Vol.46, No.4, 2022-Table of Contents

On the Cover

Tauopathies comprise a spectrum of genetic and sporadic neurodegenerative diseases mainly characterized by hyperphosphorylated TAU protein accumulations and aggregations in neurons and/or glia. Gene-therapy, in particular adeno-associated virus/AAV-based, is an effective medical approach for difficult-to-treat genetic diseases for which there are no convincing traditional therapies, such as tauopathies. We outline a future vision for the application of this promising therapeutic approach for genetic and sporadic tauopathies: Upon admission, patients suffering from a difficult to treat neurologic disease will be subjected to (epi)genetic and clinical profiling to match their disease entity to a known genetic disease. Next, iPSC/AAV-based studies will help to design and validate (patient-tailored if necessary) gene-therapy approach, with a pipeline set up for fast (pre-)clinical studies.
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  • AAV-based gene therapy approaches for genetic forms of tauopathies and related neurogenetic disorders
  • Abstract Tauopathies comprise a spectrum of genetic and sporadic neurodegenerative diseases mainly characterized by the presence of hyperphosphorylated TAU protein aggregations in neurons or glia. Gene therapy, in particular adeno-associated virus (AAV)-based, is an effective medical approach for difficult-to-treat genetic diseases for which there are no convincing traditional therapies, such as tauopathies. Employing AAV-based gene therapy to treat, in particular, genetic tauopathies has many potential therapeutic benefits, but also drawbacks which need to be addressed in order to successfully and efficiently adapt this still unconventional therapy for the various types of tauopathies. In this Viewpoint, we briefly introduce some potentially treatable… More
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  • Toward an optimized strategy of using various airway mucus clearance techniques to treat critically ill COVID-19 patients
  • Abstract Coronavirus disease 2019 (COVID-19) caused by acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is still threatening the human life and society throughout the world. For those critically ill patients, mechanical ventilation (MV) is essential to provide life support during treatment. However, both the virus infection and MV disrupt the balance between secretion and elimination of airway mucus and lead to mucus accumulation in the lung. Postmortem examination verified that the lungs in patients died of COVID-19 are indeed filled with sticky mucus, suggesting a great need to improve airway mucus clearance in critically ill COVID-19 patients. Therefore, it may be helpful… More
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  • Future perspectives on cell therapy for autism spectrum disorder
  • Abstract Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in social communication, abnormal to absent verbal communication, the presence of repetitive stereotypic verbal and non-verbal behaviors and restricted interests, with onset early in life. We showed cognitive and behavioral characteristics of ASD by impairment of communication, cognition, perception, motor skills, executive function, theory of mind and emotion control. Recently, pathogenesis of immune pathology in the brains of individuals with ASD has been focused. New therapeutic approaches in the viewpoints of immune modulation and microglial function are logical for novel treatments for individuals with ASD. Cell therapies such… More
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  • Study of cytoskeleton from microscopic point of view: Our experience
  • Abstract The manuscript deals with our studies and experiences in the assessment of cytoskeleton in different cellular models and situations. The immunofluorescent study of several cytoskeletal proteins was relevant in the evaluation of a therapy for osteoarthritis, in case of alkaptonuria and in testing the efficacy of docetaxel in neuroblastoma cancer cells leading to apoptosis. A relevant part of our experience focus on the study of cytoskeleton in seminiferous epithelium and spermatozoa, identifying alterations affecting blood-testis barrier after a silver nanoparticle treatment, chromosomal segregation in case of varicocele, sperm motility and diagnosing systematic sperm defects as “Primary ciliary dyskinesia” and “Dysplasia… More
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  • Impact of chitosan-based nanocarriers on cytoskeleton dynamics: Current status and challenges
  • Abstract Chitosan-based nanocarriers (CS-NCs) show a promising role in improving drugs and bioactive compounds delivery for therapy. However, the effects exerted by CS-NCs at the cellular level, including their recognition and uptake, have not been fully investigated yet. Many factors, including size, shape, concentration, and surface chemistry of CS-NCs, play an important role in determining the types of intracellular signals triggered. The mechanism of uptake and the involvement of the cytoskeleton during the CS-NCs endocytosis variates among the different cell types as well as further effects observed inside cells. In the present work, we discuss the effects induced by CS-NCs per… More
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  • Stem cells in intervertebral disc regeneration–more talk than action?
