Exosomes derived from umbilical cord-derived mesenchymal stem cells exposed to diabetic microenvironment enhance M2 macrophage polarization and protect against diabetic nephropathy.

The role of mesenchymal-stem-cell-derived exosomes (MSCs-Exo) in the regulation of macrophage polarization has been recognized in several diseases. There is emerging evidence that MSCs-Exo partially prevent the progression of diabetic nephropathy (DN). This study aimed to investigate whether exosomes secreted by MSCs pre-treated with a diabetic environment (Exo-pre) have a more pronounced protective effect against DN by regulating the balance of macrophages. Exo-pre and Exo-Con were isolated from the culture medium of UC-MSCs pre-treated with a diabetic mimic environment and natural UC-MSCs, respectively. Exo-pre and Exo-Con were injected into the tail veins of db/db mice three times a week for 6 weeks. Serum creatinine and serum urea nitrogen levels, the urinary protein/creatinine ratio, and histological staining were used to determine renal function and morphology. Macrophage phenotypes were analyzed by immunofluorescence, western blotting, and quantitative reverse transcription polymerase chain reaction. In vitro, lipopolysaccharide-induced M1 macrophages were incubated separately with Exo-Con and Exo-pre. We performed microRNA (miRNA) sequencing to identify candidate miRNAs and predict their target genes. An miRNA inhibitor was used to confirm the role of miRNAs in macrophage modulation. Exo-pre were more potent than Exo-Con at alleviating DN. Exo-pre administration significantly reduced the number of M1 macrophages and increased the number of M2 macrophages in the kidney compared to Exo-Con administration. Parallel outcomes were observed in the co-culture experiments. Moreover, miR-486-5p was distinctly expressed in Exo-Con and Exo-pre groups, and it played an important role in macrophage polarization by targeting PIK3R1 through the PI3K/Akt pathway. Reducing miR-486-5p levels in Exo-pre abolished macrophage polarization modulation. Exo-pre administration exhibited a superior effect on DN by remodeling the macrophage balance by shuttling miR-486-5p, which targets PIK3R1.

Global trends in research of venous thromboembolism associated with lower limb joint arthroplasty: A bibliometric analysis.

This study aims to visualize publications related to venous thromboembolism (VTE) and lower limb joint arthroplasty to identify research frontiers and hotspots, providing references and guidance for further research. We retrieved original articles published from 1985 to 2022 and their recorded information from the Web of Science Core Collection. The search strategy used terms related to knee or hip arthroplasty and thromboembolic events. Microsoft Excel was used to analyze the annual publications and citations of the included literature. The rest of the data were analyzed using the VOSviewer, citespace and R and produced visualizations of these collaborative networks. We retrieved 3543 original articles and the results showed an overall upward trend in annual publications. The United States of America had the most significant number of publications (Np) and collaborative links with other countries. McMaster University had the greatest Np. Papers published by Geerts WH in 2008 had the highest total link strength. Journal of Arthroplasty published the most articles on the research of VTE associated with lower limb joint arthroplasty. The latest research trend mainly involved "general anesthesia" "revision" and "tranexamic acid." This bibliometric study revealed that the research on VTE after lower limb joint arthroplasty is developing rapidly. The United States of America leads in terms of both quantity and quality of publications, while European and Canadian institutions and authors also make significant contributions. Recent research focused on the use of tranexamic acid, anesthesia selection, and the VTE risk in revision surgeries.

Causal role of immune cells in psoriasis: a Mendelian randomization analysis.

Background: A growing body of evidence has shown that immune cells are linked to psoriasis. It is, however, still unclear if these associations reflect a relationship of cause and effect. Objective: We employed a two-sample Mendelian randomization (MR)-based study to elucidate the probable causative connection between immune cells and psoriasis. Methods: Summary information for psoriasis (Ncase = 5,427, Ncontrol = 479,171) was obtained from the European Bioinformatics Institute. Summarized statistical information on 731 immune cell features, including morphological parameters (MP; n = 32), relative cell number (n = 192), median fluorescence intensity (MFI) of surface antigens (n = 389), and absolute cell number (n = 118), was obtained from the genome-wide association studies (GWAS) catalog. The research consisted of forward MR analysis, in which immune cell traits were used as the exposure factor, and psoriasis was the outcome, as well as reverse MR analysis, in which psoriasis was used as the exposure factor, and immune cell traits were the outcome. We ran numerous sensitivity analyses to ascertain the study results for robustness, heterogeneity, and potential multiple-biological effects. Result: This research determined a probable causative connection between immune cells and psoriasis. In particular, we identified 36 distinct types of immune cells that are potentially causally linked to psoriasis. Conclusion: Our findings indicate strong causal correlations between 36 immunological phenotypes and psoriasis, thus, directing future clinical trials.

