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1.
BMC Genomics ; 22(1): 640, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34481473

RESUMO

BACKGROUND: Fatty liver disease prevalently occurs in commercial postpartum dairies, resulting in a worldwide high culling rate because of their subsequent limitations of production and reproduction performance. RESULTS: Fatty liver-specific proteome and acetylome analysis revealed that energy metabolism suppression closely associated with mitochondrial dysfunction and inflammation activation were shown to be remarkable biological processes underlying the development of fatty liver disease, furthermore, acetylation modification of proteins could be one of the main means to modulate these processes. Twenty pivotal genetic factors/genes that differentially expressing and being acetylation modified in liver were identified and proposed to regulate the pathogenesis of fatty liver dairies. These proteins were confirmed to be differentially expressing in individual liver tissue, eight of which being validated via immunohistochemistry assay. CONCLUSIONS: This study provided a comprehensive proteome and acetylome profile of fatty liver of dairy cows, and revealed potential important biological processes and essential regulators in the pathogenesis of fatty liver disease. Expectantly, understanding the molecular mechanisms of the pathogenesis of fatty liver disease in dairies, as an animal model of non-alcoholic fatty liver disease (NAFLD) in human beings, which is a clinico-pathologically defined process associated with metabolic syndrome, could inspire and facilitate the development of efficacious therapeutic drugs on NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Proteoma , Animais , Bovinos , Feminino , Humanos , Inflamação , Mitocôndrias , Hepatopatia Gordurosa não Alcoólica/genética
2.
Zhongguo Zhong Yao Za Zhi ; 46(12): 3034-3042, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467693

RESUMO

To explore the mechanism of anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium based on network pharmacology and inflammatory or pain mouse models. The effective components of Zanthoxyli Pericarpium were screened out by TCMSP database. And their potential corresponding targets were predicted by PharmMapper software. The possible targets relating to inflammation and pain were mainly collected through DrugBank, TTD and DisGeNET databases. The "active ingredient-gene-disease" network diagram was constructed by Cytoscape 3.7.0 software. The network pharmacology results showed 5 potential effective compounds, which were related to 29 targets; 132 targets relating to inflammation and pain were screened out in the DrugBank, TTD and DisGeNET databases. The network analysis results indicated that the phosphatidylinositol 3-kinase catalytic subunit gamma isoform(PIK3 CG) gene may be the key to the anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium. The anti-inflammatory and analgesic effects of essential oil extract and dichloromethane extract of Zanthoxyli Pericarpium were explored through the mouse model of inflammation induced by xylene or carrageenan and the mouse model of pain induced by acetic acid or formalin. The experimental results showed that essential oil extract and dichloromethane extract of Zanthoxyli Pericarpium could reduce xylene-induced ear swelling and carrageenan-induced paw swelling and decrease the number of writhing responses in mice induced by acetic acid and the licking foot time of mice in phase Ⅱ induced by formalin. Western blot results showed that Zanthoxyli Pericarpium extract could inhibit the expressions of PIK3 CG, phosphonated nuclear factor kappaB(p-NF-κB) and phosphonated p38(p-p38 MAPK) protein. The present study showed the anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium through multiple components and targets, so as to provide a pharmacodynamic basis for the study of Zanthoxyli Pericarpium and its mechanism.


Assuntos
Medicamentos de Ervas Chinesas , Óleos Voláteis , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Inflamação/tratamento farmacológico , Inflamação/genética , Camundongos , Extratos Vegetais
3.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4238-4243, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467738

RESUMO

Wuwei Ganlu, a formula for medicated bath, consists of medicinal materials of Ephedra sinica, Platycladus orientalis, Myricaria squamosa, Artemisia carvifolia, and Rhododendron anthopogonoides, which is effective in inducing perspiration, resisting inflammation, relieving pain, regulating yellow water disease, and activating blood circulation. On this basis, a variety of formulas for Tibetan medicated bath have been derived for the treatment of diseases in internal organs, joints, nerves, etc. Modern studies have confirmed that Wuwei Ganlu has a good therapeutic efficacy on knee osteoarthritis(KOA). The present study explored the mechanism of Wuwei Ganlu in treating KOA based on network pharmacology and molecular docking. Firstly, the chemical components of Wuwei Ganlu were obtained through literature mining and database retrieval, and corresponding potential targets were predicted according to the BATMAN-TCM database. The protein-protein interaction(PPI) network was obtained after the potential targets were input into the STRING database. The network function modules were analyzed by the Molecular Complex Detection(MCODE) algorithm, and the functions of the modules were annotated to analyze the action mode of Wuwei Ganlu. Secondly, the related targets of KOA were collected through the DisGeNET database, and the overlapping targets were confirmed to analyze the mechanism of Wuwei Ganlu in treating KOA. Finally, the key targets were selected for molecular docking with the main components of Wuwei Ganlu to verify the component-target interaction. A total of 550 chemical components and 1 365 potential targets of Wuwei Ganlu were obtained. PPI analysis indicated that this formula could exert the effects of oxidation-reduction, inflammation resistance, bone absorption, bone mineralization, etc. Nineteen common targets were obtained from the intersection of potential targets of Wuwei Ganlu and KOA disease targets. It was found that the Wuwei Ganlu mainly acts on nuclear factor-κB(NF-κB), interleukin-1 beta(IL1ß), tumor necrosis factor(TNF), IL6, IL1 receptor antagonist(IL1 RN), and prostaglandin-endoperoxide synthase-2(PTGS2) to treat KOA. Among the 550 chemical components of Wuwei Ganlu, 252 potential active components were docked with TNF and 163 with PTGS2, indicating good binding of the components with potential key targets. The study preliminarily explored the mechanism of Wuwei Ganlu in treating KOA to provide a reference for the further development and utilization of Tibetan medicated bath that has been included in the UN Intangible Cultural Heritage.


