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1.
Small ; : e2405525, 2024 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-39479727

RESUMO

Low-cost photovoltaic materials and additive-free, non-halogenated solvent processing of photoactive layers are crucial for the large-scale commercial application of organic solar cells (OSCs). However, high-efficiency OSCs that possess all these advantages remain scarce due to the lack of insight into the structure-property relationship. In this work, three fully non-fused ring electron acceptors (NFREAs), DTB21, DTB22, and DTB23, are reported by utilizing a simplified 1,4-di(thiophen-2-yl)benzene (DTB) core with varied alkoxy chain lengths on the thiophene bridge. The material-only costs of these acceptors are only 11-13$ per gram. Importantly, DTB22 has an exciton diffusion length (LD) of up to 25.5 nm. The DTB21 and DTB23 exhibit decreased LDs of 20.1 and 23.1 nm, respectively. After blending with the polymer donor PBQx-TF, the PBQx-TF:DTB22 film exhibits the fastest hole transfer and the longest carrier recombination lifetime among these OSCs. Consequently, the optimal PBQx-TF:DTB22-based OSC achieves an excellent PCE of 17.00%, which is among the highest values for fully NFREAs. In contrast, the PBQx-TF:DTB21- and PBQx-TF:DTB23-based OSCs show relatively lower PCEs of 15.13% and 15.63%, respectively. Notably, all these OSCs are fabricated using toluene as the solvent, without any additives. Additionally, the DTB22-based OSC also demonstrates good stability, retaining 95% of its initial efficiency after 500 h without encapsulation in a glovebox.

2.
World Neurosurg ; 190: e315-e322, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39059721

RESUMO

OBJECTIVE: Screw loosening is a common complication of pedicle screw internal fixation surgery. This study aimed to investigate whether the application of a porous scaffold structure can increase the contact area between screws and bone tissue by comparing the bone ingrowth and screw-bone interface of porous scaffold core pedicle screws (PSCPSs) and hollow lateral hole pedicle screws (HLHPSs) in the lumbar spine of Bama pigs. METHODS: Sixteen pedicle screws of both types were implanted into the bilateral pedicles of the L1-4 vertebrae of 2 Bama pigs. All Bama pigs were sacrificed and the lumbar spine was freed into individual vertebrae at 16 weeks postoperatively. After the vertebrae were made into screw-centered specimens, micro-computed tomography analysis and histological observation were performed to assess the screw-bone interface and bone growth around and within the screws. RESULTS: We found that the bone condition around PSCPSs and HLHPSs did not show significant differences on micro-computed tomography three-dimensional reconstruction images. CT transverse views showed different bone growth inside the 2 screws. In PSCPSs, bone tissue was seen to fill the internal pores and was evenly distributed around each strut. Inside HLHPSs, bone growth was confined to 1 side of the screw and did not fill the entire cavity. Osteometric analysis showed that bone volume fraction and trabecular number, the parameters representing bone mass, were higher in PSCPSs than in HLHPSs. These differences were not statistically significant (P > 0.05). Histological observations visualized that the osseointegration within PSCPSs was superior to that of HLHPSs, and the tight integration of bone tissue with the porous scaffold resulted in a larger screw-bone integration area in PSCPSs than in HLHPSs. CONCLUSIONS: Compared with HLHPSs, PSCPSs possessing a porous scaffold core could promote bone ingrowth and osseointegration, resulting in an effective enhancement of the combined area of the screw-bone interface.


Assuntos
Vértebras Lombares , Parafusos Pediculares , Microtomografia por Raio-X , Animais , Suínos , Porosidade , Vértebras Lombares/cirurgia , Vértebras Lombares/diagnóstico por imagem , Alicerces Teciduais , Interface Osso-Implante/diagnóstico por imagem
3.
Orthop Surg ; 16(7): 1718-1725, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38766934

