Hyperglycemia-Suppressed SMARCA5 Disrupts Transcriptional Homeostasis to Facilitate Endothelial Dysfunction in Diabetes.

BACKGROUND: Dysfunction of vascular endothelial cells (ECs) plays a central role in the pathogenesis of cardiovascular complications in diabetes. SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 (SMARCA5) is a key regulator of chromatin structure and DNA repair, but its role in ECs remains surprisingly unexplored. The current study was designed to elucidate the regulated expression and function of SMARCA5 in diabetic ECs. METHODS: SMARCA5 expression was evaluated in ECs from diabetic mouse and human circulating CD34+ cells using quantitative reverse transcription polymerase chain reaction and Western blot. Effects of SMARCA5 manipulation on ECs function were evaluated using cell migration, in vitro tube formation and in vivo wound healing assays. Interaction among oxidative stress, SMARCA5 and transcriptional reprogramming was elucidated using luciferase reporter assay, electrophoretic mobility shift assay and chromatin immunoprecipitation. RESULTS: Endothelial SMARCA5 expression was significantly decreased in diabetic rodents and humans. Hyperglycemia-suppressed SMARCA5 impaired EC migration and tube formation in vitro, and blunted vasculogenesis in vivo. Contrarily, overexpression of SMARCA5 in situ by a SMARCA5 adenovirus-incorporated hydrogel effectively promoted the rate of wound healing in a dorsal skin punch injury model of diabetic mice. Mechanistically, hyperglycemia-elicited oxidative stress suppressed SMARCA5 transactivation in a signal transducer and activator of transcription 3 (STAT3)-dependent manner. Moreover, SMARCA5 maintained transcriptional homeostasis of several pro-angiogenic factors through both direct and indirect chromatin-remodeling mechanisms. In contrast, depletion of SMARCA5 disrupted transcriptional homeostasis to render ECs unresponsive to established angiogenic factors, which ultimately resulted in endothelial dysfunction in diabetes. CONCLUSION: Suppression of endothelial SMARCA5 contributes to, at least in part, multiple aspects of endothelial dysfunction, which may thereby exacerbate cardiovascular complications in diabetes.

Study on the inhibition mechanism of eucalyptus tannins against Microcystis aeruginosa.

Microcystis aeruginosa is the competitively dominant algal species in eutrophic waters and poses a serious threat to the aquatic ecological environment. To investigate the effects of eucalyptus tannins (TFL) and black water in eucalyptus plantations on M. aeruginosa, this study exposed M. aeruginosa to different concentrations (0 (control), 20, 50, 80, 110, and 140 mg L-1) of tannic acid (TA; hydrolyzed tannins, HT; reagent tannin), epigallocatechin gallate (EGCG; condensed tannins, CT; reagent tannin), eucalyptus tannins (TFL, complex tannin) and mixed TFL + Fe3+ solution (tannin: Fe3+ molar ratio = 1:10). The cell density, chlorophyll-a (Chl-a) content, superoxide dismutase (SOD) activity, malondialdehyde (MDA) and soluble protein (SP) contents of algae under tannin stress were determined, and the algal cell density treated with under the combination of TFL and Fe3+ was determined. The results showed a reduction in the Chl-a content of algal cells, which inhibited photosynthesis; leading to membrane lipid peroxidation; and the complexation of soluble proteins resulting in blocked protein synthesis were the main mechanisms by which tannins inhibited the growth of M. aeruginosa. TFL achieved the same inhibition of algal cells as the tannin reagent at the same concentration. At 4 d, TFL at 80 mg L-1 and above could achieve more than 54.87 % algal density inhibition. The inhibition rate of 80 mg L-1 and above TFL + Fe3+ on algal density was more than 75 %, indicating that TFL + Fe3+ had a stronger inhibitory effect on algal density. The results may facilitate the resource utilization of eucalyptus harvesting residues, explorations of the potential application of eucalyptus tannins in the control of M. aeruginosa, and provide new ideas for ecological algal inhibition in eucalyptus plantations.

Electrochemical Sensors and Biosensors for the Analysis of Tea Components: A Bibliometric Review.

Tea is a popular beverage all around the world. Tea composition, quality monitoring, and tea identification have all been the subject of extensive research due to concerns about the nutritional value and safety of tea intake. In the last 2 decades, research into tea employing electrochemical biosensing technologies has received a lot of interest. Despite the fact that electrochemical biosensing is not yet the most widely utilized approach for tea analysis, it has emerged as a promising technology due to its high sensitivity, speed, and low cost. Through bibliometric analysis, we give a systematic survey of the literature on electrochemical analysis of tea from 1994 to 2021 in this study. Electrochemical analysis in the study of tea can be split into three distinct stages, according to the bibliometric analysis. After chromatographic separation of materials, electrochemical techniques were initially used only as a detection tool. Many key components of tea, including as tea polyphenols, gallic acid, caffeic acid, and others, have electrochemical activity, and their electrochemical behavior is being investigated. High-performance electrochemical sensors have steadily become a hot research issue as materials science, particularly nanomaterials, and has progressed. This review not only highlights these processes, but also analyzes and contrasts the relevant literature. This evaluation also provides future views in this area based on the bibliometric findings.

