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1.
Cell Discov ; 9(1): 2, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609376

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Antibody resistance dampens neutralizing antibody therapy and threatens current global Coronavirus (COVID-19) vaccine campaigns. In addition to the emergence of resistant SARS-CoV-2 variants, little is known about how SARS-CoV-2 evades antibodies. Here, we report a novel mechanism of extracellular vesicle (EV)-mediated cell-to-cell transmission of SARS-CoV-2, which facilitates SARS-CoV-2 to escape from neutralizing antibodies. These EVs, initially observed in SARS-CoV-2 envelope protein-expressing cells, are secreted by various SARS-CoV-2-infected cells, including Vero E6, Calu-3, and HPAEpiC cells, undergoing infection-induced pyroptosis. Various SARS-CoV-2-infected cells produce similar EVs characterized by extra-large sizes (1.6-9.5 µm in diameter, average diameter > 4.2 µm) much larger than previously reported virus-generated vesicles. Transmission electron microscopy analysis and plaque assay reveal that these SARS-CoV-2-induced EVs contain large amounts of live virus particles. In particular, the vesicle-cloaked SARS-CoV-2 virus is resistant to neutralizing antibodies and able to reinfect naïve cells independent of the reported receptors and cofactors. Consistently, the constructed 3D images show that intact EVs could be taken up by recipient cells directly, supporting vesicle-mediated cell-to-cell transmission of SARS-CoV-2. Our findings reveal a novel mechanism of receptor-independent SARS-CoV-2 infection via cell-to-cell transmission, provide new insights into antibody resistance of SARS-CoV-2 and suggest potential targets for future antiviral therapeutics.

2.
Nat Commun ; 14(1): 390, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36693830

RESUMO

Statins play an important role in the treatment of diabetic nephropathy. Increasing attention has been given to the relationship between statins and insulin resistance, but many randomized controlled trials confirm that the therapeutic effects of statins on diabetic nephropathy are more beneficial than harmful. However, further confirmation of whether the beneficial effects of chronic statin administration on diabetic nephropathy outweigh the detrimental effects is urgently needed. Here, we find that long-term statin administration may increase insulin resistance, interfere with lipid metabolism, leads to inflammation and fibrosis, and ultimately fuel diabetic nephropathy progression in diabetic mice. Mechanistically, activation of insulin-regulated phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway leads to increased fatty acid synthesis. Furthermore, statins administration increases lipid uptake and inhibits fatty acid oxidation, leading to lipid deposition. Here we show that long-term statins administration exacerbates diabetic nephropathy via ectopic fat deposition in diabetic mice.

3.
Biomark Res ; 11(1): 10, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36694213

RESUMO

BACKGROUND: Cumulative preclinical and clinical evidences showed radiotherapy might augment systemic antitumoral responses to immunotherapy for metastatic non-small cell lung cancer, but the optimal timing of combination is still unclear. The overall infiltration and exhausted subpopulations of tumor-infiltrating CD8+ T cells might be a potential biomarker indicating the response to immune checkpoint inhibitors (ICI), the alteration of which is previously uncharacterized during peri-irradiation period, while dynamic monitoring is unavailable via repeated biopsies in clinical practice. METHODS: Basing on tumor-bearing mice model, we investigated the dynamics of overall infiltration and exhausted subpopulations of CD8+ T cells after ablative irradiation. With the understanding of distinct metabolic characteristics accompanied with T cell exhaustion, we developed a PET radiomics approach to identify and visualize T cell exhaustion status. RESULTS: CD8+ T cell infiltration increased from 3 to 14 days after ablative irradiation while terminally exhausted populations significantly predominated CD8+ T cells during late course of this infiltrating period, indicating that 3-7 days post-irradiation might be a potential appropriate window for delivering ICI treatment. A PET radiomics approach was established to differentiate T cell exhaustion status, which fitted well in both ICI and irradiation settings. We also visualized the underlying association of more heterogeneous texture on PET images with progressed T cell exhaustion. CONCLUSIONS: We proposed a non-invasive imaging predictor which accurately assessed heterogeneous T cell exhaustion status relevant to ICI treatment and irradiation, and might serve as a promising solution to timely estimate immune-responsiveness of tumor microenvironment and the optimal timing of combined therapy.

