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1.
J Inflamm Res ; 17: 3101-3113, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774443

RESUMO

Purpose: This study aimed to assess liver involvement and investigate its correlation with rapidly progressive interstitial lung disease (RP-ILD) and mortality in anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5 positive) DM patients. Patients and Methods: This retrospective study included 159 patients diagnosed with anti-MDA5 positive DM or anti-synthetase syndrome (ASyS). Clinical features and laboratory findings were compared between patients with anti-MDA5 positive DM and patients with ASyS. In the anti-MDA5 positive DM cohort, clinical features and laboratory findings between patients with liver involvement and without liver involvement were further compared. The effects of liver involvement on the overall survival (OS) and development of RP-ILD were also analyzed using Kaplan-Meier method and Cox regression analysis. Results: Levels of serum aspartate aminotransferase (AST), alanine transaminase (ALT), γ-glutamyl transferase (γGT) and alkaline phosphatase (ALP) were all significantly higher in patients with anti-MDA5 positive DM than those in patients with ASyS. In our cohort of anti-MDA5 positive DM patents, 31 patients (34.4%) were complicated with liver involvement. Survival analysis revealed that serum ferritin >1030.0 ng/mL (p<0.001), ALT >103.0 U/l (p<0.001), AST >49.0 U/l (p<0.001), γGT >82.0 U/l (p<0.001), ALP >133.0 U/l (p<0.001), lactate dehydrogenase (LDH)>474.0 U/l (p<0.001), plasma albumin (ALB) <35.7 g/l (p<0.001) and direct bilirubin (DBIL) >2.80 µmol/l (p=0.002) predicted poor prognosis. The incidence of RP-ILD increased remarkably in patients with liver involvement compared to patients without liver involvement (58.1% vs 22.0%, p=0.001). Multivariate analysis revealed that elevated serum ALT level was an independent risk factor for mortality (HR 6.0, 95% CI 2.3, 16.2, p<0.001) and RP-ILD (HR 5.9, 95% CI 2.2, 15.9, p<0.001) in anti-MDA5 positive DM patents. Conclusion: Liver involvement is common in patients with anti-MDA5 positive DM. Elevated serum ALT level was an independent risk factor for RP-ILD and mortality in patients with anti-MDA5 positive DM.

2.
Immun Inflamm Dis ; 12(3): e1220, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38506409

RESUMO

OBJECTIVE: To investigate the effect of therapeutic hypercapnia on the expression and function of gamma delta T (γδ T) cells during ischemia-reperfusion injury (IRI) after lung transplantation. METHODS: We randomly divided male Wistar rats into three groups (n = 6 in each group), the control group (group N), the IRI group (group I), and the therapeutic hypercapnia group (group H). We then assessed pulmonary edema, neutrophil infiltration, wet-to-dry (W/D) weight ratio, and microscopic histopathology and separately measured the levels of γδT cell surface antigen (TCR) and Interleukin-17 (IL-17) using flow cytometry and enzyme-linked immunosorbent assays (ELISAs). RESULTS: The infiltration of neutrophils and the expression of TCR and IL-17 were significantly increased in the I group compared to the control, and the biopsy edema in group I was more severe. Arterial partial pressure of oxygen (PaO2) was decreased after reperfusion in group I compared with the control group. W/D weight ratio, neutrophil infiltration, and the expression of TCR and IL-17 decreased drastically in the H group compared to the I group. CONCLUSION: Our findings suggest that γδ T lymphocytes were directly involved in lung injury. In addition, therapeutic hypercapnia effectively reduced the expression of γδ T cells and IL-17, and this has the potential to become a treatment strategy for IRI and an intervention to improve lung function.


Assuntos
Hipercapnia , Interleucina-17 , Ratos , Masculino , Animais , Interleucina-17/metabolismo , Hipercapnia/terapia , Hipercapnia/metabolismo , Hipercapnia/patologia , Ratos Wistar , Pulmão/patologia , Receptores de Antígenos de Linfócitos T
3.
J Cell Mol Med ; 28(5): e18092, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38303549

RESUMO

Endoplasmic reticulum stress (ERS) and unfolded protein response are the critical processes of tumour biology. However, the roles of ERS regulatory genes in pancreatic adenocarcinoma (PAAD) remain elusive. A novel ERS-related risk signature was constructed using the Lasso regression analysis. Its prognostic value, immune effect, metabolic influence, mutational feature and therapeutic correlation were comprehensively analysed through multiple bioinformatic approaches. The biofunctions of KDELR3 and YWHAZ in pancreatic cancer (PC) cells were also investigated through colony formation, Transwell assays, flow cytometric detection and a xenograft model. The upstream miRNA regulatory mechanism of KDELR3 was predicted and validated. ERS risk score was identified as an independent prognostic factor and could improve traditional prognostic model. Meanwhile, it was closely associated with metabolic reprogramming and tumour immune. High ERS risk enhanced glycolysis process and nucleotide metabolism, but was unfavourable for anti-tumour immune response. Moreover, ERS risk score could act as a potential biomarker for predicting the efficacy of ICBs. Overexpression of KDELR3 and YWHAZ stimulated the proliferation, migration and invasion of SW1990 and BxPC-3 cells. Silencing KDELR3 suppressed tumour growth in a xenograft model. miR-137 could weaken the malignant potentials of PC cells through inhibiting KDELR3 (5'-AGCAAUAA-3'). ERS risk score greatly contributed to PAAD clinical assessment. KDELR3 and YWHAZ possessed cancer-promoting capacities, showing promise as a novel treatment target.

