RESUMEN
Dysregulated Epiregulin (EREG) can activate epidermal growth factor receptor (EGFR) and promote tumor progression in head and neck squamous cell carcinoma (HNSCC). However, the mechanisms underlying EREG dysregulation remain largely unknown. Here, we showed that dysregulated EREG was highly associated with enhanced PDL1 in HNSCC tissues. Treatment of HNSCC cells with EREG resulted in upregulated PDL1 via the c-myc pathway. Of note, we found that N-glycosylation of EREG was essential for its stability, membrane location, biological function, and upregulation of its downstream target PDL1 in HNSCC. EREG was glycosylated at N47 via STT3B glycosyltransferases, whereas mutations at N47 site abrogated N-glycosylation and destabilized EREG. Consistently, knockdown of STT3B suppressed glycosylated EREG and inhibited PDL1 in HNSCC cells. Moreover, treatment of HNSCC cells with NGI-1, an inhibitor of STT3B, blocked STT3B-mediated glycosylation of EREG, leading to its degradation and suppression of PDL1. Finally, combination of NGI-1 treatment with anti-PDLl therapy synergistically enhanced the efficacy of immunotherapy of HNSCC in vivo. Taken together, STT3B-mediated N-glycosylation is essential for stabilization of EREG, which mediates PDL1 upregulation and immune evasion in HNSCC.
Asunto(s)
Antígeno B7-H1 , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Regulación hacia Arriba , Animales , Humanos , Ratones , Antígeno B7-H1/metabolismo , Western Blotting , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , Epirregulina , Glicosilación , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/metabolismo , Evasión Inmune , Sialiltransferasas/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismoRESUMEN
OBJECTIVE: This study aimed to clarify the relationship between FADD amplification and overexpression and the tumor immune microenvironment. METHODS: Immunohistochemical staining and bioanalysis were used to analyze the association between FADD expression in tumor cells and cells in tumor microenvironment. RNA-seq analysis was used to detect the differences in gene expression upon FADD overexpression. Flow cytometry and multicolor immunofluorescence staining (mIHC) were used to detect the differences in CD8+ T-cell infiltration in FADD-overexpressed cells or tumor tissues. RESULTS: Overexpression of FADD significantly promoted tumor growth. Cells with high FADD expression presented high expression of CD276 and FGFBP1 and low expression of proinflammatory factors (such as IFIT1-3 and CXCL8), which reduced the percentage of CD8+ T cells and created a "cold tumor" immune microenvironment, thus promoting tumor progression. In vivo and in vitro experiment confirmed that tumor tissues with excessive FADD expression exhibited CD8+ T-cell exclusion in the microenvironment. CONCLUSION: Our preliminary investigation has discovered the association between FADD expression and the immunosuppressive microenvironment in HNSCC. Due to the high frequent amplification of the chromosomal region 11q13.3, where FADD is located, targeting FADD holds promise for improving the immune-inactive state of tumors, subsequently inhibiting HNSCC tumor progression.
RESUMEN
How microzooplanktonic ciliate adaptative strategies differ across diatom bloom and non-diatom bloom areas in the Arctic Ocean remains poorly documented. To address this gap, two different situations were categorized in the Arctic Ocean at summer 2023: diatom bloom stations (DBS) (genus Thalassiosira, chain-like) and non-diatom bloom stations (nDBS). Total abundance of ciliate at 3 m and 25 m in DBS was 2.8 and 1.8 folds higher than in nDBS, respectively. Aloricate ciliates were singled out in both DBS and nDBS, whilst their average abundance and biomass of large size-fraction (>50 µm) in former were 4.5-5.6 folds higher than in latter. Regarding tintinnids, high abundance of Ptychocylis acuta (Bering Strait species) mainly occurred at DBS, coupled with distribution of co-occurring Pacific-origin species Salpingella sp.1, collectively suggested a strong intrusion of Pacific Inflow during summer 2023. Additionally, presence of high abundance of Acanthostomella norvegica and genus Parafavella in nDBS might indicate the trajectory of the Transpolar Drift. Alternatively, tintinnids can serve as credible bioindicators for either monitoring currents or evaluating microzooplankton Borealization. Average abundance of total ciliate within 15-135 µm body-size spectrum in DBS was higher than nDBS. Moreover, spearman's rank correlation between biotic and abiotic analysis revealed that temperature and dissolved oxygen at DBS determined tintinnid species richness and ciliate total abundance, respectively. The results clearly demonstrate that remarkable divergences in large size-fraction of ciliate abundance between DBS and nDBS validate their irreplaceable role in controlling phytoplankton outbreak and associated biological processes in polar seas.
