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1.
Ann Transl Med ; 9(10): 841, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34164475

RESUMO

Background: As a common malignant bone sarcoma, osteosarcoma (OS) affects the health and lives of many people. Here, we probed the effects of long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) and microRNA-758 (miR-758) on OS metastasis, and examined possible downstream effector. Methods: Quantitative reverse transcription PCR (qRT-PCR) was performed to detect the expressions of XIST and miR-758 in OS tissues and cells. Cell transfection was carried out to alter the levels of XIST and miR-758 in OS cells, and cell viability, migration, and invasion were assessed. Subsequently, qRT-PCR and a dual-luciferase reporter assay were conducted to analyze the regulatory effects of XIST on miR-758 and miR-758 on Rab16. Finally, we investigated whether Rab16 was the downstream effector of XIST/miR-758 axis. Results: XIST was highly expressed in OS tissues and cells, but the opposite was seen for miR-758. In OS cells, migration, invasion, and epithelial-mesenchymal transformation (EMT) was promoted by overexpression of XIST and miR-758 inhibitor, but were inhibited by XIST knockdown and miR-758 mimics. XIST regulated miR-758 expression, and miR-758 regulated Rab16 expression in OS cells. Overexpression of Rab16 reversed the effects of miR-758 mimics on OS cell migration and invasion. Conclusions: XIST contributed to OS cell migration, invasion, and EMT via regulation of miR-758/Rab16.

2.
Life Sci ; 277: 119490, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33862114

RESUMO

AIMS: Sepsis-associated encephalopathy (SAE) is one of the most common complications of sepsis, and it might lead to long-term cognitive dysfunction and disability. This study aimed to explore the role of S100 calcium binding protein B (S100B)/RAGE/ceramide signaling pathway in SAE. MAIN METHODS: FPS-ZM1 (an inhibitor of RAGE), myriocin and GW4869 (an inhibitor of ceramide) were used to explore the role of S100B/RAGE/ceramide in acute brain injury and long-term cognitive impairment in sepsis. In addition, Mdivi-1 (inhibitor of Drp1) and Drp1 siRNA were utilized to assess the effects of C2-ceramide on neuronal mitochondria, and to explore the specific underlying mechanism in C2 ceramide-induced death of HT22 mouse hippocampal neuronal cells. KEY FINDINGS: Western blot analysis showed that sepsis significantly up-regulated S100B and RAGE. Nissl staining and Morris water maze (MWM) test revealed that inhibition of RAGE with FPS-ZM1 markedly attenuated cecal ligation and puncture (CLP)-induced brain damage and cognitive dysfunction. Furthermore, FPS-ZM1 relieved sepsis-induced C2-ceramide accumulation and abnormal mitochondrial dynamics. Moreover, inhibition of ceramide also showed similar protective effects both in vivo and in vitro. Furthermore, Mdivi-1 and Drp1 siRNA significantly reduced C2-ceramide-induced neuronal mitochondrial fragmentation and cell apoptosis in vitro. SIGNIFICANCE: This study confirmed that S100B regulates mitochondrial dynamics through RAGE/ceramide pathway, in addition to the role of this pathway in acute brain injury and long-term cognitive impairment during sepsis.


Assuntos
Ceramidas/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo , Encefalopatia Associada a Sepse/metabolismo , Animais , Apoptose/efeitos dos fármacos , Encéfalo/metabolismo , Encefalopatias/complicações , Encefalopatias/metabolismo , Lesões Encefálicas/metabolismo , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Neurônios/metabolismo , Sepse/complicações , Encefalopatia Associada a Sepse/complicações , Encefalopatia Associada a Sepse/fisiopatologia , Transdução de Sinais
3.
Metab Brain Dis ; 36(4): 601-608, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33475982

RESUMO

Micro-RNA125b (miR-125b) and tumor protein p53 (p53) are involved in the regulation of mitochondrial dynamics; however, the mechanism of their possible interaction during oxidative stress remains unclear. In this study, we investigated the role and mechanism of miR-125b and p53 in oxidative stress-induced mitochondrial damage in immortalized mouse hippocampal HT22 cells. Following stimulation with H2O2, we observed downregulation of miR-125b expression, upregulation of p53 expression, mitochondria were damaged and increased cell death. Overexpression of miR-125b alleviated mitochondrial damage and inhibited p53 expression. Furthermore, confocal and electron microscopy showed that overexpression of p53 eliminated the protective effect of miR-125b on the mitochondria. Thus, miR-125b alleviates abnormal mitochondrial homeostasis in H2O2-treated HT22 cells by suppressing p53 expression. Our data reveal a new model by which miR-125b influences mitochondrial dynamics.


