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Age-related macular degeneration (AMD) causes severe blindness in the elderly due to choroidal neovascularization (CNV), which results from the dysfunction of the retinal pigment epithelium (RPE). While normal RPE depends exclusively on mitochondrial oxidative phosphorylation for energy production, the inflammatory conditions associated with metabolic reprogramming of the RPE play a pivotal role in CNV. Although mitochondrial pyruvate dehydrogenase kinase (PDK) is a central node of energy metabolism, its role in the development of CNV in neovascular AMD has not been investigated. In the present study, we used a laser-induced CNV mouse model to evaluate the effects of Pdk4 gene ablation and treatment with pan-PDK or specific PDK4 inhibitors on fluorescein angiography and CNV lesion area. Among PDK isoforms, only PDK4 was upregulated in the RPE of laser-induced CNV mice, and Pdk4 gene ablation attenuated CNV. Next, we evaluated mitochondrial changes mediated by PDK1-4 inhibition using siRNA or PDK inhibitors in inflammatory cytokine mixture (ICM)-treated primary human RPE (hRPE) cells. PDK4 silencing only in ICM-treated hRPE cells restored mitochondrial respiration and reduced inflammatory cytokine secretion. Likewise, GM10395, a specific PDK4 inhibitor, restored oxidative phosphorylation and decreased ICM-induced upregulation of inflammatory cytokine secretion. In a laser-induced CNV mouse model, GM10395 significantly alleviated CNV. Taken together, we demonstrate that specific PDK4 inhibition could be a therapeutic strategy for neovascular AMD by preventing mitochondrial metabolic reprogramming in the RPE under inflammatory conditions.
Assuntos
Neovascularização de Coroide , Modelos Animais de Doenças , Degeneração Macular , Piruvato Desidrogenase Quinase de Transferência de Acetil , Epitélio Pigmentado da Retina , Animais , Humanos , Camundongos , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Neovascularização de Coroide/tratamento farmacológico , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Fosforilação Oxidativa/efeitos dos fármacos , Reprogramação MetabólicaRESUMO
Particulate matter (PM) poses significant health risks, especially fine particles (PM2.5) that can cause severe lung injuries. Lupeol, a phytosterol from medicinal plants, has potential anti-cancer properties. This study investigated lupeol's protective effects against PM2.5-induced lung damage. Mice received lupeol following intratracheal PM2.5 exposure. Results showed lupeol reduced lung damage, lowered wet/dry (W/D) weight ratio, and suppressed increased permeability caused by PM2.5. Additionally, lupeol decreased plasma inflammatory cytokines, total protein concentration in bronchoalveolar lavage fluid (BALF), and PM2.5-induced lymphocyte proliferation. Lupeol also reduced expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and autophagy-related proteins microtubule-associated protein 1 A/1 B-light chain 3 (LC3) II and Beclin 1, while increasing phosphorylated mammalian target of rapamycin (mTOR) phosphorylation. These findings suggest lupeol's potential as a therapeutic agent for PM2.5-induced lung damage via modulation of the TLR4-MyD88 and mTOR-autophagy pathways.
Assuntos
Material Particulado , Triterpenos Pentacíclicos , Pneumonia , Receptor 4 Toll-Like , Animais , Triterpenos Pentacíclicos/farmacologia , Material Particulado/toxicidade , Receptor 4 Toll-Like/metabolismo , Pneumonia/tratamento farmacológico , Pneumonia/metabolismo , Pneumonia/induzido quimicamente , Camundongos , Masculino , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Serina-Treonina Quinases TOR/metabolismo , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Autofagia/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Citocinas/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Proteína Beclina-1/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , LupanosRESUMO
Background: To report a novel surgical technique for recurrent pupillary optic capture after flanged intraocular lens (IOL) fixation. Methods: In this retrospective case series, we detail our use of two parallel 7-0 polypropylene sutures passed between the iris plane and the optic of scleral-fixated IOL to address pupillary optic capture. Flanges were created using ophthalmic cautery to secure it to the sclera without suture. Results: Two eyes with pupillary optic capture underwent a sutureless surgical technique using 7-0 polypropylene flanges. No recurrences of pupillary optic capture were observed during the 1-year follow-up. Conclusion: Our sutureless surgical technique using a 7-0 polypropylene flange was an effective, efficient, and less invasive approach for treating recurrent pupillary optic capture.
