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A 24-year-old man was found to have an ileocecal ulcer by colonoscopy. A pathological diagnosis of diffuse large B-cell lymphoma (DLBCL) with diffuse positive reaction of Epstein-Barr encoding region (EBER) by in situ hybridization was made based on analysis of the specimen. Acquired immunodeficiency syndrome (AIDS) complicated by pneumocystis jirovecii pneumonia was also diagnosed. As no other significant lymphomatous lesions were identified by further examination, a clinical diagnosis of EBV-positive mucocutaneous ulcer (EBVMCU) was made. Rather than performing systemic chemotherapy, the lesion was closely monitored and antiretroviral therapy (ART) for AIDS was started with the hope of treating the lesion through immune reconstitution. The lesion had completely disappeared by day 79 after starting ART, and has not recurred for over 3 years. EBVMCU is known to develop secondary to various immunosuppressive states including AIDS. Here we report a rare case of EBVMCU detected at diagnosis of AIDS that entered complete remission after immune reconstitution by ART.
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Síndrome da Imunodeficiência Adquirida , Infecções por Vírus Epstein-Barr , Infecções por HIV , Linfoma Difuso de Grandes Células B , Masculino , Humanos , Adulto Jovem , Adulto , Úlcera/etiologia , Herpesvirus Humano 4 , Remissão Espontânea , Síndrome da Imunodeficiência Adquirida/complicações , Recidiva Local de Neoplasia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológicoRESUMO
The pathological hallmark of psoriasis is the infiltration of neutrophils into the skin. Some neutrophil-derived microRNAs (miRNAs) serve as biomarkers for various diseases, but none have been reported for psoriasis. In this study, we investigated the involvement of miRNAs released from neutrophils in psoriasis pathogenesis. We compared the expression of miRNAs in the sera of patients with psoriasis with that in healthy individuals and found that the expression of 2 miRNAs-miR-223 and miR-1290-was significantly upregulated in the sera of patients with psoriasis. The serum levels of these miRNAs positively correlated with the PASI and CRP levels. We used all-trans retinoic acid to induce the differentiation of human promyelocytic leukemia HL-60 cells into neutrophil-like cells and found that the release of both miRNAs increased during differentiation. Furthermore, the release of miR-1290 was increased by TNF-α in neutrophil-like cells and human neutrophils. Treatment with the miR-1290 precursor promoted the proliferation of human keratinocytes, increased the proportion of S-phase cells, and upregulated the phosphorylation of extracellular signal-regulated kinase 1/2. These results suggest that miR-1290 plays a vital role in regulating neutrophil differentiation and keratinocyte proliferation and could be a serum marker of psoriasis severity.
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Diferenciação Celular , Proliferação de Células , Queratinócitos , MicroRNAs , Neutrófilos , Psoríase , Humanos , Psoríase/patologia , Psoríase/genética , Psoríase/sangue , Psoríase/metabolismo , MicroRNAs/metabolismo , MicroRNAs/genética , Queratinócitos/metabolismo , Neutrófilos/metabolismo , Masculino , Feminino , Células HL-60 , Pessoa de Meia-Idade , Adulto , Biomarcadores/metabolismo , Biomarcadores/sangue , Regulação para Cima , Estudos de Casos e Controles , Fator de Necrose Tumoral alfa/metabolismoRESUMO
This study aimed to clarify the relationship between the sequential organ failure assessment (SOFA) score and the length of intensive care unit (ICU) and hospital stays and verify whether the SOFA score can indicate the optimal length of ICU stay. Medical resource input was evaluated as the medical treatment score, converted by volume, within 2 days after ICU admission. After classifying emergency patients into surgical and nonsurgical categories, the relationship between medical resources, SOFA score, and ICU and hospital stay lengths was analyzed. Medical resource input was high when the SOFA score was high after ICU admission. A positive correlation was confirmed between the SOFA score and length of ICU stay in surgical and nonsurgical patients. Nonsurgical patients are more likely to be discharged within the diagnosis procedure combination hospital stages I and II if medical resources are high in the initial stages of ICU admission. The SOFA score affects medical resource input and the length of ICU stay. The early input of medical resources after ICU admission reduces the length of hospital stay in the diagnosis procedure combination, suggesting that the SOFA score is a valuable indicator of the optimal length of ICU stay.
