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Auditory neuropathy (AN) is a unique type of language developmental disorder, with no precise rate of genetic contribution that has been deciphered in a large cohort. In a retrospective cohort of 311 patients with AN, pathogenic and likely pathogenic variants of 23 genes were identified in 98 patients (31.5% in 311 patients), and 14 genes were mutated in two or more patients. Among subgroups of patients with AN, the prevalence of pathogenic and likely pathogenic variants was 54.4% and 56.2% in trios and families, while 22.9% in the cases with proband-only; 45.7% and 25.6% in the infant and non-infant group; and 33.7% and 0% in the bilateral and unilateral AN cases. Most of the OTOF gene (96.6%, 28/29) could only be identified in the infant group, while the AIFM1 gene could only be identified in the non-infant group; other genes such as ATP1A3 and OPA1 were identified in both infant and non-infant groups. In conclusion, genes distribution of AN, with the most common genes being OTOF and AIFM1, is totally different from other sensorineural hearing loss. The subgroups with different onset ages showed different genetic spectrums, so did bilateral and unilateral groups and sporadic and familial or trio groups.
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Pérdida Auditiva Central , Mutación , Humanos , Femenino , Masculino , Pérdida Auditiva Central/genética , Lactante , Niño , Preescolar , Estudios Retrospectivos , Adolescente , Proteínas de la Membrana/genética , Estudios de CohortesRESUMEN
Exploring and developing novel strategies for constructing heterostructure electrocatalysts is still challenging for water electrolysis. Herein, a creative etching treatment strategy is adopted to construct NiSe2 /Ni0.85 Se heterostructure. The rich heterointerfaces between NiSe2 and Ni0.85 Se emerge strong electronic interaction, which easily induces the electron transfer from NiSe2 to Ni0.85 Se, and tunes the charge-state of NiSe2 and Ni0.85 Se. In the NiSe2 /Ni0.85 Se heterojunction nanomaterial, the higher charge-state Ni0.85 Se is capable of affording partial electrons to combine with hydrogen protons, inducing the rapid formation of H2 molecule. Accordingly, the lower charge-state NiSe2 in the NiSe2 /Ni0.85 Se heterojunction nanomaterial is more easily oxidized into high valence state Ni3+ during the oxygen evolution reaction (OER) process, which is beneficial to accelerate the mass/charge transfer and enhance the electrocatalytic activities towards OER. Theoretical calculations indicate that the heterointerfaces are conducive to modulating the electronic structure and optimizing the adsorption energy toward intermediate H* during the hydrogen evolution reaction (HER) process, leading to superior electrocatalytic activities. To expand the application of the NiSe2 /Ni0.85 Se-2h electrocatalyst, urea is served as the adjuvant to proceed with the energy-saving hydrogen production and pollutant degradation, and it is proven to be a brilliant strategy.
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This study aimed to identify and quantify free fatty acids (FFAs), secretory phospholipase A2 group IIa (sPLA2-IIa) and cytosolic phospholipase A2 (cPLA2) in serum of superior limbic keratoconjunctivitis (SLK) patients and explored the association between FFAs, sPLA2-IIa and cPLA2 variations and SLK. Targeted metabolomic analysis of FFAs in serum was performed by gas chromatography tandem mass spectrometry (GC-MS/MS) analysis on 16 SLK patients (43.88 ± 7.88 years; female: 62.50%) and 25 healthy controls (43.12 ± 7.88 years; female: 64.00%). Qualitative and absolute quantitative results of FFAs were obtained and classified according to gender and thyroid tests. Differential lipid metabolites, metabolomic pathways and biomarkers were further evaluated. The serum sPLA2-IIa and cPLA2 were determined by enzyme linked immunosorbent assay (ELISA). Among 40 FFAs identified, 6 FFAs showed significant changes (P < 0.05) in SLK patients, including 4 decreased and 2 increased. They were mainly related to unsaturated fatty acid biosynthesis, α-linolenic acid and linoleic acid metabolism, and fatty acid biosynthesis. When dividing the data by gender or abnormal thyroid tests, some comparable FFAs alterations displayed in SLK patients. The ROC analysis revealed that the AUC values of linoleic acid, γ-linolenic acid, cis-8,11,14-eicosatrienoic acid, stearic acid, and palmitic acid, were all greater than 0.8. The serum concentrations of sPLA2-IIa and cPLA2 in patients with SLK were significantly higher than that in healthy controls. Lipidomics disturbance might be the potential mechanism of SLK. Serum FFA biomarkers associated with SLK have potential for the diagnosis and treatment of the disease.