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This study aimed to compare the outcomes of flanged intraocular lens (IOL) fixation with new IOL exchange after dislocated IOL removal and repositioned dislocated IOL in patients with IOL dislocation. Eighty-nine eyes that underwent flanged IOL fixation were retrospectively included, with 51 eyes in the exchanged IOL group and 38 eyes in the repositioned IOL group. In both groups, best-corrected visual acuity (BCVA) improved at 1, 3, 6, and 12 months postoperatively and did not differ between the two groups at any of these time points. However, at 1 week postoperatively, BCVA in the repositioned IOL group improved compared with baseline, whereas that in the exchanged IOL group did not. Moreover, there were lesser changes in the corneal endothelial cell density (ECD) and corneal astigmatism in the repositioned IOL group than in the exchanged IOL group. The IOL positions, including IOL tilt and IOL decentration, were not different between the groups. Flanged IOL fixation with new IOL exchange and with repositioned dislocated IOL for patients with IOL dislocation had similar visual outcomes and IOL position. However, the latter had a smaller corneal ECD decrease and astigmatic change. This technique was effective in treating IOL dislocation while minimizing corneal injury.
Assuntos
Subluxação do Cristalino , Lentes Intraoculares , Humanos , Implante de Lente Intraocular/métodos , Estudos Retrospectivos , Acuidade Visual , Subluxação do Cristalino/cirurgia , Técnicas de Sutura , Complicações Pós-Operatórias/cirurgiaRESUMO
Background: Existing research on the association between cognitive function and physical activity in the older adults population with disabilities is limited. Additionally, there is a need to explore avenues for enhancing the longevity and quality of life among these individuals. Objective: This study aimed to investigate the independent and joint associations between cognitive function and levels of physical activity in the older adults population with disabilities. Methods: A total of 315 older adults adults (men = 182, women = 133), identified with disabilities based on medical evaluation, were recruited from the first survey of the Korean Longitudinal Study of Aging (KLoSA). Participants underwent assessments for cognitive function, physical activity (PA), activities of daily living (ADLs), instrumental activities of daily living (IADLs), and grip strength. Results: ADLs (p < 0.001) and IADLs (p < 0.001) scores were significantly higher in the male normal cognitive group compared to both the male and female cognitive impairment groups. In an unadjusted model, disabled older adults individuals who did not meet the recommended PA guidelines showed an increased odds ratio for cognitive dysfunction (OR = 2.29, 95% CI = 1.32-3.97). Those participating in PA at least 1 day per week also demonstrated an elevated odds ratio (OR = 1.22, 95% CI = 1.08-1.38) for cognitive dysfunction compared to those who engaged in regular PA. A negative correlation was observed between K-MMSE scores and grip strength (r = 0.448, p < 0.001). Conclusion: This study provides robust evidence that disabled older adults individuals who do not meet the recommended guidelines for PA or who do not participate in PA at least once a week have an increased likelihood of cognitive impairment compared to those who are regularly active.
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Disfunção Cognitiva , Pessoas com Deficiência , Humanos , Masculino , Feminino , Idoso , Estudos Longitudinais , Qualidade de Vida , Atividades Cotidianas , Disfunção Cognitiva/epidemiologia , Exercício FísicoRESUMO
Measuring patients' core body temperature during surgery is essential and commonly performed with an esophageal temperature probe. The probe must be placed in the lower third of the esophagus for accurate measurement. In this case report, we describe our experience of discovering an inadvertently malpositioned esophageal temperature probe in the right inferior lobar bronchus, which led to ventilation-related problems in a patient undergoing prostate surgery.