RESUMO

OBJECTIVE: Screw loosening is a common complication of internal fixation of pedicle screw. Therefore, the development of a pedicle screw with low loosening rate and high biosafety is of great clinical significance. This study aimed to investigate whether the application of a porous scaffold structure can improve the stability of pedicle screws by comparing the biomechanical properties of novel porous scaffold core pedicle screws (PSCPSs) with those of hollow lateral hole pedicle screws (HLHPSs) in a porcine lumbar spine. METHODS: Thirty-two pedicle screws of both types were implanted bilaterally into the L1-4 vertebrae of four Bama pigs, with our newly designed PSCPSs on the right and HLHPSs on the left. All the Bama pigs were sacrificed 16 weeks postoperatively, and the lumbar spine was freed into individual vertebrae. Biomechanical properties of both the pedicle screws were evaluated using pull-out tests, as well as cyclic bending and pull-out tests, while the mechanical properties were assessed using three-point bending tests. The data generated were statistically analyzed using paired-sample t-tests and two independent sample t-tests. RESULTS: We found that the maximal pull-out forces before and after cyclic bending of the PSCPSs (1161.50 ± 337.98 N and 1075.25 ± 223.33 N) were significantly higher than those of the HLHPSs (948.38 ± 194.32 N and 807.13 ± 242.75 N) (p < 0.05, p < 0.05). In 800 cycles of the bending tests, neither PSCPS nor HLHPS showed loosening or visible detachment, but their maximal pull-out forces after cyclic bending tests decreased compared to those in cycles without cyclic bending tests (7.43% and 14.89%, respectively), with no statistical significance (p > 0.05 and p > 0.05, respectively). Additionally, both screws buckled rather than broke in the three-point bending tests, with no statistically significant differences between the maximal bending load and modulus of elasticity of the two screws (p > 0.05 and p > 0.05, respectively). CONCLUSIONS: Compared with the HLHPSs, the PSCPSs have greater pull-out resistance and better fatigue tolerance with appropriate mechanical properties. Therefore, PSCPSs theoretically have significant potential for clinical applications in reducing the incidence of loosening after pedicle screw implantation.


Assuntos
Vértebras Lombares , Parafusos Pediculares , Animais , Suínos , Fenômenos Biomecânicos , Vértebras Lombares/cirurgia , Porosidade , Teste de Materiais
4.
Orthop Surg ; 15(1): 328-336, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36411506

RESUMO

OBJECTIVE: Although pedicle screws are widely used to reconstruct the stability of the spine, screw loosening is a common complication after spine surgery. The main objective of this study was to investigate whether the application of the hollow lateral hole structure had the potential to improve the stability of the pedicle screw by comparing the biomechanical properties of the novel lateral hole pedicle screws (LHPSs) with those of the solid pedicle screws (SPSs) in beagle dogs. METHODS: The cancellous bone of the distal femur, proximal femur, distal tibia, and proximal tibia were chosen as implantation sites in beagle dogs. In each of 12 dogs, four LHPSs, and four SPSs were implanted into both lower limbs. At 1, 2, and 3 months after surgery, four dogs were randomly sampled and sacrificed. The LHPS group and SPS group were subdivided into four subgroups according to the length of their duration of implantation (0, 1, 2, 3 months). The biomechanical properties of both pedicle screws were evaluated by pull-out and the cyclic bending tests. RESULTS: The results of the study showed that no significant difference was found between LHPSs (276.62 ± 50.11 N) and SPSs (282.47 ± 42.98 N) in pull-out tests at time 0 (P > 0.05). At the same time point after implantations, LHPSs exhibited significantly higher maximal pullout strength than SPSs (month 1: 360.51 ± 25.63 vs 325.87 ± 28.11 N; month 2: 416.59 ± 23.78 vs 362.12 ± 29.27 N; month 3: 447.05 ± 38.26 vs 376.63 ± 32.36 N) (P < 0.05). Moreover, compared with SPSs, LHPSs withstood more loading cycles (month 2: 592 ± 21 vs 534 ± 48 times; month 3: 596 ± 10 vs 543 ± 59 times), and exhibiting less displacement before loosening at month 2 (1.70 ± 0.17 vs 1.96 ± 0.10 mm) and 3 (1.69 ± 0.19 vs 1.92 ± 0.14 mm) (P < 0.05), but no significant difference in time 0 and month 1 (P > 0.05). CONCLUSIONS: The pedicle screw with the hollow lateral hole structure could allow bone to grow into the inner architecture, which improved biomechanical properties by extending the contact area between screw and bone tissue after implantation into the cancellous bone. It indicated that LHPS could reduce loosening of the pedicle screws in long term after surgery.


