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1.
J Adv Res ; 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38609049

RESUMEN

INTRODUCTION: Helicobacter pylori (H. pylori) infection has been associated with gastric carcinogenesis. However, the precise involvement of LRP8, the low-density lipoprotein receptor-related protein 8, in H. pylori pathogenesis and gastric cancer (GC) remains poorly understood. OBJECTIVES: To investigate the potential role of LRP8 in H. pylori infection and gastric carcinogenesis. METHODS: Three-dimensional human-derived gastric organoids (hGO) and gastric cancer organoids (hGCO) were synthesized from the tissues obtained from human donors. In this work, multi-omics combined with in vivo and in vitro studies were conducted to investigate the potential involvement of LRP8 in H. pylori-induced GC. RESULTS: We found that H. pylori infection significantly upregulated the expression of LRP8 in human GC tissues, cells, organoids, and mouse gastric mucous. In particular, LRP8 exhibited a distinct enrichment in cancer stem cells (CSC). Functionally, silencing of LRP8 affected the formation and proliferation of tumor spheroids, while increased expression of LRP8 was associated with increased proliferation and stemness of GC cells and organoids. Mechanistically, LRP8 promotes the binding of E-cadherin to ß-catenin, thereby promoting nuclear translocation and transcriptional activity of ß-catenin. Furthermore, LRP8 interacts with the cytotoxin-associated gene A (CagA) to form the CagA/LRP8/ß-catenin complex. This complex further amplifies H. pylori-induced ß-catenin nuclear translocation, leading to increased transcription of inflammatory factors and CSC markers. Clinical analysis demonstrated that abnormal overexpression of LRP8 is correlated with a poor prognosis and resistance to 5-Fluorouracil in patients with GC. CONCLUSION: Our findings provide valuable information on the molecular intricacies of H. pylori-induced gastric carcinogenesis, offering potential therapeutic targets and prognostic markers for GC.

2.
Life Sci Space Res (Amst) ; 38: 29-38, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37481305

RESUMEN

Understanding the structural and antibiotic resistance changes of microbial communities in space environments is critical for identifying potential pathogens that may pose health risks to astronauts and for preventing and controlling microbial contamination. The research to date on microbes under simulated space factors has primarily been carried out on single bacterial species under the individual effects of microgravity or low-dose radiation. However, microgravity (MG) and low-dose ionizing radiation (LDIR) coexist in the actual spacecraft environment, and microorganisms coexist as communities in the spacecraft environment. Thus, the microbial response to the real changes present during space habitation has not been adequately explored. To address this knowledge gap, we compared the dynamics of community composition and antibiotic resistance of synthetic bacterial communities under simulated microgravit, low-dose ionizing radiation, and the conditions combined, as it occurs in spacecraft. To ensure representative bacteria were selected, we co-cultured of 12 bacterial strains isolated from spacecraft cleanrooms. We found that the weakened competition between communities increased the possibility of species coexistence, community diversity, and homogeneity. The number of Bacilli increased significantly, while different species under the combined conditions showed various changes in abundance compared to those under the individual conditions. The resistance of the synthetic community to penicillins increased significantly under low doses of ionizing radiation but did not change significantly under simulated microgravity or the combined conditions. The results of functional predictions revealed that antibiotic biosynthesis and resistance increased dramatically in the community under space environmental stress, which confirmed the results of the drug sensitivity assays. Our results show that combined space environmental factors exert different effects on the microbial community structure and antibiotic resistance, which provides new insights into our understanding of the mechanisms of evolution of microorganisms in spacecraft, and is relevant to effective microbial pollution prevention and control strategies.


