Dystrophin deficiency alters the sarcolemma structure, leading to muscle dystrophy, muscle disuse, and ultimately death. Beyond limb muscle deficits, patients with Duchenne muscular dystrophy have numerous transit disorders. Many studies have highlighted the strong relationship between gut microbiota and skeletal muscle. The aims of this study were: i) to characterize the gut microbiota composition over time up to 1 year in dystrophin-deficient mdx mice, and ii) to analyze the intestine structure and function and expression of genes linked to bacterial-derived metabolites in ileum, blood, and skeletal muscles to study interorgan interactions. Mdx mice displayed a significant reduction in the overall number of different operational taxonomic units and their abundance (α-diversity). Mdx genotype predicted 20% of β-diversity divergence, with a large taxonomic modification of Actinobacteria, Proteobacteria, Tenericutes, and Deferribacteres phyla and the included genera. Interestingly, mdx intestinal motility and gene expressions of tight junction and Ffar2 receptor were down-regulated in the ileum. Concomitantly, circulating inflammatory markers related to gut microbiota (tumor necrosis factor, IL-6, monocyte chemoattractant protein-1) and muscle inflammation Tlr4/Myd88 pathway (Toll-like receptor 4, which recognizes pathogen-associated molecular patterns) were up-regulated. Finally, in mdx mice, adiponectin was reduced in blood and its receptor modulated in muscles. This study highlights a specific gut microbiota composition and highlights interorgan interactions in mdx physiopathology with gut microbiota as the potential central metabolic organ.

This work aims to investigate the accuracy of quantitative SPECT imaging of177Lu in the presence of90Y, which occurs in dual-isotope radiopharmaceutical therapy (RPT) involving both isotopes. We used the GATE Monte Carlo simulation toolkit to conduct a phantom study, simulating spheres filled with177Lu and90Y placed in a cylindrical water phantom that was also filled with activity of both radionuclides. We simulated multiple phantom configurations and activity combinations by varying the location of the spheres, the concentrations of177Lu and90Y in the spheres, and the amount of background activity. We investigated two different scatter window widths to be used with triple energy window (TEW) scatter correction. We also created multiple realizations of each configuration to improve our assessment, leading to a total of 540 simulations. Each configuration was imaged using a simulated Siemens SPECT camera. The projections were reconstructed using the standard 3D OSEM algorithm, and errors associated with177Lu activity quantification and contrast-to-noise ratios (CNRs) were determined. In all configurations, the quantification error was within ± 6% of the no-90Y case, and we found that quantitative accuracy may slightly improve when90Y is present because of reduction of errors associated with TEW scatter correction. The CNRs were not significantly impacted by the presence of90Y, but they were increased when a wider scatter window width was used for TEW scatter correction. The width of the scatter windows made a small but statistically significant difference of 1%-2% on the recovered177Lu activity. Based on these results, we can conclude that activity quantification of177Lu and lesion detectability is not degraded by the presence of90Y.

The liver neutralizes endogenous and exogenous toxins and metabolites, being metabolically interconnected with many organs. Numerous clinical and experimental studies show a strong association between Non-alcoholic fatty liver disease (NAFLD) and loss of skeletal muscle mass known as sarcopenia. Liver transplantation solves the hepatic-related insufficiencies, but it is unable to revert sarcopenia. Knowing the mechanism(s) by which different organs communicate with each other is crucial to improve the drug development that still relies on the two-dimensional models. However, those models fail to mimic the pathological features of the disease. Here, both liver and skeletal muscle cells were encapsulated in gelatin methacryloyl and carboxymethylcellulose to recreate the disease\'s phenotype in vitro. The 3D hepatocytes were challenged with non-esterified fatty acids (NEFAs) inducing features of Non-alcoholic fatty liver (NAFL) such as lipid accumulation, metabolic activity impairment and apoptosis. The 3D skeletal muscle tissues incubated with supernatant from fatty hepatocytes displayed loss of maturation and atrophy. This study demonstrates the connection between the liver and the skeletal muscle in NAFL, narrowing down the players for potential treatments. The tool herein presented was employed as a customizable 3D in vitro platform to assess the protective effect of albumin on both hepatocytes and myotubes.

Background: Crosstalk of circular RNAs (circRNAs) and microRNAs (miRNAs) refers to the communication and co-regulation between them. circRNAs can act as miRNAs sponges, and miRNAs can mediate circRNAs. They interact to regulate gene expression and participate in the occurrence and development of various human diseases. Methods: Publications on the crosstalk between miRNAs and circRNAs in human diseases were collected from Web of Science. The collected material was limited to English articles and reviews. CiteSpace and Microsoft Excel were used for bibliographic analysis. Results: A total of 1,013 papers satisfied the inclusion criteria. The publication outputs and types of researched diseases were analyzed, and bibliographic analysis was used to characterize the most active journals, countries, institutions, keywords, and references. The annual number of publications remarkably increased from 2011 to 2020. Neoplasm was the main research hotspot (n = 750 publications), and Biochemical and Biophysical Research Communications published the largest number of papers (n = 64) on this topic. Nanjing Medical University ranked first among institutions actively engaged in this field by publishing 72 papers, and China contributed 96.84% of the 1,013 papers (n = 981 publications) analyzed. Burst keywords in recent years included glioblastoma, miR-7, skeletal muscle, and non-coding RNA. Conclusion: Crosstalk between miRNAs and circRNAs in human diseases is a popular research topic. This study provides important clues on research trends and frontiers.