Assuntos
Parafusos Pediculares , Cães , Animais , Coluna Vertebral , Fenômenos Biomecânicos , Teste de Materiais , Vértebras Lombares/cirurgia
5.
Front Immunol ; 13: 869846, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439158

RESUMO

Objective: In this study, we aimed to explore the alterations in gut microbiota composition and cytokine responses related to disease progression, severity, and outcomes in patients with hypertensive intracerebral hemorrhage (ICH). Methods: Fecal microbiota communities of 64 patients with ICH, 46 coronary heart disease controls, and 23 healthy controls were measured by sequencing the V3-V4 region of the 16S ribosomal RNA (16S rRNA) gene. Serum concentrations of a broad spectrum of cytokines were examined by liquid chips and ELISA. Relationships between clinical phenotypes, microbiotas, and cytokine responses were analyzed in the group with ICH and stroke-associated pneumonia (SAP), the major complication of ICH. Results: In comparison with the control groups, the gut microbiota of the patients with ICH had increased microbial richness and diversity, an expanded spectrum of facultative anaerobes and opportunistic pathogens, and depletion of anaerobes. Enterococcus enrichment and Prevotella depletion were more significant in the ICH group and were associated with the severity and functional outcome of ICH. Furthermore, Enterococcus enrichment and Prevotella depletion were also noted in the SAP group in contrast to the non-SAP group. Enterococci were also promising factors in the prognosis of ICH. The onset of ICH induced massive, rapid activation of the peripheral immune system. There were 12 cytokines (Eotaxin, GM-CSF, IL-8, IL-9, IL-10, IL-12p70, IL-15, IL-23, IL-1RA, IP-10, RANTES, and TNF-α) changed significantly with prolongation of ICH, and the Th2 responses correlated with the 90-day outcomes. Cytokines TNF-α, IP-10, IL-1RA, IL-8, IL-18, and MIP-1ß in SAP group significantly differed from non-SAP group. Among these cytokines, only IP-10 levels decreased in the SAP group. Enterococcus was positively associated with IL-1RA and negatively associated with IP-10, while Prevotella was inversely associated in both the ICH and SAP groups. Conclusion: This study revealed that gut dysbiosis with enriched Enterococcus and depleted Prevotella increased the risk of ICH and subsequently SAP. The altered gut microbiota composition and serum cytokine profiles are potential biomarkers that reflect the inciting physiologic insult/stress involved with ICH.


Assuntos
Microbioma Gastrointestinal , Hemorragia Intracraniana Hipertensiva , Humanos , Proteína Antagonista do Receptor de Interleucina 1 , RNA Ribossômico 16S/genética , Fator de Necrose Tumoral alfa , Quimiocina CXCL10 , Interleucina-8 , Progressão da Doença , Prevotella , Citocinas , Enterococcus , Imunidade
6.
Injury ; 53(3): 1094-1097, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34689988

RESUMO

OBJECTIVE: To explore the clinical characteristics and the short-term efficacy of posterior operation for traumatic lumbar spondylolisthesis. METHODS: All 28 patients (between January 2013 and June 2018) were treated with lumbar pedicle screw fixation combined with posterior intervertebral fusion. The clinical data and imaging materials of these patients were retrospectively analyzed. RESULTS: The mean follow-up period was 24.3 months (12-36 months). The average VAS score and JOA score were significantly improved after surgery, and the difference was statistically significant (P<0.05).The last follow-up X-ray showed that 16 cases were degree 0 and 12 cases were degree I according to Meyerding grading, which were statistically improved compared with preoperative. Postoperative CT indicated lumbar internal fixation well, and the lumbar fusion rate was 100%. The Frankel grading of neurological function was significantly improved compared with preoperative. CONCLUSION: Acute traumatic lumbar spondylolisthesis is caused by severe trauma and mostly occurred at L4/L5 and L5/S1 level. Early posterior reduction, decompression and intervertebral fusion can achieve satisfactory clinical and radiological outcome.


