RESUMO
Background: Myopia is associated with scleral weakness and thinness, leading to visual impairment. Currently, posterior scleral reinforcement (PSR) remains the primary treatment for this condition. However, clinical practice commonly faces challenges such as insufficient donor availability and inadequate strength of allogeneic sclera materials. Therefore, in this study, we evaluated the cytokine expression and biomechanical characteristics of two types of scleral reinforcement materials (demineralized bone matrix (DBM) and allogeneic sclera) to identify the optimal material for PSR. Methods: Seventy-two two-week-old New Zealand rabbits were utilized in this study. Each rabbit eye was assigned to either an experimental group or an untreated group (no surgical intervention), which were further divided into DBM, allogenic sclera, and control groups (surgery without implantation). Samples were analyzed during different postoperative periods including the inflammatory response period at week 2, angiogenesis period at week 4, collagen formation period at week 12, and connective tissue proliferation period at week 24. Refractive power and axial length of the experimental eyes were measured at 2, 4, 12,and 24 weeks postoperatively while implanted slices with attached sclera from the DBM and Sclera group experimental eyes were collected. The same area of sclera was obtained from the sham group for immunohistochemical analysis and western blot detection to analyze levels of bFGF (Basic Fibroblast Growth Factor), CTGF (Connective Tissue Growth Factor), TGF-ß (Transforming Growth Factor ß),and Collagen I along with respective elasticity modulus and ultimate strength of the implant slice taken. Results: There were no significant differences (P > .05) in axial length and refractive power between the DBM and allogenic groups before 24 weeks, while a significant difference (P < .05) was observed compared to the control group. The levels of bFGF, CTGF, and TGF-ß in the DBM and sclera groups were significantly higher than those in the control group (P < .05). After 24 weeks, histological analyses revealed a strong connection between the implants and sclera with collagen formation. The elasticity modulus and ultimate strength of both DBM and scleral groups were significantly higher than those of the control group (P < .05). Furthermore, the DBM group exhibited a higher elastic modulus and ultimate strength compared to the scleral group (P < .05). The synthesis of collagen can be effectively promoted by bFGF, CTGF, and TGF-ß, leading to increased elastic modulus and ultimate strength which helps prevent posterior scleral expansion, thereby controlling further axial growth delay complications occurrence. Conclusion: The cytokine expression profile along with biomechanical characteristics make DBM an ideal material for posterior scleral reinforcement due to its low antigenicity, excellent biocompatibility without obvious postoperative rejection reaction as well as its ability to closely associate with autologous sclera making it widely available from various sources.
RESUMO
Phytosterols are vital structural and regulatory components in plants. Zea mays produces a series of phytosterols that are specific to corn. However, the underline biosynthetic mechanism remains elusive. In this study, we identified a novel sterol methyltransferase from Z. mays (ZmSMT1-2) which showed a unique feature compared with documented plant SMTs. ZmSMT1-2 showed a substrate preference for cycloartenol. Using S-adenosyl-L-methionine (AdoMet) as a donor, ZmSMT1-2 converted cycloartenol into alkylated sterols with unique side-chain architectures, including Δ25(27) (i.e., cyclolaudenol and cycloneolitsol) and Δ24(25) (i.e., cyclobranol) sterols. Cycloneolitsol is identified as a product of SMTs for the first time. Our discovery provides a previously untapped mechanism for phytosterol biosynthesis and adds another layer of diversity of sterol biosynthesis.
