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1.
Int J Mol Sci ; 22(19)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34639105

RESUMO

Keloids are a common form of pathologic wound healing and are characterized by an excessive production of extracellular matrix. This study examined the major contributing mechanism of human keloid pathogenesis using transcriptomic analysis. We identified the upregulation of mitochondrial oxidative stress response, protein processing in the endoplasmic reticulum, and TGF-ß signaling in human keloid tissue samples compared to controls, based on ingenuity pathway and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Electron microscopic examinations revealed an increased number of dysmorphic mitochondria and expanded endoplasmic reticulum (ER) in human keloid tissue samples than that in controls. Western blot analysis performed using human tissues suggested noticeably higher ER stress signaling in keloids than in normal tissues. Treatment with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, significantly decreased scar formation in rabbit models, compared to normal saline and steroid injections. In summary, our findings demonstrate the contributions of mitochondrial dysfunction and dysregulated ER stress signaling in human keloid formation and the potential of TUDCA in the treatment of keloids.

2.
Int J Mol Sci ; 22(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34299127

RESUMO

Reelin is a secretory protein involved in a variety of processes in forebrain development and function, including neuronal migration, dendrite growth, spine formation, and synaptic plasticity. Most of the function of Reelin is focused on excitatory neurons; however, little is known about its effects on inhibitory neurons and inhibitory synapses. In this study, we investigated the phosphatidylinositol 3-kinase/Akt pathway of Reelin in primary cortical and hippocampal neurons. Individual neurons were visualized using immunofluorescence to distinguish inhibitory neurons from excitatory neurons. Reelin-rich protein supplementation significantly induced the phosphorylation of Akt and ribosomal S6 protein in excitatory neurons, but not in most inhibitory neurons. In somatostatin-expressing inhibitory neurons, one of major subtypes of inhibitory neurons, Reelin-rich protein supplementation induced the phosphorylation of S6. Subsequently, we investigated whether or not Reelin-rich protein supplementation affected dendrite development in cultured inhibitory neurons. Reelin-rich protein supplementation did not change the total length of dendrites in inhibitory neurons in vitro. Finally, we examined the development of inhibitory synapses in primary hippocampal neurons and found that Reelin-rich protein supplementation significantly reduced the density of gephyrin-VGAT-positive clusters in the dendritic regions without changing the expression levels of several inhibitory synapse-related proteins. These findings indicate a new role for Reelin in specific groups of inhibitory neurons and the development of inhibitory synapses, which may contribute to the underlying cellular mechanisms of RELN-associated neurological disorders.


Assuntos
Moléculas de Adesão Celular Neuronais/metabolismo , Dendritos/fisiologia , Proteínas da Matriz Extracelular/metabolismo , Potenciais Pós-Sinápticos Inibidores , Proteínas do Tecido Nervoso/metabolismo , Inibição Neural , Plasticidade Neuronal , Neurônios/fisiologia , Serina Endopeptidases/metabolismo , Sinapses/fisiologia , Animais , Moléculas de Adesão Celular Neuronais/genética , Proteínas da Matriz Extracelular/genética , Hipocampo/citologia , Hipocampo/fisiologia , Camundongos , Camundongos Endogâmicos ICR , Proteínas do Tecido Nervoso/genética , Neurogênese , Neurônios/citologia , Serina Endopeptidases/genética , Transdução de Sinais
3.
Cells ; 10(6)2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073755

RESUMO

Interleukin-4 (IL-4) and IL-13 are the major T helper 2 (Th2) cytokines, and they are involved in the regulation of metabolism in the adipose tissue. The liver contains diverse innate and adaptive immune cells, but it remains to be determined whether Th2 cytokines modulate energy metabolism in the liver. Here, using gene expression data from the Gene Expression Omnibus (GEO) and the BXD mouse reference population, we determined that the Th2 cytokines IL-4 and IL-13 increase the secretion of fibroblast growth factor 21 (FGF21) in the liver. In vitro experiments confirmed that FGF21 was highly expressed in response to IL-4 and IL-13, and this response was abolished by the Janus kinase (JAK)-signal transducer and activator of transcription 6 (STAT6) blockade. Moreover, FGF21 expression in response to Th2 cytokines was augmented by selective peroxisome proliferator-activated receptor α (PPARα) inhibition. In vivo administration of IL-4 increased FGF21 protein levels in the liver in a STAT6-dependent manner, but FGF21 secretion in response to IL-4 was not observed in the epididymal white adipose tissue (eWAT) despite the activation of STAT6. Intraperitoneal administration of IL-33, an activator of type 2 immune responses, significantly increased the level of FGF21 in the serum and liver after 24 h, but repeated administration of IL-33 attenuated this effect. Taken together, these data demonstrate that the IL-4/IL-13-STAT6 axis regulates metabolic homeostasis through the induction of FGF21 in the liver.

