Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Toxins (Basel) ; 15(10)2023 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-37888651

RESUMO

Karenia mikimotoi is a common species of red tide dinoflagellate that causes the mass mortality of marine fauna in coastal waters of Republic of Korea. Despite continuous studies on the ecophysiology and toxicity of K. mikimotoi, the underlying molecular mechanisms remain poorly understood. Red sea bream, Pagrus major, is a high-value aquaculture fish species, and the coastal aquaculture industry of red sea bream has been increasingly affected by red tides. To investigate the potential oxidative effects of K. mikimotoi on P. major and the molecular mechanisms involved, we exposed the fish to varying concentrations of K. mikimotoi and evaluated its toxicity. Our results showed that exposure to K. mikimotoi led to an accumulation of reactive oxygen species (ROS) and oxidative DNA damage in the gill tissue of P. major. Furthermore, we found that K. mikimotoi induced the activation of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, in the gill tissue of P. major, with a significant increase in activity at concentrations above 5000 cells/mL. However, the activity of glutathione S-transferase did not significantly increase at the equivalent concentration. Our study confirms that oxidative stress and DNA damage is induced by acute exposure to K. mikimotoi, as it produces ROS and hypoxic conditions in P. major. In addition, it was confirmed that gill and blood samples can be used as biomarkers to detect the degree of oxidative stress in fish. These findings have important implications for the aquaculture of red sea bream, particularly in the face of red tide disasters.


Assuntos
Dinoflagellida , Perciformes , Animais , Dinoflagellida/genética , Espécies Reativas de Oxigênio , Proliferação Nociva de Algas , Estresse Oxidativo , Dano ao DNA
2.
Exp Mol Med ; 55(8): 1720-1733, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37524868

RESUMO

Autophagy functions in cellular quality control and metabolic regulation. Dysregulation of autophagy is one of the major pathogenic factors contributing to the progression of nonalcoholic fatty liver disease (NAFLD). Autophagy is involved in the breakdown of intracellular lipids and the maintenance of healthy mitochondria in NAFLD. However, the mechanisms underlying autophagy dysregulation in NAFLD remain unclear. Here, we demonstrate that the hepatic expression level of Thrap3 was significantly increased in NAFLD conditions. Liver-specific Thrap3 knockout improved lipid accumulation and metabolic properties in a high-fat diet (HFD)-induced NAFLD model. Furthermore, Thrap3 deficiency enhanced autophagy and mitochondrial function. Interestingly, Thrap3 knockout increased the cytosolic translocation of AMPK from the nucleus and enhanced its activation through physical interaction. The translocation of AMPK was regulated by direct binding with AMPK and the C-terminal domain of Thrap3. Our results indicate a role for Thrap3 in NAFLD progression and suggest that Thrap3 is a potential target for NAFLD treatment.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia/genética , Dieta Hiperlipídica/efeitos adversos , Metabolismo dos Lipídeos , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fatores de Transcrição/metabolismo , Humanos , Células Hep G2
3.
J Vet Sci ; 24(3): e42, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37271510

RESUMO

Lumpy skin disease (LSD) is one of the most important emerging transboundary diseases. Recently, LSD has emerged in many countries in the northern hemisphere. The LSD virus has a huge genome and is highly resistant to environmental conditions. The virus is also host-specific and large ruminants, such as cattle and domestic water buffalo, are particularly susceptible. In addition, wild ruminants can serve as potential reservoirs for spreading the LSD virus. The emergence might be related to climate change in various regions because LSD is an arthropod-borne infectious disease. This disease causes enormous economic losses, such as leather damage, decreased milk production, abortion, and death in infected ruminants. The economic importance of LSD in the bovine industry has forced countries to develop and implement control strategies against the disease. With the recent global spread and the economic impact, LSD will be discussed intensively. In addition, effective preventive measures are suggested based on the presence or absence of LSD outbreaks.


