Purposeof the Review Hemostasis plays a central role in maintaining a normal physiological vasculature, especially during and after vascular injury. Low-density lipoprotein (LDL) receptor-related protein 1 (LRP1) is a transmembrane protein of the LDL family that exhibits multifunctional characteristics that affect endocytosis, signal transduction, and the formation of synthetic cell phenotypes in the vascular wall. Studies have shown that LRP1 is particularly important in various pathways and processes that contribute to the maintenance of vascular homeostasis. Recent Findings LRP1 is pivotal to the pathophysiology of vascular disease that impairs vascular integrity. Recent studies have shown that LRP1 can also act as a coactivator, affecting transcription of other important proteins. Current research uses LRP1-deficient models to specifically study the mechanisms of LRP1 in multiple pathways including vascular cells, helping to guide potential therapeutic targets following vascular injury. Summary This review aims to highlight the broad physiological role that LRP1 plays in vessel integrity, cellular function, and various metabolic and signaling pathways. The review also provides insights into the pathophysiology of vascular diseases, especially those resulting from LRP1 deficiency or dysfunction.
Purpose of the Review This review recapitulates the complex pathophysiology of type 2 diabetes mellitus associated with a prothrombotic and proinflammatory phenotype. It focuses on the roles played by platelets and neutrophils in these pathologies and then focuses on recent advances in therapeutic interventions. Recent Findings Platelets, fundamental to the process of hemostasis (and thrombosis), have been increasingly implicated with inflammatory responses. Similarly, neutrophils, the first line of defense against pathogen invasions, forming a crucial role in body’s inflammatory immune responses, have been progressively associated with coagulation and thrombotic reactions. Interestingly, these two cells also interact with each other in their microenvironment, forming platelet-neutrophil complexes, to achieve full functionality. The incidence of these complexes is found to be higher in patients with diabetes mellitus, promoting associated complications. Summary This review attempts to understand the interplay of these cells in a diabetic, hyperglycemic milieu, concluding with a look back at the available therapeutic interventions to address the complications.
Purpose of Review Signaling pathways serve to communicate information about extracellular conditions into the cell, to both the nucleus and cytoplasmic processes to control cell responses. Genetic mutations in signaling network components are frequently associated with cancer and can result in cells acquiring an ability to divide and grow uncontrollably. Because signaling pathways play such a significant role in cancer initiation and advancement, their constituent proteins are attractive therapeutic targets. In this review, we discuss how signaling pathway modeling can assist with identifying effective drugs for treating diseases, such as cancer. An achievement that would facilitate the use of such models is their ability to identify controlling biochemical parameters in signaling pathways, such as molecular abundances and chemical reaction rates, because this would help determine effective points of attack by therapeutics. Recent Findings We summarize the current state of understanding the sensitivity of phosphorylation cycles with and without sequestration. We also describe some basic properties of regulatory motifs including feedback and feedforward regulation. Summary Although much recent work has focused on understanding the dynamics and particularly the sensitivity of signaling networks in eukaryotic systems, there is still an urgent need to build more scalable models of signaling networks that can appropriately represent their complexity across different cell types and tumors.
Nanotechnology offers enormous opportunities in regulation of the physical, mechanical, electrical, and biological properties of tissue engineering scaffolds. Nanoscale structures have been used as delivery agents that can be incorporated in the scaffolds to deliver the required signaling molecules for tissue regeneration. Purpose of Review Purpose of the present review is to discuss the requirements for a tissue engineering construct and how the nanoscale delivery systems facilitate achieving it. Review also depicts the various types of nanostructures explored for the delivery of growth factors, cell differentiation agents, genes, and antimicrobials so as to enable efficient tissue regeneration. How the dynamic nature of tissue can be extrapolated in the scaffold by the use of nanodelivery systems are also presented. Recent Findings Among various nanostructures, polymer and lipid based have been widely used as delivery systems for tissue engineering due to their easily customizable biodegradability and functionalization. Though the inorganic nano-systems offer advantages in terms of imaging and trigger responsiveness, toxicity issues limit their extensive use. Though there are many literatures available on nanoscale delivery systems for tissue engineering, none of them has reached a level of clinical translation. Summary Nanotechnology-based delivery systems opened wide opportunities to alter the characteristics of tissue engineering scaffolds and cellular behavior, ultimately to achieve a better control over neotissue formation. A thorough examination is crucial to establish product safety, effectiveness, or other attributes before they reach clinics.
Purpose of Review COVID-19 has rapidly evolved into a global pandemic infecting over two hundred and forty-four million individuals to date. In addition to the respiratory sequelae and systemic infection that ensues, an alarming number of micro and macrovascular thrombotic complications have been observed. This review examines the current understanding of COVID-19-associated thrombotic complications, potential mechanisms, and pathobiological basis for thromboses development. Recent Findings The endothelium plays a major role in the process due to direct and indirect injury. The immune system also contributes to a pro-thrombotic environment with immune cell dysregulation leading to excessive formation of cytokines, also called cytokine storm, and an eventual promotion of a hypercoagulable environment, known as immunothrombosis. Additionally, neutrophils play an important role by forming neutrophil extracellular traps, which are shown to be pro-thrombotic and further enhanced in COVID-19 patients. A disruption of the fibrinolysis system has also been observed. Summary Multiple pathways likely contribute synergistically to form a pro-thrombotic milieu. A better understanding of these factors and the complex interplay between them will lead to the improvement of diagnostic and therapeutic interventions.
