Correlation between characteristics of intracranial atherosclerotic plaques and ischemic stroke in high-resolution vascular wall MRI.

BACKGROUND: Intracranial atherosclerotic stenosis is a major cause of ischemic stroke, accounting for 30% of ischemic strokes in Asian populations. PURPOSE: To investigate the relationship between the degree of arterial stenosis and enhancement grade of intracranial atherosclerotic disease (ICAD), the plaque characteristics in different remodeling patterns, and its potential impact. MATERIAL AND METHODS: A total of 210 patients diagnosed with ICAD were enrolled in this retrospective study. Patients were divided into the middle cerebral artery (MCA) group (101 cases), posterior cerebral artery (PCA) group (14 cases), basilar artery (BA) group (71 cases), and intracranial segment of vertebral artery (VA) group (90 cases) according to the difference of diseased vessels. Data on presence or absence of ischemic infarction, intracranial vascular position of lesions, plaque characteristics, ICAD enhancement grade, remodeling index, and degree of arterial stenosis were collected for analysis. RESULTS: The incidence of ischemic infarction in enhancement grade 2 was significantly higher than that in enhancement grade 1 in MCA group (P = 0.019). Enhancement grade 2 of ICAD was an independent risk factor for the development of ischemic infarction (odds ratio = 4.60; 95% confidence interval: 1.91-11.03; P = 0.001). There was no significant statistical difference in infarct rate between different remodeling modalities (P>0.05). CONCLUSION: Enhancement grade of ICAD is significantly associated with the degree of stenosis and the occurrence of ischemic stroke, which varies in different intracranial vessels. The pattern of vascular remodeling varies among different intracranial vessels, and the pattern of vascular remodeling has a significant impact on plaque characteristics.

A Study on the Persistent Trigeminal Artery and Its Classification Based on Magnetic Resonance Angiograph Images.

BACKGROUND: The persistent trigeminal artery (PTA) is the most common remnant of primitive circulation, communicating the developing carotid and vertebrobasilar junction. PURPOSE: This study aimed to evaluate the implementation of magnetic resonance angiography for the detection of PTA and to reclassify the variations based on Weon typing. Moreover, the correlation of various Weon types with the posterior cerebral artery (PCA), Willis ring, basilar artery (BA) dysplasia, and the relationship between PTA and arteriosclerosis were analyzed. METHODS: From November 2017 to October 2019, a total of 48,184 patients underwent magnetic resonance angiography examination in our hospital, and 79 patients were diagnosed with PTA. Of these, 70 patients with complete radiological and clinical information were included in this study. RESULTS: Among the 70 patients with complete data, 27 were classified as Weon type I (38.6%), 7 as type II (10%), 14 as type III (20%), 8 as type IV (11.4%), and 3 as type V (4.3%: type Va, 1 case; type Vb, 2 cases). The remaining 11 cases were PCA with mixed blood supply, so the new type VI was divided into 3 subtypes: type VIa, type VIb, and type VIc, and each subtype of type V was further refined into 4 subtypes. There were 32 cases of PTA with BA dysplasia, including 14 with type I (51.9%), 5 with type II (71.4%), 2 with type III (14.3%), 5 with type IV (62.5%), and 6 with type VI (54.5%). Cerebral infarction was found in 55 cases (78.6%) of PTA, among which 11 had a cerebral infarction in the posterior circulation blood supply area. There were 46 cases (65.7%) accompanied by intracranial arteriosclerosis, and in 6 cases, arteriosclerosis mainly occurred in the posterior circulation. CONCLUSIONS: We redefined the classification of PTA based on Weon typing for a better understanding of clinical symptoms and surgical risks. Moreover, PTA was correlated with the fetal origin of PCA, BA dysplasia, and posterior circulation arteriosclerosis. These factors may increase the incidence of cerebral infarction in the posterior circulation blood supply area.

HR-MRI findings of intracranial artery stenosis and distribution of atherosclerotic plaques caused by different etiologies.

