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1.
World Neurosurg ; 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31442642

RESUMO

BACKGROUND: There are no standardized criteria to predict the prognosis of patients with low-grade gliomas. Therefore, novel prognostic biomarkers that can guide follow-up schedules and therapeutic approaches are urgently required in patients with low-grade gliomas. METHODS: One hundred and nineteen patients with World Health Organization (WHO) II gliomas were recruited between January 2010 and December 2016 from Xiangya Hospital for this study. We collected neutrophil and lymphocyte values from the full blood counts measured 24 h before surgery. Neutrophil-to-lymphocyte ratios (NLRs) were then calculated. The significance of the NLR was determined based on a nonparametric test. The Kaplan-Meier method was used to estimate survival rates. The influence of the NLR on progression-free survival (PFS) and overall survival (OS) was evaluated using univariate and multivariate Cox proportional hazards models. RESULTS: Preoperative NLRs were upregulated in patients with WHO II gliomas who relapsed or died. Preoperative NLRs were also significantly correlated with age, preoperative neutrophil values, and preoperative lymphocyte values. Compared with the low preoperative NLR group, patients with WHO II gliomas in the high preoperative NLR group had significantly higher relapse and lower survival rates. Additionally, the preoperative NLR and tumor type were independent prognostic parameters of PFS for WHO II gliomas, while only the preoperative NLR was an independent prognostic parameter of OS for WHO II gliomas. CONCLUSIONS: High preoperative NLRs were significantly associated with greater relapse and poor prognosis in patients with WHO II gliomas.

2.
Med Sci Monit ; 25: 6281-6290, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31432800

RESUMO

The anterior transpedicular screws (ATPS) fixation is a valuable discovery in the field of lower cervical spine (LCS) reconstruction, as it has the advantages of both anterior and posterior approaches. In recent years, with in-depth research on ATPS fixation related to anatomy, biomechanical tests, and clinical applications, its firm stability and excellent biomechanical properties have been recognized by more and more surgeons. Although ATPS fixation has been gradually applied in clinic settings under the promotion of emerging distinctive instruments, its long-term efficacy still needs to be further clarified due to the lack of large sample size studies and long-term follow-up. Nevertheless, it is believed that with the maturity of digital devices and the development of precision medicine, ATPS fixation has a promising prospect.

3.
Oncogene ; 38(35): 6270-6282, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31316145

RESUMO

The involvement of mammalian target of rapamycin (mTOR) in the positive regulation of oncogenesis has been well documented and thus mTOR has emerged as an attractive cancer therapeutic target. Although rapamycin and its analogues (rapalogs) are FDA-approved for the treatment of certain cancers, major success in targeting mTOR, particularly with new generation mTOR kinase inhibitors, for the effective treatment of cancers has not been achieved. Hence, a thorough understanding of the biology of the mTOR axis in cancer is still needed. It is now recognized that programmed death-ligand 1 (PD-L1) expression on cancer cells is a critical mechanism contributing to immunosuppression and immune escape via interacting with program death-1 (PD-1) on immune cells. This study has revealed a previously undiscovered role of the mTOR complex 1 (mTORC1)/p70 S6 kinase (p70S6K) in the negative regulation of PD-L1 on cancer cells and tissues. We demonstrate that disruption of this signaling pathway with mTOR inhibitors, raptor knockdown or p70S6K inhibitors elevated PD-L1 levels in some lung and other cancer cell lines. Elevation of PD-L1 by inhibition of mTORC1/p70S6K signaling is likely due to suppression of ß-TrCP-mediated proteasomal degradation of PD-L1, because inhibition of either mTORC1 or p70S6K facilitated ß-TrCP degradation accompanied with enhanced PD-L1 protein stabilization. Our current findings indicate the complexity of the mTOR axis in cancer, which should be considered when targeting this axis for effective cancer treatment. Our findings also suggest a strong scientific rationale for enhancing PD-1/PD-L1-targeted cancer immunotherapy through co-targeting mTORC1/p70S6K signaling.

