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1.
Sci Rep ; 13(1): 1012, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36653462

RESUMO

Chest computed tomography (CT) is effective for assessing the severity of coronavirus disease 2019 (COVID-19). However, the clinical factors reflecting the disease progression of COVID-19 pneumonia on chest CT and predicting a subsequent exacerbation remain controversial. We conducted a retrospective cohort study of 450 COVID-19 patients. We used an automated image processing tool to quantify the COVID-19 pneumonia lesion extent on chest CT at admission. The factors associated with the lesion extent were estimated by a multiple regression analysis. After adjusting for background factors by propensity score matching, we conducted a multivariate Cox proportional hazards analysis to identify factors associated with severe disease after admission. The multiple regression analysis identified, body-mass index (BMI), lactate dehydrogenase (LDH), C-reactive protein (CRP), and albumin as continuous variables associated with the lesion extent on chest CT. The standardized partial regression coefficients for them were 1.76, 2.42, 1.54, and 0.71. The multivariate Cox proportional hazards analysis identified LDH (hazard ratio, 1.003; 95% confidence interval, 1.001-1.005) as a factor independently associated with the development of severe COVID-19 pneumonia. Increased serum LDH at admission may be useful in real-world clinical practice for the simple screening of COVID-19 patients at high risk of developing subsequent severe disease.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico por imagem , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios X/métodos , L-Lactato Desidrogenase , Progressão da Doença
2.
Anal Biochem ; 664: 115035, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36621706

RESUMO

High pressure is known to dissociate several oligomeric proteins, and regarded as an important tool to shift the oligomerization equilibrium. Native polyacrylamide gel electrophoresis (native PAGE) at high pressure can characterize the dissociates and clearly discriminate the aggregates. However, a band smearing of migration profiles often hinders more detailed analyses (Miwa et al., High Pressure Res. (2019) 39, 218-224). In this paper, we focused on the band smearing dependent on the migration velocity so as to extract both thermodynamic and kinetic parameters. We systematically perturbed the migration velocity by changing the gel concentration and carried out numerical analysis for a series of the migration profiles based on a simple dissociation reaction scheme with limited thermodynamic and kinetic parameters. Then, complete volumetric properties on oligomerization process can be available. We term the present analysis method as a high-pressure native PAGE velocity method. We also report the application of this method to revisit the pressure dissociation of tetrameric lactate dehydrogenase (LDH) from pig heart.


Assuntos
L-Lactato Desidrogenase , Proteínas , Animais , Suínos , Eletroforese em Gel de Poliacrilamida Nativa , Cinética , Termodinâmica , Eletroforese em Gel de Poliacrilamida
3.
Sci Rep ; 13(1): 768, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36641500

RESUMO

The level of lactate dehydrogenase (LDH) has been proved to be positively associated with albuminuria, which represents glomerular endothelial damage in hypertension (HTN). In this study, the relationship between LDH and endothelial function evaluated by flow-mediated dilation (FMD) was investigated in hypertensives. 1507 subjects (aged 61.2 ± 12.5 years) were enrolled. All hypertensives (n = 1216) were subdivided into 3 groups: LDH1 (lowest tertile of LDH, n = 399), LDH2 (mediate tertile of LDH, n = 409) and LDH3 (highest tertile of LDH, n = 408). Meanwhile, 291 normotensives served as controls. FMD of right anterior tibial artery was assessed by high-resolution color Doppler ultrasound. The level of LDH in hypertensives was significantly higher than normotensives (p < 0.001). Whereas, FMD was obviously more blunted in hypertensives (p < 0.001). There was an increasing trend of FMD < 8% from control, LDH1, LDH2 to LDH3 group (χ2 = 36.751, p < 0.001). Stepwise multiple liner regression analysis demonstrated an independent correlation between LDH and FMD in hypertensives (ß = - 0.145, p < 0.05). After stratified analysis, the relevance persisted in the male, young and middle-aged, hypertensives with grade 2 HTN, duration of HTN < 3 years, metabolic syndrome and those without statin therapy. In conclusion, the level of LDH was inversely correlated with FMD among hypertensives. Those hypertensives with increased LDH need to be scanned for target organ damage, such as microalbuminuria and endothelial dysfunction, and more frequent following up are also recommended.