Assuntos
Metiltransferases , Fitosteróis , Triterpenos , Zea mays , Zea mays/metabolismo , Fitosteróis/metabolismo , Fitosteróis/química , Metiltransferases/metabolismo , Metiltransferases/química , Metiltransferases/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/química , Especificidade por Substrato , S-Adenosilmetionina/metabolismo , S-Adenosilmetionina/químicaRESUMO
Artificial intelligence (AI)-based diagnostic systems have been reported to improve fundus disease screening in previous studies. This multicenter prospective self-controlled clinical trial aims to evaluate the diagnostic performance of a deep learning system (DLS) in assisting junior ophthalmologists in detecting 13 major fundus diseases. A total of 1493 fundus images from 748 patients were prospectively collected from five tertiary hospitals in China. Nine junior ophthalmologists were trained and annotated the images with or without the suggestions proposed by the DLS. The diagnostic performance was evaluated among three groups: DLS-assisted junior ophthalmologist group (test group), junior ophthalmologist group (control group) and DLS group. The diagnostic consistency was 84.9% (95%CI, 83.0% ~ 86.9%), 72.9% (95%CI, 70.3% ~ 75.6%) and 85.5% (95%CI, 83.5% ~ 87.4%) in the test group, control group and DLS group, respectively. With the help of the proposed DLS, the diagnostic consistency of junior ophthalmologists improved by approximately 12% (95% CI, 9.1% ~ 14.9%) with statistical significance (P < 0.001). For the detection of 13 diseases, the test group achieved significant higher sensitivities (72.2% ~ 100.0%) and comparable specificities (90.8% ~ 98.7%) comparing with the control group (sensitivities, 50% ~ 100%; specificities 96.7 ~ 99.8%). The DLS group presented similar performance to the test group in the detection of any fundus abnormality (sensitivity, 95.7%; specificity, 87.2%) and each of the 13 diseases (sensitivity, 83.3% ~ 100.0%; specificity, 89.0 ~ 98.0%). The proposed DLS provided a novel approach for the automatic detection of 13 major fundus diseases with high diagnostic consistency and assisted to improve the performance of junior ophthalmologists, resulting especially in reducing the risk of missed diagnoses. ClinicalTrials.gov NCT04723160.
RESUMO
PURPOSE: The dysregulation of NF-κB signaling activity plays an important role in the pathogenesis of diabetic retinopathy (DR). This study explored the association between NEDD4L and IκBα in DR. METHODS: The rat model of diabetes was established and altered retinal vascular permeability in these rats was examined through an Evans blue dye assay. A range of glucose concentrations were used to treat retinal vascular endothelial cells (RVECs). The cells viability and apoptosis were assessed through MTT and flow cytometry, while shifts in cell permeability were examined by transendothelial resistance (TEER) and FITC dextran assay. The interaction of NEDD4L and IκBα was tested by Co-IP, while mRNA and protein levels were assessed via qPCR and Western blotting, respectively. RESULTS: High glucose suppressed proliferative activity of RVECs, and promoted apoptosis and the protein level of NEDD4L and NF-κB p65, but decreased IκBα. NEDD4L knockdown reversed the changes in inflammation, oxidative stress, and permeability in RVECs exposed to high glucose. Similarly, NEDD4L silencing reverted observed TEER decreases, increased monolayer permeability to FITC dextran, and ZO-1 and Claudin-5 downregulation in response to high glucose. Conversely, the impact of NEDD4L overexpression was reversed by the NF-κB inhibitor PDTC treatment. NEDD4L induced the ubiquitination of IκBα in an IKK-2-dependent manner. Moreover, siNEDD4L treatment alleviated the symptoms of DR through the inactivation of NF-κB signaling in vivo. CONCLUSIONS: NEDD4L could enhance inflammation, oxidative stress, and permeability in the retinal vascular endothelium by facilitating the ubiquitination of IκBα in an IKK-2-dependent manner. Our results support a role for NEDD4L in the pathogenesis of DR.
Assuntos
Diabetes Mellitus , Retinopatia Diabética , Animais , Ratos , Diabetes Mellitus/metabolismo , Retinopatia Diabética/metabolismo , Células Endoteliais/metabolismo , Glucose/farmacologia , Inflamação/metabolismo , NF-kappa B/metabolismo , Inibidor de NF-kappaB alfa/genética , Inibidor de NF-kappaB alfa/metabolismo , UbiquitinaçãoRESUMO
PURPOSE: To examine whether and how carbohydrate response element-binding protein (ChREBP) plays a role in diabetic retinopathy. METHODS: Western blotting was used to detect ChREBP expression and location following high glucose stimulation of Human Retinal Microvascular Endothelial Cells (HRMECs). Flow cytometry, TUNEL staining, and western blotting were used to evaluate apoptosis following ChREBP siRNA silencing. Cell scratch, transwell migration, and tube formation assays were used to determine cell migration and angiogenesis. Diabetic models for wild-type (WT) and ChREBP knockout (ChKO) mice were developed. Retinas of WT and ChKO animals were cultivated in vitro with vascular endothelial growth factor + high glucose to assess neovascular development. RESULTS: ChREBP gene knockdown inhibited thioredoxin-interacting protein and NOD-like receptor family pyrin domain containing protein 3 expression in HRMECs, which was caused by high glucose stimulation, reduced apoptosis, hindered migration, and tube formation, and repressed AKT/mTOR signaling pathway activation. Compared with WT mice, ChKO mice showed suppressed high glucose-induced alterations in retinal structure, alleviated retinal vascular leakage, and reduced retinal neovascularization. CONCLUSIONS: ChREBP deficiency decreased high glucose-induced apoptosis, migration, and tube formation in HRMECs as well as structural and angiogenic responses in the mouse retina; thus, it is a potential therapeutic target for diabetic retinopathy.
