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1.
J Healthc Eng ; 2021: 3361755, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745495

RESUMO

Mental health issues are alarmingly on the rise among undergraduates, which have gradually become the focus of social attention. With the emergence of some abnormal events such as more and more undergraduates' suspension, and even suicide due to mental health issues, the social attention to undergraduates' mental health has reached a climax. According to the questionnaire of undergraduates' mental health issues, this paper uses keyword extraction to analyze the management and plan of undergraduates' mental health. Based on the classical TextRank algorithm, this paper proposes an improved TextRank algorithm based on upper approximation rough data-deduction. The experimental results show that the accurate rate, recall rate, and F1 of proposed algorithm have been significantly improved, and the experimental results also demonstrate that the proposed algorithm has good performance in running time and physical memory occupation.

2.
Materials (Basel) ; 14(21)2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34771979

RESUMO

Iron ore tailings (IOTs) are gradually used as building materials to solve the severe ecological and environmental problems caused by their massive accumulation. However, the bulk density of IOT as aggregate is too large, which seriously affects the concrete properties. Therefore, in this paper, the effect of hydroxypropyl methylcellulose (HPMC) on the workability, mechanical properties, and durability of concrete prepared from IOT recycled aggregate was studied. The action mechanism of HPMC on the workability and the mechanical properties of the IOT concrete was analyzed by mercury intrusion porosimetry (MIP) and scanning electron microscope (SEM). The results show that HPMC can effectively improve the segregation problem caused by the sinking and air entrainment of IOT aggregate and improve the crack resistance of concrete with little effect on its compressive strength and electric flux. These results are due to the air-entraining thickening effect of HPMC, which improves the slurry viscosity, hinders the sinking of aggregate, and improves the workability. At the same time, HPMC film, after concrete hardening, will bridge the slurry and aggregate through physical and chemical effects, hinder the propagation of microcracks, and improve the crack resistance.

3.
Molecules ; 26(21)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34770750

RESUMO

Lithium-sulfur batteries (LSBs) are considered one of the most promising candidates for next-generation energy storage owing to their large energy capacity. Tremendous effort has been devoted to overcoming the inherent problems of LSBs to facilitate their commercialization, such as polysulfide shuttling and dendritic lithium growth. Pouch cells present additional challenges for LSBs as they require greater electrode active material utilization, a lower electrolyte-sulfur ratio, and more mechanically robust electrode architectures to ensure long-term cycling stability. In this review, the critical challenges facing practical Li-S pouch cells that dictate their energy density and long-term cyclability are summarized. Strategies and perspectives for every major pouch cell component-cathode/anode active materials and electrode construction, separator design, and electrolyte-are discussed with emphasis placed on approaches aimed at improving the reversible electrochemical conversion of sulfur and lithium anode protection for high-energy Li-S pouch cells.

4.
Anim Sci J ; 92(1): e13660, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34786795

RESUMO

Complement pathways participate in the regulation of innate immune system, and complement activation is inhibited in normal pregnancy. The liver plays key roles in the modulation of immunity and tolerance, but it is unclear that early pregnancy induces the changes in expression of complement components in the ovine maternal liver. The aim of the present study was to explore the expression of complement components in the liver using quantitative real-time polymerase chain reaction (PCR), Western blot, and immunohistochemistry. Maternal livers were collected on Day 16 of the estrous cycle and Days 13, 16, and 25 of gestation. The results indicated that early pregnancy suppressed the expression of C1q, C1r, C1s, C2, C4a, C5b, and C9 in the maternal liver, but C3 expression was increased. In addition, C3 protein was located in the endothelial cells of the proper hepatic arteries and portal veins and hepatocytes. In summary, the downregulaltion of C1q, C1r, C1s, C2, C4a, C5b, and C9 may be involved in the suppression of complement activation, and upregulation of C3 is related to the modulation of maternal immune tolerance in ovine liver.

