Adenine base editor-based correction of the cardiac pathogenic Lmna c.1621C > T mutation in murine hearts.

Base editors are emerging as powerful tools to correct single-nucleotide variants and treat genetic diseases. In particular, the adenine base editors (ABEs) exhibit robust and accurate adenine-to-guanidine editing capacity and have entered the clinical stage for cardiovascular therapy. Despite the tremendous progress using ABEs to treat heart diseases, a standard technical route toward successful ABE-based therapy remains to be fully established.

Sorafenib induces cardiotoxicity through RBM20-mediated alternative splicing of sarcomeric and mitochondrial genes.

Sorafenib, a multi-targeted tyrosine kinase inhibitor, is a first-line treatment for advanced solid tumors, but it induces many adverse cardiovascular events, including myocardial infarction and heart failure. These cardiac defects can be mediated by alternative splicing of genes critical for heart function. Whether alternative splicing plays a role in sorafenib-induced cardiotoxicity remains unclear.

Off-target effects in CRISPR/Cas9 gene editing.

Gene editing stands for the methods to precisely make changes to a specific nucleic acid sequence. With the recent development of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, gene editing has become efficient, convenient and programmable, leading to promising translational studies and clinical trials for both genetic and non-genetic diseases. A major concern in the applications of the CRISPR/Cas9 system is about its off-target effects, namely the deposition of unexpected, unwanted, or even adverse alterations to the genome.

All-in-One Theranostic Platform Based on Hollow Microcapsules for Intragastric-Targeting Antiulcer Drug Delivery, CT Imaging, and Synergistically Healing Gastric Ulcer.

Bismuth-containing therapies are suggested as first-line and rescue alternatives for gastric ulcer (GU) treatment and Helicobacter pylori eradication. The current treatment strategy is called quadruple therapy and includes proton pump inhibitors, bismuth, and two broad-band antibiotics. This fact may affect medication compliance, leading to a resistance rate of more than 25% to clarithromycin or metronidazole.

Protective Effects of Antrodia cinnamomea and Its Constituent Compound Dehydroeburicoic Acid 32 Against Alcoholic Fatty Liver Disease.

Background: Alcoholic fatty liver disease (AFLD), a leading chronic hepatic disease, affects an increasing number of people, and no effective drugs for the treatment of AFLD are available. Antrodia cinnamomea (AC) can inhibit AFLD, but its mechanisms and the effective compound in AC are unknown.

Objective: We aimed to explore the anti-AFLD mechanism of AC and the active compound within AC.

A Review of Research Progress on Agathis dammara and its Application Prospects for Cardiovascular Diseases and Fatty Liver Disease.

Cardiovascular diseases and fatty liver disease have become the leading causes of death in modern society. However, the currently existing drugs do not solve all issues related to these diseases; thus, it is expected that more potential drugs for clinical use will be developed. Undeniably, natural products have attracted increasing attention.

Formulation and intestinal absorption of naringenin loaded nanostructured lipid carrier and its inhibitory effects on nonalcoholic fatty liver disease.

In this study, we prepared naringenin (NGN) loaded nanostructured lipid carrier (NGN-NLC) and investigated its characterizations, transepithelial transport, intestinal absorption and inhibitory effects on nonalcoholic fatty liver disease (NAFLD) induced by a methionine choline deficient (MCD) diet in mice. The NGN-NLC, prepared by a method of emulsion-evaporation plus low temperature-solidification, displayed high drug loading capacity of 22.5 ± 1.

Naringenin attenuates non-alcoholic fatty liver disease by down-regulating the NLRP3/NF-κB pathway in mice.

Background And Purpose: Naringenin, a flavonoid compound with strong anti-inflammatory activity, attenuated non-alcoholic fatty liver disease (NAFLD) induced by a methionine-choline deficient (MCD) diet in mice. However, the mechanisms underlying this suppression of inflammation and NAFLD remain unknown.

Experimental Approach: WT and NLRP3 mice were fed with MCD diet for 7 days to induce NAFLD and were given naringenin by gavage at the same time.

