibroblasts and promote immunoregulatory and mitochondrial damage during pulmonary fibrosis. Exosomes are key factors regulating the differentiation of bone marrow mesenchymal stem cells (BMSCs) into myofibroblasts. Interestingly, exosomes derived from BMSCs under pathological and physiological conditions may promote or inhibit the EMT of type II alveolar epithelial cells and the transformation of fibroblasts into myofibroblasts to regulate pulmonary fibrosis. Thus, exosomes may become a new direction in the study of drugs for the treatment of pulmonary fibrosis.
Traffic-related air pollution (TRAP) is hypothesised to play a role in the development of allergic rhinitis (AR). Prenatal and early-life exposure to traffic-related air pollution is considered ...critical for later respiratory health. However, we could not find any articles systematically reviewing the risk of prenatal and early-life exposure to traffic-related air pollution for allergic rhinitis in children.
A systematic literature search of PubMed, Web of Science and Medline was conducted to identify studies focused on the association between prenatal and early-life exposure to TRAP and AR in children. Other inclusion criteria were: 1) original articles; 2) based upon prospective or retrospective studies or case-control studies; and 3) publications were restricted to English. Literature quality assessment was processed using the Newcastle-Ottawa Scale (NOS) evaluation scale. This systematic literature review has been registered on the prospero (crd.york.ac.uk/prospero) with the following registry number: CRD42022361179.
Only eight studies met the inclusion criteria. The exposure assessment indicators included PM2.5, PM2.5 absorbance, PM10, NOx, CO, and black carbon. On the whole, exposure to TRAP during pregnancy and the first year of life were positively associated with the development of AR in children.
This systematic review presents supportive evidence about prenatal and early-life exposure to TRAP and the risk of AR in children.
Recent studies reveal a great value of interleukin-8 (IL-8), a pro-inflammatory cytokine, as a potent biomarker for early diagnosis of oral cancer. Herein, a new electrochemical method is proposed to ...detect IL-8 by facilely incorporating DNA-templated quantum dots (QDs). In principle, target IL-8 is first treated with the reducing agent tris(2-carboxyethyl)phosphine (TCEP) to yield active thiols and then captured by antibody-functionalized magnetic beads (MBs). Thereafter, via the Michael addition reaction between the active thiol and maleimide group, a maleimide-modified DNA probe is linked to the surface of MBs, which can initiate a process of rolling circle amplification. In this way, long-range DNA strands are generated on the MB surface, subsequently recruiting DNA-templated CdTe/CdS QDs (DNA-QDs) to act as electrochemical reporters. By tracing the responses of DNA-QDs, the method allows IL-8 detection in a linear range from 5 to 5000 fg/mL with a detection limit of 3.36 fg/mL. The selectivity, reproducibility, and applicability in complex serum samples are also demonstrated to be favorable, indicating that the method may have a great potential in the future. More importantly, the use of TCEP treatment in the method not only provides a facile way to incorporate DNA-QDs, avoiding the complicated and time-consuming preparation process of antibody-DNA conjugates or functional nanomaterials; but also makes the method capable of being extended to detect other protein biomarkers in view of widespread presence of disulfides, which may hold a broad potential to facilitate efficient biosensing designs.
Herpes simplex virus 1 (HSV-1) establishes infections in humans and mice, but some non-human primates exhibit resistance via unknown mechanisms. Innate immune recognition pathways are highly ...conserved but are pivotal in determining susceptibility to DNA virus infections. We report that variation of a single amino acid residue in the innate immune sensor cGAS determines species-specific inactivation by HSV-1. The HSV-1 UL37 tegument protein deamidates human and mouse cGAS. Deamidation impairs the ability of cGAS to catalyze cGAMP synthesis, which activates innate immunity. HSV-1 with deamidase-deficient UL37 promotes robust antiviral responses and is attenuated in mice in a cGAS- and STING-dependent manner. Mutational analyses identified a single asparagine in human and mouse cGAS that is not conserved in many non-human primates. This residue underpins UL37-mediated cGAS deamidation and species permissiveness of HSV-1. Thus, HSV-1 mediates cGAS deamidation for immune evasion and exploits species sequence variation to disarm host defenses.
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•The HSV-1 UL37 tegument protein antagonizes the cGAS-STING pathway in mice•UL37 deamidates a critical Asn on cGAS of humans and mice but not many non-human primates•cGAS deamidation abolishes cGAMP synthesis and downstream innate immune activation•Variation of the cGAS UL37 deamidation site defines HSV-1 species-specific permissiveness
Natural sequence variations in immune factors may enable viral pathogens to evade or dismantle host defenses. Zhang et al. report that herpes simplex virus 1 exploits species-specific variation of a single amino acid residue in cGAS for deamidation, thereby inactivating innate defense in susceptible hosts.