Asunto(s)
Cilióforos , Diatomeas , Regiones Árticas , Cilióforos/fisiología , Diatomeas/fisiología , Eutrofización , Zooplancton/fisiología , Animales , Océanos y Mares , Tamaño Corporal , Agua de Mar/químicaRESUMEN
Neuston, situated at the air-sea interface, stands as a crucial frontier in the realm of the global warming. Despite its unique habitat, there remains a need to substantiate the composition, diel dynamic and biotic-abiotic interaction of neustonic zooplankton in the tropical seas. In this study, we present rare observational data on neustonic zooplankton (0-20 cm) in the oligotrophic tropical South China Sea (SCS) during the summer of 2022. A total of eighteen samples were collected and analyzed, revealing the presence of fourteen taxa from eight phyla. The most prevalent group was Cypridina, accounting for 33.7% of the total abundance, followed by copepods (29.0%) and jellyfish (10.9%). Within copepods, the genus Pontella exhibited the highest relative abundance (38.0%). Additionally, each neuston taxon displayed unique diel distribution patterns. Cypridina was the most abundant taxon during the night (40.4%), while it shifted to copepod dominance during the day (50.4%). Among copepods, genus Pontella and larvae were dominant groups at night (44.7%) and during the day (30.0%), respectively. Moreover, a multivariate biota-environment analysis demonstrated that temperature, pH, dissolved oxygen and Si(OH)4 significantly impacted neuston composition. Notably, both jellyfish and sea snails showed a significant positive correlation with temperature, suggesting their potential dominance in the neuston community in response to future global warming in the oligotrophic tropical seas. This study lays a robust foundation for recognizing the neuston community in the oceanic SCS, and helps evaluate the long-term risks to neuston habitats under climate changes.
Asunto(s)
Zooplancton , Animales , Zooplancton/fisiología , China , Copépodos/fisiología , Océanos y Mares , Ecosistema , Monitoreo del Ambiente , Biodiversidad , Estaciones del AñoRESUMEN
Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease. In the current study, we showed that experimental periodontitis, which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis, exacerbated hypoxia-induced pulmonary hypertension in mice. Mechanistically, periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs, contributing to pulmonary infiltration of interferon gamma positive (IFNγ+) T cells and aggravating the progression of pulmonary hypertension. In addition, we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis, and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies. Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.
Asunto(s)
Placa Dental , Hipertensión Pulmonar , Periodontitis , Humanos , Ratones , Animales , Linfocitos T/patología , Bacterias , Placa Dental/microbiologíaRESUMEN
The oceanic-to-neritic species shift of microzooplanktonic tintinnids and their interaction with relevant abiotic variables are two crucial processes in the marine ecosystem. However, these processes remain poorly documented in China's marginal seas. In the summer of 2022, we investigated the community structure of pelagic tintinnids in surface waters from the South China Sea (SCS) to the Yellow Sea (YS), passing through the East China Sea (ECS). A number of 58 species from 23 genera were identified, with 36 and 22 species belonging to oceanic and neritic genera, respectively. The abundance proportion of oceanic and neritic genera exhibited a decreasing and increasing trend, respectively, from the SCS to YS. Furthermore, four distinctive tintinnid community groups were classified based on cluster analysis using tintinnid species and abundance data, and the position of southern Taiwan Strait was identified as the "Shift Point" for oceanic-to-neritic species dominance. The top two tintinnid species in each group showed distinct variations in body size. Additionally, multivariate biotic-abiotic statistical analyses revealed that temperature determined tintinnid species richness, while temperature, salinity, Si(OH)4, and Chl a determined tintinnid abundance. Our study provides a substantial foundation for recognizing the oceanic-to-neritic species shift of tintinnids in the China's marginal seas, and highlights the role of biotic-abiotic factors in driving biogeochemical fluxes and the potential response of microzooplankton to future climate change.
