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1.
BMC Res Notes ; 14(1): 245, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193271

RESUMO

OBJECTIVE: Sepsis is a major cause of mortality for critically ill patients. This study aimed to determine whether presepsin values can predict mortality in patients with sepsis. RESULTS: Receiver operating characteristic (ROC) curve analysis, Log-rank test, and multivariate analysis identified presepsin values and Prognostic Nutritional Index as predictors of mortality in sepsis patients. Presepsin value on Day 1 was a predictor of early mortality, i.e., death within 7 days of ICU admission; ROC curve analysis revealed an AUC of 0.84, sensitivity of 89%, and specificity of 77%; and multivariate analysis showed an OR of 1.0007, with a 95%CI of 1.0001-1.0013 (p = 0.0320).


Assuntos
Avaliação Nutricional , Sepse , Biomarcadores , Humanos , Unidades de Terapia Intensiva , Receptores de Lipopolissacarídeos , Fragmentos de Peptídeos , Projetos Piloto , Prognóstico , Curva ROC , Sepse/diagnóstico
5.
Ren Fail ; 43(1): 1104-1114, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34238117

RESUMO

BACKGROUND: The clinical use of serum creatine (sCr) and cystatin C (CysC) in kidney function evaluation of critically ill patients has been in continuous discussion. The difference between estimated glomerular filtration rate calculated by sCr (eGFRcr) and CysC (eGFRcysc) of critically ill COVID-19 patients were investigated in this study. METHODS: This is a retrospective, single-center study of critically ill patients with COVID-19 admitted in intensive care unit (ICU) at Wuhan, China. Control cases were moderate COVID-19 patients matched in age and sex at a ratio of 1:1. The eGFRcr and eGFRcysc were compared. The association between eGFR and death were analyzed in critically ill cases. The potential factors influencing the divergence between eGFRcr and eGFRcysc were explored. RESULTS: A total of 76 critically ill COVID-19 patients were concluded. The mean age was 64.5 ± 9.3 years. The eGFRcr (85.45 (IQR 60.58-99.23) ml/min/1.73m2) were much higher than eGFRcysc (60.6 (IQR 34.75-79.06) ml/min/1.73m2) at ICU admission. About 50 % of them showed eGFRcysc < 60 ml/min/1.73 m2 while 25% showed eGFRcr < 60 ml/min/1.73 m2 (χ2 = 10.133, p = 0.001). This divergence was not observed in moderate group. The potential factors influencing the divergence included serum interleukin-6 (IL-6), tumor necrosis factor (TNF-α) level as well as APACHEII, SOFA scores. Reduced eGFRcr (<60 mL/min/1.73 m2) was associated with death (HR = 1.939, 95%CI 1.078-3.489, p = 0.027). CONCLUSIONS: The eGFRcr was generally higher than eGFRcysc in critically ill COVID-19 cases with severe inflammatory state. The divergence might be affected by inflammatory condition and illness severity. Reduced eGFRcr predicted in-hospital death. In these patients, we advocate for caution when using eGFRcysc.


Assuntos
COVID-19/fisiopatologia , Creatina/sangue , Cistatina C/sangue , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/diagnóstico , Idoso , Biomarcadores/sangue , COVID-19/complicações , COVID-19/mortalidade , China/epidemiologia , Estado Terminal/terapia , Feminino , Mortalidade Hospitalar , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/etiologia , Estudos Retrospectivos , Análise de Sobrevida
6.
Biomed Pharmacother ; 139: 111621, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243599

