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1.
Arch Cardiovasc Dis ; 115(1): 48-56, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34972639

RESUMO

Great attention is being paid to the evaluation of new markers in blood circulation for the estimation of tissue metabolism disturbance. This endogenous disturbance may contribute to the onset and progression of cardiometabolic disease. In addition to their role in energy production and metabolism, mitochondria play a main function in cellular mechanisms, including apoptosis, oxidative stress and calcium homeostasis. Mitochondria produce mitochondrial-derived peptides that mediate the transcriptional stress response by translocating into the nucleus and interacting with deoxyribonucleic acid. This class of peptides includes humanin, mitochondrial open reading frame of the 12S ribosomal ribonucleic acid type c (MOTS-c) and small humanin-like peptides. Mitochondrial-derived peptides are regulators of metabolism, exerting cytoprotective effects through antioxidative stress, anti-inflammatory responses and antiapoptosis; they are emerging biomarkers reflecting mitochondrial function, and the circulating concentration of these proteins can be used to diagnose cardiometabolic dysfunction. The aims of this review are: (1) to describe the emerging role for mitochondrial-derived peptides as biomarkers; and (2) to discuss the therapeutic application of these peptides.


Assuntos
Doenças Cardiovasculares , Mitocôndrias , Biomarcadores/metabolismo , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/metabolismo , Humanos , Mitocôndrias/metabolismo , Estresse Oxidativo , Peptídeos/metabolismo
2.
BMC Genomics ; 23(1): 47, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35016605

RESUMO

BACKGROUND: Cardiomyopathy is a complex type of myocardial disease, and its incidence has increased significantly in recent years. Dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) are two common and indistinguishable types of cardiomyopathy. RESULTS: Here, a systematic multi-omics integration approach was proposed to identify cardiomyopathy-related core genes that could distinguish normal, DCM and ICM samples using cardiomyopathy expression profile data based on a human metabolic network. First, according to the differentially expressed genes between different states (DCM/ICM and normal, or DCM and ICM) of samples, three sets of initial modules were obtained from the human metabolic network. Two permutation tests were used to evaluate the significance of the Pearson correlation coefficient difference score of the initial modules, and three candidate modules were screened out. Then, a cardiomyopathy risk module that was significantly related to DCM and ICM was determined according to the significance of the module score based on Markov random field. Finally, based on the shortest path between cardiomyopathy known genes, 13 core genes related to cardiomyopathy were identified. These core genes were enriched in pathways and functions significantly related to cardiomyopathy and could distinguish between samples of different states. CONCLUSION: The identified core genes might serve as potential biomarkers of cardiomyopathy. This research will contribute to identifying potential biomarkers of cardiomyopathy and to distinguishing different types of cardiomyopathy.


Assuntos
Cardiomiopatias , Cardiomiopatia Dilatada , Isquemia Miocárdica , Biomarcadores/metabolismo , Cardiomiopatias/genética , Cardiomiopatia Dilatada/genética , Humanos , Redes e Vias Metabólicas/genética
3.
Ecotoxicol Environ Saf ; 229: 113084, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34915223

RESUMO

The deficiency of effective biomarker for the toxic effects of water pollutants greatly limits the application of biological monitoring. This study aimed to investigate the possibility of circulating exosomes of indigenous fish acting as biomarker for the ecotoxicity effect of water environment. The Helong Reservoir in Guangzhou, China, was chosen as the investigating field, of which the water quality belongs to Class V (2013) (GB 3838-2002, China). The clean drinking water source of the upper reaches of the Liuxihe Reservoir was selected as the control. Indigenous fishes including Oreochromis niloticus (Nile tilapia), Labeo rohita (Rohu), Carassius auratus (Crucian carp) were sampled during the period from July 2020 to April 2021. Circulating exosomes of fish samples were isolated by using ultracentrifugation, characterized with transmission electron microscopy (TEM) and quantified by using bicinchoninic acid (BCA) assay. Oxidative stress, DNA and chromosome damage in liver, kidney, brain, gill and blood of fish samples were measured. The results showed that there were significant differences in superoxide dismutase (SOD) activity, glutathione (GSH) and malondialdehyde (MDA) contents, DNA and chromosome damage in fish samples between the Helong Reservoir and the control. Interestingly, there were also significant differences in circulating exosome levels of fish samples between them. Our data suggested that circulating exosome level of indigenous fish may be a novel biomarker for the ecotoxicity effects of water environment.