Assuntos
Hipertensão , L-Lactato Desidrogenase , Humanos , Masculino , Pessoa de Meia-Idade , Pressão Sanguínea , Dilatação , Endotélio Vascular , Vasodilatação , Feminino , Idoso
4.
Biochem Med (Zagreb) ; 33(1): 010705, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36627975

RESUMO

Introduction: The presence of macroenzymes in blood can cause diagnostic confusion. Therefore, confirming the presence of macroenzymes is important to reduce unnecessary (non-)invasive investigations. Polyethylene glycol (PEG) precipitation is a simple and fast first-line method for the detection of macroenzymes. However, there is no consensus on the upper reference limit for the PEG-precipitable activity (%PPA) of monomeric enzymes. The aim of this study was to verify a PEG precipitation protocol for the detection of macroenzymes in our laboratory by establishing upper reference limits (URLs) and determining imprecision for eight enzymes after PEG precipitation. In addition, we aimed to clinically verify the URLs using samples containing macroenzymes as identified by electrophoresis. Materials and methods: Per enzyme, at least 40 leftover blood samples from adult patients with either normal or increased enzyme activities were diluted 1:1 with 25% PEG 6000 and 1:1 with 0.9% NaCl. Mixtures were incubated for 10 min at 37°C and centrifuged. Supernatant enzyme activity was measured on Cobas c702 and the %PPA was calculated. Results: The following URLs were obtained: 26% PPA for amylase, 29% PPA for alkaline phosphatase (ALP), 61% PPA for alanine aminotransferase, 48% PPA for aspartate aminotransferase, 24% PPA for creatine kinase (CK), 55% PPA for gamma-glutamyltransferase, 65% PPA for lactate dehydrogenase, and 56% PPA for lipase. The within-lab imprecision was < 15%. Regarding the clinical verification, the two historical samples with proven macroCK showed a %PPA of 69% and 43%, respectively, and a sample with proven macroALP had a %PPA of 52%. Conclusion: In this study, URLs for monomeric enzyme activities after PEG precipitation for eight different enzymes were established. The URLs are suitable for clinical use, but are only partially in line with other studies. Therefore, our data highlight the importance of establishing laboratory-specific upper reference limits for %PPA to allow a correct interpretation.


Assuntos
Fosfatase Alcalina , Creatina Quinase , Adulto , Humanos , Aspartato Aminotransferases , L-Lactato Desidrogenase , Polietilenoglicóis
5.
World J Microbiol Biotechnol ; 39(3): 69, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607503

RESUMO

The modification of gene expression is being researched in the production of useful chemicals by metabolic engineering of the yeast Saccharomyces cerevisiae. When the expression levels of many metabolic enzyme genes are modified simultaneously, the expression ratio of these genes becomes diverse; the relationship between the gene expression ratio and chemical productivity remains unclear. In other words, it is challenging to predict phenotypes from genotypes. However, the productivity of useful chemicals can be improved if this relationship is clarified. In this study, we aimed to construct a machine-learning model that can be used to clarify the relationship between gene expression levels and D-lactic acid productivity and predict the optimal gene expression level for efficient D-lactic acid production in yeast. A machine-learning model was constructed using data on D-lactate dehydrogenase and glycolytic genes expression (13 dimensions) and D-lactic acid productivity. The coefficient of determination of the completed machine-learning model was 0.6932 when using the training data and 0.6628 when using the test data. Using the constructed machine-learning model, we predicted the optimal gene expression level for high D-lactic acid production. We successfully constructed a machine-learning model to predict both D-lactic acid productivity and the suitable gene expression ratio for the production of D-lactic acid. The technique established in this study could be key for predicting phenotypes from genotypes, a problem faced by recent metabolic engineering strategies.


Assuntos
Ácido Láctico , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Ácido Láctico/metabolismo , Glicólise , Engenharia Metabólica/métodos , L-Lactato Desidrogenase/genética , Expressão Gênica
6.
Bioelectrochemistry ; 150: 108365, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36638677