Asunto(s)
Cilióforos , Ecosistema , Océanos y Mares , China , Estaciones del AñoRESUMEN
The microbiota plays an important role in both hypertension (HTN) and periodontitis (PD), and PD exacerbates the development of HTN by oral and gut microbiota. Previous studies have focused on exploring the importance of the bacteriome in HTN and PD but overlooked the impact of the virome, which is also a member of the microbiota. We collected 180 samples of subgingival plaques, saliva, and feces from a cohort of healthy subjects (nHTNnPD), subjects with HTN (HTNnPD) or PD (PDnHTN), and subjects with both HTN and PD (HTNPD). We performed metagenomic sequencing to assess the roles of the oral and gut viromes in HTN and PD. The HTNnPD, PDnHTN, and HTNPD groups all showed significantly distinct beta diversity from the nHTNnPD group in saliva. We analyzed alterations in oral and gut viral composition in HTN and/or PD and identified significantly changed viruses in each group. Many viruses across three sites were significantly associated with blood pressure and other clinical parameters. Combined with these clinical associations, we found that Gillianvirus in subgingival plaques was negatively associated with HTN and that Torbevirus in saliva was positively associated with HTN. We found that Pepyhexavirus from subgingival plaques was indicated to be transferred to the gut. We finally evaluated viral-bacterial transkingdom interactions and found that viruses and bacteria may cooperate to affect HTN and PD. Correspondingly, HTN and PD may synergize to improve communications between viruses and bacteria.IMPORTANCEPeriodontitis (PD) and hypertension (HTN) are both highly prevalent worldwide and cause serious adverse outcomes. Increasing studies have shown that PD exacerbates HTN by oral and gut microbiota. Previous studies have focused on exploring the importance of the bacteriome in HTN and PD but overlooked the impact of the virome, even though viruses are common inhabitants in humans. Alterations in oral and gut viral diversity and composition contribute to diseases. The present study, for the first time, profiled the oral and gut viromes in HTN and/or PD. We identified key indicator viruses and their clinical implications in HTN and/or PD. We also investigated interactions between viruses and bacteria. This work improved the overall understanding of the viromes in HTN and PD, providing vital insights into the role of the virome in the development of HTN and PD.
Asunto(s)
Hipertensión , Microbiota , Periodontitis , Virus , Humanos , Viroma , Virus/genética , Microbiota/genéticaRESUMEN
Doxorubicin (DOX)-induced cardiotoxicity limits its broad use as a chemotherapy agent. The development of effective and non-invasive strategies to prevent DOX-associated adverse cardiac events is urgently needed. We aimed to examine whether and how low-intensity pulsed ultrasound (LIPUS) plays a protective role in DOX-induced cardiotoxicity. Male C57BL/6J mice were used to establish models of both acute and chronic DOX-induced cardiomyopathy. Non-invasive LIPUS therapy was conducted for four consecutive days after DOX administration. Cardiac contractile function was evaluated by echocardiography. Myocardial apoptosis, oxidative stress, and fibrosis were analyzed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining, dihydroethidium (DHE) staining, and picrosirius red staining assays. RNA-seq analysis was performed to unbiasedly explore the possible downstream regulatory mechanisms. Neutrophil recruitment and infiltration in the heart were analyzed by flow cytometry. The S100a8/a9 inhibitor ABR-238901 was utilized to identify the effect of S100a8/a9 signaling. We found that LIPUS therapy elicited a great benefit on DOX-induced heart contractile dysfunction in both acute and chronic DOX models. Chronic DOX administration increased serum creatine kinase and lactate dehydrogenase levels, as well as myocardial apoptosis, all of which were significantly mitigated by LIPUS. In addition, LIPUS treatment prevented chronic DOX-induced cardiac oxidative stress and fibrosis. RNA-seq analysis revealed that LIPUS treatment partially reversed alterations of gene expression induced by DOX. Gene ontology (GO) analysis of the downregulated genes between DOX-LIPUS and DOX-Sham groups indicated that inhibition of neutrophil chemotaxis might be involved in the protective effects of LIPUS therapy. Flow cytometry analysis illustrated the inhibitory effects of LIPUS on DOX-induced neutrophil recruitment and infiltration in the heart. Moreover, S100 calcium binding protein A8/A9 (S100a8/a9) was identified as a potential key target of LIPUS therapy. S100a8/a9 inhibition by ABR-238901 showed a similar heart protective effect against DOX-induced cardiomyopathy to LIPUS treatment. LIPUS therapy prevents DOX-induced cardiotoxicity through inhibition of S100a8/a9-mediated neutrophil recruitment to the heart, suggesting its potential application in cancer patients undergoing chemotherapy with DOX.
