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Background: Inflammatory response of central nervous system is an important component mechanism in the bladder pain of interstitial cystitis/bladder pain syndrome (IC/BPS). Exosomes transfer with microRNAs (miRNA) from mesenchymal stem cell (MSCs) might inhibit inflammatory injury of the central nervous system. Herein, the purpose of our study was to explore the therapeutic effects by which extracellular vesicles(EVs)derived from miR-9-edreched MSCs in IC/BPS and further investigate the potential mechanism to attenuate neuroinflammation. Methods: On the basis of IC/BPS model, we used various techniques including bioinformatics, cell and molecular biology, and experimental zoology, to elucidate the role and molecular mechanism of TLR4 in regulating the activation of NLRP3 inflammasome in bladder pain of IC/BPS, and investigate the mechanism and feasibility of MSC-EVs enriched with miR-9 in the treatment of bladder pain of IC/BPS. Results: The inflammatory responses in systemic and central derived by TLR4 activation were closely related to the cystitis-induced pelvic/bladder nociception in IC/BPS model. Intrathecal injection of miR-9-enreched MSCs derived exosomes were effective in the treatment of cystitis-induced pelvic/bladder nociception by inhibiting TLR4/NF-κb/NLRP3 signal pathway in central nervous system of IC/BPS mice. Conclusions: This study demonstrated that miR-9-enreched MSCs derived exosomes alleviate neuroinflammaiton and cystitis-induced bladder pain by inhibiting TLR4/NF-κb/NLRP3 signal pathway in interstitial cystitis mice, which is a promising strategy against cystitis-induced bladder pain. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a malignant tumor with high morbidity and mortality. It is well-accepted that dysregulated lncRNAs are closely related to the development of CRC. In this study, the function and mechanism of RNASEH1-AS1 in CRC were investigated. RT-qPCR and western blot detected the expression of targeted genes in tissues and cells. CCK-8, clone formation, wound healing assay, and Transwell were applied to evaluate CRC cell malignant behaviors. ChIP, RIP, and RNA pull-down validated interactions among RNASEH1-AS1, H3K27ac, CBP, BUD13, and ANXA2. Nucleoplasmic separation and FISH assay determined the location of RNASEH1-AS1 in CRC cells. IHC assay was used to detect Ki-67 expression in tumor tissues from mice. RNASEH1-AS1 was highly expressed in CRC tumor tissues and cells. RNASEH1-AS1 silencing effectively suppressed the viability, proliferation, migration, and invasion of CRC cells. In addition, CBP-mediated H3K27ac increased RNASEH1-AS1 expression in CRC cells and RNASEH1-AS1 could elevate ANXA2 expression through recruiting BUD13. Furthermore, RNASEH1-AS1 silencing inhibited malignant phenotypes of CRC cells and tumor growth in mice through decreasing ANXA2 expression and inactivating the Wnt/β-catenin pathway. Our results revealed that RNASEH1- AS1 induced by CBP-mediated H3K27ac activated Wnt/β-catenin pathway to promote CRC progression through recruiting BUD13 to stabilize ANXA2 mRNA, which provides substantial evidence of RNASEH1-AS1 in CRC. Targeting RNASEH1- AS1 might alleviate CRC progression. [ABSTRACT FROM AUTHOR]

The brain tumor segmentation task with different domains remains a major challenge because tumors of different grades and severities may show different distributions, limiting the ability of a single segmentation model to label such tumors. Semi-supervised models (e.g., mean teacher) are strong unsupervised domain-adaptation learners. However, one of the main drawbacks of using a mean teacher is that given a large number of iterations, the teacher model weights converge to those of the student model, and any biased and unstable predictions are carried over to the student. In this article, we proposed a novel unsupervised domain-adaptation framework for the brain tumor segmentation task, which uses dual student and adversarial training techniques to effectively tackle domain shift with MR images. In this study, the adversarial strategy and consistency constraint for each student can align the feature representation on the source and target domains. Furthermore, we introduced the cross-coordination constraint for the target domain data to constrain the models to produce more confident predictions. We validated our framework on the cross-subtype and cross-modality tasks in brain tumor segmentation and achieved better performance than the current unsupervised domain-adaptation and semi-supervised frameworks. [ABSTRACT FROM AUTHOR]

