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CONTEXT: Sepsis is currently one of the leading causes of death in intensive care units (ICUs). Sesamin was previously reported to inhibit inflammation. However, no studies have revealed the impact of sesamin on sepsis. OBJECTIVE: We studied the mechanism underlying the effect of sesamin on the pathophysiology of sepsis through the HMGB1/TLR4/IL-33 signalling pathway. MATERIALS AND METHODS: Fifty male BALB/c mice (n = 10 per group) were used to establish a caecal ligation and puncture (CLP) mouse model, and given daily injections of sesamin at a low, middle, or high concentration (25, 50, or 100 µM) during the seven-day study period; survival curves were generated by the Kaplan-Meier method. H&E staining and TUNEL staining were performed to assess changes in intestinal morphology intestinal damage in the mouse intestinal epithelium. Molecules related to the HMGB1/TLR4/IL-33 pathway were assessed by RT-qPCR and Western blotting. RESULTS: We found mice in the sepsis group survived for only 4 days, while those treated with sesamin survived for 6-7 days. In addition, sesamin significantly relieved the increase in the levels of MPO (21%, 33.3%), MDA (40.5% and 31.6%), DAO (1.24-fold and 2.31-fold), and pro-inflammatory cytokines such as TNF-α (75% and 79%) and IL-6 (1-fold and 1.67-fold) 24 and 48 h after sepsis induction and downregulated the expression of HMGB1, TLR4, and IL-33 while upregulating the expression of ZO-1 and occludin. DISCUSSION AND CONCLUSIONS: Sesamin improved the 7-day survival rate of septic mice, suppressed the inflammatory response in sepsis through the HMGB-1/TLR4/IL-33 signalling pathway, and further alleviated intestinal injury.
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Dioxóis/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/lesões , Lignanas/farmacologia , Sepse/tratamento farmacológico , Animais , Bactérias/efeitos dos fármacos , Linhagem Celular , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Células Epiteliais , Proteína HMGB1/metabolismo , Humanos , Inflamação/tratamento farmacológico , Interleucina-33/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ocludina/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Proteína da Zônula de Oclusão-1/metabolismoRESUMO
Human bronchial epithelium (HBE)-Dp71 anti-sense(AS)cells with stably transfected Dp71 siRNA plasmids were prepared for further exploration of Dp71 biological traits in cells other than PC12. HBE-Dp71AS cells displayed increased DNA damage induced by H2O2. Apoptosis of HBE-Dp71AS cells induced by H2O2 was increased via enhancing caspase 3, caspase 8 and caspase 9. HBE-Dp71AS cells also displayed decreased proliferation and clonogenic formation. RAD51 was proved to be a new binding partner of Dp71 by co-immunoprecipitation (Ip) and immunofluorescence. Reduced RAD51 mRNA and protein levels were observed in HBE-Dp71AS cells. Decreased lamin B1, focal adhesion kinase (FAK), phosphorylated focal adhesion kinase (p-FAK) and phosphorylated protein kinase B (p-AKT) were detected in the HBE-Dp71AS cells, which functioned together with RAD51 as the molecular explanations for the character alterations of HBE-Dp71AS cells.
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Apoptose , Dano ao DNA , Distrofina/metabolismo , Peróxido de Hidrogênio/toxicidade , Estresse Oxidativo , Rad51 Recombinase/genética , Linhagem Celular , DNA/efeitos dos fármacos , DNA/metabolismo , Reparo do DNA , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Quinase 1 de Adesão Focal/genética , Quinase 1 de Adesão Focal/metabolismo , Regulação da Expressão Gênica , Humanos , Peróxido de Hidrogênio/farmacologia , Lamina Tipo B/genética , Fosforilação , Processamento de Proteína Pós-Traducional , Rad51 Recombinase/metabolismoRESUMO
OBJECTIVE: To evaluate the safety and efficiency of citrate anticoagulant-based continuous blood purification in patients at high risk of bleeding. â© Methods: One hundred and fifty-two patients at high risk of bleeding were divided into local citrate group (group A, n=68) and heparin group (group B, n=84). Clotting function, change of pH, ionized sodium, bicarbonate ion, ionized calcium, activated clotting time (ACT) and complications were monitored before and during treatment. â© Results: Compared to the group A, the incidence of clotting in filter and chamber, the degree of bleeding or fresh bleeding were significantly reduced in the group B (P<0.05). ACT of post-filter at 4, 8 and 12 h during the treatment in the group A was significantly extended compared with that without treatment (P<0.05), while there was no significant change in group B (P>0.05). The pH value, the levels of ionized sodium, bicarbonate ion and ionized calcium during the treatment were maintained in normal range in both group A and group B.â© Conclusion: Local citrate-based continuous blood purification can achieve effective anticoagulation and decrease the incidence of bleeding. It is an ideal choice for patients at high risk of bleeding.
