A predictive model for depression in Chinese middle-aged and elderly people with physical disabilities.

BACKGROUND: Middle-aged and older adults with physical disabilities exhibit more common and severe depressive symptoms than those without physical disabilities. Such symptoms can greatly affect the physical and mental health and life expectancy of middle-aged and older persons with disabilities. METHOD: This study selected 2015 and 2018 data from the China Longitudinal Study of Health and Retirement. After analyzing the effect of age on depression, we used whether middle-aged and older adults with physical disabilities were depressed as the dependent variable and included a total of 24 predictor variables, including demographic factors, health behaviors, physical functioning and socialization, as independent variables. The data were randomly divided into training and validation sets on a 7:3 basis. LASSO regression analysis combined with binary logistic regression analysis was performed in the training set to screen the predictor variables of the model. Construct models in the training set and perform model evaluation, model visualization and internal validation. Perform external validation of the model in the validation set. RESULT: A total of 1052 middle-aged and elderly persons with physical disabilities were included in this study, and the prevalence of depression in the elderly group > middle-aged group. Restricted triple spline indicated that age had different effects on depression in the middle-aged and elderly groups. LASSO regression analysis combined with binary logistic regression screened out Gender, Location of Residential Address, Shortsightedness, Hearing, Any possible helper in the future, Alcoholic in the Past Year, Difficulty with Using the Toilet, Difficulty with Preparing Hot Meals, and Unable to work due to disability constructed the Chinese Depression Prediction Model for Middle-aged and Older People with Physical Disabilities. The nomogram shows that living in a rural area, lack of assistance, difficulties with activities of daily living, alcohol abuse, visual and hearing impairments, unemployment and being female are risk factors for depression in middle-aged and older persons with physical disabilities. The area under the ROC curve for the model, internal validation and external validation were all greater than 0.70, the mean absolute error was less than 0.02, and the recall and precision were both greater than 0.65, indicating that the model performs well in terms of discriminability, accuracy and generalisation. The DCA curve and net gain curve of the model indicate that the model has high gain in predicting depression. CONCLUSION: In this study, we showed that being female, living in rural areas, having poor vision and/or hearing, lack of assistance from others, drinking alcohol, having difficulty using the restroom and preparing food, and being unable to work due to a disability were risk factors for depression among middle-aged and older adults with physical disabilities. We developed a depression prediction model to assess the likelihood of depression in Chinese middle-aged and older adults with physical disabilities based on the above risk factors, so that early identification, intervention, and treatment can be provided to middle-aged and older adults with physical disabilities who are at high risk of developing depression.

Statins improve cardiac endothelial function to prevent heart failure with preserved ejection fraction through upregulating circRNA-RBCK1.

Heart failure with preserved ejection fraction (HFpEF) is associated with endothelial dysfunction. We have previously reported that statins prevent endothelial dysfunction through inhibition of microRNA-133a (miR-133a). This study is to investigate the effects and the underlying mechanisms of statins on HFpEF. Here, we show that statins upregulate the expression of a circular RNA (circRNA-RBCK1) which is co-transcripted with the ring-B-box-coiled-coil protein interacting with protein kinase C-1 (RBCK1) gene. Simultaneously, statins increase activator protein 2 alpha (AP-2α) transcriptional activity and the interaction between circRNA-RBCK1 and miR-133a. Furthermore, AP-2α directly interacts with RBCK1 gene promoter in endothelial cells. In vivo, lovastatin improves diastolic function in male mice under HFpEF, which is abolished by loss function of endothelial AP-2α or circRNA-RBCK1. This study suggests that statins upregulate the AP-2α/circRNA-RBCK1 signaling to suppress miR-133a in cardiac endothelial cells and prevent diastolic dysfunction in HFpEF.

Quinoxalineimide-Based Semiconducting Polymer Nanoparticles as an Effective Phototheranostic for the Second Near-Infrared Fluorescence Imaging and Photothermal Therapy.