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Hospitalização , Escores de Disfunção Orgânica , Humanos , Tempo de Internação , Hospitais , Unidades de Terapia IntensivaRESUMO
Vascular endothelial growth factor A (VEGF-A) plays pivotal roles in regulating tumor angiogenesis as well as physiological vascular function. The major VEGF-A isoforms, VEGF-A121 and VEGF-A165, in serum, plasma, and platelets have not been exactly evaluated due to the lack of the appropriate assay system. Antibodies against human VEGF-A121 and VEGF-A165 (hVEGF-A121 and hVEGF-A165) were successfully produced and Enzyme-Linked ImmunoSorbent Assay (ELISA) for hVEGF-A121 and hVEGF-A165 were separately created by these monoclonal antibodies. The measurement of recombinant hVEGF-A121 and hVEGF-A165 by the created ELISA showed no cross-reaction between hVEGF-A121 and hVEGF-A165 in conditioned media from HEK293 cells transfected with either hVEGF-A121 or hVEGF-A165 expression vector. The levels of VEGF-A121 and VEGF-A165 in serum, plasma, and platelets from 59 healthy volunteers proved that VEGF-A121 level was higher than VEGF-A165 in both plasma and serum in all the cases. VEGF-A121 or VEGF-A165 in serum represented higher level than that in plasma. In contrast, the level of VEGF-A165 was higher than VEGF-A121 in platelets. The newly developed ELISAs for hVEGF-A121 and hVEGF-A165 revealed different ratios of VEGF isoforms in serum, plasma, and platelets. Measuring these isoforms in combination provides useful information as biomarkers for diseases involving VEGF-A121 and VEGF-A165.
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Fator A de Crescimento do Endotélio Vascular , Humanos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Células HEK293 , Ensaio de Imunoadsorção Enzimática , Isoformas de ProteínasRESUMO
Objective: Autoimmune autonomic ganglionopathy (AAG) is a rare disorder characterized by autonomic failure associated with the presence of anti-ganglionic acetylcholine receptor (gAChR) antibodies; however, several studies have reported that individuals with anti-gAChR antibodies present with central nervous system (CNS) symptoms such as impaired consciousness and seizures. In the present study, we investigated whether the presence of serum anti-gAChR antibodies correlated with autonomic symptoms in patients with functional neurological symptom disorder/conversion disorder (FNSD/CD). Methods: Clinical data were collected for 59 patients presenting with neurologically unexplained motor and sensory symptoms at the Department of Neurology and Geriatrics between January 2013 and October 2017 and who were ultimately diagnosed with FNSD/CD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. Correlations between serum anti-gAChR antibodies and clinical symptoms and laboratory data were analyzed. Data analysis was conducted in 2021. Results: Of the 59 patients with FNSD/CD, 52 (88.1%) exhibited autonomic disturbances and 16 (27.1%) were positive for serum anti-gAChR antibodies. Cardiovascular autonomic dysfunction, including orthostatic hypotension, was significantly more prevalent (75.0 vs. 34.9%, P = 0.008), whereas involuntary movements were significantly less prevalent (31.3 vs. 69.8%, P = 0.007), among anti-gAChR antibody-positive compared with -negative patients. Anti-gAChR antibody serostatus did not correlate significantly with the frequency of other autonomic, sensory, or motor symptoms analyzed. Conclusions: An autoimmune mechanism mediated by anti-gAChR antibodies may be involved in disease etiology in a subgroup of FNSD/CD patients.