Assuntos
Diabetes Mellitus , Retinopatia Diabética , Animais , Humanos , Camundongos , Diabetes Mellitus/metabolismo , Retinopatia Diabética/metabolismo , Células Endoteliais/metabolismo , Glucose/metabolismo , Retina/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
CLINICAL RELEVANCE: There are many methods to control the progression of myopia. However, it is currently unknown which method could better control myopia progression: 0.02% atropine eye drops, peripheral myopic defocus design spectacle lenses (PMDSL), or orthokeratology (OK). BACKGROUND: To compare the efficacy of 0.02% atropine, PMDSL, and OK to control axial length (AL) elongation in children with myopia. METHODS: This study was analysed based on a previous cohort study (0.02% atropine group) and retrospective data (PMDSL and OK group). Overall, 387 children aged 6-14 years with myopia - 1.00D to - 6.00D in the three groups were divided into four subgroups according to age and spherical equivalent refraction (SER). The primary outcome was changed in AL over 1-year. RESULTS: The mean axial elongation was 0.30 ± 0.21 mm, 0.23 ± 0.16 mm, and 0.17 ± 0.19 mm in the 0.02% atropine, PMDSL, and OK groups, respectively. Multivariate linear regression analyses showed significant differences in axial elongation among the three groups, especially in children aged 6-10, but not in children aged 10.1-14; the corresponding axial elongation was 0.35 ± 0.21 mm, 0.23 ± 0.17 mm, and 0.21 ± 0.20 mm (P < 0.05 between any two groups, except between PMDSL and OK groups at P > 0.05) and 0.22 ± 0.20 mm, 0.21 ± 0.13 mm, and 0.13 ± 0.18 mm (P < 0.05 between any two groups, except between 0.02% atropine and PMDSL groups at P > 0.05) in children with SER from - 1.00D to - 3.00D and from - 3.01D to - 6.00D, respectively. CONCLUSIONS: Within the limits of this study design and using only the current brand of PMDSL, OK appeared to be the best method, followed by PMDSL and then 0.02% atropine, for controlling AL elongation over one year. However, different effects were found in the various age and SER subgroups.
RESUMO
Scallops have become an important aquaculture species in China because they contain high-quality protein, and scallops are important health food that combines multiple effects and high economic benefits. However, scallop aquaculture is perennially threatened by various pathogenic Vibrio species, leading to great economic losses. We obtained a strain of pathogenic bacteria, identified as Vibrio alginolyticus, from the diseased Azumapecten farreri in the scallop farming area of Huangdao District in 2018, and V. alginolyticus is one of the major shellfish pathogens. We showed that V. alginolyticus was isolated and identified as a pathogen in A. farreri for the first time. In this study, we evaluated its morphology and performed a phylogenetic analysis based on 16S rRNA gene sequencing. In addition, we performed a preliminary analysis of its pathogenic mechanisms. The Hfq protein in V. alginolyticus is an important RNA-binding protein in the quorum-sensing system that not only affects the sensitivity of Vibrio to environmental stress but also regulates a variety of functions, such as cell membrane formation, motility, and virulence towards the host. However, its effect on the pathogenesis of V. alginolyticus to A. farreri is unclear. To further investigate the pathogenic mechanism of the Hfq protein in V. alginolyticus to A. farreri, we used the CRISPR-Cas9 system to target and deplete the hfq gene fragment in V. alginolyticus and obtained the mutant strain V. ΔHfq-. We found that the peripheral flagellum of the mutant strain was lost, which reduced the motility of V. alginolyticus. Therefore, the deletion of target genes by the CRISPR/Cas9 genome editing system confirmed that the Hfq protein played a key role in reducing the ability of V. alginolyticus to infect A. farreri. In conclusion, our current findings provided valuable insights into the healthy culture of scallops.