Assuntos
Peróxido de Hidrogênio/toxicidade , MicroRNAs/biossíntese , Dinâmica Mitocondrial/fisiologia , Proteína Supressora de Tumor p53/antagonistas & inibidores , Proteína Supressora de Tumor p53/metabolismo , Animais , Linhagem Celular Transformada , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Camundongos , MicroRNAs/genética , Dinâmica Mitocondrial/efeitos dos fármacos
4.
PeerJ ; 8: e9484, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32742785

RESUMO

Background: Bone marrow adipocyte (BMA), closely associated with bone degeneration, shares common progenitors with osteoblastic lineage. However, the intrinsic mechanism of cells fate commitment between BMA and osteogenic lineage remains unclear. Methods: Gene Expression Omnibus (GEO) dataset GSE107789 publicly available was downloaded and analyzed. Differentially expressed genes (DEGs) were analyzed using GEO2R. Functional and pathway enrichment analyses of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were conducted by The Database for Annotation, Visualization and Integrated Discovery and Gene set enrichment analysis software. Protein-protein interactions (PPI) network was obtained using STRING database, visualized and clustered by Cytoscape software. Transcriptional levels of key genes were verified by real-time quantitative PCR in vitro in Bone marrow stromal cells (BMSCs) undergoing adipogenic differentiation at day 7 and in vivo in ovariectomized mice model. Results: A total of 2,869 DEGs, including 1,357 up-regulated and 1,512 down-regulated ones, were screened out from transcriptional profile of human BMSCs undergoing adipogenic induction at day 7 vs. day 0. Functional and pathway enrichment analysis, combined with modules analysis of PPI network, highlighted ACSL1, sphingosine 1-phosphate receptors 3 (S1PR3), ZBTB16 and glypican 3 as key genes up-regulated at the early stage of BMSCs adipogenic differentiation. Furthermore, up-regulated mRNA expression levels of ACSL1, S1PR3 and ZBTB16 were confirmed both in vitro and in vivo. Conclusion: ACSL1, S1PR3 and ZBTB16 may play crucial roles in early regulation of BMSCs adipogenic differentiation.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32793507

RESUMO

Effective management of infectious osteomyelitis relies on timely microorganism identification and appropriate antibiotic therapy. Extracellular vesicles (EVs) carry protein and genetic information accumulated rapidly in the circulation upon infection. Rat osteomyelitis models infected by Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Escherichia coli were established for the present study. Serum EVs were isolated 3 days after infection. The size and number of serum EVs from infected rats were significantly higher than those from controls. In addition, bacterial aggregation assay showed that the S. aureus and E. coli formed large aggregates in response to the stimulation of serum EVs from S. aureus-infected and E. coli-infected rats, respectively. Treatment of EVs-S. epidermidis led to large aggregates of S. epidermidis and E. coli, whereas stimulation of EVs-P. aeruginosa to large aggregates of S. aureus and P. aeruginosa. To evaluate the changes in EVs in osteomyelitis patients, 28 patients including 5 S. aureus ones and 21 controls were enrolled. Results showed that the size and number of serum EVs from S. aureus osteomyelitis patients were higher than those from controls. Further analysis using receiver operating characteristic curves revealed that only the particle size might be a potential diagnostic marker for osteomyelitis. Strikingly, serum EVs from S. aureus osteomyelitis patients induced significantly stronger aggregation of S. aureus and a cross-reaction with P. aeruginosa. Together, these findings indicate that the size and number of serum EVs may help in the diagnosis of potential infection and that EVs-bacteria aggregation assay may be a quick test to identify infectious microorganisms for osteomyelitis patients.


Assuntos
Vesículas Extracelulares , Osteomielite , Infecções Estafilocócicas , Animais , Biomarcadores , Escherichia coli , Humanos , Osteomielite/diagnóstico , Ratos , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus
6.
J Mol Neurosci ; 70(12): 2049-2057, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32468218

RESUMO

Sepsis can induce acute and chronic changes in the central nervous system termed sepsis-associated encephalopathy (SAE). Not only cognitive deficits but also anxiety, depression, and post-traumatic stress disorder are common in severe sepsis survivors. In this study, we demonstrated that amitriptyline, a classic tricyclic antidepressant, reduced sepsis-induced brain damage through the tropomyosin receptor kinase A (TrkA) signaling pathway. Amitriptyline ameliorated neuronal loss assessed by Nissl staining in a mouse cecal ligation and puncture (CLP)-induced sepsis model. Furthermore, amitriptyline reduced early gliosis assessed by immunofluorescence and late cognitive deficits assessed by the Morris water maze (MWM) test. Moreover, amitriptyline treatment attenuated oxidative stress indicated by less superoxide dismutase (SOD) and catalase (CAT) activity consumption and malondialdehyde (MDA) accumulation. Interestingly, those protective effects of amitriptyline could be abolished by GW441756, a TrkA signaling pathway inhibitor. Immunoblot directly showed that TrkA signaling pathway-associated proteins, such as Akt and GSK3ß, were involved in the neuroprotective effects of amitriptyline. Thus, amitriptyline appears to be an encouraging candidate to treat cognitive deficits and depression after severe sepsis.