Assuntos
Ciclídeos , Exossomos , Poluentes Químicos da Água , Animais , Biomarcadores/metabolismo , Ciclídeos/metabolismo , Carpa Dourada/metabolismo , Fígado/metabolismo , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade
4.
Life Sci ; 289: 120227, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34921866

RESUMO

BACKGROUND: Ischemic kidney injury is a common clinical condition resulting from transient interruption of the kidney's normal blood flow, leading to oxidative stress, inflammation, and kidney dysfunction. The ketogenic diet (KD), a low-carbohydrate, high-fat diet that stimulates endogenous ketone body production, has potent antioxidant and anti-inflammatory effects in distinct tissues and might thus protect the kidney against ischemia and reperfusion (IR) injury. MAIN METHODS: Male Wistar rats were fed a KD or a control diet (CD) for three days before analyzing metabolic parameters or testing nephroprotection. We used two different models of kidney IR injury and conducted biochemical, histological, and Western blot analyses at 24 h and two weeks after surgery. KEY FINDINGS: Acute KD feeding caused protein acetylation, liver AMPK activation, and increased resistance to IR-induced kidney injury. At 24 h after IR, rats on KD presented reduced tubular damage and improved kidney functioning compared to rats fed with a CD. KD attenuated oxidative damage (protein nitration, 4-HNE adducts, and 8-OHdG), increased antioxidant defenses (GPx and SOD activity), and reduced inflammatory intermediates (IL6, TNFα, MCP1), p50 NF-κB expression, and cellular infiltration. Also, KD prevented interstitial fibrosis development at two weeks, up-regulation of HSP70, and chronic Klotho deficiency. SIGNIFICANCE: Our findings demonstrate for the first time that short-term KD increases tolerance to experimental kidney ischemia, opening the opportunity for future therapeutic exploration of a dietary preconditioning strategy to convey kidney protection in the clinic.


Assuntos
Dieta Cetogênica , Regulação da Expressão Gênica , Estresse Oxidativo , Insuficiência Renal Crônica , Animais , Biomarcadores/metabolismo , Inflamação/dietoterapia , Inflamação/metabolismo , Inflamação/patologia , Isquemia/dietoterapia , Isquemia/metabolismo , Isquemia/patologia , Masculino , Ratos , Ratos Wistar , Insuficiência Renal Crônica/dietoterapia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia
5.
Gene ; 808: 145997, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34626720

RESUMO

This paper reviews theory of DNB (Dynamical Network Biomarkers) and its applications including both modern medicine and traditional medicine. We show that omics data such as gene/protein expression profiles can be effectively used to detect pre-disease states before critical transitions from healthy states to disease states by using the DNB theory. The DNB theory with big biological data is expected to lead to ultra-early precision and preventive medicine.


Assuntos
Progressão da Doença , Doença/genética , Redes Reguladoras de Genes/genética , Algoritmos , Biomarcadores/análise , Biomarcadores/metabolismo , Perfilação da Expressão Gênica/métodos , Genômica/métodos , Humanos , Proteômica/métodos , Fatores de Tempo
6.
Chemosphere ; 287(Pt 1): 132120, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34523462

RESUMO

Water environmental pollution caused by spent batteries is a nonignorable environmental issue. In this study, the early life stage of zebrafish was employed to assess the environmental risk of spent batteries after exposure to 0, 1%, 2%, 5% and 10% spent battery extract for 120 h. Our results clearly indicated that spent battery extract can significantly decrease the survival rate, hatching rate and body length and increase heart rate. Moreover, spent battery extract exposure-induced zebrafish larvae generate oxidative stress and inhibit the mRNA transcriptional levels of heat shock protein (HSP70) and metallothionein (MT) genes. These results showed that the spent batteries not only affected the survival and development performance of zebrafish at an early life stage but also caused oxidative stress and interfered with the detoxification of zebrafish. This study provided novel insight into spent battery induced toxicity in the early life stage of fish.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Biomarcadores/metabolismo , Embrião não Mamífero/metabolismo , Larva , Estresse Oxidativo , Extratos Vegetais , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade
7.
Sci Total Environ ; 806(Pt 1): 150369, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34571231