Evaluating the Significance of Viscoelasticity in Diagnosing Early-Stage Liver Fibrosis with Transient Elastography.

Transient elastography quantifies the propagation of a mechanically generated shear wave within a soft tissue, which can be used to characterize the elasticity and viscosity parameters of the tissue. The aim of our study was to combine numerical simulation and clinical assessment to define a viscoelastic index of liver tissue to improve the quality of early diagnosis of liver fibrosis. This is clinically relevant, as early fibrosis is reversible. We developed an idealized two-dimensional axisymmetric finite element model of the liver to evaluate the effects of different viscoelastic values on the propagation characteristics of the shear wave. The diagnostic value of the identified viscoelastic index was verified against the clinical data of 99 patients who had undergone biopsy and routine blood tests for staging of liver disease resulting from chronic hepatitis B infection. Liver stiffness measurement (LSM) and the shear wave attenuation fitting coefficient (AFC) were calculated from the ultrasound data obtained by performing transient elastography. Receiver operating curve analysis was used to evaluate the reliability and diagnostic accuracy of LSM and AFC. Compared to LSM, the AFC provided a higher diagnostic accuracy to differentiate early stages of liver fibrosis, namely F1 and F2 stages, with an overall specificity of 81.48%, sensitivity of 83.33% and diagnostic accuracy of 81.82%. AFC was influenced by the level of LSM, ALT. However, there are no correlation between AFC and Age, BMI, TBIL or DBIL. Quantification of the viscoelasticity of liver tissue provides reliable measurement to identify and differentiate early stages of liver fibrosis.

[Correlation between liver hardness testing results obtained by FibroTouch and FibroScan and liver pathological stage].

OBJECTIVE: To evaluate the correlation of liver hardness testing RESULTS: obtained by FibroTouch and FibroScan and the liver pathological stage. METHODS: Seventy-five patients with chronic hepatitis B who presented to our clinic between January 2011 and April 2013 were examined with FibroTouch and FibroScan to evaluate the degree of liver fibrosis. Forty-six of those patients also underwent liver biopsy examination. THE RESULTS: from technology-based testing and histopathological evaluation of the biopsy were compared by statistical analysis to determine the consistency of FibroTouch and FibroScan in regard to histological stage. RESULTS: Analysis by paired t-test showed that the RESULTS: from FibroTouch and FibroScan were not significantly different (t = -0.17, P =0.8616), and the correlation coefficient from Pearson's correlation analysis was 0.9949 (P less than 0.05), suggesting that the two technologies' RESULTS: are correlated. Based on the histopathology RESULTS: for liver fibrosis stage, the FibroTouch diagnosis of liver fibrosis more than or equal to S 1 had a receiver operating characteristic (ROC) area under the curve (AUC) of 0.889, diagnosis of liver fibrosis more than or equal to S2 had a ROC AUC of 0.941, diagnosis of liver fibrosis more than or equal to S3 had a ROC AUC of 0.908, and diagnosis of liver fibrosis more than or equal to S4 had a ROC AUC of 0.911. CONCLUSION: Compared to FibroScan, FibroTouch has a better ability for detecting liver fibrosis and a better consistency with liver pathological stage determined by histopathological analysis.

New noninvasive assessment of liver fibrosis in chronic hepatitis B: maximal accumulative respiration strain.

OBJECTIVE: A novel parameter acquired from conventional B-mode sonographic videos was introduced in this study, and its diagnostic accuracy for evaluation of hepatic fibrosis was investigated. METHODS: Twenty-eight patients with chronic hepatitis B and 8 patients with hepatic cysts in the right lobe (controls) were enrolled. B-mode sonographic videos of hepatic motion under the ensisternum in the sagittal plane were captured during peaceful breathing. Maximal accumulative respiration strain (MARS) values of hepatic tissue were obtained after image analysis. METAVIR scoring after liver biopsy was considered the standard. First, the relationship between MARS and the fibrotic stage was studied; and second, receiver operating characteristic (ROC) curves were used to assess the accuracy of MARS for evaluation of the fibrotic stage. RESULTS: When the transducer was placed in the sagittal imaging plane under the ensisternum during the whole respiratory period, the hepatic tissue motion was almost in the same plane. The MARS values (mean +/- SD) were 29.44% +/- 10.44% in the F0 group (no fibrosis; n = 8), 19.30% +/- 9.10% in the F1 group (portal fibrosis without septa; n = 8), 18.09% +/- 7.36% in the F2-F3 group (portal fibrosis with few septa or numerous septa without cirrhosis; n = 12), and 14.16% +/- 4.18% in the F4 group (cirrhosis; n = 8). The Spearman correlation coefficient between MARS and the fibrotic stage was 0.516 (P = .001). The diagnostic accuracy rates, expressed as areas under the ROC curves, were 0.87 for mild fibrosis (F >or= 1), 0.72 for substantial fibrosis (F >or= 2), and 0.75 for cirrhosis (F = 4). CONCLUSIONS: Maximal accumulative respiration strain attained from B-mode sonographic videos of hepatic tissue is a new, convenient, economical, and promising noninvasive parameter for assessment of hepatic fibrosis in patients with chronic hepatitis B.