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1.
Shanghai Kou Qiang Yi Xue ; 29(1): 97-101, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32524131

RESUMO

PURPOSE: To investigate the expression of secreted frizzle-related protein 1 (SFRP1) and macrophage migration inhibitory factor (MIF) in elderly patients with severe periodontitis and its correlation with cognitive function. METHODS: Thirty-two elderly patients with periodontitis in Qingdao Stomatological Hospital from February 2018 to February 2019 were enrolled, and divided into two groups according to the severity: mild group and severe group. All selected subjects received periodontal examination and Montreal cognitive assessment (MoCA).The expression of SFRP1 and MIF in serum was also determined. Then the correlations among SFRP1 and MIF periodontal index and cognitive function was analyzed. The data were processed by SPSS 20.0 software package. RESULTS: The probing depth (PD), clinical attachment level (CAL), sulcus bleeding index (SBI) and gingival crevicular fluid (GCF) showed significant difference between the two groups (P<0.05). The serum levels of SFRP1 and MIF in the severe group were significantly higher than those in the mild group (P<0.05). Serum SFRP1 level was positively correlated with MIF (P<0.05). Serum SFRP1 and MIF levels were positively correlated with periodontal index (P<0.05). The MoCA score of the severe group was significantly lower than that of the mild group (P<0.05). Serum SFRP1 and MIF levels were negatively correlated with MoCA score (P<0.05). CONCLUSIONS: SFRP1 and MIF are highly expressed in serum and gingival tissues of elderly patients with severe periodontitis, and are closely related to the degree of periodontal damage. Meanwhile, patients with periodontitis may have some degree of cognitive dysfunction, and SFRP1 and MIF may affect the periodontal tissue structure through Wnt/ß-catenin signal pathway and participate in the occurrence and development of cognitive dysfunction.


Assuntos
Periodontite Crônica , Idoso , Cognição , Gengiva , Líquido do Sulco Gengival , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Oxirredutases Intramoleculares , Fatores Inibidores da Migração de Macrófagos , Proteínas de Membrana , Perda da Inserção Periodontal , Índice Periodontal
2.
Shanghai Kou Qiang Yi Xue ; 29(1): 105-108, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32524133

RESUMO

PURPOSE: To investigate the expression of Bcl-2 protein and macrophage migration inhibitory factor (MIF) protein in gingival carcinoma of the elderly and its clinical significance. METHODS: Sixty-two gingival cancer tissue specimens in the elderly diagnosed in our hospital from January 2015 to September 2017 were selected as the experimental group, and 31 normal gingival tissues were selected as the control group. Immunohistochemical staining was used to detect the expression of Bcl-2 protein and MIF protein in two groups. The differences of Bcl-2 protein and MIF protein in different clinical stages, cervical lymph node metastasis and histological differentiation were analyzed. The data were analyzed with SPSS 16.0 software package for Chi-square test. RESULTS: The positive expression rates of Bcl-2 protein and MIF protein in the gingival cancer samples of the experimental group were 67.74% and 70.97%, respectively. The positive expression rates of Bcl-2 protein and MIF protein in the gingival tissues of the control group were 16.13% and 22.58%, respectively. The difference was statistically significant (P<0.05). The positive expression rate of Bcl-2 protein in gingival carcinoma tissues with different degrees of differentiation was statistically significant (P<0.05). In different degrees of differentiation, gingival carcinoma with cervical lymph node metastasis, there was significant difference in the positive expression rate of MIF protein in gingival cancer tissues (P<0.05). CONCLUSIONS: The expression of Bcl-2 and MIF protein is up-regulated in gingival cancer tissues of the elderly, which has certain relationship with the degree of tumor differentiation and cervical lymph node metastasis.


Assuntos
Neoplasias Gengivais , Idoso , Humanos , Oxirredutases Intramoleculares , Linfonodos , Metástase Linfática , Fatores Inibidores da Migração de Macrófagos
3.
Zhonghua Zhong Liu Za Zhi ; 42(4): 312-318, 2020 Apr 23.
Artigo em Chinês | MEDLINE | ID: mdl-32375447

RESUMO

Objective: To investigate the effect and mechanism of miR-451 on the proliferation and migration of human colorectal cancer cell SW480 by targeting macrophage migration inhibitory factor (MIF). Methods: Microarray analysis was used to screen differentially expressed microRNAs and messenger RNA in SW480 cells. Real-time quantitative PCR (RT-qPCR) was used to detect the expressions of miR-451 and MIF in SW480 cells before and after transfection. Cell clone formation assay and Transwell assay were used to detect the proliferation and invasion of SW480 cells, respectively. Cell scratch assay was used to detect the migration ability of SW480 cells. The TargetScan database was used to analyze the correlation between miR-451 and MIF. Dual luciferase reporter gene was used to detect the interaction of miR-451 and MIF. MTT assay was used to detect the viability of SW480 cells. Results: Compared with human normal colorectal mucosal cell FHC (1.00), the expression of miR-451 was down-regulated in SW480 cells ( 0.36±0.18, P<0.001). Knockdown of miR-451 promoted proliferation, and migration of SW480 cells. Compared with that in FHC cells, MIF expression was up-regulated in SW480 cells (2.28±0.45, P<0.001). MIF down-regulation inhibited SW480 cell proliferation, invasion and migration. MiR-451 specifically bind to the MIF 3'UTR and regulated the expression of MIF. Overexpression of miR-451 reduced while overexpression of MIF increased the viability of SW480 cells. Overexpression of MIF promoted the proliferation and migration of SW480 cells (P<0.01), reversed the effect of miR-451 suppressed proliferation and migration of SW480 cells. Conclusion: MiR-451 may regulate proliferation and migration of human colorectal cancer cells by targeting MIF.


