Background SARS-CoV2, the agent responsible for the current pandemic, is also causing respiratory distress syndrome (RDS), hyperinflammation and high mortality. It is critical to dissect the pathogenetic mechanisms in order to reach a targeted therapeutic approach. Methods In the present investigation, we evaluated the effects of SARS-CoV 2 on human bronchial epithelial cells (HBEC). We used RNA-seq datasets available online for identifying SARS-CoV 2 potential genes target on human bronchial epithelial cells. RNA expression levels and potential cellular gene pathways have been analyzed. In order to identify possible common strategies among the main pandemic viruses, such as SARS-CoV 2 , SARS-CoV1, MERS-CoV, and H1N1, we carried out a hypergeometric test of the main genes transcribed in the cells of the respiratory tract exposed to these viruses. Results The analysis showed that two mechanisms are highly regulated in HBEC: the innate immunity recruitment and the disassembly of cilia and cytoskeletal structure. The granulocyte colony-stimulating factor ( CSF3 ) and dynein heavy chain 7, axonemal ( DNAH7 ) represented respectively the most upregulated and downregulated genes belonging to the two mechanisms highlighted above. Furthermore, the carcinoembryonic antigen-related cell adhesion molecule 7 ( CEACAM7 ) that codifies for a surface protein is highly specific of SARS-CoV 2 and not for SARS-CoV1, MERS-CoV, and H1N1, suggesting a potential role in viral entry. In order to identify potential new drugs, using a machine learning approach, we highlighted Flunisolide, Thalidomide, Lenalidomide, Desoximetasone, xylazine, and salmeterol as potential drugs against SARS-CoV 2 infection. Conclusions Overall, lung involvement and RDS could be generated by the activation and down regulation of diverse gene pathway involving respiratory cilia and muscle contraction, apoptotic phenomena, matrix destructuration, collagen deposition, neutrophil and macrophages recruitment.

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Technological development of motion and posture analyses is rapidly progressing, especially in rehabilitation settings and sport biomechanics. Consequently, clear discrimination among different measurement systems is required to diversify their use as needed. This review aims to resume the currently used motion and posture analysis systems, clarify and suggest the appropriate approaches suitable for specific cases or contexts. The currently gold standard systems of motion analysis, widely used in clinical settings, present several limitations related to marker placement or long procedure time. Fully automated and markerless systems are overcoming these drawbacks for conducting biomechanical studies, especially outside laboratories. Similarly, new posture analysis techniques are emerging, often driven by the need for fast and non-invasive methods to obtain high-precision results. These new technologies have also become effective for children or adolescents with non-specific back pain and postural insufficiencies. The evolutions of these methods aim to standardize measurements and provide manageable tools in clinical practice for the early diagnosis of musculoskeletal pathologies and to monitor daily improvements of each patient. Herein, these devices and their uses are described, providing researchers, clinicians, orthopedics, physical therapists, and sports coaches an effective guide to use new technologies in their practice as instruments of diagnosis, therapy, and prevention.

Primary myelofibrosis is a Ph-negative chronic myeloproliferative neoplasm characterized by bone marrow fibrosis and associated with the involvement of several pathways, in addition to bone marrow microenvironment alterations, mostly driven by the activation of the cytokine receptor/JAK2 pathway. Identification of driver mutations has led to the development of targeted therapy for myelofibrosis, contributing to reducing inflammation, although this currently does not translate into bone marrow fibrosis remission. Therefore, understanding the clear molecular cut underlying this pathology is now necessary to improve the clinical outcome of patients. The present study aims to investigate the involvement of IGFBP-6/sonic hedgehog /Toll-like receptor 4 axis in the microenvironment alterations of primary myelofibrosis. We observed a significant increase in IGFBP-6 expression levels in primary myelofibrosis patients, coupled with a reduction to near-normal levels in primary myelofibrosis patients with JAK2V617F mutation. We also found that both IGFBP-6 and purmorphamine, a SHH activator, were able to induce mesenchymal stromal cells differentiation with an up-regulation of cancer-associated fibroblasts markers. Furthermore, TLR4 signaling was also activated after IGFBP-6 and purmorphamine exposure and reverted by cyclopamine exposure, an inhibitor of the SHH pathway, confirming that SHH is involved in TLR4 activation and microenvironment alterations. In conclusion, our results suggest that the IGFBP-6/SHH/TLR4 axis is implicated in alterations of the primary myelofibrosis microenvironment and that IGFBP-6 may play a central role in activating SHH pathway during the fibrotic process.

Motoneuronal loss is the main feature of amyotrophic lateral sclerosis, although pathogenesis is extremely complex involving both neural and muscle cells. In order to translationally engage the sonic hedgehog pathway, which is a promising target for neural regeneration, recent studies have reported on the neuroprotective effects of clobetasol, an FDA-approved glucocorticoid, able to activate this pathway via smoothened. Herein we sought to examine functional, cellular, and metabolic effects of clobetasol in a neurotoxic mouse model of spinal motoneuronal loss. We found that clobetasol reduces muscle denervation and motor impairments in part by restoring sonic hedgehog signaling and supporting spinal plasticity. These effects were coupled with reduced pro-inflammatory microglia and reactive astrogliosis, reduced muscle atrophy, and support of mitochondrial integrity and metabolism. Our results suggest that clobetasol stimulates a series of compensatory processes and therefore represents a translational approach for intractable denervating and neurodegenerative disorders.