OBJECTIVE: To investigate the etiology of intracranial artery stenosis and the distribution characteristics of intracranial artery atherosclerotic stenosis using high-resolution magnetic resonance imaging (HR-MRI). METHODS: A total of 262 patients with intracranial artery stenosis that underwent HR-MRI from November 2019 to December 2020 were retrospectively enrolled. The etiology of intracranial anterior and posterior circulation artery stenosis was analyzed, and the relationship between the location of plaques and the distribution characteristics of plaques and the occurrence of ischemic stroke was summarized. RESULTS: A total of 276 plaques were identified with HR-MRI. There were 101 cases (36.59%) in the middle cerebral artery (MCA), 14 cases (5.07%) in the posterior cerebral artery (PCA), 90 cases (32.62%) in vertebral artery (VA), and 71 cases (25.72%) in the basilar artery (BA). The infarct rate of ventral and superior wall MCA plaques was higher than that of dorsal and inferior wall (63.33% vs 31.25% P = 0.021) (100.00% vs 50% P = 0.022). MCA with plaques throughout the course had the greatest degree of stenosis (P < 0.001). Sphenoid segment (M1) of MCA was most susceptible (85 cases, 84.16%), MCA plaques were most common in the proximal M1 segment (35 cases, 34.65%), and most BA plaques were found in the distal segment (28 cases, 39.44%). PCA plaques were most frequently involved in traffic anterior segment (P1) (7 cases, 50.00%). CONCLUSION: HR-MRI could provide accurate imaging reference for clinical evaluation of intracranial arterial stenosis and formulation of treatment plans. The intracranial arterial plates mostly appeared in the middle cerebral artery and vertebral artery. Middle cerebral arteries with atherosclerotic plaques are more likely to narrow.

Preparation, toxicity reduction and radiation therapy application of gold nanorods.

Gold nanorods (GNRs) have a broad application prospect in biomedical fields because of their unique properties and controllable surface modification. The element aurum (Au) with high atomic number (high-Z) render GNRs ideal radiosensitive materials for radiation therapy and computed tomography (CT) imaging. Besides, GNRs have the capability of efficiently converting light energy to heat in the near-infrared (NIR) region for photothermal therapy. Although there are more and more researches on GNRs for radiation therapy, how to improve their biocompatibility and how to efficiently utilize them for radiation therapy should be further studied. This review will focuse on the research progress regarding the preparation and toxicity reduction of GNRs, as well as GNRs-mediated radiation therapy.

Open microfluidic coculture reveals paracrine signaling from human kidney epithelial cells promotes kidney specificity of endothelial cells.

Endothelial cells (ECs) from different human organs possess organ-specific characteristics that support specific tissue regeneration and organ development. EC specificity is identified by both intrinsic and extrinsic cues, among which the parenchyma and organ-specific microenvironment are critical contributors. These extrinsic cues are, however, largely lost during ex vivo cultures. Outstanding challenges remain to understand and reestablish EC organ specificity for in vitro studies to recapitulate human organ-specific physiology. Here, we designed an open microfluidic platform to study the role of human kidney tubular epithelial cells in supporting EC specificity. The platform consists of two independent cell culture regions segregated with a half wall; culture media are added to connect the two culture regions at a desired time point, and signaling molecules can travel across the half wall (paracrine signaling). Specifically, we report that in the microscale coculture device, primary human kidney proximal tubule epithelial cells (HPTECs) rescued primary human kidney peritubular microvascular EC (HKMEC) monolayer integrity and fenestra formation and that HPTECs upregulated key HKMEC kidney-specific genes (hepatocyte nuclear factor 1 homeobox B, adherens junctions-associated protein 1, and potassium voltage-gated channel subfamily J member 16) and endothelial activation genes (vascular cell adhesion molecule-1, matrix metalloproteinase-7, and matrix metalloproteinase-10) in coculture. Coculturing with HPTECs also promoted kidney-specific genotype expression in human umbilical vein ECs and human pluripotent stem cell-derived ECs. Compared with culture in HPTEC conditioned media, coculture of ECs with HPTECs showed increased upregulation of kidney-specific genes, suggesting potential bidirectional paracrine signaling. Importantly, our device is compatible with standard pipettes, incubators, and imaging readouts and could also be easily adapted to study cell signaling between other rare or sensitive cells.