Assuntos
Fusão Vertebral , Espondilolistese , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Fusão Vertebral/métodos , Espondilolistese/diagnóstico por imagem , Espondilolistese/cirurgia , Resultado do Tratamento
7.
BMJ Open ; 9(5): e024932, 2019 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-31076468

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of removing blood stasis (RBS) herbal medicine for the treatment of acute intracerebral haemorrhage (AICH) within a 6-hour time window. STUDY DESIGN: A randomised, multicentre, double-blind, placebo-controlled study performed in 14 hospitals in China. PARTICIPANTS AND INTERVENTIONS: Patients with AICH were randomly assigned to receive a placebo, the ICH-1 (Intracerebral Haemorrhage) formula (eight herbs, including the RBS herbs hirudo and tabanus) or the ICH-2 formula (six herbs without the RBS herbs hirudo and tabanus) within 6 hours of ICH onset. OUTCOMES: The primary safety outcome was the incidence of haematoma enlargement at 24 hours and at 10 days after treatment. The secondary outcome was the incidence of poor prognosis (mortality or modified Rankin Scale score ≥5) assessed at 90 days after symptom onset. RESULTS: A total of 324 subjects were randomised between October 2013 and May 2016: 105 patients received placebo; 108 patients received the ICH-1 formula; and 111 patients received the ICH-2 formula. The incidence of haematoma enlargement at 24 hours was 7.8% in the placebo group, 12.3% in the ICH-1 group and 7.5% in the ICH-2 group; the incidence of haematoma enlargement on day 10 was 1.1% in the placebo group, 1.1% in the ICH-1 group, and 3.1% in the ICH-2 group, with no significant differences among the groups (P>0.05). The mortality rates were 3.8% in the placebo group, 2.8% in the ICH-1 group, and 0.9% in the ICH-2 group; the incidences of poor prognosis were 7.1% in the placebo group, 6.0% in the ICH-1 group and 4.8% in the ICH-2 group at 3 months, with no significant differences among the groups (p>0.05). However, the overall frequency of treatment-emergent adverse events in the ICH-1 group (12.1%) was higher among the three groups (5.8% and 2.8%, respectively, p<0.05). All three cases of serious adverse events were in the ICH-1 group. CONCLUSIONS: Ultra-early administration of ICH-1 formula for AICH patients did not exert significant beneficial effects on clinical outcomes but increased the risk of bleeding, which probably resulted from the inclusion of RBS herbal medicines in ICH-1. TRIALREGISTRATION NUMBER: NCT01918722.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Hemorragia Cerebral , Medicamentos de Ervas Chinesas , Hematoma , Hemorragia , Fitoterapia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/mortalidade , China , Método Duplo-Cego , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/estatística & dados numéricos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/classificação , Feminino , Hematoma/diagnóstico , Hematoma/etiologia , Hematoma/prevenção & controle , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mortalidade , Fitoterapia/efeitos adversos , Fitoterapia/métodos , Tempo para o Tratamento , Resultado do Tratamento
8.
Neuroreport ; 28(14): 910-916, 2017 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-28777258

RESUMO

Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal cell apoptosis. The antisense RNA of brain-derived neurotrophic factor (BDNF-AS) is a natural antisense transcript that is transcribed opposite the gene that encodes BDNF. The aim of this study was to determine whether knockdown of BDNF-AS can suppress hypoxia/reoxygenation (H/R)-induced neuronal cell apoptosis and whether this is mediated by the BDNF-TrkB-PI3K/Akt pathway. We detected the expression of BDNF and BDNF-AS in brain tissue from 20 patients with cerebral infarction and five patients with other diseases (but no cerebral ischemia). We found that BDNF expression was significantly downregulated in patients with cerebral infarction, whereas the expression of BDNF-AS was significantly upregulated. In both human cortical neurons (HCN2) and human astrocytes, H/R significantly induced the expression of BDNF-AS, but significantly decreased BDNF expression. H/R also significantly induced apoptosis and reduced the mitochondrial membrane potential in these cells. Following downregulation of BDNF-AS by siRNA in human cortical neurons and human astrocyte cells, BDNF expression was significantly upregulated and the H/R-induced upregulation of BDNF-AS was significantly attenuated. BDNF-AS siRNA inhibited H/R-induced cell apoptosis and ameliorated the H/R-induced suppression of mitochondrial membrane potential. H/R inhibited the expression of BDNF, p-AKT/AKT, and TrKB, and this inhibition was recovered by BDNF-AS siRNA. In summary, this study indicates that BDNF-AS siRNA induces activation of the BDNF-TrkB-PI3K/Akt pathway following H/R-induced neurotoxicity. These findings will be useful toward the application of BDNF-AS siRNA for the treatment of neurodegenerative diseases.