4.
CNS Neurosci Ther ; 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36601664

RESUMO

AIMS: Cerebral venous thrombosis (CVT) is a major cause of stroke in young and middle-aged adults. This study aimed to evaluate the prevalence of post-CVT employability decline and identify factors associated with unemployment. METHODS: We identified patients first diagnosed with acute/subacute CVT at Xuanwu Hospital, Capital Medical University (January 2018 to June 2021) and invited all survivors to a clinical 6-months follow-up visit after onset. Baseline data were collected from all patients at admission. A modified Rankin Scale (mRS) and employment status were used to assess functional outcomes. Multivariate logistic regression was used to identify independent factors associated with unemployment. RESULTS: A total of 303 CVT patients were eligible for this study, 131 (42.23%) patients could not return to work 6-month after discharge. After adjusting for age and sex in multivariate analysis, motor deficits, aphasia, mental disorders, CVT recurrence, National Institutes of Health Stroke Scale (NIHSS) score at admission, and mRS 0-2 at 6-month follow-up were independently associated with employment after CVT. Among 263 patients whose mRS showed a favorable outcome, 102 patients were unable to return to their previous work and the risk factors for impaired ability to return to work were aphasia and CVT recurrence. CONCLUSIONS: Impaired employability after CVT was associated with motor deficits, aphasia, mental status disorders, and NIHSS score at admission. Even if they recover from CVT without physical disability, patients with a good functional prognosis have a higher risk of employment failure due to their higher rates of aphasia and CVT recurrence.

5.
Arch Oral Biol ; 147: 105629, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36680836

RESUMO

OBJECTIVE: Periodontitis is an inflammatory disease, characterized by periodontal pocket formation and alveolar bone resorption, is one of the most common oral diseases. Interleukin-37 (IL-37) is a novel inflammatory suppressor that plays an important role in many inflammatory diseases. This study aimed to investigate the role of IL-37 in periodontitis DESIGN: A mouse model of periodontitis was established by Porphyromonas gingivalis. After four weeks treatment of recombinant human IL-37 (rhIL-37), the effects of IL-37 on the gingival index and tooth loosening degree of periodontitis mice were observed. H&E staining and micro-CT scanning were used to analyze the bone resorption of the maxillary. The number of osteoclasts was counted by TRAP staining and the differentiation of osteoclasts was evaluated by immunohistochemistry. The expression of inflammatory cytokines was detected by ELISA, and the protein expressions of the NF-κB/NLRP3 pathway were analyzed by WB. RESULTS: RhIL-37 significantly decreased the gingival index and tooth mobility degree, inhibited maxillary bone resorption, decreased the number of osteoclasts and the expression of calcitonin receptor (CTR), periodontal cathepsin K (CTSK) and receptor activator of NF-κB ligand (RANKL), and increased the expression of osteoprotegerin (OPG) in periodontitis mice. At the same time, rhIL-37 significantly decreased the expression of IL-1ß, IL-6 and TNF-α, and increased the expression of IL-10 in the gingival tissue of periodontitis mice. In addition, rhIL-37 significantly inhibited the protein expressions of p-p65, NLRP3, ASC, caspase-1 and IL-1ß in periodontitis mice. CONCLUSION: IL-37 may alleviate alveolar bone resorption and inflammation response in periodontitis through the NF-κB/NLRP3 pathway.

6.
Eur J Neurosci ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36656284

RESUMO

How speaking two languages affects executive functions has been a long-standing debate and the mechanisms underlying the observed cognitive advantages of bilingualism remain unspecified. Here, using multivariate pattern classification methods, we decoded spatial patterns of neural signals associated with Flanker task performance in mono-dialectal and bi-dialectal speakers of Chinese. While univariate approach to even-related potentials (ERPs) showed no between-group difference, decoding accuracy of ERPs was reduced in bi-dialectal as compared to mono-dialectal speakers in both congruent-neutral and incongruent-neutral classifications. There was no effect of bidialectalism, however, on decoding accuracy of alpha-band oscillations, an electrophysiological index implicated in inhibition. Behavioural data analyzed using the Drift Diffusion Model (DDM) showed facilitating effects of bidialectalism on non-decision times but no effect on drift rates. These findings demonstrate that using two dialects on a daily basis enhances general attentional deployment rather than affecting specific component of executive functions such as inhibitory control. Given that the two dialects of Chinese differed almost exclusively in phonology, the bidialectalism effect was most likely motivated by resolving phonological competition at lexical processing level.

