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1.
J Vasc Res ; 60(4): 183-192, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37660689

RESUMO

OBJECTIVE: The aim of the study was to evaluate the effect of the RhoA/ROCK inhibitor Fasudil on retinal neovascularization (NV) in vivo and angiogenesis in vitro. METHODS: C57BL/6 was used to establish an OIR model. First, RhoA/ROCK expression was first examined and compared between OIR and healthy controls. Then, we evaluated the effect of Fasudil on pathological retinal NV. Whole-mount retinal staining was performed. The percentage of NV area, the number of neovascular tufts (NVT), and branch points (BP) were quantified. Finally, human umbilical vein endothelial cells (HUVECs) were used to investigate the effect of Fasudil on angiogenesis. RESULTS: Real-time PCR and Western blotting showed that ROCK expression in retinal tissue was statistically upregulated in OIR. Furthermore, we found that Fasudil attenuated the percentage of NV area, the number of NVT, and BP significantly. In addition, Fasudil could suppress the proliferation and migration of HUVECs induced by VEGF. CONCLUSIONS: RhoA/ROCK might be involved in the pathogenesis of OIR. And its inhibitor Fasudil could suppress retinal NV in vivo and angiogenesis in vitro. Fasudil may be a potential treatment strategy for retinal vascular diseases.


Assuntos
Neovascularização Retiniana , Humanos , Animais , Camundongos , Neovascularização Retiniana/genética , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/patologia , Neovascularização Patológica/patologia , Retina/metabolismo , Células Endoteliais da Veia Umbilical Humana , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
2.
Mol Biol Rep ; 50(12): 10277-10285, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37971567

RESUMO

BACKGROUND: Recent reports suggest that peroxisome proliferator-activated receptor-γ (PPAR-γ) could promote microglial M2 polarization to inhibit inflammation. However, the specific molecular mechanisms that trigger PPAR-γ's anti-inflammatory ability in microglia are yet to be expounded. Thus, in this study, we aimed to explore the molecular mechanisms behind the anti-inflammatory effects of PPAR-γ in hypoxia-stimulated rat retinal microglial cells. METHODS AND RESULTS: We used shRNA expressing lentivirus to knock down PPAR-γ and CD200 genes, and we assessed hypoxia-induced polarization markers release - M1 (iNOS, IL-1ß, IL-6, and TNF-α) and M2 (Arg-1, YM1, IL-4, and IL-10) by RT-PCR. We also monitored PPAR-γ-related signals (PPAR-γ, PPAR-γ in cytoplasm or nucleus, CD200, and CD200Rs) by Western blot and RT-PCR. Our results showed that hypoxia enhanced PPAR-γ and CD200 expressions in microglial cells. Moreover, PPAR-γ agonist 15d-PGJ2 elevated CD200 and CD200R1 expressions, whereas sh-PPAR-γ had the opposite effect. Following hypoxia, expressions of M1 markers increased significantly, while those of M2 markers decreased, and the above effects were attenuated by 15d-PGJ2. Conversely, knocking down PPAR-γ or CD200 inhibited the polarization of microglial cells to M2 phenotype. CONCLUSION: Our findings demonstrated that PPAR-γ performed an anti-inflammatory function in hypoxia-stimulated microglial cells by promoting their polarization to M2 phenotype via the CD200-CD200R1 pathway.


Assuntos
Microglia , PPAR gama , Animais , Ratos , Anti-Inflamatórios/farmacologia , Hipóxia/genética , Hipóxia/metabolismo , Microglia/metabolismo , Fenótipo , PPAR gama/genética , PPAR gama/metabolismo
3.
BMC Ophthalmol ; 23(1): 13, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624415