Assuntos
Medicamentos de Ervas Chinesas , Osteoartrite do Joelho , Bases de Dados Factuais , Humanos , Inflamação , Simulação de Acoplamento Molecular
4.
Medicine (Baltimore) ; 100(35): e27059, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477138

RESUMO

ABSTRACT: Prolidase enzyme activity is important for collagen resynthesis. In late stages of osteoarthritis (OA) its activity is decreased.To evaluate prolidase expression in knees of patients undergoing total arthroplasty for OA, and compare with young people undergoing knee arthroscopy due to traumatic injuries.In this cross-sectional study we included 20 patients with OA grade IV who underwent total knee arthroplasty and 20 controls of young patients who underwent arthroscopy for another reason besides OA. All participants were evaluated by knee ultrasound before the procedure. During the procedure, synovial tissue biopsies were taken and analyzed by immunofluorescence to search inflammation. Measures of central tendency, dispersion measures and position measures were used for the case of quantitative variables. Student t test or Mann-Whitney U test, and the logistic regression of Cox, was used.Prolidase expression in the synovial biopsy was significantly lower in the OA group than in the controls (0.017 ±â€Š0.009 vs 0.062 ±â€Š0.094, P < .05). Power Doppler (PD) signal was present in the synovitis of all knee recesses of the OA group in grayscale and in 17 (85%) of knees. The mean of the micro-vessel count in patients with OA was significantly higher vs controls (11 + 5.3 vs 4 + 2.1, P = .001). The neovascularization correlated significantly with the presence of PD signal in patients with OA (1.16, 95% CI, 1.02-1.34, P = .02).The prolidase expression in the synovial membrane evaluated by immunofluorescence, in patients with late stages of knee OA, is low, which may be interpreted as an evidence of decreased collagen resynthesis.


Assuntos
Dipeptidases/análise , Osteoartrite do Joelho/patologia , Idoso , Estudos Transversais , Dipeptidases/fisiologia , Feminino , Humanos , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/fisiopatologia , Estudos Prospectivos , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Ultrassonografia/métodos
5.
Nat Commun ; 12(1): 5213, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34480023

RESUMO

Intervertebral disc degeneration is highly prevalent within the elderly population and is a leading cause of chronic back pain and disability. Due to the link between disc degeneration and senescence, we explored the ability of the Dasatinib and Quercetin drug combination (D + Q) to prevent an age-dependent progression of disc degeneration in mice. We treated C57BL/6 mice beginning at 6, 14, and 18 months of age, and analyzed them at 23 months of age. Interestingly, 6- and 14-month D + Q cohorts show lower incidences of degeneration, and the treatment results in a significant decrease in senescence markers p16INK4a, p19ARF, and SASP molecules IL-6 and MMP13. Treatment also preserves cell viability, phenotype, and matrix content. Although transcriptomic analysis shows disc compartment-specific effects of the treatment, cell death and cytokine response pathways are commonly modulated across tissue types. Results suggest that senolytics may provide an attractive strategy to mitigating age-dependent disc degeneration.


Assuntos
Envelhecimento/efeitos dos fármacos , Dasatinibe/uso terapêutico , Degeneração do Disco Intervertebral/tratamento farmacológico , Quercetina/uso terapêutico , Agrecanas/metabolismo , Envelhecimento/metabolismo , Animais , Anel Fibroso/efeitos dos fármacos , Anel Fibroso/metabolismo , Anel Fibroso/patologia , Sobrevivência Celular/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Fibrose , Inflamação , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Camundongos , Camundongos Endogâmicos C57BL , Núcleo Pulposo/efeitos dos fármacos , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Fenótipo , Transcriptoma/efeitos dos fármacos
6.
Se Pu ; 39(10): 1118-1127, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34505434

