Elevated serum levels of the NLRP3 inflammasome are associated with the severity of anti-NMDAR encephalitis in children.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common autoimmune encephalitis, mainly impacting young females and children. The involvement of the Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and related cytokines in pediatric individuals with this condition remains unclear. METHODS: We collected information from 27 children who had anti-NMDAR encephalitis and 12 individuals with non-inflammatory neurological disorders as controls. We used an enzyme-linked immunosorbent assay (ELISA) to identify NLRP3 inflammasome, interleukin (IL)-1ß, and IL-18 expression in cerebrospinal fluid (CSF) and matching serum samples. The modified Rankin Scale (mRS) score was performed throughout the acute phase and at the 6-month follow-up to determine the severity of the disease. The area under the curve (AUC) of the receiver operating characteristic curve was utilized to calculate the prediction efficacy. RESULTS: When compared to controls, individuals with anti-NMDAR encephalitis had significantly increased serum expression of the NLRP3 inflammasome (p < 0.001), IL-1ß (p < 0.05), and IL-18 (p < 0.01). In the acute phase, mRS scores were correlated positively with serum levels of NLRP3 inflammasome (p = 0.008), IL-1ß (p = 0.023), and IL-18 (p < 0.001). A positive connection was also found between serum levels of NLRP3 inflammasome and IL-1ß (p = 0.005). Furthermore, the expression of IL-1ß and IL-18 in serum correlated with the 6-month follow-up outcome. The AUC for NLRP3 inflammasome in distinguishing patients with severe neurologic impairments from those with moderate impairments was 0.808 (95 % CI: 0.645-0.972). CONCLUSION: In our investigation, children with anti-NMDAR encephalitis have more severe first clinical presentations when their serum concentrations of the NLRP3 inflammasome and related cytokines were higher. These findings provide a potential role for the NLRP3 inflammasome pathway in the pathogenesis of NMDAR encephalitis and provide a basis for targeted therapeutic interventions.

Oxidative stress induces mitochondrial iron overload and ferroptotic cell death.

Oxidative stress has been shown to induce cell death in a wide range of human diseases including cardiac ischemia/reperfusion injury, drug induced cardiotoxicity, and heart failure. However, the mechanism of cell death induced by oxidative stress remains incompletely understood. Here we provide new evidence that oxidative stress primarily induces ferroptosis, but not apoptosis, necroptosis, or mitochondria-mediated necrosis, in cardiomyocytes. Intriguingly, oxidative stress induced by organic oxidants such as tert-butyl hydroperoxide (tBHP) and cumene hydroperoxide (CHP), but not hydrogen peroxide (H2O2), promoted glutathione depletion and glutathione peroxidase 4 (GPX4) degradation in cardiomyocytes, leading to increased lipid peroxidation. Moreover, elevated oxidative stress is also linked to labile iron overload through downregulation of the transcription suppressor BTB and CNC homology 1 (Bach1), upregulation of heme oxygenase 1 (HO-1) expression, and enhanced iron release via heme degradation. Strikingly, oxidative stress also promoted HO-1 translocation to mitochondria, leading to mitochondrial iron overload and lipid reactive oxygen species (ROS) accumulation. Targeted inhibition of mitochondrial iron overload or ROS accumulation, by overexpressing mitochondrial ferritin (FTMT) or mitochondrial catalase (mCAT), respectively, markedly inhibited oxidative stress-induced ferroptosis. The levels of mitochondrial iron and lipid peroxides were also markedly increased in cardiomyocytes subjected to simulated ischemia and reperfusion (sI/R) or the chemotherapeutic agent doxorubicin (DOX). Overexpressing FTMT or mCAT effectively prevented cardiomyocyte death induced by sI/R or DOX. Taken together, oxidative stress induced by organic oxidants but not H2O2 primarily triggers ferroptotic cell death in cardiomyocyte through GPX4 and Bach1/HO-1 dependent mechanisms. Our results also reveal mitochondrial iron overload via HO-1 mitochondrial translocation as a key mechanism as well as a potential molecular target for oxidative stress-induced ferroptosis in cardiomyocytes.

