Recent advances in optical aptasensors for biomarkers in early diagnosis and prognosis monitoring of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) accounts for approximately 90% of all primary liver cancers and is one of the main malignant tumor types globally. It is essential to develop rapid, ultrasensitive, and accurate strategies for the diagnosis and surveillance of HCC. In recent years, aptasensors have attracted particular attention owing to their high sensitivity, excellent selectivity, and low production costs. Optical analysis, as a potential analytical tool, offers the advantages of a wide range of targets, rapid response, and simple instrumentation. In this review, recent progress in several types of optical aptasensors for biomarkers in early diagnosis and prognosis monitoring of HCC is summarized. Furthermore, we evaluate the strengths and limitations of these sensors and discuss the challenges and future perspectives for their use in HCC diagnosis and surveillance.

Baicalin modulates let-7i-3p/PI3K/Akt/NF-KB signaling axis to reduce NLRP3 inflammasome activation in fibroblast like synoviocytes of rheumatoid arthritis / 中国药理学通报

Aim To study the effect of baicalin on the activation of NLRP3 inflammasomes in human fibroblast like synoviocytes of rheumatoid arthritis ( HFLS-RA) and its mechanism. Methods To confirm that baicalin alleviated the activation of NLRP3 inflammasome in HFLS-RA, immunofluorescence was used to observe the expression of NLRP3 before and after baicalin treatment. Western blot was used to detect the protein expression of p-PI3K, p-Akt, NF-κB p65, NL-RP3, ASC and caspase-1 after baicalin treatment for 48 h, and ELISA was employed to detect the contents of IL-1 and IL-18 in the supernatents. In order to explore the mechanism of baicalin alleviating the activation of NLRP3 inflammasome, double luciferin and Westen blot analysis were applied to verify the corresponding relationship between let-7i-3p and PIK3CA. RT-qPCR was utilized to determine the expression of let-7i-3p and PI3K before and after baicalin intervention. let-7i-3p interference was used to verify whether baicalin mitigated the activation of enhanced NLRP3 inflammasomes. Results Baicalin (50, 100 mg · L

Autophagy Modulates the Migration of Retinal Pericytes Induced by Advanced Glycation End Products.

Retinal pericyte migration occurs in the early stage of diabetic retinopathy (DR), which is one of the important causes of pericyte loss. Autophagy has been found to play essential roles in the regulation of many types of cell migration. In this study, we explored the relationship between autophagy and retinal pericyte migration. In diabetic rats, the retinas became thinner, and the level of autophagy in each cell layer increased. In the primary culture of bovine retinal pericytes, we found that advanced glycation end products (AGEs) increased the migratory cell ability without influencing cell viability, which also increased the phosphorylation of focal adhesion kinase (FAK) and the expression of matrix metalloproteinase (MMP)-2 and decreased the expression of vinculin. AGEs-induced retinal pericyte autophagy and the inhibition of autophagy with chloroquine significantly inhibited cell migration, reversed AGEs-induced FAK phosphorylation, and changed vinculin and MMP-2 protein expression. These results provide a new insight into the migration mechanism of retinal pericytes. The early control of autophagy has a potential effect on regulating pericyte migration, which may contribute to keeping the integrity of retinal vessels in DR.

Investigating the impact of oral health on pregnancy and offspring outcomes: protocol for the Lifetime Impact of ORal heAlth (LIORA) cohort study.