5.
Esophagus ; 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34800196

RESUMO

BACKGROUND: Benign esophageal strictures result from caustic or radiation injury or surgical procedures. Statins have anti-inflammatory and anti-fibrotic activities. We examined the role of rosuvastatin in preventing benign esophageal fibrosis and stricture formation in a rabbit model. METHODS: Twenty-six rabbits were assigned to control and rosuvastatin groups. The rabbits in the rosuvastatin group were administered rosuvastatin 5 mg/day, 2 weeks prior to the esophageal stricture phase. Esophageal strictures were established by applying 4% sodium hydroxide solution to the middle esophagus. Esophagography was performed to evaluate the degree of esophageal stenosis, and histopathologic assessment of esophageal tissue damage was performed with hematoxylin-eosin and Masson staining. The expressions of transforming growth factor-ß1 (TGF-ß1), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) were examined by immunohistochemistry. RESULTS: The incidence of strictures was significantly lower in the rosuvastatin group. Esophagography demonstrated mild stenosis in the narrowest inner esophageal diameter in the rosuvastatin group than in the control group, and Masson staining demonstrated significantly less collagen deposition in the rosuvastatin group. In addition, immunohistochemistry results showed that the expressions of TGF-ß1, CTGF, and α-SMA significantly reduced in the rosuvastatin group. CONCLUSIONS: The present study demonstrated that rosuvastatin prevents benign esophageal stricture formation. This effect may be exerted through the anti-fibrotic activity of rosuvastatin, which may be exerted by the inhibition of CTGF and α-SMA production induced by TGF-ß1.

6.
Biochem Biophys Res Commun ; 583: 7-13, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34715498

RESUMO

Rheumatoid arthritis (RA) is an inflammatory disease that causes hyperplasia of synovial tissue and cartilage destruction. This research was to investigate the effects of lncRNA GAS5/miR-361-5p/PDK4 on rheumatoid arthritis. By qRT-PCR, GAS5 and PDK4 were found to be overexpressed in synovial tissue, fibroblast-like synoviocytes of RA patients and LPS-induced chondrocytes, while the miR-361-5p expression was significantly reduced. GAS5 overexpression resulted in a decrease in the proliferation and Bcl-2 protein expression, and an increase in the Bax protein level. On the contrary, miR-361-5p sponged by GAS5 could accelerate chondrocyte proliferation, inhibit apoptosis. PDK4 targeted by miR-361-5p could inhibit RA, and partially eliminated the effect of miR-361-5p on RA. Our study suggested that GAS5 suppressed RA by competitively adsorbing miR-361-5p to modulate PDK4 expression.

7.
Sci Rep ; 11(1): 21273, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34711868

RESUMO

Increasingly, researchers are using innovative methods to census marine life, including identification of environmental DNA (eDNA) left behind by organisms in the water column. However, little is understood about how eDNA is distributed in the ocean, given that organisms are mobile and that physical and biological processes can transport eDNA after release from a host. Particularly in the vast mesopelagic ocean where many species vertically migrate hundreds of meters diurnally, it is important to link the location at which eDNA was shed by a host organism to the location at which eDNA was collected in a water sample. Here, we present a one-dimensional mechanistic model to simulate the eDNA vertical distribution after its release and to compare the impact of key biological and physical parameters on the eDNA vertical and temporal distribution. The modeled vertical eDNA profiles allow us to quantify spatial and temporal variability in eDNA concentration and to identify the most important parameters to consider when interpreting eDNA signals. We find that the vertical displacement by advection, dispersion, and settling has limited influence on the eDNA distribution, and the depth at which eDNA is found is generally within tens of meters of the depth at which the eDNA was originally shed from the organism. Thus, using information about representative vertical migration patterns, eDNA concentration variability can be used to answer ecological questions about migrating organisms such as what depths species can be found in the daytime and nighttime and what percentage of individuals within a species diurnally migrate. These findings are critical both to advance the understanding of the vertical distribution of eDNA in the water column and to link eDNA detection to organism presence in the mesopelagic ocean as well as other aquatic environments.

8.
J Biomed Res ; 35(5): 361-370, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34628403

RESUMO

Superficial esophageal squamous cell carcinoma (SESCC) is defined as carcinoma with mucosal or submucosal invasion, regardless of regional lymph node metastasis (LNM). The lymph node status is not only a key factor to determine the training strategy, but also the most important prognostic factor in esophageal cancer. In this study, we establish a clinical nomogram for predicting LNM in patients with SESCC. A predictive model was established based on the training cohort composed of 711 patients who underwent esophagectomy for SESCC from December 2009 to June 2018. A prospective cohort of 203 patients from June 2018 to January 2019 was used for validation. Favorable calibration and well-fitted decision curve analysis were conducted and good discrimination was observed (concordance index [C-index], 0.860; 95% confidence interval [CI], 0.825-0.894) through internal validation. The external validation cohort presented good discrimination (C-index, 0.916; 95% CI, 0.860-0.971). This model may facilitate the prediction of LNM in patients with SESCCs.

