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A concise and practical synthetic method has been developed for 8-azachromones, including 8-azaflavones, which have emerged as a promising class of compounds. Using commercially available nicotinates as the starting material, 8-azachromones were obtained in only three steps. The key intramolecular O-arylation reaction was achieved by nucleophilic attack of enolates to C2 of N-oxides under PyBrop or Ac2O activation conditions. These studies provide the basis for the access to 8-azachromones, enabling future work including the discovery and development of novel chromonoid drugs or other functional materials.
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Ulcerative colitis (UC) is a subtype of inflammatory bowel disease. Previous studies have suggested a link between senescence process and the body's inflammatory reaction, indicating that senescence may exacerbate UC, yet the relation between UC and senescence remains unclear. Tedizolid Phosphate (TED), a novel oxazolidinone antimicrobial, is indicated in acute bacterial skin infections, its impact on senescence is not known. Our research revealed that the UC inducer dextran sulfate sodium (DSS) triggers senescence in both colon epithelial NCM460 cells and colon tissues, and TED that screened from a compound library demonstrated a strong anti-senescence effect on DSS treated NCM460 cells. As an anti-senescence medication identified in this research, TED efficiently alleviated UC and colonic senescence in mice caused by DSS. By proteomic analysis and experimental validation, we found that DSS significantly inhibits the AMPK signaling pathway, while TED counteracts senescence by restoring AMPK activity. This research verified that the development of UC is accompanied with colon tissue senescence, and TED, an anti-senescence medication, can effectively treat UC caused by DSS and alleviate colon senescence. Our work suggests anti-senescence strategy is an effective approach for UC treatment.
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Proteínas Quinases Ativadas por AMP , Senescência Celular , Colite Ulcerativa , Colo , Sulfato de Dextrana , Transdução de Sinais , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Transdução de Sinais/efeitos dos fármacos , Colo/efeitos dos fármacos , Colo/patologia , Senescência Celular/efeitos dos fármacos , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Linhagem Celular , Masculino , Oxazolidinonas/farmacologia , Oxazolidinonas/uso terapêutico , Organofosfatos/farmacologia , Organofosfatos/uso terapêutico , Modelos Animais de DoençasRESUMO
OBJECTIVES: This study aims to investigate the impact of mesenchymal stem cell (MSC)-derived exosomes (Exo) on cerebral ischemia and reperfusion (I/R) injury, along with the underlying mechanism. METHODS: An animal model of cerebral ischemia was induced using middle cerebral artery occlusion (MCAO), and a cell model utilizing Neuro-2a cells was established through oxygen-glucose deprivation/reoxygenation (OGD/R). Exosomes isolated from mouse MSCs were administered to mice or used to stimulate Neuro-2a cells. Exosomes from MSCs transfected with miR-NC, miR-486-5p mimics, miR-486-5p inhibitor, or phosphatase and tensin homolog (PTEN) short hairpin RNAs (sh-PTEN) were employed to stimulate Neuro-2a cells. The regulatory axis of miR-486-5p and PTEN was confirmed through rescue experiments. RESULTS: Exo-miR-486-5p mimics alleviated cerebral I/R injury, improving neurological deficits and reducing the infarct ratio. Furthermore, Exo-miR-486-5p mimics attenuated OGD/R-induced defects in cell viability and inhibited apoptosis in Neuro-2a cells. These mimics also reduced levels of lactate dehydrogenase (LDH) and malondialdehyde (MDA) while enhancing superoxide dismutase (SOD) activity, both in brain tissue homogenates of mice and cell supernatants. Mechanistically, PTEN was identified as a target of miR-486-5p, and the downregulation of PTEN notably elevated Exo-miR-486-inhibitor-induced reductions in cell viability while mitigating cell apoptosis. CONCLUSION: The results of this study demonstrate the potential of exosomes derived from MSCs to protect against cerebral I/R injury via the miR-486-5p and PTEN axis.