Down-regulation of microRNA-155 attenuates retinal neovascularization via the PI3K/Akt pathway.

PURPOSE: We aimed to investigate the anti-angiogenic properties of miR-155 via in vitro and in vivo studies. METHODS: miR-155 was knocked down using lentivirus-mediated RNA interference. The proliferation, migration, and tube formation of human retinal microvascular endothelial cells (HRMECs) were measured using BrdU, Transwell, and Matrigel assays, respectively. An oxygen-induced retinopathy (OIR) model was induced using neonatal C57BL/6J pups. Anti-miR-155 was intravitreally injected on postnatal day 12, and the retinal non-perfused areas and extent of neovascularization were measured on postnatal day 18 using transcardiovascular fluorescein isothiocyanate (FITC)-dextran perfusion and retina sections. A laser-induced choroidal neovascularization (CNV) model was induced in adult C57BL/6J mice. To evaluate the leakage areas, fundus fluorescein angiography was performed on day 14 after anti-miR-155 intravitreal injection. The neovascularization area of the CNV model was also examined in confocal and retina section studies. The expression levels of SHIP1 and p-Akt (Thr308, Ser473, and Thr450) were evaluated both in vitro and in vivo. RESULTS: The expression of miR-155 was elevated in HRMECs after treatment with vascular endothelial growth factor (VEGF) and in neovascularized mouse model retinas. Anti-miR-155 lentivirus reduced the VEGF-induced proliferation, migration, and tube formation abilities of HRMECs. Anti-miR-155 attenuated retinal neovascularization in in vivo CNV and OIR models. In VEGF-treated HRMECs and retina neovascularization models, p-Akt (Ser473) was significantly upregulated, while SHIP1 was downregulated. Conversely, the inhibition of miR-155 restored the expression of SHIP1 and reduced the phosphorylation of effectors in the Akt (Ser473) signaling pathway. CONCLUSIONS: The results revealed that the downregulation of miR-155 attenuated retinal neovascularization via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway.

Suppressing autophagy protects photoreceptor cells from light-induced injury.

Autophagy, a conserved cellular self-degradation process, not only serves to protect cells at critical times during development and nutrient stress, but also contributes to cell death. Photoreceptor cells are unique neurons which when directly exposed to the light, transduces light stimuli into visual signal. However, intense light exposure can be cytotoxic to the retina. So far, the precise mechanism underlying retina light injury remains unknown, and the effective therapy is still unavailable. Here, we found that visible light exposure activated the mitogen-activated protein kinases (MAPK) pathway and led to remarkable autophagy in photoreceptor cells (661W cells). Directly blocking autophagy with 3MA or LY294002 markedly attenuated light-induced death in 661W cells. Among the activated downstream factors of MAPK pathway, ERK, not JNK or p-38, played a critical role in light-induced death mechanism. Inhibiting the activation of ERK with its specific inhibitor PD98059 significantly suppressed light-induced autophagy and protected 661W cells from light injury. These results indicate that autophagy is an essential event in light-induced photoreceptor death and that directly blocking autophagy or suppressing autophagy by inhibiting the ERK pathway could effectively attenuates light-induced damage. These observations may have a potential application in the treatment of retinal light injury.

High intensity interval training vs. moderate intensity continuous training on aerobic capacity and functional capacity in patients with heart failure: a systematic review and meta-analysis.