INTRODUCTION: Oral health is a fundamental component of well-being, and is closely associated with overall health and quality of life. Oral health may also affect the next generation. The children of mothers with poor oral health are likely to also have poor oral health as they go through life. We aim to investigate associations between maternal oral health and general health, pregnancy outcomes, offspring oral health and offspring general health. METHODS AND ANALYSIS: The Lifetime Impact of Oral Health study is a prospective, observational cohort study being done at a single centre in Chongqing, China. A total of 1000 pregnant women will be recruited in their first trimester (11-14 weeks gestation). After obtaining informed consent, general and oral health assessments will be undertaken. Maternal lifestyle, demographic data and biospecimens (blood, hair, urine, nail clippings, saliva, dental plaque, buccal, vaginal and anal swabs) will be collected. Pregnancy outcomes will be recorded at the time of delivery. Cord blood and placenta samples will be collected. The offspring will be followed up for general and oral health examinations, neurodevelopmental assessments and biospecimen (dental plaque, saliva, buccal swabs, exfoliated primary dentition, urine, hair, nail clippings) collection until they are 15 years old. Biological samples will undergo comprehensive metabolomic, microbiome and epigenome analyses. Associations between maternal oral health and general health, pregnancy outcomes, offspring oral health and offspring general health will be investigated and the underlying mechanisms explored. ETHICS AND DISSEMINATION: This project has been approved by the Research Ethics Committee of the Affiliated Hospital of Stomatology of Chongqing Medical University (CQHS-REC-2021 LSNo.23). Participants will be required to provide informed consent to participate in the study. Dissemination of findings will take the form of publications in peer-reviewed journals and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2100046898.

How likely is septic shock to develop in a patient with Fournier's gangrene? A risk prediction model based on a 7-year retrospective study.

Background: Fournier's gangrene (FG) is a rare life-threatening form of necrotizing fasciitis. The risk factors for septic shock in patients with FG are unclear. This study aimed to identify potential risk factors and develop a prediction model for septic shock in patients with FG. Methods: This retrospective cohort study included patients who were treated for FG between May 2013 and May 2020 at the Sixth Affiliated Hospital, Sun Yat-sen University (Guangzhou, China). The patients were divided into a septic shock group and a non-septic shock group. An L1-penalized logistic regression model was used to detect the main effect of important factors and a penalized Quadratic Discriminant Analysis method was used to identify possible interaction effects between different factors. The selected main factors and interactions were used to obtain a logistic regression model based on the Bayesian information criterion. Results: A total of 113 patients with FG were enrolled and allocated to the septic shock group (n = 24) or non-septic shock group (n = 89). The best model selected identified by backward logistic regression based on Bayesian information criterion selected temperature, platelets, total bilirubin (TBIL) level, and pneumatosis on pelvic computed tomography/magnetic resonance images as the main linear effect and Na+ × TBIL as the interaction effect. The area under the ROC curve of the probability of FG with septic shock by our model was 0.84 (95% confidence interval, 0.78-0.95). The Harrell's concordance index for the nomogram was 0.864 (95% confidence interval, 0.78-0.95). Conclusion: We have developed a prediction model for evaluation of the risk of septic shock in patients with FG that could assist clinicians in identifying critically ill patients with FG and prevent them from reaching a crisis state.

A novel role of FoxO3a in the migration and invasion of trophoblast cells: from metabolic remodeling to transcriptional reprogramming.

BACKGROUND: The forkhead box O3a protein (FoxO3a) has been reported to be involved in the migration and invasion of trophoblast, but its underlying mechanisms unknown. In this study, we aim to explore the transcriptional and metabolic regulations of FoxO3a on the migration and invasion of early placental development. METHODS: Lentiviral vectors were used to knock down the expression of FoxO3a of the HTR8/SVneo cells. Western blot, matrigel invasion assay, wound healing assay, seahorse, gas-chromatography-mass spectrometry (GC-MS) based metabolomics, fluxomics, and RNA-seq transcriptomics were performed. RESULTS: We found that FoxO3a depletion restrained the migration and invasion of HTR8/SVneo cells. Metabolomics, fluxomics, and seahorse demonstrated that FoxO3a knockdown resulted in a switch from aerobic to anaerobic respiration and increased utilization of aromatic amino acids and long-chain fatty acids from extracellular nutrients. Furthermore, our RNA-seq also demonstrated that the expression of COX-2 and MMP9 decreased after FoxO3a knockdown, and these two genes were closely associated with the migration/invasion progress of trophoblast cells. CONCLUSIONS: Our results suggested novel biological roles of FoxO3a in early placental development. FoxO3a exerts an essential effect on trophoblast migration and invasion owing to the regulations of COX2, MMP9, aromatic amino acids, energy metabolism, and oxidative stress.

Development and Validation of a BMI-Based Figure Rating Scale for Chinese Adolescents.