RESUMEN
Microbial food webs (MFW) play an indispensable role in marine pelagic ecosystem, yet their composition and response to abiotic variables were poorly documented in the oligotrophic tropical Western Pacific. During winter of 2015, we conducted a survey to examine key components of MFW, including Synechococcus, Prochlorococcus, picoeukaryotes, heterotrophic prokaryotes (HP), heterotrophic/pigmented nanoflagellates and ciliates, across water column from surface to 2000 m. Each MFW component exhibited unique vertical distribution pattern, with abundance ratio varying over six and three orders of magnitude across Pico/Microplankton (1.6 ± 1.0 × 106) and Nano/Microplankton (3.2 ± 2.8 × 103), respectively. Furthermore, HP was main component for MFW in the bathypelagic (>1000 m) zone. Multivariate biota-environment analysis demonstrated that environmental variables, particularly temperature, significantly impacted MFW composition, suggesting that bottom-up control (resource availability) dominated the water column. Our study provides benchmark information for future environmental dynamics forcing on MFW in the oligotrophic tropical seas.
Asunto(s)
Ecosistema , Cadena Alimentaria , Plancton , Océanos y Mares , AguaRESUMEN
Hypertension is closely related to metabolic dysregulation, which is associated with microbial dysbiosis and altered host-microbiota interactions. However, plasma metabolite profiles and their relationships to oral/gut microbiota in hypertension have not been evaluated in depth. Plasma, saliva, subgingival plaques, and feces were collected from 52 hypertensive participants and 24 healthy controls in a cross-sectional cohort. Untargeted metabolomic profiling of plasma was performed using high-performance liquid chromatography-mass spectrometry. Microbial profiling of oral and gut samples was determined via 16S rRNA and metagenomic sequencing. Correlations between metabolites and clinic parameters/microbiota were identified using Spearman's correlation analysis. Metabolomic evaluation showed distinct clusters of metabolites in plasma between hypertensive participants and control participants. Hypertensive participants had six significantly increased and thirty-seven significantly decreased plasma metabolites compared to controls. The plasma metabolic similarity significantly correlated with the community similarity of microbiota. Both oral and gut microbial community composition had significant correlations with metabolites such as Sphingosine 1-phosphate, a molecule involved in the regulation of blood pressure. Plasma metabolites had a larger number of significant correlations with bacterial genera than fungal genera. The shared oral/gut bacterial genera had more correlations with metabolites than unique genera but shared fungal genera and metabolites did not show clear clusters. The hypertension group had fewer correlations between plasma metabolites and bacteria/fungi than controls at species level. The integrative analysis of plasma metabolome and oral/gut microbiome identified unreported alterations of plasma metabolites in hypertension and revealed correlations between altered metabolites and oral/gut microbiota. These observations suggested metabolites and microbiota may become valuable targets for therapeutic and preventive interventions of hypertension.
