The Chains of Ferroptosis Interact in the Whole Progression of Atherosclerosis.

Atherosclerosis (AS), a category of cardiovascular disease (CVD) that can cause other more severe disabilities, increasingly jeopardizes human health. Owing to its imperceptible and chronic symptoms, it is hard to determine the pathogenesis and precise therapeutics for AS. A novel type of programmed cell death called ferroptosis was discovered in recent years that is distinctively different from other traditional cell death pathways in morphological and biochemical aspects. Characterized by iron overload, redox disequilibrium, and accumulation of lipid hydroperoxides (L-OOH), ferroptosis influences endothelial cells, vascular smooth muscle cells (VSMCs), and macrophages, as well as inflammation, partaking in the pathology of many cardiovascular diseases such as atherosclerosis, stroke, ischemia-reperfusion injury, and heart failure. The mechanisms behind ferroptosis are so sophisticated and interwoven that many molecules involved in this procedure are unknown. This review systematically depicts the initiation and modulation of ferroptosis and summarizes the contribution of ferroptosis to AS, which may open a feasible approach for target treatment in the alleviation of AS progression.

The therapeutic efficacy and clinical translation of mesenchymal stem cell-derived exosomes in cardiovascular diseases.

Exosomes, mainly derived from mesenchymal stem cells, provide a good reference for cardiac function repair and clinical application in cardiac and vascular diseases by regulating cardiomyocyte viability, inflammatory levels, angiogenesis, and ventricular remodeling after a heart injury. This review presents the cardioprotective efficacy of mesenchymal stem cell-originated exosomes and explores the underlying molecular mechanisms. Furthermore, we expound on several efficient approaches to transporting exosomes into the heart in clinical application and comment on the advantages and disadvantages of each method.

Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Alleviate Diabetic Kidney Disease in Rats by Inhibiting Apoptosis and Inflammation.

BACKGROUND AND AIMS: Previous studies have confirmed the anti-inflammation effect of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exo). We aimed to investigate the therapeutic effect of BMSC-Exo on diabetic kidney disease (DKD), as well as the underlying mechanisms. METHODS: SD rats were induced by streptozotocin combined with a high-fat diet to establish a diabetes disease model. BMSCs-Exo were injected via tail veins at a weekly dose of 100 µg for 12 weeks. Pathological changes in the rat kidneys were evaluated using HE, Masson, and Periodic Acid-Schiff and immunohistochemical staining. TUNEL staining and western blot were used to evaluate the expression levels of apoptosis-related proteins in the rat kidney cells. The TNF-α level was detected by PCR and NF-κB (p65) by western blotting to examine the inflammatory responses in the renal tissue. RESULTS: BMSCs-Exo significantly alleviated the renal structural damage and the distribution of apoptotic cells in diabetic rats. Furthermore, BMSCs-Exo increased the expression of pro-apoptosis protein Bax and decreased the expression of apoptosis-executing protein Cleaved Caspase 9 and Cleaved caspase 3. In addition, the transcription level of TNF-α in kidney tissue and NF-κB (p65) expression was also decreased through BMSCs-Exo treatment. Besides, the levels of glucose (GLU), creatinine (Cr), and burea nitrogen (BUN) in diabetic rats were decreased by the BMSC-Exo treatment. CONCLUSIONS: BMSCs-Exo may alleviate diabetic kidney damage by inhibiting apoptosis and inflammation.

The cGAS-STING Pathway: A Ubiquitous Checkpoint Perturbing Myocardial Attributes.

As an innate immune route of defense against microbial infringement, cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS)- stimulator of interferon genes (STING) signaling does not simply participate in amplifying inflammatory responses via releasing type-I interferon (IFN) or enhance the expression of pro-inflammatory genes, but also interplays with multifarious pathophysiological activities, such as autophagy, apoptosis, pyroptosis, ferroptosis, and senescence in a broad repertoire of cells like endothelial cells, macrophages and cardiomyocyte. Thus, the cGAS-STING pathway is closely linked with aberrant heart morphologically and functionally via these mechanisms. The past few decades have witnessed an increased interest in the exact relationship between the activation of the cGAS-STING pathway and the initiation or development of certain cardiovascular diseases (CVD). A group of scholars has gradually investigated the perturbation of myocardium affected by the overactivation or suppression of the cGAS-STING. This review focuses on how the cGAS-STING pathway interweaves with other pathways and creates a pattern of dysfunction associated with cardiac muscle. This sets treatments targeting the cGAS-STING pathway apart from traditional therapeutics for cardiomyopathy and achieves better clinical value.

cGAS-STING Pathway Performance in the Vulnerable Atherosclerotic Plaque.