The phenotype and related gene expressions of macrophages in adipose tissue of T2D mice following MSCs infusion.

BACKGROUND: Infusion of mesenchymal stem cells (MSCs) induces polarization of M2 macrophages in adipose tissue of type 2 diabetes (T2D) mice. Studies have shown that M2 macrophages were divided into four sub-phenotypes (M2a, M2b, M2c and M2d) with different functions, and manuscripts have also confirmed that macrophages co-cultured with MSCs were not matched with known four phenotype macrophages. Therefore, our study explored the phenotype and related gene expressions of macrophages in the adipose tissue of T2D mice with/without MSCs infusion. METHODS: We induced a T2D mouse model by using high-fat diets and streptozotocin (STZ) injection. The mice were divided into three groups: the control group, the T2D group, and the MSCs group. MSCs were systemically injected once a week for 6 weeks. The phenotype of macrophages in adipose tissue was detected via flow cytometric analysis. We also investigated the gene expression of macrophages in different groups via SMART-RNA-sequencing and quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). RESULTS: The present study found that the macrophages of adipose tissue in the MSCs group were polarized to the M2 phenotype mixed with four sub-phenotypes. Besides, M2a and M2c held a dominant position, while M2b and M2d (tumor-associated macrophages, TAMs) exhibited a decreasing trend after infusion of MSCs. Moreover, the MSCs group did not appear to express higher levels of tumor-associated, inflammation-associated, or fibrosis-associated genes in comparison to the T2D group. CONCLUSION: The present results unveiled that the macrophage phenotype was inclined to be present in a hybridity state of four M2 sub-phenotypes and the genes related to tumor-promoting, pro-inflammation and pro-fibrosis were not increased after MSCs injection.

The impact of adult children's support on the psychological health of rural older adult people in China.

Background: Family old-age care is dominant in Chinese rural society, and children's support is an important force in family old-age care. However, the migration of a large number of young and middle-aged rural laborers has undermined the traditional arrangements for old-age care in rural areas and affected the psychological health of the older adult. Methods: 2014 China Longitudinal Aging Social Survey targets Chinese citizens aged 60 or older and covers 28 provinces in mainland China. In this paper, the database of the CLASS was selected for empirical analysis to explore the impact of children's support on the depression level and loneliness of rural older adults through multiple linear regression, and was divided into two groups according to children's migration to analyze heterogeneity. Results: Children's financial support facilitates the maintenance of mental health among rural older adults. Children's support promotes mental health among rural older adults, but this association does not exist among older adults without children's migration. Individual characteristics of older people have a greater impact on mental health. Discussion: Our study firstly compares the differences of children's migration status between children's support and mental health among the older adult in rural China. In order to improve the mental health of the older adult, it is necessary to create a favorable atmosphere of love and respect for the older adult, improve the social security system in rural areas, and give full play to the strengths of the social forces, so as to ensure that the older adult have a sense of worthiness and enjoyment in their old age.

The association between brachial-ankle pulse-wave velocity and adverse cardiovascular events in 5719 community participants a prospective cohort study.