Assuntos
Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Oxirredutases Intramoleculares/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , MicroRNAs/genética , Invasividade Neoplásica
4.
PLoS One ; 15(3): e0230285, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32160261

RESUMO

The aim of this study was to determine the association between secretory phospholipase A2 group IIA (sPLA2-IIA) and eicosanoid pathway metabolites in patients with bacterial sepsis syndrome (BSS). Levels of sPLA2-IIA, eicosanoids prostaglandin (PG)E2, PGD synthase were quantified in the sera from patients confirmed to have bacterial sepsis (BS; N = 45), bacterial severe sepsis/septic shock (BSS/SS; N = 35) and healthy subjects (N = 45). Cyclooxygenase (COX)-1 and COX-2 activities were analyzed from cell lysate. Serum levels of sPLA2-IIA, PGE2, and PGDS increased significantly in patients with BS and BSS/SS compared to healthy subjects (p<0.05). COX-2 activity was significantly increased in patients with BS compared to healthy subjects (p<0.05), but not COX-1 activity. Binary logistic regression analysis showed that sPLA2-IIA and PGE2 were independent factors predicting BSS severity. In conclusion, high level of sPLA2-IIA is associated with eicosanoid metabolism in patients with BSS.


Assuntos
Bacteriemia/sangue , Dinoprostona/sangue , Fosfolipases A2 do Grupo II/sangue , Adulto , Idoso , Bacteriemia/patologia , Biomarcadores/sangue , Ciclo-Oxigenase 1/sangue , Ciclo-Oxigenase 2/sangue , Feminino , Humanos , Oxirredutases Intramoleculares/sangue , Lipocalinas/sangue , Masculino , Pessoa de Meia-Idade
5.
Molecules ; 25(2)2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31936865

RESUMO

Recent preclinical and clinical observations have offered relevant insights on the etiopathogenesis of late onset Alzheimer's disease (AD) and upregulated immunoinflammatory events have been described as underlying mechanisms involved in the development of AD. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine produced by several cells of the innate and adaptive immune system, as well as non-immune cells. In the present review, we highlight experimental, genetic, and clinical studies on MIF in rodent models of AD and AD patients, and we discuss emerging therapeutic opportunities for tailored modulation of the activity of MIF, that may potentially be applied to AD patients. Dismantling the exact role of MIF and its receptors in AD may offer novel diagnostic and therapeutic opportunities in AD.


Assuntos
Doença de Alzheimer , Oxirredutases Intramoleculares , Fatores Inibidores da Migração de Macrófagos , Receptores Imunológicos , Regulação para Cima/imunologia , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Doença de Alzheimer/imunologia , Doença de Alzheimer/patologia , Animais , Modelos Animais de Doenças , Humanos , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/imunologia , Fatores Inibidores da Migração de Macrófagos/genética , Fatores Inibidores da Migração de Macrófagos/imunologia , Macrófagos , Receptores Imunológicos/genética , Receptores Imunológicos/imunologia , Roedores
6.
Zool Res ; 41(1): 39-50, 2020 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-31709785