Multifunctional theranostics play a critical role in improving the efficacy of photothermal therapy and tumor fluorescence imaging; however, they require the integration of complex components into a single theranostic system, and their response in the second near-infrared (NIR-II) region is constrained by wavelengths of a photosensitizer. To address this issue, we herein developed a novel multifunctional thiazole-fused quinoxalineimide semiconducting polymer (named PQIA-BDTT), which exhibits NIR-II fluorescence and photothermal properties. PQIA-BDTT nanoparticles achieved an impressively high photothermal conversion efficiency (72.6%) in laser (1064 nm)-induced photothermal therapy at a safe maximum permissible exposure, demonstrating their capability as an effective photothermal agent. Moreover, PQIA-BDTT nanoparticles can be used as a reference for NIR-II fluorescence imaging under a low laser fluence. The tumor size and location in 4T1 mice intravenously injected with the PQIA-BDTT nanoparticles could be precisely identified through NIR-II fluorescence imaging, which also exhibited remarkable photothermal antitumor efficacy by in vitro and in vivo therapy. Overall, this study demonstrates that introducing a thiazole-fused quinoxalineimide acceptor unit into a donor-acceptor conjugated polymer is an effective strategy for the synthesis of novel multifunctional theranostic systems, which provides a novel platform for designing theranostic agents for biomedical applications.

One-Dimensional Local Binary Pattern and Common Spatial Pattern Feature Fusion Brain Network for Central Neuropathic Pain.

Central neuropathic pain (CNP) after spinal cord injury (SCI) is related to the plasticity of cerebral cortex. The plasticity of cortex recorded by electroencephalogram (EEG) signal can be used as a biomarker of CNP. To analyze changes in the brain network mechanism under the combined effect of injury and pain or under the effect of pain, this paper mainly studies the changes of brain network functional connectivity in patients with neuropathic pain and without neuropathic pain after SCI. This paper has recorded the EEG with the CNP group after SCI, without the CNP group after SCI, and a healthy control group. Phase-locking value has been used to construct brain network topological connectivity maps. By comparing the brain networks of the two groups of SCI with the healthy group, it has been found that in the [Formula: see text] and [Formula: see text] frequency bands, the injury increases the functional connectivity between the frontal lobe and occipital lobes, temporal, and parietal of the patients. Furthermore, the comparison of brain networks between the group with CNP and the group without CNP after SCI has found that pain has a greater effect on the increased connectivity within the patients' frontal lobes. Motor imagery (MI) data of CNP patients have been used to extract one-dimensional local binary pattern (1D-LBP) and common spatial pattern (CSP) features, the left and right hand movements of the patients' MI have been classified. The proposed LBP-CSP feature method has achieved the highest accuracy of 98.6% and the average accuracy of 91.5%. The results of this study have great clinical significance for the neural rehabilitation and brain-computer interface of CNP patients.

Mechanism of inhibition of CRISPR-Cas9 by anti-CRISPR protein AcrIIC1.

CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR associated) systems are bacterial and archaeal defense mechanisms against invading phages and viruses. To overcome these defenses, phages and other mobile genetic elements (MGEs) have evolved multiple anti-CRISPR proteins (Acrs) that can inhibit the function of CRISPR-Cas systems. The AcrIIC1 protein has been shown to be able to inhibit the activity of Neisseria meningitidis Cas9 (NmeCas9) in both bacteria and human cells. Here, we solve the structure of AcrIIC1 in complex with the HNH domain of NmeCas9 using X-ray crystallography. The structure shows that AcrIIC1 binds to the catalytic sites of the HNH domain, preventing it from accessing the DNA target. In addition, our biochemical data show that AcrIIC1 is a broad-spectrum inhibitor targeting Cas9 enzymes from different subtypes. Taken together, the structure and biochemical analysis reveal the molecular mechanism of AcrIIC1-mediated Cas9 inhibition and provide new insights into regulatory tools for Cas9-based applications.

Circularly Polarized Luminescent Eu4(LR)4 Cage for Enantiomeric Excess and Concentration Simultaneous Determination of Chiral Diamines.

