Morinda officinalis polysaccharide promotes the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells via microRNA-210-3p/scavenger receptor class A member 3.

Morinda officinalis polysaccharide (MOP) is the bioactive ingredient extracted from the root of Morinda officinalis, and Morinda officinalis is applied to treat osteoporosis (OP). The purpose of this study was to determine the role of MOP on human bone marrow mesenchymal stem cells (hBMSCs) and the underlying mechanism. HBMSCs were isolated from bone marrow samples of patients with OP and treated with MOP. Quantitative real-time polymerase chain reaction was adopted to quantify the expression of microRNA-210-3p (miR-210-3p) and scavenger receptor class A member 3 (SCARA3) mRNA. Cell Counting Kit-8 assay was employed to detect cell viability; Terminal-deoxynucleotidyl Transferase Mediated Nick End Labeling assay and flow cytometry were adopted to detect apoptosis; Alkaline Phosphatase (ALP) activity assay kit was applied to detect ALP activity; Western blot was executed to quantify the expression levels of SCARA3, osteogenic and adipogenic differentiation markers. Ovariectomized rats were treated with MOP. Bone mineral density (BMD), serum tartrate-resistant acid phosphatase 5b (TRACP 5b), and N-telopeptide of type I collagen (NTx) levels were assessed by BMD detector and Enzyme-linked immunosorbent assay kits. It was revealed that MOP could promote hBMSCs' viability and osteogenic differentiation and inhibit apoptosis and adipogenic differentiation. MOP could also upregulate SCARA3 expression through repressing miR-210-3p expression. Treatment with MOP increased the BMD and decreased the TRACP 5b and NTx levels in ovariectomized rats. MOP may boost the osteogenic differentiation and inhibit adipogenic differentiation of hBMSCs by miR-210-3p/SCARA3 axis.

Circ_0001955 promotes the progression of non-small cell lung cancer via miR-769-5p/EGFR axis.

To elaborate on the role of circular RNA 0001955 (circ_0001955) on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells and its underlying mechanism. Circ_0001955 expression in NSCLC was screened out through bioinformatics analysis based on GEO database. Circ_0001955, microRNA-769-5p (miR-769-5p), and epidermal growth factor receptor (EGFR) expression in NSCLC tissues and cell lines was examined using quantitative real-time PCR (qRT-PCR) and Western blot. Cell proliferation and apoptosis were examined using the CCK-8 method, BrdU experiment and flow cytometry analysis, respectively. Bioinformatics prediction, dual-luciferase reporter gene experiment and RNA immunoprecipitation (RIP) experiments were applied to validate the targeting relationship between miR-769-5p and circ_0001955 and the 3' UTR of EGFR. Pearson's correlation analysis was employed to validate the correlations among them. Circ_0001955 expression was up-regulated in NSCLC tissues and cell lines, and its overexpression was strongly associated with increased tumor TNM stage and lymph node metastasis. Circ_0001955 overexpression enhanced the proliferation and restrained the apoptosis in NSCLC cells, whereas knocking down circ_0001955 exerted the opposite effects. Circ_0001955 directly targeted miR-769-5p and negatively regulated its expression. EGFR, a target gene of miR-769-5p, could be indirectly and positively regulated by circ_0001955. Correlation analysis indicated that circ_0001955 was negatively correlated with miR-769-5p expression, while circ_0001955 was positively correlated with EGFR expression. Circ_0001955 facilitates the proliferation and represses the apoptosis of NSCLC cells by modulating miR-769-5p/EGFR axis.

LPS-inducible circAtp9b is highly expressed in osteoporosis and promotes the apoptosis of osteoblasts by reducing the formation of mature miR-17-92a.

BACKGROUND: Circular RNA circAtp9b is an enhancer of LPS-induced inflammation, which promotes osteoporosis (OS). This study explored the role of circAtp9b in OS. METHODS: RT-qPCR was performed to detect the expression of circAtp9b and microRNA (miR)-17-92a (both mature and premature) in OS and healthy controls. The subcellular location of circAtp9b was assessed by nuclear fractionation assay. The direct interaction between circAtp9b and premature miR-17-92a was detected by RNA pull-down assay. The role of circAtp9b in regulating the maturation of miR-17-92a in osteoblasts was explored by overexpression assay and RT-qPCR. Cell apoptosis was analyzed by cell apoptosis assay. RESULTS: OS patients exhibited upregulation of circAtp9b and premature miR-17-92a, but downregulation of mature miR-17-92a. In osteoblasts, circAtp9b suppressed the maturation of miR-17-92a. LPS upregulated circAtp9b and premature miR-17-92a, and downregulated mature miR-17-92a in osteoblasts. CircAtp9b was detected in both nucleus and cytoplasm, and it directly interacted with premature miR-17-92a. Overexpression of circAtp9b reduced the effects of miR-17-92a on the apoptosis of osteoblasts induced by LPS. CONCLUSION: CircAtp9b is LPS-inducible and upregulation of circAtp9b in OS promotes the apoptosis of osteoblasts by reducing the formation of mature miR-17-92a.

Catalpol promotes mitochondrial biogenesis in chondrocytes.