  • Abstract Pain and lifestyle changes are common consequences of intervertebral disc degeneration (IVDD) and affect a large part of the aging population. The stemness of cells is exploited in the field of regenerative medicine as key to treat degenerative diseases. Transplanted cells however often face delivery and survival challenges, especially in tissues with a naturally harsh microniche environment such as the intervertebral disc. Recent interest in the secretome of stem cells, especially cargo protected from microniche-related decay as frequently present in degenerating tissues, provides new means of rejuvenating ailing cells and tissues. Exosomes, a type of extracellular vesicles with purposeful cargo… More
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  • Controversies in therapeutic application of mesenchymal stem cell-derived secretome
  • Abstract Though mesenchymal stem cells (MSCs) are considered as an important pillar of regenerative medicine, their regenerative potential has been shown to be limited in several pathological conditions. The adverse properties of MSC-based cell therapy have drawn attention to the therapeutic use of MSC-derived secretome. However, MSC-originated exosomes and microvesicles can also possess a significant impact on disease development, including cancer. By interchanging secretome, MSCs can interact with tumor cells and promote mutual exchange/induction of cellular markers. In addition, enzymes secreted into and activated within exosomes can result in the acquisition of new tumor cell properties. Therefore, therapeutic applications of MSC-derived… More
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  • Mesenchymal stem cells derived secretome as an innovative cell-free therapeutic approach
  • Abstract The paracrine and immunomodulatory cytokines secreted by mesenchymal stem cells (MSCs), generally referred to as the MSCs derived secretome, has substantial potential for the treatment of many chronic and degenerative diseases. MSCs secretome contains both common and disease specific cytokines and modulators that can be beneficial against a wide range of chronic diseases. Herein, we discuss the MSCs secretome composition profile and its translational applicability and the challenges surrounding its use in clinical settings. More
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  • The versatility of mesenchymal stem cells: From regenerative medicine to COVID, what is next?
  • Abstract Mesenchymal stem cells (MSCs) play key roles in regenerative medicine by promoting tissue healing. MSCs can be isolated from different adult tissues and they are able to differentiate into several lineages. Due to their anti-inflammatory, angiogenic and immune-modulatory properties, MSCs are suitable for tissue engineering applications and, when associated with biomaterials, their benefits can be improved. Moreover, recently, MSCs have been studied for new clinical applications, such as in the treatment of patients with COVID-19. MSCs regenerative potential has been attributed to their secretome, which comprises extracellular matrix, soluble proteins and several elements, including the release of extracellular vesicles. Even… More
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  • Dental-derived stem cells and biowaste biomaterials: What’s next in bone regenerative medicine applications
  • Abstract The human teeth and oral cavity harbor various populations of mesenchymal stem cells (MSCs), so called dental-derived stem cells (D-dSCs) with self-renewing and multilineage differentiation capabilities. D-dSCs properties involves a strong paracrine component resulting from the high levels of bioactive molecules they secrete in response to the local microenvironment. Altogether, this viewpoint develops a general picture of current innovative strategies to employ D-dSCs combined with biomaterials and bioactive factors for regenerative medicine purposes, and offers information regarding the available scientific data and possible applications. More
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  • LINC complex independent perinuclear actin organization and cell migration
  • Abstract The link of the metazoan nucleus to the actin cytoskeleton is highly important for actin polymerization and migration of multiple cell types as well as for mechanotransduction and even affects the cellular transcriptome. Several mechanisms of organization of actin filaments next to the nuclear envelope have been identified. Among these mechanisms the most studied one is the Linker of nucleoskeleton and cytoskeleton (LINC) complex-dependent perinuclear actin organization. However, recently additional mechanisms have been identified: an Actin-related protein-2/3 (Arp2/3)-dependent perinuclear actin polymerization during migration of dendritic cells and a perinuclear actin rim that is formed in response to external force application… More
