Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 12.374
Filtrar
1.
Nat Commun ; 12(1): 5078, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34426578

RESUMO

Genome-wide association studies (GWAS) have identified loci for kidney disease, but the causal variants, genes, and pathways remain unknown. Here we identify two kidney disease genes Dipeptidase 1 (DPEP1) and Charged Multivesicular Body Protein 1 A (CHMP1A) via the triangulation of kidney function GWAS, human kidney expression, and methylation quantitative trait loci. Using single-cell chromatin accessibility and genome editing, we fine map the region that controls the expression of both genes. Mouse genetic models demonstrate the causal roles of both genes in kidney disease. Cellular studies indicate that both Dpep1 and Chmp1a are important regulators of a single pathway, ferroptosis and lead to kidney disease development via altering cellular iron trafficking.


Assuntos
Dipeptidases/genética , Ferroptose/genética , Loci Gênicos , Predisposição Genética para Doença , Nefropatias/genética , Proteínas de Transporte Vesicular/genética , Animais , Nitrogênio da Ureia Sanguínea , Cromatina/metabolismo , Cisplatino , Metilação de DNA/genética , Dipeptidases/deficiência , Dipeptidases/metabolismo , Ácido Fólico , Edição de Genes , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Haploinsuficiência/genética , Humanos , Ferro/metabolismo , Rim/patologia , Nefropatias/induzido quimicamente , Camundongos , Necroptose/genética , Especificidade de Órgãos , Mapeamento Físico do Cromossomo , Piroptose/genética , Locos de Características Quantitativas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Transporte Vesicular/deficiência , Proteínas de Transporte Vesicular/metabolismo
2.
Int J Mol Sci ; 22(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34298988

RESUMO

This study evaluated the biocompatibility and biological performance of novel additive-manufactured bioabsorbable iron-based porous suture anchors (iron_SAs). Two types of bioabsorbable iron_SAs, with double- and triple-helical structures (iron_SA_2_helix and iron_SA_3_helix, respectively), were compared with the synthetic polymer-based bioabsorbable suture anchor (polymer_SAs). An in vitro mechanical test, MTT assay, and scanning electron microscope (SEM) analysis were performed. An in vivo animal study was also performed. The three types of suture anchors were randomly implanted in the outer cortex of the lateral femoral condyle. The ultimate in vitro pullout strength of the iron_SA_3_helix group was significantly higher than the iron_SA_2_helix and polymer_SA groups. The MTT assay findings demonstrated no significant cytotoxicity, and the SEM analysis showed cells attachment on implant surface. The ultimate failure load of the iron_SA_3_helix group was significantly higher than that of the polymer_SA group. The micro-CT analysis indicated the iron_SA_3_helix group showed a higher bone volume fraction (BV/TV) after surgery. Moreover, both iron SAs underwent degradation with time. Iron_SAs with triple-helical threads and a porous structure demonstrated better mechanical strength and high biocompatibility after short-term implantation. The combined advantages of the mechanical superiority of the iron metal and the possibility of absorption after implantation make the iron_SA a suitable candidate for further development.


Assuntos
Implantes Absorvíveis , Materiais Biocompatíveis , Âncoras de Sutura , Alanina Transaminase/sangue , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Fenômenos Biomecânicos , Nitrogênio da Ureia Sanguínea , Fosfatos de Cálcio/química , Fosfatos de Cálcio/toxicidade , Sulfato de Cálcio/administração & dosagem , Sulfato de Cálcio/química , Sulfato de Cálcio/toxicidade , Creatinina/sangue , Desenho de Equipamento , Fêmur/diagnóstico por imagem , Fêmur/ultraestrutura , Ferro , Lasers , Teste de Materiais , Microscopia Eletrônica de Varredura , Estrutura Molecular , Osseointegração , Polímeros/química , Polímeros/toxicidade , Porosidade , Coelhos , Distribuição Aleatória , Resistência à Tração , Vísceras , Microtomografia por Raio-X
3.
J Vet Med Sci ; 83(8): 1290-1294, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34148912

RESUMO

A 13-year-old, female, mixed-breed dog with a huge cranial mediastinal mass underwent radiotherapy (RT). On the following day, the dog presented with lethargy and anorexia. Hematological examination revealed elevated levels of blood urea nitrogen, creatinine, inorganic phosphorus, potassium, lactate dehydrogenase, creatine phosphokinase and aspartate aminotransferase, decreased calcium level, and metabolic acidosis. Urine output markedly decreased. The patient recovered with fluid therapy and diuretic therapy; however, died suddenly from an unknown cause 11 days after RT completion. Histopathological examination after necropsy showed thymoma in the cranial mediastinum and extensive tubular necrosis of both kidneys which may be due to RT-induced tumor lysis syndrome (TLS). This report suggests that the risk of TLS should be evaluated in dogs with thymoma who undergo RT.