Undoubtably, it is challenging to simultaneously determine the identity, enantiomeric excess (ee), and total concentration of an enantiomer by just one optical measurement. Herein, we design a chiral tetrahedron Eu4(LR)4 with circularly polarized luminescence (CPL), which presents highly selective/stereoselective, rapid, and "turn-on" CPL response to chiral diamines, rather than the monoamino compounds, such as monoamines or amino alcohols. By recording the left- and right-CPL intensities of the Eu3+ ion at 591 nm, the enantiomeric composition and concentration of chiral diamines can be simultaneously determined by monitoring the glum value and total emission intensity (IL + IR), respectively. Spectroscopy analyses demonstrate that the variations of glum depend on the inversion and maintenance of configuration around the Eu3+ ion (Δ â†” Λ), while the "turn-on" response arises from the raising of the T1 state of the ligand. The molecule/electron structural variations are proposed from the synergetic supramolecular interactions of NH2 groups with pendant diols and trifluoroacetyl groups.

[Effect of Curcumin on the Proliferation, Apoptosis, and Cell Cycle of Human Acute Myeloid Leukemia Cell Line K562].

OBJECTIVE: To investigate the effects of curcumin on the proliferation, apoptosis, and cell cycle of human acute myeloid leukemia cell line K562. METHODS: MTT method was used to detect the proliferation inhibition of logarithmic growth phase human acute myeloid leukemia K562 cells, flow cytometry was used to detect the cell cycle, Annexin V-FITC was used to detect the apoptosis rate, and real-time fluorescent quantitative PCR and Western blot were used to detect the expression of Bax, BCL-2 and caspase-3 mRNA and protein, respectively. RESULTS: The inhibition rate of cell proliferation in curcumin 10, 20, and 40 µmol/L group for 24 h and 48 h were higher than that in the control group (curcumin 0 µmol/L), and the cell proliferation inhibition rate was concentration-time dependent (r=0.879, r=0.914). The proportion of G0/G1 cells and apoptosis rate of K562 cells in the curcumin 10, 20, and 40 µmol/L group were higher than those in the control group, and showed drug concentration dependent (r=0.856, r=0.782). The expression of Bax and Caspase-3 mRNA in the curcumin 10, 20, and 40 µmol/L group was higher, while BCL-2 mRNA was lower than those in the control group, and showed drug concentration dependent (r=0.861, r=0.748, r=-0.817). The gray value of Bax protein expression in the curcumin 10, 20, and 40 µmol/L group was higher than that in the control group, while the gray value of BCL-2 and Caspase-3 protein expression was lower than that in the control group, and showed drug concentration dependent (r=0.764, r=-0.723, r=-0.831). CONCLUSION: Curcumin can inhibit the proliferation of human acute myeloid leukemia cell line K562 cells, block the cell cycle at G0/G1 phase, promote cell apoptosis, and induce apoptosis by regulating Bax, BCL-2, and Caspase-3.

Clivus-involved immunoglobulin G4 related hypertrophic pachymeningitis mimicking meningioma: A case report.

BACKGROUND: Immunoglobulin G4 related disease (IgG4-RD) is a fibroinflammatory disease with markedly elevated serum IgG4 levels and fibrous tissue proliferation, accompanied by numerous plasma cells. IgG4 related hypertrophic pachymeningitis (IgG4-RHP) is relatively rare and indistinguishable from other phymatoid diseases before the operation. The risk of long-term immunosuppression needs to be balanced with disease activity. CASE SUMMARY: A 40-year-old man presented with headache and bilateral abducent paralysis. He was also diagnosed with pulmonary tuberculosis 10 years ago and was on regular treatment for the same. Before the operation and steroid therapy, the patient was suspected of having tubercular meningitis at a local hospital. A clivus lesion was found via brain magnetic resonance imaging (MRI) at this presentation. He was preliminarily diagnosed with meningioma and underwent Gamma Knife Surgery. Transnasal endoscopic resection was performed to treat deterioration of nerve function. Postoperative pathologic examination suggested IgG4-RD. Moreover, the serum IgG4 was elevated at 1.90 g/L (reference range: 0.035-1.500 g/L). After steroid therapy for 2 mo, the lesion size diminished on MRI, and the function of bilateral abducent nerves recovered. CONCLUSION: IgG4-RHP is relatively rare and indistinguishable before the operation. Elevated serum IgG4 levels and imaging examination help in the diagnosis of IgG4-RHP. Surgery is necessary when lesions progress and patients start to develop cranial nerve function deficit.