4.
Endocrinol Metab (Seoul) ; 36(3): 661-671, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34154043

RESUMO

BACKGROUND: The nature and role of the mitochondrial stress response in adipose tissue in relation to obesity are not yet known. To determine whether the mitochondrial unfolded protein response (UPRmt) in adipose tissue is associated with obesity in humans and rodents. METHODS: Visceral adipose tissue (VAT) was obtained from 48 normoglycemic women who underwent surgery. Expression levels of mRNA and proteins were measured for mitochondrial chaperones, intrinsic proteases, and components of electron-transport chains. Furthermore, we systematically analyzed metabolic phenotypes with a large panel of isogenic BXD inbred mouse strains and Genotype-Tissue Expression (GTEx) data. RESULTS: In VAT, expression of mitochondrial chaperones and intrinsic proteases localized in inner and outer mitochondrial membranes was not associated with body mass index (BMI), except for the Lon protease homolog, mitochondrial, and the corresponding gene LONP1, which showed high-level expression in the VAT of overweight or obese individuals. Expression of LONP1 in VAT positively correlated with BMI. Analysis of the GTEx database revealed that elevation of LONP1 expression is associated with enhancement of genes involved in glucose and lipid metabolism in VAT. Mice with higher Lonp1 expression in adipose tissue had better systemic glucose metabolism than mice with lower Lonp1 expression. CONCLUSION: Expression of mitochondrial LONP1, which is involved in the mitochondrial quality control stress response, was elevated in the VAT of obese individuals. In a bioinformatics analysis, high LONP1 expression in VAT was associated with enhanced glucose and lipid metabolism.

5.
Thyroid ; 31(5): 772-786, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33256569

RESUMO

Background: Mitochondrial stress is known to activate the mitochondrial unfolded protein response (UPRmt). The UPRmt results in the secretion of mitochondrial cytokines (mitokines), which can promote a hormetic response cell nonautonomously, and has been reported to be protumorigenic. Growth differentiation factor 15 (GDF15) is a well-characterized mitokine, which is reported to have a mitohormetic effect. Thus, we investigated whether GDF15 induction could prime a subpopulation of thyroid cancer cells to provide invasive advantages. Methods: The UPRmt, including mitokine expression, was assessed in the context of thyroid cancer in vitro and in vivo. GDF15 expression in 266 patients with papillary thyroid carcinoma (PTC) was determined by immunohistochemistry. The serum levels of GDF15 were measured in healthy subjects and PTC patients. In addition, our own and The Cancer Genome Atlas data were analyzed to determine the expression level of GDF15 in thyroid cancers. The role of GDF15 in tumor aggressiveness was investigated by observing the effects of GDF15 knockdown in BCPAP, TPC-1, 8505C, and FRO cells. Results: Pharmacological inhibition of mitochondrial oxidative phosphorylation function in thyroid cancer cells robustly increased GDF15 expression. The expression of GDF15 was associated with activation of the mitochondrial integrated stress response pathway in PTC patients. Circulating GDF15 levels were significantly higher in PTC patients than in the controls, and tumor expression of GDF15 was related to tumor aggressiveness. In vitro and in vivo knockdown of GDF15 in a thyroid cancer model showed decreased viability, migration, and invasion compared with the control cells via regulation of STAT3. Conclusions: In this study, we demonstrated that GDF15 is a mitokine induced in thyroid cancer cells upon mitochondrial stress. GDF15-induced STAT3 activation determined tumor progression in thyroid cancer. The GDF15-STAT3 signaling axis may be a target in aggressiveness of thyroid cancer.