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Isquemia Encefálica , Exossomos , MicroRNAs , Traumatismo por Reperfusão , Animais , Exossomos/genética , MicroRNAs/genética , Traumatismo por Reperfusão/genética , Isquemia Encefálica/genética , Apoptose , ReperfusãoRESUMO
Ulcerative colitis (UC) is a chronic inflammatory disease that is increasing in prevalence globally. Senescence is characterized by a specific chronic, low-grade, "sterile" inflammatory state known as inflammaging, suggesting that senescence may exacerbate the severity of UC. However, the link between UC and senescence remains unclear. Valnemulin (VAL) is a semi-synthetic derivative of a naturally occurring diterpenoid antibiotic (pleuromutilin), which can inhibit peptidyl transferase. Studies investigating the potential of valnemulin to inhibit senescence and alleviate colitis are currently limited. In this study, we revealed that dextran sulfate sodium (DSS), an inducer of UC, induces senescence in both colon epithelial NCM460 cells and colon tissues. Additionally, VAL, identified from a compound library, exhibited robust anti-senescence activity in DSS-treated NCM460 cells. Identified in our study as an anti-senescence agent, VAL effectively mitigated DSS-induced UC and colonic senescence in mice. Through network pharmacology analysis and experimental validation, the potential signaling pathway (AMPK/NF-κB) for VAL in treating UC was identified. We discovered that DSS significantly inhibited the AMPK signaling pathway and activated the NF-κB signaling pathway. However, supplementation with VAL remarkably restored AMPK activity and inhibited the NF-κB signaling pathway, which led to the inhibition of senescence. In summary, our study demonstrated that DSS-induced UC stimulates the senescence of colonic tissues, and VAL can effectively alleviate DSS-induced colonic damage and reduce colonic senescence. Our research findings provide a new perspective for targeting anti-senescence in the treatment of UC.
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In this study, we assembled and annotated the chloroplast (cp) genomes of four Ligustrum species, L. sinense, L. obtusifolium, L. vicaryi, and L. ovalifolium 'Aureum'. Including six other published Ligustrum species, we compared various characteristics such as gene structure, sequence alignment, codon preference, and nucleic acid diversity, and performed positive-selection genes screening and phylogenetic analysis. The results showed that the cp genome of Ligustrum was 162,185-166,800 bp in length, with a circular tetrad structure, including a large single-copy region (86,885-90,106 bp), a small single-copy region (11,446-11,499 bp), and a pair of IRa and IRb sequences with the same coding but in opposite directions (31,608-32,624 bp). This structure is similar to the cp genomes of most angiosperms. We found 132-137 genes in the cp genome of Ligustrum, including 89-90 protein-coding genes, 35-39 tRNAs, and 8 rRNAs. The GC content was 37.93-38.06% and varied among regions, with the IR region having the highest content. The single-nucleotide (A/T)n was dominant in simple-sequence repeats of the Ligustrum cp genome, with an obvious A/T preference. Six hotspot regions were identified from multiple sequence alignment of Ligustrum; the ycf1 gene region and the clpP1 exon region can be used as potential DNA barcodes for the identification and phylogeny of the genus Ligustrum. Branch-site model and Bayes empirical Bayes (BEB) analysis showed that four protein-coding genes (accD, clpP, ycf1, and ycf2) were positively selected, and BEB analysis showed that accD and rpl20 had positively selected sites. A phylogenetic tree of Oleaceae species was constructed based on the whole cp genomes, and the results were consistent with the traditional taxonomic results. The phylogenetic results showed that genus Ligustrum is most closely related to genus Syringa. Our study provides important genetic information to support further investigations of the phylogenetic development and adaptive evolution of Ligustrum species.