[Expression Level and Correlation of miR-211, miR-155, C-myc in Acute T Lymphocytic Leukemia].

OBJECTIVE: To investigate the expression and correlation of miR-211, miR-155, and C-myc in acute T lymphocytic leukemia (T-ALL), aiming to provide evidence for the diagnosis and treatment. METHODS: A total of 96 T-ALL patients who were diagnosed and treated in People's Hospital of Zhengzhou from June 2014 to June 2017 were selected, and 69 healthy volunteers who had a physical examination were selected as control group in the same period. Real-time fluorescent quantitative PCR (RT-PCR) was used to determine the expression levels of miR-211, miR-155, and C-myc in peripheral blood mononuclear cells in each group. Kaplan-Meier was used to analyze the survival of T-ALL patients and correlation of miR-211, miR-155, and C-myc with prognosis. Pearson correlation analysis was used to evaluate the correlation of miR-211, miR-155, and C-myc with disease risk. RESULTS: The expression levels of miR-211 mRNA, miR-155 mRNA, and C-myc mRNA in T-ALL group were higher than those in the control group (P<0.01), those in non-remission group were higher than those in remission group (P<0.01), and those in high-risk group were also higher than those in low-risk group and intermediate-risk group (P<0.01). The survival time of T-ALL patients with low miR-211 expression was longer than that with high miR-211 expression (P<0.01), that with low miR-155 expression was longer than that with high miR-155 expression (P<0.01), and that with low C-myc expression was also longer than that with high C-myc expression (P<0.01). The high expression of miR-211, miR-155, and C-myc was linearly positively correlated with high risk of disease (r=0.749, 0.781, 0.804). CONCLUSION: The expressions of miR-211, miR-155, and C-myc are up-regulated in T-ALL patients, closely related to prognosis, and linearly positively correlated with disease risk.

A framework for motor imagery with LSTM neural network.

BACKGROUND AND OBJECTIVE: How to learn robust representations from brain activities and to improve algorithm performance are the most significant issues for brain-computer interface systems. METHODS: This study introduces a long short-term memory recurrent neural network to decode the multichannel electroencephalogram or electrocorticogram for implementing an effective motor imagery-based brain-computer interface system. The unique information processing mechanism of the long short-term memory network characterizes spatio-temporal dynamics in time sequences. This study evaluates the proposed method using publically available electroencephalogram/electrocorticogram datasets. RESULTS: The decoded features coupled with a gradient boosting classifier could obtain high recognition accuracies of 99% for electroencephalogram and 100% for electrocorticogram, respectively. CONCLUSIONS: The results demonstrated that the proposed model can estimate robust spatial-temporal features and obtain significant performance improvement for motor imagery-based brain-computer interface systems. Further, the proposed method is of low computational complexity.

Expression Level and Correlation of miR-211, miR-155, C-myc in Acute T Lymphocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression and correlation of miR-211, miR-155, and C-myc in acute T lymphocytic leukemia (T-ALL), aiming to provide evidence for the diagnosis and treatment.@*METHODS@#A total of 96 T-ALL patients who were diagnosed and treated in People's Hospital of Zhengzhou from June 2014 to June 2017 were selected, and 69 healthy volunteers who had a physical examination were selected as control group in the same period. Real-time fluorescent quantitative PCR (RT-PCR) was used to determine the expression levels of miR-211, miR-155, and C-myc in peripheral blood mononuclear cells in each group. Kaplan-Meier was used to analyze the survival of T-ALL patients and correlation of miR-211, miR-155, and C-myc with prognosis. Pearson correlation analysis was used to evaluate the correlation of miR-211, miR-155, and C-myc with disease risk.@*RESULTS@#The expression levels of miR-211 mRNA, miR-155 mRNA, and C-myc mRNA in T-ALL group were higher than those in the control group (P<0.01), those in non-remission group were higher than those in remission group (P<0.01), and those in high-risk group were also higher than those in low-risk group and intermediate-risk group (P<0.01). The survival time of T-ALL patients with low miR-211 expression was longer than that with high miR-211 expression (P<0.01), that with low miR-155 expression was longer than that with high miR-155 expression (P<0.01), and that with low C-myc expression was also longer than that with high C-myc expression (P<0.01). The high expression of miR-211, miR-155, and C-myc was linearly positively correlated with high risk of disease (r=0.749, 0.781, 0.804).@*CONCLUSION@#The expressions of miR-211, miR-155, and C-myc are up-regulated in T-ALL patients, closely related to prognosis, and linearly positively correlated with disease risk.

