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Colorectal cancer (CRC) is a common and highly metastatic cancer affecting people worldwide. Drug resistance and unwanted side effects are some of the limitations of current treatments for CRC. Naringenin (NAR) is a naturally occurring compound found in abundance in various citrus fruits such as oranges, grapefruits, and tomatoes. It possesses a diverse range of pharmacological and biological properties that are beneficial for human health. Numerous studies have highlighted its antioxidant, anticancer, and anti‐inflammatory activities, making it a subject of interest in scientific research. This review provides a comprehensive overview of the effects of NAR on CRC. The study's findings indicated that NAR: (1) interacts with estrogen receptors, (2) regulates the expression of genes related to the p53 signaling pathway, (3) promotes apoptosis by increasing the expression of proapoptotic genes (Bax, caspase9, and p53) and downregulation of the antiapoptotic gene Bcl2, (4) inhibits the activity of enzymes involved in cell survival and proliferation, (5) decreases cyclin D1 levels, (6) reduces the expression of cyclin‐dependent kinases (Cdk4, Cdk6, and Cdk7) and antiapoptotic genes (Bcl2, x‐IAP, and c‐IAP‐2) in CRC cells. In vitro CDK2 binding assay was also performed, showing that the NAR derivatives had better inhibitory activities on CDK2 than NAR. Based on the findings of this study, NAR is a potential therapeutic agent for CRC. Additional pharmacology and pharmacokinetics studies are required to fully elucidate the mechanisms of action of NAR and establish the most suitable dose for subsequent clinical investigations. Significance statement: The review discusses the molecular and biochemical processes related to naringenin (NAR's) effects on colorectal cancer (CRC), emphasizing its diverse pharmacological and biological properties. NAR interacts with estrogen receptors, regulates gene expression related to the p53 signaling pathway, promotes apoptosis, inhibits enzymes involved in cell survival and proliferation, decreases cyclin D1 levels, and reduces the expression of cyclin‐dependent kinases and antiapoptotic genes in CRC cells. In vitro studies demonstrate that NAR derivatives have better inhibitory activities on CDK2 than NAR, suggesting their potential as therapeutic agents for CRC. [ABSTRACT FROM AUTHOR]

Mitogen‐activated protein kinase 7 (MAPK7) is a serine/threonine protein kinase that belongs to the MAPK family and plays a vital role in various cellular processes such as cell proliferation, differentiation, gene transcription, apoptosis, metabolism, and cell survival. The elevated expression of MAPK7 has been associated with the onset and progression of multiple aggressive tumors in humans, underscoring the potential of targeting MAPK7 pathways in therapeutic research. This pursuit holds promise for the advancement of anticancer drug development by developing potential MAPK7 inhibitors. To look for potential MAPK7 inhibitors, we exploited structure‐based virtual screening of natural products from the ZINC database. First, the Lipinski rule of five criteria was used to filter a large library of ~90,000 natural compounds, followed by ADMET and pan‐assay interference compounds (PAINS) filters. Then, top hits were chosen based on their strong binding affinity as determined by molecular docking. Further, interaction analysis was performed to find effective and specific compounds that can precisely bind to the binding pocket of MAPK7. Consequently, two compounds, ZINC12296700 and ZINC02123081, exhibited significant binding affinity and demonstrated excellent drug‐like properties. All‐atom molecular dynamics simulations for 200 ns confirmed the stability of MAPK7‐ZINC12296700 and MAPK7‐ZINC02123081 docked complexes. According to the molecular mechanics Poisson–Boltzmann surface area investigation, the binding affinities of both complexes were considerable. Overall, the result suggests that ZINC12296700 and ZINC02123081 might be used as promising leads to develop novel MAPK7 inhibitors. Since these compounds would interfere with the kinase activity of MAPK7, therefore, may be implemented to control cell growth and proliferation in cancer after required validations. [ABSTRACT FROM AUTHOR]

In recent decades, in many countries of the world there has been an increase in the incidence of colorectal cancer (CRC). The annual occurrence of 50 new cases of colorectal cancer per 100,000 population determines a 5% population risk of developing the disease throughout life 1. An alarming fact is that for the 100 newly diagnosed patients with CRC, more than 70 deaths occur, of which, in the 1st year from the moment of diagnosis, about 40%. This circumstance is due to the fact that when patients first go to the doctor, advanced forms of CRC (stage III-IV) are diagnosed in 62.4% of patients. In 25-30% of patients, distant metastases are detected at the time of surgery. In recent years, there has been a tendency to expand indications for organ-preserving operations in the CRC.At the same time, it is necessary to formulate clear criteria for their implementation on the basis of a comparative analysis of long-term treatment results, the frequency of local regional relapses, the development and implementation of techniques using staplers, as well as the justification of indications for the use of combined and complex treatment programs that increase the radicalism and ablasticity of surgical interventions. [ABSTRACT FROM AUTHOR]

