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1.
Biosci Rep ; 44(4)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38567515

RESUMO

The complex metabolic relationship between the retinal pigment epithelium (RPE) and photoreceptors is essential for maintaining retinal health. Recent evidence indicates the RPE acts as an adjacent lactate sink, suppressing glycolysis in the epithelium in order to maximize glycolysis in the photoreceptors. Dysregulated metabolism within the RPE has been implicated in the pathogenesis of age-related macular degeneration (AMD), a leading cause of vision loss. In the present study, we investigate the effects of four cytokines associated with AMD, TNFα, TGF-ß2, IL-6, and IL-1ß, as well as a cocktail containing all four cytokines, on RPE metabolism using ARPE-19 cells, primary human RPE cells, and ex vivo rat eyecups. Strikingly, we found cytokine-specific changes in numerous metabolic markers including lactate production, glucose consumption, extracellular acidification rate, and oxygen consumption rate accompanied by increases in total mitochondrial volume and ATP production. Together, all four cytokines could potently override the constitutive suppression of glycolysis in the RPE, through a mechanism independent of PI3K/AKT, MEK/ERK, or NF-κB. Finally, we observed changes in glycolytic gene expression with cytokine treatment, including in lactate dehydrogenase subunit and glucose transporter expression. Our findings provide new insights into the metabolic changes in the RPE under inflammatory conditions and highlight potential therapeutic targets for AMD.


Assuntos
Degeneração Macular , Epitélio Pigmentado da Retina , Humanos , Ratos , Animais , Epitélio Pigmentado da Retina/metabolismo , 60645 , Citocinas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Degeneração Macular/genética , Degeneração Macular/metabolismo , Lactatos/metabolismo
2.
Ann Card Anaesth ; 27(2): 128-135, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38607876

RESUMO

INTRODUCTION: Extra Corporeal Membrane Oxygenation (ECMO) has long been used for cardiorespiratory support in the immediate post-paediatric cardiac surgery period with a 2-3% success as per the ELSO registry. Success in recovery depends upon the optimal delivery of critical care to paediatric patients and a comprehensive healthcare team. METHODOLOGY: The survival benefit of children placed on central veno arterial (VA) ECMO following elective cardiac surgeries for congenital heart disease (n = 672) was studied in a cohort of 29 (4.3%) cases from the period of Jan 2018 to Dec 2022 in our cardiac surgical centre. Indications for placing these patients on central VA ECMO included inability to wean from cardiopulmonary bypass (CPB), low cardiac output syndrome, severe pulmonary arterial hypertension, significant bleeding, anaphylaxis, respiratory failure and severe pulmonary edema. RESULTS: The mean time to initiation of ECMO was less than 5 h and the mean duration of ECMO support was 56 h with a survival rate of 58.3%. Amongst perioperative complications, sepsis and arrhythmia on ECMO were found to be negatively associated with survival. Improvements in the pH, PaO2 levels and serum lactate levels after initiation of ECMO were associated with survival benefits. CONCLUSION: The early initiation of ECMO for paediatric cardiotomies could be a beacon of hope for families and medical teams confronting these challenging situations. Improvement in indicators of adequate perfusion and ventricular recoveries like pH and serum lactate and absence of arrhythmia and sepsis are associated with good outcomes.


Assuntos
Oxigenação por Membrana Extracorpórea , Hipertensão Pulmonar , Sepse , Humanos , Criança , Arritmias Cardíacas , Poder Psicológico , Lactatos
3.
Clin Exp Pharmacol Physiol ; 51(6): e13855, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38636942