Assuntos
Doenças dos Bovinos , Doenças Transmissíveis Emergentes , Doença Nodular Cutânea , Vírus da Doença Nodular Cutânea , Animais , Bovinos , Doença Nodular Cutânea/epidemiologia , Doença Nodular Cutânea/prevenção & controle , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/prevenção & controle , Doenças Transmissíveis Emergentes/veterinária , Vírus da Doença Nodular Cutânea/genética , Surtos de Doenças/veterinária , Doenças dos Bovinos/epidemiologia
4.
Mitochondrial DNA B Resour ; 8(1): 113-115, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36685645

RESUMO

Here, we sequenced and annotated the complete mitochondrial genome for the sea-pen, Cavernularia obesa (Valenciennes, 1850). The complete mitogenome of C. obesa is 18,641 bp, with 34.7% of GC ratio. The mitogenome comprises 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a non-coding region. Phylogenomic analysis based on 19 in-group taxa belonging to the orders Alcyonacea and Pennatulacea has congruent with published phylogenetic relationship for Octocorallia, which C. obesa was grouped to members of the Pennatulacea. This mitogenome resource will be useful for future phylogenetic studies of water fleas.

5.
Mitochondrial DNA B Resour ; 7(6): 918-920, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35692647

RESUMO

We report the complete mitochondrial genome information of the rainbow krib, Pelvicachromis pulcher (Boulenger 1901). Illumina HiSeq genome sequencing allowed the assembly of a circular mitogenome of 17,196 base pairs (bp) from P. pulcher consisting of 47% GC nucleotides, 13 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a putative control region in the typical teleost gene composition. The gene order of the P. pulcher mitogenome was identical to that of other cichlid species. A maximum likelihood phylogenetic tree based on mitochondrial PCGs showed a relationship of P. pulcher with a cichlid Tylochromis polylepis (Boulenger 1900), suggesting that more complete mitogenomes are needed to explore mitogenome evolution in West African tribes and riverine cichlids, as this genomic information is the first complete mitogenome in the tribe Chromidotilapiini.

6.
Environ Sci Technol ; 56(6): 3503-3513, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35245034

RESUMO

In this study, the toxicity of hexavalent chromium [Cr(VI)] reduced by citric acid in ice was measured using representative aquatic model invertebrates (i.e., rotifer, water flea, amphipod, and polychaete) and a vertebrate (zebrafish) by analyzing short- and/or long-term endpoints that are frequently applied to each animal. Cr(VI) reduction in the presence of citric acid was markedly enhanced in the ice phase compared to that in an aqueous solution through the freeze concentration effect. The highly concentrated Cr(VI) and citric acid in ice grain boundaries were also confirmed using in situ cryogenic confocal Raman spectroscopy. Overall, exposure to Cr(VI) resulted in higher acute and/or chronic effects on aquatic animals, such as drastic mortality, growth inhibition, and decrease in offspring number, whereas the animals were increasingly tolerant to Cr(VI) that was reduced in the ice phase. Sublethal concentrations of Cr(VI) significantly decreased the antioxidant capacity in the aquatic animals. However, when the same concentrations of Cr(VI) were reduced in ice, these treatments showed no modulation or increase in the antioxidant defense system. Taken together, our results suggest that Cr(VI) reduction into Cr(III) was successfully achieved in ice and that this methodology can decrease the actual toxicity of Cr(VI) in aquatic animals.


Assuntos
Gelo , Poluentes Químicos da Água , Animais , Antioxidantes , Cromo/química , Cromo/toxicidade , Ácido Cítrico , Oxirredução , Poluentes Químicos da Água/química , Peixe-Zebra
7.
Mitochondrial DNA B Resour ; 7(1): 167-169, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35005235

RESUMO

Here, we report the complete mitogenome information of the six-line wrasse Pseudocheilinus hexataenia (Bleeker, 1857). Genome sequencing using the Illumina HiSeq platform allowed the assembly of a circular mitochondrial genome of 17,111 bp from P. hexataenia, consisting of 54% AT nucleotides, 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a putative control region in the typical Labriformes gene composition. The gene order of the P. hexataenia mitochondrion was identical to that of the Labridae mitogenomes. Phylogenetic reconstruction places P. hexataenia with a close relationship with the mitogenome of the goldsinny wrasse, Ctenolabrus rupestris.