RESUMO

D-dopachrome tautomerase (DDT), a member of the macrophage migration inhibitory factor (MIF) protein superfamily, is a newly described cytokine with chemokine-like characteristics. However, research on fish DDT remains limited. In this study, we identified a DDT homolog (LjDDT) from the Japanese sea bass, Lateolabrax japonicus. Sequence analysis showed that LjDDT had typical sequence features of known DDT and MIF homologs and was most closely related to DDT of rock bream ( Oplegnathus fasciatus). LjDDT transcripts were detected in all tested tissues of healthy Japanese sea bass, with the highest expression found in the liver. Upon infection with Vibrio harveyi, LjDDT transcripts were significantly down-regulated in the three tested tissues, including the liver, spleen, and head kidney. Recombinant LjDDT (rLjDDT) and the corresponding antibody (anti-rLjDDT) were subsequently prepared. The administration of 100 µg/g anti-rLjDDT had a statistically significant protective effect on the survival of V. harveyi-infected fish. Moreover, rLjDDT was able to induce the migration of monocytes/macrophages (MO/MФ) and lymphocytes both in vitro and in vivo, but without significant influence on the migration of neutrophils. rLjDDT exhibited chemotactic activity for lipopolysaccharide (LPS) -stimulated M1-type MO/ MΦ in vitro, but not for cAMP-stimulated M2-type MO/MΦ. Furthermore, the knockdown of LjCD74, but not LjCXCR4, significantly down-regulated the rLjDDT-enhanced migration of MO/MΦ and relieved the rLjMIF-inhibited migration of MO/MΦ. These results indicate that LjCD74 may be the major chemotactic receptor of LjDDT and LjMIF in Japanese sea bass MO/MΦ. Combined rLjDDT+ rLjMIF treatment had no significant effect on the migration of MsiRNA, LjCD74si-, or LjCXCR4sitreated MO/MΦ compared to the control group, suggesting that the roles of LjDDT and LjMIF may be antagonistic. In conclusion, our study demonstrates for the first time that DDT may play a role in the immune responses of fish against bacterial infection through chemotactic recruitment of MO/MΦ via mediation of CD74 as an antagonist of MIF.


Assuntos
Oxirredutases Intramoleculares/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Sequência de Aminoácidos , Animais , Movimento Celular , Relação Dose-Resposta a Droga , Peixes , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/farmacologia , Linfócitos/efeitos dos fármacos , Linfócitos/fisiologia , Fatores Inibidores da Migração de Macrófagos/química , Fatores Inibidores da Migração de Macrófagos/farmacologia , RNA Mensageiro , Vibrio , Vibrioses/enzimologia , Vibrioses/microbiologia , Vibrioses/veterinária
7.
Curr Pharm Biotechnol ; 21(2): 169-178, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31612825

RESUMO

BACKGROUND: Melanin protects the skin against the harmful effects of ultraviolet irradiation. However, melanin overproduction can result in several aesthetic problems, including melasma, freckles, age spots and chloasma. Therefore, development of anti-melanogenic agents is important for the prevention of serious hyperpigmentation diseases. Sesamolin is a lignan compound isolated from sesame seeds with several beneficial properties, including potential for melanin inhibition. OBJECTIVE: The aim of this study was to evaluate the anti-melanogenic effect of sesamolin in cell culture in vitro and the underlying mechanism of inhibition using molecular docking simulation. METHODS: Melanogenesis was induced by 3-isobutyl-1-methylxanthine in B16F10 melanoma cells, and the inhibitory effects of sesamolin were evaluated using zymography, a tyrosinase inhibitory activity assay, western blotting, and real-time reverse transcription-polymerase chain reaction analysis. Docking simulations between sesamolin and tyrosinase were performed using Autodock vina. RESULTS: Sesamolin significantly inhibited the expression of melanogenesis-related factors tyrosinase, and tyrosinase-related proteins 1 and 2 at the mRNA and protein levels. Treatment of melanoma cells with 50 µM sesamolin demonstrated the strongest inhibition against intercellular tyrosinase and melanin synthesis without exerting cytotoxic effects. Sesamolin significantly reduced mushroom tyrosinase activity in a dose-dependent manner via a competitive inhibition mechanism. Tyrosinase docking simulations supported that sesamolin (-6.5 kcal/mol) bound to the active site of tyrosinase more strongly than the positive control (arbutin, -5.7 kcal/mol). CONCLUSION: Sesamolin could be developed as a melanogenesis inhibiting agent owing to its dual function in blocking the generation of melanogenesis-related enzymes and inhibiting the enzymatic response of tyrosinase.


Assuntos
Antineoplásicos/farmacologia , Dioxóis/farmacologia , Oxirredutases Intramoleculares/antagonistas & inibidores , Melaninas/biossíntese , Monofenol Mono-Oxigenase/antagonistas & inibidores , Oxirredutases/antagonistas & inibidores , 1-Metil-3-Isobutilxantina , Agaricales/enzimologia , Animais , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Dioxóis/isolamento & purificação , Relação Dose-Resposta a Droga , Humanos , Melanoma Experimental/patologia , Simulação de Acoplamento Molecular
8.
Am J Physiol Cell Physiol ; 318(1): C94-C102, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31618079

