Bone tissue engineering uses the principles and methods of engineering and life sciences to study bone structure, function and growth mechanism for the purposes of repairing, maintaining and ...improving damaged bone tissue. Scaffolds not only provide structural support for stem cells in cell adhesion and proliferation and bone formation, but also serve as a microenvironment for guiding stem cell differentiation and tissue regeneration and for controlling tissue structure. This review presents the research status of the scaffold microenvironment for bone-related stem cells based on bone tissue engineering. Scaffold materials and the stem cell microenvironment are described in this review, and the existing shortcomings are also simply mentioned.
Sirt1 is a member of the sirtuin family of proteins and has important roles in numerous biological processes. Sirt1
mice display an increased frequency of abnormal spermatozoa, but the mechanism of ...Sirt1 in spermiogenesis remains largely unknown. Here, we report that Sirt1 might be directly involved in spermiogenesis in germ cells but not in steroidogenic cells. Germ cell-specific Sirt1 knockout mice were almost completely infertile; the early mitotic and meiotic progression of germ cells in spermatogenesis were not obviously affected after Sirt1 depletion, but subsequent spermiogenesis was disrupted by a defect in acrosome biogenesis, which resulted in a phenotype similar to that observed in human globozoospermia. In addition, LC3 and Atg7 deacetylation was disrupted in spermatids after knocking out Sirt1, which affected the redistribution of LC3 from the nucleus to the cytoplasm and the activation of autophagy. Furthermore, Sirt1 depletion resulted in the failure of LC3 to be recruited to Golgi apparatus-derived vesicles and in the failure of GOPC and PICK1 to be recruited to nucleus-associated acrosomal vesicles. Taken together, these findings reveal that Sirt1 has a novel physiological function in acrosome biogenesis.
Peptide amphiphiles (PAs), functionalized with alkyl chains, are capable of self-assembling into various nanostructures. Recently, PAs have been considered as ideal drug carriers due to their good ...biocompatibility, specific biological functions, and hypotoxicity to normal cells and tissues. Meanwhile, the nanocarriers formed by PAs are able to achieve controlled drug release and enhanced cell uptake in response to the stimulus of the physiological environment or specific biological factors in the location of the lesion. However, the underlying detailed drug delivery mechanism, especially from the aspect of primary and secondary structures of PAs, has not been systematically summarized or discussed. Focusing on the relationship between the primary and secondary structures of PAs and stimuli-responsive drug delivery applications, this review highlights the recent advances, challenges, and opportunities of PA-based functional drug nanocarriers, and their potential pharmaceutical applications are discussed.
The ectoplasmic specialization (ES) is essential for Sertoli-germ cell communication to support all phases of germ cell development and maturity. Its formation and remodeling requires rapid ...reorganization of the cytoskeleton. However, the molecular mechanism underlying the regulation of ES assembly is still largely unknown. Here, we show that Sertoli cell-specific disruption of autophagy influenced male mouse fertility due to the resulting disorganized seminiferous tubules and spermatozoa with malformed heads. In autophagy-deficient mouse testes, cytoskeleton structures were disordered and ES assembly was disrupted. The disorganization of the cytoskeleton structures might be caused by the accumulation of a negative cytoskeleton organization regulator, PDLIM1, and these defects could be partially rescued by Pdlim1 knockdown in autophagy-deficient Sertoli cells. Altogether, our works reveal that the degradation of PDLIM1 by autophagy in Sertoli cells is important for the proper assembly of the ES, and these findings define a novel role for autophagy in Sertoli cell-germ cell communication.
Gliomas originating in the neuroepithelium account for about 80% of brain malignancies and are the most common cancer of the central nervous system. Clinical management of gliomas remains challenging ...despite significant advances in comprehensive therapies, including radiotherapy, chemotherapy, and surgery. The ITGB4 (Integrin subunit beta 4) gene encodes a receptor for laminins and its upregulation in tumor tissues is associated with poor prognosis. However, its role in glioma is not well understood. First, we performed a pan cancer analysis of ITGB4 expression in The Cancer Genome Atlas (TCGA) dataset. Survival analysis was done on Chinese Glioma Genome Atlas (CGGA) and TCGA. Immunohistochemistry was then used to validate the expression and role of ITGB4 in glioma. We finally analyzed the possible mechanism by immune infiltration and single-cell sequencing analysis. Here, we found that ITGB4 is upregulated in glioma and accurately predicts the prognosis of lower grade glioma (LGG). Univariate and multivariate Cox regression analyses showed that ITGB4 is a risk factor for LGG. Immunohistochemical analysis confirmed that ITGB4 accurately predicts LGG prognosis. Non-negative matrix factorization (NMF) cluster analysis showed that ITGB4 was closely related to immune related genes. Immune cell infiltration and single cell sequencing analyses indicated that ITGB4 may be closely related to the microenvironment of gliomas, especially tumor-associated fibroblasts. ITGB4 is a promising diagnostic and therapeutic factor in LGG patients.