8.
Sci Total Environ ; 807(Pt 3): 150988, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-34656572

RESUMO

Numerous studies have assessed the detrimental effects of microplastics (MPs) on aquatic invertebrates due to their ubiquitous and persistent nature. In this study, the toxic effects of MPs were examined on the polyp and ephyrae of the marine hydrozoan Sanderia malayensis. The jellyfish were exposed to different sizes (1-6 µm) of non-functionalized polystyrene microbeads at a concentration of 1 × 104 particles mL-1. The MPs randomly attached to the external and internal parts of the jellyfish body, and the longest MP attachment was 52 days during the depuration after initial exposure (for 24 h). Consistent seventeen-day exposure to MPs significantly reduced the asexual reproduction of the S. malayensis polyps. To assess if the MPs can stimulate nematocyst discharge in polyp and ephyrae stages via direct contact, they were exposed to particle sizes up to 430 µm. None of the MPs or their aggregates, including the 430 µm particles, induced nematocyst discharge. These results suggest that prolonged exposure to relatively high MP concentrations affects the early stages of jellies and provides evidence for the no effect on nematocyst discharge.


Assuntos
Microplásticos , Poliestirenos , Animais , Nematocisto , Plásticos , Reprodução Assexuada
9.
Mitochondrial DNA B Resour ; 6(12): 3487-3489, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869886

RESUMO

In this study, the complete 16,583 bp mitochondrial genome of Lamprologus signatus (Poll, 1952) was determined from a specimen sourced from Lake Tanganyika. The mitogenome contains 37 genes [13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, and 22 transfer RNA (tRNA) genes] and a putative control region, which consists of 27.1% A, 27.0% T, 29.9% C, and 16.0% G, with a total G + C content of 45.9%. A maximum likelihood phylogenetic tree based on mitochondrial PCGs suggested that L. signatus is clustered with members of the tribes Haplochromini and Tropheini. As this is the first report of the entire mitogenome in the tribe Lamprologini, the complete mitochondrial sequence information of L. sigantus will be useful in determining phylogenetic relationships of Pseudocrenilabrinae tribes.

10.
Elife ; 102021 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-34964438

RESUMO

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and imbalances in lipid metabolism in the liver. Although nuclear receptors (NRs) play a crucial role in hepatic lipid metabolism, the underlying mechanisms of NR regulation in NAFLD remain largely unclear. Methods: Using network analysis and RNA-seq to determine the correlation between NRs and microRNA in human NAFLD patients, we revealed that MIR20B specifically targets PPARA. MIR20B mimic and anti-MIR20B were administered to human HepG2 and Huh-7 cells and mouse primary hepatocytes as well as high-fat diet (HFD)- or methionine-deficient diet (MCD)-fed mice to verify the specific function of MIR20B in NAFLD. We tested the inhibition of the therapeutic effect of a PPARα agonist, fenofibrate, by Mir20b and the synergic effect of combination of fenofibrate with anti-Mir20b in NAFLD mouse model. Results: We revealed that MIR20B specifically targets PPARA through miRNA regulatory network analysis of nuclear receptor genes in NAFLD. The expression of MIR20B was upregulated in free fatty acid (FA)-treated hepatocytes and the livers of both obesity-induced mice and NAFLD patients. Overexpression of MIR20B significantly increased hepatic lipid accumulation and triglyceride levels. Furthermore, MIR20B significantly reduced FA oxidation and mitochondrial biogenesis by targeting PPARA. In Mir20b-introduced mice, the effect of fenofibrate to ameliorate hepatic steatosis was significantly suppressed. Finally, inhibition of Mir20b significantly increased FA oxidation and uptake, resulting in improved insulin sensitivity and a decrease in NAFLD progression. Moreover, combination of fenofibrate and anti-Mir20b exhibited the synergic effect on improvement of NAFLD in MCD-fed mice. Conclusions: Taken together, our results demonstrate that the novel MIR20B targets PPARA, plays a significant role in hepatic lipid metabolism, and present an opportunity for the development of novel therapeutics for NAFLD. Funding: This research was funded by Korea Mouse Phenotyping Project (2016M3A9D5A01952411), the National Research Foundation of Korea (NRF) grant funded by the Korea government (2020R1F1A1061267, 2018R1A5A1024340, NRF-2021R1I1A2041463, 2020R1I1A1A01074940, 2016M3C9A394589324), and the Future-leading Project Research Fund (1.210034.01) of UNIST.