Pediatric myasthenia gravis with a combination of AChR and RyR is associated with an earlier onset and lower CSR rate: A cohort study in southwest China.

BACKGROUND: The clinical manifestations and prognosis of myasthenia gravis are related to antibodies, and children are affected differently than adults. The presence of ryanodine receptor and titin antibodies in adults indicates late onset and severe disease related to thymoma, but their role in children is rarely reported. METHODS: This study collected a cohort of children according to inclusion and exclusion criteria, consisting of antibody-negative, AChR-positive, and AChR with or without titin and RyR antibodies. The differences among groups in general conditions, clinical manifestation, treatment and prognosis were compared. RESULTS: In total, 171 patients were included: 33 patients (19.30%) were antibody-negative, 84 patients (49.12%) were positve for AChR antibody, 22 patients (12.87%) were positve for AChR and RyR antibodies, 5 patients (2.92%) were positve for AChR and Titin antibodies, and 27 patients (15.79%) were positve for AChR, RyR and Titin antibodies. The median onset age of all the patients was 57.8 (9-177) months, and patients with AChR and RyR antibodies (p = 0.02) and AChR, RyR and Titin antibodies (p = 0.0006) had a younger onset age than patients with AChR antibodies. The rate of generalized MG and MG-ADL before treatment in the AChR-, RyR- and Titin antibody-positive groups was distinctly higher than that in the AChR antibody-positive group (p = 0.038, p = 0.0325). The rate of IVIG use in the AChR-, RyR- and Titin antibody-positive groups (p = 0.0388) was higher than that in the AChR antibody-positive group. The rate of immunosuppressant use in the AChR and RyR antibody-positive group (p = 0.0415) and in the AChR, RyR and Titin antibody-positive group (p = 0.0006) was higher than that in the AChR antibody-positive group. Plasmapheresis was performed in 1 case in the AChR-, RyR- and Titin antibody-positive groups. The CSR rate in the AChR and RyR antibody-positive group (p = 0.0423) and in the AChR, RyR and Titin antibody-positive group (p = 0.0152) was significantly lower than that in the AChR antibody-positive group. Gender, ptosis severity, and CSR time were not significantly different between groups. CONCLUSIONS: We summarized one of the largest cohorts of pediatric MG patients and compared the clinical phenotype of patients with antibody-negative, AChR-positive, and AChR with or without titin and RyR antibodies. The results showed that patients with AChR and RyR antibodies had a younger onset age, a higher immunosuppressant use rate and a lower CSR rate.

Clinical and electroencephalography characteristics of 41 children with epileptic spasms onset after 1 year of age.

The incidence of epileptic spasms (ES) that begin after the first year of life is much lower than that before 1 year of age. The aim of this study was to identify clinical and electroencephalography (EEG) characteristics, etiologies, treatments, and prognoses in pediatric patients with ES onset after 1 year of age. Forty-one children were retrospectively identified in Children's Hospital of Chongqing Medical University between January 1, 2020 and December 1, 2021. ES onset after 1 year of age have diverse presentations. Although most occur in clusters, are symmetrical and flexional, and occur frequently during awakening, some are characterized as isolated and asymmetrical, have a tonic component, and can also occur during sleep. The hypsarrhythmia variants and focal or multifocal discharges occur alternately in the interictal period, and the focal spikes and slow waves predominated in the unilateral temporal or frontotemporal areas. These patients had diverse etiologies, including structural (51.2 % of patients) and genetic (22.0 %) ones, and 11 patients (26.8 %) had an unknown etiology. No patients in our study had an infectious or immune-mediated etiology. Forty-eight percent of patients responded to hydrocortisone and/or adrenocorticotropic hormone. The efficacy of antiepileptic drug therapy was lower in patients who did not receive concurrent steroid therapy. However, ES onset after 1 year of age caused by a tumor, brain malformation, or other focal lesions, may be cured by focal cortical resection despite a lack of clearly localized EEG surface anomalies. Delays in motor, language, and cognitive development, or behavioral problems were observed in all but three patients.

Phenotypic Spectrum of CASPR2 and LGI1 Antibodies Associated Neurological Disorders in Children.