Assuntos
Doenças do Cão , Timoma , Neoplasias do Timo , Síndrome de Lise Tumoral , Animais , Nitrogênio da Ureia Sanguínea , Creatinina , Doenças do Cão/etiologia , Doenças do Cão/radioterapia , Cães , Feminino , Timoma/radioterapia , Timoma/veterinária , Neoplasias do Timo/radioterapia , Neoplasias do Timo/veterinária , Síndrome de Lise Tumoral/etiologia , Síndrome de Lise Tumoral/veterinária
4.
BMC Oral Health ; 21(1): 310, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34134686

RESUMO

BACKGROUND: This retrospective observational study aims to assess platelet count, mean platelet volume (MPV), blood biochemical tests for liver and kidney function in Chinese oral lichen planus (OLP) patients. METHODS: Eighty pathologically confirmed OLP patients and 51 healthy controls were enrolled. Data on full blood count and biochemical tests were obtained from the electronic medical record system of the hospital. RESULTS: MPV was elevated in OLP patients compared to controls (10.68 ± 0.97 fL versus 10.33 ± 0.89 fL, P = 0.042) while platelet count showed no difference between them. Red-form OLP group had increased blood urea nitrogen (BUN, 5.24 ± 1.15 mmol/L versus 4.69 ± 0.98 mmol/L, P = 0.036) than white-form OLP group. By contrast, there were no differences between those two groups in the other variables including MPV, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine. In terms of C-reactive protein (CRP), 92.5% of the OLP patients had a value of less than 3.48 mg/L. Besides, 75% of the OLP patients were overweight with body mass index (BMI) more than 25 kg/m2. CONCLUSIONS: These findings indicate MPV might play roles in inflammation in OLP. The red-form OLP might be associated with damage or reduction of kidney function.


Assuntos
Líquen Plano Bucal , Nitrogênio da Ureia Sanguínea , Humanos , Volume Plaquetário Médio , Estudos Retrospectivos
5.
Medicine (Baltimore) ; 100(22): e25991, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087843

RESUMO

BACKGROUND: Several studies have reported good results for angiotensin II receptor blockers (ARB) combined with tripterygium glycosides (TGs) in the treatment of diabetic nephropathy (DN). However, because a small number of cases were included in each study, the statistical power was limited. Therefore, we performed a protocol for meta-analysis to further evaluate the clinical efficacy and safety of combined ARB and TGs in treatment of DN. METHODS: The protocol was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement guidelines. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, Science Direct up to April 2021. Outcome measures were 24-h urinary total protein, urinary albumin excretion rate, serum creatinine, blood urea nitrogen, albumin, hemoglobin A1c, ß2-microglobulin and serum glutamic pyruvic transaminase. The risk of bias assessment of the included studies was performed by two authors independently using the tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0). We performed meta-analysis using STATA 11.0. RESULTS: The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings. CONCLUSION: The findings will provide helpful evidence for the application of combined ARB and TGs in the treatment of DN. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/ARGE3.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Nefropatias Diabéticas/tratamento farmacológico , Glicosídeos/uso terapêutico , Tripterygium , Antagonistas de Receptores de Angiotensina/administração & dosagem , Antagonistas de Receptores de Angiotensina/efeitos adversos , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Quimioterapia Combinada , Glicosídeos/administração & dosagem , Glicosídeos/efeitos adversos , Humanos , Testes de Função Renal , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
6.
Nutrients ; 13(5)2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34063516

RESUMO

The Taiwan Tilapia is an important aquaculture product in Taiwan. The aquatic by-products generated during Tilapia processing, such as fish bones and skin, are rich in minerals and protein. We aimed to explore the effect of a dietary supplement, comprising a mixture of fermented Tilapia by-products and Monostroma nitidum oligosaccharides as the raw materials, combined with physical training on exercise performance and fatigue. We used a mouse model that displays a phenotype of accelerated aging. Male senescence-accelerated mouse prone-8 (SAMP8) mice were divided into two control groups-with or without physical training-and supplemented with different doses (0.5 times: 412 mg/kg body weight (BW)/day; 1 time: 824 mg/kg BW/day; 2 times: 1648 mg/kg BW/day) of fermented Tilapia by-products and Monostroma nitidum oligosaccharide-containing mixture and combined with exercise training groups. Exercise performance was determined by testing forelimb grip strength and with a weight-bearing exhaustive swimming test. Animals were sacrificed to collect physical fatigue-related biomarkers. Mice dosed at 824 or 1648 mg/kg BW/day showed improvement in their exercise performance (p < 0.05). In terms of biochemical fatigue indicators, supplementation of 824 or 1648 mg/kg BW/day doses of test substances could effectively reduce blood urea nitrogen concentration and lactate concentration and increase the lactate ratio (p < 0.05) and liver glycogen content post-exercise (p < 0.05). Based on the above results, the combination of physical training and consumption of a dietary supplementation mixture of fermented Tilapia by-products and Monostroma nitidum oligosaccharides could improve the exercise performance of mice and help achieve an anti-fatigue effect.