Assuntos
Fenofibrato/farmacologia , Hipolipemiantes/farmacologia , Metabolismo dos Lipídeos , MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/genética , PPAR alfa/genética , Animais , Feminino , Humanos , Masculino , Camundongos , MicroRNAs/metabolismo , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , PPAR alfa/metabolismo
11.
Exp Mol Med ; 53(10): 1602-1611, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34697388

RESUMO

Transcription-replication conflicts lead to DNA damage and genomic instability, which are closely related to human diseases. A major source of these conflicts is the formation of R-loops, which consist of an RNA-DNA hybrid and a displaced single-stranded DNA. Although these structures have been studied, many aspects of R-loop biology and R-loop-mediated genome instability remain unclear. Here, we demonstrate that thyroid hormone receptor-associated protein 3 (Thrap3) plays a critical role in regulating R-loop resolution. In cancer cells, Thrap3 interacts with DEAD-box helicase 5 (DDX5) and localizes to R-loops. Arginine-mediated methylation of DDX5 is required for its interaction with Thrap3, and the Thrap3-DDX5 axis induces the recruitment of 5'-3' exoribonuclease 2 (XRN2) into R-loops. Loss of Thrap3 increases R-loop accumulation and DNA damage. These findings suggest that Thrap3 mediates resistance to cell death by preventing R-loop accumulation in cancer cells.


Assuntos
Estruturas R-Loop , Fatores de Transcrição , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , DNA/genética , Proteínas de Ligação a DNA/metabolismo , Instabilidade Genômica , Humanos , RNA , Fatores de Transcrição/genética
12.
Artigo em Inglês | MEDLINE | ID: mdl-34284068

RESUMO

Coexistence of metals and microplastics (MPs) in aquatic environments represents a growing concern; however, little is known regarding the risks associated with their combined effects. Here, the effects of five metals (As, Cd, Cu, Pb, and Zn), alone or combined with MPs for various premixing durations (30 and 60 days), on the juvenile and adult stages of the marine mysid Neomysis awatschensis were evaluated. The toxicity (50% lethal concentration for 96 h) and bioconcentration of metals premixed with MPs were measured, and their effects on the antioxidant defense and cholinergic systems were examined. Metal toxicity increased with increasing premixing period with MPs, and juveniles were more sensitive to exposure to metals premixed with MPs than adults. Metal bioconcentration in the mysid body increased following co-exposure with MPs. Metals premixed with MPs significantly increased intracellular malondialdehyde content at both stages but decreased glutathione content in juveniles. At both stages, catalase and superoxide dismutase activity was suppressed following co-exposure to metals and MPs, except under the Cu treatment. Moreover, co-exposure inhibited acetylcholinesterase activity at both stages, suggesting cholinergic impairment. Taken together, metals and MPs produce synergistic detrimental effects on marine mysids in a stage-specific manner. Further studies are warranted to elucidate the role of MPs as a vector for contaminants and stimulator of toxicity in aquatic organisms.