6.
PLoS One ; 15(9): e0239555, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32966311

RESUMO

OBJECTIVE: To investigate the thicknesses of the ganglion cell-inner plexiform layer (GC-IPL) and retinal nerve fiber layer (RNFL) of the fellow eyes of patients with unilateral exudative age-related macular degeneration (AMD). METHODS: A total of 107 patients with unilateral exudative AMD [34 of typical choroidal neovascularization (tCNV), Group A; 73 of polypoidal choroidal vasculopathy (PCV), Group B] and 73 normal control eyes (Group C) were included. Drusen and subretinal drusenoid deposits were assessed in all participants using fundus photography, autofluorescence, and optical coherence tomography (OCT). The GC-IPL and RNFL thicknesses were measured using Cirrus HD-OCT and compared among groups. Linear regression analyses were used to evaluate the factors associated with GC-IPL thicknesses. RESULTS: The average GC-IPL thicknesses of Groups A, B, and C were 77.09 ± 3.87, 80.10 ± 6.61, and 80.88 ± 6.50 µm, respectively (p = 0.022). Sectoral GC-IPLs and central macular thicknesses (CMTs) were significantly different among groups (all, p <0.05), whereas none of the RNFL parameters differed significantly (all, p >0.05). Multivariate linear regression analyses revealed that age (p <0.001), CMT (p <0.001), and tCNV (p = 0.013) were significantly associated with average GC-IPL thickness, and the rate of reduction of GC-IPL thickness with increasing age in the fellow eyes of tCNV patients was higher than those in the PCV and control groups. CONCLUSIONS: Unilateral tCNV patients exhibited statistically significant reduction of the GC-IPL thickness in the fellow eyes, compared to values of the fellow eyes of unilateral PCV patients or control patients. RNFL values trended to be lower but did not reach statistical significance.


Assuntos
Degeneração Macular/diagnóstico por imagem , Retina/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neovascularização de Coroide/diagnóstico por imagem , Neovascularização de Coroide/patologia , Feminino , Angiofluoresceinografia , Humanos , Degeneração Macular/patologia , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Retina/patologia , Células Ganglionares da Retina/patologia , Neurônios Retinianos/patologia , Estudos Retrospectivos , Tomografia de Coerência Óptica
7.
Neuroreport ; 31(10): 762-769, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32453020

RESUMO

The mammalian neocortex is composed of six major layers of neurons. Each group of neurons in the cortical layers has distinct characteristics based on the expression of specific genes and connectivity patterns of neural circuits. Neuronal subtype transition and regional identity acquisition are established by temporal cues and interaction between several transcription factors during neurogenesis. The impairment of cortical lamination or neural circuits results in a wide range of neurodevelopmental disorders such as autism, schizophrenia, and certain forms of childhood epilepsy. Despite continuous efforts to classify neurons with the aid of genetic and epigenetic analyses, the neuron-specific properties associated with post-transcriptional modification remain unclear. In the present study, the distribution of phosphorylated S6-positive layers across the neocortex was examined using several layer markers. The development of pS6 S235/236 layers in layer V and the subplate was spatiotemporally regulated in the mouse brain. In addition, enhanced phosphorylation of ribosomal protein S6 in Ctip2-positive layer V neurons in vivo was sustained under in-vitro conditions using a culture of primary cortical neurons.

8.
Diabetologia ; 63(4): 837-852, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31925461

RESUMO

AIMS/HYPOTHESIS: Mitochondrial oxidative phosphorylation (OxPhos) is essential for energy production and survival. However, the tissue-specific and systemic metabolic effects of OxPhos function in adipocytes remain incompletely understood. METHODS: We used adipocyte-specific Crif1 (also known as Gadd45gip1) knockout (AdKO) mice with decreased adipocyte OxPhos function. AdKO mice fed a normal chow or high-fat diet were evaluated for glucose homeostasis, weight gain and energy expenditure (EE). RNA sequencing of adipose tissues was used to identify the key mitokines affected in AdKO mice, which included fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15). For in vitro analysis, doxycycline was used to pharmacologically decrease OxPhos in 3T3L1 adipocytes. To identify the effects of GDF15 and FGF21 on the metabolic phenotype of AdKO mice, we generated AdKO mice with global Gdf15 knockout (AdGKO) or global Fgf21 knockout (AdFKO). RESULTS: Under high-fat diet conditions, AdKO mice were resistant to weight gain and exhibited higher EE and improved glucose tolerance. In vitro pharmacological and in vivo genetic inhibition of OxPhos in adipocytes significantly upregulated mitochondrial unfolded protein response-related genes and secretion of mitokines such as GDF15 and FGF21. We evaluated the metabolic phenotypes of AdGKO and AdFKO mice, revealing that GDF15 and FGF21 differentially regulated energy homeostasis in AdKO mice. Both mitokines had beneficial effects on obesity and insulin resistance in the context of decreased adipocyte OxPhos, but only GDF15 regulated EE in AdKO mice. CONCLUSIONS/INTERPRETATION: The present study demonstrated that the adipose tissue adaptive mitochondrial stress response affected systemic energy homeostasis via cell-autonomous and non-cell-autonomous pathways. We identified novel roles for adipose OxPhos and adipo-mitokines in the regulation of systemic glucose homeostasis and EE, which facilitated adaptation of an organism to local mitochondrial stress.