RESUMO

In coastal systems, pollutants as pharmaceutical drugs exert changes from the molecular to the organism level in marine bivalves. Besides pollutants, coastal systems are prone to changes in environmental parameters, as the alteration of salinity values because of Climate Change. Together, these stressors (pharmaceutical drugs and salinity changes) can exert different threats than each stressor acting individually; for example, salinity can change the physical-chemical properties of the drugs and/or the sensitivity of the organisms to them. However, limited information is available on this subject, with variable results, and for this reason, this study aimed to evaluate the impacts of salinity changes (15, 25 and 35) on the effects of the antiepileptic carbamazepine (CBZ, 1 µg/L) and the antihistamine cetirizine (CTZ, 0.6 µg/L), when acting individually and combined (CBZ + CTZ), in the edible clam Ruditapes philippinarum. After 28 days of exposure, drugs concentrations, bioconcentration factors and biochemical parameters, related to clam's metabolic capacity and oxidative stress were evaluated. The results showed that clams under low salinity suffered more changes in metabolic, antioxidant and biotransformation activities, in comparison with the remaining salinities under study. However, limited impacts were observed when comparing drug effects at low salinity. Indeed, it seemed that CTZ and CBZ + CTZ, under high salinity (salinity 35) were the worst exposure conditions for the clams, since they caused higher levels of cellular damage. It stands out that salinity changes altered the impact of pharmaceutical drugs on marine bivalves.


Assuntos
Bivalves , Preparações Farmacêuticas , Poluentes Químicos da Água , Animais , Anticonvulsivantes , Biomarcadores/metabolismo , Bivalves/metabolismo , Antagonistas dos Receptores Histamínicos , Estresse Oxidativo , Salinidade , Poluentes Químicos da Água/toxicidade
8.
Chemosphere ; 287(Pt 4): 132356, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34600009

RESUMO

Nanoplastics (NP) (1-100 nm) are a growing global concern, and their adverse effects in marine organisms are still scarce. This study evaluated the effects of polystyrene nanoplastics (10 µg/L; 50 nm nPS) in the marine mussel Mytilus galloprovincialis after a 21 - day exposure. The hydrodynamic diameter and zeta potential of nPS were analysed, over time, in seawater and ultrapure water. A multibiomarker approach (genotoxicity (the comet assay) was assessed in mussel haemocytes, and the antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)), biotransformation enzyme (glutathione - S - transferase (GST)), and oxidative damage (LPO)) was assessed in gills and digestive glands to evaluate the toxicity of nPS towards mussels. In seawater, aggregation of nPS is favoured and consequently the hydrodynamic diameter increases. Genotoxicity was highly noticeable in mussels exposed to nPS, presenting a higher % tail DNA when compared to controls. Antioxidant enzymes are overwhelmed after nPS exposure, leading to oxidative damage in both tissues. Results showed that mussel tissues are incapable of dealing with the effects that this emerging stressor pursues towards the organism. The Integrated Biomarker Response index, used to summarise the biomarkers analysed into one index, shows that nPS toxicity towards mussels are both tissue and time dependent, being that gills are the tissue most compromised.


Assuntos
Mytilus , Nanopartículas , Poluentes Químicos da Água , Animais , Biomarcadores/metabolismo , Brânquias/metabolismo , Mytilus/metabolismo , Nanopartículas/toxicidade , Estresse Oxidativo , Poliestirenos/metabolismo , Poliestirenos/toxicidade , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade
9.
Cytokine ; 149: 155755, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34773859