RESUMO

PURPOSE: To compare the use of single­pass four­throw (SFT) and traditional double-pass two-throw knotting (DTT) techniques in pupilloplasty for traumatic mydriasis combined with lens dislocation, and to evaluate the learning curve between the two knotting techniques by wet lab. METHOD: The eyes of 45 patients (45 eyes) were divided into two groups according to the knotting technique used: single­pass four­throw (22 eyes) or traditional double-pass-two-throw knotting (23 eyes). Combined phacoemulsification and pupilloplasty with pars plana vitrectomy were performed in traumatic mydriasis patients with lens dislocation. Preoperative and postoperative corrected distance visual acuity (CDVA), pupil diameter, intraocular pressure (IOP), pupilloplasty time, and complications were compared. Twenty ophthalmology residents were randomized to perform a pupilloplasty suturing exam with or without SFT knotting techniques in porcine eyes. RESULT: All cases had a minimum follow­up period of 6 months (range 6-12 months). There was no significant difference in the CDVA (P = 0.55), postoperative pupil diameter (P = 0.79), IOP (P > 0.05), anterior chamber exudate degree, and loosening or shedding of the line knot between the two groups. The duration of the pupilloplasty was 22.32 ± 4.58 min in the SFT group and 30.35 ± 5.55 min in the traditional group, which was a significant difference (P < 0.01). The residents in the SFT group had higher test scores and fewer surgical mistakes (P < 0.05). CONCLUSION: The SFT knotting technique has a similar treatment effect and safety as the traditional technique but requires a shorter time and is easier to perform in pupilloplasty surgery.


Assuntos
Extração de Catarata , Oftalmopatias , Traumatismos Oculares , Subluxação do Cristalino , Midríase , Humanos , Midríase/cirurgia , Iris/cirurgia , Vitrectomia , Traumatismos Oculares/cirurgia , Oftalmopatias/cirurgia , Subluxação do Cristalino/cirurgia , Estudos Retrospectivos
4.
BMC Ophthalmol ; 23(1): 516, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38114950

RESUMO

BACKGROUND: Here we described a new threading technique for the universal fixation of any posterior chamber intraocular lens (IOL). METHODS: Twenty-seven eyes of 27 patients whose surgery done by Surgeon A with the needle-guided method or the suture needle retrograde threading (SNRT) method for intrascleral IOL fixation were enrolled in the first group. Thirty-four eyes of 34 patients whose surgery done by Surgeon A, Surgeon B or Surgeon C with the SNRT method for intrascleral IOL fixation were grouped into three sub-groups by surgeon. Information regarding age, sex, best-available visual acuity (BCVA), intraocular pressure (IOP), past ophthalmological history, threading time (from puncturing to externalizing suture) and complications during and after the surgery were gathered. RESULTS: The analysis showed that the threading time was less in the SNRT group than needle-guided group by Surgeon A. There was one eye with suture needle slipping from the guide needle when guiding out of the eye. The threading procedure was completed one time without suture ruptures or loop slippage in the SNRT group operated by Surgeon A. And using the SNRT method, Surgeon A, Surgeon B, and Surgeon C did not show any significant difference in threading time. No complications (e.g., vitreous hemorrhage, hyphemia, retinal detachment, suprachoroidal hemorrhage, or hypotony) were observed during surgery or postoperatively in all cases. No leakage occurred at the site of the puncture after the operation. CONCLUSIONS: The described technique appears to be a safe, simple, easy-to-learn, and universal surgical method, which is suitable for various types of IOLs.


Assuntos
Implante de Lente Intraocular , Lentes Intraoculares , Humanos , Implante de Lente Intraocular/métodos , Esclera/cirurgia , Olho Artificial , Técnicas de Sutura , Suturas , Estudos Retrospectivos , Complicações Pós-Operatórias/cirurgia
5.
Inflamm Res ; 71(4): 397-407, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35275225

RESUMO

PURPOSE: Our study aimed to investigate the function of Cavin-1 and SOCS3 in macrophages/microglia M2 polarization and further explored the relevant mechanism. METHODS: Expression levels of Cavin-1 and SOCS3 in macrophages/microglia were measured by western blotting and RT-PCR, respectively. Then, Cavin-1 or SOCS3 was gene silenced by a siRNA approach, and gene silencing efficiency was determined by western blotting. Next, co-immunoprecipitation (Co-IP) was employed to further analyze the interaction between Cavin-1 and SOCS3. Finally, the activation of STAT6/PPAR-γ signaling was evaluated using western blotting, and the M2 macrophages/microglia polarization was validated by measuring the mRNA expression of M2 markers by RT-PCR. RESULTS: In the polarization process of macrophages/microglia to M2 phenotype, both Cavin-1 and SOCS3 increased synchronously at protein and mRNA level, reached the peak at the 6 h, and then decreased. After Cavin-1 or SOCS3 silencing, the expression of Cavin-1 and SOCS3 declined. These results suggested that Cavin-1 and SOCS3 were positively correlated in macrophages/microglia, and this conjecture was verified by Co-IP. Besides, Cavin-1 silencing not only suppressed the activation of STAT6/PPAR-γ pathway, but also suppressed the release of anti-inflammatory factors. Finally, we found that SOCS3 overexpression reversed the inhibitory effect of Cavin-1 silencing on the release of anti-inflammatory factors in M2 macrophages/microglia. CONCLUSIONS: Cavin-1 and SOCS3 are actively involved in the process of M2 macrophages/microglia polarization. As a SOCS3 interacting protein, Cavin-1 can promote M2 macrophages/microglia polarization via SOCS3.


