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The utilization of cold plasma (CP) treatment to promote covalent conjugation of ovalbumin (OVA) and gallic acid (GA), as well as its functionality, were investigated. Results demonstrated that CP significantly enhanced the covalent grafting of OVA and GA. The maximum conjugation of GA, 24.33 ± 2.24 mg/g, was achieved following 45 s of CP treatment. Covalent conjugation between GA and OVA were confirmed through analyses of total sulfhydryl (-SH) group, Fourier transform infrared (FTIR) spectroscopy, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Unfolding of the OVA molecule occurred upon conjugation with GA, as evidenced by multiple spectroscopy analyses. Additionally, conjugation with GA resulted in significant improvements in the antioxidant activity and emulsifying properties of OVA. This study demonstrated that CP is a robust and sustainable technique for promoting the covalent conjugate of polyphenols and proteins, offering a novel approach to enhance the functional properties of proteins.
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Ácido Gálico , Ovalbumina , Gases em Plasma , Ácido Gálico/química , Ovalbumina/química , Gases em Plasma/química , Antioxidantes/química , AnimaisRESUMO
Implementing topological superconductivity (TSC) and Majorana states (MSs) is one of the most significant and challenging tasks in both fundamental physics and topological quantum computations. In this work, taking the obstructed atomic insulator (OAI) Nb_{3}Br_{8}, s-wave superconductor (SC) NbSe_{2}, and ferromagnetic insulator (FMI) CrI_{3} as an example, we propose a new setup to realize the 2D chiral TSC and MSs in the SC/OAI/FMI heterostructure, which could avoid the subband problem effectively and has the advantage of huge Rashba spin-orbit coupling. As a result, the TSC phase can be stabilized in a wide region of chemical potential and Zeeman splitting, and four distinct TSC phases with superconducting Chern number N=-1,-2,-3, 3 can be achieved. Moreover, a 2D Bogoliubov-de Gennes Hamiltonian based on the triangular lattice of obstructed Wannier charge centers, combined with the s-wave superconductivity paring and Zeeman splitting, is constructed to understand the whole topological phase diagram analytically. These results expand the application of OAIs and pave a new way to realize the TSC and MSs with unique advantages.
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One key difficulty in realizing Majorana zero modes (MZMs) is the required high magnetic field, which causes serious issues, e.g., shrinks the superconducting gap, reduces topological region, and weakens their robustness against disorders. In this Letter, we propose that the Meissner effect can bring the topological superconducting phase to a superconductor/topological-insulator/superconductor (SC/TI/SC) hybrid system. Remarkably, the required magnetic field strength (<10 mT) to support MZMs has been reduced by several orders of magnitude compared to that (>0.5 T) in the previous schemes. Tuning the phase difference between the top and bottom superconductors can control the number and position of the MZMs. In addition, we account for the electrostatic potential in the superconductor/topological-insulator (SC/TI) interface through the self-consistent Schrödinger-Poisson calculation, which shows the experimental accessibility of our proposal. Our proposal only needs a small magnetic field of less than 10 mT and is robust against the chemical potential fluctuation, which makes the SC/TI/SC hybrid an ideal Majorana platform.
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BACKGROUND: Immunoglobulin light chain (AL) amyloidosis is a rare disease characterized by deposition of ALs essentially in any organ or tissue, with cardiac involvement being very frequent (61%). Early diagnosis is of high importance because early initiation of treatment in AL amyloidosis may improve outcomes. Despite the administration of immunotherapeutic agents, in particular bortezomib and daratumumab, which have improved the outcomes of AL amyloidosis, anti-plasma cell therapy remains suboptimal for some patients. CASE SUMMARY: We report the case of a 55-year-old man presenting with heart failure who was diagnosed with cardiac AL amyloidosis by an endomyocardial biopsy. He experienced a short-term hematological remission with no organ response after being administered a bortezomib-daratumumab containing regimen. The treatment was switched to pomolidomide due to pulmonary involvement and progressive pleural effusion, in which flow cytometry analysis showed abnormal plasma cells. After two cycles of this regimen, the pleural effusion was controlled effectively with no recurrence. CONCLUSION: This case emphasizes the crucial role of endomyocardial biopsy in early diagnosis of cardiac amyloidosis and suggests that pomolidomide may be an effective treatment for patients with AL amyloidosis that is relapsed/refractory to both bortezomib and daratumumab.