Background: Reliable and individualized biomarkers are crucial for identifying early cognitive impairment in subcortical small-vessel disease (SSVD) patients. Personalized brain age prediction can effectively reflect cognitive impairment. Thus, the present study aimed to investigate the association of brain age with cognitive function in SSVD patients and assess the potential value of brain age in clinical assessment of SSVD. Materials and methods: A prediction model for brain age using the relevance vector regression algorithm was developed using 35 healthy controls. Subsequently, the prediction model was tested using 51 SSVD patients [24 subjective cognitive impairment (SCI) patients and 27 mild cognitive impairment (MCI) patients] to identify brain age-related imaging features. A support vector machine (SVM)-based classification model was constructed to differentiate MCI from SCI patients. The neurobiological basis of brain agerelated imaging features was also investigated based on cognitive assessments and oxidative stress biomarkers. Results: The gray matter volume (GMV) imaging features accurately predicted brain age in individual patients with SSVD (R² = 0.535, p < 0.001). The GMV features were primarily distributed across the subcortical system (e.g., thalamus) and dorsal attention network. SSVD patients with age acceleration showed significantly poorer Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA) scores. The classification model based on GMV features could accurately distinguish MCI patients from SCI patients (area under the curve = 0.883). The classification outputs of the classification model exhibited significant associations with MoCA scores, Trail Making Tests A and B scores, Stroop Color and Word Test C scores, information processing speed total scores, and plasma levels of total antioxidant capacity in SSVD patients. Conclusion: Brain age can be accurately quantified using GMV imaging data and shows potential clinical value for identifying early cognitive impairment in SSVD patients. [ABSTRACT FROM AUTHOR]

This research aimed to evaluate the right ventricular segmentation ability of magnetic resonance imaging (MRI) images based on deep learning and evaluate the influence of curcumin (Cur) on the psychological state of patients with pulmonary hypertension (PH). The heart MRI images were detected based on the You Only Look Once (YOLO) algorithm, and then the MRI image right ventricle segmentation algorithm was established based on the convolutional neural network (CNN) algorithm. The segmentation effect of the right ventricle in cardiac MRI images was evaluated regarding intersection-over-union (IOU), Dice coefficient, accuracy, and Jaccard coefficient. 30 cases of PH patients were taken as the research object. According to different treatments, they were rolled into control group (conventional treatment) and Cur group (conventional treatment + Cur), with 15 cases in each group. Changes in the scores of the self-rating anxiety scale (SAS) and self-rating depression scale (SDS) of the two groups of patients before and after treatment were analyzed. It was found that the average IOU of the heart target detection frame of the MRI image and the true bounding box before correction was 0.7023, and the IOU after correction was 0.9016. The Loss of the MRI image processed by the CNN algorithm was 0.05, which was greatly smaller than those processed by other algorithms. The Dice coefficient, Jaccard coefficient, and accuracy of the MRI image processed by CNN were 0.89, 0.881, and 0.994, respectively. The MRI images of PH patients showed that the anterior wall of the right ventricle was notably thickened, and the main pulmonary artery was greatly widened. After treatment, the SAR and SDS scores of the two groups were lower than those before treatment (P < 0.05), and the SAR and SDS scores of the curcumin group were lower than those of the control group (P < 0.05). To sum up, the right ventricular segmentation ability of MRI images based on deep learning was improved, and Cur can remarkably alleviate the psychological state of PH patients, which provided a reference for the diagnosis and treatment for PH patients. [ABSTRACT FROM AUTHOR]

Background/Aims: Based on the theory of constitution in Traditional Chinese Medicine (TCM), the Chinese Han population has been classified into nine constitutions. Of these, Yang deficiency constitution mainly exhibit cold intolerance while Yin deficiency constitution mainly exhibit heat intolerance. Some studies have been carried out to explore the modern genetic and biological basis of such constitution classification, but more remains to be done. MicroRNA (miRNA) serves as post-transcriptional regulators of gene expression and may play a role in the classification process. Here, we examined miRNA expression profile of saliva to further improve the comprehensiveness of constitution classification. Methods: Saliva was collected from Chinese Han individuals with Yang deficiency, Yin deficiency and Balanced constitutions (n=5 each), and miRNA expression profile was determined using the Human miRNA OneArray®v7. Based on 1.5 Fold change, means log2∣Rati∣≥0.585 and P-value<0.05, differentially expressed miRNA was screened. Target genes were predicted using DIANATarBasev7.0 and analysis of KEGG pathway was carried out using DIANA-mirPathv.3. Results: We found that 81 and 98 differentially expressed miRNAs were screened in Yang deficiency and Yin deficiency constitution, respectively. Among them, 16 miRNAs were identical and the others were unique. In addition, the target genes that are regulated by the unique miRNAs were significantly enriched in 27 and 20 signaling pathways in Yang deficiency and Yin deficiency constitution, respectively. Thyroid hormone signaling pathway is present in both constitutions. These unique miRNAs that regulated target genes of thyroid hormone signaling pathway may be associated with cold intolerance or heat intolerance. Conclusion: The results of our study show that Yang deficiency and Yin deficiency constitutions exhibit systematic differences in miRNA expression profile. Moreover, the distinct characteristics of TCM constitution may be explained, in part, by differentially expressed miRNAs. [ABSTRACT FROM AUTHOR]