RESUMO

Alterations in xanthine oxidase activity are known to be pathologically influential on coronary artery disease (CAD), but the association between purine-related blood metabolites and CAD has only been partially elucidated. We performed global metabolomics profiling and network analysis on blood samples from the Wonju and Pyeongchang (WP) cohort study (n = 2055) to elucidate the importance of purine related metabolites associated with potential CAD risk. Then, 5 selected serum metabolites were quantified from the WP cohort, Shinchon cohort (n = 259), and Shinchon case control (n = 424) groups to develop machine learning models for 10-year risk prediction, relapse within 10 years and diagnosis of the disease via 100 repeated 5-fold cross-validations of logistic models. The combination of purine metabolite levels or only xanthine levels in blood could be applied for machine learning model development for major adverse cardiac and cerebrovascular event (MACCE, cerebrovascular death, nonfatal myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass graft, and stroke) risk prediction, relapse of MACCEs among patients with myocardial infarction history and diagnosis of stable CAD. In particular, our research provided initial evidence that blood xanthine and uric acid levels play different roles in the development of machine learning models for primary/secondary prevention or diagnosis of CAD. In this research, we determined that purine-related metabolites in blood are applicable to machine learning model development for CAD risk prediction and diagnosis. Also, our work advances current CAD biomarker discovery strategies mainly relying on clinical features; emphasizes the differential biomarkers in first/secondary prevention or diagnosis studies.


Assuntos
Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Purinas/metabolismo , Idoso , Biomarcadores/metabolismo , Estudos de Casos e Controles , Estudos de Coortes , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Feminino , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Intervenção Coronária Percutânea/métodos , Prognóstico , Medição de Risco/métodos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia
7.
Nanoscale ; 13(28): 12279-12287, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34251003

RESUMO

Rapid diagnosis of preeclampsia is necessary to ensure timely administration of appropriate care and prevent the potentially catastrophic complications of the condition affecting both mothers and babies. While the diagnostic superiority of angiogenic blood biomarkers such as placental growth factor has recently been demonstrated, there is an urgent need to develop point-of-care (PoC) technologies that allow rapid, quantitative, and accurate testing for these markers within local communities. Towards addressing this need, here we report on a fully integrated biodiagnostic platform based on nanoscale indium oxide field effect transistor (FET) sensors. The high-performance FET sensors are integrated with blood sample processing cartridges that minimize the need for operator intervention during the assay and eliminate the need for analytical equipment. Within 40 minutes and from 30 µL of blood, the FET platform could reliably measure PlGF with a limit of detection of 0.06 pg mL-1 and a five order of magnitudes dynamic range. Pilot clinical validation in four preeclamptic pregnancies confirmed that the accuracy and reliability of the FET platform, paving the way for further development to a much-needed point-of-care preeclampsia testing.


Assuntos
Pré-Eclâmpsia , Biomarcadores , Feminino , Humanos , Fator de Crescimento Placentário , Testes Imediatos , Pré-Eclâmpsia/diagnóstico , Gravidez , Reprodutibilidade dos Testes
8.
Sci Rep ; 11(1): 14471, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34262116

RESUMO

Early detection of severe forms of COVID-19 is absolutely essential for timely triage of patients. We longitudinally followed-up two well-characterized patient groups, hospitalized moderate to severe (n = 26), and ambulatory mild COVID-19 patients (n = 16) at home quarantine. Human D-dimer, C-reactive protein (CRP), ferritin, cardiac troponin I, interleukin-6 (IL-6) levels were measured on day 1, day 7, day 14 and day 28. All hospitalized patients were SARS-CoV-2 positive on admission, while all ambulatory patients were SARS-CoV-2 positive at recruitment. Hospitalized patients had higher D-dimer, CRP and ferritin, cardiac troponin I and IL-6 levels than ambulatory patients (p < 0.001, p < 0.001, p = 0.016, p = 0.035, p = 0.002 respectively). Hospitalized patients experienced significant decreases in CRP, ferritin and IL-6 levels from admission to recovery (p < 0.001, p = 0.025, and p = 0.001 respectively). Cardiac troponin I levels were high during the acute phase in both hospitalized and ambulatory patients, indicating a potential myocardial injury. In summary, D-dimer, CRP, ferritin, cardiac troponin I, IL-6 are predictive laboratory markers and can largely determine the clinical course of COVID-19, in particular the prognosis of critically ill COVID-19 patients.