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BACKGROUND: Tuberculosis is a bacterial infection involving multiple organs and systems. Its hematological presentation mainly includes anemia and leukocytosis. Evans syndrome is a rare autoimmune disease characterized by autoimmune hemolytic anemia, immune thrombocytopenia, and neutropenia, with positive results for the direct Coombs test and platelet antibodies. The cooccurrence of tuberculosis and Evans syndrome is rarely reported. CASE PRESENTATION: A 69-year-old female presented with a fever and shortness of breath. Her chest computerized tomography scan showed extensive miliary nodules in the bilateral lung fields. She rapidly developed respiratory failure that required endotracheal intubation and mechanical ventilation. The acid-fast bacilli sputum smear results indicated a grade of 3+. Later on, blood testing revealed hemolytic anemia, a positive direct Coombs test result, and the presence of the platelet antibody IgG. This patient was diagnosed as having disseminated pulmonary tuberculosis and Evans syndrome. She successfully recovered after treatment with antituberculosis drugs and glucocorticoids. CONCLUSIONS: Tuberculosis can occur together with Evans syndrome. Affected patients should receive both antituberculosis and immunosuppressive drugs.
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Anemia Hemolítica Autoimune , Trombocitopenia , Tuberculose Miliar , Tuberculose Pulmonar , Idoso , Anemia Hemolítica Autoimune/complicações , Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/tratamento farmacológico , Feminino , Humanos , Trombocitopenia/complicações , Trombocitopenia/diagnóstico , Trombocitopenia/tratamento farmacológico , Tuberculose Miliar/tratamento farmacológico , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológicoRESUMO
BACKGROUND: Pulmonary tuberculosis is a chronic infectious disease caused by mycobacterium tuberculosis in the lungs. The present study aims to investigate the correlation between serum 25-hydroxyvitamin D3 (25-VD3) and the severity and short-term prognosis of tuberculosis. METHODS: The clinical data of 261 pulmonary tuberculosis patients, who were admitted to the Tuberculosis Diagnosis and Treatment Center of our hospital from January 1, 2017 to December 31, 2020, was retrospectively collected. Taking the median of 25-VD3 at admission (11.40 ng/mL) as the cutoff value, these patients were divided into two groups: high 25-VD3 group (> 11.40 ng/mL, n = 131) and low 25-VD3 group (≤ 11.40 ng/mL, n = 130). Then, Pearson's correlation analysis was performed using SPSS to determine the correlation between the 25-VD3 level and the length of hospitalization and Acute Physiology and Chronic Health Evaluation II (APACHE II) score of pulmonary tuberculosis patients. According to the clinical outcome after 28 days of treatment, these patients were divided again into two groups: improvement group (n = 170) and death group (n = 91). Then, Pearson's correlation analysis through SPSS was performed to determine the relationship between the 25-VD3 level and short-term prognosis of pulmonary tuberculosis patients. RESULTS: Compared to the low 25-VD3 group, pulmonary tuberculosis patients in the high 25-VD3 group were younger, had a higher percentage of improvement after 28 days of treatment, and had a lower APACHE II score (p < 0.05). However, the 25-VD3 level was not significantly correlated to the length of hospital stay of pulmonary tuberculosis patients (correlation coefficient r = 0.020, p = 0.746) and was significantly negatively correlated to the APACHE II score (correlation coefficient r = -0.211, p = 0.001). In addition, the age and APACHE II score of patients were lower in the improvement group, when compared to the death group, while the 25-VD3 level was higher and the length of hospital stay was longer, when compared to the death group (p < 0.01). The logistic regression analysis revealed that the length of hospital stay, APACHE II score, and 25-VD3 level are independent risk factors that affect the prognosis of pulmonary tuberculosis patients (p < 0.05). CONCLUSIONS: In summary, 25-VD3 is closely correlated to the severity of tuberculosis, and this can be used to evaluate and predict the prognosis of patients.
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Calcifediol , Tuberculose Pulmonar , Humanos , Unidades de Terapia Intensiva , Prognóstico , Curva ROC , Estudos Retrospectivos , Tuberculose Pulmonar/diagnósticoRESUMO
Cadmium is one of the most toxic heavy metal contaminants in soils and water bodies and poses a serious threat to ecosystems and humans. However, cadmium is also an important resource widely used in many industries. The recovery of cadmium in the form of high-value products is considered as an ideal disposal strategy for Cd-contaminated environments. In this work, Pistia stratiotes was used to recycle cadmium from wastewaters through phytoaccumulation and then transformed into carbon-supported cadmium sulfide photocatalyst (CdS@C) through carbonization and hydrothermal reaction. The CdS@C photocatalyst contained a mixture of cubic and hexagonal CdS with lower band gap energy (2.14 eV) and high electron-hole separation efficiency, suggesting an excellent photoresponse ability and photocatalytic efficiency. The impressive stability and photocatalytic performance of CdS@C were demonstrated in efficient photodegradation of organic pollutants. â¢OH and O2â¢- were confirmed as the major active species for organic pollutants degradation during CdS@C photocatalysis. This work provides new insights into addressing Cd contaminated water bodies and upcycling in the form of photocatalyst.