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Genoma de Cloroplastos , Ligustrum , Filogenia , Ligustrum/genética , Genoma de Cloroplastos/genética , Teorema de BayesRESUMO
OBJECTIVE: To explore if folic acid/polyamide-amine (FA/PAMAM) enhances the therapeutic effect of miR-7gene therapy for glioma in vivo. METHODS: The miR-7 gene was transfected into U251 glioma cells by FA/PAMAM. The efficiency of gene transfection was assessed by fluorescence microscopy. The miR-7 level was detect by quantitative RT-PCR. Intracranial glioma models were established in thymectomized mice, and FA/PAMAM nanoparticles were transplanted into the tumors in situ 3 days later. The animal survival was recorded and the gross tumor volume and degree of edema were observed by MRI. Apoptosis in the glioma cells and expression of proliferating cell nuclear antigen (PCNA), matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) were assessed by immunohistochemistry, and EGFR and AKT-2 protein expression was detected by Western blot assay. RESULTS: Compared with the liposomes, the FA/PAMAM nanoparticles were more efficient to transfer miR-7 gene into U251 glioma cells, MRI showed that the tumor growth was much slower in the FA/PAMAM/miR-7 group, and the animal survival time was longer. The apoptosis rate was (5.3 ± 0.9)% in the control group, (11.4 ± 2.4)% in the liposome/miR-7 group, and (17.7 ± 3.7)% in the FA/PAMAM/miR-7 group. The immunohistochemical assay showed that the levels of PCNA, MMP-2 and MMP-9 protein in the FA/PAMAM/miR-7 group were (34.6 ± 5.4)%, (24.5 ± 4.1)%, (25.4 ± 5.1)%, respectively, significantly lower than those in the liposome/miR-7 group (49.3 ± 5.9)%, (31.7 ± 7.1)% and (39.4 ± 6.4)%, respectively, and those in the control group (57.3 ± 7.4)%, (45.4 ± 6.9)% and (55.1 ± 7.3)%, respectively (all P < 0.05). The expressions of EGFR and AKT-2 proteins were 1.09 ± 0.12 and 0.62 ± 0.10 in the control group, 0.63 ± 0.11 and 0.43 ± 0.07 in the liposome/miR-7 group, and significantly deceased (0.47 ± 0.09 and 0.31 ± 0.04, respectively) in the FA/PAMAM/miR-7 group (all P < 0.05). CONCLUSION: Compared with the liposomes, FA/PAMAM can transfect miR-7 into glioma cells with a higher efficiency in vivo, makes a longer time of the drug action, and shows a certain inhibitory effect on the growth of glioma, therefore, might become a new drug targeting agent in gene therapy forglioma.
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Apoptose , Neoplasias Encefálicas/patologia , Terapia Genética/métodos , Glioma/patologia , MicroRNAs/genética , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Dendrímeros/química , Receptores ErbB/metabolismo , Ácido Fólico/química , Glioma/genética , Glioma/metabolismo , Humanos , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Nus , MicroRNAs/metabolismo , Nanopartículas , Transplante de Neoplasias , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Timectomia , TransfecçãoRESUMO
OBJECTIVE: To establish an ion chromatography (IC) method for determination of ammonia in air of workplace. METHODS: Ammonia in workplace air was collected in silica gel tube, desorbed with 10 mmol/L methanesulfonic acid by ultrasonic for 10 min, determined by IC. RESULTS: The linearity range was 0.02-1.00 microg/ml. The linear equation was Y = 12041X-187 (r = 0.9997). The limit of quantification was 0.13 mg/m3 (the air volume was 1.5 L). Collection efficiency was 100%. Extraction efficiency was 99%. The relative standard deviation was 4.2%-6.3%. The penetration capacity was more than 264 microg. Sample could be stored for 14 days at least by ambient storage. CONCLUSION: This method is convenient, applicable and sensitive, suitable to determinate ammonia in air of workplace.
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Poluentes Ocupacionais do Ar/análise , Amônia/análise , Local de Trabalho , Cromatografia Gasosa/métodos , Manejo de EspécimesRESUMO
BACKGROUND: We undertook a comparative biomechanical study of type B1 fractures around femoral prostheses following cemented hip arthroplasty using the Ortho-Bridge System (OBS) and a locking compression plate/locking attachment plate structure (LCP + LAP). We aimed to investigate the biomechanical characteristics and advantages of the OBS compared with LCP + LAP when treating this fracture type. METHODS: An OBS fixation model was designed based on OBS and LCP + LAP fixation characteristics. The LCP + LAP combination (Group A) and three different OBS combinations (Groups B, C, and D) were used to fix a B1 fracture model with a femoral periprosthetic fracture. Axial compression and torsion experiments were then performed using simple and comminuted fracture models. The axial compression failure experiment was carried out, and the model stiffness during axial compression, torsion angle in torsion test, and vertical load in the final failure test were collected. RESULTS: When simulating simple oblique fractures, no significant difference was found among the four groups in terms of stiffness in the axial compression experiment (P = 0.257). The torsion angle of the LCP + LAP system was significantly higher compared with the OBS system (P < 0.05). When simulating a comminuted fracture, the experimental data for axial compression showed that the rigidity measurements of the three combinations of the OBS system were higher compared with the LCP + LAP system (P = 0.000) and that the torsion angles of three combinations of the OBS system were smaller compared with the LCP + LAP system (P < 0.05). In the axial compression failure test, the fixed failure mode of the LCP + LAP system was the destruction of the contact cortex at the fracture site, whereas the failure modes in the three OBS combinations involved fracture around the screws above the osteotomy and destruction of the contact cortex at the fracture site. CONCLUSIONS: The findings revealed that the OBS produced superior biomechanical outcomes compared with LCP + LAP, especially for the bridging two-rod dual cortex. According to the performance observed after model axial compression destruction, the OBS was fixed and provided greater stress dispersion, which might make it more suitable for facilitating early functional movement and avoiding the failure of internal fixation.