RESUMO

Two dehydrogenase enzymes (glucose, GDH, and lactate, LDH, dehydrogenases) encapsulated within alginate hydrogels were deposited on glassy carbon electrodes. The as-prepared enzyme modified alginate hydrogels were utilized as electrochemiluminescence (ECL)-based biosensors for the indirect detection of glucose and lactic acid upon reaction between NADH and tris(2,2'-bipyridyl) ruthenium (II) [Ru(bpy)3]2+. The ECL response was obtained from the redox reaction between the substrate, the cofactor NAD+ and the encapsulated enzyme. The production of NADH resulting from the enzymatic reaction led to the ECL emission upon reaction with [Ru(bpy)3]2+. The biosensors showed good stability and repeatability, with linear range between 0.56 and 4.2 µM and limit of detection of 0.84 µM for glucose, and linear range between 5 and 30 µM with a limit of detection of 2.52 µM for lactic acid. These ECL-based biosensors showed good sensitivity when tested in the presence of common interfering species. These biosensors were utilized in artificial sweat and were characterized by good reproducibility and repeatability. The results herein presented suggest that the dehydrogenases encapsulated within alginate hydrogels have potential for the development of biocompatible sensors for detection of glucose and lactic acid in physiological fluids.


Assuntos
Técnicas Biossensoriais , Rutênio , 2,2'-Dipiridil , Lactato Desidrogenases , Rutênio/química , Hidrogéis , Medições Luminescentes/métodos , Glucose , NAD , Reprodutibilidade dos Testes , L-Lactato Desidrogenase , Técnicas Biossensoriais/métodos , Ácido Láctico
7.
J Infect Public Health ; 16(1): 136-142, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36521329

RESUMO

INTRODUCTION: Since the beginning of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic an important tool for patients with Coronavirus Disease 2019 (COVID-19) has been the computed tomography (CT) scan, but not always available in some settings The aim was to find a cut-off that can predict worsening in patients with COVID-19 assessed with a computed tomography (CT) scan and to find laboratory, clinical or demographic parameters that may correlate with a higher CT score. METHODS: We performed a multi-center, observational, retrospective study involving seventeen COVID-19 Units in southern Italy, including all 321 adult patients hospitalized with a diagnosis of COVID-19 who underwent at admission a CT evaluated using Pan score. RESULTS: Considering the clinical outcome and Pan score, the best cut-off point to discriminate a severe outcome was 12.5. High lactate dehydrogenase (LDH) serum value and low PaO2/FiO2 ratio (P/F) resulted independently associated with a high CT score. The Area Under Curve (AUC) analysis showed that the best cut-off point for LDH was 367.5 U/L and for P/F 164.5. Moreover, the patients with LDH> 367.5 U/L and P/F < 164.5 showed more frequently a severe CT score than those with LDH< 367.5 U/L and P/F> 164.5, 83.4%, vs 20%, respectively. CONCLUSIONS: A direct correlation was observed between CT score value and outcome of COVID-19, such as CT score and high LDH levels and low P/F ratio at admission. Clinical or laboratory tools that predict the outcome at admission to hospital are useful to avoiding the overload of hospital facilities.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Adulto , Humanos , SARS-CoV-2 , L-Lactato Desidrogenase , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
8.
J Med Chem ; 66(1): 596-610, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36538511

RESUMO

Lactate dehydrogenase (LDH) is a key glycolytic enzyme and biomarker of aggressive cancers. LDHA and LDHB are two main LDH subunits, and both are frequently overexpressed in tumors and essential for tumor growth. A number of LDHA/B small-molecule inhibitors have been developed. Here, we report the discovery of the first LDH proteolysis targeting chimera (PROTAC) degrader, compound 22 (MS6105). 22 potently degraded LDHA in a time- and ubiquitin-proteasome system-dependent manner. Using an unbiased global proteomic study, we confirmed that 22 degraded both LDHA and LDHB significantly. 22 was significantly more potent than the parent LDH inhibitor in suppressing the growth of both quasi-mesenchymal state and epithelial state pancreatic cancer cell lines. Furthermore, 22 was bioavailable in mice through intraperitoneal injection. Overall, 22 could be a valuable chemical tool for the research community to explore pathophysiological functions of LDH in vitro and in vivo.


Assuntos
L-Lactato Desidrogenase , Neoplasias Pancreáticas , Animais , Camundongos , Proteômica , Linhagem Celular Tumoral , Neoplasias Pancreáticas/tratamento farmacológico , Proteólise
9.
Int J Cancer ; 150(7): 1166-1173, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34605002