Background: Exercise training is commonly employed as a efficacious supplementary treatment for individuals suffering from heart failure, but the optimal exercise regimen is still controversial. The objective of the review was to compare the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on the exercise capacity, cardiac function, quality of life (QoL) and heart rate among patients with heart failure with reduced ejection fraction. Methods: A systematic search was performed using the following eight databases from their inception to July 5, 2023: PubMed, Web of Science, Embase, Cochrane Library, Clinical Trials, China Knowledge Network, Wan fang Data, and the China Biology Medicine databases. The meta-analysis results were presented as mean difference (MD) and 95% confidence interval (CI). The Cochrane Risk of Bias tool was used for the included studies. The Grading of Recommendations Assessment, Development, and Evaluations was used to assess the certainty of evidence. Results: Thirteen randomized controlled trials were included in the study. The results showed that HIIT had a significant positive effect on peak oxygen uptake (MD = 1.78, 95% CI for 0.80-2.76), left ventricular ejection fraction (MD = 3.13, 95% CI for 1.25-5.02), six-minute walk test (MD = 28.13, 95% CI for 14.56-41.70), and Minnesota Living with Heart Failure Questionnaire (MD = -4.45, 95% CI for -6.25 to -2.64) compared to MICT. However, there were no statistically significant differences observed in resting heart rate and peak heart rate. Conclusions: HIIT significantly improves peak oxygen uptake, left ventricular ejection fraction, six-minute walk test, and Minnesota Living with Heart Failure Questionnaire in patients with heart failure with reduced ejection fraction. Additionally, HIIT exhibits greater effectiveness in improving peak oxygen uptake among patients with lower body mass index. Systematic Review Registration: https://www.doi.org/10.37766/inplasy2023.7.0100, identifier (INPLASY2023.7.0100).

The AMPK-dependent inhibition of autophagy plays a crucial role in protecting photoreceptor from photooxidative injury.

Excessive light exposure can potentially cause irreversible damage to the various photoreceptor cells, and this aspect has been considered as an important factor leading to the progression of the different retinal diseases. AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR) are crucial intracellular signaling hubs involved in the regulation of cellular metabolism, energy homeostasis, cellular growth and autophagy. A number of previous studies have indicated that either AMPK activation or mTOR inhibition can promote autophagy in most cases. In the current study, we have established an in vitro as well as in vivo photooxidation-damaged photoreceptor model and investigated the possible influence of visible light exposure in the AMPK/mTOR/autophagy signaling pathway. We have also explored the potential regulatory effects of AMPK/mTOR on light-induced autophagy and protection achieved by suppressing autophagy in photooxidation-damaged photoreceptors. We observed that light exposure led to a significant activation of mTOR and autophagy in the photoreceptor cells. However, intriguingly, AMPK activation or mTOR inhibition significantly inhibited rather than promoting autophagy, which was termed as AMPK-dependent inhibition of autophagy. In addition, either indirectly suppressing autophagy by AMPK activation/ mTOR inhibition or directly blocking autophagy with an inhibitor exerted a significant protective effect on the photoreceptor cells against the photooxidative damage. Neuroprotective effects caused by the AMPK-dependent inhibition of autophagy were also verified with a retinal light injured mouse model in vivo. Overall, our findings demonstrated that AMPK / mTOR pathway could inhibit autophagy through AMPK-dependent inhibition of autophagy to significantly protect the photoreceptors from photooxidative injury, which may aid to further develop novel targeted retinal neuroprotective drugs.

Visual impairment and blindness caused by retinal diseases: A nationwide register-based study.