RESUMO

Cardiac microvascular endothelial cells (CMECs) are important cells surrounding the cardiomyocytes in the heart that maintain microenvironment homeostasis. Salvianic acid A sodium (SAAS) has been reported to prevent myocardial infarction (MI) injury. However, the role of SAAS on CMEC proliferation remains unclear. CEMCs exposed to oxygen glucose deprivation (OGD) were used to explore the angiogenic abilities of SAAS. In vivo, C57BL/6 mice were divided into three groups: sham, MI and SAAS + MI groups. Compared to OGD group, SAAS led to a reduction in the apoptotic rate and an increase of the proliferation in vitro. Additionally, SAAS increased the protein levels of Bcl2, HIF-1α and vascular endothelial growth factor (VEGF) with the reduction of Bax. In terms of the specific mechanisms, SAAS might inhibit HIF-1α ubiquitination and enhance the HIF-1α/VEGF signalling pathway to increase CMEC proliferation. Furthermore, SAAS increased the density of vessels, inhibited myocardial fibrosis and improved cardiac dysfunction in vivo. The present study has revealed that SAAS could potentially be used as an active substance to facilitate CMEC proliferation post-MI.


Assuntos
Lactatos , Infarto do Miocárdio , Fator A de Crescimento do Endotélio Vascular , Camundongos , Animais , Células Endoteliais/metabolismo , Sódio/metabolismo , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Proliferação de Células , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
4.
Food Microbiol ; 121: 104513, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38637075

RESUMO

Saccharomyces cerevisiae is a major actor in winemaking that converts sugars from the grape must into ethanol and CO2 with outstanding efficiency. Primary metabolites produced during fermentation have a great importance in wine. While ethanol content contributes to the overall profile, other metabolites like glycerol, succinate, acetate or lactate also have significant impacts, even when present in lower concentrations. S. cerevisiae is known for its great genetic diversity that is related to its natural or technological environment. However, the variation range of metabolic diversity which can be exploited to enhance wine quality depends on the pathway considered. Our experiment assessed the diversity of primary metabolites production in a set of 51 S. cerevisiae strains from various genetic backgrounds. Results pointed out great yield differences depending on the metabolite considered, with ethanol having the lowest variation. A negative correlation between ethanol and glycerol was observed, confirming glycerol synthesis as a suitable lever to reduce ethanol yield. Genetic groups were linked to specific yields, such as the wine group and high α-ketoglutarate and low acetate yields. This research highlights the potential of using natural yeast diversity in winemaking. It also provides a detailed data set on production of well known (ethanol, glycerol, acetate) or little-known (lactate) primary metabolites.


Assuntos
Saccharomyces cerevisiae , Vinho , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Vinho/análise , Fermentação , Glicerol/metabolismo , Carbono/metabolismo , Etanol/metabolismo , Acetatos/metabolismo , Lactatos
5.
Cancer Res ; 84(7): 950-952, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558131

RESUMO

Acute myeloid leukemia (AML) is one of the most prevalent blood cancers, characterized by a dismal survival rate. This poor outcome is largely attributed to AML cells that persist despite treatment and eventually result in relapse. Relapse-initiating cells exhibit diverse resistance mechanisms, encompassing genetic factors and, more recently discovered, nongenetic factors such as metabolic adaptations. Leukemic stem cells (LSC) rely on mitochondrial metabolism for their survival, whereas hematopoietic stem cells primarily depend on glycolysis. Furthermore, following treatments such as cytarabine, a standard in AML treatment for over four decades, drug-persisting leukemic cells exhibit an enhanced reliance on mitochondrial metabolism. In this issue of Cancer Research, two studies investigated dependencies of AML cells on two respiratory substrates, α-ketoglutarate and lactate-derived pyruvate, that support mitochondrial oxidative phosphorylation (OXPHOS) following treatment with the imipridone ONC-213 and the BET inhibitor INCB054329, respectively. Targeting lactate utilization by interfering with monocarboxylate transporter 1 (MCT1 or SLC16A1) or lactate dehydrogenase effectively sensitized cells to BET inhibition in vitro and in vivo. In addition, ONC-213 affected αKGDH, a pivotal NADH-producing enzyme of the TCA cycle, to induce a mitochondrial stress response through ATF4 activation that diminished the expression of the antiapoptotic protein MCL1, consequently promoting apoptosis of AML cells. In summary, targeting these mitochondrial dependencies might be a promising strategy to kill therapy-naïve and treatment-resistant OXPHOS-reliant LSCs and to delay or prevent relapse. See related articles by Monteith et al., p. 1101 and Su et al., p. 1084.