RESUMO

Cancer is a risk factor for venous thromboembolism (VTE). Plasma tumor DNA (ptDNA) is an independent predictor of outcome in metastatic castration-resistant prostate cancer (mCRPC). We aimed to investigate the association between ptDNA and VTE in mCRPC. This prospective biomarker study included 180 mCRPC patients treated with abiraterone and enzalutamide from April 2013 to December 2018. We excluded patients with a previous VTE history and/or ongoing anticoagulation therapy. Targeted next-generation sequencing was performed to determine ptDNA fraction from pretreatment plasma samples. VTE risk based on survival analysis was performed using cumulative incidence function and estimating sub-distributional hazard ratio (SHR). At a median follow-up of 58 months (range 0.5-111.0), we observed 21 patients who experienced VTE with a cumulative incidence at 12 months of 17.1% (95% confidence interval [CI] 10.3-23.9). Elevated ptDNA, visceral metastasis, prior chemotherapy and lactate dehydrogenase (LDH) were significantly associated with higher VTE incidence compared to patients with no thrombosis (12-month estimate, 18.6% vs 3.5%, P = .0003; 44.4% vs 14.8%, P = .015; 24.7% vs 4.5%, P = .006; and 30.0% vs 13.5%, P = .05, respectively). In the multivariate analysis including ptDNA level, visceral metastases, number of lesions and serum LDH, high ptDNA fraction was the only independent factor associated with the risk of thrombosis (HR 5.78, 95% CI 1.63-20.44, P = .006). These results first suggest that baseline ptDNA fraction in mCRPC patients treated with abiraterone or enzalutamide may be associated with increased VTE risk. These patients may be followed-up more closely for the VTE risk, and the need for a primary thromboprophylaxis should be taken into account in mCRPC with elevated ptDNA.


Assuntos
DNA de Neoplasias/sangue , Neoplasias de Próstata Resistentes à Castração/complicações , Tromboembolia Venosa/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/patologia , Risco
10.
Ann Palliat Med ; 11(11): 3444-3454, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36464962

RESUMO

BACKGROUND: Corrected QT (QTc) interval prolongation is one of the common causes of sudden cardiac death in patients with maintenance hemodialysis (MHD) patients. However, there are few studies on QTc prolongation in MHD patients. The concentration of lactate dehydrogenase (LDH) in hemodialysis population increased, and LDH was associated with the mortality of MHD patients. This study aimed to investigate the relationship between QTc interval prolongation and LDH in MHD patients. METHODS: This is a cross-sectional observational study. Patients who underwent MHD for more than 3 months in the Second Affiliated Hospital of Nantong University from November 2012 to November 2019 with complete data were selected as the research subjects. The patients were divided into the normal QTc interval group and the QTc interval prolongation group. The general data of patients and clinical laboratory indicators were collected retrospectively from the electronic medical record system. Pearson correlation analysis and binary logistic regression were used to analyze the correlation between LDH and QTc interval prolongation; the cut-off value of LDH predicting QTc interval prolongation was calculated by receiver operating characteristic (ROC) curve. RESULTS: The LDH level in the prolonged QTc interval group was significantly higher than that in the normal group (301.96±110.91 vs. 215.39±67.65, t=-8.03, P<0.001). QTc interval and LDH (r=0.386) were positively correlated. Binary logistic regression analysis showed that LDH, serum potassium <4 mmol/L, serum phosphorus, and left ventricular end-diastolic diameter (LVDd) were independent related factors for QTc interval prolongation. The ROC curve results showed that LDH =220 U/L was the best cutoff point for predicting QTc interval prolongation in MHD patients, with a sensitivity of 81.45% and a specificity of 59.35%. Binary logistic regression analysis showed that the LDH >220 U/L group was 6.34 times more likely to have QTc interval prolongation than the LDH ≤220 U/L group (OR 6.34, 95% CI: 3.47-11.58, P<0.001). CONCLUSIONS: LDH in MHD patients is closely related to QTc interval prolongation. Serum LDH, ionic calcium, serum phosphorus and potassium may predict QTc interval prolongation. Monitoring related indicators can remind clinicians to intervene as soon as possible to reduce the potential risk of arrhythmia and sudden cardiac death (SCD).