RESUMO

This study analyzed the levels at admission of biomarkers for their association with and ability to predict risk of severe outcomes, including admission to the ICU, need for invasive mechanical ventilation (IMV), need for vasopressor use (VU), and in-hospital mortality (IHM) in 700 patients hospitalized with COVID-19. Biomarker data split by outcomes was compared using Mann-Whitney U tests; frequencies of biomarker values were compared using Chi-square tests and multivariable logistic regression analysis was performed to look at the impact of biomarkers by outcome. Patients that suffered IHM were more likely to have reduced platelet numbers and high blood urea nitrogen (BUN) levels among patients admitted to the ICU. Risk factors for mortality were related to hyper-coagulability (low platelet count and increased D-dimer) and decreased respiratory (PaO2/FiO2 ratio) and kidney function (BUN). Association with risks of other severe outcomes were as follows: ICU with hyper-inflammation (IL-6) and decreased respiratory function; IMV with low platelet count, abnormal neutrophil-lymphocyte ratio with reduced respiratory function, VU with inflammatory markers (IL-6), and low platelet count with respiratory function. Our studies confirmed the association of biomarkers of hematological, inflammatory, coagulation, pulmonary and kidney functions with disease severity. Whether these biomarkers have any mechanistic or causal role in the disease progress requires further investigation.


Assuntos
Biomarcadores/metabolismo , COVID-19/metabolismo , COVID-19/patologia , Idoso , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Inflamação/metabolismo , Inflamação/patologia , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença
10.
Am J Surg Pathol ; 46(1): 89-96, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34081038

RESUMO

Approximately 20% of patients with symptomatic syndrome-associated coronavirus-2 (SARS-CoV-2) infection have gastrointestinal bleeding and/or diarrhea. Most are managed without endoscopic evaluation because the risk of practitioner infection outweighs the value of biopsy analysis unless symptoms are life-threatening. As a result, much of what is known about the gastrointestinal manifestations of coronavirus disease-2019 (COVID-19) has been gleaned from surgical and autopsy cases that suffer from extensive ischemic injury and/or poor preservation. There are no detailed reports describing any other gastrointestinal effects of SARS-CoV-2 even though >3,000,000 people have died from COVID-19 worldwide. The purpose of this study is to report the intestinal findings related to SARS-CoV-2 infection by way of a small case series including one with evidence of direct viral cytopathic effect and 2 with secondary injury attributed to viral infection. Infection can be confirmed by immunohistochemical stains directed against SARS-CoV-2 spike protein, in situ hybridization for spike protein-encoding RNA, and ultrastructural visualization of viruses within the epithelium. It induces cytoplasmic blebs and tufted epithelial cells without inflammation and may not cause symptoms. In contrast, SARS-CoV-2 infection can cause gastrointestinal symptoms after the virus is no longer detected, reflecting systemic activation of cytokine and complement cascades rather than direct viral injury. Reversible mucosal ischemia features microvascular injury with hemorrhage, small vessel thrombosis, and platelet-rich thrombi. Systemic cytokine elaboration and dysbiosis likely explain epithelial cell injury that accompanies diarrheal symptoms. These observations are consistent with clinical and in vitro data and contribute to our understanding of the protean manifestations of COVID-19.


Assuntos
COVID-19/patologia , Enteropatias/patologia , Enteropatias/virologia , Intestinos/patologia , Intestinos/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Biópsia , COVID-19/diagnóstico , COVID-19/imunologia , Citocinas/metabolismo , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/imunologia , Hemorragia Gastrointestinal/patologia , Hemorragia Gastrointestinal/virologia , Humanos , Enteropatias/diagnóstico , Enteropatias/imunologia , Intestinos/imunologia , Isquemia/diagnóstico , Isquemia/imunologia , Isquemia/patologia , Isquemia/virologia , Masculino , Trombose/diagnóstico , Trombose/imunologia , Trombose/patologia , Trombose/virologia
11.
Environ Pollut ; 292(Pt A): 118341, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34637832

RESUMO

With the development of marine oil industry, oil spill accidents will inevitably occur, further polluting the intertidal zone and causing biological poisoning. The muddy intertidal zone and Boleophthalmus pectinirostris were selected as the research objects to conduct indoor acute exposure experiments within 48 h of crude oil pollution. Statistical analysis was used to reveal the activity changes of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) in the gills and liver of mudskipper. Then, integrated biomarker response (IBR) indicators were established to comprehensively evaluate the biological toxicity. The results showed that the activities of SOD, CAT and GST in livers were higher than those in gills, and the maximum induction multipliers of SOD, CAT and GPx in livers appeared earlier than those in gills. Both SOD and GPx activities were induced at low pollutant concentrations and inhibited at high pollutant concentrations. For the dose-effect, the change trends of CAT and SOD were roughly inversed. There was substrate competition between GPx and CAT, with opposite trends over time. The activating mechanism of GST was similar to that of GPx, and the activation time was earlier than that of GPx. In terms of dose-effect trends, the IBR showed that the antioxidant enzymes activities in biological tissues were induced by low and inhibited by high pollutant concentrations. Overall, SOD and GPx in gills and CAT and GST in livers of the mudskippers were suitable as representative markers to comprehensively analyze and evaluate the biotoxicity effects of oil pollution in the intertidal zone. The star plots and IBR values obtained after data standardization were consistent with the enzyme activity differences, which can be used as valid supplementary indexes for biotoxicity evaluation. These research findings provide theoretical support for early indicators of biological toxicity after crude oil pollution in intertidal zones.


