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1.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(1): 1-10, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38433624

RESUMO

Objective To investigate the impact of Pseudomonas aeruginosa(PA) infection on the function of pulmonary vascular endothelial cells,and explore the mechanism of this bacterium in exacerbating lung inflammation in mice. Methods Two hours after human lung microvascular endothelial cell(HULEC-5a) were infected with the PA strain PAO1,the mRNA levels of autophagy-related gene 5(ATG5),6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3),and calcium adhesion protein 5(CDH5) were determined by reverse transcription real-time fluorescent quantitative PCR(RT-qPCR).The protein levels of ATG5,PFKFB3,and vascular endothelial calcium adhesion protein(VE-cadherin) were detected by immunofluorescence.After the expression of ATG5 and PFKFB3 was respectively knocked down by small interfering RNA(siRNA),RT-qPCR was employed to measure the mRNA levels of ATG5,PFKFB3,and CDH5,and immunofluorescence to detect the protein levels of PFKFB3 and VE-cadherin.In addition,the lactate assay kit was used to determine the level of lactate in the cells.After mice were infected with PAO1,lung inflammation was assessed through histopathological section staining.Confocal microscopy was employed to capture and analyze fluorescence-labeled PFKFB3 and VE-cadherin in endothelial cells. Results Compared with the control group,the HULEC-5a cells infected with PAO1 showed up-regulated mRNA and protein levels of PFKFB3(all P<0.05),down-regulated mRNA level of CDH5(P=0.023),disrupted continuity and down-regulated protein level of VE-cadherin(P<0.001),and elevated lactate level(P=0.017).Compared with PAO1-infected HULEC-5a cells,knocking down PFKFB3 led to the up-regulated mRNA level of CDH5(P=0.043),lowered lactate level(P=0.047),and restored continuity of VE-cadherin;knocking down ATG5 led to up-regulated mRNA and protein levels of PFKFB3(P=0.013 and P=0.003),elevated lactate level(P=0.015),and down-regulated mRNA level of CDH5(P=0.020) and protein level of VE-cadherin(P=0.001).The HE staining results showed obvious red blood cell leakage,inflammatory cell infiltration,alveolar septal widening,and partial detachment of vascular endothelial cells in the alveoli of PA-infected mice.Immunofluorescence staining showed up-regulated expression of PFKFB3 and decreased fluorescence signal of VE-cadherin in endothelial cells of infected mice compared with normal mice. Conclusion PA may regulate the PFKFB3 pathway via AGT5 to disrupt the function of pulmonary vascular endothelial cells,thereby exacerbating the inflammation in the lungs of mice.


Assuntos
Pneumonia , Infecções por Pseudomonas , Humanos , Animais , Camundongos , Células Endoteliais , Pseudomonas aeruginosa , Cálcio , Fatores de Transcrição , Pulmão , Lactatos , RNA Mensageiro
2.
Eur Rev Med Pharmacol Sci ; 28(4): 1392-1397, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38436172

RESUMO

OBJECTIVE: The Pleth Variability Index (PVI) can guide the approach to hypovolemia, which is sometimes the cause and sometimes the result of major diseases; further studies are needed on this index. Therefore, in the present study, we aimed to evaluate the prognostic value of PVI and its relationship with 28-day mortality. PATIENTS AND METHODS: A total of 158 patients were included. Patients were divided into two groups according to 28-day mortality. Patients who died within 28 days were assigned to Group M (Mortal), while those who survived were included in Group S (Survive). Patients' demographics, definitive diagnosis, arterial blood pressure, fingertip oxygen saturation, PVI, fingertip blood glucose, fever, pulse, shock index, and serum lactate level were recorded. RESULTS: Regarding demographics, no statistically significant difference was found between the two groups in terms of age, gender, and Body Mass Index (BMI) (p=0.356, p=0.966, and p=0.977, respectively). The rate of intubation, the use of vasopressors, Acute Physiology and Chronic Health Evaluation (APACHE) II score, shock index, and PVI values were statistically significantly higher in Group M compared to Group S (for all, p<0.001). Glasgow Coma Score (GCS), Perfusion Index (PI), and length of stay were statistically significantly lower in Group M than in Group S (p<0.001, p<0.001, and p=0.025, respectively). PVI predicted 28-day mortality with 83.8% sensitivity and 97.9% specificity. CONCLUSIONS: PVI, serum lactate level, PI, APACHE II, GCS, and need for vasopressors were independent risk factors for 28-day mortality in the Intensive Care Unit (ICU). PVI and serum lactate have a prognostic value in predicting mortality.


