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1.
Cell Mol Biol (Noisy-le-grand) ; 67(2): 178-186, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34817319

RESUMO

The growing complexity of metastasis has sparked tremendous interest in unraveling of the underlying mechanisms which play fundamental role in cancer progression and metastasis. Ground-breaking discoveries in metastasis research have greatly enhanced our understanding about intricate nature of metastasis. Bioactive chemicals obtained from citrus fruits have gained noteworthy appreciation because of significant cancer chemopreventive roles. Deregulated oncogenic signaling cascades play central role in metastasis. Emerging evidence has started to shed light on the metastasis inhibitory properties of naringin, naringenin, tangeretin, nobiletin, hesperidin and hesperetin in different cancer cell lines and xenografted mice. Wnt/?-catenin, TGF/SMAD and NOTCH signaling cascades have been shown to play linchpin role in carcinogenesis and metastasis. There is emerging evidence related to pharmacological targeting of Wnt/?-catenin, TGF/SMAD and NOTCH by citrus-derived bioactive components. These findings are indeed encouraging and will enable researchers to gain further insights into pharmacological targeting of oncogenic pathways to inhibit and prevent metastasis.

2.
Int J Biol Macromol ; 193(Pt A): 789-798, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34743939

RESUMO

Metabolic syndrome (MetS) is a pathological condition of a variety of metabolic abnormalities, which requires more urgent treatment and intervention. Fucoidan has been recommended as a supplement for health enhancement and disease management. Here, we first propose that the beneficial effect of low molecular weight fucoidan fraction LF2 in regulating metabolic syndrome induced by high-fat diet is similar to that of metformin, in terms of molecular mechanism and gut microbiota. The study found that LF2 significantly reduces fasting blood glucose, enhances insulin sensitivity and restores insulin homeostasis and lipid homeostasis. Moreover, LF2 reduced liver oxidative stress and inflammation, and improved hepatocyte steatosis. To decipher the mechanism behind this therapeutic effect, both the molecular mechanisms and gut microbiota were further analyzed. LF2 inhibited the activation of PI3K-Akt-mTOR axis and decreased the expression of SREBP-1c and PPARγ in liver. Interestingly, we found that LF2 and metformin have similar effects on gut microbiota, increasing the proportion of Verrucomicrobia and enriching the abundance of Akkermansia muciniphila, which is beneficial to host health. Collectively, our research clarifies the new application of fucoidan as a functional food for anti-MetS, and provides a new insight for fucoidan to exert systemic therapeutic effects from the perspective of molecular mechanism and gut microbiota.

3.
Physiol Behav ; : 113648, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34798128

RESUMO

The response to visually evoked innate fear is essential for survival and impacts the cognition and behavior of animals to threats in the environment. However, contradictory findings of the interaction of fear and executive behaviors were reported by previous studies. To address this question, the present study investigated the effect of looming stimuli-driven visually innate fear on reward-associated conditioned response and reversal learning in mice with low or high motivation for sucrose. The mice with low motivation exposed to looming stimuli displayed reduced efficiency in the test of conditional response in the fixed ratio 1 schedule and impaired executive motivation as tested in the progressive ratio schedule of reinforcement. However, the high motivated mice exposed to looming stimuli showed an unaffected conditional response but an increased executive motivation. In the reversal learning program, looming stimuli at the middle stage caused deficits in cognitive flexibility in the mice with low and high motivation. Therefore, these results illuminate the impact of visually evoked innate fear on conditional response and reversal learning and further show that the impacts are relevant to internal motivation and external fear stimuli.

