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1.
Vet Microbiol ; 251: 108916, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33197868

RESUMO

PA-X is a fusion protein encoded by a +1 frameshifted open reading frame (X-ORF) in PA gene. The X-ORF can be translated in full-length (61 amino acids, aa) or truncated (41 aa) form. However, the role of C-Terminal 20 aa of PA-X in virus function has not yet been fully elucidated. To this end, we constructed the contemporary influenza viruses with full and truncated PA-X by reverse genetics to compare their replication and pathogenicity. The full-length PA-X virus in MDCK and human A549 cells conferred 10- to 100-fold increase in viral replication, and more virulent and caused more severe inflammatory responses in mice relative to corresponding truncated PA-X virus, suggesting that the terminal 20 aa could play a role in enhancing viral replication and contribute to virulence.

2.
Hematology ; 25(1): 438-445, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33210974

RESUMO

Objectives: We aimed to determine the clinical and genetic characteristics of a boy diagnosed with the ß-thalassemia trait. He also had hereditary spherocytosis (HS) that had been overlooked for 7 years. Methods: Blood samples collected from the proband and his family were assessed by laboratory tests, and next-generation sequencing (NGS) and Sanger sequencing. Results: The ß-thalassemia trait was complicated with HS in the proband. Compound heterozygous mutations of the Spectrin Alpha, Erythrocytic 1 (SPTA1) gene, c.83G > A and c.190G > A in the proband were inherited from his mother and father, respectively, and he also had the heterozygous c.126_129delCTTT mutation in the Hemoglobin Subunit Beta (HBB) gene. The c.190G > A mutation has not yet been added to the Human Gene Mutation Database (HGMD®). The heterozygous HBB c.126_129delCTTT mutation was inherited from his mother, and his older brother also had this mutation. Conclusion: Compared with other patients with either HS or ß-thalassemia, this proband with both HS and the ß-thalassemia trait had very complicated laboratory findings, which resulted in HS being overlooked for 7 years. Genetic testing is invaluable for the differential diagnosis of hereditary anemias with overlapping clinical features.

3.
Mol Genet Genomic Med ; : e1548, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33220166

RESUMO

BACKGROUND: Numerous microRNAs (miRNAs) have been identified as functional molecules in Alzheimer's disease (AD) pathogenesis. This study aimed to investigate the diagnostic value of microRNA-485-3p (miR-485-3p) in AD patients, evaluate the effect of miR-485-3p on neuronal viability and neuroinflammation, as well as the underlying molecular mechanisms. METHODS: Quantitative Real-Time PCR was used to estimate expression of miR-485-3p and AKT3. A ROC analysis was used to evaluate the diagnostic value of miR-485-3p. The correlation of miR-485-3p with patients' MMSE score and inflammatory response was analyzed. Using Aß-treated SH-SY5Y and BV2 cells models, the effects of miR-485-3p on neuronal proliferation, apoptosis, and neuroinflammation were explored. A luciferase reporter assay was used to confirm the target gene of miR-485-3p in both SH-SY5Y and BV2 cells. RESULTS: Serum miR-485-3p expression was significantly upregulated in AD patients and cell models, which had a high diagnostic accuracy and correlated with MMSE score and inflammatory response in AD patients. The knockdown of miR-485-3p in SH-SY5Y and BV2 cells was found to significantly reverse the effect of Aß treatment on neuronal viability and neuroinflammation. AKT3 was determined as a target of miR-485-3p, which might mediate the biological function of miR-485-3p in AD pathogenesis. CONCLUSION: All the data indicated that increased serum miR-485-3p serves as a diagnostic biomarker in AD patients, and knockdown of miR-485-3p exerts a neuroprotective role by improving neuronal viability and weakening neuroinflammation, which may be mediated by AKT3. This study may provide a novel biomarker and therapeutic target for AD therapy.