Assuntos
Glicemia , Unidades de Terapia Intensiva , Humanos , Prognóstico , APACHE , Lactatos
3.
Radiol Imaging Cancer ; 6(2): e230056, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38426887

RESUMO

Purpose To characterize the metabolomic profiles of two hepatocellular carcinoma (HCC) rat models, track evolution of these profiles to a stimulated tumor state, and assess their effect on lactate flux with hyperpolarized (HP) carbon 13 (13C) MRI. Materials and Methods Forty-three female adult Fischer rats were implanted with N1S1 or McA-RH7777 HCC tumors. In vivo lactate-to-pyruvate ratio (LPR) was measured with HP 13C MRI at 9.4 T. Ex vivo mass spectrometry was used to measure intratumoral metabolites, and Ki67 labeling was used to quantify proliferation. Tumors were first compared with three normal liver controls. The tumors were then compared with stimulated variants via off-target hepatic thermal ablation treatment. All comparisons were made using the Mann-Whitney test. Results HP 13C pyruvate MRI showed greater LPR in N1S1 tumors compared with normal liver (mean [SD], 0.564 ± 0.194 vs 0.311 ± 0.057; P < .001 [n = 9]), but not for McA-RH7777 (P = .44 [n = 8]). Mass spectrometry confirmed that the glycolysis pathway was increased in N1S1 tumors and decreased in McA-RH7777 tumors. The pentose phosphate pathway was also decreased only in McA-RH7777 tumors. Increased proliferation in stimulated N1S1 tumors corresponded to a net increase in LPR (six stimulated vs six nonstimulated, 0.269 ± 0.148 vs 0.027 ± 0.08; P = .009), but not in McA-RH7777 (eight stimulated vs six nonstimulated, P = .13), despite increased proliferation and metastases. Mass spectrometry demonstrated relatively increased lactate production with stimulation in N1S1 tumors only. Conclusion Two HCC subtypes showed divergent glycolytic dependency at baseline and during transformation to a high proliferation state. This metabolic heterogeneity in HCC should be considered with use of HP 13C MRI for diagnosis and tracking. Keywords: Molecular Imaging-Probe Development, Liver, Abdomen/GI, Oncology, Hepatocellular Carcinoma © RSNA, 2024 See also commentary by Ohliger in this issue.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratos , Feminino , Animais , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Ácido Pirúvico/metabolismo , Imageamento por Ressonância Magnética , Ratos Endogâmicos F344 , Lactatos
4.
Sci Rep ; 14(1): 5833, 2024 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-38461349

RESUMO

Renal replacement therapy (RRT) is a crucial treatment for sepsis-associated acute kidney injury (S-AKI), but it is uncertain which S-AKI patients should receive immediate RRT. Identifying the characteristics of patients who may benefit the most from RRT is an important task. This retrospective study utilized a public database and enrolled S-AKI patients, who were divided into RRT and non-RRT groups. Uplift modeling was used to estimate the individual treatment effect (ITE) of RRT. The validity of different models was compared using a qini curve. After labeling the patients in the validation cohort, we characterized the patients who would benefit the most from RRT and created a nomogram. A total of 8289 patients were assessed, among whom 591 received RRT, and 7698 did not receive RRT. The RRT group had a higher severity of illness than the non-RRT group, with a Sequential Organ Failure Assessment (SOFA) score of 9 (IQR 6,11) vs. 5 (IQR 3,7). The 28-day mortality rate was higher in the RRT group than the non-RRT group (34.83% vs. 14.61%, p < 0.0001). Propensity score matching (PSM) was used to balance baseline characteristics, 458 RRT patients and an equal number of non-RRT patients were enrolled for further research. After PSM, 28-day mortality of RRT and non-RRT groups were 32.3% vs. 39.3%, P = 0.033. Using uplift modeling, we found that urine output, fluid input, mean blood pressure, body temperature, and lactate were the top 5 factors that had the most influence on RRT effect. The area under the uplift curve (AUUC) of the class transformation model was 0.068, the AUUC of SOFA was 0.018, and the AUUC of Kdigo-stage was 0.050. The class transformation model was more efficient in predicting individual treatment effect. A logistic regression model was developed, and a nomogram was drawn to predict whether an S-AKI patient can benefit from RRT. Six factors were taken into account (urine output, creatinine, lactate, white blood cell count, glucose, respiratory rate). Uplift modeling can better predict the ITE of RRT on S-AKI patients than conventional score systems such as Kdigo and SOFA. We also found that white blood cell count is related to the benefits of RRT, suggesting that changes in inflammation levels may be associated with the effects of RRT on S-AKI patients.