Asunto(s)
Microbioma Gastrointestinal , Hipertensión , Microbiota , Humanos , Estudios Transversales , ARN Ribosómico 16S/genéticaRESUMEN
Magnetotactic bacteria (MTB) within the Nitrospirota phylum play important roles in biogeochemical cycles due to their outstanding ability to biomineralize large amounts of magnetite magnetosomes and intracellular sulfur globules. For several decades, Nitrospirota MTB were believed to only live in freshwater or low-salinity environments. While this group have recently been found in marine sediments, their physiological features and ecological roles have remained unclear. In this study, we combine electron microscopy with genomics to characterize a novel population of Nitrospirota MTB in a coral reef area of the South China Sea. Both phylogenetic and genomic analyses revealed it as representative of a novel genus, named as Candidatus Magnetocorallium paracelense XS-1. The cells of XS-1 are small and vibrioid-shaped, and have bundled chains of bullet-shaped magnetite magnetosomes, sulfur globules, and cytoplasmic vacuole-like structures. Genomic analysis revealed that XS-1 has the potential to respire sulfate and nitrate, and utilize the Wood-Ljungdahl pathway for carbon fixation. XS-1 has versatile metabolic traits that make it different from freshwater Nitrospirota MTB, including Pta-ackA pathway, anaerobic sulfite reduction, and thiosulfate disproportionation. XS-1 also encodes both the cbb3-type and the aa3-type cytochrome c oxidases, which may function as respiratory energy-transducing enzymes under high oxygen conditions and anaerobic or microaerophilic conditions, respectively. XS-1 has multiple copies of circadian related genes in response to variability in coral reef habitat. Our results implied that XS-1 has a remarkable plasticity to adapt the environment and can play a beneficial role in coral reef ecosystems.
RESUMEN
Periodontitis and hypertension often occur as comorbidities, which need to be treated at the same time. To resolve this issue, a controlled-release composite hydrogel approach is proposed with dual antibacterial and anti-inflammatory activities as a resolution to achieve the goal of co-treatment of comorbidities. Specifically, chitosan (CS) with inherent antibacterial properties is cross-linked with antimicrobial peptide (AMP)-modified polyethylene glycol (PEG) to form a dual antibacterial hydrogel (CS-PA). Subsequently, curcumin loaded into biodegradable nanoparticles (CNP) are embedded in the hydrogel exhibiting high encapsulation efficiency and sustained release to achieve long-term anti-inflammatory activities. In a mouse model of periodontitis complicated with hypertension, CS-PA/CNP is applied to gingival sulcus and produced an optimal therapeutic effect on periodontitis and hypertension simultaneously. The therapeutic mechanisms are deeply studied and indicated that CS-PA/CNP exerted excellent immunoregulatory effects by suppressing the accumulation of lymphocytes and myeloid cells and enhanced the antioxidant capacity and thus the anti-inflammatory capacity of macrophages through the glutathione metabolism pathway. In conclusion, CS-PA/CNP has demonstrated its superior therapeutic effects and potential clinical translational value in the co-treatment of periodontitis and hypertension, and also serves as a drug delivery platform to provide combinatorial therapeutic options for periodontitis with complicated pathogenesis.
Asunto(s)
Quitosano , Hipertensión , Nanopartículas , Periodontitis , Animales , Ratones , Hidrogeles/uso terapéutico , Hidrogeles/química , Nanopartículas/uso terapéutico , Nanopartículas/química , Antibacterianos/química , Quitosano/química , Periodontitis/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Comorbilidad , Hipertensión/tratamiento farmacológicoRESUMEN
Though diel variations are geographically widespread phenomena among phytoplankton and zooplankton, knowledge is limited regarding diel variations in planktonic ciliate (microzooplankton) community structure. In this study, we analyzed diel variations in community structure of planktonic ciliates in the northern South China Sea (nSCS) and tropical Western Pacific (tWP). Hydrological characteristics during day and night were slightly different over both the nSCS and tWP, while ciliate average abundance at night was clearly higher than in the day in the upper 200 m. In both the nSCS and tWP, abundance proportions of large size-fraction (> 30 µm) aloricate ciliates at night were higher than in the day. While for tintinnids, abundance proportion of large lorica oral diameter at night were lower than in the day. The relationship between environmental factors and ciliate abundance pointed out that depth and temperature were main factors influencing aloricate ciliate and tintinnid in both day and night. For some dominant tintinnid species, chlorophyll a was another important factor influencing their diel vertical distribution. Our results provide fundamental data for better understanding the mechanisms of planktonic ciliate community diel variation in the tropical Western Pacific Ocean.
