Current Medicinal Chemistry - Volume 29, Issue 25, 2022

In living cells, redox potential is vitally important for normal physiological processes that are closely regulated by antioxidants, free amino acids, and proteins that either have reactive oxygen and nitrogen species capturing capability or can be compartmentalized. Although hundreds of experiments support the regulatory role of free radicals and their derivatives, several authors continue to claim that these perform only harmful and non-regulatory functions. In this paper, we demonstrate that countless intracellular and extracellular signal pathways are directly or indirectly linked to regulated redox processes. We also briefly discuss how artificial oxidative stress can have important therapeutic potential and the possible negative effects of popular antioxidant supplements. Next, we present the argument supported by a large number of studies that many of the major components of innate immunity and fever are essentially associated with redox processes. Our goal is to point out that the production of excess or unregulated free radicals and reactive species can be secondary processes due to the perturbed cellular signal pathways. However, research on pharmacology should consider the important role of redox mechanisms in the innate immune system and fever.

Hepatocellular carcinoma is a malignancy associated with high mortality and increasing incidence. Early detection of this disease could help increase survival and overall patient benefit. Non-invasive strategies for the diagnosis of this medical condition are of utmost importance. In this scope, the detection of hepatocellular carcinoma biomarkers can provide a useful diagnostic tool. Aptamers are short, single-stranded DNAs or RNAs that can specifically bind selected analytes and act as pseudo-biorecognition elements that can be employed for electrode functionalization. Also, other types of DNA sequences can be used to construct DNA-based biosensors applied for the quantification of hepatocellular carcinoma biomarkers. Herein, we analyze recent examples of aptasensors and DNA biosensors for the detection of hepatocellular carcinoma biomarkers, like micro- RNAs, long non-coding RNAs, exosomes, circulating tumor cells, and proteins. The literature data are discussed comparatively in a critical manner, highlighting the advantages of using electrochemical biosensors in diagnosis, as well as the use of nanomaterials and biocomponents in the functionalization of electrodes for improved sensitivity and selectivity.

Bromodomain and extra-terminal domain (BET) proteins are a well-studied family of proteins associated with a variety of diseases, including malignancy and chronic inflammation. Currently, numerous pan BET inhibitors have exhibited potent efficacy in several in vivo preclinical models and entered clinical trials but have largely stalled due to their adverse events. Therefore, the development of new selective inhibitors and PROTACs (Proteolysis Targeting Chimeras) targeting BET is urgently needed. In the present review, we summarize the BET protein structure and the recent development in BET inhibitors, focusing mainly on BRD4-selective inhibitors and PROTAC degraders.

Cancer is a deadly disease that is often caused by the accumulation of various genetic mutations and pathological alterations. The death rate can only be reduced when it is detected in the early stages, because cancer treatment when the tumor has not metastasized in many regions of the body is more effective. However, early cancer detection is fraught with difficulties. Advances in artificial intelligence (AI) have developed a new scope for efficient and early detection of such a fatal disease. AI algorithms have a remarkable ability to perform well on a variety of tasks that are presented or fed to the system. Numerous studies have produced machine learning and deep learning-assisted cancer prediction models to detect cancer from previously accessible data with better accuracy, sensitivity, and specificity. It has been observed that the accuracy of prediction models in classifying fed data as benign, malignant, or normal is improved by implementing efficient image processing techniques and data segmentation augmentation methodologies, along with advanced algorithms. In this review, recent AI-based models for the diagnosis of the most prevalent cancers in the breast, lung, brain, and skin have been analysed. Available AI techniques, data preparation, modeling processes, and performance assessments have been included in the review.

Among primary bone malignancies, osteosarcoma (OS) is the most common form causing morbidity and mortality in both adults and children. The interesting point about this malignancy is that nearly 10-20% of its newly diagnosed cases have developed metastasis. This adds up to the fact that the survival rate of both metastatic and non-metastatic patients of osteosarcoma has not changed in the past 30 years; therefore, it has been suggested that we need to revise our therapeutic options for OS. In recent years, diverse signaling pathways have drawn the attention of the scientific community since they can be great candidates for treating complicated diseases, such as cancer. In this review, we have tried to explain the pathophysiology of osteosarcoma with the help of different signaling pathways taking part in its initiation/progression and explore how this pathway can be targeted for providing more efficient methods.

Exosomes and liposomes are vesicular nanoparticles that can encapsulate functional cargo. The chemical similarities between naturally occurring exosomes and synthetic liposomes have accelerated the development of exosome mimetics as a therapeutic drug delivery platform under physiological and pathological environments. To maximise the applications of exosomes and liposomes in the clinical setting, it is essential to look into their basic chemical properties and utilise these characteristics to optimise the preparation, loading, modification and hybridisation. This review summarises the chemical and biological properties of both exosomal and liposomal systems as well as some of the challenges related to their production and application. This article concludes with a discussion on potential perspectives for the integration of exosomal and liposomal technologies in mapping better approaches for their biomedical use, especially in therapeutics.