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Fraturas do Fêmur , Fraturas Cominutivas , Fraturas Periprotéticas , Fenômenos Biomecânicos , Placas Ósseas , Fraturas do Fêmur/cirurgia , Fixação Interna de Fraturas , Humanos , Fraturas Periprotéticas/cirurgiaRESUMO
Background: Among the surgical methods for femoral fractures, the Ortho-Bridge System (OBS) appears to heal fractures via an uncommon process. We compared its effectiveness and biomechanical aspects to those of a locking compression plate (LCP) and explained the healing process demonstrated by the OBS. Methods: Eleven femoral shaft fracture cases treated with OBS between July 2017 and May 2020 were retrospectively reviewed. Clinical and radiographic data were collected during regular postoperative follow-up visits and assessed via the Harris Hip Score and Knee Society Score. We performed biomechanical experiments of OBS. We simulated different fracture conditions and selected appropriate screw holes at the fracture's far and near segments. The OBS module was placed according to the position of LCP's locking hole at both ends of the fracture; then, a static three-point bending test was performed. Results: All patients had contralateral callus growth with secondary fracture healing. Healing time was 3-5 months with excellent hip and knee function. When the key screw distance was 22-34 mm, the OBS was significantly less stiff than the LCP (P < 0.05). The stiffness of LCP and OBS decreased significantly when the key screw distance was 49-82 mm, with the LCP being slightly stronger (P < 0.05). Conclusions: Femoral shaft fracture treatment with OBS demonstrated secondary healing. When the distance between the key screws was 20-40 mm, the elasticity was higher in OBS than in LCP, possibly producing axial micro-motion to stimulate callus formation and promote fracture healing, which differ from the plate's primary healing process.
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OBJECTIVE: To explore the role and function of stromal cell-derived factor-1 (SDF-1) in stem cells migrating into injured brain area. METHODS: Rat-derived nerve stem cells (NSCs) were isolated and cultured routinely. Transwell system was used to observe the migration ability of NSCs into injured nerve cells. Immunocytochemistry was used to explore the expression of chemotactic factor receptor-4 (CXCR-4) in NSCs. In vivo, we applied immunofluorescence technique to observe the migration of NSCs into injured brain area. Immunofluorescence technique and Western blotting were used to test expression level of SDF-1. After AMD3100 (a special chemical blocker) blocking CXCR-4, the migration ability of NSCs was tested in vivo and in vitro, respectively. RESULTS: NSCs displayed specific tropism for injured nerve cells or traumatic brain area in vivo and in vitro. The expression level of SDF-1 in traumatic brain area increased remarkably and the expression level of CXCR-4 in the NSCs increased simultaneously. After AMD3100 blocking the expression of CXCR-4, the migration ability of NSCs decreased significantly both in vivo and in vitro. CONCLUSIONS: SDF-1 may play a key role in stem cells migrating into injured brain area through specially combining with CXCR-4.
