Current Medicinal Chemistry - Volume 30, Issue 38, 2023

Atopic dermatitis is epidermal hyperplasia, skin barrier dysfunction, and the aberrant activation of immune cells. Janus kinase (JAK) is a family of cytoplasmic nonreceptor tyrosine kinases that consists of four members, such as JAK1, JAK2, JAK3, and TYK2. The JAK signaling pathway plays a critical role in a wide range of autoimmune and inflammatory diseases, including atopic dermatitis. Abrocitinib is an orally bioavailable and selective JAK1 inhibitor, and it was approved in January, 2022, for the treatment of atopic dermatitis. The chemical structure and physical properties of abrocitinib, its synthesis, mechanism of action, and pharmacokinetic profile are summarized.

This review encapsulates an extensive variety of substances identified as mutual prodrugs or codrugs, wherein two, or sometimes three, biologically active moieties are linked using an assortment of metabolically unstable bridging entities. Following the administration of the mutual prodrugs, these undergo a bridge cleavage releasing the active molecules, which then elicit their respective biological effects. In some cases, the released drugs act synergistically, other times the biological activity of only one of the drugs is elicited, and in such cases, the accompanying drug serves only as a carrier, which may have an affinity to the desired receptor. The most promising results are commonly observed when the two released drugs are efficacious at similar concentrations and particularly when the two drugs are effective against similar diseases. For instance, the best results are observed, when two analgesics, two anticancer agents, two drugs for the treatment of cardiac conditions, etc., are the substances comprising the codrug. Mutual prodrugs/ codrugs described herein have been reported, primarily since the year 2000, as potential drugs for use against a plethora of diseases including pain, inflammation, cancer, bacterial infections, sickle cell anemia, Alzheimer’s disease, and others.

Long non-coding RNA (lncRNA) is a kind of biomolecule that can regulate important life activities such as cell proliferation, apoptosis, differentiation, aging, and body development. It has been found that lncRNAs are closely related to various diseases. In cardiovascular diseases, lncRNAs affect the expression level of related genes in atherosclerotic plaques, which are closely related to endothelial dysfunction, smooth muscle cell proliferation, macrophage dysfunction, abnormal lipid metabolism, and cellular autophagy, thus participating in regulating the occurrence and development of AS. In view of this, investigating the role of lncRNAs in regulating cardiac gene networks on cardiovascular system diseases has attracted much clinical attention and may be a novel target for AS therapy. This paper focuses on lncRNAs related to AS, explores the relationship between lncRNAs and AS, suggests the role of lncRNAs in the prevention and treatment of AS, and expects the application of more lncRNAs as the marker in the clinical diagnosis and treatment of AS.

Atherosclerosis (AS) is the major factor of cardiovascular disease (CVD) and is characterized by a progressive and chronic inflammatory process in the arterial wall. Recent studies have shown that disruption of the mitochondrial membrane potential (deltapsi (m)) directly affects the electron transport chain (ETC), which in turn leads to oxidative stress, and furthermore, its alteration leads to apoptosis and activation of the NLRP3 inflammasome, thereby promoting the development of AS. Here, this review describes how deltapsi (m) contributes to the development of AS by mediating oxidative stress, apoptosis, and NLRP3 inflammasome activation, and potential AS intervention strategies by targeting oxidative stress, apoptosis, and NLRP3 inflammasome activation induced by deltapsi (m).

Gastrointestinal (GI) cancers are one of the most common human malignancies and a leading cause of morbidity and mortality worldwide. One of the most prominent hallmarks of cancer and a basic trait of almost all GI malignancies is genomic/epigenomics alterations. DNA methylation is highlighted as a fundamental mechanism underlying the inactivation of several tumor-suppressor gene signaling pathways. Thus, sites of DNA methylation can be triggered for cancer therapy. Available therapeutic procedures for GI cancer show unsatisfactory efficacy, and some treatments are associated with severe side effects, including ulceration or bleeding. Therefore, it is essential to find alternative treatments. There is growing evidence indicating that some chemopreventive phytochemicals can combat cancer. One of the most systematically investigated nutraceuticals for its advantages in managing different diseases is curcumin (CUR). CUR is well known for its potent anticancer characteristics by targeting epigenetic mechanisms, with DNA methylation at the forefront. Prior investigations have indicated that CUR treatment can benefit GI cancers by controlling several signaling pathways related to oxidative stress and epigenomics pathways. The present literature displays recent evidence regarding DNA methylation alterations by CUR and its potential role in GI cancer prevention and treatment.