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In terrestrial animals, the lacrimal drainage apparatus evolved to serve as conduits for tear flow; however, little is known about the ontogenesis of this system. Here, we define the anatomy of the fully formed tear duct in mice, characterize crucial morphogenetic events for the development of tear duct components and identify the site for primordial tear duct (PTD) initiation. We report that the PTD originates from the orbital lacrimal lamina, a junction formed by the epithelia of the maxillary and lateral nasal processes. We demonstrate that Prickle1, a key component of planar cell polarity signaling, is expressed in progenitors of the PTD and throughout tear duct morphogenesis. Disruption of Prickle1 stalls tear duct elongation; in particular, the loss of basement membrane deposition and aberrant cytoplasmic accumulation of laminin are salient. Altered cell adhesion, cytoskeletal transport systems, vesicular transport systems and cell axis orientation in Prickle1 mutants support the role of Prickle1 in planar cell polarity. Taken together, our results highlight a crucial role of Prickle1-mediated polarized basement membrane secretion and deposition in PTD elongation.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Membrana Basal/embriología , Polaridad Celular/fisiología , Proteínas con Dominio LIM/metabolismo , Conducto Nasolagrimal/embriología , Organogénesis/fisiología , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Membrana Basal/citología , Adhesión Celular/fisiología , Citoesqueleto/genética , Citoesqueleto/metabolismo , Proteínas con Dominio LIM/genética , Ratones , Conducto Nasolagrimal/citologíaRESUMEN
Heteroatoms Fe, F co-doped NiO hollow spheres (Fe, F-NiO) are designed, which simultaneously integrate promoted thermodynamics by electronic structure modulation with boosted reaction kinetics by nano-architectonics. Benefiting from the electronic structure co-regulation of Ni sites by introducing Fe and F atoms in NiO , as the rate-determined step (RDS), the Gibbs free energy of OH* intermediates (ΔGOH* ) for Fe, F-NiO catalyst is significantly decreased to 1.87 eV for oxygen evolution reaction (OER) compared with pristine NiO (2.23 eV), which reduces the energy barrier and improves the reaction activity. Besides, densities of states (DOS) result verifies the bandgap of Fe, F-NiO(100) is significantly decreased compared with pristine NiO(100), which is beneficial to promote electrons transfer efficiency in electrochemical system. Profiting by the synergistic effect, the Fe, F-NiO hollow spheres only require the overpotential of 215 mV for OER at 10 mA cm-2 and extraordinary durability under alkaline condition. The assembled Fe, F-NiO||Fe-Ni2 P system only needs 1.51 V to reach 10 mA cm-2 , also exhibits outstanding electrocatalytic durability for continuous operation. More importantly, replacing the sluggish OER by advanced sulfion oxidation reaction (SOR) not only can realize the energy saving H2 production and toxic substances degradation, but also bring additional economic benefits.
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A20, also called TNFAIP3, is a crucial regulator of inflammation in various diseases but has not evidenced its function in the cornea. We aimed to evaluate the existence and the functions of A20 in human corneal epithelial (HCE-T) cells. After being treated with lipopolysaccharide (LPS) in different concentrations or at separate times, cells were collected to analyze A20 expressions. We then constructed the A20 knockdown system by siRNA and the A20 overexpressing system by lentivirus transduction. Systems were further exposed to medium with or without LPS for indicated times. Next, we evaluated the production of inflammatory cytokines (IL-6 and IL-8) by qRT-PCR and ELISA. Also, the translocation of P65 and the phosphorylation of P65, P38 and JNK were observed in two systems. In addition, we used the nuclear factor kappa-B (NF-κB) antagonist TPCA-1 for the pretreatment in cells and then detected the A20 expressions. We found a low basal expression of A20 in HCE-T cells, and the expressions could be dose-dependently induced by LPS, peaking at 4 h in protein level after stimulation. Both the A20 knockdown and A20 overexpressing systems were confirmed to be effective. After the LPS treatment, productions of IL-6 and IL-8 were enhanced in the A20 knockdown system and reduced in the A20 overexpressing system. A20 reduced the translocation of P65 into the nucleus and the phosphorylation of P65, P38 and JNK. Furthermore, TPCA-1 pretreatment reduced the expression of A20 in cells. We concluded that A20 is a potent regulator for corneal epithelium's reaction to inflammation, and it thus is expected to be a potential therapy target for ocular surface diseases.