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Exploration of effective ways to integrate various functional species into hydrogen-bonded organic frameworks (HOFs) is critically important for their applications but highly challenging. In this study, according to the "bottle-around-ship" strategy, core-shell heterostructure of upconversion nanoparticles (UCNPs) and HOFs was fabricated for the first time via a ligand-grafting stepwise method. The UCNPs "core" can effectively upconvert near-infrared (NIR) irradiation (980â nm) into visible light (540â nm and 653â nm), which further excites the perylenediimide-based HOF "shell" through resonance energy transfer. In this way, the nanocomposite inherits the high porosity, excellent photothermal and photodynamic efficiency, NIR photoresponse from two parent materials, achieving intriguing NIR-responsive bacterial inhibition toward Escherichia coli. This study may shed light on the design of functional HOF-based composite materials, not only enriching the HOF library but also broadening the horizon of their potential applications.
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Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Imidas/farmacologia , Nanoestruturas/química , Perileno/análogos & derivados , Fármacos Fotossensibilizantes/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Ligação de Hidrogênio , Imidas/síntese química , Imidas/química , Raios Infravermelhos , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Perileno/síntese química , Perileno/química , Perileno/farmacologia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Propriedades de SuperfícieRESUMO
BACKGROUND: Disseminated nocardiosis is liable to be misdiagnosed owing to the non-specific clinical manifestations and laboratory/imaging findings. Metagenomic next-generation sequencing (mNGS) is a culture-independent and rapid method for direct identification of all microorganisms in clinical specimens. CASE PRESENTATION: A 72-year-old man was admitted to our hospital on February 20, 2019 with a history of recurrent cough, expectoration, fever, and diarrhea since 1 month, and unconsciousness since 1 week. Contrast-enhanced magnetic resonance imaging of head showed multiple lesions in the bilateral cerebral hemispheres, brainstem, and cerebellar hemispheres. The presumptive diagnosis was disseminated tuberculosis, although all tests for mycobacterium were negative. However, the patient did not benefit from antituberculosis treatment. Repeat MRI showed multiple abnormal signals in the brain and progression of meningeal thickening. Cerebrospinal fluid and bronchoalveolar lavage fluid specimens were subsequently sent for PMSeq metagenomics sequencing; the results indicated Nocardia. farcinica as the predominant pathogen. The anti-TB treatment was stopped and the patient was prescribed sulphamethoxazole in combination with linezolid and meropenem for nocardiosis. He showed gradual neurological improvement and was transferred to Huashan Hospital. He was discharged from the hospital on April 19, 2019, but died of persistent diarrhea on May 26, 2019. CONCLUSIONS: Patients with suspected nocardiosis do not always respond to conventional treatment; therefore, mNGS can facilitate diagnosis and timely treatment decision-making.
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Nocardiose , Nocardia , Tuberculose , Idoso , Erros de Diagnóstico , Humanos , Masculino , Metagenômica , Nocardia/genética , Nocardiose/diagnóstico , Nocardiose/tratamento farmacológicoRESUMO
Functionalization of hydrogen-bonded organic frameworks (HOFs) for specific applications has been a long-lasting challenge in HOF materials. Here, an efficient way to integrate functional species in the HOF structure through constructing an anionic framework is presented. The obtained HOFs, taking PFC-33 (PFC = porous materials from FJIRSM,CAS) as an example, integrate a porphyrin photosensitizer as a porous backbone and a commercial biocide as counterions in the structure. The permanent channels and the electrostatic interaction between the framework and the counterions provide PFC-33 ion-responsive biocide-release behavior in various physiological environments, thus exhibiting synergistic photodynamic and chemical antimicrobial efficiency. The unbonded carboxyl groups residing on the HOF surface further allow for manipulating the interfacial interaction between the PFC-33 and the polymer matrix for membrane fabrication. Therefore, a polyHOF membrane with high stability, desired flexibility, and good permeability is obtained, which demonstrates noticeable bacterial inhibition toward Escherichia coli. This study may shed light on the functionalization of HOF materials for broad application potentials.