Assuntos
Crustáceos/efeitos dos fármacos , Metais/farmacocinética , Metais/toxicidade , Microplásticos/toxicidade , Poluentes Químicos da Água/toxicidade , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/metabolismo , Proteínas de Artrópodes/metabolismo , Crustáceos/metabolismo , Ecotoxicologia , Biomarcadores Ambientais , Enzimas/metabolismo , Glutationa/metabolismo , Dose Letal Mediana , Malondialdeído/metabolismo , Metais/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Testes de Toxicidade Aguda , Poluentes Químicos da Água/farmacocinética
13.
J Ethnopharmacol ; 278: 114238, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34048878

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Vernicia fordii (Hemsl.) Airy Shaw (V. fordii) is also known as the tung tree and its leaves and fruit are used as an oriental treatment for dyspepsia, edema, and skin diseases, which are known as diabetic complications. AIM OF THE STUDY: In this study, we aimed to investigate the methanolic extract (VF5) of the leaves of V. fordii as an insulin secretagogue and its probable mechanism and verify the effect in HFD-fed mice. MATERIALS AND METHODS: The insulin secretagogue activity of different doses of VF5 (0.1, 0.3 and 1.0 µg/ml) was assessed using in vitro insulin secretion assay and confirmed the anti-diabetic effect in mice fed HFD for 4 weeks with different doses of VF5 (10, 20 and 50 mg/kg oral) for another 6 weeks. Glbenclamide (30 mg/kg, oral) was used as positive control drug. The possible mechanisms were evaluated by using Gö6983 (10 µM), U73122 (10 µM) and nifedipine (10 µM). The major constituents of VF5 were analyzed by UPLC-QToF-MS and 1H and 13C NMR spectroscopy. RESULTS: UPLC-QToF-MS and NMR spectroscopy analysis indicated that one of the main active components of VF5 was tigliane-diterpene esters. VF5 functioned as an insulin secretagogue and enhanced mitochondria respiration and insulin homeostasis. We confirmed that VF5 preserved the ß-cell and reduced the ß-cell expansion which caused by metabolic stress under HFD. The antidiabetic role of VF5 in HFD fed mice was assessed by glucose tolerance test (GTT) and insulin tolerance test (ITT), fasting plasma insulin level, fasting blood glucose level, AKT signal in peripheral tissue in the absence of toxic effects. Mechanistically, insulinotropic effect of VF5 was mediated by activation of PKCα via intracellular Ca2+ influx and enhanced mitochondria function. CONCLUSION: VF5 exhibits potent insulin secretagogue function and improves insulin sensitivity and protection of pancreatic ß-cells from metabolic stress without toxicity. Taken together, our study suggests that VF5 could be potentially used for treating diabetes and metabolic diseases through improving ß-cell function.


Assuntos
Aleurites/química , Diabetes Mellitus Experimental/tratamento farmacológico , Secreção de Insulina/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Diabetes Mellitus Experimental/fisiopatologia , Relação Dose-Resposta a Droga , Teste de Tolerância a Glucose , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Resistência à Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Estresse Fisiológico/efeitos dos fármacos
14.
Exp Mol Med ; 52(6): 940-950, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32504039

RESUMO

The endoplasmic reticulum (ER) stress response is an adaptive mechanism that is activated upon disruption of ER homeostasis and protects the cells against certain harmful environmental stimuli. However, critical and prolonged cell stress triggers cell death. In this study, we demonstrate that Flightless-1 (FliI) regulates ER stress-induced apoptosis in colon cancer cells by modulating Ca2+ homeostasis. FliI was highly expressed in both colon cell lines and colorectal cancer mouse models. In a mouse xenograft model using CT26 mouse colorectal cancer cells, tumor formation was slowed due to elevated levels of apoptosis in FliI-knockdown (FliI-KD) cells. FliI-KD cells treated with ER stress inducers, thapsigargin (TG), and tunicamycin exhibited activation of the unfolded protein response (UPR) and induction of UPR-related gene expression, which eventually triggered apoptosis. FliI-KD increased the intracellular Ca2+ concentration, and this upregulation was caused by accelerated ER-to-cytosolic efflux of Ca2+. The increase in intracellular Ca2+ concentration was significantly blocked by dantrolene and tetracaine, inhibitors of ryanodine receptors (RyRs). Dantrolene inhibited TG-induced ER stress and decreased the rate of apoptosis in FliI-KD CT26 cells. Finally, we found that knockdown of FliI decreased the levels of sorcin and ER Ca2+ and that TG-induced ER stress was recovered by overexpression of sorcin in FliI-KD cells. Taken together, these results suggest that FliI regulates sorcin expression, which modulates Ca2+ homeostasis in the ER through RyRs. Our findings reveal a novel mechanism by which FliI influences Ca2+ homeostasis and cell survival during ER stress.