OBJECTIVE: In a previous study, we observed the presence of simultaneous increases in intracranial pressure (ICP) and the heart rate (HR), which we denominated cardio-cerebral crosstalk (CC), and we related the number of such events to patient outcomes in a paediatric cohort. In this chapter, we present an extension of this work to an adult cohort from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study.
METHODS: We implemented a sliding window algorithm to detect CC events. We considered subwindows of 10-min observations. If simultaneous increases of at least 20% in ICP and HR occurred with respect to the minimum ICP and HR values in the time windows, a CC event was detected. Correlation between the number of CC events and mortality was then obtained.
RESULTS: The cohort consisted of 226 adults (aged 16-85 years). The number of CC events that were detected varied (mean 50, standard deviation 58). A point biserial correlation coefficient of -0.13 between mortality and CC was found. Although the correlation was weaker than that seen in the paediatric cohort (-0.30), the negative direction was replicated.
CONCLUSIONS: In this work, we first extracted CC events from ICP and HR observations of adult patients with traumatic brain injury and related the number of CC events to patient outcomes. Consistency with the previous results in the paediatric cohort was observed. The more crosstalk events occurred, the better the patient outcome was.

Many cancers commonly metastasize to bone. After entering the bone, cancer cells can interact with surrounding stromal cells, which ultimately influences metastasis progression. Extracellular vesicles, direct cell contact and gap junctions, and cytokines are all mechanisms of intercellular communication that have been observed to occur in the bone microenvironment. These methods of cellular crosstalk can occur between cancer cells and a variety of stromal cells, with each interaction having a different impact on cancer progression. Communication between cancer cells and bone-resident cells has previously been implicated in processes such as cancer cell trafficking and arrest in bone, cancer cell dormancy, cancer cell reactivation, and proliferation. In this chapter we review innovative techniques and model systems that can be used to study bidirectional crosstalk between cancer cells and stromal cells in the bone, with an emphasis specifically on bone-metastatic breast cancer. Investigating how metastatic cancer cells interact with, and are influenced by, the bone microenvironment is crucial to better understanding of the progression of bone metastasis.

Our study aims to evaluate the endothelial cell-podocyte crosstalk in proliferative lupus nephritis (LN). The semi-quantification scores of glomerular endothelial cell injury and the foot process width (FPW) were processed in 110 proliferative LN patients. Podocytes were stimulated with LN-derived IgG. Glomerular endothelial cells were treated with podocyte-conditioned medium (PCM), and then podocytes were incubated with endothelial cell-conditioned medium (ECM). The levels of vascular endothelial growth factor-A (VEGF-A) in PCM and endothelin-1 in ECM were analyzed, and the injury of podocyte and glomerular endothelial cells were further evaluated. The pathological score of glomerular endothelial cell injury was correlated with FPW in LN complicated with thrombotic microangiopathy. In vitro study showed the following: 1. Stimulation of podocytes by IgG from LN led to decline in the expression of nephrin with cytoskeleton rearrangement, and reduction of VEGF-A levels. 2. Exposure of glomerular endothelial cells to PCM incubated with LN-derived IgG (PCM-LN) induced more endothelin-1 secretion and disruption of intercellular tight junction. 3. Exposure of podocytes to ECM stimulated with PCM-LN could induce cytoskeleton redistribution with decrease of nephrin. In conclusion, the pathological glomerular endothelial cell lesions were associated with FPW and the VEGF-endothelin-1 system might play a critical role in the endothelial cell-podocyte crosstalk in LN.

The heart is a complex pluricellular organ composed of cardiomyocytes and non-myocytes including fibroblasts, endothelial cells and immune cells. Myocytes are responsible for electrical conduction and contractile force generation, while the other cell types are responsible for matrix deposition, vascularization, and injury response. Myocytes and non-myocytes are known to communicate and exert mutual regulatory effects. In concert, they determine the structural, electrical and mechanical characteristics in the healthy and remodelled myocardium. Dynamic crosstalk between myocytes and non-myocytes plays a crucial role in stress/injury-induced hypertrophy and fibrosis development that can ultimately lead to heart failure and arrhythmias. Investigations of heterocellular communication in the myocardium are hampered by the intricate interspersion of the different cell types and the complexity of the tissue architecture. In vitro models have facilitated investigations of cardiac cells in a direct and controllable manner and have provided important functional and mechanistic insights. However, these cultures often lack regulatory input from the other cell types as well as additional topographical, electrical, mechanical and biochemical cues from the cardiac microenvironment that all contribute to modulating cell differentiation, maturation, alignment, function and survival. Advancements in the development of more complex pluricellular physiological platforms that incorporate diverse cues from the myocardial microenvironment are expected to lead to more physiologically relevant cardiac tissue-like in vitro models for mechanistic biological research, disease modelling, therapeutic target identification, drug testing and regeneration.