Experimental Biology and Medicine

The covalently closed circular RNA has recently been proposed as a pivotal player in tumorigenesis. In the current study, we found that circ-CDYL was notably elevated in multiple myeloma tissue and plasma samples and had good diagnostic and prognostic efficacy. Functional assays showed that circ-CDYL enhanced the viability and DNA synthesis of multiple myeloma cells and inhibited apoptosis. Mechanically, cytoplasmic circ-CDYL was co-localized with miR-1180, and circ-CDYL absorbed miR-1180 to upregulate yes-associated protein (YAP), thereby facilitating multiple myeloma progression. Importantly, we further confirmed the existence of this circ-CDYL/miR-1180/YAP regulatory axis in vivo by using the xenograft tumor model. Taken together, our data demonstrate that circ-CDYL is novel promoter of multiple myeloma, and targeting circ-CDYL and its associated network implicates the therapeutic possibility for multiple myeloma patients.

Coronavirus disease 2019 (COVID-19) is an illness caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was first identified as a cluster of respiratory illness in Wuhan City, Hubei Province, China, in December 2019, and has rapidly spread across the globe to greater than 200 countries. Healthcare providers are at an increased risk for contracting the disease due to occupational exposure and require appropriate personal protective equipment (PPE), including N95 respirators. The rapid worldwide spread of high numbers of COVID-19 cases has facilitated the need for a substantial supply of PPE that is largely unavailable in many settings, thereby creating critical shortages. Creative solutions for the decontamination and safe reuse of PPE to protect our frontline healthcare personnel are essential. Here, we describe the development of a process that began in late February 2020 for selecting and implementing the use of hydrogen peroxide vapor (HPV) as viable method to reprocess N95 respirators. Since pre-existing HPV decontamination chambers were not available, we optimized the sterilization process in an operating room after experiencing initial challenges in other environments. Details are provided about the prioritization and implementation of processes for collection and storage, pre-processing, HPV decontamination, and post-processing of filtering facepiece respirators. Important lessons learned from this experience include, developing an adequate reserve of PPE for effective reprocessing and distribution, and identifying a suitable location with optimal environmental controls (i.e. operating room). Collectively, information presented here provides a framework for other institutions considering decontamination procedures for N95 respirators.

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 dental health professionals.

Obesity involves genetic and environmental factors. The co-expression gene network in relevant tissues in different obesity groups provides an entrance for profiling and identifying associated pathways and genes. We aim to identify the meaningful co-expressed gene network in mRNA extracted from adipose tissues representing different obesity phenotypes in a new tree shrew model. Furthermore, to find the potential drug target based on analyzing the possible pathways and hub genes responsible for obesity. Ten tree shrews were selected from F1 populations and divided into three groups based on their Lee’s index for mRNA sequencing. We identified clusters of highly correlated genes (modules) in differently expressed genes by weighted gene co-expression network analysis. Three modules were firmly correlated with not less than one obesity phenotype (associations ranging from −0.94 to 0.85, P < 0.01). The genes from the blue module (including 481 genes) are mostly enriched in the ribosome pathway. The genes from the brown module (including 389 genes) are mostly enriched in the lysosome pathway. The genes from the turquoise module (including 1781 genes) are mostly enriched in the ubiquitin-mediated proteolysis pathway. The hub gene in each module was determined, including UBA52 in the blue module, AKT1 in the brown module, and LRRK2 in the turquoise module. After profiling and analyzing the co-expression gene network of obese tree shrew, we identified differently expressed genes and pathways (ribosome, lysosome and ubiquitin-mediated proteolysis pathway) that might be involved in the development of obesity. Further study of the differently expressed genes and pathways might provide new targets for the prevention and therapy of obesity.

Orbital venous malformation results from the aberrant angiogenesis in the orbit; however, the detailed molecular mechanism is still not clear. In this study, tissue samples from 27 patients with orbital venous malformation were collected and subjected to whole exome sequencing. Melanocortin 4 receptor was the gene with highest incidence (7/27) of mutation identified in this series. A total of four types of mutations were found in the coding region and the 5ʹ-untranslated region of melanocortin 4 receptor. All these mutations resulted in the upregulation of melanocortin 4 receptor expression. In vitro assays using human umbilical vein endothelial cells demonstrated that the endothelial properties including cell proliferation, cell cycle, cell migration, and tube formation are positively correlated with the expression level of melanocortin 4 receptor. Melanocortin 4 receptor mutations resulted in increased cAMP production in a cell-based assay. By RNA sequencing technique, melanocortin 4 receptor was found to modulate the downstream genes of PI3K/AKT/mTOR pathway, including p21, cyclin B1, ITGA10, and ITGA11, which are known to regulate the endothelial properties. These data demonstrated that mutations in melanocortin 4 receptor modulate the downstream signaling pathway, facilitate the angiogenic activity of endothelial cells, and therefore is one potential mechanism of orbital venous malformation pathogenesis.