Assuntos
Microglia , Receptores Ativados por Proliferador de Peroxissomo , Anti-Inflamatórios/farmacologia , Macrófagos , Microglia/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , RNA Mensageiro/metabolismo
6.
Mol Biol Rep ; 47(11): 8963-8973, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33161529

RESUMO

To investigate the functional role of fasudil in optic nerve crush (ONC), and further explore its possible molecular mechanism. After ONC injury, the rats were injected intraperitoneally either with fasudil or normal saline once a day until euthanized. RGCs survival was assessed by retrograde labeling with FluoroGold. Retinal glial cells activation and population changes (GFAP, iba-1) were measured by immunofluorescence. The expressions of cleaved caspase 3 and 9, p-ERK1/2 and p-AKT were detected by western blot. The levels of the pro-inflammatory cytokines were determined using real-time polymerase chain reaction. Fasudil treatment inhibited RGCs apoptosis and reduced RGCs loss demonstrated by the decreased apoptosis-associated proteins expression and the increased fluorogold labeling of RGCs after ONC, respectively. In addition, the ONC + fasudil group compared had a significantly lower expression of GFAP and iba1 compared with the ONC group. The levels of pro-inflammatory cytokines were significantly reduced in the ONC + fasudil group than in the ONC group. Furthermore, the phosphorylation levels of ERK1/2 and AKT (p-ERK1/2 and p-AKT) were obviously elevated by the fasudil treatment. Our study demonstrated that fasudil attenuated glial cell-mediated neuroinflammation by up-regulating the ERK1/2 and AKT signaling pathways in rats ONC models. We conclude that fasudil may be a novel treatment for traumatic optic neuropathy.


Assuntos
1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , Inflamação/prevenção & controle , Neuroglia/metabolismo , Nervo Óptico/metabolismo , Proteínas Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Expressão Gênica/efeitos dos fármacos , Inflamação/genética , Inflamação/metabolismo , Masculino , Compressão Nervosa , Neuroglia/citologia , Fármacos Neuroprotetores/farmacologia , Nervo Óptico/patologia , Traumatismos do Nervo Óptico/metabolismo , Traumatismos do Nervo Óptico/fisiopatologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Células Ganglionares da Retina/citologia , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/metabolismo
7.
BMC Ophthalmol ; 19(1): 133, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31226968

RESUMO

BACKGROUND: To evaluate the subfoveal choroidal thickness (SFCT) in eyes with macular edema (ME) secondary to retinal vein occlusion(RVO), and to investigate the short term response after a single intravitreal ranibizumab (IVR) injection. What is more, to compare SFCT and SFCT change between central RVO (CRVO) and branch RVO (BRVO). METHODS: In the retrospective study, we had collected 36-six treatment-naïve patients with unilateral ME secondary to RVO (including 19 CRVO and 17 BRVO). All patients had received IVR injection after newly diagnosed. The SFCT was measured at the onset and after 2 weeks of IVR injection. Paired t test was performed to compare the SFCT of RVO eyes and fellow eyes, as well as the SFCT of pre-injection and post-injection. In further, independent t test was used to compare SFCT and SFCT change between CRVO eyes and BRVO eyes. RESULTS: The mean SFCT at the onset was 326.03 ± 30.86 µm in CRVO eyes, which was significantly thicker than that in contralateral fellow eyes (p < 0.01, paired t test), and reduced to 294.15 ± 30.83 µm rapidly after 2 weeks of IVR injection (p < 0.01, paired t test). Similarly, the SFCT in BRVO eyes was significantly thicker than that in contralateral eyes at the onset, and decreased significantly after IVR injection. However, our findings showed that there was no statistically significant difference in SFCT and SFCT reduction after IVR injection between CRVO eyes and BRVO eyes. CONCLUSIONS: The SFCT in eyes with ME secondary to CRVO and BRVO was significantly thicker than that in fellow eyes, and decreased significantly within a short time in response to a single IVR injection. In further, the study showed that SFCT and SFCT change had no correlation with RVO subtypes.