4.
Heliyon ; 9(10): e20878, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37867884

RESUMO

Background: Although opioids provide effective analgesia for abdominal surgery, they also present serious unwanted side effects. Ultrasound-guild quadratus lumborum block (QLB) and transversus abdominis plane block (TAPB) have been proven to offer long-lasting and efficient analgesia during abdominal surgery. However, the clinical efficacy of ultrasound-guided QLB and TAPB combined with opioid-free anesthesia (OFA) in abdominal surgery remains unclear. Objective: This study aimed to investigate the impact of ultrasound-guided QLB and TAPB combined with opioid-free anesthesia (OFA) on the clinical efficacy of abdominal surgery. Methods: A total of 122 patients scheduled for abdominal surgery at People's Hospital of Wanning between March 2021 and April 2022 were enrolled in this study. Participants were randomly divided into two groups: the experimental group (QLB/TAPB + OFA, 62 patients) and the control group (opioid anesthesia, 60 patients). The clinical efficacy of the QLB/TAPB combined with OFA technique was evaluated by analyzing patients' vital signs, postoperative consciousness recovery time, numeric rating scale (NRS) score, and immune function in both groups. Results: We observed that systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) in experimental group were significantly higher than those in control group after induction (p < 0.05). Heart rate (HR) in experimental group was significantly lower than in the control group at intraoperative 1h (p < 0.05). Additionally, bispectral index (BIS), state entropy (SE), and response entropy (RE) levels in the experimental group were significantly higher than those in the control group (p < 0.05). Furthermore, extubation and awakening time were significantly shorter in the experimental group compared to the control group (p < 0.05). The NRS scores in the experimental group were markedly lower than those in the control group. Moreover, IL-6 and CRP levels in the experimental group were obviously lower than in the control group after postoperative 1d (p < 0.05). Interestingly, IL-6 (p < 0.001), CRP (p < 0.001), and PCT (p = 0.037) levels in female patients of the experimental group were all significantly lower than those in the control group after postoperative 1d. Conclusions: Ultrasound-guided QLB and TAPB combined with OFA technique can reduce pain intensity and enhance the patients' immune function in abdominal surgery.

5.
Medicine (Baltimore) ; 102(43): e35172, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37904423

RESUMO

BACKGROUND: Currently, there is no gold standard for monitoring noxious stimulation during surgery, and the surgical pleth index (SPI) is only one of many monitoring methods. It is commonly used in the monitoring of conventional opiate anesthesia, but its effectiveness in opioid-free anesthesia (OFA) has not been evaluated. Therefore, the aim of this study was to observe the guidance value of the surgical pleth index in opioid-free anesthesia for patients undergoing lower abdominal or pelvic surgery. METHODS: A total of 122 patients who underwent lower abdominal or pelvic surgery in our hospital between March 2021 and July 2022 were selected and equally divided into OFA (F) and control (C) groups according to the random number table method. Both groups underwent ultrasound-guided unilateral/bilateral quadratus lumborum block in the supine position according to the surgical field. In group F, 0.50% lidocaine and 0.20% ropivacaine (in 20 mL of 0.9% normal saline) were injected on each side. In group C, 20 mL 0.9% normal saline was injected on each side. Group F received general anesthesia without opioids and group C received general anesthesia with opioids. BP, pulse oxygen saturation, PETCO2, reactionentropy, stateentropy, and SPI values; Steward score; dosage of propofol, dexmedetomidine, rocuronium, and diltiazem; extubation time; and awake time were monitored in both groups. RESULTS: There were no significant differences in the general data between the 2 groups (P > .05). There were no significant differences in SPI values at T0, T1, T2, T3, T4, and T5 or the number of cases requiring additional remifentanil, propofol, and diltiazem between the 2 groups (P > .05). The stateentropy, reactionentropy, and Steward scores were higher in group F than in group C at T4 and T5, while the extubation and awake times were lower in group F than in group C (P < .05). The heart rate and SPI of group F were lower than that of group C at T3 (P < .05). CONCLUSION: The guiding value of SPI in OFA was similar to its use in opiated anesthesia. Its clinical efficacy is exact, vital signs are stable, enabling rapid, and complete regaining of consciousness.


Assuntos
Analgésicos Opioides , Propofol , Humanos , Anestesia Geral , Diltiazem , Solução Salina
6.
J Thorac Cardiovasc Surg ; 162(2): e143-e156, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32414595

