Apigenin inhibits angiogenesis in retinal microvascular endothelial cells through regulating of the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway.

BACKGROUND: Diabetic retinopathy (DR) is a common cause of visual impairment. Apigenin has been shown to have antiangiogenic effects in various diseases. Our study aimed to investigate the role of apigenin in DR and elucidate the underlying mechanism. METHODS: Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) to establish a DR model. HRMECs were treated with apigenin. Then we knocked down or overexpressed miR-140-5p and HDAC3, and added PI3K/AKT inhibitor LY294002. The expression levels of miR-140-5p, HDAC3, and PTEN were measured using qRT-PCR. Western blot analysis was performed to assess the expression of HDAC3, PTEN, and PI3K/AKT pathway-related proteins. Finally, cell proliferation and migration were evaluated using MTT, wound-healing assay, and transwell assay, while angiogenesis was examined using the tube formation assay. RESULTS: HG treatment resulted in reduced miR-140-5p expression and overexpression of miR-140-5p suppressed proliferation, migration, and angiogenesis of the HG-induced HRMECs. Apigenin treatment significantly restored the decreased level of miR-140-5p caused by HG treatment and inhibited proliferation, migration, and angiogenesis of the HG-induced HRMECs by upregulating miR-140-5p. Moreover, miR-140-5p targeted HDAC3, and overexpression of miR-140-5p reversed the HG-inducted upregulation of HDAC3 expression. HDAC3 was found to bind to the promoter region of PTEN, inhibiting its expression. Knockdown of HDAC3 suppressed the PI3K/AKT pathway by elevating PTEN expression. Furthermore, apigenin inhibited angiogenesis in DR cell models through the regulating of the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. CONCLUSIONS: Apigenin effectively suppressed angiogenesis in HG-induced HRMECs by modulating the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. Our study may contribute to the development of novel therapeutic approaches and identification of potential targets for the treatment of DR.

Codon Usage Analysis Reveals Distinct Evolutionary Patterns and Host Adaptation Strategies in Duck Hepatitis Virus 1 (DHV-1) Phylogroups.

Duck hepatitis virus 1 (DHV-1) is a major threat to the global poultry industry, causing significant economic losses due to high mortality rates in young ducklings. To better understand the evolution and host adaptation strategies of DHV-1, we conducted a comprehensive codon usage analysis of DHV-1 genomes. Our phylogenetic analysis revealed three well-supported DHV-1 phylogroups (Ia, Ib, and II) with distinct genetic diversity patterns. Comparative analyses of the codon usage bias and dinucleotide abundance uncovered a strong preference for A/U-ended codons and a biased pattern of dinucleotide usage in the DHV-1 genome, with CG dinucleotides being extremely underrepresented. Effective number of codons (ENC) analysis indicated a low codon usage bias in the DHV-1 ORF sequences, suggesting adaptation to host codon usage preferences. PR2 bias, ENC plot, and neutrality analyses revealed that both mutation pressure and natural selection influence the codon usage patterns of DHV-1. Notably, the three DHV-1 phylogroups exhibited distinct evolutionary trends, with phylogroups Ia and Ib showing evidence of neutral evolution accompanied by selective pressure, while the phylogroup II evolution was primarily driven by random genetic drift. Comparative analysis of the codon usage indices (CAI, RCDI, and SiD) among the phylogroups highlighted significant differences between subgroups Ia and Ib, suggesting distinct evolutionary pressures or adaptations influencing their codon usage. These findings contribute to our understanding of DHV-1 evolution and host adaptation, with potential implications for the development of effective control measures and vaccines.

Association of Childhood IgA Vasculitis With Allergic Rhinitis and Chronic Rhinosinusitis.

Introduction: Immunoglobulin A vasculitis (IgAV) is related to chronic inflammation; however, little is known about the associations between IgAV and allergic rhinitis (AR) or chronic rhinosinusitis (CRS). We evaluated the relationships among IgAV, AR, and CRS in children. Methods: The clinical data of children with IgAV who were hospitalized from January to December 2019 were analyzed retrospectively. Four groups were created, the simple AR, simple CRS, AR + CRS, and non-AR or non-CRS groups, to explore the relationships among IgAV, AR, and CRS. Results: We included 504 children with IgAV; and 357 (70.8%) were combined with AR or CRS, including 51 with simple AR, 70 with simple CRS, and 236 with AR + CRS. The incidences of renal involvement and recurrent rash were significantly higher in the simple AR group than in the non-AR or non-CRS group (P < 0.001). The incidences of renal involvement and recurrent rash were significantly higher in the AR + CRS group than in the non-AR or non-CRS group (P < 0.001). The incidences of renal involvement between the simple CRS group and non-AR or non-CRS group did not differ significantly, but that of recurrent rash was significantly higher than that in the other groups (P < 0.001). Age, abdominal pain, recurrent rash, simple AR, and AR combined with CRS were risk factors for renal involvement (all odds ratio [OR] > 1, P < 0.05). Conclusion: Chronic rhinitis may be related to the pathogenesis of IgAV, and AR or CRS may be the triggering factors of IgAV. AR may be a risk factor for renal involvement and recurrent rash in patients with IgAV.

