Journal of cellular and molecular medicine
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β-thalassaemia is a prevalent hereditary haematological disease caused by mutations in the human haemoglobin β (HBB) gene. Among them, the HBB IVS2-654 (C > T) mutation, which is in the intron, creates an aberrant splicing site. Bone marrow transplantation for curing β-thalassaemia is limited due to the lack of matched donors. ⋯ The corrected iPSCs kept pluripotency and genome stability. Moreover, they could differentiate normally. Through CRISPR/Cas9 system and ssODN, our study provides improved strategies for gene correction of β-Thalassaemia, and the expression of the HBB gene can be restored, which can be used for gene therapy in the future.
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Exosomes are served as substitutes for stem cell therapy, playing important roles in mediating heart repair during myocardial infarction injury. Evidence have indicated that lipopolysaccharide (LPS) pre-conditioning bone marrow-derived mesenchymal stem cells (BMSCs) and their secreted exosomes promote macrophage polarization and tissue repair in several inflammation diseases; however, it has not been fully elucidated in myocardial infarction (MI). ⋯ Compared with Exo, L-Exo had superior therapeutic effects on polarizing M2 macrophage in vitro and attenuated the post-infarction inflammation and cardiomyocyte apoptosis by mediating macrophage polarization in mice MI model. Consequently, we have confidence in the perspective that low concentration of LPS pre-conditioning BMSC-derived exosomes may develop into a promising cell-free treatment strategy for clinical treatment of MI.
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Exosome-derived miRNAs are regarded as biomarkers for the diagnosis and prognosis of many human cancers. However, its function in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, differentially expressed miRNAs from urinal exosomes were identified using next-generation sequencing (NGS) and verified using urine samples of ccRCC patients and healthy donors. ⋯ Heat-shock protein 5 (HSPA5) was found to be a direct target gene of miR-30c-5p. The depletion of HSPA5 caused by miR-30c-5p inhibition reversed the promoting effect of ccRCC growth. In conclusion, urinary exosomal miR-30c-5p acts as a potential diagnostic biomarker of early-stage ccRCC and may be able to modulate the expression of HSPA5, which is correlated with the progression of ccRCC.
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In this study, microarray data analysis, real-time quantitative PCR and immunohistochemistry were used to detect the expression levels of SSRP1 in colorectal cancer (CRC) tissue and in corresponding normal tissue. The association between structure-specific recognition protein 1 (SSRP1) expression and patient prognosis was examined by Kaplan-Meier analysis. SSRP1 was knocked down and overexpressed in CRC cell lines, and its effects on proliferation, cell cycling, migration, invasion, cellular energy metabolism, apoptosis, chemotherapeutic drug sensitivity and cell phenotype-related molecules were assessed. ⋯ Furthermore, SSRP1 induced apoptosis and SSRP1 knockdown augmented the sensitivity of CRC cells to 5-fluorouracil and cisplatin. Moreover, we explored the molecular mechanisms accounting for the dysregulation of SSRP1 in CRC and identified microRNA-28-5p (miR-28-5p) as a direct upstream regulator of SSRP1. We concluded that SSRP1 promotes CRC progression and is negatively regulated by miR-28-5p.
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Review
Depression in sleep disturbance: A review on a bidirectional relationship, mechanisms and treatment.
Sleep disturbance is the most prominent symptom in depressive patients and was formerly regarded as a main secondary manifestation of depression. However, many longitudinal studies have identified insomnia as an independent risk factor for the development of emerging or recurrent depression among young, middle-aged and older adults. ⋯ In clinical practice, pharmacological therapies, including hypnotics and antidepressants, and non-pharmacological therapies are typically applied. A better understanding of the pathophysiological mechanisms between sleep disturbance and depression can help psychiatrists better manage this comorbidity.