Evidence suggests that oxidative stress is involved in the pathogenesis of Parkinson disease (PD). Simvastatin has been suggested to protect against oxidative stress in several diseases. However, the molecular mechanisms by which simvastatin protects against neuropathology and oxidative damage in PD are poorly elucidated. In this study, we aimed to investigate the potential neuroprotective effects of simvastatin owing to its anti-oxidative properties in 6-hydroxydopamine (6-OHDA)-treated SH-SY5Y cells and mice. The results of 20,70-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescence and CCK-8 assay demonstrated that simvastatin reduced intracellular reactive oxygen species (ROS) levels and reversed apoptosis in 6-OHDA-treated SH-SY5Y cells. Mechanistic studies revealed that 6-OHDA-induced activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase/p38 mitogen-activated protein kinase (MAPK) pathway was inhibited and nuclear factor-kB (NF-kB) nuclear transcription decreased in SH-SY5Y cells after simvastatin treatment. Enhanced expression levels of superoxide dismutase (SOD), heme oxygenase-1 (HO-1), peroxisome proliferator-activated receptor-g coactivator-1a (PGC-1a) and glutamatecysteine ligase modifier subunit (GCLM) were observed after simvastatin treatment in 6-OHDA-treated SH-SY5Y cells. In vivo studies revealed that administration of simvastatin by gavage decreased limb-use asymmetry and apomorphineinduced rotations in 6-OHDA-lesioned mice. Simvastatin increased dopaminergic neurons and reduced protein tyrosine nitration and gliosis in the midbrain of PD mice. An inhibitory effect on activation of the NADPH oxidase/p38 MAPK was observed, and increased antioxidant protein expression in the midbrain were seen in the simvastatin plus 6-OHDA group compared with the 6-OHDA-lesioned group. Taken together, these results demonstrate that simvastatin might inhibit the activation of NADPH oxidase/p38 MAPK pathway, enhance antioxidant protein expression and protect against oxidative stress, thereby providing a novel antioxidant mechanism that has therapeutic validity. [ABSTRACT FROM AUTHOR]

Tetramethylpyrazine (TMP) is a traditional Chinese herbal medicine with strong antiinflammatory and cartilage protection activities, and thus a promising candidate for treating osteoarthritis. However, TMP is rapidly cleared from the joint cavity after intra-articular injection and requires multiple injections to maintain efficacy. The aim of this study was to encapsulate TMP into poly (lactic-co-glycolic acid) (PLGA) microspheres to enhance the TMP retention in the joint, reducing injection frequencies and decreasing dosage. TMP microspheres were prepared by emulsion/solvent evaporation method. The intra-articular retention of the drug was assessed by detecting the drug concentration distributed in the joint tissue at different time points. The therapeutic effect of TMP microspheres was evaluated by the swelling of knee joints and histologic analysis in papain-induced OA rat model. The prepared freezedried microspheres with a particle size of about 10 μm can effectively prolong the retention time of the drug in the articular cavity to 30 d, which is 4.7 times that of the TMP solution. Intra-articular injection of TMP microspheres efficiently relieved inflammatory symptoms, improved joint lesions and decreased the depletion of proteoglycan. In conclusion, intraarticular injection of TMP loaded microspheres was a promising therapeutic method in the treatment of OA. [ABSTRACT FROM AUTHOR]

