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Ependymoma is the third most common pediatric primary brain tumor, with its most aggressive subtype being posterior fossa group A (PFA). Extraneural metastasis of pediatric PFA ependymoma is rare. Herein, we present a case of a 9-year-old girl with PFA ependymoma characterized by a lack of trimethylation of histone H3 at lysine 27 and elevated chromosome X open reading frame 67 expression. Despite multiple surgeries and radiotherapies, the patient had a rapid recurrence and developed osseous and pulmonary metastases, which may be attributed to the homozygous deletion of cyclindependent kinase (CDK) inhibitor 2A/B and CDK12 mutation. Importantly, the CDK12 mutation observed in the patient may be indicative of the need for further work-up to consider chemotherapy rather than administering poly (adenosine diphosphate-ribose) polymerase inhibitors. Taken together, this is the first report of pediatric PFA ependymoma with extraneural metastases, wherein we clarified the diagnostic procedures of this newly identified PFA ependymoma and provided new cues to study the invasiveness of this disease and treatment selection for such patients. [ABSTRACT FROM AUTHOR]

Background: Few studies have investigated the use of dexmedetomidine in patient-controlled intravenous analgesia (PCIA) after thoracic surgery. This study to evaluate the effect of dexmedetomidine combined with sufentanil for PCIA after thoracotomy under general anaesthesia. Methods: Ninety-seven adults patients scheduled for thoracotomy surgery. All two groups received PCIA with either sufentanil alone (control group) or combining dexmedetomidine with sufentanil (dexmedetomidine group). Hemodynamic measurements, visual analog scale (VAS) scores at rest and at coughing, Ramsay sedation score (RSS), analgesic consumption, and postoperative nausea and vomiting (PONV) as well as drug-related adverse effects were compared at 2, 6, 12, 24, 36 and 48 h postoperatively. Results: In the patients of the dexmedetomidine group, compared to the control group, the pain scores at rest or at coughing during 48 h postoperatively were lower (P < 0.001), the sedation scores were lower, the consumption of sufentanil and rescue meperidine were lower, and the number of episode of moderate PONV was three times lower. No signs of toxicity or local complications were observed. There was a non-significant trend for a lower HR and BP in the dexmedetomidine group vs. Control. Conclusion: The combining dexmedetomidine with sufentanil for post-thoracotomy PCIA can improve pain control together with the decrease in sufentanil requirements, and improve postoperative patient's satisfaction compared with sufentanil alone in PCIA. Trial Registration: This trial was retrospectively registered on 27 April 2016 at the Chinese Clinical Trial Register (number: ChiCTR-ONC-16008376). [ABSTRACT FROM AUTHOR]

Context: Dendrobium candidum (D.candimum) widely is a functional drug. The curative effect of D. candidum on lupus nephritis has been studied in vivo. Materials and Method: The DBA/2 and B6D2F1 mice were used for this in vivo experiment. The 50% effective dose (ED50) was used to check the effective concentration for this study. Then the SCr, BUN, TC, TG, IL-6, IL-12, TNF-α, and IFN-γ levels were determined by kits. The output of urine protein was determined by means of Coomassie Brilliant Blue, and the auto-antibody dsDNA was determined with titer plate technology and indirect immunofluorescence. The NF-κB, IκB-α, TGF-β1, Fas, and FasL expressions were measured by RT-PCR and western blot assay. The component analysis of D. candidum was determined by nuclear magnetic resonance. Results: Based on the ED50 result at 329 mg/kg, 200 and 400 mg/kg doses were chosen for this study. SCr, BUN, TC and TG levels of 400 mg/kg D. candidum mice were lower than control mice, TP and ALB levels were higher than control mice. The control and 400 mg/kg treated mice tested positive for dsDNA at the end of sixth and tenth week after the experiment began. The glomerular number of 400 mg/kg treated mice was more than control group. Treatment with 400 mg/kg D. candidum reduced IL-6, IL-12, TNF-α and IFN-γcytokine levels as compared to control mice. D. candidum decreased NF-κb, TGF-β1, Fas, FasL and increased IκB-α expressions in kidney tissue. There were 11 compounds in dry D. candidum, these compounds might make the curative effects of lupus nephritis. Conclusion: D. candidum showed a potential curative effect on lupus nephritis. It could be used as a health medicine on lupus nephritis. [ABSTRACT FROM AUTHOR]