4.
Pharmacol Res ; : 105298, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33220422

RESUMO

Closely associated with visceral obesity, hepatic steatosis resulting from non-alcoholic fatty liver disease (NAFLD) exacerbates insulin resistance. Developing effective drugs to treat NAFLD is imperative. Here, we investigated the pharmacological mechanism of ugonin J (UJ) in controlling metabolic disorder and ameliorating NAFLD pathophysiology in diet-induced obese mice. The effects of UJ were assessed in 5-week-old C57BL/6 J mice fed a high-fat diet (HFD) for 12 weeks. UJ treatment averted HFD-induced body weight gain by reducing fat deposition in adipose tissues and reduced HFD-induced hyperlipidemia and hepatic inflammation. UJ also improved HFD-induced glucose tolerance and insulin resistance. Moreover, the mode of action of UJ was analyzed in palmitate (PA)-induced steatotic human HuS-E/2 hepatocytes and in hyperglycemia-simulating rat BRIN-BD11 pancreatic ß cells. In PA-induced steatotic human hepatocytes, UJ treatment promoted lipid clearance via pAMPK, pACC and CPT-1 upregulation and SREBP-1c downregulation. Interestingly, UJ upregulated Akt activity in hepatocytes and increased insulin secretion from ß cells in acute insulin secretion tests. Taken together, UJ improved adipocyte hypertrophy, hyperinsulinemia, hyperglycemia, hyperlipidemia and fat deposition in livers. UJ also reduced fatty acid accumulation by modulating key metabolic regulators. Our findings demonstrated the therapeutic potential of UJ for the treatment of NAFLD and diet-induced metabolic disorders.

5.
J Agric Food Chem ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33170671

RESUMO

As one of the empirical models of the chronic central inflammatory response, a spinal cord injury (SCI) deteriorates the neuronal survival and results in irreversible motor and sensory dysfunction below the injury area. Our previous studies have reported that maize bran feruloylated oligosaccharides (FOs) exert significant anti-inflammatory activities both in diabetes and colitis. However, no direct evidence of FOs alleviating central nervous inflammation was stated. This study aimed to investigate the therapeutic effect of FOs on SCI and its potential mechanism. Our results indicated that 4 weeks of FO administration effectively mitigated the inflammatory response via decreasing the number of microglia (labelled with Iba1), result in the expression of IL-1α, IL-2, IL-6, IL-18 and TNF-α downregulating, but the level of IL-10 and BDNF increases in the injured spinal cord. Moreover, FOs enhanced neuronal survival, ameliorated the scar cavities, and improved behaviors, including Basso mouse scale (BMS) scores and the gait of mice after SCI. Together, these results demonstrated that administration of FOs showed superior functional recovery effects in a SCI model. Also, FOs may modulate inflammatory activities by regulating the expression of proinflammatory factors, decreasing the production of inflammatory cells, and promoting functional recovery through the MAPK pathway following SCI.

6.
Yi Chuan ; 42(11): 1133-1139, 2020 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-33229319

RESUMO

Medical Genetics bridges basic research and clinical studies. It is one of the important basic courses for medical students. To cultivate students' self-regulated learning ability and improve the teaching quality of Medical Genetics, a presentation-assimilation-discussion (PAD) class mode is adopted in the teaching process. In the teaching setup, we gave students the proceedings and time guarantee for self-regulated learning, and guided the students through teaching, discussion and homework for their independent learning. The resulting evaluation of "Self-Regulated Learning Scale for College Students" shows that the students' learning motivation and learning strategy are enhanced compared with those before the implementation of PAD teaching, the total score of the evaluation is significantly increased, the students' self-regulated learning ability is improved, and satisfactory teaching results are achieved. We conclude that PAD class could contribute to students' self-regulated learning.

7.
J Cell Physiol ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230845

RESUMO

Hepatic stellate cell (HSC) activation plays an important role in the pathogenesis of liver fibrosis, and epithelial-mesenchymal transition (EMT) is suggested to potentially promote HSC activation. Superoxide dismutase 3 (SOD3) is an extracellular antioxidant defense against oxidative damage. Here, we found downregulation of SOD3 in a mouse model of liver fibrosis induced by carbon tetrachloride (CCl4 ). SOD3 deficiency induced spontaneous liver injury and fibrosis with increased collagen deposition, and further aggravated CCl4 -induced liver injury in mice. Depletion of SOD3 enhanced HSC activation marked by increased α-smooth muscle actin and subsequent collagen synthesis primarily collagen type I in vivo, and promoted transforming growth factor-ß1 (TGF-ß1)-induced HSC activation in vitro. SOD3 deficiency accelerated EMT process in the liver and TGF-ß1-induced EMT of AML12 hepatocytes, as evidenced by loss of E-cadherin and gain of N-cadherin and vimentin. Notably, SOD3 expression and its pro-fibrogenic effect were positively associated with sirtuin 1 (SIRT1) expression. SOD3 deficiency inhibited adenosine monophosphate-activated protein kinase (AMPK) signaling to downregulate SIRT1 expression and thus involving in liver fibrosis. Enforced expression of SIRT1 inhibited SOD3 deficiency-induced HSC activation and EMT, whereas depletion of SIRT1 counteracted the inhibitory effect of SOD3 in vitro. These findings demonstrate that SOD3 deficiency contributes to liver fibrogenesis by promoting HSC activation and EMT process, and suggest a possibility that SOD3 may function through modulating SIRT1 via the AMPK pathway in liver fibrosis.

