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1.
Curr Med Sci ; 39(5): 784-793, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31612397

RESUMO

Huai Qi Huang (HQH) exerts great effects in clinic, such as anti-inflammation, immune-regulation, anti-cancer, and so on. However, the mechanism by which HQH protects juvenile idiopathic arthritis (JIA) is obscure. Thus, we explored deeply the protective mechanisms in juvenile collagen-induced arthritis (CIA) rat model. Pyroptosis is Gasdermin D (GSDMD)-dependent programmed cell death, involved in many diseases, such as sepsis. We investigated whether GSDMD-induced pyroptosis take part in mechanisms of juvenile CIA arthritis. Juvenile Wistar rats (3-4 weeks) were injected intradermally with fully emulsified bovine type II collagen and complete Freund's adjuvant to establish CIA rat models. Later, the CIA rats received oral administration of HQH (4.16 g/kg) once a day from the day 21 of modeling, with the treatment lasting for 28 days. Varieties of indicators were measured for evaluation of anti-inflammation effect of HQH, including hind paw swelling, arthritis scores, micro CT, and histopathological changes and the level of pro-inflammatory cytokines in the serum, including tumor necrosis factor alpha (TNF-±) and interleukin-18 (IL-18). The expression of GSDMD and caspase-1 in the joint synovial tissues was detected. The results demonstrated that the expression of the pyroptotic protein GSDMD and its upstream caspase-1 was significantly increased in the synovial tissues of CIA rats. The treatment of HQH ameliorated the symptoms in CIA rats, reduced levels of pro-inflammatory cytokines and hind paw swelling, down-regulated the expression of GDSMD and caspase-1. GSDMD-induced pyroptosis participated in the pathogenesis of CIA rats. The study supported that HQH can effectively improve joints inflammation of juvenile collagen-induced arthritis rats by inhibiting pyroptosis pathway in the joint synovial tissues.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31589566

RESUMO

Toxoplasma gondii is one of protozoan parasites resulting in zoonosis, which can infect nearly all of warm-blooded hosts, including humans and raccoon dogs (Nyctereutes procyonoides). However, related reports on prevalence and genetic characterization of T. gondii strains in raccoon dogs were few in China. The aim of this study was to survey the prevalence and genetic characterization of T. gondii strains in domestic raccoon dogs from Jilin, Liaoning, and Hebei provinces, northern China. During April 2016 to November 2017, a total of 337 tissue samples collected from domestic raccoon dogs were detected with B1 gene using a nested PCR. And the positive samples were genotyped at 11 genetic markers (SAG1, 5'-and 3'-SAG2, alternative SAG2, SAG3, BTUB, GRA6, L358, PK1, c22-8, c29-2, and Apico) using multilocus PCR-restriction fragment length polymorphism technology. Sixteen out of 337 sika deer (4.75%) were positive with B1 gene by nest PCR. Furthermore, four positive DNA samples were completely typed through further being genotyped, in which three samples were identified as ToxoDB Genotype #9, and one sample was confirmed as ToxoDB Genotype #10. The results of molecular detection not only revealed the existence of T. gondii in domestic raccoon dogs in Jilin, Liaoning, and Hebei for the first time, but also provided the information of genetic diversity. This study also indicated that ToxoDB Genotype #9 as a kind of potential reservoir for T. gondii transmission, may be main genotype in domestic raccoon dogs in China, posing a risk of infection in human health.

3.
Int J Biol Macromol ; 140: 647-652, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31446101

RESUMO

This study investigated effects of mango peel powder on starch digestion properties and quality characteristics of bread, and discussed underneath mechanisms. Starch digestion rate and extent of bread were evaluated in vitro, and bread quality characteristics, including moisture content, volume, color and texture, were evaluated. The results showed that adding mango peel powder could significantly reduce starch digestion rate and digestion extent in bread, and the reduction degree was positively related to the amount of mango peel powder applied. Bread moisture content was improved by mango peel powder, while bread volume was reduced. Bread color was also impacted, showing increased L*, a* and b* values. And incorporation of mango peel powder apparently affected bread texture, resulting in increased hardness and chewiness, as well as decreased cohesiveness. These influences were generally proportional to the amount of mango peel powder applied. When <5% of mango peel powder was incorporated, bread quality was not dramatically changed, although starch digestibility was significantly inhibited. More mango peel powder could further reduce starch digestion; however, bread quality might be deteriorated. These results would provide guidelines for the development of low glycemic index foods, and be beneficial in facilitating comprehensive application of mango peel.

