Protective effects of nattokinase against microvasculopathy and neuroinflammation in diabetic retinopathy.

AIMS: Diabetic retinopathy (DR) is a significant global public health concern. Alternative, safe, and cost-effective pharmacologic approaches are warranted. We aimed to investigate the therapeutic potential of nattokinase (NK) for early DR and the underlying molecular mechanism. METHODS: A mouse model of diabetes induced by streptozotocin was utilized and NK was administered via intravitreal injection. Microvascular abnormities were evaluated by examining the leakage from blood-retinal barrier dysfunction and loss of pericytes. Retinal neuroinflammation was examined through the assessment of glial activation and leukostasis. The level of high mobility group box 1 (HMGB1) and its downstream signaling molecules was evaluated following NK treatment. RESULTS: NK administration significantly improved the blood-retinal barrier function and rescued pericyte loss in the diabetic retinas. Additionally, NK treatment inhibited diabetes-induced gliosis and inflammatory response and protected retinal neurons from diabetes-induced injury. NK also improved high glucose-induced dysfunction in cultured human retinal micrangium endothelial cells. Mechanistically, NK regulated diabetes-induced inflammation partially by modulating HMGB1 signaling in the activated microglia. CONCLUSIONS: This study demonstrated the protective effects of NK against microvascular damages and neuroinflammation in the streptozotocin-induced DR model, suggesting that NK could be a potential pharmaceutical agent for the treatment of DR.

RIP3-mediated microglial necroptosis promotes neuroinflammation and neurodegeneration in the early stages of diabetic retinopathy.

Diabetic retinopathy (DR) is a leading cause of blindness that poses significant public health concerns worldwide. Increasing evidence suggests that neuroinflammation plays a key role in the early stages of DR. Microglia, long-lived immune cells in the central nervous system, can become activated in response to pathological insults and contribute to retinal neuroinflammation. However, the molecular mechanisms of microglial activation during the early stages of DR are not fully understood. In this study, we used in vivo and in vitro assays to investigate the role of microglial activation in the early pathogenesis of DR. We found that activated microglia triggered an inflammatory cascade through a process called necroptosis, a newly discovered pathway of regulated cell death. In the diabetic retina, key components of the necroptotic machinery, including RIP1, RIP3, and MLKL, were highly expressed and mainly localized in activated microglia. Knockdown of RIP3 in DR mice reduced microglial necroptosis and decreased pro-inflammatory cytokines. Additionally, blocking necroptosis with the specific inhibitor GSK-872 improved retinal neuroinflammation and neurodegeneration, as well as visual function in diabetic mice. RIP3-mediated necroptosis was activated and contributed to inflammation in BV2 microglia under hyperglycaemic conditions. Our data demonstrate the importance of microglial necroptosis in retinal neuroinflammation related to diabetes and suggest that targeting necroptosis in microglia may be a promising therapeutic strategy for the early stages of DR.

Mediating Effect of Sleep Quality on the Relationship Between Electronic Screen Media Use and Academic Performance Among College Students.

OBJECTIVE: We aimed to examine the effects of sleep quality on the association between pre-bedtime electronic screen media use for entertainment and academic performance among college students. We hypothesized that sleep quality mediates the association between pre-bedtime electronic screen media entertainment use and academic performance among college students. METHODS: This was a cross-sectional survey with 1385 participants (age 19.99 ± 1.4 years [range, 17-24 years] and 36.82% males) conducted at Shantou University. The levels of academic performance were based on self-reported academic class ranking from average grades of their last final major examinations. Poor sleep quality was defined as a total score of the Pittsburgh Sleep Quality Index >7. The pre-bedtime prolonged electronic screen media use for entertainment (PESM-E) was defined as the use of electronic screen media for entertainment longer than 60 minutes/night after 10:00 p.m. during the past 6 months. RESULTS: College students with pre-bedtime PESM-E were 1.28-fold more likely to have a poor academic performance than those who used electronic screen media less than 60 minutes (95% confidence interval [CI]: 1.04-1.57, P=0.020). Furthermore, pre-bedtime PESM-E was significantly associated with poor sleep quality (adjusted odds ratio [AOR]=1.87, 95% CI: 1.27-2.74, P=0.001) after controlling for confounders. Mediation model showed that poor sleep quality accounted for 53.08% of the effect of pre-bedtime PESM-E on lower levels of academic performance (Sobel Z=2.04, P=0.041). CONCLUSION: Pre-bedtime PESM-E is associated with poor academic performance in college students, and this association is mediated by poor sleep quality. Our findings highlight the importance of limiting the use of electronic screen media before bedtime in college students.

Design of chemically defined synthetic substrate surfaces for the in vitro maintenance of human pluripotent stem cells: A review.

Human pluripotent stem cells (hPSCs) have the potential of long-term self-renewal and differentiation into nearly all cell types in vitro. Prior to the downstream applications, the design of chemically defined synthetic substrates for the large-scale proliferation of quality-controlled hPSCs is critical. Although great achievements have been made, Matrigel and recombinant proteins are still widely used in the fundamental research and clinical applications. Therefore, much effort is still needed to improve the performance of synthetic substrates in the culture of hPSCs, realizing their commercial applications. In this review, we summarized the design of reported synthetic substrates and especially their limitations in terms of cell culture. Moreover, much attention was paid to the development of promising peptide displaying surfaces. Besides, the biophysical regulation of synthetic substrate surfaces as well as the three-dimensional culture systems were described.