Background: Very few studies have discussed transforaminal endoscopic discectomy (TED) in the treatment of common peroneal nerve paralysis induced by lumbar disk herniation (LDH). This study aimed to evaluate the efficacy of TED in the treatment of LDH combined with common peroneal nerve paralysis. Materials and methods: The clinical and follow-up data of 32 patients with common peroneal nerve paralysis induced by LDH undergoing TED from March 2011 to April 2014 were retrospectively analyzed in this study. Follow-up was conducted immediately after the surgery, as well as 3, 12, and 24 months postoperatively. The parameters (including muscle strength recovery of the anterior tibial muscle, leg pain visual analog scale score, neurological function Japanese Orthopaedic Association [JOA] score, MacNab scores in the last follow-up, and the intraoperative and postoperative complications) were recorded. Results: Three patients (9.4%) had the anterior tibial muscle strength recovered to ≥ grade 4 immediately after the surgery. The anterior tibial muscle strength of patients recovered to basically stable form in the 6-month postoperative follow-up and that in the last follow-up were as follows: one case of grade 1, one case of grade 2, 28 cases of grade 4, and two cases of grade 5. The visual analog scale scores of leg pain were significantly reduced immediately after the surgery and also on 3, 12, and 24 months compared with preoperative period (all P<0.05). The postoperative JOA scores in the last follow-up were significantly higher than the preoperative JOA scores (P<0.05), and there were nine excellent cases (28.2%), 21 good cases (65.6%), one fair case (3.1%) and one poor case (3.1%) in the last follow-up, with an overall excellent and good rate of 93.8%. Conclusion: TED, which can offer sufficient decompression of the nerve root, has excellent overall clinical effects in treating common peroneal nerve paralysis induced by LDH. [ABSTRACT FROM AUTHOR]

Background: The endometrial regenerative cell (ERC) is a novel type of adult mesenchymal stem cell isolated from menstrual blood. Previous studies demonstrated that ERCs possess unique immunoregulatory properties in vitro and in vivo, as well as the ability to differentiate into functional hepatocyte-like cells. For these reasons, the present study was undertaken to explore the effects of ERCs on carbon tetrachloride (CCl4)-induced acute liver injury (ALI). Methods: An ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl4. Transplanted ERCs were intravenously injected (1 million/mouse) into mice 30 min after ALI induction. Liver function, pathological and immunohistological changes, cell tracking, immune cell populations and cytokine profiles were assessed 24 h after the CCl4 induction. Results: ERC treatment effectively decreased the CCl4-induced elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and improved hepatic histopathological abnormalities compared to the untreated ALI group. Immunohistochemical staining showed that over-expression of lymphocyte antigen 6 complex, locus G (Ly6G) was markedly inhibited, whereas expression of proliferating cell nuclear antigen (PCNA) was increased after ERC treatment. Furthermore, the frequency of CD4+ and CD8+ T cell populations in the spleen was significantly down-regulated, while the percentage of splenic CD4+CD25+FOXP3+ regulatory T cells (Tregs) was obviously up-regulated after ERC treatment. Moreover, splenic dendritic cells in ERC-treated mice exhibited dramatically decreased MHC-II expression. Cell tracking studies showed that transplanted PKH26-labeled ERCs engrafted to lung, spleen and injured liver. Compared to untreated controls, mice treated with ERCs had lower levels of IL-1β, IL-6, and TNF-α but higher level of IL-10 in both serum and liver. Conclusions: Human ERCs protect the liver from acute injury in mice through hepatocyte proliferation promotion, as well as through anti-inflammatory and immunoregulatory effects. [ABSTRACT FROM AUTHOR]