Assuntos
Antioxidantes , Petróleo , Animais , Biomarcadores/metabolismo , Peroxidação de Lipídeos , Estresse Oxidativo , Petróleo/toxicidade
12.
Environ Pollut ; 292(Pt A): 118328, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34653587

RESUMO

The Mytilus mussels are spread all over the world and many related species coexist in several areas and can produce hybrid offspring. Mussels have been used for decades in national and international programs to monitor chemical contamination in the environment. Differences in bioaccumulation and biotransformation abilities between species and their hybrids should be evaluated to assess the comparability of the results obtained within the international biomonitoring programs. The objective of this study was to characterize bioaccumulation abilities and biomarker responses in Mytilus edulis, Mytilus galloprovincialis and their hybrids via an in situ transplantation experimentation on their progenies. Four mussel groups (M. edulis, M. galloprovincialis and two hybrids batches) issued from genetically characterized parents were transplanted for one year in Charente Maritime (France) to ensure their exposure to identical sources of contamination. The bioaccumulation of several families of contaminants (trace metals, polycyclic aromatic hydrocarbons, polybrominated diphenyl ethers, polychlorinated biphenyls), the response of several biomarkers (DNA strand breaks level, lysosomal membrane stability, metallothionein content, acetylcholine esterase activity) and some physiological parameters (growth, mortality, gonadal development), were analyzed. Differences were observed between species, however they were contaminant-specific. Variations in contaminants levels were observed between progenies, with higher levels of Cu, PBDE, PCB in M. edulis, and higher levels of Cd, Hg, Zn in M galloprovincialis. This study demonstrated that variations in contaminant bioaccumulation and different biomarker responses exist between Mytilus species in the field. Data on species or the presence of hybrid individuals (or introgression) is an important additional parameter to add to biomonitoring programs databases.


Assuntos
Mytilus edulis , Mytilus , Poluentes Químicos da Água , Animais , Bioacumulação , Biomarcadores/metabolismo , Ecotoxicologia , Monitoramento Ambiental , Mytilus/metabolismo , Mytilus edulis/metabolismo , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
13.
Environ Pollut ; 292(Pt B): 118453, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34737025

RESUMO

Whether propylene oxide (PO) exposure is associated with hyperglycemia were rarely explored. We aimed to determine the relationship between PO exposure and glucose metabolism, and potential role of oxidative stress. Among 3294 Chinese urban adults, urinary PO metabolite (N-Acetyl-S-(2-hydroxypropyl)-L-cysteine, 2HPMA), biomarkers of oxidative DNA damage (8-oxo-7,8-dihydro-20-deoxyguanosine, 8-OHdG) and lipid peroxidation (8-isoprostane, 8-iso-PGF2α) in urine were determined. The associations of 2HPMA with 8-OHdG, 8-iso-PGF2α, fasting plasma glucose (FPG), and risk of diabetes were explored. The roles of 8-OHdG and 8-iso-PGF2α on association of 2HPMA with FPG and risk of diabetes were detected. After adjusted for potential confounders, each 1-unit increase in log-transformed concentration of 2HPMA was associated with a 0.15-mmol/L increase in FPG level, and the adjusted OR (95% CI) of diabetes by the associations of log-transformed urinary 2HPMA concentrations was 1.47 (95% CI: 1.03-2.11). Combination effects of 2HPMA with 8-OHdG or 8-iso-PGF2α on risk of diabetes were detected, and elevated 8-iso-PGF2α significantly mediated 34.5% of the urinary 2HPMA-associated FPG elevation. PO exposure was positively associated with FPG levels and risk of diabetes. PO exposure combined with DNA oxidative damage or lipid peroxidation may increase the risk of diabetes, and lipid peroxidation may partially mediate the PO exposure-induced FPG elevation.