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Interleucina-6 , Lipopolisacáridos , Humanos , Células Epiteliales/metabolismo , Inflamación/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lipopolisacáridos/farmacología , FN-kappa B/metabolismoRESUMEN
Objective: To investigate the effect of sodium polyanethol sulfonate (SPS) on herpes simplex virus type 1 (HSV-1) infection in vitro. Methods: Human corneal epithelial (HCE-T) cells and Vero cells were infected with HSV-1 [HSV-1 f strain, HSV-1f; HSV-1-H129 with green fluorescent protein (GFP) knock-in, HSV-1g]. SPS was added to the culture medium at various concentrations in time-of-addition assay. Experiments including photography of fluorescence in HSV-1g or plaque formation by HSV-1f, western blot assays, real-time RT-PCR assays, cytopathic effect inhibition assays, cytotoxicity assays, and viral absorption and penetration assays were performed to explore the antiviral effect and mechanism of the compounds. Results: We identified that SPS reduced the replication of HSV-1 in HCE-T and Vero cells in a dose-dependent manner. HSV-1g fluorescence was reduced by 66.3% and 65.4% in HCE-T and Vero cells, respectively, after treatment with 0.4 µg/ml SPS. Furthermore, the viral fluorescence intensities were inhibited by SPS in a dose-dependent manner when the viruses or cells were preincubated with SPS. Relative levels of the ICP4 protein and VP16 mRNA were decreased by SPS in a dose-dependent manner. Moreover, the IC50 values of SPS for HSV-1g and HSV-1f in HCE-T cells were 0.69±0.09 µg/ml and 1.63±0.44 µg/ml, respectively. Even 10,000 µg/ml SPS had no obvious cytotoxicity toward HCE-T and Vero cells. Importantly, viral absorption and penetration assays showed that the relative fluorescence intensity of HSV-1g was significantly reduced by SPS in a dose-dependent manner in the absorption test, but no change was observed in the penetration test. Conclusions: SPS inhibits HSV-1 replication in HCE-T and Vero cells, indicating that SPS has the potential for treating HSV-1 infection, particularly HSV-1 keratitis.
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Herpes Simple , Herpesvirus Humano 1 , Animales , Chlorocebus aethiops , Humanos , Células Vero , Polianetolsulfonato/farmacología , Replicación Viral , Antivirales/farmacología , Sodio/farmacologíaRESUMEN
Realizing the synergy between active site regulation and rational structural engineering is essential in the electrocatalysis community but still challenging. Here, a matrix-confined co-pyrolysis strategy based on molecular bridging is demonstrated to realize highly dispersed Fe atoms on stereoassembled carbon framework. Both polyacrylonitrile matrix and organic linker from metal-organic frameworks (MOFs) provide sufficient N-anchoring sites for the generation of Fe-N4 moieties. A high Fe loading of 2.9â wt.% is readily achieved based on the scalable approach without post-treatment. Owing to the presence of highly exposed Fe-N-C sites and well-tuned pore structures, isolated Fe atoms on porous carbon nanofiber framework (Fe-SA/NCF) exhibits decent oxygen reduction activity and stability in alkaline conditions via a near four-electron path, demonstrating superior performance as air cathode for zinc-air batteries (ZABs) to commercial Pt/C catalyst.
