Monodisperse Polyaspartic Acid Derivative Microspheres for Potential Tumor Embolization Therapy.

Polyaspartic acid derivatives are a well-known kind of polypeptide with good biocompatibility and biodegradability, and thus have been widely used as biomedical materials, including drug-loaded nano-scale micelles or macroscopic hydrogels. In this work, for the first time, monodisperse polyaspartic acid derivative microspheres with diameter ranging from 120 to 350 µm for potential tumor embolization therapy are successfully prepared by single emulsion droplet microfluidic technique. The obtained microsphere shows fast cationic anticancer drug doxorubicin hydrochloride loading kinetics with high loading capacity, which is much better than those of the commercial ones. Additionally, drug release behaviors of the drug-loaded microspheres with different diameters in different media are also studied and discussed in detail. These results provide some new insights for the preparation and potential application of polyaspartic acid derivative-based monodisperse microspheres, especially for their potential application as embolic agent.

Dapagliflozin ameliorates myocardial infarction injury through AMPKα-dependent regulation of oxidative stress and apoptosis.

Dapagliflozin (DAPA) has been demonstrated to reduce cardiovascular mortality and heart failure hospitalization rates in diabetic patients. However, the mechanism underlying its cardio-protective effect in non-diabetic patients remains unclear. Our study aimed to explore the cardio-protective impact of DAPA on myocardial infarction in non-diabetic mice. We induced myocardial infarction in C57BL/6 mice by ligating the descending branch of the left coronary artery. After surgery, the animals were randomly treated with either saline or DAPA. We employed echocardiography, Western blot analysis, and tissue staining to assess post-infarction myocardial injury. Additionally, we investigated the mechanism of action through cell experiments. Compared to the myocardial infarction group, DAPA treatment significantly attenuated ventricular remodeling and improved cardiac function. By mitigating myocardial oxidative stress and apoptosis, DAPA may activate the AMPKα signaling pathway, thereby exerting a protective effect. These findings suggest that DAPA could serve as a novel therapeutic approach for patients with cardiac infarction.

Molecular and functional characterization of heat-shock protein 70 in Aphis gossypii under thermal and xenobiotic stresses.

Aphis gossypii, a globally distributed and economically significant pest of several crops, is known to infest a wide range of host plants. Heat shock proteins (Hsps), acting as molecular chaperones, are essential for the insect's environmental stress responses. The present study investigated the molecular characteristics and expression patterns of AgHsp70, a heat shock protein gene, in Aphis gossypii. Our phylogenetic analysis revealed that AgHsp70 shared high similarity with homologs from other insects, suggesting a conserved function across species. The developmental expression profiles of AgHsp70 in A. gossypii showed that the highest transcript levels were observed in the fourth instar nymphs, while the lowest levels were detected in the third instar nymphs. Heat stress and exposure to four different xenobiotics (2-tridecanone, tannic acid, gossypol, and flupyradifurone (4-[(2,2-difluoroethyl)amino]-2(5H)-furanone)) significantly up-regulated AgHsp70 expression. Knockdown of AgHsp70 using RNAi obviously increased the susceptibility of cotton aphids to 2-tridecanone, gossypol and flupyradifurone. Dual-luciferase reporter assays revealed that gossypol and flupyradifurone significantly enhanced the promoter activity of AgHsp70 at a concentration of 10 mg/L. Furthermore, we identified the transcription factor heat shock factor (HSF) as a regulator of AgHsp70, as silencing AgHSF reduced AgHsp70 expression. Our results shed light on the role of AgHsp70 in xenobiotic adaptation and thermo-tolerance.

Revealing the Nature of Active Oxygen Species and Reaction Mechanism of Ethylene Epoxidation by Supported Ag/α-Al2O3 Catalysts.

The oxygen species on Ag catalysts and reaction mechanisms for ethylene epoxidation and ethylene combustion continue to be debated in the literature despite decades of investigation. Fundamental details of ethylene oxidation by supported Ag/α-Al2O3 catalysts were revealed with the application of high-angle annular dark-field-scanning transmission electron microscopy-energy-dispersive X-ray spectroscopy (HAADF-STEM-EDS), in situ techniques (Raman, UV-vis, X-ray diffraction (XRD), HS-LEIS), chemical probes (C2H4-TPSR and C2H4 + O2-TPSR), and steady-state ethylene oxidation and SSITKA (16O2 → 18O2 switch) studies. The Ag nanoparticles are found to carry a considerable amount of oxygen after the reaction. Density functional theory (DFT) calculations indicate the oxidative reconstructed p(4 × 4)-O-Ag(111) surface is stable relative to metallic Ag(111) under the relevant reaction environment. Multiple configurations of reactive oxygen species are present, and their relevant concentrations depend on treatment conditions. Selective ethylene oxidation to EO proceeds with surface Ag4-O2* species (dioxygen species occupying an oxygen site on a p(4 × 4)-O-Ag(111) surface) only present after strong oxidation of Ag. These experimental findings are strongly supported by the associated DFT calculations. Ethylene epoxidation proceeds via a Langmuir-Hinshelwood mechanism, and ethylene combustion proceeds via combined Langmuir-Hinshelwood (predominant) and Mars-van Krevelen (minor) mechanisms.