7.
Sci Rep ; 13(1): 436, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624121

RESUMO

We aimed to explore whether superfluous sympathetic activity affects myoblast differentiation, fusion, and myofiber types using a continuous single-dose isoprenaline exposure model in vitro and to further confirm the role of distinct NFATs in ISO-mediated effects. Compared with delivery of single and interval single, continuous single-dose ISO most obviously diminished myotube size while postponing myoblast differentiation/fusion in a time- and dose-dependent pattern, accompanied by an apparent decrease in nuclear NFATc1/c2 levels and a slight increase in nuclear NFATc3/c4 levels. Overexpression of NFATc1 or NFATc2, particularly NFATc1, markedly abolished the inhibitory effects of ISO on myoblast differentiation/fusion, myotube size and Myh7 expression, which was attributed to a remarkable increase in the nuclear NFATc1/c2 levels and a reduction in the nuclear NFATc4 levels and the associated increase in the numbers of MyoG and MEF2C positive nuclei within more than 3 nuclei myotubes, especially in MEF2C. Moreover, knockdown of NFATc3 by shRNA did not alter the inhibitory effect of ISO on myoblast differentiation/fusion or myotube size but partially recovered the expression of Myh7, which was related to the slightly increased nuclear levels of NFATc1/c2, MyoG and MEF2C. Knockdown of NFATc4 by shRNA prominently increased the number of MyHC +, MyoG or MEF2C + myoblast cells with 1 ~ 2 nuclei, causing fewer numbers and smaller myotube sizes. However, NFATc4 knockdown further deteriorated the effects of ISO on myoblast fusion and myotube size, with more than 5 nuclei and Myh1/2/4 expression, which was associated with a decrease in nuclear NFATc2/c3 levels. Therefore, ISO inhibited myoblast differentiation/fusion and myotube size through the NFAT-MyoG-MEF2C signaling pathway.


Assuntos
Fibras Musculares Esqueléticas , Transdução de Sinais , Isoproterenol/farmacologia , Isoproterenol/metabolismo , Diferenciação Celular , Fibras Musculares Esqueléticas/metabolismo , Mioblastos/metabolismo , RNA Interferente Pequeno/metabolismo
8.
Ecotoxicol Environ Saf ; 251: 114533, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36638563

RESUMO

Microplastic pollution has attracted mounting concerns worldwide. Microplastics may concentrate organic and metallic contaminants; thus, affecting their transport, fate and organismal exposure. To better understand organic contaminant-microplastic interactions, our study explored the sorption of selected polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), α-hexabromocyclododecane (α-HBCDD), and organophosphate flame retardants (OPFRs) on high-density polyethylene (HDPE) and polyvinylchloride (PVC) microplastics under saline conditions. Sorption isotherms determined varied between chemicals and between HDPE and PVC microplastics. Log Freundlich sorption coefficients (Log KF) for the targeted chemicals ranged from 2.01 to 5.27 L kg-1 for HDPE, but were significantly lower for PVC, i.e., ranging from Log KF data (2.84 - 8.58 L kg-1). Significant correlations between chemicals' Log KF and Log Kow (octanol-water partition coefficient) indicate that chemical-dependent sorption was largely influenced by their hydrophobicity. Sorption was evaluated using three size classes (< 53, 53 - 300, and 300 - 1000 µm) of lab-fragmented microplastics. Particle size did not significantly affect sorption isotherms, but influenced the time to reach equilibrium and the predicted maximum sorption, likely related to microplastic surface areas. The presence of biofilms on HDPE particles significantly enhanced contaminant sorption capacity, indicating more complex sorption dynamics in the chemical-biofilm-microplastic system. Our findings offer new insights into the chemical-microplastic interactions in marine environment.