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Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Membranas Artificiais , Compostos Orgânicos/química , Compostos Orgânicos/farmacologia , Ligação de Hidrogênio , Eletricidade EstáticaRESUMO
INTRODUCTION: Nosocomial Enterococcus faecium (E faecium) infections are common among immunocompromised patients; however, sepsis caused by E faecium is rarely encountered in the clinical setting. PATIENT CONCERNS: A 69-year-old woman with a previous history of tuberculosis (TB), developed symptoms of recurrent fever, paroxysmal cough, and exertional dyspnea for over 2 months before she presented to the hospital. DIAGNOSIS: The patient was initially misdiagnosed with recurrent TB, and did not respond to anti-TB therapy. Culture results of blood, endotracheal necrotic tissue, and urine confirmed a diagnosis of multifocal E faecium infection. INTERVENTIONS: On definitive diagnosis, the patient received intensive antimicrobial combination treatment with linezolid, teicoplanin, caspofungin, and voriconazole on the basis of antimicrobial susceptibility results. OUTCOMES: After transient improvement, the patient's condition deteriorated due to secondary infections, and the patient died after discharge against medical advice. CONCLUSION: E faecium bacteremia may cause sepsis in immunocompromised patients, and has a high mortality rate. Careful pathogen detection and early initiation of treatment is crucial to good patient outcome.
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Enterococcus faecium/isolamento & purificação , Infecções por Bactérias Gram-Positivas/diagnóstico , Sepse/microbiologia , Idoso , Antibacterianos/uso terapêutico , Diagnóstico Diferencial , Feminino , Infecções por Bactérias Gram-Positivas/complicações , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Sepse/tratamento farmacológico , Tuberculose Pulmonar/diagnósticoRESUMO
We propose a realization of the lattice-symmetry-assisted second-order topological superconductors with corner Majorana zero modes (MZM) based on two-dimensional topological insulators (2DTI). The lattice symmetry can naturally lead to the anisotropic coupling of edge states along different directions to the in-plane magnetic field and conventional s-wave pairings, thus leading to a single MZM located at the corners for various lattice patterns. In particular, we focus on the 2DTI with D_{3d} lattice symmetry and found different types of gap opening for the edge states along the armchair and zigzag edges in a broad range of parameters. As a consequence, a single MZM exists at the corner between the zigzag and armchair edges, and is robust against weakly broken lattice symmetry. We propose to realize such corner MZMs in a variety of polygon patterns, such as triangles and quadrilaterals. We further show their potentials in building the Majorana network through constructing the Majorana Y junction under an in-plane magnetic field.
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As a promising method for treating intractable epilepsy, the inhibitory effect of low-frequency stimulation (LFS) is well known, although its mechanisms remain unclear. Excessive levels of cerebral glutamate are considered a crucial factor for epilepsy. Therefore, we designed experiments to investigate the crucial parts of the glutamate cycle. We evaluated glutamine synthetase (GS, metabolizes glutamate), glutaminase (synthesizes glutamate), and glutamic acid decarboxylase (GAD, a γ-aminobutyric acid [GABA] synthetase) in different regions of the brain, including the dentate gyrus (DG), CA3, and CA1 subregions of the hippocampus, and the cortex, using western blots, immunohistochemistry, and enzyme activity assays. Additionally, the concentrations of glutamate, GABA, and glutamine (a product of GS) were measured using high-performance liquid chromatography (HPLC) in the same subregions. The results indicated that a transiently promoted glutamate cycle was closely involved in the progression from focal to generalized seizure. Low-frequency stimulation (LFS) delivered to the ventral hippocampus had an antiepileptogenic effect in rats exposed to amygdaloid-kindling stimulation. Simultaneously, LFS could partly reverse the effects of the promoted glutamate cycle, including increased GS function, accelerated glutamate-glutamine cycling, and an unbalanced glutamate/GABA ratio, all of which were induced by amygdaloid kindling in the DG when seizures progressed to stage 4. Moreover, glutamine treatment reversed the antiepileptic effect of LFS with regard to both epileptic severity and susceptibility. Our results suggest that the effects of LFS on the glutamate cycle may contribute to the antiepileptogenic role of LFS in the progression from focal to generalized seizure.
