We determine the angiopoietin 2 (ANGPT2) gene as a new susceptibility gene for neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV).
A total of 34 ...haplotype-tagging single-nucleotide polymorphisms (SNPs) were first genotyped in an exploratory Hong Kong Chinese cohort. Suggestive SNPs were replicated in a Shantou Chinese cohort and an Osaka Japanese cohort, with a total of 2343 subjects. The SNP rs800292 in the complement factor H (CFH) gene was genotyped in all the subjects. Genetic association and gene-gene interaction were analyzed.
In the Hong Kong cohort, four SNPs in ANGPT2 (rs13255574, rs4455855, rs13269021, and rs11775442) were nominally associated with nAMD and PCV. The four ANGPT2 SNPs showed the same trends of association in the Shantou and Osaka cohorts. Combining the data from the 3 study cohorts revealed that SNPs rs4455855 and rs13269021 achieved study-wise significance (P < 0.0016), conferring an approximately 1.3-fold of increased risk for nAMD and PCV. Interaction analysis revealed the CFH SNP rs800292 has a highly significant interaction with the ANGPT2 SNP rs13269021 in nAMD and PCV in the combined analysis. Subsequent stratification analysis confirmed the interaction.
This study reveals ANGPT2 as a new susceptibility gene for nAMD and PCV, and it may affect disease susceptibility in association with CFH. Thus, this report provides new insights into the genetic architecture of nAMD and PCV.
Previously, we identified RAD21
from a peripheral sclerocornea pedigree. Injection of this
variant mRNA into
embryos disrupted the organization of corneal stroma fibrils. To understand the mechanisms ...of RAD21-mediated corneal stroma defects, gene expression and chromosome conformation analysis were performed using cells from family members affected by peripheral sclerocornea. Both gene expression and chromosome conformation of cell adhesion genes were affected in cells carrying the heterozygous
variant. Since cell migration is essential in early embryonic development and sclerocornea is a congenital disease, we studied neural crest migration during cornea development in
embryos. In
embryos injected with
mutant mRNA, neural crest migration was disrupted, and the number of neural crest-derived periocular mesenchymes decreased significantly in the corneal stroma region. Our data indicate that the RAD21
variant contributes to peripheral sclerocornea by modifying chromosome conformation and gene expression, therefore disturbing neural crest cell migration, which suggests RAD21 plays a key role in corneal stroma development.
This case report illustrates the presence of intranodal thyroid tissues in ipsilateral cervical lymph nodes after hemithyroidectomy for multinodular goiter in an adolescent patient. It highlights the ...rare radiological finding of thyroid tissues within cervical lymph nodes detected by ultrasonography and computed tomography, which is a great mimicker of nodal metastasis.
Osteoporosis is a systemic skeletal disease where there is low bone mass and deterioration of bone microarchitecture, leading to an increased risk of a fragility fracture. The aim of this clinical ...guideline from Fragility Fracture Network Hong Kong SAR, is to provide evidence-based recommendations on the post-acute treatment of the osteoporotic fracture patient that presents for clinical care at the Fracture Liaison Service (FLS). It is now well established that the incidence of a second fracture is especially high after the first 2 years of the initial osteoporotic fracture. Therefore, the recent osteoporotic fracture should be categorized as “very-high” re-fracture risk. Due to the significant number of silent vertebral fractures in the elderly population, it is also recommended that vertebral fracture assessment (VFA) should be incorporated into FLS. This would have diagnostic and treatment implications for the osteoporotic fracture patient. The use of a potent anti-osteoporotic agent, and preferably an anabolic followed by an anti-resorptive agent should be considered, as larger improvements in BMD is strongly associated with a reduction in fractures. Managing other risk factors including falls and sarcopenia are imperative during rehabilitation and prevention of another fracture. Although of low incidence, one should remain vigilant of the atypical femoral fracture. The aging population is increasing worldwide, and it is expected that the treatment of osteoporotic fractures will be routine. The recommendations are anticipated to aid in the daily clinical practice for clinicians.
Fragility fractures have become a common encounter in clinical practise in the hospital setting. This article provides recommendations on the post-acute management of fragility fracture patients at the FLS.
The cornea and sclera are distinct adjacent tissues, yet their stromal cells originate from common neural crest cells (NCCs). Sclerocornea is a disease characterized by an indistinguishable boundary ...between the cornea and sclera. Previously, we identified a RAD21 mutation in a sclerocornea pedigree. Here, we investigated the impacts of RAD21 on NCC activities during eye development. RAD21 deficiency caused upregulation of PCDHGC3. Both RAD21 knockdown and PCDHGC3 upregulation disrupted the migration of NCCs. Transcriptome analysis indicated that WNT9B had 190.9-fold higher expression in scleral stroma than in corneal stroma. WNT9B was also significantly upregulated by both RAD21 knockdown and PCDHGC3 overexpression, and knock down of WNT9B rescued the differentiation and migration of NCCs with RAD21 deficiency. Consistently, overexpressing wnt9b in Xenopus tropicalis led to ocular developmental abnormalities. In summary, WNT9B is a determinant factor during NCC differentiation into corneal keratocytes or scleral stromal cells and is affected by RAD21 expression.
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•Established a stable differentiation protocol from hESCs to corneal keratocytes•RAD21 deficiency affected the proliferation and migration ability of NCCs•Increased scleral markers after RAD21 knockdown during NCC differentiation to cornea•WNT9B is a crucial mediator during ocular NCC differentiation
Cell biology; Developmental biology
Purpose: To test the psychometric properties of the International Prostate Symptom Score (Hong Kong Chinese version 2) (IPSS) in Chinese male patients with benign prostatic hyperplasia (BPH) under ...secondary care.