Assuntos
Injúria Renal Aguda , Sepse , Humanos , Estudos Retrospectivos , Prognóstico , Terapia de Substituição Renal/efeitos adversos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Sepse/complicações , Sepse/terapia , Lactatos , Unidades de Terapia Intensiva
5.
Cell Death Dis ; 15(3): 209, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480704

RESUMO

Metabolic reprogramming, a hallmark of cancer, is closely associated with tumor development and progression. Changes in glycolysis play a crucial role in conferring radiation resistance to tumor cells. How radiation changes the glycolysis status of cancer cells is still unclear. Here we revealed the role of TAB182 in regulating glycolysis and lactate production in cellular response to ionizing radiation. Irradiation can significantly stimulate the production of TAB182 protein, and inhibiting TAB182 increases cellular radiosensitivity. Proteomic analysis indicated that TAB182 influences several vital biological processes, including multiple metabolic pathways. Knockdown of TAB182 results in decreased lactate production and increased pyruvate and ATP levels in cancer cells. Moreover, knocking down TAB182 reverses radiation-induced metabolic changes, such as radioresistant-related lactate production. TAB182 is necessary for activating LDHA transcription by affecting transcription factors SP1 and c-MYC; its knockdown attenuates the upregulation of LDHA by radiation, subsequently suppressing lactate production. Targeted suppression of TAB182 significantly enhances the sensitivity of murine xenograft tumors to radiotherapy. These findings advance our understanding of glycolytic metabolism regulation in response to ionizing radiation, which may offer significant implications for developing new strategies to overcome tumor radioresistance.


Assuntos
L-Lactato Desidrogenase , Proteômica , Humanos , Animais , Camundongos , L-Lactato Desidrogenase/metabolismo , Lactato Desidrogenase 5/metabolismo , Linhagem Celular Tumoral , Glicólise , Lactatos , Tolerância a Radiação/genética
6.
BMC Urol ; 24(1): 59, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481182

RESUMO

BACKGROUND: Bladder cancer (BC) is one of the most common malignancies of the genitourinary system. Phosphofructokinase 1 (PFK-1) is one of member of PFK, which plays an important role in reprogramming cancer metabolism, such as lactylation modification. Zinc finger E-box-binding homeobox 1 (ZEB1) has been demonstrated to be a oncogene in many cancers. Therefore, this study was performed to explore the effects of PFK-1 on the lactylation of ZEB1 in BC development. METHODS: Cell viability was measured using the CCK-8 kit. The glucose assay kit and lactate assay kit were used to detect glucose utilization and lactate production. The DNA was purified and quantified by qRT-PCR. RESULTS: In the present study, we found that ZEB1 expression levels were significantly elevated in bladder cancer cells. Impaired PFK-1 expression inhibits proliferation, migration, and invasion of BC cells and suppresses tumour growth in vivo. We subsequently found that knockdown of PFK-1 decreases glycolysis, including reduced glucose consumption, lactate production and total extracellular acidification rate (ECAR). Mechanistically, PFK-1 inhibits histone lactylation of bladder cancer cells, and thus inhibits the transcription activity of ZEB1. CONCLUSION: Our results suggest that PFK-1 can inhibit the malignant phenotype of bladder cancer cells by mediating the lactylation of ZEB1. These findings suggested PFK-1 to be a new potential target for bladder cancer therapy.


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Linhagem Celular Tumoral , Movimento Celular , Neoplasias da Bexiga Urinária/patologia , Fosfofrutoquinase-1/genética , Fosfofrutoquinase-1/metabolismo , Lactatos , Glucose , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo
7.
J UOEH ; 46(1): 17-21, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38479870

RESUMO

Elevated lactate levels are associated with a poor prognosis in patients with sepsis and shock. Intravenous glycerol administration is often used in Japan to treat patients with acute stroke or brain trauma, but such treatment can cause elevated lactate levels. We experienced a case of transient hyperlactatemia induced by intravenous glycerol administration in a patient with brain trauma. A 74-year-old woman underwent decompressive craniotomy because of loss of consciousness and brain edema. Glycerol was administered after the operation for management of the brain edema. Although the patient's hemodynamics remained stable, her lactate level decreased and increased repeatedly. We recognized that the elevation in her lactate level was associated with the administration of intravenous glycerol. This case suggests that intravenous glycerol administration can induce transient hyperlactatemia.