RESUMO

Matrix metalloproteinases (MMP) are important for cardiac remodeling. Recently, microRNA (miR)-451a has been found to inhibit the expression of both MMP-2 and MMP-9 in human malignancies, but its role in cardiomyocytes has not been explored. We hypothesized that miR-451a modulates MMP-2 and MMP-9 levels in human cardiomyocytes. The role of miR-451a on regulation of MMP-2 and MMP-9 was evaluated in two separate pathological models using Cor.4U human inducible pluripotent stem cell-derived cardiomyocytes (hiPS-CMs): 1) endothelin-1 (ET-1), and 2) 48-h hypoxia (1% O2). Both models were transfected with synthetic miR-451a mimics or scramble control. Expression of both mRNA and miR was determined by quantitative real-time polymerase chain reaction and protein activity by (MMP-2/9) activity assay. Bioinformatic analyses were performed using Targetscan 7.1 and STRING 10.5. hiPS-CMs stimulated by hypoxia increased both MMP-2 and MMP-9 expression levels compared with normoxia (P < 0.05), whereas ET-1 stimulation only increased the MMP-9 level compared with vehicle controls (P < 0.05). miR-451a mimics prevented the increase of MMP-2 and MMP-9 expression in both models. Protein activity of MMP-2 and MMP-9 was confirmed to be lower following treatment with miR-451a mimic compared with scramble-controls. Six of 28 predicted gene transcripts of miR-451a were linked to MMP-2 and MMP-9; Macrophage migration inhibitory factor (MIF) was the only predicted target of miR-451a that was increased by ET-1 and hypoxia and reduced following miR-451a mimic transfection. miR-451a prevent the increase of MMP-2 and MMP-9 in human cardiomyocytes during pathological stress. The modulation by miR-451a on MMP-2 and MMP-9 is caused by MIF.


Assuntos
Cardiomegalia/enzimologia , Células-Tronco Pluripotentes Induzidas/enzimologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/metabolismo , Miócitos Cardíacos/enzimologia , Cardiomegalia/genética , Cardiomegalia/patologia , Diferenciação Celular , Hipóxia Celular , Linhagem Celular , Endotelina-1/toxicidade , Ativação Enzimática , Regulação Enzimológica da Expressão Gênica , Humanos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/patologia , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/metabolismo , Fatores Inibidores da Migração de Macrófagos/genética , Fatores Inibidores da Migração de Macrófagos/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , MicroRNAs/genética , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Transdução de Sinais
9.
Toxicol Lett ; 319: 197-203, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31785464

RESUMO

The chemical warfare agent sulfur mustard (SM) affects all cells in the epidermis including melanocytes which are responsible for melanin synthesis. After exposure to SM, pigment abnormalities like hypo- and hyperpigmentation can occur. The underlying molecular pathomechanisms of SM exposure on human melanogenesis have not been elucidated so far. In our study, we investigated the effect of SM on human melanocytes and melanogenesis. Normal human epidermal melanocytes (NHEM) were used as in vitro model and they were exposed to different concentrations of SM (4.5 µM-100 µM). Melanin production was analyzed by absorption measurements at 405 nm. In addition, quantitative real-time PCR (qPCR) and Western blot experiments were performed to determine the expression of essential melanogenesis-related proteins including tyrosinase (TYR), tyrosinase-related protein (TRP) 1 and 2 and microphthalmia transcription factor (MITF). Our findings demonstrated that exposure to low SM concentrations increased melanin synthesis accompanied with an increase in protein expression. In contrast, high SM concentrations led to decreased melanin content and a downregulation in expression of all investigated melanogenesis-associated proteins. We concluded that low SM concentrations may cause hyperpigmentation while high SM concentrations decreased melanin content which may explain hypopigmented skin areas in SM exposed patients.


Assuntos
Substâncias para a Guerra Química/toxicidade , Melaninas/biossíntese , Gás de Mostarda/toxicidade , Células Cultivadas , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hiperpigmentação/induzido quimicamente , Hipopigmentação/induzido quimicamente , Oxirredutases Intramoleculares/efeitos dos fármacos , Melaninas/genética , Melanócitos/efeitos dos fármacos , Melanócitos/metabolismo , Fator de Transcrição Associado à Microftalmia/biossíntese , Fator de Transcrição Associado à Microftalmia/genética , Monofenol Mono-Oxigenase/biossíntese , Monofenol Mono-Oxigenase/genética , Tripsina/biossíntese , Tripsina/genética
10.
Gen Comp Endocrinol ; 287: 113352, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31794733

RESUMO

Several prostaglandins (PGs) have been identified in different insect species. However, their biosynthesis and physiological roles in insects remain unclear. PGD2 is synthesized by isomerization from PGH2 in mammals. This study identified a PGD2 synthase (SePGDS) in a lepidopteran insect, Spodoptera exigua. It showed sequence homology (32.8%) with human PGDS. Based on its conserved active site residues, its N-terminal tyrosine (Y8) was predicted to mediate electron relay from glutathione to PGH2 substrate, which was distinct from the catalysis of PGE2 (=PGD2 isomer) synthase (SePGES). SePGDS was highly expressed in larval and adult stages. RNA interference (RNAi) of SePGDS expression resulted in immunosuppression of cellular immune responses by suppressing the expression of actin polymerization-associated genes. It also suppressed the expression of some antimicrobial genes. Such immunosuppression induced by RNAi treatment was specifically rescued by the addition of PGD2, but not its precursor, arachidonic acid. Such RNAi treatment in adults prevented egg development in females by inhibiting choriogenesis. RNAi treatment also suppressed nurse cell dumping to growing oocytes. However, the addition of PGD2 rescued egg development of RNAi-treated females. These results suggest that SePGDS is responsible for the production of PGD2 which mediates immune and reproductive processes of S. exigua.