Background: Retinal disorders cause substantial visual burden globally. Accurate estimates of the vision loss due to retinal diseases are pivotal to inform optimal eye health care planning and allocation of medical resources. The purpose of this study is to describe the proportion of visual impairment and blindness caused by major retinal diseases in China. Methods: A nationwide register-based study of vitreoretinal disease covering all 31 provinces (51 treating centres) of mainland China. A total of 28 320 adults diagnosed with retinal diseases were included. Participants underwent standardised ocular examinations, which included best-corrected visual acuity (BCVA), dilated-fundus assessments, and optical coherence tomography. Visual impairment and blindness are defined using BCVA according to the World Health Organization (WHO) (visual impairment: <20/63-≥20/400; blindness: <20/400) and the United States (visual impairment: <20/40-≥20/200; blindness: <20/200) definitions. The risk factors of vision loss were explored by logistic regression analyses. Results: Based on the WHO definitions, the proportions for unilateral visual impairment and blindness were 46% and 18%, respectively, whereas those for bilateral visual impairment and blindness were 31% and 3.3%, respectively. Diabetic retinopathy (DR) accounts for the largest proportion of patients with visual impairment (unilateral visual impairment: 32%, bilateral visual impairment: 60%) and blindness (unilateral blindness: 35%; bilateral blindness: 64%). Other retinal diseases that contributed significantly to vision loss included age-related macular degeneration, myopic maculopathy, retinal vein occlusion, and rhegmatogenous retinal detachment and other macular diseases. Women (bilateral vision loss: P = 0.011), aged patients (unilateral vision loss: 45-64 years: P < 0.001, ≥65 years: P < 0.001; bilateral vision loss: 45-64 years: P = 0.003, ≥65 years: P < 0.001 (reference: 18-44 years)) and those from Midwest China (unilateral and bilateral vision loss: both P < 0.001) were more likely to suffer from vision loss. Conclusions: Retinal disorders cause substantial visual burden among patients with retinal diseases in China. DR, the predominant retinal disease, is accountable for the most prevalent visual disabilities. Better control of diabetes and scaled-up screenings are warranted to prevent DR. Specific attention should be paid to women, aged patients, and less developed regions.

Corporate Social Responsibility and Consumer Emotional Marketing in Big Data Era: A Mini Literature Review.

In the digital era, big data can strengthen the awareness of corporate social responsibility (CSR) and make CSR more transparent to consumers. While big data continues to deepen the business transformation of enterprises, it is also a process of constantly understanding consumption and public expectations. In this process, the cognitive structure of enterprises is constantly adjusted, no longer simply pursuing performance but constantly realizing the expectations of users and society in order to maintain performance. Through mass media, corporate media, and other platforms, CSR is easier to affect consumers' emotions. By reviewing the theory of emotional marketing and related research, this paper focuses on the different emotional ties between CSR and consumers and their different effects on consumers. This paper further emphasizes the profound significance of emotional marketing theory for understanding CSR in the era of big data. In addition, this paper also calls for more research based on big data technology, broken down by consumer needs - more specific attention to the different impacts of CSR on different consumers.

Zeolitic imidazolate framework-8/bacterial cellulose composites for iodine loading and their antibacterial performance.

Bacterial cellulose (BC), produced by bacteria and fungi, is a promising material in the biomedical field. However, non-antibacterial activity limits its broad applications. Herein, antibacterial composites (BC/ZIF-8-iodine) were prepared by loading iodine into zeolitic imidazolate framework-8 (ZIF-8) modified BC (BC/ZIF-8). BC/ZIF-8-iodine was well characterized by SEM, XRD, FTIR, XPS, Raman and contact angle analyses. The increase of ZIF-8 content augmented the loading capacity of iodine in BC/ZIF-8-iodine. Meanwhile, the adsorbed iodine can be released from BC/ZIF-8-iodine composites, following the Higuchi equation. A reduced sublimation of iodine was observed in BC/ZIF-8-iodine composites, indicating their good iodine preservation ability. BC/ZIF-8-iodine composites exhibited strong antibacterial activity towards Escherichia coli, Staphylococcus aureus and Candida albicans. XPS and Raman analyses indicated that the adsorbed iodine of BC/ZIF-8-iodine composites was in the form of I3-. The expected iodine loading, release and preservation behaviors of BC/ZIF-8-iodine composites ensure their antibacterial performance and suggest potential clinical applications.

Determinants of Dietary Adherence Among Chinese Patients After Bariatric Surgery Based on the Attitude-Social Influence-Efficacy Model.