The annual rainfall is low and the fresh water resources are scarce for the rainfed farming in dry zone of northern China, which seriously affects the sowing and growth of spring com. In order to solve this problem, the technology of ridge-mulching and side-sowing of spring com is put forward, the supporting compound operation seeder is developed, and the effect of different speed on the quality of sowing is tested and analyzed. Under the test conations described in this paper, the seeding operation with a high speed (up to 6 km/h) can be realized, and the quality of the seeding operation can meet the requirements of the national standards. The application of this machine can solve the problem of "drought damage at the booting stage" for spring corn, thereby realizing the deep fusion of farming machine and agronomy in dry farming of northern China, and achieving the integration of farming machine and agronomy. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects reproductive dysfunction and metabolism in women of childbearing age. An increasing number of studies have suggested that the bone morphogenetic protein 15 (BMP15) signalling pathway serves an important role in the pathogenesis of PCOS; however, the full mechanism remains unknown. The present study revealed that intrinsic follicular dysplasia may be associated with regulation disorders of ovarian granulosa cell apoptosis. Compared with the control group, body mass index, luteinising hormone and testosterone levels were significantly increased (P<0.05). The percentage of S phase cells was significantly higher, cells in G2/M phase cells was significantly lower, and cells undergoing apoptosis was significantly higher in the PCOS group compared with the control group (P<0.05). The expression levels of B-cell lymphoma 2 was significantly decreased in granulosa cells of PCOS group, whereas the expression of caspase-3 was higher than the control group (P<0.05). The rate of apoptosis of granulosa cells was measured by a terminal deoxynucleotide transferase dUTP nick-end labelling assay. The relative mRNA expression levels of BMP receptor 2 and SMAD1 were significantly decreased in granulosa cells in the PCOS group compared with the control (P<0.05). In addition, the expression of BMP15 in follicular fluid and Smad1 in granulosa cells was significantly decreased in the PCOS group compared with the control (P<0.05). The data suggested that the BMP15/Smad1 signalling pathway may be involved in granulosa cell apoptosis, and may be a target for clinical treatment for PCOS. [ABSTRACT FROM AUTHOR]

Transforming growth factor b-activated kinase 1 (TAK1), a vital upstream integrator of multiple pro-inflammatory signaling pathways, mediates the production of pro-inflammatory cytokines, chemokines, and adhesion molecules. Investigations targeting TAK1 provide new therapeutic options for chronic inflammatory disorders, autoimmune diseases, and cancer. However, the role and mechanism of the TAK1 inhibitor 5Z-7-oxozeaenol in treating autoimmune demyelinating diseases remain unclear. This work aimed to identify whether 5Z-7-oxozeaenol exerts neuroprotective effects on experimental autoimmune encephalomyelitis (EAE) in mice. Here, we demonstrate that 5Z-7-oxozeaenol efficiently alleviates the symptoms of EAE by decreasing the levels of pro-inflammatory cytokines in splenocytes and central nervous system, diminishing the number of activated microglia and inhibiting the p38MAPK, JNK, and ERK signaling pathways. Furthermore, we demonstrate that administration during the symptomatic time window is required for 5Z-7-oxozeaenol efficacy. These results suggest that TAK1 inhibition may provide a potent approach toward treating autoimmune demyelinating diseases. [ABSTRACT FROM AUTHOR]

Introduction Follicular dendritic cells are non-phagocytic, non-lymphoid cells of the immune system that are necessary for antigen presentation and the regulation of reactions in the germinal centers of the lymph nodes. Follicular dendritic cell sarcoma is an unusual cancer, particularly in the intra-abdominal region. In the present report we describe an unusual case of retroperitoneal follicular dendritic cell sarcoma that emphasizes the difficulty of diagnosing and treating this tumor. Retroperitoneal follicular dendritic cell sarcoma has only been rarely reported in the literature to date. Case presentation A 46-year-old Chinese woman of Han ethnicity presented with chronic right lower quadrant abdominal pain over the preceding 4 weeks. The tumor was resected and submitted to histopathological examination. The case was verified as retroperitoneal follicular dendritic cell sarcoma by microscopic examination and immunohistochemical analysis. After diagnosis, she received postoperative radiotherapy and chemotherapy. She has survived 3 years postoperatively, although she has a pulmonary metastasis. Conclusions Retroperitoneal follicular dendritic cell sarcoma may demonstrate aggressive potential. This study indicated that postoperative adjuvant radiotherapy and chemotherapy could extend the survival of a patient with retroperitoneal follicular dendritic cell sarcoma. [ABSTRACT FROM AUTHOR]

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The article discusses a microarray analysis of the expression profiles of microribonucleic acids (miRNAs) in brain tissue following focal cerebral ischemia/reperfusion injury. Real-time PCR was conducted to confirm the microarray data. The study showed that miRNAs can regulate bcl-2 and caspase-3 expression in brain tissue following cerebral ischemia.