Figure rating scales (FRS) have been widely used to measure body dissatisfaction. In the current study, an FRS based on body mass index (BMI) and body shape of Chinese adolescents (C-BMI-FRS) was developed and validated. The perceived actual figure chosen from C-BMI-FRS by 2,237 Chinese adolescents aged 15-18 years old correlated strongly with BMI (r = .83 in girls and r = .80 in boys). Additionally, there was a strong relation between actual and ideal figure discrepancy (AID) scores and measures of body satisfaction (r = -.54 in girls, r = -.28 in boys) and eating disorder symptoms (r = .54 in girls, and r = .52 in boys). There also were moderate associations of AID scores with self-esteem (r = -.16) and negative affect (r = .18) in girls. Test-retest reliability over an 8- to 10 -week interval exceeded .57 for actual figure, ideal figure, and AID scores. Overall, findings support the utility of C-BMI-FRS as a measure of body dissatisfaction among Chinese adolescents.

Validation of the Chinese Version of the Body Image Concern Inventory.

The Body Image Concern Inventory (BICI) was developed to assess dysmorphic appearance concern and has been found to be a reliable and valid instrument in Western societies. To examine the psychometric properties of a new Chinese BICI, the BICI was administered to 1,231 Chinese young adults (Study 1) and 47 female patients with eating disorders and 56 matched controls (ED; Study 2). In study 1, Cronbach's alpha of .92 and test-retest reliability of .73 over a 6-month interval was observed for the total scale. Confirmatory factor analysis supported a 3-factor model for the BICI: avoidant behaviors (AB), safety behaviors against perceived flaws (SB), and negative appearance evaluation (NE). In study 2, ED patients scored significantly higher on the BICI total and three subscale scores than controls. In addition, AB best differentiated ED patients and matched controls (Cohen's d = 1.52); SB best differentiated between the non-clinical female and male groups (Cohen's d = 0.75); NE was most closely associated with level of negative affect and subjective well-being (inverse relationship) in both clinical and non-clinical groups. In conclusion, the Chinese BICI is a reliable and valid tool for evaluating dysmorphic appearance concern among Chinese speakers.

Scalp Acupuncture Protects Against Neuronal Ferroptosis by Activating The p62-Keap1-Nrf2 Pathway in Rat Models of Intracranial Haemorrhage.

Intracerebral haemorrhage (ICH) can be a catastrophic event; even if the initial stages of the pathology were well-managed, a number of patients experience varied residual neurological deficits following the insult. Ferroptosis is a recently identified type of cell demise which is tightly linked to the neurological impairment associated with ICH. In the current work, the prophylactic impact of scalp acupuncture (SA) therapy on autologous blood injection murine models of ICH was investigated in order to establish whether SA could mitigate the secondary damage arising following ICH by moderating ferroptosis. The pathophysiological mechanisms associated with this process were also explored. Ludmila Belayev tests were utilised for the characterisation of neurological damage. Haematoxylin-eosin staining was employed in order to determine the cerebral impact of the induced ICH. Malondialdehyde (MDA) and iron titres in peri-haemorrhagic cerebral tissues were appraised using purchased assay kits. Transmission electron microscopy delineated mitochondrial appearances within nerve cell bodies from the area of haemorrhage. Western blotting techniques were utilised to assay the degree of protein expression of NeuN, sequestosome 1 (p62), nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1). The frequencies of Nrf2, GPX4 and FTH1 positive cells, respectively, were documented with immunohistochemical staining. The results demonstrated that therapy with SA after ICH mitigated MDA and iron sequestration, diminished the appearance of contracted mitochondria with increased outer mitochondrial membrane diameter within the nerve cell bodies, and suppressed neuronal ferroptosis. The pathways responsible for these effects may encompass amplified p62, Nrf2, GPX4 and FTH1 expression, together with decreased Keap1 expression. Application of SA reduced identified neurobehavioural abnormalities after ICH; no disparities were observed between the consequences of SA therapy and deferoxamine delivery. It can be surmised that intervention with SA enhanced recovery after ICH by triggering the antioxidant pathway, p62/Keap1/Nrf2, and causing FTH1 and GPX4 upregulation, factors that participate in diminishing excess iron and thus in mitigating lipid peroxidation insults arising from ferroptosis following ICH.

