BMSCs-derived Exosome CISH Alleviates Myocardial Infarction by Inactivating the NF-κB Pathway to Stimulate Macrophage M2 Polarization.

Current myocardial infarction (MI) treatments are suboptimal, necessitating deeper pathogenesis understanding of MI. This research explored how exosomes (Exo) derived from bone marrow mesenchymal stem cells (BMSCs) contribute to MI mitigation and their therapeutic potential. Isolated BMSCs was identified by microscope, flow cytometry, alizarin red and oil red O staining. Exo were identified by TEM, NTA and western blot. HE staining, masson staining, and cardiac function parameters were used to assess the cardiac function in MI mice. TUNEL staining, western blot and qRT-PCR were used to detect apoptosis, inflammatory factors and M1/M2 markers. The NF-κB pathway activation was detected through western blot assays. Immunofluorescence, qRT-PCR, western blot, and flow cytometry were employed to evaluate macrophage polarization. MI mice showed cardiac injury, increased apoptosis and inflammation, while BMSCs-Exo treatment alleviated these effects. In MI mice, the macrophage M1 polarization was increased and the NF-κB pathway was activated, whereas BMSCs-Exo treatment reversed these changes. Furthermore, CISH expression was reduced in MI mice, but was elevated with BMSCs-Exo treatment. In vitro, LPS shifted RAW264.7 cells to M1 phenotype and activated the NF-κB pathway, yet BMSCs-Exo shifted them to M2 phenotype and inhibited the NF-κB pathway. Mechanistically, BMSCs-Exo induced macrophage M2 polarization by transmitting CISH to inhibit NF-κB activation. BMSCs-Exo mitigates MI by transmitting CISH to inhibit the NF-κB pathway, promoting macrophages to M2 type. This implies BMSCs-Exo could be a useful treatment for MI, and CISH could be a potential therapy target.

Colchicine ameliorates short-term abdominal aortic aneurysms by inhibiting the expression of NLRP3 inflammasome components in mice.

BACKGROUND: Abdominal aortic aneurysms (AAA) are often associated with chronic inflammation and pose a significant risk to affected individuals. Colchicine, known for its anti-inflammatory properties, has shown promise in managing cardiovascular diseases. However, its specific role in the development of AAA remains poorly understood. METHODS AND RESULTS: In this study, we employed a short-term AAA model induced by angiotensin II (Ang II, 1000 ng/kg/min) and calcium chloride (CaCl2, 0.5 mol/l) in male ApoE-/- and C57BL/6 mice (8-12 weeks old) to investigate the effects of colchicine on AAA progression. Colchicine (0.4 mg/kg) was administered orally once daily, starting on the same day as AAA induction. After a 4-week duration, we observed a significant reduction in AAA diameter, degradation of elastic fibers, and expression of components related to the Nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome in the vessel wall of colchicine-treated mice compared to the saline group. Mechanistically, colchicine (5 µm/l, for 24h) inhibited the expression of NLRP3 inflammasome components through the P38-ERK/MicroRNA145-toll-like receptor 4 (TLR4) pathway in RAW264.7 cells. CONCLUSIONS: Our study demonstrates the effectiveness of colchicine in suppressing NLRP3 inflammasome components, thereby delaying AAA progression in the Ang II and CaCl2-induced short-term model. These findings suggest the potential of colchicine as a pharmacological treatment option for AAA.

Correction: Exosomal miR-25-3p from mesenchymal stem cells alleviates myocardial infarction by targeting proapoptotic proteins and EZH2.

Since online publication of this article, the authors noticed that an incorrect image was used during the compilation of Fig. 2a, which was caused during manuscript preparation. The correct Fig. 2a is shown below.

Exosomal miR-25-3p from mesenchymal stem cells alleviates myocardial infarction by targeting pro-apoptotic proteins and EZH2.