Assuntos
Corioide/patologia , Edema Macular/patologia , Oclusão da Veia Retiniana/patologia , Adulto , Idoso , Inibidores da Angiogênese/uso terapêutico , Feminino , Humanos , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , Ranibizumab/uso terapêutico , Oclusão da Veia Retiniana/complicações , Oclusão da Veia Retiniana/tratamento farmacológico , Estudos Retrospectivos
8.
Inflamm Res ; 66(11): 1011-1019, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28780681

RESUMO

OBJECTIVE: The aims of the present study were to detect the interaction of Wip1 and NF-κB P65 in retina of an LPS-induced astrocytes activation model. METHODS: The interaction between Wip1 and nuclear factor kappa B (NF-κB) P65 was observed in lipopolysaccharide (LPS)-stimulated primary rat astrocytes derived from retina. The expressions of Wip1 and NF-κB P65 were evaluated using Western blot and RT-PCR. Small interfering RNA (siRNA) against Wip1 was transfected into astrocytes to clarify the phosphorylation status and nuclear translocation of NF-κB P65 and expressions of these proinflammatory factors. Meanwhile, expression of Wip1 was assessed following treatment with NF-κB inhibitor. RESULTS: Wip1 and phospho-NF-κB P65 (p-P65) expressions were significantly increased and colocalization in astrocytes after LPS treatment. The expression of p-P65 was augmented by transfected with Wip1 siRNA followed by LPS. Furthermore, pre-treatment with Wip1 siRNA further enhanced LPS-induced NF-κB P65 translocation into the nuclei and proinflammatory cytokine release. Finally, inhibition of NF-κB decreases Wip1 expression and transcription in primary astrocytes. CONCLUSION: These data provide a mechanism for the role for a negative feedback loop of Wip1 and NF-κB in LPS-induced astrocytic activation.


Assuntos
Astrócitos/metabolismo , Fator de Transcrição RelA/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Células Cultivadas , Citocinas/genética , Lipopolissacarídeos/farmacologia , Proteína Fosfatase 2C , Ratos
9.
Inflamm Res ; 65(7): 521-32, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26956766

RESUMO

OBJECTIVE: Based on recent information, CD200Fc, a CD200R1 agonist, could attenuate the inflammatory response of microglial cells in autoimmune diseases and neuro-degeneration. However, the exact molecular mechanisms responsible for the anti-inflammatory activity of CD200Fc in microglial cells have not been elucidated. In the present study, we investigated the anti-inflammatory effects and the molecular mechanisms of CD200Fc in lipopolysaccharide (LPS)-stimulated rat primary microglial cells. METHODS: The cell viability was measured by MTT assay. The LPS-induced cytokines release (IL-1ß, IL-6, TNF-α, iNOS, MCP-1, and COX-2) was monitored by ELISA or real-time PCR, while NF-κB-related signals (MyD88, p-TAK1, TRIF, p-TBK1, p-IRF3, p-IκB, and NF-κB-P65) were assessed by real-time PCR, western blot and/or Immunofluorescent staining. RESULTS: CD200Fc and/or LPS exerted no significant cytotoxicity on microglial cells. LPS reduced the CD200R1 expression in microglial cells, and this effect was attenuated by CD200Fc. In addition, CD200Fc inhibited LPS-induced expression of TLR4 and its adapter molecules (MyD88 and p-TAK1, TRIF, p-TBK1, and p-IRF3), and abolished its interactions with MyD88, TAK1, and TRIF in microglial cells. CD200Fc also attenuated LPS-induced protein expression of p-IκB and NF-κB-P65 translocation to nucleus in microglial cells. Moreover, CD200Fc suppressed the LPS-induced release of inflammatory mediators in microglial cells, including IL-1ß, IL-6, TNF-α, iNOS, MCP-1, and COX-2. CONCLUSION: These results indicated that CD200Fc displayed an anti-inflammatory effect in LPS-induced microglial cells by blocking TLR4-mediated NF-κB activation.