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Antibiotics are one of the important factors that can alter the diversity and composition of ocular surface microbiota. At present, there are a few studies about the antibiotic effect on ocular surface microbiota, including its time-dependent changes. However, these limited studies have revealed various results, and more experiments are required. In this study, we used 16 S rRNA sequencing method to investigate the effects of topical ceftazidime and tobramycin-vancomycin mixtures on the ocular surface microbiota and the temporal changes of the microbiota after discontinuing antibiotic treatment in rabbits. Seventeen healthy rabbits were treated with 5% ceftazidime and a mixture of 0.3% tobramycin-5% vancomycin (CTV) eye drops on one eye four times a day for 7 days. Swab samples of conjunctiva sacs were collected before antibiotic treatment (D0), 12 h after the last antibiotic treatment (D8) and two further time points on Day 15 (D15) and Day 30 (D30). We found that the species diversity of the ocular surface microbiota increased significantly at D8 and was restored at D15, namely, one week after antibiotic cessation. The community structure of the ocular surface microbiota changed after treatment with CTV but recovered at D30. At D8, the relative abundances of 13 bacterial phyla of the initial top 20 phyla and 11 bacterial genera of the initial top 20 genera were significantly different from the relative abundances of the phyla and genera at D0. Furthermore, the relative abundance of the dominant phylum Epsilonbacteraeota obviously decreased, while Proteobacteria and Bacteroidetes markedly increased. For dominant genera, the relative abundance of Helicobacter notably decreased, while Acinetobacter and Pasteurella greatly increased. Thirteen altered bacterial phyla and 7 of 11 altered bacterial genera recovered to preantibiotic levels at D30. In addition, there was a group of nondominant and rare bacteria enriched at D8, and most of them were restored at D30. In conclusion, the species diversity, community structure and composition of the ocular surface microbiota changed greatly after exposure to CTV, but they tended to be restored within weeks after discontinuing antibiotic treatment.
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Microbiota , Tobramicina , Animales , Antibacterianos , Bacterias/genética , Ceftazidima , Microbiota/genética , ARN Ribosómico 16S/genética , Conejos , Vancomicina/farmacologíaRESUMEN
Cardiac fibrosis is a pathological process of multiple cardiovascular diseases, which may lead to heart failure. Studies have shown that microRNAs (miRNAs) play critical roles in regulating mitophagy and cardiac fibrosis. We found that miR-24-3p expression was significantly downregulated in transverse aortic constriction (TAC) mice and cardiac fibroblasts (CFs) treated with Ang â ¡. We also found that, apart from improving cardiac structure and function, forced expression of miR-24-3p not only reduced the levels of collagen and α-SMA but also inhibited proliferation and migration of CFs. Next, our research proved that miR-24-3p suppressed the progression of mitophagy, autophagic flux, and the levels of mitophagy-related proteins in cardiac fibrosis models. Further analysis showed that PHB2 was a direct target of miR-24-3p. Finally, experiments showed that the knockdown of PHB2 reversed Ang â ¡-induced fibrosis in CFs. The results of our study suggests that increased expression of miR-24-3p contributes to the reduction of cardiac fibrosis and that it might be targeted therapeutically to alleviate cardiac fibrosis.
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MicroARNs , Prohibitinas/metabolismo , Animales , Células Cultivadas , Fibroblastos/metabolismo , Fibrosis , Ratones , Ratones Endogámicos C57BL , MicroARNs/metabolismo , Mitofagia , Miocardio/metabolismoRESUMEN
PURPOSE: Superior limbic keratoconjunctivitis (SLK) is an uncommon and often overlooked chronic ocular surface disease. This retrospective consecutive case series study on Chinese patients aimed to characterize the features of this disease, including those undescribed in previous literature. METHODS: Two hundred thirty-six patients diagnosed with SLK were enrolled into this consecutive case study from 2016 to 2019. The demographics, symptoms, Ocular Surface Disease Index, and ocular signs were collected and analyzed. A scoring system (SLK scale index, SSI) that integrated five major sign scores was applied to evaluate SLK severity. RESULTS: Of the 236 SLK patients, dryness was the most common complaint (59.3%). Of 459 SLK eyes, superior limbus/conjunctival staining (SCS) was present in 98% eyes, followed by the superior tarsal conjunctival alterations (85.2%) and superior bulbar conjunctiva hyperemia (80.8%). Approximately 63% of eyes were accompanied by corneal staining. Superior bulbar conjunctivochalasis was a relatively rare sign (41.6%). Among the five major signs, only the prevalence of SCS gradually increased with its severity. In addition, fluorescein staining at the inferior limbus and adjacent conjunctiva (ICS) was found positive in 163 eyes of 84 patients (36%) who had significantly higher SSI than those without ICS (p = 0.013). CONCLUSIONS: We found that SCS is the most common out of the 5 typical signs of SLK. ICS, a new sign, occurred in one-third of patients. SCS, a simple marker of SLK, as well as SSI, an integrated evaluation system, had the advantage of evaluating the severity and objectively characterizing SLK in clinical practice.