Assuntos
Amitriptilina/farmacologia , Antidepressivos Tricíclicos/farmacologia , Receptor trkA/metabolismo , Encefalopatia Associada a Sepse/tratamento farmacológico , Transdução de Sinais , Amitriptilina/uso terapêutico , Animais , Antidepressivos Tricíclicos/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Catalase/metabolismo , Gliose/tratamento farmacológico , Glicogênio Sintase Quinase 3 beta/metabolismo , Indóis/farmacologia , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-akt/metabolismo , Superóxido Dismutase/metabolismo
7.
Scanning ; 2020: 9147871, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32426086

RESUMO

In this paper, the effect of Er addition (0.2, 0.5, 0.65, 0.8, 1.0, and 1.5 wt. %) on the microstructure evolution and tensile properties of as-cast hypereutectic Al-10Si-0.8Fe alloy was investigated. The phases and their morphologies in these alloys were identified by XRD and SEM equipped with EDX with the help of metallographic analysis techniques; the length of the secondary phase (LSP) and secondary dendrite arm spacing (SDAS) of α-Al grain were quantified. The results indicated that the second phases (primary Si, eutectic Si, and iron-rich phases) and α-Al grain were significantly refined when the addition of Er increased from 0 to 0.8 wt. %. The mean LSP and SADS values were decreased to a minimum value when the Er addition reached 0.8 wt. %. However, the second phases and α-Al grain became coarser when the level of Er increased more than 0.8 wt. %. The analysis of XRD shows that Er mainly exists in the form of Er2Si compound. The microstructure modification also has a significant effect on the mechanical properties of the alloy. The yield strength (YS), ultimate tensile strength (UTS), and elongation (EL) increase from 52.86 MPa, 163.84 MPa, and 3.45% to 71.01 MPa, 163.84 MPa, and 5.65%, respectively. From the fracture surface, the promotions of mechanical properties are due to the dispersion and pinning reinforcement caused by the Er2Si phase.

8.
Sci Rep ; 10(1): 7718, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32382007

RESUMO

We investigated the role of dynamic changes of serum levels S100B protein in brain injury and poor outcome of sepsis. This is a prospective cohort study designed to include 104 adult patients with sepsis who are admitted to ICU from Jan 2015 to Aug 2016. Sepsis was defined as sepsis 3.0. Patients with a GCS score of <15, or at least one positive CAM-ICU score were thought to have brain dysfunction. 59 patients were diagnosed with SAE and the rest 45 patients were diagnosed with non-SAE. Serum S100B was measured on day 1 and 3 after ICU admission. Primary outcomes included brain dysfunction and 28-day/180-day mortality. The SAE group showed a significantly higher APACHE II score, SOFA scores, length of ICU stay, 28-day and 180-day mortality, serum S100B levels on day 1 and day 3. S100B levels on day 1 of 0.226 µg/L were diagnostic for SAE with 80.0% specificity and 66.1% sensitivity, and the area under (AUC) the curve was 0.728, S100B levels on day 3 of 0.144 µg/L were diagnostic for SAE with 84.44% specificity and 69.49% sensitivity, and the AUC was 0.819. In addition, the AUC for S100B on day 3 for predicting 180-day mortality was larger than for S100B on day 1 (0.731 vs. 0.611). Multiple logistic regression analysis showed that S100B3 (p = 0.001) but not S100B1 (p = 0.927) were independently correlated with SAE. Kaplan-Meier survival analysis showed that patients with S100B levels higher than 0.144 µg/L had a lower probability of survival at day 180. There were more patients with encephalopathy and a higher 28-day or 180-day mortality in the ΔS100B + group than in the ΔS100B- group. Multiple logistic regression analysis showed that SAE and IL-6 on day 3 were independently correlated with S100B dynamic increase. These findings suggest that elevated serum S100B levels on day 3 and the dynamic changes of serum S100B levels from day three to one were more associated with brain dysfunction and mortality than that on day 1 in patients with sepsis.