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Laparoscopia , Neoplasias da Próstata , Robótica , Masculino , Humanos , Próstata , Temperatura Corporal , Temperatura , Prostatectomia/efeitos adversos , Esôfago/diagnóstico por imagem , Esôfago/cirurgia , Neoplasias da Próstata/cirurgiaAssuntos
Laringoscópios , Lactente , Recém-Nascido , Humanos , Estudos Prospectivos , Laringoscopia , IntubaçãoRESUMO
Activation of hypoxia-inducible factor 1α (HIF1α) contributes to blood-retinal barrier (BRB) breakdown and pathological neovascularization responsible for vision loss in ischemic retinal diseases. During disease progression, mitochondrial biology is altered to adapt to the ischemic environment created by initial vascular dysfunction, but the mitochondrial adaptive mechanisms, which ultimately contribute to the pathogenesis of ischemic retinopathy, remain incompletely understood. In the present study, it is identified that expression of mitochondrial chaperone tumor necrosis factor receptor-associated protein 1 (TRAP1) is essential for BRB breakdown and pathologic retinal neovascularization in mouse models mimicking ischemic retinopathies. Genetic Trap1 ablation or treatment with small molecule TRAP1 inhibitors, such as mitoquinone (MitoQ) and SB-U015, alleviate retinal pathologies via proteolytic HIF1α degradation, which is mediated by opening of the mitochondrial permeability transition pore and activation of calcium-dependent protease calpain-1. These findings suggest that TRAP1 can be a promising target for the development of new treatments against ischemic retinopathy, such as retinopathy of prematurity and proliferative diabetic retinopathy.
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Retinopatia Diabética , Doenças Retinianas , Neovascularização Retiniana , Animais , Camundongos , Barreira Hematorretiniana , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Isquemia , Neovascularização Patológica/metabolismo , Retina/patologia , Doenças Retinianas/metabolismo , Doenças Retinianas/patologia , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/patologiaRESUMO
This study aimed to analyze the duration and causes of persistent subretinal fluid (PSF) after scleral buckle (SB) surgery in patients with macula-involving rhegmatogenous retinal detachment (RRD). Sixty-one eyes of 61 patients with macula-involving RRD who underwent SB surgery between 2016 and 2022 were reviewed retrospectively. PSF was confirmed on optical coherence tomography. The PSF duration after surgery and the analysis of relevant ocular and systemic factors were conducted according to the PSF duration. The mean duration of PSF was 5.9 ± 4.6 months in all eyes and 8.1 ± 5.0 months in eyes not treated with external subretinal fluid (SRF) drainage, which was significantly longer than 4.5 ± 3.7 months in those subjected to external SRF drainage. The mean best-corrected visual acuity improved significantly 3 months after surgery. There were significant visual improvements in the external SRF drainage group compared to the non-drainage group during all follow-up periods. Longstanding shallow RRD was significantly associated with longer PSF duration after SB surgery. External SRF drainage during SB surgery can effectively reduce SRF, shorten the duration of PSF, and accelerate visual improvement.
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Descolamento Retiniano , Humanos , Descolamento Retiniano/cirurgia , Líquido Sub-Retiniano , Estudos Retrospectivos , Acuidade Visual , Recurvamento da Esclera , Tomografia de Coerência Óptica/métodos , Vitrectomia , DrenagemRESUMO
The effects of cholesterol variability on cataracts, dementia, and osteoporosis remain controversial. Using a common data model, we investigated the effects of variations in cholesterol levels on the development of cataracts, dementia, and osteoporosis. Patients who received statin therapy between 2011 and 2020 and those with 3 or more tests for total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels were included. The patients were divided into those with a coefficient of variation (CV) of TC higher than the mean (high-CV group) and those with a lower CV of TC (low-CV group). Moreover, 1:1 propensity score matching was conducted based on demographic variables. Cataract, dementia, or osteoporosis was defined as having a diagnostic, drug, or surgical code based on the cohort definition. Of the 12,882 patients, cataracts, dementia, and osteoporosis were developed in 525 (4.1%), 198 (1.5%), and 438 (3.4%) patients, respectively. The stratified Cox proportional hazards model showed that the incidences of cataracts and osteoporosis were 1.38 and 1.45 times greater in the high-CV group than in the low-CV group, respectively. Our study revealed that TC variability is associated with developing cataracts and osteoporosis.