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Queratoconjuntivitis , Limbo de la Córnea , Escleritis , China/epidemiología , Conjuntiva , Humanos , Queratoconjuntivitis/diagnóstico , Estudios RetrospectivosRESUMEN
Type 1 diabetes (T1D) is an autoimmune disease leading to an insulin deficiency that causes hyperglycemia and associated symptoms. It is considered the most common type of diabetes, with the 4Ts (going to the toilet a lot, being really thirsty, feeling more tired than usual, losing weight or looking thinner than usual) being the most prevalent symptoms. Non-specific signs and symptoms are also possible, and delaying or missing the diagnosis can have a devastating effect on a child's health. Children with a definitive diagnosis of diabetes often require medical treatment for problems such as ketoacidosis, hypoglycemia and hyperglycemia. To reach glycated hemoglobin (HbA1c) values of 48 mmol/mol, lifetime rigorous monitoring and management of blood glucose levels via insulin replacement treatment is needed in T1D. Physical and psychosocial issues arise frequently with a diabetes diagnosis, resulting in poor management. Nurses play a significant role in detecting diabetes in a number of healthcare settings, resulting in quick diagnoses and prompt initiation of treatment. Not only do they provide critical assistance to help children and their families with the diagnosis, they also place particular emphasis on managing difficult days and common problems with ongoing management. Nurses can provide invaluable assistance managing this chronic condition by coping with day-to-day challenges.
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Diabetes Mellitus Tipo 1 , Hiperglucemia , Hipoglucemia , Rol de la Enfermera , Glucemia , Niño , Diabetes Mellitus Tipo 1/enfermería , Diabetes Mellitus Tipo 1/terapia , Hemoglobina Glucada , Humanos , Hipoglucemiantes , InsulinaRESUMEN
BACKGROUND: The goals of this work were to report the demographic characteristics of patients with clinically diagnosed endophthalmitis with or without intraocular foreign bodies (IOFBs) and to analyze the causative microorganisms. METHODS: A retrospective analysis was conducted on 1257 patients with clinically diagnosed posttraumatic endophthalmitis who were admitted to Zhongshan Ophthalmic Center between January 1, 2013, and August 31, 2020. RESULTS: Of the 1257 patients with clinically diagnosed posttraumatic endophthalmitis, 452 (36.0%) patients had IOFBs. Male dominance was more common among the patients with IOFBs than the patients without IOFBs. The average age of the patients with IOFBs was older than that of the patients without IOFBs. The most common microbial pathogens in these two groups were Gram-positive cocci and Gram-negative bacilli. Gram-positive bacilli were more common in the patients with IOFBs than in those without IOFBs (17.9 vs. 9.4%), and Bacillus spp. accounted for 12.6 and 5.5%, respectively. Fungi were less abundant in the patients with IOFBs than in those without IOFBs (8.0 vs. 15.6%). CONCLUSIONS: Patients with IOFBs were mostly male and older than those without IOFBs. Gram-positive bacilli were more common and fungi were less common in patients with IOFBs than in those without IOFBs.