4.
Gene ; 710: 114-121, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31153885

RESUMO

Mastitis impairs animal health and results in economic loss. Lipopolysaccharide (LPS) may cause immune response and inflammation in the bovine mammary gland. Hydrogen sulfide (H2S) is the third gasotransmitter that acts as an anti-inflammation regulator in many cells. Despite the importance of H2S in regulating inflammation, the effect and mechanism of exogenous H2S on LPS-induced inflammation in bovine mammary epithelial cells are unknown. In the present study, with NaHS as a donor of H2S, the bovine mammary epithelial cell line (MAC-T) was applied as an in vitro model to study the role of H2S on LPS-induced MAC-T cells. The results verified that the cell viability was diminished by LPS but restored by exogenous H2S at a physiologically relevant concentration (10 µM). Additionally, the production of H2S was mitigated in the LPS-induced MAC-T cells. Meanwhile, exogenous H2S decreased the intracellular ROS production and mRNA expression levels of the pro-inflammatory cytokines, TNF-α, IL-1ß, IL-8, and IL-6. Furthermore, exogenous H2S inhibited the mRNA expression of TLR4 and activation of NF-κB signaling pathway. In summary, exogenous H2S exerts anti-inflammatory effects through attenuating oxidative stress and blocking the TLR4/NF-κB pathway in the LPS-induced bovine mammary epithelial cells. Our findings might clarify new prophylactic approaches for mastitis.


Assuntos
Anti-Inflamatórios/farmacologia , Sulfeto de Hidrogênio/farmacologia , Lipopolissacarídeos/efeitos adversos , Glândulas Mamárias Animais/citologia , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Bovinos , Linhagem Celular , Citocinas/genética , Regulação para Baixo , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Glândulas Mamárias Animais/efeitos dos fármacos , Glândulas Mamárias Animais/imunologia , NF-kappa B/genética , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
5.
World Neurosurg ; 129: e821-e830, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31203058

RESUMO

BACKGROUND: Lactate dehydrogenase (LDH) is a nonspecific inflammatory biomarker and has been reported to be useful in predicting community-acquired pneumonia and Mycoplasma pneumoniae pneumonia. The connection between LDH level and postoperative pneumonia (POP) in patients with aneurysmal subarachnoid hemorrhage (aSAH) is still unclear. The aim of this study was to assess feasibility of predicting POP in patients with aSAH using LDH. METHODS: Admission serum LDH level was obtained in 647 patients with aSAH enrolled in a prospective observational study. The relationship between LDH level and POP was analyzed. RESULTS: POP occurred in 187 patients (28.90%). Patients with POP had significantly higher LDH levels than patients without POP (261.26 ± 126.51 U/L vs. 189.00 ± 69.20 U/L, P < 0.001). Multivariate analysis showed that LDH level remained a significant independent factor associated with POP in patients with aSAH, even after adjusting for possible confounding factors. Receiver operating characteristic curve analysis showed that LDH level had a sensitivity of 63.6% and a specificity of 71.3% for predicting POP based on best threshold of 203.5 U/L. There were additive interactions between elevated LDH level and World Federation of Neurosurgical Societies grade or mechanical ventilator use. When patients were classified by World Federation of Neurosurgical Societies grade or mechanical ventilator use, regardless of World Federation of Neurosurgical Societies grade (

6.
Med Sci Monit ; 25: 4233-4243, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31172985

RESUMO

BACKGROUND This study aimed to retrospectively assess the feasibility and efficacy of three-dimensional (3D) printing technology in the treatment of high-energy trans-syndesmotic ankle fracture dislocation - "log-splitter" injury - and to evaluate the efficacy and prognosis. MATERIAL AND METHODS We included 29 patients (17 males and 12 females; mean age, 44.0±13.2 years) with log-splitter injury from June 2011 to December 2016, divided into a routine group (n=13) and a 3D printing group (n=16) according to the surgical method used. Operation time, intraoperative blood loss, fluoroscopy times, fracture union time, functional outcomes based on AOFAS (American Orthopedic Foot and Ankle Society) score, and postoperative complications were observed and recorded. RESULTS Compared with the routine treatment group, 3D printing technology had better safety and efficacy for the treatment of log-splitter injury and the advantages of shorter operation time, less intraoperative blood loss, fewer fluoroscopies needed, and higher rate of good functional outcome (P<0.001, P<0.001, P<0.001, and P=0.017, respectively). However, no significant difference was noted in the rate of anatomical reduction, mean AOFAS score at the last follow-up (mean time, 19.9±2.8 months), or postoperative complications between the 2 groups (P=0.370, P=0.156, and P=0.485, respectively). CONCLUSIONS Surgery assisted by 3D printing technology to treat log-splitter injury is feasible and effective, and may be a good optional approach to formulate a reasonable personalized surgical plan and to optimize the outcomes.

