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The gut fungi play important roles in human health and are involved in energy metabolism. This study aimed to examine gut mycobiome composition in obese subjects in two geographically different regions in China and to identify specific gut fungi associated with obesity. A total of 217 subjects from two regions with different urbanization levels [Hong Kong (HK): obese, n = 59; lean, n = 59; Kunming (KM): obese, n = 50; lean, n = 49. Mean body mass index (BMI) for obesity = 33.7] were recruited. We performed deep shotgun metagenomic sequencing on fecal samples to compare gut mycobiome composition and trophic functions in lean and obese subjects across these two regions. The gut mycobiome of obese subjects in both HK and KM were altered compared to those of lean subjects, characterized by a decrease in the relative abundance of Nakaseomyces, Schizosaccharomyces pombe, Candida dubliniensis and an increase in the abundance of Lanchanceathermotolerans, Saccharomyces paradox, Parastagonospora nodorum and Myceliophthorathermophila. Reduced fungal - bacterial and fungal - fungal correlations as well as increased negative fungal-bacterial correlations were observed in the gut of obese subjects. Furthermore, the anti-obesity effect of fungus S. pombe was further validated using a mouse model. Supplementing high-fat diet-induced obese mice with the fungus for 12 weeks led to a significant reduction in body weight gain (p < 0.001), and an improvement in lipid and glucose metabolism compared to mice without intervention. In conclusion, the gut mycobiome composition and functionalities of obese subjects were altered. These data shed light on the potential of utilizing fungus-based therapeutics for the treatment of obesity. S. pombe may serve as a potential fungal probiotic in the prevention of diet-induced obesity and future human trials are needed.
Sujet(s)
Fèces , Champignons , Microbiome gastro-intestinal , Mycobiome , Obésité , Obésité/microbiologie , Humains , Animaux , Champignons/classification , Champignons/isolement et purification , Champignons/génétique , Mâle , Souris , Chine , Femelle , Fèces/microbiologie , Adulte , Bactéries/classification , Bactéries/isolement et purification , Bactéries/génétique , Adulte d'âge moyen , Souris de lignée C57BL , Indice de masse corporelleRÉSUMÉ
BACKGROUND: Variations exist in the response of patients with Crohn's disease (CD) to ustekinumab (UST) treatment, but the underlying cause remains unknown. Our objective was to investigate the involvement of immune cells and identify potential biomarkers that could predict the response to interleukin (IL) 12/23 inhibitors in patients with CD. METHODS: The GSE207022 dataset, which consisted of 54 non-responders and 9 responders to UST in a CD cohort, was analyzed. Differentially expressed genes (DEGs) were identified and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Least absolute shrinkage and selection operator (LASSO) regression was used to screen the most powerful hub genes. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performances of these genes. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used to estimate the proportions of immune cell types. These significantly altered genes were subjected to cluster analysis into immune cell-related infiltration. To validate the reliability of the candidates, patients prescribed UST as a first-line biologic in a prospective cohort were included as an independent validation dataset. RESULTS: A total of 99 DEGs were identified in the integrated dataset. GO and KEGG analyses revealed significant enrichment of immune response pathways in patients with CD. Thirteen genes (SOCS3, CD55, KDM5D, IGFBP5, LCN2, SLC15A1, XPNPEP2, HLA-DQA2, HMGCS2, DDX3Y, ITGB2, CDKN2B and HLA-DQA1), which were primarily associated with the response versus nonresponse patients, were identified and included in the LASSO analysis. These genes accurately predicted treatment response, with an area under the curve (AUC) of 0.938. T helper cell type 1 (Th1) cell polarization was comparatively strong in nonresponse individuals. Positive connections were observed between Th1 cells and the LCN2 and KDM5D genes. Furthermore, we employed an independent validation dataset and early experimental verification to validate the LCN2 and KDM5D genes as effective predictive markers. CONCLUSIONS: Th1 cell polarization is an important cause of nonresponse to UST therapy in patients with CD. LCN2 and KDM5D can be used as predictive markers to effectively identify nonresponse patients. TRIAL REGISTRATION: Trial registration number: NCT05542459; Date of registration: 2022-09-14; URL: https://www. CLINICALTRIALS: gov .