Assuntos
Lesões Encefálicas/sangue , Interleucina-6/sangue , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Encefalopatia Associada a Sepse/sangue , Lesões Encefálicas/epidemiologia , Lesões Encefálicas/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Encefalopatia Associada a Sepse/epidemiologia , Encefalopatia Associada a Sepse/patologia
9.
Pulm Pharmacol Ther ; 62: 101918, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32251714

RESUMO

Sepsis is among the most devastating events in intensive care units. As a complication of sepsis, acute lung injury (ALI) is common and highly associated with poor outcome. The present study demonstrated that abnormal mitochondrial dynamics play a pivotal role in lipopolysaccharide (LPS)-induced ALI. Inhibiting the mitochondrial fission with the specific inhibitor-1 (Mdivi-1) ameliorated ALI as assessed by hematoxylin and eosin (H&E) staining and wet/dry ratio. Furthermore, Mdivi-1 reduced mitogen-activated protein kinases (MAPKs) activation, oxidative stress and apoptosis in the lungs. Plasma pro-inflammation cytokines were also reduced significantly in Mdivi-1-treated mice. In vitro study revealed that Mdivi-1 protected the macrophages from LPS-induced MAPKs activation, oxidative stress and cell apoptosis. Mdivi-1 also inhibited the release of pro-inflammatory cytokines. Morphological analysis showed that Mdivi-1 rescued the macrophages from LPS-induced mitochondrial fragmentation. Moreover, LPS treatment induced significant phosphorylation of Drp1 at Ser616, dephosphorylation at Ser637 and translocation of Drp1 from the cytoplasm to mitochondria, while Mdivi-1 inhibited those effects. Thus, modification of fission to rebuild mitochondrial homeostasis may offer an innovative opportunity for developing therapeutic strategies against ALI.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Apoptose/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Quinazolinonas/uso terapêutico , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Citocinas/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Modelos Animais , Células RAW 264.7
10.
Surg Infect (Larchmt) ; 21(9): 773-777, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32125944

RESUMO

Background: This study investigated the association between post-traumatic chronic osteomyelitis (COM) and peripheral leukocyte telomere length (PLTL) and explored factors associated with PLTL in COM. Methods: A total of 56 patients with post-traumatic COM of the extremity and 62 healthy control subjects were recruited. The PLTL was measured by real-time PCR. Binary logistic regression analysis was used to identify factors in correlation with telomere length. Sex, age, white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and infection duration were included as independent variables in the logistic regression model. Results: Post-traumatic COM patients had significantly shorter PLTLs (5.39 ± 0.40) than healthy control subjects (5.69 ± 0.46; p < 0.001). Binary logistic regression analysis showed that PLTL had a statistically significant association with age (B = -0.072; p = 0.013) and CRP (B = -0.061; p = 0.033). The logistic regression model was statistically significant and explained 31.4% (Nagelkerke R2) of the change in telomere length and correctly classified 69.6% of the cases. Conclusions: Patients with post-traumatic COM have shorter PLTLs than healthy subjects. The PLTL erosion of post-traumatic COM was partially explained by age and CRP.


Assuntos
Leucócitos/patologia , Osteomielite/genética , Osteomielite/patologia , Telômero/genética , Proteína C-Reativa , Humanos , Contagem de Leucócitos
11.
Biochem Biophys Res Commun ; 520(1): 171-178, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31582222

RESUMO

SS-31 is a kind of mitochondrion-targeted peptide. Recent studies indicated significant neuroprotective effects of SS-31. In this study, we investigated that SS-31 protected the murine cultured microglial cells (BV-2) against lipopolysaccharide (LPS)-induced inflammation and oxidative stress through stabilizing mitochondrial morphology. The morphological study showed that SS-31 preserved LPS-induced mitochondrial ultrastructure by reducing the fission protein 1 (Fis1) expression. Flow cytometry and Western blot verified that SS-31 defended the BV-2 cells against LPS-stimulated inflammation and oxidative stress via suppressing Fis1. To sum up, our study represents that SS-31 preserves BV-2 cells from LPS-stimulated inflammation and oxidative stress by down-regulating the Fis1 expression.