RESUMO

The late endosomal/lysosomal adaptor MAPK and mTOR activator 1 (LAMTOR1) is an important regulator protein in the response to energy stress. Public gene expression data shows that the expression of LAMTOR1 is abnormally high in nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC); hence, LAMTOR1 may play an important role in the development of NASH and HCC. Therefore, exploring the LAMTOR1 regulatory mechanism in the progression of NASH and malignant transformation of liver inflammation may be crucial for translational medicine. First, a NASH mouse model was established by feeding a methionine choline-deficient (MCD) diet. Hematoxylin-eosin staining of liver tissues showed successful modeling of inflammatory injury in the mouse liver. Immunoblot analysis confirmed LAMTOR1- and LAMTOR1-mediated protein expression in LAMTOR1 specifically depleted mouse livers. Subsequently, metabolic profiling of liver tissues was performed using an ultra-performance liquid chromatography-time-of-flight mass spectrometry strategy. Based on the retention time, m/z value, and tandem mass spectra, 134 metabolites were identified. Among these, the levels of 45 metabolite were significantly influenced by hepatic LAMTOR1 depletion. According to the metabolomics results, uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) was significantly upregulated in LAMTOR1-depleted (LAMTOR1LKO) hepatocyte tissues. As the final product of the hexosamine biosynthetic pathway (HBP), alteration in UDP-GlcNAc levels may regulate LAMTOR1 and metabolic regulatory genes downstream of HBP. Moreover, there was an obvious increase in the levels of several methylation-related metabolites. Thus, upregulated S-adenosylmethionine, S-adenosylhomocysteine, and N6,N6,N6-trimethyl-L-lysine indicated that LAMTOR1 may regulate the process of DNA or protein methylation. In addition, downregulation of 9-oxo-octadecadienoate, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) was also observed in LAMTOR1LKO mice liver tissues. Alterations in polyunsaturated fatty acids, such as EPA and DHA, link LAMTOR1 to inflammatory and immune processes, which are known to play important roles in NASH pathogenesis. These metabolic disorders demonstrated that LAMTOR1 significantly contributed to the metabolic mechanism of NASH. Furthermore, gene expression correlations were analyzed to interpret the regulatory role of LAMTOR1 from the perspective of genetic networks. Owing to a paucity of liver whole-transcriptome studies in NASH, correlation analysis was performed based on HCC transcriptome data from public databases. First, a negatively regulated relationship was observed between LAMTOR1 and MAT1A (R=-0.47). MAT1A encodes methionine adenosyltransferase 1A, an essential enzyme that catalyzes the formation of S-adenosylmethionine. Based on the upregulation of UDP-GlcNAc under hepatocyte LAMTOR1 depletion, it was predicted that LAMTOR1 positively influenced MGAT1 (R=0.47), a gene encoding alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase. Together with changes in succinyladenosine caused by hepatocyte LAMTOR1 deletion, predicted correlation results showed that LAMTOR1 may also participate in the pathogenesis through the positive regulatory relationship with ADSL (R=0.59). The ADSL gene provides instructions for making an enzyme called adenylosuccinate lyase, which can dephosphorylate the substrate succinyladenosine. In this study, LAMTOR1 was identified to specifically regulate multiple key metabolic pathways based on both NASH mouse models and gene expression correlations. These results illustrate the important role of LAMTOR1 in the progression of NASH and malignant transformation of liver inflammation, which provides a theoretical basis for the diagnosis and treatment of NASH or possible NASH-driven HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Cromatografia Líquida , Modelos Animais de Doenças , Inflamação , Fígado , Espectrometria de Massas , Metionina , Camundongos
7.
J Refract Surg ; 37(9): 590-594, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34506241

RESUMO

PURPOSE: To determine patient preference and treatment outcomes with an intracanalicular dexamethasone 0.4 mg insert compared to a standard steroid drop regimen in the contralateral eye following bilateral photorefractive keratectomy (PRK). METHODS: In this randomized, prospective, self-controlled, open-label interventional study, one eye received the dexamethasone insert and the second eye received prednisolone acetate 1% taper following bilateral PRK surgery. Postoperative evaluations were performed on day 3, day 4, month 1, and month 3. Phone call surveys were performed on week 2. The Comparison of Ophthalmic Medications for Tolerability questionnaire was used to determine patient preference between postoperative regimens and postoperative pain. Corneal endpoints included time to epithelialization, presence of corneal haze, sodium fluorescein staining, and modified Standardized Patient Evaluation of Eye Dryness (SPEED) scores. Both corrected distance visual acuity (CDVA) and uncorrected distance visual acuity (UDVA) were assessed. RESULTS: Twenty patients participated in the study. At month 3, 70% of patients preferred the dexamethasone insert, 20% preferred prednisolone acetate, and 10% expressed no preference. Patient surveys did not show a difference in postoperative pain between the study group and control group. No statistical difference was shown in time to epithelialization, 90-day CDVA or UDVA, postoperative corneal haze, corneal staining, or modified SPEED scores. CONCLUSIONS: In patients undergoing PRK, there was preference toward a dexamethasone insert in place of topical prednisolone acetate for the postoperative steroid treatment. There were no statistically or clinically significant differences between the two cohorts in regard to healing time or visual outcomes. [J Refract Surg. 2021;37(9):590-594.].