BACKGROUND: The brachial-ankle pulse-wave velocity (baPWV) is regarded as the gold standard in the evaluation of arterial stiffness. Its prognostic significance for major adverse cardiovascular events (MACE) has been demonstrated. However, the factors influencing the association between baPWV and MACE risk have not been determined. In this study, we investigated the association of baPWV and MACE risk and whether it is affected by the risk factors for different cardiovascular diseases (CVDs). METHODS: This was a prospective cohort study that initially enrolled 6850 participants from 12 communities in Beijing. The participants were divided into three subgroups according to their baPWV values. The primary outcome was the first occurrence of MACE, defined as hospitalization from cardiovascular diseases, first occurrence of a nonfatal myocardial infarction, or nonfatal stroke. Cox proportional hazards regression and restricted cubic spline analyses were used to examine the association between baPWV and MACE. The effect of CVD risk factors on the relationship between baPWV and MACE was explored in subgroup analyses. RESULTS: The final study population consisted of 5719 participants. During a median follow-up of 34.73 months, MACE occurred in 169 participants. The restricted cubic spline analysis indicated a positive linear relationship between baPWV and MACE risk. After adjustment for cardiovascular risk factors, the hazard ratio (HR) for MACE risk per SD increase in baPWV was 1.272 [95% confidence interval (CI): 1.149-1.407, P  < 0.001], and the HR for MACE in the high-baPWV vs. the low-baPWV group was 1.965 (95% CI: 1.296-2.979, P  = 0.001). Adding baPWV to the conventional cardiovascular risk factors significantly improved the model's prediction performance and the net reclassification (NRI) [NRI: 0.379 (95% CI: 0.072-0.710), P  = 0.025] in MACE discrimination. However, in the subgroup analysis, two CVD risk factors, stable coronary heart disease and hypertension, showed significant interaction effects ( Pinteraction both < 0.05). This result indicated that the effect of CVD risk factors must be taken into account when assessing the relationship between baPWV and MACE. CONCLUSION: baPWV is a potential marker to improve the identification of MACE risk in the general population. A positive linear correlation was firstly determined between baPWV and MACE risk, but it may not be valid in participants with stable coronary heart disease and hypertension.

Association between hemoglobin glycation index and 5-year major adverse cardiovascular events: the REACTION cohort study.

BACKGROUND: The hemoglobin glycation index (HGI) was developed to quantify glucose metabolism and individual differences and proved to be a robust measure of individual glycosylated hemoglobin (HbA1c) bias. Here, we aimed to explore the relationship between different HGIs and the risk of 5-year major adverse cardiovascular events (MACEs) by performing a large multicenter cohort study in China. METHODS: A total of 9791 subjects from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a Longitudinal Study (the REACTION study) were divided into five subgroups (Q1-Q5) with the HGI quantiles (≤5th, >5th and ≤33.3th, >33.3th and ≤66.7th, >66.7th and ≤95th, and >95th percentile). A multivariate logistic regression model constructed by the restricted cubic spline method was used to evaluate the relationship between the HGI and the 5-year MACE risk. Subgroup analysis between the HGI and covariates were explored to detect differences among the five subgroups. RESULTS: The total 5-year MACE rate in the nationwide cohort was 6.87% (673/9791). Restricted cubic spline analysis suggested a U-shaped correlation between the HGI values and MACE risk after adjustment for cardiovascular risk factors ( χ2 = 29.5, P <0.001). After adjustment for potential confounders, subjects with HGIs ≤-0.75 or >0.82 showed odds ratios (ORs) for MACE of 1.471 (95% confidence interval [CI], 1.027-2.069) and 2.222 (95% CI, 1.641-3.026) compared to subjects with HGIs of >-0.75 and ≤-0.20. In the subgroup with non-coronary heart disease, the risk of MACE was significantly higher in subjects with HGIs ≤-0.75 (OR, 1.540 [1.039-2.234]; P = 0.027) and >0.82 (OR, 2.022 [1.392-2.890]; P <0.001) compared to those with HGIs of ≤-0.75 or >0.82 after adjustment for potential confounders. CONCLUSIONS: We found a U-shaped correlation between the HGI values and the risk of 5-year MACE. Both low and high HGIs were associated with an increased risk of MACE. Therefore, the HGI may predict the 5-year MACE risk.

Analysis of metal(loid) pollution and possibilities of electrokinetic phytoremediation of abandoned coking plant soil.

