Nanoparticles with SGLT2 inhibitory activity: Possible benefits and future.

AIM: Nano-drug delivery is a rapidly growing approach in medicine that helps design and develop newer forms of drugs with more efficacy and lower adverse effects. Sodium-glucose cotransporter-2 inhibitors are an emerging class of antidiabetic agents that reduce the blood glucose levels by damping glucose reabsorption in renal proximal tubules. METHODS AND RESULTS: This mechanism might be followed by some adverse effects that could be prevented by nano-drug delivery. Although we have still limited evidence about nanoforms of sodium-glucose cotransporter-2 inhibitors, current knowledge strongly suggests that nanotechnology can help us design more effective drugs with lower side effects. In recent years, several studies have explored the possible benefits of nanoforms of sodium-glucose cotransporter-2 inhibitors. However, clinical trials are yet to be conducted. CONCLUSION: In the current review, we present the latest findings on the development and benefits of nanoforms of sodium-glucose cotransporter-2 inhibitors.

Long Non-Coding RNAs in Colorectal Cancer: Navigating the Intersections of Immunity, Intercellular Communication, and Therapeutic Potential.

This comprehensive review elucidates the intricate roles of long non-coding RNAs (lncRNAs) within the colorectal cancer (CRC) microenvironment, intersecting the domains of immunity, intercellular communication, and therapeutic potential. lncRNAs, which are significantly involved in the pathogenesis of CRC, immune evasion, and the treatment response to CRC, have crucial implications in inflammation and serve as promising candidates for novel therapeutic strategies and biomarkers. This review scrutinizes the interaction of lncRNAs with the Consensus Molecular Subtypes (CMSs) of CRC, their complex interplay with the tumor stroma affecting immunity and inflammation, and their conveyance via extracellular vesicles, particularly exosomes. Furthermore, we delve into the intricate relationship between lncRNAs and other non-coding RNAs, including microRNAs and circular RNAs, in mediating cell-to-cell communication within the CRC microenvironment. Lastly, we propose potential strategies to manipulate lncRNAs to enhance anti-tumor immunity, thereby underlining the significance of lncRNAs in devising innovative therapeutic interventions in CRC.

Phenotype Diversity of Macrophages in Osteoarthritis: Implications for Development of Macrophage Modulating Therapies.

Chronic inflammation is implicated in numerous human pathologies. In particular, low-grade inflammation is currently recognized as an important mechanism of osteoarthritis (OA), at least in some patients. Among the signs of the inflammatory process are elevated macrophage numbers detected in the OA synovium compared to healthy controls. High macrophage counts also correlate with clinical symptoms of the disease. Macrophages are central players in the development of chronic inflammation, pain, cartilage destruction, and bone remodeling. However, macrophages are also involved in tissue repair and remodeling, including cartilage. Therefore, reduction of macrophage content in the joints correlates with deleterious effects in OA models. Macrophage population is heterogeneous and dynamic, with phenotype transitions being induced by a variety of stimuli. In order to effectively use the macrophage inflammatory circuit for treatment of OA, it is important to understand macrophage heterogeneity and interactions with surrounding cells and tissues in the joint. In this review, we discuss functional phenotypes of macrophages and specific targeting approaches relevant for OA treatment development.

Novel Models of Crohn's Disease Pathogenesis Associated with the Occurrence of Mitochondrial Dysfunction in Intestinal Cells.

Crohn's disease remains one of the challenging problems of modern medicine, and the development of new and effective and safer treatments against it is a dynamic field of research. To make such developments possible, it is important to understand the pathologic processes underlying the onset and progression of Crohn's disease at the molecular and cellular levels. During the recent years, the involvement of mitochondrial dysfunction and associated chronic inflammation in these processes became evident. In this review, we discuss the published works on pathogenetic models of Crohn's disease. These models make studying the role of mitochondrial dysfunction in the disease pathogenesis possible and advances the development of novel therapies.

Cytokines in Abdominal Aortic Aneurysm: Master Regulators With Clinical Application.