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Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Excitação Neurológica/metabolismo , Convulsões/metabolismo , Animais , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Giro Denteado/metabolismo , Progressão da Doença , Estimulação Elétrica , Glutamato Descarboxilase/metabolismo , Glutamina/metabolismo , Hipocampo/fisiopatologia , Excitação Neurológica/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley , Convulsões/fisiopatologia , Ácido gama-Aminobutírico/metabolismoRESUMO
OBJECTIVE: Studies have demonstrated that Tai Chi exercise improves blood lipid level with inconsistent results. A meta-analysis was conducted to quantify the effects of Tai Chi on blood lipid profiles in humans. METHODS: We screened the databases of PubMed, EMBASE, Cochrane Library (Central), Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang data, and Clinicaltrials.gov for randomized controlled trials with Physiotherapy Evidence Database (PEDro) score more than 3 points up to June 2015. Six studies involving 445 subjects were included. Most trials applied 12-week Tai Chi intervention courses. RESULTS: In comparison with the control group, blood triglyceride (TG) level difference between follow-up and baseline was statistically significantly lower in the Tai Chi practicing group (weighted mean difference (WMD) -16.81 mg/dl; 95% confidence intervals (CI) -31.27 to -2.35 mg/dl; P=0.02). A trend to improving total cholesterol (TC) reduction was found with Tai Chi (WMD -7.96 mg/dl; 95% CI -17.30 to 1.39 mg/dl; P=0.10). However, no difference was found in blood low-density lipoprotein cholesterol (LDL-C) or high-density lipoprotein cholesterol (HDL-C). CONCLUSIONS: Tai Chi exercise lowered blood TG level with a trend to decrease blood TC level. Our data suggest that Tai Chi has the potential to implement meaningful blood lipid modification and serve as an adjunctive exercise modality. The relationship between Tai Chi exercise regimen and lipid profile change might have a scientific priority for future investigation.
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Lipídeos/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Tai Chi Chuan , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Humanos , Triglicerídeos/sangueRESUMO
The prognosis of patients exposed to a sub-threshold dose of a proconvulsant is difficult to establish. In this study, we investigated the effect of a single sub-threshold dose of the proconvulsant pilocarpine (PILO) on the progression of seizures that were subsequently induced by daily electrical stimulation (kindling) of the amygdaloid formation. Male SpragueDawley rats were each implanted with an electrode in the right basolateral amygdala and an indwelling cannula in the right ventricle. The animals were randomized into groups and were administered one of the following treatments: saline, PILO, saline+L-α-aminoadipic acid (L-AAA; one dosage tested), PILO+L-AAA, or PILO+L-methionine sulfoximine (three dosages tested). Amygdaloid stimulation and electroencephalography were performed once daily. We performed immunohistochemistry and western blot for glial fibrillary acidic protein and glutamine synthetase (GS). We also assayed the enzymic activity of GS in discrete brain regions. An intraperitoneal injection of a sub-threshold PILO dose enhanced the progression of amygdaloid-kindling seizures and was accompanied by an increase in reactive-astrocyte and GS (content and activity) in the hippocampus and piriform cortex. L-AAA and L-methionine sulfoximine, inhibitors of astrocytic and GS function, respectively, abolished the effect of PILO on amygdaloid-kindling seizures. We conclude that one sub-threshold dose of a proconvulsant may enhance the progression of subsequent epilepsy and astrocytic GS may play a role in this phenomenon. Thus, a future therapy for epilepsy could be inhibition of astrocytes and/or GS.
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Astrócitos/efeitos dos fármacos , Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Glutamato-Amônia Ligase/metabolismo , Excitação Neurológica/efeitos dos fármacos , Agonistas Muscarínicos/toxicidade , Pilocarpina/toxicidade , Ácido 2-Aminoadípico/farmacologia , Animais , Astrócitos/enzimologia , Complexo Nuclear Basolateral da Amígdala/enzimologia , Cateteres de Demora , Modelos Animais de Doenças , Estimulação Elétrica , Eletrodos Implantados , Imunofluorescência , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Excitação Neurológica/metabolismo , Cloreto de Lítio , Masculino , Metionina Sulfoximina/farmacologia , Ratos Sprague-Dawley , Lobo Temporal/efeitos dos fármacos , Lobo Temporal/enzimologiaRESUMO
UNLABELLED: The expression of vascular endothelial growth factor (VEGF) under hypoxia in the placenta with intrahepatic cholestasis of pregnancy (ICP) was observed, and mechanisms of ICP fetal distress were discussed. METHODS: Different culturing times were established in hypoxia incubator, and protein expressions of VEGF in placental tissue were observed using immunohistochemical S-P method. RESULTS: After 4 h hypoxic culture, VEGF protein expression in ICP group was higher than the normal group with significant difference (P < 0.05). With the extension of hypoxic exposure, VEGF protein expression in both groups was suppressed, but no distinction in-between. Regression analyses indicated a noticeable effect of CG on VEGF expression, the higher the CG was, the lower the VEGF protein expression was (P < 0.05). CONCLUSIONS: Short term hypoxia induces up-regulation of VEGF expression in ICP placenta, and this adaptive change is probably a protective mechanism of fetus in ICP.