Assuntos
Adipócitos/metabolismo , Proteínas de Ciclo Celular/genética , Metabolismo Energético/genética , Obesidade/genética , Adipócitos/patologia , Animais , Proteínas de Ciclo Celular/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Obesos , Obesidade/metabolismo , Obesidade/prevenção & controle , Especificidade de Órgãos/genética , Fosforilação Oxidativa
9.
Br J Ophthalmol ; 104(5): 600-603, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31409648

RESUMO

AIM: To determine the longitudinal changes in the axial length (AL) in patients with high myopia without any other ophthalmic disease METHODS: Participants were divided into two groups: a high myopia group (60 eyes) without myopic degeneration, such as chorioretinal atrophy or posterior staphyloma, and a control group (60 eyes). Both groups were further divided into subgroups according to the AL: subgroup 1 (≥27.5 mm), subgroup 2 (26.0-27.5 mm), subgroup 3 (24.5-26.0 mm) and subgroup 4 (<24.5 mm). The ALs were measured five times at 1-year interval using an IOL master, and the AL was fitted with linear mixed models. RESULTS: In the high myopia group, the AL showed a relatively constant increase at each visit, and they were significantly different with previous measurements at most visits, whereas the control group showed no significant change of AL. Subgroups 1,2 and 3 showed significant changes in AL over time (0.064, 0.032 and 0.012 mm/y, respectively). In univariate analyses, age, best-corrected visual acuity, baseline AL and anterior chamber depth were significantly correlated with changes in the AL in the high myopia group. In multivariate analysis, only baseline AL remained significant (p<0.001). CONCLUSIONS: Myopic eyes, including moderately myopic eyes, showed a consistent increase in AL over 4 years, and eyes with a longer baseline AL showed a greater increase in AL than eyes with a shorter AL.


Assuntos
Comprimento Axial do Olho/diagnóstico por imagem , Miopia Degenerativa/diagnóstico , Refração Ocular/fisiologia , Adulto , Biometria/métodos , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Miopia Degenerativa/fisiopatologia , Estudos Prospectivos , Fatores de Tempo , Tomografia de Coerência Óptica/métodos , Adulto Jovem
10.
Arch Pharm Res ; 42(12): 1031-1039, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31786745

RESUMO

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter that is required for the control of synaptic excitation/inhibition and neural oscillation. GABA is synthesized by glutamic acid decarboxylases (GADs) that are widely distributed and localized to axon terminals of inhibitory neurons as well as to the soma and, to a lesser extent, dendrites. The expression and activity of GADs is highly correlated with GABA levels and subsequent GABAergic neurotransmission at the inhibitory synapse. Dysregulation of GADs has been implicated in various neurological disorders including epilepsy and schizophrenia. Two isoforms of GADs, GAD67 and GAD65, are expressed from separate genes and have different regulatory processes and molecular properties. This review focuses on the recent advances in understanding the structure of GAD, its transcriptional regulation and post-transcriptional modifications in the central nervous system. This may provide insights into the pathological mechanisms underlying neurological diseases that are associated with GAD dysfunction.


