Thermally activated delayed fluorescence emitters: a thionation approach toward next-generation photosensitizers.

Achieving highly efficient intersystem crossing (ISC) remains a key focus in the design of heavy atom-free photosensitizers (PSs) for various photophysical and photochemical applications. Herein, we report a general and robust molecular design strategy for obtaining photoactivatable heavy atom-free PSs by performing a simple sulfur substitution of carbonyl oxygen atoms of a thermally activated delayed fluorescence (TADF) emitter. This thionation led to a significant fluorescence loss, resulting in an increased ISC transformation. Upon white-light irradiation, the sulfur-substituted TADF compound (S-AIOH-Cz) exhibited a long-lived fluorescence turn-on response, a long-lasting triplet state lifetime and a superior reactive oxygen species (ROS) generation ability, which is desirable for time-resolved fluorescence imaging and photodynamic disinfection against antimicrobial resistance.

The role of sirt1 in the retinal ganglion cells cultured by high glucose.

OBJECTIVE: To observe the effect of sirt1 on retinal ganglion cells (RGC) with high glucose culture and to explore the role of sirt1 in the development of diabetic retinopathy. Method RGC was infected by sirt1 lentivirus overexpression vector pLV5-sirt1 and interference vector pLV3-si-sirt1. The normal control group and control virus vector group were set up at the same time. After 48 h of infection, the viability of RGC was detected by CCK8 kit, the apoptosis rate was detected by FCM analysis, and the protein expression of p53, FOXO3a, NF-κ B, caspase-3 was detected by Western blot. RESULTS: After RGC were infected with lentivirus, the cell viability of lentivirus overexpression vector pLV5-sirt1 was significantly higher than that of the high glucose group and the sirt1 overexpression control group, while the cell viability of interference vector pLV3-si-sirt1 was significantly lower than that of the high glucose group and the sirt1 interference control group (P < 0.05). At the same time, the apoptosis rate of RGC cells infected by lentivirus overexpression vector pLV5-sirt1 was lower than that of the high glucose group and the control virus vector group, while the apoptosis rate of the interference vector pLV3-si-sirt1 cells was significantly higher than that of the high glucose group and the control virus vector group (P < 0.05). The results of Western blotting showed that the expression of p53, FOXO3a, NF-κ B and caspase-3 in RGC cells decreased significantly after infection with pLV5-sirt1 compared with the high glucose group and the control virus vector group, while the expression of p53, FOXO3a, NF-κB and caspase-3 in RGC cells increased significantly after infection with pLV3-si-sirt1 (P < 0.05). CONCLUSION: Sirt1 can inhibit the apoptosis of RGCs through regulating the expression of some apoptotic cytokinessome, and it can be used as a candidate gene for the biotherapy of retinal diseases.

Activation of Sirtuin1 by lyceum barbarum polysaccharides in protection against diabetic cataract.

ETHNOPHARMACOLOGICAL RELEVANCE: Lycium barbarum polysaccharide (LBP) extracted from the Lycium barbarum L. has been widely used to improve diabetes and its relative complications. However, the mechanisms have not fully understood. A recent study has demonstrated that LBP upregulates suituin 1 (SIRT1). OBJECTIVE: This study was to define the role of Sirt1 and its downstream signaling pathways in diabetic cataract using in vitro and in vivo models. MATERIALS AND METHODS: Human lens epithelial cell line SRA01/04 cells were cultured under high glucose (HG) medium with treatment of LBP or vehicle. Cell viability, apoptosis, protein and/or mRNA levels of Sirt1, BAX, Bcl-2, active-caspase-3, FOXO1, p27 and acetylated p53 were measured. SIRT1 upregulated- and knocked-down cells were generated and tested in high glucose culture. Diabetes mellitus was induced in rats by streptozotocin injection. Body weight, blood glucose levels, lens transparency and retinal function were assessed and SIRT1, as well as the aforementioned biomarkers were measured using Western blotting and qPCR in the animal lens samples. RESULTS: The results showed that HG decreased cell viability and LBP prevented the decrease. The reduced viability in HG cultured SRA01/04 cells was associated with increased levels of BAX, active caspase 3, FOXO1, p27, and p53 and decreased levels of SIRT1 and Bcl-2. Further experiments using sirt1 gene modulated cells showed that upregulation of Sirt1 improved viability, increase cell division as reflected by an increased proportion of S phase in the cell cycle, reduced the number of apoptotic cell death and suppressed p53 acetylation and caspase 3 activation. Opposite results were observed in SIRT1 knock-down cells. Treating diabetic animals with LBP reduced body weight loss and blood glucose content in diabetic animals. Similarly, LBP hindered the development of cataract in lenses and improved retinal function. The beneficial effect of LBP on diabetic cataract was associated with the supression of p53, caspase 3, FOXO1, BAX, p27 and elevation of SIRT1 and Bcl-2, which were consistent with the in vitro findings. CONCLUSION: Our findings showed that diabetes caused cataract is associated with suppression of SIRT1 and Bcl-2 and activation of other cell death related genes. LBP prevented diabetic cataract in animals by upregulating Sirt1 and Bcl-2 and suppressing cell death related genes.