RESUMO

BACKGROUND: c-Jun N-terminal kinase 1 (JNK1) and JNK2 regulate distinct pathological processes in lung diseases. Here we discriminated the respective roles of these kinases in lung transplantation-induced ischemia-reperfusion injury (IRI). METHODS: Rat pulmonary microvascular endothelial cells were transfected with JNK1 small-interfering RNA (siRNA) and JNK2 siRNA and then subjected to in vitro IRI. For the isoform confirmed to aggravate IRI, the delivery of short-hairpin RNA (shRNA) plasmid was performed by intratracheal administration 48 hours before transplantation into donor rats. After a 3-hour reperfusion, the samples were collected. RESULTS: JNK1 siRNA decreased but JNK2 siRNA increased JNK phosphorylation and activity, phosphorylated and total c-Jun, and activator protein-1 activity. Although JNK1 siRNA decreased apoptosis and the levels of malondialdehyde, interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF-α), it increased the levels of superoxide dismutase, S-phase percentage, and cyclin D1; JNK2 siRNA had a converse effect. JNK1 siRNA decreased the level of lactate dehydrogenase and increased the levels of VE-cadherin, nitric oxide, phosphorylated nitric oxide synthase, and cell viability; JNK2 si RNA had a converse effect. Compared with the control group, the JNK1 shRNA group exhibited a higher lung oxygenation index and lower lung apoptosis index, injury score, wet weight:dry weight ratio, and levels of IL-1, IL-6, and TNF-α. CONCLUSIONS: JNK1 aggravated, but JNK2 alleviated, IRI through differential regulation of the JNK1 pathway in in vitro ischemia-reperfusion. JNK1 silence attenuated lung graft dysfunction by inhibiting inflammation and apoptosis. These findings provide a theoretical basis for devising therapeutic strategies against IRI after lung transplantation.


Assuntos
Células Endoteliais/enzimologia , Pulmão/irrigação sanguínea , Microvasos/enzimologia , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Proteína Quinase 9 Ativada por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Traumatismo por Reperfusão/enzimologia , Fator de Transcrição AP-1/metabolismo , Animais , Apoptose , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Células Endoteliais/patologia , Mediadores da Inflamação/metabolismo , Isoenzimas , Transplante de Pulmão/efeitos adversos , Microvasos/patologia , Proteína Quinase 8 Ativada por Mitógeno/genética , Proteína Quinase 9 Ativada por Mitógeno/genética , Fosforilação , Ratos , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia , Transdução de Sinais
7.
J Cell Mol Med ; 24(21): 12355-12367, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32961025

RESUMO

Diabetes is a disorder of glucose metabolism, and over 90% are type 2 diabetes. Diabetic cardiomyopathy (DCM) is one of the type 2 diabetes complications, usually accompanied by changes in myocardial structure and function, together with cardiomyocyte apoptosis. Our study investigated the effect of curcumin on regulating oxidative stress (OS) and apoptosis in DCM. In vivo, diabetes was induced in an experimental rat model by streptozoticin (STZ) together with high-glucose and high-fat (HG/HF) diet feeding. In vitro, H9c2 cardiomyocytes were cultured with high-glucose and saturated free fatty acid palmitate. Curcumin was orally or directly administered to rats or cells, respectively. Streptozoticin -induced diabetic rats showed metabolism abnormalities and elevated markers of OS (superoxide dismutase [SOD], malondialdehyde [MDA], gp91phox , Cyt-Cyto C), enhanced cell apoptosis (Bax/Bcl-2, Cleaved caspase-3, TUNEL-positive cells), together with reduced Akt phosphorylation and increased Foxo1 acetylation. Curcumin attenuated the myocardial dysfunction, OS and apoptosis in the heart of diabetic rats. Curcumin treatment also enhanced phosphorylation of Akt and inhibited acetylation of Foxo1. These results strongly suggest that apoptosis was increased in the heart of diabetic rats, and curcumin played a role in diabetic cardiomyopathy treatment by modulating the Sirt1-Foxo1 and PI3K-Akt pathways.


Assuntos
Apoptose/efeitos dos fármacos , Curcumina/farmacologia , Cardiomiopatias Diabéticas/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Glicemia/metabolismo , Sobrevivência Celular , Diabetes Mellitus Experimental , Masculino , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Sirtuína 1/metabolismo
8.
Med Sci Monit ; 26: e920039, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32310911

RESUMO

BACKGROUND Lung injury after cardiopulmonary bypass (CPB) is a serious postoperative complication and can affect the postoperative recovery. The purpose of this study was to explore whether erythropoietin (EPO) has an effect on lung injury caused by CPB. MATERIAL AND METHODS Sixty patients who received the CPB were randomly divided into a saline group and the EPO group. All the patients received saline or EPO preoperatively, respectively. The ventilation function, including dynamic compliance, peak airway pressure, and plateau pressure, were recorded. The level of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1ß, and IL-10 in serum and arterial blood gas were analyzed. The mechanical ventilation time in the intensive care unit (ICU), the length of time spent in the ICU, the time from operation to discharge, and the total time of hospitalization were recorded. Adverse events in the ICU were monitored and recorded. RESULTS EPO significantly decreased the level of TNF-alpha and IL-1ß, but increased the level of IL-10 after CPB. EPO significantly improved pulmonary ventilated function and gas exchange function after CPB. EPO significantly shortened the mechanical ventilation time and stay in the ICU. CONCLUSIONS Preoperative EPO injection reduced lung injury and promoted lung function in patients who underwent CPB. The protection effect of EPO may be associated with inhibition of inflammatory response.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Eritropoetina/uso terapêutico , Lesão Pulmonar/tratamento farmacológico , Adulto , Idoso , Ponte Cardiopulmonar/métodos , China , Citocinas/sangue , Eritropoetina/metabolismo , Feminino , Humanos , Mediadores da Inflamação/sangue , Interleucina-1beta , Pulmão/patologia , Lesão Pulmonar/etiologia , Lesão Pulmonar/metabolismo , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Respiração Artificial/efeitos adversos , Procedimentos Cirúrgicos Torácicos/efeitos adversos , Fator de Necrose Tumoral alfa
9.
Front Pharmacol ; 10: 1091, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31607927