4.
J Pharm Biomed Anal ; 175: 112791, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31398629

RESUMO

The anti-rheumatic fraction (ARF), is responsible for the anti-inflammatory and analgesic effects of Dianbaizhu derived from the aerial part of Gaultheria leucocarpa var. yunnanensis (Ericaceae). The gastrointestinal metabolism of ARF was investigated in vitro through simulating a series of models-gastric juice, intestinal juice, and human intestinal bacteria, analyzed by HPLC-DAD and UPLC-LTQ-Orbitrap-MSn. ARF includes three categories: methyl salicylate glycosides, organic acids and the others. The primordial and metabolic components of ARF bio-transformed by simulated gastric fluid (36 and 13), intestinal fluid (29 and 7) and two human fecal bacteria (34 and 34, 40 and 25) were characterized, respectively. The methyl salicylate glycosides, MSTG-B, MSTG-A and gaultherin, with terminal-xylosyl-moiety in sugar chain were always being found in the whole gastrointestinal incubation processing. The metabolites were formed through hydrolysis of ester and glucosidic bond, as well as methylation, hydroxylation, acetylation, sulfation, reduction, decarboxylation, deglycosylation and glucuronidation. The metabolic conversion effect of the four index compounds, MSTG-B, MSTG-A, gaultherin, and chlorogenic acid by human intestinal bacteria exhibited much stronger. Those markers' variation in content-time curve in volunteer A gut flora were faster than that in volunteer B's. These results indicate that ARF is relatively stable in the gastrointestinal tract.

5.
Chem Biodivers ; 16(9): e1900254, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31381251

RESUMO

The genus Thymus (Lamiaceae) comprises about 214 species throughout the world, mainly found in North Africa, Europe, and temperate Asia zone. They are traditionally used as food additives and folk medicines. This review comprehensively summarizes information about traditional uses, chemical constituents, and biological activities of this genus and provides recommendations for future investigations. All information was gathered from scientific databases including Google Scholar, Sci-Finder, Web of Science, ScienceDirect, and CNKI. Volatile oils are the most concerned constituents of this genus. Flavonoids, phenylpropanoids, tannins, organic acids, terpenoids, and phytosterols were also summarized. This genus plants possessed a variety of activities including antimicrobial, antioxidant, anti-inflammatory, cytotoxic, analgesic, and antidiabetic. In brief, this review will be helpful to provide valuable data for explorations and create more interests towards Thymus genus in the future.

6.
Cells ; 8(9)2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31461941

RESUMO

The human nasal epithelium is the primary site of exposure to influenza virus, the initiator of host responses to influenza and the resultant pathologies. Influenza virus may cause serious respiratory infection resulting in major complications, as well as severe impairment of the airways. Here, we elucidated the global transcriptomic changes during H3N2 infection of human nasal epithelial cells from multiple individuals. Using RNA sequencing, we characterized the differentially-expressed genes and pathways associated with changes occurring at the nasal epithelium following infection. We used in vitro differentiated human nasal epithelial cell culture model derived from seven different donors who had no concurrent history of viral infections. Statistical analysis highlighted strong transcriptomic signatures significantly associated with 24 and 48 h after infection, but not at the earlier 8-h time point. In particular, we found that the influenza infection induced in the nasal epithelium early and altered responses in interferon gamma signaling, B-cell signaling, apoptosis, necrosis, smooth muscle proliferation, and metabolic alterations. These molecular events initiated at the infected nasal epithelium may potentially adversely impact the airway, and thus the genes we identified could serve as potential diagnostic biomarkers or therapeutic targets for influenza infection and associated disease management.