Assuntos
Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/genética , Citarabina/farmacologia , Ciclo do Ácido Cítrico , Lactatos , Recidiva
6.
Vet Med Sci ; 10(3): e1434, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38567942

RESUMO

BACKGROUND: No tick-borne pathogens (TBPs) causing haemolytic anaemia in cattle have been reported, except Theileria orientalis and complete blood count (CBC) profile is the only haematological parameter to determine the severity of regenerative haemolytic anaemia. OBJECTIVES: To identify the causative agents of TBP-induced haemolytic anaemia and determine haematological parameters that indicate haemolytic anaemia in grazing cattle. METHODS: Eighty-two Korean indigenous cattle (Hanwoo) were divided into two groups: grazing (n = 67) and indoor (n = 15) groups. CBC and serum biochemistry were performed. PCR was conducted using whole blood-extracted DNA to investigate the prevalence of TBPs. RESULTS: TBP-induced haemolytic anaemia was observed in the grazing group. In grazing cattle, co-infection (43.3%, 29/67) was most frequently detected, followed by T. orientalis (37.6%, 25/67) and Anaplasma phagocytophilum infections (1.5%, 1/67). In indoor cattle, only co-infection (20%, 3/15) was identified. Grazing cattle exhibited regenerative haemolytic anaemia with marked monocytosis, mild neutropenia, and thrombocytopenia. According to grazing frequency, the 1st-time grazing group had more severe anaemia than the 2nd-time grazing group. Elevations in indirect bilirubin and L-lactate due to haemolytic anaemia were identified, and correlations with the respective markers were determined in co-infected grazing cattle. CONCLUSIONS: Quantitative evaluation of haematocrit, mean corpuscular volume, and reticulocytes (markers of regenerative haemolytic anaemia in cattle) was performed for the first time. Our results show that, in addition to T. orientalis, A. phagocytophilum is strongly associated with anaemia. The correlation between haemolytic anaemia severity and haematological parameters (indirect bilirubin, reticulocytes, and L-lactate) was confirmed.


Assuntos
Anemia Hemolítica , Doenças dos Bovinos , Coinfecção , Theileriose , Carrapatos , Bovinos , Animais , Theileriose/epidemiologia , Doenças dos Bovinos/epidemiologia , Coinfecção/veterinária , Anemia Hemolítica/etiologia , Anemia Hemolítica/veterinária , Bilirrubina , Lactatos
7.
Sci Rep ; 14(1): 8507, 2024 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-38605071

RESUMO

While cellular metabolism was proposed to be a driving factor of the activation and differentiation of B cells and the function of the resulting antibody-secreting cells (ASCs), the study of correlations between cellular metabolism and functionalities has been difficult due to the absence of technologies enabling the parallel measurement. Herein, we performed single-cell transcriptomics and introduced a direct concurrent functional and metabolic flux quantitation of individual murine B cells. Our transcriptomic data identified lactate metabolism as dynamic in ASCs, but antibody secretion did not correlate with lactate secretion rates (LSRs). Instead, our study of all splenic B cells during an immune response linked increased lactate metabolism with acidic intracellular pH and the upregulation of apoptosis. T cell-dependent responses increased LSRs, and added TLR4 agonists affected the magnitude and boosted LSRhigh B cells in vivo, while resulting in only a few immunoglobulin-G secreting cells (IgG-SCs). Therefore, our observations indicated that LSRhigh cells were not differentiating into IgG-SCs, and were rather removed due to apoptosis.