Mesenchymal stem cell (MSC) therapy is a promising approach against myocardial infarction (MI). Studies have demonstrated that MSCs can communicate with other cells by secreting exosomes. In the present study, we aimed to identify exosomal microRNAs that might contribute to MSC-mediated cardioprotective effects. Primary cardiomyocytes were deprived of oxygen and glucose to mimic MI in vitro. For the animal model of MI, the left anterior descending artery was ligated for 1 h, followed by reperfusion for 12 h. MSC-derived exosomes were used to treat primary cardiomyocytes or mice. Cardioprotection-related microRNAs were determined, followed by target gene identification and functional studies with quantitative PCR, western blotting, MTT assay, flow cytometry assay, chromatin immunoprecipitation and dual-luciferase assay. We found that MSC co-culture reduced OGD-induced cardiomyocyte apoptosis and inflammatory responses. Cardioprotection was also observed upon treatment with MSC-derived exosomes in vitro and in vivo. In line with this, exosome uptake led to a significant increase in miR-25-3p in cardiomyocytes. Depletion of miR-25-3p in MSCs abolished the protective effects of exosomes. Mechanistically, miR-25-3p directly targeted the pro-apoptotic genes FASL and PTEN and reduced their protein levels. Moreover, miR-25-3p decreased the levels of EZH2 and H3K27me3, leading to derepression of the cardioprotective gene eNOS as well as the anti-inflammatory gene SOCS3. Inhibition of EZH2 or overexpression of miR-25-3p in cardiomyocytes was sufficient to confer cardioprotective effects in vitro and in vivo. We concluded that exosomal miR-25-3p from MSCs alleviated MI by targeting pro-apoptotic proteins and EZH2.

Correction: Exosomal miR-25-3p from mesenchymal stem cells alleviates myocardial infarction by targeting pro-apoptotic proteins and EZH2.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

One pot preparation of magnetic chitosan-cystamine composites for selective recovery of Au(III) from the aqueous solution.

A novel magnetic chitosan adsorbent (CDF-CS) was synthesized by inserting magnetic particles into the crosslinked compound of chitosan (CS) and cystamine based on one-step method for selectively recovering Au(III) from aqueous solution. The characterization and adsorption mechanism of CDF-CS were studied by SEM-EDS, VSM, FT-IR and XPS, respectively. The experimental results show that the adsorption capacity of CDF-CS is still large in a wide range of pH values (from 1 to 7) and has a higher adsorption capacity for Au(III) than the raw chitosan, the maximum adsorption capacity of CDF-CS for Au(III) was 478.47 mg/g about 6 h at pH = 7.0. The adsorption behavior is most consistent with this pseudo-second-order kinetic model. The adsorption process of gold ions by CDF-CS follows the Langmuir adsorption isotherm. Furthermore, the thermodynamic parameter indicates that the adsorption reaction of gold ions by CDF-CS is an endothermic chemisorption. CDF-CS has great potential for removing gold ions from aqueous solutions due to the excellent repeatability and selectivity. Finally, the adsorption mechanism is that chelation reaction and ion exchange mainly occurred between CDF-CS and Au(III). Therefore, CDF-CS is very promising in recovery of Au(III) from aqueous solutions.

Efficient and Selective Adsorption of Gold Ions from Wastewater with Polyaniline Modified by Trimethyl Phosphate: Adsorption Mechanism and Application.

The selective recovery of gold from wastewater is necessary because it is widely used in various fields. In this study, a new polymeric adsorbent (TP-AFC) was prepared by modifying polyaniline with trimethyl phosphate for the selective recovery of gold from wastewater. Bath experiments were carried out to explore the adsorption capacity and mechanism. The optimum pH of adsorption is 4. The adsorption equilibrium is reached at 840 min. The maximum adsorption capacity is 881 mg/g and the adsorption was a spontaneous endothermic process. The adsorption process fitted well with pseudo second-order kinetic and the Langmuir-models. The single-layer chemisorption governed the adsorption process. In addition, the application in wastewater indicated that the interfering ions had no effect on the adsorption of gold ions. TP-AFC has good selectivity. The interaction mechanism was mainly ion exchange and complexation. In general, TP-AFC was successfully prepared and has an excellent future in practical application.

Effect of intravenous transplantation of hUCB-MSCs on M1/M2 subtype conversion in monocyte/macrophages of AMI mice.

BACKGROUND: The transplantation of stem cells is effective in the treatment of acute myocardial infarction (AMI). But the mechanisms of stem cell transplantation for the treatment of AMI have not been clearly confirmed. This article is to compare cardiac function, myocardial fibrosis, inflammatory cell infiltration, apoptotic index, and M1 macrophage to M2 macrophage ratios 4 weeks after hUCB-MSCs transplantation in Mice with AMI. METHODS: Mice model of AMI was divided into two groups randomly. Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) were transplanted to the intervention group via mice tail vein, and saline solution was used for the control group. Masson staining calculated the proportion of the remaining myocardium and collagen volume fraction (CVF) in the infarct area, flow cytometry and immunofluorescence staining to analyze M1 / M2 subtype and its ratio were performed. Serum IL-6 and galectin-3 levels were determined using ELISA. RESULTS: The results showed that heart function of the intervention group was significantly better than that of the control group, and the degree of fibrosis and inflammation in the intervention group were lower than those in the control group. The ratio of monocyte M1/M2 in peripheral blood, spleen and myocardial tissue in hUCB-MSCs transplantation was significantly lower than that of the control group. But there is no significant difference in the apoptotic index between two groups. The ELISA results showed that serum IL-6 (97.98 ± 5.94 pg/ml) and galectin-3 levels (69.94 ± 5.11 ng/ml) were lower in the intervention group than in the control group (IL-6: 118.2 ± 5.03 pg/ml; galectin-3: 83.14 ± 2.76 ng / ml). However, compared with the control group, only IL-6 showed a significant decrease in the intervention group (p = 0.032). CONCLUSION: Intravenous transplantation of hUCB-MSCs can reduce inflammatory response by stimulating the conversion of intracardiac and extracardiac macrophage subtype M1 / M2, decrease the serum IL-6 and galectin-3 levels, improve cardiac function and protect the infarcted myocardium.