Methods: A prospective longitudinal study was done by interviewing subjects at baseline, at 2 week after baseline for assessing test-retest reliability and at 26 week after baseline for assessing responsiveness. All subjects were interviewed to complete a structured questionnaire including IPSS, Short Form-12 Health Survey version 2 (SF-12v2) and Depression Anxiety Stress Scale (DASS).
Results: The IPSS HRQOL score had weak correlations with SF-12v2 summary and DASS domain scores. For reliability analysis, Cronbach's alpha coefficient was 0.90 for the seven symptom-related items. The intraclass correlation coefficients of the IPSS total symptom score and HRQOL score were 0.90 and 0.86, respectively. For sensitivity, statistically significant differences were detected between the subjects with BPH and those without for IPSS total symptom score (effect size = 0.68) but not the IPSS HRQOL score. The areas under ROC curves for the IPSS total symptom and HRQOL scores were 0.67 and 0.60, respectively.
Conclusions: The IPSS was valid, reliable instrument in Chinese patients with BPH. The IPSS total symptom score, but not the HRQOL score, is sensitive in differentiating subgroups.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Predominant loss of neutral CO2 has been observed under conditions of low-energy collision-induced dissociation from a prototypical molecular radical cation of the tripeptide aspartylglycylarginine ...(DGR+). The decarboxylation occurs mainly from the side chain of the aspartic acid residue and partially from the C-terminal carboxyl group. The structural and mechanistic features that facilitate CO2 loss from the Asp side chain of DGR+ and its chemically modified analogs incorporating methylation have been elucidated using a combination of Rice–Ramsperger–Kassel–Marcus modeling and density functional theory at the B3LYP/6-31++G(d,p) level. Current mechanistic investigations suggest that the loss of CO2 from the side chain of the aspartic acid residue involves hydrogen atom transfer from its carboxyl oxygen atom in conjunction with α-centered radical transfer to the β-centered radical on the aspartic acid side chain. Minor CO2 loss from the C-terminal carboxyl group occurs through the DGαR+ isomer, with the radical migrating to the α-carbon of the middle Gly residue. Barriers against the CO2 loss from the side chain of the aspartic acid residue and from the C-terminus of DGαR+ are approximately 30 and 36kcalmol−1, respectively.
Ocular inflammation is a common complication of various eye diseases with wide consequences from irritations to potentially sight-threatening complications. Green tea is a popular beverage throughout ...the world. One of the proven health benefits of consuming green tea extract (GTE) is anti-inflammation. Catechins are the biologically active constituents of GTE. In
and
studies, GTE and catechins present inhibition of inflammatory responses in the development of ocular inflammation including infectious, non-infectious or autoimmune, and oxidative-induced complications. Research on the ocular inflammation in animal models has made significant progress in the past decades and several key disease mechanisms have been identified. Here we review the experimental investigations on the effects of GTE and catechins on various ocular inflammation related diseases including glaucoma, age-related macular degeneration, uveitis and ocular surface inflammation. We also review the pharmacokinetics of GTE constituents and safety of green tea consumption. We discuss the insights and perspectives of these experimental results, which would be useful for future development of novel therapeutics in human.
The molecular events occurring following the disruption of DNA replication forks are poorly characterized, despite extensive use of replication inhibitors such as hydroxyurea in the treatment of ...malignancies. Here, we identify a key role for the FBH1 helicase in mediating DNA double-strand break formation following replication inhibition. We show that FBH1-deficient cells are resistant to killing by hydroxyurea, and exhibit impaired activation of the pro-apoptotic factor p53, consistent with decreased DNA double-strand break formation. Similar findings were obtained in murine ES cells carrying disrupted alleles of Fbh1. We also show that FBH1 through its helicase activity co-operates with the MUS81 nuclease in promoting the endonucleolytic DNA cleavage following prolonged replication stress. Accordingly, MUS81 and EME1-depleted cells show increased resistance to the cytotoxic effects of replication stress. Our data suggest that FBH1 helicase activity is required to eliminate cells with excessive replication stress through the generation of MUS81-induced DNA double-strand breaks.
•We identified flavonols as an ideal scaffold for FABP4 inhibitors development.•Hyperoside has been identified as a promising FABP4 inhibitor.•Hyperoside promoted adipogenesis in adipocytes via the ...FABP4/PPARγ pathway.
The inhibition of fatty acid binding protein 4 (FABP4) by using small molecules could potentially provide therapeutic opportunities for metabolic disorders treatment. According to the results of our in-house virtual screening on the herbal molecules database, this study reports flavonols as an ideal scaffold for FABP4 inhibitors development. Among the popular flavonols examined, we identified hyperoside as a promising FABP4 inhibitor. Identical to the well-known FABP4 inhibitor BMS309403, hyperoside induced lipid accumulation and upregulated peroxisome proliferator-activated receptor γ (PPARγ) protein expression during the adipocyte differentiation process. Furthermore, both PPARγ antagonist and FABP4 overexpression attenuated hyperoside-induced adipogenesis, indicating that hyperoside promoted adipogenesis in adipocytes via the FABP4/PPARγ pathway. We anticipate hyperoside to be a promising, novel FABP4 inhibitor for antidiabetic drug development.
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