Urolithin A ameliorates diabetic retinopathy via activation of the Nrf2/HO-1 pathway.

Diabetic retinopathy (DR) is a progressive microvascular complication of diabetes mellitus and is characterised by excessive inflammation and oxidative stress. Urolithin A (UA), a major metabolite of ellagic acid, exerts anti-inflammatory and antioxidant functions in various human diseases. This study, for the first time, uncovered the role of UA in DR pathogenesis. Streptozotocin-induced diabetic rats were used to determine the effects of UA on blood glucose levels, retinal structures, inflammation, and oxidative stress. High glucose (HG)-induced human retinal endothelial cells (HRECs) were used to elucidate the anti-inflammatory and antioxidant mechanisms of UA in DR in vitro. The in vivo experiments demonstrated that UA injection reduced blood glucose levels, decreased albumin and vascular endothelial growth factor concentrations, and ameliorated the injured retinal structures caused by DR. UA administration also inhibited inflammation and oxidative damage in the retinal tissues of diabetic rats. Similar anti-inflammatory and antioxidant effects of UA were observed in HRECs induced by HG. Furthermore, we found that UA elevated the levels of nuclear Nrf2 and HO-1 both in vivo and in vitro. Nrf2 silencing reversed the inhibitory effects of UA on inflammation and oxidative stress during DR progression. Together, our findings indicate that UA can ameliorate DR by repressing inflammation and oxidative stress via the Nrf2/HO-1 pathway, which suggests that UA could be an effective drug for clinical DR treatment.

Extracellular vesicles secreted from mesenchymal stem cells exert anti-apoptotic and anti-inflammatory effects via transmitting microRNA-18b in rats with diabetic retinopathy.

Diabetic retinopathy (DR) is a major cause of visual deficits and blindness in the working-age population and inflammatory response is a key event during DR. In this study, we investigated the anti-inflammatory properties of small extracellular vesicles (sEVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) in a diabetic rat model and human retinal microvascular endothelial cells. After development of DR in rats subjected to diabetes induction with streptozotocin (STZ), the DR rats were treated with different concentrations of hUCMSC-sEVs. Our results showed that the treatment of the retinas of DR rats with hUCMSC-sEVs not only reduced the level of vascular leakage in the retinas of rats but also decreased the retinal thickness as well as the associated inflammation. Further, our in vitro evidences suggest that hUCMSC-sEVs repress high glucose (HG)-induced cell inflammation and apoptosis. Subsequently, we analyzed the differentially expressed microRNAs (miRNAs) in the hUCMSC-sEVs by microarray and performed in silico studies to predict the target mRNA of miR-18b. Our findings also revealed that the expression of miR-18b was significantly elevated in the retina of diabetic rats after sEV treatment. In addition, miR-18b was found to target mitogen-activated protein kinase kinase kinase 1 (MAP3K1), thereby inhibiting NF-κB p65 phosphorylation to alleviate DR. Overall, this study highlights the potential of hUCMSCs-sEVs as biomaterials for anti-inflammatory and anti-apoptotic effects in DR by transferring miR-18b.

Correlation Between the Triglyceride-Glucose Index and High Risk of Cardiovascular Disease: A Cohort Study of 102,061 Subjects from Tianjin, China.

OBJECTIVE: This study aims to investigate the correlation between triglyceride-glucose index (TyG) and the risk of cardiovascular disease (CVD). METHODS: A total of 102,061 permanent residents of Tianjin, China, aged 35-75 years were surveyed. A questionnaire, physical examination, and blood tests for biochemical markers were conducted for all subjects. The risk of CVD was judged based on the results, identifying the population with a high risk of CVD. TyG was calculated for all subjects who were then grouped into TyG quartiles. The correlation between TyG and the detection rate of subjects with a high risk of CVD was analyzed using the chi-square test and Pearson's correlation analysis. The cut-off points and the magnitude of the predictive effect of TyG in determining a high risk of CVD were identified by calculating the TyG through analysis of the receiver operator characteristic (ROC) curve. RESULTS: The surveyed population consisted of 39,598 males (38.8%) and 62,463 females (61.2%). The average age was 55.84 ± 10.27 years. A statistically significant difference in the incidence of a high CVD risk between subjects in the four groups divided by the TyG levels was identified (p < 0.01). Pearson's correlation analysis showed that TyG was correlated with all risk factors for CVD (p < 0.01). The maximum Youden's J statistic for determining the high risk of CVD was found at a TyG of 9.04 (specificity 0.575, sensitivity 0.754). The area under the ROC curve was 0.780 (confidence interval [CI]: 0.777, 0.783, p < 0.01). CONCLUSION: TyG index is closely related to the aggregation of cardiovascular risk factors and is correlated with the judgment results of the screening population's high risk of CVD, suggesting that more attention should be paid to the identification and control of multiple risk factors in the population with significantly elevated TyG.