Analysis on occupational noise deafness in a provincial occupational disease diagnosis institution from 2016 to 2020 / 中国职业医学

@#Objective - （ ） To analyze the epidemiological characteristics of occupational noise induced deafness ONID （ ） diagnosed by Guangdong Province Hospital of Occupational Disease Prevention and Control GDHOD from 2016 to 2020 and - Methods the reasons non ONID diagnosis. The data of ONID patients diagnosed in GDHOD from 2016 to 2020 were collected “ from the Occupational Disease Report Card in the Occupational Disease and Occupational Health Information Monitoring ” “ ” - System subsystem of the China Disease Prevention and Control Information System . The data of non ONID subjects were ， collected from the occupational disease diagnosis archives in the same hospital and the relevant data were analyzed Results ， ， （ ） retrospectively. Of the 1 432 subjects 824 subjects were diagnosed as ONID patients mainly of mild ONID 86.0% . （M） ， M Male patients accounted for 88.0%. The median of diagnosis age was 45.0 years old and of length of employment of ， ， ， diagnosis was 8.3 years. ONID patients were mainly found in Zhongshan Dongguan Zhuhai Jiangmen and Guangzhou City in ， ， （ ） the Pearl River Delta accounting for 67.6%. The cases distributed in 519 enterprises mainly on manufacturing 90.2% . ， - ， ； Among the 139 enterprises each enterprise had 2 11 patients worked within five years accounting for 53.9% 91.1% of the -， - - - ONID patients were distributed in large medium and small enterprises. ONID patients mainly worked in non public enterprises that accounted for 91.3%. There were 606 subjects could not be diagnosed as ONID. The main reasons for not being （ ）， diagnosed were that the weighted value of better ear hearing threshold was less than 26 dB 34.8% the working history of （ ）， occupational noise exposure was less than three years 31.5% the weighted value of better ear hearing threshold was less thanConclusion 26 dB and the average hearing threshold of binaural high frequency was less than 40 dB 16.2% . The ONID ， ， -， - patients have the characteristics of group aggregation. The Pearl River Delta manufacturing industry large medium and - - ： small non public enterprises are the key points of ONID prevention. The main reasons for not being diagnosed as ONID were ， the working history of occupational noise exposure was less than three years the weighted value of better ear hearing threshold ， - was less than 26 dB and the average high frequency hearing threshold of both ears was less than 40 dB.

Resting frontal EEG asymmetry and schizotypal traits: a test-retest study.

Introduction: Increase in right relative to left frontal electroencephalography (EEG) activity has been observed in patients with schizophrenia, both in cognitive tasks and during rest; and this lateralisation may be related to the severity of schizotypal traits. Methods: We used the Schizotypal Personality Questionnaire (SPQ) to assess schizotypal traits, and examined the correlation between these traits and resting EEG frontal asymmetry (left-right) in 52 college students, as well as the reliability of this correlation over a three-month interval. Results: A higher total score on the SPQ was correlated with reduced asymmetry in different frequency bands: gamma and beta2 frequency bands at baseline, and delta and alpha frequency bands three months later. Additionally, the reduced left relative to right frontal gamma and beta2 asymmetry was correlated with the participants' verbal fluency ability. However, this correlation was no longer statistically significant after the total SPQ score was controlled. Conclusions: These findings suggest that resting frontal EEG asymmetry is correlated with powers in different frequency bands, and may be an endophenotype for schizophrenia spectrum disorders.

Neuroprotective Role of GLP-1 Analog for Retinal Ganglion Cells via PINK1/Parkin-Mediated Mitophagy in Diabetic Retinopathy.