In this study, the spatial distribution of eight metal(loid)s in the soil of an abandoned coking plant in Shanxi, China, was mapped, and the ecological and health risks of the coking plant were assessed. The results showed that the soil Pb content of the coking plant greatly exceeded the background value, and Hg, Cd and Pb were the most polluting factors contributing to the considerable ecological risk level. There was also a non-carcinogenic risk in the coking plant, in which oral intake was the main pathway, and As, Pb and Cr were the main contributors. As the main contributor to ecological risk and non-carcinogenic risks and the most polluting metal, Pb was selected as a priority pollutant in the coking plant. Based on the detected concentration of Pb in the coking plant soil and in consideration of phytostabilization, ryegrass, alfalfa and castor were employed to study the phytoremediation and electrokinetic-enhanced phytoremediation effect in a series of Pb-contaminated soils (0, 100, 200, 300 and 400 mg/kg). It was found that the underground parts of alfalfa and castor had stronger Pb enrichment ability, and their biomass and Pb absorption capacity were improved in electrokinetic remediation methods. The Pb absorption capacities of the tested plants and the promotion efficiencies of electrokinetic-enhanced phytoremediation followed the order castor > ryegrass > alfalfa. Under the optimal electrical conditions, the remediation efficiency of castor was increased by 106 %, 83 %, 51 % and 48 % in 100, 200, 300, and 400 mg/kg Pb-contaminated soils, respectively.

Mining the vaccination willingness of China using social media data.

OBJECTIVE: Vaccination is one of the most powerful and effective protective measures against Coronavirus disease 2019 (COVID-19). Currently, several blogs hold content on vaccination attitudes expressed on social media platforms, especially Sina Weibo, which is one of the largest social media platforms in China. Therefore, Weibo is a good data source for investigating public opinions about vaccination attitudes. In this paper, we aimed to effectively mine blogs to quantify the willingness of the public to get the COVID-19 vaccine. MATERIALS AND METHODS: First, data including 144,379 Chinese blogs from Weibo, were collected between March 24 and April 28, 2021. The data were cleaned and preprocessed to ensure the quality of the experimental data, thereby reducing it to an experimental dataset of 72,496 blogs. Second, we employed a new fusion sentiment analysis model to analyze the sentiments of each blog. Third, the public's willingness to get the COVID-19 vaccine was quantified using the organic fusion of sentiment distribution and information dissemination effect. RESULTS: (1) The intensity of bloggers' sentiment toward COVID-19 vaccines changed over time. (2) The extremum of positive and negative sentiment intensities occurred when hot topics related to vaccines appeared. (3) The study revealed that the public's willingness to get the COVID-19 vaccine and the actual vaccination doses shares a linear relationship. CONCLUSION: We proposed a method for quantifying the public's vaccination willingness from social media data. The effectiveness of the method was demonstrated by a significant consistency between the estimates of public vaccination willingness and actual COVID-19 vaccination doses.

Quinoa husk peptides reduce melanin content via Akt signaling and apoptosis pathways.

To improve the treatment of pigmentation disorders, looking for natural and safe inhibitors of melanin synthesis has become an area of research interest. The quinoa husk peptides reportedly elicit various biological activities (e.g., anti-cancer, antioxidant, anti-hypertensive, and so forth), but its effects on melanin inhibition remain unknown. In the current study, we purified quinoa husk peptides with 30 and 80% ethanol using a macroporous adsorption resin (DA201-C). Component screening revealed that the 80%-ethanol fraction (i.e., QHP fraction) contained numerous short peptides (84.41%) and hydrophobic amino acids (45.60%), while eliciting a superior tyrosinase [TYR]-inhibition rate, 2,2-diphenyl-1-picryhydrazil-scavenging rate, reducing activity, and chelating capacity compared to the 30% fraction and was thus applied in subsequent analyses. Differentially expressed genes in the QHP fraction were primarily enriched in the Akt-signaling pathways based on transcriptomics. Thus, we assessed the expression of related proteins and genes in A375 cells and rat skin cells following treatment with QHP.

Development and validation of a new predictive model for macrosomia at late-term pregnancy: A prospective study.