Asunto(s)
Nave Espacial , Ingravidez , Bacterias , Farmacorresistencia Microbiana , Radiación Ionizante
3.
Sci Total Environ ; 890: 164147, 2023 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-37211108

RESUMEN

Bacterial interactions occurring on and around seeds are integral to plant fitness, health and productivity. Although seed- and plant-associated bacteria are sensitive to environmental stress, the effects of microgravity, as present during plant cultivation in space, on microbial assembly during seed germination are not clear. Here, we characterized the bacterial microbiome assembly process and mechanisms during seed germination of two wheat varieties under simulated microgravity by 16S rRNA gene amplicon sequencing and metabolome analysis. We found that the bacterial community diversity, and network complexity and stability were significantly decreased under simulated microgravity. In addition, the effects of simulated microgravity on the plant bacteriome of the two wheat varieties tended to be consistent in seedlings. At this stage, the relative abundance of Oxalobacteraceae, Paenibacillaceae, Xanthomonadaceae, Lachnospiraceae, Sphingomonadaceae and Ruminococcaceae decreased, while the relative abundance of Enterobacteriales increased under simulated microgravity. Analysis of predicted microbial function revealed that simulated microgravity exposure leads to lower sphingolipid signaling and calcium signaling pathways. We also found that simulated microgravity drove the strengthening of deterministic processes in microbial community assembly. Importantly, some specific metabolites exhibited significant changes under simulated microgravity, suggesting that bacteriome assembly is mediated, at least in part, by metabolites altered by microgravity. The data we present here moves us closer to a holistic understanding of the plant bacteriome under microgravity stress at plant emergence, and provides a theoretical basis for the precise utilization of microorganisms in microgravity to improve plant adaptation to the challenge of cultivation in space.


Asunto(s)
Sphingomonadaceae , Ingravidez , Germinación , Triticum , ARN Ribosómico 16S , Semillas
4.
Environ Pollut ; 329: 121613, 2023 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-37087089

RESUMEN

Understanding the microbial communities and antibiotic resistance genes (ARGs) in spacecraft assembly cleanrooms is crucial for spacecraft microbial control and astronaut safety. However, there have been few reports of ARG profiles and their relationship with microbiomes in such environments. In the present study, we assessed the bacterial community and ARGs in the air dust and surface environments of a typical spacecraft assembly cleanroom. Our results show a significant difference in bacterial composition between surfaces and air dust, as they belong to two distinct ecostates. Bacillus and Acinetobacter were significantly enriched in the air samples. Bacterial community network analysis revealed lower topological parameters and robustness of bacterial networks in the air samples. We also observed different distribution patterns of some typical ARGs between surface and air dust samples. Notably, the ermB gene exhibited a relatively high copy number and was enriched in the surface environment, compared to that in the air. Overall, our study provides insight into the complex microbial community and the distribution and transfer of ARGs in spacecraft assembly cleanrooms, and offers important input for developing control strategies against ARGs.


Asunto(s)
Microbiota , Nave Espacial , Antibacterianos , Bacterias/genética , Polvo , Genes Bacterianos , Microbiota/genética
5.
Front Cardiovasc Med ; 10: 1103567, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36970339