Assuntos
Encéfalo/metabolismo , Glutamato Descarboxilase/metabolismo , Transmissão Sináptica , Ácido gama-Aminobutírico/metabolismo , Animais , Encéfalo/enzimologia , Humanos
11.
Sci Rep ; 9(1): 15814, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676848

RESUMO

To evaluate changes in peripapillary microvascular parameters in diabetes mellitus (DM) patients using optical coherence tomography angiography (OCTA). Seventy-one diabetic patients (40 in the no diabetic retinopathy [DR] group and 31 in the non-proliferative DR [NPDR] group) and 50 control subjects. OCTA (Zeiss HD-OCT 5000 with AngioPlex) 6 × 6 mm scans centered on the optic disc were analyzed. Peripapillary vessel density (VD), perfusion density (PD) in superficial capillary plexus (SCP) were automatically calculated. The average macular ganglion cell-inner plexiform layer (mGC-IPL) and peripapillary retinal nerve fiber layer (pRNFL) thicknesses of the no DR and NPDR groups were significantly thinner than those of the control group. The no DR and NPDR groups showed lower peripapillary VD and PD in SCP compared with the control group. Using univariate regression analyses, the average mGC-IPL thickness, the pRNFL thickness, the no DR group and NPDR group were significant factors that affected the peripapillary VD and PD in SCP. Multivariate regression analyses showed that the grade of DR was a significant factor affecting the peripapillary VD and PD in SCP. OCTA revealed that peripapillary microvascular parameters in the no DR and NPDR groups were lower than those of normal controls. The peripapillary VD and PD in SCP were correlated with the mGC-IPL thickness, the pRNFL thickness, and the no DR and NPDR groups. Changes in peripapillary OCTA parameters may help with understanding the pathophysiology of DM and evaluating a potentially valuable biomarker for patients with subclinical DR.


Assuntos
Retinopatia Diabética/fisiopatologia , Microvasos/fisiopatologia , Tomografia de Coerência Óptica/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Korean J Ophthalmol ; 33(3): 214-221, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31179652

RESUMO

PURPOSE: To investigate the clinical features and surgical outcomes of encapsulated bleb excision with collagen matrix implantation performed in patients with failed Ahmed glaucoma valve (AGV) implantation. METHODS: Eighteen eyes of 18 patients underwent encapsulated bleb excision and collagen matrix implantation. Patients were divided into two groups by reference to intraocular pressure (IOP) after preoperative ocular massage: group 1, patients who exhibited substantial IOP reductions; and group 2, patients who did not show substantial changes in IOP. Needling was conducted in group 2. The clinical features of the two groups were compared, including IOP changes after ocular massage and needling, AGV status, and surgical outcomes 6 months after surgery. RESULTS: The mean preoperative IOP among the 18 patients was 30.6 ± 5.7 mmHg. After ocular massage, the IOPs decreased by 22 and 26 mmHg in the two patients in group 1 and the 16 patients in group 2 showed a mean IOP reduction of 1.6 ± 2.2 mmHg (p = 0.013). IOPs decreased after needling in group 2 (range, 6 to 30 mmHg; p < 0.001). Fibrovascular tissue ingrowth into the AGV was observed in the two patients in group 1 and the same ingrowth was observed in 10 of the 16 patients in group 2. Six months after surgery the mean IOP among the 18 patients decreased significantly (19.1 ± 3.2 mmHg, p < 0.001). There was no significant difference in the mean postoperative IOP at 6 months between group 1 (14.0 ± 2.8 mmHg) and group 2 (19.8 ± 2.6 mmHg, p = 0.052). CONCLUSIONS: Encapsulated bleb excision with collagen matrix implantation resulted in a significant IOP-lowering effect 6 months after surgery. Fibrovascular ingrowth into the AGV was common but did not seem to be a major cause of AGV implantation failure.


Assuntos
Colágeno/administração & dosagem , Implantes para Drenagem de Glaucoma/efeitos adversos , Glaucoma/cirurgia , Pressão Intraocular/fisiologia , Implantação de Prótese/métodos , Acuidade Visual , Adulto , Idoso , Feminino , Seguimentos , Glaucoma/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Adulto Jovem
13.
Invest Ophthalmol Vis Sci ; 60(2): 823-829, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30807638

