Roles of m6A modification in regulating PPER pathway in cadmium-induced pancreatic ß cell death.

Cadmium can lead to the death of pancreatic ß cells, thus affecting the synthesis and secretion of insulin. However, the specific mechanisms underlying the cadmium-induced pancreatic ß cell death have not been fully understood. In this study, roles of m6A modification in regulating protein processing in endoplasmic reticulum (PPER) pathway in cadmium-induced pancreatic ß cell death were explored. Our results demonstrated that cell viability and RNA m6A modification level were decreased, while apoptosis rates increased after CdSO4 treatment in pancreatic ß cells (NIT-1). In addition, expressions of Bcl-2, Xbp1, Col3a1, Bax, Chop, Dnajb1, and Hsp90aa1 were all significantly changed in CdSO4 treatment cells. The m6A agonist entacapone (Ent) can prominently reverse the cytotoxicity effects of CdSO4 and alleviate the changes of protein expression induced by CdSO4 treatment. By contrast, m6A inhibitor 3-Deazaadenosine (DAA) can synergistically enhance the cytotoxicity of CdSO4 and aggravate the disorder of protein levels caused by CdSO4 treatment. Interestingly, the results of the immunoprecipitation experiment indicate that Ythdc2, one of m6A binding proteins, may regulate the PPER pathway molecules in an m6A-dependent manner. In summary, our findings provide new directions for the prevention and treatment of the impairment of pancreatic ß cell function induced by cadmium.

Prevalence and Angiographic Characteristics of Coronary Artery Ectasia among Patients with Coronary Artery Disease: A Retrospective Analysis between 2014 and 2022.

Coronary artery ectasia (CAE) is defined as segmental dilatation with a diameter of 1.5-fold greater than that of an adjacent normal segment. Whether CAE is a unique clinical finding or results from other clinical entities remains to be determined. The purpose of the study was to investigate the prevalence, and clinical and angiographic characteristics of CAE in patients with coronary artery disease (CAD). Among the 8,845 coronary angiograms reviewed between the years 2014 and 2022, 142 patients had CAE yielding a detection rate of 4.9% among 2,870 CAD angiograms, and 28 patients had isolated CAE showing a detection rate of 0.32% (28/8,845) among total coronary angiography procedures. Overall, the incidence of CAE was 1.92% (170/8,845). The most commonly affected coronary artery by ectasia was the right coronary artery (RCA) (46.28%) among CAE coexisting with CAD cohort. The proportion of obesity, family history of CAD, and the proportion of hyperlipidemia in CAD patients who had ectasia were significantly higher than that in CAD patients who did not have ectasia (P < 0.05). In conclusion, CAE is an uncommon finding in coronary angiography, most commonly affecting the RCA. The obesity, family history of CAD, and the coexistence of hyperlipidemia were independent variables associated with CAE in CAD patients.

Changes of LncRNAs during the Process of Antioxidants Antagonize Cadmium-Induced Oxidative Damage in Islet ß Cells.

Long non-coding RNAs (LncRNAs) play important regulatory roles in oxidative damage. Resveratrol, curcumin, and cyanidin are phytogenic antioxidants widely existing in nature and they have been proved to antagonize certain heavy metal-induced oxidative damage in cells. However, can they antagonize oxidative damage induced by cadmium in islet ß cells? Are their mechanisms of antagonizing oxidative damage related to LncRNAs? In this study, we first detected the cell viability of each group by CCK8 assay. Next, reactive oxygen species (ROS) were detected by the fluorescent probe. The contents of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) were detected according to the instructions of corresponding kits. At last, the levels of LncRNAs were detected by fluorescence quantitative real-time polymerase chain reaction (qPCR). The results showed that resveratrol, curcumin and cyanidin were able to reverse the reduction of cell viability induced by cadmium (CdSO4). Further determination revealed that SOD activities of the resveratrol+CdSO4, curcumin+CdSO4, and cyanidin+CdSO4 treatment groups increased significantly, and ROS levels and MDA contents dramatically decreased when compared with single CdSO4-treated group. More importantly, the levels of three CdSO4-elevated LncRNAs (NONMMUT029382, ENSMUST00000162103, ENSMUST00000117235) were all decreased and levels of three CdSO4-inhibited LncRNAs (NONMMUT036805, NONMMUT014565, NONMMUT065427) were increased after the pretreatment of resveratrol, curcumin and cyanidin. In summary, resveratrol, curcumin and cyanidin may effectly reverse the cadmium-induced oxidative damage and suggest that phytogenic antioxidants may prevent cells from cadmium-induced oxidative damage through changing the levels of LncRNAs.

Natural diterpenoid EKO activates deubiqutinase ATXN3 to preserve vascular endothelial integrity and alleviate diabetic retinopathy through c-fos/focal adhesion axis.

Diabetic retinopathy (DR) is one of the most prevalent severe diabetic microvascular complications caused by hyperglycemia. Deciphering the underlying mechanism of vascular injury and finding ways to alleviate hyperglycemia induced microvascular complications is of great necessity. In this study, we identified that a compound ent-9α-hydroxy-15-oxo-16-kauren-19-oic acid (EKO), the diterpenoid isolated and purified from Pteris semipinnata L., exhibited good protective roles against vascular endothelial injury associated with diabetic retinopathy in vitro and in vivo. To further uncover the underlying mechanism, we used unbiased transcriptome sequencing analysis and showed substantial impairment in the focal adhesion pathway upon high glucose and IL-1ß stimulation. EKO could effectively improve endothelial focal adhesion pathway by enhancing the expression of two focal adhesion proteins Vinculin and ITGA11. We found that c-fos protein was involved in regulating the expression of Vinculin and ITGA11, a transcription factor component that was downregulated by high glucose and IL-1ß stimulation and recovered by EKO. Mechanically, EKO facilitated the binding of deubiquitylation enzyme ATXN3 to c-fos protein and promoted its deubiquitylation, thereby elevating its protein level to enhance the expression of Vinculin and ITGA11. Besides, EKO effectively suppressed ROS production and restored mitochondrial function. In vivo studies, we confirmed EKO could alleviate some of the indicators of diabetic mice. In addition, protein levels of ATXN3 and focal adhesion Vinculin molecule were also verified in vivo. Collectively, our findings addressed the endothelial protective role of natural diterpenoid EKO, with emphasize of mechanism on ATXN3/c-fos/focal adhesion signaling pathway as well as oxygen stress suppression, implicating its therapeutic potential in alleviating vascular endothelium injury and diabetic retinopathy.