Assuntos
Suplementos Nutricionais , Fadiga/dietoterapia , Alimentos e Bebidas Fermentados , Oligossacarídeos/farmacologia , Tilápia , Animais , Biomarcadores/sangue , Nitrogênio da Ureia Sanguínea , Osso e Ossos , Modelos Animais de Doenças , Fadiga/metabolismo , Fermentação , Ácido Láctico/sangue , Masculino , Camundongos , Condicionamento Físico Animal , Natação , Taiwan
7.
Virol J ; 18(1): 117, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34088317

RESUMO

BACKGROUND: To date, specific cytokines associated with development of acute respiratory distress syndrome (ARDS) and extrapulmonary multiple organ dysfunction (MOD) in COVID-19 patients have not been systematically described. We determined the levels of inflammatory cytokines in patients with COVID-19 and their relationships with ARDS and extrapulmonary MOD. METHODS: The clinical and laboratory data of 94 COVID-19 patients with and without ARDS were analyzed. The levels of inflammatory cytokines (interleukin 6 [IL-6], IL-8, IL-10, and tumor necrosis factor α [TNF-α]) were measured on days 1, 3, and 5 following admission. Seventeen healthy volunteers were recruited as controls. Correlations in the levels of inflammatory cytokines with clinical and laboratory variables were analyzed, furthermore, we also explored the relationships of different cytokines with ARDS and extrapulmonary MOD. RESULTS: The ARDS group had higher serum levels of all 4 inflammatory cytokines than the controls, and these levels steadily increased after admission. The ARDS group also had higher levels of IL-6, IL-8, and IL-10 than the non-ARDS group, and the levels of these cytokines correlated significantly with coagulation parameters and disseminated intravascular coagulation (DIC). The levels of IL-6 and TNF-α correlated with the levels of creatinine and urea nitrogen, and were also higher in ARDS patients with acute kidney injury (AKI). All 4 inflammatory cytokines had negative correlations with PaO2/FiO2. IL-6, IL-8, and TNF-α had positive correlations with the APACHE-II score. Relative to survivors, non-survivors had higher levels of IL-6 and IL-10 at admission, and increasing levels over time. CONCLUSIONS: The cytokine storm apparently contributed to the development of ARDS and extrapulmonary MOD in COVID-19 patients. The levels of IL-6, IL-8, and IL-10 correlated with DIC, and the levels of IL-6 and TNF-α were associated with AKI. Relative to survivors, patients who died within 28 days had increased levels of IL-6 and IL-10.


Assuntos
COVID-19/sangue , Síndrome da Liberação de Citocina/sangue , Citocinas/sangue , Síndrome do Desconforto Respiratório/sangue , Injúria Renal Aguda/diagnóstico , Idoso , Nitrogênio da Ureia Sanguínea , COVID-19/patologia , Creatinina/sangue , Síndrome da Liberação de Citocina/diagnóstico , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/patologia , Feminino , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Síndrome do Desconforto Respiratório/patologia , Estudos Retrospectivos , SARS-CoV-2 , Fator de Necrose Tumoral alfa/sangue
8.
Am J Physiol Cell Physiol ; 321(1): C117-C133, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34010066

RESUMO

Sepsis is a life-threatening condition that can lead to several organ failures including kidney. In this study, we investigated the roles of GAS5 and miR-579-3p in regulating cell pyroptosis in the sepsis-induced renal injury model. Lipopolysaccharide (LPS) treatment or cecal ligation and puncture (CLP) surgery was used to create the in vitro and in vivo sepsis-induced renal injury model. The interactions between GAS5 and miR-579-3p, and miR-579-3p and SIRT1 were determined by bioinformatic prediction, luciferase reporter assay, and RIP assay. In vitro cell pyroptosis was examined by flow cytometry marked with active caspase-1 and PI. The protein levels of IL-1ß and IL-18 induced by cell pyroptosis were quantified using ELISA assay. In vivo renal injuries were evaluated with HE and TUNEL stainings, bacterial load in serum and creatinine, and blood urea nitrogen content analyses. Expression levels of GAS5, miR-579-3p, pyroptosis, and SIRT1/PGC-1a/Nrf2 pathway-related molecules were evaluated by qRT-PCR or Western blot. GAS5 and SIRT1 were downregulated, whereas miR-579-3p was upregulated in in vitro and in vivo sepsis-induced renal injury models. GAS5 negatively and directly regulated miR-579-3p to reduce cell pyroptosis via the activation of SIRT1/PGC-1a/Nrf2 pathway. In addition, miR-579-3p suppressed PGC-1a/Nrf2 pathway to induce cell pyroptosis by directly targeting SIRT1. What's more, overexpression of GAS5, or knockdown of miR-579-3p, enhanced SIRT1 expression that led to the improved survival rate, reduced the weight loss, and relieved renal injuries in septic mice. Overexpression of GAS5 demonstrated protective effects against sepsis-induced renal injury via downregulating miR-579-3p and activating SIRT1/PGC-1α/Nrf2 pathway to inhibit cell pyroptosis.