The chondrocyte mitochondrial dysfunction has been considered to be associated with the pathogenesis of joint diseases. Catalpol is an active traditional Chinese medicine ingredient named Di-Huang, which is used widely to treat different diseases. In this study, we found the addition of catalpol in chondrocytes induced the expression of crucial mitochondrial regulators, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor-1 (NRF1), and mitochondrial transcription factor A (TFAM). Catalpol promoted mitochondrial biogenesis, as revealed by the induction on the mitochondrial DNA/nuclear DNA (mtDNA/nDNA) and the expression of several mitochondrial genes including translocase of outer mitochondrial membrane 22 (Tomm22), translocase of outer mitochondrial membrane 70 (Tomm70), mitochondrial import inner membrane translocase subunit 50 (Timm50), NADH dehydrogenase [ubiquinone] iron-sulphur protein 3 (NDUFS3), adenosine triphosphate (ATP) synthase subunit D (ATP5d), and cytochrome B. Consequently, catalpol increased cytochrome c oxidase activity, the mitochondrial respiratory rate, and the extracellular ATP production, indicating that catalpol boosted mitochondrial function. Mechanistically, catalpol increased the activation of the cAMP-responsive element-binding protein (CREB), and the inhibition of CREB abolished catalpol-mediated promotion on mitochondrial biogenesis. In summary, this study demonstrated that catalpol has the potential to be used in the treatment of joint diseases.

Neuroprotective effect of Na+ /H+ exchangers isoform-1 inactivation against 6-hydroxydopamine-induced mitochondrial dysfunction and neuronal apoptosis in Parkinson's disease models.

Parkinson's disease (PD) is a disabling neurodegenerative disease mainly caused by degeneration of mesencephalic dopaminergic neurons in the substantia nigra pars compacta (SNpc). The neuroprotective role of Na+ /H+ exchangers isoform-1 (NHE1) inactivation in cerebral ischemic damage has been elucidated. The current study aimed to investigate the impacts of NHE1 in PD. In this study, 6-hydroxydopamine (6-OHDA)-induced PD rat models were established to attempt to illuminate the role and underlying mechanisms of NHE1 in SNpc neurons of PD. Meanwhile, nerve growth factor-stimulated PC12 cells followed by 6-OHDA treatment was used to mimic PD in vitro. Results showed that the protein levels of NHE1 were significantly increased in the SNpc neurons of rats and differentiated PC12 cells after 6-OHDA treatment. Inactivation of NHE1 with chemical inhibitor HOE642 suppressed SNpc neuronal loss and NHE1 expression in PD rats. The overlays of tyrosine hydroxylase and NHE1 displayed that NHE1 expression was not colocalized but closely associated with TH. Besides, treatment with HOE642 relieved the dyskinesia, mitochondrial dysfunction, and neuronal apoptosis. Further in vitro evidence confirmed that inhibition of NHE1 by genetic-knockdown prevented mitochondrial dysfunction and apoptosis. Our study represents the first experimental evidence of a potential role for NHE1 in the pathogenesis of PD.

Indolent T cell lymphoproliferative disorder of the gastrointestinal tract: an uncommon case with lymph node involvement and the classic Hodgkin's lymphoma.

Here we describe an unusual case of an indolent CD8+ T-cell lymphoproliferative disorder in the gastrointestinal tract (ITCLD-GT) accompanied by neck lymph node infiltration and new onset of classic Hodgkin's lymphoma after two years follow-up. Previously, this 42-year-old Asian man suffered from diarrhea and abdominal pain for two years. Intestinal biopsies showed a group of small to intermediate-sized lymphocytes which were monomorphic as well as arranged in a nodular pattern with no clear boundary and were diagnosed as ITCLD-GT. He did not receive chemotherapy or have any disease progression in the gastrointestinal tract (GIT) during the follow-up until a development of neck lymphadenopathy, which led to an eventual mixed cellularity type of Hodgkin's lymphoma, one type of classic HL diagnosis. Interestingly, besides the Hodgkin's cells, the same pathological T-cells in the GIT were present in the Hodgkin's lymphoma lesions. These two pathological T cells in GIT and neck lymph node had the identical histopathological and molecular abnormalities that confirmed the abenteric distant infiltration of ITCLD-GT to the neck lymph node in this patient. This is the first case of ITCLD-GT that has a definite distant lymph node invasion. ITCLD-GT usually has a relatively good prognosis but patients with ITCLD-GT may have abenteric distant infiltration. Thus, long-term follow-up and further study of the underlying mechanisms of this process are necessary.

Down regulation of miR-218, miR-124, and miR-144 relates to Parkinson's disease via activating NF-κB signaling.

Parkinson's disease (PD) is a neurological degenerative disorder that is partially induced by inflammation in the neural system. To explore the roles of disordered microRNAs in the development of PD, we screened 10 miRNAs in the brain samples of 15 postmortem PD patients and 10 postmortem healthy controls by qRT-PCR. The direct targets of miRNAs were predicted by informatics tools and further confirmed by dual luciferase assay and immunoblotting. The function of miRNAs in regulating NF-κB/p65 translocation was examined by immunoblotting, and the overactivation of NF-κB signaling was examined by ELISA. The relationship between dysregulated miRNAs and cytokines was analyzed by correlation analysis. Three miRNAs were found to be reduced in the brains of patients with PD. KPNB1, KPNA3, and KPNA4 were identified as direct targets of miR-218, miR-124, and miR-144. Additionally, KPNA3 was identified as a direct target of miR-124, and KPNA4 was a direct target of both miR-124 and miR-218. The p65 translocation from the cytoplasm to the nucleus was repressed by miR-124, miR-218, and miR-144 in the SH-SY5Y cells. The NF-κB signaling pathway was overactivated after miRNA inhibitor transfection. The upregulation of KPNB1, KPNA3, and KPNA4 in the brain samples of PD patients was confirmed by immunoblotting, and negative correlations were found between dysregulated miRNAs and cytokines. In conclusion, we identified that the downregulation of miR-218, miR-124, and miR-144 in the brain was related to PD via activation of NF-κB signaling, helping to unveil the role played by dysregulated miRNAs in the pathogenesis of PD and provide new potential targets for PD treatment.