Assuntos
Células Produtoras de Anticorpos , Linfócitos B , Animais , Camundongos , Apoptose , Imunoglobulina G/metabolismo , Lactatos/metabolismo
8.
J Cancer Res Clin Oncol ; 150(4): 199, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627278

RESUMO

PURPOSE: Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant and fatal liver tumor with increasing incidence worldwide. Lactate metabolism has been recently reported as a crucial contributor to tumor progression and immune regulation in the tumor microenvironment. However, it remains poorly identified about the biological functions of lactate metabolism in iCCA, which hinders the development of prognostic tools and therapeutic interventions. METHODS: The univariate Cox regression analysis and Boruta algorithm were utilized to identify key lactate metabolism-related genes (LMRGs), and a prognostic signature was constructed based on LMRG scores. Genomic variations and immune cell infiltration were evaluated in the high and low LMRG score groups. Finally, the biological functions of key LMRGs were verified with in vitro and in vivo experiments. RESULTS: Patients in the high LMRG score group exhibit a poor prognosis compared to those in the low LMRG score group, with a high frequency of TP53 and KRAS mutations. Moreover, the infiltration and function of NK cells were compromised in the high LMRG score group, consistent with the results from two independent single-cell RNA sequencing datasets and immunohistochemistry of tissue microarrays. Experimental data revealed that lactate dehydrogenase A (LDHA) knockdown inhibited proliferation and migration in iCCA cell lines and tumor growth in immunocompetent mice. CONCLUSION: Our study revealed the biological roles of LDHA in iCCA and developed a reliable lactate metabolism-related prognostic signature for iCCA, offering promising therapeutic targets for iCCA in the clinic.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Animais , Camundongos , Prognóstico , Colangiocarcinoma/genética , Lactato Desidrogenase 5 , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos , Lactatos , Microambiente Tumoral/genética
9.
J Vis Exp ; (205)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38587369

RESUMO

Over the recent decades, the development of animal models allowed us to better understand various pathologies and identify new treatments. Hemorrhagic shock, i.e., organ failure due to rapid loss of a large volume of blood, is associated with a highly complex pathophysiology involving several pathways. Numerous existing animal models of hemorrhagic shock strive to replicate what happens in humans, but these models have limits in terms of clinical relevance, reproducibility, or standardization. The aim of this study was to refine these models to develop a new model of hemorrhagic shock. Briefly, hemorrhagic shock was induced in male Wistar Han rats (11-13 weeks old) by a controlled exsanguination responsible for a drop in the mean arterial pressure. The next phase of 75 min was to maintain a low mean arterial blood pressure, between 32 mmHg and 38 mmHg, to trigger the pathophysiological pathways of hemorrhagic shock. The final phase of the protocol mimicked patient care with an administration of intravenous fluids, Ringer Lactate solution, to elevate the blood pressure. Lactate and behavioral scores were assessed 16 h after the protocol started, while hemodynamics parameters and plasmatic markers were evaluated 24 h after injury. Twenty-four hours post-hemorrhagic shock induction, the mean arterial and diastolic blood pressure were decreased in the hemorrhagic shock group (p < 0.05). Heart rate and systolic blood pressure remained unchanged. All organ damage markers were increased with the hemorrhagic shock (p < 0.05). The lactatemia and behavioral scores were increased compared to the sham group (p < 0.05). In conclusion, we demonstrated that the protocol described here is a relevant model of hemorrhagic shock that can be used in subsequent studies, particularly to evaluate the therapeutic potential of new molecules.