Assuntos
Edema Encefálico , Lesões Encefálicas Traumáticas , Hiperlactatemia , Humanos , Feminino , Idoso , Hiperlactatemia/induzido quimicamente , Hiperlactatemia/complicações , Glicerol/efeitos adversos , Edema Encefálico/complicações , Lactatos , Estudos Retrospectivos
8.
PLoS One ; 19(3): e0298617, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38470900

RESUMO

BACKGROUND: The understanding of shock indices in patients with septic shock is limited, and their values may vary depending on cardiac function. METHODS: This prospective cohort study was conducted across 20 university-affiliated hospitals (21 intensive care units [ICUs]). Adult patients (≥19 years) with septic shock admitted to the ICUs during a 29-month period were included. The shock index (SI), diastolic shock index (DSI), modified shock index (MSI), and age shock index (Age-SI) were calculated at sepsis recognition (time zero) and ICU admission. Left ventricular (LV) function was categorized as either normal LV ejection fraction (LVEF ≥ 50%) or decreased LVEF (<50%). RESULTS: Among the 1,194 patients with septic shock, 392 (32.8%) who underwent echocardiography within 24 h of time zero were included in the final analysis (normal LVEF: n = 246; decreased LVEF: n = 146). In patients with normal LVEF, only survivors demonstrated significant improvement in SI, DSI, MSI, and Age-SI values from time zero to ICU admission; however, no notable improvements were found in all patients with decreased LVEF. The completion of vasopressor or fluid bundle components was significantly associated with improved indices in patients with normal LVEF, but not in those with decreased LVEF. In multivariable analysis, each of the four indices at ICU admission was significantly associated with in-hospital mortality (P < 0.05) among patients with normal LVEF; however, discrimination power was better in the indices for patients with lower lactate levels (≤ 4.0 mmol/L), compared to those with higher lactate levels. CONCLUSIONS: The SI, DSI, MSI, and Age-SI at ICU admission were significantly associated with in-hospital mortality in patients with septic shock and normal LVEF, which was not found in those with decreased LVEF. Our study emphasizes the importance of interpreting shock indices in the context of LV function in septic shock.


Assuntos
Choque Séptico , Adulto , Humanos , Volume Sistólico , Função Ventricular Esquerda , Estudos Prospectivos , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Lactatos
9.
Sci Rep ; 14(1): 5975, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472356

RESUMO

Inspiratory muscles pre-activation (IMPA) has been studied to improve subsequent performance in swimming. However, the effects of IMPA on various parameters in swimmers are still unknown. Therefore, this study aimed to investigate the effects of IMPA on the mechanical parameters, physiological responses, and their possible correlations with swimming performance. A total of 14 young swimmers (aged 16 ± 0 years) underwent a 30-s all-out tethered swimming test, preceded or not by IMPA, a load of 40% of the maximal inspiratory pressure (MIP), and with a volume of 2 sets of 15 repetitions. The mechanical (strength, impulse, and fatigue index) and physiological parameters (skin temperature and lactatemia) and the assessment of perceived exertion and dyspnea were monitored in both protocols. The IMPA used did not increase the swimming force, and skin temperature, decrease blood lactate concentration, or subjective perception of exertion and dyspnea after the high-intensity tethered swimming exercises. Positive correlations were found between mean force and blood lactate (without IMPA: r = 0.62, P = 0.02; with IMPA: r = 0.65, P = 0.01). The impulse was positively correlated with blood lactate (without IMPA: r = 0.71, P < 0.01; with IMPA: r = 0.56, P = 0.03). Our results suggest that new IMPA protocols, possibly with increased volume, should be developed in order to improve the performance of young swimmers.


Assuntos
Desempenho Atlético , Natação , Humanos , Natação/fisiologia , Temperatura Cutânea , Desempenho Atlético/fisiologia , Músculos , Dispneia , Lactatos
10.
Eur Radiol Exp ; 8(1): 44, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38472611

RESUMO

BACKGROUND: Magnetic resonance (MR) imaging of deuterated glucose, termed deuterium metabolic imaging (DMI), is emerging as a biomarker of pathway-specific glucose metabolism in tumors. DMI is being studied as a useful marker of treatment response in a scan-rescan scenario. This study aims to evaluate the repeatability of brain DMI. METHODS: A repeatability study was performed in healthy volunteers from December 2022 to March 2023. The participants consumed 75 g of [6,6'-2H2]glucose. The delivery of 2H-glucose to the brain and its conversion to 2H-glutamine + glutamate, 2H-lactate, and 2H-water DMI was imaged at baseline and at 30, 70, and 120 min. DMI was performed using MR spectroscopic imaging on a 3-T system equipped with a 1H/2H-tuned head coil. Coefficients of variation (CoV) were computed for estimation of repeatability and between-subject variability. In a set of exploratory analyses, the variability effects of region, processing, and normalization were estimated. RESULTS: Six male participants were recruited, aged 34 ± 6.5 years (mean ± standard deviation). There was 42 ± 2.7 days between sessions. Whole-brain levels of glutamine + glutamate, lactate, and glucose increased to 3.22 ± 0.4 mM, 1.55 ± 0.3 mM, and 3 ± 0.7 mM, respectively. The best signal-to-noise ratio and repeatability was obtained at the 120-min timepoint. Here, the within-subject whole-brain CoVs were -10% for all metabolites, while the between-subject CoVs were -20%. CONCLUSIONS: DMI of glucose and its downstream metabolites is feasible and repeatable on a clinical 3 T system. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05402566 , registered the 25th of May 2022. RELEVANCE STATEMENT: Brain deuterium metabolic imaging of healthy volunteers is repeatable and feasible at clinical field strengths, enabling the study of shifts in tumor metabolism associated with treatment response. KEY POINTS: • Deuterium metabolic imaging is an emerging tumor biomarker with unknown repeatability.  • The repeatability of deuterium metabolic imaging is on par with FDG-PET.  • The study of deuterium metabolic imaging in clinical populations is feasible.