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BACKGROUND: Rupture of an atherosclerotic plaque and subsequent exposure of the subendothelial prothrombotic matrix to blood cause arterial thrombosis. Circulating platelets play an indispensable role in the growth of arterial thrombi partially owing to their unique ability to adhere to the subendothelial matrix and to aggregate to each other under flow conditions. Recently, the Total Thrombus-formation Analysis System (T-TAS) was developed for ex vivo analysis of the thrombogenic potential of whole blood samples under flow conditions. Despite the potential clinical utility of the T-TAS in assessing the risk for thrombosis and bleeding, reference intervals for T-TAS analysis in healthy individuals have not been determined. METHODS: In total, 122 whole blood samples were collected from healthy volunteers ranging in age from 25 to 45 years. T-TAS analysis and hematological, physiological, and lifestyle assessments were conducted in these subjects. Whole blood samples anticoagulated with hirudin were perfused into a collagen-coated microchip (PL chip). The time to 10 kPa and the area under the flow pressure curve up to 10 min (AUC10) were analyzed as representative variables for thrombogenic potential. Reference intervals, which were defined as 2.5-97.5 percentiles, were determined. Additionally, univariate and multivariate analyses were performed to identify factors associated with the AUC10 in the T-TAS. RESULTS: The time to 10 kPa and the AUC10 widely varied, even in healthy volunteers. The reference intervals were 1.50-4.02 min and 223.4-456.8, respectively, at a shear rate of 1500 s- 1. Univariate and multivariate analyses showed that platelet counts were most significantly associated with the AUC10 of the T-TAS. The presence of one or more cardiovascular risk factors of a high body mass index, a high pulse pressure, high fasting serum glucose levels, high low-density lipoprotein-cholesterol levels, a history of smoking, and no habitual exercise, had the second largest effect on the AUC10 of the T-TAS. CONCLUSIONS: Healthy volunteers who had any cardiovascular risk factors showed augmented thrombogenicity, even in artificial uniform capillaries, compared with those without any risk factors in the T-TAS.
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BACKGROUND AND AIMS: The early and reliable detection of chronic kidney disease is important. In the present study, we aimed to compare the diagnostic results for proteinuria and hematuria between the dipstick test used in primary occupational health examinations and the quantitative tests used in more thorough examinations in clinics. METHODS: We conducted a single-center observational study of male staff (N = 573) at Kagoshima University who underwent a health examination in 2017. Both dipsticks and biochemical methods were used to assess proteinuria and hematuria. RESULTS: For the dipstick test, the sensitivity, specificity, and positive predictive value were 55.6%, 92.4% and 10.4% for proteinuria, and 64.3%, 98.3% and 66.7% for hematuria, respectively. Four participants for whom false-negative results were obtained using dipsticks for proteinuria, and two of these had 3+ urinary glucose. CONCLUSION: Qualitative tests for proteinuria and hematuria had low sensitivities and positive predictive values. Therefore, for the early and reliable detection of chronic kidney disease, the use of quantitative urine tests should be considered during occupational health examinations.
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Platelet functions are thought to contribute to clinical outcomes after heart surgery. This study was conducted to assess the pivotal roles of vascular endothelial growth factor-A (VEGF-A) and microRNA-126 (miR-126) during coronary artery bypass grafting (CABG). Whole blood was collected for platelet isolation from 67 patients who underwent CABG surgery between July 2013 and March 2014. VEGF-A and miR-126 levels in serum, plasma, and platelets were measured at various time points and compared with clinical characteristics. The platelet count was decreased at 3 days after CABG. This dynamic change in platelet count was larger after conventional coronary artery bypass (CCAB) than off-pump coronary artery bypass (OPCAB). VEGF-A in the same number of platelets (IP-VEGF-A) was increased at 3 days after CABG, followed by an increase of VEGF-A in serum (S-VEGF-A) at 7 days after surgery. The miR-126-3p level in serum (S-miR-126-3p) increased rapidly after CABG and then decreased below preoperative levels. The IP-VEGF-A level on day 7 after CABG in patients with peripheral artery disease (PAD), who suffered from endothelial dysfunction, was higher compared with patients without PAD. Conversely, S-miR-126-3p on day 7 after surgery was lower in patients with PAD than in patients without PAD. Low levels of S-miR-126-3p due to endothelial dysfunction may lead to high IP-VEGF-A, which is closely related to complications after CABG.