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Coagulação Sanguínea/efeitos dos fármacos , Ácido Cítrico/uso terapêutico , Hemodiafiltração/efeitos adversos , Hemorragia/prevenção & controle , Anticoagulantes/farmacologia , Bicarbonatos/sangue , Testes de Coagulação Sanguínea , Cálcio/sangue , Citratos , Feminino , Hemodiafiltração/métodos , Hemofiltração , Hemorragia/etiologia , Heparina/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Masculino , Valores de Referência , Diálise Renal , Sódio/sangue , Resultado do TratamentoRESUMO
Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder poising burgeoning health problem to humans. Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases. Since the roles of lncRNA in NAFLD remain unknown, they were investigated in the study. Microarray expression profiling of mRNAs and lncRNAs was conducted using RNA extracted from patients with and without NAFLD. One thousand seven hundred thirty-five lncRNAs and 1485 mRNA were found differentially expressed in NAFLD samples compared with those in control samples. Among them 535 and 1,200 lncRNAs were upregulated and downregulated in NAFLD, respectively; 760 and 725 mRNAs were upregulated and downregulated in NAFLD, respectively. Moreover, seven lncRNAs and seven mRNAs that were highly up- or downregulated in NAFLD samples were validated by quantitative real-time polymer chain reactions. Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology analysis for the differentially expressed mRNAs showed that these RNAs are involved in various metabolic processes, cellular components, and molecular functions. Our findings indicate that the expression profiles of lncRNAs have changed in NAFLD as compared with normal liver, and the identified regulated RNAs may provide novel insight into the molecular mechanisms underlying the disease and potential novel diagnostic or therapeutic targets for NAFLD.
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Hepatopatia Gordurosa não Alcoólica/metabolismo , RNA Longo não Codificante/metabolismo , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Genoma Humano , Humanos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , RNA Longo não Codificante/genética , TranscriptomaRESUMO
BACKGROUND: Pathogenesis and treatment of inflammatory gut barrier failure is an important problem in critical care. In this study, we examined the role of pioglitazone, an agonist of peroxisome proliferator-activated receptor gamma, in gut barrier failure during experimental peritonitis in rats. MATERIALS AND METHODS: Male rats were randomly divided into three groups as follows: sham, sepsis, and sepsis + pioglitazone. Sepsis was achieved by means of the cecal ligation and puncture (CLP). Pioglitazone was administered intraperitoneally (10 mg/kg/d) for 7 d before the experiment. Animals were killed at 24 h or followed 72 h for survival. The tissue level of tumor necrosis factor-α, interleukin-6, superoxide dismutase, malondialdehyde, and myeloperoxidase was measured. Intestinal mucosa injury was assessed histologically. The plasma fluorescein isothiocyanate-dextran, D-lactic acid, and intestinal diamine oxidase were determined to evaluate the permeability and integrity of intestinal mucosal epithelium. Vena cava blood and tissue samples were used to monitor bacterial translocation. RESULTS: Intestinal inflammation, oxidize stress, neutrophil infiltration, morphology injury, and impaired permeability of the small intestine in the CLP group were found more severe than those in the sham group. Application of pioglitazone not only minimized all the indicators of intestinal injury and barrier failure but also improved the survival of septic rats induced by CLP. CONCLUSIONS: Our novel findings suggest that pioglitazone could protect against intestinal injury and maintain intestinal barrier integrity and might be a useful strategy to ameliorate intestinal failure in polymicrobial sepsis.