Assuntos
Miopia , Ceratectomia Fotorrefrativa , Humanos , Inflamação , Lasers de Excimer/uso terapêutico , Miopia/cirurgia , Dor Pós-Operatória/tratamento farmacológico , Estudos Prospectivos , Refração Ocular , Resultado do Tratamento
8.
Neurol India ; 69(4): 894-901, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34507408

RESUMO

Background: Biomarkers of systemic inflammation (BMSIs), including haemogram cell counts (CC, e.g., absolute neutrophil count) and cell count-ratios (CCR, e.g., the neutrophil-lymphocyte ratio, etc.), have been found to have prognostic significance in many solid-organ cancers. Aims: In this three-part study, we first examined if the CCs and CCRs were altered in patients with glioblastoma (GBM) when compared with healthy controls. Second, we evaluated for any correlation between the BMSIs and patient- and tumour-related factors. Third, we evaluated the influence of the CCs and CCRs on survival. Methods: This was a retrospective analysis of patients who underwent surgery/biopsy for a newly diagnosed brain tumour that was subsequently confirmed to be GBM (Cases). Controls were healthy individuals who underwent pre-employment screening blood tests. Statistical Methods: Parametric tests were used to compare normally distributed continuous variables, whereas non-normally distributed variables were compared using non-parametric tests. Thresholds for the BMSIs were determined using X-tile analysis. Cox regression using the proportional hazards model was used for survival analyses around the determined thresholds. Results: All CCs and CCRs were altered in Cases compared with Controls. Presentation with raised intracranial pressure, altered sensorium, poor performance status, loss of ATRX, and lack of p53 overexpression was associated with an inflammatory phenotype of changes in the BMSIs. The inflammatory phenotype of changes was associated with poor survival. Conclusions: A significant inflammatory response was found in patients with GBM and correlated with clinical features, the molecular profile of the tumour and poor survival.


Assuntos
Glioblastoma , Biomarcadores , Humanos , Inflamação , Linfócitos , Prognóstico , Estudos Retrospectivos
9.
Cesk Slov Oftalmol ; 77(4): 163-168, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34507492

RESUMO

Immune mediated inflammatory diseases are categorized into autoimmune and autoinflammatory. Autoimmune etiology is represented by autoreactive lymphocytes or autoantibodies, e.g. primary Sjögrens syndrome or rheumatoid arthritis. Ocular specific diseases with presumed autoimmune origin are sympathetic ophthalmia or birdshot chorioretinopathy. Autoinflammatory diseases are caused by mutations in regulatory genes for specific immunity. Hereditary periodic fevers represent monogenic autoinflammatory diseases; eye specific is Blau syndrome also named sarcoidosis with early onset. This article reviews the actual knowledge about immune mediated uveitides, their immunological mechanisms and the possible trigger role of infection in autoimmune inflammation. Immune privilege provides a protection of the eye against any strong immune reaction to foreign antigen, based on physical, immune, humoral and molecular mechanisms. Antigens hidden within the eye are revealed in case of damage of hematoretinal barrier caused by infection or mechanical insult. These ocular antigens have not been set as tolerable during the development and immune reaction is initiated subsequently. Current studies demonstrate that uveogenic trigger might be generated by own microbiome, particularly when dysregulated, so called dysbiosis. There is a known association between idiopathic inflammatory bowel disease with ankylosing spondylitis and anterior uveitis in humans. Intensive research is focused on microbiome and immune mediated inflammatory disease to influence therapeutically the intestinal microbiome. The animal models are used to study the immunopathological mechanisms of uveitis and the new therapeutic strategies, because of relatively low incidence of immune mediated uveitis in humans.


Assuntos
Oftalmia Simpática , Sarcoidose , Sinovite , Uveíte , Animais , Humanos , Inflamação , Uveíte/etiologia
10.
Georgian Med News ; (316-317): 142-146, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34511461

RESUMO

In review provides data on pathophysiological relationships of intestinal microbiota with body weight regulation in patients with abdominal obesity. In manuscript discusses the leading mechanisms by which the gut microbiota can contribute to obesity and metabolic diseases, analyzes its components, including gastrointestinal peptides, short-chain fatty acids, bile acids, farnesoid receptors, etc. Western diet high in salt, dysbiosis and endotoxemia can be powerful pro-inflammatory factors responsible for the development of insulin resistance and weight gain. It is promising to prescribe agonists of gastrointestinal peptides, probiotics and prebiotics, which in abdominal obesity are able to inhibit dysbiosis, regulate immune functions, and protect the organism from low-intensity chronic inflammation.