Assuntos
Inflamação , Lipopolissacarídeos/metabolismo , Microglia/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Oligopeptídeos/farmacologia , Estresse Oxidativo , Animais , Lentivirus/metabolismo , Camundongos , Microglia/metabolismo , Mitocôndrias/metabolismo , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico/metabolismo , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo
12.
Stem Cells Int ; 2019: 1839627, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31360172

RESUMO

Introduction: The effects of erythropoietin (EPO) on the behaviors of bone marrow mesenchymal stem cells (BMSCs) subjected to mechanical stretch remain unclear. This study was therefore aimed at establishing the dose-response effect of EPO stimulation on rat BMSCs and investigating the effects of mechanical stretch combined with EPO on the proliferation and osteogenic differentiation of BMSCs. Material and Methods: The proliferation and osteogenic differentiation of rat BMSCs were examined and compared using EPO with different concentrations. Thereafter, BMSCs were subjected to 10% elongation using a Flexcell strain unit, combined with 20 IU/ml EPO. The proliferation of BMSCs was detected by Cell Counting Kit-8, colony formation assay, and cell cycle assay; meanwhile, the mRNA expression levels of Ets-1, C-myc, Ccnd1, and C-fos were detected by reverse transcription and real-time quantitative PCR (qPCR). The osteogenic differentiation of BMSCs was detected by alkaline phosphatase (ALP) staining, and the mRNA expression levels of ALP, OCN, COL, and Runx2 were detected by qPCR. The role of the extracellular signal-regulated kinases 1/2 (ERK1/2) in the osteogenesis of BMSCs stimulated by mechanical stretch combined with 20 IU/ml EPO was examined by Western blot. Results: Our results showed that effects of EPO on BMSCs included a dose-response relationship, with the 20 IU/ml EPO yielding the largest. Mechanical stretch combined with 20 IU/ml EPO promoted proliferation and osteogenic differentiation of BMSCs. The increase in ALP, mineral deposition, and osteoblastic genes induced by the mechanical stretch-EPO combination was inhibited by U0126, an ERK1/2 inhibitor. Conclusion: EPO was able to promote the proliferation and osteogenic differentiation of BMSCs, and these effects were enhanced when combined with mechanical stretch. The underlying mechanism may be related to the activation of the ERK1/2 signaling pathway.

13.
J Crit Care ; 52: 172-179, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31078998

RESUMO

PURPOSE: We investigated the role of serum Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-Terminal Hydrolase-L1 (UCH-L1) in diagnosis of sepsis-associated encephalopathy(SAE), predicting prognosis and long-term quality of life with patients of sepsis. MATERIALS AND METHODS: This is a prospective single center study entailed 105 patients whosuffered from sepsis from Jan 2015 to Aug 2016. Serum concentrations of GFAP and UCH-L1 for diagnosis of SAE and predicting prognosis and long-term quality of life with patients of sepsis were analyzed. RESULTS: The serum concentrations of GFAP and UCH-L1 were higher in SAE group than in no-SAE group (p < .001). GFAP and UCH-L1 produced an AUC of 0.824 and 0.812 respectively for diagnosis of SAE with optimal cut-off values 0.532 ng/ml and 7.72 ng/ml respectively. The optimal cut-off values of GFAP and UCH-L1 to distinguish patients with survivors from non-survivors were 0.536 ng/ml and 8.06 ng/ml with an area under the curve of 0.773 and 0.746. Patients with a higher GFAP levels had worse long-term usual activities and patients with a higher UCH-L1 levels had more long-term pain (P = .026). CONCLUSIONS: Serum concentrations GFAP and UCH-L1 early elevated and associated with sepsis-associated encephalopathy, poor prognosis and quality of life.


Assuntos
Proteína Glial Fibrilar Ácida/metabolismo , Encefalopatia Associada a Sepse/diagnóstico , Ubiquitina Tiolesterase/metabolismo , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Qualidade de Vida , Encefalopatia Associada a Sepse/sangue
14.
J Intensive Care Med ; 34(11-12): 938-945, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-28718340

RESUMO

BACKGROUND: Sepsis and sepsis-associated encephalopathy (SAE) are common intensive care unit (ICU) diseases; the morbidity and mortality are high. The present study analyzed the sensitivity of different diagnostic criteria of sepsis 1.0 and 3.0, epidemiological characteristics of sepsis and SAE, and explored its risk factors for death, short-term, and long-term prognosis. METHODS: The retrospective study included patients in ICU from January 2015 to June 2016. After excluding 58 patients, 175 were assigned to either an SAE or a non-SAE group (patients with sepsis but no encephalopathy). The sensitivity of the diagnostic criteria was compared between sepsis 1.0 and 3.0, respectively. Between-group differences in baseline data, Acute Physiology and Chronic Health Evaluation II score (APACHE II score), Sequential Organ Failure Assessment score (SOFA score), etiological data, biochemical indicators, and 28-day and 180-day mortality rates were analyzed. Survival outcomes and long-term prognosis were observed, and risk factors for death were analyzed through 180-day follow-up. RESULTS: The sensitivity did not differ significantly between the diagnostic criteria of sepsis 1.0 and 3.0 (P = .286). The 42.3% incidence of SAE presented a significantly high APACHE II and SOFA scores as well as 28-day mortality and 180-day mortality (all P < .001). The incidence of death was 37.1%. The multivariate stepwise regression analysis demonstrated that the risk of death in SAE group was significantly higher than the non-SAE group (P < .001). Sepsis-associated encephalopathy is a risk factor for sepsis-related death (relative risk [RR] = 2.868; 95% confidence interval: 1.730-4.754; P < .001). Although males showed a significantly high rate of 28-day and 180-day mortality (P = .035 and .045), it was not an independent risk factor for sepsis-related death (P = .072). The long-term prognosis of patients with sepsis was poor with decreased quality of life. No significant difference was observed in prognosis between the SAE and non-SAE groups (P > .05). CONCLUSION: Both diagnostic criteria cause misdiagnosis, and the sensitivity did not differ significantly. The incidence of SAE was high, and 28-day and 180-day mortality rates were significantly higher than those without SAE. Sepsis-associated encephalopathy is a risk factor for poor outcome. The overall long-term prognosis of patients with sepsis was poor, and the quality of life decreased.