Assuntos
Anti-Inflamatórios/farmacologia , Imunoglobulina G/farmacologia , Microglia/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Receptor 4 Toll-Like/antagonistas & inibidores , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Lipopolissacarídeos , Microglia/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Ratos Sprague-Dawley , Receptores Imunológicos/metabolismo , Transdução de Sinais
10.
Inflamm Res ; 65(9): 709-15, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27207279

RESUMO

OBJECTIVE: To evaluate the expression and possible roles of Wip1 in retinal astrocytes after optic nerve crush (ONC). METHODS: Expressions of Wip1, GFAP, and p-p65 in ONC model were analyzed by Western blot and immunofluorescence. The mRNA expressions of the pro-inflammatory cytokines (IL-8, TNF-α, IL-6 and IL-1ß) were analyzed by RT-PCR. RESULTS: Wip1 was up-regulated at 14 days after ONC by Western blot and immunofluorescence. The changes of Wip1 were striking in astrocytes. Furthermore, the protein expression level of p-p65 was paralleled with Wip1 in a time-dependent manner by ONC. In addition, co-localization of Wip1 with Phospho-NF-κB-p65 (p-p65) was detected. Finally, the mRNA expressions of the pro-inflammatory cytokines (IL-8, TNF-α, IL-6 and IL-1ß) were significantly increased in retina after ONC. CONCLUSIONS: These data were consistent with the hypothesis that Wip1 was implicated in neuroinflammation of retinal astrocytes after ONC via NF-κB signaling pathway.


Assuntos
NF-kappa B/metabolismo , Traumatismos do Nervo Óptico/metabolismo , Proteína Fosfatase 2C/metabolismo , Retina/metabolismo , Animais , Astrócitos/metabolismo , Citocinas/genética , Proteína Glial Fibrilar Ácida/metabolismo , Inflamação/metabolismo , Masculino , Ratos Sprague-Dawley , Retina/citologia , Transdução de Sinais , Regulação para Cima
11.
J Med Case Rep ; 18(1): 171, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38504363

RESUMO

BACKGROUND: Aeromonas veronii is a very rare and highly pathogenic microorganism. We investigate the clinical characteristics and significance of endogenous endophthalmitis caused by Aeromonas veronii in our patient. CASE PRESENTATION: A 30-year-old Asian women with systemic lupus erythematosus, uremia, and hypertension developed acute infectious endophthalmitis caused by Aeromonas veronii. After emergency vitrectomy and antibiotic therapy, the clinical condition worsened requiring enucleation. CONCLUSIONS: Aeromonas veronii can cause infection in the human eye, which can manifest as acute endophthalmitis. Early diagnosis and targeted therapy are important for successful treatment.


Assuntos
Aeromonas , Endoftalmite , Infecções por Bactérias Gram-Negativas , Humanos , Feminino , Adulto , Aeromonas veronii , Endoftalmite/diagnóstico , Endoftalmite/tratamento farmacológico , Antibacterianos/uso terapêutico , Vitrectomia , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico
12.
Int Immunopharmacol ; 126: 111287, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38041956

RESUMO

Loss of retinal ganglion cells (RGCs) is a primary cause of visual impairment in glaucoma, the pathological process is closely related to neuroinflammation and apoptosis. B-cell activating factor (BAFF) is a fundamental survival factor mainly expressed in the B cell lineage. Evidence suggests its neuroprotective effect, but the expression and role in the retina have not yet been investigated. In this study, we adopt optic nerve crush (ONC) as an in vivo model and oxygen-glucose deprivation/reoxygenation (OGD/R) of RGCs as an in vitro model to investigate the expression and function of BAFF. We found that BAFF and its receptors were abundantly expressed in the retina and BAFF inhibition exacerbated the caspase 3-mediated RGCs apoptosis, glial cell activation and pro-inflammatory cytokines expression, which may be caused by the activation of the NF-κB pathway in vivo. In addition, we found that BAFF treatment could alleviate RGCs apoptosis, pro-inflammatory cytokines expression and NF-κB pathway activation, which could be reversed the effect by blockade of the NF-κB pathway in vitro. Meanwhile, we found that microglia induced to overexpress BAFF in the inflammatory microenvironment in a time-dependent manner. Taken together, our results indicated that BAFF deficiency promoted RGCs apoptosis and neuroinflammation through activation of NF-κB pathway in ONC retinas, suggesting that BAFF may serve as a promising therapeutic target for the treatment of glaucoma.