Assuntos
Microbioma Gastrointestinal , Obesidade Abdominal , Probióticos , Disbiose , Humanos , Inflamação , Obesidade , Probióticos/uso terapêutico
11.
Arthritis Res Ther ; 23(1): 226, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465395

RESUMO

OBJECTIVE: To compare C-reactive protein (CRP) and matrix metalloproteinase-generated neoepitope of CRP (CRPM) as biomarkers of inflammation and radiographic severity in patients with knee osteoarthritis. METHODS: Participants with symptomatic osteoarthritis (n=25) of at least one knee underwent knee radiographic imaging and radionuclide etarfolatide imaging to quantify inflammation of the knees and other appendicular joints. For purposes of statistical analysis, semi-quantitative etarfolatide and radiographic imaging scores were summed across the knees; etarfolatide scores were also summed across all joints to provide a multi-joint synovitis measure. Multiple inflammation and collagen-related biomarkers were measured by ELISA including CRP, CRPM, MMP-generated neoepitopes of type I collagen and type III collagen in serum (n=25), and CD163 in serum (n=25) and synovial fluid (n=18). RESULTS: BMI was associated with CRP (p=0.001), but not CRPM (p=0.753). Adjusting for BMI, CRP was associated with radiographic knee osteophyte score (p=0.002), while CRPM was associated with synovitis of the knee (p=0.017), synovitis of multiple joints (p=0.008), and macrophage marker CD163 in serum (p=0.009) and synovial fluid (p=0.03). CRP correlated with MMP-generated neoepitope of type I collagen in serum (p=0.045), and CRPM correlated with MMP-generated neoepitope of type III collagen in serum (p<0.0001). No biomarkers correlated with age, knee pain, or WOMAC pain. CONCLUSIONS: To our knowledge, this is the first time that CRPM has been shown to be associated with knee and multi-joint inflammation based on objective imaging (etarfolatide) and biomarker (CD163) measures. These results demonstrate the capability of biomarker measurements to reflect complex biological processes and for neoepitope markers to more distinctly reflect acute processes than their precursor proteins. CRPM is a promising biomarker of local and systemic inflammation in knee OA that is associated with cartilage degradation and is independent of BMI. CRPM is a potential molecular biomarker alternative to etarfolatide imaging for quantitative assessment of joint inflammation.


Assuntos
Proteína C-Reativa , Osteoartrite do Joelho , Biomarcadores , Humanos , Inflamação/diagnóstico por imagem , Articulação do Joelho , Metaloproteinases da Matriz , Osteoartrite do Joelho/diagnóstico por imagem
12.
Mater Sci Eng C Mater Biol Appl ; 128: 112254, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474816

RESUMO

Numerous therapeutic strategies have been developed for osteoarthritis (OA) management, including intra-articular (IA) injections. The ideal IA formulation should control cartilage degradation and restore synovial fluid viscosity. To this end, we propose to combine thermo-sensitive polymers (poloxamers) with hyaluronic acid (HA) to develop suitable beta-lapachone (ßLap) loaded IA formulations. The development of IA formulations with these components entails several difficulties: low ßLap solubility, unknown ßLap therapeutic dose and the bonded commitment of easy administration and viscosupplementation. An optimized formulation was designed using artificial intelligence tools based on the experimental results of a wide variety of hydrogels and its therapeutic capacity was evaluated on an ex vivo OA model. The formulation presented excellent rheological properties and significantly decreased the secretion of degradative (MMP13) and pro-inflammatory (CXCL8) molecules. Therefore, the developed formulation is a promising candidate for OA treatment restoring the synovial fluid rheological properties while decreasing inflammation and cartilage degradation.


Assuntos
Ácido Hialurônico , Osteoartrite , Inteligência Artificial , Humanos , Hidrogéis , Inflamação/tratamento farmacológico , Osteoartrite/tratamento farmacológico
13.
Mater Sci Eng C Mater Biol Appl ; 128: 112359, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474906

RESUMO

Lipid metabolism in macrophages has been increasingly emphasized in exerting an anti-inflammatory effect and accelerating fracture healing. 12-lipoxygenase (12-LOX) is expressed in several cell types, including macrophages, and oxidizes polyunsaturated fatty acids (PUFAs) to generate both pro- and anti-inflammatory lipid mediators, of which the n-3 PUFAs play an important part in tissue homeostasis/fibrosis. Although mechanical factor regulates the lipid metabolic axis of inflammatory cells, specifically matrix stiffness influences macrophages metabolic responses, little is known about how matrix stiffness affects the 12-LOX-mediated early inflammation in bone repair. In the present study, demineralized bone matrix (DBM) scaffolds with different matrix stiffness were constructed by controlling the duration of decalcification (0 h (control), 1 h (high), 12 h (medium), and 5 d (low)) to repair the defected rat skull. The expression of inflammatory cytokines and macrophages polarization were analyzed. The lipid metabolites and lipid mediators' biosynthesis by matrix stiffness-regulated were further detected. The results showed that the low matrix stiffness could polarize macrophages into an anti-inflammatory phenotype, promote the expression of anti-inflammatory cytokines and specialized pro-resolving lipid mediators (SPMs) biosynthesis beneficial for the osteogenesis of mesenchymal stem cells (MSCs). After treated with ML355, the expression of anti-inflammatory cytokines/proteins and SPMs biosynthesis in macrophages cultured on low-matrix stiffness scaffolds were repressed, and there were almost no statistical differences among all groups. Findings from this study support that matrix stiffness regulates bone repair by modulating 12-LOX-mediated early inflammation, which suggest a direct mechanical impact of matrix stiffness on macrophages lipid metabolism and provide a new insight into the clinical application of SPMs for bone regeneration.