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Endoftalmitis , Cuerpos Extraños en el Ojo , Lesiones Oculares Penetrantes , Cuerpos Extraños en el Ojo/complicaciones , Lesiones Oculares Penetrantes/complicaciones , Femenino , Humanos , Masculino , Estudios Retrospectivos , Agudeza VisualRESUMEN
Nurses and the nursing profession are the ultimate components of the healthcare system, especially in the operating room, and nurses are exposed to many risks and hazards in the course of performing their jobs. Overall, this appeared to be negligible across the world. Our study aims to give an overview of the risks and safety concerns of operating room nurses as reported in the literature and to look at the strategies or countermeasures that can be taken to surmount them. Major needle and sharps injuries. radiation and surgical smoke exposure, back pain, excessive workloads and patient handling-related injuries were reported extensively. Appropriate precautions, adequate training and experience, enactment of local protocols and policies, creation of a favorable working atmosphere, adequate rest and colleague support can all help overcome these concerns to an extent. At the institutional and political level, effective countermeasures should be taken to guarantee the welfare of competent operators for improved healthcare. Further studies are also required of operating room staff on the risk of chronic diseases and illness in those individuals who have been exposed to atmospheric gasses and smoke.
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Enfermeras y Enfermeros , Quirófanos , Humanos , Carga de TrabajoRESUMEN
OBJECTIVE: To investigate the effect of lipopolysaccharide (LPS) on human herpesvirus 1 (HHV-1) infection in epithelial cells. METHODS: Two strains of HHV-1, HHV-1 F strain (HHV-1f) and HHV-1 strain-H129 with GFP knock-in (HHV-g4), were used to infect HCE-T and VERO cells at MOIs of 0.04 and 0.02, respectively. After 1 h, 0, 10, 50, and 100 µg/ml LPS was added to serum-free medium and the cells were cultured for up to 24 h. GFP fluorescence of HHV-g4 in cells was examined under a fluorescence microscope and imaged. HHV-1f titer was determined by quantitative real-time polymerase chain reaction (qPCR) in HCE-T cells and plaque assays in VERO cells. The expression of the viral ICP4 protein of HHV-1f was detected by Western blot assay. IL-6 and IL-10 levels in culture medium were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Similar changes but at different degrees were found in HCE-T and VERO cells that were infected with HHV-1. GFP fluorescence of HHV-g4 and cell lesions increased in a dose-dependent manner. Virus titer was also enhanced by LPS stimulation in HCE-T and VERO cells. ICP4 expression was promoted at higher LPS concentrations (P = 0.04). In addition, viral infection resulted in increased expression of IL-6 in a dose-dependent manner at 12 and 24 h (P = 0.01), while IL-10 expression was unaffected by either HHV-1 infection or LPS stimulation. CONCLUSION: LPS promotes HHV-1 infection in epithelial cells, which suggests that gram-negative bacteria on ocular surfaces may aggravate HHV-1 infection.
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Células Epiteliales/metabolismo , Herpes Simple/metabolismo , Herpesvirus Humano 1/fisiología , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Animales , Chlorocebus aethiops , Células Epiteliales/virología , Herpes Simple/genética , Herpes Simple/virología , Herpesvirus Humano 1/efectos de los fármacos , Herpesvirus Humano 1/genética , Humanos , Proteínas Inmediatas-Precoces/genética , Proteínas Inmediatas-Precoces/metabolismo , Interleucina-6/genética , Células Vero , Replicación ViralRESUMEN
BACKGROUND: C5a is important for antineutrophil cytoplasmic antibody (ANCA)-mediated activation of neutrophils. The present study aimed to assess the role of macrophage migration inhibitory factor (MIF) in ANCA-mediated activation of C5a-primed neutrophils. The effects of MIF on ANCA-mediated neutrophil respiratory burst and degranulation were determined. In addition, the effect of a MIF antagonist on the activation of C5a-primed neutrophils was assessed. RESULTS: MIF treatment resulted in increased membrane proteinase-3 (mPR3) expression on neutrophils and enhanced myeloperoxidase (MPO) amounts in neutrophil culture supernatants. The concentration of MIF was significantly higher in the neutrophils supernatant primed with C5a (negative control: 14.2 ± 1.16 ng/ml; C5a: 45.8 ± 2.8 ng/ml, P < 0.001 vs. negative control; C5a + IgG: 44.8 ± 1.93 ng/ml, P < 0.001 vs. negative control; C5a + MPO-ANCA: 73.0 ± 5.5 ng/ml, P < 0.001 vs. C5a; and C5a + PR3-ANCA: 69.4 ± 5.35 ng/ml, P < 0.001 vs. C5a). MIF primed neutrophils to undergo respiratory burst and degranulation in response to ANCA. Indeed, mean fluorescence intensity (a measure of respiratory burst) was significantly higher in MIF-primed neutrophils activated with MPO-ANCA-positive IgG or PR3-ANCA-positive IgG compared with non-primed neutrophils. Meanwhile, a MIF antagonist reduced oxygen radical production in C5a-primed neutrophils treated with patient-derived ANCA-positive IgG. CONCLUSIONS: MIF can prime neutrophils to undergo ANCA-mediated respiratory burst and degranulation. Blocking MIF resulted in reduced ANCA-mediated activation of C5a-primed neutrophils. These findings indicated that the interaction between MIF and C5a may contribute to ANCA-mediated neutrophil activation.