GLP-1 analogs have been widely used to treat patients with type 2 diabetes in recent years and studies have found that GLP-1 analogs have multiple organ benefits. However, the role of GLP-1 analogs in diabetic retinopathy (DR), a common complication of diabetes mellitus (DM), remains controversial. Retinal ganglion cells (RGCs) are the only afferent neurons responsible for transmitting visual information to the visual center and are vulnerable in the early stage of DR. Protection of RGC is vital for visual function. The incretin glucagon-like peptide-1 (GLP-1), which is secreted by L-cells after food ingestion, could lower blood glucose level through stimulating the release of insulin. In the present study, we evaluated the effects of GLP-1 analog on RGCs both in vitro and in vivo. We established diabetic rat models in vivo and applied an RGC-5 cell line in vitro. The results showed that in high glucose conditions, GLP-1 analog alleviated the damage of RGCs. In addition, GLP-1 analog prevented mitophagy through the PINK1/Parkin pathway. Here we demonstrated the neuroprotective effect of GLP-1 analog, which may be beneficial for retinal function, and we further elucidated a novel mechanism in GLP-1 analog-regulated protection of the retina. These findings may expand the multi-organ benefits of GLP-1 analogs and provide new insights for the prevention of DR.

Semantic processing event-related potential features in patients with schizophrenia and bipolar disorder.

Impairment in semantic association has been reported in bipolar disorder (BD) and schizophrenia (SZ) patients and could underlie abnormal speech patterns in both disorders. In this study, we compared the electrophysiological semantic processing features in patients with these two disorders. Participants (n = 61; BD = 19; SZ = 19; healthy controls [HCs] = 23) were administered a semantic judgment task and event-related potentials (ERPs) were recorded. Responses of the two patient groups were significantly slower than HCs, but comparable behavioral semantic priming effects were observed in both patient groups. The N400 priming effect was observed in all groups, with a delayed peak in the two patient groups. The N400 effect was enhanced for both BD and SZ patients over the left frontal and frontal pole region, but SZ patients showed additional reduction of N400 over the right posterior and occipital regions. The N400 mean amplitudes for related targets correlated with less severe negative symptoms in patients with SZ. Discriminant functional analysis using reaction time and N400 measures successfully classified 82% of the participants into their respective clinical groups. These results suggest that patients with BD and SZ have both overlapping and distinctive semantic processing dysfunction. These findings are consistent with the continuum conceptualization of these disorders, but also offer some support for the traditional Kraepelinian dichotomy.

Associations Between Thyroid Hormones Within the Euthyroid Range and Indices of Obesity in Obese Chinese Women of Reproductive Age.

Background: A number of researches have reported that thyroid hormones are associated with obesity. However, the relationship of serum levels of thyroid hormones in the normal range with obesity and parameters of obesity in women of childbearing age remains controversial. The purpose of this study was to examine serum levels of thyroid hormones within the normal range in obese Chinese women of reproductive age and to investigate the relationship between concentration of thyroid hormones and indices of obesity, including body mass index (BMI), waist-to-hip ratio (WHR), insulin resistance, blood glucose, blood lipids, and blood pressure. Methods: One hundred fifty-one obese women of reproductive age and 160 nonobese women of reproductive age were enrolled in this study. Serum levels of thyroid-stimulating hormone (TSH) of all subjects were within the normal reference range (0.35-4.94 mIU/L). The serum levels of free triiodothyronine (FT3), free thyroxine (FT4), and TSH, height, body weight, BMI, waist and hip circumferences, WHR, fasting blood glucose (FBG), fasting insulin (FI), homeostasis model assessment of insulin resistance (HOMA-IR), total triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured in all subjects. Quantile regression analysis was used to analyze the associations of serum levels of FT3, FT4, and TSH with values of BMI, WHR, FBG, FI, HOMA-IR, TG, TC, LDL-C, HDL-C, SBP, and DBP. Results: In the group of obese women, serum levels of FT4 were lower (P < 0.001) and serum levels of TSH were higher (P < 0.001) compared with nonobese controls. After adjusting for covariables, quantile regression analysis showed that serum levels of FT4 were inversely associated with BMI values between the quantile levels of 0.29 and 0.60 of BMI (i.e., BMI level of 22.49 and 28.31 kg/m2, respectively). Meanwhile, we found that serum levels of TSH positively correlated with BMI values after the quantile level of 0.51 (i.e., BMI level of 27.06 kg/m2), positively associated with TC after the quantile level of 0.6 (i.e., TC level of 4.86 mM), and positively associated with LDL-C after the quantile level of 0.39 (i.e., LDL level of 1.96 mM). No significant associations were found between serum levels of thyroid hormones and values of WHR, FBG, FI, HOMA-IR, TG, HDL-C, SBP, and DBP. Conclusions: FT4 and TSH play an important role in regulating the weight in women with normal thyroid function during their reproductive years. Women with decreased serum FT4 or increased serum TSH levels have a higher risk of developing obesity. Besides, TSH has a significant influence on metabolism of blood lipids. Women with higher serum levels of TSH have a higher risk of incidence of lipid metabolism disorders.