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Mucosa Intestinal/metabolismo , PPAR gama/agonistas , Sepse/tratamento farmacológico , Tiazolidinedionas/uso terapêutico , Amina Oxidase (contendo Cobre)/metabolismo , Animais , Translocação Bacteriana/efeitos dos fármacos , Modelos Animais de Doenças , Interleucina-6/biossíntese , Intestinos/imunologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Permeabilidade , Peroxidase/análise , Pioglitazona , Ratos , Ratos Sprague-Dawley , Sepse/metabolismo , Sepse/mortalidade , Fator de Necrose Tumoral alfa/biossínteseRESUMO
The prevalence of chronic diseases is currently a major public health issue worldwide and is exploding with the population growth and aging. Dietary patterns are well known to play a important role in our overall health and well-being, and therefore, poor diet and malnutrition are among the most critical risk factors for chronic disease. Thus, dietary recommendation and nutritional supplementation have significant clinical implications for the targeted treatment of some of these diseases. Multiple dietary patterns have been proposed to prevent chronic disease incidence, like Dietary Approaches to Stop Hypertension (DASH) and Diabetes Risk Reduction Diet (DRRD). Among them, the MedDiet, which is one of the most well-known and studied dietary patterns in the world, has been related to a wide extent of health benefits. Substantial evidence has supported an important reverse association between higher compliance to MedDiet and the risk of chronic disease. Innovative strategies within the healthcare framework of predictive, preventive, and personalized medicine (PPPM/3PM) view personalized dietary customization as a predictive medical approach, cost-effective preventive measures, and the optimal dietary treatment tailored to the characteristics of patients with chronic diseases in primary and secondary care. Through a comprehensive collection and review of available evidence, this review summarizes health benefits of MedDiet in the context of PPPM/3PM for chronic diseases, including cardiovascular disease, hypertension, type 2 diabetes, obesity, metabolic syndrome, osteoporosis, and cancer, thereby a working hypothesis that MedDiet can personalize the prevention and treatment of chronic diseases was derived.
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The present study aimed to investigate the effect of curcumin on sepsis-induced acute lung injury (ALI) in rats, and explore its possible mechanisms. Male Sprague-Dawley rats were randomly divided into the following five experimental groups (n = 20 per group): animals undergoing a sham cecal ligature puncture (CLP) (sham group); animals undergoing CLP (control group); or animals undergoing CLP and treated with vehicle (vehicle group), curcumin at 50 mg/kg (low-dose curcumin [L-Cur] group), or curcumin at 200 mg/kg (high-dose curcumin [H-Cur] group).At 6, 12, 24 h after CLP, blood, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The lung wet/dry weight (W/D) ratio, protein level, and the number of inflammatory cells in the BALF were determined. Optical microscopy was performed to examine the pathologic changes in lungs. Myeloperoxidase (MPO) activity, malondialdehyde (MDA) content, as well as superoxidase dismutase (SOD) activity were measured in lung tissues. The expression of inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), interluekin-8 (IL-8), and macrophage migration inhibitory factor (MIF) were determined in the BALF. Survival rates were recorded at 72 h in the five groups in another experiment. Treatment with curcumin significantly attenuated the CLP-induced pulmonary edema and inflammation, as it significantly decreased lung W/D ratio, protein concentration, and the accumulation of the inflammatory cells in the BALF, as well as pulmonary MPO activity. This was supported by the histopathologic examination, which revealed marked attenuation of CLP-induced ALI in curcumin treated rats. In addition, curcumin significantly increased SOD activity with significant decrease in MDA content in the lung. Also, curcumin caused down-regulation of the inflammatory cytokines TNF-α, IL-8, and MIF levels in the lung. Importantly, curcumin improved the survival rate of rats by 40%-50% with CLP-induced ALI. Taken together, these results demonstrate the protective effects of curcumin against the CLP-induced ALI. This effect can be attributed to curcumin ability to counteract the inflammatory cells infiltration and, hence, ROS generation and regulate cytokine effects.