Grape Seed Polyphenols Ameliorated Dextran Sulfate Sodium-Induced Colitis via Suppression of Inflammation and Apoptosis.

Background: Ulcerative colitis (UC) is an inflammatory bowel disease. Its onset is typically gradual, usually followed by periods of spontaneous remission and subsequent relapses. Grape seed polyphenols (GSP), a natural product extracted from grape seeds, have strong anti-inflammatory functions.

Mechanisms underlying the inhibitory effects of probucol on elastase-induced abdominal aortic aneurysm in mice.

Background And Purpose: Abdominal aortic aneurysm (AAA) is a degenerative disease with irreversible and progressive dilation of the artery. But there are few options for efficacious treatment except for traditional surgery. Probucol has been widely applied to treat hyperlipidaemia and atherosclerosis in clinic, but whether it can protect against AAA remains unknown.

Hollow Microcapsules with Ulcerative Colitis Therapeutic Effects Made of Multifunctional Turkish Galls Extraction.

Ulcerative colitis (UC) has been listed as one of the refractory diseases of modern society by the World Health Organization. Our previous studies found that Turkish galls Gallotannins (TGTs) have a significant effect on anti-UC. Here, TGTs were extracted using a simple method and TGTs-Fe microcapsules were prepared by a self-assembly technique.

Rosa rugosa flavonoids exhibited PPARα agonist-like effects on genetic severe hypertriglyceridemia of mice.

Ethnopharmacological Relevance: Rosa rugosa Thunb. is a traditional Chinese medicine that was used in the treatment of cardiovascular diseases and relative risk factors such as diabetes, hyperlipidemia, hypertension, and inflammation. Rosa rugosa flavonoids (RRFs) are the main components in Rosa rugosa Thunb.

Polyurethane Nanoparticle-Loaded Fenofibrate Exerts Inhibitory Effects on Nonalcoholic Fatty Liver Disease in Mice.

Polyurethane (PU) nanoparticles are potential drug carriers. We aimed to study the in vitro and in vivo efficacy of biodegradable PU nanoparticles loaded with fenofibrate (FNB-PU) on nonalcoholic fatty liver disease (NAFLD). FNB-PU was prepared by a green process, and its preventive effects on NAFLD were investigated on HepG2 cells and mice.

Preventive effects of astragaloside IV and its active sapogenin cycloastragenol on cardiac fibrosis of mice by inhibiting the NLRP3 inflammasome.

Cardiac fibrosis is a common feature of many cardiac pathophysiologic conditions. Recently, it has been shown that the activation of NLRP3 inflammasome plays an important role in the pathophysiology of cardiac fibrosis. Here, the inhibitory effects and possible mechanism of astragaloside IV (AST) and its active sapogenin cycloastragenol (CAG) on isoproterenol (ISO)-induced cardiac fibrosis were investigated.

A review of molecular imaging of atherosclerosis and the potential application of dendrimer in imaging of plaque.

Despite the fact that technological advancements have been made in diagnosis and treatment, cardiovascular diseases (CVDs) remain the leading cause of mortality and morbidity worldwide. Early detection of atherosclerosis (AS), especially vulnerable plaques, plays a crucial role in the prevention of acute coronary syndrome (ACS). Targeting the critical cytokines and molecules that are upregulated during the biological process of AS by in vivo molecular imaging has been widely used in plaque imaging.

Thermosensitive Hydrogel Containing Doxycycline Exerts Inhibitory Effects on Abdominal Aortic Aneurysm Induced By Pancreatic Elastase in Mice.

Doxycycline (DOX) is reported to exert therapeutic effects against abdominal aortic aneurysm (AAA), a severe degenerative disease. In this study, a DOX hydrogel formulation of DOX/PECT is studied, and its phase transition behavior and in vitro release profiles are explored. In addition, the anti-AAA effects and bioavailability of DOX/PECT are evaluated in an elastase induced AAA mouse model.

Grape-seed Polyphenols Play a Protective Role in Elastase-induced Abdominal Aortic Aneurysm in Mice.

