Purinergic P2X7 receptor involves in anti-retinal photodamage effects of berberine.

Berberine (BBR) is a Chinese herb with antioxidant and anti-inflammatory properties. In a previous study, we found that BBR had a protective effect against light-induced retinal degeneration in BALB/c mice. The purinergic P2X7 receptor (P2X7R) plays a key role in retinal degeneration via inducing oxidative stress, inflammatory changes, and cell death. The aim of this study was to investigate whether BBR can induce protective effects in light damage experiments and whether P2X7R can get involved in these effects. C57BL/6 J mice and P2X7 knockout (KO) mice on the C57BL/6 J background were used. We found that BBR preserved the outer nuclear layer (ONL) thickness and retinal ganglion cells following light stimulation. Furthermore, BBR significantly suppressed photoreceptor apoptosis, pro-apoptotic c-fos expression, pro-inflammatory responses of Mϋller cells, and inflammatory factors (TNF-α, IL-1ß). In addition, protein levels of P2X7R were downregulated in BBR-treated mice. Double immunofluorescence showed that BBR reduced overexpression of P2X7R in retinal ganglion cells and Mϋller cells. Furthermore, BBR combined with the P2X7R agonist BzATP blocked the effects of BBR on retinal morphology and photoreceptor apoptosis. However, in P2X7 KO mice, BBR had an additive effect resulting in thicker ONL and more photoreceptors. The data suggest that the P2X7 receptor is involved in retinal light damage, and BBR inhibits this process by reducing histological impairment, cell death, and inflammatory responses.

Targeting purinergic receptors to attenuate inflammation of dry eye.

Inflammation is one of the potential factors to cause the damage of ocular surface in dry eye disease (DED). Increasing evidence indicated that purinergic A1, A2A, A3, P2X4, P2X7, P2Y1, P2Y2, and P2Y4 receptors play an important role in the regulation of inflammation in DED: A1 adenosine receptor (A1R) is a systemic pro-inflammatory factor; A2AR is involved in the activation of the MAPK/NF-kB pathway; A3R combined with inhibition of adenylate cyclase and regulation of the mitogen-activated protein kinase (MAPK) pathway leads to regulation of transcription; P2X4 promotes receptor-associated activation of pro-inflammatory cytokines and inflammatory vesicles; P2X7 promotes inflammasome activation and release of pro-inflammatory cytokines IL-1ß and IL-18; P2Y receptors affect the phospholipase C(PLC)/IP3/Ca2+ signaling pathway and mucin secretion. These suggested that purinergic receptors would be promising targets to control the inflammation of DED in the future.

Quantitative Analysis of Internet of Things Technology on the National Economic Accounting: A Prediction Model Based on the FCM-BP Neural Network Algorithm.

The development of Internet of Things (IoT) technology is of great significance for modern financial settlements based on information technology. The IoT technology, which can provide a convenient approach for accounting, has the advantages of intelligent processing, reliable transmission, and comprehensive perception. For national economic accounting, a new integrated system for monitoring the environment is developed and designed by using embedded development technology and sensor technology. The system uses a wireless sensor network environment monitoring system IoT platform with embedded internal processors. Analyze and design the system as a whole, including the construction of the basic platform of the system, the design of the internal plates and circuits of the system, the monitoring design of the input node, and the monthly design of the output interface calculation. Finally, a physical model is built, and data measurement and analysis are carried out under different conditions, and the evaluation and advantage analysis of the system's operating status are given. The system can carry out all-round, multilevel and three-dimensional real-time monitoring of the construction site environment, including dust, PM2.5, temperature, humidity, wind speed, carbon dioxide, and other indicators in the construction site environment. In addition, the system can upload various monitoring data to the detection system through the internal network. The system has the functions of monitoring, alarming, recording, querying, and counting of the target monitoring station and can also be linked with the environmental control device. The construction site staff can conduct real-time supervision through the mobile terminal and computer terminal management platform. In addition, it can also meet the role of real-time remote monitoring and online guidance and regulation. It has reference value for the safety and management of the actual operation process of the project.

Potential mechanisms of macular degeneration protection by fatty fish consumption.