Sujet(s)
Biologie informatique , Maladie de Crohn , ARN messager , Ustékinumab , Adulte , Femelle , Humains , Mâle , Analyse de regroupements , Biologie informatique/méthodes , Maladie de Crohn/génétique , Maladie de Crohn/traitement médicamenteux , Analyse de profil d'expression de gènes , Gene Ontology , Muqueuse intestinale/métabolisme , Muqueuse intestinale/anatomopathologie , Études prospectives , Reproductibilité des résultats , ARN messager/génétique , ARN messager/métabolisme , Courbe ROC , Transcriptome/génétique , Ustékinumab/usage thérapeutique , Ustékinumab/pharmacologieRÉSUMÉ
Lung adenocarcinoma (LUAD) is characterized by a high incidence rate and mortality. Recently, POC1 centriolar protein A (POC1A) has emerged as a potential biomarker for various cancers, contributing to cancer onset and development. However, the association between POC1A and LUAD remains unexplored. We extracted The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) data sets to analyse the differential expression of POC1A and its relationship with clinical stage. Additionally, we performed diagnostic receiver operator characteristic (ROC) curve analysis and Kaplan-Meier (KM) survival analysis to assess the diagnostic and prognostic value of POC1A in LUAD. Furthermore, we investigated the correlation between POC1A expression and immune infiltration, tumour mutation burden (TMB), immune checkpoint expression and drug sensitivity. Finally, we verified POC1A expression using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). Cell experiments were conducted to validate the effect of POC1A expression on the proliferation, migration and invasion of lung cancer cells. POC1A exhibited overexpression in most tumour tissues, and its overexpression in LUAD was significantly correlated with late-stage presentation and poor prognosis. The high POC1A expression group showed lower levels of immune infiltration but higher levels of immune checkpoint expression and TMB. Moreover, the high POC1A expression group demonstrated sensitivity to multiple drugs. In vitro experiments confirmed that POC1A knockdown led to decreased proliferation, migration, and invasion of lung cancer cells. Our findings suggest that POC1A may contribute to tumour development by modulating the cell cycle and immune cell infiltration. It also represents a potential therapeutic target and marker for the diagnosis and prognosis of LUAD.
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Adénocarcinome pulmonaire , Tumeurs du poumon , Humains , Adénocarcinome pulmonaire/génétique , Cycle cellulaire , Protéines du cycle cellulaire/génétique , Protéines du cycle cellulaire/métabolisme , Division cellulaire , Protéines du cytosquelette/génétique , Protéines du cytosquelette/métabolisme , Tumeurs du poumon/génétique , Régulation positive/génétiqueRÉSUMÉ
Solid tumors, especially those with aberrant MYCN activation, often harbor an immunosuppressive microenvironment to fuel malignant growth and trigger treatment resistance. Despite this knowledge, there are no effective strategies to tackle this problem. We found that chemokine-like factor (CKLF) is highly expressed by various solid tumor cells and transcriptionally up-regulated by MYCN. Using the MYCN-driven high-risk neuroblastoma as a model system, we demonstrated that as early as the premalignant stage, tumor cells secrete CKLF to attract CCR4-expressing CD4+ cells, inducing immunosuppression and tumor aggression. Genetic depletion of CD4+ T regulatory cells abolishes the immunorestrictive and protumorigenic effects of CKLF. Our work supports that disrupting CKLF-mediated cross-talk between tumor and CD4+ suppressor cells represents a promising immunotherapeutic approach to battling MYCN-driven tumors.