[Optimum nitrogen application rate to maximum yield and environment protection for winter wheat in Weibei dryland, China.] / æ¸­åŒ—æ—±å¡¬å ¼é¡¾å†¬å°éº¦äº§é‡å’ŒçŽ¯å¢ƒæ•ˆç›Šçš„å†œç”°é€‚å®œæ°®è‚¥ç”¨é‡.

To get the optimum nitrogen (N) fertilization rate which could guarantee wheat yield and protect environment, we examined wheat yield, N use efficiency, apparent N loss and soil N balance in Weibei dryland with a 3-year field experiment. The results showed that annual wheat yield increased and then decreased as N application rate increased in all the years with different annual rainfall, but the cumulative apparent N use efficiency significantly decreased. Higher yield and N use efficiency were obtained at the fertilization rate of 150 kg·hm-2. Residual nitrate-N concentrations significantly increased with the increases of N application rate. When the N application rate was between 75 and 150 kg·hm-2, the apparent N loss and loss rate were nearly the same, but if N application rate was higher than 150 kg·hm-2, the apparent loss and loss rate significantly increased. In conclusion, N application rate at 150 kg·hm-2 in Weibei dryland could guarantee high yield and N use efficiency, and simultaneously maintain residual nitrate-N concentration and reduce apparent N loss.

[Characteristics of Key Size Spectrum of PM2.5 Affecting Winter Haze Pollution in Taiyuan].

PM2.5 is generally considered as a main pollutant causing the formation of haze. Based on meteorological parameters, aerosol distribution, and PM monitoring data in Taiyuan during November and December 2016, the characteristics of the key size spectrum of PM2.5 affecting haze were discussed. During the observation period, haze was frequent and serious. Heavy haze time accounts for 25.35% of the total haze time. Haze events occurred frequently when the relative humidity was greater than 80% and wind speed was less than 1.5 m·s-1, especially for severe haze. Mild and moderate level haze occurred frequently when the relative humidity was less than 80% and greater than 40% and when wind speed was less than 1.5 m·s-1. Slight haze mainly occurred when the relative humidity was 20%-40% and the wind speed was 1.25-2.55 m·s-1. The average mass concentration of PM2.5 was 209.45 µg·m-3, which was three times the level during non-haze events. With an increase in the haze level, the mass concentration of PM2.5 and the ratio of PM2.5/PM10 increased. PM1 was the key particle size affecting haze in the low humidity environment. PM0.5 was the key particle size that affects slight haze, mild haze, and moderate haze in the high humidity environment, while PM1 was the key particle size that affects heavy haze. The contribution of surface concentration to visibility decreased with high humidity, but the particle size increased by moisture absorption leading to an increase in the extinction efficiency factor, which compensated for the lack of surface concentration. The increase in the particle size parameter was an important factor for PM2.5 affecting the haze pollution with high humidity.

Exenatide Delays the Progression of Nonalcoholic Fatty Liver Disease in C57BL/6 Mice, Which May Involve Inhibition of the NLRP3 Inflammasome through the Mitophagy Pathway.

