Current Pathobiology Reports

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...

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the SARS-CoV-2 betacoronavirus and has taken over 761,426 American lives as of the date of publication and will likely result in long-term, if not permanent, tissue damage for countless patients. COVID-19 presents with diverse and multisystemic pathologic processes, including a hyperinflammatory response, acute respiratory distress syndrome (ARDS), vascular injury, microangiopathy, tissue fibrosis, angiogenesis, and widespread thrombosis across multiple organs, including the lungs, heart, kidney, liver, and brain...

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...

Nanoparticles have revolutionized biomedicine especially in the field of drug delivery due to their intriguing properties such as systemic stability, level of solubility, and target site specificity. It can, however, be both beneficial and damaging depending on the properties in different environments, thus highlighting the importance of nanotoxicology studies before use in humans. Different types of nanoparticles have been used in drug delivery, and this review summarizes the recent toxicity studies of these nanoparticles...

Purpose of Review: Partial differential equation (PDE) mathematical models of biological systems and the simulation approaches used to solve them are widely used to test hypotheses and infer regulatory interactions based on optimization of the PDE model against the observed data. In this review, we discuss the ability of powerful machine learning methods to accelerate the parametric screening of biophysical informed- PDE systems. Recent Findings: A major shortcoming in more broad adaptation of PDE-based models is the high computational complexity required to solve and optimize the models and it requires many simulations to traverse the very high-dimensional parameter spaces during model calibration and inference tasks...

Purpose of Review: Computational and mathematical modeling have become a critical part of understanding in-host infectious disease dynamics and predicting effective treatments. In this review, we discuss recent findings pertaining to the biological mechanisms underlying infectious diseases, including etiology, pathogenesis, and the cellular interactions with infectious agents. We present advances in modeling techniques that have led to fundamental disease discoveries and impacted clinical translation...

Purpose of review: Alcohol use continues to rise globally. We review the current literature on the effect of alcohol on bone health, homeostasis and fracture repair to highlight what has been learned in people and animal models of alcohol consumption. Recent findings: Recently, forkhead box O (FoxO) has been found to be upregulated and activated in mesenchymal stem cells (MSC) exposed to alcohol. FoxO has also been found to modulate Wnt/β-catenin signaling, which is necessary for MSC differentiation...

Purpose of review: Chronic alcohol use is a worldwide problem with multifaceted consequences including multiplying medical costs and sequelae, societal effects like drunk driving and assault, and lost economic productivity. These large-scale outcomes are driven by the consumption of ethanol, a small permeable molecule that has myriad effects in the human body, particularly in the liver and brain. In this review, we have summarized effects of acute and chronic alcohol consumption on epigenetic mechanisms that may drive pathobiology of Alcohol Use Disorder (AUD) while identifying areas of need for future research...

Purpose of review: Diabetes is a common and prevalent medical condition as it affects many lives around the globe. Specifically, type-2 Diabetes (T2D) is characterized by chronic systemic inflammation alongside hyperglycemia and insulin resistance in the body, which can result in atherosclerotic legion formation in the arteries and thus progression of related conditions called diabetic vasculopathies. T2D patients are especially at risk for vascular injury; adjunct in many of these patients heir cholesterol and triglyceride levels reach dangerously high levels and accumulate in the lumen of their vascular system...

Purpose of review: This article is to review recent technical developments and their clinical applications in cancer imaging quantitative measurement of cellular and vascular properties of the tumors. Recent findings: Rapid development of fast Magnetic Resonance Imaging (MRI) technologies over last decade brought new opportunities in quantitative MRI methods to measure both cellular and vascular properties of tumors simultaneously. Summary: Diffusion MRI (dMRI) and dynamic contrast enhanced (DCE)-MRI have become widely used to assess the tissue structural and vascular properties, respectively...

PURPOSE OF THE REVIEW: We present an overview of recent advances in positron emission tomography (PET) diagnostics as applied to the study of cancer, specifically as a tool to study in vivo cancer biology and to direct targeted cancer therapy. The review is directed to translational and clinical cancer investigators who may not be familiar with these applications of PET cancer diagnostics, but whose research might benefit from these advancing tools. RECENT FINDINGS: We highlight recent advances in 3 areas: (1) the translation of PET imaging cancer biomarkers to clinical trials; (2) methods for measuring cancer metabolism in vivo in patients; and (3) advances in PET instrumentation, including total-body PET, that enable new methodologies...