Objectives: The clinical data of patients with double-positive for leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies is limited, particularly for children. This study aimed to investigate and summarize the clinical features and long-term prognosis of children's LGI1 and CASPR2 antibodies related to neurological disorders. Methods: We collected the clinical data and prognosis of patients with dual positive antibodies of CASPR2 and LGI1, hospitalized in the Department of Neurology, Children's Hospital of Chongqing Medical University. Furthermore, we summarized the clinical phenotypes of this disorder in children by reviewing the published literature. Results: Two patients presenting with variable neurological symptoms including pain, hypertension, profuse sweating, irritability, and dyssomnia from Children's Hospital of Chongqing Medical University were enrolled in this study. Together with the two patients, we identified 17 children with dual CASPR2 and LGI1 antibodies, including 12 males and 5 females. At the onset, the median age was 4.1 years (range 1-16, interquartile range 2.5-13.5), with 9 children younger than 5 years and 6 adolescents. Of the 17 patients, 11 were diagnosed with Morvan syndrome, 4 with acquired neuromyotonia, 1 with Guillain-Barré syndrome, and 1 with Guillain-Barré syndrome combined with Morvan syndrome. Dysautonomia (14/17, 82.3%), pain (13/17, 76.4%), sleep disorders (13/17, 76.4%), encephalopathy (12/17, 70.5%), and weight loss (10/17, 58.8%) were the most frequently described symptoms overall. No tumors were identified. Of the 17 patients, 13 received immunotherapy comprising IVIG combination of IVMP during the acute symptomatic phase followed by oral prednisolone to maintain remission (n = 7), the combination of IVIG, IVMP, oral prednisolone and methotrexate (n = 1), the combination of IVIG, IVMP, and mycophenolate mofetil (n = 1), the combination of IVIG, IVMP, oral prednisolone, and rituximab (n = 1), IVIG only (n = 2), IVMP only (n = 1). Median modified Rankin Scale (mRS) scores in the acute phase were 3 (range 1-4) and improved gradually. Over the follow-up (median 8.6 months, range 1-36 months), 52.9% (9/17) of the patients recovered completely; one patient relapsed and showed immunotherapy-dependent. Conclusion: LGI1 and CASPR2 double-positive antibodies associated with the neurological diseases can occur in children of all ages and involve multiple nervous systems. Morvan syndrome is the most common phenotype of this disorder. The long-term outcomes are mostly favorable upon immunotherapy.

Clinical Features and Outcomes in Pediatric Autoimmune Encephalitis Associated With CASPR2 Antibody.

Background: Contactin-associated protein-like 2 (CASPR2) neurological autoimmunity has been associated with various clinical syndromes involving central and peripheral nervous system. CASPR2 antibody-associated autoimmune encephalitis is mostly reported in adults. Analysis of the clinical presentation and prognostic data of CASPR2 antibody-associated autoimmune encephalitis in children remains important. Methods: A single-center retrospective review of children diagnosed with CASPR2 antibody-associated autoimmune encephalitis from June 1st, 2018 to October 31st, 2020. Results: Six patients were identified. The median age was 12 years (range 1.8-14), with an overall male predominance of 83% (5/6). Commonest clinical features were psychiatric symptoms (6/6), movement disorders (4/6), altered consciousness (3/6), sleep disorders (3/6), and headache (3/6). Four patients (4/6) received first-line therapy alone (steroids combined with intravenous immunoglobulins), and two patients (2/6) received second-line therapy (rituximab, mycophenolate mofetil, or cyclophosphamide). All patients showed no peripheral nervous system involvement. One patient had comorbidities with systemic lupus erythematosus. No evidence of neoplastic disease was found in the whole cohort. All patients had favorable outcomes (modified Rankin Score 0-2) with recurrence rate at 0%, respectively. Conclusion: CASPR2 antibody-associated autoimmune encephalitis is rare in children. Our findings suggest that this type of encephalitis seems to occur more frequently in older children. Patients respond well to immunotherapy and usually demonstrate a favorable clinical outcome. Associated tumors are extremely rare.

Adenovirus Infection-associated Central Nervous System Disease in Children.

