The 10 most-cited articles in Experimental Biology and Medicine, 2020

Hepatic fibrogenesis is a pathophysiological outcome of chronic liver injury hallmarked by excessive accumulation of extracellular matrix proteins. Fibrosis is a dynamic process that involves cross-talk between parenchymal cells (hepatocytes), hepatic stellate cells, sinusoidal endothelial cells and both resident and infiltrating immune cells. In this review, we focus on key cell-types that contribute to liver fibrosis, cytokines, and chemokines influencing this process and what it takes for fibrosis to regress. We discuss how mitochondria and metabolic changes in hepatic stellate cells modulate the fibrogenic process. We also briefly review how the presence of fibrosis affects development of hepatocellular carcinoma. Impact statement Advanced liver fibrosis results in cirrhosis, portal hypertension, and liver failure and often requires liver transplantation. Advanced liver fibrosis and cirrhosis are also major risk factors for hepatocellular carcinoma (HCC). Hepatic stellate cells (HSCs) play a pivotal role in the pathogenesis of liver fibrosis. In this review, we summarize the…

Hesperidin belongs to flavanones class of flavonoids and is known to possess broad-spectrum applicability to prevent dreadful diseases such as cardiovascular disease, neurodegeneration, and cancer. The reported anticancer effects of hesperidin have been found to be associated with its anti-oxidant and anti-inflammatory activities. Hesperidin interacts with numerous recognized cellular targets and inhibits cancer cell proliferation by inducing apoptosis and cell cycle arrest. In addition, evidence has suggested its promising role in inhibiting tumor cell metastasis, angiogenesis, and chemoresistance. The present mini-review highlights the ongoing development to identify hesperidin targets in cancer. Furthermore, the potential of nano technology-based hesperidin combinations and delivery systems will also be discussed. Overall, this review highlights all the possible molecular targets affected by hesperidin in tumor cells on a single platform. Impact statement Experimental findings from numerous studies have demonstrated the anticancer effects of hesperidin (Hesp) to be associated…

Acute traumatic spinal cord injury is a devastating event without effective therapeutic approach. The feeble plasticity of spinal cord microvascular endothelial cells (SCMECs) after trauma is one of the major causes for the exacerbation of spinal cord injury. Therefore, improving the plasticity and regeneration of SCMECs is crucial to promote recovery after spinal cord injury. For the present study, we explored the influence of exosomes derived from neural stem cells (NSCs-Exos) on the spinal cord microvascular regeneration after spinal cord injury and determined the underlying mechanisms. After the primary NSCs and SCMECs were extracted, exosomes were isolated from NSCs conditioned medium and used to co-incubated with the SCMECs in vitro, and then the effect of exosomes on the angiogenic activities of SCMECs was measured. The candidate molecules involved in the NSCs-Exos-mediated angiogenesis were screened using Western blotting. The effect of NSCs-Exos on angiogenesis and spinal cord functional recovery after injury in vivo was analyzed. The results demonstrated that NSCs-Exos…

BRAF mutations are relatively common in many cancers, particularly melanoma, colorectal cancer, and thyroid cancer and to a lesser extent in lung cancer. These mutations can be targeted by BRAF and MEK inhibitors, which exhibit good clinical activity. There are conflicting reports of the various relative rates of BRAF Class I mutations (V600 locus), defined as those that exhibit extremely strong kinase activity by stimulating monomeric activation of BRAF, Class II, define as non-V600 mutations that activate BRAF to signal as a RAS-independent dimer, and Class III mutations, defined as “kinase-dead” with low kinase activity as compared to wild type BRAF. Prospective studies have largely focused on patients with tumors harboring Class I BRAF mutations (limited to the V600 locus) where response rates up to 70% with BRAF plus MEK inhibition have been demonstrated. We report on the relative prevalence of various types of BRAF mutations across human cancers in a cohort of 114,662 patients that received comprehensive genomic profiling using next-generation sequencing. Of these patients,…

Hypoxia or low oxygen concentration in tumor microenvironment has widespread effects ranging from altered angiogenesis and lymphangiogenesis, tumor metabolism, growth, and therapeutic resistance in different cancer types. A large number of these effects are mediated by the transcription factor hypoxia inducible factor 1⍺ (HIF-1⍺) which is activated by hypoxia. HIF1⍺ induces glycolytic genes and reduces mitochondrial respiration rate in hypoxic tumoral regions through modulation of various cells in tumor microenvironment like cancer-associated fibroblasts. Immune evasion driven by HIF-1⍺ further contributes to enhanced survival of cancer cells. By altering drug target expression, metabolic regulation, and oxygen consumption, hypoxia leads to enhanced growth and survival of cancer cells. Tumor cells in hypoxic conditions thus attain aggressive phenotypes and become resistant to chemo- and radio- therapies resulting in higher mortality. While a number of new therapeutic strategies have succeeded in targeting hypoxia, a significant improvement of these needs a more detailed…