Sphingosine 1-phosphate (S1P) plays an important role in hepatocarcinogenesis. We previously demonstrated that S1P induced epithelial–mesenchymal transition of hepatocellular carcinoma (HCC) cells ...via an MMP-7/Syndecan-1/TGF-β autocrine loop. In the present study, we investigated the regulative role of S1P in cell survival and progression of HCC cells, and tested whether syndecan-1 is required in the S1P action. After transfected with syndecan-1 shRNA, HepG2 and SMMC7721 cells were treated with S1P for 72 h, and then cell proliferation was detected by CCK8 assay, and cell cycle progression and cell apoptosis were detected by flow cytometry. The levels of apoptosis markers including cleaved-Caspase-3 and cleaved-PARP in SMMC7721 cells were examined by western blotting. Results showed that S1P significantly enhanced cell proliferation in HCC cells, which was significantly inhibited by syndecan-1 shRNA. S1P induced the cell proportion in S phase in HCC cells, whereas S1P decreased the proportion of cells in both early and late apoptosis. Syndecan-1 shRNA induced the G2/M arrest in the presence of S1P. In the syndecan-1 shRNA transfected HCC cells, the proportions of late and early apoptotic cells, and levels of cleaved-Caspase-3 and cleaved-PARP were significantly increased in cells with or without S1P treatment. Thus, S1P augments the proportion of cells in S phase of the cell cycle that might translate to enhance HCC cell proliferation and inhibit the cell apoptosis via syndecan-1.
Wilson's disease (WD) is a hereditary disorder that results in the accumulation of copper. The pathogenic mechanism is not well understood, and diagnosing the disease can be challenging, as it shares ...similarities with more prevalent conditions. To explore the metabolomic features of WD and differentiate it from other diseases related to copper metabolism, we conducted targeted and untargeted metabolomic profiling using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS). We compared the metabolomic profiles of two subgroups of WD patients, namely hepatic WD (H-WD) and neurological WD (N-WD), H-WD patients and liver cirrhosis patients (who exhibit similar symptoms but have normal copper levels), and N-WD patients and Parkinson's disease patients (who exhibit similar symptoms but have normal copper levels). Our pairwise comparisons revealed distinct metabolomic profiles for male and female WD patients, H-WD and N-WD patients, N-WD and Parkinson's disease patients, and H-WD and liver cirrhosis patients. We then employed logistic regression analysis, receiver operating characteristic (ROC) analysis, and model construction to identify candidate diagnostic biomarkers that differentiate H-WD from liver cirrhosis and N-WD from Parkinson's disease. Based on the spatial distribution of data obtained via PLS-DA analysis, we discovered variations in hydrophilic metabolites (aminoacyl-tRNA biosynthesis; alanine, aspartate, and glutamate metabolism; phenylalanine metabolism; arginine biosynthesis; and nicotinate and nicotinamide) and lipophilic metabolites (TG(triglyceride) (16:0_16:1_22:6), TG (16:0_16:0_22:6), and TG (16:0_16:1_22:5)) between H-WD and N-WD. Moreover, WD patients display metabolic traits that distinguish it from comparable conditions (liver cirrhosis and Parkinson's disease). Our analysis reveals significant variations in the levels of metabolites in critical metabolic pathways and numerous lipids in WD.ROC analysis indicates that three metabolites may be considered as candidate biomarkers for diagnosing WD.
Pneumoconiosis patients have a high prevalence of pulmonary infections, which can complicate diagnosis and treatment. And there is no comprehensive study of the microbiome of patients with ...pneumoconiosis. The application of metagenomic next-generation sequencing (mNGS) fills the gap to some extent by analyzing the lung microbiota of pneumoconiosis population while achieving accurate diagnosis.
We retrospectively analyzed 44 patients with suspected pneumoconiosis complicated with pulmonary infection between Jan 2020 and Nov 2022. Bronchoalveolar lavage fluid (BALF) specimens from 44 patients were collected and tested using the mNGS technology.
Among the lung microbiome of pneumoconiosis patients with complicated pulmonary infection (P group), the most frequently detected bacteria and fungi at the genus level were
and
, at the species level were
and
, respectively, and the most frequently detected DNA virus was
. There was no significant difference in α diversity between the P group and the non-pneumoconiosis patients complicated with pulmonary infection group (Non-P group) in pulmonary flora, while
0.01 for β diversity analysis, and the differential species between the two groups were
and
. In addition, we monitored a high distribution of
and
in the P group, while herpes virus was detected in the majority of samples.
Overall, we not only revealed a comprehensive lung microbiome profile of pneumoconiosis patients, but also compared the differences between their microbiome and that of non-pneumoconiosis complicated with pulmonary infection patients. This provides a good basis for a better understanding of the relationship between pneumoconiosis and microorganisms, and for the search of potential biomarkers.