9.
Microbiol Spectr ; : e0344822, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36645283

RESUMO

Microbiota has recently emerged as a critical factor associated with multiple malignancies. Nasopharyngeal carcinoma (NPC) is highly associated with Epstein-Barr virus (EBV); the oncovirus resides and is transmitted in the oral cavity. However, the alternation of oral microbiota in NPC patients and its potential link to EBV reactivation and host cell response under the simultaneous existence of EBV and specific bacteria is largely unknown. Here, oral microbiota profiles of 303 NPC patients and controls with detailed clinical information, including serum EBV anti-virus capsid antigen (VCA) IgA level, were conducted. A distinct microbial community with lower diversity and imbalanced composition in NPC patients was observed. Notably, among enriched bacteria in patients, Streptococcus sanguinis was associated with anti-VCA IgA, an indicator of NPC risk and EBV reactivation. By measuring the concentration of its metabolite, hydrogen peroxide (H2O2), in the saliva of clinical patients, we found the detection rate of H2O2 was 2-fold increased compared to healthy controls. Further coculture assay of EBV-positive Akata cells with bacteria in vitro showed that S. sanguinis induced EBV lytic activation by its metabolite, H2O2. Host and EBV whole genome-wide transcriptome sequencing and EBV methylation assays showed that H2O2 triggered the host cell signaling pathways, notably tumor necrosis factor alpha (TNF-α) via NF-κB, and induced the demethylation of the global EBV genome and the expression of EBV lytic-associated genes, which could result in an increase of virus particle release and potential favorable events toward tumorigenesis. In brief, our study identified a characterized oral microbial profile in NPC patients and established a robust link between specific oral microbial alteration and switch of latency to lytic EBV infection status in the oral cavity, which provides novel insights into EBV's productive cycle and might help to further clarify the etiology of NPC. IMPORTANCE EBV is classified as the group I human carcinogen and is associated with multiple cancers, including NPC. The interplays between the microbiota and oncovirus in cancer development remain largely unknown. In this study, we investigate the interactions between resident microbes and EBV coexistence in the oral cavity of NPC patients. We identify a distinct oral microbial feature for NPC patients. Among NPC-enriched bacteria, we illustrated that a specific species, S. sanguinis, associated with elevated anti-IgA VCA in patients, induced EBV lytic activation by its by-product, H2O2, and activated the TNF-α/NF-κB pathway of EBV-positive B cells in vitro, together with increased detection rate of H2O2 in patients' oral cavities, which strengthened the evidence of bacteria-virus-host interaction in physiological circumstances. The effects of imbalanced microbiota on the EBV latent-to-lytic switch in the oral cavity might create the likelihood of EBV infection in epithelial cells at the nasopharynx and help malignant transition and cancer development.

10.
Food Chem ; 410: 135418, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36652800

RESUMO

Polyguluronate (PG) is an acidic homopolymer of α-(1,4)-l-guluronate separated from alginate. In this study, PG was first grafted with soy protein isolate (SPI) through the Maillard reaction to obtain a new glycoprotein (SPI-PG). Then, this novel glycoprotein was used to prepare nanoparticles to encapsulate the resveratrol (RES). Our results showed that SPI-PG-RES had better pH stability, storage stability and ionic stability than SPI-RES. In vitro digestion experiments showed that the RES bioavailability of SPI-PG-RES was much higher than that of free RES and SPI-RES. Furthermore, the in vitro antioxidant capacity of SPI-PG-RES was much stronger than that of free RES and SPI-RES. In addition, SPI-PG-RES was more effective in preventing the symptoms of DSS-induced colitis than RES and SPI-RES. These results suggested that the protein nanoparticles prepared using SPI-PG were a stable and effective hydrophobic polyphenol carrier and could be applied to food-grade components in functional foods and nutritional supplements.

11.
Bioresour Technol ; 370: 128569, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36592865

RESUMO

Food waste was used to produce ethanol by yeast fermentation and volatile fatty acids (VFAs) by hydrolytic acidogenesis for chain elongation. Effectiveness of mole ratio of ethanol in yeast fermentation effluent (YFE) to VFAs in hydrolytic acidification effluent (HAE) on chain elongation was examined. The ideal YFE to HAE ratio for chain elongation was 2:1, the highest n-caproate production was 169.76 mg COD/g vS and the food waste utilization was 65.43 %. Electron transfer and carbon distribution did not completely correspond to n-caproate production, suggesting timely product extraction. The abundance of Romboutsia and Clostridium_sensu_stricto_12 increased as chain elongation progressed, which was critical for the chain elongation to n-caproate. The food waste shunting ratio of yeast fermentation to hydrolytic acidogenesis was 6:5, and 572.6 CNY can be created through chain elongation from shunting fermentation of 1 t food waste. This study proposed a new approach for efficient producing n-caproate from food waste.