Study Design: A prospective cohort study.Objective: In this study, we employed diffusion basis spectrum imaging (DBSI) to quantitatively assess axon/myelin injury, cellular inflammation, and axonal loss of cervical spondylotic myelopathy (CSM) spinal cords.Summary Of Background Data: A major shortcoming in the management of CSM is the lack of an effective diagnostic approach to stratify treatments and to predict outcomes. No current clinical diagnostic imaging approach is capable of accurately reflecting underlying spinal cord pathologies.Methods: Seven patients with mild (mJOA ≥15), five patients with moderate (14≥mJOA ≥11), and two patients with severe (mJOA <11) CSM were prospectively enrolled. Given the low number of severe patients, moderate and severe patients were combined for comparison with seven age-matched controls and statistical analysis. We employed the newly developed DBSI to quantitatively measure axon and myelin injury, cellular inflammation, and axonal loss.Results: Median DBSI-inflammation volume is similar in control (266 μL) and mild CSM (171 μL) subjects, with a significant overlap of the middle 50% of observations (quartile 3 - quartile 1). This was in contrast to moderate CSM subjects that had higher DBSI-inflammation volumes (382 μL; P = 0.033). DBSI-axon volume shows a strong correlation with clinical measures (r = 0.79 and 0.87, P = 1.9 x 10-5 and 2 x 10-4 for mJOA and MDI, respectively). In addition to axon and myelin injury, our findings suggest that both inflammation and axon loss contribute to neurological impairment. Most strikingly, DBSI-derived axon volume declines as severity of impairment increases.Conclusion: DBSI-quantified axonal loss may be an imaging biomarker to predict functional recovery following decompression in CSM. Our results demonstrate an increase of about 60% in the odds of impairment relative to the control for each decrease of 100 μL in axon volume.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

Background: Endometrial regenerative cells (ERCs) is an attractive novel type of adult mesenchymal stem cells that can be non-invasively obtained from menstrual blood and are easily replicated at a large scale without tumorigenesis. We have previously reported that ERCs exhibit unique immunoregulatory properties in experimental studies in vitro and in vivo. In this study, the protective effects of ERCs on renal ischemia-reperfusion injury (IRI) were examined.Methods: Renal IRI in C57BL/6 mice was induced by clipping bilateral renal pedicles for 30 min, followed by reperfusion for 48 h. ERCs were isolated from healthy female menstrual blood, and were injected (1 million/mouse, i.v.) into mice 2 h prior to IRI induction. Renal function, pathological and immunohistological changes, cell populations and cytokine profiles were evaluated after 48 h of renal reperfusion.Results: Here, we showed that as compared to untreated controls, administration of ERCs effectively prevented renal damage after IRI, indicated by better renal function and less pathological changes, which were associated with increased serum levels of IL-4, but decreased levels of TNF-α, IFN-γ and IL-6. Also, ERC-treated mice displayed significantly less splenic and renal CD4(+) and CD8(+) T cell populations, while the percentage of splenic CD4(+)CD25(+) regulatory T cells and infiltrating M2 macrophages in the kidneys were significantly increased in ERC-treated mice.Conclusions: This study demonstrates that the novel anti-inflammatory and immunoregulatory effects of ERCs are associated with attenuation of renal IRI, suggesting that the unique features of ERCs may make them a promising candidate for cell therapies in the treatment of ischemic acute kidney injury in patients. [ABSTRACT FROM AUTHOR]