Assuntos
Araquidonato 12-Lipoxigenase , Células-Tronco Mesenquimais , Animais , Regeneração Óssea , Inflamação , Osteogênese , Ratos
14.
Rev Assoc Med Bras (1992) ; 67(3): 411-417, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34468607

RESUMO

OBJECTIVE: This study aimed to examine inflammation markers in patients with polycystic ovary syndrome (PCOS) and to compare them with healthy women. METHODS: This prospective study was conducted by examining patients who applied to the Near East University Gynecology and Obstetrics Outpatient Clinic between January 2019 and January 2020. A total of 110 PCOS patients with 135 control groups were compared in terms of metabolism, hormonal factors, and inflammation markers. RESULTS: The neutrophil count, neutrophil-lymphocyte ratio (NLR), platelet, platelet-lymphocyte ratio (PLR), platelecrit (PCT), erythrocyte cell distribution width, platelet distribution width, mean platelet volume, and C-reactive protein (CRP) values were found to be statistically significantly higher in patients with PCOS. There was a positive correlation between inflammation markers and serum androgens. Also, a positive correlation was observed between inflammation markers and cardiovascular risk parameters. In receiver operating characteristic curve analysis, the most valuable parameter in distinguishing PCOS patients from healthy controls was serum CRP levels [areas under the curve (AUC)=0.928, 95%CI 0.894-0.963, p<0.001, 92.6% sensitivity, and 82.7% specificity]. CONCLUSIONS: Serum CRP, neutrophil count, and PCT and NLR levels are valuable markers that show the inflammatory process in PCOS patients.


Assuntos
Síndrome do Ovário Policístico , Biomarcadores , Feminino , Humanos , Inflamação , Contagem de Leucócitos , Gravidez , Estudos Prospectivos
15.
Chemosphere ; 282: 131133, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34470170

RESUMO

The rapid development of carbon nanotubes (CNTs) in the field of fish disease control and prevention raises concerns about the toxicity and safe use in fish. This study was performed to assess the effect on histological changes, oxidative stress related markers in response to various concentrations of amine-functionalized single carbon nanotubes (NH2 f-SWCNT) (1, 10 and 100 mg kg-1 fish) in Channel Catfish (Ietalurus Punetaus) for up to 10 days. Moreover, pro-inflammatory cytokine genes and apoptotic genes were analyzed to obtain a better understanding of molecular mechanism of NH2 f-SWCNT induced toxicity. As a result, intraperitoneal (i.p.) administration of NH2 f-SWCNT caused dose-dependent and time-dependent injuries in the sampled tissues. In comparison with the control groups, decrease of catalase (CAT) activity and superoxide dismutase (SOD), and increase of malondialdehyde (MDA) and lactin dehydrogenase (LDH) were observed in all treatments. Real-time PCR assay showed inflammatory response with dose-dependent increase of tumor necrosis factor alpha (TNFα) and transient increase of interleukin 1ß (IL-1ß) in the liver. NH2 f-SWCNT administration induced increase of p38 as well as caspase-3 in all treatments compared to the control groups, indicating the involvement of p38-MAPK cascade and caspase-3 cascade in liver cell apoptosis. Overall, we conclude that NH2 f-SWCNT exert effects by direct injury and indirectly oxidative stress, resulting in inflammation and apoptosis, which provides data for understanding of the biological mechanisms underlying the toxicity of CNTs in fish.


Assuntos
Ictaluridae , Nanotubos de Carbono , Aminas , Animais , Apoptose , Inflamação/induzido quimicamente , Nanotubos de Carbono/toxicidade , Estresse Oxidativo
16.
Chin J Physiol ; 64(4): 167-176, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34472447