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Chimiokines , Protéines à domaine MARVEL , Protéine du proto-oncogène N-Myc , Neuroblastome , Humains , Lignée cellulaire tumorale , Chimiokines/métabolisme , Régulation de l'expression des gènes tumoraux , Protéines à domaine MARVEL/métabolisme , Protéine du proto-oncogène N-Myc/métabolisme , Neuroblastome/métabolisme , Neuroblastome/anatomopathologie , Neuroblastome/thérapie , Microenvironnement tumoralRÉSUMÉ
Gut bacteriome dysbiosis is known to be implicated in the pathogenesis of inflammatory bowel disease (IBD). Crohn's disease (CD) is an IBD subtype with extensive mucosal inflammation, yet the mucosal virome, an empirical modulator of the bacteriome and mucosal immunity, remains largely unclear regarding its composition and role. Here, we exploited trans-cohort CD patients and healthy individuals to compositionally and functionally investigate the small bowel (terminal ileum) virome and bacteriome. The CD ileal virome was characterised by an under-representation of both lytic and temperate bacteriophages (especially those targeting bacterial pathogens), particularly in patients with flare-up. Meanwhile, the virome-bacteriome ecology in CD ileal mucosa was featured by a lack of Bifidobacterium- and Lachnospiraceae-led mutualistic interactions between bacteria and bacteriophages; surprisingly it was more pronounced in CD remission than flare-up, underlining the refractory and recurrent nature of mucosal inflammation in CD. Lastly, we substantiated that ileal virions from CD patients causally exacerbated intestinal inflammation in IBD mouse models, by reshaping a gut virome-bacteriome ecology preceding intestinal inflammation (microbial trigger) and augmenting microbial sensing/defence pathways in the intestine cells (host response). Altogether, our results highlight the significance of mucosal virome in CD pathogenesis and importance of mucosal virome restoration in CD therapeutics.
Sujet(s)
Bactériophages , Maladie de Crohn , Maladies inflammatoires intestinales , Humains , Animaux , Souris , Maladie de Crohn/anatomopathologie , Virome , Maladies inflammatoires intestinales/anatomopathologie , Muqueuse intestinale/métabolisme , Iléum/anatomopathologie , Bactéries , Inflammation/anatomopathologieRÉSUMÉ
Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. Currently, chemotherapy remains to be the primary treatment for TNBC, but drug resistance is common while patient prognosis is poor. With the development of proteomics technology, phosphoproteomics research has made great progress and has been widely used in the study of tumor mechanism, diagnosis and treatment. Similarly, phosphoproteomics plays a significant role in the studies of the occurrence, development, targeted therapy, and drug resistance mechanisms of TNBC. This article summarizes the research progress of phosphoproteomics in TNBC, with the aim to facilitate the research on the mechanism and treatment of TNBC based on phosphoproteomics.
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Tumeurs du sein triple-négatives , Humains , Pronostic , Tumeurs du sein triple-négatives/diagnostic , Tumeurs du sein triple-négatives/traitement médicamenteux , FemelleRÉSUMÉ
This study aimed to develop an enhanced environmental dry eye (EDE) model that accurately reproduces the etiology of prolonged visual fatigue and investigates the underlying pathological features. A total of 40 adult SPF-grade Wistar rats were randomly assigned to control (n = 20) and model (n = 20) groups. Rats in the control group were maintained under normal conditions, while rats in the model group were exposed to a controlled frontal airflow of 2-4 m/s from a fan for 7.5 h daily while placed on a suspended cylindrical wire mesh frame. Various assessments were performed at different time points during the 14-day experiment, including blink frequency, tear secretion (phenol red thread test), tear film breakup time (BUT), fluorescein staining (FL), corneal epithelial status (light microscopy), ultrastructure of corneal epithelial cells (electron microscopy), and expression levels of inflammatory cytokines (IL-1ß, TNF-α) in tears (enzyme-linked immunosorbent assay). Additionally, mRNA and protein expression levels of MMP-9, IL1ß, IL6, TNF-α, IFN-γ, and caspase-3 in corneal tissues were quantified (real-time quantitative PCR and Western blotting). Compared to the control group, the model group rats exhibited significant decreases in blink frequency (P < 0.001), tear secretion (Schirmer I test) values (P < 0.001), and tear film breakup time levels (P < 0.001). There was also a significant increase in fluorescein staining scores (P < 0.001) in the model group. Histological examination revealed distinct differences of the corneal epithelium between groups. The corneal epithelium of the model group appeared thicker, with disorganized cell arrangement in the superficial and basal layers, partial defects or detachment of superficial epithelial cells, and a rough, uneven surface. Scanning electron microscopy observations showed a rough corneal epithelial surface with numerous cracks and scattered vesicular-like structures in the model group. Furthermore, the model group rats exhibited a significant increase in expression of IL-1ß and TNF-α in tears (P < 0.001), and upregulated expression levels of MMP-9, TNF-α, IL-1ß, caspase-3, IL-6, and IFN-γ at both the mRNA and protein levels in corneal tissues (P < 0.001). In conclusion, the modified "wire-meshing cylindrical board" model effectively overcomes the limitations of the traditional "jogging board " dry eye model and successfully simulates the etiology of prolonged visual fatigue. This innovative EDE model demonstrates a high degree of relevance to dry eye conditions resulting from prolonged visual tasks, with a high success rate of model induction. Moreover, it proves to be a simple, practical, and easily replicable model, making it highly suitable for further studies on prolonged visual fatigue and facilitating its widespread adoption in research and clinical applications.