Assuntos
Injúria Renal Aguda/genética , MicroRNAs/genética , Fator 2 Relacionado a NF-E2/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , RNA Longo não Codificante/genética , Sepse/genética , Sirtuína 1/genética , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/patologia , Animais , Nitrogênio da Ureia Sanguínea , Caspase 1/genética , Caspase 1/metabolismo , Creatinina/sangue , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Regulação da Expressão Gênica , Genes Reporter , Humanos , Interleucina-18/genética , Interleucina-18/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Lipopolissacarídeos/farmacologia , Luciferases/genética , Luciferases/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Piroptose/genética , RNA Longo não Codificante/metabolismo , Sepse/metabolismo , Sepse/mortalidade , Sepse/patologia , Transdução de Sinais , Sirtuína 1/metabolismo , Análise de Sobrevida
9.
Biomed Pharmacother ; 140: 111686, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34015581

RESUMO

OBJECTIVES: The present study examined the effects of ferulic acid (FA) and Zinc oxide nanoparticles (ZnO-NPs) and a combination of both on renal ischemia/reperfusion injury (IRI) in rats and their possible underlying mechanisms. METHODS: two-hundreds male Sprague Dawley rats were randomly allocated into the 5 groups; i) sham group, ii) control (IRI) group (occlusion of the left renal pedicle for 45 min), iii) FA group as IRI group with FA (100 mg/Kg oral 24 hrs before ischemia), iv) ZnO-NPs group as IRI group with ZnO-NPs single 5 mg/Kg i.p. 2 hrs before ischemia and v) FA + ZnO-NPs group as IRI group with both FA and ZnO-NPs in the same previous doses. According to the reperfusion times, each group was further subdivided into 4 hr, 24 hr, 48 hr and 7 days reperfusion subgroups. RESULTS: administration of either FA or ZnO-NPs caused significant improvement in the elevated serum creatinine and BUN and malondialdehyde (MDA) concentrations and expression of TNF-α, Bax, caspase-3 in kidney tissues with significant rise in the creatinine clearance, the activities of catalase (CAT) and superoxide dismutase (SOD) and the expression of HO-1, HIF-1α genes and proliferation marker (ki67) in kidney tissues compared to IRI group (p < 0.05). Moreover, a combination of both agents produced more significant improvement in the studied parameters than each agent did alone (p < 0.05). CONCLUSIONS: Both FA and ZnO-NPs exerted cytoprotective effects against ischemic kidney injury and a combination of both exhibited more powerful renoprotective effect. This renoprotective effect might be due to suppression of oxidative stress, enhancement of cell proliferation (ki67), upregulation of antioxidant genes (Nrf2, HO-1 and HIF-1α) and downregulation of inflammatory cytokine (TNF-α) and apoptotic genes (caspase-3 and Bax).


Assuntos
Ácidos Cumáricos/farmacologia , Nefropatias/tratamento farmacológico , Nanopartículas/administração & dosagem , Traumatismo por Reperfusão/tratamento farmacológico , Óxido de Zinco/farmacologia , Animais , Antioxidantes/metabolismo , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Rim/efeitos dos fármacos , Rim/metabolismo , Nefropatias/sangue , Nefropatias/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/sangue , Superóxido Dismutase/metabolismo
10.
Int Immunopharmacol ; 97: 107697, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33933847

RESUMO

BACKGROUND: Toward the end of December 2019, a novel type of coronavirus (2019-nCoV) broke out in Wuhan, China. Here, the hematological characteristics of patients with severe and critical 2019-nCoV pneumonia in intensive care unit (ICU) were investigated, which may provide the necessary basis for its diagnosis and treatment. METHODS: We collected data on patients with confirmed 2019-nCoV pneumonia in the ICU of Leishenshan Hospital in Wuhan from February 25 to April 2, 2020. Real-time reverse-transcription polymerase chain reaction was used to confirm the presence of 2019-nCoV, and various hematological characteristics were analyzed. RESULTS: All patients tested positive for 2019-nCoV using nasopharyngeal swabs or sputum after admission, and interstitial pneumonia findings were noted on chest computed tomography. Sex, age and comorbidities were not significantly different between the severe and critical groups. In terms of prognosis, the survival rate of patients in the severe group reached 100%, whereas that of patients in the critical group was only 13.33% after positive treatment. Furthermore, lymphocyte percentage, blood urea nitrogen, calcium, D-dimer, myohemoglobin, procalcitonin, and IL-6 levels were high-risk factors for disease progression in critical patients. Finally, lymphocyte percentage and blood urea nitrogen, calcium, myohemoglobin, and IL-6 levels were closely associated with patient prognosis. CONCLUSIONS: 2019-nCoV pneumonia should be considered a systemic disease. Patients with more complications were more likely to develop critical disease. Lymphocyte percentage and blood urea nitrogen, calcium, myohemoglobin, and IL-6 levels can be monitored to prevent progression critical disease.


Assuntos
COVID-19/sangue , COVID-19/diagnóstico , Unidades de Terapia Intensiva , Adulto , Idoso , Nitrogênio da Ureia Sanguínea , COVID-19/mortalidade , Cálcio/sangue , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hemoglobinas/metabolismo , Humanos , Interleucina-6/sangue , Modelos Logísticos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Prognóstico , Estudos Retrospectivos , Fatores de Risco
11.
Toxicol Appl Pharmacol ; 424: 115594, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34044073