OBJECTIVE: This study is aimed at investigating whether exenatide (Exe) delays the progression of nonalcoholic fatty liver disease (NAFLD) in C57BL/6 mice by targeting the NLRP3 inflammasome through the autophagy/mitophagy pathway. METHODS: Thirty male C57BL/6 mice were randomly divided into three groups: control group (n = 10), model group (n = 10), and Exe (exenatide) group (n = 10). Mouse models of NAFLD and diabetes were established using a high-fat diet and streptozocin. RESULTS: The levels of fasting blood glucose (FBG), total cholesterol (TC), and triglyceride (TG) in the serum were significantly reduced after Exe treatment. The body weight, liver weight/body weight, and number of lipid droplets in the liver significantly decreased in Exe-treated mice. Treatment with Exe markedly reduced the levels of liver lipids, malondialdehyde (MDA), and alanine aminotransferase (ALT) in serum and livers. The number of autophagosomes increased significantly in the Exe group. The expression of LC3A/B-II/I, Beclin-1, Parkin, and BNIP3L increased significantly, whereas NLRP3 and IL-1ß proteins were suppressed after Exe treatment. CONCLUSION: We successfully established a mouse model of NAFLD and diabetes. Exe may reduce oxidative stress injury and inhibit the NLRP3 inflammasome by enhancing the autophagy/mitophagy pathway in liver, which has a protective effect on the liver in NAFLD and diabetes in C57BL/6 mice.

Liraglutide attenuates the migration of retinal pericytes induced by advanced glycation end products.

Retinal pericyte migration represents a novel mechanism of pericyte loss in diabetic retinopathy (DR), which plays a crucial role in the early impairment of the blood-retinal barrier (BRB). Glucagon-like peptide-1 (GLP-1) has been shown to protect the diabetic retina in the early stage of DR; however, the relationship between GLP-1 and retinal pericytes has not been discussed. In this study, advanced glycation end products (AGEs) significantly increased the migration of primary bovine retinal pericytes without influencing cell viability. AGEs also significantly enhanced phosphatidylinositol 3-kinase (PI3K)/Akt activation, and changed the expressions of migration-related proteins, including phosphorylated focal adhesion kinase (p-FAK), matrix metalloproteinase (MMP)-2 and vinculin. PI3K inhibition significantly attenuated the AGEs-induced migration of retinal pericytes and reversed the overexpression of MMP-2. Glucagon-like peptide-1 receptor (Glp1r) was expressed in retinal pericytes, and liraglutide, a GLP-1 analog, significantly attenuated the migration of pericytes by Glp1r and reversed the changes in p-Akt/Akt, p-FAK/FAK, vinculin and MMP-2 levels induced by AGEs, indicating that the protective effect of liraglutide was associated with the PI3K/Akt pathway. These results provided new insights into the mechanism underlying retinal pericyte migration. The early use of liraglutide exerts a potential bebefical effect on regulating pericyte migration, which might contribute to mechanisms that maintain the integrity of vascular barrier and delay the development of DR.

Effects of downregulation of HIF-2α gene on biological behaviors of hepatoma cells induced by hypoxia in vitro / 中国免疫学杂志

Objective:To explore the effects of hypoxia-inducible factor 2α genes on under hypoxia on proliferation,apoptosis, cell cycle distribution and migration of invasiveness of human hepatocellular carcinoma cell HepG2.Methods: Human hepatoma cell line HepG2 induced by cobalt chloride (CoCl2) was selected as the research object,construction of siRNA specific carrier HIF-2α, transfection of HepG2 cells under hypoxia.Real-time PCR,Western blot method in the detection of before and after transfection in each group of HIF-2α mRNA and protein expression;MTT method to detect the proliferation of HepG2 cells before and after transfection;apoptosis rate and distribution of cell cycle of HepG2 cells before and after transfection were detected by flow cytometry;Transwell test was used to detect the invasion and migration ability of HepG2 cells before and after transfection.Results: Under hypoxia,significant increased HIF-2α expression in hepatocellular carcinoma HepG2 cells.Specific transfection of HIF-2α siRNA in HepG2 cells after HIF-2α mRNA and protein expression levels were significantly inhibit cell proliferation decreased,apoptosis rate increased in the ratio of G0/G1 phase cells increased synthesis phase (S) and late (G2/M) synthesis cell ratio decreased,which in vitro invasion and migration of cells was inhibited.Conclusion:Expression of HIF-2α increases in hepatocellular carcinoma HepG2 cells under hypoxia. Specific siRNA can be cut by HIF-2α gene expression in HepG2 cells under hypoxia,to inhibit HepG2 cell proliferation,invasion, migration,and change the distribution of cell cycle and induce its apoptosis.