Assuntos
Diabetes Mellitus , Jejum , Adulto , Biomarcadores/metabolismo , Glicemia , Dano ao DNA , Dinoprosta , Compostos de Epóxi , Humanos , Peroxidação de Lipídeos , Estresse Oxidativo
14.
J Toxicol Environ Health A ; 85(1): 29-42, 2022 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-34445936

RESUMO

The aim of this study was to investigate changes in the intracellular metabolism resulting from cisplatin (CDDP)-induced nephrotoxicity in normal kidney tubular epithelial NRK-52E cells. Cytotoxicity, cell cycle analysis, and apoptotic cell death were all evaluated in NRK-52E cells treated with CDDP. Subsequently, proton nuclear magnetic resonance (1H-NMR) spectroscopy was used to investigate cellular metabolic profiles. CDDP-induced nephrotoxicity was determined in vivo model. Cytotoxicity in the NRK-52E cells significantly rose following treatment with CDDP and these increases were found to be concentration-dependent. Both p53 and Bax protein expression was increased in CDDP-treated NRK-52E cells, correlating with enhanced cellular apoptosis. In addition, a number of metabolites were altered in both media and cell lysates in these cells. In cell lysates, citrate, creatinine, and acetate levels were dramatically reduced following treatment with 20 µM CDDP concentrations, while glutamate level was elevated. Lactate and acetate levels were significantly increased in culture media but citrate concentrations were reduced following high 20 µM CDDP concentrations incubation. In addition, excretion of clusterin, calbindin, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), selenium binding protein 1 (SBP1), and pyruvate kinase M2 (PKM2) into the culture media was significantly increased in CDDP-treated cells while expression of acetyl CoA synthetase 1 (AceCS1) was markedly reduced in these cells. These findings suggest that acetate-dependent metabolic pathway may be a reliable and useful biomarker for detecting CDDP-induced nephrotoxicity. Taken together, data demonstrate that the discovery of novel biomarkers by metabolite profiling in target cells may contribute to the detection of nephrotoxicity and new drug development.


Assuntos
Injúria Renal Aguda/metabolismo , Cisplatino/toxicidade , Acetatos/metabolismo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Metabolômica , Modelos Biológicos , Ratos
15.
J Toxicol Environ Health A ; 85(1): 1-13, 2022 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-34445937

RESUMO

Prenatal exposure to valproic acid (VPA) has been implicated in the manifestation of autism spectrum disorder (ASD)-like behavioral and functional changes both in human and rodents including mice and rats. The objective of this study was to determine metabolomics profiling and biomarkers related to VPA-induced symptoms resembling ASD using proton nuclear magnetic resonance (1H-NMR) spectral data. VPA was administered to pregnant rats at gestation day 12.5 and effects measured subsequently in male 4-week-old offspring pups. The sociability of VPA-treated animals was significantly diminished and exhibited ASD-like behavior as evidenced by reduction of social adaptation disorder and lack of social interactions. To find biomarkers related to ASD, the following were collected prefrontal brain cortices, urine bladder and blood samples directly from heart puncture. In all samples, principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) displayed significant clustering pattern differences between control and treated groups. Valine, taurine, myo-inositol, 3-hydroxybutyrate and 1,3-dihydroxyacetone were significantly decreased in brain cortices in treated rats. Serum metabolites of glucose, creatine phosphate, lactate, glutamine and threonine were significantly increased in VPA-administered animals. Urinary metabolites of pimelate, 3-hydroxyisovalerate and valerate were significantly reduced in VPA-treated rat, whereas galactose and galactonate levels were elevated. Various metabolites were associated with mitochondrial dysfunction metabolism and central nervous system disorders. Data demonstrated that VPA-induced alterations in endogenous metabolites of serum, urine, and brain cortex which might prove useful as biomarkers for symptoms resembling ASD as a model of this disorder.