6.
World J Surg Oncol ; 19(1): 311, 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34686186

RESUMO

BACKGROUND: Gastric cancer (GC), a common malignancy of the human digestive system, represents the second leading cause of cancer-related deaths worldwide. Early detection of GC has a significant impact on clinical outcomes. The aim of this study was to identify potential GC biomarkers. METHODS: In this study, we conducted a multi-step analysis of expression profiles in GC clinical samples downloaded from TCGA database to identify differentially expressed miRNAs (DEMs) and differentially expressed mRNAs (DEGs). Potential prognostic biomarkers from the available DEMs were then established using the Cox regression method. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the biological role of the predicted target genes of the miRNA biomarkers. Then, the prognostic DEM-mediated regulatory network was constructed based on transcription factor (TF)-miRNA-target interaction. Subsequently, the consensus genes were further determined based on the overlap between DEGs and these target genes of DEMs. Besides, expression profile, co-expression analysis, immunity, and prognostic values of these prognostic genes were also investigated to further explore the roles in the mechanism of GC tumorigenesis. RESULTS: We got five miRNAs, including miR-23b, miR-100, miR-143, miR-145, and miR-409, which are associated with the overall survival of GC patients. Subsequently, enrichment analysis of the target genes of the miRNA biomarkers shown that the GO biological process terms were mainly enriched in mRNA catabolic process, nuclear chromatin, and RNA binding. In addition, the KEGG pathways were significantly enriched in fatty acid metabolism, extracellular matrix (ECM) receptor interaction, and proteoglycans in cancer pathways. The transcriptional regulatory network consisting of 68 TFs, 4 DEMs, and 58 targets was constructed based on the interaction of TFs, miRNAs, and targets. The downstream gene ETS1 of miR-23b and TCF4 regulated by ETS1 were obtained by the regulatory network construction and co-expression analysis. High expression of ETS1 and TCF4 indicated poor prognosis in GC patients, particularly in the advanced stages. The expression of ETS1 and TCF4 was correlated with CD4+ T cells, CD8+ T cells, and B cells. CONCLUSIONS: miR-23b, ETS1, and TCF4 were identified as the prognostic biomarkers. ETS1 and TCF4 had potential immune function in GC, which provided a theoretical basis for molecular-targeted combined immunotherapy in the future.


Assuntos
MicroRNAs , Neoplasias Gástricas , Biomarcadores Tumorais/genética , Linfócitos T CD8-Positivos , Biologia Computacional , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , Prognóstico , Proteína Proto-Oncogênica c-ets-1/genética , Neoplasias Gástricas/genética , Fator de Transcrição 4/genética
7.
Cell Death Dis ; 12(10): 909, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611139

RESUMO

Prostate cancer is a common malignant tumor, which can spread to multiple organs in the body. Metastatic disease is the dominant reason of death for patients with prostate cancer. Prostate cancer usually transfers to bone. Bone metastases are related to pathologic fracture, pain, and reduced survival. There are many known targets for prostate cancer treatment, including androgen receptor (AR) axis, but drug resistance and metastasis eventually develop in advanced disease, suggesting the necessity to better understand the resistance mechanisms and consider multi-target medical treatment. Because of the limitations of approved treatments, further research into other potential targets is necessary. Metastasis is an important marker of cancer development, involving numerous factors, such as AKT, EMT, ECM, tumor angiogenesis, the development of inflammatory tumor microenvironment, and defect in programmed cell death. In tumor metastasis, programmed cell death (autophagy, apoptosis, and necroptosis) plays a key role. Malignant cancer cells have to overcome the different forms of cell death to transfer. The article sums up the recent studies on the mechanism of bone metastasis involving key regulatory factors such as macrophages and AKT and further discusses as to how regulating autophagy is crucial in relieving prostate cancer bone metastasis.

8.
Anal Methods ; 13(42): 4994-5002, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34633400

RESUMO

In this work, a covalent organic framework (COF) TAPT-TFP-COF containing a triazine ring was prepared by a typical Schiff base condensation reaction of 1,3,5-tris-(4-aminophenyl)triazine (TAPT) and 1,3,5-triformyl phloroglucinol (TFP). The TAPT-TFP-COF and carboxyl-functionalized multi-wall carbon nanotubes (COOH-MWCNTs) were drip-coated on glassy carbon electrode respectively to develop a novel and simple electrochemical sensor in order to simultaneously detect dopamine (DA) and paracetamol (PA). COOH-MWCNTs interconnected the TAPT-TFP-COF and acted as bridges between the COF particles, which had a good synergistic effect and accelerated electron transfer. Under optimal conditions, linear responses were obtained over the concentration range 1-190 µM for DA and PA with limits of detection (LOD) of 0.14 µM and 0.19 µM, respectively. Furthermore, the fabricated sensor possesses outstanding repeatability and high selectivity, and can be applied for the determination of DA and PA in dopamine injection and acetaminophen drugs with satisfactory recoveries.