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Colestase Intra-Hepática/metabolismo , Hipóxia/metabolismo , Placenta/metabolismo , Complicações na Gravidez/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Feminino , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Recém-Nascido , GravidezRESUMO
Osteosarcoma is the most common bone tumors in children and adolescents. Despite intensive chemotherapy, patients with advanced disease still have a poor prognosis, illustrating the need for alternative therapies. In this study, we explored the use of antibodies that block CD47 with a tumor growth suppressive effect on osteosarcoma. We first found that up-regulation of CD47 mRNA levels in the tumorous tissues from eight patients with osteosarcoma when compared with that in adjacent non-tumorous tissues. Further western-blot (WB) and immunohistochemistry (IHC) demonstrated that CD47 protein level was highly expressed in osteosarcoma compared to normal osteoblastic cells and adjacent non-tumorous tissues. Osteosarcoma cancer stem cell markers staining shown that the majority of CD44+ cells expressed CD47 albeit with different percentages (ranging from 80% to 99%). Furthermore, high CD47 mRNA expression levels were associated with a decreased probability of progression-free and overall survival. In addition, blockade of CD47 by specific Abs suppresses the invasive ability of osteosarcoma tumor cells and further inhibits spontaneous pulmonary metastasis of KRIB osteosarcoma cells in vivo. Finally, CD47 blockade increases macrophage phagocytosis of osteosarcoma tumor cells.In conclusion, our findings demonstrate that CD47 is a critical regulator in the metastasis of osteosarcoma and suggest that targeted inhibition of this antigen by anti-CD47 may be a novel immunotherapeutic approach in the management of this tumor.
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Anticorpos/farmacologia , Antígeno CD47/imunologia , Invasividade Neoplásica/imunologia , Metástase Neoplásica/patologia , Osteossarcoma/patologia , Animais , Anticorpos/imunologia , Antígeno CD47/biossíntese , Antígeno CD47/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Intervalo Livre de Doença , Humanos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Osteossarcoma/mortalidade , Fagocitose/imunologia , RNA Mensageiro/biossíntese , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Idiopathic scoliosis is the most common pediatric spinal deformity affecting 1% to 3% of the population, and adolescent idiopathic scoliosis (AIS) accounts for approximately 80% of these cases; however, the etiology and pathogenesis of AIS are still uncertain. The current study aims to identify the relationship between G protein-coupled receptor 126 (GPR126) gene and AIS predisposition, to identify the relationship between the genotypes of the GPR126 SNPs and the clinical phenotypes of AIS. We conducted a case-control study and genotyped twenty SNPs of GPR126 gene including ten exonic SNPs and ten intronic polymorphisms in 352 Chinese sporadic AIS patients and 149 healthy controls. We provided evidence for strong association of three intronic SNPs of the GPR126 gene with AIS susceptibility: rs6570507 A > G (p =0 .0035, OR = 1.729), rs7774095 A > C (p = 0.0078, OR = 1.687), and rs7755109 A > G (p = 0.0078, OR = 1.687). However, we did not identify any significant association between ten exonic SNPs of GPR126 and AIS. Linkage disequilibrium analysis indicated that rs7774095 A > C and rs7755109 A > G could be parsed into one block. The association between the intronic haplotype and AIS was further confirmed in an independent population with 110 AIS individuals and 130 healthy controls (p = 0.046, OR = 1.680). Furthermore, molecular mechanisms underlying intronic SNP regulation of GPR126 gene were studied. Although intronic SNPs associated with AIS didn't influence GPR126 mRNA alternative splicing, there was a strong association of rs7755109 A > G with decreased GPR126 mRNA level and protein levels. Our findings indicate that genetic variants of GPR126 gene are associated with AIS susceptibility in Chinese populations. The genetic association of GPR126 gene and AIS might provide valuable insights into the pathogenesis of adolescent idiopathic scoliosis.