Assuntos
Sistemas CRISPR-Cas , Vibrio alginolyticus , Vibrio alginolyticus/genética , Filogenia , RNA Ribossômico 16S , TecnologiaRESUMO
Purpose: It is well documented that angiotensin II (Ang II) elevation promotes apoptosis of podocytes in vivo and vitro, but the potential mechanism is still oscular. The current study is aimed at probing into the assignment of cysteine-rich protein 61 (Cyr61) in Ang II-induced podocyte apoptosis. Methods: Podocytes were treated with Ang II (10-6 mol/L) for 48 hours to establish an injury model in vitro. Western blot assays were detected the expression of Cyr61, Cyt-c, Bax, and Bcl-2. Gene microarray was used to analyze the expression of mRNAs after treatment with Ang II. CRISPR/Cas9 technology was used to knock down Cyr61 and overexpress TXNIP gene, respectively. Results: The expression of Cyr61, TXNIP, Cyt-c, and Bax in podocytes treated with Ang II were upregulated, but the expression and apoptotic rates of Bcl-2 in podocytes were inhibited. The level of the above factors was not significantly different after the knockdown of Cyr61 with Ang II in podocytes. In Ang II group, when knocked down Cyr61, the expressed level of TXNIP, Cyt-c, and Bax was diminished after Ang II treatment; interestingly Bcl-2 expression and podocyte apoptotic rate were reduced. Under the stimulation of Ang II, the expression of Cyt-c and Bax were growing, whereas Bcl-2 was reduced, and the apoptotic rates were higher in the TXNIP overexpression group. Cyt-c and Bax were put on, whereas that of Bcl-2 was to be cut down when the Cyr61 was knockdown, and the apoptotic rates were gained in the TXNIP overexpression+Cyr61 knockdown group. Conclusions: The results of the study extrapolate that Cyr61 plays a dominant role in Ang II-induced podocyte apoptosis. Additionally, Cyr61 may mediate the Ang II-induced podocyte apoptosis by promoting the expression of TNXIP.
Assuntos
Angiotensina II , Podócitos , Regulação para Cima , Angiotensina II/farmacologia , Podócitos/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Apoptose/genéticaRESUMO
Background: Several studies have shown that various concentrations of low-concentration atropine can reduce myopia progression and control axial elongation safely and efficiently in children. The aim of this study was to evaluate the effects of 0.02% and 0.01% atropine on ocular biometrics. Methods: Cohort study. 138 and 142 children were randomized to use either 0.02% or 0.01% atropine eye drops, respectively. They wore single-vision (SV) spectacles, with one drop of atropine applied to both eyes nightly. Controls (N = 120) wore only SV spectacles. Ocular and corneal astigmatism were calculated using Thibos vector analysis and split into J0 and J45. Results: The changes in cycloplegic spherical equivalent refraction (SER) and axial length (AL) were -0.81 ± 0.52D, -0.94 ± 0.59D, and -1.33 ± 0.72D; and 0.62 ± 0.29â mm, 0.72 ± 0.31â mm, and 0.89 ± 0.35â mm in the 0.02% and 0.01% atropine and control groups, respectively (all P < 0.05). Both anterior chamber depth (ACD) and ocular astigmatism (including J0) increased, and lens power decreased in the three groups (all P < 0.05). However, there were no differences in the changes in ACD, ocular astigmatism, and lens power among the three groups (all P > 0.05). Intraocular pressure (IOP), corneal curvature, ocular astigmatism J45, and corneal astigmatism (including J0 and J45) remained stable over time in the three groups (all P > 0.05). The contributions to SER progression from the changes in AL, lens and corneal power of the three groups were similar (P > 0.05). The contribution of AL change alone to the change in SER was 56.3%, 63.4% and 78.2% in the above corresponding three groups. Conclusions: After 2 years, 0.02% and 0.01% atropine had no clinical effects on corneal and lens power, ocular and corneal astigmatism, ACD or IOP compared to the control group. 0.02% and 0.01% atropine helped to control myopia progression mainly by reducing AL elongation.