With balanced spatial resolution, penetration depth, and imaging speed, photoacoustic computed tomography (PACT) is promising for clinical translation such as in breast cancer screening, functional brain imaging, and surgical guidance. Typically using a linear ultrasound (US) transducer array, PACT has great flexibility for hand-held applications. However, the linear US transducer array has a limited detection angle range and frequency bandwidth, resulting in limited-view and limited-bandwidth artifacts in the reconstructed PACT images. These artifacts significantly reduce the imaging quality. To address these issues, existing solutions often have to pay the price of system complexity, cost, and/or imaging speed. Here, we propose a deep-learning-based method that explores the Wasserstein generative adversarial network with gradient penalty (WGAN-GP) to reduce the limited-view and limited-bandwidth artifacts in PACT. Compared with existing reconstruction and convolutional neural network approach, our model has shown improvement in imaging quality and resolution. Our results on…

As a new optical coherence tomography (OCT) modality, OCT angiography (OCTA) provides a noninvasive method to detect microvascular distortions correlated with eye conditions. By providing unparalleled capability to differentiate individual plexus layers in the retina, OCTA has demonstrated its excellence in clinical management of diabetic retinopathy, glaucoma, sickle cell retinopathy, diabetic macular edema, and other eye diseases. Quantitative OCTA analysis of retinal and choroidal vasculatures is essential to standardize objective interpretations of clinical outcome. Quantitative features, including blood vessel tortuosity, blood vessel caliber, blood vessel density, vessel perimeter index, fovea avascular zone area, fovea avascular zone contour irregularity, vessel branching coefficient, vessel branching angle, branching width ratio, and choroidal vascular analysis have been established for objective OCTA assessment. Moreover, differential artery–vein analysis has been recently demonstrated to improve OCTA performance for objective detection and classification of eye diseases.…

Remodeling of extracellular matrix in the womb facilitates the dramatic morphogenesis of maternal and placental tissues necessary to support fetal development. In addition to providing a scaffold to support tissue structure, extracellular matrix influences pregnancy outcomes by facilitating communication between cells and their microenvironment to regulate cellular adhesion, migration, and invasion. By reviewing the functions of extracellular matrix during key developmental milestones, including fertilization, embryo implantation, placental invasion, uterine growth, and labor, we illustrate the importance of extracellular matrix during healthy pregnancy and development. We also discuss how maladaptive matrix expression contributes to infertility and obstetric diseases such as implantation failure, preeclampsia, placenta accreta, and preterm birth. Recently, advances in engineering the biotic–abiotic interface have potentiated the development of microphysiological systems, known as organs-on-chips, to represent human physiological and pathophysiological conditions in vitro. These…

The novel Coronavirus pandemic defines a new risk for all dental practitioners, hygienists, and dental assistants. As an increasing number of dentists are now developing this disease, we wanted to provide some measures to manage this risk in the dental practice, by undergoing a review of the current literature. This minireview searches the literature for articles that both defined the infection risk in the dental practice and provided evidence on the efficacy of some procedures on reducing the infection risk. Several articles have already pointed out some necessary measures: fewer patients have to be admitted to the practice, a short triage should be carried out, and the appropriate measures of protection have to be used. On the basis of the literature collected, a short questionnaire and a flowchart is proposed to define the risk that each patient carries, and to appropriately adapt each procedure based on the patient’s risk. The literature is still limited on this subject, but on the basis of what is available, dental practices have to adapt to the situation in order to protect…

It has been noted for quite some time that DNA methylation levels decline with age. The significance of this change remained unknown until it became possible to measure methylation status of specific sites on the DNA. It was observed that while the methylation of some sites does indeed decrease with age, that of others increase or remain unchanged. The application of machine learning methods to these quantitative changes in multiple sites, allowed the generation of a highly accurate estimator of age, called the epigenetic clock. The application of this clock on large human epidemiological data sets revealed that discordance between the predicted (epigenetic age) and chronological age is associated with many age-related pathologies, particularly when the former is greater than the latter. The epigenetic clock clearly captures to some degree, biological features that accompany the ageing process. Despite the ever-increasing scope of pathologies that are found to be associated with accelerated epigenetic ageing, the basic principles that underlie the ticking of the clock remain…