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Asthénopie , Syndromes de l'oeil sec , Rats , Animaux , Matrix metalloproteinase 9/génétique , Matrix metalloproteinase 9/métabolisme , Caspase-3/génétique , Caspase-3/métabolisme , Facteur de nécrose tumorale alpha/métabolisme , Asthénopie/métabolisme , Rat Wistar , Syndromes de l'oeil sec/métabolisme , Larmes/métabolisme , Fluorescéine/métabolisme , Interleukine-1 bêta/métabolisme , ARN messager/métabolismeRÉSUMÉ
The Shandong Peninsula is located on the western coast of the Pacific and is adjacent to the Bohai Sea (BS) and the Yellow Sea (YS) to the east. The East Asian finless porpoise Neophocaena asiaeorientalis sunameri, a subspecies of the narrow-ridged finless porpoise N. asiaeorientalis, is the dominant cetacean resident along the Shandong Peninsula. However, there is insufficient monitoring data to determine the status of the cetacean species in this region. Based on the publicly available literature, media, and internet social website, this study investigated the spatial-temporal distribution of porpoise stranding and bycatch along the coast of the Shandong Peninsula. Data on over five hundred porpoises from two hundred reports between 2000 and 2018 were compiled and analyzed. Results showed that the bycatch and stranding of porpoises occurred widely across the peninsula throughout all months and increased rapidly between 2010 and 2017. The incidents were more frequent in the area where the BS and YS converged during the spring and early summer than in other seasons. The mean body length of bycaught porpoises was smaller than that of those found stranded. Fishing activities could be the principal cause of local finless porpoise incidents. However, limited data hindered a quantitative evaluation of the living conditions of finless porpoises in this area. Establishing a comprehensive monitoring system, which includes standardized reporting, rescue operations, and scientific research, is essential to finless porpoise protection along the Shandong Peninsula.
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Background: Lung adenocarcinoma (LUAD) has high morbidity and mortality. Current studies indicate nucleoporin 107 (NUP107) is involved in the construction of nuclear pore complex, and NUP107 overexpression contributes to the growth and development in most types of cancers, but its effect in LUAD has not been elucidated. Methods: Differences in NUP107 expression were investigated using the Cancer Genome Atlas (TCGA) and multiple Gene Expression Omnibus (GEO) data sets. Enrichment analysis were implemented to probe the NUP107 function. The association of NUP107 with the degree of immune cell infiltration was investigated by the TIMER database, single-sample gene set enrichment analysis (ssGSEA), and ESTIMATE. The association of NUP107 expression with tumor mutation burden (TMB), TP53, and immune checkpoint was analyzed. Single-cell RNA sequencing data were used to detect NUP107 expression in different cell clusters. Finally, we performed real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) to prove the difference of NUP107 expression. Results: NUP107 was overexpressed in LUAD and mainly expressed in cancer stem cell (CSC). Overexpression of NUP107 in LUAD suggested a poorer prognosis. Functional enrichment analysis pointed out that NUP107 was mainly linked to the regulation of cell cycle. Both immune cell infiltration and TMB were found to be in connection with NUP107. Cases in the group with high NUP107 expression had poorer immune infiltration, but had higher expression of immune checkpoints, TMB, and proportion of TP53 mutations. Conclusion: NUP107 is a sensitive diagnostic and prognostic factor for LUAD and may be involved in tumor progression through its effects on cell cycle and immune infiltration.