Assuntos
Apoptose/fisiologia , Isquemia Encefálica/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Encéfalo/metabolismo , RNA Longo não Codificante/metabolismo , Traumatismo por Reperfusão/metabolismo , Astrócitos/metabolismo , Astrócitos/patologia , Encéfalo/patologia , Isquemia Encefálica/patologia , Isquemia Encefálica/terapia , Fator Neurotrófico Derivado do Encéfalo/antagonistas & inibidores , Fator Neurotrófico Derivado do Encéfalo/genética , Células Cultivadas , Técnicas de Silenciamento de Genes , Humanos , Glicoproteínas de Membrana/metabolismo , Potencial da Membrana Mitocondrial/fisiologia , Neurônios/metabolismo , Neurônios/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno , Receptor trkB/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/terapia , Transdução de Sinais
9.
Cancer Cell Int ; 17: 49, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28450809

RESUMO

BACKGROUND: Tumour radiosensitivity would be particularly useful in optimizing the radiation dose during radiotherapy. The aim of the current study was to evaluate the potential value of phosphorylated H2AX (γH2AX) and ATM (pATM) in assessing 12C6+ radiosensitivity of tumour cells. METHODS: Human cervical carcinoma HeLa cells, hepatoma HepG2 cells, and mucoepidermoid carcinoma MEC-1 cells were irradiated with different doses of 12C6+. The survival fraction was assayed with clonogenic survival method and the foci of γH2AX and pATM was visualized using immunocytochemical methods. Flow cytometry was used to assay γH2AX, pATM and the cell cycle. RESULTS: The survival fraction decreased immediately in dose-dependent manner, but in turn, significantly increased during 24 h after 12C6+ irradiation. Both γH2AX and pATM foci accumulated linearly with doses and with a maximum induction at 0.5 h for γH2AX and 0.5 or 4 h for pATM, respectively, and a fraction foci kept for 24 h. The expression of γH2AX and pATM was in relation to cell cycle. The G0/G1 phase cells had the highest expression of γH2AX after 0.5 h irradiation and then decreased to a lower level at 24 h after irradiation. An obvious increase of pATM in G2/M phase was shown after 24 h of 2 and 4 Gy irradiation. The significant G2/M phase arrest was shown. There was a close relationship between the clonogenic survival and γH2AX and pATM expression both in timing and dose in response to 12C6+. CONCLUSIONS: The rate of γH2AX and pATM formation and loss may be an important factor in the response of cells to 12C6+. pATM and γH2AX are effective radiation biomarkers in assessing the radiosensitivity of 12C6+ in human tumor cells.

10.
Infect Agent Cancer ; 12: 8, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28138337

RESUMO

BACKGROUND: The mortality of cervical cancer in Longnan is as high as 39/10 million, ranking first in China. METHODS: Between 2012 to 2016, 329 samples with cervicitis, cervical intraepithelial neoplasia grade 1 to 3 (CINI to III), and invasive squamous cell carcinoma (SCC) were collected. HPV genotypes were examined with a validated kit for 23 different HPV subtypes. RESULTS: Compared to cervicitis, the HPV positivity is significantly higher in CINI, CIN II/III, and SCC (38.60%, 74.60%, 87.50% and 89.05%, P < 0.001) and the positivity is also higher in SCC compared to CINI (P < 0.01). The most frequently detected genotypes were HPV16 in cervicitis, HPV16, 58 and 52 in CINI and CIN II/III, and HPV16, 58 and 18 in SCC groups. HPV16 positivity in cervicitis, CINI, CIN II/III, and SCC patients were 45.46%, 46.81%, 60.32% and 78.69%, respectively. Compared to cervicitis and CINI, the odds ratios (OR) for SCC in HPV16 positive patients were 2.96 (95% confidence interval [CI]: 1.09-8.00, P < 0.05) and 4.20 (95% confidence interval [CI]: 2.05-8.61, P < 0.001), respectively. In addition, the multiple infections in cervicitis, CINI, CINII/III and SCC group are 9.09%, 27.66%, 26.98% and 25.41% and HPV16 + 58 was the most common combinations. CONCLUSION: These findings highlight the key role of HPV16, 58, 52 and 18 in the development of CIN and SCC in Longnan women and a fully aware of regional differences in HPV genotype distribution are tasks for cervical cancer control and prevention.