BACKGROUND: Adenovirus (Adv) is a frequent etiology of acute respiratory tract infections. Although rare, neurologic manifestations are known to occur during Adv infection. METHODS: We retrospectively analyzed clinical, laboratory, outcome and the relationship between clinical characteristics and viral detection results in the cerebrospinal fluid (CSF) in children with Adv-associated central nervous system (CNS) dysfunction. RESULTS TWENTYONE: (1.5%) cases had Adv-associated CNS manifestations. The median age was 1.4 years and 20 (95%) were less than 5 years of age. Six (28%) were male. The most frequently cited CNS symptoms were altered consciousness (100%) and seizure (14.3%). Fourteen cases (73.7%) had abnormal electroencephalogram examination and 6 cases (37.5%) had abnormal imaging. None of the patients had received cidofovir administration. Twenty children recovered without sequelae and 1 patient died of respiratory failure. Patients with positive Adv polymerase chain reaction (n = 11) presented lower onset age compared with that of patients with negative Adv polymerase chain reaction (n = 10) in the CSF. Clinical manifestation, laboratory findings, imaging studies and electroencephalogram showed no significant difference between the 2 groups. CONCLUSION: Adv is a rare cause of CNS disease in children, mainly causing altered consciousness. Adv was detected in more cases in the respiratory tract than the CSF, but the majority of patients had the virus detected in both. The lack of Adv in the CSF does not exclude CNS involvement. Furthermore, the viral detection results in the CSF do not seem useful as an indicator of the severity of CNS disease.

ATRA induces the differentiation of hepatic progenitor cells by upregulating microRNA-200a.

Hepatic progenitor cells (HPCs) are potential seed cells for hepatocyte transplantation treatment of liver diseases. ATRA can induce the differentiation and mature function of hepatic progenitor cells, but the mechanism is still poorly understood. Here, by using microRNA array to analyze the expression profiles of microRNA (miR), we found that miR-200 family molecules in HPCs were upregulated after ATRA treatment, especially miR-200a-3p, 200c-3p, and 141-3p. ATRA induction could downregulate the expression of hepatic stem markers Oct4 and AFP, and improve the expression of hepatic markers ALB, CK18, and TAT, and the activity of ALB-GLuc, as well as indocyanine green uptake and glycogen storage function of HPCs. These above effects of ATRA on HPC differentiation were almost inhibited by blocking of miR-200a-3p, but not miR-200c-3p and 141-3p using antagomir. Cell autophagy is associated with ATRA regulation in HPCs, compared with control group, the expression of LC3 and Beclin1 increased in ATRA-treated HPCs, and orange and red fluorescent spot, which represents autophagy flow, also enhanced after ATRA treatment. However, ATRA-induced cell autophagy level was inhibited in antagomir-200a-3p+ATRA-treated cells. Therefore, the present study indicates that antagomir-200a-3p is related to ATRA-induced hepatic differentiation of HPCs through regulating cell autophagy, supporting the possible use of ATRA as a key inducer in HPC-based therapy of liver diseases.

Analysis and discussion of the rare complication of autoimmune encephalitis: Two case reports.

RATIONALE: Autoimmune encephalitis related to many antibodies against neuronal cell surface or synaptic proteins, it is increasingly recognized as the cause of a variety of neuropsychiatric syndromes. PATIENT CONCERNS: The two pediatric cases were about autoimmune encephalitis with rare complication. One patient was a 11-year-old girl and was diagnosed with Voltage-Gated Potassium Channel complex (VGKC) antibody-mediated encephalitis with rhabdomyolysis; the other was also a 11-year-old girl and was diagnosed with anti- N-methyl-D-aspartate receptor (NMDAR) encephalitis. DIAGNOSES: Both patients were diagnosed as autoimmune encephalitis with rare complication. INTERVENTIONS: Intravenous methylprednisolone, oral prednisone and intravenous immunoglobulin was administered to both patients. OUTCOMES: One patient was discharged after a half month's hospitalization; the other was finally with intestinal function failure, gradually developed multiple organ failure, and eventually died. LESSONS: The pathogenic mechanism of autoimmune encephalitis associated with autoimmune disease is not fully understood, but may be related to a common immune pathological mechanism with variance in susceptibility caused by genetic or environmental factors.

