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51.
Laura Pastor Elisabeth Vera Jose M. Marin David Sanz-Rubio 《International journal of molecular sciences》2021,22(2)
Lung diseases (LD) are one of the most common causes of death worldwide. Although it is known that chronic airway inflammation and excessive tissue repair are processes associated with LD such as asthma, chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF), their specific pathways remain unclear. Extracellular vesicles (EVs) are heterogeneous nanoscale membrane vesicles with an important role in cell-to-cell communication. EVs are present in general biofluids as plasma or urine but also in secretions of the airway as bronchoalveolar lavage fluid (BALF), induced sputum (IS), nasal lavage (NL) or pharyngeal lavage. Alterations of airway EV cargo could be crucial for understanding LD. Airway EVs have shown a role in the pathogenesis of some LD such as eosinophil increase in asthma, the promotion of lung cancer in vitro models in COPD and as biomarkers to distinguishing IPF in patients with diffuse lung diseases. In addition, they also have a promising future as therapeutics for LD. In this review, we focus on the importance of airway secretions in LD, the pivotal role of EVs from those secretions on their pathophysiology and their potential for biomarker discovery. 相似文献
52.
Pao-Jen Kuo Cheng-Shyuan Rau Shao-Chun Wu Chia-Wei Lin Lien-Hung Huang Tsu-Hsiang Lu Yi-Chan Wu Chia-Jung Wu Chia-Wen Tsai Ching-Hua Hsieh 《International journal of molecular sciences》2021,22(17)
Macrophages emerge in the milieu around innervated neurons after nerve injuries. Following nerve injury, autophagy is induced in macrophages and affects the regulation of inflammatory responses. It is closely linked to neuroinflammation, while the immunosuppressive drug tacrolimus (FK506) enhances nerve regeneration following nerve crush injury and nerve allotransplantation with additional neuroprotective and neurotrophic functions. The combined use of FK506 and adipose-derived stem cells (ADSCs) was employed in cell therapy for organ transplantation and vascularized composite allotransplantation. This study aimed to investigate the topical application of exosomes secreted by ADSCs following FK506 treatment (ADSC-F-exo) to the injured nerve in a mouse model of sciatic nerve crush injury. Furthermore, isobaric tags for relative and absolute quantitation (iTRAQ) were used to profile the potential exosomal proteins involved in autophagy. Immunohistochemical analysis revealed that nerve crush injuries significantly induced autophagy in the dorsal root ganglia and dorsal horn of the spinal segments. Locally applied ADSC-F-exo significantly reduced autophagy of macrophages in the spinal segments after nerve crush injury. Proteomic analysis showed that of the 22 abundant exosomal proteins detected in ADSC-F-exo, heat shock protein family A member 8 (HSPA8) and eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) are involved in exosome-mediated autophagy reduction. 相似文献
53.
Cheng-Shyuan Rau Pao-Jen Kuo Shao-Chun Wu Lien-Hung Huang Tsu-Hsiang Lu Yi-Chan Wu Chia-Jung Wu Chia-Wei Lin Chia-Wen Tsai Ching-Hua Hsieh 《International journal of molecular sciences》2021,22(16)
Exosomes secreted by adipose-derived stem cells (ADSC-exo) reportedly improve nerve regeneration after peripheral nerve injury. Herein, we investigated whether pretreatment of ADSCs with FK506, an immunosuppressive drug that enhances nerve regeneration, could secret exosomes (ADSC-F-exo) that further augment nerve regeneration. Designed exosomes were topically applied to injured nerve in a mouse model of sciatic nerve crush injury to assess the nerve regeneration efficacy. Outcomes were determined by histomorphometric analysis of semi-thin nerve sections stained with toluidine blue, mouse neurogenesis PCR array, and neurotrophin expression in distal nerve segments. Isobaric tags for relative and absolute quantitation (iTRAQ) were used to profile potential exosomal proteins facilitating nerve regeneration. We observed that locally applied ADSC-exo and ADSC-F-exo significantly enhanced nerve regeneration after nerve crush injury. Pretreatment of ADSCs with FK506 failed to produce exosomes possessing more potent molecules for enhanced nerve regeneration. Proteomic analysis revealed that of 192 exosomal proteins detected in both ADSC-exo and ADSC-F-exo, histone deacetylases (HDACs), amyloid-beta A4 protein (APP), and integrin beta-1 (ITGB1) might be involved in enhancing nerve regeneration. 相似文献
54.
Evidence for distinct DNA- and RNA-based mechanisms of 5-fluorouracil cytotoxicity in Saccharomyces cerevisiae 总被引:1,自引:0,他引:1
5-Fluorouracil (5FU) is an effective chemotherapeutic drug developed as an inhibitor of thymidylate synthetase (TS). Inhibition of TS leads to 'thymine-less death', a condition resulting from depletion of dTTP pools and misincorporation of dUTP into newly synthesized or repaired DNA. 5FU is also incorporated into RNA and a growing body of evidence suggests that RNA-based effects play a significant role in its cytotoxicity. Indeed, recent experiments in yeast showed that defects in the nuclear RNA exosome subunit Rrp6p cause hypersensitivity to 5FU. The present study asked whether the 5FU hypersensitivity of an rrp6-Delta yeast strain reflects the DNA- or RNA-based effects of 5FU. Genetic analyses suggest that while a DNA repair mutation, apn1-Delta, causes sensitivity to 5FU-induced DNA damage, an rrp6-Delta mutation causes hypersensitivity, due to the RNA-based effects of 5FU. Analysis of a strain with normal DNA and RNA metabolism grown in the presence of 5FU shows that UMP suppresses the 5FU-induced defect more than dTMP, suggesting that the RNA-based toxicity of 5FU predominates in these cells. These findings underscore the importance of understanding the RNA-based mechanism of 5FU cytotoxicity and highlight the use of yeast as a model system for elucidating its details. 相似文献
55.
