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1.
Crit Rev Eukaryot Gene Expr ; 34(7): 1-16, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39072405

RESUMO

The aim of the present study was to explore the molecular mechanisms by which miR-193b-3p-trans-fected bone marrow mesenchymal stem cells (BMSCs) transplantation improves neurological impairment after traumatic brain injury (TBI) through sphingosine-1-phosphate receptor 3 (S1PR3)-mediated regulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway at the cellular and animal levels. BMSCs were transfected with miR-193b-3p. A TBI cell model was established by oxygen-glucose deprivation (OGD)-induced HT22 cells, and a TBI animal model was established by controlled cortical impact (CCI). Cell apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL), and cell activity was detected by a cell counting kit 8 (CCK-8) assay. Western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of related proteins and genes. In this study, transfection of miR-193b-3p into BMSCs significantly enhanced BMSCs proliferation and differentiation. Transfection of miR-193b-3p reduced the levels of the interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-alpha (TNF-α) inflammatory factors in cells and mouse models, and it inhibited neuronal apoptosis, which alleviated OGD-induced HT22 cell damage and neural function damage in TBI mice. Downstream experiments showed that miR-193b-3p targeting negatively regulated the expression of S1PR3, promoted the activation of the PI3K/AKT/mTOR signaling pathway, and inhibited the levels of apoptosis and inflammatory factors, which subsequently improved OGD-induced neuronal cell damage and nerve function damage in TBI mice. However, S1PR3 overexpression or inhibition of the PI3K/AKT/mTOR signaling pathway using the IN-2 inhibitor weakened the protective effect of miR-193b-3p-transfected BMSCs on HT22 cells. Transplantation of miR-193b-3p-transfected BMSCs inhibits neurological injury and improves the progression of TBI in mice through S1PR3-mediated regulation of the PI3K/AKT/mTOR pathway.


Assuntos
Lesões Encefálicas Traumáticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , MicroRNAs , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Receptores de Esfingosina-1-Fosfato , Serina-Treonina Quinases TOR , Animais , Humanos , Masculino , Camundongos , Apoptose , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/genética , Lesões Encefálicas Traumáticas/terapia , Modelos Animais de Doenças , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Receptores de Esfingosina-1-Fosfato/metabolismo , Receptores de Esfingosina-1-Fosfato/genética , Serina-Treonina Quinases TOR/metabolismo
2.
Mediators Inflamm ; 2024: 7459054, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38549714

RESUMO

Background: Cerebral ischemia-reperfusion injury is a common complication of ischemic stroke that affects the prognosis of patients with ischemic stroke. The lipid-soluble diterpene Tanshinone IIA, which was isolated from Salvia miltiorrhiza, has been indicated to reduce cerebral ischemic injury. In this study, we investigated the molecular mechanism of Tanshinone IIA in alleviating reperfusion-induced brain injury. Methods: Middle cerebral artery occlusion animal models were established, and neurological scores, tetrazolium chloride staining, brain volume quantification, wet and dry brain water content measurement, Nissl staining, enzyme-linked immunosorbent assay, flow cytometry, western blotting, and reverse transcription-quantitative polymerase chain reaction were performed. The viability of cells was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assays, while cell damage was measured by lactate dehydrogenase release in the in vitro oxygen glucose deprivation model. In addition, enzyme-linked immunosorbent assay, flow cytometry, western blotting, and reverse transcription-quantitative polymerase chain reaction were used to evaluate the therapeutic effect of Tanshinone IIA on ischemia/reperfusion (I/R) induced brain injury, as well as its effects on the inflammatory response and neuronal apoptosis, in vivo and in vitro. Furthermore, this study validated the targeting relationship between miR-124-5p and FoxO1 using a dual luciferase assay. Finally, we examined the role of Tanshinone IIA in brain injury from a molecular perspective by inhibiting miR-124-5p or increasing FoxO1 levels. Results: After treatment with Tanshinone IIA in middle cerebral artery occlusion-reperfusion (MCAO/R) rats, the volume of cerebral infarction was reduced, the water content of the brain was decreased, the nerve function of the rats was significantly improved, and the cell damage was significantly reduced. In addition, Tanshinone IIA effectively inhibited the I/R-induced inflammatory response and neuronal apoptosis, that is, it inhibited the expression of inflammatory cytokines IL-1ß, IL-6, TNF-α, decreased the expression of apoptotic protein Bax and Cleaved-caspase-3, and promoted the expression of antiapoptotic protein Bcl-2. In vitro oxygen-glucose deprivation/reoxygenation (OGD/R) cell model, Tanshinone IIA also inhibited the expression of inflammatory factors in neuronal cells and inhibited the occurrence of neuronal apoptosis. In addition, Tanshinone IIA promoted the expression of miR-124-5p. Transfection of miR-124-5p mimic has the same therapeutic effect as Tanshinone IIA and positive therapeutic effect on OGD cells, while transfection of miR-124-5p inhibitor has the opposite effect. The targeting of miR-124-5p negatively regulates FoxO1 expression. Inhibition of miR-124-5p or overexpression of FoxO1 can weaken the inhibitory effect of Tanshinone IIA on brain injury induced by I/R, while inhibition of miR-124-5p and overexpression of FoxO1 can further weaken the effect of Tanshinone IIA. Conclusion: Tanshinone IIA alleviates ischemic-reperfusion brain injury by inhibiting neuroinflammation through the miR-124-5p/FoxO1 axis. This finding provides a theoretical basis for mechanistic research on cerebral ischemia-reperfusion injury.