Age-related macular degeneration (AMD) is a progressive retinal disease that is a leading cause of visual impairment and severe vision loss. The number of people affected by AMD is increasing and constitutes a huge worldwide health problem. The beneficial effects of fish consumption on AMD have been revealed over the past decades, and in this review, we summarizes the beneficial effects of fatty fish on AMD and its mechanism of action. Fatty fish affects the development of AMD by inhibiting neovascularization, interacting with retinal pigment epithelial (RPE) cells, displacing Omega-6, and inducing cellular responses. It is recommended that people at high risk or with moderate or more severe AMD should consider eating more fatty fish in addition to maintaining a healthy lifestyle of weight control and smoking cessation and the need to promote new models of personalized AMD prevention and treatment.

ATP and Adenosine in the Retina and Retinal Diseases.

Extracellular ATP and its ultimate degradation product adenosine are potent extracellular signaling molecules that elicit a variety of pathophysiological pathways in retina through the activation of P2 and P1 purinoceptors, respectively. Excessive build-up of extracellular ATP accelerates pathologic responses in retinal diseases, whereas accumulation of adenosine protects retinal cells against degeneration or inflammation. This mini-review focuses on the roles of ATP and adenosine in three types of blinding diseases including age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR). Several agonists and antagonists of ATP receptors and adenosine receptors (ARs) have been developed for the potential treatment of glaucoma, DR and AMD: antagonists of P2X7 receptor (P2X7R) (BBG, MRS2540) prevent ATP-induced neuronal apoptosis in glaucoma, DR, and AMD; A1 receptor (A1R) agonists (INO-8875) lower intraocular pressure in glaucoma; A2A receptor (A2AR) agonists (CGS21680) or antagonists (SCH58261, ZM241385) reduce neuroinflammation in glaucoma, DR, and AMD; A3 receptor (A3R) agonists (2-Cl-lB-MECA, MRS3558) protect retinal ganglion cells (RGCs) from apoptosis in glaucoma.

Sodium Ferulate Protects against Angiotensin II-Induced Cardiac Hypertrophy in Mice by Regulating the MAPK/ERK and JNK Pathways.

Background and Objective. It has been reported that sodium ferulate (SF) has hematopoietic function against anemia and immune regulation, inflammatory reaction inhibition, inhibition of tumor cell proliferation, cardiovascular and cerebrovascular protection, and other functions. Thus, this study aimed to investigate the effects of SF on angiotensin II- (AngII-) induced cardiac hypertrophy in mice through the MAPK/ERK and JNK signaling pathways. Methods. Seventy-two male C57BL/6J mice were selected and divided into 6 groups: control group, PBS group, model group (AngII), model + low-dose SF group (AngII + 10 mg/kg SF), model + high-dose SF group (AngII + 40 mg/kg SF), and model + high-dose SF + agonist group (AngII + 40 mg/kg SCU + 10 mg/kg TBHQ). After 7 d/14 d/28 days of treatments, the changes of blood pressure and heart rates of mice were compared. The morphology of myocardial tissue and the apoptosis rate of myocardial cells were observed. The mRNA and protein expressions of atrial natriuretic peptide (ANP), transforming growth factor-ß (TGF-ß), collagen III (Col III), and MAPK/ERK and JNK pathway-related proteins were detected after 28 days of treatments. Results. SF improved the mice's cardiac abnormality and decreased the apoptosis rate of myocardial cells in a time- and dose-dependent manner (all P < 0.05). MAPK/ERK pathway activator inhibited the protective effect of SF in myocardial tissue of mice (P < 0.05). SF could inhibit the expression of p-ERK, p-p38MAPK, and p-JNK and regulate the expressions of ANP, TGF-ß, and Col III (all P < 0.05). Conclusion. Our findings provide evidence that SF could protect against AngII-induced cardiac hypertrophy in mice by downregulating the MAPK/ERK and JNK pathways.

Complete mitochondrial genome sequence of the heart failure model of cardiomyopathic Syrian hamster (Mesocricetus auratus).