9.
BMC Med Genomics ; 14(1): 256, 2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34715861

RESUMO

BACKGROUND: Lethal respiratory failure is primarily caused by a deficiency of pulmonary surfactant, and is the main cause of neonatal death among preterm infants. Pulmonary surfactant metabolism dysfunction caused by variants in the ABCA3 gene is a rare disease with very poor prognosis. Currently, the mechanisms associated with some ABCA3 variants have been determined, including protein mistrafficking and impaired phospholipid transport. However, some novel variants and their underlying pathogenesis has not been fully elucidated yet. In this study we aimed to identify the genetic features in a family with lethal respiratory failure. METHODS: We studied members of two generations of a Chinese family, including a female proband, her parents, her monozygotic twin sister, and her older sister. Trio whole exome sequencing (WES) were used on the proband and her parents to identify the ABCA3 variants. Sanger sequencing and real-time quantitative polymerase chain reaction (PCR) were used on the monozygotic twin sister of proband to validate the ABCA3 synonymous variant and exon deletion, respectively. The potential pathogenicity of the identified synonymous variant was predicted using the splice site algorithms dbscSNV11_AdaBoost, dbscSNV11_RandomForest, and Human Splicing Finder (HSF). RESULTS: All patients showed severe respiratory distress, which could not be relieved by mechanical ventilation, supplementation of surfactant, or steroid therapy, and died at an early age. WES analysis revealed that the proband had compound heterozygous ABCA3 variants, including a novel synonymous variant c.G873A (p.Lys291Lys) in exon 8 inherited from the mother, and a heterozygous deletion of exons 4-7 inherited from the father. The synonymous variant was consistently predicted to be a cryptic splice donor site that may lead to aberrant splicing of the pre-mRNA by three different splice site algorithms. The deletion of exons 4-7 of the ABCA3 gene was determined to be a likely pathogenic variant. The variants were confirmed in the monozygotic twin sister of proband by Sanger sequencing and qPCR respectively. The older sister of proband was not available to determine if she also carried both ABCA3 variants, but it is highly likely based on her clinical course. CONCLUSIONS: We identified a novel synonymous variant and a deletion in the ABCA3 gene that may be responsible for the pathogenesis in patients in this family. These results add to the known mutational spectrum of the ABCA3 gene. The study of ABCA3 variants may be helpful for the implementation of patient-specific therapies.

10.
J Nanobiotechnology ; 19(1): 335, 2021 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34689765

RESUMO

Photothermal therapy (PTT), which converts light energy to heat energy, has become a new research hotspot in cancer treatment. Although researchers have investigated various ways to improve the efficiency of tumor heat ablation to treat cancer, PTT may cause severe damage to normal tissue due to the systemic distribution of photothermal agents (PTAs) in the body and inaccurate laser exposure during treatment. To further improve the survival rate of cancer patients and reduce possible side effects on other parts of the body, it is still necessary to explore PTAs with high selectivity and precise treatment. In this review, we summarized strategies to improve the treatment selectivity of PTT, such as increasing the accumulation of PTAs at tumor sites and endowing PTAs with a self-regulating photothermal conversion function. The views and challenges of selective PTT were discussed, especially the prospects and challenges of their clinical applications.

11.
Materials (Basel) ; 14(17)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34500898

RESUMO

In this paper iron tailing sand (TS) are used as aggerate to develop ultra high-performance concrete (UHPC). The mix proportion of UHPC is designed and TS were added by 25%, 50%, 75% and 100% (wt.%, i.e., weight percentage) to replace natural river sand. Firstly, the influence of TS on the slurry behavior was carried out. The experimental result indicates that with the continuously increasing content of TS, the workability of slurry decreases, while the air content increases. Considering the workability, the optimal replacing dosage of TS should be less than 50%. Then, tests for the hardened specimens were taken. The compressive behavior and micro-porosity deteriorate with increasing content of TS, and the compressive strength had a positive linear relationship with the workability, which indicated that the decline the compressive behavior is mainly due to the loss of flowability. Finally, autogenous shrinkages of UHPC with different TS dosage were also tested. At the same time, the micro-structure of specimens was discussed, which was deteriorate with the increasing dosage of TS. Therefore, comprehensively considering the compressive behavior, micro-structure and shrinkage behavior, as much as 50% of the aggregate could be replaced by TS when developing UHPC.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34585820