Antioxidant activity of various parts of Cinnamomum cassia extracted with different extraction methods.

The aim of this study was to investigate the antioxidant activities of various parts (barks, buds, and leaves) of Cinnamomum cassia extracted with ethanol and supercritical fluid extraction (SFE). For the antioxidant activity comparison, IC50 values of the SFE and ethanol extracts in the DPPH scavenging assay were 0.562-10.090 mg/mL and 0.072-0.208 mg/mL, and the Trolox equivalent antioxidant capacity (TEAC) values were 6.789-58.335 mmole Trolox/g and 133.039-335.779 mmole Trolox/g, respectively. In addition, the total flavonoid contents were 0.031-1.916 g/ 100 g dry weight of materials (DW) and 2.030-3.348 g/ 100 g DW, and the total phenolic contents were 0.151-2.018 g/ 100 g DW and 6.313-9.534 g/ 100 g DW in the SFE and ethanol extracts, respectively. Based on the results, the ethanol extracts of Cinnamon barks have potential value as an antioxidant substitute and this study also provide a better technique to extract the natural antioxidant substances from C. cassia.

Epicardial adipose tissue characteristics and CT high-risk plaque features: correlation with coronary thin-cap fibroatheroma determined by intravascular ultrasound.

To investigate the correlation of epicardial adipose tissue (EAT) characteristics and high-risk plaque features characterized by coronary CT angiography (CCTA) for identifying the presence of thin-cap fibroatheroma (TCFA). Patients who underwent both CCTA and intravascular ultrasound (IVUS) within 4 weeks were retrospectively included. CT-derived quantitative and qualitative parameters, including diameter stenosis, low attenuation plaque (LAP), napkin-ring sign (NRS), positive remodeling and spotty calcification, were recorded. EAT volume and density were also measured. TCFA lesions and non-TCFA lesions were determined by IVUS. Multivariate regression analysis was used to determine the independent predictors of TCFA lesions. Sixty-eight patients (mean age: 68.6 ± 9.7 years; 40 males) with 91 lesions were finally included in our study. For CT-derived plaque features, LAP (77.8% versus 25%, p < 0.001) and NRS (40.7% versus 9.4%, p < 0.001) was more frequently presented in TCFA lesions than was in non-TCFA lesions. For EAT characteristics, EAT volume (110 ± 14 cm3 versus 98 ± 12 cm3, p < 0.001) was significantly larger whereas EAT density (-77 ± 4 HU versus -80 ± 5, p = 0.003) was markedly higher in TCFA lesions. According to multivariate logistic regression analysis, LAP, EAT volume and EAT density were significant predictors (odds ratio: 9.758, 1.095 and 1.202, all p value < 0.05) for the presence of TCFA lesions. EAT volume and density was greater in patients with TCFA lesions whereas LAP and NRS was more frequently presented. In addition, EAT characteristics and LAP were independent predictors of vulnerable plaques as determined by IVUS.

The value of quantified plaque analysis by dual-source coronary CT angiography to detect vulnerable plaques: a comparison study with intravascular ultrasound.

BACKGROUND: To investigate the diagnostic performance of quantified plaque analysis and high-risk plaque characterization by coronary computed tomography angiography (CCTA) for identifying thin-cap fibroatheroma (TCFA). METHODS: Patients who underwent both CCTA and intravascular ultrasound (IVUS) within 4 weeks were retrospectively included. CT-derived quantitative and qualitative parameters, including diameter stenosis, minimal lumen area (MLA), low attenuation plaque (LAP) volume napkin-ring sign (NRS), positive remodeling (PR) and spotty calcification, were recorded. TCFA lesions and non-TCFA lesions were determined by IVUS. Multivariate regression analysis was used to determine the independent predictors of TCFA lesions. RESULTS: Sixty-five patients (mean age: 69.8±9.2 years, 29 females) with 89 lesions were finally included. LAP and NRS were more frequently presented in the group of TCFA lesions. The mean LAP volume of TCFA lesions was significantly larger than that of non-TCFA lesions [16.5 (11.0-23.0) vs. 0 (0-1.5) mm3, P<0.001]. According to multivariate logistic regression analysis, LAP volume was the only significant predictor for IVUS-confirmed vulnerable plaques (odds ratio =3.294, 95% confidence interval: 1.177-9.223, P=0.023). LAP volume showed largest area under curve (AUC) for diagnosing TCFA lesions (AUC =0.901, 95% confidence interval: 0.819-0.954, P<0.0001). When using >8 mm3 as the best cutoff value, the diagnostic accuracy, sensitivity and specificity of LAP volume for predicting TCFA lesions were 91.0% (81/89), 84.6% (22/26) and 96.8% (61/63) respectively. CONCLUSIONS: CT-derived LAP volume of TCFA lesions was significantly higher than those of non-TCFA lesions. LAP volume was the strongest predictor for TCFA lesions as validated by IVUS.