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Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/prevenção & controle , Anti-Inflamatórios não Esteroides/uso terapêutico , Curcumina/uso terapêutico , Sepse/complicações , Lesão Pulmonar Aguda/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Líquido da Lavagem Broncoalveolar , Curcumina/farmacologia , Relação Dose-Resposta a Droga , Interleucina-8/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Fatores Inibidores da Migração de Macrófagos/metabolismo , Masculino , Malondialdeído/metabolismo , Modelos Animais , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: To investigate the possible risk factors for death among liver or kidney recipients with bloodstream infections (BSIs). METHODS: A retrospective study of 138 episodes of bloodstream infections documented in 103 patients was conducted to assess potential risk factors for mortality. The risk factors were identified by logistic regression analysis. RESULTS: The mean age of the patients was 12-66 (42.3±12.7) years. The majority of infections were nosocomial (78.6%). The BSIs-related mortality rate was 39.8% (41/103). The following variables were identified as risk factors for BSIs-related mortality by univariate analysis: intraabdominal/ biliary focus (P=0.003), polymicrobial infection (P<0.001), liver transplant (P<0.001), platelet count <50000/mm3 (P<0.001), and septic shock (P<0.001). Platelet count < 50000/mm3 (P=0.002) and septic shock (P<0.001) showed significantly difference between the mortality group and the survival groups in the multivariate logistic regression analysis. CONCLUSION: Decreased platelet count and septic shock are risk factors for increased
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Bacteriemia/mortalidade , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Adolescente , Adulto , Idoso , Bacteriemia/epidemiologia , Bacteriemia/etiologia , Causas de Morte , Criança , China/epidemiologia , Feminino , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/etiologia , Infecções por Bactérias Gram-Negativas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Choque Séptico/epidemiologia , Trombocitopenia/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: To explore the risk factors for septic shock in patients with solid organ transplantation and complication of bacteremias. METHODS: Clinical data of 98 solid organ transplant cases with complication of bacteremias were retrospectively studied. All episodes of bacteremias met the CDC criteria. Six possible risk factors contributing to septic shock were evaluated by univariate analysis and multivariate logistic regression analysis. RESULTS: Among the 98 patients, 133 times of bacteremias have been reported and 39 patients developed septic shock. Among the 39 patients with septic shock, 43.5%, 38.5%, 15.4% and 2.6% of bacteremias were induced by multiple bacteria, gram-negative bacteria, gram-positive bacteria and fungi, respectively. The lung was the main source of bacteremias (41.8%), followed by intraabdominal/ biliary focus (24.5%). Risk factors for developing septic shock included the bacteremias happened in the 2nd to 8th week post transplant (P=0.014), polymicrobial etiology (P=0.001), intra-abdominal/ biliary focus (P=0.011), and liver transplant (P=0.002). Only bacteremias occurred in the 2nd to 8th week post transplant and polymicrobial etiology were significant risk factors by multivariate analysis. CONCLUSION: Risk factors for developing septic shock in bacteremias after SOT are early-onset (the 2nd-8th week post transplant) and polymicrobial etiology.
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Bacteriemia/complicações , Transplante de Órgãos/efeitos adversos , Choque Séptico/complicações , Humanos , Análise Multivariada , Estudos Retrospectivos , Fatores de RiscoRESUMO
Aims: To explore the population pharmacokinetics of colistin sulfate and to optimize the dosing strategy for critically ill patients. Methods: The study enrolled critically ill adult patients who received colistin sulfate intravenously for more than 72 h with at least one measurement of plasma concentration. Colistin concentrations in plasma or urine samples were measured by ultraperformance liquid chromatography tandem mass spectrometry (LC-MS/MS). The population pharmacokinetics (PPK) model for colistin sulfate was developed using the Phoenix NLME program. Monte Carlo simulation was conducted to evaluate the probability of target attainment (PTA) for optimizing dosing regimens. Results: A total of 98 plasma concentrations from 20 patients were recorded for PPK modeling. The data were adequately described by a two-compartment model with linear elimination. During modeling, creatinine clearance (CrCL) and alanine aminotransferase (ALT) were identified as covariates of the clearance (CL) and volume of peripheral compartment distribution (V2), respectively. In addition, colistin sulfate was predominantly cleared by the nonrenal pathway with a median urinary recovery of 10.05% with large inter-individual variability. Monte Carlo simulations revealed a greater creatinine clearance associated with a higher risk of sub-therapeutic exposure to colistin sulfate. The target PTA (≥90%) of dosage regimens recommended by the label sheet was achievable only in patients infected by pathogens with MIC ≤0.5 mg/L or with renal impairments. Conclusion: Our study showed that the dose of intravenous colistin sulfate was best adjusted by CrCL and ALT. Importantly, the recommended dosing regimen of 1.0-1.5 million units daily was insufficient for patients with normal renal functions (CrCL ≥80 ml/min) or those infected by pathogens with MIC ≥1.0 mg/L. The dosage of colistin sulfate should be adjusted according to renal function and drug exposure.