Introduction: Much attention is paid to pharmacokinetic (FK) researches for studying the processes of supply, distribution, biotransformation and excretion of medications at the present time, as well as identifying links between medical substances concentration and (or) its metabolites in biological fluids and tissues, and its pharmacological effect. In the treatment of rheumatoid arthritis (RA), non-steroidal anti-inflammatory drugs (NSAID) are widely used for a symptom therapy, where Diclofenac Sodium (DS) is most commonly prescribed. Duration of anti-inflammatory effect, effectiveness of NSAID in whole are directly dependent on the level of effective concentration of medications and circulation duration in blood in free form. The Aim of the present research work is to study in a comparative aspect certain indicators of Diclofenac Sodium pharmacokinetics in patients with rheumatoid arthritis with gastric microbiocenosis disorders (gastric dysbiosis) and without disorders (without dysbiosis). Materials and Method: 38 patients at the age from 18 to 60 years were examined, with I-II-III degree of disease activity. In addition to the general clinical examination, an immune-enzyme method and urease test were carried out to determine Helicobacter Pylori and highly effective liquid chromatography to determine Diclofenac pharmacokinetics. Results: Conducted researches and analysis of their results indicate that in conditions of rheumatoid arthritis, particularly, in the presence of comorbid states, there is a decrease in the metabolism rate and an extension of NSAID half-excretion period, which increases the risk of side effects, especially to the gastrointestinal tract, and significantly affects the disease course and the results of the treatment. Conclusion: In conditions of rheumatoid arthritis with comorbid states, there is more frequent occurrence of the NSAID side effects. Research conducted and analysis of their results indicate that in conditions of rheumatoid arthritis, particularly at comorbid states, there are reasonable changes in the NSAID pharmacokinetics. The decreasing of metabolic rate and the extension of the NSAID half-excretion increases the risk of side effects, especially on the side of the GIT, which significantly affects the disease course and results of the treatment. This circumstance dictates the need to take these results into account in the treatment of the studied pathology and in the development of a personalized approach to the treatment of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

The problem of clinical and instrumental evaluation of the surgical treatment effectiveness of chronic generalized periodontitis using RANK-RANKL-OPG biomarkers is discussed in the article. Currently, the important role of Pro - and anti-inflammatory cytokines in the regulation of the immune-inflammatory response has been established 2. Progressive destruction of bone tissue in patients with periodontal diseases is associated with a combination of cytokines IL-1β, IL-6, TNF and prostaglandins E2. The use of Alhadaya in complex therapy with surgical treatment will allow to control the level of biomarkers of bone inflammation, which will allow to use this method for the diagnosis of periodontal diseases and as the outcome of treatment, in addition to traditional research method (clinical, functional, x-ray, densitometric). [ABSTRACT FROM AUTHOR]

Microproteins, known as micropeptides, are small protein molecules encoded by short open reading frames. These recently identified molecules have been proven to be an essential part of the human proteome that participates in multiple processes, such as DNA repair, mitochondrial respiration, and regulating different signaling pathways. A growing body of studies has evidenced that microproteins exhibit dysregulated expression levels in various malignancies and contribute to tumor progression. It has been reported that microproteins interact with many proteins, such as enzymes (e.g., adenosine triphosphate synthase) and signal transducers (e.g., c‐Jun), and regulate malignant cell metabolism, proliferation, and metastasis. Moreover, microproteins have been found to play a significant role in multidrug resistance in vitro and in vivo by their activity in DNA repair pathways. Considering that, this review intended to summarize the roles of microproteins in different aspects of tumorigenesis with diagnostic and therapeutic perspectives. [ABSTRACT FROM AUTHOR]

Natural products, medicinal plants, and phytoconstituents serve as important sources and accelerators for anticancer drug discovery, especially when they are combined with virtual screening and molecular simulations against molecular drug targets. Proto-oncogene serine/threonine-protein kinase Pim1 (PIM1) is involved in cell survival and proliferation, with great relevance for oncogenesis. PIM1 plays a major role in the progression of various common complex human cancers, including prostate cancer, acute myeloid leukemia, and other hematopoietic malignancies. The overexpression of PIM1 leads to cancer progression, and thus it is considered as a potential target for drug design and development purposes. Here, we report original in silico findings by employing structure-based virtual screening to discover potential phytoconstituents from the medicinal plants-based compounds, which could inhibit the PIM1 activity, using the IMPPAT (a curated database of Indian Medicinal Plants, Phytochemistry And Therapeutics) database. The initial hits were selected based on their binding affinity toward PIM1 calculated through the molecular docking approach. Subsequently, interaction analyses and molecular dynamics (MD) simulation for 100 ns was carried out to study the conformational dynamics and complex stability of PIM1 with the identified compounds. Importantly, we found that PIM1 forms stable protein-ligand complexes with the phytoconstituents Dehydrotectol and Nordracorubin in particular. Our findings suggest that identified phytoconstituents Dehydrotectol and Nordracorubin bind to PIM1 in ATP-competitive binding mode. These findings and the compounds reported herein warrant further exploration as promising scaffolds for anticancer drug design, discovery, and development.

Carbonic anhydrase II (CAII) is one of the zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide, leading to the formation of bicarbonate and proton. CAII plays a significant role in health and disease. For example, CAII helps to maintain eye pressure while regulating the pH of the tumor microenvironment, and by extension, contributing to cancer progression. Owing to its remarkable role in cancer, visual health, and other human diseases, CAII can serve as an attractive therapeutic target. We report an original study based on high-throughput virtual screening of natural compounds from the ZINC database in search of potential inhibitors of CAII. We selected the hits based on the physicochemical, absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, pan-assay interference compound (PAINS) patterns, and interaction analysis. Importantly, two natural compounds were identified, ZINC08918123 and ZINC00952700, bearing considerable affinity and specific interactions to the residues of the CAII-binding pocket with well-organized conformational fitting compatibility. We investigated the conformational dynamics of CAII in complex with the identified compounds through molecular dynamics simulation, which revealed the formation of a stable complex preserved throughout the 100 ns trajectories. The stability of the protein/ligand complexes is maintained by significant numbers of noncovalent interactions throughout the simulations. In conclusion, natural compounds identified in the present study specifically and computer-assisted drug design broadly offer a reliable resource and strategy to discover potential promising therapeutic inhibitors of CAII to cure various cancers and glaucoma after further experimental validation and clinical studies.