Advances in the application of upconversion nanoparticles for detecting and treating cancers.

The detection and treatment of cancer cells at an early stage are crucial for prolonging the survival time and improving the quality of life of patients. Upconversion nanoparticles (UCNPs) have unique physical and chemical advantages and likely provide a platform for detecting and treating cancer cells at an early stage. In this paper, the principle of UCNPs as chemical sensors based on fluorescence resonance energy transfer (FRET) has been briefly introduced. Research progress in such chemical sensors for detecting and analyzing bioactive substances and heavy metal ions at the subcellular level has been summarized. The principle of UCNP-based nanoprobe-targeting of cancer cells has been described. The research progress in using nanocomposites for cancer cell detection, namely cancer cell targeted imaging and tissue staining, has been discussed. In the field of cancer treatment, the principles and research progress of UCNPs in photodynamic therapy and photothermal therapy of cancer cells are systematically discussed. Finally, the prospects for UCNPs and remaining challenges to UCNP application in the field of cancer diagnosis and treatment are briefly described. This review provides powerful theoretical guidance and useful practical information for the research and application of UCNPs in the field of cancer.

Effects of quantum dots on the ROS amount of liver cancer stem cells.

Liver cancer (LC) is a serious disease that threatens human lives. LC has a high recurrence rate and poor prognosis. LC stem cells (LCSCs) play critical roles in these processes. However, the mechanism remains unclear. Reactive oxygen species (ROS) can be used to determine cell apoptosis and proliferation. However, studies of the effects of exogenous nanomaterials on LCSC ROS changes are rarely reported. In this work, quantum dots (QDs) were prepared using a hydrothermal method, and QDs were further modified with polyethylene glycol (PEG) and bovine serum albumin (BSA) using a chemical approach. The effects of QDs, PEG-modified QDs (PEG@QDs) and BSA-modified QDs (BSA@QDs) on the amounts of ROS in liver cancer PLC/PRF/5 (PLC) cells and liver cancer stem cells (LCSCs) were principally investigated. The results showed that when the concentration of QDs, PEG@QDs, and BSA@QDs were 10nM and 90nM, the ROS amount in PLC cells increased by approximately 2- to 5-fold. However, when the concentrations of these nanomaterials were 10nM and 90nM, ROS levels in LCSCs were reduced by approximately 50%. This critical path potentially leads to drug resistance and recurrence of LC. This work provides an important indication for further study of LC drug resistance and recurrence.

Effects of surface modification of quantum dots on viability and migration of triple-negative breast cancer cells.

Triple-negative breast cancer (BC) shows strong metastasis and has a bad prognosis. There are few effective approaches until date to detect BC cells at an early stage. Quantum dots (QDs) are one of the most promising nanomaterials for the detection of BC cells. QDs are usually modified with some functional molecules, such as PEG and BSA, to decrease or possibly eliminate their toxicity. Although a large number of studies have investigated the cytotoxicity of QDs, the effects of surface modification of QDs on biological behaviors of triple-negative BC cells remain unclear. In this work, QDs were prepared using the hydrothermal method and chemically modified with PEG and BSA. The optical performance of QDs was recorded with a digital camera. Their absorption and fluorescence (FL) properties were analyzed by UV-Vis spectrometer and FL spectrophotometer, respectively. The effects of QDs and surface modification on viability and migration were principally investigated. The possible mechanism was primarily analyzed. The results show that QDs exhibit excellent optical performance under ultraviolet irradiation. Surface modification slightly reduces the photon count reaching the QDs surface. Moreover, surface modification results in a blue-shift of FL peak of QDs, which is ascribed to the change in surface chemical environment because of PEG and BSA modifications. In addition, QDs, PEG coated QDs (PEG@CdTe) and BSA coated QDs (BSA@CdTe) can reduce viability and inhibit migration of BC cells. The inhibition effects are time- and concentration-dependent. In addition, PEG and BSA modified QDs exhibit lower inhibition effects on BC cells, as compared with unmodified QDs. In this process, Reactive oxygen species (ROS) does not appear to play an important role, and other pathways should be considered. This work provides experimental support and useful clinical guidance for QDs-applications in BC detection.