8.
PLoS One ; 15(11): e0241294, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33147244

RESUMO

PURPOSE: Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that regulates intraocular pressure (IOP) by altering extracellular matrix (ECM) homeostasis within the trabecular meshwork (TM). We hypothesized that the lower IOP previously observed in SPARC -/- mice is due to a greater outflow facility. METHODS: Mouse outflow facility (Clive) was determined by multiple flow rate infusion, and episcleral venous pressure (Pe) was estimated by manometry. The animals were then euthanized, eliminating aqueous formation rate (Fin) and Pe. The C value was determined again (Cdead) while Fin was reduced to zero. Additional mice were euthanized for immunohistochemistry to analyze ECM components of the TM. RESULTS: The Clive and Cdead of SPARC -/- mice were 0.014 ± 0.002 µL/min/mmHg and 0.015 ± 0.002 µL/min/mmHg, respectively (p = 0.376, N/S). Compared to the Clive = 0.010 ± 0.002 µL/min/mmHg and Cdead = 0.011 ± 0.002 µL/min/mmHg in the WT mice (p = 0.548, N/S), the Clive and Cdead values for the SPARC -/- mice were higher. Pe values were estimated to be 8.0 ± 0.2 mmHg and 8.3 ± 0.7 mmHg in SPARC -/- and WT mice, respectively (p = 0.304, N/S). Uveoscleral outflow (Fu) was 0.019 ± 0.007 µL/min and 0.022 ± 0.006 µL/min for SPARC -/- and WT mice, respectively (p = 0.561, N/S). Fin was 0.114 ± 0.002 µL/min and 0.120 ± 0.016 µL/min for SPARC -/- and WT mice (p = 0.591, N/S). Immunohistochemistry demonstrated decreases of collagen types IV and VI, fibronectin, laminin, PAI-1, and tenascin-C within the TM of SPARC -/- mice (p < 0.05). CONCLUSIONS: The lower IOP of SPARC -/- mice is due to greater aqueous humor outflow facility through the conventional pathway. Corresponding changes in several matricellular proteins and ECM structural components were noted in the TM of SPARC -/- mice.

10.
Neuropsychologia ; : 107671, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33189733

RESUMO

Neuroimaging evidence has suggested that Chinese-language processing differs from that of its alphabetic-language counterparts. However, the underlying white matter pathway correlations between semantic and phonological fluency in Chinese-language processing remain unknown. Thus, we investigated the differences between two verbal fluency tests on 50 participants with amnestic mild cognitive impairment (aMCI) and 36 healthy controls (HC) with respect to five groups (ventral and dorsal stream fibers, frontal-striatal fibers, hippocampal-related fibers, and the corpus callosum) of white matter microstructural integrity. Diffusion spectrum imaging was used. The results revealed a progressive reduction in advantage in semantic fluency relative to phonological fluency from HC to single-domain aMCI to multidomain aMCI. Common and dissociative white matter correlations between tests of the two types of fluency were identified. Both types of fluency relied on the corpus callosum and ventral stream fibers, semantic fluency relied on the hippocampal-related fibers, and phonological fluency relied on the dorsal stream and frontal-striatal fibers. The involvement of bilateral tracts of interest as well as the association with the corpus callosum indicate the uniqueness of Chinese-language fluency processing. Dynamic associations were noted between white matter tract involvement and performance on the two fluency tests in four time blocks. Overall, our findings suggest the clinical utility of verbal fluency tests in geriatric populations, and they elucidate both task-specific and language-specific brain-behavior associations.