RESUMEN

Background: Atrial fibrillation (AF) and heart failure (HF) often coexist. The treatment of AF in patients with HF has been challenging because of the ongoing debate about the merits of catheter ablation vs. drug therapy. Methods: The Cochrane Library, PubMed, and www.clinicaltrials.gov were searched until June 14, 2022. Inclusion criteria were catheter ablation compared with drug therapy in adults with AF and HF in randomized controlled trials (RCTs). Primary outcomes consisted of all-cause mortality, re-hospitalization, change in left ventricular ejection fraction (LVEF), and AF recurrence. Secondary outcomes referred to quality of life [QoL; measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ)], six-minute walk distance (6MWD), and adverse events. The PROSPERO registration ID was CRD42022344208. Findings: In total, nine RCTs with 2,100 patients met the inclusion criteria, with 1,062 for catheter ablation and 1,038 for medication. According to the meta-analysis, catheter ablation significantly reduced all-cause mortality compared with drug therapy [9.2% vs. 14.1%, OR: 0.62, (95% CI: 0.47-0.82), P = 0.0007, I 2 = 0%], improved LVEF [MD: 5.65%, (95% CI: 3.32-7.98), P < 0.00001, I 2 = 86%], reduced AF recurrence [41.6% vs. 61.9%, OR: 0.23, (95% CI: 0.11-0.48), P < 0.0001, I 2 = 82%], decreased the MLHFQ score [MD: -6.38, (95% CI: -11.09 to -1.67), P = 0.008, I2 = 64%] and increased 6MWD [MD: 17.55, (95% CI: 15.77-19.33), P < 0.0001, I 2 = 37%]. Catheter ablation did not increase the re-hospitalization [30.4% vs. 35.5%, OR: 0.68, (95% CI: 0.42-1.10), P = 0.12, I 2 = 73%] and adverse events [31.5% vs. 30.9%, OR: 1.06, (95% CI: 0.83-1.35), P = 0.66, I 2 = 48%]. Interpretation: In AF patients with HF, catheter ablation improves exercise tolerance, QoL, and LVEF and significantly reduced all-cause mortality and AF recurrence. Although the differences were not statistically significant, the study found lower re-hospitalization and approximate adverse events with improved catheter ablation tendency. PROSPERO registration ID: CRD42022344208.

6.
Microbiome ; 10(1): 169, 2022 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-36224642

RESUMEN

BACKGROUND: Chinese Lunar Palace 1 (LP1) is a ground-based bio-regenerative life support system (BLSS) test bed integrating highly efficient plant cultivation, animal protein production, urine nitrogen recycling, and bioconversion of solid waste. To date, there has been no molecular method-based detailed investigation of the fungal community and mycotoxin potential in BLSS habitats. To ensure safe BLSS design for actual space missions, we analyzed the LP1 surface mycobiome and mycotoxin potential during the Lunar Palace 365 project through internal transcribed spacer region 1 (ITS1) amplicon sequencing and quantitative polymerase chain reaction (qPCR) with primers specific for idh, ver1, nor1, tri5, and ITS1. RESULTS: The LP1 system exhibited significant differences in fungal community diversity compared to other confined habitats, with higher fungal alpha diversity and different community structures. Significant differences existed in the surface fungal communities of the LP1 habitat due to the presence of different occupant groups. However, there was no significant difference between fungal communities in the plant cabin with various occupants. Source tracker analysis shows that most of the surface fungi in LP1 originated from plants. Regardless of differences in occupants or location, there were no significant differences in mycotoxin gene copy number. CONCLUSIONS: Our study reveals that plants are the most crucial source of the surface fungal microbiome; however, occupant turnover can induce significant perturbations in the surface fungal community in a BLSS. Growing plants reduced fungal fluctuations, maintaining a healthy balance in the surface fungal microbiome and mycotoxin potential. Moreover, our study provides data important to (i) future risk considerations in crewed space missions with long-term residency, (ii) an optimized design and planning of a space mission that incorporates crew shifts and plant growth, and (iii) the expansion of our knowledge of indoor fungal communities with plant growth, which is essential to maintain safe working and living environments. Video Abstract.


Asunto(s)
Micobioma , Micotoxinas , Animales , Hongos/genética , Luna , Micobioma/genética , Nitrógeno , Plantas , Residuos Sólidos
7.
Mol Cell Probes ; 66: 101863, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36252912