Background: Ureolytic activity of rumen bacteria leads to rapid urea conversion to ammonia in the rumen of dairy cows, resulting possible toxicity, excessive ammonia excretion to the environment, and poor nitrogen utilization. The present study investigated immunization of dairy cows against urease in the rumen as an approach to mitigate bacterial ureolytic activity therein. Results: Most alpha subunit of rumen urease (UreC) proteins shared very similar amino acid sequences, which were also highly similar to that of H. pylori. Anti-urease titers in the serum and the saliva of the immunized cows were evaluated following repeated immunization with the UreC of H. pylori as the vaccine. After the fourth booster, the vaccinated cows had a significantly reduced urease activity (by 17%) in the rumen than the control cows that were mock immunized cows. The anti-urease antibody significantly reduced ureolysis and corresponding ammonia formation in rumen fluid in vitro. Western blotting revealed that the H. pylori UreC had high immunological homology with the UreC from rumen bacteria. Conclusions: Vaccine developed based on UreC of H. pylori can be a useful approach to decrease bacterial ureolysis in the rumen. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine the preventive effect of the traditional Chinese medicine, Dendrobium candidum Wall ex Lindl. (D. candidum), on CCl4-induced hepatic damage in mice. The CCl4-induced hepatic damage mice were treated with D. candidum, and the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), triglyceride (TG) and total cholesterol (TC) were determined. In addition, serum cytokine levels of interleukin (IL)-6, IL-12, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were analyzed with kits, while liver tissues were analyzed using hematoxylin and eosin staining and reverse transcription polymerase chain reaction (RT-PCR). Furthermore, the contents of D. candidum were determined by nuclear magnetic resonance (NMR). D. candidum was demonstrated to successfully prevent hepatic damage in mice. The serum levels of AST, ALT and LDH were significantly decreased when the mice were treated with 200 and 400 mg/kg D. candidum, as compared with the control mice (P<0.05). The lowest enzymatic activities were exhibited in the 400 mg/kg D. candidum group, which produced similar results to the positive control drug, silymarin. In addition, in the 400 mg/kg D. candidum group, the highest levels of TG and TC were observed among the treated groups. D. candidum-treated groups also demonstrated reduced levels of the serum proinflammatory cytokines, IL-6, IL-12, TNF-α and IFN-γ. The sections of liver tissue examined during histopathology in the high concentration 400 mg/kg D. candidum group recovered well from CCl4 damage; however, the sections in the 200 mg/kg D. candidum group revealed necrosis to a more serious degree. RT-PCR analysis was conducted on inflammation-associated genes, including nuclear factor (NF)-κB, IκB-α, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, in the livers of the mice. The 400 mg/kg D. candidum group demonstrated significantly decreased mRNA expression levels of NF-κB, iNOS and COX-2, but an increased expression level of IκB-α when compared with the CCl4-treated control group. Furthermore, using NMR, 11 compounds were identified in the D. candidum leaf, whose functional contents may aid the preventive effect observed in the current study. Therefore, D. candidum may potentially contribute to the prevention of CCl4-induced hepatic damage in vivo. [ABSTRACT FROM AUTHOR]

Dendrobium candidum Wall ex Lindl. was purchased for the evaluation of azoxymethane (AOM)- and dextran sulfate sodium (DSS)-induced colon carcinogenesis in C57BL/6 mice. The body weights of the AOM- and DSS-induced colon cancer control groups were lighter than those of the untreated mice. D. candidum increased the body weights of the mice compared with the control group, and reduced the levels of the serum proinflammatory cytokines, IL-6, IL-12, TNF-α and IFN-γ, compared with the colon cancer control group. Reverse transcription-polymerase chain reaction and western blot analyses of the apoptotic-related genes, bax, bcl-2, caspase-3 and caspase-9, were performed in the colon tissues. The high-concentration D. candidum group showed a significant increase in the mRNA and protein expression levels of bax, caspase-3 and caspase-9 and decreased expression levels of bcl-2 compared with the control group. These results indicate that D. candidum Wall ex Lindl. exhibits preventive effects against colon carcinogenesis in mice. [ABSTRACT FROM AUTHOR]

Clinical evidence suggests that cortical excitability is increased in depressives. We investigated its cellular basis in a mouse model of depression. In a modified version offorced swimming (FS), mice were initially forced to swim for 5 consecutive days and then were treated daily with repetitive transcranial magnetic stimulation (riMS) or sham treatment for the following 4 weeks without swimming. On day 2 through day 5, the mice manifested depression-like behaviors. The next and last FS was performed 4 weeks later, which revealed a 4 week maintenance of depression-like behavior in the sham mice. In slices from the sham controls, excitability in cingulate cortex pyramidal cells was elevated in terms of membrane potential and frequencies of spikes evoked by current injection. Depolarized resting potential was shown to depend on suppression oflarge conductance calcium-activated potassium (BK) channels. This BK channel suppression was confirmed by measuring spike width, which depends on BK channels. Chronic riMS treatment during the 4 week period significantly reduced the depression-like behavior. In slices obtained from the riMS mice, normal excitability and BK channel activity were recovered. Expression of a scaffold protein Homer1a was reduced by the FS and reversed by riMS in the cingulate cortex. Similar recovery in the same behavioral, electrophysiological, and biochemical features was observed after chronic imipramine treatment. The present study demonstrated that manifestation and disappearance of depression-like behavior are in parallel with increase and decrease in cortical neuronal excitability in mice and suggested that regulation ofBK channels by Homer1a is involved in this parallelism. [ABSTRACT FROM AUTHOR]