Assuntos
Proteínas de Insetos/metabolismo , Oxirredutases Intramoleculares/metabolismo , Lipocalinas/metabolismo , Animais , Feminino , Spodoptera
11.
J Sci Food Agric ; 100(2): 672-681, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31583701

RESUMO

BACKGROUND: Hibiscus sabdariffa is commonly used in daily life and its extract is applied widely in food and cosmetics. However, it has not been evaluated for its anti-aging effects. RESULTS: Hibiscus sabdariffa calyx aqueous extract (HSCAE) has shown potential collagenase activity suppression effects, together with tyrosinase activity inhibition, and anti-oxidation as a free radical scavenger. The current investigation demonstrated that HSCAE was not cytotoxic in skin fibroblasts, and it significantly decreased ultraviolet B (UVB)-induced reactive oxygen species (ROS) on a flow cytometry assay. Moreover, HSCAE reduced matrix metalloproteinase (MMP) expression, increased tissue inhibition of metalloproteinase (TIMP)-1 level, and enhanced collagen content by inhibiting collagenase activity. It also blocked mRNA and protein expressions of melanin production pathway key factors, including the microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP-1), and dopachrome tautomerase-2 (TRP-2). CONCLUSION: These results demonstrated, for the first time, the potential of HSCAE as a natural antioxidant with the ability to maintain collagen production and to decrease melanin syntheses under UVB radiation, for anti-aging effects. © 2019 Society of Chemical Industry.


Assuntos
Depuradores de Radicais Livres/farmacologia , Hibiscus/química , Extratos Vegetais/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Animais , Linhagem Celular , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Humanos , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/metabolismo , Camundongos , Monofenol Mono-Oxigenase/genética , Monofenol Mono-Oxigenase/metabolismo , Oxirredutases/genética , Oxirredutases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Envelhecimento da Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos
12.
Glia ; 68(1): 95-110, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31479164

RESUMO

We have previously reported that prostaglandin D2 Synthase (L-PGDS) participates in peripheral nervous system (PNS) myelination during development. We now describe the role of L-PGDS in the resolution of PNS injury, similarly to other members of the prostaglandin synthase family, which are important for Wallerian degeneration (WD) and axonal regeneration. Our analyses show that L-PGDS expression is modulated after injury in both sciatic nerves and dorsal root ganglia neurons, indicating that it might play a role in the WD process. Accordingly, our data reveals that L-PGDS regulates macrophages phagocytic activity through a non-cell autonomous mechanism, allowing myelin debris clearance and favoring axonal regeneration and remyelination. In addition, L-PGDS also appear to control macrophages accumulation in injured nerves, possibly by regulating the blood-nerve barrier permeability and SOX2 expression levels in Schwann cells. Collectively, our results suggest that L-PGDS has multiple functions during nerve regeneration and remyelination. Based on the results of this study, we posit that L-PGDS acts as an anti-inflammatory agent in the late phases of WD, and cooperates in the resolution of the inflammatory response. Thus, pharmacological activation of the L-PGDS pathway might prove beneficial in resolving peripheral nerve injury.


Assuntos
Oxirredutases Intramoleculares/biossíntese , Lipocalinas/biossíntese , Ativação de Macrófagos/fisiologia , Regeneração Nervosa/fisiologia , Neuropatia Ciática/enzimologia , Animais , Feminino , Oxirredutases Intramoleculares/genética , Lipocalinas/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Traumatismos dos Nervos Periféricos/genética , Traumatismos dos Nervos Periféricos/metabolismo , Traumatismos dos Nervos Periféricos/patologia , Neuropatia Ciática/genética , Neuropatia Ciática/patologia
13.
Phytochemistry ; 169: 112152, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31606607

RESUMO

The CYP74 family of cytochromes P450 includes four fatty acid hydroperoxide metabolizing enzymes: allene oxide synthase (AOS), hydroperoxide lyase (HPL), divinyl ether synthase, and epoxyalcohol synthase (EAS). All P450s have six substrate recognition sites (SRSs) in their structures. Some CYP74 mutations in SRSs leading to their interconversions including substitutions in "F/L toggle" (SRS-1 region) were reported before. For further elucidation of the role of this site in CYP74 catalysis, the effect of Phe/Leu mutation on the specificity of selected AOSs was studied in the present work. Mutant forms of ZmAOS1 (CYP74A19, Zea mays), LeAOS3 (CYP74C3, Lycopersicon esculentum), and PpAOS2 (CYP74A8, Physcomitrella patens) acquired partial EAS activity. Mutant forms of ZmAOS1 and PpAOS2 possessed additional HPL activities. The results validate the significance of the "F/L toggle" as a catalytic determinant of CYP74s, as well as the importance of the conserved Phe at this site for the AOS catalysis.