RESUMO
BACKGROUND: Phakic intraocular lens (pIOL) implantation has been commonly prescribed and is considered as a safe and effective option for correcting high myopia. However, it is associated with multiple complications. CASE SUMMARY: This report describes a case of full-thickness macular hole (MH) in a patient with a history of bilateral pIOL implantation for the correction of myopia of -12.00 diopters in both eyes 7 mo ago. The MH closed after pars plana vitrectomy with internal limiting membrane removal and the best-corrected visual acuity improved to 20/40 in the left eye. CONCLUSION: In rare cases, MH can occur following pIOL. In this present case report, we analyzed the formation process of MH following the surgery and emphasized that it is important to inform highly myopic patients about the risk of MH occurrence while being aware of the symptoms of this complication.
RESUMO
Objective: The effects of TGF-ß2 on mechanical properties of sclerotic desmocytes isolated from healthy and myopic guinea pigs were investigated in order to further understand the pathogenesis of myopia. To study the effect of TGF-ß2 on the mechanical properties of posterior scleral fibroblasts in experimental myopia. Methods: A lens-induced myopia (LIM) animal model was developed in 12 guinea pigs, with the opposite eye serving as a self-control (SC). Five untreated guinea pigs served as normal controls. Lenses were removed 30 days after model onset. Primary scleral fibroblasts were isolated and passaged twice and then treated with vehicle control or 1, 10, or 100 ng/mL TGF-ß2. After 24 h, micropipette aspiration was used to investigate the viscoelastic properties of the cells. Results: Scleral fibroblasts from LIM exhibited significantly higher equilibrium moduli and apparent viscosities relative to SC without TGF-ß2 treatment. Treatment of LIM or SC scleral fibroblasts with 1 or 10 ng/mL TGF-ß2 led to significantly different (p < 0.05) equilibrium moduli and apparent viscosities compared with vehicle control, whereas no significant differences were observed upon treatment with 100 ng/mL TGF-ß2. LIM cells treated with 1 and 10 ng/mL TGF-ß2 exhibited lower equilibrium moduli and apparent viscosities compared with similarly treated SC cells, but LIM cells and SC cells treated with 100 ng/mL TGF-ß2 had similar mechanical properties. Conclusions: The addition of 1 and 10 ng/mL TGF-ß2 can lower the equilibrium modulus and apparent viscosity of scleral fibroblasts in the normal eye.
Assuntos
Miopia , Fator de Crescimento Transformador beta2 , Animais , Modelos Animais de Doenças , Fibroblastos , Cobaias , Miopia/patologia , EscleraRESUMO
Background: Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD). Currently, microalbuminuria is mainly used as a diagnostic indicator of DN, but there are still limitations and lack of immune-related diagnostic markers. In this study, we aimed to explore diagnostic biomarkers associated with immune infiltration of DN. Methods: Immune-related differentially expressed genes (DEGs) were derived from those at the intersection of the ImmPort database and DEGs identified from 3 datasets, which were based on the Gene Expression Omnibus (GEO). Functional enrichment analyses were performed; a protein-protein interaction (PPI) network was constructed; and hub genes were identified by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). After screening the key genes using least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE), a prediction model for DN was constructed. The predictive performance of the model was quantified by receiver-operating characteristic curve, decision curve analysis, and nomogram. Next, infiltration of 22 types of immune cells in DN kidney tissue was evaluated using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT). Expression of diagnostic markers was analyzed in DN and control patient groups to determine the genes with the maximum diagnostic potential. Finally, we explored the correlation between diagnostic markers and immune cells. Results: Overall, 191 immune-related DEGs were identified, that primarily positively regulated with cell adhesion, T cell activation, leukocyte proliferation and migration, urogenital system development, lymphocyte differentiation and proliferation, and mononuclear cell proliferation. Gene sets were related to the PI3K-Akt, MAPK, Rap1, and WNT signaling pathways. Finally, CCL19, CD1C, and IL33 were identified as diagnostic markers of DN and recognized in the 3 datasets [area under the curve (AUC) =0.921]. Immune cell infiltration analysis demonstrated that CCL19 was positively correlated with macrophages M1 (R=0.47, P<0.001) and macrophages M2 (R=0.75, P<0.001). CD1C was positively correlated with macrophages M1 (R=0.47, P<0.05), macrophages M2 (R=0.75, P<0.01), and monocytes (R=0.42, P<0.01). IL33 was positively correlated with macrophages M1 (R=0.45, P<0.05), macrophages M2 (R=0.74, P<0.01), and monocytes (R=0.41, P<0.01). Conclusions: Our results provide evidence that CCL19, CD1C, and IL33, which are associated with immune infiltration, are the potential diagnostic biomarkers for DN candidates.