Safety and Efficacy of Rapamycin-Eluting Vertebral Stents in Patients With Symptomatic Extracranial Vertebral Artery Stenosis.

Background and Purpose: Drug-eluting stents generally have superior performance to bare metal stents in the treatment of vertebral artery stenosis (VAS). This prospective, multicenter, and single-arm clinical trial was initiated to assess in-stent restenosis (ISR) and midterm outcome after rapamycin-eluting stent placement in patients with symptomatic extracranial VAS. Methods: The subjects underwent angiographic follow-up at 6 months and final clinical follow-up at 12 months. The primary efficacy endpoint was ISR at 6 months. Secondary endpoints included technical success, target lesion-related transient ischemic attack (TIA), stroke, or death, and all-cause TIA, stroke, or death during the 12-month follow-up period. Results: A total of 104 stents were implanted in the 101 patients and 83 patients (82.2%) completed angiographic follow-up at 6 months. The technical success rate was 86.1% (87/101); mean in-stent stenosis rate was 25.1 ± 17.1% and ISR rate was 5.9% (95% CI: 0.8-10.9%). All the patients with ISR were completely asymptomatic and no stent fractures were observed during angiographic follow-up. At the 12-month clinical follow-up, target lesion-related TIA, stroke, or death had occurred in two (2.0%) patients and all-cause TIA, stroke, or death had occurred in six (6.1%) patients. Conclusion: The placement of rapamycin-eluting stents in patients with symptomatic extracranial VAS yields favorable ISR results and showed a trend of favorable safety outcomes including low rates of perioperative complications and late stroke. However, further study is needed to establish the long-term clinical benefits of this stent in the treatment of VA disease.

Corrigendum to "Neuroprotective Effects of the Sonic Hedgehog Signaling Pathway in Ischemic Injury through Promotion of Synaptic and Neuronal Health".

[This corrects the article DOI: 10.1155/2020/8815195.].

In vitro studies of maleidride-forming enzymes.

In vitro assays of enzymes involved in the biosynthesis of maleidrides from polyketides in fungi were performed. The results show that the enzymes are closely related to primary metabolism enzymes of the citric acid cycle in terms of stereochemical preferences, but with an expanded substrate selectivity. A key citrate synthase can react both saturated and unsaturated acyl CoA substrates to give solely anti substituted citrates. This undergoes anti-dehydration to afford an unsaturated precursor which is cyclised in vitro by ketosteroid-isomerase-like enzymes to give byssochlamic acid.

Neuroprotective Effects of the Sonic Hedgehog Signaling Pathway in Ischemic Injury through Promotion of Synaptic and Neuronal Health.

Cerebral ischemia is a common cerebrovascular condition which often induces neuronal apoptosis, leading to brain damage. The sonic hedgehog (Shh) signaling pathway has been reported to be involved in ischemic stroke, but the underlying mechanisms have not been fully elucidated. In the present study, we demonstrated that expressions of Shh, Ptch, and Gli-1 were significantly downregulated at 24 h following oxygen-glucose deprivation (OGD) injury in neurons in vitro, effects which were associated with increasing numbers of apoptotic cells and reactive oxygen species generation. In addition, expressions of synaptic proteins (neuroligin and neurexin) were significantly downregulated at 8 h following OGD, also associated with concomitant neuronal apoptosis. Treatment with purmorphamine, a Shh agonist, increased Gli-1 in the nucleus of neurons and protected against OGD injury, whereas the Shh inhibitor, cyclopamine, produced the opposite effects. Activation of Shh signals promoted CREB and Akt phosphorylation; upregulated the expressions of BDNF, neuroligin, and neurexin; and decreased NF-κB phosphorylation following OGD. Notably, this activation of Shh signals was accompanied by improved neurobehavioral responses along with attenuations in edema and apoptosis at 48 h postischemic insult in rats. Taken together, these results demonstrate that activation of the Shh signaling pathway played a neuroprotective role in response to ischemic exposure via promotion of synaptic and neuronal health.