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Ponte de Artéria Coronária sem Circulação Extracorpórea , Ponte de Artéria Coronária/métodos , MicroRNAs/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Plaquetas/química , Plaquetas/fisiologia , Humanos , MicroRNAs/química , MicroRNAs/genética , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/análiseRESUMO
PURPOSE: Recently, the estimated total atrial conduction time measured using tissue Doppler imaging (PA-TDI duration) has been reported as a more accurate predictor of atrial fibrillation (AF) recurrence after catheter ablation than left atrial volume index (LAVI). The PA-TDI duration is considered to reflect electrical and structural remodeling in the right atrium (RA) and left atrium (LA). We sought to investigate the association between AF recurrence and PA-TDI duration after AF ablation. METHODS: We studied 209 patients who underwent radiofrequency ablation for paroxysmal AF and 75 patients who underwent second ablation for AF recurrence. We assessed the duration from the onset of the P wave on the surface electrocardiogram to the atrial electrogram in distal coronary sinus (CS) (PA-CSd duration) indicating electrical remodeling of the atrium, the PA-CS proximal duration (PA-CSp duration) representing electrical remodeling of RA, and the conduction time in CS (proximal to distal) (CSp-CSd duration) reflecting electrical remodeling of LA. We also measured LAVI as a marker of structural remodeling of LA. RESULTS: The PA-TDI duration had a positive correlation with PA-CSd duration. In the patients with AF recurrence, PA-TDI duration, PA-CSd duration, and CSp-CSd duration in the second ablation were significantly longer than those in the first (p < 0.01, respectively), whereas there was no significant difference in LAVI and PA-CSp duration between the first and second ablation sessions. CONCLUSION: A prolonged PA-TDI duration after AF ablation may indicate advanced electrical remodeling of LA, and may predict AF recurrence after ablation in patients with paroxysmal AF.
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Fibrilação Atrial , Remodelamento Atrial , Ablação por Cateter , Apêndice Atrial , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/cirurgia , Humanos , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: Turbulent blood flow in patients with aortic valve stenosis (AS) results in morphological and functional changes in platelets and coagulation factors. The aim of this study is to determine how shear stress affects platelets and coagulation factors. METHODS: We retrospectively evaluated data from 78 patients who underwent AVR to treat AS between March 2008 and July 2017 at Kagoshima University Hospital. RESULTS: Platelet (PLT) count obviously decreased at three days after AVR, and increased above preoperative levels at the time of discharge. In contrast, platelet distribution width (PDW), mean platelet volume (MPV), and platelet large cell ratio (P-LCR) increased three days after AVR, then decreased to below preoperative levels. No differences were evident between groups with higher (HPPGâ>â100âmmHg) and lower (LPPGâ<â100âmmHg) peak pressure gradients (PPG) before AVR, whereas PLT count, PDW, MPV and P-LCR improved more in the HPPG group. Plateletcrit (PCT), which represents the total volume of platelets, increased after AVR due to decreased shear stress. High increasing rate of PCT was associated with lower PLT count, higher PDW and lower fibrinogen. CONCLUSION: Shear stress affects PLT count, PDW, and fibrinogen in patients with AS.
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Estenose da Valva Aórtica/sangue , Plaquetas/imunologia , Contagem de Plaquetas/métodos , Idoso , Animais , Feminino , Humanos , Masculino , Camundongos , Estudos RetrospectivosRESUMO
We report an AIDS patient with a high HIV RNA copy number in the plasma who was successfully treated for prolonged Mycobacterium avium bacteremia and other complications. An HIV-infected patient with high fever, anemia, high alkaline phosphatase, cystic lung lesions, hepatitis B virus infection and Kaposi's sarcoma was referred to our hospital. PCR of the blood revealed Mycobacterium avium bacteremia and the time to blood culture positivity was 8 days. The HIV-1 RNA copy number in the plasma was more than ten million copies/ml and the CD4-positive T cell count was 21 cells/µL. Although the high fever resolved five days after therapy for Mycobacterium avium was started, the fever recurred just before starting anti-retroviral therapy (ART) including dolutegravir. The patient experienced repeated but self-limiting bouts of severe inflammation. Mycobacteremia was intermittently detected up to 79 days, suggesting that the recurrent episodes of inflammation were due to the intermittent dissemination of mycobacteria, and that persistent treatment is needed. Five months after the beginning of ART, the HIV-1 RNA copy number in the plasma was still 28,000 copies/ml. An HIV drug-resistance test revealed sensitivity to all anti-retroviral drugs. Eleven months after the initiation of ART, the HIV RNA copy number in the plasma decreased to 45 copies/mL and the CD4-positive T cell count recovered to 205 cells/µL. Our case also suggests that dolutegravir can be effective in cases with prolonged high levels of HIV RNA. Our findings emphasize that prompt diagnosis and persistent therapy for mycobacterial infection are important for successful treatment.