11.
Nurse Educ Pract ; 49: 102916, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33197708

RESUMO

Professional skill development and socialization require appropriate guidance and learning. We aimed to examine the effect of self-appraisal of the clinical simulation care task (CSCT-SA) action program on the self-learning effectiveness, self-reflection and insight, caring behavior, nursing competence, and professional socialization of novice nursing students. This study has a single-group longitudinal research design. Five measurement variables, including students' self-learning effectiveness, self-reflection and insight, caring behavior, nursing competence, and professional socialization, were assessed at the baseline, middle, and termination points of the study. The generalized estimating equation and a latent growth curve model were used to examine research hypotheses. A total of 92 students (22 male and 70 female students) completed three point surveys. Students' learning effectiveness, self-reflection and insight, caring behavior, nursing competence, and professional socialization presented a positive growth trajectory throughout the CSCT-SA action program series. In addition, latent growth curve analyses indicated that the levels of nursing competence and professional socialization, as well as the changes in these variables, were positively associated with each other. Findings support the key role played by nursing competence in enhancing students' professional socialization, which suggests that such competence should be improved to promote professional socialization.

12.
Medicine (Baltimore) ; 99(47): e23309, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33217865

RESUMO

Laparoscopic anterior resection of rectum (AR) is one of surgical approaches for deeply infiltrating endometriosis (DIE). Up to date, no clinical trials have clearly analyzed the short-term and long-term complications post-surgically, indications or feasibilities for surgical procedure, or post-operative recovery. The aims of this trial were to evaluate the indications for laparoscopic AR, the short-term and long-term complications post-surgically, post-operative recovery.We conducted a prospective study of 29 patients. They were divided into 2 groups. The period of follow-up was 12 months post-surgery. In our study, we recruited patents with laparoscopic AR experiencing failure of medical treatment (3 months) or associated infertility (>2cycles). The operative data and short term and long term complications were recorded. The outcomes of laparoscopic AR group were assessed by questionnaires, such as NRS (numeric rating scale), KESS (Knowles-Eccersley-Scott Symptom Questionnaire), VAS (visual analogue scale), WCS (Wexner constipation score) and ABS (Abdominal Bloating Score), which were compared with the outcomes of medicine group at set time points of baseline, 3 months, 6 months, 9 months and 12 months. The overall outcomes of the two groups were assessed with 5-point Likert Scale.Patients in surgery group were recovery rapidly without serious short term or long term complications. All of NRS, KESS, VAS, WCS, and ABS in surgery group were getting better greatly than that in medicine group (3.04 ±â€Š1.91 vs 5.41 ±â€Š3.01, 5.64 ±â€Š1.54 vs 7.01 ±â€Š1.03, 0.50 ±â€Š0.38 vs 3.58 ±â€Š2.01, 4.43 ±â€Š1.02 vs 8.92 ±â€Š2.45, and 0.61 ±â€Š0.34 vs 1.42 ±â€Š0.71) at 3 months post-operation. However, the advantage of surgery group was almost vanished at 12 months (4.02 ±â€Š2.53 vs 5.99 ±â€Š2.31, 7.42 ±â€Š3.17 vs 10.98 ±â€Š2.53, 1.59 ±â€Š1.3 vs 2.23 ±â€Š1.59, 6.01 ±â€Š2.53 vs 7.90 ±â€Š3.25, and 1.31 ±â€Š1.05 vs 1.39 ±â€Š1.02). Furthermore, we compared the overall outcomes between the 2 groups with 5-point Likert Scale, with confirmation of the advantage at 3 months post-surgically. Additionally, we compared these questionnaires, with the finding that VAS and 5-point Likert Scale of surgery group had the same changes. Finally, a table of indications for laparoscopic AR were tabulated according our clinical experience.Patients can receive benefit from both medicine and laparoscopic AR. However, laparoscopic AR has obvious advantage of rapid symptom relief. Further studies and clinical data collections are required for indications and feasibility of combined therapy.