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  • Cell adhesion in renal tubular epithelial cells: Biochemistry, biophysics or both
  • Abstract Changes in cell-cell and cell-substrate adhesion markers are increasingly used to characterize disease onset and progression. However, these relationships depend on both the biochemical and molecular association between cells and between cells and their extracellular matrix, as well as the biophysical and mechanical properties orchestrated by cytoskeletal, membrane and matrix components. To fully appreciate the role of cell adhesion when determining normal physiology and the impact of disease on cellular function, it is important to consider both biochemical and biophysical attributes of the system being investigated. In this short viewpoint we reflect on our experiences assessing cell-cell and/or cell-matrix interactions… More
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  • Phylogenetic analysis and target gene prediction of miR477 gene family in grape
  • Abstract To understand the molecular characteristics of the miR477 gene family of grape (Vvi-miR477) and to predict its target genes, the Vvi-miR477 genes were identified from previous small RNA sequencing data, then phylogenetic analysis and prediction of target gene were conducted. The Vvi-miR477 family consists of two precursor sequences and three mature sequences. The miR477 family members were mostly 19-22nt in length. The sequence is relatively conservative. Vvi-MIR477a and Vvi-MIR477b are located on chromosomes 1 and 2, respectively. These precursor sequences can form the typical stable stem-loop structure. Their minimum folding free energy is −39.10 kcal/mol and −50.90 kcal/mol, respectively. The… More
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  • BDLR: lncRNA identification using ensemble learning
  • Abstract Long non-coding RNAs (lncRNAs) play an important role in many life activities such as epigenetic material regulation, cell cycle regulation, dosage compensation and cell differentiation regulation, and are associated with many human diseases. There are many limitations in identifying and annotating lncRNAs using traditional biological experimental methods. With the development of high-throughput sequencing technology, it is of great practical significance to identify the lncRNAs from massive RNA sequence data using machine learning method. Based on the Bagging method and Decision Tree algorithm in ensemble learning, this paper proposes a method of lncRNAs gene sequence identification called BDLR. The identification results… More
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  • Puerarin inactivates NLRP3-mediated pyroptotic cell death to alleviate cerebral ischemia/reperfusion (I/R) injury through modulating the LncRNA DUXAP8/miR-223-3p axis
  • Abstract NLRP3 inflammasome-mediated cell pyroptosis aggravates the development of cerebral ischemia/reperfusion (I/R) injury, and the aim of this study is to investigate the potential utilization of the Chinese medicine, Puerarin, in treating this disease. Through conducting in vitro and in vivo experiments, the present study illustrated that Puerarin regulated LncRNA double homeobox A pseudogene 8 (DUXAP8)/miR-223-3p axis to inactivate NLRP3-mediated pyroptotic cell death, resulting in the attenuation of I/R injury. Specifically, the cerebral I/R injury in rat models and hypoxia/reoxygenation (H/R) in primary hippocampus neuron (PHN) cells were inducted, which were subsequently exposed to Puerarin treatment. As expected, we validated that… More
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  • Dihydroartemisinin ameliorates palmitate-induced apoptosis in cardiomyocytes via regulation on miR-133b/Sirt1 axis
  • Abstract Excessive fat ectopically deposited in the non-adipose tissues is considered as one of the leading causes of myopathy. The aim of this study was to investigate the role of Dihydroartemisinin (DHA) in palmitate (PAL)-incubated H9c2 cells (lipotoxicity-induced cell injury model). Cell viability of PAL-treated cells was determined by MTT assay, and apoptotic regulators were examined by qRT-PCR and western blot analysis, in the absence or in the presence of DHA, respectively. Expression levels of miR-133b and Sirt1 were also evaluated by qRT-PCR and western blotting examination. PAL decreased the viability of H9c2 cells and enhanced the expression of apoptotic genes.… More
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  • Identification of a 10-pseudogenes signature as a novel prognosis biomarker for ovarian cancer