Identification of Differentially Expressed Genes and Key Pathways in the Dorsal Root Ganglion After Chronic Compression.

Neuropathic pain (NP) is caused by primary or secondary impairment of the peripheral or central nervous systems. Its etiology is complex and involves abnormal patterns of gene expression and pathway activation. Using bioinformatics analysis, we aimed to identify NP-associated changes in genes and pathways in L4 and L5 dorsal root ganglia (DRG) in a rat model of NP induced by chronic compression of the DRG (CCD). Genome-wide transcriptional analyses were used to elucidate the molecular mechanisms underlying NP. We screened differentially expressed genes (DEGs) 7 days after CCD in comparison with sham-operated controls. Quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting were used to confirm the presence of key DEGs. Kyoto Encyclopedia of Genes and Genomes (KEGG)-pathway analysis of DEGs and global signal transduction network analysis of DEGs were also conducted. The CCD group developed clear mechanical and thermal allodynia in the ipsilateral hind paw compared with the sham group. This comparison identified 1,887 DEGs, with 1156 upregulated and 731 downregulated DEGs, and 123 DEG-enriched pathways. We identified the key candidate genes that might play a role in the development of NP, namely syndecan 1 (Sdc1), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma (Pi3k), Janus kinase 2 (Jak2), jun proto-oncogene, AP-1 transcription factor subunit (Jun), and interleukin 6 (IL-6) by analyzing the global signal transduction network. RT-qPCR and western blot analysis confirmed the microarray results. The DEGs Sdc1, Pi3k, Jak2, Jun, and IL-6, and the cytokine signaling pathway, the neuroactive ligand-receptor interaction, the toll-like receptor signaling pathway, and the PI3K-Akt signaling pathway may have decisive modulatory roles in both nerve regeneration and NP. These results provide deeper insight into the mechanism underlying NP and promising therapeutic targets for its treatment.

Purmorphamine Attenuates Neuro-Inflammation and Synaptic Impairments After Hypoxic-Ischemic Injury in Neonatal Mice via Shh Signaling.

Purmorphamine (PUR), an agonist of the Smoothened (Smo) receptor, has been shown to function as a neuroprotectant in acute experimental ischemic stroke. Its role in hypoxic-ischemic (HI) brain injury in neonatal mice remains unknown. Here we show that PUR attenuated acute brain injury, with a decrease in Bax/Bcl-2 ratio as well as inhibition of caspase-3 activation. These beneficial effects of PUR were associated with suppressing neuro-inflammation and oxidative stress. PUR exerted long-term protective effects upon tissue loss and improved neurobehavioral outcomes as determined at 14 and 28 days post-HI insult. Moreover, PUR increased synaptophysin (Syn) and postsynaptic density (PSD) protein 95 expression in HI-treated mice and attenuated synaptic loss. PUR upregulated the expression of Shh pathway mediators, while suppression of the Shh signaling pathway with cyclopamine (Cyc) reversed these beneficial effects of PUR on HI insult. Our study suggests a therapeutic potential for short-term PUR administration in HI-induced injury as a result of its capacity to exert multiple protective actions upon acute brain injury, long-term memory deficits, and impaired synapses. Moreover, we provide evidence indicating that one of the mechanisms underlying these beneficial effects of PUR involves activation of the Shh signaling pathway.

Molecular basis of methylation and chain-length programming in a fungal iterative highly reducing polyketide synthase.