Novel 2019 coronavirus has created havoc across the globe since its emergence in December 2019 in Wuhan, China, and fast spreading potential. While we were able to identify the causative agent within a few days of the disease outbreak, several questions still remain unanswered. In this review, we discuss the extent of virus spread, current statistics, SARS-CoV-2 genome organization, comparison between the novel coronavirus and causative agents involved in previous outbreaks, ongoing clinical trials and myths associated with the virus. Lastly, we provide insights into the future perspectives which could prove useful for the scientific community as they work on finding the cure against the disease.

The recent outbreak of coronavirus disease (COVID 19), spreading from China all around the world in early 2020, has led scientists to investigate the immuno-mediated mechanisms underlying the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) infection. Depending on the amount of cytokines released as the result of the immunological activation induced by SARS-CoV2, three major clinical phenotypes can be identified: “mild”,symbolized as a “drizzle” of cytokines, severe as a “storm”, and critical as a “hurricane”. In patients with mild symptoms, the release of pro-inflammatory cytokines is balanced to obtain a defense response against the virus which is often self-limiting and overcomes without tissue damage. In severe phenotype, resembling a “cytokine-release syndrome”, SARS-CoV2 causes the lysis of the immune-mediators leading to a cytokine storm able to induce lung epithelium damage and acute respiratory distress syndrome. In critical patients, the immune response may become uncontrolled, thus the cytokine burst resembles a form of secondary hemophagocytic lymphohistiocytosis which may result in a multi organ failure. In addition to the standard of care, an immune-modulatory therapy tailored to each one of the different phenotypes should be used in order to prevent or reduce the release of cytokines responsible for organ damage and disease progression.

Excessive dietary fat intake is related to metabolic dysfunction and enhances susceptibility to hypertension and cognitive impairment. Although there are sex differences in the prevalence and progression of these diseases, few studies have investigated sex differences in cardio-metabolic and cognitive parameters in rats with high-fat diet-induced metabolic dysfunction. To better reflect actual clinical conditions, sex-differences in rats with high-fat diet-induced metabolic dysfunction were evaluated. Male and female Sprague-Dawley rats were fed a high-fat diet to induce metabolic dysfunction and intraperitoneally injected with N-nitro-L-arginine methyl ester and scopolamine to model vulnerability to hypertension and cognitive impairment, respectively, whereas control rats were fed a regular diet and treated with distilled water and 0.9% saline. Male experimental rats showed significantly higher systolic blood pressure than female experimental animals. More importantly, acetylcholine-induced relaxation of carotid arteries was decreased only in the male experimental rats, revealing a significant difference compared with female experimental rats. These findings provide evidence for individualized sex-based management of patients with metabolic dysfunction and susceptibilities to hypertension and cognitive impairment.

Our previous study demonstrated that the mammalian target of rapamycin complex 1 (mTORC1) pathway is activated in peritoneal fibrosis under high glucose condition. This study aimed to investigate whether valsartan inhibits high glucose-induced peritoneal fibrosis via decreasing the activity of the mTORC1 pathway. We used high glucose peritoneal dialysis solution in a mouse peritoneal dialysis model to induce peritoneal fibrosis in vivo and high glucose in human peritoneal mesothelial cells (HPMCs) to stimulate extracellular matrix accumulation in vitro. After injections of peritoneal dialysis solution containing 4.25% glucose for four weeks, mice showed typical features of peritoneal fibrosis, including markedly increased peritoneal thickness, excessive matrix deposition, increased peritoneal permeability, and higher expression of extracellular matrix proteins, such as α-smooth muscle actin (α-SMA) and collagen I. Oral gavage of valsartan significantly ameliorated these pathological changes at both week 6 and week 8. These effects of valsartan were closely correlated with a decrease in the activation of the mTORC1 signal, which was mediated by the downregulation of the protein expression of phosphorylated (p)-mTOR, p-eukaryotic initiation factor 4E-binding protein 1, and p-p70 S6 kinase 1. Further research showed that the protein expression of mTORC1 signal was positively correlated with the expression of both α-SMA and collagen I in the peritoneum. In vitro, high glucose increased the protein expression of α-SMA and collagen I in a dose-dependent manner, while valsartan significantly inhibited high glucose-induced extracellular matrix accumulation in HPMCs. The effect was also accompanied by a decrease in the activation of the mTORC1 signal. Furthermore, the mTOR agonist MHY1485 reversed the downregulation of extracellular matrix components in HPMCs, even in the presence of valsartan. We conclude that valsartan exerts a protective effect against high glucose-induced peritoneal fibrosis via suppressing the activity of the mTORC1 pathway.