13.
Mol Cell Biol ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33139493

RESUMO

Pre-eclampsia (PE) is a hypertensive disorder of uncertain etiology that is the leading cause of maternal and fetal morbidity or mortality. The dysregulation of microRNAs (miRNAs) has been highlighted as a potential factor involved in the development of PE. Therefore, our study investigated a novel miRNA, miR-183 and its underlying association with PE. Expression of miR-183, forkhead box P1 (FOXP1) and G protein subunit gamma 7 (GNG7) in placental tissues of patients with PE was determined. Gain- and loss-of-function experiments were conducted to explore modulatory effects of miR-183, FOXP1, and GNG7 on the viability, invasion, and angiogenesis of trophoblast cells in PE. Finally, we undertook in vivo studies to explore effects of FOXP1 in the PE model. The results revealed poor expression of FOXP1 and significant elevations in miR-183 and GNG7 expression in placental tissues of PE patients. FOXP1 was observed to promote proliferation, invasion, and angiogenesis in human chorionic trophoblastic cells. miR-183 resulted in depletion of FOXP1 expression, while FOXP1 was capable of restraining GNG7 expression and promoting the mTOR pathway. The findings confirmed the effects of FOXP1 on PE. In conclusion, miR-183 exhibits an inhibitory role in PE through suppression of FOXP1 and upregulation of GNG7.

14.
Dalton Trans ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33150903

RESUMO

The separation of C2H2 and CO2 is of industrial significance but is highly challenging due to their close similarities in physical-chemical properties. Metal-organic frameworks (MOFs) with tailored pore structures and tunable pore surfaces for the separation of C2H2/CO2 mixture are described in this perspective article. In terms of adsorption selectivity, MOF is classified into C2H2-selective MOF and CO2-selective MOF, which are discussed separately. Herein, we intend to present a short summary of the important advancements in C2H2/CO2 separation with MOFs. The relationship between the separation performance and structural features of MOFs, together with the separation mechanisms, has been discussed in detail. The challenges, research trends and opportunities in C2H2/CO2 separation with MOFs are highlighted.

15.
Math Biosci Eng ; 17(5): 5395-5413, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-33120558

RESUMO

Instantaneous frequency can well track and reflect the transient information of signal, so it plays an important role in the analysis and processing of the non-stationary signal. In this paper, the single component signal is compared with the Second Order Differential Equation in polar coordinates. Based on this, a threshold segmentation instantaneous frequency calculation method is proposed. This method is mainly for characteristics of the non-stationary signal, use the change of the area around the signal and the x axis to determine the amplitude mutation point of each single component signal, and perform segmentation. Simulations, mathematical derivations and experimental tests are used to highlight the performance of the proposed method. It is not only simple in calculation, but also can reduce the unnecessary influence of non-stationary signal amplitude mutation on instantaneous frequency, and can effectively judge the fault of rolling bearing in fault diagnosis.

16.
Math Biosci Eng ; 17(5): 5864-5882, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-33120580

RESUMO

The high sampling frequency of traditional Nyquist sampling theory not only puts greater requirements on the sampling equipment, but also generates a large amount of data, which increases the difficulty of information transmission and storage. To this end, this paper proposes a rolling bearing fault signal detection method based on compressed sensing combined with a neural network. Based on the theory of compressed sensing, the observations obtained from compression sampling are divided into two sets of data. Given the one set of data, the predictive ability of the nonlinear time series through the neural network can predict the second set of observed values. The predicted observations are used to reconstruct the signal, thereby reducing the amount of data to be stored and transmitted and realizing secondary compression of the signal.

17.
Interact Cardiovasc Thorac Surg ; 31(5): 718-726, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33051664

RESUMO

OBJECTIVES: An optimal ventilation strategy that causes as little mechanical stress and inflammation as possible is critical for patients undergoing pneumonectomy. The aim of this study was to determine whether adaptive support ventilation (ASV) can provide protective ventilation to the remaining lung after pneumonectomy with minimal mechanical stress and less inflammation than volume-control ventilation (VCV). METHODS: In this study, 15 pigs were randomly allocated to 3 groups (n = 5 for each group): the control group, the VCV group and the ASV group. After left pneumonectomy, the VCV group was treated with the volume-control set to 20 ml/kg, and the ASV group with the mode set to achieve 60% of the minute ventilation of 2 lungs. RESULTS: The ASV group had lower alveolar strain than the VCV group. The ASV group exhibited less lung injury and greater alveolar fluid clearance than the VCV group (13.3% vs -17.8%; P ≤ 0.018). Ventilator-induced lung injury was associated with changes in the cytokine levels in the exhaled breath condensate, differential changes in plasma and changes in the cytokines in the bronchoalveolar lavage fluid. Expression of 3 microRNAs (miR449b-3p, P ≤ 0.001; miR451-5p, P = 0.027; and miR144-5p, P = 0.008) was increased in the VCV group compared with the ASV group. CONCLUSIONS: The ASV mode was capable of supporting rapid, shallow breathing patterns to exert lung-protective effects in a porcine postpneumonectomy model. Further investigation of microRNAs as biomarkers of ventilator-induced lung injury is warranted.