RESUMEN

Papillary thyroid cancer (PTC) is a common malignancy. MicroRNAs (miRNAs) may act as oncogenes or tumor suppressor genes. However, the role of miR-451a in PTC is not fully understood. Hence, the objective of the study was to research the effect and mechanism of miR-451a in PTC. Differentially expressed miRNAs between GSE113629 and GSE103996 databases were assessed by Venn diagram. miR-451a and its downstream target genes were assessed by RT-PCR and Western blot. The proliferation, invasion, and apoptosis were determined by CCK-8, EdU, transwell, and flow cytometry assays. Dual-luciferase reporter assay were used to evaluated the target of miR-451a. Xenografted tumors was used to explore the function of miR-451a in vivo. Pathological changes and related protein expression were measured by HE staining and immunohistochemistry. MiR-451a was downregulated in PTC tissues and blood, and low expression of miR-451a was related to short overall survival, serious lymph node metastasis and high TNM grade in PTC patients. Moreover, increase of miR-451a restrained the proliferation and invasion and accelerated the apoptosis. Furthermore, miR-451a repressed VEGF signaling pathway. Importantly, miR-451a was demonstrated to target DCBLD2 and AKT1. Overexpression of DCBLD2 and AKT1 could restore the effect of miR-451a on PTC cells. In addition, miR-451a reduced the growth of xenografted tumors in vivo. The data suggested that miR-451a attenuated the proliferation, invasion and promoted apoptosis in PTC cells via inhibiting DCBLD2 and AKT1.


Asunto(s)
Carcinoma Papilar , MicroARNs , Neoplasias de la Tiroides , Humanos , Apoptosis/genética , Carcinoma Papilar/genética , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Proteínas de la Membrana/genética , MicroARNs/genética , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo
8.
Environ Microbiol ; 24(8): 3355-3368, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35437853

RESUMEN

To improve nutrient utilization and pathogenic resistance of plants in space, it is crucial to understand the effects of microgravity on the plant root microbiome. However, the finer details of whether and how microgravity affects the root microbiome remain unclear. Here, we found that simulated microgravity elicits no significant changes in fungal community composition and diversity, whether rhizosphere or endophytic. However, simulated microgravity caused a significant change in the composition and diversity of endophytic bacteria of wheat seedlings, but not in rhizosphere bacteria. The alteration of endophytic bacterial communities demonstrates that wheat seedlings adopt strategies to recruit additional endophytic Enterobacteriaceae and increase the stability of the endophytic bacterial network to respond to the challenge of simulated microgravity. Furthermore, our results also suggest that the corresponding changes in endophytic bacteria under simulated microgravity are closely related to a significant decrease in metabolites of the host's carbon metabolism, flavonoid biosynthesis, benzoxazinoid biosynthesis, and tryptophan metabolism pathways. Our findings reveal details important to our understanding of the impact of gravity on the microbial community of plant seedlings and the theoretical basis for manipulation of microorganisms to ensure efficient plant production in space.


Asunto(s)
Triticum , Ingravidez , Bacterias/genética , Bacterias/metabolismo , Raíces de Plantas/microbiología , Plantas , Rizosfera , Plantones , Microbiología del Suelo
9.
Microbiol Spectr ; 10(2): e0025422, 2022 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-35254118

RESUMEN

The long-term exposure to enclosed environments may lead to chronic stress in crewmembers and affect their physical and mental state. Salivary microbiome and biomarkers of immune function are increasingly used in human health research. The "Lunar Palace 365" project, which was a 370-day, multicrew, enclosed experiment carried out in a ground-based bioregenerative life support system platform named Lunar Palace 1 (LP1). We investigated the temporal dynamics of the salivary microbiota and cytokines in the third phase of the "Lunar Palace 365" experiment, including 1 month before entering LP1 and 1 month after leaving Lp1. Results reveal no regular temporal change pattern in these parameters (highly abundant phyla and genera) during the experiment. Although the crewmembers' oral microbiota temporally changed, it recovered quickly after the study subjects left the enclosed environment. The levels of IL-6, IL-10, and TNF-α in crewmembers' saliva decreased after leaving the normal environment for the enclosed environment, indicating that their oral inflammatory response level was reduced. There were significant individual differences in crewmembers' salivary microbiota, however, the shared living space reduced these differences. Moreover, air microbiota might have also played a significant role in reducing the individual differences. In summary, the enclosed environment did not result in persistent changes in human salivary microbiota and oral immunity. This study provides some insights for studying the effect of enclosed controlled environments on human immunity and microbiome. IMPORTANCE Long-term exposure to space environments may influence the human microbiome, the human immune system, and the intricate balance between the two, causing impaired immunity and increased disease susceptibility. It was previously believed that the main potential factors of long-term spaceflight on human health were microgravity and radiation. However, the effects of long-term enclosed environments on human health were unclear. Bioregenerative life support systems (BLSS) is a good experimental model for studying the effects of enclosed environments on human systemic microbiota and immune disorders. We monitored the microbiota and cytokines in the saliva of crewmembers before they entered BLSS, during their stay in BLSS, and after leaving BLSS. The results indicated long-term closed environment will not cause persistent changes in human salivary microbiota and immunity.