Zinc oxide (ZnO) quantum dot (QD) is a promising inexpensive inorganic nanomaterials, of which potential toxic effects on biological systems and human health should be evaluated before biomedical ...application. In this study, the cytotoxicity of ZnO QDs was assessed using HeLa cervical cancer cell and HEK-293T human embryonic kidney cell lines. Cell viability was significantly decreased by treatment with 50 µg/ml ZnO QDs after only 6 h, and the cytotoxicity of ZnO QDs was higher in HEK-293T than in HeLa cells. ZnO QDs increased the level of reactive oxygen species and decreased the mitochondria membrane potential in a dose-dependent manner. Several gene expression involved in apoptosis was regulated by ZnO QDs, including bcl-2 gene and caspase. In HeLa cells, ZnO QDs significantly increased early and late apoptosis, but only late apoptosis was affected in HEK-293T cells. These findings will be helpful for future research and application of ZnO QDs in biomedicine.
Under chronic stress, the appearance of depression-like behaviors may be related to the decline of the brain's reward circuit function which caused by long-term lack of reward. However, the effect of ...reward treatment on depressive-like behaviors induced by chronic stress and its molecular mechanism in the brain remain poorly understood. Here, accompanying with companion was used to imitate a reward to study the effect of reward on depression-like behaviors induced by chronic unpredicted mild stress (CUMS), and high-throughput sequencing was used to analyze the miRNA and mRNA profiles in ventral tegmental area (VTA) harvested from depression-like and resilient behaviors mice. We observed that CUMS-induced depression-like behaviors were ameliorated by accompanying with companion in mice, and 202 differentially expressed genes (DEGs) were found to be associated with depression-like behaviors, 27 DEGs associated with resilience, 159 DEGs associated with accompanying with companion. Importantly, we also obtained 228 differentially expressed miRNAs that associated with accompanying with companion. Furthermore, the miRNA-mRNA network associated with companion was established in ventral tegmental area, based on the miRNA and mRNA profiles. Altogether, our results uncover a new way to ameliorate depression-like behavior, as well as many potential drug targets to prevent or treat depression.
The discovery of circular RNAs and exploration of their biological functions are increasingly attracting attention in cell bio-sciences. Owing to their unique characteristics of being highly ...conserved, having a relatively longer half-life, and involvement in RNA maturation, transportation, epigenetic regulation, and transcription of genes, it has been accepted that circRNAs play critical roles in the variety of cellular processes. One of the critical importance of these circRNAs is the presence of small open reading frames that enable them to encode peptides/proteins. In particular, these encoded peptides/proteins mediate essential cellular activities such as proliferation, invasion, epithelial-mesenchymal transition, and apoptosis and develop an association with the development and progression of cancers by modulating diverse signaling pathways. In addition, these peptides have potential roles as biomarkers for the prognosis of cancer and are being used as drug targets against tumorigenesis. In the present review, we thoroughly discussed the biogenesis of circRNAs and their functional mechanisms along with a special emphasis on the reported chimeric peptides/proteins encoded by circRNAs. Additionally, this review provides a perspective regarding the opportunities and challenges to the potential use of circRNAs in cancer diagnosis and therapeutic targets in clinics.
Psychological stress can cause adverse health effects in animals and humans. Accumulating evidence suggests that psychological stress in female mice is associated with ovarian developmental ...abnormalities accompanied by follicle and oocyte defects. Oocyte and early embryonic development are impaired in mice facing psychological stress, likely resulting from hormone signalling disorders, reactive oxygen species (ROS) accumulation and alterations in epigenetic modifications, which are primarily mediated by the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-ovarian (HPO) axes. The present evidence suggests that psychological stress is increasingly becoming the most common causative factor for female subfertility. Here, we review recent progress on the impact of psychological stress on female reproduction, particularly for oocyte and early embryonic development in female mice. This review highlights the connection between psychological stress and reproductive health and provides novel insight on human subfertility.
Dysfunction of the endothelium is regarded as an important factor in the pathogenesis of vascular disease in diabetes mellitus (DM). Unfortunately, prevention of the progression of vascular ...complications of DM remains pessimistic. Ferulic acid and astragaloside IV, isolated from traditional Chinese medicine Angelica sinensis and Radix astragali respectively, exhibit potential cardio-protective and anti-hyperglycemic properties. In the present study, we investigated the protective effects and underlying mechanism of ferulic acid and astragaloside IV against vascular endothelial dysfunction in diabetic rats. After the diabetic rat model was established using streptozotocin, sixty rats were divided into 6 groups (control, model, ferulic acid, astragaloside IV, ferulic acid + astragaloside IV, and metformin) and treated for 10 weeks. Blood samples were collected to measure levels of hemoglobin A1c (HbAlc), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), low density lipoproteins (Ox-LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine (Cr), nitric oxide (NO) and endothelial nitric oxide synthase (eNOS), and abdominal aorta tissue samples were collected for observing histological morphology changes of endothelium and detecting gene and protein expression of nuclear factor-κB (NF-κB) P65, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor α (TNF-α). We found that ferulic acid combined with astragaloside IV was capable of improving the structure of the aortic endothelium wall, attenuating the increase of HbAlc, TG, TC, LDL-C and Ox-LDL, promoting the release of NO and eNOS, and inhibiting over-activation of MCP-1, TNF-α, and NF-κB P65, without damage to liver and kidney function. In conclusion, ferulic acid combined with astragaloside IV exhibited significant protective effects against vascular endothelial dysfunction in diabetic rats through the NF-κB pathway involving decrease of Ox-LDL, increase of NO and eNOS, and activation of NF-κB P65, MCP-1 and TNF-α.
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