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Lesões Encefálicas/patologia , Quimiocina CXCL12/fisiologia , Neurônios/citologia , Células-Tronco/fisiologia , Animais , Movimento Celular , Células Cultivadas , Quimiocina CXCL12/análise , Ratos , Receptores CXCR4/análise , Receptores CXCR4/fisiologia , TropismoRESUMO
OBJECTIVE: To promote stem cells differentiation into neurons and enhance neuromotor function after brain injury through brain-derived neurotrophic factor (BDNF) induction. METHODS: Recombinant adenovirus vector was applied to the transfection of BDNF into human-derived umbilical cord mesenchymal stem cells (UCMSCs). Enzyme linked immunosorbent assay (ELISA) was used to determine the secretion phase of BDNF. The brain injury model of athymic mice induced by hydraulic pressure percussion was established for transplantation of stem cells into the edge of injury site. Nerve function scores were obtained, and the expression level of transfected and non-transfected BDNF, proportion of neuron specific enolase (NSE) and glial fibrillary acidic protein (GFAP), and the number of apoptosis cells were compared respectively. RESULTS: The BDNF expression achieved its stabilization at a high level 72 hours after gene transfection. The mouse obtained a better score of nerve function, and the proportion of the NSE-positive cells increased significantly (P<0.05), but GFAP-positive cells decreased in BDNF-UCMSCs group compared with the other two groups (P<0.05). At the site of high expression of BDNF, the number of apoptosis cells decreased markedly. CONCLUSION: BDNF gene can promote the differentiation of the stem cells into neurons rather than glial cells, and enhance neuromotor function after brain injury.
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Lesões Encefálicas/terapia , Fator Neurotrófico Derivado do Encéfalo/genética , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Neurônios/citologia , Adenoviridae/genética , Animais , Apoptose , Lesões Encefálicas/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/análise , Diferenciação Celular , Proteína Glial Fibrilar Ácida , Humanos , Camundongos , Proteínas do Tecido Nervoso/análise , Fosfopiruvato Hidratase/análise , TransfecçãoRESUMO
We describe a novel extracranial (EC)-to-intracranial (IC) bypass technique between the occipital artery and upper posterior circulation (UPC) for revascularization of the posterior circulation through the presigmoid approach. Five formalin-fixed human heads were examined to demonstrate the detailed anatomy of the occipital artery and UPC and illustrate the step-by-step bypass procedure. The occipital artery, a branch of the external carotid artery, can be anastomosed to the P2/P3 segment of the posterior cerebral artery and S1/S2 segments of the superior cerebellar artery as an alternative to EC bypass donor segments for treatment of affection requiring revascularization. Presigmoid approach for the anastomosis of the occipital artery to the UPC provides a shorter distance, due to resection of some bones.
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Revascularização Cerebral/métodos , Anastomose Cirúrgica/métodos , Cadáver , Artéria Carótida Externa/cirurgia , Humanos , Masculino , Procedimentos Neurocirúrgicos/métodos , Artéria Cerebral Posterior/cirurgiaRESUMO
A one-pot protocol for the dearomative double nucleophilic addition to pyridines and quinolines, providing convenient, regioselective and diastereoselective access to tetrahydropyridines and tetrahydroquinolines under reductant-free conditions is described. This method also offers a new strategy for the general dearomatization of nitrogen heteroaromatics.
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Genistein, a potent antioxidant compound, protects dopaminergic neurons in a mouse model of Parkinson's disease. However, the mechanism underlying this action remains unknown. This study investigated human SH-SY5Y cells overexpressing the A53T mutant of α-synuclein. Four groups of cells were assayed: a control group (without any treatment), a genistein group (incubated with 20 µM genistein), a rotenone group (treated with 50 µM rotenone), and a rotenone + genistein group (incubated with 20 µM genistein and then treated with 50 µM rotenone). A lactate dehydrogenase release test confirmed the protective effect of genistein, and genistein remarkably reversed mitochondrial oxidative injury caused by rotenone. Western blot assays showed that BCL-2 and Beclin 1 levels were markedly higher in the genistein group than in the rotenone group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling revealed that genistein inhibited rotenone-induced apoptosis in SH-SY5Y cells. Compared with the control group, the expression of NFE2L2 and HMOX1 was significantly increased in the genistein + rotenone group. However, after treatment with estrogen receptor and NFE2L2 channel blockers (ICI-182780 and ML385, respectively), genistein could not elevate NFE2L2 and HMOX1 expression. ICI-182780 effectively prevented genistein-mediated phosphorylation of NFE2L2 and remarkably suppressed phosphorylation of AKT, a protein downstream of the estrogen receptor. These findings confirm that genistein has neuroprotective effects in a cell model of Parkinson's disease. Genistein can reduce oxidative stress damage and cell apoptosis by activating estrogen receptors and NFE2L2 channels.