The biomechanical effects of different membrane layer structures and material constitutive modeling on patient-specific cerebral aneurysms.

The prevention, control and treatment of cerebral aneurysm (CA) has become a common concern of human society, and by simulating the biomechanical environment of CA using finite element analysis (FEA), the risk of aneurysm rupture can be predicted and evaluated. The target models of the current study are mainly idealized single-layer linear elastic cerebral aneurysm models, which do not take into account the effects of the vessel wall structure, material constitution, and structure of the real CA model on the mechanical parameters. This study proposes a reconstruction method for patient-specific trilaminar CA structural modeling. Using two-way fluid-structure interaction (FSI), we comparatively analyzed the effects of the differences between linear and hyperelastic materials and three-layer and single-layer membrane structures on various hemodynamic parameters of the CA model. It was found that the numerical effects of the different CA membrane structures and material constitution on the stresses and wall deformations were obvious, but does not affect the change in its distribution pattern and had little effect on the blood flow patterns. For the same material constitution, the stress of the three-layer membrane structure were more than 10.1% larger than that of the single-layer membrane structure. For the same membrane structure, the stress of the hyperelastic material were more than 5.4% larger than that of the linear elastic material, and the displacement of the hyperelastic material is smaller than that of the linear elastic material by about 20%. And the maximum value of stress occurred in the media, and the maximum displacement occurred in the intima. In addition, the upper region of the tumor is the maximum rupture risk region for CA, and the neck of the tumor and the bifurcation of the artery are also the sub-rupture risk regions to focus on. This study can provide data support for the selection of model materials for CA simulation and analysis, as well as a theoretical basis for clinical studies and subsequent research methods.

Molecular genetics of familial nystagmus complicated with cataract and iris anomalies.

PURPOSE: Familial nystagmus complicated with cataract and iris anomalies are genetically heterogeneous, and the pathophysiological mechanisms remain unclear. It is anticipated that mutations in the paired box 6 (PAX6) gene play a major role in pathogenesis of malformations in anterior segment of the eye. In this study, we analyzed PAX6 in a Chinese pedigree of nystagmus, cataract and iris anomalies. This study will provide insights into the genetic basis of this disease. METHODS: Complete ophthalmologic examinations were performed on four patients (excluding one dead patient) and four unaffected individuals in this four-generation family. All coding exons of PAX6 were amplified by polymerase chain reaction (PCR), sequenced and compared with reference database. The variations detected were evaluated in available family members as well as 110 normal controls. Possible changes in structure and function of the protein induced by amino acid variance were predicted by bioinformatics analysis. RESULTS: Nystagmus, cataract or iris anomalies were found in all patients of this family, but the severity was different among these patients. A novel missense mutation in PAX6 was identified in all affected individuals but not in asymptomatic members and 110 normal controls. This mutation causes an amino acid substitution of proline to glutamine at position 118 (p.P118Q) of the paired domain of the PAX6 protein. Such a change may cause structural and functional changes of the protein based on bioinformatics analysis. CONCLUSIONS: This study added a novel mutation to the existing spectrum of PAX6 mutations, suggesting that a mutation in PAX6 correlated with anterior segment disorders observed in this family.

MIAPS: a web-based system for remotely accessing and presenting medical images.

MIAPS (medical image access and presentation system) is a web-based system designed for remotely accessing and presenting DICOM image. MIAPS is accessed with web browser through the Internet. MIAPS provides four features: DICOM image retrieval, maintenance, presentation and output. MIAPS does not intent to replace sophisticated commercial and open source packages, but it provides a web-based solution for teleradiology and medical image sharing. The system has been evaluated by 39 hospitals in China for 10 months.

Arg124Cys mutation of the TGFBI gene in a Chinese pedigree of Reis-Bücklers corneal dystrophy.

AIM: To analyze mutations in transforming growth factor beta-induced (TGFBI) gene in a Chinese pedigree with Reis-Bücklers corneal dystrophy (RBCD, also known as GCD3). METHODS: In a five-generation Chinese family, eight members were identified with RBCD and the rest were unaffected. All members of the family underwent complete ophthalmologic examinations. Exons of TGFBI were amplified by polymerase chain reaction, sequenced, and compared with a reference database. RESULTS: A single heterozygous C>T (R124C) point mutation was found in exon 4 of TGFBI in all the affected members of the pedigree, but not in the unaffected members. CONCLUSION: R124C which was a known mutation for lattice corneal dystrophy type I, segregated with the RBCD in this pedigree. This elucidated the correlation between genotype and phenotype in a Chinese family of RBCD.