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Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Complemento C5a/inmunología , Oxidorreductasas Intramoleculares/metabolismo , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Neutrófilos/inmunología , Degranulación de la Célula , Células Cultivadas , Humanos , Oxidorreductasas Intramoleculares/antagonistas & inhibidores , Isoxazoles/farmacología , Factores Inhibidores de la Migración de Macrófagos/antagonistas & inhibidores , Mieloblastina/genética , Mieloblastina/metabolismo , Activación Neutrófila , Peroxidasa/genética , Peroxidasa/metabolismo , Estallido RespiratorioRESUMEN
Ocular surface disease is one major type of eye diseases. Different etiologies trigger distinct pathological responses of the ocular surface. We previously reported that genetically engineered mice with ablation of Prickle 1 manifested precocious eyelid opening with ensuing cornea dysplasia. The current study aimed to characterize the molecular traits and the direct cause of ocular pathology associated with precocious eyelid opening in the Prickle 1 mutant mouse. Prickle 1 mutant mice exhibited a slew of ocular surface pathology including cell proliferation, cell fate transformation and inflammatory infiltration coinciding with the timing of the precocious eyelid opening. Forced eyelid opening in wild type mice did not induce cornea pathology comparable to that of the Prickle 1 mutants. Necrotic tissue debris was found associated with the lesioned cornea. RNAseq analysis of the mutant cornea revealed an expression profile shared by a range of dermatological diseases involving immune responses and cancer. Taken together, the data suggest that the necrotic eyelid debris plays an important role in ocular pathogenesis of the Prickle 1 mutant mouse, which may represent a type of non-infectious keratoconjunctivitis caused by damaged autologous tissues. Additionally, Prickle 1 mutant cornea pathogenesis may offer molecular insights into other types of epithelial pathogenesis.
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Proteínas Adaptadoras Transductoras de Señales/genética , Córnea/patología , Párpados/fisiología , Queratoconjuntivitis/genética , Proteínas con Dominio LIM/genética , Animales , Animales Recién Nacidos , Conjuntiva/patología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/fisiología , Células Caliciformes/patología , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Queratoconjuntivitis/fisiopatología , Metaplasia , Ratones , Ratones Endogámicos C57BL , Necrosis/patología , Factor de Transcripción PAX6/genética , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
5,10,15,20-Tetrakis(4-carboxyl phenyl)porphyrin (Por) modified Co(OH)2 deposited on the surface of GO nanocomposites (Por/Co(OH)2/GO) were prepared and characterized by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and XRD. For the first time, H2TCPP/Co(OH)2/GO is found to have enhanced peroxidase-like activity and catalyze the oxidation of the substrate 3,3,5,5-tetramethylbenzidine (TMB) by hydrogen peroxide (H2O2). Notably, the colorless TMB rapidly transformed into blue oxTMB in just 60 s, which was easily observed visually. The catalytic kinetics of H2TCPP/Co(OH)2/GO is in accord with the Michaelis-Menten equation. The catalytic mechanism of H2TCPP/Co(OH)2/GO nanocomposites is attributed to hydroxyl radicals (ËOH), due to decomposition of H2O2, which is verified by using terephthalic acid as a fluorescent probe. What's more, H2O2 can be detected in a wide linear detection range from 5 to 35 mM with a detection limit of 0.385 mM. Furthermore, based on the excellent peroxidase-like activity of H2TCPP/Co(OH)2/GO, a colorimetric sensor is established to sensitively detect glutathione (GSH) in a linear range from 10 to 300 µM with a low detection limit of 9.5 µM.