[Twist regulates proliferation, migration and invasion of osteosarcoma cells in vitro].

OBJECTIVE: To investigate the role of Twist in regulating the proliferation, migration, and invasion of osteosarcoma cells with different levels of malignancy. METHODS: The baseline expressions of Twist in 3 different osteosarcoma cell lines (143B, MG63 and TE85) were detected using real-time PCR and Western blotting. The cells were infected with the recombinant adenoviruses Ad-Twist or Ad-siTwist for Twist overexpression or knockdown, respectively, and the cell growth curves were drawn to assess the cell proliferation. The migration abilities and invasiveness of the cells were evaluated using wound healing assay and Transwell assay. Luc-labeled 143B cells infected with Ad-Twist or Ad-siTwist were intrathecally injected to establish nude mouse models bearing osteosarcoma xenografts, in which the tumor formation was monitored using living body imaging technique. RESULTS: The baseline expressions of Twist in the 3 osteosarcoma cells were significantly higher than that in C3H10 cells (P<0.05). Twist expression was the highest in 143B cells followed by MG63 cells, and was the lowest in TE85 cells, indicating its positive correlation with the level of malignancy of the osteosarcoma cells. Ad-Twist or Ad-siTwist infection efficiently enhanced or lowered Twist expressions at both mRNA and protein levels in osteosarcoma cells (P<0.05). Twist overexpression resulted in enhanced proliferation, migration and invasion abilities of osteosarcoma cells, and Twist knockdown obviously inhibited the cell proliferation, migration and invasion. In nude mice, 143B cells with Twist overexpression showed accelerated tumor formation compared with the control cells, while Twist knockdown significantly inhibited the tumor formation ability of the cells. CONCLUSION: Twist overexpression can promote the proliferation, migration, invasion and tumorigenicity of osteosarcoma cells.

Dynamic Changes of Astrocytes and Adenosine Signaling in Rat Hippocampus in Post-status Epilepticus Model of Epileptogenesis.

It is of great importance to explore the development of epileptogenesis, and the adenosine and adenosine kinase (ADK) system seems to play a key role in this process. The aim of this study is to explore the dynamic changes of astrocytes and adenosine signaling during epileptogenesis in rat hippocampus in a post-status epileptogenesis (SE) model. Rat SE models were built and killed for experiments at 1 day (acute phase of epileptogenesis), 5 days (latent phase), 4 weeks (chronic phase), and 8 weeks (late chronic phase of epileptogenesis) after SE induction. Immunofluorescence staining, high-performance liquid chromatography, and Western blotting were performed to assess changes of astrocytes, adenosine, ADK, and ADK receptors (including A1R, A2aR, A2bR, and A3R) in hippocampus. The expression level of glial fibrillary acidic protein significantly increased from latent to late chronic phase. The concentration of adenosine sharply increased in acute phase and gradually decreased in the remaining phases of post-SE, being significantly lower than in the control group in late chronic phase. Protein levels of A1R and A2aR in post-SE models increased in acute phase, whereas A2bR and A3R protein expression decreased in latent phase, chronic phase, and late chronic phase following post-SE epileptogenesis. Protein expression of ADK significantly increased during latent phase, chronic phase, and late chronic phase of post-SE epileptogenesis. In conclusion, the levels of adenosine and protein expression of A1R and A2R significantly increased during acute phase of post-SE. During the remaining phases of post-SE epileptogenesis, there was imbalance among astrocytes, adenosine, adenosine receptors, and ADK. Regulation of the ADK/adenosine system may provide potential treatment strategies for epileptogenesis.

Adsorptive removal of sulfate from acid mine drainage by polypyrrole modified activated carbons: Effects of polypyrrole deposition protocols and activated carbon source.