Asunto(s)
Microbiota , Vuelo Espacial , Citocinas , Humanos , Sistemas de Manutención de la Vida , Saliva
11.
Environ Microbiome ; 17(1): 4, 2022 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-35081988

RESUMEN

BACKGROUND: Understanding the dynamics of airborne microbial communities and antibiotic resistance genes (ARGs) in space life support systems is important because potential pathogens and antibiotic resistance pose a health risk to crew that can lead to mission failure. There have been few reports on the distribution patterns of microbiomes and ARGs in space life support systems. In particular, there have been no detailed investigations of microbiomes and/or antibiotic resistance based on molecular methods in long-term confined bioregenerative life support systems (BLSSs). Therefore, in the present study, we collected air dust samples from two crew shifts, different areas, and different time points in the "Lunar Palace 365" experiment. We evaluated microbial diversity, species composition, functional potential, and antibiotic resistance by combining cultivation-independent analyses (amplicon, shot-gun sequencing, and qPCR). RESULTS: We found that the bacterial community diversity in the Lunar Palace1 (LP1) system was higher than that in a controlled environment but lower than that in an open environment. Personnel exchange led to significant differences in bacterial community diversity, and source tracking analysis revealed that most bacteria in the air derived from the cabin crew and plants, but no differences in microbial function or antibiotic resistance were observed. Thus, human presence had the strongest effect on the succession of microbial diversity in the BLSSs. CONCLUSIONS: Our results highlight that microbial diversity in BLSSs is heavily influenced by changes in crew and is unique from other open and controlled environments. Our findings can be used to help develop safe, enclosed BLSS that meet the requirements of human survival and habitation in outer space. In addition, our results can further enhance our understanding of the indoor air microbial community and effectively maintain a safe working and living environment, including plant growth.

13.
Appl Microbiol Biotechnol ; 106(1): 441-453, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34870738

RESUMEN

As the core food crop of a bioregenerative life support system (BLSS), wheat is susceptible to pathogen infection due to the lack of effective microbial communities in the confined and isolated environment. Therefore, a thorough understanding of the dynamic changes in wheat rhizosphere fungi is of great significance for improving wheat production and ensuring the stability of the BLSS. In the current study, we collected samples of rhizosphere fungi in the four growth stages of wheat grown in the "Lunar Palace 365" experiment. We employed bioinformatics methods to analyze the samples' species composition characteristics, community network characteristics, and FUNGuild function analysis. We found that the species composition of rhizosphere fungi in the wheat at the tillering stage changed greatly in the closed and isolated environment, while the species composition in the seedling, flowering, and mature stage were relatively stable. The results of the FUNGuild function analysis showed that the functions of rhizosphere fungi changed during wheat development. The rhizosphere fungal community was centered on Ascomycota, Mortierellomycota, and Chytridiomycota, and the community showed the characteristics of a "small world" arrangement. The stage of wheat seedlings is characterized by a greater abundance, diversity, and complexity of the network of interactions in the rhizosphere mycorrhiza community, while the tillering stage exhibited a greater clustering coefficient. Based on the changes in species composition, guild function regulation, and community structure differences of the wheat rhizosphere fungi in the BLSS, our study identified the critical fungal species during wheat development, providing a reference for ensuring the health and yield of plants in the BLSS system. KEY POINTS: • The diversity, composition, FUNguild, and network structure of rhizosphere fungi were analyzed. • Ascomycota, Mortierellomycota, and Chytridiomycota were the center of the rhizosphere fungal community network. • The effects of different wheat developmental stages on the community composition, function, and network structure of rhizosphere fungi were examined.