Assuntos
Transtorno do Espectro Autista/metabolismo , Modelos Animais de Doenças , Ácido Valproico/toxicidade , Animais , Transtorno do Espectro Autista/etiologia , Biomarcadores/metabolismo , Encéfalo/metabolismo , Feminino , Masculino , Exposição Materna/efeitos adversos , Metabolômica , Espectroscopia de Prótons por Ressonância Magnética , Ratos
16.
Endocrinology ; 163(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34647995

RESUMO

Seminal plasma contains a high concentration of extracellular vesicles (EVs). The heterogeneity of small EVs or the presence of nonvesicular extracellular matter (NV) pose major obstacles in understanding the composition and function of seminal EVs. In this study, we employed high-resolution density gradient fractionation to accurately characterize the composition and function of seminal EVs and NV. We found that the seminal EVs could be divided into 3 different subtypes-namely, high-density EV (EV-H), medium-density EV (EV-M), and low-density EV (EV-L)-after purification using iodixanol, while NV was successfully isolated. EVs and NV display different features in size, shape, and expression of some classic exosome markers. Both EV-H and NV could markedly promote sperm motility and capacitation compared with EV-M and EV-L, whereas only the NV fraction induced sperm acrosome reaction. Proteomic analysis results showed that EV-H, EV-M, EV-L, and NV had different protein components and were involved in different physiological functions. Further study showed that EV-M might reduce the production of sperm intrinsic reactive oxygen species through glutathione S-transferase mu 2. This study provides novel insights into important aspects of seminal EVs constituents and sounder footing to explore their functional properties in male fertility.


Assuntos
Vesículas Extracelulares/metabolismo , Proteômica/métodos , Sêmen/metabolismo , Motilidade Espermática , Reação Acrossômica , Biomarcadores/metabolismo , Biotinilação , Biologia Computacional , Exossomos/metabolismo , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Humanos , Masculino , Fosforilação , Proteínas Tirosina Fosfatases/química , Proteoma , Espécies Reativas de Oxigênio , Espermatozoides/metabolismo , Espermatozoides/fisiologia , Ácidos Tri-Iodobenzoicos/farmacologia
17.
PLoS One ; 16(12): e0261730, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34941945

RESUMO

In this study we investigate how ß-catenin-dependent WNT signalling impacts midbrain dopaminergic neuron (mDA) specification. mDA cultures at day 65 of differentiation responded to 25 days of the tankyrase inhibitor XAV969 (XAV, 100nM) with reduced expression of markers of an A9 mDA phenotype (KCNJ6, ALDH1A1 and TH) but increased expression of the transcriptional repressors NR0B1 and NR0B2. Overexpression of NR0B1 and or NR0B2 promoted a loss of A9 dopaminergic neuron phenotype markers (KCNJ6, ALDH1A1 and TH). Overexpression of NR0B1, but not NR0B2 promoted a reduction in expression of the ß-catenin-dependent WNT signalling pathway activator RSPO2. Analysis of Parkinson's disease (PD) transcriptomic databases shows a profound PD-associated elevation of NR0B1 as well as reduced transcript for RSPO2. We conclude that reduced ß-catenin-dependent WNT signalling impacts dopaminergic neuron identity, in vitro, through increased expression of the transcriptional repressor, NR0B1. We also speculate that dopaminergic neuron regulatory mechanisms may be perturbed in PD and that this may have an impact upon both existing nigral neurons and also neural progenitors transplanted as PD therapy.


Assuntos
Receptor Nuclear Órfão DAX-1/biossíntese , Neurônios Dopaminérgicos/metabolismo , Regulação para Baixo , Células-Tronco Embrionárias Humanas/metabolismo , Doença de Parkinson/metabolismo , Regulação para Cima , Via de Sinalização Wnt , beta Catenina/metabolismo , Biomarcadores/metabolismo , Receptor Nuclear Órfão DAX-1/genética , Humanos , Doença de Parkinson/genética , beta Catenina/genética
18.
Cells ; 10(12)2021 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-34943848

RESUMO

Drug repositioning is one of the leading strategies in modern therapeutic research. Instead of searching for completely novel substances and demanding studies of their biological effects, much attention has been paid to the evaluation of commonly used drugs, which could be utilized for more distinct indications than they have been approved for. Since treatment approaches for cancer, one of the most extensively studied diseases, have still been very limited, great effort has been made to find or repurpose novel anticancer therapeutics. One of these are cardiac glycosides, substances commonly used to treat congestive heart failure or various arrhythmias. Recently, the antitumor properties of cardiac glycosides have been discovered and, therefore, these compounds are being considered for anticancer therapy. Their mechanism of antitumor action seems to be rather complex and not fully uncovered yet, however, autophagy has been confirmed to play a key role in this process. In this review article, we report on the up-to-date knowledge of the anticancer activity of cardiac glycosides with special attention paid to autophagy induction, the molecular mechanisms of this process, and the potential employment of this phenomenon in clinical practice.