RESUMO

Despite the success in the tactics of treating COVID-19, there are many unexplored issues related to the development and progression of the process in the lungs, brain, and other organs, as well as the role of individual elements, in particular, nitric oxide (NO), and in the pathogenesis of organ damage. Based on the analyzed literature data, we considered a possible pathophysiological mechanism of action of NO and its derivatives in COVID-19. It can be noted that hyperimmune systemic inflammation and "cytokine storm" are enhanced by the production of NO, products of its oxidation ("nitrosative stress"). It is noted in the work that as a result of the oxidation of NO, a large amount of the toxic compound peroxynitrite is formed, which is a powerful proinflammatory agent. Its presence significantly damages the endothelium of the vascular walls and also oxidizes lipids, hemoglobin, myoglobin, and cytochrome, binds SH-groups of proteins, and damages DNA in the target cells. This is confirmed by the picture of the vessels of the lungs on computed tomography and the data of biochemical studies. In case of peroxynitrite overproduction, inhibition of the synthesis of NO and its metabolic products seems to be justified. Another aspect considered in this work is the mechanism of damage by the virus to the central and peripheral nervous system, which remains poorly understood but may be important in understanding the consequences, as well as predicting brain functions in persons who have undergone COVID-19. According to the analyzed literature, it can be concluded that brain damage is possible due to the direct effect of the virus on the peripheral nerves and central structures, and indirectly through the effect on the endothelium of cerebral vessels. Disturbances in the central nervous regulation of immune responses may be associated with the insufficient function of the acetylcholine anti-inflammatory system. It is proposed to further study several approaches to influence various links of NO exchange, which are of interest for theoretical and practical medicine.


Assuntos
COVID-19 , Óxido Nítrico , Humanos , Inflamação , SARS-CoV-2
17.
Chin J Physiol ; 64(4): 194-201, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34472450

RESUMO

Chronic kidney disease is one of the major global health problems. Chronic renal failure is stimulated by many cytokines and chemokines. Adropin and spexin (SPX) are peptides hormones. These peptides could affect inflammatory conditions, but this is unclear. Due to the limited information, we planned to investigate the impact of adropin and SPX hormones on systemic inflammation in adenine induced chronic kidney failure rat model. Chronic kidney failure was induced by administering adenine hemisulfate. Renal functions were measured by an autoanalyzer. Granulocyte colony-stimulating factor (G-CSF), interferon-gamma (IFN-γ), interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17A, tumor necrosis factor-alpha, Eotaxin, growth-regulated oncogene-alpha, IP-10, monocyte chemoattractant protein (MCP)-1, MCP-3, macrophage inflammatory protein (MIP)-1α, MIP-2, and RANTES levels were determined by Luminex. We observed an increase in 24-h urine volume and serum creatinine. Blood urea nitrogen (BUN) and urine protein levels were also significantly higher in the chronic kidney failure (CKF) group. Urine protein and 24-h urine volume were reduced with adropin and SPX treatments. Furthermore, G-CSF, IFN-γ, IL-4, IL-5, IL-10, IL-12, IL-17A, and GRO-α significantly increased by CKF induction; however, these cytokines and chemokines significantly decreased by adropin treatment in the CKF group. Furthermore, adropin increased IP-10, MCP-1, MIP-1α, and MIP-2 levels. In addition, SPX treatment had a more limited effect, decreasing only G-CSF, IFN-γ, and IL-5 levels. The combined adropin + SPX treatment significantly reduced G-CSF, IFN-γ, IL-4, IL-5, IL-12, and IL-17A. Furthermore, IP-10, MCP-1, MCP-3, and MIP-2 were significantly increased by these combined treatments. Our findings indicate that renal functions and inflammatory response were modulated by adropin and SPX peptides. These peptides may have protective effects on systemic inflammation and renal failure progression.


Assuntos
Adenina , Falência Renal Crônica , Adenina/toxicidade , Animais , Citocinas , Hormônios , Inflamação , Ratos
18.
Zhen Ci Yan Jiu ; 46(8): 649-55, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34472749

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Zusanli"(ST36) and "Sanyinjiao"(SP6) on serum TNF-α, IL-1ß, and IL-6 and expression of synovial matrimetalloproteinases (MMPs) and articular morphology in collagen-induced arthritis (CIA) rats, so as to explore its mechanisms underlying relief of arthritis. METHODS: Thirty male SD rats were randomly divided into normal control, CIA model and EA groups (n=10 rats per group). The arthritis model was induced by multi-point intradermal injection of bovine type Ⅱ collagen emulsion. EA (2 Hz/100 Hz, 1 mA) was applied to bilateral ST36 and SP6 for 30 min, once a day for 28 days. The hind-limb paw volume was measured and the arthritis index (AI) score given according to the swelling degree, rigidity and deformity of the ankle joint (0-4 points). After EA intervention, the morphological damage of the affected ankle joints was revealed by H.E. staining, safranin O-fast green staining, and tartrate-resistant acid phosphatase (TRAP) staining, separately. The levels of serum TNF-α, IL-1ß, and IL-6 were measured by ELISA, and the expression levels of MMP-1, MMP-3, MMP-13, and receptor activator of nuclear factor Kappa B ligand (RANKL) in the synovial tissue were detected by Western blot. RESULTS: Compared with the normal control group, the paw volume, AI score, TRAP-revealed number of osteoclasts, contents of serum TNF-α, IL-1ß and IL-6, and expression levels of MMP-1, MMP-3, MMP-13 and RANKL proteins were significantly increased in the model group (P<0.01, P<0.05). Following the intervention, the paw volume, AI score, number of osteoclasts, contents of serum TNF- α, IL-1ß and IL-6, and expression levels of MMP-1, MMP-3, MMP-13 and RANKL proteins were significantly decreased in the EA group (P<0.05, P<0.01) in contrast to the model group. H.E. and safranin O-fast green staining showed rough articular cartilage surface with thinned cartilage layer, obvious hyperplasia of the synovial tissue with many inflammatory cells, and serious damage and degradation of the cartilage matrix in the model group, these situations were relatively milder in the EA group. CONCLUSION: EA of ST36 and SP6 can reduce the articular damage in collagen-induced arthritis rats, which is associated with its function in reducing inflammatory response and down-regulating the expression of synovial MMP-1, MMP-3, MMP-13 and RANKL proteins.


