The 10 most-cited articles in Experimental Biology and Medicine, 2023

The evolution of medical knowledge about oral microbiota has increased awareness of its important role for the entire human body health. A wide range of microbial species colonizing the oral cavity interact both with each other and with their host through complex pathways. Usually, these interactions lead to a harmonious coexistence (i.e. eubiosis). However, several factors - including diet, poor oral hygiene, tobacco smoking, and certain medications, among others - can disrupt this weak homeostatic balance (i.e. dysbiosis) with potential implications on both oral (i.e. development of caries and periodontal disease) and systemic health. This article is thus aimed at providing an overview on the importance of oral microbiota in mediating several physiological and pathological conditions affecting human health. In this context, strategies based on oral hygiene and diet as well as the role of probiotics supplementation are discussed.

The ever-increasing number of chemicals has raised public concerns due to their adverse effects on human health and the environment. To protect public health and the environment, it is critical to assess the toxicity of these chemicals. Traditional in vitro and in vivo toxicity assays are complicated, costly, and time-consuming and may face ethical issues. These constraints raise the need for alternative methods for assessing the toxicity of chemicals. Recently, due to the advancement of machine learning algorithms and the increase in computational power, many toxicity prediction models have been developed using various machine learning and deep learning algorithms such as support vector machine, random forest, k-nearest neighbors, ensemble learning, and deep neural network. This review summarizes the machine learning- and deep learning-based toxicity prediction models developed in recent years. Support vector machine and random forest are the most popular machine learning algorithms, and hepatotoxicity, cardiotoxicity, and carcinogenicity are the frequently modeled toxicity…

Acetaminophen (APAP), a widely used antipyretic and analgesic drug in clinics, is relatively safe at therapeutic doses; however, APAP overdose may lead to fatal acute liver injury. Currently, N-acetylcysteine (NAC) is clinically used as the main antidote for APAP poisoning, but its therapeutic effect remains limited owing to rapid disease progression and the general diagnosis of advanced poisoning. As is well known, APAP-induced hepatotoxicity (AIH) is mainly caused by the toxic metabolite N-acetyl- p-benzoquinone imine (NAPQI), and the toxic mechanisms of AIH are complicated. Several cellular processes are involved in the pathogenesis of AIH, including liver metabolism, mitochondrial oxidative stress and dysfunction, sterile inflammation, endoplasmic reticulum stress, autophagy, and microcirculation dysfunction. Mitochondrial oxidative stress and dysfunction are the major cellular events associated with APAP-induced liver injury. Many biomolecules involved in these biological processes are potential therapeutic targets for AIH. Therefore, there is an urgent need to comprehensively…

S100B is a 21-kDa protein that is produced and secreted by astrocytes and widely used as a marker of brain injury in clinical and experimental studies. The majority of these studies are based on measurements in blood serum, assuming an associated increase in cerebrospinal fluid and a rupture of the blood–brain barrier (BBB). Moreover, extracerebral sources of S100B are often underestimated. Herein, we will review these interpretations and discuss the routes by which S100B, produced by astrocytes, reaches the circulatory system. We discuss the concept of S100B as an alarmin and its dual activity as an inflammatory and neurotrophic molecule. Furthermore, we emphasize the lack of data supporting the idea that S100B acts as a marker of BBB rupture, and the need to include the glymphatic system in the interpretations of serum changes of S100B. The review is also dedicated to valorizing extracerebral sources of S100B, particularly adipocytes. Furthermore, S100B per se may have direct and indirect modulating roles in brain barriers: on the tight junctions that regulate paracellular…

The blood–brain barrier (BBB) is a critical physiochemical interface that regulates communication between the brain and blood. It is comprised of brain endothelial cells which regulate the BBB’s barrier and interface properties and is surrounded by supportive brain cell types including pericytes and astrocytes. Recent reports have suggested that the BBB undergoes dysfunction during normative aging and in disease. In this review, we consider the effect of cellular senescence, one of the nine hallmarks of aging, on the BBB. We first characterize known normative age–related changes at the BBB, and then evaluate changes in neurodegenerative diseases, with an emphasis on if/how cellular senescence is influencing these changes. We then discuss what insight has been gained from in vitro and in vivo studies of cellular senescence at the BBB. Finally, we evaluate mechanisms by which cellular senescence in peripheral pathologies can indirectly or directly affect BBB function.

