Samuelsenmoreno2167
1% of individuals with osteoarthritis and 7.7% of those without osteoarthritis had suffered at least one fracture (log-rank P-value<0.001). There was a positive and significant association between osteoarthritis and fracture in the overall sample [hazard ratio (HR)=1.55, 95% confidence interval (CI)=1.50-1.60]. These findings were corroborated in all sex, age, and osteoarthritis joint site subgroups.
Intervention is urgently needed to reduce the risk of fracture in adults with osteoarthritis, and further research is warranted in order to gain more of an insight into the mediators involved in the relationship between osteoarthritis and fracture.
Intervention is urgently needed to reduce the risk of fracture in adults with osteoarthritis, and further research is warranted in order to gain more of an insight into the mediators involved in the relationship between osteoarthritis and fracture.
To assess the potential of near-infrared spectroscopy (NIRS) for in vivo arthroscopic monitoring of cartilage defects.
Sharp and blunt cartilage grooves were induced in the radiocarpal and intercarpal joints of Shetland ponies and monitored at baseline (0 weeks) and at three follow-up timepoints (11, 23, and 39 weeks) by measuring near-infrared spectra in vivo at and around the grooves. The animals were sacrificed after 39 weeks and the joints were harvested. Spectra were reacquired ex vivo to ensure reliability of in vivo measurements and for reference analyses. Additionally, cartilage thickness and instantaneous modulus were determined via computed tomography and mechanical testing, respectively. The relationship between the ex vivo spectra and cartilage reference properties was determined using convolutional neural network.
In an independent test set, the trained networks yielded significant correlations for cartilage thickness (ρ=0.473) and instantaneous modulus (ρ=0.498). These networks were used tge degeneration after damage than intercarpal joints.
Astaxanthin is a natural carotenoid, can readily cross the blood-brain barrier and exerts a powerful neuroprotective effect. In this study, experiments were performed to explore the underlying molecular mechanisms of which Astaxanthin inhibiting the microglia M1 activation.
BV2 cells and mice were pre-treated with Astaxanthin and treated by Lipopolysaccharide (LPS). The expressions of M1-related factors (pro-inflammatory cytokines and M1 markers) were measured by RT-qPCR and western blot. The target association between miR-31-5p and Numb was explored via luciferase activity assay. MiR-31-5p mimic was transfected into BV2 cells, then the cells were treated with Astaxanthin in combination with LPS. The expression of M1-related factors and Notch pathway-related molecules were measured via RT-qPCR, western blot and immunofluorescence assay.
Precondition of BV2 cells with Astaxanthin inhibited the expression of M1-related factors triggered by LPS. In addition, Astaxanthin decreased the number of Iba1-positive microglia and downregulated the levels of M1-related factors in hippocampus in LPS-treated mice. Further investigation revealed that Astaxanthin-mediated suppression of M1-related factors levels was reversed by miR-31-5p mimic in BV2 cells stimulated by LPS. Subsequently, we verified that miR-31-5p repressed Numb expression by binding to the 3'-UTR of Numb mRNA. Also, Astaxanthin suppressed the expression of Notch1, Hes1 and Hes5 and improved the expression of Numb in BV2 cells challenged by LPS, but this alteration can be reversed by miR-31-5p mimic.
Our study demonstrated that down-regulating miR-31-5p by Astaxanthin could be a potential therapeutic approach to suppress neuroinflammation via regulating microglia M1 activation.
Our study demonstrated that down-regulating miR-31-5p by Astaxanthin could be a potential therapeutic approach to suppress neuroinflammation via regulating microglia M1 activation.
Intracerebral hemorrhage (ICH) induces serious neuroinflammation and damage of blood-brain barrier. We aim to investigate the role of brown fat enriched lncRNA 1 (Blnc1) in the development of ICH in mice.
An ICH model was established with autologous blood injection in C57BL/6 mice, and Blnc1 siRNA was injected intracranially. Blnc1 levels were detected and brain injury was evaluated at day 3. Primary brain microvascular endothelial cells (BMVECs) were isolated from new born mice and gain- and loss-of-function experiments were performed to investigate the role of Blnc1. Then, ICH cell model was established by treating BMVECs with oxygen and glucose deprivation (OGD) plus hemin, and Blnc1 siRNA was transfected into the cells. BMVEC functions, including viability, invasion, apoptosis, permeability and secretion of inflammatory cytokines were analyzed.
Blnc1 was upregulated in perihematomal edema, hematoma and microvessel in the brain of ICH mice. Blnc1 negatively regulated viability and migration, and facilitated apoptosis, permeability and inflammatory cytokine secretion in BMVECs. Silencing Blnc1 restrained OGD plus hemin-caused reduction of BMVEC viability and migration and the induction of apoptosis, permeability and inflammation response, and suppressed PPAR-γ/SIRT6-mediated FoxO3 activation, which could be reversed by T0070907 (PPAR-γ inhibitor). Downregulation of Blnc1 ameliorated ICH-induced nerve injury, brain edema, blood brain barrier destruction, inflammation response and hematoma. Moreover, Blnc1 levels were positively correlated with PPAR-γ levels, and Blnc1 interference suppressed PPAR-γ/SIRT6-mediated activation of FoxO3 signaling in ICH mice.
Silencing Blnc1 alleviated nerve injury and inflammatory response caused by ICH through activating PPAR-γ/SIRT6/FoxO3 pathway.
Silencing Blnc1 alleviated nerve injury and inflammatory response caused by ICH through activating PPAR-γ/SIRT6/FoxO3 pathway.
Long non-coding RNAs (lncRNAs) have been reported to be involved in regulating epilepsy. The purpose of this study is to investigate the possibly regulatory mechanism of small nucleolar RNA host gene 1 (SNHG1) on epilepsy.