9.
PLoS One ; 16(10): e0258922, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34705855

RESUMO

BACKGROUND: Studies relating obesity to cognition in older people show conflicting results, which may be explained by the choice of obesity indicators. OBJECTIVES: This study aimed to investigate the relationship between obesity-related indicators and cognitive impairment, especially between different age or gender subgroups, and explore whether obesity-related indicators were related to specific cognitive domains. METHODS: This was a cross-sectional study on 1753 participants aged ≥ 60 years (41.0% men; aged 71.36 ± 5.96 years). Obesity-related indicators included body mass index (BMI), waist circumference (WC), calf circumference (CC), waist to hip ratio (WHR), waist to calf circumstance ratio (WCR), fat to fat-free mass ratio (FM/FFM). The Mini-Mental State Examination scale (MMSE) was used to assess cognitive function. Cognitive impairment was defined as a score ≤ 17 for illiterates, ≤ 20 for participants with primary school education, and ≤ 24 for those with junior high school degrees or above. Multiple logistic regression analysis was used to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic splines were used to analyze and visualize the linear relationships. RESULTS: The prevalence of cognitive impairment was 18.77%. In the fully adjusted model, CC was negatively associated with cognitive impairment (OR = 0.94, 95% CI: 0.90-0.98). Further analysis showed that CC correlated positively with recall and place orientation. A higher FM/FFM was found to be associated with a higher prevalence of cognitive impairment (OR: 1.44, 95%CI: 0.88-2.35, P for trend = 0.029); this association was notable in women (P for trend = 0.002) and the oldest (P for trend = 0.009), and so did the potential effect of BMI on cognitive impairment (70-80 years: P for trend = 0.011; ≥ 80 years: P for trend = 0.013). No statistically significant association was found between cognitive impairment and WC, WHR, or WCR. CONCLUSION: CC and FM/FFM were associated with cognitive impairment in older people. Future research needs to distinguish the effects of fat and muscle mass on cognitive function, with special attention to different ages and genders.

10.
Biochim Biophys Acta Biomembr ; 1863(12): 183757, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34478732

RESUMO

GLUT1 is a major glucose facilitator expressed ubiquitously among tissues. Upregulation of its expression plays an important role in the development of many types of cancer and metabolic diseases. Thioredoxin-interacting protein (TXNIP) is an α-arrestin that acts as an adaptor for GLUT1 in clathrin-mediated endocytosis. It regulates cellular glucose uptake in response to both intracellular and extracellular signals via its control on GLUT1-4. In order to understand the interaction between GLUT1 and TXNIP, we generated GLUT1 lipid nanodiscs and carried out isothermal titration calorimetry and single-particle electron microscopy experiments. We found that GLUT1 lipid nanodiscs and TXNIP interact in a 1:1 ratio and that this interaction requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2 or PIP2).

11.
Carbohydr Polym ; 273: 118567, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34560978

RESUMO

Diffuse alveolar injury and pulmonary fibrosis (PF) are the main causes of death of Covid-19 cases. In this study a low molecular weight fucoidan (LMWF) with unique structural was obtained from Laminaria japonica, and its anti- PF and anti-epithelial-mesenchymal transition (EMT) bioactivity were investigated both in vivo and in vitro. After LWMF treatment the fibrosis and inflammatory factors stimulated by Bleomycin (BLM) were in lung tissue. Immunohistochemical and Western-blot results found the expression of COL2A1, ß-catenin, TGF-ß, TNF-α and IL-6 were declined in mice lung tissue. Besides, the phosphorylation of PI3K and Akt were inhibited by LMWF. In addition, the progression of EMT induced by TGF-ß1 was inhibited by LMWF through down-regulated both TGF-ß/Smad and PI3K/AKT signaling pathways. These data indicate that unique LMWF can protect the lung from fibrosis by weakening the process of inflammation and EMT, and it is a promising therapeutic option for the treatment of PF.