Objective: Fetal macrosomia is defined as a birth weight more than 4,000 g and is associated with maternal and fetal complications. This early metabolic disease may influence the entire life of the infant. Currently, macrosomia is predicted by using the estimated fetal weight (EFW). However, the EFW is inaccurate when the gestational week is gradually increasing. To assess precisely the risk of macrosomia, we developed a new predictive model to estimate the risk of macrosomia. Methods: We continuously collected data on 655 subjects who attended regular antenatal visits and delivered at the Second Hospital of Hebei Medical University (Shijiazhuang, China) from November 2020 to September 2021. A total of 17 maternal features and 2 fetal ultrasonographic features were included at late-term pregnancy. The 655 subjects were divided into a model training set and an internal validation set. Then, 450 pregnant women were recruited from Handan Central Hospital (Handan, China) from November 2021 to March 2022 as the external validation set. The least absolute shrinkage and selection operator method was used to select the most appropriate predictive features and optimize them via 10-fold cross-validation. The multivariate logistical regressions were used to build the predictive model. Receiver operating characteristic (ROC) curves, C-indices, and calibration plots were obtained to assess model discrimination and accuracy. The model's clinical utility was evaluated via decision curve analysis (DCA). Results: Four predictors were finally included to develop this new model: prepregnancy obesity (prepregnancy body mass index ≥ 30 kg/m2), hypertriglyceridemia, gestational diabetes mellitus, and fetal abdominal circumference. This model afforded moderate predictive power [area under the ROC curve 0.788 (95% confidence interval [CI] 0.736, 0.840) for the training set, 0.819 (95% CI 0.744,0.894) for the internal validation set, and 0.773 (95% CI 0.713,0.833) for the external validation set]. On DCA, the model evidenced a good fit with, and positive net benefits for, both the internal and external validation sets. Conclusions: We developed a predictive model for macrosomia and performed external validation in other regions to further prove the discrimination and accuracy of this predictive model. This novel model will aid clinicians in easily identifying those at high risk of macrosomia and assist obstetricians to plan accordingly.

Bone and mineral metabolism in patients with primary aldosteronism: A systematic review and meta-analysis.

Purpose: Patients with primary aldosteronism (PA) tend to exhibit a high prevalence of osteoporosis (OP) that may vary by whether PA is unilateral or bilateral, and responsive to PA treatment. To explore relationships between bone metabolism, PA subtypes, and treatment outcomes, we performed a systematic review and meta-analysis. Methods: The PubMed, Embase, and Cochrane databases were searched for clinical studies related to PA and bone metabolism markers. Articles that met the criteria were screened and included in the systematic review; the data were extracted after evaluating their quality. R software (ver. 2022-02-16, Intel Mac OS X 11.6.4) was used for the meta-analysis. Results: A total of 28 articles were subjected to systematic review, of which 18 were included in the meta-analysis. We found that PA patients evidenced a lower serum calcium level (mean difference [MD] = -0.06 mmol/L, 95% confidence interval [CI]: -0.10 ~ -0.01), a higher urine calcium level (MD = 1.29 mmol/24 h, 95% CI: 0.81 ~ 1.78), and a higher serum parathyroid hormone (PTH) level (MD = 2.16 pmol/L, 95% CI: 1.57 ~ 2.75) than did essential hypertension (EH) subjects. After medical treatment or adrenal surgery, PA patients exhibited a markedly increased serum calcium level (MD = -0.08 mmol/L, 95% CI: -0.11 ~ -0.05), a decreased urine calcium level (MD = 1.72 mmol/24 h, 95% CI: 1.00 ~ 2.44), a decreased serum PTH level (MD = 2.67 pmol/L, 95% CI: 1.73 ~ 3.62), and an increased serum 25-hydroxyvitamin D (25-OHD) level (MD = -6.32 nmol/L, 95% CI: -11.94 ~ -0.70). The meta-analysis showed that the ser um PTH level of unilateral PA patients was significantly higher than that of bilateral PA patients (MD = 0.93 pmol/L, 95% CI: 0.36 ~ 1.49) and the serum 25-OHD lower than that of bilateral PA patients (MD = -4.68 nmol/L, 95% CI: -7.58 ~ 1.77). There were, however, no significant differences between PA and EH patients of 25-OHD, or BMD of femoral neck and lumbar spine. BMDs of the femoral neck or lumbar spine did not change significantly after treatment. The meta-analytical results were confirmed via sensitivity and subgroup analyses. Conclusion: Excess aldosterone was associated with decreased serum calcium, elevated urinary calcium, and elevated PTH levels; these effects may be enhanced by low serum 25-OHD levels. The risks of OP and fracture might be elevated in PA patients, especially unilateral PA patients, but could be reduced after medical treatment or adrenal surgery. In view, however, of the lack of BMD changes, such hypothesis needs to be tested in further studies.