7.
Stroke ; 50(7): 1887-1890, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31182001

RESUMO

Background and Purpose- Hypoxic-ischemic brain damage is a well-recognized physiopathologic mechanism after aneurysmal subarachnoid hemorrhage (aSAH). The Ngb (neuroglobin) is a hemoprotein predominantly expressed in the brain with a high affinity for oxygen. Relationship between serum Ngb level and brain metabolism in aSAH patients has not been investigated previously. Methods- Thirty-six consecutive severe aSAH patients (Glasgow Coma Scale score ≤8 on admission) with multimodal neuromonitoring and 36 matched healthy subjects were included. Serum Ngb level was analyzed in combination with other time-matched cerebral microdialysis parameters, brain tissue oxygen tension, and 12-month neurological outcomes. Results- Serum Ngb level was correlated positively with cerebral microdialysis parameters and brain tissue oxygen tension ( P<0.001). Poor functional outcome (modified Rankin Scale score >3) 12 months after aSAH was associated with higher Ngb level but independent of age, sex, and disease severity ( P<0.001). A similar association was found between high Ngb level and neuropsychological test results indicative of impairments in cognition, visual conceptualization, and frontal executive functions ( P<0.001). Conclusions- Ngb may be a potential biomarker for reflecting brain tissue oxygen tension, brain metabolism, and functional outcome in severe aSAH patients and merits further study in the context of aSAH.

8.
J Am Chem Soc ; 141(19): 7731-7735, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31042868

RESUMO

The reactions of nitrosoarenes with transition-metal species are fundamentally important for their relevance to metal-catalyzed transformations of organo-nitrogen compounds in organic synthesis and also the metabolization of nitroarenes and anilines in biology. In addition to the well-known reactivity of metal-mediated N-O bond activation and cleavage of nitrosoarenes, we present herein the first observation of a nitrosoarene C-N bond oxidative addition reaction upon the interaction of a three-coordinate cobalt(0) species [(IPr)Co(vtms)2] with 2,4,6-tri( tert-butyl)-1-nitroso-benzene (Ar*NO). The reaction produces a cobalt nitrosyl aryl complex, [(IPr)Co(Ar*)(NO)] (1), with a bis(nitrosoarene)cobalt complex, [(IPr)Co(η2-ONAr)(κ1- O-ONAr)] (2), as an intermediate. Spectroscopic characterizations, DFT calculations, and kinetic studies revealed that the redox non-innocence of nitrosoarene induces a stepwise pathway for the C-N bond oxidative addition reaction.

9.
Yonsei Med J ; 60(6): 585-591, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31124343

RESUMO

PURPOSE: The aim of this study was to explore the function of microRNA-27b (miR-27b) in fibroblast-like synoviocytes (FLSs) stimulated by tumor necrosis factor α (TNF-α). MATERIALS AND METHODS: mRNA expression of miR-27b in FLS cells (MH7A) treated with or without TNF-α was determined by q-PCR. MiR-27b mimics was transfected into MH7A cells to upregulate miR-27b expression. MTT assay and flow cytometry analysis were performed to investigate the effect of miR-27b on MH7A cell viability and apoptosis. The targets of miR-27b were predicted by TargetScan. The direct regulation of miR-27b on IL-1ß expression was verified by luciferase assay. The protein expression levels of apoptosis-related proteins, IL-1ß, and NF-κB signaling-related proteins were detected by Western blot. RESULTS: We discovered that miR-27b expression was decreased in MH7A cells stimulated by TNF-α. Upregulation of miR-27b by miR-27b mimics significantly inhibited the proliferation and promoted the apoptosis of TNF-α-stimulated MH7A cells. Consistently, upregulation of miR-27 decreased the level of Bcl-2 and increased Bax and caspase-3 expression in MH7A cells stimulated by TNF-α. Luciferase assay revealed that IL-1ß was indeed a target of miR-27b. By quantitative real-time PCR and Western blot, we found that the expression of IL-1ß is negatively regulated by miR-27b. Moreover, the NF-κB signaling pathway was significantly inhibited by miR-27b. CONCLUSION: Taken together, our results illustrated that enhanced miR-27b expression results in the suppression of proliferation and the promotion of apoptosis in FLSs stimulated by TNF-α, partially by regulating IL-1ß expression and NF-κB signaling.