Assuntos
COVID-19/complicações , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Polissacarídeos/administração & dosagem , Polissacarídeos/química , Fibrose Pulmonar/complicações , Fibrose Pulmonar/tratamento farmacológico , SARS-CoV-2 , Células A549 , Animais , Bleomicina/efeitos adversos , COVID-19/virologia , Sobrevivência Celular/efeitos dos fármacos , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Citocinas/farmacologia , Modelos Animais de Doenças , Humanos , Inflamação/tratamento farmacológico , Pulmão/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peso Molecular , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/mortalidade , Transdução de Sinais/efeitos dos fármacos
12.
J Cancer ; 12(19): 5874-5878, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34476000

RESUMO

Introduction: Lung lesions and undiagnosed mesothorax lymphadenopathy is an issue that several doctors face in the everyday clinical practice. PET-CT and CT of the thorax are usually the first examinations to identify characteristics of the lesions before biopsy. Patients and Methods: We performed a retrospective study with 450 patients that had EBUS-TBNA with 22G, Upgraded 22G and 19G needles with and without PET-CT in order to identify the cost effeteness of performing EBUS-TBNA before or after PET-CT. All centers used the same PET-CT equipment and EBUS-TBNA system. Three types of needle were used for the endoscopy in order to identify similarities and differences for the cost-effectiveness. The costs in every center for every examination and materials were the same. Results: There were more block slices for 19G>22Gupgraded>21G>22G and there was cost-effectiveness when in general PET-CT was performed prior to biopsy of any lesion. 19G needle was more effective for lymphomas, while 22Gupgraded and 21G needles were more cost-effective when used for smaller lesions for primary lung cancer of metastatic disease. Conclusions: We have been using PET-CT and EBUS-TBNA in the everyday clinical practice according to the current guidelines for initial disease staging and re-staging. However; we can also use both in a cost effective method based on the initial radiologic findings.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34504533

RESUMO

Objective: To explore the clinical effect of root canal therapy combined with full crown restoration in patients with cracked teeth and chronic pulpitis. Methods: From May 2018 to June 2020, 87 patients with cracked teeth and chronic pulpitis in our hospital were selected; the patients were randomly divided into the control group and the research group by random number method. The control group only used root canal therapy; the research group used root canal therapy combined with full crown restoration. The therapeutic effect, levels of inflammatory factors, chewing function, periodontal index, complications, and quality of life were compared between the two groups. Results: The total effective rate of the research group (97.78%) was better than the total effective rate of the control group (85.71%) (P < 0.05). Compared with before treatment, the serum levels of interleukin-1ß (IL-1ß), IL-6, and C-reactive protein (CRP) of the two groups of patients decreased after treatment. After treatment, compared with the control group, the serum levels of IL-1ß, IL-6, and CRP in the research group decreased (P < 0.05). Compared with before treatment, the bite force of teeth and chewing efficiency of the two groups of patients increased after treatment. After treatment, compared with the control group, the bite force of teeth and chewing efficiency of the research group increased (P < 0.05). Compared with before treatment, the plaque index (PLI), probing depth (PD), gingival sulcus bleeding index (BI), and gingival index (GI) of the two groups of patients decreased after treatment. After treatment, compared with the control group, the PLI, PD, BI, and GI of the research group decreased (P < 0.05). The total incidence of complications in the research group was (11.11%), and the total incidence of complications in the control group was (16.67%); there was no significant difference between the two groups (P > 0.05). After treatment, compared with the control group, the quality of life scores of the patients in the research group were reduced (P < 0.05). Conclusion: Root canal therapy and full crown restoration have a definite curative effect in patients with cracked teeth and chronic pulpitis, which can improve the inflammatory response, restore chewing function, maintain periodontal health, improve the quality of life, and do not increase the incidence of complications, so it has good application value.

14.
J Comput Assist Tomogr ; 45(6): 888-893, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34469908

RESUMO

OBJECTIVE: To compare image quality and radiation dose of split-filter TwinBeam dual-energy (SF-TBDE) with those of single-energy images (SECT) in the contrast-enhanced chest computed tomography (CT). METHODS: Two hundred patients who underwent SF-TBDE (n = 100) and SECT (n = 100) contrast-enhanced chest scanning were retrospectively analyzed. The contrast-to-noise ratio (CNR) and figure of merit (FOM)-CNR of 5 structures (lung, aorta, pulmonary artery, thyroid, and erector spinae) were calculated and subjectively evaluated by 2 independent radiologists. Radiation dose was compared using volume CT dose index and size-specific dose estimate. RESULTS: The CNR and FOM-CNR of lung and erector spinae in SF-TBDE were higher than those of SECT (P < 0.001). The differences in the subjective image quality between the 2 groups were not significant (P = 0.244). Volume CT dose index and size-specific dose estimate of SF-TBDE were lower than those of SECT (6.60 ± 1.56 vs 7.81 ± 3.02 mGy, P = 0.001; 9.25 ± 1.60 vs. 10.55 ± 3.54; P = 0.001). CONCLUSIONS: The SF-TBDE CT can provide similar image quality at a lower radiation dose compared with SECT.