7.
JCI Insight ; 4(19)2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31465302

RESUMO

CD8+ tumor-infiltrating lymphocytes (TILs) correlate with relapse-free survival (RFS) in most cancer types, including breast cancer. However, subset composition, functional status, and spatial location of CD8+ TILs in relation to RFS in human breast tumors remain unclear. Spatial tissue analysis via quantitative immunofluorescence showed that infiltration of CD8+ T cells into cancer islands was more significantly associated with RFS than CD8+ T cell infiltration into either tumor stroma or total tumor. Localization into cancer islands within tumors is mediated by expression of the integrin CD103, which is a marker for tissue-resident memory T cells (TRMs). Analysis of fresh tumor samples revealed that CD8+ TRMs are functionally similar to other CD8+ TILs, suggesting that the basis of their protective effect is their spatial distribution rather than functional differences. Indeed, CD103+ TRMs, as compared with CD103-CD8+ TILs, are enriched within cancer islands, and CD8+ TRM proximity to cancer cells drives the association of CD8+ TIL densities with RFS. Together, these findings reveal the importance of cancer island-localized CD8+ TRMs in surveillance of the breast tumor microenvironment and as a critical determinant of RFS in patients with breast cancer.

8.
Nat Commun ; 10(1): 3844, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31451689

RESUMO

External fields are introduced to catalytic processes to improve catalytic activities. The light field effect plays an important role in electrocatalytic processes, but is not fully understood. Here we report a series of photo-coupled electrocatalysts for CO2 reduction by mimicking the structure of chlorophyll. The porphyrin-Au catalyst exhibits a high turnover frequency of 37,069 h-1 at -1.1 V and CO Faradaic efficiency (FE) of 94.2% at -0.9 V. Under visible light, the electrocatalyst reaches similar turnover frequency and FE with potential reduced by ~ 130 mV. Interestingly, the light-induced positive shifts of 20, 100, and 130 mV for porphyrin-Co, porphyrin-Cu, and porphyrin-Au electrocatalysts are consistent with their energy gaps of 0, 1.5, and 1.7 eV, respectively, suggesting the porphyrin not only serves as a ligand but also as a photoswitch to regulate electron transfer pathway to the metal center.

9.
Trials ; 20(1): 518, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429790

RESUMO

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is a syndrome characterized by significant forgetfulness that does not meet the criteria of dementia. Individuals with aMCI are at greater risk of progressing to dementia. Current studies suggest that good sleep quality is linked with preserved cognition in the elderly, and sleep complaints are common among the elderly with amnesia. Therefore, improving their sleep may be helpful for maintaining and improving their cognitive capacity. According to the theory of traditional Chinese medicine, Yi-Zhi-An-Shen is an herbal compound which may ameliorate forgetfulness and sleep disorders. As growing evidence indicates that the gut microbiome is associated with major mental symptoms, a hypothesis was proposed that Yi-Zhi-An-Shen granules (YZASG) might work by alternating microbial abundance and diversity. In this study, the investigators intend to assess the efficacy of YZASG on global cognition in the elderly suffering from aMCI and evaluate its safety as well as its potential mechanisms via sleep quality, fecal microbial 16S ribosomal DNA and metagenomics analyses, and serum markers. METHODS/DESIGN: This study is a randomized, double-blind, placebo-controlled clinical trial. A total of 80 patients (aged 60-85 years) will be recruited and allocated randomly to a treatment group and a placebo group in a 1:1 ratio and will then be administered YZASG or isodose placebo three times a day. The intervention course is 16 weeks, with an 18 months follow-up. The primary outcome is the Alzheimer's Disease Assessment Scale-Cognitive Subscale. Secondary outcome measures are the Mini-Mental State Examination, Montreal Cognitive Assessment, Pittsburgh Sleep Quality Index, serum concentrations of immunological factors and inflammatory cytokines, and fecal microbiota. Fecal microbiota will only be collected at the baseline and endpoint of the intervention. DISCUSSION: The results of this trial will be conducive to assessing the safety and effectiveness on cognition of YZASG in intervening aMCI among the elderly and determining if it takes effect via the improvement of sleep quality, regulation of gut microbiota, and concentration of certain serum markers. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03601000 . Registered on 26 July 2018.