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Doenças Cardiovasculares , Catarata , Demência , Osteoporose , Humanos , Doenças Cardiovasculares/epidemiologia , Incidência , Colesterol , HDL-Colesterol , Demência/epidemiologia , Catarata/epidemiologia , Osteoporose/epidemiologia , TriglicerídeosRESUMO
Insulin resistance as a hallmark of type 2 DM (T2DM) plays a role in dementia by promoting pathological lesions or enhancing the vulnerability of the brain. Numerous studies related to insulin/insulin-like growth factor 1 (IGF-1) signaling are linked with various types of dementia. Brain insulin resistance in dementia is linked to disturbances in Aß production and clearance, Tau hyperphosphorylation, microglial activation causing increased neuroinflammation, and the breakdown of tight junctions in the blood-brain barrier (BBB). These mechanisms have been studied primarily in Alzheimer's disease (AD), but research on other forms of dementia like vascular dementia (VaD), Lewy body dementia (LBD), and frontotemporal dementia (FTD) has also explored overlapping mechanisms. Researchers are currently trying to repurpose anti-diabetic drugs to treat dementia, which are dominated by insulin sensitizers and insulin substrates. Although it seems promising and feasible, none of the trials have succeeded in ameliorating cognitive decline in late-onset dementia. We highlight the possibility of repositioning anti-diabetic drugs as a strategy for dementia therapy by reflecting on current and previous clinical trials. We also describe the molecular perspectives of various types of dementia through the insulin/IGF-1 signaling pathway.
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Doença de Alzheimer , Resistência à Insulina , Insulinas , Humanos , Fator de Crescimento Insulin-Like I/uso terapêutico , Reposicionamento de Medicamentos , Doença de Alzheimer/metabolismoRESUMO
A woman in her early 70s presented with a right fifth rib fracture along with left scapular body and glenoid fractures resulting from a traffic accident. She had no history of lung disease. The patient underwent multi-incisional video-guided arthroscopic fracture reduction and screw fixation in the right lateral decubitus position under general anesthesia, and surgery was followed by chest tube insertion. Left-sided pneumothorax was found during routine postoperative radiography despite the absence of relevant symptoms or signs such as hypoxia, chest pain, or respiratory difficulty. We herein report this unusual case with a brief literature review.
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Fraturas Ósseas , Pneumotórax , Humanos , Feminino , Artroscopia/efeitos adversos , Artroscopia/métodos , Ombro/diagnóstico por imagem , Ombro/cirurgia , Pneumotórax/diagnóstico por imagem , Pneumotórax/etiologia , Pneumotórax/cirurgia , Anestesia Geral/efeitos adversosRESUMO
In this study, the potential protective effects of cirsilineol (CSL), a natural compound found in Artemisia vestita, were examined on lipopolysaccharide (LPS)-induced inflammatory responses. CSL was found to have antioxidant, anticancer, and antibacterial properties, and was lethal to many cancer cells. We assessed the effects of CSL on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in LPS-activated human umbilical vein endothelial cells (HUVECs). We also examined the effects of CSL on the expression of iNOS, tumor necrosis factor (TNF)-α, and interleukin (IL)-1ß in the pulmonary histological status of LPS-injected mice. The results showed that CSL increased HO-1 production, inhibited luciferase-NF-κB interaction, and reduced COX-2/PGE2 and iNOS/NO levels, leading to a decrease in signal transducer and activator of transcription (STAT)-1 phosphorylation. CSL also enhanced the nuclear translocation of Nrf2, elevated the binding activity between Nrf2 and antioxidant response elements (AREs), and reduced IL-1ß expression in LPS-treated HUVECs. We found that CSL's suppression of iNOS/NO synthesis was restored by inhibiting HO-1 through RNAi. In the animal model, CSL significantly decreased iNOS expression in the pulmonary biostructure, and TNF-α level in the bronchoalveolar lavage fluid. These findings indicate that CSL has anti-inflammatory properties by controlling iNOS through inhibition of both NF-κB expression and p-STAT-1. Therefore, CSL may have potential as a candidate for developing new clinical substances to treat pathological inflammation.