RESUMO

Purpose: To evaluate changes in peripapillary microvascular parameters in the fellow eyes of patients with unilateral retinal vein occlusion (RVO) using optical coherence tomography angiography (OCTA) and to determine the relationships between peripapillary microvasculature and retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness. Methods: Eighty-three patients with unilateral RVO (50 patients with branch RVO and 33 with central RVO) and 83 normal controls were enrolled. OCTA (Cirrus HD-OCT 5000 with AngioPlex) 6 × 6-mm scans centered on the optic disc were acquired. Peripapillary vessel density (VD) and perfusion density (PD) were automatically calculated. Results: The average RNFL and GC-IPL thicknesses in the fellow eyes of RVO patients were significantly thinner than in normal controls (93.5 vs. 96.6 µm, P = 0.013 and 81.3 vs. 84.1 µm, P = 0.003, respectively). In the fellow eyes of patients with unilateral RVO, the peripapillary VD of the inner ring, outer ring, and full area (17.47, 18.50, and 17.89, respectively) were significantly lower than those of controls (17.87, 18.87, and 18.27, respectively). The peripapillary PD of the inner ring, outer ring, and full area (0.456, 0.467, and 0.456, respectively) were also significantly lower than those of controls (0.468, 0.476, and 0.466, respectively). RNFL and GC-IPL thicknesses were correlated with both peripapillary VD and PD. Conclusions: OCTA revealed that peripapillary microvascular parameters in the fellow eyes of patients with unilateral RVO were decreased, and GC-IPL and RNFL thinning were also observed. The RNFL and GC-IPL thicknesses were positively correlated with both peripapillary VD and PD.


Assuntos
Disco Óptico/irrigação sanguínea , Retina/patologia , Oclusão da Veia Retiniana/patologia , Vasos Retinianos/patologia , Tomografia de Coerência Óptica/métodos , Idoso , Feminino , Angiofluoresceinografia , Humanos , Masculino , Microvasos/diagnóstico por imagem , Microvasos/patologia , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Disco Óptico/diagnóstico por imagem , Tamanho do Órgão , Retina/diagnóstico por imagem , Células Ganglionares da Retina/patologia , Oclusão da Veia Retiniana/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagem
14.
Neurochem Res ; 44(2): 509, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30506452

RESUMO

The original version of this article unfortunately contained a mistake. The funding information was incorrect in the Acknowledgement section of this article. The corrected text is given below.

15.
Retina ; 39(8): 1496-1503, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29668525

RESUMO

PURPOSE: To investigate the efficacy and safety of a primary core vitrectomy technique for combined phacovitrectomy in eyes showing a poor red reflex because of dense vitreous hemorrhage before cataract surgery. METHODS: A total of 156 eyes from 156 patients, who underwent combined phacovitrectomy because of cataract and dense vitreous hemorrhage, and who were followed up for at least 6 months were included. The patients were divided into a primary phacoemulsification group (Group A, 80 eyes) who underwent phacoemulsification first followed by total vitrectomy and a primary vitrectomy group (Group B, 76 eyes) who underwent core vitrectomy first followed by cataract surgery and followed by total vitrectomy. A conventional 23-gauge combined phacovitrectomy was performed in all patients. The operation time, including the total continuous curvilinear capsulorhexis time and total cataract surgery time, and the incidence of surgery-related complications were evaluated in the two groups. RESULTS: Diabetic retinopathy was the most common cause for vitreous hemorrhage in both groups (Group A: 51 eyes; Group B: 39 eyes). The total continuous curvilinear capsulorhexis time (P = 0.001) and total cataract surgery time (P = 0.036) were significantly shorter in Group B than in Group A. Among the complications, radial tears occurred more frequently in Group A than Group B, but these differences were not statistically significant (P = 0.211). Pupil size reduction during cataract surgery was greater in Group B than in Group A (P = 0.034). There were no significant differences in posterior capsular ruptures or posterior capsular opacities between the two groups. Other postoperative complications were not observed in either group until 6 months after surgery. CONCLUSION: Primary core vitrectomy combined with phacovitrectomy of patients who had dense vitreous hemorrhage helped to obtain a good red reflex and enabled surgeons to perform successful cataract surgery. In addition, primary core vitrectomy was an easy and safe technique, which reduced the surgery time and surgery-related complications. This surgical technique would, therefore, be helpful to vitreoretinal surgeons.