MicroRNA-133a and Myocardial Infarction.

Myocardial infarction (MI) is the leading cause of morbidity and mortality in the world. The infarcted heart displays typical cell death cascades characterized by a loss of cells and fibrotic scarring in the myocardium. Cardiac hypertrophy and fibrosis largely contribute to ventricular wall thickening and stiffening, altogether defining an adverse cardiac remodeling that ultimately leads to impaired cardiac function and subsequent heart failure. Finding a strategy to promote therapeutic, instead of detrimental, cardiac remodeling may pose as a potent MI treatment. Accumulating evidence shows that microRNAs (miRNAs) may play an essential role in cardiovascular diseases. In particular, microRNA-133a (miR-133a) is one of the most abundant miRNAs in the heart. Multiple studies have demonstrated that miR-133a participates in the early pathology of MI, as well as in subsequent cardiac remodeling. In this review, we summarize recent research progress highlighting the regulatory effects of miR-133a in ischemic myocardial diseases, such as inhibiting angiogenesis, apoptosis, fibrosis, hypertrophy, and inflammation, while promoting therapeutic cardiac remodeling. The goal is to elicit a critical discussion on the translational direction of miRNA-mediated treatments towards a safe and effective MI therapy.

Kinetic, Isotherm, and Thermodynamic Studies for Ag(I) Adsorption Using Carboxymethyl Functionalized Poly(glycidyl methacrylate).

Industrial wastewater contains large amounts of silver ions. Here, a new adsorbent was synthesized by functionalizing poly(glycidyl methacrylate) with carboxymethyl groups. The adsorbent was used to recover Ag(I) in wastewater. Fourier transform infrared spectroscopy, zeta potential, scanning electron microscopy, and X-ray photoelectron spectroscopy were used to characterize the adsorbent. The experimental parameters affecting the adsorption are solution pH, contact time, and initial silver ion concentration. The optimum pH for adsorption of Ag(I) is pH 4. The maximum adsorption capacity at pH 4 is 157.05 mg/g, and the adsorption reaches equilibrium at 300 min. The kinetics and isotherms of the adsorption process were described by pseudo second-order, Langmuir and D-R models, respectively. The adsorption process was a single layer chemical adsorption, exothermic, feasible, and spontaneous. The adsorption mechanism is electrostatic or chelation. The adsorbent selectively absorbed Ag(I) from coexisting ions (Cu2+, Ni2+, Co2+, Zn2+). Finally, the removal rate of silver ions decreased from 79.29% to 65.01% after four repetitive experiments, which proved that the adsorbent had good reusability. The adsorbent has great potential benefit in removing Ag(I).

Synergistic growth-suppressive effects of quercetin and cisplatin on HepG2 human hepatocellular carcinoma cells.

Quercetin, a natural flavonoid, exhibits anticancer effects. The aim of this study is to determine whether the combination of quercetin with cisplatin, a conventional chemotherapeutic drug, would have synergistic suppressive effects on hepatocellular carcinoma (HCC) cells. To this end, HepG2 cells were exposed to quercetin (50 µM) or cisplatin (10 µM) alone or combination of both and cell proliferation and apoptosis were investigated. Our data revealed that the combination of quercetin and cisplatin was significantly (P < 0.05) effective in inducing growth suppression and apoptosis in HepG2 cells, when compared with single agent treatment. Quercetin combined with cisplatin modulated the expression of numerous genes involved in cell cycle progression and apoptosis. Treatment with quercetin rather than cisplatin resulted in a marked elevation of p16 expression in HepG2 cells. Targeted reduction of p16 using RNA interference technology partially reversed quercetin-induced cell cycle G1 arrest and apoptosis in HepG2 cells. In conclusion, quercetin has suppressive activity against HCC cells through p16-mediated cell cycle arrest and apoptosis and its combination with cisplatin yielded synergistic inhibitory effects in suppressing cell growth and inducing apoptosis.