Michiko Horiguchi Yuko Okada Yuya Turudome Kentaro Ushijima 《International journal of molecular sciences》2021,22(20)
Type 1 diabetes mellitus is characterized by the destruction of pancreatic β-cells and requires the regeneration of these destroyed pancreatic β-cells for radical treatment. The degeneration of organelles in stem cells compromises stem cell quality; however, organelles in the mesenchymal stem cells of patients with type 1 diabetes mellitus have not been characterized previously. In this study, we use transmission electron microscopy to evaluate the degeneration of organelles in adipose-derived stem cells of patients with type 1 diabetes mellitus (T1DM ADSCs). Compared to adipose-derived stem cells from healthy humans, T1DM ADSCs degenerate differently, characterized by prominent enlarged spherical vesicles. The exosomes of T1DM ADSCs are found to be enlarged, reduced in number, and increased in the percentage of those positive for tetraspanin CD9. The findings of this study provide insight into the characteristics of stem cells in patients with type 1 diabetes mellitus. 相似文献
56.
Kenzui Taniue Tanzina Tanu Yuki Shimoura Shuhei Mitsutomi Han Han Rika Kakisaka Yusuke Ono Nobue Tamamura Kenji Takahashi Youichiro Wada Yusuke Mizukami Nobuyoshi Akimitsu 《International journal of molecular sciences》2022,23(1)
The RNA exosome is a multi-subunit ribonuclease complex that is evolutionally conserved and the major cellular machinery for the surveillance, processing, degradation, and turnover of diverse RNAs essential for cell viability. Here we performed integrated genomic and clinicopathological analyses of 27 RNA exosome components across 32 tumor types using The Cancer Genome Atlas PanCancer Atlas Studies’ datasets. We discovered that the EXOSC4 gene, which encodes a barrel component of the RNA exosome, was amplified across multiple cancer types. We further found that EXOSC4 alteration is associated with a poor prognosis of pancreatic cancer patients. Moreover, we demonstrated that EXOSC4 is required for the survival of pancreatic cancer cells. EXOSC4 also repressed BIK expression and destabilized SESN2 mRNA by promoting its degradation. Furthermore, knockdown of BIK and SESN2 could partially rescue pancreatic cells from the reduction in cell viability caused by EXOSC4 knockdown. Our study provides evidence for EXOSC4-mediated regulation of BIK and SESN2 mRNA in the survival of pancreatic tumor cells. 相似文献
57.
Martin Vokurka Luk Lacina Jan Brbek Michal Kol Yi Zhen Ng Karel Smetana Jr. 《International journal of molecular sciences》2022,23(2)
Cancer-associated fibroblasts (CAFs) are an essential component of the tumour microenvironment. They represent a heterogeneous group of cells that are under the control of cancer cells and can reversely influence the cancer cell population. They affect the cancer cell differentiation status, and the migration and formation of metastases. This is achieved through the production of the extracellular matrix and numerous bioactive factors. IL-6 seems to play the central role in the communication of noncancerous and cancer cells in the tumour. This review outlines the role of exosomes in cancer cells and cancer-associated fibroblasts. Available data on the exosomal cargo, which can significantly intensify interactions in the tumour, are summarised. The role of exosomes as mediators of the dialogue between cancer cells and cancer-associated fibroblasts is discussed together with their therapeutic relevance. The functional unity of the paracrine- and exosome-mediated communication of cancer cells with the tumour microenvironment represented by CAFs is worthy of attention. 相似文献
58.
Miquel Saumell-Esnaola Diego Delgado Gontzal García del Cao Maider Beitia Joan Salls Imanol Gonzlez-Burguera Pello Snchez Maider Lpez de Jesús Sergio Barrondo Mikel Snchez 《International journal of molecular sciences》2022,23(5)
Platelet-Rich Plasma (PRP) is enriched in molecular messengers with restorative effects on altered tissue environments. Upon activation, platelets release a plethora of growth factors and cytokines, either in free form or encapsulated in exosomes, which have been proven to promote tissue repair and regeneration. Translational research on the potential of exosomes as a safe nanosystem for therapeutic cargo delivery requires standardizing exosome isolation methods along with their molecular and morphological characterization. With this aim, we isolated and characterized the exosomes released by human PRP platelets. Western blot analysis revealed that CaCl2-activated platelets (PLT-Exos-Ca2+) released more exosomes than non-activated ones (PLT-Exos). Moreover, PLT-Exos-Ca2+ exhibited a molecular signature that meets the most up-to-date biochemical criteria for platelet-derived exosomes and possessed morphological features typical of exosomes as assessed by transmission electron microscopy. Array analysis of 105 analytes including growth factors and cytokines showed that PLT-Exos-Ca2+ exhibited lower levels of most analytes compared to PLT-Exos, but relatively higher levels of those consistently validated as components of the protein cargo of platelet exosomes. In summary, the present study provides new insights into the molecular composition of human platelet-derived exosomes and validates a method for isolating highly pure platelet exosomes as a basis for future preclinical studies in regenerative medicine and drug delivery. 相似文献
59.
EB(Epstein-Barr)病毒普遍性感染人类并引发多种病毒相关性癌症,其中鼻咽癌与EB病毒感染相关性最高,并在我国广东等地区发病率极高,是我国重点防治的十大恶性肿瘤之一.截至目前,没有任何一款上市可接种的EB病毒防治性疫苗,针对EB病毒相关疾病的免疫治疗手段在临床试验中也收效甚微.近年来,纳米颗粒基因改造技术的飞... 相似文献
60.