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Next-generation risk assessment (NGRA) for environmental chemicals involves a weight of evidence (WoE) framework integrating a suite of new approach methodologies (NAMs) based on points of departure (PoD) obtained from in vitro assays. Among existing NAMs, the omic-based technologies are of particular importance based on the premise that any apical endpoint change indicative of impaired health must be underpinned by some alterations at the omics level, such as transcriptome, proteome, metabolome, epigenome and genome. Transcriptomic assay plays a leading role in providing relatively conservative PoDs compared with apical endpoints. However, it is unclear whether and how parameters measured with other omics techniques predict the cellular response to chemical perturbations, especially at exposure levels below the transcriptomically defined PoD. Multi-omics coverage may provide additional sensitive or confirmative biomarkers to complement and reduce the uncertainty in safety decisions made using targeted and transcriptomics assays. In the present study, we conducted multi-omics studies of transcriptomics, proteomics and phosphoproteomics on two prototype compounds, coumarin and 2,4-dichlorophenoxyacetic acid (2,4-D), with multiple chemical concentrations and time points, to understand the sensitivity of the three omics techniques in response to chemically-induced changes in HepG2. We demonstrated that, phosphoproteomics alterations occur not only earlier in time, but also more sensitive to lower concentrations than proteomics and transcriptomics when the HepG2 cells were exposed to various chemical treatments. The phosphoproteomics changes appear to approach maximum when the transcriptomics alterations begin to initiate. Therefore, it is proximal to the very early effects induced by chemical exposure. We concluded that phosphoproteomics can be utilized to provide a more complete coverage of chemical-induced cellular alteration and supplement transcriptomics-based health safety decision making.
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Intervenants d'urgence , Protéomique , Humains , Protéomique/méthodes , Transcriptome , Protéome , Analyse de profil d'expression de gènesRÉSUMÉ
OBJECTIVE: To compare the clinical efficacy of acupuncture, Chinese medication and combination of acupuncture and medication in the treatment of dry eye complicated with computer vision syndrome (CVS). METHODS: A total of 152 patients with dry eye complicated with CVS were randomly divided into an acupuncture-medication group (38 cases, 1 case was removed), an acupuncture group (38 cases, 1 case dropped off), a Chinese medication group (38 cases, 1 case was removed), and a western medication group (38 cases, 1 case dropped off). In the western medication group, sodium hyaluronate eye drop combined with esculin and digitalis glycosides eye drop were used. In the acupuncture group, acupuncture was applied at bilateral Taiyang (EX-HN 5)ï¼ Cuanzhu (BL 2), Fengchi (GB 20), Qimen (LR 14) , and Hegu (LI 4) etc., once a day. In the Chinese medication group, Yiqi Congming decoction formula ganule was given orally, one dose a day. In the acupuncture-medication group, acupuncture combined with Yiqi Congming decoction formula granule were used. All groups were treated for 14 d. The non-invasive first tear film break-up time (NIBUT f), non-invasive average tear film break-up time (NIBUT av), tear meniscus height (TMH), ocular surface disease index (OSDI) score, and CVS symptom score were compared between the patients of each group before and after treatment. RESULTS: After treatment, the NIBUT f, NIBUT av, and TMH were increased compared with those before treatment in the patients of the 4 groups (P<0.01); the NIBUT f and NIBUT av in the acupuncture-medication group and the acupuncture group were higher than those in the Chinese medication group and the western medication group (P<0.05), and the TMH in the acupuncture-medication group and the Chinese medication group were higher than those in the acupuncture group and the western medication group (P<0.05). After treatment, the OSDI scores, the various scores and total scores of CVS (except for head symptom score in the western medication group) were decreased compared with those before treatment in the patients of the 4 groups (P<0.01). The OSDI score, total score, eye symptom score, and body symptom score of CVS in the acupuncture-medication group were lower than those in the acupuncture group, the Chinese medication group, and the western medication group (P<0.01, P<0.05), the head symptom score of the acupuncture-medication group was lower than that in the western medication group (P<0.05), and the CVS physical symptom scores and mental cognitive symptom scores of the acupuncture-medication group and the acupuncture group were lower than those in the Chinese medication group and the western medication group (P<0.05). CONCLUSION: Acupuncture has advantages in improving NIBUT f, NIBUT av, and CVS physical symptoms and cognitive symptoms, and the Chinese medication has advantage in improving TMH. The combination of acupuncture and Chinese medication has better effects compared with monotherapy.