10.
Int J Mol Sci ; 20(15)2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31362365

RESUMO

Accumulating evidence indicates that epithelial splicing regulatory protein 1 (ESRP1) can inhibit the epithelial-to-mesenchymal transition (EMT), thus playing a central role in regulating the metastatic progression of tumors. However, it is still not clear whether ESRP1 directly influences the cell cycle, or what the possible underlying molecular mechanisms are. In this study, we showed that ESRP1 protein levels were significantly correlated with the Ki-67 proliferative index (r = -0.521; p < 0.01), and that ESRP1 overexpression can significantly inhibit cervical carcinoma cell proliferation and induced G1-phase arrest by downregulating cyclin A2 expression. Importantly, ESRP1 can bind to GGUGGU sequence in the 3'UTR of the cyclin A2 mRNA, and ESRP1 overexpression significantly decreases the stability of the cyclin A2 mRNA. In addition, our experimental results confirm that ESRP1 overexpression results in enhanced CDC20 expression, which is known to be responsible for cyclin A2 degradation. This study provides the first evidence that ESRP1 overexpression induces G1-phase cell cycle arrest via reducing the stability of the cyclin A2 mRNA, and inhibits cervical carcinoma cell proliferation. The findings suggest that the ESRP1/cyclin A2 regulatory axis may be essential as a regulator of cell proliferation, and may thus represent an attractive target for cervical cancer prevention and treatment.

11.
BMC Infect Dis ; 19(1): 622, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307416

RESUMO

BACKGROUND: Cell-surface mucins are expressed in apical epithelial cells of the respiratory tract, and contribute a crucial part of the innate immune system. Despite anti-inflammatory or antiviral functions being revealed for certain cell-surface mucins such as MUC1, the roles of other mucins are still poorly understood, especially in viral infections. METHODS: To further identify mucins significant in influenza infection, we screened the expression of mucins in human nasal epithelial cells infected by H3N2 influenza A virus. RESULTS: We found that the expression of MUC15 was significantly upregulated upon infection, and specific only to active infection. While MUC15 did not interact with virus particles or reduce viral replication directly, positive correlations were observed between MUC15 and inflammatory factors in response to viral infection. Given that the upregulation of MUC15 was only triggered late into infection when immune factors (including cytokines, chemokines, EGFR and phosphorylated ERK) started to peak and plateau, MUC15 may potentially serve an immunomodulatory function later during influenza viral infection. CONCLUSIONS: Our study revealed that MUC15 was one of the few cell-surface mucins induced during influenza infection. While MUC15 did not interact directly with influenza virus, we showed that its increase coincides with the peak of immune activation and thus MUC15 may serve an immunomodulatory role during influenza infection.


Assuntos
Vírus da Influenza A Subtipo H3N2/fisiologia , Influenza Humana/patologia , Mucinas/metabolismo , Animais , Células Cultivadas , Quimiocinas/metabolismo , Citocinas/metabolismo , Cães , Células Epiteliais/classificação , Células Epiteliais/metabolismo , Receptores ErbB/metabolismo , Humanos , Influenza Humana/metabolismo , Células Madin Darby de Rim Canino , Mucinas/antagonistas & inibidores , Mucinas/genética , Cavidade Nasal/citologia , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/farmacologia , Regulação para Cima , Replicação Viral/efeitos dos fármacos
12.
Arch Biochem Biophys ; 671: 152-161, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31283910

RESUMO

Hypertrophic scars are dermal fibrosis diseases that protrude from the surface of the skin and irregularly extend to the periphery, seriously affecting the appearance and limb function of the patient. In this study, we found that microRNA-130a (miR-130a) was increased in hypertrophic scar tissues and derived primary fibroblasts, accompanied by up-regulation of collagen1/3 and α-SMA. Inhibition of miR-130a in hypertrophic scars fibroblasts suppressed the expression of collagen1/3 and α-SMA as well as the cell proliferation. Bioinformatics analysis combined with luciferase reporter gene assay results indicated that CYLD was a target gene of miR-130a, and the miR-130a mimic could reduce the level of CYLD. In contrast to miR-130a, the expression of CYLD was downregulated in hypertrophic scars and their derived fibroblasts. Overexpressing CYLD inhibited the expression of collagen 1/3 and α-SMA, slowed cell proliferation, and inhibited Akt activity. As expected, further study showed that the overexpression of CYLD could prevent the pro-fibroproliferative effects of miR-130a. Consistent with the in vitro results, the inhibitor of miR-130a effectively ameliorated excessive collagen deposition in bleomycin-induced skin fibrosis mouse model. Taken together, our results indicate that miR-130a promotes collagen secretion, myofibroblast transformation and cell proliferation by targeting CYLD and enhancing Akt activity. Therefore, the miR-130a/CYLD/Akt pathway may serve as a novel entry point for future skin fibrosis research.