Evolutionary conservation of nested MIR159 structural microRNA genes and their promoter characterization in Arabidopsis thaliana.

MicroRNAs (miRNAs) are endogenous small RNAs, that are vital for gene expression regulation in eukaryotes. Whenever a pri-miRNA precursor includes another miRNA precursor, and both of these precursors may generate independent, non-overlapping mature miRNAs, we named them nested miRNAs. However, the extent of nested miR159 structural evolutionary conservation and its promoter characterization remains unknown. In this study, the sequence alignment and phylogenetic analysis reveal that the MIR159 family is ancient, and its nested miR159 structures are evolutionary conserved in different plant species. The overexpression of ath-MIR159a, including the 1.2 kb downstream region, has no effect on rescuing the mir159ab phenotype. The promoter truncation results revealed that the 1.0 kb promoter of ath-MIR159a is sufficient for rescuing the mir159ab phenotype. The cis-regulatory elements in the ath-miR159a promoters indicated functions related to different phytohormones, abiotic stresses, and transcriptional activation. While the MybSt1 motif-containing region is not responsible for activating the regulation of the miR159a promoter. The qRT-PCR results showed that overexpression of ath-MIR159a led to high expression levels of miR159a.1-5 and miR159a.1-3 and complemented the growth defect of mir159ab via downregulation of MYB33 and MYB65. Furthermore, continuously higher expression of the miR159a.2 duplex in transgenic lines with the curly leaf phenotype indicates that miR159a.2 is functional in Arabidopsis and suggests that it is possible for a miRNA precursor to encode several regulatory small RNAs in plants. Taken together, our study demonstrates that the nested miR159 structure is evolutionary conserved and miRNA-mediated gene regulation is more complex than previously thought.

Nested miRNA Secondary Structure Is a Unique Determinant of miR159 Efficacy in Arabidopsis.

MicroRNAs (miRNAs) are 20- to 24-nucleotide small RNAs, and whenever a pri-miRNA precursor includes another miRNA precursor, and both of these precursors may generate independent non overlapping mature miRNAs, we called them nested miRNAs. However, the functional and regulatory roles of nested miRNA structures in plants are still unknown. In this study, the Arabidopsis nested miR159a structure, which consists of two nested miRNAs, miR159a.1, and miR159a.2, was used as a model to determine miRNA-mediated gene silencing in plants. Complementation analysis of nested miR159a structures revealed that the miR159a structure can differentially complement the mir159ab phenotype, and a duplex nested structure in the tail end region of the pre-miR159a fold back may have a possible dominant function, indicating the importance of the flanking sequence of the stem in the cleavage of the mature miRNA. Furthermore, continuously higher expression of the miR159a.2 duplex in the severe leaf curl phenotype indicates that miR159a.2 is functional in Arabidopsis and suggests that in plants, a miRNA precursor may encode multiple regulatory small RNAs. Taken together, our study demonstrates that the nested miR159a structure regulated by duplex mutations of miR159a has a unique pattern and provides novel insight into silencing efficacy of Arabidopsis miR159a.

Therapeutic effects of alteplase intravenous thrombolysis on different types of acute cerebral infarction: a controlled randomized analysis.

OBJECTIVE: To test the effects of alteplase (PA) intravenous thrombolysis on different types of acute cerebral infarction (ACI). METHODS: One hundred and ten patients with the ACI admitted from April 2018 to April 2019 were selected and randomly assigned to a research group and a reference group equally. The two groups received conventional treatment with a subcutaneous injection of low molecular weight heparin calcium of 5000 IU, and the research group received additional PA intravenous thrombolysis treatment. The therapeutic effects of the two groups were compared. RESULTS: There were no significant differences in terms of general information and National Institutes of Health Stroke Scale (NIHSS) score at T0 (P>0.05) between the two groups; the research group garnered better results in the NIHSS scores at T1, T2, T3, and T4 than the reference group (P<0.001); a decrease was found in the Modified Rankin Scale (MRS) after treatment (P<0.001), with lower scores in the research group (P<0.001); the research group obtained a higher total effective rate than the reference group (P<0.05). Remarkably higher Barthel scores of the two groups after treatment were found (P<0.001), with higher scores collected from the research group (P<0.001); patients in the research group enjoyed a lower incidence of bleeding events than the reference group (P<0.05). The levels of Interleukin-1ß (IL-1ß), high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor alpha (TNF-α), superoxide dismutase (SOD), glutathione peroxidase (GSH-px), and malondialdehyde (MDA) were apparently optimized after treatment, with superior results observed in the research group (P<0.05). CONCLUSION: PA intravenous thrombolysis effectively improves the neurological function of patients with different types of ACI and their quality of life, and reduces bleeding events, which is worthy of promotion.