15.
Metab Brain Dis ; 36(8): 2243-2253, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34529220

RESUMO

Nociceptin opioid peptide (NOP) receptor modulates pain transmission and is considered a prospective target for pain management. Under acute pain conditions in rodents, however, no definitive conclusions about effects of systemically intervening NOP receptors on nociception, classical opioid-induced antinociception, tolerance and physical dependence have been drawn. Given that opioid analgesia has sex differences, and females experience greater pain and consume more opioids, clarifying these issues in females will help develop novel analgesics. To clarify the role of NOP receptors on the pharmacological profiles of µ-opioid receptor agonists, in this study, a selective agonist (SCH221510) and antagonist (SB612111) of the NOP receptor were subcutaneously administered in female mice in multiple animal models. In hot-plate test, neither SCH221510 (3 and 10 mg/kg, sc) nor SB612111 (10 mg/kg, sc) produced significant antinociception. SCH221510 (3 mg/kg, sc) attenuated but SB612111 (10 mg/kg, sc) enhanced morphine-induced antinociception, with rightward and leftward shift of morphine dose-response curves, respectively. SCH221510 (3 mg/kg, sc) combined with morphine (10 mg/kg, sc) accelerated the development of morphine antinociceptive tolerance. Conversely, SB612111 (10 mg/kg, sc) delayed morphine tolerance development. Neither SCH221510 (3 mg/kg, sc) nor SB612111 (10 mg/kg, sc) statistically significantly altered the development of morphine-induced physical dependence. Therefore, systemic activation of NOP receptors attenuated morphine antinociception to acute thermal stimuli, facilitated morphine-induced antinociceptive tolerance but did not robustly alter physical dependence in female mice. Systemic blockade of NOP receptors produced opposite actions. These findings demonstrate that N/OFQ-NOP receptor system plays diverse roles in modulating pharmacological profiles of µ-opioid receptor agonists.

16.
Molecules ; 26(17)2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34500750

RESUMO

A phenazine-1-carboxylic acid intermediate was synthesized from the reaction of aniline and 2-bromo-3-nitro-benzoic acid. It was then esterified and reacted with hydrazine hydrate to afford phenazine-1-carboxylic hydrazine. Finally, 10 new hydrazone compounds 3a-3j were obtained by the condensation reaction of phenazine-1-carboxylic acid hydrazide and the respective aldehyde-containing compound. The structures were characterized by 1H and 13C NMR spectroscopy, MS and single crystal X-ray diffraction. The antitumor activity of the target compounds in vitro (HeLa and A549) was determined by thiazolyl blue tetrazolium bromide. The results showed that compound (E)-N'-(2-hydroxy-4-(2-(piperidine-1-yl) ethoxy) benzyl) phenazine-1-carbonyl hydrazide 3d exhibited good cytotoxic activity.


Assuntos
Hidrazonas/farmacologia , Células A549 , Antineoplásicos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Hidrazonas/síntese química , Hidrazonas/química , Estrutura Molecular , Fenazinas/síntese química , Fenazinas/química , Fenazinas/farmacologia , Relação Estrutura-Atividade
17.
Front Immunol ; 12: 687961, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335589