Exchange of 32 different sub-fragments of the C-methyltransferase (C-MeT), pseudo-ketoreductase (ΨKR) and ketoreductase (KR) catalytic domains of the tenellin iterative Type I polyketide synthase non ribosomal peptide synthetase (PKS-NRPS) TENS by homologous fragments from the desmethylbassianin (DMBS) and militarinone (MILS) PKS-NRPS led to the creation of chimeric synthetases in which programming fidelity was altered, resulting in the production of mixtures of products with different methylation patterns and chain lengths. Swap of KR domain subfragments with the homologous fragments from the KR of the heptaketide militarinone synthetase resulted in the synthesis of penta, hexa and heptaketides. The results of these and previous experiments are rationalised by considering the existence of competition for acyl-carrier protein (ACP) bound substrates between different catalytic domains of the PKS. In particular, competition between the C-MeT and ketoreductase domains (KR) can account for methylation programming, and competition between the KR and the off-loading NRPS accounts for chain-length selectivity.

Wnt1 inhibits vascular smooth muscle cell calcification by promoting ANKH expression.

AIMS: Wnt signaling plays a critical role in vascular calcification (VC). Wnt factors induce different physiological and pathological effects on cardiovascular functions. Wnt1, a ligand of Wnt/ß-catenin signaling, promotes pro-angiogenesis and reduces myocardial infarction. The role of Wnt1 on VC in chronic kidney disease (CKD) is not fully understood. METHODS AND RESULTS: We used human vascular smooth muscle cells (VSMCs) and a rat model of chronic renal failure (CRF), and observed a native protective mechanism by which VC is reduced via the activation of Wnt1 and its transcriptional target ANKH inorganic pyrophosphate transport regulator (ANKH) gene. ANKH is an essential calcification inhibitor that effluxes inorganic pyrophosphate (PPi) from VSMCs to play an inhibitory role in VC. Vascular ANKH and plasma PPi were significantly downregulated in the rat model of CRF. The knockdown or inhibition of ANKH reversed the effect of Wnt1 on VC in VSMCs. Clinical analysis revealed low plasma levels of Wnt1 and PPi were associated with CKD in patients. Applying a Wnt/ß-catenin signaling agonist can alleviate the progression of VC. CONCLUSION: This work reveals the ANKH regulation of Wnt1 in VSMCs is essential for blocking VC. Our findings may contribute to the development of medications that target Wnt signaling and/or ANKH to inhibit VC.

CircRNA­0044073 is upregulated in atherosclerosis and increases the proliferation and invasion of cells by targeting miR­107.

Circular RNAs (circRNAs) are endogenous non­coding RNAs implicated in atherosclerosis. The aim of the present study was to explore the function of circRNA­0044073 in atherosclerosis. Reverse transcription quantitative polymerase chain reaction assays were used to measure the expression levels of circRNA­0044073, microRNA (miRNA/miR)­107, janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), B­cell lymphoma 2 (Bcl­2) and v­myc avian myelocytomatosis viral oncogene homolog (c­myc) in in blood cells from patients with atherosclerosis. RNA pull­down and luciferase reporter assays were then used to determine the association between circRNA and miR expression, and miR and gene expression, respectively. Matrigel invasion assay and flow cytometry were used to analyze cell invasion and cell cycle. Western blot analysis and ELISA were used to evaluate the expression levels of proteins. It was identified that the expression of circRNA­0044073 was upregulated and the expression of miR­107 was downregulated in atherosclerotic blood cells. Overexpression of circRNA­0044073 promoted the proliferation of human vascular smooth muscle cells (HUVSMCs) and human vascular endothelial cells (HUVECs), while overexpression of miR­107 inhibited their proliferation. In addition, circRNA­0044073 suppressed the levels of miR­107 via a sponge mechanism. Lipopolysaccharide (LPS) affected the proliferation of HUVSMCs and HUVECs, and also resulted in changes in circRNA­0044073 expression levels. CircRNA­0044073 promoted the proliferation and invasion of HUVSMCs and HUVECs in spite of the opposite effect observed with LPS treatment. The JAK/STAT signaling pathway was activated in patients with atherosclerosis. CircRNA­0044073 favored the activation of the JAK/STAT signaling pathway and inflammation in HUVSMCs and HUVECs. These data indicate that circRNA­0044073 is upregulated in atherosclerosis and promotes the proliferation and invasion of cells by targeting miR­107 and activating the JAK/STAT signaling pathway, potentially offering a target for novel treatment strategies against atherosclerosis.