Assuntos
Abietanos , Lesões Encefálicas Traumáticas , Isquemia Encefálica , AVC Isquêmico , MicroRNAs , Traumatismo por Reperfusão , Humanos , Ratos , Animais , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , MicroRNAs/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/complicações , Oxigênio/metabolismo , Reperfusão/efeitos adversos , Glucose/metabolismo , Água , Apoptose
3.
BMC Pulm Med ; 22(1): 388, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36289489

RESUMO

BACKGROUND: Neutrophil infiltration accelerates the inflammatory response and is highly correlated to the development of acute lung injury (ALI). Budesonide (BUD) and N-acetylcysteine (NAC) both inhibit the inflammatory response to alleviate ALI, so we further investigated whether their combination is better for ALI. METHODS: In this study, we investigated the effect and mechanism of Combined BUD and NAC therapy on LPS-induced ALI. Rat ALI model and neutrophil abnormal activation model were established by lipopolysaccharide (LPS). BUD and NAC were treated alone or in combination, or cells were transfected with miR-196b-5p mimic or si-Socs3 to evaluate the efficacy and mechanism of BUD and NAC alone or in combination. Histopathological observation of lungs was performed by Hematoxylin Eosin (HE) staining. The quantity of neutrophils and inflammatory factors level in bronchoalveolar lavage fluid (BALF) were determined by Richter-Gimza complex stain and Enzyme-Linked Immunosorbnent Assay (ELISA), respectively. ReverseTranscription-PolymeraseChainReaction (RT-qPCR) was utilized to assess miR-196b-5p and inflammatory factor mRNA levels. The expression level of Socs3 was detected by immunohistochemistry or Western Blot. RESULTS: BUD and NAC combined treatment had a better effect on neutrophil recruitment and inflammatory response in LPS-induced ALI than did BUD and NAC alone. Transfection of the miR-196b-5p mimic reversed the effect of combined BUD and NAC. In conclusion, the combination of BUD and NAC is a better treatment for ALI. CONCLUSIONS: Combination therapy with BUD and NAC ameliorates LPS-induced ALI by attenuating neutrophil recruitment through the miR-196b-5p/Socs3 molecular axis.