Assuntos
L-Lactato Desidrogenase , Síndrome do QT Longo , Humanos , Estudos Transversais , Estudos Retrospectivos , Morte Súbita Cardíaca , Diálise Renal/efeitos adversos , Potássio , Fósforo , Síndrome do QT Longo/etiologia , Eletrocardiografia
11.
J Cancer Res Ther ; 18(Supplement): S215-S218, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36510967

RESUMO

Introduction: Lactate dehydrogenase (LDH) is an enzyme seen within every cell during their normal metabolic function. It is always confined within the cell cytoplasm and it becomes extracellular only when a cell dies. The extracellular presence of LDH is related to cell necrosis and tissue breakdown. Therefore, we designed a study to estimate and compare LDH levels in the saliva of patients with oral cancer, oral leukoplakia (OL), and smokers without lesions and in controls. Materials and Methods: A total of 81 subjects of both genders, between the ages of 20 and 70 years, were included in the study. The study group was divided into four: group I-controls (n = 20), Group II-smokers (n = 20), Group III-subjects with OL (n = 20), and Group IV-subjects with oral squamous cell carcinoma (OSCC) (n = 21). Five milliliters of unstimulated salivary sample was collected from each participant, and salivary LDH level was measured. The obtained values were tabulated and statistically analyzed. P < 0.05 was considered to be statistically significant. Results: The difference in LDH levels among the four groups was found to "BE" statistically significant. LDH values showed a marked increase in the leukoplakia group (49.79 ± 19.88 IU/L) and OSCC group (106.97 ± 32.75 IU/L) when compared to controls and smokers. Conclusion: We found that salivary LDH was increased in patients with leukoplakia and OSCC. Smoking alone did not produce any alterations in salivary LDH. It is possible that salivary LDH could be a potential biomarker to identify early premalignant or malignant changes in smokers.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Feminino , Masculino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , L-Lactato Desidrogenase , Leucoplasia Oral/patologia , Saliva/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo
12.
Clin Lab ; 68(12)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36546752

RESUMO

BACKGROUND: As a common pediatric respiratory disease, Mycoplasma pneumoniae pneumonia (MPP) accounts for 20 - 30% of acquired pneumonia in children, with a rising morbidity rate annually. We aimed to explore the correlations of different serological parameters with the severity and prognosis of MPP children. METHODS: A total of 108 MPP children were divided into severe group (n = 58) and mild group (n = 50). The serum levels of triglycerides, HDL-C, LDL-C, erythrocyte sedimentation rate (ESR), D-dimer (DD), lactate dehydrogenase (LDH), interleukin-6 (IL-6), galectin-3 (Gal-3), homocysteine (Hcy), and procalcitonin (PCT) were measured. Receiver operating characteristic (ROC) curves were plotted to analyze their predictive values for poor prognosis. They were followed up for 6 months and assigned into good and poor prognosis groups. Multivariate logistic regression analysis was performed to explore the serological parameters affecting prognosis. A prediction model was established. RESULTS: In acute and recovery phases, the levels of ESR, DD, LDH, IL-6, Gal-3, Hcy, and PCT in the severe group were significantly higher than those in the mild group (p < 0.05). Prediction combining various serological parameters had the highest value for poor prognosis. ESR, DD, LDH, IL-6, Gal-3, Hcy, and PCT levels were independent risk factors. The concordance index of the nomogram model established using these factors was 0.745 (95% CI: 0.684 - 0.830). The area under the ROC curve was 0.726 (95% CI: 0.701 - 0.815). The predicted probability of the model was consistent with the actual one, showing high accuracy. CONCLUSIONS: Serum levels of ESR, DD, LDH, IL-6, Gal-3, Hcy, and PCT are closely correlated with the severity and prognosis of MPP children, which provide references for prognostic evaluation. Prediction combining these indices is more valuable than that using a single index.


Assuntos
Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Humanos , Criança , Interleucina-6 , Prognóstico , Pneumonia por Mycoplasma/diagnóstico , Pró-Calcitonina , L-Lactato Desidrogenase , Estudos Retrospectivos
13.
Int J Mol Sci ; 23(24)2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36555705

RESUMO

Cell migration is an essential part of the complex and multistep process that is the development of cancer, a disease that is the second most common cause of death in humans. An important factor promoting the migration of cancer cells is TNF-α, a pro-inflammatory cytokine that, among its many biological functions, also plays a major role in mediating the expression of MMP9, one of the key regulators of cancer cell migration. It is also known that TNF-α is able to induce the Warburg effect in some cells by increasing glucose uptake and enhancing the expression and activity of lactate dehydrogenase subunit A (LDHA). Therefore, the aim of the present study was to investigate the interrelationship between the TNF-α-induced promigratory activity of cancer cells and their glucose metabolism status, using esophageal cancer cells as an example. By inhibiting LDHA activity with sodium oxamate (SO, also known as aminooxoacetic acid sodium salt or oxamic acid sodium salt) or siRNA-mediated gene silencing, we found using wound healing assay and gelatin zymography that LDHA downregulation impairs TNF-α-dependent tumor cell migration and significantly reduces TNF-α-induced MMP9 expression. These effects were associated with disturbances in the activation of the ERK1/2 signaling pathway, as we observed by Western blotting. We also reveal that in esophageal cancer cells, SO effectively reduces the production of lactic acid, which, as we have shown, synergizes the stimulating effect of TNF-α on MMP9 expression. In conclusion, our findings identified LDHA as a regulator of TNF-α-induced cell migration in esophageal cancer cells by the ERK1/2 signaling pathway, suggesting that LDHA inhibitors that limit the migration of cancer cells caused by the inflammatory process may be considered as an adjunct to standard therapy in esophageal cancer patients.