Assuntos
Cálcio/metabolismo , Neoplasias Colorretais/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Proteínas dos Microfilamentos/metabolismo , Transativadores/metabolismo , Animais , Apoptose/genética , Apoptose/fisiologia , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Neoplasias Colorretais/genética , Estresse do Retículo Endoplasmático/genética , Humanos , Immunoblotting , Masculino , Camundongos , Proteínas dos Microfilamentos/genética , Transativadores/genética , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Mar Pollut Bull ; 156: 111276, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32510415

RESUMO

Effects of zinc pyrithione (ZnPT) and inorganic Zn (ZnCl2) were evaluated on a marine polychaete at sublethal concentrations for 14 days. ZnPT decreased the burrowing activity and AChE activity with higher acute toxicities, implying its cholinergic effect. Both ZnPT and ZnCl2 increased MDA levels at higher concentrations, suggesting lipid peroxidation and oxidative stress. In the ZnPT-treated polychaete, enzymatic activities of CAT and SOD were elevated with an increase in DNA damage, whereas the levels of GSH, GPx, GR, and GST were decreased. However, in the ZnCl2-treated polychaete, the level of GSH and enzymatic activities of CAT, SOD, GPx, GR, and GST were significantly elevated to resist cellular damage. During 97 days depuration experiment, significant mortality and growth retardation were observed in the ZnPT-exposed polychaete. Overall, ZnPT was found to be more toxic than ZnCl2 with the harmful impact on antioxidant defense system and DNA stability in marine polychaete.


Assuntos
Compostos Organometálicos , Poluentes Químicos da Água , Antioxidantes , Dano ao DNA , Peroxidação de Lipídeos , Estresse Oxidativo , Piridinas
16.
Cells ; 9(2)2020 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-32024237

RESUMO

Peroxisome proliferator-activated receptor γ (PPARγ) is a master regulator of adipose tissue biology. In obesity, phosphorylation of PPARγ at Ser273 (pSer273) by cyclin-dependent kinase 5 (CDK5)/extracellular signal-regulated kinase (ERK) orchestrates diabetic gene reprogramming via dysregulation of specific gene expression. Although many recent studies have focused on the development of non-classical agonist drugs that inhibit the phosphorylation of PPARγ at Ser273, the molecular mechanism of PPARγ dephosphorylation at Ser273 is not well characterized. Here, we report that protein phosphatase Mg2+/Mn2+-dependent 1A (PPM1A) is a novel PPARγ phosphatase that directly dephosphorylates Ser273 and restores diabetic gene expression which is dysregulated by pSer273. The expression of PPM1A significantly decreases in two models of insulin resistance: diet-induced obese (DIO) mice and db/db mice, in which it negatively correlates with pSer273. Transcriptomic analysis using microarray and genotype-tissue expression (GTEx) data in humans shows positive correlations between PPM1A and most of the genes that are dysregulated by pSer273. These findings suggest that PPM1A dephosphorylates PPARγ at Ser273 and represents a potential target for the treatment of obesity-linked metabolic disorders.


Assuntos
Diabetes Mellitus/genética , PPAR gama/metabolismo , Proteína Fosfatase 2C/metabolismo , Serina/metabolismo , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Regulação da Expressão Gênica , Células HEK293 , Humanos , Resistência à Insulina/genética , Camundongos , Obesidade/genética , Fosforilação , Ligação Proteica , Proteína Fosfatase 2C/genética
17.
J Minim Invasive Gynecol ; 27(2): 473-481, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30959198