Abdominal aortic aneurysm (AAA) is a kind of disease characterized by aortic dilation, whose pathogenesis is linked to inflammation. This study aimed to determine whether grape-seed polyphenols (GSP) has anti-AAA effects and what mechanism is involved, thus to find a way to prevent occurrence and inhibit expansion of small AAA. In our study, AAA was induced by incubating the abdominal aorta of the mice with elastase, and GSP was administrated to the mice by gavage at different doses beginning on the day of the AAA inducement.

Nanoliposome improves inhibitory effects of naringenin on nonalcoholic fatty liver disease in mice.

To prepare naringenin nanoliposome (NRG-Nanolipo) and investigate its inhibitory effects on nonalcoholic fatty liver disease (NAFLD). NRG-Nanolipo was prepared by thin-film rehydration method. Its characterizations and effects on NAFLD in mice induced by methionine choline deficient diet were investigated.

Rosa rugosa flavonoids alleviate myocardial ischemia reperfusion injury in mice by suppressing JNK and p38 MAPK.

Objective: Although Rosa rugosa has been applied for preventing coronary artery disease, the pharmacological mechanism is little explored. In this study, the effects and mechanisms of Rosa rugosa flavonoids (RRF) on myocardial ischemia reperfusion injury (MIRI) were investigated.

Methods: Mice were pretreated by intragastric administration of 600 mg/kg RRF for 7 days.

Alpha-Tocopheryl Succinate-Conjugated G5 PAMAM Dendrimer Enables Effective Inhibition of Ulcerative Colitis.

Ulcerative colitis (UC) is a severe inflammatory disease in colon, however, the therapeutic efficacy of the standard-of-care in clinic for UC patients is unsatisfactory. To explore new drugs for effective and safe treatment of UC, alpha-tocopheryl succinate (α-TOS) is conjugated to generation 5 (G5) poly(amidoamine) (PAMAM) dendrimer to construct a nanodevice of G5-NH-acetamide (Ac)-TOS. The inhibitory effects of the G5-NH-Ac-TOS on UC are evaluated in vivo in a dextran sulfate sodium induced UC mouse model, and its mechanisms are explored in vitro in lipopolysaccharide stimulated mouse peritoneal macrophages.

Recombinant high-density lipoproteins and their use in cardiovascular diseases.

The unique anti-atherosclerosis abilities and other cardioprotective properties make high-density lipoprotein (HDL) a promising solution in treating cardiovascular diseases. A number of studies showed that HDL-based therapy was well tolerated and has great potential in the future. Among all these new agents, the most studied ones including recombinant HDL, recombinant human apolipoproteins, apolipoprotein mimetic peptides and recombinant HDL used as contrast agents in cardiovascular imaging are discussed here.

Fenofibrate nanoliposome: Preparation and its inhibitory effects on nonalcoholic fatty liver disease in mice.

The aim was to prepare fenofibrate nanoliposome (FNB-Nanolipo) and investigate its characterizations, oral pharmacokinetic (PK) profiles as well as preventive and therapeutic effects on nonalcoholic fatty liver disease (NAFLD) induced by a methionine choline deficient (MCD) diet in mice. The prepared FNB-Nanolipo showed high drug loading capacity and sustained in vitro FNB release profile. Compared to FNB crude drug at equal doses, the FNB-Nanolipo given at 20 mg/kg/day (beginning on the same day when the MCD diet feeding started and lasted for 7 days) or 40 mg/kg/day (beginning after 7 days of the MCD diet feeding and lasting for another 7 days together with the MCD diet) increased plasma FNB concentration of the mice by 11.

Recent Advances in Dendrimer Research for Cardiovascular Diseases.

Dendrimers, as a type of artificially synthesized polymers, have been increasingly attracting attention in many research fields, including the material and medical sciences, due to their unique characteristics that include their highly branched and well-defined molecular architecture, multivalency and tunable chemical compositions. These advantages make dendrimers potential carriers for the delivery of therapeutic and diagnostic agents. Herein, we review the recent advances in dendrimer research for the prevention and treatment of cardiovascular diseases, with special focus on their applications as carriers for drug and gene delivery, as contrast agents, and as potential new drugs.