Assuntos
Choque Hemorrágico , Ratos , Masculino , Humanos , Animais , Ratos Wistar , Reprodutibilidade dos Testes , Ressuscitação/métodos , Soluções Isotônicas/uso terapêutico , Lactatos , Modelos Animais de Doenças
10.
Arq Bras Cardiol ; 121(2): e20230247, 2024.
Artigo em Português, Inglês | MEDLINE | ID: mdl-38597532

RESUMO

BACKGROUND: Cardiac surgery patients may be exposed to tissue hypoperfusion and anaerobic metabolism. OBJECTIVE: To verify whether the biomarkers of tissue hypoperfusion have predictive value for prolonged intensive care unit (ICU) stay in patients with left ventricular dysfunction who underwent coronary artery bypass surgery. METHODS: After approval by the institution's Ethics Committee and the signing of informed consent, 87 patients with left ventricular dysfunction (ejection fraction < 50%) undergoing coronary artery bypass surgery were enrolled. Hemodynamic and metabolic biomarkers were collected at five time points: after anesthesia, at the end of the surgery, at ICU admission, and at six and twelve hours after. An analysis of variance for repeated measures followed by a Bonferroni post hoc test was used for repeated, continuous variables (hemodynamic and metabolic variables) to determine differences between the two groups over the course of the study period. The level of statistical significance adopted was 5%. RESULTS: Thirty-eight patients (43.7%) who presented adverse outcomes were older, higher Euro score (p<0.001), and elevated ΔpCO2 as analyzed 12 hours after ICU admission (p<0.01), while increased arterial lactate concentration at 6 hours postoperatively was found to be a negative predictive factor (p<0.01). CONCLUSIONS: Euro SCORE, six-hour postoperative arterial lactate, 12-hour postoperative ΔPCO2, and eRQ are independent predictors of adverse outcomes in patients with left ventricular dysfunction after cardiac surgery.


FUNDAMENTO: Pacientes submetidos à cirurgia cardíaca podem estar expostos à hipoperfusão tecidual e metabolismo anaeróbico. OBJETIVO: Verificar se os biomarcadores de hipoperfusão tecidual têm valor preditivo para permanência prolongada na Unidade de Terapia Intensiva (UTI) em pacientes com disfunção ventricular esquerda submetidos à cirurgia de bypass da artéria coronária. MÉTODOS: Após aprovação pelo comitê de ética institucional e assinatura do termo de consentimento, 87 pacientes com disfunção ventricular esquerda (fração de ejeção <50%) submetidos à cirurgia de bypass coronário foram incluídos. Biomarcadores hemodinâmicos e metabólicos foram coletados em cinco momentos: após anestesia, ao final da cirurgia, na admissão na UTI, e a seis e 12 horas depois. Uma análise de variância para medidas repetidas seguida de um teste post-hoc de Bonferroni foi usado para variáveis contínuas repetidas (variáveis metabólicas e hemodinâmicas) para determinar diferenças entre os dois grupos ao longo do estudo. O nível de significância adotado foi de 5%. RESULTADOS: Trinta e oito pacientes (43,7%) que apresentaram desfechos adversos eram mais velhos, apresentaram um Euroscore mais alto (p<0,001), e gradiente venoarterial de CO2 (ΔPCO2) elevado, analisados 12 horas após a admissão na UTI (p<0,01), enquanto uma concentração de lactato arterial aumentada seis horas após a cirurgia foi um fator preditivo negativo (p<0,01). CONCLUSÕES: EuroSCORE, lactato arterial seis horas após a cirurgia, ΔPCO212 horas após a cirurgia e QRe são preditores independentes de desfechos adversos em pacientes com disfunção ventricular esquerda após cirurgia cardíaca.


Assuntos
Ponte de Artéria Coronária , Disfunção Ventricular Esquerda , Humanos , Ponte de Artéria Coronária/efeitos adversos , Disfunção Ventricular Esquerda/etiologia , Perfusão , Biomarcadores , Lactatos
11.
BMC Anesthesiol ; 24(1): 130, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580909