Assuntos
COVID-19/sangue , COVID-19/diagnóstico , Assistência Ambulatorial , Biomarcadores/sangue , Proteína C-Reativa/análise , Diagnóstico Precoce , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Seguimentos , Hospitalização , Humanos , Interleucina-6/sangue , Estudos Longitudinais , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Medicina de Precisão , Prognóstico , Quarentena , SARS-CoV-2 , Índice de Gravidade de Doença , Troponina I/sangue
9.
Pak J Pharm Sci ; 34(1(Special)): 429-433, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34275790

RESUMO

SARS-Covid-19 infection got spread in many countries and WHO declared it as a serious global Pandemic. Pro-inflammatory cytokines storm generated by Covid-19 infection hyper-activates inflammatory response in host body, resulting in elevated release of inflammatory biomarkers. Present article describes the characteristic profile of these inflammatory and related biomarkers in a total of 48 critically ill Covid-19 patients, (Male = 38, F = 10), with mildly ill to severe, critically ill status and thus grouped accordingly. Inflammatory Biomarkers, Ferritin, ProCalcitonin, C-Reactive Protein, coagulation marker-D-Dimer, chemical analytes, Protein, Albumin, BUN, Bilirubin, Creatinine, and enzymes, Lactate Dehydrogenase, γ-Glutamyl transpeptidases, Alkaline phosphatase were routine analyzed by standard methods described earlier. D-dimer, Ferritin, CRP and Procalcitonin exhibited variable alterations (P<0.05 to P<0.001), more markedly in critically ill patients than in the mild and severe. Biochemical analytes and enzymatic parameters showed elevated levels (P<0.05 to P<0.01) mostly in critically ill category of patients when compared with mild or severe, except total protein and albumin, which remained non-significant. It is concluded that cytokine, chemokines and pro-inflammatory markers, which released in abnormally high concentrations in Covid-19 patients of variable syndrome intensity, are significant indicators of disease severity, progression and success of treatments. As the pharmacological options may vary with the different stages of the disease therefore identifying the correct stage of the disease may be very useful in selecting the best option.


Assuntos
COVID-19/sangue , Citocinas/sangue , Mediadores da Inflamação/sangue , Biomarcadores/sangue , COVID-19/virologia , Estado Terminal , Feminino , Humanos , Masculino , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
10.
J Cardiothorac Surg ; 16(1): 198, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284809

RESUMO

BACKGROUND: Poor glycemic control has been associated with an increased risk of wound complications after various types of operations. However, it remains unclear how hemoglobin A1c (HbA1c) and preoperative glycemia can be used in clinical decision-making to prevent sternal wound complications (SWC) following off-pump coronary artery bypass grafting (OPCAB). METHODS: We conducted a retrospective study of 1774 consecutive patients who underwent OPCAB surgery between January 2010 and November 2016. A new four-grade classification for SWC was used. The associations of HbA1c and preoperative glycemia with incidence and grade of SWC were analysed using logistic regression analysis and proportional odds models, respectively. RESULTS: During a median follow-up of 326 days (interquartile range (IQR) 21-1261 days), SWC occurred in 133/1316 (10%) of non-diabetes and 82/458 (18%) of diabetes patients (p < 0.001). Higher HbA1c was significantly associated with a higher incidence of SWC (odds ratio, OR 1.24 per 1% increase, 95% confidence interval, CI 1.04;1.48, p = 0.016) as well as a higher grade of SWC (OR 1.25, 95% CI 1.06;1.48, p = 0.010). There was no association between glycemia and incidence (p = 0.539) nor grade (p = 0.607) of SWC. Significant modifiers of these effects were found: HbA1c was associated with SWC in diabetes patients younger than 70 years (OR 1.41, 95% CI 1.17;1.71, p < 0.001), whereas it was not in those older than 70 years. Glycemia was associated with SWC in patients who underwent non-urgent surgery (OR 2.48, 95% CI 1.26;4.88, p = 0.009), in diabetes patients who received skeletonised grafts (OR 4.83, 95% CI 1.28;18.17, p = 0.020), and in diabetes patients with a BMI < 30 (OR 2.19, 95% CI 1.01;4.76, p = 0.047), whereas it was not in the counterparts of these groups. CONCLUSIONS: Under certain conditions, HbA1c and glycemia are associated SWC following OPCAB. These findings are helpful in planning the procedure with minimal risk of SWC.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Tomada de Decisões , Diabetes Mellitus/epidemiologia , Hemoglobina A Glicada/metabolismo , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Comorbidade , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Diabetes Mellitus/sangue , Feminino , Humanos , Incidência , Masculino , Razão de Chances , Período Pré-Operatório , Estudos Retrospectivos , Resultado do Tratamento
11.
BMC Neurol ; 21(1): 274, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34243715