RESUMO

Developing new materials for the fabrication of resistive random-access memory is of great significance in this period of big data. Herein, we present a novel design strategy of embedding donor (D) and acceptor (A) fragments into imine-linked frameworks to construct resistive switching covalent organic frameworks (COFs) for high-performance memristors. Two D-A-type two-dimensional COFs, COF-BT-TT and COF-TT-TVT, were designed and synthesized using a conventional solvothermal approach, and high-quality thin films of these materials deposited on ITO substrate exhibited great potential as an active layer for memristors. Rewritable memristors based on 100 nm thick COF-TT-BT and COF-TT-TVT films showed a high ON/OFF current ratio (ca. 105 and 104 ) and low driving voltage (1.30 and 1.60 V). The cycle period and retention time for COF-TT-BT-based rewritable devices were as high as 319 cycles and 3.3×104  s at a constant voltage of 0.1 V (160 cycles and 1.2×104  s for the COF-TT-TVT memristor).

13.
Appl Microbiol Biotechnol ; 105(18): 6853-6870, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34477941

RESUMO

In wild strains of Bacillus, a handful of extracellular natural products act as signals that can regulate multicellular behavior, but relatively little is known about molecular mechanisms' detail. We proposed a previously unreported molecular mechanism for triggering multicellularity in B. velezensis Bs916 by an endogenous cyclic lipopeptide, bacillomycin L. The genome-wide effect on gene expression was caused by the disruption of bacillomycin L gene cluster, and 100 µg/mL bacillomycin L was revealed by quantitative transcriptomics. A total of 878 differentially expressed genes among Bs916, Δbl, and Δbl + 100BL were identified and grouped into 9 functional categories. The transcription levels of 40 candidate genes were further evaluated by RT-qPCR analysis. The expression of eight candidate genes regulated by bacillomycin L in a dose-dependent manner was revealed by LacZ fusion experiment. Although the addition of bacillomycin L could not completely restore the expression levels of the differentially regulated genes in △bl, our results strongly suggest that bacillomycin L acts as a tuning signal of swarming motility and complex biofilm formation by indirectly regulating the expression levels of some two-component systems (TCSs) connector genes, particularly including several Raps that potentially regulate the phosphorylation levels of three major regulators ComA, DegU, and Spo0A.Key points• Proposed model for bacillomycin L regulation in B. velezensis Bs916.• Bacillomycin L can act as an extracellular signal to regulate the phosphorylation levels of three major regulators, ComA, DegU, and Spo0A and control the multicellular processes of vegetative growth, competent, motility, matrix production, sporulation, and autolysis.


Assuntos
Bacillus , Lipopeptídeos , Peptídeos Catiônicos Antimicrobianos , Bacillus/genética , Bacillus subtilis , Peptídeos Cíclicos
14.
Front Vet Sci ; 8: 722840, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552976

RESUMO

Peste des petits ruminants virus (PPRV), belonging to the genus Morbillivirus in the family Paramyxoviridae, causes severe infectious disease in small ruminants and has been rapidly spreading in many parts of Africa, the Middle East, and Asia. Although vaccination is considered to be an effective means of controlling PPR, the heat-sensitive nature of the vaccines against PPRV greatly limits their application in areas with a hot climate. In the present study, we investigated the anti-PPRV effects of favipiravir and sought to identify the underlying mechanisms in vitro using the Vero cell line. MTT assays, Western blotting, indirect immunofluorescence assays, virus plaque formation assays, and qRT-PCR were used to assess the effects of favipiravir on the life cycle of PPRV and the expression of RNA-dependent RNA polymerase (RdRp). Additionally, the expression levels of JAK1, STAT1, phosphorylated (p)-STAT1, PI3K, AKT, and p-AKT, as well as those of signaling molecules acting downstream of the JAK/STAT and PI3K/AKT signaling pathways, were determined by Western blotting and qRT-PCR. The results indicated that, in PPRV-infected, favipiravir-treated Vero cells, the attachment, invasion, replication, and release of PPRV were significantly inhibited, as was the expression of RdRp, when compared with that in untreated PPRV-infected cells. Furthermore, in favipiravir-treated cells, the expression of JAK1 and STAT1 was downregulated, whereas that of p-STAT1 was significantly upregulated. Similarly, the expression levels of PKR, IRF9, ISG54, and MxA proteins that are associated with innate antiviral activity in host cells were also markedly increased. Moreover, with favipiravir treatment, the expression of PI3K and p-AKT and the p-AKT/AKT ratio were significantly decreased, whereas the expression of AKT was noticeably upregulated. The expression of GSK3, NF-κB p65, p-NF-κB p65, and BAD was also increased with favipiravir treatment, while the expression of CREB, p-CREB, p-GSK3, and Bcl-2 was slightly decreased. In addition, all the p-GSK3/GSK3, p-CREB/CREB, p-NF-κB/NF-κB, and p-BAD/BAD ratios were significantly reduced in favipiravir-treated cells. These results implied that the antiviral effectivity of favipiravir against PPRV is mediated by the JAK/STAT and PI3K/AKT pathways and that favipiravir has potential for use as an effective antiviral agent against PPRV.