Assuntos
Neoplasias Esofágicas , Fator de Necrose Tumoral alfa , Humanos , Lactato Desidrogenase 5 , Fator de Necrose Tumoral alfa/farmacologia , L-Lactato Desidrogenase/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/farmacologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células
14.
Acta Cir Bras ; 37(8): e370805, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36515323

RESUMO

PURPOSE: To evaluate the impact of one-time high load exercise on skeletal muscle injury and analysis its mechanism in different genders. METHODS: Twenty-four male and 24 female rats were divided randomly into four groups respectively: control, 0 h, 6 h, and 24 h after exercise. The activities of creatine kinase (CK), lactate dehydrogenase (LDH), and myohemoglobin (MYO) in serum, the expression level of oxidative stress markers, mitochondrial respiratory chain complex enzyme, and the apoptosis related protein in quadriceps were detected. RESULTS: The results showed that the activities of CK, LDH and MYO in serum increased immediately after exercise and restored faster in female rats. More obvious structural disorder and apoptosis in male rats were showed. Malondialdehyde (MDA) and superoxide dismutase (SOD) were increased while catalase (CAT) and glutathione (GSH) were decreased in male rats. SOD, CAT and GSH were increased in female rats. Mitochondrial complex enzyme activity was decreased in males and increased in females. CONCLUSIONS: The skeletal muscle injury in both genders of rat could be induced by one-time high load exercise due to the mitochondrial respiratory enzyme dysfunction and oxidative stress, which was relatively mild and recovered quicker in female rats.


Assuntos
Músculo Esquelético , Estresse Oxidativo , Ratos , Feminino , Masculino , Animais , Músculo Esquelético/lesões , Malondialdeído/metabolismo , Superóxido Dismutase/metabolismo , Creatina Quinase , L-Lactato Desidrogenase , Glutationa/metabolismo
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(6): 1791-1796, 2022 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-36476905

RESUMO

OBJECTIVE: To explore the correlation between the changes of T lymphocyte subsets and cytokines in patients with MM and immune function status, biochemical indicators, and their relationships with clinical stage and prognosis, which is expected to provide a scientific basis for the prognosis analysis and condition monitoring of MM patients. METHODS: The clinical data of 89 MM patients in two hospitals were collected, and 36 healthy people without tumor or infectious diseases were selected as the control group. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) were used to detect the changes of core members of peripheral blood T lymphocyte subsets and cytokine levels, respectively. At the same time, automatic biochemical analyzer and automatic blood cell analyzer were used to detect serum ß2-microglobulin (ß2-MG), lactate dehydrogenase (LDH), albumin (ALB), creatinine (CRE) and hemoglobin (HGB) levels, and the relationship between T lymphocyte subsets and the above indexes and their clinical significance were analyzed. RESULTS: The proportions of NK cells and CD8+T lymphocytes in the peripheral blood of MM patients were significantly higher than that of the control group (P<0.01), the proportion of CD4+T and the ratio of CD4+/CD8+ were lower than those of the control group (P<0.05); however, there was no significant difference in the numbers CD3+T cells compared with the control group (P>0.05). The proportion of CD4+T and ratios of CD4+/CD8+ in MM patients were lower than those of normal controls, and were negatively correlated with MM staging (r=-0.964, r=-0.653), that is, the later the MM staging, the more obvious their levels were reduced, while CD8+T and NK cells were positively correlated with MM staging (r=0.891, r=0.728), that is, the later the MM staging, the more significant their levels increased. The levels of Treg cells (CD4+CD25highCD127low/-T cells/CD4+T cells) of MM patients in the disease stage Ⅰ, Ⅱ and Ⅲ were (5.87±0.92)%, (7.97±1.32)%, (11.52±4.71)% respectively, the difference was statistically significant compared with control group (P<0.05), and the level of Treg cells in MM patients with stage III was significantly higher than that in controls and patients with other disease stages (P<0.01). The proportion of Treg cells (CD4+CD25highCD127low/-T cells/CD4+T cells) in MM patients was positively correlated with the concentration of ß2-MG and LDH (r=0.793, r=0.536), but had no significant correlation with HGB, ALB and CRE. The serum levels of IL-6, IL-10 and TNF-α in MM patients were significantly higher than those in the control group (P<0.05), which were closely related to MM staging(r=0.839, r=0.917, r=0.746), that is, the later the MM staging, the higher the levels; The serum IFN-γ level was negatively correlated with the stage of MM (r=-0.689), and its level gradually decreased with the increase of the disease stage and degree (P<0.01). There was no significant correlation between the levels of IL-2 and IL-4 and the disease stage, but they were all up-regulated compared with the control group (P<0.05). CONCLUSION: The abnormal regulation of the core members of T lymphocyte subsets and the levels of various cytokines are closely related to the disease progression and poor prognosis of MM patients, which is an effective indicator for the disease monitoring of MM patients.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Citocinas , L-Lactato Desidrogenase , Subpopulações de Linfócitos T
16.
Molecules ; 27(23)2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36500643