RESUMO

BACKGROUND: Ischemic stroke, including transient ischemic attack (TIA) and acute-phase cerebral infarction (aCI), is a serious health problem in the aging society. Thus, this study aimed to identify TIA and aCI biomarkers. METHODS: In 19 patients with TIA, candidate antigens recognized by serum IgG autoantibodies were screened using a human aortic endothelial cell cDNA library. Through amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA), serum antibody levels against the candidate antigens were examined in healthy donor (HD), TIA, and aCI cohorts (n = 285, 92, and 529). The plasma antibody levels in the Japan Public Health Center-based Prospective Cohort Study (1991-1993) were also examined. RESULTS: The candidate antigens were aldolase A (ALDOA) and fumarate hydratase (FH). In AlphaLISA, patients with TIA or aCI had higher anti-ALDOA antibody (ALDOA-Ab) and anti-FH antibody (FH-Ab) levels than the HDs (P < 0.05). In a multivariate logistic regression analysis, the ALDOA-Ab (odds ratio [OR]: 2.46, P = 0.0050) and FH-Ab (OR: 2.49, P = 0.0037) levels were independent predictors of TIA. According to the case-control study, the ALDOA-Ab (OR: 2.50, P < 0.01) and FH-Ab (OR: 2.60, P < 0.01) levels were associated with aCI risk. In a correlation analysis, both ALDOA-Abs and FH-Abs were well associated with hypertension, coronary heart disease, and habitual smoking. These antibody levels also correlated well with maximum intima-media thickness, which reflects atherosclerotic stenosis. CONCLUSIONS: ALDOA-Abs and FH-Abs can be novel potential biomarkers for predicting atherosclerotic TIA and aCI.


Assuntos
Autoanticorpos/sangue , Infarto Cerebral , Ataque Isquêmico Transitório , Biomarcadores/sangue , Estudos de Casos e Controles , Infarto Cerebral/sangue , Infarto Cerebral/epidemiologia , Frutose-Bifosfato Aldolase/imunologia , Humanos , Ataque Isquêmico Transitório/sangue , Ataque Isquêmico Transitório/epidemiologia
12.
Sci Rep ; 11(1): 14250, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244563

RESUMO

Triaging and prioritising patients for RT-PCR test had been essential in the management of COVID-19 in resource-scarce countries. In this study, we applied machine learning (ML) to the task of detection of SARS-CoV-2 infection using basic laboratory markers. We performed the statistical analysis and trained an ML model on a retrospective cohort of 5148 patients from 24 hospitals in Hong Kong to classify COVID-19 and other aetiology of pneumonia. We validated the model on three temporal validation sets from different waves of infection in Hong Kong. For predicting SARS-CoV-2 infection, the ML model achieved high AUCs and specificity but low sensitivity in all three validation sets (AUC: 89.9-95.8%; Sensitivity: 55.5-77.8%; Specificity: 91.5-98.3%). When used in adjunction with radiologist interpretations of chest radiographs, the sensitivity was over 90% while keeping moderate specificity. Our study showed that machine learning model based on readily available laboratory markers could achieve high accuracy in predicting SARS-CoV-2 infection.


Assuntos
Teste para COVID-19 , COVID-19 , Aprendizado de Máquina , Modelos Biológicos , SARS-CoV-2/metabolismo , Adolescente , Adulto , Biomarcadores/sangue , COVID-19/sangue , COVID-19/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Tórax/diagnóstico por imagem
13.
Sci Rep ; 11(1): 14232, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244584