Assuntos
Alimentos , Eliminação de Resíduos , Fermentação , Caproatos , Saccharomyces cerevisiae , Ácidos Graxos Voláteis , Etanol , Reatores Biológicos
12.
Med Biol Eng Comput ; 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36650410

RESUMO

The motor imagery brain-computer interface (MI-BCI) provides an interactive control channel for spinal cord injury patients. However, the limitations of feature extraction algorithms may lead to low accuracy and instability in decoding electroencephalogram (EEG) signals. In this study, we examined the classification performance of an MI-BCI system by focusing on the distinction of the left and right foot kinaesthetic motor imagery tasks in five subjects. Feature extraction was performed using the common space pattern (CSP) and the Tikhonov regularisation CSP (TRCSP) spatial filters. TRCSP overcomes the CSP problems of noise sensitivity and overfitting. Moreover, support vector machine (SVM) and linear discriminant analysis (LDA) were used for classification and recognition. We constructed four combined classification methods (TRCSP-SVM, TRCSP-LDA, CSP-SVM, and CSP-LDA) and evaluated them by comparing their accuracies, kappa coefficients, and receiver operating characteristic (ROC) curves. The results showed that the TRCSP-SVM method performed significantly better than others (average accuracy 97%, average kappa coefficient 0.91, and average area under ROC curve (AUC) 0.98). Using TRCSP instead of standard CSP improved accuracy by up to 10%. This study provides insights into the classification of EEG signals. The results of this study can aid lower limb MI-BCI systems in rehabilitation training.

14.
Chemosphere ; 317: 137913, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36682640

RESUMO

Amino antioxidants (AAOs), a suite of emerging organic contaminants, have been widely used in numerous industrial and commercial products to inhibit oxidation and corrosion. Recently, their environmental ubiquity, health risks, bioaccumulative and toxic potential have led to mounting public concern. This review summarizes the current state of knowledge on the production and usage, environmental occurrence, bioavailability, human exposure, and aquatic toxicity of representative AAOs, and provides suggestions for future research directions. Previous studies have revealed widespread distribution of many AAOs in various environmental matrixes, including air, water, sediment, dust, and biota. In addition to parent compounds, their degradation products, such as 2-anilino-5-(1,3-dimethylbutylamino)-1,4-benzoquinone (6PPD-Q) and 4-nitrodiphenylamine (4-NO2-DPA), have also been detected at high levels in multiple compartments. Dust ingestion and air inhalation are the two most well-investigated routes for human exposure to AAOs and their transformation products, while studies on other pathways (e.g., skin contact and dietary intake) still remain extremely limited. Moreover, AAO burdens in human tissue have been poorly documented. Toxicological data have shown that a few AAOs may cause teratogenic, developmental, reproductive, endocrinic, neuronic, and genetic toxicity to aquatic organisms, and the toxic capacities of degradation products differ from their precursors. Future studies should focus on elucidating AAO exposure for humans and associated health risks. Additionally, more attention should be given to AAO transformation products (particularly those quinoid derivatives possessing substantial affinity with DNA) and to the effects of complex mixtures of these chemicals.