Assuntos
APACHE , Escores de Disfunção Orgânica , Encefalopatia Associada a Sepse/mortalidade , Sepse/mortalidade , Adulto , Idoso , Feminino , Mortalidade Hospitalar , Humanos , Incidência , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prognóstico , Qualidade de Vida , Estudos Retrospectivos , Fatores de Risco , Sepse/patologia , Encefalopatia Associada a Sepse/patologia
15.
Exp Ther Med ; 15(6): 5377-5383, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29805550

RESUMO

It is understood that mechanical loading may affect tendon properties. However, how different mechanical loading conditions may affect tendons remains unknown. The present study aimed to investigate the effect of treadmill running at various intensities on rat Achilles tendon. A total of 18 male Wistar rats were randomly assigned to one of three groups: Control (CON), medium-intensity running (MIR), and high-intensity running (HIR). Following 8 weeks of treadmill running protocols, all Achilles tendons were harvested for histological observation and gene expression analysis. Significant morphological changes were observed with regular and large diameter collagen fibrils in the MIR group, whereas irregular and small diameter collagen fibrils were observed in the HIR group. Collagen type I was significantly upregulated in the MIR group compared with the CON group, and downregulated in the HIR group compared with the CON or MIR groups (P<0.05). However, collagen type III was significantly upregulated in the HIR group in comparison with the CON or MIR groups (P<0.05). Furthermore, the expression of matrix metallopeptidase-13 was significantly increased in the MIR and HIR groups compared with the CON group (P<0.05). The expression of tissue inhibitor of metalloproteinases-1 was increased in the MIR group compared with the CON group, but decreased in the HIR group compared with the CON and MIR groups (P<0.05). Additionally, decorin expression was significantly higher in the MIR group compared with the CON group, and significantly decreased in the HIR group compared with the CON or MIR groups (P<0.05). A converse pattern of changes in biglycan expression was identified among the three groups. Aggrecan expression was significantly higher in the HIR group compared with the CON or MIR groups (P<0.05). These findings indicated that moderate exercise may induce increased collagen synthesis and organize regular and large collagen fibers, thus benefiting the Achilles tendon. However, overuse during exercise may result in collagen degradation and disturbance, which predisposes individuals to injury.

16.
Mol Med Rep ; 17(6): 7911-7917, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29620182

RESUMO

Decorin is widely understood to affect collagen fibrillogenesis. However, little is understood about its response to various mechanical loading conditions. In the present study, 36 Wistar rats were randomly divided into control (CON), moderate treadmill running (MTR) and strenuous treadmill running (STR) groups. Animals in the MTR and STR groups were subjected to a 4­ or 8­week treadmill running protocol. Subsequently, all Achilles tendons were harvested to perform histological and biochemical analyses. Decorin expression was markedly increased in the MTR group compared with the CON group at 4 and 8 weeks. Conversely, decorin expression was markedly decreased in the STR group compared with the CON and MTR group at 4 and 8 weeks. Furthermore, between the two time points, decorin expression levels were significantly increased in the MTR group, whereas they were markedly decreased in the STR group. These results suggested that MTR exercise may induce increased decorin expression via a balance of MMP­2 and TIMP­2, improving tendon structure and function. However, STR exercise may result in degradation of decorin due to an imbalance of MMP­2 and TIMP­2, with a bias to MMP­2, resulting in a predisposition to tendinopathy.