PURPOSE: To explore main determinants of dietary adherence among Chinese patients after bariatric surgery based on the Attitude-Social influence-Efficacy (ASE) model. METHODS: A cross-sectional survey was conducted by using convenience sampling method to select 288 participants in a tertiary hospital in Jiangsu, China. General information and disease-related information were collected as well as applying the Dietary Adherence Scale after Bariatric Surgery (DASBS) and Attitude-Social influence-Efficacy Questionnaire after Bariatric Surgery (ASEQBS). Univariate analysis, correlation analysis, and multivariate analysis were used to identify determinants of dietary adherence among patients after bariatric surgery. RESULTS: A total of 288 questionnaires were effectively collected. The mean DASBS score was 54.90 ± 10.08 among post-bariatric patients. Univariate analysis results showed that education level, time since surgery, smoking, exercise, participation in peer support groups, and participation in nutrition counseling had significant effects on postoperative diet adherence level of patients (P < 0.05). The correlation analysis results showed that the total score of dietary adherence was positively correlated with the total score of intention, attitude, social influence, and self-efficacy, and the correlation coefficients were 0.511, 0.550, 0.460, and 0.484, respectively (P < 0.05). The results of multiple linear regression analysis showed that time since surgery, attitude, intention, social influence, exercise, and self-efficacy entered the regression equation (P < 0.05). The standardized regression coefficients of attitude and intention are 0.237 and 0.196, respectively. The regression model could explain 44.0% of the total variation. CONCLUSION: The dietary adherence of Chinese post-bariatric patients is at an upper-middle level, which needs to be further improved. Time since surgery, exercise, intention, attitude, social influence, and self-efficacy had significant effects on patients' dietary adherence. Attitude had the greatest effect on dietary adherence, followed by intention. The results shed light on that these factors should be emphasized to take personalized intervention strategy in designing dietary intervention program, in order to improve the patient's dietary adherence and surgical outcomes.

Trajectory Analysis and Predictors of the Percentage of Body Fat Among Chinese Sleeve Gastrectomy Patients.

BACKGROUND: The weight loss in Chinese patients after sleeve gastrectomy is different, and the differences can be evaluated through the trajectories of the percentage of body fat (BF%). Patients' baseline psychosocial factors may be associated with these trajectories. MATERIALS AND METHODS: We selected 267 patients who received sleeve gastrectomy for the first time. The BF% at baseline and 1, 3, 6, 12 months after surgery and baseline psychosocial variables were retrospectively collected. The trajectory model was established according to BF% based on the growth mixture model. The baseline psychosocial variables were compared among different trajectory classes. RESULTS: Four types of trajectory classes were obtained. The differences in preoperative dietary self-efficacy, exercise self-efficacy, depression, social support, working status, alcohol consumption, and gender among the classes were statistically significant. The pairwise comparison of the above variables revealed that the differences of gender, dietary self-efficacy and exercise self-efficacy among classes were highly effective. CONCLUSION: Female gender, low dietary self-efficacy and low exercise self-efficacy were predictors for poor BF% trajectory in sleeve gastrectomy patients. Health professionals can early identify patients who are most likely to lose weight in a not-ideal manner based on the above predictors.

Effects of a 12-Week Transtheoretical Model-Based Exercise Training Program in Chinese Postoperative Bariatric Patients: a Randomized Controlled Trial.

PURPOSE: This study aims to investigate the effectiveness of the transtheoretical model (TTM)-based exercise training on TTM variables, exercise adherence, and physical function in patients in the early stages after bariatric surgery (BS). MATERIALS AND METHODS: We conducted a single-blinded, prospective, randomized controlled trial (RCT) to evaluate the effects of TTM-based exercise training on BS patients immediately after surgery. Participants (n = 120) were randomized into a TTM-based exercise training group (n = 60) and a control group (n = 60). Main outcomes included TTM variables (measured by exercise stages of change (ESCs), exercise self-efficacy (ESE), and decisional balance), exercise adherence, and physical function (determined by the 6-min walk distance (6MWD)). Secondary outcomes were physical activity, anthropometrics, and body composition. We performed all analyses in accordance with the intention-to-treat principle. RESULTS: Retention rates for the interventions were 91.7% for the intervention group and 90.0% for the control group. Compared with the control group, the 12-week TTM-based intervention significantly helped participants advance through ESCs, demonstrate higher ESE, perceive more benefits and fewer barriers to exercise, and show higher exercise adherence and better physical function afterward (all P < 0.05). However, we observed no statistically significant difference between the two groups in anthropometric parameters or body composition after intervention. CONCLUSION: The TTM-based exercise intervention had significant positive effects on the TTM variables, which could further help increase patients' exercise adherence and physical function immediately after BS. TRIAL REGISTRATION: This study was retrospectively registered at the Chinese Clinical Trial Registry (website: www.chictr.org.cn , registry number: ChiCTR2000039319).