RESUMO

Oxidative stress and inflammation in kidney are the main causes for hyperuricemic nephropathy (HN). Baicalin and baicalein, two flavonoids, have anti-inflammatory and anti-oxidative effects and they are interconvertible in the body. In this study, both baicalin and baicalein were administered by intragastric administration (i.g.) or intraperitoneal injection (i.p.) at the dose of 50 mg kg-1, once a day for 15 consecutive days to HN mice, a model established by i.g. of yeast extract combined with i.p. of potassium oxonate. In HN mice, baicalin and baicalein reduced serum uric acid (SUA) levels and protected kidneys by anti-inflammatory and anti-oxidative effects. Mechanistically, the effect of baicalin and baicalein on reducing SUA levels might due to their inhibitory effect on xanthine oxidase (XO) activity in vivo and in vitro. Furthermore, the mechanisms of baicalin and baicalein against HN were analyzed with network pharmacology and molecular docking technology. The network pharmacology indicated that the protective effects of baicalin and baicalein against HN were mainly related to their down-regulating effects on TLRs, NF-κB, MAPK, PI3K/AKT and NOD-like receptor signaling pathways. Molecular docking indicated high binding affinity of baicalin/baicalein to targets such as AKT1 and MAPK1. In summary, baicalin and baicalein are promising drug candidates for the treatment of HN by inhibiting XO activity, reducing inflammation and cell apoptosis through down-regulating TLRs/NLRP3/NF-κB, MAPK, PI3K/AKT/NF-κB pathways.


Assuntos
Flavanonas/farmacologia , Flavonoides/farmacologia , Nefropatias/tratamento farmacológico , Simulação de Acoplamento Molecular , Alopurinol/farmacologia , Animais , Nitrogênio da Ureia Sanguínea , Fígado/enzimologia , Camundongos , Ácido Úrico/sangue , Xantina Oxidase/antagonistas & inibidores
12.
Medicine (Baltimore) ; 100(18): e25819, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950987

RESUMO

ABSTRACT: Respiratory failure is the major cause of death in patients with coronavirus disease (COVID-19). Data on factors affecting the need for oxygen therapy in early-stage COVID-19 are limited. This study aimed to evaluate the factors associated with the need for oxygen therapy in patients with COVID-19.This is a retrospective study of consecutive COVID-19 patients who were hospitalized between February 27 and June 28, 2020, in South Korea. Logistic regression analyses were performed to identify the factors associated with the need for oxygen therapy.Of the 265 patients included in the study, 26 (9.8%) received oxygen therapy, and 7 of these patients (29.2%) were transferred to a step-up facility, and 3 (11.5%) died. The median age of all patients was 46 years (IQR, 30-60 years), and the median modified early warning score at admission was 1 (IQR, 1-2). In a multivariate logistic regression analysis, being a current smoker (odds ratio [OR] 7.641, 95% confidence interval [CI] 1.686-34.630, P = .008), heart rate (OR 1.053, 95% CI 1.010-1.097, P = .014), aspartate aminotransferase values (OR 1.049, 95% CI 1.008-1.092, P = .020), blood urea nitrogen levels (OR 1.171, 95% CI 1.073-1.278, P < .001), and chest radiographic findings (OR 3.173, 95% CI 1.870-5.382, P < .001) were associated with oxygen therapy.In patients with less severe COVID-19, the need for oxygen therapy is affected by smoking and elevated values of aspartate aminotransferase and blood urea nitrogen. Further research is warranted on the risk factors for deterioration in COVID-19 to efficiently allocate medical resources.


Assuntos
COVID-19/terapia , Oxigenoterapia , Pneumonia Viral/terapia , Adulto , Aspartato Aminotransferases/sangue , Nitrogênio da Ureia Sanguínea , COVID-19/mortalidade , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Fumar/efeitos adversos
13.
Int J Mol Sci ; 22(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33947045

RESUMO

Upstream stimulatory factor 1 (USF1) is a transcription factor that is increased in high-glucose conditions and activates the transforming growth factor (TGF)-ß1 promoter. We examined the effects of synthetic pyrrole-imidazole (PI) polyamides in preventing USF1 binding on the TGF-ß1 promoter in Wistar rats in which diabetic nephropathy was established by intravenous administration of streptozotocin (STZ). High glucose induced nuclear localization of USF1 in cultured mesangial cells (MCs). In MCs with high glucose, USF1 PI polyamide significantly inhibited increases in promoter activity of TGF-ß1 and expression of TGF-ß1 mRNA and protein, whereas it significantly decreased the expression of osteopontin and increased that of h-caldesmon mRNA. We also examined the effects of USF1 PI polyamide on diabetic nephropathy. Intraperitoneal injection of USF1 PI polyamide significantly suppressed urinary albumin excretion and decreased serum urea nitrogen in the STZ-diabetic rats. USF1 PI polyamide significantly decreased the glomerular injury score and tubular injury score in the STZ-diabetic rats. It also suppressed the immunostaining of TGF-ß1 in the glomerulus and proximal tubules and significantly decreased the expression of TGF-ß1 protein from kidney in these rats. These findings indicate that synthetic USF1 PI polyamide could potentially be a practical medicine for diabetic nephropathy.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Inativação Gênica , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Fatores Estimuladores Upstream/antagonistas & inibidores , Albuminúria/etiologia , Albuminúria/prevenção & controle , Animais , Nitrogênio da Ureia Sanguínea , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/urina , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Ensaio de Desvio de Mobilidade Eletroforética , Glucose/farmacologia , Hemoglobina A Glicada/análise , Glomérulos Renais/química , Túbulos Renais/química , Masculino , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Osteopontina/análise , Regiões Promotoras Genéticas , Ligação Proteica/efeitos dos fármacos , Ratos , Transcrição Genética , Fator de Crescimento Transformador beta1/genética , Fatores Estimuladores Upstream/metabolismo
14.
BMC Infect Dis ; 21(1): 473, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34034670