Assuntos
Artrite Experimental , Eletroacupuntura , Animais , Artrite Experimental/genética , Artrite Experimental/terapia , Bovinos , Inflamação/genética , Inflamação/terapia , Masculino , Ratos , Ratos Sprague-Dawley , Membrana Sinovial
19.
Front Endocrinol (Lausanne) ; 12: 726967, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484128

RESUMO

In March 2020, the WHO declared coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a global pandemic. Obesity was soon identified as a risk factor for poor prognosis, with an increased risk of intensive care admissions and mechanical ventilation, but also of adverse cardiovascular events. Obesity is associated with adipose tissue, chronic low-grade inflammation, and immune dysregulation with hypertrophy and hyperplasia of adipocytes and overexpression of pro-inflammatory cytokines. However, to implement appropriate therapeutic strategies, exact mechanisms must be clarified. The role of white visceral adipose tissue, increased in individuals with obesity, seems important, as a viral reservoir for SARS-CoV-2 via angiotensin-converting enzyme 2 (ACE2) receptors. After infection of host cells, the activation of pro-inflammatory cytokines creates a setting conducive to the "cytokine storm" and macrophage activation syndrome associated with progression to acute respiratory distress syndrome. In obesity, systemic viral spread, entry, and prolonged viral shedding in already inflamed adipose tissue may spur immune responses and subsequent amplification of a cytokine cascade, causing worse outcomes. More precisely, visceral adipose tissue, more than subcutaneous fat, could predict intensive care admission; and lower density of epicardial adipose tissue (EAT) could be associated with worse outcome. EAT, an ectopic adipose tissue that surrounds the myocardium, could fuel COVID-19-induced cardiac injury and myocarditis, and extensive pneumopathy, by strong expression of inflammatory mediators that could diffuse paracrinally through the vascular wall. The purpose of this review is to ascertain what mechanisms may be involved in unfavorable prognosis among COVID-19 patients with obesity, especially cardiovascular events, emphasizing the harmful role of excess ectopic adipose tissue, particularly EAT.


Assuntos
COVID-19/metabolismo , Cardiomiopatias/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/complicações , COVID-19/imunologia , Cardiomiopatias/imunologia , Cardiomiopatias/patologia , Cardiopatias/imunologia , Cardiopatias/metabolismo , Cardiopatias/patologia , Humanos , Inflamação , Gordura Intra-Abdominal/patologia , Obesidade/complicações , Obesidade/imunologia , Obesidade/patologia , Pericárdio , Prognóstico , SARS-CoV-2/metabolismo , Serina Endopeptidases/metabolismo
20.
Talanta ; 235: 122719, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34517587

RESUMO

Here, a dual lock-and-key fluorescence probe was developed for visualizing the inflammatory process in myocardial H9C2 cells. The probe possessed two-photon properties, viscosity sensitivity, and hydrogen peroxide (H2O2) responsiveness. A thiocarbamate spacer between fluorophore and H2O2 responsive unit enabled the release of carbonyl sulfide (COS). This rapidly converts to the anti-inflammatory hydrogen sulfide (H2S) by the ubiquitous enzyme carbon anhydrase. The probe displayed a dual response towards hydrogen peroxide and viscosity in vitro. No obvious fluorescence changes were observed towards either hydrogen peroxide or viscosity alone. In cellular experiments, the probe demonstrated good biocompatibility, low toxicity, and was shown responses towards exogenous and endogenous hydrogen peroxide under viscosity conditions. LPS induced cell inflammation showed it was able to effectively alleviate the inflammation-caused damage by releasing H2S and eliminating H2O2. The new protocol demonstrates its promising to achieve diagnosis and treatment of cellular inflammatory process.


Assuntos
Corantes Fluorescentes , Sulfeto de Hidrogênio , Fluorescência , Células HeLa , Humanos , Peróxido de Hidrogênio , Inflamação/tratamento farmacológico , Viscosidade
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