Inhibitory effects of safranal on laser-induced choroidal neovascularization and human choroidal microvascular endothelial cells and related pathways analyzed with transcriptome sequencing.

AIM: To determine the effects of safranal on choroidal neovascularization (CNV) and oxidative stress damage of human choroidal microvascular endothelial cells (HCVECs) and its possible mechanisms. METHODS: Forty-five rats were used as a laser-induced CNV model for testing the efficacy and safety of safranal (0.5 mg/kg·d, intraperitoneally) on CNV. CNV leakage on fluorescein angiography (FA) and CNV thickness on histology was compared. HCVECs were used for a H2O2-induced oxidative stress model to test the effect of safranal in vitro. MTT essay was carried to test the inhibition rate of safranal on cell viability at different concentrations. Tube formation was used to test protective effect of safranal on angiogenesis at different concentrations. mRNA transcriptome sequencing was performed to find the possible signal pathway. The expressions of different molecules and their phosphorylation level were validated by Western blotting. RESULTS: On FA, the average CNV leakage area was 0.73±0.49 and 0.31±0.11 mm2 (P=0.012) in the control and safranal-treated group respectively. The average CNV thickness was 127.4±18.75 and 100.6±17.34 µm (P=0.001) in control and safranal-treated group. Under the condition of oxidative stress, cell proliferation was inhibited by safranal and inhibition rates were 7.4%-35.4% at the different concentrations. For tube formation study, the number of new branches was 364 in control group and 35, 42, and 17 in 20, 40, and 80 µg/mL safranal groups respectively (P<0.01). From the KEGG pathway bubble graph, the PI3K-AKT signaling pathway showed a high gene ratio. The protein expression was elevated of insulin receptor substrate (IRS) and the phosphorylation level of PI3K, phosphoinositide-dependent protein kinase 1/2 (PDK1/2), AKT and Bcl-2 associated death promoter (BAD) was also elevated under oxidative stress condition but inhibited by safranal. CONCLUSION: Safranal can inhibit CNV both in vivo and in vitro, and the IRS-PI3K-PDK1/2-AKT-BAD signaling pathway is involved in the pathogenesis of CNV.

Investigating Fibroblast-Induced Collagen Gel Contraction Using a Dynamic Microscale Platform.

Mechanical forces have long been recognized as fundamental drivers in biological processes, such as embryogenesis, tissue formation and disease regulation. The collagen gel contraction (CGC) assay has served as a classic tool in the field of mechanobiology to study cell-induced contraction of extracellular matrix (ECM), which plays an important role in inflammation and wound healing. In a conventional CGC assay, cell-laden collagen is loaded into a cell culture vessel (typically a well plate) and forms a disk-shaped gel adhering to the bottom of the vessel. The decrement in diameter or surface area of the gel is used as a parameter to quantify the degree of cell contractility. In this study, we developed a microscale CGC assay with an engineered well plate insert that uses surface tension forces to load and manipulate small volumes (14 µL) of cell-laden collagen. The system is easily operated with two pipetting steps and the microscale device moves dynamically as a result of cellular forces. We used a straightforward one-dimensional measurement as the gel contraction readout. We adapted a conventional lung fibroblast CGC assay to demonstrate the functionality of the device, observing significantly more gel contraction when human lung fibroblasts were cultured in serum-containing media vs. serum-free media (p ≤ 0.05). We further cocultured eosinophils and fibroblasts in the system, two important cellular components that lead to fibrosis in asthma, and observed that soluble factors from eosinophils significantly increase fibroblast-mediated gel contraction (p ≤ 0.01). Our microscale CGC device provides a new method for studying downstream ECM effects of intercellular cross talk using 7- to 35-fold less cell-laden gel than traditional CGC assays.