In this study we sequenced the complete mitochondrial genome sequencing of a heart failure model of cardiomyopathic Syrian hamster (Mesocricetus auratus) for the first time. The total length of the mitogenome was 16,267 bp. It harbored 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 non-coding control region.

Noise alters guinea pig's blood-labyrinth barrier ultrastructure and permeability along with a decrease of cochlear Claudin-5 and Occludin.

BACKGROUND: Noise exposure (NE) is a severe modern health hazard that induces hearing impairment. However, the noise-induced ultrastructural changes of blood-labyrinth barrier (BLB) and the potential involvements of tight junction proteins (TJP) remain inconclusive. We investigated the effects of NE on not only the ultrastructure of cochlea and permeability of BLB but also the expression of TJP within the guinea pig cochlea. RESULTS: Male albino guinea pigs were exposed to white noise for 4 h or 2 consecutive days (115 dB sound pressure level, 6 hours per day) and the hearing impairments and light microscopic change of BLB were evaluated with auditory brainstem responses (ABR) and the cochlear sensory epithelia surface preparation, respectively. The cochlear ultrastructure and BLB permeability after NE 2d were revealed with transmission electron microscope (TEM) and lanthanum nitrate-tracing techniques, respectively. The potential alterations of TJPs Claudin-5 and Occludin were quantified with immunohistochemistry and western blot. NE induced significant hearing impairment and NE 2d contributed to significant outer hair cell (OHC) loss that is most severe in the first row of outer hair cells. Furthermore, the loosen TJ and an obvious leakage of lanthanum nitrate particles beneath the basal lamina were revealed with TEM. Moreover, a dose-dependent decrease of Claudin-5 and Occludin was observed in the cochlea after NE. CONCLUSIONS: All these findings suggest that both decrease of Claudin-5 and Occludin and increased BLB permeability are involved in the pathologic process of noise-induced hearing impairment; however, the causal relationship and underlying mechanisms should be further investigated.

Mechanical stretch suppresses microRNA-145 expression by activating extracellular signal-regulated kinase 1/2 and upregulating angiotensin-converting enzyme to alter vascular smooth muscle cell phenotype.

Phenotype modulation of vascular smooth muscle cells (VSMCs) plays an important role in the pathogenesis of various vascular diseases, including hypertension and atherosclerosis. Several microRNAs (miRNAs) were found involved in regulating the VSMC phenotype with platelet-derived growth factor (PDGF) treatment, but the role of miRNAs in the mechanical stretch-altered VSMC phenotype is not clear. Here, we identified miR-145 as a major miRNA contributing to stretch-altered VSMC phenotype by miRNA array, quantitative RT-PCR and gain- and loss-of-function methods. Our data demonstrated that 16% stretch suppressed miR-145 expression, with reduced expression of contractile markers of VSMCs cultured on collagenI; overexpression of miR-145 could partially recover the expression in stretched cells. Serum response factor (SRF), myocardin, and Kruppel-like factor 4 (KLF4) are major regulators of the VSMC phenotype. The effect of stretch on myocardin and KLF4 protein expression was altered by miR-145 mimics, but SRF expression was not affected. In addition, stretch-activated extracellular signal-regulated kinase 1/2 (ERK1/2) and up-regulated angiotensin-converting enzyme (ACE) were confirmed to be responsible for the inhibition of miR-145 expression. Mechanical stretch inhibits miR-145 expression by activating the ERK1/2 signaling pathway and promoting ACE expression, thus modulating the VSMC phenotype.

Prognostic significance of TBX2 expression in non-small cell lung cancer.

T-box2 (TBX2) expression has been reported to be related to aggressive tumor features. However, the role of TBX2 in non-small-cell lung cancer (NSCLC) tumorigenesis has never been elucidated. So we aimed at investigating the potential role of TBX2 in NSCLC. TBX2 expression was evaluated by qRT-PCR and Western blotting in 50 paired fresh lung cancer tissues as well as immunohistochemistry on 212 paraffin-embedded sections. We showed that the expression level of TBX2 was significantly increased in NSCLC as compared with the adjacent noncancerous tissue. Positive expression level of TBX2 was associated with histological type, lymph node metastasis and distant metastasis. Kaplan-Meier survival curves showed that positive expression level of TBX2 was associated with poor overall survival (OS) and progression-free survival of NSCLC patients. Results showed that TBX2 positivity was an independent prognostic factor for OS (HR 1.87, 95% CI 1.004-3.153, p = 0.012). On the basis of these results, we suggested that TBX2 protein expression may be an unfavorable independent prognostic parameter for NSCLC.

