Assessment of retinal neurodegeneration with spectral-domain optical coherence tomography: a systematic review and meta-analysis.

OBJECTIVES: To comprehensively assess diabetic retinopathy neurodegeneration (DRN) as quantified by retinal neuronal and axonal layers measured with spectral-domain optical coherence tomography (SD-OCT) in subjects with diabetes mellitus (DM). METHODS: Articles on the topic of examining macular ganglion cell-inner plexiform layer (m-GCIPL), macular retinal nerve fibre layer (m-RNFL), macular ganglion cell complex (m-GCC), and peripapillary RNFL (p-RNFL) measured with SD-OCT in DM subjects without DR (NDR) or with non-proliferative DR (NPDR) were searched in PubMed and Embase up to November 31, 2019. Standardized mean difference (SMD) as effect size were pooled using random-effects model. RESULTS: Thirty-six studies searched from online databases and the CUHK DM cohort were included in the meta-analysis. In the comparison between NDR and control, macular measures including mean m-GCIPL (SMD = -0.26, p = 0.003), m-RNFL (SMD = -0.26, p = 0.046), and m-GCC (SMD = -0.28; p = 0.009) were significantly thinner in the NDR group. In the comparison between NPDR and NDR, only mean p-RNFL was significantly thinner in the NPDR group (SMD = -0.27; p = 0.03), but not other macular measures. CONCLUSIONS: Thinning of retinal neuronal and axonal layers at macula as measured by SD-OCT are presented in eyes with NDR, supporting DRN may be the early pathogenesis in the DM patients without the presence of clinical signs of DR. In the future, these SD-OCT measures may be used as surrogates of DRN to stratify DM patients with a high risk of DR, and may be used as a therapeutic target if neuroprotection treatment for DR is available.

2,3,7,8-Tetrachlorodibenzo-para-dioxin increases aromatase (CYP19) mRNA stability in MCF-7 cells.

Dioxins are industrial pollutants that can be bio-accumulative in our food chain. Humans can be exposed to this class of pollutant through contaminated food, air, drinking water, etc. Displaying both pro- and anti-estrogenic properties, these pollutants are also known as endocrine disruptors. The link between breast cancer and TCDD exposure has not been resolved, although TCDD is classified as 'known human carcinogen'. Estrogen is a documented risk factor for breast carcinogenesis. In the present study, effect of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) on estrogen synthesis was investigated in the breast cancer cells MCF-7. Our results showed that TCDD increased the aromatase activity in a time- and dose-dependent manner. Real-time PCR and western blot analysis verified the induced expression by 2-3-fold; however, gene reporter assay revealed that the promoter activity of exons I.3 and II was not elevated. Further investigation indicated that TCDD slowed down the CYP19 mRNA degradation with concurrent activation of ERK. The ERK inhibitor U0126 could reverse the extended stability of the transcripts. In summary this study demonstrated that TCDD might induce a post-transcriptional regulatory mechanism of gene expression in breast cancer cells.

Oestrogen receptor alpha is required for biochanin A-induced apolipoprotein A-1 mRNA expression in HepG2 cells.

Epidemiological studies have indicated that soya consumption may produce a better plasma lipid profile. The effect may be attributed to the phyto-oestrogens in soya. The red clover (Trifolium pratense) isoflavone biochanin A has a chemical structure similar to those phyto-oestrogens found in soya beans, and is marketed as a nutraceutical for alleviating postmenopausal symptoms. In the present study we investigated the effect of biochanin A on the mRNA expression of ApoA-1 in the hepatic cell line HepG2. Real-time PCR revealed that biochanin A increased ApoA-1 mRNA abundance in cells expressing oestrogen receptor (ER) alpha. Without ERalpha transfection, biochanin A had no effect on mRNA abundance. In order to study the transcriptional control, a fragment of the 5'-flanking region of the ApoA-1 gene was amplified and inserted in a firefly luciferase reporter plasmid. The reporter assay indicated that the transactivation of the ApoA-1 promoter was induced by biochanin A in HepG2 cells transfected with the ERalpha expression plasmid. This induction was reduced by the anti-oestrogen ICI 182,780, whereas the inhibitors of protein kinase (PK) C, PKA, or mitogen-activated kinase (ERK) had no suppressive effect. The present study illustrated that biochanin A might up regulate hepatic apoA-1 mRNA expression through an ER-dependent pathway.