RESUMO

Background: Emergence agitation (EA) is a common pediatric complication after sevoflurane anesthesia that can be prevented with dexmedetomidine. However, an inappropriate dose of dexmedetomidine can cause prolonged sedation and cardiovascular complications. Thus, we evaluated the optimal dose (ED95) of dexmedetomidine for preventing EA with sevoflurane and remifentanil anesthesia after pediatric tonsillectomy and adenoidectomy. Methods: We enrolled American Society of Anesthesiologists (ASA) I and II children 3-7 years of age who underwent tonsillectomy with adenoidectomy. During induction, dexmedetomidine was infused for 10 min. Anesthesia was induced with sevoflurane and maintained with sevoflurane and remifentanil, resulting in a bispectral spectrum index (BIS) range from 40 to 60. Extubation time, surgical and anesthetic duration time, and duration time in the postanesthesia care unit (PACU) stay were recorded. EA [measured with Pediatric Anaesthesia Emergence Delirium (PAED) scores] and pain [measured with Face, Legs, Activity, Cry, Consolability (FLACC) scores] were assessed at extubation (E0), 15 min after extubation (E1), and 30 min after extubation (E2). If EA occurred, the next surgical procedure included increased dexmedetomidine by 0.1 µg/kg, and if not, the drug was reduced by 0.1 µg/kg. Results: The 50% effective dose (ED50) of dexmedetomidine for preventing EA after sevoflurane and remifentanil anesthesia for tonsillectomy and adenoidectomy was 0.13 µg/kg, and its 95% confidence interval is 0.09-0.19 µg/kg; ED95 was 0.30 µg/kg, and its 95% confidence interval is 0.21-1.00 µg/kg. Conclusion: Intravenous dexmedetomidine infusion at ED50 (0.13 µg/kg) or ED95 (0.30 µg/kg) during induction for 10 min can prevent half or almost all EA after sevoflurane and remifentanil anesthesia during pediatric tonsillectomy and adenoidectomy.

10.
Surgery ; 165(5): 1014-1026, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30824287

RESUMO

BACKGROUND: Lung ischemia-reperfusion injury is a complex pathophysiologic process associated with high morbidity and mortality. We have demonstrated elsewhere that diabetes mellitus aggravated ischemia-induced lung injury. Oxidative stress and mitochondrial dysfunction are drivers of diabetic lung ischemia-reperfusion injury; however, the pathways that mediate these events are unexplored. In this study using a high-fat diet-fed model of streptozotocin-induced type 2 diabetes in rats, we determined the effect of hydrogen sulfide on lung ischemia-reperfusion injury with a focus on Sirtuin3 signaling. METHODS: Rats with type 2 diabetes were exposed to GYY4137, a slow release donor of hydrogen sulfide with or without administration of the Sirtuin3 short hairpin ribonucleic acid plasmid, and then subjected to a surgical model of ischemia-reperfusion injury of the lung (n = 8). Lung function, oxidative stress, inflammation, cell apoptosis, and mitochondrial function were measured. RESULTS: Compared with nondiabetic rats, animals with type 2 diabetes at baseline exhibited significantly decreased Sirtuin3 signaling in lung tissue and increased oxidative stress, apoptosis, inflammation, and mitochondrial dysfunction (P < .05 each). In addition, further impairment in Sirtuin3 signaling was found in diabetic rats subjected to this model of lung ischemia-reperfusion. Simultaneously, the indexes showed further aggravation. Treatment with hydrogen sulfide restored Sirtuin3 expression and decreased lung ischemia-reperfusion injury in animals with type 2 diabetes mellitus by improving lung functional recovery, decreasing oxidative damage, suppressing inflammation, ameliorating cell apoptosis, and preserving mitochondrial function (P < .05). Conversely, these protective effects were largely reversed in Sirtuin3 knockdown rats. CONCLUSION: Impaired lung Sirtuin3 signaling associated with type 2 diabetic conditions was further attenuated by an ischemia-reperfusion insult. Hydrogen sulfide ameliorated reperfusion-induced oxidative stress and mitochondrial dysfunction via activation of Sirtuin3 signaling, thereby decreasing lung ischemia-reperfusion damage in rats with a model of type II diabetes.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Sulfeto de Hidrogênio/farmacologia , Lesão Pulmonar/prevenção & controle , Mitocôndrias/efeitos dos fármacos , Sirtuínas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica/efeitos adversos , Avaliação Pré-Clínica de Medicamentos , Humanos , Sulfeto de Hidrogênio/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/patologia , Lesão Pulmonar/etiologia , Lesão Pulmonar/patologia , Masculino , Mitocôndrias/metabolismo , Morfolinas/farmacologia , Compostos Organotiofosforados/farmacologia , Estresse Oxidativo/efeitos dos fármacos , RNA Interferente Pequeno/metabolismo , Ratos , Traumatismo por Reperfusão/complicações , Transdução de Sinais/efeitos dos fármacos , Sirtuínas/genética , Estreptozocina/toxicidade
11.
J Thorac Cardiovasc Surg ; 157(2): 803-814, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30391008