Purpose of Review: We discuss recent advancements in structural biology methods for investigating sites of protein-protein interactions. We will inform readers outside the field of structural biology about techniques beyond crystallography, and how these different technologies can be utilized for drug development. Recent Findings: Advancements in cryo-electron microscopy (cryoEM) and micro-electron diffraction (microED) may change how we view atomic resolution structural biology, such that well-ordered macrocrystals of protein complexes are not required for interface identification...

Purpose of Review: Cardiovascular disease (CVD) involves a broad range of clinical manifestations resulting from a dysfunctional vascular system. Overproduction of reactive oxygen and nitrogen species are causally implicated in the severity of vascular dysfunction and CVD. Antioxidant therapy is an attractive avenue for treatment of CVD associated pathologies. Implementation of targeted nano-antioxidant therapies has the potential to overcome hurdles associated with systemic delivery of antioxidants...

Purpose of Review: Light microscopy plays an essential role in clinical diagnosis and understanding the pathogenesis of cancer. Conventional bright-field microscope is used to visualize abnormality in tissue architecture and nuclear morphology, but often suffers from many limitations. This review focuses on the potential of new imaging techniques to improve basic and clinical research in pathobiology. Recent findings: Light microscopy has significantly expanded its ability in resolution, imaging volume, speed and contrast...

Purpose of review: Recent studies demonstrate that normal human tissues accumulate substantial numbers of somatic mutations with aging, to levels comparable to their corresponding cancers. If mutations cause cancer, how do tissues avoid cancer when mutations are unavoidable? Recent findings: The small intestines (SI) and colon accumulate similar numbers of replication errors, but SI adenocarcinoma is much rarer than colorectal cancer. Both the small and large intestines are subdivided into millions of small neighborhoods (crypts) that are maintained by small numbers of stem cells...

Purpose of Review: The challenges presented to the lung by the space environment are the effects of prolonged absence of gravity, the challenges of decompression stress associated with spacewalking, and the changes in the deposition of inhaled particulate matter. Recent Findings: Although there are substantial changes in the function of the lung in partial gravity, the lung is largely unaffected by sustained exposure, returning rapidly to a normal state after return to 1G...

PURPOSE OF REVIEW: Orthopaedic trauma is a major cause of morbidity and mortality worldwide. Although many fractures tend to heal if treated appropriately either by nonoperative or operative methods, delayed or failed healing, as well as infections, can lead to devastating complications. Tissue engineering is an exciting, emerging field with much scientific and clinical relevance in potentially overcoming the current limitations in the treatment of orthopaedic injuries. RECENT FINDINGS: While direct translation of bone tissue engineering technologies to clinical use remains challenging, considerable research has been done in studying how cells, scaffolds, and signals may be used to enhance acute fracture healing and to address the problematic scenarios of nonunion and critical-sized bone defects...

Purpose of Review: Stem cells have been proposed as sources for tissue replacement when healing does not occur. These cells could contribute directly to skin structures via differentiation, or via producing trophic factors that would 'educate' the micro-environment to encourage tissue repair. Studies in animals have supported both mechanisms, but translation to humans has been challenged by poor cell survival after transplantation. However, the improvement noted with even transient existence suggests another new possibility, that of suppressing the inflammatory response that limits regenerative healing...

Microbial metabolites influence the function of epithelial, endothelial and immune cells in the intestinal mucosa. Microbial metabolites like SCFAs and B complex vitamins direct macrophage polarization whereas microbial derived biogenic amines modulate intestinal epithelium and immune response. Aberrant bacterial lipopolysaccharide-mediated signaling may be involved in the pathogenesis of chronic intestinal inflammation and colorectal carcinogenesis. Our perception of human microbes has changed from that of opportunistic pathogens to active participants maintaining intestinal and whole body homeostasis...

Purpose of Review: Myofibroblasts are the fundamental drivers of fibrosing disorders; there is great value in better defining epigenetic networks involved in myofibroblast behavior. Complex epigenetic paradigms, which are likely organ and/or disease specific, direct pathologic myofibroblast phenotypes. In this review, we highlight epigenetic regulators and the mechanisms through which they shape myofibroblast phenotype in fibrotic diseases of different organs. Recent Findings: Hundreds of genes and their expression contribute to the myofibroblast transcriptional regime influencing myofibroblast phenotype...