Assuntos
Glucose , Glutamina , Humanos , Masculino , Deutério , Voluntários Saudáveis , Glucose/metabolismo , Glutamatos , Lactatos
11.
Int J Mol Sci ; 25(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38473877

RESUMO

Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease due to the absence of effective therapies. A more comprehensive understanding of molecular events, encompassing the dysregulation of microRNAs (miRs) and metabolic reprogramming, holds the potential to unveil precise mechanisms underlying mCRPC. This study aims to assess the expression of selected serum exosomal miRs (miR-15a, miR-16, miR-19a-3p, miR-21, and miR-141a-3p) alongside serum metabolomic profiling and their correlation in patients with mCRPC and benign prostate hyperplasia (BPH). Blood serum samples from mCRPC patients (n = 51) and BPH patients (n = 48) underwent metabolome analysis through 1H-NMR spectroscopy. The expression levels of serum exosomal miRs in mCRPC and BPH patients were evaluated using a quantitative real-time polymerase chain reaction (qRT-PCR). The 1H-NMR metabolomics analysis revealed significant alterations in lactate, acetate, citrate, 3-hydroxybutyrate, and branched-chain amino acids (BCAAs, including valine, leucine, and isoleucine) in mCRPC patients compared to BPH patients. MiR-15a, miR-16, miR-19a-3p, and miR-21 exhibited a downregulation of more than twofold in the mCRPC group. Significant correlations were predominantly observed between lactate, citrate, acetate, and miR-15a, miR-16, miR-19a-3p, and miR-21. The importance of integrating metabolome analysis of serum with selected serum exosomal miRs in mCRPC patients has been confirmed, suggesting their potential utility for distinguishing of mCRPC from BPH.


Assuntos
MicroRNAs , Hiperplasia Prostática , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , MicroRNAs/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Soro/metabolismo , Citratos , Lactatos , Acetatos
12.
PeerJ ; 12: e17008, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38464757

RESUMO

This study aimed to compare the mechanical (lifting velocity and maximum number of repetitions), physiological (muscular activation, lactate, heart rate, and blood pressure), and psychological (rating of perceived exertion) responses to upper-body pushing exercises performed wearing a sports elastomeric garment or a placebo garment. Nineteen physically active young adults randomly completed two training sessions that differed only in the sports garment used (elastomeric technology or placebo). In each session, subjects performed one set of seated shoulder presses and another set of push-ups until muscular failure. The dependent variables were measured immediately after finishing the set of each exercise. Compared to the placebo garment, the elastomeric garment allowed participants to obtain greater muscular activation in the pectoralis major (push-ups: p = 0.04, d = 0.49; seated shoulder press: p < 0.01, d = 0.64), triceps brachialis (push-ups, p < 0.01, d = 0.77; seated shoulder press: p < 0.01, d = 0.65), and anterior deltoid (push-ups: p < 0.01, d = 0.72; seated shoulder press: p < 0.01, d = 0.83) muscles. Similarly, participants performed more repetitions (push-ups: p < 0.01; d = 0.94; seated shoulder press: p = 0.03, d = 0.23), with higher movement velocity (all p ≤ 0.04, all d ≥ 0.47), and lower perceived exertion in the first repetition (push-ups: p < 0.01, d = 0.61; seated shoulder press: p = 0.05; d = 0.76) wearing the elastomeric garment compared to placebo. There were no between-garment differences in most cardiovascular variables (all p ≥ 0.10). Higher diastolic blood pressure was only found after the seated shoulder press wearing the elastomeric garment compared to the placebo (p = 0.04; d = 0.49). Finally, significantly lower blood lactate levels were achieved in the push-ups performed wearing the elastomeric garment (p < 0.01; d = 0.91), but no significant differences were observed in the seated shoulder press (p = 0.08). Overall, the findings of this study suggest that elastomeric technology integrated into a sports garment provides an ergogenic effect on mechanical, physiological, and psychological variables during the execution of pushing upper-limb resistance exercises.


