Up-regulation of miR-155 protects against chronic heart failure by inhibiting HIF-1α.

BACKGROUND: Despite a crucial role of miR-155 in human cancers, its function in heart failure (HF) is still under investigation. This study was designed to explore its association with HF. METHODS: The abdominal transverse aortic constriction (TAC) was adopted for establishment of mouse HF models. qRT-PCR and WB were adopted to detect the changes of miR-155, HIF-1α, Cle-caspase-3, BCL2 and Bax levels in myocardial cells and heart tissues. The changes of cardiac function were checked by ultrasound. Additionally, luciferase reporter gene was adopted for interaction analysis of miR-155 with HIF-1α, and in situ end labelling method was used for detecting myocardial apoptosis. RESULTS: MiR-155 in myocardial tissue of HF mice was significantly down regulated. In HF mice injected with agomiR-155, the up-regulation of miR-155 strongly improved cardiac function, and also significantly lowered the protein levels of apoptosis-associated markers, C-caspase-3 and Bax, but up regulated Bcl-2. Additionally, HIF-1α was identified as the direct target of miR-155. As expected, over-expression of HIF-1α greatly reversed the effects of agomiR-155 on cardiac function and the expression of apoptosis-associated markers in heart tissues of HF mice. CONCLUSION: MiR-155 overexpression can suppress myocardial cell apoptosis through HIF-1α, and strongly alleviate the cardiac function damage in HF mice, indicating the potential of miR-155/HIF-1α axis to be a target for the diagnosis and therapy of HF.

UCNPs-based nanoreactors with ultraviolet radiation-induced effect for enhanced ferroptosis therapy of tumor.

The limitations of light source limit the clinical application of optical therapy technology. How to improve the application efficiency of radiant light has become the focus of researchers. Here, we synthesize a kind of UCNPs@PVP-GOx-PpIX-Fe3+ (UPGPF) nanoreactors with rare earth upconversion nanoparticles (UCNPs) as the substrate for the enhancement of ferroptosis effect by the synergistic starvation/photodynamic therapies. Firstly, glucose oxidase (GOx) and Fe3+ loaded in UPGPF nanoreactors are used to directly face the problems of insufficient H2O2 level in tumor tissue and low Fenton reaction efficiency. Further, UCNPs can absorb NIR light at 980 nm and convert low-energy photons into high-energy photons, thereby cleverly generating ultraviolet (UV) radiation induction in vivo, which can produce a synergistic effect of enhancing iron death. The in vivo experimental results of breast cancer model mice show that the UPGPF nanoreactors have significant anticancer effect and good biosafety. With the help of the optical conversion characteristics of UCNPs, this kind of treatment idea of building a UV radiation-induced microplatform in the tumor microenvironment, which leads to the synergistic enhancement of iron death effect, provides a promising innovative design strategy for tumor research.

Biodegradable CuMoO4 Nanodots with Multienzyme Activities for Multimodal Treatment of Tumor.

Due to their complexity and variability, tumors need to be treated with multimodal combined therapy, which requires the development of therapeutic agents that can provide multimodal therapeutic effects. Herein, CuMoO4 nanodots smaller than 10 nm that can be prepared by simple hydrothermal method are reported. These nanodots can be well dispersed in water and have good biosafety and biodegradability. Further studies show that these nanodots also present multienzyme activities, such as catalase, peroxidase and glutathione peroxidase. In addition, CuMoO4 nanodots exhibit high photothermal conversion efficiency (41%) under 1064 nm near-infrared laser irradiation. In vitro and in vivo experimental results indicate that CuMoO4 nanodots can effectively inhibit the instinctive regulation of tumor cells to oxidative stress, provide sustained treatment to achieve photothermal synergistic ferroptosis, and trigger immune responses to immunogenic cell death. It is worth mentioning that the CuMoO4 nanodots also cause cuproptosis of tumor cells. This study provides a promising nanoplatform for multimodal combined therapy of cancer.

Effects of Enalapril on TLR2/NF-κB Signaling Pathway and Inflammatory Factors in Rabbits with Chronic Heart Failure.

Chronic heart failure (CHF) refers to the state of persistent heart failure, which is a complex clinical syndrome of various advanced heart diseases. The toll-like receptor 2 (TLR2)/nuclear transcription factor-κB (NF-κB) signal transduction pathway is one of the pathological mechanisms of CHF. Adriamycin can significantly induce the upregulation of TLR2 expression. Angiotensin-converting enzyme inhibitors (ACEI) are commonly used drugs for the treatment of CHF. In our study, the CHF model was established by injection of doxorubicin into the rabbit ear vein. The effect of enalapril on the TLR2/NF-κB signaling pathway in CHF rabbits has been analyzed and determined. Our research results showed that enalapril reduced the inflammatory response by inhibiting the activation of the TLR2/NF-κB signaling pathway, thereby improving cardiac structure, myocardial remodeling, and cardiac function.

Effect of oxidation ditch and anaerobic-anoxic-oxic processes on CX3R-type disinfection by-product formation during wastewater treatment.

The high chlorine dosages in wastewater treatment plants during the COVID-19 pandemic may result in increased formation of disinfection by-products (DBPs), posing great threat to the aquatic ecosystem of the receiving water body and the public health in the downstream area. However, limited information is available on the effect of biological wastewater treatment processes on the formation of CX3R-type DBPs. This study investigated the effect of oxidation ditch (OD) and anaerobic-anoxic-oxic (AAO), two widely used biological wastewater treatment processes, on the formation of five classes of CX3R-type DBPs, including trihalomethanes (THMs), haloacetic acids (HAAs), haloacetaldehydes (HALs), haloacetonitriles (HANs) and halonitromethanes (HNMs), during chlorination. Experimental results showed that biological treatment effectively reduced the dissolved organic carbon (DOC) and UV254, while it increased the dissolved organic nitrogen (DON), and therefore the ratio of DON/DOC. In addition, increases in the contents of soluble microbial product- and humic acid-like matters, and the transformation of high molecular weight (MW) fractions in the dissolved organic matter into low MW fractions were observed after OD and AAO processes. Although biological treatment effectively decreased the formation of Cl-THMs, Cl-HAAs, Cl-HANs and Cl-HNMs, the formation of DBCM, DBAA, BDCAA, DBCAA, DCAL, TCAL and DBAN (where C = chloro, B = bromo, D = di, T = tri) all increased significantly, due to the increased formation reactivity. Moreover, biological treatment increased the ratio of bromide/DOC and bromine incorporation into THMs, HAAs and DHANs except for HALs and THANs. Different from previous studies, this study revealed that biological treatment increased the formation of some DBPs, especially brominated DBPs, despite the efficient removal of organic matters. It provides insights into the DBP risk control in wastewater treatment, particularly during the COVID-19 pandemic.