RESUMO

BACKGROUND: Until now, the influential factors associated with pleural adenosine deaminase (ADA) activity among children remain unclear. This retrospective study was therefore conducted aiming to investigate the factors associated with negative pleural ADA results in the diagnosis of childhood pleural tuberculosis (TB). METHODS: Between January 2006 and December 2019, children patients with definite or possible pleural TB were recruited for potential analysis. Then, patients were stratified into two categories: negative pleural ADA results group (experimental group, ≤40 U/L) and positive pleural ADA results group (control group, > 40 U/L). Univariate and multivariate logistic regression analyses were performed to estimate risk factors for negative pleural ADA results. RESULTS: A total of 84 patients with pleural TB were recruited and subsequently classified as experimental (n = 17) and control groups (n = 67). Multivariate analysis (Hosmer-Lemeshow goodness-of-fit test: χ2 = 1.881, df = 6, P = 0.930) revealed that variables, such as chest pain (age-adjusted OR = 0.0510, 95% CI: 0.004, 0.583), pleural total protein (≤45.3 g/L, age-adjusted OR = 27.7, 95% CI: 2.5, 307.7), pleural lactate dehydrogenase (LDH, ≤505 U/L, age-adjusted OR = 59.9, 95% CI: 4.2, 857.2) and blood urea nitrogen (≤3.2 mmol/L, age-adjusted OR = 32.0, 95% CI: 2.4, 426.9), were associated with negative pleural ADA results when diagnosing childhood pleural TB. CONCLUSION: Our findings demonstrated that chest pain, pleural total protein, pleural LDH, and blood urea nitrogen were associated with a negative pleural ADA result for the diagnosis of pleural TB among children. When interpreting pleural ADA levels in children with these characteristics, a careful clinical assessment is required for the pleural TB diagnosis.


Assuntos
Adenosina Desaminase/análise , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pleural/diagnóstico , Adolescente , Nitrogênio da Ureia Sanguínea , Estudos de Casos e Controles , Dor no Peito , Criança , Feminino , Humanos , L-Lactato Desidrogenase/análise , Modelos Logísticos , Masculino , Análise Multivariada , Derrame Pleural/microbiologia , Estudos Retrospectivos , Fatores de Risco , Escarro/microbiologia , Tuberculose Pleural/microbiologia , Tuberculose Pleural/patologia
15.
Biomed Pharmacother ; 139: 111636, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33957566

RESUMO

This study was designed to reveal the protective effects of dietary supplementation of curcumin against renal cell tumours and oxidative stress induced by renal carcinogen iron nitrilotriacetate (Fe-NTA) in ddY male mice. The results showed that mice treated with a renal carcinogen, Fe-NTA, a 35% renal cell tumour incidence was noticed, whereas renal cell tumour occurrence was elevated to 80% in Fe-NTA promoted and N-diethylnitrosamine (DEN)-initiated mice as compared with saline- treated mice. No incidence of tumours has been observed in DEN-initiated non-promoted mice. Diet complemented with 0.5% and 1.0% curcumin fed prior to, during and after treatment with Fe-NTA in DEN-initiated animals, tumour incidence was reduced dose-dependently to about 45% and 30% respectively. Immunohistochemical studies also revealed the increased formation of 4-hydroxy-2-nonenal (HNE)-modified protein adducts and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in kidney tissue of mice treated with an intraperitoneal injection of Fe-NTA (6.0 mg Fe/kg body weight.). Furthermore, Fe-NTA treatment of mice also resulted in significant elevation of malondialdehyde (MDA), serum urea, and creatinine and decreases renal glutathione. However, the changes in most of these parameters were attenuated dose-dependently by prophylactic treatment of animals with 0.5% and 1% curcumin diet, this may be due to its antioxidative impact of curcumin. These results suggest that intake of curcumin is beneficial for the prevention of renal cell tumours and oxidative stress damage mediated by renal carcinogen, Fe-NTA.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Antioxidantes/uso terapêutico , Carcinoma de Células Renais/induzido quimicamente , Carcinoma de Células Renais/tratamento farmacológico , Curcumina/uso terapêutico , Neoplasias Renais/induzido quimicamente , Neoplasias Renais/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , 8-Hidroxi-2'-Desoxiguanosina , Aldeídos , Animais , Anticarcinógenos/farmacologia , Nitrogênio da Ureia Sanguínea , Carcinógenos , Creatinina/sangue , Dieta , Dietilnitrosamina , Relação Dose-Resposta a Droga , Compostos Férricos , Masculino , Camundongos , Ácido Nitrilotriacético/análogos & derivados
16.
J Zoo Wildl Med ; 52(1): 241-252, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33827182