Assuntos
Treinamento de Força , Adulto Jovem , Humanos , Ombro/fisiologia , Levantamento de Peso/fisiologia , Lactatos , Vestuário
13.
Commun Biol ; 7(1): 325, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486093

RESUMO

Regulating metabolic disorders has become a promising focus in treating intervertebral disc degeneration (IDD). A few drugs regulating metabolism, such as atorvastatin, metformin, and melatonin, show positive effects in treating IDD. Glutamine participates in multiple metabolic processes, including glutaminolysis and glycolysis; however, its impact on IDD is unclear. The current study reveals that glutamine levels are decreased in severely degenerated human nucleus pulposus (NP) tissues and aging Sprague-Dawley (SD) rat nucleus pulposus tissues, while lactate accumulation and lactylation are increased. Supplementary glutamine suppresses glycolysis and reduces lactate production, which downregulates adenosine-5'-monophosphate-activated protein kinase α (AMPKα) lactylation and upregulates AMPKα phosphorylation. Moreover, glutamine treatment reduces NP cell senescence and enhances autophagy and matrix synthesis via inhibition of glycolysis and AMPK lactylation, and glycolysis inhibition suppresses lactylation. Our results indicate that glutamine could prevent IDD by glycolysis inhibition-decreased AMPKα lactylation, which promotes autophagy and suppresses NP cell senescence.


Assuntos
Degeneração do Disco Intervertebral , Ratos , Animais , Humanos , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Ratos Sprague-Dawley , Glutamina , Proteínas Quinases Ativadas por AMP , Autofagia , Lactatos/farmacologia , Lactatos/uso terapêutico
14.
Biochem Biophys Res Commun ; 706: 149741, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38471204

RESUMO

The chromosome passenger complex (CPC) is a kinase complex formed by Aurora B, borealin, survivin and inner centromere protein (INCENP). The CPC is active during mitosis and contributes to proper chromosome segregation via the phosphorylation of various substrates. Overexpression of each CPC component has been reported in most cancers. However, its significance remains unclear, as only survivin is known to confer chemoresistance. This study showed that the overexpression of borealin, a CPC component, stabilized survivin protein depending on its interaction with survivin. Unexpectedly, the accumulation of survivin by borealin overexpression did not affect the well-characterized functions of survivin, such as chemoresistance and cell proliferation. Interestingly, the overexpression of borealin promoted lactate production but not the overexpression of the deletion mutant that lacks the ability to bind to survivin. Consistent with these findings, the expression levels of glycolysis-related genes were enhanced in borealin-overexpressing cancer cells. Meanwhile, the overexpression of survivin alone did not promote lactate production. Overall, the accumulation of the borealin-survivin complex promoted glycolysis in squamous cell carcinoma cells. This mechanism may contribute to cancer progression via excessive lactate production.


Assuntos
Carcinoma de Células Escamosas , Centrômero , Humanos , Survivina/genética , Survivina/metabolismo , Centrômero/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Proteínas de Ciclo Celular/metabolismo , Mitose , Fosforilação , Aurora Quinase B/genética , Aurora Quinase B/metabolismo , Carcinoma de Células Escamosas/genética , Lactatos
15.
PLoS One ; 19(3): e0300568, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38512920

RESUMO

OBJECTIVES: To analyze outcomes in patients with normal preoperative left ventricular ejection fraction (LVEF) undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO) therapy due to postcardiotomy cardiogenic shock (PCCS) related to coronary malperfusion. METHODS: Retrospective single-center analysis in patients with normal preoperative LVEF treated with VA-ECMO for coronary malperfusion-related PCCS between May 1998 and May 2018. The primary outcome was 30-day mortality, which was compared using the Kaplan-Meier method and the log-rank test. Multivariable logistic regression was performed to identify predictors of mortality. RESULTS: During the study period, a total of 62,125 patients underwent cardiac surgery at our institution. Amongst them, 59 patients (0.1%) with normal preoperative LVEF required VA-ECMO support due to coronary malperfusion-related PCCS. The mean duration of VA-ECMO support was 6 days (interquartile range 4-7 days). The 30-day mortality was 50.8%. Under VA-ECMO therapy, a complication composite outcome of bleeding, re-exploration for bleeding, acute renal failure, acute liver failure, and sepsis occurred in 51 (86.4%) patients. Independent predictors of 30-day mortality were lactate levels > 9.9 mmol/l before VA-ECMO implantation (odds ratio [OR]: 3.3; 95% confidence interval [CI] 1.5-7.0; p = 0.002), delay until revascularization > 278 minutes (OR: 2.9; 95% CI 1.3-6.4; p = 0.008) and peripheral arterial artery disease (OR: 3.3; 95% 1.6-7.5; p = 0.001). CONCLUSIONS: Mortality rates are high in patients with normal preoperative LVEF who develop PCCS due to coronary malperfusion. The early implantation of VA-ECMO before the development of profound tissue hypoxia and early coronary revascularization increases the likelihood of survival. Lactate levels are useful to define optimal timing for the VA-ECMO initiation.