15.
ACS Appl Mater Interfaces ; 13(35): 41657-41668, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34432426

RESUMO

Triboelectric nanogenerators (TENGs) are newly developed energy-harvesting mechanisms, which can efficiently transmute irregular mechanical energy into scarce electrical energy. However, the electrical performance of TENGs shows a decreasing tendency with the increase in temperature, and the negative effect caused by friction heat and operating environmental thermal stresses for the output performance, durability, and reliability are still a bottleneck, restricting the practical application of TENG electronic devices. Especially for wearable TENG devices, the heat-induced temperature rise evokes extreme discomfort and even hazards to human health. To effectively suppress the thermal negative effect and maintain the high-temperature steady electrical performance of TENGs, a novel thermo-regulating TENG (Tr-TENG) based on phase change materials (PCMs) is designed. The results state clearly that the Tr-TENG can maintain steady output performance without deterioration by the introduction of PCMs, during continuous heating and natural cooling, while the output performance of conventional TENG is decayed by 18.33%. More importantly, the Tr-TENG possesses high-efficiency thermal management ability, resulting in its improved durability, reliability, and thermal comfort. This study creates new possibilities for the development of advanced multifunctional TENGs with attractive characteristics and desirable performances and promotes the application of TENG electronic devices in harsh environments.

16.
Oxid Med Cell Longev ; 2021: 3843145, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394825

RESUMO

Previous studies have established the pathogenic role of advanced glycation end products (AGEs) accumulation in intervertebral disc degeneration (IDD). Emerging evidence indicates that ER-phagy serves as a crucial cellular adaptive mechanism during stress conditions. This study is aimed at investigating the role of FAM134B-mediated ER-phagy in human nucleus pulposus (NP) cells upon AGEs treatment and exploring its regulatory mechanisms. We observed that AGEs treatment resulted in significantly increased apoptosis, senescence, and ROS accumulation in human NP cells; meanwhile, the enhanced apoptosis and senescence by AGEs treatment could be partially alleviated with the classic ROS scavenger NAC administration. Furthermore, we confirmed that FAM134B-mediated ER-phagy was activated under AGEs stimulation via ROS pathway. Importantly, it was also found that FAM134B overexpression could efficiently relieve intracellular ROS accumulation, apoptosis, and senescence upon AGEs treatment; conversely, FAM134B knockdown markedly resulted in opposite effects. In conclusion, our data demonstrate that FAM134B-mediated ER-phagy plays a vital role in AGEs-induced apoptosis and senescence through modulating cellular ROS accumulation, and targeting FAM134B-mediated ER-phagy could be a promising therapeutic strategy for IDD treatment.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34410548