Brain tumors are often fatal. Therefore, accurate brain tumor image segmentation is critical for the diagnosis, treatment, and monitoring of patients with these tumors. Magnetic resonance imaging (MRI) is a commonly used imaging technique for capturing brain images. Both machine learning and deep learning techniques are popular in analyzing MRI images. This article reviews some commonly used machine learning and deep learning techniques for brain tumor MRI image segmentation. The limitations and advantages of the reviewed machine learning and deep learning methods are discussed. Even though each of these methods has a well-established status in their individual domains, the combination of two or more techniques is currently an emerging trend.

Bacterial cell wall formation is essential for cellular survival and morphogenesis. The peptidoglycan (PG), a heteropolymer that surrounds the bacterial membrane, is a key component of the cell wall, and its multistep biosynthetic process is an attractive antibacterial development target. Penicillin-binding proteins (PBPs) are responsible for cross-linking PG stem peptides, and their central role in bacterial cell wall synthesis has made them the target of successful antibiotics, including β-lactams, that have been used worldwide for decades. Following the discovery of penicillin, several other compounds with antibiotic activity have been discovered and, since then, have saved millions of lives. However, since pathogens inevitably become resistant to antibiotics, the search for new active compounds is continuous. The present review highlights the ongoing development of inhibitors acting mainly in the transpeptidase domain of PBPs with potential therapeutic applications for the development of new antibiotic agents. Both the critical aspects of the strategy, design, and…

Curcumin, an antitumor agent, has been shown to inhibit cell growth and metastasis in osteosarcoma. However, there is no evidence of curcumin and its regulation of cell ferroptosis and nuclear factor E2–related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathways in osteosarcoma. This study aimed to investigate the effects of curcumin on osteosarcoma both in vitro and in vivo. To explore the effects and mechanisms of curcumin on osteosarcoma, cells (MNNG/HOS and MG-63) and xenograft mice models were established. Cell viability, cell apoptosis rate, cycle distribution, cell migration, cell invasion, reactive oxygen species, malonaldehyde and glutathione abilities, and protein levels were detected by cell counting kit-8, flow cytometry, wound healing, transwell assay, respectively. Nrf2 and GPX4 expressions were detected using an immunofluorescence assay. Nrf2/GPX4-related protein levels were detected using western blotting. The results showed that curcumin effectively decreased cell viability and increased apoptosis rate. Meanwhile, curcumin inhibited tumor volume in…

The lung is the primary organ for the metastasis of osteosarcoma. Although the application of neoadjuvant chemotherapy and surgery has remarkably improved the survival rate of patients with osteosarcoma, prognosis is still poor for those patients with metastasis. In this study, we performed further bioinformatics analysis on single-cell RNA sequencing (scRNA-seq) data published before, containing 75,317 cells from two osteosarcoma lung metastasis and five normal lung tissues. First, we classified 17 clusters, including macrophages, T cells, endothelial cells, and so on, indicating highly intratumoral heterogeneity in osteosarcoma lung metastasis. Next, we found macrophages in osteosarcoma lung metastasis did not have significant M1 or M2 polarizations. Then, we identified that T cells occupied the most abundant among all cell clusters, and found CD8 + T cells exhibited a low expression level of immune checkpoints in osteosarcoma lung metastasis. What is more, we identified C2_Malignant cells, and found CD63 might play vital roles in determining the infiltration of T cells and…

Ubiquitination is an intricately regulated post-translational modification that involves the covalent attachment of ubiquitin to a substrate protein. The complex dynamic nature of the ubiquitination process regulates diverse cellular functions including targeting proteins for degradation, cell cycle, deoxyribonucleic acid (DNA) damage repair, and numerous cell signaling pathways. Ubiquitination also serves as a crucial mechanism in protein quality control. Dysregulation in ubiquitination could result in lethal disease conditions such as cancers and neurodegenerative diseases. Therefore, the ubiquitination cascade has become an attractive target for therapeutic interventions. Enormous efforts have been made to detect ubiquitination involving different detection techniques to better grasp the underlying molecular mechanisms of ubiquitination. This review discusses a wide range of techniques stretching from the simplest assays to real-time assays. This includes western blotting/immunoblotting, fluorescence assays, chemiluminescence assays, spectrophotometric assays, and nanopore…