  • Abstract The outcomes of ovarian cancer are complicated and usually unfavorable due to their diagnoses at a late stage. Identifying the efficient prognostic biomarkers to improve the survival of ovarian cancer is urgently warranted. The survival-related pseudogenes retrieved from the Cancer Genome Atlas database were screened by univariate Cox regression analysis and further assessed by least absolute shrinkage and selection operator (LASSO) method. A risk score model based on the prognostic pseudogenes was also constructed. The pseudogene-mRNA regulatory networks were established using correlation analysis, and their potent roles in the ovarian cancer progression were uncovered by functional enrichment analysis. Lastly, ssGSEA… More
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  • Small RNA sequencing revealed aberrant piRNA expression profiles in deciduas of recurrent spontaneous abortion patients
  • Abstract Piwi-interacting RNAs (piRNAs) is a novel class of non-coding RNAs. However, changes in piRNA expression profiles in recurrent spontaneous abortion (RSA) have not yet been investigated. The aim of this study was to identify differentially expressed piRNAs in deciduas of RSA patients. Decidua tissues were collected by curettage from recruited RSA patients and normal early pregnant (NEP) women with their informed consent. Small RNA sequencing was used to evaluate the differences in piRNA expression profiles between RSA and NEP. The present results demonstrated that the counts of total piRNA reads in RSA samples were increased compared with those in NEP… More
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  • Acute exacerbation of chronic obstructive pulmonary disease was associated with respiratory syncytial virus infection and the upregulation of TLR3
  • Abstract Respiratory syncytial virus (RSV) infection is known as a risk factor for chronic obstructive pulmonary disease (COPD). RSV infection induces the upregulation of Toll-like receptor 3 (TLR3). This study aimed to investigate the association of TLR3 with RSV induced acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Serum/sputum samples from AECOPD patients, stable chronic obstructive pulmonary disease (SCOPD) patients, and healthy controls were collected. Nested PCR was used to detect RSV. The lung function parameters were assessed by blood gas and lung function analysis. The expression levels of inflammatory factors in sputum and serum samples were determined by enzyme-linked immunosorbent… More
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  • Inhibitory of EV-A71 virus-induced apoptosis by ZVAD through ROS mediated signaling pathways
  • Abstract Emerging evidence that Enterovirus A 71 (EV-A71) infection closely related to apoptosis. The ZVAD is a caspase inhibitor that can prevent apoptosis. The aims of this project were to evaluate the mechanism of the ZVAD inhibited EV-A71 virus and to provide experiment basis for finding new antiviral drugs. In this study, after treated with ZVAD in EV-A71 infected Vero cells, the viral replication was reduced, and the cell viability was higher than EV-A71 group. Additionally, ZVAD decreased the cell apoptosis and the level of inflammatory cytokines induced by EV-A71 in the infected Vero cells. ZVAD inhibited cell apoptosis by regulating… More
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  • Nicotinic acid induces apoptosis of glioma cells via the calcium-dependent endoplasmic reticulum stress pathway
  • Abstract Malignant glioma is one of the most common and deadly tumors in the central nervous system while developing effective treatments for this devastating disease remains a challenge. Previously, we demonstrated that the vitamin nicotinic acid (NA) inhibits glioma invasion. Here, we show that high-dose NA induces apoptosis of malignant glioma cells in vitro and in vivo. In cultured U251 glioma cells treated with NA, we detected ER stress that was likely caused by elevated intracellular calcium levels. The elevated calcium can be attributed to the activation of TRPV1, a cation channel that has been implicated in cutaneous flushing caused by… More
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  • Ang-(1-7) exerts anti-inflammatory and antioxidant activities on high glucose-induced injury by prohibiting NF-κB-IL-1β and activating HO-1 pathways in HUVECs
  • Abstract Previous reports have suggested that Ang-(1-7) may have a protective effect in endothelial cells against high glucose (HG)-induced cell injury thanks to a modulatory mechanism in the NF-κB signaling pathway. In this study, we have examined whether NF-κB-IL-1β and Heme oxygenase-1 (HO-1) pathways contribute to the protection of Ang-(1-7) against hyperglycemia-induced inflammation and oxidative stress in human umbilical vein endothelial cells (HUVECs). Our results indicate that time-varying exposures of HUVECs, from 1 h to 24 h, to high glucose concentrations result in an increased expression of phosphorylated (p)-p65 and HO-1 in a time-dependent manner. As an inhibitor of NF-κB, pyrrolidinedithiocarbamic… More