RESUMO

The acidic tumor microenvironment (TME) is unfriendly to the activity and function of immune cells in the TME. Here, we report inorganic nanozymes (i.e., SnSe NSs) that mimic the catalytic activity of lactate dehydrogenase to degrade lactate to pyruvate, contributing to the metabolic treatment of tumors. As found in this study, SnSe NSs successfully decreased lactate levels in cells and tumors, as well as reduced tumor acidity. This is associated with activation of the immune response of T cells, thus alleviating the immunosuppressive environment of the TME. More importantly, the nanozyme successfully inhibited tumor growth in mutilate mouse tumor models. Thus, SnSe NSs show a promising result in lactate depletion and tumor suppression, which exemplifies its potential strategy in targeting lactate for metabolic therapy.


Assuntos
Neoplasias , Microambiente Tumoral , Camundongos , Animais , L-Lactato Desidrogenase/metabolismo , Neoplasias/metabolismo , Ácido Láctico/metabolismo , Ácidos
17.
Front Immunol ; 13: 1061544, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505495

RESUMO

Introduction: Neutrophils are critical for host immune defense; yet, aberrant neutrophil tissue infiltration triggers tissue damage. Neutrophils are heterogeneous functionally, and adopt 'normal' or 'pathogenic' effector function responses. Understanding neutrophil heterogeneity could provide specificity in targeting inflammation. We previously identified a signaling pathway that suppresses neutrophilmediated inflammation via integrin-mediated Rap1b signaling pathway. Methods: Here, we used Rap1-deficient neutrophils and proteomics to identify pathways that specifically control pathogenic neutrophil effector function. Results: We show neutrophil acidity is normally prevented by Rap1b during normal immune response with loss of Rap1b resulting in increased neutrophil acidity via enhanced Ldha activity and abnormal neutrophil behavior. Acidity drives the formation of abnormal invasive-like protrusions in neutrophils, causing a shift to transcellular migration through endothelial cells. Acidity increases neutrophil extracellular matrix degradation activity and increases vascular leakage in vivo. Pathogenic inflammatory condition of ischemia/reperfusion injury is associated with increased neutrophil transcellular migration and vascular leakage. Reducing acidity with lactate dehydrogenase inhibition in vivo limits tissue infiltration of pathogenic neutrophils but less so of normal neutrophils, and reduces vascular leakage. Discussion: Acidic milieu renders neutrophils more dependent on Ldha activity such that their effector functions are more readily inhibited by small molecule inhibitor of Ldha activity, which offers a therapeutic window for antilactate dehydrogenase treatment in specific targeting of pathogenic neutrophils in vivo.