11.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(7): 821-826, 2016 07.
Artigo em Chinês | MEDLINE | ID: mdl-30634209

RESUMO

OBJECTIVE: To study the safety of using Chinese drugs for breaking blood expelling stasis (CDBBES) in hypertension patients with intracerebral hemorrhage within 6 h, and to observe whether they would result in hematoma enlargement. METHODS: A prospective randomized double-blind controlled clinical study was employed. Totally 128 cerebral hemorrhage patients within 6 h were recruited from 8 research centers from October 2013 to March 2015, and finally 76 of them were included. These patients were assigned to 3 groups by simple random sampling, group A, B, and C. Patients in group A (26 cases) took whole CDBBES recipe (containing leeches and equivalent insects). Those in group B (25 cases) took CDBBES recipe (removing leech and gradfly). Those in group C (25 cases) took placebos. Medication lasted for 10 successive days. The hematoma enlargement rate within 24 h, the occurrence of adverse reactions and adverse events were observed. To guarantee the safety of this trial, an interim analysis of first level unblinding was used. RESULTS: The hematoma enlargement rate was 11. 5% (3/26) in group A, 16. 0% (4/25) in group B, and 20. 0% (5/25) in group C. There was no statistical difference in the hematoma enlargement rate among the 3 groups (X² =0. 823, P =0. 682). Adverse reactions and adverse events occurred in 7 cases, 1 patient with acute myocardial infarction, 1 with chest op- pression and palpitation, 2 with diarrhea in group A. No patient had adverse reaction or adverse event in group B. And diarrhea occurred in 3 patients of group C. CONCLUSION: The interim analysis of first level unblinding showed that hematoma enlargement within 6 h was not resulted from using CDBBES.


Assuntos
Hemorragia Cerebral , Hematoma , Hipertensão , Medicina Tradicional Chinesa , Hemorragia Cerebral/tratamento farmacológico , Método Duplo-Cego , Hematoma/tratamento farmacológico , Humanos , Hipertensão/complicações , Estudos Prospectivos
12.
Mol Med Rep ; 13(2): 1427-33, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26648565

RESUMO

NogoA is a myelin­associated protein, which is important in the inhibition of axonal fiber growth and in regeneration following injury of the mammalian central nervous system. A previous study suggested that NogoA may be key in the process of Parkinson's disease (PD), which is the second most common chronic neurodegenerative disorder worldwide. The regulatory mechanism underlying the effect of NogoA on the process of PD remains to be fully elucidated. The present study aimed to investigate the effect and underlying mechanism of NogoA on cellular viability, apoptosis and autophagy induced by 1-methyl-4-phenylpyridinium (MPP+) in PC12 cells, a commonly used in vitro PD model. PC12 cells were treated with 1 mM MPP+ for 24 h and the cells were harvested for western blotting. The results demonstrated that the protien expression levels of NogoA were increased in the PC12 cells treated with MPP+. Subsequently, NogoA small interfering RNA was synthesized and transfected into PC12 cells to silence the expression of NogoA. NogoA knockdown significantly reduced the MPP+­induced decrease in cell viability and apoptosis, detected using a cell counting kit­8 and flow cytometric analysis, respectively. Interference in the expression of NogoA increased the MPP+­induced decrease in mitochondrial membrane potential, determined quantitatively by flow cytometry using JC-1 dye, and the protein levels of Beclin­1. In addition, MPP+ treatment activated the mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Knockdown of NogoA significantly inhibited the expression levels of mTOR and STAT3. Furthermore, overexpression of NogoA had similar neurotoxic effects on the PC12 cells as MPP+ treatment. Treatment with rapamycin, an inhibitor of the mTOR/STAT3 signaling pathway had a similar effect to that of NogoA knockdown in the MPP+­treated PC12 cells. Taken together, the results from the present study demonstrated that NogoA may regulate MPP+­induced neurotoxicity in PC12 cells via the mTOR/STAT3 signaling pathway and provided an explanation regarding the regulatory mechanism of NogoA on the process of PD.