RESUMO

OBJECTIVE: Endothelial progenitor cells (EPCs) can improve endothelial integrity. This study aimed to examine the effects and the mechanism of EPCs on lung ischemia-reperfusion injury (LIRI). METHODS: Wistar rats were randomized into the sham or the left lung transplantation group. The recipients were randomized and treated with vehicle as the LIRI group, with EPC as the EPC group, or with N5-(1-iminoethyl)-l-ornithine-pretreated EPC as the EPC/L group (n = 8 per group). The ratios of arterial oxygen partial pressure to fractional inspiratory oxygen were measured. The lung wet-to-dry weight ratios, protein levels, and injury, as well as the levels of plasma cytokines, were examined. The levels of endothelin (ET)-1, endothelial nitric oxide synthase (eNOS), phosphorylated eNOS, inducible NOS, phosphorylated myosin light chain, nuclear factor-κBp65, Bax, Bcl-2, cleaved caspase-3, and myeloperoxidase in the graft lungs were detected. RESULTS: Compared with the LIRI group, EPC treatment significantly increased the ratios of arterial oxygen partial pressure to fractional inspiratory oxygen and decreased the lung wet-to-dry weight ratios and protein levels in the grafts, accompanied by increasing eNOS expression and phosphorylation, but decreasing endothelin-1, inducible NOS, phosphorylated nuclear factor-kBp65, phosphorylated myosin light chain expression, and myeloperoxidase activity. EPCs reduced lung tissue damage and apoptosis associated with decreased levels of Bax and cleaved caspase-3 expression, but increased Bcl-2 expression. EPC treatment significantly reduced the levels of serum proinflammatory factors, but elevated levels of interleukin-10. In contrast, the protective effect of EPCs were mitigated and abrogated by N5-(1-iminoethyl)-l-ornithine pretreatment. CONCLUSIONS: Data indicated that EPC ameliorated LIRI by increasing eNOS expression.


Assuntos
Células Progenitoras Endoteliais/transplante , Transplante de Pulmão/efeitos adversos , Óxido Nítrico Sintase Tipo III/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Transplante de Células-Tronco , Animais , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Sobrevivência Celular , Células Cultivadas , Modelos Animais de Doenças , Células Progenitoras Endoteliais/enzimologia , Células Progenitoras Endoteliais/patologia , Sobrevivência de Enxerto , Mediadores da Inflamação/metabolismo , Masculino , NF-kappa B/metabolismo , Fosforilação , Ratos Wistar , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/patologia , Transdução de Sinais
12.
J Thorac Cardiovasc Surg ; 157(1): 272-284, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30396739

RESUMO

BACKGROUND: Cardiopulmonary bypass can result in lung injury. This prospective, double-blinded, randomized trial aimed to evaluate the protective effect of inhaled budesonide on lung injury after cardiopulmonary bypass. METHODS: Sixty patients, aged 25 to 65 years, requiring cardiopulmonary bypass were randomized to groups treated with saline or budesonide inhalation preoperatively. The respiratory mechanics were recorded. Bronchoalveolar lavage fluid was collected before cardiopulmonary bypass and after sternal closure. Serum and bronchoalveolar lavage fluid levels of proinflammatory and anti-inflammatory factors were analyzed. The primary end point was the lowest ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen after cardiopulmonary bypass. The durations of ventilation and postoperative recovery time were noted. RESULTS: Budesonide significantly improved respiratory mechanics after cardiopulmonary bypass. Budesonide improved the partial pressure of arterial oxygen to the fraction of inspired oxygen ratio from 8 to 48 hours after the operation. Budesonide shortened the durations of mechanical ventilation and postoperative recovery time. Budesonide decreased the levels of proinflammatory factors while increasing the levels of anti-inflammatory factors in bronchoalveolar lavage fluid and serum (all P < .05). The macrophage and neutrophil counts, and protein and elastase concentrations were decreased by budesonide treatment. CONCLUSIONS: Budesonide treatment shortened the durations of mechanical ventilation, inhibited local and systemic inflammation, and improved respiratory function after cardiopulmonary bypass.


Assuntos
Broncodilatadores/uso terapêutico , Budesonida/uso terapêutico , Ponte Cardiopulmonar/efeitos adversos , Lesão Pulmonar/prevenção & controle , Administração por Inalação , Adulto , Idoso , Líquido da Lavagem Broncoalveolar/química , Broncodilatadores/administração & dosagem , Budesonida/administração & dosagem , Proteína C-Reativa/análise , Ponte Cardiopulmonar/métodos , Complemento C3a/análise , Complemento C5a/análise , Método Duplo-Cego , Feminino , Humanos , Interleucina-1beta/análise , Interleucina-1beta/sangue , Tempo de Internação , Lesão Pulmonar/etiologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Cuidados Pré-Operatórios/métodos , Respiração Artificial , Fenômenos Fisiológicos Respiratórios/efeitos dos fármacos , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/sangue
13.
Chin J Integr Med ; 24(11): 815-821, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30062633