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Flavonas , Inflamação , Animais , Humanos , Camundongos , Ciclo-Oxigenase 2/metabolismo , Células Endoteliais/metabolismo , Heme Oxigenase-1/metabolismo , Inflamação/tratamento farmacológico , Lipopolissacarídeos/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Flavonas/farmacologiaRESUMO
Acute lung injury (ALI) is a frequent and challenging aspect of sepsis that currently lacks effective treatments. Procyanidin B2 (PB2) has anti-inflammatory and antioxidant properties. The aim of this study was to determine the effectiveness and mechanism of action of PB2 in treating sepsis-induced ALI using animal experiments. A sepsis-induced ALI mouse model was used by administering lipopolysaccharide (LPS) and then evaluating the levels of inflammatory cytokines and lung injury through measurements of cytokine levels using enzyme-linked immunosorbent assay (ELISA), Western blot and real-time PCR, as well as by the examination of relevant signaling pathways. The animal experiments showed that PB2 protected the lungs from injury caused by LPS and reduced the levels of various inflammatory cytokines in both the serum and lung tissue. Western blot analysis showed that PB2 reduced the expression of TLR4/NF-κB and increased the expression of PI3K/Akt, and also inhibited the Hippo and Rho signaling pathways. The results of the study showed that PB2 helps to treat sepsis-induced ALI by controlling cytokine storms and reducing inflammation by altering the expressions of the TLR4/NF-κB, PI3K/Akt, Hippo and Rho signaling pathways. This research provides a foundation for the further investigation of PB2's mechanism and its potential use in treating sepsis.
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Lesão Pulmonar Aguda , Sepse , Camundongos , Animais , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Lipopolissacarídeos/farmacologia , Receptor 4 Toll-Like/metabolismo , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/induzido quimicamente , Transdução de Sinais , Pulmão/metabolismo , Citocinas/metabolismo , Sepse/complicações , Sepse/tratamento farmacológicoRESUMO
A small natural substance called cirsilineol (CSL), which was discovered in the plant Artemisia vestita, is lethal to many cancer cells and has antioxidant, anticancer, and antibacterial properties. Here, we investigated the underlying mechanisms of the antithrombotic action of CSL. We demonstrated that CSL has antithrombotic efficacy comparable to rivaroxaban, a direct blood coagulation factor Xa (FXa) inhibitor employed as a positive control, in inhibiting the enzymatic activity of FXa and the platelet aggregation induced by adenosine diphosphate (ADP) and U46619, a thromboxane A2 analog. The expression of P-selectin, the phosphorylation of myristoylated alanine-rich C kinase substrate by U46619 or ADP, and the activation of PAC-1 in platelets were inhibited by CSL. Nitric oxide production was increased by CSL in ADP- or U46619-treated human umbilical vein endothelial cells (HUVECs), although excessive endothelin-1 secretion was suppressed. CSL demonstrated strong anticoagulant and antithrombotic effects in a mouse model of arterial and pulmonary thrombosis. Our findings suggest that CSL is a potential pharmacological candidate for a novel class of anti-FXa and antiplatelet medications.
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Sarcopenic obesity (SO) is characterized by atrophic skeletal muscle impairment (sarcopenia) and obesity, which is associated with adverse outcomes of morbidity and mortality in elderly people. We investigated the effects of melatonin and exercise training on SO in 32-week-old senescence-accelerated mouse-prone-8 (SAMP8) mice fed a normal diet or a high-fat diet for 16 weeks. Melatonin, exercise, or melatonin and exercise for 8 weeks displayed reductions in the SO-induced impairment of skeletal muscle function and atrophy. Specifically, a decrease in mitochondrial calcium retention capacity in skeletal muscles observed in the HFD-con group was attenuated in melatonin and/or exercise intervention groups. More importantly, HFD-con mice displayed a lower number of Pax7+ satellite cells (SCs) and higher expression of p16ink than P8ND mice, which were attenuated by melatonin and/or exercise interventions. The cellular senescence in SC-derived primary myoblasts from HFD-con mice was significantly attenuated in myoblasts from the melatonin and/or exercise groups, which was reproduced in a senescence model of H2O2-treated C2C12 myoblasts. Our results suggest that melatonin and exercise training attenuate SO-induced skeletal muscle dysfunction, at least in part, through preserving the SC pool by inhibiting cellular senescence and attenuating mitochondrial dysfunction.