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Naringin exhibited various pharmacological activities. However, its biological function and underlying mechanism in regulating macrophage polarization remain elusive. This study aimed to investigate the regulatory network between naringin and macrophage polarization in sepsis-induced intestinal injury. Cecal ligation and puncture (CLP) was used to establish the animal model of sepsis. Chromatin immunoprecipitation and a luciferase reporter assay were used to determine the interplay between peroxisome proliferator-activated receptor γ (PPARγ) and miR-21 promoter, as well as miR-21 and its target genes. Naringin enhanced the overall survival of septic mice and alleviated the CLP-induced inflammatory response and intestinal damage. This was accompanied by the increased expression of PPARγ in the intestines and the stimulation of ileal macrophages toward the M2 phenotype. Furthermore, in lipopolysaccharide-stimulated bone marrow-derived macrophages, naringin stimulated M2 polarization. Mechanistically, PPARγ inhibition attenuated the promotion of M2 polarization caused by naringin, and the naringin/PPARγ regulatory work was compromised by miR-21 inhibition. The present study suggested that naringin promoted M2 polarization via the PPARγ/miR-21 axis, thus relieving sepsis-induced intestinal injury. This study provides novel insights into the mechanism by which naringin alleviated sepsis-induced intestinal injury through regulation of macrophage polarization.
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Acute pancreatitis (AP) is an inflammatory, complicated pancreatic disease, carrying significant morbidity and mortality. However, the molecular and cellular mechanisms involved in AP pathogenesis remain to be elucidated. Here, we explore the role of FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) in AP progression. Caerulein with or without LPS- induced or taurolithocholic acid 3-sulfate (TLC-S)-induced AP mouse models and cell models were performed for the validation of FENDRR expression in vivo and in vitro, respectively. Histopathological examinations of pancreatic tissues were performed to evaluate the severity of AP. Transmission electron microscopy was utilized to visualize the autophagic vacuoles. siRNA specifically targeting FENDRR was further applied. Flow cytometry was employed to assess cell apoptosis. ELISA, immunoflureoscence, and western blotting analysis were also performed to determine the levels of inflammatory cytokines and autophagy activity. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays were carried out to reveal the epigenetic regulation of FENDRR on ATG7. Additionally, silencing FENDRR was also verified in AP mouse models. Higher FENDRR and impaired autophagy were displayed in both AP mouse models and cell models. FENDRR knockdown dramatically attenuated caerulein- or TLC-S-induced AR42J cells apoptosis and autophagy suppression. Further mechanistic experiments implied that the action of FENDRR is moderately attributable to its repression of ATG7 via direct interaction with the epigenetic repressor PRC2. Moreover, the silencing of FENDRR significantly induced the promotion of ATG7, thus alleviating the development of AP in vivo. Our study highlights FENDRR as a novel target that may contribute to AP progression, suggesting a therapeutic target for AP treatment.