Asunto(s)
Cilióforos , Plancton , Clorofila A , Biodiversidad , Estaciones del Año , ChinaRESUMEN
Despite the planktonic ciliate importance in the microzooplankton compartment, their full-depth vertical distribution in the Arctic Ocean was poorly documented as well as the related variations in different water masses. The full-depth community structure of planktonic ciliates was investigated in the Arctic Ocean during summer 2021. The ciliate abundance and biomass decreased rapidly from 200 m to bottom. Five water masses were identified throughout the water column and each one exhibited a unique ciliate community structure. Aloricate ciliates were singled out as the dominant group with average abundance proportion to total ciliates at each depth >95%. Large (>30 µm) and small (10-20 µm) size-fractions of aloricate ciliates were abundant in shallow and deep waters, respectively, which revealed an anti-phase relationship in vertical distribution. Three new record tintinnid species were found during this survey. Pacific-origin species Salpingella sp.1 and Arctic endemic species Ptychocylis urnula occupied the top abundance proportion in the Pacific Summer Water (44.7%) and three water masses (≥38.7%, Mixed Layer Water, Remnant Winter Water, Atlantic-origin Water), respectively. The habitat suitability of tintinnid abundant species was characterised by the Bio-index revealing a distinct death-zone for each species. Variations in survival habitat of abundant tintinnids can be regarded as indicators for the future Arctic climate change. These results provide fundamental data on the microzooplankton response to the intrusion of Pacific waters into the Arctic Ocean upon its rapid warming.
Asunto(s)
Cilióforos , Plancton , Ecosistema , Agua , Regiones Árticas , Océanos y MaresRESUMEN
Marine viruses make up an essential compartment of the marine ecosystem. They are the most abundant organisms and represent one of the biggest sources of unknown biodiversity. Viruses also have an important impact on bacterial and algal mortality in the ocean, and as such have a major influence on microbial diversity and biogeochemical cycling. However, little is known about the abundance and distribution patterns of viruses across the oceans and seas. Over the last 20 years, flow cytometry has been the technique of choice to detect and count the viral particles in natural samples. Nevertheless, due to their small size, the detection of marine viruses is still extremely challenging. In this article we describe how a new generation of flow cytometer which uses the side scatter (SSC) of violet photons from a 405 nm laser beam helps to improve the resolution for detecting marine viruses. To the best of our knowledge, this is the first report where virioplankton has been detected in aquatic samples using flow cytometry with a 405 nm violet SSC instead of a 488 nm blue SSC.
Asunto(s)
Ecosistema , Virus , Océanos y MaresRESUMEN
Phenotypic modulation of vascular smooth muscle cells (VSMCs) plays critical roles in the pathogenesis of aortic aneurysm (AA). The function of nuclear receptor corepressor1 (NCOR1) in regulation of VSMC phenotype and AA is unclear. Herein, using smooth muscle NCOR1 knockout mice, we demonstrated that smooth muscle NCOR1 deficiency decreased both mRNA and protein levels of contractile genes, impaired stress fibers formation and RhoA pathway activation, reduced synthesis of elastin and collagens, and induced the expression and activity of MMPs, manifesting a switch from contractile to degradative phenotype of VSMCs. NCOR1 modulated VSMC phenotype through 3 different mechanisms. First, NCOR1 deficiency increased acetylated FOXO3a to inhibit the expression of Myocd, which downregulated contractile genes. Second, deletion of NCOR1 derepressed NFAT5 to induce the expression of Rgs1, thus impeding RhoA activation. Third, NCOR1 deficiency increased the expression of Mmp12 and Mmp13 by derepressing ATF3. Finally, a mouse model combined apoE knockout mice with angiotensin II was used to study the role of smooth muscle NCOR1 in the development of AA. The results showed that smooth muscle NCOR1 deficiency increased the incidence of aortic aneurysms and exacerbated medial degeneration in angiotensin II-induced AA mouse model. Collectively, our data illustrated that NCOR1 interacts with FOXO3a, NFAT5, and ATF3 to maintain contractile phenotype of VSMCs and suppress AA development. Manipulation of smooth muscle NCOR1 may be a potential approach for AA treatment.