Different subtypes of non-small cell lung cancer (NSCLC) have distinct sites of origin, histologies, genetic and epigenetic changes. In this study, we explored the mechanisms of ECT2 dysregulation ...and compared its prognostic value in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). In addition, we also investigated the enrichment of ECT2 co-expressed genes in KEGG pathways in LUAD and LUSC. Bioinformatic analysis was performed based on data from the Cancer Genome Atlas (TCGA)-LUAD and TCGA-LUSC. Results showed that ECT2 expression was significantly upregulated in both LUAD and LUSC compared with normal lung tissues. ECT2 expression was considerably higher in LUSC than in LUAD. The level of ECT2 DNA methylation was significantly lower in LUSC than in LUAD. ECT2 mutation was observed in 5% of LUAD and in 51% of LUSC cases. Amplification was the predominant alteration. LUAD patients with ECT2 amplification had significantly worse disease-free survival (p = 0.022). High ECT2 expression was associated with unfavorable overall survival (OS) (p<0.0001) and recurrence-free survival (RFS) (p = 0.001) in LUAD patients. Nevertheless, these associations were not observed in patients with LUSC. The following univariate and multivariate analysis showed that the high ECT2 expression was an independent prognostic factor for poor OS (HR: 2.039, 95%CI: 1.457-2.852, p<0.001) and RFS (HR: 1.715, 95%CI: 1.210-2.432, p = 0.002) in LUAD patients, but not in LUSC patients. Among 518 genes co-expressed with ECT2 in LUAD and 386 genes co-expressed with ECT2 in LUSC, there were only 98 genes in the overlapping cluster. Some of the genes related KEGG pathways in LUAD were not observed in LUSC. These differences might help to explain the different prognostic value of ECT2 in LUAD and LUSC, which are also worthy of further studies.
Surgical site infections (SSIs) are among the most prevalent postoperative complications, with significant morbidity and mortality worldwide. In the past half century, hyperbaric oxygen therapy ...(HBOT), the administration of 100% oxygen intermittently under a certain pressure, has been used as either a primary or alternative therapy for the management or treatment of chronic wounds and infections. This narrative review aims to gather information and evidence supporting the role of HBOT in the treatment of SSIs. We followed the Scale for the Quality Assessment of Narrative Review Articles (SANRA) guidelines and scrutinized the most relevant studies identified in Medline (via PubMed), Scopus, and Web of Science. Our review indicated that HBOT can result in rapid healing and epithelialization of various wounds and has potential beneficial effects in the treatment of SSIs or other similar infections following cardiac, neuromuscular scoliosis, coronary artery bypass, and urogenital surgeries. Moreover, it was a safe therapeutic procedure in most cases. The mechanisms related to the antimicrobial activity of HBOT include direct bactericidal effects through the formation of reactive oxygen species (ROS), the immunomodulatory effect of HBOT that increase the antimicrobial effects of the immune system, and the synergistic effects of HBOT with antibiotics. We emphasized the essential need for further studies, especially randomized clinical trials and longitudinal studies, to better standardize HBOT procedures as well as to determine its full benefits and possible side effects.
Isoalantolactone (IATL) is one of multiple isomeric sesquiterpene lactones and is isolated from inula helenium. IATL has multiple functions such as antibacterial, antihelminthic and antiproliferative ...activities. IATL also inhibits pancreatic cancer proliferation and induces apoptosis by increasing ROS production. However, the detailed mechanism of IATL-mediated pancreatic cancer apoptosis remains largely unknown.
In current study, pancreatic carcinoma cell lines (PANC-1, AsPC-1, BxPC-3) and a mouse xenograft model were used to determine the mechanism of IATL-mediated toxic effects.
IATL (20μM) inhibited pancreatic adenocarcinoma cell lines proliferation in a time-dependent way; while scratch assay showed that IATL significantly inhibited PANC-1 scratch closure (P<0.05); Invasion assays indicated that IATL significantly attenuated pancreatic adenocarcinoma cell lines invasion on matrigel. Signal analysis showed that IATL inhibited pancreatic adenocarcinoma cell proliferation by blocking EGF-PI3K-Skp2-Akt signal axis. Moreover, IATL induced pancreatic adenocarcinoma cell apoptosis by increasing cytosolic Caspase3 and Box expression. This apoptosis was mediated by inhibition of canonical wnt signal pathway. Finally, xenograft studies showed that IATL also significantly inhibited pancreatic adenocarcinoma cell proliferation and induced pancreatic adenocarcinoma cell apoptosis in vivo.
IATL inhibits pancreatic cancer proliferation and induces apoptosis on cellular and in vivo models. Signal pathway studies reveal that EGF-PI3K-Skp2-Akt signal axis and canonical wnt pathway are involved in IATL-mediated cellular proliferation inhibition and apoptosis. These studies indicate that IATL may provide a future potential therapy for pancreatic cancer.
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