Assuntos
Facoemulsificação , Vitrectomia/métodos , Hemorragia Vítrea/cirurgia , Idoso , Capsulorrexe , Catarata/complicações , Feminino , Seguimentos , Humanos , Complicações Intraoperatórias , Implante de Lente Intraocular , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Pseudofacia/fisiopatologia , Estudos Retrospectivos , Acuidade Visual/fisiologia , Hemorragia Vítrea/complicações , Hemorragia Vítrea/fisiopatologia
16.
Neurochem Res ; 43(12): 2460-2472, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30426349

RESUMO

Upon synaptic stimulation and glutamate release, glutamate receptors are activated to regulate several downstream effectors and signaling pathways resulting in synaptic modification. One downstream intracellular effect, in particular, is the expression of immediate-early genes (IEGs), which have been proposed to be important in synaptic plasticity because of their rapid expression following synaptic activation and key role in memory formation. In this study, we screened a natural compound library in order to find a compound that could induce the expression of IEGs in primary cortical neurons and discovered that psoralidin, a natural compound isolated from the seeds of Psoralea corylifolia, stimulated synaptic modulation. Psoralidin activated mitogen-activated protein kinase (MAPK) signaling, which in turn induced the expression of neuronal IEGs, particularly Arc, Egr-1, and c-fos. N-methyl-D-aspartate (NMDA) receptors activation and extracellular calcium influx were implicated in the psoralidin-induced intracellular changes. In glutamate dose-response curve, psoralidin shifted glutamate EC50 to lower values without enhancing maximum activity. Interestingly, psoralidin increased the density, area, and intensity of excitatory synapses in primary hippocampal neurons, which were mediated by NMDA receptor activation and MAPK signaling. These results suggest that psoralidin triggers synaptic remodeling through activating NMDA receptor and subsequent MAPK signaling cascades and therefore could possibly serve as an NMDA receptor modulator.


Assuntos
Benzofuranos/farmacologia , Córtex Cerebral/metabolismo , Cumarínicos/farmacologia , Genes Precoces/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/metabolismo , Sinapses/metabolismo , Animais , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Expressão Gênica , Genes Precoces/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Gravidez , Sinapses/efeitos dos fármacos
17.
Mycobiology ; 46(2): 122-128, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29963313

RESUMO

Arbuscular mycorrhizal fungi (AMF) are well-known for their ability to improve plant growth and help plants withstand abiotic stress conditions. Unlike other fungi and bacteria, AMF cannot be stored, as they are obligate biotrophs. Long-term preservation of AMF spores is challenging and may lead to the loss of viability and efficiency. This study aimed to understand the effect of prolonged subculture of AMF species on the growth and glomalin-related soil protein (GRSP) from red pepper (Capsicum annuum L.). AMF spores were mass-produced using different techniques and subcultured in pots with sorghum sudangrass as the host plant for 3 years. Experimental soil samples were collected from natural grassland. Five different AMF inocula were used in triplicate as treatments. After 70 days of growth, red pepper plants were harvested and plant dry weight, plant nutrient content, mycorrhizal colonization, AMF spore count, and soil glomalin content were determined. AMF-treated plants displayed higher dry weight than controls, with only fruit dry weight being significantly different. Similarly, significant differences in phosphorous and potassium contents of the above-ground plant parts were observed between mycorrhizal and control treatments. In addition, soil GRSP content was significantly higher in plants inoculated with Rhizophagus sp. and Gigaspora margarita. The increased plant growth and GRSP content suggest that AMF can be maintained for 3 years without losing their efficiency if subcultured regularly with different symbiotic host plants.

18.
Nat Commun ; 9(1): 1551, 2018 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-29674655

RESUMO

Oxidative functions of adipose tissue macrophages control the polarization of M1-like and M2-like phenotypes, but whether reduced macrophage oxidative function causes systemic insulin resistance in vivo is not clear. Here, we show that mice with reduced mitochondrial oxidative phosphorylation (OxPhos) due to myeloid-specific deletion of CR6-interacting factor 1 (Crif1), an essential mitoribosomal factor involved in biogenesis of OxPhos subunits, have M1-like polarization of macrophages and systemic insulin resistance with adipose inflammation. Macrophage GDF15 expression is reduced in mice with impaired oxidative function, but induced upon stimulation with rosiglitazone and IL-4. GDF15 upregulates the oxidative function of macrophages, leading to M2-like polarization, and reverses insulin resistance in ob/ob mice and HFD-fed mice with myeloid-specific deletion of Crif1. Thus, reduced macrophage oxidative function controls systemic insulin resistance and adipose inflammation, which can be reversed with GDF15 and leads to improved oxidative function of macrophages.