Polypyrrole modified activated carbon was used to remove sulfate from acid mine drainage water. The polypyrrole modified activated carbon created positively charged functionality that offered elevated sorption capacity for sulfate. The effects of the activated carbon type, approach of polymerization, preparation temperature, solvent, and concentration of oxidant solution over the sulfate adsorption capacity were studied at an array of initial sulfate concentrations. A hardwood based activated carbon was the more favorable activated carbon template, and this offered better sulfate removal than when using bituminous based activated carbon or oak wood activated carbon as the template. The hardwood-based activated carbon modified with polypyrrole removed 44.7 mg/g sulfate, and this was five times higher than for the pristine hardwood-based activated carbon. Various protocols for depositing the polypyrrole onto the activated carbon were investigated. When ferric chloride was used as an oxidant, the deposition protocol that achieved the most N+ atomic percent (3.35%) while also maintaining the least oxygen atomic percent (6.22%) offered the most favorable sulfate removal. For the rapid small scale column tests, when processing the AMD water, hardwood-based activated carbon modified with poly pyrrole exhibited 33 bed volume compared to the 5 bed volume of pristine activated carbons.

Impact of hypertonic saline on postoperative complications for patients undergoing upper gastrointestinal surgery.

The aim of this study was to explore the impact of 3% hypertonic saline (HS) intragastric administration for patients who underwent upper gastrointestinal surgery.During the postoperative period, 3% HS has been suggested as a means to improve the intestinal edema and reduce gastrointestinal complications.The medical records of 111 patients with HS intragastric administration following upper gastrointestinal surgery and 268 patients, served as control, were reviewed retrospectively. Propensity score matching was performed to adjust for selected baseline variables. Clinical outcomes, including early gastrointestinal function recovery, postoperative complications, and length of hospital stay, were compared according to the HS intragastric administration or not.HS intragastric administration was associated with prompt postoperative gastrointestinal function recovery, including first flatus (risk ratio [RR], 1.32; 95% confidence interval [CI], 0.89-1.65; P = 0.048) and feeding within 3 postoperative days (RR (95% CI), 0.57 (0.49-0.77); P = 0.036). Early ileus occurred in 25 of 108 patients with HS treatment versus 36 of 108 patients without HS treatment (RR (95% CI), 1.43 (0.63-2.15); P = 0.065). The patients with HS experienced a lower overall postoperative complication (odds ratio [OD] 0.57; 95% CI, 0.33-1.09; P = 0.063), including trend toward a decrease for infectious complications (15[13.9] vs 23[21.3]; P = 0.11; OD, 0.59; 95% CI, 0.29-1.22). There was a decreased incidence of anastomotic leakage (1[0.9] vs 7[6.5]; P = 0.033) and postoperative ileuas (5[4.6%] vs 11[10.2%]; P = 0.096) in the HS administration patients.Our study demonstrated beneficial postoperative clinical effects of HS intragastric administration in patients who had undergone upper gastrointestinal surgery, such as prompt postoperative gastrointestinal function recovery and reduced overall postoperative complications, which may be attributed to a reduced intestinal edema.

New multiplex real-time PCR approach to detect gene mutations for spinal muscular atrophy.

BACKGROUND: Spinal muscular atrophy (SMA) is the most common autosomal recessive disease in children, and the diagnosis is complicated and difficult, especially at early stage. Early diagnosis of SMA is able to improve the outcome of SMA patients. In our study, Real-time PCR was developed to measure the gene mutation or deletion of key genes for SMA and to further analyse genotype-phenotype correlation. METHODS: The multiple real-time PCR for detecting the mutations of survival of motor neuron (SMN), apoptosis inhibitory protein (NAIP) and general transcription factor IIH, polypeptide 2 gene (GTF2H2) was established and confirmed by DNA sequencing and multiplex ligation-dependent probe amplification (MLPA). The diagnosis and prognosis of 141 hospitalized children, 100 normal children and further 2000 cases of dry blood spot (DBS) samples were analysed by this multiple real-time PCR. RESULTS: The multiple real-time PCR was established and the accuracy of it to detect the mutations of SMN, NAIP and GTF2H2 was at least 98.8 % comparing with DNA sequencing and MLPA. Among 141 limb movement disorders children, 75 cases were SMA. 71 cases of SMA (94.67 %) were with SMN c.840 mutation, 9 cases (12 %) with NAIP deletion and 3 cases (4 %) with GTF2H2 deletion. The multiple real-time PCR was able to diagnose and predict the prognosis of SMA patients. Simultaneously, the real-time PCR was applied to detect trace DNA from DBS and able to make an early diagnosis of SMA. CONCLUSION: The clinical and molecular characteristics of SMA in Southwest of China were presented. Our work provides a novel way for detecting SMA in children by using real-time PCR and the potential usage in newborn screening for early diagnosis of SMA.