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Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Bacteriemia/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , RNA Viral/sangue , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/imunologia , Adulto , Antibacterianos/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Bacteriemia/complicações , Contagem de Linfócito CD4 , Retinite por Citomegalovirus/complicações , Retinite por Citomegalovirus/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Inflamação/complicações , Masculino , Mycobacterium avium/isolamento & purificação , Infecção por Mycobacterium avium-intracellulare/complicações , Oxazinas , Piperazinas , Piridonas , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: A striking difference has been observed in structure and functional properties between plasma and platelet von Willebrand factor (VWF). While the existing evidence has revealed a clinical relevance of plasma VWF-Ag in liver regeneration (LR) and different cancers, this study was designed to explore the properties of intra-platelet (IP) and serum VWF-Ag in patients with hepatocellular carcinoma (HCC) undergoing partial hepatectomy. METHODS: A total of 40 patients undergoing partial hepatectomy were prospectively recruited from 3 institutions. VWF-Ag concentrations were evaluated mainly in serum and platelet extracts. Patients were followed-up for postoperative liver dysfunction and HCC recurrence. RESULTS: We observed a post-resection increase in the concentration of VWF-Ag in serum and platelet. Patients with postoperative liver dysfunction had substantially reduced serum and IP VWF-Ag concentrations. After a 2-year follow-up, patients with higher post-resection serum and IP VWF-Ag concentrations were found to develop early HCC recurrence. Likewise, IP VWF-Ag was able to independently predict post-resection early HCC recurrence. CONCLUSION: This multicenter, prospective, pilot study demonstrates a bivalent property of IP VWF in LR and oncological outcome; low preoperative VWF appeared to have a negative association on post-resection liver dysfunction, whereas, patients with higher post-resection VWF-Ag concentrations were found to have early HCC recurrence.
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Plaquetas/metabolismo , Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/sangue , Regeneração Hepática/fisiologia , Fator de von Willebrand/metabolismo , Idoso , Antígenos/sangue , Antígenos/imunologia , Plaquetas/patologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Estudos de Coortes , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Estudos Prospectivos , Fator de von Willebrand/imunologiaRESUMO
Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world and has a high risk of thromboembolism. The most effective approach, catheter ablation, requires evaluation by electrocardiography. The aim of our study was to investigate novel clinical markers that predict restoration of sinus rhythm (SR) after catheter ablation. Seventy-eight consecutive patients with AF underwent catheter ablation and were separated into 2 groups: restored SR and recurrent AF. The levels of 4 blood proteins (serum or plasma) and 3 mature microRNAs (miRNAs) and their primary miRNAs (pri-miRNAs) in serum were measured before and after ablation, and the associations between each parameter were analyzed statistically. Soluble thrombomodulin (s-TM) and plasminogen activator inhibitor-1 (PAI-1) levels increased above baseline after ablation in both the restored SR (s-TM 11.55 [2.92] vs 13.75 [3.38], P < .001; PAI-1 25.74 [15.25] vs 37.79 [19.56], P < .001) and recurrent AF (s-TM 10.28 [2.78] vs 11.67 [3.37], P < .001; PAI-1 26.16 [15.70] vs 40.74 [22.55], P < .001) groups. Levels of C-reactive protein and asymmetric dimethylarginine were not significantly changed. Pri-miR-126 levels significantly decreased after ablation in the recurrent AF group, but the other miRNAs and pri-miRNAs did not. The measurement of s-TM and pri-miR-126 in blood was a useful tool to reflect the condition of AF patients with catheter ablation.