Assuntos
Decorina/farmacologia , Condicionamento Físico Animal , Esforço Físico/efeitos dos fármacos , Animais , Comportamento Animal , Biomarcadores , Imuno-Histoquímica , Masculino , Ratos
17.
Biochem Biophys Res Commun ; 496(3): 865-871, 2018 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-29395086

RESUMO

Sepsis is one of the most common reasons for mortality in Intensive Care Units. As a common but severe neurological complication, sepsis associated encephalopathy (SAE) has always been ignored and there is no generally accepted treatment. In this study, we demonstrated that Mdivi-1 ameliorated brain damage assessed by Nissl staining. Furthermore, Mdivi-1 reduced TUNEL-positive cells in hippocampus, and inhibited S100 calcium binding protein B (S100B) and neuron-specific enolase (NSE) release into plasma. Biochemical analysis also showed that Mdivi-1 protected hippocampus from oxidative stresses. Western blot analysis revealed that Mdivi-1, as a Drp1 inhibitor, inhibited LPS induced dynamin-related GTPase (Drp1) increase. Interestingly, it can also attenuate LPS induced optic atrophy 1 (OPA1) and phosphorylated Drp1 (p-Drp1) decrease. Thus Mdivi-1 protected rats from SAE, and this protective effect could be associated with its inhibition of Drp1 and its activation of p-Drp1 and OPA1. Mitochondrial dynamics may be a potential pharmacological therapeutic target for treating SAE.


Assuntos
Encéfalo/metabolismo , Encéfalo/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Quinazolinonas/administração & dosagem , Encefalopatia Associada a Sepse/tratamento farmacológico , Encefalopatia Associada a Sepse/patologia , Animais , Encéfalo/efeitos dos fármacos , Relação Dose-Resposta a Droga , Dinaminas/metabolismo , Lipopolissacarídeos , Masculino , Mitocôndrias/patologia , Fármacos Neuroprotetores/administração & dosagem , Ratos , Ratos Sprague-Dawley , Encefalopatia Associada a Sepse/metabolismo , Resultado do Tratamento
18.
Brain Res ; 1678: 56-63, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29030054

RESUMO

BACKGROUND: The CD38/cADPR pathway has been found to play roles in various inflammatory conditions. However, whether CD38 plays a protective or detrimental effect in the central nervous system (CNS) is controversial. The aim of this study was to determine the effect of CD38/cADPR pathway in sepsis associated brain injury. MATERIALS AND METHODS: Male Sprague-Dawley rats were undergone cecal ligation and puncture (CLP) or sham laparotomies. NAD+, cADPR and CD38 were measured in the hippocampus of septic rats at 0, 6, 12, 24, and 48h after CLP surgery. Rats were divided into the sham, CLP group, CLP+ CD38 expression lentivirus (CLP+ CD38 LV), CLP+ CD38 interference lentivirus (CLP+ CD38 Ri), CLP+ negative control lentivirus (CLP+NC) and the CLP+8-Br-cADPR groups. The Western blots of Bcl-2, Bax and iNOS, TUNEL assays, malondialdehyde (MDA) and superoxide dismutase (SOD) assays, transmission electron microscope analysis were performed in the hippocampus of rats. RESULTS: NAD+, cADPR and CD38 levels increased significantly in the hippocampus of septic rats as early as 12-24h after CLP surgery. CD38 knockdown or blocking cADPR with 8-Br-cADPR significantly reduced apoptosis, MDA and SOD activity, iNOS expression and ultrastructural morphology damages in the hippocampus of septic rats. CONCLUSIONS: In this study, we found that the CD38/cADPR pathway was activated in sepsis associated brain injury. Blocking this pathway protected the hippocampus from apoptosis, oxidative stress and ultrastructural morphology damages in septic rats.


Assuntos
ADP-Ribosil Ciclase 1/metabolismo , ADP-Ribosil Ciclase/metabolismo , ADP-Ribose Cíclica/metabolismo , Glicoproteínas de Membrana/metabolismo , Sepse/metabolismo , Sepse/prevenção & controle , ADP-Ribosil Ciclase/antagonistas & inibidores , ADP-Ribosil Ciclase 1/antagonistas & inibidores , Animais , Apoptose , Lesões Encefálicas/complicações , Lesões Encefálicas/metabolismo , Ceco/cirurgia , ADP-Ribose Cíclica/análogos & derivados , ADP-Ribose Cíclica/antagonistas & inibidores , ADP-Ribose Cíclica/farmacologia , Modelos Animais de Doenças , Hipocampo/metabolismo , Masculino , Glicoproteínas de Membrana/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
19.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 42(11): 1263-1269, 2017 Nov 28.
Artigo em Chinês | MEDLINE | ID: mdl-29187652