RESUMO
OBJECTIVE: The characteristics of the early changes in preclinical diabetic retinopathy (DR) are poorly known. This study aimed to analyse the changes in the structure and function of the fundus in diabetic patients without diabetic retinopathy (NDR). METHODS: This prospective study enrolled patients with type 2 diabetes and healthy controls from April to December 2020. Retinal sensitivity was measured by microperimetry. The peripapillary retinal nerve fibre layer (p-RNFL) thickness, macular retinal thickness, and retinal volume were measured by optical coherence tomography (OCT). The vessel density (VD) and perfusion density (PD) of the peripapillary area, as well as the foveal avascular zone (FAZ) area, FAZ perimeter, and FAZ circularity, were measured by optical coherence tomographic angiography (OCTA). RESULTS: A total of 71 cases (100 eyes) were enrolled in the study, including 34 cases (51 eyes) in the NDR group and 37 cases (49 eyes) in the control group. The mean retinal sensitivity was lower in the NDR group than in the control group for all sectors (all p < .001). Compared with controls, the NDR group showed thinner p-RNFL in the T sector (76.24 ± 14.29 vs. 85.47 ± 19.66 µm, p = .035). The NDR group had a thinner retina in the N2 sector (304.55 ± 16.07 vs. 312.02 ± 12.30 µm, p = .010). The PD of DCP was lower in the N2 sector in the NDR group (44.92 ± 11.77 vs. 50.27 ± 6.37%, p = .044). The VD was higher in the NDR group in RPCP-S/N/I, and the PD was higher in the RPCP-S/N (all p < .05). The frequencies of perifoveal capillary drop-out, notched or punched out borders of the superficial FAZ, and loss of smooth contour were all higher in the NDR group (all p < .05). CONCLUSION: The structure (p-RNFL thickness, VD, and PD) and function (retinal sensitivity) display some changes in diabetic patients even if they had not been found to have DR.Key messagesDecreased retinal sensitivity was observed in diabetic patients before the onset of diabetic retinopathy.Compared with the control group, we found the changes in vessel density or perfusion density in a certain area, whether in SCP, DCP, or RPCP in the NDR group.Before the onset of diabetic retinopathy, the structure and function of the retina in diabetic patients had changed.
Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/etiologia , Angiofluoresceinografia/métodos , Humanos , Estudos Prospectivos , Retina/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagemRESUMO
BACKGROUND: To evaluate the effects of 0.02% and 0.01% atropine eye drops on ocular and corneal astigmatism over 2 years. METHODS: A prospective clinic-controlled trail. The cohort study assessed 400 myopic children and divided them into three groups: 138 and 142 children were randomized to use either 0.02% or 0.01% atropine eye drops, respectively. They wore single-vision (SV) spectacles, with one drop of atropine applied to both eyes once nightly. Control children (n = 120) only wore SV spectacles. Spherical equivalent refractive errors (SER) and corneal curvature were measured every 4 months. The SER and corneal curvature were assessed by cycloplegic autorefraction and IOLMaster. Ocular and corneal astigmatism were calculated by Thibos vector analysis and then split into its power vector components, J0 (with-the-rule astigmatism) and J45 (oblique). RESULTS: After 2 years, the ocular astigmatism increased by -0.38 ± 0.29 D, -0.47 ± 0.38 D, -0.41 ± 0.35 D in the 0.02%, 0.01% atropine groups and control group, respectively (p = 0.15). The corresponding corneal astigmatism increased by -0.20 ± 0.34 D, -0.28 ± 0.35 D and -0.26 ± 0.26 D (p = 0.18). The ocular astigmatism J0 increased by 0.19 ± 0.28 D, 0.22 ± 0.36 D, 0.18 ± 0.31 D in the 0.02% atropine, 0.01% atropine and control groups, respectively (p = 0.65). The corresponding corneal astigmatism J0 increased by -0.05 ± 0.34 D, -0.11 ± 0.37 D and -0.13 ± 0.30 D (p = 0.23). There was a small but significant increase in ocular astigmatism (including J0) (all P < 0.05), but there were no changes in the ocular astigmatism J45 and corneal astigmatism (including J0 and J45) in the three groups over time (all p > 0.05). However, there were no significant differences in the changes in ocular astigmatism (including J0) among the three groups. CONCLUSIONS: Treatment with 0.02% and 0.01% atropine had no clinically significant effect on ocular and corneal astigmatism over 2 years. TRIAL REGISTRATION: The First Affiliated Hospital of Zhengzhou University, ChiCTR-IPD-16008844 . Registered 14/07/2016.