A tooth-whitening process using hydrogen peroxide (H2O2) enhanced by a direct-current cold atmospheric-pressure plasma microjet (PMJ) is presented. Compared with the conventional clinical method of using H2O2 alone, a significant improvement of the tooth-whitening process was observed when the PMJ was used in the process. The tooth-surface temperature was monitored for safety considerations and did not exceed 37 °C at a distance of 1 cm between the exit nozzle of the plasma source and the tooth for a treatment time of 20 min. No apparent differences in the tooth-surface morphology and microhardness were observed between teeth treated with and without the PMJ. The use of the PMJ with H2O2 resulted in an enhanced production of reactive hydroxyl (OH) radicals. This plasma-enhanced tooth-whitening method may be a promising new method for clinical applications. [ABSTRACT FROM AUTHOR]

The PRL (phosphatase of regenerating liver) phosphatases constitute a novel class of small, prenylated phosphatases that are implicated in promoting cell growth, differentiation, and tumor invasion, and represent attractive targets for anticancer therapy. Here we describe the crystal structures of native PRL-1 as well as the catalytically inactive mutant PRL-1/C104S in complex with sulfate. PRL-1 exists as a trimer in the crystalline state, burying 1140 Ų of accessible surface area at each dimer interface. Trimerization creates a large, bipartite membrane-binding surface in which the exposed C-terminal basic residues could cooperate with the adjacent prenylation group to anchor PRL-1 on the acidic inner membrane. Structural and kinetic analyses place PRL-1 in the family of dual specificity phopsphatases with closest structural similarity to the Cdc14 phosphatase and provide a molecular basis for catalytic activation of the PRL phosphatases. Finally, native PRL-1 is crystallized in an oxidized form in which a disulfide is formed between the active site Cys104 and a neighboring residue Cys49, which blocks both substrate binding and catalysis. Biochemical studies in solution and in the cell support a potential regulatory role of this intramolecular disulfide bond formation in response to reactive oxygen species such as H2O2. [ABSTRACT FROM AUTHOR]

Jumonji domain-containing 3 (JMJD3/KDM6B) is a histone demethylase that plays an important role in regulating development, differentiation, immunity, and tumorigenesis. However, the mechanisms responsible for the epigenetic regulation of inflammation during mastitis remain incompletely understood. Here, we aimed to investigate the role of JMJD3 in the lipopolysaccharide (LPS)-induced mastitis model. GSK-J1, a small molecule inhibitor of JMJD3, was applied to treat LPSinduced mastitis in mice and in mouse mammary epithelial cells in vivo and in vitro. Breast tissues were then collected for histopathology and protein/gene expression examination, and mouse mammary epithelial cells were used to investigate the mechanism of regulation of the inflammatory response. We found that the JMJD3 gene and protein expression were upregulated in injured mammary glands during mastitis. Unexpectedly, we also found JMJD3 inhibition by GSK-J1 significantly alleviated the severity of inflammation in LPS-induced mastitis. These results are in agreement with the finding that GSK-J1 treatment led to the recruitment of histone 3 lysine 27 trimethylation (H3K27me3), an inhibitory chromatin mark, in vitro. Furthermore, mechanistic investigation suggested that GSK-J1 treatment directly interfered with the transcription of inflammatory-related genes by H3K27me3 modification of their promoters. Meanwhile, we also demonstrated that JMJD3 depletion or inhibition by GSK-J1 decreased the expression of toll-like receptor 4 and negated downstream NF-κB proinflammatory signaling and subsequently reduced LPSstimulated upregulation of Tnfa, Il1b, and Il6. Together, we propose that targeting JMJD3 has therapeutic potential for the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]