RESUMO

Native to Southeast Asia, the Sunda pangolin (Manis javanica) is critically endangered largely because of poorly regulated wildlife trade, consumptive practices, and use in traditional Chinese medicine. Efforts to rescue and rehabilitate animals confiscated from the illegal trade are complicated by a general lack of knowledge surrounding the normal health and disease processes unique to the species. To provide clinical reference intervals for normal health states of Sunda pangolins, biochemical parameters were determined from rescued individuals in Vietnam that had undergone a 14-day observation period and met a set of criteria for release back into the wild. Blood samples were collected from 42 apparently healthy Sunda pangolins while anesthetized or awake. Packed cell volume (PCV) and total solids (TS) were determined manually, and serum biochemistry values were determined in-house with a benchtop analyzer. Additional biochemical and mineral parameters not included in the primary panel were determined from a subset of 10 pangolins through an external diagnostic laboratory. Overall reference intervals were calculated for PCV and TS (n = 29) and for standard serum biochemistry parameters (n = 42). Females and males demonstrated significant variation with respect to body mass, potassium (K+), and phosphorus, whereas age was a significant source of variation in alkaline phosphatase. Seasonal variation in glucose (GLU), creatinine (CRE), total proteins, sodium, calcium, and K+ was also observed. Comparisons between anesthetized and awake pangolins demonstrated significant variation in GLU, CRE, and K+. The parameters determined in this study can serve as a clinical reference for ex situ Sunda pangolin conservation efforts. In the context of wildlife rehabilitation, serial bloodwork allows for continued monitoring of patient health and should inform decision making regarding release readiness and timing.


Assuntos
Minerais/sangue , Pangolins/sangue , Criação de Animais Domésticos , Animais , Animais Selvagens , Glicemia , Nitrogênio da Ureia Sanguínea , Creatina/sangue , Espécies em Perigo de Extinção , Enzimas/sangue , Feminino , Hematócrito , Masculino , Valores de Referência , Vietnã
17.
Am J Emerg Med ; 47: 198-204, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33895701

RESUMO

INTRODUCTION: Early prediction of patients' prognosis in the emergency department (ED) is important. Patients' conditions such as dehydration help predict prognosis. The ratio of serum blood urea nitrogen to creatinine (BUN/Cr ratio) and inferior vena cava (IVC) diameter is often used to determine dehydration. Also, serum albumin levels reflect nutritional conditions such as dehydration. In this study, we evaluated the performance of BUN/Cr ratio, IVC diameter ratio, and BUN/Albumin ratio as predictive markers for in-hospital mortality and ICU admission among various diseases in ED. MATERIAL AND METHODS: This retrospective cohort study utilized data from patients who had abdominal and pelvic computed tomography (APCT) performed at our institution from 2015 to 2018. The measurement of IVC diameter from computed tomography, the BUN/Cr ratio, and the BUN/Albumin ratio were calculated. Differences in the performance among the BUN/Cr ratio, the IVC diameter ratio, and the BUN/Albumin ratio for predicting outcomes were evaluated by the area under the receiver operating characteristic (AUROC) curve. RESULTS: A total of 914 patients were enrolled and 78 patients (8.5%) were admitted to the ICU, and 71 patients (7.8%) died during the clinical process. Multivariate logistic regression showed that only the BUN/Albumin ratio was a significant predictor of inhospital mortality and ICU admission. CONCLUSION: Among dehydration markers the BUN/Albumin ratio is a simple and useful tool for predicting the outcomes of patients visiting the ED.


Assuntos
Albuminas/análise , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Mortalidade Hospitalar , Veia Cava Inferior/patologia , Adulto , Idoso , Biomarcadores/sangue , Desidratação/sangue , Desidratação/diagnóstico , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Veia Cava Inferior/diagnóstico por imagem
18.
Can J Gastroenterol Hepatol ; 2021: 6643595, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33824864

RESUMO

Background: Changes in BUN have been proposed as a risk factor for complications in acute pancreatitis (AP). Our study aimed to compare changes in BUN versus the Bedside Index for Severity in Acute Pancreatitis (BISAP) score and the Acute Physiology and Chronic Health Evaluation-II score (APACHE-II), as well as other laboratory tests such as haematocrit and its variations over 24 h and C-reactive protein, in order to determine the most accurate test for predicting mortality and severity outcomes in AP. Methods: Clinical data of 410 AP patients, prospectively enrolled for study at our institution, were analyzed. We define AP according to Atlanta classification (AC) 2012. The laboratory test's predictive accuracy was measured using area-under-the-curve receiver-operating characteristics (AUC) analysis and sensitivity and specificity tests. Results: Rise in BUN was the only score related to mortality on the multivariate analysis (p=0.000, OR: 12.7; CI 95%: 4.2-16.6). On the comparative analysis of AUC, the rise in BUN was an accurate test in predicting mortality (AUC: 0.842) and persisting multiorgan failure (AUC: 0.828), similar to the BISAP score (AUC: 0.836 and 0.850) and APACHE-II (AUC: 0.756 and 0.741). The BISAP score outperformed both APACHE-II and rise in BUN at 24 hours in predicting severe AP (AUC: 0.873 vs. 0.761 and 0.756, respectively). Conclusion: Rise in BUN at 24 hours is a quick and reliable test in predicting mortality and persisting multiorgan failure in AP patients.