Assuntos
Glaucoma , Células Ganglionares da Retina , Humanos , Células Ganglionares da Retina/metabolismo , NF-kappa B/metabolismo , Fator Ativador de Células B/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , Doenças Neuroinflamatórias , Nervo Óptico/patologia , Apoptose
13.
Case Rep Ophthalmol ; 15(1): 170-175, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38433780

RESUMO

Introduction: Prolonged exposure to a complete button battery can cause severe tissue necrosis in the eye and permanent impairment of visual function. The main mechanism of injury is the current generated by the hydrolysis of tissue fluid at the negative electrode and the production of hydroxide ions. Case Presentation: A 3-year-old girl went to the local hospital because of swelling and pain in her right eye of 12-h duration. The local doctor performed an orbital CT (computed tomography) scan and found a foreign body between the right eyelid and the eyeball. The foreign body was removed immediately under general anesthesia. In addition, it was found that the foreign body was a button battery, but it prolonged 39 h from the onset of the child's symptoms. The child underwent a second operation in our hospital and received amniotic membrane transplantation combined with conjunctival flap coverage. Topical corticosteroid and antibiotic eye ointment were continued for 3 months after surgery. Local pigmentation was seen, there was no symblepharon, but the cornea was still opaque and the visual acuity was only FC (finger count). In this particular case, heavy metal testing conducted on the child's blood fortunately revealed that the levels were within the normal range. Conclusion: Early detection and urgent removal of button battery are crucial in order to minimize exposure time. We should also be concerned about heavy metals in the blood. Children should be kept away from button batteries as much as possible to avoid such injury.

14.
Biomed Pharmacother ; 170: 116042, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38118351

RESUMO

Glaucoma, a prevalent cause of permanent visual impairment worldwide, is characterized by the progressive degeneration of retinal ganglion cells (RGCs). NADPH oxidase (NOX) 1 and NOX4 are pivotal nodes in various retinal diseases. Setanaxib, a potent and highly selective inhibitor of NOX1 and NOX4, can impede the progression of various diseases. This study investigated the efficacy of setanaxib in ameliorating retinal ischemia-reperfusion (I/R) injury and elucidated its underlying mechanisms. The model of retinal I/R induced by acute intraocular hypertension and the oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary RGCs were established. By suppressing NOX1 and NOX4 expression in RGCs, setanaxib mitigated I/R-induced retinal neuronal loss, structural disruption, and dysfunction. Setanaxib reduced TUNEL-positive cells, upregulated Bcl-2, and inhibited Bax, Bad, and cleaved-caspase-3 overexpression after I/R injury in vitro and in vivo. Moreover, setanaxib also significantly reduced cellular senescence, as demonstrated by downregulating SA-ß-gal-positive and p16-INK4a expression. Furthermore, setanaxib significantly suppressed ROS production, Hif-1α and FOXO1 upregulation, and NRF2 downregulation in damaged RGCs. These findings highlight that the setanaxib effectively inhibited NOX1 and NOX4, thereby regulating ROS production and redox signal activation. This inhibition further prevents the activation of apoptosis and senescence related factors in RGCs, ultimately protecting them against retinal I/R injury. Consequently, setanaxib exhibits promising potential as a therapeutic intervention for glaucoma.


Assuntos
Glaucoma , Traumatismo por Reperfusão , Doenças Retinianas , Humanos , Espécies Reativas de Oxigênio/metabolismo , Células Ganglionares da Retina , Estresse Oxidativo , Apoptose , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Doenças Retinianas/tratamento farmacológico , Doenças Retinianas/metabolismo , Isquemia/metabolismo , Reperfusão , Glaucoma/tratamento farmacológico , Glaucoma/metabolismo , NADPH Oxidase 4/metabolismo , NADPH Oxidase 1
15.
Heliyon ; 10(5): e27114, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38434304

RESUMO

Aims: Retinal ischemia/reperfusion (I/R) injury is implicated in the etiology of various ocular disorders. Prior research has demonstrated that bone marrow tyrosine kinase on chromosome X (BMX) contributes to the advancement of ischemic disease and inflammatory reactions. Consequently, the current investigation aims to evaluate BMX's impact on retinal I/R injury and clarify its implied mechanism of action. Main methods: This study utilized male and female systemic BMX knockout (BMX-/-) mice to conduct experiments. The utilization of Western blot assay and immunofluorescence labeling techniques was employed to investigate variations in the expression of protein and tissue localization. Histomorphological changes were observed through H&E staining and SD-OCT examination. Visual function changes were assessed through electrophysiological experiments. Furthermore, apoptosis in the retina was identified using the TUNEL assay, as well as the ELISA technique, which has been utilized to determine the inflammatory factors level. Key findings: Our investigation results revealed that the knockdown of BMX did not yield a significant effect on mouse retina. In mice, BMX knockdown mitigated the negative impact of I/R injury on retinal tissue structure and visual function. BMX knockdown effectively reduced apoptosis, suppressed inflammatory responses, and decreased inflammatory factors subsequent to I/R injury. The outcomes of the current investigation revealed that BMX knockdown partially protected the retina through downregulating phosphorylation of AKT/ERK/STAT3 pathway. Significance: Our investigation showed that BMX-/- reduces AKT, ERK, and STAT3 phosphorylation, reducing apoptosis and inflammation. Thus, this strategy protected the retina from structural and functional damage after I/R injury.