RESUMO

OBJECTIVE: To evaluate the efficacy of Xuebijing Injection (, XBJ) on the lung injury induced by cardiopulmonary bypass (CPB). METHODS: Fifty patients undergoing CPB were randomized to either the saline group or XBJ group according to a random number table (25 cases in each group). The patients in the saline group received saline and patients in XBJ group received XBJ at 12 h prior to the operation, at the beginning of the operation, and at 12 h after the second injection. The PaO2/FiO2 at extubation 3 days post-operation, duration of ventilation in the intensive care unit (ICU), and lengths of stay in the ICU and hospital were recorded. The levels of inflammatory mediators including interleukin (IL)-1ß, IL-8, IL-10, and C-reactive protein (CRP) in bronchoalveolar lavage fluid (BALF) and plasma were measured. The neutrophil count and elastase neutrophil elastase in BALF were also measured. In addition, adverse events were monitored. RESULTS: The PaO2/FiO2 in the XBJ group was higher than that in the saline group from 12 to 72 h post-operation (all P<0.05). The blood levels of IL-1ß, IL-8, and CRP in the XBJ group from 12 to 72 h were all significantly lower than those in the saline group (all P<0.05). In contrast, the level of the anti-inflammatory cytokine IL-10 was significantly higher in the XBJ group than in the saline group (P<0.05). In addition, 4 patients presented with atelectasis in the saline group and none in the XBJ group. Ten patients experienced mild acute respiratory distress syndrome (ARDS) during hospitalization, and 5 patients with mild ARDS were in the XBJ group (P<0.05). CONCLUSION: XBJ shows protective potential against lung injury in patients who undergo CPB surgery, possibly through the downregulation of inflammatory mediators, reduction in neutrophil infiltration, and upregulation of IL-10 (Trial registry: ChiCTR-TRC-14004628).


Assuntos
Ponte Cardiopulmonar/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Lesão Pulmonar/prevenção & controle , Adulto , Idoso , Proteína C-Reativa/análise , Citocinas/biossíntese , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Mediadores da Inflamação/análise , Injeções , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
14.
Medicine (Baltimore) ; 97(25): e11218, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29924051

RESUMO

BACKGROUND: We have previously shown that epidural dexmedetomidine, when used as an adjunct to levobupivacaine for control of postoperative pain after open colonic resection, improves recovery of gastrointestinal motility compared with morphine. METHODS: Sixty patients undergoing laparoscopic colonic resection were enrolled and allocated randomly to treatment with dexmedetomidine (group D) or morphine (group M). Group D received an epidural loading dose of dexmedetomidine (5 mL, 0.5 µg/kg), followed by continuous epidural administration of dexmedetomidine (80 µg) in 0.125% levobupivacaine (240 mL) at a rate of 5 mL/h for 2 days. Group M received an epidural loading dose of morphine (5 mL, 0.03 mg/kg) followed by continuous epidural administration of morphine (4.5 mg) in 0.125% levobupivacaine (240 mL) at a rate of 5 mL/h for 2 days. Verbal rating score (VRS) of pain, postoperative analgesic requirements, side effects related to analgesia, and time to postoperative first flatus (FFL) and first feces (FFE) were recorded. RESULTS: VRS and postoperative analgesic requirements were not significantly different between the treatment groups. In contrast, FFL and FFE were significant delayed in group M compared with group D (P < .05). Patients in group M also had a significantly higher incidence of nausea, vomiting, and pruritus (P < .05). No neurological deficits were observed in either group. CONCLUSIONS: Compared with morphine, epidural dexmedetomidine is a better adjunct to levobupivacaine for control of postoperative pain after laparoscopic colonic resection.


Assuntos
Bupivacaína/análogos & derivados , Colo/cirurgia , Dexmedetomidina/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Morfina/farmacologia , Dor Pós-Operatória/tratamento farmacológico , Idoso , Analgesia Epidural/efeitos adversos , Analgésicos não Narcóticos/farmacologia , Analgésicos Opioides/farmacologia , Anestésicos Locais/uso terapêutico , Bupivacaína/administração & dosagem , Bupivacaína/uso terapêutico , Dexmedetomidina/administração & dosagem , Feminino , Humanos , Laparoscopia/métodos , Levobupivacaína , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem , Manejo da Dor/métodos
15.
Mol Med Rep ; 17(5): 7191-7201, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29568898

RESUMO

Adiponectin (APN) has been associated with the pathogenesis of acute brain, liver and heart injury. However, the role of APN in lung ischemia-reperfusion injury (LIRI) in diabetes mellitus remains unclear. To investigate this, the present study evaluated the effects of APN on lung dysfunction and pathological alterations in rats with type 2 diabetes mellitus via lung ischemia/reperfusion (I/R). The lung­protective effects of APN globular domain (gAPN) in rats with type 2 diabetes mellitus were also investigated by measuring the oxygenation index, inflammatory cytokines, lung edema, histopathology, oxidative stress, apoptosis and the protein expression levels of phosphorylated 5'adenosine monophosphate­activated protein kinase (p­AMPK), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS). The results of the present study demonstrated that the diabetes mellitus rats + I/R (DIR) group exhibited greater concentrations of tumor necrosis factor­α and interleukin­6, and increases in the wet­weight to dry­weight ratio, lung injury score, oxidative stress and cellular apoptosis. These effects were accompanied by lower pulmonary oxygenation compared with the normal rat + I/R (NIR) group (P<0.05). Additionally, all of these alterations were attenuated in the NIR + gAPN and DIR + gAPN groups compared with in the NIR and DIR groups, respectively. In the DIR group, the expression levels of p­AMPK/AMPK and eNOS were significantly downregulated, and the levels of iNOS were upregulated, compared with those of the NIR group. Treatment with APN activated AMPK, increased eNOS expression and attenuated iNOS expression. The results of the present study demonstrated that APN exerted protective effects against LIRI via its anti­inflammatory, antioxidative stress and anti­apoptotic activities. These protective effects of APN were eliminated in rats with type 2 diabetes mellitus, in which LIRI was exacerbated. The present study indicated that APN may be a potential therapeutic agent for LIRI in type 2 diabetes mellitus.