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Fibrilação Atrial/sangue , Fibrilação Atrial/terapia , Proteínas Sanguíneas/análise , Ablação por Cateter , MicroRNA Circulante/sangue , Endotélio Vascular/fisiologia , Idoso , Fibrilação Atrial/diagnóstico , Biomarcadores/sangue , Feminino , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/sangue , Taquicardia Sinusal/diagnóstico , Trombomodulina/sangueRESUMO
PURPOSE: Platelet derived growth factor-BB (PDGF-BB) has emerged as one of the key cytokines in malignant transformation of different cells. PDGF-BB also exhibits a potent mitogenic effect on liver cells; studies have advocated clinical implications of monitoring serum PDGF-BB (sPDGF-BB) in patients with liver disease. We thus investigated the predictive relevance of perioperative sPDGF-BB after curative resection of hepatocellular carcinoma (HCC). METHODS: We evaluated perioperative sPDGF-BB in a prospective homogenous cohort of 40 patients diagnosed with HCC. During the first two-year follow-up, patients were evaluated every three months for postresection HCC recurrence. RESULTS: Patients who developed recurrence during two-year follow-up were found to have lower concentration of sPDGF-BB than those without recurrence in both pre- and postoperative settings (P < 0.05 and P < 0.001, resp.). We validated that the reduced postoperative sPDGF-BB (< 2133.29 pg/mL) was associated with an increased incidence of postresection HCC recurrence [area under curve (AUC) > 0.8, 95% confidence interval (CI) = 0.68 - 0.94, P < 0.001]; furthermore, we were able to demonstrate that postoperative sPDGF-BB was an independent predictor of HCC recurrence (hazard ratio = 5.64, 95% CI = 1.56 - 20.30, P < 0.01). CONCLUSIONS: These findings provide a new insight into an association between diminished perioperative sPDGF-BB and HCC recurrence. Patients with low perioperative sPDGF-BB progressed early HCC recurrence. Therefore, evaluating perioperative sPDGF-BB may provide useful clinical information to characterize patients with postresection HCC recurrence.
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BACKGROUND: Inhalation of aerosolized Legionella pneumophila, a Gram-negative bacterium, can cause severe pneumonia. During infection, L. pneumophila replicates intracellularly in macrophages. The involvement of host microRNAs (miRNAs) in L. pneumophila infection is not fully understood. METHODS: The human macrophage-like cell line U937 was infected with L. pneumophila. The levels of miRNA and messenger RNA (mRNA) were measured using reverse transcriptase polymerase chain reaction. Release of lactate dehydrogenase was used to evaluate cytotoxicity. The expression of RICTOR and related proteins was examined by western blotting of cell lysates. RESULTS: L. pneumophila infection upregulated the expression of miR-218 and the host genes SLIT2 and SLIT3 in U937â¯cells. The expression of RICTOR, a component of the mechanistic target of rapamycin complex 2 (mTORC2), decreased during L. pneumophila infection. RICTOR protein expression was inhibited by the overexpression of miR-218, whereas knockdown of miR-218 restored the downregulation of RICTOR by L. pneumophila. L. pneumophila infection induced the expression of the proinflammatory cytokines IL-6 and TNF-alpha, which was modulated by knockdown of miR-218 or RICTOR. CONCLUSIONS: Our study revealed the involvement of miR-218 in regulating the inflammatory response of macrophages against L. pneumophila infection. These findings suggest potential novel roles for miR-218 and RICTOR as therapeutic targets of L. pneumophila infection.
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Legionella pneumophila , Doença dos Legionários/metabolismo , Macrófagos/metabolismo , MicroRNAs/metabolismo , Proteína Companheira de mTOR Insensível à Rapamicina/metabolismo , Citocinas , Interações Hospedeiro-Patógeno , Humanos , Inflamação , Doença dos Legionários/patologia , Doença dos Legionários/virologia , Macrófagos/microbiologia , Macrófagos/patologia , MicroRNAs/análise , RNA Mensageiro/análise , Células U937RESUMO
Liver pathophysiology can, directly and indirectly, impose morphological or biochemical abnormalities of the platelets. Conversely, platelets are also able to regulate the promitogenic and profibrotic signals on liver pathobiology. Platelet contribution to the liver pathophysiology is typically facilitated by the platelet-derived growth factors that are sequestered in different subsets of alpha and dense granules, and the release of these growth factors is synchronized according to the stage and type of liver disease or injury. Thus, platelets harbor clinically relevant information with potential diagnostic and prognostic implications in liver diseases. Hepatocellular carcinoma (HCC) largely influences the platelet kinetics, and a growing body of evidence has recognized its association with HCC occurrence or prognosis. This narrative review summarizes the progress made on implicating platelet as a diagnostic and prognostic tool for HCC; the review also dissects the contradictory results from earlier studies and reflects how combining platelet-based information may enable more reliable test for diagnostic and prognostic evaluation of HCC.