Asunto(s)
Micorrizas , Rizosfera , Hongos/genética , Raíces de Plantas , Microbiología del Suelo , Triticum
14.
Biomaterials ; 279: 121178, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34656857

RESUMEN

Although synthesized nanotherapeutics (NTs) are attractive for the oral treatment of colon diseases, their clinical translations are constrained by the unsatisfactory therapeutic outcomes, potential adverse effects, and high cost of mass production. Here, we report the development of tea leaf-derived natural NTs with desirable particle sizes (140.0 nm) and negative surface charge (-14.6 mV). These natural exosome-like NTs were found to contain large amounts of lipids, some functional proteins, and many bioactive small molecules. Specifically, galactose groups on the surface of NTs could mediate their specific internalization by macrophages via galactose receptor-mediated endocytosis. Moreover, these NTs were able to reduce the production of reactive oxygen species, inhibit the expression of pro-inflammatory cytokines, and increase the amount of anti-inflammatory IL-10 secreted by macrophages. Orally administered NTs could efficiently inhibit the inflammatory bowel responses, restore disrupted colonic barriers and enhance the diversity and overall abundance of gut microbiota, thereby preventing or alleviating inflammatory bowel disease and colitis-associated colon cancer. The present study brings new insights to the facile application of a versatile and robust natural nanoplatform for the prevention and treatment of colon diseases.


Asunto(s)
Colitis , Enfermedades Inflamatorias del Intestino , Animales , Colitis/tratamiento farmacológico , Colitis/prevención & control , Colon , Citocinas , Modelos Animales de Enfermedad , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/prevención & control , Hojas de la Planta ,
15.
Life Sci Space Res (Amst) ; 31: 113-120, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34689943

RESUMEN

To travel beyond the Earth and realize long-term survival in deep space, humans need to construct Bioregenerative Life Support System (BLSS), which reduces the requirement for supplies from the Earth by in situ regenerating oxygen, water and food needed by astronauts, and prevents pollution to extraterrestrial bodies by recycling waste. Since the 1960s, the USSR/Russia, the United States, Europe, Japan, and China carried out a number of studies with abundant achievements in BLSS systematic theories, plants/animals/microorganisms unit technologies, design/construction, and long-term operation/regulation. China's "Lunar Palace 365″ experiment realized Earth-based closed human survival for a year, with a material closure of >98%. However, a lot of research work is still needed to ultimately realize BLSS application in space, especially given the space experiment of BLSS never carried out, and the overall impact of space environment on BLSS unknown. Lunar exploration projects such as lunar village and lunar research station are successively proceeding. Therefore, future BLSS research will focus on lunar probe payload carrying experiments to study mechanisms of small uncrewed closed ecosystem in space and clarify the impact of space environmental conditions on the ecosystem, so as to correct the design and operation parameters of Earth-based BLSS. Such research will provide theoretical and technological support for BLSS application in crewed deep space exploration.


Asunto(s)
Sistemas Ecológicos Cerrados , Vuelo Espacial , Animales , Astronautas , Ecosistema , Humanos , Sistemas de Manutención de la Vida , Estados Unidos
16.
Cancer Sci ; 112(9): 3569-3584, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34251747