Assuntos
Apoptose , Fibroblastos/patologia , MicroRNAs/genética , Sinoviócitos/patologia , Fator de Necrose Tumoral alfa/farmacologia , Regulação para Cima/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Sequência de Bases , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , MicroRNAs/metabolismo , NF-kappa B/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sinoviócitos/efeitos dos fármacos , Sinoviócitos/metabolismo , Regulação para Cima/efeitos dos fármacos
10.
Biosci Rep ; 39(6)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31092699

RESUMO

Introduction: The treatment strategy for low-grade gliomas (LGGs) is still controversial, and there are no standardized criteria to predict the prognosis of patients with LGGs. Magnetic resonance imaging (MRI) is a routine test for preoperative diagnosis for LGG and can reflect the destructive features for the tumor. In the present study, we aimed to explore the relationship between the MRI features and prognosis in patients with LGG.Methods: Clinical data of 80 patients with pathologically proved LGGs between January 2010 and December 2016 were analyzed retrospectively. MRI features were classified as contrast enhancement pattern (focal enhancement, diffuse enhancement and ring-like enhancement), necrosis and cysts based on the preoperative MR images. Kaplan-Meier method and multivariate analysis were performed on the data by SPSS software to explore the prognostic significance of MRI features.Results: Patients with cystic LGG had a significantly longer 5-year progression-free survival (PFS) than that with no cyst (90.9 ± 8.7 vs 65.7 ± 9.1%, P=0.045). Multivariate analysis further verified cyst as an independent prognosis factor for PFS (P=0.027, hazard ratio [HR] = 0.084). Additionally, patients with ring-like enhancement exhibited significantly longer 5-year PFS time in the Kaplan-Meier survival curves (100 vs 67.2 ± 7.7%, P=0.049). There was no significant difference in PFS and overall survival (OS) between patients with or without necrosis.Conclusion: Our study suggests that cyst formation and ring-like enhancement on preoperative MR images can be useful to predict a favorable prognosis in patients with LGGs.

11.
Huan Jing Ke Xue ; 40(5): 2357-2367, 2019 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-31087877

RESUMO

Four laboratory-scale autotrophic nitrogen removal bioreactors were implemented to investigate performance differences and microbial mechanisms under different temperatures (30, 25, 20, and 15℃). The results showed that the reactor performance under 30℃ was higher than others. When the temperature decreased from 30℃ to 25℃, total nitrogen removal efficiency reduced from 73% to 66%, and total nitrogen removal rate from 2.29 kg·(m3·d)-1 to 1.72 kg·(m3·d)-1. The morphology and particle size of the sludge did not change significantly (SMD:from 80.85 µm to 79.95 µm). When the temperature was 20℃, the total nitrogen removal efficiency reduced to 42%, the total nitrogen removal rate reduced to 1.18 kg·(m3·d)-1, and the sludge disintegration phenomenon occurred with particle size reduction (SMD:63.21 µm). When the temperature was 15℃, the total nitrogen removal efficiency reduced to 37%, and the total nitrogen removal rate got as low as 1.00 kg·(m3·d)-1. In addition to that, the reactor operation was difficult. The analysis of microbial community structure showed that the influence of temperature on anaerobic ammonia oxidizing bacteria is greater than that on ammonia oxidizing bacteria. This sensitivity to temperature of the anaerobic ammonia oxidizing bacteria was the main reason for the decreased performance under low temperature conditions.


Assuntos
Desnitrificação , Microbiota , Nitrogênio/isolamento & purificação , Temperatura Ambiente , Águas Residuárias , Anaerobiose , Animais , Processos Autotróficos , Reatores Biológicos/microbiologia , Oxirredução , Esgotos/microbiologia , Suínos
12.
Inorg Chem ; 58(11): 7634-7644, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31083985

RESUMO

Iron terminal imido species are typically implicated as reaction intermediates in iron-catalyzed transformations. While a large body of work has been devoted to mid- and high-valent iron imidos, to date the chemistry of iron(II) imidos has remained largely unexplored due to the difficulty in accessing them. Herein, we present a study on the two-coordinate iron(II) imido complex [(IPr)Fe(NArTrip)] (3; IPr = 1,3-bis(2',6'-diisopropylphenyl)imidazol-2-ylidene; ArTrip = 2,6-bis(2',4',6'-triisopropylphenyl)phenyl) prepared from the reaction of an iron(0) complex with the bulky azide ArTripN3. Spectroscopic investigations in combination with DFT calculations established a high-spin S = 2 ground spin state for 3, consistent with its long Fe-N multiple bond of 1.715(2) Å revealed by X-ray diffraction analysis. Complex 3 exhibits unusual activity of nitrene transfer and C-H bond activation in comparison to the reported iron imido complexes. Specifically, the reactions of 3 with CH2═CHArCF3, an electron-deficient alkene, and CO, a strong π acid, readily afford nitrene transfer products, ArCF3CH═CHNHArTrip and ArTripNCO, respectively, yet no similar reaction occurs when 3 is treated with electron-rich alkenes and PMe3. Moreover, 3 is inert toward the weak C(sp3)-H bonds in 1,4-cyclohexadiene, THF, and toluene, whereas it can cleave the stronger C(sp)-H bond in p-trifluoromethylphenylacetylene to form an iron(II) amido alkynyl complex. Interestingly, intramolecular C(sp3)-H bond functionalization was observed by adding ( p-Tol)2CN2 to 3. The unique reactivity of 3 is attributed to its low-coordinate nature and the high negative charge population on the imido N atom, which render its iron-imido unit nucleophilic in nature.