RESUMO

Graft-versus-host disease (GVHD) is a pathology in which chemokines and their receptors play essential roles in directing the migration of alloreactive donor T cells into GVHD organs, thereby leading to further target tissue damage. Currently, acute GVHD (aGVHD) remains a major cause of high morbidity and mortality in patients who underwent allogeneic hematopoietic cell transplantation (alloHCT). The identification of immune cells that correlate with aGVHD is important and intriguing. To date, the involvement of innate-like γδ T cells in the pathogenesis of aGVHD is unclear. Herein, we found that primary human γδ T cells did not directly trigger allogeneic reactions. Instead, we revealed that γδ T cells facilitated the migration of CD4 T cells via the SDF-1-CXCR4 axis. These results indicate indirect regulation of γδ T cells in the development of aGVHD rather than a direct mechanism. Furthermore, we showed that the expression of CXCR4 was significantly elevated in γδ T cells and CD4 and CD8 T cells in recipients who experienced grades II-IV aGVHD after alloHCT. Consistently, CXCR4-expressing γδ T cells and CD4 T cells were induced in the target organs of mice suffering aGVHD. The depletion of γδ T cells in transplant grafts and treatment with AMD3100, an inhibitor of CXCR4 signaling, delayed the onset of aGVHD and prolonged survival in mice. Taken together, these findings suggest a role for γδ T cells in recruiting alloreactive CD4 T cells to target tissues through the expression of CXCR4. Our findings may help in understanding the mechanism of aGVHD and provide novel therapeutic targets.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Quimiocina CXCL12/metabolismo , Quimiotaxia de Leucócito , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfócitos Intraepiteliais/metabolismo , Receptores CXCR4/metabolismo , Adolescente , Adulto , Animais , Benzilaminas/farmacologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Células Cultivadas , Técnicas de Cocultura , Ciclamos/farmacologia , Modelos Animais de Doenças , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/metabolismo , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Linfócitos Intraepiteliais/efeitos dos fármacos , Linfócitos Intraepiteliais/imunologia , Masculino , Camundongos Endogâmicos NOD , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Receptores CXCR4/antagonistas & inibidores , Transdução de Sinais , Transplante Homólogo , Adulto Jovem
19.
Int J Biol Macromol ; 189: 649-656, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34450152

RESUMO

Crude exopolysaccharides from extracellular polymeric substances produced by the marine bacterium Bacillus sp. H5 were fractionated using DEAE-Sepharose FF and Sephadex G-75 chromatography. The high molecular weight fraction (89.0 kD) from the neutral fraction was designated EPS5SH; it contained mannose, glucosamine, glucose, and galactose in a molar ratio of 1.00: 0.02: 0.07: 0.02. Infra-red, gas chromatography-mass spectrometry, electrospray ionisation-tandem mass spectrometry analysis and nuclear magnetic resonance revealed EPS5SH was a mannan with α-(1 â†’ 4)-Manp, α-(1 â†’ 2)-Manp, α-(1 â†’ 4, 6)-Manp and ß-terminal-Manp. Preliminary in vitro experiments revealed that EPS5SH significantly upregulated nitric oxide synthesis and release of pro-inflammatory factors in murine macrophage RAW264.7 cells. Western blot experiments verified the immunostimulatory effects of EPS5SH through the modulation of the NF-κB and MAPK signalling pathways. In conclusion, EPS5SH was a novel immunostimulatory mannan.

20.
Nat Immunol ; 22(9): 1127-1139, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34413521

RESUMO

Follicular helper T (TFH) cells are a specialized subset of CD4+ T cells that essentially support germinal center responses where high-affinity and long-lived humoral immunity is generated. The regulation of TFH cell survival remains unclear. Here we report that TFH cells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis, a form of programmed cell death that is driven by iron-dependent accumulation of lipid peroxidation. Glutathione peroxidase 4 (GPX4) is the major lipid peroxidation scavenger and is necessary for TFH cell survival. The deletion of GPX4 in T cells selectively abrogated TFH cells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased TFH cell numbers and promoted antibody responses in immunized mice and young adults after influenza vaccination. Our findings reveal the central role of the selenium-GPX4-ferroptosis axis in regulating TFH homeostasis, which can be targeted to enhance TFH cell function in infection and following vaccination.


Assuntos
Ferroptose/fisiologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Selênio/farmacologia , Células T Auxiliares Foliculares/fisiologia , Adolescente , Adulto , Animais , Sobrevivência Celular/imunologia , Criança , Feminino , Centro Germinativo/citologia , Centro Germinativo/imunologia , Homeostase/efeitos dos fármacos , Homeostase/genética , Humanos , Imunidade Humoral/imunologia , Vacinas contra Influenza/imunologia , Peroxidação de Lipídeos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/fisiologia , Ovalbumina , Células T Auxiliares Foliculares/imunologia , Vacinação , Adulto Jovem
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