Assuntos
Oxirredutases Intramoleculares/metabolismo , Leucina/genética , Fenilalanina/genética , Biocatálise , Oxirredutases Intramoleculares/genética , Mutação , Especificidade por Substrato
14.
Food Chem ; 309: 125737, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31780227

RESUMO

Chlorophyll degradation is the main reason for postharvest yellowing of broccoli. To uncover the role of jasmonic acid (JA) on the degradation of chlorophyll, broccoli flowers were treated with exogenous methyl jasmonate (MeJA) and diethyldithiocarbamic acid (DIECA). We found a surge of endogenous JA content with the yellowing process, and a significant correlation between JA and chlorophyll content. MeJA treatments led to increased endogenous JA, increased allene oxide cyclase (AOC) activity, and enhanced expression of JA synthesis genes. MeJA caused a stronger reduction in the maximum quantum yield (Fv/Fm), fluorescence decline ratio (Rfd), and total chlorophyll content, advanced the peak of pheide a oxygenase (PAO) activity, and up-regulated the expression of chlorophyll degradation genes. The DIECA treatment resulted in lower endogenous levels of JA, and AOC and 12-oxo-phytodienoic acid reductase (OPR) activity. This study revealed that the potential role of JA on broccoli yellowing is to promote the chlorophyll degradation.


Assuntos
Brassica/metabolismo , Clorofila/metabolismo , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Acetatos/farmacologia , Brassica/efeitos dos fármacos , Clorofila/química , Ciclopentanos/química , Ciclopentanos/farmacologia , Ditiocarb/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Oxirredutases Intramoleculares/metabolismo , Oxigenases/metabolismo , Oxilipinas/química , Oxilipinas/farmacologia
15.
BMC Genomics ; 20(1): 962, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823726

RESUMO

BACKGROUND: Melanocytes are derived from neural crest stem cells in the embryonic stage. In mature melanocytes, a series of complex enzyme-catalyzed reactions leads to the production of melanins, which determine the hair and skin colors of animals. The process of melanogenesis is complex and can be regulated by mRNA, microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) genes. MiRNAs are a type of endogenous noncoding RNA approximately 22 nt in size that predominantly regulate gene expression by inhibiting translation. miR-380-3p is a candidate miRNA potentially related to melanogenesis. To better understand the mechanism of miR-380-3p melanogenesis regulation, plasmids to overexpress or knockdown miR-380-3p were transfected into alpaca melanocytes, and their effects on melanogenesis were evaluated. RESULTS: In situ hybridization identified a positive miR-380-3p signal in alpaca melanocyte cytoplasm. Luciferase activity assays confirmed that SOX6 is targeted by miR-380-3p. miR-380-3p overexpression and knockdown in alpaca melanocytes respectively downregulated and upregulated SOX6 expression at the mRNA and protein levels. Additionally, miR-380-3p overexpression and knockdown, respectively, in alpaca melanocytes decreased and increased the mRNA levels of melanin transfer-related genes, including microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosine-related protein-1 (TYRP1), and dopachrome tautomerase (DCT). In contrast, miR-380-3p overexpression and knockdown respectively increased and decreased the mRNA levels of ß-catenin. Additionally, the effect of miR-380-3p on melanogenesis was assessed by Masson-Fontana melanin staining. CONCLUSIONS: The results demonstrated that miR-380-3p targeted SOX6 to regulate melanogenesis by influencing ß-catenin and MITF transcription and translation, which reduced the expression of downstream genes, including TYR, TYRP1, and DCT. These results provide insights into the mechanisms through which miR-380-3p controls melanogenesis.


Assuntos
Melaninas/metabolismo , Melanócitos/metabolismo , MicroRNAs/genética , Fatores de Transcrição SOXD/genética , Regiões 3' não Traduzidas , Animais , Camelídeos Americanos , Células Cultivadas , Expressão Gênica , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Oxirredutases Intramoleculares/genética , Masculino , MicroRNAs/metabolismo , Fator de Transcrição Associado à Microftalmia/genética , Fator de Transcrição Associado à Microftalmia/metabolismo , Monofenol Mono-Oxigenase/genética , Oxirredutases/genética , Fatores de Transcrição SOXD/metabolismo , Pele/citologia , Pele/metabolismo , Pele/patologia , beta Catenina/genética , beta Catenina/metabolismo
16.
Crit Care ; 23(1): 410, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842964