RESUMO

STUDY OBJECTIVE: MONOFIX, a new absorbable barbed suture device, has a triangular stopper at the end to hold the suture to the tissue without hooking the looped end or knotting. The aim of this study was to compare the biomechanical strength and histologic features of MONOFIX with other barbed suture devices using a porcine model. DESIGN: Well-designed, controlled trial without randomization. SETTING: Animal laboratory in university hospital. SUBJECTS: Sixteen, 60-kg, mature female domestic pigs (skin closure group) and 5, 60-kg, mature female domestic pigs (fascial closure group). INTERVENTIONS: In the skin closure group, 3-0 MONOFIX versus 2 widely used 3-0 absorbable barbed sutures (3-0 V-Loc 180 or Stratafix). In the fascial closure group, 2-0 MONOFIX versus 1 widely used 2-0 absorbable barbed sutures (2-0 Stratafix). MEASUREMENTS AND MAIN RESULTS: In the skin closure group, the biomechanical wound strength of skin sutured with size 3-0 MONOFIX, V-Loc 180, or Stratafix was evaluated by postoperative day assessment (days 0, 3, 7, 14, and 28). In the fascial closure group, pigs underwent 2 paramedian incisions and were sutured with 2-0 MONOFIX or with 2-0 Stratafix to evaluate histologic reaction. At 6 weeks the tissues around the suture line were excised and microscopically evaluated. The biomechanical strength of the MONOFIX had similar tissue tensile strength compared with the control, regardless of postoperative day. In the fascial closure model, there was no significant difference in the average tissue reaction score between MONOFIX and Stratafix (1.2 ± .3 vs 1.3 ± .3, p = .478). CONCLUSION: This study demonstrated that MONOFIX has equivalent tensile strength and histologic reaction when compared with commonly used barbed suture devices. Accordingly, this preclinical study suggests that the use of MONOFIX is a safe alternative to other barbed suture devices.


Assuntos
Técnicas de Fechamento de Ferimentos Abdominais/instrumentação , Modelos Animais , Sus scrofa , Técnicas de Sutura , Suturas , Animais , Fenômenos Biomecânicos , Procedimentos Cirúrgicos Dermatológicos/instrumentação , Procedimentos Cirúrgicos Dermatológicos/métodos , Desenho de Equipamento , Fáscia/patologia , Fasciotomia/instrumentação , Fasciotomia/métodos , Feminino , Humanos , Laparoscopia/instrumentação , Laparoscopia/métodos , Pele/patologia , Deiscência da Ferida Operatória , Técnicas de Sutura/efeitos adversos , Técnicas de Sutura/instrumentação , Suturas/efeitos adversos , Suínos , Resistência à Tração
18.
Fish Shellfish Immunol ; 92: 469-479, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31252041

RESUMO

In this study, potential immunological and hematological effects of different concentrations (0, 1, 10, and 50 µg L-l) of waterborne zinc pyrithione (ZnPT) were studied in the blood of the olive flounder Paralichthys olivaceus over 30 days. Reduced alternative complement activity (ACH50) and lysozyme activity were measured in fish exposed to 10 and/or 50 µg L-l of ZnPT for 20 days. Decreased levels of total Ig were also observed in response to 10 and/or 50 µg L-l ZnPT during the exposure period. Levels of cortisol, a marker of stress, were significantly increased by 10 and 50 µg L-l ZnPT from day 10, and by 1 µg L-l exposure on day 30. The levels of red blood cells (RBCs) and white blood cells (WBCs) decreased following exposure to 10 and/or 50 µg L-l ZnPT, while no significant change was observed in hemoglobin level. Concentrations of total protein and albumin were significantly reduced with 50 µg L-l ZnPT at day 20. Alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase activities were significantly increased following exposure to 10 and/or 50 µg L-l ZnPT. Lipid peroxidation was induced by ZnPT, and higher concentrations (10 and 50 µg L-l) significantly increased intracellular malondialdehyde levels during exposure. Regarding the subsequent antioxidant response, intracellular glutathione levels increased significantly in response to 10 and 50 µg L-l ZnPT on days 20 and 30. Similarly, catalase and superoxide dismutase activity was significantly increased in response to 10 and 50 µg L-l ZnPT after day 10. Taken together, changes in the studied parameters suggested the immunotoxicity of ZnPT, with modulations observed in hematological homeostasis and oxidative stress induction in the blood of olive flounder.