Assuntos
Adiponectina/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Lesão Pulmonar/complicações , Lesão Pulmonar/prevenção & controle , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Citocinas/análise , Diabetes Mellitus Tipo 2/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Lesão Pulmonar/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologia
16.
Int J Clin Exp Pathol ; 11(10): 4926-4933, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31949568

RESUMO

Oral squamous cell carcinoma (OSCC) is the most common type and most threatening head and neck cancer worldwide. Here, we aim to study the relationship between the WNT7A-ß-Catenin signaling pathway and the chemotherapy resistance of OSCC patients. We analyzed 42 OSCC patients and 19 adjacent non-tumor tissues, evaluated the expression levels of WNT7A mRNA, and subsequently studied WNT7A dependent cisplatin resistance in OSCC cell line KB cells. Moreover, we also utilized an in vivo mouse model to validate our findings. We first found a significant upregulation of WNT7A mRNA in OSCC patients. Our results showed that the knockdown of WNT7A sensitized KB cells to cisplatin. Moreover, our results revealed that nuclear ß-catenin was dramatically reduced and cleaved caspase-3 and cleaved PARP were dramatically induced when WNT7A was knocked down in cisplatin treated KB cells. Besides, we found that the knockdown of WNT7A significantly reduced the weight and volumes of xenograft tumors. Moreover, we examined apoptotic cells and found that the combination of WNT7A knockdown and cisplatin treatment resulted in many more apoptotic cells than cisplatin treatment alone, suggesting that the knockdown of WNT7A sensitized KB cells to cisplatin treatment in vivo. Our results revealed that inhibition of WNT7A-ß-catenin signaling sensitizes OSCC to cisplatin, which has provided insights into the molecular diagnosis and treatment of OSCC.

17.
Anesthesiology ; 128(1): 130-139, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29023354

RESUMO

BACKGROUND: Hypercapnia alleviates pulmonary ischemia-reperfusion injury, regulates T lymphocytes, and inhibits immune reaction. This study aimed to evaluate the effect of hypercapnia on acute cellular rejection in a rat lung transplantation model. METHODS: Recipient rats in sham-operated (Wistar), isograft (Wistar to Wistar), and allograft (Sprague-Dawley to Wistar) groups were ventilated with 50% oxygen, whereas rats in the hypercapnia (Sprague-Dawley to Wistar) group were administered 50% oxygen and 8% carbon dioxide for 90 min during reperfusion (n = 8). Recipients were euthanized 7 days after transplantation. RESULTS: The hypercapnia group showed a higher oxygenation index (413 ± 78 vs. 223 ± 24), lower wet weight-to-dry weight ratio (4.23 ± 0.54 vs. 7.04 ± 0.80), lower rejection scores (2 ± 1 vs. 4 ± 1), and lower apoptosis index (31 ± 6 vs. 57 ± 4) as compared with the allograft group. The hypercapnia group showed lower CD8 (17 ± 4 vs. 31 ± 3) and CD68 (24 ± 3 vs. 43 ± 2), lower CD8 T cells (12 ± 2 vs. 35 ± 6), and higher CD4/CD8 ratio (2.2 ± 0.6 vs. 1.1 ± 0.4) compared to the allograft group. Tumor necrosis factor-α (208 ± 40 vs. 292 ± 49), interleukin-2 (30.6 ± 6.7 vs. 52.7 ± 8.3), and interferon-γ (28.1 ± 4.9 vs. 62.7 ± 10.1) levels in the hypercapnia group were lower than those in allograft group. CD4, CD4 T cells, and interleukin-10 levels were similar between groups. CONCLUSIONS: Hypercapnia ameliorated acute cellular rejection in a rat lung transplantation model.


Assuntos
Rejeição de Enxerto/metabolismo , Hipercapnia/metabolismo , Transplante de Pulmão/efeitos adversos , Pulmão/metabolismo , Linfócitos T/metabolismo , Aloenxertos/imunologia , Aloenxertos/metabolismo , Aloenxertos/patologia , Animais , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Hipercapnia/imunologia , Hipercapnia/patologia , Pulmão/imunologia , Pulmão/patologia , Transplante de Pulmão/tendências , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Especificidade da Espécie , Linfócitos T/imunologia
18.
Exp Lung Res ; 43(9-10): 439-446, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29236548