Abdominal aortic aneurysm (AAA) is a potentially life-threatening disorder with a mostly asymptomatic course where the abdominal aorta is weakened and bulged. Cytokines play especially important roles (both positive and negative) among the molecular actors of AAA development. All the inflammatory cascades, extracellular matrix degradation and vascular smooth muscle cell apoptosis are driven by cytokines. Previous studies emphasize an altered expression and a changed epigenetic regulation of key cytokines in AAA tissue samples. Such cytokines as IL-6, IL-10, IL-12, IL-17, IL-33, IL-1ß, TGF-ß, TNF-α, IFN-γ, and CXCL10 seem to be crucial in AAA pathogenesis. Some data obtained in animal studies show a protective function of IL-10, IL-33, and canonical TGF-ß signaling, as well as a dual role of IL-4, IFN-γ and CXCL10, while TNF-α, IL-1ß, IL-6, IL-12/IL-23, IL-17, CCR2, CXCR2, CXCR4 and the TGF-ß noncanonical pathway are believed to aggravate the disease. Altogether data highlight significance of cytokines as informative markers and predictors of AAA. Pathologic serum/plasma concentrations of IL-1ß, IL-2, IL-6, TNF-α, IL-10, IL-8, IL-17, IFN-γ, and PDGF have been already found in AAA patients. Some of the changes correlate with the size of aneurysms. Moreover, the risk of AAA is associated with polymorphic variants of genes encoding cytokines and their receptors: CCR2 (rs1799864), CCR5 (Delta-32), IL6 (rs1800796 and rs1800795), IL6R (rs12133641), IL10 (rs1800896), TGFB1 (rs1800469), TGFBR1 (rs1626340), TGFBR2 (rs1036095, rs4522809, rs1078985), and TNFA (rs1800629). Finally, 5 single-nucleotide polymorphisms in gene coding latent TGF-ß-binding protein (LTBP4) and an allelic variant of TGFB3 are related to a significantly slower AAA annual growth rate.

Mitochondrial Implications in Cardiovascular Aging and Diseases: The Specific Role of Mitochondrial Dynamics and Shifts.

Cardiovascular disease has been, and remains, one of the leading causes of death in the modern world. The elderly are a particularly vulnerable group. The aging of the body is inevitably accompanied by the aging of all its systems, and the cardiovascular system is no exception. The aging of the cardiovascular system is a significant risk factor for the development of various diseases and pathologies, from atherosclerosis to ischemic stroke. Mitochondria, being the main supplier of energy necessary for the normal functioning of cells, play an important role in the proper functioning of the cardiovascular system. The functioning of each individual cell and the organism as a whole depends on their number, structure, and performance, as well as the correct operation of the system in removing non-functional mitochondria. In this review, we examine the role of mitochondria in the aging of the cardiovascular system, as well as in diseases (for example, atherosclerosis and ischemic stroke). We pay special attention to changes in mitochondrial dynamics since the shift in the balance between fission and fusion is one of the main factors associated with various cardiovascular pathologies.

The Role of KLF2 in the Regulation of Atherosclerosis Development and Potential Use of KLF2-Targeted Therapy.

Kruppel like factor 2 (KLF2) is a mechanosensitive transcription factor participating in the regulation of vascular endothelial cells metabolism. Activating KLF2 in endothelial cells induces eNOS (endothelial nitric oxide synthase) expression, subsequent NO (nitric oxide) release, and vasodilatory effect. In addition, many KLF2-regulated genes participate in the anti-thrombotic, antioxidant, and anti-inflammatory activities, thereby preventing atherosclerosis development and progression. In this review, we summarise recent evidence suggesting that KLF2 plays a major role in regulating atheroprotective effects in endothelial cells. We also discuss several recently identified repurposed drugs and natural plant-based bioactive compounds with KLF2-mediated atheroprotective activities. Herein, we present a comprehensive overview of the role of KLF2 in atherosclerosis and as a pharmacological target for different drugs and natural compounds and highlight the potential application of these phytochemicals for the treatment of atherosclerosis.

Functional Phenotypes of Intraplaque Macrophages and Their Distinct Roles in Atherosclerosis Development and Atheroinflammation.

Macrophages are the key inflammatory cell type involved in all stages of atherosclerosis development and progression, as demonstrated by numerous studies. Correspondingly, macrophages are currently regarded as a promising therapeutic target for the development of new treatment approaches. The macrophage population is heterogeneous and dynamic, as these cells can switch between a number of distinct functional states with pro- and anti-atherogenic activity in response to various stimuli. An atherosclerotic plaque microenvironment defined by cytokine levels, cell-to-cell interactions, lipid accumulation, hypoxia, neoangiogenesis, and intraplaque haemorrhage may guide local macrophage polarization processes within the lesion. In this review, we discuss known functional phenotypes of intraplaque macrophages and their distinct contribution to ahteroinflammation.