RESUMO

OBJECTIVE: To investigate the effects of Cordyceps sinensis (CS) on cellular apoptosis and Sirt1 expression in HK2 cells followed by ischemia-reperfusion (I/R).
 Methods: HK2 cells were incubated with different concentrations of CS (10, 20, 40, 80, 160, 320 mg/L) for 24 hours, and the optimal concentration of CS was selected by measuring cell proliferation. The confluent HK2 cells were incubated with 0.01 µmol/L antimycin A for 2 hours to induce ischemia in vitro, and then the reperfusion was achieved by incubating cells with glucose-replete complete growth medium for 24 hours. HK2 cells were divided into 4 groups: a control group, an I/R group, an I/R+CS (160 mg/L) group, and an I/R+CS (160 mg/L)+Sirtinol (25 µmol/L) group. Twenty-four hours later, total RNA and protein were collected. The cell proliferation was evaluated by MTT assay; the mRNA and protein expression of Sirt1 and the cleaved caspase-3 were measured by qRT-PCR and Western blot, respectively. The cellular apoptosis rate was determined by Annexin V-FITC/PI double staining and flow cytometry.
 Results: Certain concentrations (10-160 mg/L) of CS did not show effect on the proliferation of HK2 cells (P>0.05), while 320 mg/L of CS inhibited cell proliferation significantly (P<0.01); compared with the control group, the mRNA and protein expressions of Sirt1 and the cleaved caspase-3 in the I/R group were up-regulated (P<0.01) and the apoptosis rate was extremely high; compared with the I/R group, CS significantly up-regulated Sirt1 mRNA and protein expression (P<0.01) while down-regulated cleaved caspase-3 mRNA and protein levels (P<0.01), and reduced apoptosis rate (P<0.05). The effects of CS were blocked in the presence of sirtinol, an inhibitor of CS.
 Conclusion: CS protects HK2 cells from I/R injury through activation of Sirt1 pathway.


Assuntos
Apoptose , Cordyceps , Traumatismo por Reperfusão/prevenção & controle , Sirtuína 1/metabolismo , Antifúngicos , Antimicina A , Benzamidas/farmacologia , Caspase 3/genética , Caspase 3/metabolismo , Proliferação de Células , Células Cultivadas , Cordyceps/efeitos dos fármacos , Humanos , Isquemia/induzido quimicamente , Naftóis/farmacologia , RNA Mensageiro/metabolismo , Traumatismo por Reperfusão/metabolismo , Sirtuína 1/genética
20.
Int J Mol Med ; 40(4): 1261-1269, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28849179

RESUMO

Sepsis causes many early deaths; both macrophage mitochondrial damage and oxidative stress responses are key factors in its pathogenesis. Although the exact mechanisms responsible for sepsis-induced mitochondrial damage are unknown, the nuclear transcription factor, interferon regulatory factor-1 (IRF-1) has been reported to cause mitochondrial damage in several diseases. Previously, we reported that in addition to promoting systemic inflammation, IRF-1 promoted the apoptosis of and inhibited autophagy in macrophages. In the present study, we hypothesized that lipopolysaccharide (LPS)-induced IRF-1 activation in macrophages may promote mitochondrial damage and oxidative stress. In vitro, LPS was found to promote IRF-1 activation, reactive oxygen species (ROS) production, adenosine triphosphate (ATP) depletion, superoxide dismutase (SOD) consumption, malondialdehyde (MDA) accumulation and mitochondrial depolarization in macrophages in a time- and dose-dependent manner. These effects were abrogated in cells in which IRF-1 was knocked down. Furthermore, IRF-1 overexpression increased LPS-induced oxidative stress responses and mitochondrial damage. In vivo, peritoneal macrophages obtained from IRF-1 knockout (KO) mice produced less ROS and had less mitochondrial depolarization and damage following the administration of LPS, when compared to their wild-type (WT) counterparts. In addition, IRF-1 KO mice exhibited a decreased release of mitochondrial DNA (mtDNA) following the administration of LPS. Thus, IRF-1 may be a critical factor in augmenting LPS-induced oxidative stress and mitochondrial damage in macrophages.


Assuntos
Fator Regulador 1 de Interferon/genética , Lipopolissacarídeos/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Sepse/genética , Trifosfato de Adenosina/antagonistas & inibidores , Trifosfato de Adenosina/biossíntese , Animais , Regulação da Expressão Gênica , Fator Regulador 1 de Interferon/deficiência , Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/patologia , Masculino , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Estresse Oxidativo , Cultura Primária de Células , Células RAW 264.7 , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Sepse/induzido quimicamente , Sepse/metabolismo , Sepse/patologia , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
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