Assuntos
Astigmatismo , Doenças da Córnea , Astigmatismo/tratamento farmacológico , Atropina/uso terapêutico , Criança , Estudos de Coortes , Córnea , Humanos , Soluções Oftálmicas , Estudos Prospectivos , Refração OcularRESUMO
BACKGROUND: Podocyte injury is a major biomarker of primary glomerular disease, which leads to massive proteinuria and kidney failure. The increased production of the chemokine, fractalkine (FKN, CX3CL1), is a hallmark of multiple inflammatory diseases. However, the underlying mechanism of FKN in podocyte injury remains unknown. METHODS: In this study, we performed an LPS infusion model in FKN knockout (FKN-/-, FKN-KO) mice. In cultured podocytes, we used plasmids to knockdown FKN and treated the podocytes with PI3K/Akt inhibitor (LY294002). Haematoxylin and eosin (HE) staining, Western Bolt, Co-immunoprecipitation (Co-IP), Immunofluorescence staining and flow cytometric analysis were employed to establish the role of FKN in podocyte injury. RESULTS: LPS stimulation resulted in kidney damage, increased the expression of the Bcl-2 family apoptosis protein, and decreased podocyte marker protein (nephrin, podocin and WT1) abundance compared with the WT mice. LPS-induced FKN-KO mice exhibited reduced lethality and inflammatory cell infiltration, podocyte apoptosis, and PI3K/Akt signal pathway inhibition compared to WT mice. In cultured podocytes, the interaction between FKN and the PI3K/Akt signalling pathway was well confirmed. FKN knockdown reduced podocyte apoptosis by regulating the Bcl-2 family; however, this protective effect was reversed by the co-administration of a PI3K/Akt inhibitor (LY294002). CONCLUSION: Overall, these findings reveal a novel mechanistic property of FKN, PI3K/Akt signalling, and podocyte apoptosis.
Assuntos
Injúria Renal Aguda , Podócitos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/genética , Injúria Renal Aguda/prevenção & controle , Animais , Apoptose , Quimiocina CX3CL1 , Lipopolissacarídeos/farmacologia , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia , Podócitos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/farmacologia , Transdução de SinaisRESUMO
The present study aimed to explore the role of long noncoding RNA metastasis associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) in high glucose (HG)induced ARPE19 cell damage. ARPE19 cells were cultured and treated with HG (25 mmol/l glucose). MALAT1 expression was silenced following transfection of small interfering RNA. Cell apoptosis was measured using flow cytometry. The cellular levels of reactive oxygen species (ROS), malondialdehyde and superoxide dismutase activity were all measured to examine oxidative stress. Gene expression levels of MALAT1 were determined by reverse transcriptionquantitative (RTq)PCR, while expression of tumor necrosis factor (TNF)α, monocyte chemotactic protein 1 (MCP1), intercellular cell adhesion molecule 1 (ICAM1) and vascular endothelial growth factor (VEGF) was detected using RTqPCR and western blotting. MALAT1 expression was markedly increased in ARPE19 cells treated with HG. HG treatment caused increased apoptosis and elevated ROSinduced stress in ARPE19 cells and these effects could be partly attenuated by MALAT1 knockdown. Increased gene expression levels of TNFα, MCP1, ICAM1 and VEGF induced by HG were also alleviated by MALAT1 inhibition. Therefore, lncRNA MALAT1 is the key factor in ARPE19 cell damage caused by HG and may be a promising therapeutic target for clinical DR therapy. However, further studies are still required to reveal the detailed mechanisms underlying lncRNA MALAT1 function.