16.
Biomed Pharmacother ; 165: 115052, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37399715

RESUMO

Reactive oxygen species (ROS) overproduction plays an essential role in the etiology of ischemic/hypoxic retinopathy caused by acute glaucoma. NADPH oxidase (NOX) 4 was discovered as one of the main sources of ROS in glaucoma. However, the role and potential mechanisms of NOX4 in acute glaucoma have not been fully elucidated. Therefore, the current study aims to investigate the NOX4 inhibitor GLX351322 that targets NOX4 inhibition in acute ocular hypertension (AOH)-induced retinal ischemia/hypoxia injury in mice. Herein, NOX4 was highly expressed in AOH retinas, particularly the retinal ganglion cell layer (GCL). Importantly, the NOX4 inhibitor GLX351322 reduced ROS overproduction, inhibited inflammatory factor release, suppressed glial cell activation and hyperplasia, inhibited leukocyte infiltration, reduced retinal cell senescence and apoptosis in damaged areas, reduced retinal degeneration and improved retinal function. This neuroprotective effect is at least partially associated with mediated redox-sensitive factor (HIF-1α, NF-κB, and MAPKs) pathways by NOX4-derived ROS overproduction. These results suggest that inhibition of NOX4 with GLX351322 attenuated AOH-induced retinal inflammation, cellular senescence, and apoptosis by inhibiting the activation of the redox-sensitive factor pathway mediated by ROS overproduction, thereby protecting retinal structure and function. Targeted inhibition of NOX4 is expected to be a new idea in the treatment of acute glaucoma.


Assuntos
Glaucoma , Hipertensão Ocular , Doenças Retinianas , Camundongos , Animais , Espécies Reativas de Oxigênio/metabolismo , NADPH Oxidase 4/metabolismo , Doenças Retinianas/tratamento farmacológico , Glaucoma/complicações , Glaucoma/tratamento farmacológico , Hipertensão Ocular/complicações , Hipertensão Ocular/tratamento farmacológico , Oxirredução , Inflamação/tratamento farmacológico , NADPH Oxidases/metabolismo
17.
Ophthalmology ; 119(12): 2493-9, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22902176

RESUMO

BACKGROUND: To evaluate the association between plasma total homocysteine (tHcy) levels, serum folic acid, vitamin B(12) and vitamin B(6) levels, methylenetetrahydrofolate reductase (MTHFR) C677T genotype and risk of primary open-angle glaucoma (POAG). CLINICAL RELEVANCE: There are conflicting reports on the association of Hcy, folic acid, vitamin B(12), vitamin B(6), MTHFR, and risk of POAG. We conducted this meta-analysis to derive a more precise estimation of the association. METHODS: Pertinent articles were identified through a systematic search of the EMBASE and Medline databases. Results were pooled using meta-analytic methods. The main outcome measure included tHcy, folic acid, vitamin B(12) and vitamin B(6) levels, and MTHFR C677T genotype. RESULTS: Twelve studies were eligible for Hcy, 6 studies for folic acid, 6 studies for vitamin B(12), 3 studies for vitamin B(6), and 10 studies for MTHFR. The combined results showed that plasma tHcy levels in POAG were 2.05 µmol/L (95% confidence interval [CI], 0.63-3.47) higher than in controls. There was no difference between serum folic acid, vitamin B(6), and vitamin B(12) levels in POAG and controls. The weighted mean difference with 95% CI were 0.34 µmol/L (-0.37 to 1.05), 2.75 µmol/L (-3.68 to 9.18), and 0.97 µmol/L (-30.45 to 32.40), respectively. The MTHFR 677TT genotype was not associated with the risk of POAG (odds ratio, 1.10; 95% CI, 0.83-1.47). CONCLUSIONS: We found that POAG is associated with elevated plasma tHcy levels, but not serum folic acid, vitamin B(12), vitamin B(6) levels, or MTHFR C677T genotype. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.