Sujet(s)
Thérapie par acupuncture , Syndromes de l'oeil sec , Humains , Syndromes de l'oeil sec/traitement médicamenteux , Syndromes de l'oeil sec/étiologie , Ordinateurs , Résultat thérapeutique , Points d'acupuncture , Solutions ophtalmiquesRÉSUMÉ
The human gut microbiome varies substantially across individuals and populations and differentially tames our immunity at steady-state. Hence, we hypothesize that the large heterogeneity of gut microbiomes at steady-state may shape our baseline immunity differentially, and then mediate discrepant immune responses and symptoms when one encounters a viral infection, such as SARS-CoV-2 infection. To validate this hypothesis, we conducted an exploratory, longitudinal microbiome-COVID-19 study involving homogenous young participants from two geographically different regions in China. Subjects were recruited and sampled of fecal specimens before the 3-week surge window of COVID-19 (between December 11 and December 31, 2022) in China, and then were followed up for assessment of COVID-19 and post-COVID-19 manifestations. Our data showed that the baseline gut microbiome composition was intricately associated with different COVID-19 manifestations, particularly gastrointestinal involvement and post-COVID-19 lingering symptoms, in both an individual- and population-dependent manner. Our study intriguingly for the first time highlight that the gut microbiome at steady-state may prepare us differentially for weathering a respiratory viral infection.
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COVID-19 , Microbiome gastro-intestinal , Microbiote , Humains , SARS-CoV-2 , Chine/épidémiologieRÉSUMÉ
Soman, a warfare nerve agent, poses a significant threat by inducing severe brain damage that often results in death. Nonetheless, our understanding of the biological changes underlying persistent neurocognitive dysfunction caused by low dosage of soman remains limited. This study used mice to examine the effects of different doses of soman over time. Phosphoproteomic analysis of the mouse brain is the first time to be used to detect toxic effects of soman at such low or ultra-low doses, which were undetectable based on measuring the activity of acetylcholinesterase at the whole-animal level. We also found that phosphoproteome alterations could accurately track the soman dose, irrespective of the sampling time. Moreover, phosphoproteome revealed a rapid and adaptive cellular response to soman exposure, with the points of departure 8-38 times lower than that of acetylcholinesterase activity. Impaired long-term potentiation was identified in phosphoproteomic studies, which was further validated by targeted quantitative proteomics, immunohistochemistry, and immunofluorescence analyses, with significantly increased levels of phosphorylation of protein phosphatase 1 in the hippocampus following soman exposure. This increase in phosphorylation inhibits long-term potentiation, ultimately leading to long-term memory dysfunction in mice.
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Agents neurotoxiques , Soman , Souris , Animaux , Soman/toxicité , Acetylcholinesterase/métabolisme , Potentialisation à long terme , Hippocampe , AnticholinestérasiquesRÉSUMÉ
Anti-cancer therapies are usually intertwined with prolonged use of drugs, which may lead to different clinical outcomes. Recently in Cell and Cell Host & Microbe, Nguyen et al. and Vallet et al., respectively, deconvolute the drug effects on gut microbiome dynamics underpinning clinical outcomes after allogeneic hematopoietic stem cell transplantation.