RESUMO

BACKGROUND: There is a compelling unmet medical need for biomarker-based models to risk-stratify patients with acute respiratory distress syndrome. Effective stratification would optimize participant selection for clinical trial enrollment by focusing on those most likely to benefit from new interventions. Our objective was to develop a prognostic, biomarker-based model for predicting mortality in adult patients with acute respiratory distress syndrome. METHODS: This is a secondary analysis using a cohort of 252 mechanically ventilated subjects with the diagnosis of acute respiratory distress syndrome. Survival to day 7 with both day 0 (first day of presentation) and day 7 sample availability was required. Blood was collected for biomarker measurements at first presentation to the intensive care unit and on the seventh day. Biomarkers included cytokine-chemokines, dual-functioning cytozymes, and vascular injury markers. Logistic regression, latent class analysis, and classification and regression tree analysis were used to identify the plasma biomarkers most predictive of 28-day ARDS mortality. RESULTS: From eight biologically relevant biomarker candidates, six demonstrated an enhanced capacity to predict mortality at day 0. Latent-class analysis identified two biomarker-based phenotypes. Phenotype A exhibited significantly higher plasma levels of angiopoietin-2, macrophage migration inhibitory factor, interleukin-8, interleukin-1 receptor antagonist, interleukin-6, and extracellular nicotinamide phosphoribosyltransferase (eNAMPT) compared to phenotype B. Mortality at 28 days was significantly higher for phenotype A compared to phenotype B (32% vs 19%, p = 0.04). CONCLUSIONS: An adult biomarker-based risk model reliably identifies ARDS subjects at risk of death within 28 days of hospitalization.


Assuntos
Biomarcadores/análise , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Medição de Risco/métodos , APACHE , Adulto , Biomarcadores/sangue , Citocinas/análise , Citocinas/sangue , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/análise , Proteína Antagonista do Receptor de Interleucina 1/sangue , Interleucina-1beta/análise , Interleucina-1beta/sangue , Interleucina-6/análise , Interleucina-6/sangue , Interleucina-8/análise , Interleucina-8/sangue , Oxirredutases Intramoleculares/análise , Oxirredutases Intramoleculares/sangue , Análise de Classes Latentes , Modelos Logísticos , Fatores Inibidores da Migração de Macrófagos/análise , Fatores Inibidores da Migração de Macrófagos/sangue , Masculino , Pessoa de Meia-Idade , Nicotinamida Fosforribosiltransferase/análise , Nicotinamida Fosforribosiltransferase/sangue , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/sangue , Síndrome do Desconforto Respiratório do Adulto/sangue , Síndrome do Desconforto Respiratório do Adulto/epidemiologia , Medição de Risco/normas , Receptores de Esfingosina-1-Fosfato/análise , Receptores de Esfingosina-1-Fosfato/sangue , Proteínas de Transporte Vesicular/análise , Proteínas de Transporte Vesicular/sangue
17.
Genes (Basel) ; 10(11)2019 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752120

RESUMO

Duchenne muscular dystrophy (DMD) is a progressive hereditary muscular disease with X-linked recessive inheritance, that leads patients to premature death. The loss of dystrophin determines membrane instability, causing cell damage and inflammatory response. Macrophage migration inhibitory factor (MIF) is a cytokine that exerts pleiotropic properties and is implicated in the pathogenesis of a variety of diseases. Recently, converging data from independent studies have pointed to a possible role of MIF in dystrophic muscle disorders, including DMD. In the present study, we have investigated the modulation of MIF and MIF-related genes in degenerative muscle disorders, by making use of publicly available whole-genome expression datasets. We show here a significant enrichment of MIF and related genes in muscle samples from DMD patients, as well as from patients suffering from Becker's disease and limb-girdle muscular dystrophy type 2B. On the other hand, transcriptomic analysis of in vitro differentiated myotubes from healthy controls and DMD patients revealed no significant alteration in the expression levels of MIF-related genes. Finally, by analyzing DMD samples as a time series, we show that the modulation of the genes belonging to the MIF network is an early event in the DMD muscle and does not change with the increasing age of the patients, Overall, our analysis suggests that MIF may play a role in vivo during muscle degeneration, likely promoting inflammation and local microenvironment reaction.


Assuntos
Redes Reguladoras de Genes/imunologia , Oxirredutases Intramoleculares/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Distrofia Muscular de Duchenne/imunologia , Transdução de Sinais/genética , Estudos de Casos e Controles , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Voluntários Saudáveis , Humanos , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/imunologia , Fatores Inibidores da Migração de Macrófagos/genética , Fatores Inibidores da Migração de Macrófagos/imunologia , Fibras Musculares Esqueléticas/imunologia , Fibras Musculares Esqueléticas/patologia , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/imunologia , Distrofia Muscular do Cíngulo dos Membros/patologia , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/patologia , Miotonia Congênita/genética , Miotonia Congênita/imunologia , Miotonia Congênita/patologia , Transdução de Sinais/imunologia
18.
Arch Biochem Biophys ; 676: 108126, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31589830