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  • CDK5 inhibition promotes osteoblastic differentiation of MSCs and blocks the migration of osteosarcoma MG-63 cells
  • Abstract CDK5 belongs to the cyclin-dependent kinase family. CDK5 is multifunctional and plays an important role in neural differentiation. However, the role of CDK5 in osteoblastic differentiation remains unclear. The present study investigated functions and molecular mechanism of CDK5 in osteoblastic differentiation. It was found that, CDK5 inhibition promoted the expression of Runx2, ALP, OCN and OPN of MSCs and the mineralization of MC-3T3E1 cells and MSCs. CDK5 inhibition enhanced the development of F-actin, nuclear localization of β-catenin and YAP, as well as the expression of RMRP RNA. When F-actin was suppressed by Blebbistatin, the nuclear localization of YAP and β-catenin,… More
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  • IR780 loaded hollow MnO2 nanoparticles for dual-mode imaging and enhanced photodynamic therapy of oral squamous cell carcinoma
  • Abstract Photodynamic therapy (PDT) has emerged as a novel therapeutic modality for cancer treatment, but its therapeutic efficacy is severely limited by the hypoxic tumor microenvironment (TME). Here we designed an innovative multifunctional nano-platform which consists of a hollow MnO2 shell and internal photosensitizer IR780. It is not only used for multimodal imaging of oral squamous cell carcinoma (OSCC), but also for adjustment hypoxic TME to enhance cancer treatment. Hollow MnO2 can promote decomposition of tumor endogenous H2O2 to relieve tumor hypoxia, thereby enhancing the effect of photodynamic therapy. Photosensitizer IR780 generates singlet oxygen under laser irradiation to kill tumor cells,… More
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  • The role of baicalin on carbon tetrachloride induced liver fibrosis
  • Abstract The effect of the baicalin, a bio-active flavonoid extracted from Scutellaria baicalensis Georgi, on the carbon tetrachloride (CCl4) induced liver fibrosis was investigated. To compare the effect of baicalin on the liver fibrosis, five different groups of rats treated by 100, 200, and 400 mg/kg baicalin were studied. Upon CCl4 treatment, the levels of procollagen type III, aspartate aminotransferase, aminotransferase, hyaluronic acid, and hydroxyproline were significantly increased, whereas the superoxide dismutase and glutathione peroxidase content were decreased. These changes in the biochemical parameters, which are associated with liver function, were significantly attenuated by the baicalin treatment, suggesting that baicalin can… More
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  • Modified enzymatic collagen digestion-mediated isolation of osteocytes
  • Abstract This study established a method for isolating large numbers of high-purity osteocytes from high-density bone. Bone fragments derived from mice tibia and femurs were alternately digested with type I collagenase and EDTA nine times, and the digested cells and bone chips (BC) were cultured, digested, and passaged when cells were fully grown. The types of cells obtained were identified by morphology, viable cell counts, alkaline phosphatase staining, and biochemical activity analyses, and specific osteocyte and osteoblast markers were evaluated by quantitative real-time polymerase chain reaction. Our results showed that among the cells obtained from the third digestion (fractions 7–9) of… More
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  • Tissue specific prediction of N6-methyladenine sites based on an ensemble of multi-input hybrid neural network
  • Abstract N6-Methyladenine is a dynamic and reversible post translational modification, which plays an essential role in various biological processes. Because of the current inability to identify m6A-containing mRNAs, computational approaches have been developed to identify m6A sites in DNA sequences. Aiming to improve prediction performance, we introduced a novel ensemble computational approach based on three hybrid deep neural networks, including a convolutional neural network, a capsule network, and a bidirectional gated recurrent unit (BiGRU) with the self-attention mechanism, to identify m6A sites in four tissues of three species. Across a total of 11 datasets, we selected different feature subsets, after optimized… More
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