Assuntos
Antioxidantes/metabolismo , Linguados/imunologia , Homeostase/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Compostos Organometálicos/efeitos adversos , Piridinas/efeitos adversos , Poluentes Químicos da Água/efeitos adversos , Animais , Biomarcadores/sangue , Desinfetantes/efeitos adversos , Relação Dose-Resposta a Droga , Linguados/metabolismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-31055069

RESUMO

Sea-Nine™ 211 is an emerging biocide that has an adverse impact on aquatic environments. In this study, the marine polychaete Perinereis aibuhitensis was exposed to Sea-Nine (0.1, 1, and 10 µg L-1), and acute toxicity and biochemical responses such as changes in the intracellular contents of malondialdehyde (MDA) and glutathione (GSH) and enzymatic activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), and acetylcholinesterase (AChE) were evaluated over a period of 14 d. Determined median lethal doses, LC50 were 268 µg L-1, 142 µg L-1, and 55 µg L-1 at 24 h, 96 h, and 14 d, respectively. The MDA content increased significantly in a dose- and time-dependent manner, indicative of lipid peroxidation-related oxidative damage. Significantly higher intracellular GSH levels and antioxidant defense-related enzyme (CAT, SOD, GPx, GR, and GST) activities were observed after exposure to 10 µg L-1 Sea-Nine. In contrast, Sea-Nine treatment significantly reduced AChE activity at the highest concentration of Sea-Nine used (10 µg L-1). Taken together, these results indicate that sublethal concentrations of Sea-Nine are toxic to marine polychaetes through potential lipid peroxidation, induction of oxidative stress, and modulation of the cholinergic system. Our results can contribute to biomonitoring of aquatic environments and ecotoxicological research through the measurements of polychaete cellular defenses against waterborne biocides.


Assuntos
Desinfetantes/toxicidade , Poliquetos/efeitos dos fármacos , Tiazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Relação Dose-Resposta a Droga , Esquema de Medicação , Glutationa/metabolismo , Malondialdeído/metabolismo , Tiazóis/administração & dosagem , Poluentes Químicos da Água/administração & dosagem
20.
PLoS One ; 14(4): e0214236, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30964867

RESUMO

Chlorothalonil is a thiol-reactive antifoulant that disperses widely and has been found in the marine environment. However, there is limited information on the deleterious effects of chlorothalonil in marine mollusks. In this study, we evaluated the effects of chlorothalonil on the gill tissues of the Pacific oyster, Crassostrea gigas and the blue mussel, Mytilus edulis after exposure to different concentrations of chlorothalonil (0.1, 1, and 10 µg L-1) for 96 h. Following exposure to 1 and/or 10 µg L-1 of chlorothalonil, malondialdehyde (MDA) levels significantly increased in the gill tissues of C. gigas and M. edulis compared to that in the control group at 96 h. Similarly, glutathione (GSH) levels were significantly affected in both bivalves after chlorothalonil exposure. The chlorothalonil treatment caused a significant time- and concentration-dependent increase in the activity of enzymes, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR), in the antioxidant defense system. Furthermore, 10 µg L-1 of chlorothalonil resulted in significant inhibitions in the enzymatic activity of Na+/K+-ATPase and acetylcholinesterase (AChE). These results suggest that chlorothalonil induces potential oxidative stress and changes in osmoregulation and the cholinergic system in bivalve gill tissues. This information will be a useful reference for the potential toxicity of chlorothalonil in marine bivalves.


Assuntos
Acetilcolinesterase/metabolismo , Organismos Aquáticos/enzimologia , Crassostrea/enzimologia , Brânquias/enzimologia , Mytilus edulis/enzimologia , Nitrilas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Antioxidantes/metabolismo , Organismos Aquáticos/efeitos dos fármacos , Crassostrea/efeitos dos fármacos , Brânquias/efeitos dos fármacos , Glutationa/metabolismo , Malondialdeído/metabolismo , Mytilus edulis/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...