15.
Artigo em Inglês | MEDLINE | ID: mdl-36648604

RESUMO

C50 carotenoids, as unique bioactive molecules, have many biological properties, including antioxidant, anticancer, and antibacterial activity, and have a wide range of potential uses in the food, cosmetic, and biomedical industries. The majority of C50 carotenoids are produced by the sterile fermentation of halophilic archaea. This study aims to look at more cost-effective and manageable ways of producing C50 carotenoids. The basic medium, carbon source supplementation, and optimal culture conditions for Halorubrum sp. HRM-150 C50 carotenoids production by open fermentation were examined in this work. The results indicated that Halorubrum sp. HRM-150 grown in natural brine medium grew faster than artificial brine medium. The addition of glucose, sucrose, and lactose (10 g/L) enhanced both biomass and carotenoids productivity, with the highest level reaching 4.53 ± 0.32 µg/mL when glucose was added. According to the findings of orthogonal studies based on the OD600 and carotenoids productivity, the best conditions for open fermentation were salinity 20-25%, rotation speed 150-200 rpm, and pH 7.0-8.2. The up-scaled open fermentation was carried out in a 7 L medium under optimum culture conditions. At 96 h, the OD600 and carotenoids productivity were 9.86 ± 0.51 (dry weight 10.40 ± 1.27 g/L) and 7.31 ± 0.65 µg/mL (701.40 ± 21.51 µg/g dry weight, respectively). When amplified with both universal bacterial primer and archaeal primer in the open fermentation, Halorubrum remained the dominating species, indicating that contamination was kept within an acceptable level. To summarize, open fermentation of Halorubrum is a promising method for producing C50 carotenoids.

16.
AoB Plants ; 15(1): plac057, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36654987

RESUMO

The proteins with DNA-binding preference to the consensus DNA sequence (A/T) GATA (A/G) belong to a GATA transcription factor family, with a wide array of biological processes in plants. Cassava (Manihot esculenta) is an important food crop with high production of starch in storage roots. Little was however known about cassava GATA domain-containing genes (MeGATAs). Thirty-six MeGATAs, MeGATA1 to MeGATA36, were found in this study. Some MeGATAs showed a collinear relationship with orthologous genes of Arabidopsis, poplar and potato, rice, maize and sorghum. Eight MeGATA-encoded proteins (MeGATAs) analysed were all localized in the nucleus. Some MeGATAs had potentials of binding ligands and/or enzyme activity. One pair of tandem-duplicated MeGATA17-MeGATA18 and 30 pairs of whole genome-duplicated MeGATAs were found. Fourteen MeGATAs showed low or no expression in the tissues. Nine analysed MeGATAs showed expression responses to abiotic stresses and exogenous phytohormones. Three groups of MeGATA protein interactions were found. Fifty-three miRNAs which can target 18 MeGATAs were identified. Eight MeGATAs were found to target other 292 cassava genes, which were directed to radial pattern formation and phyllome development by gene ontology enrichment, and autophagy by Kyoto Encyclopaedia of Genes and Genomes enrichment. These data suggest that MeGATAs are functional generalists in interactions between cassava growth and development, abiotic stresses and starch metabolism.

17.
J Gynecol Oncol ; 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36659830

RESUMO

OBJECTIVE: Endometrial cancer (EC) is a common gynecological malignant tumor. CircRNAs play crucial roles in cancer progression and metastasis. However, the biological functions of circRNAs in EC remain largely unknown. METHODS: CircSMAD2, miR-1277-5p, MFGE8 and relative maker protein expression in EC tissues or cell lines were analyzed by quantitative real-time polymerase chain reaction and Western blot. In vitro and in vivo functional assays, including EDU, CCK8, colony formation, transwell, tube formation and tumor xenograft assays, were conduct to explore the effects of circSMAD2 on EC. Mechanism assays were conducted to confirm the binding between miR-1277-5p and circSMAD2 or MFGE8 expression. RESULTS: Upregulation of circSMAD2 was uncovered in both EC tissues and cell lines. Functionally, silencing of circSMAD2 apparently inhibited the proliferation, migration, invasion and angiogenesis of EC cell lines in vitro. Mechanistically, circSMAD2 sponged miR-1277-5p to upregulate MFGE8 expression. The decrease of miR-1277-5p and increase of MFGE8 were observed both in EC tissues and cell lines. Then MFGE8 knockdown or miR-1277-5p upregulation suppressed EC cell oncogenic biological behavior. Rescue experiments showed that miR-1277-5p mimics countervailed the anticancer effects of circSMAD2 silencing on EC. Besides that, MFGE8 overexpression also attenuated the inhibitory action of miR-1277-5p mimic in EC. Moreover, knockdown of circSMAD2 inhibited EC growth in vivo. CONCLUSION: CircSMAD2 functions as an oncogene in promoting the progression of EC through miR-1277-5p/MFGE8 axis.