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Cobalto/química , Grafito/química , Hidróxidos/química , Nanocompuestos/química , Peroxidasas/química , Porfirinas/química , Bencidinas/química , Materiales Biomiméticos , Técnicas Biosensibles/métodos , Catálisis , Glutatión/análisis , Peróxido de Hidrógeno/química , Radical Hidroxilo/química , Cinética , Límite de Detección , Oxidación-Reducción , Sensibilidad y Especificidad , Propiedades de SuperficieRESUMEN
BACKGROUND: Although several studies have assessed the effect of Tai Chi in management of chronic obstructive pulmonary disease (COPD), these studies have a wide sample variation and convey inconclusive results. This study aims to determine if a 3-month Tai Chi program improves lung function, exercise capacity, and health related quality of life (HRQoL) in people with COPD. METHODS: A randomised controlled, single blind trial was undertaken. Patients were randomly allocated to either Tai Chi group (n=26) or control group (n=24). Participants in the Tai Chi group received a Tai Chi exercise program three times weekly for 3-months while participants in the control group were advised to maintain their routine activities. Outcome measures included lung function, 6-minute walk distance (6WMD) and COPD Assessment Test (CAT). The measurements took place at baseline and immediately after the 3-month intervention period. RESULTS: Of 50 participants, 46 completed the intervention. Compared to control, Tai Chi significantly increased 6WMD (mean difference 60.5m, 95% CI 30.27-78.69), and reduced score of CAT (mean difference 14 points, 95% CI 11-24). An 86% compliance to the Tai Chi training was noted and no adverse events were observed in Tai Chi group. CONCLUSIONS: The Tai Chi program is a safe, effective and feasible method to improve exercise capacity and health-related quality of life in people with COPD.
Asunto(s)
Tolerancia al Ejercicio , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Calidad de Vida , Taichi Chuan , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Pruebas de Función RespiratoriaRESUMEN
PURPOSE: To investigate the potential protective effects of curcumin on the retina in diabetic rats. METHODS: An experimental diabetic rat model was induced by a low dose of streptozotocin combined with a high-energy diet. Rats which had blood glucose levels ≥11.6 mmol/L were used as diabetic rats. The diabetic rats were randomly divided into 3 groups: diabetic rats with no treatment (DM), diabetic rats treated with 100 mg/kg curcumin (DM + Cur 100 mg/kg), and diabetic rats treated with 200 mg/kg curcumin (DM + Cur 200 mg/kg). Curcumin was orally administered daily for 16 weeks. After 16 weeks of administration, the rats were euthanized, and eyes were dissected. Retinal histology was examined, and the thickness of the retina was measured. Ultrastructural changes of retinal ganglion cells, inner layer cells, retinal capillary, and membranous disks were observed by electron microscopy. Malondialdehyde, superoxide dismutase, and total antioxidant capacity were measured by ELISA. Expression levels of vascular endothelial growth factor (VEGF) in retina tissues were examined by immunohistochemical staining and ELISA. Expression levels of Bax and Bcl-2 in retina tissues were determined by immunohistochemical staining and Western blotting. RESULTS: Curcumin reduced the blood glucose levels of diabetic rats and decreased diabetes-induced body weight loss. Curcumin prevented attenuation of the retina in diabetic rats and ameliorated diabetes-induced ultrastructure changes of the retina, including thinning of the retina, apoptosis of the retinal ganglion cells and inner nuclear layer cells, thickening of retinal capillary basement membrane and disturbance of photoreceptor cell membranous disks. We also found that curcumin has a strong antioxidative ability in the retina of diabetic rats. It was observed that curcumin attenuated the expression of VEGF in the retina of diabetic rats. We also discovered that curcumin had an antiapoptotic effect by upregulating the expression of Bcl-2 and downregulating the expression of Bax in the retina of diabetic rats. CONCLUSIONS: Taken together, these results suggest that curcumin may have great therapeutic potential in the treatment of diabetic retinopathy which could be attributed to the hypoglycemic, antioxidant, VEGF-downregulating and neuroprotection properties of curcumin.