Mechanical stretch modulates microRNA 21 expression, participating in proliferation and apoptosis in cultured human aortic smooth muscle cells.

OBJECTIVES: Stretch affects vascular smooth muscle cell proliferation and apoptosis, and several responsible genes have been proposed. We tested whether the expression of microRNA 21 (miR-21) is modulated by stretch and is involved in stretch-induced proliferation and apoptosis of human aortic smooth muscle cells (HASMCs). METHODS AND RESULTS: RT-PCR revealed that elevated stretch (16% elongation, 1 Hz) increased miR-21 expression in cultured HASMCs, and moderate stretch (10% elongation, 1 Hz) decreased the expression. BrdU incorporation assay and cell counting showed miR-21 involved in the proliferation of HASMCs mediated by stretch, likely by regulating the expression of p27 and phosphorylated retinoblastoma protein (p-Rb). FACS analysis revealed that the complex of miR-21 and programmed cell death protein 4 (PDCD4) participated in regulating apoptosis with stretch. Stretch increased the expression of primary miR-21 and pre-miR-21 in HASMCs. Electrophoretic mobility shift assay (EMSA) demonstrated that stretch increased NF-κB and AP-1 activities in HASMCs, and blockade of AP-1 activity by c-jun siRNA significantly suppressed stretch-induced miR-21 expression. CONCLUSIONS: Cyclic stretch modulates miR-21 expression in cultured HASMCs, and miR-21 plays important roles in regulating proliferation and apoptosis mediated by stretch. Stretch upregulates miR-21 expression at least in part at the transcription level and AP-1 is essential for stretch-induced miR-21 expression.

Intravascular ultrasound area strain imaging used to characterize tissue components and assess vulnerability of atherosclerotic plaques in a rabbit model.

The purpose of this study was to investigate the association of area strain and tissue components and vulnerability of atherosclerotic plaques in a rabbit model. Forty purebred New Zealand rabbits underwent balloon-induced abdominal aorta endothelium injury, then a high-cholesterol diet for 24 weeks. Intravascular ultrasound (IVUS) images of abdominal aortas were acquired in situ and two consecutive frames near the end-diastole were used to construct an IVUS elastogram. Histologic slices matched with corresponding IVUS images were stained for fatty and collagen components, smooth muscle cells (SMCs) and macrophages. Regions-of-interest (ROIs) in plaques were classified as fibrous, fibro-fatty or fatty according to histologic study. Vulnerability indexes of ROIs were calculated as (fat + macrophage)/(collagen + SMCs). The area strain of these ROIs was calculated by use of an in-house-designed software system with a block-matching-based algorithm. Area strain was significantly higher in fatty ROIs (0.056 ± 0.003) than in fibrous (0.019 ± 0.002, p < 0.001) or fibro-fatty ROIs (0.033 ± 0.003, p < 0.001). The sensitivity and specificity of area strain for fatty ROIs characterization was 75.0% and 80.2% (area under the curve [AUC] 0.858, 95% confidence interval [CI] = 0.800-0.916, p < 0.001) and 75.0% and 75.3% (AUC 0.859, 95% CI = 0.801-0.917, p < 0.001) for fibrous ROIs, as demonstrated by receiver operating characteristic curve analysis. Area strain was positively correlated with vulnerability index (r(2) = 0.495, p < 0.001), fatty components (r(2) = 0.332, p < 0.001) and macrophage infiltration (r(2) = 0.406, p < 0.001); and negatively correlated with collagen and SMC composition (r(2) = 0.115 and r(2) = 0.169, p < 0.001, respectively). Area strain calculation with IVUS elastography based on digital B-mode analysis is feasible and can be useful for tissue characterization and plaque vulnerability assessment.