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The anti-inflammatory and antioxidant effects of exendin-4 (Ex-4) have been reported previously. However, whether (Ex-4) has anti-inflammatory and antioxidant effects on high-altitude cerebral edema (HACE) remains poorly understood. In this study, two rat models of HACE were established by placing rats in a hypoxic environment with a simulated altitude of either 6000- or 7000-m above sea level (MASL) for 72 hours. An altitude of 7000 MASL with 72-hours of hypoxia was found to be the optimized experimental paradigm for establishing HACE models. Then, in rats where a model of HACE was established by introducing them to a 7000 MASL environment with 72-hours of hypoxia treatment, 2, 10 and, 100 µg of Ex-4 was intraperitoneally administrated. The open field test and tail suspension test were used to test animal behavior. Routine methods were used to detect change in inflammatory cells. Hematoxylin-eosin staining was performed to determine pathological changes to brain tissue. Wet/dry weight ratios were used to measure brain water content. Evans blue leakage was used to determine blood-brain barrier integrity. Enzyme-linked immunosorbent assay (ELISA) was performed to measure markers of inflammation and oxidative stress including superoxide dismutase, glutathione, and malonaldehyde values, as well as interleukin-6, tumor necrosis factor-alpha, cyclic adenosine monophosphate levels in the brain tissue. Western blot analysis was performed to determine the levels of occludin, ZO-1, SOCS-3, vascular endothelial growth factor, EPAC1, nuclear factor-kappa B, and aquaporin-4. Our results demonstrate that Ex-4 preconditioning decreased brain water content, inhibited inflammation and oxidative stress, alleviated brain tissue injury, maintain blood-brain barrier integrity, and effectively improved motor function in rat models of HACE. These findings suggest that Ex-4 exhibits therapeutic potential in the treatment of HACE.
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8-Azacoumarins have emerged as a promising class of compounds but are rarely explored due to challenging access. A novel, general, and practical method is provided for this class of compounds. The key lactonization step employs trans-acrylic acid attached pyridine N-oxides as the starting material, with acetic anhydride as both the activation agent and the solvent. Multiple transformations were involved in this reaction, including conjugate addition, nucleophilic aromatic substitution, and elimination. These studies provide the basis for access to 8-azacoumarins, enabling future work including the discovery and development of novel coumarin-type drugs, fluorescent probes, photolabile protecting groups, and other active molecules.
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Compostos Azo/química , Cumarínicos , Estrutura MolecularRESUMO
The generation of cubicon pulses from an Yb fiber chirped pulse amplification system at pulse energies up to 200 microJ is demonstrated. After pulse compression 650 fs pulses with a pulse energy of 100 microJ are obtained, where pulse compression relies on the compensation of third-order dispersion mismatch between the stretcher and compressor via self-phase modulation of the cubicon pulses in the fiber amplifier. Values of self-phase modulation well in excess of pi can be tolerated for cubicon pulses, allowing for the nonlinear compensation of very large levels of dispersion mismatch between pulse stretcher and compressor.
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Connexin 43 (Cx43) and aquaporin-4 (AQP4) have important roles in the formation of glioma-induced brain edema; however, the association between these two factors in the development of edema has remained to be elucidated. In the present study, immunofluorescence and western blot analysis revealed that in a rat model of intracranial C6 glioma, Cx43 expression levels were low to undetectable and AQP4 expression levels were low in glioma cells. Significantly higher Cx43 and AQP4 levels were detected in the tissue surrounding the glioma. To further investigate the potential interaction between Cx43 and AQP4, normal glial cells and C6 glioma cells were cultured in hypotonic medium. Reverse transcription quantitative polymerase chain reaction indicated that AQP4 and Cx43 mRNA expression levels increased as a function of time in normal glial cells and C6 glioma cells in a hypotonic environment. However, the increase observed in normal glial cells was significantly lower than that observed in C6 glioma cells. Furthermore, AQP4 expression levels changed prior to alterations in Cx43 expression. Following AQP4 silencing in C6 cells, the increase in Cx43 expression was significantly attenuated (P<0.05). In normal cells, Cx43 silencing did not influence AQP4 expression (P>0.05). Therefore, it was hypothesized that AQP4 and Cx43 had two distinct mechanisms underlying brain edema formation within and surrounding the glioma. Cx43 may be a downstream effector of AQP4. The elucidation of this pathway may aid in the development of drugs targeting the interaction between AQP4 and Cx43, providing novel therapeutic possibilities for glioma-induced brain edema.