RESUMO

BACKGROUND: Skin mottling is a common manifestation of peripheral tissue hypoperfusion, and its severity can be described using the skin mottling score (SMS). This study aims to evaluate the value of the SMS in detecting peripheral tissue hypoperfusion in critically ill patients following cardiac surgery. METHODS: Critically ill patients following cardiac surgery with risk factors for tissue hypoperfusion were enrolled (n = 373). Among these overall patients, we further defined a hypotension population (n = 178) and a shock population (n = 51). Hemodynamic and perfusion parameters were recorded. The primary outcome was peripheral hypoperfusion, defined as significant prolonged capillary refill time (CRT, > 3.0 s). The characteristics and hospital mortality of patients with and without skin mottling were compared. The area under receiver operating characteristic curves (AUROC) were used to assess the accuracy of SMS in detecting peripheral hypoperfusion. Besides, the relationships between SMS and conventional hemodynamic and perfusion parameters were investigated, and the factors most associated with the presence of skin mottling were identified. RESULTS: Of the 373-case overall population, 13 (3.5%) patients exhibited skin mottling, with SMS ranging from 1 to 5 (5, 1, 2, 2, and 3 cases, respectively). Patients with mottling had lower mean arterial pressure, higher vasopressor dose, less urine output (UO), higher CRT, lactate levels and hospital mortality (84.6% vs. 12.2%, p < 0.001). The occurrences of skin mottling were higher in hypotension population and shock population, reaching 5.6% and 15.7%, respectively. The AUROC for SMS to identify peripheral hypoperfusion was 0.64, 0.68, and 0.81 in the overall, hypotension, and shock populations, respectively. The optimal SMS threshold was 1, which corresponded to specificities of 98, 97 and 91 and sensitivities of 29, 38 and 67 in the three populations (overall, hypotension and shock). The correlation of UO, lactate, CRT and vasopressor dose with SMS was significant, among them, UO and CRT were identified as two major factors associated with the presence of skin mottling. CONCLUSION: In critically ill patients following cardiac surgery, SMS is a very specific yet less sensitive parameter for detecting peripheral tissue hypoperfusion.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Hipotensão , Choque Séptico , Humanos , Estado Terminal , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Hipotensão/diagnóstico , Hipotensão/complicações , Lactatos
12.
Eur Radiol Exp ; 8(1): 46, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38594558

RESUMO

BACKGROUND: Monitoring pyruvate metabolism in the spleen is important for assessing immune activity and achieving successful radiotherapy for cervical cancer due to the significance of the abscopal effect. We aimed to explore the feasibility of utilizing hyperpolarized (HP) [1-13C]-pyruvate magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to evaluate pyruvate metabolism in the human spleen, with the aim of identifying potential candidates for radiotherapy in cervical cancer. METHODS: This prospective study recruited six female patients with cervical cancer (median age 55 years; range 39-60) evaluated using HP [1-13C]-pyruvate MRI/MRS at baseline and 2 weeks after radiotherapy. Proton (1H) diffusion-weighted MRI was performed in parallel to estimate splenic cellularity. The primary outcome was defined as tumor response to radiotherapy. The Student t-test was used for comparing 13C data between the groups. RESULTS: The splenic HP [1-13C]-lactate-to-total carbon (tC) ratio was 5.6-fold lower in the responders than in the non-responders at baseline (p = 0.009). The splenic [1-13C]-lactate-to-tC ratio revealed a 1.7-fold increase (p = 0.415) and the splenic [1-13C]-alanine-to-tC ratio revealed a 1.8-fold increase after radiotherapy (p = 0.482). The blood leukocyte differential count revealed an increased proportion of neutrophils two weeks following treatment, indicating enhanced immune activity (p = 0.013). The splenic apparent diffusion coefficient values between the groups were not significantly different. CONCLUSIONS: This exploratory study revealed the feasibility of HP [1-13C]-pyruvate MRS of the spleen for evaluating baseline immune potential, which was associated with clinical outcomes of cervical cancer after radiotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04951921 , registered 7 July 2021. RELEVANCE STATEMENT: This prospective study revealed the feasibility of using HP 13C MRI/MRS for assessing pyruvate metabolism of the spleen to evaluate the patients' immune potential that is associated with radiotherapeutic clinical outcomes in cervical cancer. KEY POINTS: • Effective radiotherapy induces abscopal effect via altering immune metabolism. • Hyperpolarized 13C MRS evaluates patients' immune potential non-invasively. • Pyruvate-to-lactate conversion in the spleen is elevated following radiotherapy.