RESUMO

COVID-19 pandemic exerts a health care emergency around the world. The illness severity is heterogeneous. It is mostly unknown why some individuals who are positive for SARS-CoV-2 antibodies stay asymptomatic while others show moderate to severe disease symptoms. Reliable biomarkers for early detection of the disease are urgently needed to attenuate the virus's spread and help make early treatment decisions. Bioactive sphingolipids play a crucial role in the regulation of viral infections and pro-inflammatory responses involved in the severity of COVID-19. However, any roles of sphingolipids in COVID-19 development or detection remain unknown. In this study, lipidomics measurement of serum sphingolipids demonstrated that reduced sphingosine levels are highly associated with the development of symptomatic COVID-19 in the majority (99.24%) SARS-CoV-2-infected patients compared to asymptomatic counterparts. The majority of asymptomatic individuals (73%) exhibited increased acid ceramidase (AC) in their serum, measured by Western blotting, consistent with elevated sphingosine levels compared to SARS-CoV-2 antibody negative controls. AC protein was also reduced in almost all of the symptomatic patients' serum, linked to reduced sphingosine levels, measured in longitudinal acute or convalescent COVID-19 samples. Thus, reduced sphingosine levels provide a sensitive and selective serologic biomarker for the early identification of asymptomatic versus symptomatic COVID-19 patients.


Assuntos
Ceramidase Ácida/sangue , COVID-19 , Portador Sadio , Metabolismo dos Lipídeos , SARS-CoV-2/metabolismo , Esfingolipídeos/sangue , Esfingosina/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , COVID-19/sangue , COVID-19/diagnóstico , Portador Sadio/sangue , Portador Sadio/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
ACS Appl Mater Interfaces ; 13(27): 31379-31392, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34197081

RESUMO

Osteoarthritis (OA) is treated with the intra-articular injection of steroids such as dexamethasone (DEX) to provide short-term pain management. However, DEX treatment suffers from rapid joint clearance. Here, 20 × 10 µm, shape-defined poly(d,l-lactide-co-glycolide)acid microPlates (µPLs) are created and intra-articularly deposited for the sustained release of DEX. Under confined conditions, DEX release is projected to persist for several months, with only ∼20% released in the first month. In a highly rigorous murine knee overload injury model (post-traumatic osteoarthritis), a single intra-articular injection of Cy5-µPLs is detected in the cartilage surface, infrapatellar fat pad/synovium, joint capsule, and posterior joint space up to 30 days. One intra-articular injection of DEX-µPL (1 mg kg-1) decreased the expression of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, and matrix metalloproteinase (MMP)-13 by approximately half compared to free DEX at 4 weeks post-treatment. DEX-µPL also reduced load-induced histological changes in the articular cartilage and synovial tissues relative to saline or free DEX. In sum, the µPLs provide sustained drug release along with the capability to precisely control particle geometry and mechanical properties, yielding long-lasting benefits in overload-induced OA. This work motivates further study and development of particles that provide combined pharmacological and mechanical benefits.


Assuntos
Cartilagem Articular/metabolismo , Dexametasona/química , Dexametasona/metabolismo , Portadores de Fármacos/química , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Animais , Biomarcadores/metabolismo , Preparações de Ação Retardada , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Injeções Intra-Articulares , Camundongos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Estresse Mecânico
15.
Int J Mol Sci ; 22(13)2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34198988

RESUMO

Secreted frizzled-related protein 5 (SFRP5), an antagonist of the noncanonical WNT pathway, has a controversial role in liver disease. The aim of this study was to analyze the role of SFRP5 and the noncanonical WNT pathway in nonalcoholic fatty liver disease (NAFLD). Plasma SFRP5 levels were determined by ELISA in women with normal weight (NW; n = 20) and morbid obesity (MO; n = 69). Women with MO were subclassified according to hepatic histology into normal liver (NL; n = 28), NAFLD (n = 41) (simple steatosis (SS; n = 24), and nonalcoholic steatohepatitis (NASH; n = 17)). We used RT-qPCR to evaluate the hepatic mRNA expression of SFRP5, WNT5A, and JNK in women with MO. SFRP5 levels were lower in NW than in MO patients who underwent a very low-calorie diet before surgery. Hepatic SFRP5 mRNA expression was higher in SS than in NL or NASH; additionally, patients with hepatic inflammation or ballooning presented lower SFRP5 abundance. WNT5A and JNK expression was enhanced in NAFLD compared with NL. In conclusion, circulating SFRP5 levels depend on the diet, and hepatic SFRP5 seems to have a protective role in the first steps of NAFLD; however, SFRP5 could be deregulated in an advanced stage while WNT5A and JNK are activated, promoting liver damage.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade Mórbida/complicações , Obesidade Mórbida/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/sangue , Adipocinas/metabolismo , Biomarcadores , Índice de Massa Corporal , Suscetibilidade a Doenças , Humanos , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , MAP Quinase Quinase 4/metabolismo , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , RNA Mensageiro/genética , Proteína Wnt-5a/metabolismo
16.
Int J Mol Sci ; 22(13)2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34199004