RESUMEN

The abundance and type of immune cells in the tumor microenvironment (TME) significantly influence immunotherapy and tumor progression. However, the role of immune cells in the TME of gastric cancer (GC) is poorly understood. We studied the correlations, proportion, and infiltration of immune and stromal cells in GC tumors. Data analyses showed a significant association of infiltration levels of specific immune cells with the pathological characteristics and clinical outcomes of GC. Furthermore, based on the difference in infiltration levels of immune and stromal cells, GC patients were divided into two categories, those with "immunologically hot" (hot) tumors and those with "immunologically cold" (cold) tumors. The assay for transposase-accessible chromatin using sequencing and RNA sequencing analyses revealed that the hot and cold tumors had altered epigenomic and transcriptional profiles. Claudin-3 (CLDN3) was found to have high expression in the cold tumors and negatively correlated with CD8+ T cells in GC. Overexpression of CLDN3 in GC cells inhibited the expression of MHC-I and CXCL9. Finally, the differentially expressed genes between hot and cold tumors were utilized to generate a prognostic model, which predicted the overall survival of GC as well as patients with immunotherapy. Overall, we undertook a comprehensive analysis of the immune cell infiltration pattern in GC and provided an accurate model for predicting the prognosis of GC patients.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Claudina-3/metabolismo , Linfocitos Infiltrantes de Tumor/inmunología , Transducción de Señal/genética , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/metabolismo , Microambiente Tumoral/inmunología , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Quimiocina CXCL9/metabolismo , Claudina-3/genética , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Pronóstico , RNA-Seq , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Transcriptoma , Transfección
17.
Appl Microbiol Biotechnol ; 105(9): 3705-3715, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33893837

RESUMEN

The general public spends one-third of its time under artificial lighting, which lacks bands beneficial to human health, and long-term exposure will have a negative impact on bone health. Here, we report the effects of long-term, low-dose ultraviolet (UV) supplementation to white light-emitting diode (LED) light exposure on intestinal microorganisms and bone metabolism, as well as the correlations between the two. Normal and ovariectomized rats were irradiated with LED white light with or without supplementation with UV. The effects of UV supplementation on the intestinal flora and the relationship between the intestinal flora and bone were investigated by measuring the intestinal flora, bone metabolism markers, and bone histomorphology. UV supplementation affected the bone density and bone mass by changing the relative content of Firmicutes, Saccharibacteria, and Proteobacteria; however, the intestinal flora were not the only factors affecting bone. Ultraviolet supplementation changed the composition and function of the gut flora in the bone loss model. By increasing the synthesis of short-chain fatty acids and affecting immunomodulatory, intestinal flora directly or indirectly regulate the activity of osteoclasts and thus mediate UV-mediated improvements in bone metabolism. Our work shows that UV supplementation affects bone density by influencing the intestinal flora, introducing a novel strategy to develop healthier artificial light sources and prevent bone loss. KEY POINTS: • We measured the bone metabolism markers and bone histomorphometry of rats. • The diversity, composition, and function of intestinal flora were analyzed. • The relationship between gut microbiota and host bone physiology was analyzed.


Asunto(s)
Microbioma Gastrointestinal , Animales , Densidad Ósea , Suplementos Dietéticos , Ácidos Grasos Volátiles , Ratas , Rayos Ultravioleta
18.
Appl Microbiol Biotechnol ; 105(9): 3843-3857, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33914137

RESUMEN

Wheat is the core food crop in bioregenerative life support systems (BLSSs). In confined isolation environments, wheat growth suffers from a lack of stable microbial communities and is susceptible to pathogenic infections due to the culture substrate's limitations. To overcome this limitation, the time series changes of wheat rhizosphere microorganisms in wheat production must be understood. In the present study, we examined the rhizosphere microbial samples from wheat at four different growth stages from plants collected from a BLSS plant cabin. We employed bioinformatics analysis strategies to analyze the characteristics of species composition, function prediction, and community network. The species composition of wheat rhizosphere microorganisms was relatively stable in the seedling, tillering, and flowering stages in confined isolation environments. However, we observed marked microbial changes at mature stages. The results of functional prediction analysis suggest that the rhizosphere microbial community function of "Energy metabolism" gradually decreased, and the function of "Transmembrane transport" gradually increased during wheat development. The construction of the rhizosphere microbial community is non-random, scale-free and has the characteristics of a small world. We found the tillering stage to be more complex than the other stages. Our study reveals the composition characteristics, functional changes, and community structure fluctuations of rhizosphere bacteria at different development stages of wheat in the isolated and controlled environment, providing a theoretical basis for the efficient production of BLSS plant systems. KEY POINTS: • We collected wheat rhizosphere microorganisms at different stages in a confined isolation environment. • The diversity, composition, function, and network structure of rhizosphere bacteria were analyzed. • The effect of different wheat stages on the composition, function, and network structure of rhizosphere microorganisms was speculated.