The important role of Ca2+ in pathogenic store-operated calcium entry (SOCE) is well-established. Among the proteins involved in the calcium signaling pathway, Stromal interacting molecule 1 (STIM1) is a critical endoplasmic reticulum transmembrane protein. STIM1 is activated by the depletion of calcium stores and then binds to another calcium protein, Orai1, to form a channel through which the extracellular Ca2+ can enter the cytoplasm to replenish the calcium store. Multiple studies have shown that increased STIM1 facilitates the aberrant proliferation and apoptosis of vascular smooth cells (VSMC) and macrophages which can promote the formation of rupture-prone plaque. Together with regulating the cytosolic Ca2+ concentration, STIM1 also activates STING through altered intracellular Ca2+ concentration, a critical pro-inflammatory molecule. The cGAS-STING pathway is linked with cellular proliferation and phenotypic conversion of VSMC and enhances the progression of atherosclerosis plaque. In summary, we conclude that STIM1/cGAS-STING is involved in the progression of AS and plaque vulnerability.

Luteolin as an adjuvant effectively enhances CTL anti-tumor response in B16F10 mouse model.

Luteolin, a naturally found dietary flavonoid, has a wide range of beneficial biological effects, including effects against tumors and oxidants. Studies proved that luteolin can modulate immune responses. In this study, we investigated the function of luteolin as an antitumor vaccine adjuvant (to treat malignant melanoma) in vitro and in vivo. We found that Luteolin may activated the PI3K-Akt pathways in APCs (Antigen Presenting Cells), induced the activation of APCs, enhanced CTL (Cytotoxic T Lymphocyte) responses, and inhibited tolerogenic T cells. To prove the role of CD8+T cells in immune process, we sorted the CD8+T cells from the immunized mice and transferred them to the B16F10 tumor-bearing mice, the result showed that the survival rate was improved. We also observed that in the mice immunized with Luteolin as an adjuvant, the tumor growth was significantly reduced. Taken together, the result demonstrated that luteolin showed promising properties as a vaccine adjuvant for treating malignant melanoma.

Identification of ZG16B as a prognostic biomarker in breast cancer.

Zymogen granule protein 16B (ZG16B) has been identified in various cancers, while so far the association between ZG16B and breast cancer hasn't been explored. Our aim is to confirm whether it can serve as a prognostic biomarker in breast cancer. In this study, Oncomine, Cancer Cell Line Encyclopedia (CCLE), Ualcan, and STRING database analyses were conducted to detect the expression level of ZG16B in breast cancer with different types. Kaplan-Meier plotter was used to analyze the prognosis of patients with high or low expression of ZG16B. We found that ZG16B was significantly upregulated in breast cancer. Moreover, ZG16B was closely associated with foregone biomarkers and crucial factors in breast cancer. In the survival analysis, high expression of ZG16B represents a favorable prognosis in patients. Our work demonstrates the latent capacity of ZG16B to be a biomarker for prognosis of breast cancer.

Identification of NCAPH as a biomarker for prognosis of breast cancer.

Non-SMC condensin I complex subunit H (NCAPH) is a structural component of chromosomes during mitosis, which up-regulates in various cancers. However, the role of NCAPH in breast cancer still hasn't been clearly explored. Our aim is to confirm the value of NCAPH as a prognostic biomarker of breast cancer. We revealed the high expression of NCAPH in breast cancer by using Oncomine, Ualcan and GOBO analysis. Quantitative Real-time PCR (qRT-PCR) analysis was conducted to detect the mRNA expression of NCAPH in MCF-7 and MCF-10A cells, and thus higher mRNA level of NCAPH in MCF-7 cells was confirmed. STRING and gene enrich analysis were conducted to explore the interaction between NCAPH and other proteins, hence the functionality of NCAPH in mitosis is demonstrated. With Kaplan-Meier plotter we found that upregulation of NCAPH is indicative of a poor prognosis especially in hormone receptor positive breast cancer. We confirmed the potential competence of NCAPH as a promising biomarker in breast cancer prognosis.