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Proteína 7 Relacionada à Autofagia/metabolismo , Autofagia , Epigênese Genética , Pâncreas/metabolismo , Pancreatite/metabolismo , Complexo Repressor Polycomb 2/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Proteína 7 Relacionada à Autofagia/genética , Linhagem Celular , Ceruletídeo , Citocinas/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Masculino , Camundongos Endogâmicos C57BL , Pâncreas/ultraestrutura , Pancreatite/induzido quimicamente , Pancreatite/genética , Pancreatite/patologia , Complexo Repressor Polycomb 2/genética , RNA Longo não Codificante/genética , Transdução de SinaisRESUMO
AIMS: The objective of this study is to explore the association between documented diabetes, fasting plasma glucose (FPG), and the clinical outcomes of Coronavirus disease 2019 (COVID-19). METHODS: This retrospective study included 255 patients with COVID-19. Of these, 214 were admitted to isolation wards and 41were admitted to intensive care units (ICUs). Demographic, clinical, treatment, and laboratory data were collected and compared between ICU and non-ICU patients. Multivariable logistic regression models were used to explore the risk factors associated with poor clinical outcomes (ICU admission or death). RESULTS: There were significant changes in several clinical parameters in ICU patients (leukopenia, lymphopenia, elevated D-dimer, as well as higher levels of FPG, cardiac troponin, serum ferritin, IL-6, and high-sensitivity C-reactive protein)compared with non-ICU patients. The prevalence of known diabetes was substantially higher in ICU than non-ICU patients (31.7% vs. 17.8%, P = 0.0408). Multivariable regression analysis showed that a history of diabetes [odds ratio (OR), 0.099; 95% confidence interval (CI), 0.016-0.627; P = 0.014], high FPG at admission (OR, 1.587; 95% CI, 1.299-1.939, P < 0.001), high IL-6 (OR, 1.01; 95% CI, 1.002-1.018, P = 0.013), and D-dimer higher than 1 mg/L at admission (OR, 4.341; 95% CI, 1.139-16.547, P = 0.032) were independent predictors of poor outcomes. Cox proportional hazards analysis showed that compared with FPG < 7 mmol/L, FPG levels of 7.0-11.1 mmol/L and ≥ 11.1 mmol/L were associated with an increased hazard ratio (HR) for poor outcome (HR, 5.538 [95% CI, 2.269-13.51] and HR, 11.55 [95% CI, 4.45-29.99], respectively). CONCLUSION: Hyperglycemia and a history of diabetes on admission predicted poor clinical outcomes in COVID-19.
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Glicemia/metabolismo , Infecções por Coronavirus/metabolismo , Diabetes Mellitus/metabolismo , Hiperglicemia/metabolismo , Unidades de Terapia Intensiva , Pneumonia Viral/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , COVID-19 , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Diabetes Mellitus/epidemiologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hospitalização , Humanos , Hiperglicemia/epidemiologia , Interleucina-6/metabolismo , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mortalidade , Análise Multivariada , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: In recent years, the incidence of fungal infection has been increasing, often invading one or more systems of the body. However, it is rare for lymph nodes to be invaded without the involvement of other organs. CASE SUMMARY: A 21-year-old man was admitted to hospital for repeated cough for 2 mo and abdominal pain for 1 mo. Physical examination revealed multiple lymph nodes enlargement, especially those in the left neck and groin. CT scan showed multiple lymph nodes enlargement in the chest, especially left lung, abdominal cavity, and retroperitoneum. The first lymph node biopsy revealed granulomatous lesions of lymph nodes, so intravenous infusion of Cefoperazone tazobactam combined with anti-tuberculosis drugs were given. Because fever and respiratory failure occurred 4 d after admission, mechanical ventilation was given, and Caspofungin and Voriconazole were used successively. However, the disease still could not be controlled. On the 11th day of admission, the body temperature reached 40° C. After mycosis of lymph nodes was confirmed by the second lymph node biopsy, Amphotericin B was given, and the patient recovered and was discharged from the hospital. CONCLUSION: No fixed target organ was identified in this case, and only lymph node involvement was found. Caspofungin, a new antifungal drug, and the conventional first choice drug, Voriconazole, were ineffective, while Amphotericin B was effective.
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BACKGROUND: Pericardial infection caused by Acinetobacter baumannii is rare, particularly that of carbapenem-resistant A baumannii (CRAB). CASE PRESENTATION: We describe a rare case of purulent pericarditis due to CRAB in a 76-year-old man with acute myocardial infarction and acute kidney injury. The man was admitted to the intensive care unit for a catheter-related bloodstream infection. Pericardial effusion was detected via the bedside X-ray and ultrasound, and pericardiocentesis was performed. Cultures of the pericardial fluid, catheter tip, and blood independently revealed the presence of CRAB. These findings confirmed a diagnosis of purulent pericarditis. CONCLUSIONS: Clinicians should be reminded that CRAB infection can lead to purulent pericarditis, particularly in patients with congestive heart failure or renal insufficiency.