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Plaquetas/metabolismo , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Humanos , Cinética , Contagem de Linfócitos , Contagem de Plaquetas , Prognóstico , Serotonina/metabolismoRESUMO
Endothelial cells (ECs) form monolayers and line the interior surfaces of blood vessels in the entire body. In most mammalian systems, the capacity of endothelial cells to divide is limited and endothelial cells are prone to be senescent. Aging of ECs and resultant endothelial dysfunction lead to a variety of vascular diseases such as atherosclerosis, diabetes mellites, hypertension, and ischemic injury. However, the mechanism by which ECs get old and become senescent and the impact of endothelial senescence on the vascular function are not fully understood. Recent research has unveiled the crucial roles of miRNAs, which are small non-coding RNAs, in regulating endothelial cellular functions, including nitric oxide production, vascular inflammation, and anti-thromboformation. In this review, how senescent-related miRNAs are involved in controlling the functions of ECs will be discussed.
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Endothelial dysfunction is observed in several cardiovascular diseases, where endothelium-dependent vasodilation is impaired by oxidative stress. However, the time course of endothelial function during the perioperative period of a minor-to-moderate surgery, and the effects of atherosclerotic risk factors and employed general anesthetics on recovery of endothelial function, are unknown. Endothelial function of 30 patients was evaluated as the reactive hyperemia index (RHI) of reactive hyperemia peripheral arterial tonometry. RHI was measured on day before surgery (control), immediately after surgery (Day 0), day after surgery (Day 1), and day 4 after surgery (Day 4) in patients with no functional limitations who were scheduled for oral and maxillofacial surgery of around 3 hours. Sevoflurane- or propofol-based anesthesia supplemented with an opioid analgesic remifentanil was employed. The control RHI was 2.26 ± 0.64. The RHI significantly decreased to the lowest level on Day 0 (1.52 ± 0.28), recovered on Day 1 (2.07 ± 0.58), and improved further on Day 4 (2.55 ± 0.83). Multiple linear regression analysis revealed that recovery of the RHI from Day 0 to Day 4 was impaired by diabetes mellitus (P = 0.0313), obesity (BMI ≥ 25; P = 0.0166), hyperuricemia (uric acid ≥ 6.0 mg/dL; P = 0.0416) and sevoflurane-based anesthesia (P = 0.0308). These findings suggest that endothelial function as evaluated by the RHI is severely suppressed on the day of a minor-to-moderate surgery, and that it improves until the 4th postoperative day on average. Recovery of endothelial function is impaired by diabetes mellitus, obesity, hyperuricemia, and sevoflurane-based anesthesia.
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Anestésicos Inalatórios/efeitos adversos , Diabetes Mellitus/fisiopatologia , Endotélio Vascular/fisiopatologia , Hiperuricemia/complicações , Éteres Metílicos/efeitos adversos , Obesidade/complicações , Adulto , Idoso , Anestesia/efeitos adversos , Anestésicos Inalatórios/administração & dosagem , Aterosclerose/fisiopatologia , Feminino , Humanos , Hiperemia/fisiopatologia , Masculino , Manometria , Éteres Metílicos/administração & dosagem , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Bucais/efeitos adversos , Estudos Prospectivos , Recuperação de Função Fisiológica/efeitos dos fármacos , Fatores de Risco , SevofluranoRESUMO
INTRODUCTION: Mounting evidence highlights platelet involvement in liver regeneration via interaction with liver cells, growth factors release, and signaling contributions. Existing research suggests a compelling biological rationale for utilizing platelet biology, with the goal of improving liver function and accelerating its regenerative potential. Despite its expanding application in several clinical areas, the contribution of the platelet and its therapeutic implementation in liver regeneration so far has not yet fulfilled the initial high expectations. Areas covered: This review scrutinizes the progress, current updates, and discusses how recent understanding - particularly in the clinical implications of platelet-based therapy - may enable strategies to introduce and harness the therapeutic potential of the platelet during liver regeneration. Expert commentary: Several clinical and translational studies have facilitated a platform for the development of platelet-based therapy to enhance liver regeneration. While some of these therapies are effective to augment liver regeneration, the others have had some detrimental outcomes. The existing evidence represents a challenge for future projects that are focused on directly incorporating platelet-based therapies to induce liver regeneration.