Search

Recent studies on biphenyl-containing compounds, a type of PD-1/PD-L1 blocker which binds to PD-L1 and induces dimerisation, have focussed on its immune function. Herein, 10 novel biphenyl derivatives were designed and synthesised. The results of the CCK-8 showed that compounds have different anti-tumour activities for tumour cells in the absence of T cells. Particularly, 12j–4 can significantly induce the apoptosis of MDA-MB-231 cells (IC50 = 2.68 ± 0.27 μM). In further studies, 12j–4 has been shown to prevent the phosphorylation of AKT by binding to cytoplasmic PD-L1, which induces apoptosis in MDA-MB-231 cells through non-immune pathways. The inhibition of AKT phosphorylation restores the activity of GSK-3β, ultimately resulting in the degradation of PD-L1. Besides, in vivo study indicated that 12j–4 repressed tumour growth in nude mice. As these biphenyls exert their anti-tumour effects mainly through non-immune pathways, they are worthy of further study as PD-L1 inhibitors.

AIM: To observe and compare the changes of foveal retinal and choroidal thickness in patients with pregnancy-induced hypertension(PIH)by enhanced depth imaging optical coherence tomography(EDI-OCT). METHODS: Totally 150 patients(289 eyes)diagnosed with pregnancy-induced hypertension were identified by fundus examination and EDI-OCT after mydriasis. The patients were divided into four groups for the Duke-Elder class: P1(vasospasm), P2(angiosclerosis), P3(retinopathy), and control group P0(normal fundus). The average retinal nerve fiber layer thickness in each quadrant, foveal retinal and choroidal thickness were measured by EDI-OCT respectively. RESULTS: There were 36(72 eyes, 24.9%)of 150 women with pregnancy-induced hypertension had no retinal changes, and 114(217 eyes, 75.1%)of 150 cases identified by clinical examinations as having retinal findings. The retinal and choroidal thickness varied with different stages of fundus changes. The RNFL thickness of central subfield(CSF), the foveal retina and choroid were significantly higher in angiosclerosis stage than that in normal fundus group(PPCONCLUSION: EDI-OCT is one important tool for the study of fundus changes in PIH. Findings in the morphology changes of retina and choroid with the help of EDI-OCT may indicate more about retinal microcirculation changes caused by pregnancy-induced hypertension in depth.

AIM: To assess the morphological features, classification, and contrastive analysis between the features of optical coherence tomography(OCT)and fundus fluorescein angiography(FFA)in clinically high myopic maculopathy. METHODS: Totally 61 patients(101 eyes)with clinically high myopic maculopathy. Distant vision was examined through E Standard Logarithm Eyesight Table. Integrated optometry to determine the dioptre and best corrected visual acuity(BCVA). Axial length(AL)measurements obtained through IOL-Master. Fundus examinations performed in patients with high myopia after pupil dilation. OCT and FFA were done separately in each case of myopic maculopathy on the same day. FFA and indocyanine green angiogrsphy(FFA& ICGA)was done if need be. The correlation between FFA types and OCT types were analyzed, and their associations with dioptre, BCVA, AL and central foveal thickness were evaluated. RESULTS: The prevalence of lacquer crack type was higher in the OCT type 1(57.14%)than in the choroidal neovascularization(CNV)type and macular atrophy type(21.43%)of fluorescein angiography, the difference was statistically significant(PPPPPCONCLUSION: There was a significant correlation between the features of OCT and FFA in high myopicmaculopathy. The analysis of clinically high myopic maculopathy based on combination of OCT and FFA can provide information that may be useful to make sure the nature of high myopia, disclose the pathogenesis and to optimize the treatment for each type.

OBJECTIVE:   Many studies have linked cytokine interleukin-1B gene polymorphisms to H. pylori-related gastric cancer development. The current study evaluated the characterization of whole genomic expression profiles of the premalignant condition: H. pylori-related chronic atrophic gastritis (CAG) with IL-1B-31CC/-511TT genotypes. METHODS: IL-1B-31/-511 gene polymorphisms were determined by DNA sequences. RNA was extracted and expression profiles were performed using Agilent human whole genomic oligonucleotide microarrays (G4112F). The expression of three samples with H. pylori infection was compared to that of three samples without H. pylori infection from samples of six CAG patients, all with IL-1B-31CC/-511TT genotypes. Differentially expressed genes related to H. pylori-induced CAG with IL-1B-31CC/-511TT genotypes were screened and analyzed further by Gene Ontology (GO) and pathway. Validation of the microarray data was performed using qRT-PCR. RESULTS: A total of 124 differentially expressed genes and 32 GO term annotations were identified between H. pylori positive and negative groups in the six CAG samples with IL-1B-31CC/-511TT genotypes. The signaling pathways identified were oxidative phosphorylation and epithelial cell signaling in H. pylori infection. Five overlapping genes were contained in identified GO terms and pathways: ATP6V0B, NDUFS5, NDUFV2, ATP6V1F and ATP6V1G1. Comparisons of qRT-PCR data and the previously reported data with the results of gene chips support the validity of our microarray data. CONCLUSION: The H. pylori-related CAG with IL-1B-31CC/-511TT genotypes has shown to be the more malignant phenotype than H. pylori negative CAG with IL-1B-31CC/-511TT genotypes. Mitochondrial energy metabolism probably plays a crucial role as it is the molecular mechanism of host–bacterial interactions. [ABSTRACT FROM AUTHOR]