RESUMO

PURPOSE: Lung ischemia-reperfusion injury (LIRI) after lung transplantation can lead to primary graft dysfunction. Budesonide can improve endothelial function to reduce lung injury. This study was aimed to examine the effects of budesonide on LIRI and potential mechanisms. METHODS: Wistar rats were randomized and transplanted with syngeneic left lung or received the sham surgery. The recipients were instilled with saline or budesonide immediately after reperfusion. The mean arterial pressure (MAP), blood gas, and lung histology were analyzed. The ratios of wet to dry lung weights, the levels of total proteins, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-10, and neutrophil elastase in bronchoalveolar lavage fluid (BALF) were measured. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), and xanthine oxidase (XO) in the lung, and the levels of plasma lymphocyte function-associated antigen (LFA)-1 and P-selectin were determined. RESULTS: Compared with the saline group, treatment with budesonide significantly increased blood PaO2, but reduced PaCO2, and mitigated lung damages after reperfusion, the levels of BALF proteins, and the ratios of wet to dry lung weights in rats. Furthermore, treatment with budesonide significantly decreased the levels of MDA, MPO, and XO in the lung and the levels of TNF-α, IL-1ß, IL-6, and neutrophil elastase, but increased IL-10 in the BALF, accompanied by significantly reduced levels of serum P-selectin and LFA-1 in rats. CONCLUSIONS: Budesonide effectively mitigated LIRI and ameliorated the lung function by attenuating oxidative stress and inflammation following syngeneic lung transplantation.


Assuntos
Budesonida/farmacologia , Transplante de Pulmão/efeitos adversos , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Gasometria , Líquido da Lavagem Broncoalveolar/química , Budesonida/administração & dosagem , Budesonida/uso terapêutico , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
19.
Oncotarget ; 8(38): 63587-63595, 2017 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-28969013

RESUMO

OBJECT: In this study, we aimed to investigate the beneficial effects of dexmedetomidine on somato-visceral sensory block characteristcs, postoperative analgesia and stress response of intrathecal bupivacaine administration in women undergoing cesarean section, and to find out which dose is better. METHODS: Sixty parturients with the American Society of Anesthesiologists (ASA) physical status I or II were anesthetized with intrathecal bupivacaine(10mg) alone or in combination with dexmedetomidine (3 µg and 5 µg) to undergo cesarean section. The anesthetic parameters, postoperative analgesia and stress responses were monitored. RESULTS: Co-administration of dexmedetomidine(3 µg and 5 µg) prolonged the duration of motor and sensory block compared with bupivacaine(10mg) alone. Less supplemental dose of lidocaine and fentanyl were required in dexmedetomidine(3 µg and 5 µg) co-administration groups. Visceral traction response and abdominal muscle relaxation in operation were better in dexmedetomidine(3 µg and 5 µg) co-administration groups. No difference in haemodynamics was detected among groups. There was no significant difference in Apgar scores, neonatal umbilical pH, oxygen pressure, carbon dioxide pressure and lactate level among groups. Postoperative plasma IL-6 and cortisol levels were lower in dexmedetomidine(3 µg and 5 µg) co-administration groups. At 6 hour after operation the visual analogue scale (VAS) was smaller in dexmedetomidine(3 µg and 5 µg) co-administration groups. The uterine contraction pain at 6 and 12 hour after operation and supplemental analgesics had no difference across three groups. No difference of side effects(shivering, nausea and vomiting, itching), the first anal aerofluxus time and intraoperation tramadol dose were detected among the three groups. CONCLUSION: The use of dexmedetomidine especially at the dose of 3µg as an adjuvant to bupivacaine in cesarean surgery provides better intraoperative somato-visceral sensory block characteristcs and postoperative analgesia, which produced no influence on Apgar scores, side effects and stress response.

20.
J Surg Res ; 216: 9-17, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28807219

RESUMO

BACKGROUND: Lung ischemia-reperfusion injury (LIRI) is a pathologic process that is observed in several clinical conditions, and p38 mitogen-activated protein kinase (MAPK) is involved. Diabetes mellitus (DM) results in an increased incidence of ischemia-induced organ damage. The aims of this study were to examine the effects of DM on LIRI in a rat model of DM and to explore the possible mechanisms in relation to the p38 MAPK pathway. METHODS: Forty rats were randomly divided into the following five groups (n = 8 each): a control + sham group, a control + IR group (CIR), a DM + sham group, a DM + IR group (DIR), and a DM + IR + SB203580 group. The control and streptozotocin-induced diabetic rats underwent a sham operation or left hilum occlusion for 90 min followed by reperfusion for 4 h. SB203580 was used to inhibit the p38 MAPK pathway. The pulmonary oxygenation index, inflammatory cytokines in the serum, lung edema, histopathology, oxidant stress, apoptosis, and phosphorylated/total-p38 MAPK protein levels were measured. RESULTS: The DIR group displayed greater concentrations of tumor necrosis factor-α, interleukin-6, and intercellular adhesion molecule-1 and increases in the wet weight-to-dry weight ratio, lung injury scores, malondialdehyde levels, and cellular apoptosis, and these effects were accompanied by lower pulmonary oxygenation compared with the CIR group (P < 0.05). In the DIR group, the expression levels of p38 MAPK protein were significantly upregulated compared with those of the CIR group. Additionally, all of these alterations were attenuated in the DM + IR + SB203580 group compared with the DIR group. CONCLUSIONS: Diabetes exacerbates LIRI by activating the p38 MAPK pathway.


Assuntos
Diabetes Mellitus Experimental/complicações , Lesão Pulmonar/enzimologia , Traumatismo por Reperfusão/enzimologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Biomarcadores/metabolismo , Diabetes Mellitus Experimental/enzimologia , Pulmão/irrigação sanguínea , Pulmão/enzimologia , Pulmão/patologia , Lesão Pulmonar/complicações , Lesão Pulmonar/patologia , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/patologia
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