Objective:To observe the effects of SARS-CoV-2 infection on the morphology, proliferation, apoptosis, cell cycle, and immune response function of mouse retinal photoreceptor cells (661w cells).Methods:A cell experiment. Logarithmic growth phase 661w cells were cultured in vitro and transfected with angiotensin-converting enzyme 2 (ACE2) overexpressing lentivirus to construct ACE2 overexpressing 661w cells that could be infected with SARS-CoV-2 pseudovirus (hereafter referred to as 'pseudovirus’). The 661w cells were divided into three groups: the normal group (untreated), the siACE2 group (overexpressing ACE2 and not infected with the pseudovirus) and the infected group (overexpressing ACE2 and infected with the pseudovirus), in which the infected group was 5 TU/ml pseudovirus group, 15 TU/ml pseudovirus group, 30 TU/ml pseudovirus group and 50 TU/ml pseudovirus group, and the cells were infected with the pseudovirus for 12, 24, 48 and 72 h, respectively. The infected group was infected with 5 TU/ml pseudovirus group, 15 TU/ml pseudovirus group, 30 TU/ml pseudovirus group and 50 TU/ml pseudovirus group, respectively, for 12, 24, 48 and 72 h. Fluorescence microscopy was used to observe the transfection efficiency of ACE2; protein immunoblotting (Western blot) was used to detect the relative expression level of ACE2 in the cells; light microscope was used to observe the morphology of the cells in the normal and the infected groups; cell proliferation was detected by Cell Counting Kit-8 (CCK8) assay; flow cytometry was used to detect the cell cycle; Western blot and real-time quantitative polymerase chain reaction (qPCR) were used to detect the relative expression of interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), B lymphocytoma-2 (Bcl-2), Bcl-2-associated X-protein (Bax) proteins and mRNA in the cells of siACE2 group, infected group (30 TU/ml pseudovirus group); qPCR was used to detect the relative expression of nuclear factor ( NF)- κB1 and NF-κB2, as well as NF- kB enhancer ( P65) and precursor protein ( P100) in cells of the siACE2 group and the infected group (30 TU/ml pseudovirus group). One-way ANOVA was used for comparison between multiple groups; t-test was used for comparison between two groups. Results:Compared with the siACE2 group, the cells in the infected group showed different degrees of crumpling, and with the increase of the concentration and time of pseudovirus induction, the crumpling of the cells worsened, and the number of cells decreased. Compared with the normal group, the cells in the infected group showed a gradual decrease in cell viability with the prolongation of pseudovirus induction time, and the difference was no statistically significant ( F=0.840, 0.412, 1.498, 1.138; P>0.05), and the apoptotic index of the cells induced in the 30 and 50 TU/ml pseudovirus group was significantly elevated, and the difference was statistically significant ( F=2.523, 6.716, 3.477, 3.421; P<0.05). At 72 h of pseudovirus induction, compared with the siACE2 group, the G1 phase cells in the 30 TU/ml pseudovirus group were significantly increased, and the difference was statistically significant ( t=3.812, P<0.05); the relative expression of IL-6, TNF-α, Bax protein and mRNA in the cells was up-regulated ( t=7.601, 6.039, 3.088, 5.193, 6.427, 7.667; P<0.05), the relative expression of Bcl-2 protein and mRNA was down-regulated ( t=3.614, 6.777; P<0.05), and the relative expression of NF-κB1, NF-κB2, P65, and P100 mRNA was significantly up-regulated with statistically significant differences ( t=3.550, 3.074, 3.307, 4.218; P<0.05). Conclusion:SARS-CoV-2 infection may inhibit photoreceptor cell proliferation, promote apoptosis and cycle blockade by activating the NF-κB signalling pathway.

Despite being a common therapy for hepatocellular carcinoma (HCC), insufficient thermal ablation can leave behind tumor residues that can cause recurrence. This is believed to augment M2 inflammatory macrophages that usually play a pro-tumorigenic role. To address this problem, we designed d-mannose-chelated iron oxide nanoparticles (man-IONPs) to polarize M2-like macrophages into the antitumor M1 phenotype. In vitro and in vivo experiments demonstrated that man-IONPs specifically targeted M2-like macrophages and accumulated in peri-ablation zones after macrophage infiltration was augmented under insufficient microwave ablation (MWA). The nanoparticles simultaneously induced polarization of pro-tumorigenic M2 macrophages into antitumor M1 phenotypes, enabling the transformation of the immunosuppressive microenvironment into an immunoactivating one. Post-MWA macrophage polarization exerted robust inhibitory effects on HCC progression in a well-established orthotopic liver cancer mouse model. Thus, combining thermal ablation with man-IONPs can salvage residual tumors after insufficient MWA. These results have strong potential for clinical translation.

AIM: To investigate the preventive effect and optimal drug dose of lipoic acid-niacin(N2L)against blue light-induced retinal damage in SD rats, and to explore its possible protective mechanism.METHODS: A total of 36 specific pathogen free-grade male SD rats of 150-200 g were selected and randomly divided into normal control group, blue light injury group, N2L low-dose group(1.0 mg/kg), N2L medium-dose group(2.5 mg/kg), N2L high-dose group(5.0 mg/kg), and physiological saline group, with 6 rats in each group. The normal control group was reared in a 12 h dark and light cycle, and the rest of the groups received 9 h of daily light exposure, 3 h of blue light irradiation with a wavelength of 455 nm and an intensity of 3000±50 lx, and 12 h of darkness to establish the injury model, and were exposed to light exposure for 14 d. For 14 consecutive durations, a 1 mL dose of the corresponding drug was injected intraperitoneally. The rats were reared for another 5 d with a regular 12 h light-dark cycle and were examined by electroretinography. Specimens were prepared by over anesthesia, HE staining, and the thickness of the outer nuclear layer was observed under a optical microscope; superoxide dismutases(SOD)activity was detected by CheKineTM SOD Activity Assay Kit; and the retinal Caspase-3, quinone oxidoreductase 1(NQO1), glutathione S transferase(GST), Bcl-2, and Bax protein expression in rat retina were detected by Western blot.RESULTS: The amplitude of b-wave in dark-vision ERG 3.0 and 10.0(cd·s)/m2 stimulated light, b-wave in bright-vision ERG 3.0(cd·s)/m2 stimulated light, and the amplitude of the 2nd wave peak of oscillatory potential were significantly lower in blue light injury group than that in the normal control group(all P<0.01), while the amplitude was significantly higher in the N2L medium-dose group than in the blue light injury group(all P<0.05), and was not statistically different from that of the normal control group; the thickness of the retina in the blue light injury group was decreased in the ONL compared with that of the normal control group(P<0.001), while in the N2L medium dose group, it was thicker than that of the blue light injury group(P<0.001), and there was no statistically significant difference from the normal control group; SOD activity was significantly higher in the N2L medium-dose group than in the remaining 5 groups(P<0.05); the expression of Caspase-3, Bax, and NQO1 in the blue light injury group was higher than that of the normal control group(all P<0.01), and expression of Bax and Caspase-3 was significantly lower in the N2L medium-dose group compared with the blue light injury group(all P<0.001), whereas GST, NQO1 and Bcl-2 were significantly increased(all P<0.01).CONCLUSION:A concentration of 2.5 mg/kg N2L can effectively antagonize the damaging effect of blue light on the retina of SD rats, and it is expected to be a preventive and curative drug for it.