Asunto(s)
Aneurisma de la Aorta , Músculo Liso Vascular , Ratones , Animales , Músculo Liso Vascular/metabolismo , Angiotensina II/metabolismo , Aneurisma de la Aorta/metabolismo , Aneurisma de la Aorta/patología , Ratones Noqueados , Fenotipo , Ratones Noqueados para ApoE , Homeostasis , Células Cultivadas , Co-Represor 1 de Receptor Nuclear/metabolismoRESUMEN
INTRODUCTION: Considerable evidence has linked periodontitis (PD) to hypertension (HTN), but the nature behind this connection is unclear. Dysbiosis of oral microbiota leading to PD is known to aggravate different systematic diseases, but the alteration of oral microbiota in HTN and their impacts on blood pressure (BP) remains to be discovered. OBJECTIVES: To characterize the alterations of oral and gut microbiota and their roles in HTN. METHODS: We performed a cross-sectional (95 HTN participants and 39 controls) and a 6-month follow-up study (52 HTN participants and 26 controls) to analyze the roles of oral and gut microbiota in HTN. Saliva, subgingival plaques, and feces were collected for 16S rRNA gene sequencing or metagenomic analysis. C57BL/6J mice were pretreated with antibiotics to deplete gut microbiota, and then transplanted with human saliva by gavage to test the impacts of abnormal oral-gut microbial transmission on HTN. RESULTS: BP in participants with PD was higher than no PD in both cross-sectional and follow-up cohort. Relative abundances of 14 salivary genera, 15 subgingival genera and 10 gut genera significantly altered in HTN and those of 7 salivary genera, 12 subgingival genera and 6 gut genera significantly correlated with BP. Sixteen species under 5 genera were identified as oral-gut transmitters, illustrating the presence of oral-gut microbial transmission in HTN. Veillonella was a frequent oral-gut transmitter stably enriched in HTN participants of both cross-sectional and follow-up cohorts. Saliva from HTN participants increased BP in hypertensive mice. Human saliva-derived Veillonella successfully colonized in mouse gut, more abundantly under HTN condition. CONCLUSIONS: PD and oral microbiota are strongly associated with HTN, likely through oral-gut transmission of microbes. Ectopic colonization of saliva-derived Veillonella in the gut may aggravate HTN. Therefore, precise manipulations of oral microbiota and/or oral-gut microbial transmission may be useful strategies for better prevention and treatment of HTN.