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Aquaporina 4/metabolismo , Edema Encefálico/etiologia , Neoplasias Encefálicas/patologia , Conexina 43/metabolismo , Glioma/patologia , Animais , Aquaporina 4/antagonistas & inibidores , Aquaporina 4/genética , Edema Encefálico/diagnóstico por imagem , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico por imagem , Linhagem Celular Tumoral , Conexina 43/antagonistas & inibidores , Conexina 43/genética , Glioma/complicações , Glioma/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Camundongos , Interferência de RNA , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Radiografia , Ratos , Ratos Sprague-Dawley , Transplante HeterólogoRESUMO
A dural arteriovenous fistula (DAVF) presenting with parkinsonism and dementia is rare; thus, is easily misdiagnosed. The present study reports the case of a 62-year-old male with mobility disabilities and a cognitive disorder. The initial symptoms were progressive symmetrical limb stiffness and weakness without significant limb tremor, and subsequently the appearance of progressive memory loss, behavioral abnormalities and a decline in the activities of daily living. Cranial magnetic resonance imaging (MRI) revealed an enlarged vascular shadow at the meninges of the left temporal lobe. In addition, digital subtraction angiography (DSA) revealed a DAVF in the left temporal region, fed by the bilateral middle meningeal arteries and meningeal branches of the vertebral artery, which were enlarged abnormally, with poor venous reflux to the superior sagittal sinus. The patient was treated with transarterial embolization therapy. Intraoperative angiography showed almost complete embolization of the DAVF. At day 3 following the surgery, the muscle tension of the bilateral limbs decreased significantly. After two weeks, the memory ability of the patient had recovered to the level prior to the onset, and the gait was stable. At one month post-surgery, the patient was able to take care of himself completely, and after three months, a stereotactic treatment was conducted for the residual fistula. At the one year follow-up, neurological examination revealed that the patient had recovered normally. In conclusion, progressive parkinsonism and dementia with an abnormal flow void shadow on cranial MRI films should be considered as a possible diagnosis of a DAVF. In these cases, DSA and endovascular treatment are recommended as soon as possible.
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Previous studies show that circulating endothelial progenitor cells (EPCs) promote angiogenesis, which is a process associated with improved recovery in animal models of traumatic brain injury (TBI), and that recombinant human erythropoietin (rhEPO) plays a protective role following stroke. Thus, it was hypothesized that rhEPO would enhance recovery following brain injury in a rat model of TBI via an increase in the mobilization of EPCs and, subsequently, in angiogenesis. Flow cytometry assays using CD34- and CD133-specific antibodies were utilized to identify alterations in EPC levels, CD31 and CD34 antibody-stained brain tissue sections were used to quantify angiogenesis, and the Morris water maze (MWM) test and the modified Neurological Severity Score (mNSS) test were used to evaluate behavioral recovery. Compared with saline treatment, treatment with rhEPO significantly increased the number of circulating EPCs on days 1, 4, 7, and 14 (P < 0.05), improved spatial learning ability on days 24 and 25 (P < 0.05), and enhanced memory recovery on day 26 (P < 0.05). Moreover, rhEPO treatment decreased mNSS assessment scores on days 14, 21, and 25 (P < 0.05). There was a strong correlation between levels of circulating EPCs and CD34- and CD31-positive cells within the injured boundary zone (CD34(+) r = 0.910, P < 0.01; CD31(+) r = 0.894, P < 0.01) and the ipsilateral hippocampus (CD34(+) r = 0.841, P < 0.01; CD31(+) r = 0.835, P < 0.01). The present data demonstrate that rhEPO treatment improved functional outcomes in rats following TBI via an increase in the mobilization of EPCs and in subsequent angiogenesis.