13.
Histol Histopathol ; 34(11): 1205-1215, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31282985

RESUMO

SIRT1, a member of the sirtuin family, belongs to the NAD⁺-dependent class III histone deacetylase. SIRT1 can regulate gene expression by catalyzing non-histone and histone lysine residues deacetylation. SIRT1 also plays important roles in glucose and lipid metabolism, cell aging, tumorigenesis and inflammation. Recent studies indicate that SIRT1 can inhibit the inflammatory responses via regulating several inflammatory signaling pathways. It is closely related to the occurrence and development of sepsis and other inflammatory diseases. Research has been done on relevant signaling pathways of SIRT1 as well as its target genes during inflammation. SIRT1 is a hot spot in uncontrolled inflammatory response research. This article focuses on the role of SIRT1 in inflammation, especially its targets and involved signaling pathways in sepsis, and tries to provide more convincing evidence for the clinical treatment of sepsis and other inflammatory diseases.

14.
Cell Death Differ ; 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31332295

RESUMO

Quiescent satellite cells (SCs) that are activated to produce numerous myoblasts underpin the complete healing of damaged skeletal muscle. How cell-autonomous regulatory mechanisms modulate the balance among cells committed to differentiation and those committed to self-renewal to maintain the stem cell pool remains poorly explored. Here, we show that miR-31 inactivation compromises muscle regeneration in adult mice by impairing the expansion of myoblasts. miR-31 is pivotal for SC proliferation, and its deletion promotes asymmetric cell fate segregation of proliferating cells, resulting in enhanced myogenic commitment and re-entry into quiescence. Further analysis revealed that miR-31 posttranscriptionally suppresses interleukin 34 (IL34) mRNA, the protein product of which activates JAK-STAT3 signaling required for myogenic progression. IL34 inhibition rescues the regenerative deficiency of miR-31 knockout mice. Our results provide evidence that targeting miR-31 or IL34 activities in SCs could be used to counteract the functional exhaustion of SCs in pathological conditions.

15.
Biochem Biophys Res Commun ; 516(4): 1190-1195, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31296381

RESUMO

Growth arrest specific 7 (Gas7) protein is a cytoskeleton regulator playing a crucial role in neural cell development and function, and has been implicated in Alzheimer disease, schizophrenia and cancers. In human, three Gas7 isoforms can be expressed from a single Gas7 gene, while only the longest isoform, hGas7c, possesses an SH3 domain at the N-terminus. To date, the structure and function of hGas7 SH3 domain are still unclear. Here, we reported the solution NMR structure of hGas7 SH3 domain (hGas7-SH3), which displays a typical SH3 ß-barrel fold comprising five ß-strands and one 310-helix. Structural and sequence comparison showed that hGas7-SH3 shares high similarity with Abl SH3 domain, which binds to a high-affinity proline-rich peptide P41 in a canonical SH3-ligand binding mode through two hydrophobic pockets and a specificity site in the RT-loop. However, unlike Abl-SH3, only six residues in the RT-loop and two residues adjacent to but not in the two hydrophobic pockets of hGas7-SH3 showed significant chemical shift perturbations in NMR titrations, suggesting a low affinity and a non-canonical binding mode of hGas7-SH3 for P41. Furthermore, four peptides selected from phage-displayed libraries also bound weakly to hGas7-SH3, and the binding region of hGas7-SH3 was mainly located in the RT-loop as well. The ligand identifications through structural similarity searching and peptide library screening in this study imply that although hGas7-SH3 adopts a typical SH3 fold, it probably possesses distinctive ligand-binding specificity.