Assuntos
Lesão Pulmonar Aguda , MicroRNAs , Ratos , Animais , Lipopolissacarídeos , Acetilcisteína , Infiltração de Neutrófilos , Budesonida/farmacologia , Amarelo de Eosina-(YS)/efeitos adversos , Hematoxilina , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo
4.
Neurol Res ; 46(6): 525-537, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38563325

RESUMO

BACKGROUND: Vascular dementia (VD) is the second most common type of dementia worldwide. Previous studies have proven that transcranial direct current stimulation (tDCS) has potential applications in relieving cognitive impairment in VD animal models. The purpose of this study was to probe the mechanism by which tDCS combined with swimming exercise improves the learning and memory abilities of VD model rats. METHOD: The VD rat model was induced using the permanent bilateral common carotid artery occlusion (2-VO) method; tDCS was applied to the rats and then they took part in swimming exercises. Rat memory, platform crossing time, and platform crossing frequency were analyzed via a water maze experiment. Nerve damage in the cortex and hippocampal CA1 area of the rats was observed using Nissl staining. Western blotting, immunohistochemistry, immunofluorescence staining and reverse transcription quantitative polymerase chain reaction (RT - qPCR) were used to determine the expression of related proteins and genes. The levels of oxidative stress were detected by kits. RESULTS: We demonstrated that VD model rats treated with tDCS combined with swimming exercise exhibited significant improvement in memory, and VD model rats exhibited significantly reduced neuronal loss in the hippocampus, and reduced microglial activation and M1 polarization. tDCS combined with swimming exercise protects VD model rats from oxidative stress through the miR-223-3p/protein arginine methyltransferase 8 (PRMT8) axis and inhibits the activation of the TLR4/NF-κB signaling pathway. CONCLUSION: Our results suggest that tDCS combined with swimming exercise improved the learning and memory ability of VD model rats by regulating the expression of PRMT8 through miR-223-3p to affect microglial activation and M1 polarization.


Assuntos
Demência Vascular , Memória , MicroRNAs , Microglia , Natação , Estimulação Transcraniana por Corrente Contínua , Animais , MicroRNAs/metabolismo , MicroRNAs/genética , Masculino , Microglia/metabolismo , Demência Vascular/terapia , Ratos , Estimulação Transcraniana por Corrente Contínua/métodos , Memória/fisiologia , Ratos Sprague-Dawley , Condicionamento Físico Animal/fisiologia , Condicionamento Físico Animal/métodos , Modelos Animais de Doenças , Aprendizagem em Labirinto/fisiologia
5.
Heart Lung ; 60: 35-38, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36878105

RESUMO

BACKGROUND: Patients with coronary heart disease (CHD) are susceptible to lung function problems caused by respiratory muscle weakness. Many CHD patients show complications of respiratory muscle weakness, but the risk factors remain unclear. OBJECTIVE: To explore the risk factors for inspiratory muscle weakness in CHD. METHODS: This study enrolled 249 patients with CHD who underwent maximal inspiratory pressure (MIP) measurement between April 2021 and March 2022.According to the percentage of MIP (MIP/Predicted normal value [PNV]), patients were divided into the inspiratory muscle weakness (IMW) (n = 149) (MIP/PNV<70%) and control groups (n = 100) (MIP/PNV≥70༅). Clinical information and MIP of the two groups were collected and analyzed. RESULTS: The incidence of IMW was 59.8% (n = 149). Age (P < 0.001); history of heart failure (P < 0.001), hypertension (P = 0.04), and peripheral artery disease (PAD) (P = 0.001); left ventricular end-systolic dimension (P = 0.035); presence of segmental motion abnormality of the ventricular wall (P = 0.030); and high density lipoprotein cholesterol (P = 0.001) and N-terminal brain natriuretic peptide (NT-proBNP) levels (P < 0.001) in the IMW group were significantly higher than those in the control group. The proportion of anatomic complete revascularization (P = 0.009), left ventricular ejection fraction (P = 0.010), and alanine transaminase (P = 0.014) and triglycerides levels (P = 0.014) in the IMW group were significantly lower than those in the control group. Logistic regression analysis showed that anatomic complete revascularization (OR=0.350, 95%CI 0.157-0.781) and NT-proBNP level (OR=1.002, 95%CI 1.000-1.004) were independent risk factors for IMW. CONCLUSION: The independent risk factors for decreased IMW in patients with CAD were anatomic incomplete revascularization and NT-proBNP level.