Enrichment Extraction and Activity Study of the Different Varieties of Hericium erinaceus against HCT-8 Colon Cancer Cells.

Hericium erinaceus (HE), a widely utilized natural remedy and dietary source, has garnered significant attention for its therapeutic potential in various diseases. In this study, we employed supercritical fluid extraction (SFE) technology to isolate the bioactive compounds from HE's fruiting body. Comprehensive assessments of the antioxidant and antibacterial activities were conducted, along with in vitro investigations on the human colon cancer cell line (HCT-8). The SFE rate served as the evaluation metric, while the variables of extraction time, pressure, and temperature were systematically examined. By integrating the response surface center composite design, we successfully optimized the extraction process, yielding optimal parameters of 80 min, 30 MPa, and 35 °C, thus resulting in an extraction rate of 2.51%. These optimized conditions exhibited considerable antioxidant capacity, anticancer activity, and antibacterial potential. Furthermore, we employed graded alcohol extraction to refine the crude extracts, thereby confirming superior anticancer effects under a 70% alcohol precipitation. To elucidate the composition, Fourier-transform infrared spectroscopy (FT-IR) and gas chromatography-mass spectrometry (GC-MS) were employed to analyze the crude extracts and isolates of HE, facilitating a comparative analysis of six HE varieties. Our findings suggest that sterol derivatives hold promise as the active component against the colon cancer HCT-8 cell line. In conclusion, this study underscores the potential of HE SFE in the development of functional foods or alternative drugs for colon cancer treatment, thus opening new avenues for therapeutic interventions.

Esomeprazole inhibits endoplasmic reticulum stress and ameliorates myocardial ischemia-reperfusion injury.

Proton pump inhibitors (PPIs) are often prescribed in association with clopidogrel and aspirin to patients with myocardial infraction (MI), but their effects on heart is controversial. The purpose of this study was to investigate the effects and potential mechanism of omeprazole (OME) and esomeprazole (ESO) in myocardial ischemia reperfusion (I/R) injury. In the present study, mice were treated with OME, ESO or vehicle for 3 weeks and then subjected to myocardial I/R or sham surgery. At 1 day after surgery, echocardiography was performed to access cardiac injury. Hematoxylin and eosin (H&E) staining was performed to evaluate cardiomyocyte morphology. The IL1ß was evaluated by Immunohistochemistry (IHC). Elisa was used to detect cTnt content in serum. The expression of CD86, CD206, CHOP, ATF6, eIF2α and p eIF2α were determined by Western blot (WB). The result showed that ESO markedly improved the left ventricular ejection fraction (LVEF), shortening fraction (FS), suppressed inflammatory infiltration, endoplasmic reticulum stress (ERS) and decreased proinflammatory macrophages in I/R hearts, while OME had no significant effects on cardiac function, inflammation and ERS in the I/R heart. In conclusion, ESO but not OME pretreatment reduces the proportion of proinflammatory macrophages, inhibits endoplasmic reticulum stress, and alleviates I/R injury in mice, indicating that ESO maybe a more proper PPI than OME for application in I/R injury.

Analysis of risk factors for Gleason score upgrading after radical prostatectomy in a Chinese cohort.

BACKGROUND: To study the risk factors of Gleason score upgrading (GSU) after radical prostatectomy (RP) in a Chinese cohort. METHODS: The data of 637 patients who underwent prostate biopsy and RP in our hospital from January 2014 to January 2021 were retrospectively analyzed. The age, body mass index (BMI), prostate-specific antigen (PSA) level, testosterone (TT) level, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), eosinophil-to-lymphocyte ratio (ELR), aspartate aminotransferase/alanine transaminase (AST/ALT) ratio, clinical stage, the biopsy method, and pathological characteristics of specimens after biopsy and RP were collected for all patients. Univariate analysis and multivariate logistic regression analysis were used to analyze the risk factors of GSU after RP. The predictive efficacy was verified with the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. We performed the analysis separately in the overall cohort and in the cohort with Gleason score (GS) = 6. RESULTS: In the overall cohort, 177 patients (27.79%) had GSU, and in the GS = 6 cohort, 68 patients (60.18%) had GSU. Multivariate logistic regression analysis showed that in the overall cohort, clinical stage ≥T2c (OR = 3.201, p < 0.001), the number of positive cores ≥3 (OR = 0.435, p = 0.04), and positive rate of biopsy (OR = 0.990, p = 0.016) can affect whether GS is upgraded, and the AUC of the combination of the three indicators for predicting the occurrence of GSU was 0.627. In the GS = 6 cohort, multivariate logistic regression analysis showed that clinical stage ≥T2c (OR = 4.690, p = 0.001) was a risk factor for GSU, and the AUC predicted to occur GSU is 0.675. CONCLUSION: Clinical stage ≥T2c, the number of positive cores <3, and lower positive rate of biopsy are the risk factors of GSU. This study may provide some references for clinicians to judge the accuracy of biopsy pathological grading and formulate treatment strategies, but the specific effect still needs clinical practice certification.