16.
J Nutr ; 149(9): 1523-1532, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31175811

RESUMO

BACKGROUND: It is not clear whether dietary grape seed proanthocyanidin (GSP) affects mammalian lipid metabolism via the gut microbiota. OBJECTIVE: The aim of this study was to evaluate the contribution of the gut microbiota to the effect of dietary GSP. METHODS: This study was divided into 3 separate experiments using Duroc × Landrace × Yorkshire pigs (50% male) weaned at day 28 and then fed the same basal diet (NC). In Experiment 1, 90 pigs were fed NC or NC with 250 mg GSP/kg (GSP) or 400 mg betaine/kg [positive control (PC)] for 28 d. In Experiment 2, 30 pigs were fed NC, GSP, or GSP with antibiotics (GSP + Abx) diets for 14 d. In Experiment 3, pigs were fed NC, NC plus 1 g sodium propionate/kg (SP), or NC plus 1 g sodium butyrate/kg (SB) diet for 14 d. Serum biochemical indexes, SCFA concentrations, and microbial composition were determined. RESULTS: In Experiment 1, compared with the GSP group, visceral adipocyte area was higher in the NC (28.6%) and PC (18.2%) groups (P ≤ 0.05). Colonic propionate and butyrate concentrations were 30.2% and 3.6% higher in the GSP group than in the NC group, respectively (P ≤ 0.05). In Experiment 2, compared with the GSP group, the NC group had a 108% higher Firmicutes to Bacteroidetes ratio and had 50.4%, 61.2%, and 82.3% lower abundance of Akkermansia, Alistipes, and Bacteroides, respectively (P ≤ 0.05); antibiotics removed these effects of GSP. In Experiment 3, serum peptide YY was 19.5% higher in the SP group than in the NC group (P ≤ 0.05), and it did not differ between the SB and NC groups (P > 0.05). CONCLUSIONS: GSP affected lipid metabolism in weaned pigs, which is associated with changed gut microbiota and enhanced microbial propionate production. These findings provide potential mechanisms for GSP intake to improve lipid metabolism.

17.
Life Sci ; 231: 116570, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31207307

RESUMO

AIMS: Systemic inflammation is a main hallmark of chronic kidney disease (CKD), but the underlying mechanisms of pathogenesis of CKD-associated systemic inflammation is unclear. Current study was designed to investigate the relationship between indoxyl sulphate (IS) and CKD-associated systemic inflammation along with the protective effects of Klotho in CKD. METHODS: IS serum levels from patients were detected by high-performance liquid chromatography (HPLC), and Serum Klotho, IL-6 and TNF-α were measured separately by ELISA and Real-Time PCR analysis. Monocytes were incubated with or without Klotho, while the expressions of retinoic acid-inducible gene I (RIG-I) and NF-κB were analyzed through Western blot assay. Heterozygous kl/kl (kl/+) mice or WT mice were treated with 5/6 renal damage. Thereafter, the CKD mice were intraperitoneally injected with recombinant Klotho protein or PBS. KEY FINDINGS: It shows that in 286 CKD patients, the serum levels of inflammatory factors were positively related with IS, but negatively related with Klotho. Klotho significantly inhibited IS-induced RIG-I/NF-κB activation and productions of both IL-6 and TNF-α in cultured monocytes. In vivo, along with the increase of IS and decrease of Klotho in the serum, the activation of RIG-I/NF-κB signaling was observed in peripheral blood monocytes in both CKD mice and patients. Notably, higher levels of IL-6 and TNF-α were detected in kl+/- mice given CKD. Klotho administration has evidently attenuated RIG-I/NF-κB activation in monocytes and systemic inflammation in CKD mice. SIGNIFICANCE: The findings suggest that Klotho can suppress CKD-associated systemic inflammation through inhibiting IS-induced RIG-1/NF-κB activation and monocyte inflammatory factor release.


Assuntos
Proteína DEAD-box 58/sangue , Glucuronidase/farmacologia , Indicã/sangue , Monócitos/metabolismo , NF-kappa B/sangue , Insuficiência Renal Crônica/sangue , Uremia/sangue , Adulto , Animais , Western Blotting , Feminino , Glucuronidase/sangue , Humanos , Inflamação/sangue , Inflamação/patologia , Interleucina-6/sangue , Rim/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Monócitos/patologia , Insuficiência Renal Crônica/patologia , Transdução de Sinais , Células THP-1 , Fator de Necrose Tumoral alfa/sangue , Uremia/patologia
18.
Microb Pathog ; 135: 103613, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31254602