Quantitative real-time PCR was utilized to detect the expression of SNHG1, microRNA (miR)-181a, and B-cell lymphoma-2 (BCL-2). Through an enzyme-linked immunosorbent assay, the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and cyclooxygenase-2 (COX-2) were determined. The viability and apoptosis of CTX-TNA2 cells were measured using MTT assay and flow cytometry analysis, respectively. Western blot assay was performed to analyze the protein levels of Bcl-2, BCL2-associated X, and Caspase-3. The relationships between miR-181a and SNHG1/BCL-2 were confirmed by the dual-luciferase reporter assay.
SNHG1 expression was down-regulated in EP tissues and kainic acid (KA)-induced CTX-TNA2 cells. The apoptosis and release of inflammatory factors (TNF-α, IL-1β, IL-6, and COX-2) in KA-induced CTX-TNA2 cells were suppressed by SNHG1 overexpression and promoted by miR-181a up-regulation. In addition, we confirmed that SNHG1 targeted miR-181a, whereas BCL-2 was a target gene of miR-181a. Negative correlations between SNHG1 and miR-181a, as well as miR-181a and BCL-2 were exhibited. Both the up-regulation of miR-181a and down-regulation of BCL-2 reversed the inhibiting effects of SNHG1 on apoptosis and inflammatory response of KA-induced CTX-TNA2 cells, and the promoting effect upon cell viability.
SNHG1 alleviated the progression of EP by modulating the miR-181a/BCL-2 axis in vitro, thus SNHG1 could act as a possible therapeutic target for treating EP.
SNHG1 alleviated the progression of EP by modulating the miR-181a/BCL-2 axis in vitro, thus SNHG1 could act as a possible therapeutic target for treating EP.
MicroRNAs (miRs) play pivotal roles in breast cancer development. The dysregulation of miRs has been associated with PD-L1-mediated immune suppression. This study aimed to examine the effect of transfected miR-383-5p on breast cancer cells and T-cells and its association with clinicopathological features in affected patients.
Initially, miR-383-5p and PD-L1 expression levels were investigated in breast cancer tissues. Then, MDA-MB-231 cells were transfected with miR-383-5p mimics to perform analyses. Cell viability was investigated using the MTT assay, and the annexin V/PI staining assay was performed to examine apoptosis induction. Furthermore, the effect of miR-383-5p on cell migration and cell cycle progression was analyzed using the wound-healing assay and flow cytometry, respectively. Gene and protein expressions were studied using qRT-PCR and western blotting. Finally, the effect of miR-383-5p on T-cells, which were co-cultured with cancer cells, was investigated.
Compared to non-malignant tissues, PD-L1 was up-regulated, and miR-383-5p expression was downregulated in breast cancer tissues. Moreover, miR-383-5p reduced breast cancer cell viability via inducing apoptosis and modulating the expression of apoptosis-related genes. Besides, miR-383-5p could inhibit the migration of breast cancer cells via down-regulating metastasis-related genes. Besides, transfected miR-383-5p induced the secretion of pro-inflammatory cytokines from T-cells. Furthermore, the results showed that miR-383-5p might exert its tumor-suppressive effect via inhibiting the PI3K/AKT/mTOR pathway. The inhibitory effect of transfected miR-383-5p on the PI3K/AKT/mTOR pathway might be the underlying mechanism for inhibiting tumoral PD-L1 expression.
Overall, miR-383-5p can be a promising therapeutic agent for treating breast cancer.
Overall, miR-383-5p can be a promising therapeutic agent for treating breast cancer.
To investigate if the modification of human adipose-derived mesenchymal stem cells (hADSCs) by the antioxidants superoxide dismutase 2 (Sod2) and catalase (Cat) can attenuate the pathological conditions of intervertebral disc degeneration (IVD).
In vitro, MTT assay and qRT-PCR was used to detect cell proliferation and gene expressions in hADSCs transduced with Ad-null (an adenovirus vector containing no transgene expression cassette), Ad-Sod2 (recombinant adenovirus Sod2) and Ad-Cat. IVD mouse models were generated by needle puncture and treated with hADSCs with/without Ad-null/Ad-Sod2/Ad-Cat. IBMX solubility dmso X-ray evaluation, magnetic resonance imaging (MRI) analysis, histological analysis, immunohistochemistry, Western blots, ELISAs and qRT-PCR were performed.
hADSCs transduced with Ad-Sod2 and Ad-Cat showed enhanced cell proliferation with the upregulation of SOX9, ACAN, and COL2. In vivo, IVD mice injected with hADSCs showed increased disc height index, MRI index and mean T2 intensities, as well as the attenuated histologic grading of the annulus fibrosus (AF) and NP accompanied by the upregulation of GAG and COL2, which were further improved in the Ad-Sod2 hADSC + IVD and Ad-Cat hADSC + IVD groups. Furthermore, the increased expression of IL-1β, IL-6 and TNF-α was reduced in IVD mice injected with hADSCs. Compared with the hADSC + IVD group, the Ad-Sod2 hADSC/Ad-Cat hADSC + IVD groups had lower expression of pro-inflammatory factors.
Modification of hADSCs by the antioxidants Sod2 and Cat improved the pathological condition of intervertebral disc tissues with increased GAG and COL2 expression, as well as reduced inflammation, thereby demonstrating a therapeutic effect in IVD.
Modification of hADSCs by the antioxidants Sod2 and Cat improved the pathological condition of intervertebral disc tissues with increased GAG and COL2 expression, as well as reduced inflammation, thereby demonstrating a therapeutic effect in IVD.