RESUMO

Guanosine (Guo) is a nucleotide metabolite that acts as a potent neuromodulator with neurotrophic and regenerative properties in neurological disorders. Under brain ischemia or trauma, Guo is released to the extracellular milieu and its concentration substantially raises. In vitro studies on brain tissue slices or cell lines subjected to ischemic conditions demonstrated that Guo counteracts destructive events that occur during ischemic conditions, e.g., glutaminergic excitotoxicity, reactive oxygen and nitrogen species production. Moreover, Guo mitigates neuroinflammation and regulates post-translational processing. Guo asserts its neuroprotective effects via interplay with adenosine receptors, potassium channels, and excitatory amino acid transporters. Subsequently, guanosine activates several prosurvival molecular pathways including PI3K/Akt (PI3K) and MEK/ERK. Due to systemic degradation, the half-life of exogenous Guo is relatively low, thus creating difficulty regarding adequate exogenous Guo distribution. Nevertheless, in vivo studies performed on ischemic stroke rodent models provide promising results presenting a sustained decrease in infarct volume, improved neurological outcome, decrease in proinflammatory events, and stimulation of neuroregeneration through the release of neurotrophic factors. In this comprehensive review, we discuss molecular signaling related to Guo protection against brain ischemia. We present recent advances, limitations, and prospects in exogenous guanosine therapy in the context of ischemic stroke.


Assuntos
Guanosina/farmacologia , AVC Isquêmico/metabolismo , Fármacos Neuroprotetores/farmacologia , Animais , Biomarcadores , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/etiologia , AVC Isquêmico/patologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteína Quinase C/metabolismo , Transdução de Sinais
17.
Int J Mol Sci ; 22(13)2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34199016

RESUMO

Paeonia suffruticosa is a magnificent and long-lived woody plant that has traditionally been used to treat various diseases including inflammatory, neurological, cancer, and cardiovascular diseases. In the present study, we demonstrated the biological mechanisms of paeonoside (PASI) isolated from the dried roots of P. suffruticosa in pre-osteoblasts. Herein, we found that PASI has no cytotoxic effects on pre-osteoblasts. Migration assay showed that PASI promoted wound healing and transmigration in osteoblast differentiation. PASI increased early osteoblast differentiation and mineralized nodule formation. In addition, PASI enhanced the expression of Wnt3a and bone morphogenetic protein 2 (BMP2) and activated their downstream molecules, Smad1/5/8 and ß-catenin, leading to increases in runt-related transcription factor 2 (RUNX2) expression during osteoblast differentiation. Furthermore, PASI-mediated osteoblast differentiation was attenuated by inhibiting the BMP2 and Wnt3a pathways, which was accompanied by reduction in the expression of RUNX2 in the nucleus. Taken together, our findings provide evidence that PASI enhances osteoblast differentiation and mineralized nodules by regulating RUNX2 expression through the BMP2 and Wnt3a pathways, suggesting a potential role for PASI targeting osteoblasts to treat bone diseases including osteoporosis and periodontitis.


Assuntos
Calcificação Fisiológica/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Glicosídeos/farmacologia , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Extratos Vegetais/farmacologia , Biomarcadores , Proteína Morfogenética Óssea 2/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Glicosídeos/química , Humanos , Imuno-Histoquímica , Espectroscopia de Ressonância Magnética/efeitos adversos , Osteogênese/efeitos dos fármacos , Extratos Vegetais/química , Via de Sinalização Wnt
18.
Int J Mol Sci ; 22(13)2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34199035

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a major public health problem worldwide. NAFLD (both simple steatosis and steatohepatitis) is characterized by alterations in hepatic lipid metabolism, which may lead to the development of severe liver complications including cirrhosis and hepatocellular carcinoma. Thus, an exhaustive examination of lipid disorders in the liver of NAFLD patients is much needed. Mass spectrometry-based lipidomics platforms allow for in-depth analysis of lipid alterations in a number of human diseases, including NAFLD. This review summarizes the current research on lipid alterations associated with NAFLD and related complications, with special emphasis on the changes in long-chain and short-chain fatty acids levels in both serum and liver tissue, as well as in the hepatic expression of genes encoding the enzymes catalyzing lipid interconversions.