Assuntos
Autofagia , Glicosídeos Cardíacos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Biomarcadores/metabolismo , Humanos , Modelos Biológicos , ATPase Trocadora de Sódio-Potássio/metabolismo
19.
Isr Med Assoc J ; 23(12): 801-804, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34954920

RESUMO

BACKGROUND: Fibromyalgia syndrome (FMS) is a chronic disorder characterized by widespread musculoskeletal pain accompanied by various additional symptoms. The prevalence of FMS ranges between 2-8% of the population. The exact pathophysiology of the disease remains unknown, and under certain circumstances it is difficult for the physician to diagnose. Previous studies have shown a correlation between inflammatory biomarkers such as C-reactive protein (CRP) and FMS activity, suggesting that an inflammatory component may play a role in this disease pathogenesis. OBJECTIVES: To investigate the role of certain new inflammatory biomarkers in the diagnosis of patients with FMS. METHODS: In this study data were collected from FMS patients who were admitted to Ziv Medical Center during the period 2013 to 2019 in an attempt to find a connection between inflammatory markers detectable by a traditional complete blood count (CBC) tests such as neutrophil-lymphocytes ratio (NLR), platelet-lymphocyte ratio (PLR), mean platelet value (MPV), red cell distribution width (RDW), and C-reactive protein (CRP) and FMS. RESULTS: We found significantly higher CRP levels, MPV, and PLR and lower lymphocyte count in the FMS group compared to the control group. CONCLUSIONS: FMS has certain inflammatory components that may be useful in disease diagnosis.


Assuntos
Proteína C-Reativa/metabolismo , Fibromialgia/diagnóstico , Linfócitos/metabolismo , Neutrófilos/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Contagem de Células Sanguíneas , Plaquetas/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Índices de Eritrócitos , Feminino , Fibromialgia/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Cell Mol Life Sci ; 79(1): 28, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34936031

RESUMO

Microgravity and space radiation (SR) are two highly influential factors affecting humans in space flight (SF). Many health problems reported by astronauts derive from endothelial dysfunction and impaired homeostasis. Here, we describe the adaptive response of human, capillary endothelial cells to SF. Reference samples on the ground and at 1g onboard permitted discrimination between the contribution of microgravity and SR within the combined responses to SF. Cell softening and reduced motility occurred in SF cells, with a loss of actin stress fibers and a broader distribution of microtubules and intermediate filaments within the cytoplasm than in control cells. Furthermore, in space the number of primary cilia per cell increased and DNA repair mechanisms were found to be activated. Transcriptomics revealed the opposing effects of microgravity from SR for specific molecular pathways: SR, unlike microgravity, stimulated pathways for endothelial activation, such as hypoxia and inflammation, DNA repair and apoptosis, inhibiting autophagic flux and promoting an aged-like phenotype. Conversely, microgravity, unlike SR, activated pathways for metabolism and a pro-proliferative phenotype. Therefore, we suggest microgravity and SR should be considered separately to tailor effective countermeasures to protect astronauts' health.


Assuntos
Autofagia , Capilares/citologia , Radiação Cósmica , Células Endoteliais/efeitos da radiação , Transdução de Sinais , Ausência de Peso , Apoptose , Biomarcadores/metabolismo , Linhagem Celular , Sobrevivência Celular , Cromossomos Humanos/metabolismo , Citoesqueleto/metabolismo , Dano ao DNA , Fluorescência , Regulação da Expressão Gênica , Genoma Humano , Humanos , Masculino , Mecanotransdução Celular , Modelos Biológicos , Transdução de Sinais/efeitos da radiação , Voo Espacial , Estresse Fisiológico , Homeostase do Telômero , Transcriptoma/genética
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