Empagliflozin improves chronic hypercortisolism-induced abnormal myocardial structure and cardiac function in mice.

BACKGROUND: Chronic exposure to excess glucocorticoids is frequently associated with a specific cardiomyopathy. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has beneficial effects as it aids in the reduction of heart failure and cardiovascular mortality in hospitalized patients. The aim of this study was to investigate the effects of empagliflozin on chronic hypercortisolism-induced myocardial fibrosis and myocardial dysfunction in mice. METHODS: Male C57BL/6J mice (6 weeks old) were randomized to control, corticosterone (CORT), and empagliflozin + CORT groups. After 4 weeks of administration, heart structure and function were evaluated by echocardiography, and peripheral blood and tissue samples were collected. Expressions of Ccl2, Itgax, Mrc1, and Adgre1 mRNA in heart tissue were evaluated by RT-PCR, and signal transducer and activator of transcription 3 (STAT3) and Toll-like receptor 4 (TLR4) protein expression were analyzed by Western blotting. RESULTS: Empagliflozin effectively reduced body weight, liver triglyceride, visceral adipose volume, and uric acid in CORT-treated mice. Left ventricular hypertrophy and cardiac dysfunction were improved significantly, phosphorylated STAT3 and TLR4 were alleviated, and macrophage infiltration in the myocardium was inhibited after administration of empagliflozin in CORT-treated mice. CONCLUSION: Empagliflozin has beneficial effects on specific cardiomyopathy associated with CORT, and the results provide new evidence that empagliflozin might be a potential drug for the prevention of this disease.

Glucagon-like peptide-1 receptor agonists and risk of bone fracture in patients with type 2 diabetes: A meta-analysis of randomized controlled trials.

AIMS: To evaluate the association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and the risk of bone fracture in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We conducted a systematic literature search in PubMed, Embase, the Cochrane Library, and Web of Science from inception to 28 February 2018 and identified eligible randomized controlled trials. The following data were extracted from each study: first author, year of publication, sample size, patient characteristics, study design, intervention drug, control drug, follow-up time, and incident bone fracture events. A meta-analysis was conducted using Review Manager 5.3 software to calculate the odds ratio (OR) and 95% confidence intervals (CI) for dichotomous variables. RESULTS: A total of 38 studies with 39 795 patients with T2DM were included. There were 241 incident bone fracture cases (107 in the GLP-1 RAs group and 134 in the control group). Compared with patients who received placebo and other anti-diabetic drugs, those who received GLP-1 RAs treatment showed a pooled OR of 0.71 (95% CI, 0.56-0.91) for bone fracture. Subgroup analysis showed that treatments with liraglutide and lixisenatide were associated with significantly reduced risk of bone fractures (ORs, 0.56; 95% CI, 0.38-0.81 and 0.55; 95% CI, 0.31-0.97, respectively). However, other GLP-1 RAs did not show superiority to placebo or other anti-diabetic drugs. Moreover, these beneficial effects were dependent on the duration of GLP-1 RAs treatment, only a GLP-1 RAs treatment period of more than 52 weeks could significantly lower the risk of bone fracture in patients with T2DM (OR, 0.71; 95% CI, 0.56-0.91). CONCLUSIONS: Compared with placebo and other anti-diabetic drugs, liraglutide and lixisenatide were associated with a significant reduction in the risk of bone fractures, and the beneficial effects were dependent on the duration of treatment.

miR-125b Enhances IL-8 Production in Early-Onset Severe Preeclampsia by Targeting Sphingosine-1-Phosphate Lyase 1.