Assuntos
MicroRNAs , RNA Longo não Codificante , Apoptose/genética , Células Epiteliais/metabolismo , Glucose/metabolismo , MicroRNAs/genética , RNA Longo não Codificante/metabolismo , Pigmentos da Retina , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
PURPOSE: To study the topographical relationship between acute macular neuroretinopathy (AMN) lesions and the choroidal watershed zone (CWZ) or patchy choroidal filling (PCF) using multimodal imaging. METHODS: Lesions in patients diagnosed with AMN were clinically examined using multimodal imaging, including fundus photography, near-infrared reflectance imaging, spectral-domain optical coherence tomography (OCT), fluorescein angiography, indocyanine green angiography, OCT angiography, and microperimetry. The topographical relationship between AMN and the CWZ or PCF was evaluated. RESULTS: Seven eyes of six patients were included in the study. The mean age of the patients was 35.8 ± 11.7 years. The AMN lesions were collocated with the CWZ in five eyes and the PCF in one eye. Among these eyes, three had complete patterns, and three had partial patterns. Only one eye showed no topographical relationship between AMN and the CWZ or PCF. CONCLUSION: The colocation of AMN and CWZ/PCF suggests that the AMN lesions were within an area with a dual-watershed zone: the watershed zone between the retinal deep capillary plexus and choriocapillaris, and the choroidal watershed zone or patchy choroidal filling. This retinal area was highly vulnerable to hypoperfusion. Our results suggest a novel pathophysiological mechanism for AMN.
RESUMO
This research of mixotrophic microalgae Isochrysis 3011 with glycerol was combined with the treatment of aqua-cultural wastewater, different initial concentrations, and optimized light intensities. The algae growth rate, removal efficiencies of total nitrogen (TN) and total phosphorus (TP) were determined. Results showed that the suitable initial concentration was 0.4 g L-1, and the optimum light intensity was 60 µmol m-2 s-1. The growth of the mixotrophic group was better than that of the autotrophic culture. The biomass yield of the mixotrophic group with glycerol was 0.17 g L-1 d-1, and the removal rates of TN and TP were 73.39% and 95.61%, respectively. The content of total lipid and total protein in mixotrophic group were higher than the values of the autotrophic group. This indicates that aquaculture wastewater treatment with mixotrophic bait microalgae can obtain superior micro-algal biomass, which is also a potential technology for wastewater utilization and ecological protection.
Assuntos
Haptófitas , Microalgas , Purificação da Água , Aquicultura , Biomassa , Nitrogênio/metabolismo , Águas ResiduáriasRESUMO
OBJECTIVE: To use optical coherence tomography (OCT) to compare retinal biomarkers of choroidal neovascularization (CNV) secondary to multifocal choroiditis (MFC), myopic choroidal neovascularization (mCNV), and idiopathic choroidal neovascularization (ICNV) and to provide a basis for its clinical diagnosis and treatment. METHODS: In this retrospective case study, patients admitted to the Second Hospital of Hebei Medical University between January 2018 and January 2021 who were initially diagnosed with CNV secondary to MFC, mCNV, and ICNV were categorized into groups, by disease, for analysis. Spectral domain-OCT (SD-OCT) was used to describe and measure the morphological characteristics of CNV lesions in each group. The retinal biomarkers of CNV in MFC, mCNV, and ICNV were compared. RESULTS: Sixty-eight patients (71 eyes) were included and all eyes were diagnosed with active type 2 CNV. The MFC group had higher refraction than the ICNV group (P2 < 0.05). The choroidal thickness (CT) and CNV diameter of the MFC group were significantly greater than those of the mCNV group (P1 < 0.05). The number of eyes with sub-retinal fluids (SRF) and a "pitchfork sign" was significantly greater in the MFC group than in the mCNV group (P1 < 0.05). There was a significant difference only in CT) values between the MFC and ICNV groups (P2 < 0.001), but not in the other observation indicators (P2 > 0.05). CONCLUSIONS: OCT biomarkers, such as the diameter of the CNV, SRF, the "pitchfork sign," and CT under CNV are useful in distinguishing CNV secondary to MFC from mCNV, which can allow the timely selection of treatment in some difficult cases. There were no differences between the MFC group and ICNV group except in refractive error, which indicates that some ICNV cases may be an early stage of a type of occult chorioretinitis. Long-term follow-up is needed for ICNV patients to confirm whether there is any potential inflammation.Key messagesSometimes, it is difficult to separate MFC with CNV from myopic CNV and ICNV in clinical.OCT biomarkers, such as the diameter of the CNV, SRF, the "pitchfork sign," and CT under CNV are useful in distinguishing CNV secondary to MFC from mCNV.There were no differences between the MFC group and ICNV group except in refractive error.