Assuntos
Oxigenação por Membrana Extracorpórea , Choque Cardiogênico , Humanos , Choque Cardiogênico/etiologia , Choque Cardiogênico/terapia , Oxigenação por Membrana Extracorpórea/métodos , Estudos Retrospectivos , Função Ventricular Esquerda , Volume Sistólico , Lactatos
16.
BMC Anesthesiol ; 24(1): 109, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515021

RESUMO

BACKGROUND: In this study, we aimed to evaluate the ability of central-to-peripheral temperature gradients using thermal imaging to predict in-hospital mortality in surgical patients with septic shock. METHODS: This prospective observational study included adult patients with septic shock admitted to the intensive care unit postoperatively. Serum lactate (in mmol/L), capillary refill time (CRT) (in seconds), toe (peripheral) and canthal (central) temperature by infrared thermography and the corresponding room temperature in (Celsius [°C]) were assessed at the time of admission, 6- and 12 h after admission. The canthal-toe and room-toe temperature gradients were calculated. According to their final outcomes, patients were divided into survivors and non-survivors. The ability of canthal-toe temperature gradient (primary outcome), room-toe temperature gradient, toe temperature, serum lactate and CRT, measured at the prespecified timepoints to predict in-hospital mortality was analyzed using the area under receiver operating characteristic curve (AUC). RESULTS: Fifty-six patients were included and were available for the final analysis and 41/56 (73%) patients died. The canthal-toe and room-toe temperature gradients did not show significant accuracy in predicting mortality at any timepoint. Only the toe temperature measurement at 12 h showed good ability in predicting in-hospital mortality with AUC (95% confidence interval) of 0.72 (0.58-0.84) and a negative predictive value of 70% at toe temperature of ≤ 25.5 °C. Both serum lactate and CRT showed good ability to predict in-hospital mortality at all timepoints with high positive predictive values (> 90%) at cut-off value of > 2.5-4.3 mmol/L for the serum lactate and > 3-4.2 s for the CRT. CONCLUSION: In post-operative emergency surgical patients with septic shock, high serum lactate and CRT can accurately predict in-hospital mortality and were superior to thermal imaging, especially in the positive predictive values. Toe temperature > 25.5 °C, measured using infrared thermal imaging can exclude in-hospital mortality with a negative predictive value of 70%.


Assuntos
Choque Séptico , Adulto , Humanos , Prognóstico , Curva ROC , Lactatos , Perfusão
17.
BMC Surg ; 24(1): 94, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515100

RESUMO

BACK GROUND: Determining the optimal timing of postoperative oral feeding in trauma patients who have undergone abdominal surgery with small bowel and/or mesenteric injuries is challenging. The aim of this study is to investigate serum lactate as a factor that can predict oral feeding tolerance and prolonged postoperative ileus (PPOI) in patients who underwent surgery for small bowel and/or mesenteric injury due to trauma. METHODS: The single center retrospective observational study was conducted on 367 patients who underwent surgery for small bowel and/or mesenteric injury between January 2013 and July 2021. The patient group was divided into two groups based on whether the peak serum lactate was over 2mmol/L (18 mg/dL). In the group of lactate > 2mmol/L, it was divided into prolonged postoperative ileus (PPOI) groups and groups rather than PPOI. RESULTS: Patients in the peak serum lactate > 2 group had tendency to use vasopressors, lower initial systolic blood pressure, larger number of packed red blood cells for 24 h, higher injury severity score, higher PPOI incidence, and a tendency for delayed oral intake tolerance. In peak serum lactate greater than 2 mmol/L group, the lactate normalization time (OR 1.699, p = 0.04), quantity of FFP transfusion for 24 h (OR 1.145, p = 0.012), and creatine kinase (OR 1.001, p = 0.023) were related to PPOI. The lactate normalization time had the highest correlation. CONCLUSION: In patients undergoing surgical management for small bowel and/or mesenteric injury after trauma, serum lactate normalization time affects oral intake tolerance and prolongs postoperative ileus.