Assuntos
Ácido Pirúvico , Neoplasias do Colo do Útero , Humanos , Feminino , Pessoa de Meia-Idade , Ácido Pirúvico/metabolismo , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia , Estudos Prospectivos , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13/métodos , Lactatos
13.
Mol Biol Rep ; 51(1): 503, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38600404

RESUMO

BACKGROUND: Komagataeibacter nataicola (K. nataicola) is a gram-negative acetic acid bacterium that produces natural bacterial cellulose (BC) as a fermentation product under acidic conditions. The goal of this work was to study the complete genome of K. nataicola and gain insight into the functional genes in K. nataicola that are responsible for BC synthesis in acidic environments. METHODS AND RESULT: The pure culture of K. nataicola was obtained from yeast-glucose-calcium carbonate (YGC) agar, followed by genomic DNA extraction, and subjected to whole genome sequencing on a Nanopore flongle flow cell. The genome of K. nataicola consists of a 3,767,936 bp chromosome with six contigs and 4,557 protein coding sequences. The maximum likelihood phylogenetic tree and average nucleotide identity analysis confirmed that the bacterial isolate was K. nataicola. The gene annotation via RAST server discovered the presence of cellulose synthase, along with three genes associated with lactate utilization and eight genes involved in lactate fermentation that could potentially contribute to the increase in acid concentration during BC synthesis. CONCLUSION: A more comprehensive genome study of K. nataicola may shed light into biological pathway in BC productivity as well as benefit the analysis of metabolites generated and understanding of biological and chemical interactions in BC production later.


Assuntos
Acetobacteraceae , 60659 , Eliminação de Resíduos , Celulose/metabolismo , Filogenia , Alimentos , Sequenciamento Completo do Genoma , Lactatos
14.
Molecules ; 29(7)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38611749

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with a high degree of malignancy and poor prognosis. Tumor-associated macrophages (TAMs) have been identified as significant contributors to the growth and metastasis of TNBC through the secretion of various growth factors and chemokines. Salvianolic acid A (SAA) has been shown to have anti-cancer activities. However, the potential activity of SAA on re-polarized TAMs remains unclear. As there is a correlation between the TAMs and TNBC, this study investigates the effect of SAA on TAMs in the TNBC microenvironment. For that purpose, M2 TAM polarization was induced by two kinds of TNBC-conditioned medium (TNBC-TCM) in the absence or presence of SAA. The gene and protein expression of TAM markers were analyzed by qPCR, FCM, IF, ELISA, and Western blot. The protein expression levels of ERK and p-ERK in M2-like TAMs were analyzed by Western blot. The migration and invasion properties of M2-like TAMs were analyzed by Transwell assays. Here, we demonstrated that SAA increased the expression levels of CD86, IL-1ß, and iNOS in M2-like TAMs and, conversely, decreased the expression levels of Arg-1 and CD206. Moreover, SAA inhibited the migration and invasion properties of M2-like TAMs effectively and decreased the protein expression of TGF-ß1 and p-ERK in a concentration-dependent manner, as well as TGF-ß1 gene expression and secretion. Our current findings for the first time demonstrated that SAA inhibits macrophage polarization to M2-like TAMs by inhibiting the ERK pathway and promotes M2-like TAM re-polarization to the M1 TAMs, which may exert its anti-tumor effect by regulating M1/M2 TAM polarization. These findings highlight SAA as a potential regulator of M2 TAMs and the possibility of utilizing SAA to reprogram M2 TAMs offers promising insights for the clinical management of TNBC.


Assuntos
Ácidos Cafeicos , Lactatos , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Fator de Crescimento Transformador beta1 , Microambiente Tumoral , Macrófagos Associados a Tumor
15.
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
16.
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
17.
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
18.
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
19.
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
20.
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
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