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Infecções por Acinetobacter/diagnóstico , Acinetobacter baumannii/isolamento & purificação , Injúria Renal Aguda/diagnóstico , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Pericardite/diagnóstico , Infecções por Acinetobacter/complicações , Acinetobacter baumannii/efeitos dos fármacos , Injúria Renal Aguda/complicações , Idoso , Carbapenêmicos/farmacologia , Diagnóstico Diferencial , Farmacorresistência Bacteriana , Evolução Fatal , Humanos , Masculino , Infarto do Miocárdio sem Supradesnível do Segmento ST/complicações , Pericardiocentese , Pericardite/complicações , Pericardite/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
Gastric cancer (GC) is one of the most common cancers worldwide and results in the second greatest rate of cancerassociated mortality globally. Multidrug resistance (MDR) often develops during the chemotherapy, resulting in the failure of treatment. To investigate the molecular mechanism of MDR, the roles of microRNA (miR)1 were studied in GC. Reverse transcriptionquantitative polymerase chain reaction and western blotting were used to investigate the expression levels of miR1 and sorcin in SGC7901/ADM and SGC7901/VCR cell lines. The effect of miR1 on the half maximal inhibitory concentration (IC50), cell apoptosis rates and drug accumulation was uncovered by MTT assay and flow cytometric analysis. Furthermore, dualluciferase assay and western blotting were used to determine the target of miR1 in GC. It was demonstrated that miR1 was highly downregulated in MDR GC cell lines, including SGC7901/ADM and SGC7901/VCR. Overexpression of miR1 in MDR GC cells decreased IC50, but increased the cell apoptosis rates and promoted the drug accumulation in cancer cells. Dualluciferase activity assay indicated that sorcin was the target of miR1 in GC. In addition, overexpression of sorcin could partially reverse the effect of miR1 in MDR GC cells. The role of miR1 in MDR GC cells makes it a potential therapeutic target for a successful clinical outcome.
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Apoptose/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/antagonistas & inibidores , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Antibióticos Antineoplásicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/farmacologia , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Células Tumorais Cultivadas , Vincristina/farmacologiaRESUMO
Pulmonary fibrosis (PF) is a fibroproliferative disease which can finally end up fatal lung failure. PF is characterized by abnormal proliferation of fibroblast, dysregulated fibroblast differentiation to myofibroblast and disorganized collagen and extracellular matrix (ECM) production, deposition and degradation. JAG1/Notch signaling has been reported to play a key role in tissue fibrosis including PF. Herein, we confirmed the abnormal upregulation of JAG1 mRNA expression and protein levels in PF tissue specimens; JAG1 knockdown reduced TGF-ß1-induced α-SMA and Collagen I protein levels. From the aspect of miRNA regulation, we searched for candidate miRNAs which might target JAG1 to inhibit its expression. Among the selected miRNAs, miR-30d expression was downregulated in PF tissues; miR-30d overexpression attenuated TGF-ß1-induced primary normal human lung fibroblast (NHLF) proliferation, as well as α-SMA and Collagen I protein levels. Through directly binding to the 3'-UTR of JAG1, miR-30d significantly inhibited JAG1 mRNA expression and protein level. Furthermore, JAG1 overexpression partially reversed the effect of miR-30d on NHLF proliferation and α-SMA and Collagen I proteins upon TGF-ß1 stimulation; miR-30d could suppress TGF-ß1 function on NHLFs through blocking JAG1/Notch signaling. Rescuing miR-30d expression to suppress TGF-ß1-induced activation of JAG1/Notch signaling may present a promising strategy for PF treatment.