Assuntos
Íleus , Complicações Pós-Operatórias , Humanos , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Abdome , Íleus/etiologia , Íleus/epidemiologia , Lactatos
18.
Biosens Bioelectron ; 253: 116194, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38467100

RESUMO

The multiplexed detection of metabolites in parallel within a single biosensor plate is sufficiently valuable but also challenging. Herein, we combine the inherent light addressability of silicon with the high selectivity of enzymes, for the construction of multiplexed photoelectrochemical enzymatic biosensors. To conduct a stable electrochemistry and reagentless biosensing on silicon, a new strategy involving the immobilization of both redox mediators and enzymes using an amide bond-based hydrogel membrane was proposed. The membrane characterization results demonstrated a covalent coupling of ferrocene mediator to hydrogel, in which the mediator acted as not only a signal generator but also a renewable sacrifice agent. By adding corresponding enzymes on different spots of hydrogel membrane modified silicon and recording local photocurrents with a moveable light pointer, this biosensor setup was used successfully to detect multiple metabolites, such as lactate, glucose, and sarcosine, with good analytical performances. The limits of detection of glucose, sarcosine and lactate were found to be 179 µM, 16 µM, and 780 µM with the linear ranges of 0.5-2.5 mM, 0.3-1.5 mM, and 1.0-3.0 mM, respectively. We believe this proof-of-concept study provides a simple and rapid one-step immobilization approach for the fabrication of reagentless enzymatic assays with silicon-based light-addressable electrochemistry.


Assuntos
Técnicas Biossensoriais , Silício , Eletroquímica/métodos , Sarcosina , Técnicas Biossensoriais/métodos , Hidrogéis , Lactatos , Glucose
19.
J Sports Sci Med ; 23(1): 258-264, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38455446

RESUMO

Music is well-known to elicit ergogenic effects on exercise performance; however, the moderating role of application timing remains unclear. This study examined the effects of the timing of music on fatigue perception and performance during isometric strength exercises. Using a within-subject, randomised crossover design, twelve recreationally active young adults performed two isometric strength tasks (plank-hold and wall-sit) in three separate conditions (MEE: music played during the entire exercise task; MDF: music played during fatigue alone; CON: no music). The total time to volitional exhaustion (TTE), time to the onset of fatigue perception (TFP), heart rate, and blood lactate responses were assessed during each trial. MEE resulted in a significantly longer TTE than CON in both the plank-hold (p < 0.05, d = 0.76) and wall-sit exercises (p < 0.05, d = 0.72), whereas MDF led to a significantly longer TTE than CON in wall-sit exercises alone (p < 0.05, d = 0.60). TFP was significantly longer in MEE than in CON in both the plank-hold (p < 0.05, d = 0.54) and wall-sit exercises (p < 0.05, d = 0.64). The music condition did not influence the heart rate or blood lactate changes in any of the trials. Our results suggest that listening to music during the entire exercise can delay the onset of fatigue perception in isometric strength tasks, whereas listening to music during fatigue has only a modest effect. Athletes and exercisers should consider extending music exposure throughout the entire exercise task to maximise performance benefits.


Assuntos
Música , Adulto Jovem , Humanos , Estudos Cross-Over , Fadiga , Percepção/fisiologia , Lactatos
20.
Surg Infect (Larchmt) ; 25(2): 116-124, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38324100

RESUMO

Background: Despite the high prevalence of post-operative fever, a variety of approaches are taken as to the components of a fever evaluation, when it should be undertaken, and when empiric antibiotic agents should be started. Hypothesis: There is a lack of consensus surrounding many common components of a post-operative fever evaluation. Patients and Methods: The Surgical Infection Society membership was surveyed to determine practices surrounding evaluation of post-operative fever. Eight scenarios were posed in febrile (38.5°C), post-operative general surgery or trauma patients, with 19 possible components of work-up (physical examination, complete blood count [CBC], fungal biomarkers, lactate and procalcitonin [PCT] concentrations, cultures, imaging) and management (antibiotic agents). Each scenario was then re-considered for intensive care unit (ICU) patients (intubated/unstable hemodynamics). Agreement on a parameter (<1/4 or >3/4 of respondents) achieved consensus, positive or negative. Parameters between had equipoise; α was set at 0.05. Results: Among the examined scenarios, only CBC and physical examination received positive consensus across most scenarios. Blood/urine cultures, imaging, lactate, inflammatory biomarkers, and the empiric administration of antibiotic agents did not reach consensus; support was variable depending on the clinical scenario, illness severity, and the individual preferences of the answering clinician. The qualitative portion of the survey identified "fever threshold and duration," "clinical suspicion," and "physiologic manifestation" as the most important factors for deciding about the initiation of a fever evaluation and the potential empiric administration of antibiotic agents. Conclusions: There is consensus only for physical and examination routine laboratory work when initiating the evaluation of febrile post-operative patients. However, there are multiple components of a fever evaluation that individual respondents would select depending on the clinical scenario and severity of illness. Parameters demonstrating equipoise are potential candidates for formal guidance or pragmatic prospective trials.


Assuntos
Antibacterianos , Febre , Humanos , Autorrelato , Estudos Prospectivos , Febre/diagnóstico , Biomarcadores , Antibacterianos/uso terapêutico , Lactatos
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