Assuntos
Células Endoteliais , Neutrófilos , Humanos , Movimento Celular , Infiltração de Neutrófilos , Inflamação , L-Lactato Desidrogenase , Proteínas rap de Ligação ao GTP
18.
Artigo em Inglês | MEDLINE | ID: mdl-36498228

RESUMO

Tribulus terrestris L. (TT) ingredients have anti-inflammatory and antioxidant activities, but their effects on exercise-induced muscle damage (EIMD) in trained athletes are uncertain. The purpose of this single-blind placebo-controlled trial, in accordance with CONSORT guidelines, was to examine the effect of 6 weeks of TT supplementation on muscle metabolism, inflammation biomarkers, and oxidant status. Thirty trained male CrossFit® athletes were randomly assigned to be supplemented with 770 mg/day of TT (intervention group (IG)) or receive a placebo daily (control group (CG)) for 6 weeks. Muscle damage enzymes, inflammation biomarkers, and Total Antioxidant Status (TAS) were assessed at baseline (T1), 21 days after baseline (T2), and after 42 days (T3). Grace, a Workout of the Day, was measured in T1 and T3. Statistical significance (p < 0.05) was found between IG and CG in Lactate Dehydrogenase (LDH), C-reactive protein (CRP), and TAS levels at the end of the follow-up. Furthermore, TAS levels were significantly (p < 0.05) lower at T2 and T3 relative to baseline in the IG, also LDH and CRP increased significantly (p < 0.05) at T2 and T3 relative to baseline in the CG. No significant (p > 0.05) decreases in muscle damage or inflammation biomarkers were observed, although a slight downward trend was observed after 6 weeks for supplemented athletes. TT supplementation could attenuate the CrossFit® training program-induced oxidative stress, muscle damage, and inflammation which could be due to the natural antioxidant and anti-inflammatory properties of TT.


Assuntos
Suplementos Nutricionais , Músculos , Preparações de Plantas , Tribulus , Humanos , Masculino , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Biomarcadores , Inflamação/tratamento farmacológico , L-Lactato Desidrogenase , Músculos/metabolismo , Estresse Oxidativo , Método Simples-Cego , Atletas
19.
Nat Metab ; 4(12): 1830-1846, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36536137

RESUMO

The glycolytic enzyme lactate dehydrogenase A (LDHA) is frequently overexpressed in cancer, which promotes glycolysis and cancer. The oncogenic effect of LDHA has been attributed to its glycolytic enzyme activity. Here we report an unexpected noncanonical oncogenic mechanism of LDHA; LDHA activates small GTPase Rac1 to promote cancer independently of its glycolytic enzyme activity. Mechanistically, LDHA interacts with the active form of Rac1, Rac1-GTP, to inhibit Rac1-GTP interaction with its negative regulator, GTPase-activating proteins, leading to Rac1 activation in cancer cells and mouse tissues. In clinical breast cancer specimens, LDHA overexpression is associated with higher Rac1 activity. Rac1 inhibition suppresses the oncogenic effect of LDHA. Combination inhibition of LDHA enzyme activity and Rac1 activity by small-molecule inhibitors displays a synergistic inhibitory effect on breast cancers with LDHA overexpression. These results reveal a critical oncogenic mechanism of LDHA and suggest a promising therapeutic strategy for breast cancers with LDHA overexpression.


Assuntos
L-Lactato Desidrogenase , Neoplasias , Animais , Camundongos , Lactato Desidrogenase 5 , L-Lactato Desidrogenase/metabolismo , GTP Fosfo-Hidrolases , Isoenzimas/genética , Isoenzimas/metabolismo , Guanosina Trifosfato
20.
Biosensors (Basel) ; 12(12)2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36551112

RESUMO

The demand for glucose uptake and the accompanying enhanced glycolytic energy metabolism is one of the most important features of cancer cells. Unlike the aerobic metabolic pathway in normal cells, the large amount of pyruvate produced by the dramatic increase of glycolysis in cancer cells needs to be converted to lactate in the cytoplasm, which cannot be done without a large amount of lactate dehydrogenase (LDH). This explains why elevated serum LDH concentrations are usually seen in cancer patient populations. LDH not only correlates with clinical prognostic survival indicators, but also guides subsequent drug therapy. Besides their role in cancers, LDH is also a biomarker for malaria and other diseases. Therefore, it is urgent to develop methods for sensitive and convenient LDH detection. Here, this review systematically summarizes the clinical impact of lactate dehydrogenase detection and principles for LDH detection. The advantages as well as limitations of different detection methods and the future trends for LDH detection were also discussed.


Assuntos
L-Lactato Desidrogenase , Neoplasias , Humanos , L-Lactato Desidrogenase/metabolismo , Metabolismo Energético , Glicólise , Neoplasias/diagnóstico
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