Bromate removal from water by polypyrrole tailored activated carbon.

Bromate adsorption behavior and mechanism were examined on a novel adsorbent devised via depositing polypyrrole (Ppy) into the pores of nut shell-based activated carbon (NAC). This Ppy-tailored activated carbon (Ppy-NAC) hosted positively charged polypyrrole functionality that offered considerable sorption capacity for bromate. Specifically, the Ppy-NAC achieved a bromate loading of 62.5mg/g in the adsorption isotherm, 8.3 times higher than the pristine NAC. The adsorption isotherm data were fitted well by the Langmuir model, and the adsorption kinetics were described well by the pseudo-second-order equation. The occurrence of chloride ions in solution showed that Cl(-) exchanged with BrO3(-) during the adsorption process. The X-ray photoelectron spectroscopy (XPS) analysis and the detection of bromide in solution indicated that some of BrO3(-) were reduced to Br(-), and the produced bromide ions were released to the solution and adsorbed on the Ppy-NAC. The increase of oxygen-containing functional groups on Ppy-NAC after adsorption verified that the redox reaction occurred during the adsorption process. The mechanisms of bromate removal by the Ppy-NAC included ion exchange and reduction reaction of bromate on the Ppy-NAC surfaces.

Noggin resistance contributes to the potent osteogenic capability of BMP9 in mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are multipotent progenitors and can differentiate into osteogenic, chondrogenic, and adipogenic lineages. Bone morphogenetic proteins (BMPs) play important roles in stem cell proliferation and differentiation. We recently demonstrated that BMP9 is a potent but less understood osteogenic factor. We previously found that BMP9-induced ectopic bone formation is not inhibited by BMP3. Here, we investigate the effect of BMP antagonist noggin on BMP9-induced osteogenic differentiation. BMP antagonists noggin, chording, gremlin, follistatin, and BMP3 are highly expressed in MSCs, while noggin and follistatin are lowly expressed in more differentiated pre-osteoblast C2C12 cells. BMP9-induced osteogenic markers and matrix mineralization are not inhibited by noggin, while noggin blunts BMP2, BMP4, BMP6, and BMP7-induced osteogenic markers and mineralization. Likewise, ectopic bone formation by MSCs transduced with BMP9, but not the other four BMPs, is resistant to noggin inhibition. BMP9-induced nuclear translocation of Smad1/5/8 is not affected by noggin, while noggin blocks BMP2-induced activation of Smad1/5/8 in MSCs. Noggin fails to inhibit BMP9-induced expression of downstream targets in MSCs. Thus, our results strongly suggest that BMP9 may effectively overcome noggin inhibition, which should at least in part contribute to BMP9's potent osteogenic capability in MSCs.

Study on the multidrug resistance 1 gene transfection efficiency using adenovirus vector enhanced by ultrasonic microbubbles in vitro.

As gene delivery reagents, microbubbles have been successfully used in combination with ultrasound. Shock wave exposure has been shown to transfect cells with naked DNA in vitro, but it has not been tested whether the addition of microbubbles would enhance DNA uptake with adenovirus vector. Therefore, the aim of this study was to study the efficacy and safety of multidrug resistance 1 (MDR1) gene transfer into the bone marrow mononuclear cells of rabbits using adenovirus vector enhanced by ultrasound with microbubbles in vitro. The transfection rate of the MDR1 gene was significantly increased by ultrasound microbubbles with adenovirus. After ultrasonic irradiation, there were transient holes in the cell membrane, which disappeared after irradiation by ultrasound for 24 h. The temporary swelling of the organelles was reversible. Our in vitro findings conclusively demonstrate that the exogenous MDR1 gene transfer into the mononuclear cells of rabbits with adenovirus vector was enhanced by the ultrasonic microbubbles and this transfection technique is safe.