RESUMO

PURPOSE: Macrophage apoptosis coupled with a defective phagocytic clearance of the apoptotic cells promotes plaque necrosis in advanced atherosclerosis, which causes acute atherothrombotic vascular disease. Nonsteroidal anti-inflammatory drug sulindac derivative K-80003 treatment was previously reported to dramatically attenuate atherosclerotic plaque progression and destabilization. However, the underlying mechanisms are not fully understood. This study aimed to determine the role of K-80003 on macrophage apoptosis and elucidate the underlying mechanism. METHODS: The mouse model of vulnerable carotid plaque in ApoE-/- mice was developed in vivo. Consequently, mice were randomly grouped into two study groups: the control group and the K-80003 group (30 mg/kg/day). Samples of carotid arteries were collected to determine atherosclerotic necrotic core area, cellular apoptosis, and oxidative stress. The effects of K-80003 on RAW264.7 macrophage apoptosis, oxidative stress, and autophagic flux were also examined in vitro. RESULTS: K-80003 significantly suppressed necrotic core formation and inhibited cellular apoptosis of vulnerable plaques. K-80003 can also inhibit 7-ketocholesterol-induced macrophage apoptosis in vitro. Furthermore, K-80003 inhibited intraplaque cellular apoptosis mainly through the suppression of oxidative stress, which is a key cause of advanced lesional macrophage apoptosis. Mechanistically, K-80003 prevented 7-ketocholesterol-induced impairment of autophagic flux in macrophages, evidenced by the decreased LC3II and SQSTM1/p62 expression, GFP-RFP-LC3 cancellation upon K-80003 treatment. CONCLUSION: Inhibition of macrophage apoptosis and necrotic core formation by autophagy-mediated reduction of oxidative stress is one mechanism of the suppression of plaque progression and destabilization by K-80003.

18.
ACS Appl Mater Interfaces ; 13(34): 40922-40931, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34410699

RESUMO

The capability to manipulate the size of the electronic band gap is of importance to semiconductor technology. Among these, a wide direct band gap is particularly helpful in optoelectronic devices due to the efficient utilization of blue and ultraviolet light. Here, we reported a paraffin-enabled compressive folding (PCF) strategy to widen the band gap of two-dimensional (2D) materials. Due to the large thermal expansion coefficient of paraffin, folded 2D materials can be achieved via thermal engineering of the paraffin-assisted transfer process. It can controllably introduce 0.2-1.3% compressive strain onto folded structures depending on the temperature differences and transfer the folding product to both rigid and soft substrates. Exemplified by MoS2, its folded multilayers demonstrated blue-shifts at direct gap transition peaks, six times stronger photoluminescence intensity, almost double mobility, and 20 times higher photoresponsivity over unfolded MoS2. This PCF strategy can attain controllable widening band gap of 2D materials, which will open up novel applications in optoelectronics.

20.
Front Immunol ; 12: 679498, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149716

RESUMO

IFN-ß has been the treatment for multiple sclerosis (MS) for almost three decades, but understanding the mechanisms underlying its beneficial effects remains incomplete. We have shown that MS patients have increased numbers of GM-CSF+ Th cells in circulation, and that IFN-ß therapy reduces their numbers. GM-CSF expression by myelin-specific Th cells is essential for the development of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. These findings suggested that IFN-ß therapy may function via suppression of GM-CSF production by Th cells. In the current study, we elucidated a feedback loop between monocytes and Th cells that amplifies autoimmune neuroinflammation, and found that IFN-ß therapy ameliorates central nervous system (CNS) autoimmunity by inhibiting this proinflammatory loop. IFN-ß suppressed GM-CSF production in Th cells indirectly by acting on monocytes, and IFN-ß signaling in monocytes was required for EAE suppression. IFN-ß increased IL-10 expression by monocytes, and IL-10 was required for the suppressive effects of IFN-ß. IFN-ß treatment suppressed IL-1ß expression by monocytes in the CNS of mice with EAE. GM-CSF from Th cells induced IL-1ß production by monocytes, and, in a positive feedback loop, IL-1ß augmented GM-CSF production by Th cells. In addition to GM-CSF, TNF and FASL expression by Th cells was also necessary for IL-1ß production by monocyte. IFN-ß inhibited GM-CSF, TNF, and FASL expression by Th cells to suppress IL-1ß secretion by monocytes. Overall, our study describes a positive feedback loop involving several Th cell- and monocyte-derived molecules, and IFN-ß actions on monocytes disrupting this proinflammatory loop.


Assuntos
Autoimunidade , Comunicação Celular , Interferon beta/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Animais , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , Autoimunidade/efeitos dos fármacos , Comunicação Celular/genética , Comunicação Celular/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças/imunologia , Encefalomielite Autoimune Experimental/etiologia , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/patologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/biossíntese , Interferon beta/farmacologia , Camundongos , Camundongos Knockout , Monócitos/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos
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