18.
Biomed Pharmacother ; 159: 114202, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36621143

RESUMO

Sepsis acute kidney injury (SAKI) is a common complication of sepsis, accounting for 26-50 % of all acute kidney injury (AKI). AKI is an independent risk factor for increased mortality risk in patients with sepsis. The excessive inflammatory cascade reaction in SAKI is one of the main causes of kidney damage. Both the innate immune system and the adaptive immune system are involved in the inflammation process of SAKI. Under the action of endotoxin, neutrophils, monocytes, macrophages, T cells and other complex immune network reactions occur, and a large number of endogenous inflammatory mediators are released, resulting in the amplification and loss of control of the inflammatory response. The study of immune cells in SAKI will help improve the understanding of the immune mechanisms of SAKI, and will lay a foundation for the development of new diagnostic and therapeutic targets. This article reviews the role of known immune mechanisms in the occurrence and development of SAKI, with a view to finding new targets for SAKI treatment.

19.
Neurobiol Dis ; 177: 105993, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36627028

RESUMO

Clarifying the risk factors and mechanisms that contribute to the onset of cognitive impairment following estrogen depletion is essential for improving the quality of life of older females. In the current study, using behavioral tests, 16S rDNA sequencing, in vivo and in vitro electrophysiology, optogenetics and chemogenetics, we found that high-fat diet (HFD)-accelerated impairment of hippocampus-dependent memory, gut microbiota, and hippocampal theta rhythmogenesis in ovariectomized (OVX) mice and fecal microbiota transplantation rescued these phenomena. The identification of fasting-activated medial septal neurons showed that PV+ GABAergic neurons in the medial septal area (MSA) respond to gut sensory signals. Optogenetic activation of septohippocampal PV+ GABAergic fibers (but not cholinergic fibers) significantly rescued hippocampal theta rhythmogenesis and spatial memory in HFD-fed OVX mice. Resistant starch supplementation (RSHFD) rectified the gut Prevotellaceae and considerably alleviated reduced septal gut-responsive neurons, decreased hippocampal theta rhythm, and impaired hippocampus-dependent memory in HFD-fed OVX mice. Furthermore, chemogenetic inhibition of septal PV+ GABAergic neurons reversed the neuroprotective effects of resistant starch supplementation. These findings highlight the notable gut-sensory nature of medial septal PV+ GABAergic neurons. A HFD accelerates estrogen deficiency-induced cognitive impairment by disrupting the gut Prevotellaceae-septo-hippocampal pathway. This study contributes to a better understanding of the precise gut-brain control of cognition and cognitive impairment in postmenopausal females.

20.
Environ Pollut ; 318: 120852, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36509346

RESUMO

Sediments are the long-term sinks of microplastics (MPs) and nutrients in freshwater ecosystems. Therefore, understanding the effect of MPs on sediment nutrients is crucial. However, few studies have discussed the effects of MPs on nitrogen and phosphorus cycles in freshwater sediments. Herein, 0.5% (w/w) polyvinyl chloride (PVC), polylactic acid (PLA), and polypropylene (PP) MPs were added to freshwater sediments to evaluate their effects on microbial communities and nitrogen and phosphorus release. The potential biochemical functions of the bacterial communities in the sediments were predicted and assessed via 16S rRNA gene sequencing. The results showed that MPs significantly affected the microbial community composition and nutrient cycling in the sediments. PVC and PP MPs can promote microbial nitrification and nitrite oxidation, while PP can significantly promote alkaline phosphatase (ALP) activity and the abundance of the phosphorus-regulation (phoR) gene. PLA MPs had the potential to promote the abundance of microbial phosphorus transporter (ugpB), nitrogen fixation (nifD, nifH, and nifX), and denitrification (nirS, napA, and norB) genes and inhibit nitrification, resulting in massive accumulation and release of ammonia nitrogen. Although PLA MPs inhibited the activity of ALP and the abundance of the organophosphorus mineralization (phoD) gene, it could enhance dissimilatory iron and sulfite reduction, which may promote the release of sedimentary phosphorus. Our findings may help understand the mechanisms of nitrogen and phosphorus cycles and microbial communities driven by MPs in sediments and provide a basis for future assessments of the environmental behavior of MPs in freshwater ecosystems.


Assuntos
Microbiota , Microplásticos , Plásticos/farmacologia , Nitrogênio/farmacologia , Fósforo , RNA Ribossômico 16S , Sedimentos Geológicos/química , Poliésteres
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