RESUMO

A catalase-related allene oxide synthase (cAOS) or a hydroperoxide lyase (cHPL) fused together with an 8R-lipoxygenase is involved in the stress signaling of corals via an arachidonic acid pathway. cAOS gives rise to α-ketol and cyclopentenone, while cHPL catalyzes the cleavage of 8R-hydroperoxyeicosatetraenoic acid (8R-HpETE) to C8-oxo acid and C12 aldehyde. In silico analysis of the substrate entry sites of highly identical coral cAOS and cHPL indicated that two positively charged residues of cAOS, K60 and K107, and the corresponding residues of cHPL, E60 and K107, may be involved in the anchoring of the carboxy group of polyunsaturated fatty acid (PUFA) hydroperoxides. A mutational analysis of cAOS and cHPL revealed that K60 or E60 and K107 were not necessary in the tethering of 8R-HpETE, however, the E60 of cHPL was essential in the productive binding of PUFA hydroperoxides. The substrate preferences of cAOS and cHPL were determined with hydroperoxy derivatives of C18, C20, C22 PUFAs, anandamide (AEA), 1-arachidonoyl glycerol (1-AG) and selected methylated substrates. Although cAOS and cHPL were able to metabolize different free PUFA substrates and arachidonoyl derivatives, only cHPL catalyzed the reaction with methylated PUFA hydroperoxides. The differences in the substrate binding and preferences between cAOS and cHPL can be explained by the distinct properties of their substrate entry sites. The current study demonstrated that homologous PUFA metabolizing enzymes may contribute to the versatile usage of the substrate pool.


Assuntos
Aldeído Liases/química , Aldeído Liases/metabolismo , Catalase/química , Catalase/metabolismo , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/metabolismo , Oxirredutases Intramoleculares/química , Oxirredutases Intramoleculares/metabolismo , Homologia de Sequência de Aminoácidos , Animais , Antozoários/enzimologia , Simulação por Computador , Ácidos Graxos Insaturados/química , Ácidos Graxos Insaturados/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Simulação de Acoplamento Molecular , Ligação Proteica , Conformação Proteica , Eletricidade Estática , Especificidade por Substrato
19.
Medicina (Kaunas) ; 55(10)2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31581595

RESUMO

Background and objectives: Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT) are two pleiotropic and primarily, but not exclusively, proinflammatory cytokines belonging to the MIF family of cytokines that have recently been shown to be implicated in the pathogenesis of progressive forms of human progressive Multiple Sclerosis (MS) and the experimental model counterpart in rodents. Materials and Methods: We have presently evaluated a transcriptomic analysis of the expression of MIF, DDT, their receptors CD74 and CD44, and MIF co-receptors CXCR2, CXCR4, and CXCR7 in peripheral blood of patients with Clinically Isolated Syndrome (CIS), with rapid progression to clinical defined MS. Results: Our analysis reveals that MIF, DDT, and CD44 are overexpressed in CD4+ T cells from patients with CIS, as compared to healthy controls. Accordingly, a significant overlap was observed between the genes overexpressed in CD4+ T cells from patients with CIS and the genes belonging to the MIF regulatory network. This upregulated expression appeared to be unique for CD4+T cells, as other immune cells including CD8+ T cells, B cells, and monocytes from these patients exhibited expression levels of these molecules that were superimposable to those observed in healthy controls. Conclusions: Overall, our data suggest that the overexpression MIF cytokine family signature may occur in CD4+ T cells from patients with CIS, and that this phenomenon may be implicated in the pathogenesis of the disease, offering the possibility to represent both a diagnostic marker and a therapeutic target.


Assuntos
Receptores de Hialuronatos/metabolismo , Oxirredutases Intramoleculares/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Esclerose Múltipla/metabolismo , Regulação para Cima , Adolescente , Adulto , Biomarcadores/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Feminino , Humanos , Masculino , Esclerose Múltipla/sangue , Adulto Jovem
20.
Int J Dev Neurosci ; 78: 77-82, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499143

RESUMO

BACKGROUND: The second trimester is a period of neurogenesis and neuronal migration, which may be affected by exposure to anesthetics. Studies have suggested that multiple anesthetic exposures may have a significant impact on neuronal migration. METHODS: Pregnant C57BL/6 mice at embryonic day 14.5 were randomly divided into four groups: Con x 1, Sev x 1, Con x 2, and Sev x 2. Cortical neuronal migration in offspring mice was detected by GFP immunostaining, and the number of cells in the cortex was analyzed. RESULTS: Dual exposure to sevoflurane, not single sevoflurane exposure, caused neuronal migration deficits. Dual exposure to sevoflurane increased the expression of prostaglandin D2 synthase (Ptgds). Furthermore, Ptgds siRNA attenuated neuronal migration deficits induced by dual sevoflurane exposure. CONCLUSION: Our study suggests that multiple sevoflurane exposures in pregnant mice may induce neuronal migration deficits in offspring mice. Additional studies comprising long-term behavioral tests are required to confirm the effects of sevoflurane exposure during pregnancy.


Assuntos
Anestésicos Inalatórios/farmacologia , Movimento Celular/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Oxirredutases Intramoleculares/metabolismo , Lipocalinas/metabolismo , Neurônios/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Sevoflurano/farmacologia , Regulação para Cima/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Córtex Cerebral/metabolismo , Feminino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Neurônios/metabolismo , Gravidez
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