Assuntos
Resistência à Insulina , Macrófagos/metabolismo , Obesidade/metabolismo , Fosforilação Oxidativa , Tecido Adiposo , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Fator 15 de Diferenciação de Crescimento/genética , Fator 15 de Diferenciação de Crescimento/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Obesidade/genética , Estresse Oxidativo
19.
Neurotoxicology ; 65: 221-230, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29107683

RESUMO

Gamma-aminobutyric acid (GABA) is the main neurotransmitter of inhibitory synaptic transmission, which is critical for oscillatory activity and synchronization of neurons in neural networks. GABA is synthesized by glutamic acid decarboxylase (GAD) enzymes in the inhibitory neuron and, thus, the deregulation of GAD enzymes and subsequent change of GABAergic activity are involved in various neurological and neuropsychiatric diseases. Under hypoxic conditions, neurons undergo neuropathological alterations which can be subtle or severe. Many studies have focused on the alteration of excitatory neurons by hypoxic injury, while inhibitory neuronal changes have not been well determined. Here, we demonstrated that hypoxic conditions decrease the expression of inhibitory neuron-related proteins, including GAD enzymes, through transcript downregulation and proteasomal degradation. Hif-1α induction and glutamate release under hypoxic conditions were implicated in the mechanism of GAD enzyme level reduction. Surprisingly, these conditions altered the density and size of inhibitory synapses, which was irreversible by reoxygenation, but was mediated by glutamate activity. Our findings suggest that potential implication of the compositional and structural alterations of inhibitory neuron in the pathogenesis of various hypoxic injuries.


Assuntos
Glutamato Descarboxilase/metabolismo , Hipóxia/enzimologia , Neurônios/citologia , Neurônios/enzimologia , Sinapses/enzimologia , Sinapses/fisiologia , Animais , Proteínas de Transporte/metabolismo , Córtex Cerebral/metabolismo , Regulação para Baixo , Indução Enzimática , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Proteínas de Membrana/metabolismo , Camundongos , Cultura Primária de Células , Complexo de Endopeptidases do Proteassoma/metabolismo
20.
Diabetes ; 66(11): 2774-2788, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28874416

RESUMO

T-helper type 2 (Th2) cytokines, including interleukin (IL)-13 and IL-4, produced in adipose tissue, are critical regulators of intra-adipose and systemic lipid and glucose metabolism. Furthermore, IL-13 is a potential therapy for insulin resistance in obese mouse models. Here, we examined mediators produced by adipocytes that are responsible for regulating systemic glucose homeostasis in response to Th2 cytokines. We used RNA sequencing data analysis of cultured adipocytes to screen factors secreted in response to recombinant IL-13. Recombinant IL-13 induced expression of growth differentiation factor 15 (GDF15) via the Janus kinase-activated STAT6 pathway. In vivo administration of α-galactosylceramide or IL-33 increased IL-4 and IL-13 production, thereby increasing GDF15 levels in adipose tissue and in plasma of mice; however, these responses were abrogated in STAT6 knockout mice. Moreover, administration of recombinant IL-13 to wild-type mice fed a high-fat diet (HFD) improved glucose intolerance; this was not the case for GDF15 knockout mice fed the HFD. Taken together, these data suggest that GDF15 is required for IL-13-induced improvement of glucose intolerance in mice fed an HFD. Thus, beneficial effects of Th2 cytokines on systemic glucose metabolism and insulin sensitivity are mediated by GDF15. These findings open up a potential pharmacological route for reversing insulin resistance associated with obesity.


Assuntos
Glicemia/fisiologia , Glucose/metabolismo , Fator 15 de Diferenciação de Crescimento/metabolismo , Células Th2/fisiologia , Células 3T3-L1 , Animais , Dieta Hiperlipídica , Intolerância à Glucose , Fator 15 de Diferenciação de Crescimento/genética , Interleucina-13/genética , Interleucina-13/metabolismo , Interleucina-13/fisiologia , Interleucina-33/administração & dosagem , Interleucina-33/farmacologia , Interleucina-4/genética , Interleucina-4/metabolismo , Interleucina-4/fisiologia , Janus Quinases/genética , Janus Quinases/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Proteína Dissulfeto Redutase (Glutationa) , Interferência de RNA , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Proteínas Recombinantes/farmacologia , Fator de Transcrição STAT6/genética , Fator de Transcrição STAT6/metabolismo
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