Asunto(s)
Microbioma Gastrointestinal , Hipertensión , Microbiota , Periodontitis , Humanos , Animales , Ratones , Microbioma Gastrointestinal/fisiología , ARN Ribosómico 16S/genética , Estudios Transversales , Estudios de Seguimiento , Ratones Endogámicos C57BLRESUMEN
The mycobiome is an essential constituent of the human microbiome and is associated with various diseases. However, the role of oral and gut fungi in hypertension (HTN) remains largely unexplored. In this study, saliva, subgingival plaques, and feces were collected from 36 participants with HTN and 24 healthy controls for metagenomic sequencing. The obtained sequences were analyzed using the Kraken2 taxonomic annotation pipeline to assess fungal composition and diversity. Correlations between oral and gut fungi and clinic parameters, between fungi within the same sample types, and between different sample types were identified by Spearman's correlation analysis. Overall, the subgingival fungal microbiome had substantially higher alpha diversity than the salivary and fecal fungal microbiomes. The fungal microbiomes of the three sample types displayed distinct beta diversity from each other. Oral fungi but not gut fungi in HTN had beta diversity significantly different from that of controls. Among the fungi shared in the oral cavity and gut, Exophiala was the genus with the most notable changes. Exophiala spinifera was the most abundant salivary species in HTN. Some fungal species directly correlated with blood pressure, including gut Exophiala xenobiotica and Exophiala mesophila. The markedly impaired ecological cocorrelation networks of oral and gut fungi in HTN suggested compromised association among fungal species. Most fungi were shared in the oral cavity and gut, and their correlations suggested the potential interplays between oral and gut fungi. In conclusion, the oral cavity and intestine have unique fungal ecological environments. The fungal enrichment and ecology in HTN, the correlations between oral and gut fungi, and the associations between oral and gut fungi and clinical parameters suggest an important role that the fungal microbiome may play in HTN. IMPORTANCE Our study fills the gap in human studies investigating the oral and gut fungal microbiota in association with blood pressure. It characterizes the diversity and composition of the oral and gut fungal microbiome in human subjects, elucidates the dysbiosis of fungal ecology in a hypertensive population, and establishes oral-gut fungal correlations and fungus-clinical parameter correlations. Targeting fungi in the oral cavity and/or gut may provide novel strategies for the prevention and treatment of hypertension.
Asunto(s)
Microbioma Gastrointestinal , Hipertensión , Microbiota , Micobioma , Humanos , Microbioma Gastrointestinal/fisiología , Boca , Heces/microbiología , Hongos/genéticaRESUMEN
Synechococcus is abundant and globally widespread in various marine environments. Seasonal and spatial variations in Synechococcus abundance, pigment types, and genetic diversity were investigated based on flow cytometric analysis and high-throughput sequencing of cpcBA operon (encoding phycocyanin) and rpoC1 gene (encoding RNA polymerase) in a temperate semi-enclosed bay. Synechococcus abundance exhibited seasonal variations with the highest value in summer and the lowest value in winter, which was consistent with temperature variation. Three pigment types of Synechococcus type 1, type 2, and type 3 were distinguished based on cpcBA operon, which displayed obvious variations spatially between the inner and the outer bay. Freshwater discharge and water turbidity played important roles in regulating Synechococcus pigment types. Synechococcus assemblages were phylogenetically diverse (12 different lineages) based on rpoC1 gene and dominated by three core lineages S5.1-I, S5.1-IX, and S5.2-CB5 in different seasons. Our study demonstrated that Synechococcus abundance, pigment types, and genetic diversity displayed variations seasonally and spatially by different techniques, which were mainly driven by temperature, salinity, nutrients, and turbidity. The combination of more technical means provides more information for studying Synechococcus distribution. In this study, three pigment types of Synechococcus were discriminated simultaneously by dual lasers flow cytometer for the first time.
RESUMEN
Magnetotactic bacteria (MTB) have been found in a wide variety of marine habitats, ranging from intertidal sediments to deep-sea seamounts. Deep-sea hydrothermal fields are rich in metal sulfides, which are suitable areas for the growth of MTB. However, MTB in hydrothermal fields have never been reported. Here, the presence of MTB in sediments from the Tangyin hydrothermal field was analyzed by 16S rRNA gene amplicon analysis, metagenomics, and transmission electron microscopy. Sequencing 16S rRNA gene yielded a total of 709 MTB sequences belonging to 20 OTUs, affiliated with Desulfobacterota, Alphaproteobacteria, and Nitrospirae. Three shapes of magnetofossil were identified by transmission electron microscopy: elongated-prismatic, bullet-shaped, and cuboctahedron. All of these structures were composed of Fe3O4. A total of 121 sequences were found to be homologous to the published MTB magnetosome-function-related genes, and relevant domains were identified. Further analysis revealed that diverse MTB are present in the Tangyin hydrothermal field, and that multicellular magnetotactic prokaryote (MMPs) might be the dominant MTB.