Assuntos
Doença das Coronárias , Função Ventricular Esquerda , Humanos , Volume Sistólico , Doença das Coronárias/complicações , Doença das Coronárias/epidemiologia , Debilidade Muscular/epidemiologia , Debilidade Muscular/etiologia , Fatores de Risco , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Biomarcadores
6.
PLoS One ; 18(8): e0289818, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37556466

RESUMO

BACKGROUND: Acute lung injury (ALI) usually has a high morbidity and mortality rate, but the current treatment is relatively scarce. Both budesonide (Bud) and N-acetylcysteine (NAC) exhibit protective effects in ALI, so we further investigated whether they have a synergistic effect on ALI when used together. METHODS: Establishment of a rat model of ALI with Lipopolysaccharide (LPS). Bud and NAC were administered by nebulized inhalation alone or in combination. Subsequently, HE staining was performed to observe the pathological changes in lungs of rat. Evans blue staining was implemented to assess alveolar permeability, and the pulmonary edema was assessed by measuring the ratio of wet to dry weight of the lung. Moreover, a TUNEL kit was served to test apoptosis in lung tissues. Western blot and immunohistochemistry were analyzed for expression of scorch-related proteins and NLRP3 in lung tissue, respectively. ELISA was implemented to detect inflammatory factor levels in BALF. and RT-qPCR was utilized to assess the expression level of miR-381. After stable transfection of miR-381 inhibitor or OE-NLRP3 in BEAS-2B treated with LPS, Bud and NAC, miR-381 expression was assessed by RT-qPCR, scorch death-related protein expression was measured by western blot, cell proliferation/viability was assayed by CCK-8, apoptosis was measured by flow cytometry, and ELISA was implemented to assess inflammatory factor levels. Furthermore, the Dual-luciferase assay was used to verify the targeting relationship. RESULTS: Bud and NAC treatment alone or in combination with nebulized inhalation attenuated the increased alveolar permeability, pulmonary edema, inflammatory response and scorching in LPS-induced ALI rats, and combined treatment with Bud and NAC was the most effective. In addition, combined treatment with Bud and NAC upregulated miR-381 expression and inhibited NLRP3 expression in cellular models and LPS-induced ALI rats. Transfection of the miR-381 inhibitor and OE-NLRP3 partially reversed the protective effects of Bud and NAC combination treatment on BEAS-2B cell proliferation inhibition, apoptosis, focal death and the inflammatory response. CONCLUSION: Combined Bud and NAC nebulization therapy alleviates LPS-induced ALI by modulating the miR-381/NLRP3 molecular axis.


Assuntos
Acetilcisteína , Lesão Pulmonar Aguda , Budesonida , MicroRNAs , Edema Pulmonar , Animais , Ratos , Acetilcisteína/uso terapêutico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Budesonida/uso terapêutico , Lipopolissacarídeos/efeitos adversos , Pulmão/patologia , MicroRNAs/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Edema Pulmonar/patologia , Transdução de Sinais
7.
Am J Transl Res ; 13(7): 7819-7828, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34377259

RESUMO

OBJECTIVE: To explore the effect of an evidence-based bundled care model in patients with dysphagia after severe traumatic brain injury (TBI). METHODS: This is a prospective randomized controlled study. A total of 60 patients with dysphagia after severe TBI (traumatic brain injury) admitted to the Department of Rehabilitation Medicine were selected and randomly divided into the test group (n=30) and the control group (n=30). Patients in the control group received routine care in the Department of Rehabilitation Medicine, while patients in the test group received evidence-based bundled care on the basis of the treatment of the control group. The improvement of swallowing function (dye test in comatose patients), oral hygiene, and nutritional risk was assessed in both groups. The incidence of adverse events such as aspiration and aspiration pneumonia, as well as the length and costs of hospitalization were compared between the two groups. RESULTS: Compared with patients in the control group, swallowing function of patients in the test group was significantly improved after the care (P<0.05), and for comatose patients, the positive rate of Evans blue dye test was markedly reduced (P<0.05). Compared with patients in the control group, the oral hygiene of patients in the test group was significantly improved after care, and the nutritional risk scores were also significantly decreased (P<0.05). During hospitalization, the total incidence of adverse events, length and costs of hospitalization of patients in the test group were significantly lower than those in the control group (P<0.05). CONCLUSION: Evidence-based bundled care can effectively improve swallowing function and reduce the incidence of nutritional risks and adverse events in patients with dysphagia after severe TBI, which further promotes postoperative rehabilitation of patients.

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