The association between sleep duration and prostate cancer: A systematic review and meta-analysis.

The association between sleep duration and prostate cancer (PCa) risk is still unclear. We performed a systematic review and meta-analysis to explore if sleep duration is associated with PCa in men.A comprehensive literature search was conducted in November 2019 based on the Pubmed, Embase, and Cochrane databases. After extracting the data, the random effects model was used to calculate the pooled Risk Ratio (RR) and it's 95% confidence interval (CI) to represent the correlation between sleep duration and PCa risk.Overall, we included 6 studies in our meta-analysis. Our pooled results showed that neither short sleep (RR = 0.99; 95%CI:0.91-1.07, P = .74) nor long sleep (RR = 0.88; 95%CI:0.75-1.04, P = .15) was associated with the risk of PCa.Sleep duration has no significant effect on PCa risk. Long sleep may have a potential protective effect on PCa incidence.

Thiol-oxidation reduces the release of amylase induced by ß-adrenergic receptor activation in rat parotid acinar cells.

In parotid acinar cells, the activation of ß-adrenergic receptors induces the accumulation of intracellular cAMP, and consequently provokes the exocytotic release of amylase, a digestive enzyme. The cellular redox status plays a pivotal role in regulating various cellular functions. Cellular redox imbalance caused by the oxidation of cellular antioxidants, as a result of oxidative stress, induces significant biological damage. In this study, we examined the effects of diamide, a thiol-oxidizing reagent, on amylase release by rat parotid acinar cells. In cells treated with diamide, the formation of cAMP and the release of amylase induced by the ß-agonist isoproterenol (IPR) were partially reduced. The inhibitory effect of diamide on the IPR-induced release of amylase could be abrogated by reduced glutathione or dithiothreitol. Diamide had no effect on the amylase release induced by forskolin, an adenylate cyclase activator, or by mastoparan, a heterotrimeric GTPbinding protein activator. In cells treated with diamide, the binding affinity for [(3)H]DHA, but not the number of binding sites, was reduced. These results suggest that ß-adrenergic receptor function is reduced by thiol-oxidation, which inhibits amylase secretion by parotid acinar cells.

Involvement of phosphodiesterase 4 in beta-adrenoceptor agonist-induced amylase release in parotid acinar cells.

beta-Adrenoceptor activation increases intracellular cAMP levels and consequently induces exocytotic amylase release in parotid acinar cells. Phosphodiesterase (PDE) catalyses the hydrolysis of cAMP, which terminates the downstream signaling of this second messenger. We investigated the involvement of PDE4, a cAMP-PDE, in beta-adrenoceptor agonist-induced amylase release in mouse, rat and rabbit parotid acinar cells by using the specific PDE4 inhibitor rolipram. cAMP-PDE activity was detected in mouse, rat and rabbit parotid acinar cells. In the presence of rolipram, cAMP-PDE activity was reduced by about 31%, 38% and 33% in mouse, rat and rabbit parotid acinar cells, respectively. The increase in cAMP levels induced by the beta-adrenoceptor agonist isoproterenol was enhanced in the presence of rolipram in mouse, rat and rabbit parotid acinar cells. Isoproterenol-induced amylase release, but not constitutive amylase release, was also enhanced in the presence of rolipram in mouse, rat and rabbit parotid acinar cells. These results suggest that the rolipram-sensitive cAMP-PDE, PDE4, is involved in beta-adrenoceptor agonist-induced amylase release in parotid acinar cells.

Phosphorylation of myristoylated alanine-rich C kinase substrate is involved in the cAMP-dependent amylase release in parotid acinar cells.