Assuntos
Suscetibilidade a Doenças , Ácidos Graxos/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Biomarcadores , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/metabolismo , Progressão da Doença , Ácidos Graxos/sangue , Ácidos Graxos/química , Microbioma Gastrointestinal , Regulação da Expressão Gênica , Humanos , Metabolismo dos Lipídeos , Lipidômica/métodos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/metabolismo , Estrutura Molecular , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/etiologia
19.
Int J Mol Sci ; 22(13)2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34199046

RESUMO

Hyperglycemia may contribute to the progression of carcinomas by triggering epithelial-to-mesenchymal transition (EMT). Some proteostasis systems are involved in metastasis; in this paper, we sought to explore the mechanism of Hsp70 chaperone in EMT. We showed that knockdown of Hsp70 reduced cell migration capacity concomitantly with levels of mRNA of the Slug, Snail, and Twist markers of EMT, in colon cancer cells incubated in high glucose medium. Conversely, treatment of cells with Hsp70 inducer U-133 were found to elevate cell motility, along with the other EMT markers. To prove that inhibiting Hsp70 may reduce EMT efficiency, we treated cells with a CL-43 inhibitor of the HSF1 transcription factor, which lowered Hsp70 and HSF1 content in the control and induced EMT in carcinoma cells. Importantly, CL-43 reduced migration capacity, EMT-linked transcription factors, and increased content of epithelial marker E-cadherin in colon cancer cells of three lines, including one derived from a clinical sample. To prove that Hsp70 chaperone should be targeted when inhibiting the EMT pathway, we treated cancer cells with 2-phenylethynesulfonamide (PES) and demonstrated that the compound inhibited substrate-binding capacity of Hsp70. Furthermore, PES suppressed EMT features, cell motility, and expression of specific transcription factors. In conclusion, the Hsp70 chaperone machine efficiently protects mechanisms of the EMT, and the safe inhibitors of the chaperone are needed to hamper metastasis at its initial stage.


Assuntos
Glicemia , Transição Epitelial-Mesenquimal , Glucose/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Biomarcadores , Caderinas/metabolismo , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glucose/farmacologia , Humanos , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Ligação Proteica , Fatores de Transcrição da Família Snail/metabolismo
20.
Int J Mol Sci ; 22(13)2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34199069

RESUMO

Acute kidney injury (AKI) is a common yet complicated clinical entity with high morbidity and mortality. An essential strategy to improve AKI patients' prognoses is finding optimal biomarkers to identify AKI in a timely manner. Procalcitonin (PCT), a well-recognized biomarker for diagnosing infection and guiding antibiotics therapy, has been proposed to predict AKI development and recovery in many clinical settings. The current review provides comprehensive and updated information from relevant studies to evaluate PCT's AKI-predictive ability and the influence of infection on this predictive ability. PCT has demonstrated optimal predictive ability for AKI in various populations irrespective of infection. However, the predictive ability seems to be blunted by infection since infection and inflammation have a more potent influence than AKI on PCT elevation. We furthermore explain the complicated association between elevated PCT levels and AKI in infection and inflammation situations and recommend directions for further investigations to clarify the essential issue. In conclusion, although conflicting data exist, serum PCT level is a potential biomarker for predicting AKI in many clinical settings regardless of infection. Nevertheless, further studies are warranted to clarify the association between PCT, infection, and AKI and to confirm the utilization of PCT for AKI prediction.


Assuntos
Injúria Renal Aguda/sangue , Injúria Renal Aguda/diagnóstico , Biomarcadores , Pró-Calcitonina/sangue , Injúria Renal Aguda/etiologia , Suscetibilidade a Doenças , Humanos , Testes de Função Renal , Prognóstico , Sepse/sangue
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