RESUMO

Avian influenza viruses (AIVs) in wild birds pose a pandemic threat to humans and to the poultry industry. To assess AIV and AIV antibody prevalence in wild birds in China, a systematic review and meta-analysis were conducted. We searched PubMed, Google Scholar, Cochrane Library, Clinical Trial, VIP, CNKI, and WANFANG for published papers related to the prevalence of AIVs and their associated antibodies in wild birds in China from Mar. 10, 2005 to Sept. 20, 2018. Repeat studies, reviews, and other host studies were excluded, as well as those with inconsistent data, incomplete information, or only prevalence data or data from outside of mainland China. In total, data from 28 publications were compiled and analyzed. Based on out meta-analysis, the pooled prevalence of AIVs in wild birds in China was found to be 2.5% (571/23,024), and the pooled prevalence of AIV antibodies was 26.5% (1,210/4,566). The pooled prevalence of AIVs was significantly higher in wild birds from Central China (5.5%, 271/4, 955) compared to all other regions and the pooled prevalence of AIV antibodies was significantly in wild birds from South China (56.8%, 92/162) in comparison to all other regions. The prevalence of both AIVs and AIV antibodies in Anseriformes were higher compared to non-Anseriformes. In addition, the largest number of studies found in this review were on the HA subtypes of AIVs (H5, H7, and H9) and their associated antibodies. In summary, our findings suggest that the prevalence of AIVs and their antibodies in wild birds vary among regions and species of wild bird. Thus, further monitoring of the prevalence of AIVs and their antibodies in wild birds in China is necessary and should be used for guiding powerful and effective regulatory measures that will prevent the spread of AIVs across species.


Assuntos
Animais Selvagens/virologia , Anticorpos/sangue , Aves/virologia , Vírus da Influenza A , Influenza Aviária/epidemiologia , Influenza Aviária/imunologia , Animais , China/epidemiologia , Bases de Dados Factuais , Pandemias , Prevalência
19.
CNS Neurosci Ther ; 25(9): 1030-1041, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31218845

RESUMO

INTRODUCTION: L-glutamine is an antioxidant that plays a role in a variety of biochemical processes. Given that oxidative stress is a key component of stroke pathology, the potential of L-glutamine in the treatment of ischemic stroke is worth exploring. AIMS: In this study, we investigated the effect and mechanisms of action of L-glutamine after cerebral ischemic injury. RESULTS: L-glutamine reduced brain infarct volume and promoted neurobehavioral recovery in mice. L-glutamine administration increased the expression of heat-shock protein 70 (HSP70) in astrocytes and endothelial cells. Such effects were abolished by the coadministration of Apoptozole, an inhibitor of the ATPase activity of HSP70. L-glutamine also reduced oxidative stress and neuronal apoptosis, and increased the level of superoxide dismutase, glutathione, and brain-derived neurotrophic factor. Cotreatment with Apoptozole abolished these effects. Cell culture study further revealed that the conditioned medium from astrocytes cultured with L-glutamine reduced the apoptosis of neurons after oxygen-glucose deprivation. CONCLUSION: L-glutamine attenuated ischemic brain injury and promoted functional recovery via HSP70, suggesting its potential in ischemic stroke therapy.

20.
Mol Cell Endocrinol ; 494: 110490, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31207271

RESUMO

Diabetic nephropathy (DN) is a progressive disease, the main pathogeny of which is podocyte injury. As a calcium-dependent serine/threonine protein kinase involved in podocyte injury, protein kinase C isoform α (PKCα) was reported to regulate the phosphorylation of p66SHC. However, the role of PKCα/p66SHC in DN remains unknown. Klotho, an anti-aging protein with critical roles in protecting kidney, is expressed predominantly in the kidney and secreted in the blood. Nonetheless, the mechanism underlying amelioration of podocyte injury by Klotho in DN remains unclear. Our data showed that Klotho was decreased in STZ-treated mice and was further declined in diabetic KL ± mice. As expected, Klotho deficiency aggravated diabetes-induced proteinuria and podocyte injury, accompanied by the activation of PKCα and p66SHC. In contrast, overexpression of Klotho partially ameliorated PKCα/p66SHC-mediated podocyte injury and proteinuria. In addition, in vitro experiments showed that activation of PKCα and subsequently increased intracellular reactive oxygen species (ROS) was involved in podocytic apoptosis induced by high glucose (HG), which could be partially reversed by Klotho. Hence, we conclude that Klotho might inhibit PKCα/p66SHC-mediated podocyte injury in diabetic nephropathy.

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