Myristoylated alanine-rich C kinase substrate (MARCKS) is known as a major cellular substrate for protein kinase C (PKC). MARCKS has been implicated in the regulation of brain development and postnatal survival, cellular migration and adhesion, as well as phagocytosis, endocytosis, and exocytosis. The involvement of MARCKS phosphorylation in secretory function has been reported in Ca(2+)-mediated exocytosis. In rat parotid acinar cells, the activation of beta-adrenergic receptors provokes exocytotic amylase release via accumulation of intracellular cAMP levels. Here, we studied the involvement of MARCKS phosphorylation in the cAMP-dependent amylase release in rat parotid acinar cells. MARCKS protein was detected in rat parotid acinar cells by Western blotting. The beta-adrenergic agonist isoproterenol (IPR) induced MARCKS phosphorylation in a time-dependent manner. Translocation of a part of phosphorylated MARCKS from the membrane to the cytosol and enhancement of MARCKS phosphorylation at the apical membrane site induced by IPR were observed by immunohistochemistry. H89, a cAMP-dependent protein kinase (PKA) inhibitor, inhibited the IPR-induced MARCKS phosphorylation. The PKCdelta inhibitor rottlerin inhibited the IPR-induced MARCKS phosphorylation and amylase release. IPR activated PKCdelta, and the effects of IPR were inhibited by the PKA inhibitors. A MARCKS-related peptide partially inhibited the IPR-induced amylase release. These findings suggest that MARCKS phosphorylation via the activation of PKCdelta, which is downstream of PKA activation, is involved in the cAMP-dependent amylase release in parotid acinar cells.

The thiol-oxidizing agent diamide reduces isoproterenol-stimulated amylase release in rat parotid acinar cells.

In parotid acinar cells, activation of beta-adrenergic receptors provokes exocytotic amylase release via the accumulation of intracellular cAMP. Cellular redox status plays a pivotal role in the regulation of various cellular functions. Cellular redox imbalance caused by the oxidation of cellular antioxidants, as a result of oxidative stress, induces significant biological damages. In this study, we examined effect of diamide, a thiol-oxidizing reagent, on amylase release in rat parotid acinar cells. In the presence of diamide, isoproterenol (IPR)-induced cAMP formation and amylase release were partially reduced. Diamide had no effect on amylase release induced by forskolin and mastoparan, an adenylate cyclase activator and heterotrimeric GTP binding protein activator, respectively. In the cells pretreated with diamide, the binding affinity of [(3)H]dihydroalprenolol to beta-receptors was reduced. These results suggest that oxidative stress results in reduction of binding affinity of ligand on beta-receptor and consequently reduces protein secretory function in rat parotid acinar cells.

Role of protein kinase C-delta in isoproterenol-induced amylase release in rat parotid acinar cells.

In parotid acinar cells, beta-adrenergic receptor activation results in accumulation of intracellular cAMP. Subsequently, cAMP-dependent protein kinase (PKA) is activated and consequently amylase release is provoked. In this paper, we investigated involvement of protein kinase C-delta (PKC delta), a novel isoform of PKC, in amylase release induced by beta-adrenergic receptor stimulation. Amylase release stimulated with the beta-agonist isoproterenol (IPR) was inhibited by rottlerin, an inhibitor of PKC delta. IPR activated PKC delta and the effect of IPR were inhibited by a PKA inhibitor, H89. Myristoylated alanine-rich C kinase substrate (MARCKS), a major cellular substrate for PKC, was detected in rat parotid acinar cells, and a MARCKS inhibitor, MARCKS-related peptide, inhibited the IPR-induced amylase release. IPR stimulated MARCKS phosphorylation, which was found to be inhibited by H89 and rottlerin. These observations suggest that PKC delta activation is a downstream pathway of PKA activation and is involved in amylase release via MARCKS phosphorylation in rat parotid acinar cells stimulated with beta-adrenergic agonist.

[Experimental study of DNA synthesis in the airway cells and airway remodeling in asthmatic rats].

OBJECTIVE: To study the DNA synthesis in the airway cells of asthmatic rats after allergen stimulation in association with airway remodeling. METHODS: Double staining immunohistochemical techniques was used to determine DNA synthesis of the airway cells of 12 asthmatic and 12 normal rats. BrdU incorporation into the airway smooth muscle (ASM) and epithelium was quantified by employment of computer-assisted image analysis. RESULTS: BrdU indices in both the ASM and the epithelium of asthmatic model group were higher than those of the control group (P<0.01, P<0.05), and positive linear correlation of the BrdU indices in the ASM and epithelium with the airway diameter was observed (r=0.7828, P<0.01; r=0.5852, P<0.05), which was not found in the control group (r=-0.3755, P>0.05; r=-0.5208, P>0.05). The epithelial thickness of the model group was significantly greater than that of the control group (P<0.01). There was no significant difference in terms of airway diameter, thickness of the ASM and the area positive of alpha-smooth muscle actin between the 2 groups (P>0.05). CONCLUSION: Increased DNA synthesis and accelerated proliferation of ASM and epithelial cells in sensitized SD rats following repeated allergen challenges may lead to airway remodeling.