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Microbiome gastro-intestinal , Transplantation de cellules souches hématopoïétiquesRÉSUMÉ
OBJECTIVE: This is a retrospective study of adverse events associated with preoperative computed tomography (CT)-guided hookwire or coil localisation. We analysed the experience and process flaws in resecting ground-glass nodules (GGNs) through video-assisted thoracoscopic surgery (VATS) and determined the remedial strategy. METHODS: Adverse events were evaluated in 40 patients with 45 GGNs who underwent CT-guided hookwire or coil localisation before VATS. For lesions not successfully marked or detected, palpation, resection of the highly suspected area, segmentectomy or lobectomy was performed. RESULTS: Among all adverse events, 15 were dislodgement of the marking materials, 5 were breakaway of the marking materials, 7 were > 2 cm distance between the lesions and the tips, 3 was marking material across the two adjacent lobes, 15 were pneumothorax and 2 were certain parts of marking materials stuck into the chest wall. All GGNs were resected successfully. 20 lesions were detected by palpation. 9 GGNs were discovered after the resection of highly suspected areas. Segmentectomies and lobectomies were performed directly on 7 and 9 GGNs, respectively. CONCLUSIONS: When adverse events occur, a second intraoperative localisation, by resecting the highly suspected area either through non-anatomical resection (wedge resection) or anatomical resection (segmentectomy or lobectomy) using the VATS should be considered the alternatives for GGNs localization.
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Pneumothorax , Paroi thoracique , Humains , Études rétrospectives , Chirurgie thoracique vidéoassistée , TomodensitométrieRÉSUMÉ
The world is witnessing a global increase in the urban population, particularly in developing Asian and African countries. Concomitantly, the global burden of non-communicable diseases (NCDs) is rising, markedly associated with the changing landscape of lifestyle and environment during urbanization. Accumulating studies have revealed the role of the gut microbiome in regulating the immune and metabolic homeostasis of the host, which potentially bridges external factors to the host (patho-)physiology. In this review, we discuss the rising incidences of NCDs during urbanization and their links to the compositional and functional dysbiosis of the gut microbiome. In particular, we elucidate the effects of urbanization-associated factors (hygiene/pollution, urbanized diet, lifestyles, the use of antibiotics, and early life exposure) on the gut microbiome underlying the pathogenesis of NCDs. We also discuss the potential and feasibility of microbiome-inspired and microbiome-targeted approaches as novel avenues to counteract NCDs, including fecal microbiota transplantation, diet modulation, probiotics, postbiotics, synbiotics, celobiotics, and precision antibiotics.
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Microbiome gastro-intestinal , Microbiote , Maladies non transmissibles , Probiotiques , Humains , Microbiome gastro-intestinal/physiologie , Urbanisation , Maladies non transmissibles/thérapie , Maladies non transmissibles/traitement médicamenteux , Transplantation de microbiote fécal , Antibactériens/usage thérapeutique , Dysbiose/traitement médicamenteux , PrébiotiquesRÉSUMÉ
Oncolytic viruses (OVs) represent a type of encouraging multi-mechanistic drug for the treatment of cancer. However, attenuation of virulence, which is generally required for the development of OVs based on pathogenic viral backbones, is frequently accompanied by a compromised killing effect on tumor cells. By exploiting the property of viruses to evolve and adapt in cancer cells, we perform directed natural evolution on refractory colorectal cancer cell HCT-116 and generate a next-generation oncolytic virus M1 (NGOVM) with an increase in the oncolytic effect of up to 9690-fold. The NGOVM has a broader antitumor spectrum and a more robust oncolytic effect in a range of solid tumors. Mechanistically, two critical mutations are identified in the E2 and nsP3 genes, which accelerate the entry of M1 virus by increasing its binding to the Mxra8 receptor and antagonize antiviral responses by inhibiting the activation of PKR and STAT1 in tumor cells, respectively. Importantly, the NGOVM is well tolerated in both rodents and nonhuman primates. This study implies that directed natural evolution is a generalizable approach for developing next-generation OVs with an expanded scope of application and high safety.