Assuntos
Glaucoma de Ângulo Aberto/sangue , Glaucoma de Ângulo Aberto/genética , Homocisteína/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Complexo Vitamínico B/sangue , Idoso , Genótipo , Humanos , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco
18.
Front Genet ; 13: 989327, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36147494

RESUMO

Colorectal cancer (CRC) is a common malignant tumor worldwide. Lipid metabolism is a prerequisite for the growth, proliferation and invasion of cancer cells. However, the lipid metabolism-related gene signature and its underlying molecular mechanisms remain unclear. The aim of this study was to establish a lipid metabolism signature risk model for survival prediction in CRC and to investigate the effect of gene signature on the immune microenvironment. Lipid metabolism-mediated genes (LMGs) were obtained from the Molecular Signatures Database. The consensus molecular subtypes were established using "ConsensusClusterPlus" based on LMGs and the cancer genome atlas (TCGA) data. The risk model was established using univariate and multivariate Cox regression with TCGA database and independently validated in the international cancer genome consortium (ICGC) datasets. Immune infiltration in the risk model was developed using CIBERSORT and xCell analyses. A total of 267 differentially expressed genes (DEGs) were identified between subtype 1 and subtype 2 from consensus molecular subtypes, including 153 upregulated DEGs and 114 downregulated DEGs. 21 DEGs associated with overall survival (OS) were selected using univariate Cox regression analysis. Furthermore, a prognostic risk model was constructed using the risk coefficients and gene expression of eleven-gene signature. Patients with a high-risk score had poorer OS compared with patients in the low-risk score group (p = 3.36e-07) in the TCGA cohort and the validationdatasets (p = 4.03e-05). Analysis of immune infiltration identified multiple T cells were associated with better prognosis in the low-risk group, including Th2 cells (p = 0.0208), regulatory T cells (p = 0.0425), and gammadelta T cells (p = 0.0112). A nomogram integrating the risk model and clinical characteristics was further developed to predict the prognosis of patients with CRC. In conclusion, our study revealed that the expression of lipid-metabolism genes were correlated with the immune microenvironment. The eleven-gene signature might be useful for prediction the prognosis of CRC patients.

19.
ACS Appl Mater Interfaces ; 14(21): 24659-24667, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35584532

RESUMO

Nowadays, multifunctional, easily prepared, and highly sensitive flexible sensors have attracted extensive attention and are gradually used in various scenarios. Here, we report the design of the Ti2C3Tx/polyurethane composites prepared by a facile gas-liquid interface self-assembly. The obtained flexible sensor has a wide detection range (∼900%), a low-stress detection limit (<1%), a high sensitivity (GF = 1.3, strain from 0 to 100%), and a fast response time (<140 ms). The multifunctional stress sensor can be applied to not only wearable motion monitoring and detection of various signals but also the detection of underwater human motion, as well as different motion states and swimming frequencies of toy fish in water, demonstrating its great prospects in a variety of applications, such as human movement monitoring and marine biological detection and research.

20.
ACS Appl Mater Interfaces ; 14(3): 4680-4689, 2022 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-35034450

RESUMO

The loofah gourd is like a natural water tank that stores underground water and drains it out after aging, leaving only a three-dimensional network consisting of hollow and interconnected fibers. This phenomenon inspired us to fabricate a solar-energy-powered sorption-based atmospheric water harvesting device using a loofah sponge. Herein, moisture absorption and photothermal conversion strategies are rationally designed to fast release the absorbed water. This is accomplished by filling the hollow and connected loofah fiber with LiCl and replacing the original luffa peel with a bacterial cellulose (BC)/carbon nanotube (CNT) photothermal conversion membrane. As a result, loofah/BC/CNT (LBC)@LiCl presents a high water absorption capacity of 2.65 g g-1 at 90% relative humidity (RH) and fast water release performance of 1.33 kg m-2 h-1 under 1.0 sun. Noticeably, ∼1.92-2.40 kg LBC@LiCl can produce daily drinking water for adults (2000-2500 mL) in one night outdoors at ∼66% RH, proving that it is a feasible method to overcome the drinking water shortage of poor and arid areas using cheap and renewable biomass material.


Assuntos
Atmosfera/química , Materiais Biocompatíveis/química , Água/química , Tempo (Meteorologia) , Teste de Materiais , Processos Fotoquímicos , Molhabilidade
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