Effect of physical exercise on weight loss and physical function following bariatric surgery: a meta-analysis of randomised controlled trials.

OBJECTIVES: We performed a meta-analysis of all of the available randomised controlled trials (RCTs) to investigate whether physical exercise contributes to weight loss or physical function improvement in adults receiving bariatric surgery. METHODS: We searched PubMed, Embase, the Cochrane Library, OVID and the CINAHL up through May 2018. RCTs that assigned adults with obesity to either an exercise training group or a no-exercise group after bariatric surgery were included. The primary outcomes were weight loss and physical function. Study bias was assessed using the Cochrane risk of bias tool, and the quality of evidence was assessed using GRADEpro. RESULTS: A total of eight studies met the inclusion criteria (n=347 participants). Most of the studies carried a low risk of bias due to randomisation and blinding. Compared with those without exercise intervention after surgery, patients engaging in physical exercise were associated with greater weight loss (weighted mean difference (WMD) -1.94 kg; 95% CI -3.18 to -0.69; n=8) and longer 6 min walk distance (6MWD; WMD29.67 m; 95% CI 25.97 to 33.37; n=2) during follow-up. By subgroup analyses, the additional weight loss in exercise group was related to the starting time and type of exercise: patients engaging in exercise 1 year or more after surgery and patients received aerobic-resistance exercise experienced more weight loss. Besides, patients in exercise training group also had lower systolic blood pressure and resting heart rate after surgery. The quality of evidence for these outcomes was moderate to very low. CONCLUSIONS: Physical exercise after bariatric surgery provides 1.94 kg additional weight loss and 29.67 m longer 6MWD compared with surgery alone. Moreover, engaging in exercise 1 year or more after surgery, and a combined aerobic and resistance training programme may result in greater weight loss.

GRGM-13 comprising 13 plant and animal products, inhibited oxidative stress induced apoptosis in retinal ganglion cells by inhibiting P2RX7/p38 MAPK signaling pathway.

OBJECTIVE: To determine the effectiveness of GRGM-13 on oxidative stress induced apoptosis of retinal ganglion cells (RGCs) and revealed its possible mechanism. MATERIALS AND METHODS: Caspase-3 activity, MDA level, and glutathione peroxidase level were detected by Caspase-3 assay kit, Lipid Peroxidation MDA Assay Kit, and Total Glutathione Peroxidase Assay Kit, respectively. Protein levels of Bax, Bcl-2, p-p38 and p38 were observed by Western Blot. Reactive oxygen species assay kit was used to determine intracellular ROS level. Apoptotic cells were measured by flow cytometry. RESULTS: GRGM-13 inhibited apoptosis of RGCs and ROS level in rat retinal tissue and RGC-5 cells, and the decrease degree strengthened with the increase of GRGM-13 concentration. In addition, ROS upregulated p-p38 expression, while GRGM-13 reversed this effect. We also found that p38 inhibitor SB202190 did not change L-glutamate (Glu) or H2O2-induced ROS level, while SB202190 inhibited apoptosis of RGC-5 cells. Finally, we observed that P2 × 7R agonist BzATP reversed the inhibition effect of GRGM-13 on RGC-5 cell apoptosis, ROS level and p-p38 expression, while si-P2 × 7R inhibited oxidative stress-induced phosphorylation of p38. CONCLUSION: GRGM-13 could inhibit oxidative stress-induced RGCs apoptosis via inhibiting P2RX7/p38 MAPK pathway, which revealed the possible mechanism of GRGM-13 on stress-induced RGCs apoptosis and provided new Chinese medicine for the treatment of glaucoma.