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Melatonina , Sarcopenia , Camundongos , Animais , Sarcopenia/metabolismo , Melatonina/farmacologia , Melatonina/metabolismo , Peróxido de Hidrogênio/metabolismo , Obesidade/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Dieta Hiperlipídica/efeitos adversosRESUMO
Particulate matter (PM) is a mixture comprising both organic and inorganic particles, both of which are hazardous to health. The inhalation of airborne PM with a diameter of ≤2.5 µm (PM2.5) can cause considerable lung damage. Cornuside (CN), a natural bisiridoid glucoside derived from the fruit of Cornus officinalis Sieb, exerts protective properties against tissue damage via controlling the immunological response and reducing inflammation. However, information regarding the therapeutic potential of CN in patients with PM2.5-induced lung injury is limited. Thus, herein, we examined the protective properties of CN against PM2.5-induced lung damage. Mice were categorized into eight groups (n = 10): a mock control group, a CN control group (0.8 mg/kg mouse body weight), four PM2.5+CN groups (0.2, 0.4, 0.6, and 0.8 mg/kg mouse body weight), and a PM2.5+CN group (0.2, 0.4, 0.6, and 0.8 mg/kg mouse body weight). The mice were administered with CN 30 min following intratracheal tail vein injection of PM2.5. In mice exposed to PM2.5, different parameters including changes in lung tissue wet/dry (W/D) lung weight ratio, total protein/total cell ratio, lymphocyte counts, inflammatory cytokine levels in the bronchoalveolar lavage fluid (BALF), vascular permeability, and histology were examined. Our findings revealed that CN reduced lung damage, the W/D weight ratio, and hyperpermeability caused by PM2.5. Moreover, CN reduced the plasma levels of inflammatory cytokines produced because of PM2.5 exposure, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and nitric oxide, as well as the total protein concentration in the BALF, and successfully attenuated PM2.5-associated lymphocytosis. In addition, CN substantially reduced the expression levels of Toll-like receptors 4 (TLR4), MyD88, and autophagy-related proteins LC3 II and Beclin 1, and increased protein phosphorylation of the mammalian target of rapamycin (mTOR). Thus, the anti-inflammatory property of CN renders it a potential therapeutic agent for treating PM2.5-induced lung injury by controlling the TLR4-MyD88 and mTOR-autophagy pathways.
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Lesão Pulmonar , Animais , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Citocinas/metabolismo , Glucosídeos/farmacologia , Pulmão/patologia , Lesão Pulmonar/patologia , Fator 88 de Diferenciação Mieloide/metabolismo , Material Particulado/efeitos adversos , Receptor 4 Toll-Like/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The dynamic behaviors of brain glial cells in various neuroinflammatory conditions and neurological disorders have been reported; however, little is known about the underlying intracellular signaling pathways. Here, we developed a multiplexed kinome-wide siRNA screen to identify the kinases regulating several inflammatory phenotypes of mouse glial cells in culture, including inflammatory activation, migration, and phagocytosis of glia. Subsequent proof-of-concept experiments involving genetic and pharmacological inhibitions indicated the importance of T-cell receptor signaling components in microglial activation and a metabolic shift from glycolysis to oxidative phosphorylation in astrocyte migration. This time- and cost-effective multiplexed kinome siRNA screen efficiently provides exploitable drug targets and novel insight into the mechanisms underlying the phenotypic regulation of glial cells and neuroinflammation. Moreover, the kinases identified in this screen may be relevant in other inflammatory diseases and cancer, wherein kinases play a critical role in disease signaling pathways.