18.
Adv Biosyst ; : e2000094, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33124179

RESUMO

This study determines whether the viability of mesenchymal stem cell (MSC) in vitro is most sensitive to oxygen supply, energetic substrate supply, or accumulation of lactate. Mouse unmodified (wild type (WT)) and erythropoietin (EPO) gene-modified MSC is cultured for 7 days in normoxic (21%) and anoxic conditions. WT-MSC is cultured in anoxia for 45 days in high and regular glucose media and both have similar viability when compared to their normoxic controls at 7 days. Protein production of EPO-MSC is unaffected by the absence of oxygen. MSC doubling time and post-anoxic exposure is increased (WT: 32.3-73.3 h; EPO: 27.2-115 h). High glucose leads to a 37% increase in cell viability at 13 days and 17% at 30 days, indicating that MSC anoxic survival is affected by supply of metabolic substrate. However, after 30 days, little difference in viability is found, and at 45 days, complete cell death occurs in both the conditions. This death cannot be attributed to lack of glucose or lactate levels. MSC stemness is retained for both osteogenic and adipogenic differentiations. The absence of oxygen increases the doubling time of MSC but does not affect their viability, protein production, or differentiation capacity.

19.
Life Sci ; 262: 118519, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33010279

RESUMO

AIM: Neuroinflammation is a potent pathological process of various neurodegenerative diseases. Sulforaphane (SFN) is a natural product and acts as a neuroprotective agent to suppress inflammatory response in brain. The present study investigated the protective effect of Sulforaphane (SFN) on lipopolysaccharide (LPS)-induced neuroinflammation. MATERIALS AND METHODS: Rats were divided into three groups: control group, LPS group and LPS + SFN group. Morris water maze test was carried out to evaluate the spatial memory and learning function of rats. The inflammatory cytokines levels in hippocampal tissues, plasma were measured by ELISA. The western blot was used to detect Cezanne/NF-κB signalling. For in vitro study, the Cezanne siRNA and scrambled control were transfected into BV2 cells, and then treated with or without 20 µM SFN before exposed to LPS. The inflammatory cytokines levels and Cezanne/NF-κB signalling were detected by ELISA and western blot, respectively. Co-IP assay were applied to investigate the regulation of Cezanne on ubiquitination of TRAF6 and RIP1. KEY FINDINGS: SFN improved LPS-induced neurocognitive dysfunction in rats. It inhibited the neuroinflammation and activation of NF-κB pathway induced by LPS. The modulation of TRAF6 and RIP1 ubiquitination by Cezanne was playing a pivotal role in relation to the mechanism of SFN inhibiting NF-κB pathway. SIGNIFICANCE: The results of our study demonstrated that SFN could attenuate LPS-induced neuroinflammation through the modulation of Cezanne/NF-κB signalling.

20.
Immunity ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33096040

RESUMO

Polyreactivity is the ability of a single antibody to bind to multiple molecularly distinct antigens and is a common feature of antibodies induced upon pathogen exposure. However, little is known about the role of polyreactivity during anti-influenza virus antibody responses. By analyzing more than 500 monoclonal antibodies (mAbs) derived from B cells induced by numerous influenza virus vaccines and infections, we found mAbs targeting conserved neutralizing influenza virus hemagglutinin epitopes were polyreactive. Polyreactive mAbs were preferentially induced by novel viral exposures due to their broad viral binding breadth. Polyreactivity augmented mAb viral binding strength by increasing antibody flexibility, allowing for adaption to imperfectly conserved epitopes. Lastly, we found affinity-matured polyreactive B cells were typically derived from germline polyreactive B cells that were preferentially selected to participate in B cell responses over time. Together, our data reveal that polyreactivity is a beneficial feature of antibodies targeting conserved epitopes.

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