Assuntos
1-Metil-4-fenilpiridínio/toxicidade , Técnicas de Silenciamento de Genes , Proteínas da Mielina/metabolismo , Neurotoxinas/toxicidade , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia/efeitos dos fármacos , Proteína Beclina-1 , Sobrevivência Celular , Proteínas Ligadas por GPI/metabolismo , Inativação Gênica/efeitos dos fármacos , Proteínas Nogo , Receptor Nogo 1 , Células PC12 , Ratos , Receptores de Superfície Celular/metabolismo , Sirolimo/farmacologia
13.
Biomed Res Int ; 2015: 817914, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26583134

RESUMO

Parkinson's disease (PD) is a common degenerative disease that lacks efficient treatment. Myelin-associated neurite outgrowth inhibitor A (Nogo-A) is relevant with inhibition of nerve regeneration and may play vital role in pathogenesis of PD. The study aimed to establish the shRNA expression plasmids of Nogo-A gene and explore the regulatory effects of Nogo-A silencing on the expression of inflammation factor tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) as well as tyrosine hydroxylase (TH) in lipopolysaccharide- (LPS-) stimulated rat PC12 cells. The results showed that both mRNA and protein levels of Nogo-A in pGenesil-nogoA-shRNA group were downregulated. The viabilities of PC12 cells decreased with increase of LPS concentrations. LPS significantly increased the supernatant TNF-alpha and IL-6 concentrations and reduced TH protein expression in PC12 cells, while silencing Nogo-A could block these effects. These results suggested that LPS can activate PC12 cells to secrete inflammatory cytokines and lower the TH expression, which can be regulated by Nogo-A gene silencing. Nogo-A silencing might provide new ideas for PD treatment in the future.


Assuntos
Inflamação/genética , Interleucina-6/metabolismo , Proteínas da Mielina/genética , Doença de Parkinson/genética , Fator de Necrose Tumoral alfa/metabolismo , Tirosina 3-Mono-Oxigenase/biossíntese , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Humanos , Inflamação/induzido quimicamente , Inflamação/patologia , Interleucina-6/genética , Lipopolissacarídeos/toxicidade , Proteínas da Mielina/antagonistas & inibidores , Regeneração Nervosa/genética , Proteínas Nogo , Células PC12 , Doença de Parkinson/patologia , Doença de Parkinson/terapia , RNA Mensageiro/biossíntese , Ratos , Fator de Necrose Tumoral alfa/genética , Tirosina 3-Mono-Oxigenase/genética
14.
J Ethnopharmacol ; 149(1): 352-9, 2013 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-23850708

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Danhong injection (DHI), a Chinese Materia Medica standardized product extracted from Radix et Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Labiatae, Danshen in Chinese) and Flos Carthami (Carthamus tinctorius L., Compositae, Honghua in Chinese), has been reported to have anti-inflammatory, anti-oxidative and anti-fibrinolytic properties, which is used extensively for the treatment of cardiovascular diseases in clinic. AIM OF THIS STUDY: The present study aimed to investigate the preventive and therapeutic effects of DHI on lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice. MATERIALS AND METHODS: Lung injury was induced by intranasal instillation with 10 µg LPS. Mice were randomly divided into four groups: Control group; LPS group; LPS+5 ml/kg DHI group and LPS+10 ml/kg DHI group. The effects of DHI on LPS-induced neutrophils influx, inflammatory cytokines release, protein leakage, myeloperoxidase (MPO) and superoxide dismutase (SOD) activities, malondialdehyde (MDA) level were examined. In addition, the NF-κB activation in lung tissues was detected by Western blot. RESULTS: In LPS challenged mice, DHI significantly reduced the infiltration of activated neutrophils and decreased the levels of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF). DHI also inhibited protein extravasation in BALF, attenuated edema and the pathological changes in the lung. In addition, DHI markedly prevented LPS-induced elevation of MDA and MPO levels, as well as reduction of SOD activity. Further study demonstrated that DHI effectively inhibited the NF-κB activation in lung tissues. CONCLUSION: DHI has been demonstrated to protect mice from LPS induced acute lung injury by its anti-inflammatory and anti-oxidant activities.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Etnofarmacologia , Pulmão/efeitos dos fármacos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/patologia , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , China , Citocinas/imunologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Injeções Intraperitoneais , Lipopolissacarídeos/farmacologia , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Infiltração de Neutrófilos/efeitos dos fármacos , Tamanho do Órgão , Edema Pulmonar/imunologia , Edema Pulmonar/patologia , Edema Pulmonar/prevenção & controle
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