Asunto(s)
Microbiota , Rizosfera , Raíces de Plantas , Microbiología del Suelo , Triticum
19.
J Photochem Photobiol B ; 217: 112156, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33647735

RESUMEN

Adequate sunlight exposure helps reduce bone loss and is important to bone health. Currently, about 90% of the world population spends a major portion of daily life under artificial lighting. Unlike sunlight, LED white light, the main source of artificial lighting, has no infrared radiation, which is known to be beneficial to human health. In artificial lighting environments, infrared supplementation may be used to simulate the effects of sunlight on bone metabolism. Here, we supplemented white LED exposure with infrared light in normal and ovariectomized rats for three consecutive months and examined bone turnover, bone mass, and bone density. We also analyzed the structure and function of gut microbiota in the rats. Infrared supplementation significantly reduced the abundance of Saccharibacteria and increased the abundance of Clostridiaceae 1 and Erysipelotrichaceae bacteria. Our results indicate that changes in the gut microbiome correlate well with bone mass and bone metabolism. Our work demonstrates that infrared supplementation can have a positive effect on rat bone metabolism by affecting gut microbiota. Our findings will be important considerations in the future design of healthy lighting environments that prevent or possibly ameliorate osteoporosis.


Asunto(s)
Huesos/metabolismo , Microbioma Gastrointestinal/efectos de la radiación , Rayos Infrarrojos , Animales , Bacterias/genética , Bacterias/aislamiento & purificación , Densidad Ósea , Calcitriol/sangre , Femenino , Ovariectomía , Análisis de Componente Principal , ARN Ribosómico 16S/química , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , Ratas , Ratas Sprague-Dawley
20.
Oncol Res ; 29(2): 87-103, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-37305397

RESUMEN

The activation of some oncogenes promote cancer cell proliferation and growth, facilitate cancer progression and metastasis by induce DNA replication stress, even genome instability. Activation of the cyclic GMP-AMP synthase (cGAS) mediates classical DNA sensing, is involved in genome instability, and is linked to various tumor development or therapy. However, the function of cGAS in gastric cancer remains elusive. In this study, the TCGA database and retrospective immunohistochemical analyses revealed substantially high cGAS expression in gastric cancer tissues and cell lines. By employing cGAS high-expression gastric cancer cell lines, including AGS and MKN45, ectopic silencing of cGAS caused a significant reduction in the proliferation of the cells, tumor growth, and mass in xenograft mice. Mechanistically, database analysis predicted a possible involvement of cGAS in the DNA damage response (DDR), further data through cells revealed protein interactions of the cGAS and MRE11-RAD50-NBN (MRN) complex, which activated cell cycle checkpoints, even increased genome instability in gastric cancer cells, thereby contributing to gastric cancer progression and sensitivity to treatment with DNA damaging agents. Furthermore, the upregulation of cGAS significantly exacerbated the prognosis of gastric cancer patients while improving radiotherapeutic outcomes. Therefore, we concluded that cGAS is involved in gastric cancer progression by fueling genome instability, implying that intervening in the cGAS pathway could be a practicable therapeutic approach for gastric cancer.


Asunto(s)
Neoplasias Gástricas , Humanos , Animales , Ratones , Neoplasias Gástricas/genética , Estudios Retrospectivos , Transducción de Señal , Proliferación Celular/genética , Daño del ADN
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