Preeclampsia (PE) is one of the leading causes of maternal and perinatal mortality and morbidity. One of the main hallmarks observed in PE is impaired inflammation state. In the current study, we found that miR-125b was deregulated in placental tissues and plasma derived from PE patients, which suggest a potential association between this miRNA and the pathogenesis of PE. Overexpression of miR-125b significantly reduced SGPL1 expression, and luciferase assays confirmed that SGPL1 is a direct target of miR-125b. We also found that miR-125b enhanced IL-8 production by directly targeting sphingosine-1-phosphate lyase 1 (SGPL1), and this effect could be reversed by SGPL1 overexpression. In placentas derived from PE patients, a negative correlation of miR-125b and SGPL1 was observed, and IL-8 was validated to be increased in the circulation of PE patients. Our data demonstrated a critical role of miR-125b in IL-8 production and the development of PE.

Fuzhisan ameliorates Aß production and tau phosphorylation in hippocampal of 11month old APP/PS1 transgenic mice: A Western blot study.

Accumulation of amyloid-ß (Aß) peptide and deposition of hyperphosphorylated tau protein are two major pathological hallmarks of Alzheimer's disease (AD). Glycogen synthase kinase-3ß (GSK3ß) is increasingly thought to play a pivotal role in the pathogenesis of AD, both as a regulator of the production of Aß and through its well-established role on tau phosphorylation. The phosphoinositide 3 kinase (PI3K)/Akt pathway plays an import role in neuronal survival and cognitive function, and is known as an upstream element of GSK3ß. Fuzhisan (FZS), a Chinese herbal complex prescription, has been used for the treatment of AD for over 20years, and is known to enhance the cognitive ability in AD patients as well as in AD model rats. However, it still remains unclear whether FZS is responsible for regulation of PI3K/AKT/GSK3ß signaling and contributes to subsequent down-regulation of Aß and phosphorylated tau. Thus, we treated APP/PS1 transgenic mice, a useful model of AD-related memory impairment, with FZS by intragastrical administration for 60days and Donepezil was used as a positive control. The results showed that treatment with FZS significantly reversed the memory deficit in the Tg APP/PS1 mice in the Morris water maze test. Moreover, FZS significantly attenuated Aß production through inhibition of APP procession and phosphorylation of tau in the hippocampus of Tg APP/PS1 mice. In addition, FZS treatment also increased PI3K and pSer473-AKT levels, inhibited GSK3ß activity by increasing phosphorylation of GSK3ß at Ser9. These results indicated that the memory ameliorating effect of FZS may be, in part, by regulation the PI3K/AKT/GSK3ß signaling which may contribute to down-regulation of Aß and tau hyperphosphorylation.

Layer-by-layer supramolecular assemblies based on linear and star-shaped poly(glycerol methacrylate)s for doxorubicin delivery.

Hollow microcapsules, composed of pH responsive polyelectrolytes via a layer-by-layer (LBL) adsorption technique, were prepared. Linear or star-shaped poly(glycerol metha crylate)s (PGOHMAs) modified with 1,4-butanediamine and 1,2-ethanediamine (EDA) were synthesized and used as polycations. Poly(acrylic acid) was employed as polyanion and SiO2 (about 170 nm) as template. After LBL absorption, SiO2 cores were removed by HF treatment. The particle size and zeta potential were measured by dynamic light scattering, showing that the diameter of star-shaped amino-PGOHMA was larger than linear counterpart. The LBL assembly and core-etching process were evidenced by scanning electron microscope, transmission electron microscope, and energy dispersive spectrometer. The cytotoxicity experiments on human umbilical vein endothelial cells were carried out to evaluate the toxicity of LBL assembly. The star-shaped and EDA-modified PGOHMA exhibited better cell viability. The microcapsules were then used to load an anticancer drug, doxorubicin hydrochloride. High loading capacity (about 42%) and entrapment efficiency (84%) were obtained for star-shaped polymer-based microcapsules. The cumulative release rate was evaluated in vitro, showing faster release at an acidic condition compared to neutral pH. Confocal laser scanning microscopy evidenced the successful cellular uptake of DOX-loaded microparticles.