Assuntos
Pancreatite , APACHE , Doença Aguda , Biomarcadores , Nitrogênio da Ureia Sanguínea , Humanos , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença
19.
Am J Physiol Renal Physiol ; 320(5): F984-F1000, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33843271

RESUMO

Sepsis-associated acute kidney injury (SA-AKI) is a significant problem in the critically ill that causes increased death. Emerging understanding of this disease implicates metabolic dysfunction in its pathophysiology. This study sought to identify specific metabolic pathways amenable to potential therapeutic intervention. Using a murine model of sepsis, blood and tissue samples were collected for assessment of systemic inflammation, kidney function, and renal injury. Nuclear magnetic resonance (NMR)-based metabolomics quantified dozens of metabolites in serum and urine that were subsequently submitted to pathway analysis. Kidney tissue gene expression analysis confirmed the implicated pathways. Septic mice had elevated circulating levels of inflammatory cytokines and increased levels of blood urea nitrogen and creatinine, indicating both systemic inflammation and poor kidney function. Renal tissue showed only mild histological evidence of injury in sepsis. NMR metabolomic analysis identified the involvement of mitochondrial pathways associated with branched-chain amino acid metabolism, fatty acid oxidation, and de novo NAD+ biosynthesis in SA-AKI. Renal cortical gene expression of enzymes associated with those pathways was predominantly suppressed. Renal cortical fatty acid oxidation rates were lower in septic mice with high inflammation, and this correlated with higher serum creatinine levels. Similar to humans, septic mice demonstrated renal dysfunction without significant tissue disruption, pointing to metabolic derangement as an important contributor to SA-AKI pathophysiology. Metabolism of branched-chain amino acid and fatty acids and NAD+ synthesis, which all center on mitochondrial function, appeared to be suppressed. Developing interventions to activate these pathways may provide new therapeutic opportunities for SA-AKI.NEW & NOTEWORTHY NMR-based metabolomics revealed disruptions in branched-chain amino acid metabolism, fatty acid oxidation, and NAD+ synthesis in sepsis-associated acute kidney injury. These pathways represent essential processes for energy provision in renal tubular epithelial cells and may represent targetable mechanisms for therapeutic intervention.


Assuntos
Injúria Renal Aguda/sangue , Injúria Renal Aguda/urina , Imageamento por Ressonância Magnética/métodos , Metabolômica/métodos , Mitocôndrias/metabolismo , Sepse/complicações , Animais , Biomarcadores/sangue , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Citocinas/genética , Citocinas/metabolismo , Regulação da Expressão Gênica , Inflamação/sangue , Inflamação/metabolismo , Inflamação/urina , Masculino , Camundongos , Camundongos Endogâmicos C57BL
20.
Life Sci ; 277: 119512, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33862116

RESUMO

AIM: Tamoxifen (TAMO) is a chemotherapeutic drug used for the treatment of breast cancer. Nevertheless, there is a lack of information available in regarding its nephrotoxicity. The purpose of this work was to investigate the impact of cyanocobalamin (COB) and/or calcitriol (CAL) injections on TAMO-induced nephrotoxicity. MAIN METHODS: Animals were allocated into five groups as follows: normal control group; TAMO (45 mg/kg) administered group; TAMO+COB (6mg/kg, i.p) treated group; TAMO+CAL (0.3 µg/kg, i.p) treated group; TAMO+COB+CAL combination groups. KEY FINDINGS: Renal injury induced by TAMO was confirmed by the alteration in renal function parameters in the serum (urea and creatinine), as well as in the urine (creatinine clearance, total protein and albumin). These results were supported by histopathological examination. Upregulation of renal inflammatory parameters; tumor necrosis factor (TNF)-α, interleukin (IL)-6, C-reactive protein (CRP); and transforming growth factor (TGF)-ß1 as well as in protein expression of nuclear factor-kappa B (NF-κB) and cleaved caspase-3 were observed to a greater extent in the TAMO-treated rats compared with the control. Renal fibrosis was also evidenced by a elevation in renal L-hydroxyproline level as well as by histomorphological collagen deposition in TAMO-treated groups compared to the control group. Administration of COB and/or CAL concurrently with TAMO significantly ameliorated the deviation in the above-studied parameters and improved the histopathological renal picture. SIGNIFICANCE: Inhibition of NF-κß-mediated inflammation and caspase-3-induced apoptosis are possible renoprotective mechanisms of COB and/or CAL against TAMO nephrotoxicity, which was more noticeable in the TAMO group treated with the combination of the two vitamins in question.


Assuntos
Calcitriol/farmacologia , Tamoxifeno/efeitos adversos , Vitamina B 12/farmacologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Animais , Apoptose , Nitrogênio da Ureia Sanguínea , Calcitriol/metabolismo , Caspase 3/metabolismo , Creatinina/sangue , Feminino , Rim/patologia , Nefropatias/tratamento farmacológico , Nefropatias/metabolismo , Testes de Função Renal , NF-kappa B/metabolismo , Nefrite/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Tamoxifeno/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Vitamina B 12/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...