Assuntos
Proteína Jagged-1/metabolismo , MicroRNAs/metabolismo , Miofibroblastos/patologia , Fibrose Pulmonar/patologia , Receptores Notch/metabolismo , Regulação da Expressão Gênica/fisiologia , Humanos , Miofibroblastos/metabolismo , Fibrose Pulmonar/metabolismo , Transdução de Sinais/fisiologiaRESUMO
Sepsis is a severe and progressive disease characterized by systemic inflammatory response syndrome (SIRS). CD40 serves as a vital link between immune response and inflammation. This study was designed to investigate the potential association between a functional single-nucleotide polymorphism (SNP) of CD40 (rs1883832) and susceptibility to sepsis. We first performed a case-control study to explore the relationship between the CD40 rs1883832 polymorphism and sepsis. CD40 mRNA expression and protein expression were determined by real-time PCR and western blotting, respectively, in peripheral blood mononuclear cells (PBMCs) from sepsis patients and healthy controls. The plasma sCD40L levels in the two groups were measured by ELISA. The results showed that the frequencies of the TT genotype and the CD40 rs1883832 T allele were significantly higher in sepsis patients than in healthy controls. Plasma sCD40L levels were also significantly increased in sepsis patients. In addition, TT genotype carriers among sepsis patients displayed the highest CD40 expression at both the mRNA and protein levels, accompanied by the highest plasma sCD40L concentrations. In conclusion, the CD40 rs1883832 T allele acts as a risk factor for increased susceptibility to sepsis and may be involved in the process of sepsis through regulation of CD40 expression and plasma sCD40L levels.
Assuntos
Antígenos CD40 , Ligante de CD40 , Regulação da Expressão Gênica , Predisposição Genética para Doença , Polimorfismo Genético , Sepse , Adulto , Idoso , Povo Asiático , Antígenos CD40/sangue , Antígenos CD40/genética , Ligante de CD40/sangue , Ligante de CD40/genética , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sepse/sangue , Sepse/genéticaRESUMO
Mesenchymal stem cells (MSCs) have been reported to regulate the systemic inflammatory response and sepsis-induced immunologic injury pre-clinically. However, whether MSCs from different sources elicit identical effects remains to be elucidated. The present study compared the effect of bone marrowderived MSCs (BMSCs) and adipose tissue-derived MSCs (ADMSCs) in a murine model of lipopolysaccharide (LPS)induced sepsis. SPF BALB/c mice were induced with an injection of LPS (10 mg/kg; 1 mg/ml) via the tail vein. To compare the effect of MSCs on the septic mice, either saline, BMSCs or ADMSCs were injected via the tail vein 5 min following the administration of LPS. The survival rates and body temperatures of the mice were observed regularly up to 48 h. The serum levels of proinflammatory cytokines, including tumour necrosis factorα, interleukin (IL)6 and IL8, antiinflammatory cytokines, including IL2, IL4 and IL10, and biochemical markers, including lactate, creatinine, alanine aminotransferase and aspertate aminotransferase, were analyzed at 6 h. The BMSCs and ADMSCs significantly reduced mortality rates, bodytemperature fluctuations, serum levels of biochemical markers and the majority of cytokines. However, the levels of IL8 in the BMSC and ADMSC groups were increased and decreased, respectively. These findings suggested that BMSCs and ADMSCs ameliorated sepsis-associated organ injury and mortality, and had a similar regulatory effect on pro and antiinflammatory cytokines despite the different MSC sources. Therefore, BMSCs and ADMSCs may serve as novel treatment modalities for sepsis.
Assuntos
Tecido Adiposo/citologia , Células da Medula Óssea/citologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Sepse/terapia , Tecido Adiposo/imunologia , Animais , Células da Medula Óssea/imunologia , Separação Celular , Células Cultivadas , Imunofenotipagem , Interleucinas/sangue , Interleucinas/imunologia , Lipopolissacarídeos/imunologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/imunologia , Camundongos Endogâmicos BALB C , Sepse/sangue , Sepse/imunologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Traumatic hemorrhagic shock (HS) is a severe outcome of traumatic injury that accounts for numerous traumatic deaths. In the process of traumatic HS, both hemorrhage and trauma can trigger a complex cascade of posttraumatic events that are related to inflammatory and immune responses, which may lead to multiple organ injury or even death. From a mechanistic perspective, systemic inflammation and organ injury are involved coagulation, the complement system, impaired microcirculation and inflammatory signaling pathways. In this review, we discuss the systemic inflammation and multiple organ injury in post-traumatic HS.