Background: Excitatory amino acid transporter 1 (EAAT1) is a glutamate transporter which is a key element in the termination of the synaptic actions of glutamate. It serves to keep the extracellular glutamate concentration below neurotoxic level. However the functional significance and the change of accessibility of residues in transmembrane domain (TM) 5 of the EAAT1 are not clear yet. Methodology/Principal Findings: We used cysteine mutagenesis with treatments with membrane-impermeable sulfhydryl reagent MTSET [(2-trimethylammonium) methanethiosulfonate] to investigate the change of accessibility of TM5. Cysteine mutants were introduced from position 291 to 300 of the cysteine-less version of EAAT1. We checked the activity and kinetic parameters of the mutants before and after treatments with MTSET, furthermore we analyzed the effect of the substrate and blocker on the inhibition of the cysteine mutants by MTSET. Inhibition of transport by MTSET was observed in the mutants L296C, I297C and G299C, while the activity of K300C got higher after exposure to MTSET. Vmax of L296C and G299C got lower while that of K300C got higher after treated by MTSET. The L296C, G299C, K300C single cysteine mutants showed a conformationally sensitive reactivity pattern. The sensitivity of L296C to MTSET was potentiated by glutamate and TBOA,but the sensitivity of G299C to MTSET was potentiated only by TBOA. Conclusions/Significance: All these facts suggest that the accessibility of some positions of the external part of the TM5 is conformationally sensitive during the transport cycle. Our results indicate that some residues of TM5 take part in the transport pathway during the transport cycle. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency is associated with a variety of chronic metabolic diseases. Limited evidence regarding vitamin D deficiency exists within the Chinese population. The present study aims to examine the association between serum vitamin D concentrations and cardiometabolic risk factors in the young and middle-aged, urban Chinese population Methods: The cross-sectional relationships between serum 25-hydroxyvitamin D [25(OH)D] concentrations and indices of adiposity and cardiometabolic risk factors (e.g., body mass index, waist circumference, fasting plasma glucose, etc.) were evaluated in 601 non-diabetic adults. Result: Vitamin D deficiency or insufficiency was present in 66% of the tested population, and serum 25(OH)D levels were lower in patients who were overweight/obese or suffered metabolic syndrome when compared to individuals of healthy weight without metabolic syndrome (24.08 ± 8.08 vs 31.70 ± 11.77 ng/ml, 21.52 ± 6.9 vs 31.74 ± 10.21 ng/ml respectively). 25(OH)D was inversely associated with waist circumference, fasting glucose, fasting insulin, triglycerides and LDL-cholesterol, and it was positively associated with HDL-cholesterol in a multivariable-adjusted regression model. Conclusion: Vitamin D deficiency is common in the young and middle-aged, urban Chinese population, with high prevalence in overweight/obese individuals and patients with metabolic syndrome. Low vitamin D concentration was associated with indices of adiposity and cardiometabolic risk factors. Further studies are warranted to elucidate the cause-effect relation between vitamin D status, obesity and related metabolic disorders. [ABSTRACT FROM AUTHOR]

Background: GLT-1 is a glial glutamate transporter which maintains low synaptic concentrations of the excitatory neurotransmitter enabling efficient synaptic transmission. Based on the crystal structure of the bacterial homologue GltPh, it has been proposed that the reentrant loop HP2, which connects transmembrane domains (TM) 7 and 8, moves to open and close access to the binding pocket from the extracellular medium. However the conformation change between TM5 and TM8 during the transport cycle is not clear yet. We used paired cysteine mutagenesis in conjunction with treatments with Copper(II)(1,10-Phenanthroline)3 (CuPh), to verify the predicted proximity of residues located at these structural elements of GLT-1. Methodology/Principal Findings: To assess the proximity of transmembrane domain (TM) 5 relative to TM8 during transport by the glial glutamate transporter GLT-1/EAAT2, cysteine pairs were introduced at the extracellular ends of these structural elements. A complete inhibition of transport by Copper(II)(1,10-Phenanthroline)3 is observed in the double mutants I295C/I463C and G297C/I463C, but not in the corresponding single mutants. Glutamate and potassium, both expected to increase the proportion of inward-facing transporters, significantly protected against the inhibition of transport activity of I295C/I463C and G297C/I463C by CuPh. Transport by the double mutants I295C/I463C and G297C/I463C also was inhibited by Cd2+. Conclusions/Significance: Our results suggest that TM5 (Ile-295, Gly-297) is in close proximity to TM8 (Ile-463) in the mammalian transporter, and that the spatial relationship between these domains is altered during the transport cycle. [ABSTRACT FROM AUTHOR]