13.
Comput Methods Programs Biomed ; 175: 1-7, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31104698

RESUMO

BACKGROUND AND OBJECTIVE: Periodically rotated overlapping parallel lines with enhanced reconstruction-echo planar imaging (PROPELLER-EPI) is a promising technique for non-sedated functional imaging due to its unique advantage of motion correction. However, its multiple-blades sampling blood-oxygen-level dependent (BOLD) signal leads to low sampling rate and aliasing of higher frequency physiological signal components such as the cardiac pulsation. METHODS: In this study, we use near infrared spectroscopy (NIRS) synchronized with pulse sequences of PROPELLER-EPI, utilizing the fact that the optical sensing speed is inherently high. NIRS measures changes of oxyhemoglobin and deoxyhemoglobin to identify the transient states of on-BOLD and off-BOLD, and then labels each blade by temporal co-registration. The labeled blades from multiple epochs of a functional experiment are then used for the k-space data combination and subsequent image reconstruction. An eigenfunction model is proposed for temporal co-registration and to quantify the temporal resolution of the hemodynamic response. RESULT: The experiment of NIRS labeled PROPELLER-EPI was carried out with the optical sampling rate of 10 Hz and the magnetic pulses repetition time of 1000 ms, and the temporal resolution is 20 times better than that of the state-of-the-art sliding-window PROPELLER-EPI. We compared the functional imaging results against the conventional magnetic resonance echo planar imaging-measured activity and achieved an accuracy of 0.9. CONCLUSIONS: Using the synchronization of NIRS, the proposed imaging scheme provides an effective way to implement PROPELLER-EPI, which features motion free, high SNR, and enhanced spatial-temporal resolution.

14.
Reprod Domest Anim ; 54(7): 972-978, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31025395

RESUMO

Follicular cysts, which is a common infertility disease, can cause financial losses in pig breeding programmes. The pathogenesis and mechanisms of the formation of follicular cysts are not understood clearly. In our previous study, the concentration of retinol-binding protein 4 (RBP-4) in the follicular fluid (FF) of the ovary with follicular cysts was found to be significantly higher than that of normal ovary, thereby suggesting that RBP-4 may be a candidate biomarker for porcine follicular cysts. To study the association of RBP-4 and follicular cysts further, we detected the polymorphisms of the RBP-4 gene and the presence of follicular cysts by PCR-Restriction fragment length polymorphism (RFLP) assay. In this study, we screened the mutations of RBP-4 gene in 79 sows with follicular cysts and 100 normal sows without cysts. Results showed that +249-63G>C polymorphisms were significantly associated with follicular cysts, and sows with CC genotype in RBP-4 gene had a high risk of developing follicular cysts. Hence, our findings further proved that RBP-4 may be a novel biomarker for follicular cysts, which may be valuable for the diagnosis of follicular cysts and molecular breeding of pigs.

15.
World Neurosurg ; 127: 25-30, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30947015

RESUMO

BACKGROUND: Cervical tuberculosis accounts for only 4.2%-12% of the total incidence of spinal tuberculosis cases. Although antituberculosis drugs have been the mainstay treatment of cervical tuberculosis, they have been ineffective against the symptoms of existing spinal deformities and spinal cord compression, which often require surgical intervention. The conventional surgical methods have been anterior debridement and titanium mesh, cage bone graft fusion and internal fixation. However, all have certain deficiencies regarding the stability of fixation. CASE DESCRIPTION: We have presented the case of a 41-year-old Chinese man who had been experiencing neck pain and stiffness for 1 month. The symptoms had been accompanied by low-grade fever and repeated night sweats. The purified protein derivative test result was positive and the antituberculosis test result was negative. Imaging examination showed destruction of the C5 and C6 vertebral bodies and C5 andC6 intervertebral discs, with an intensive abscess at the C5-C6 vertebral level. After 3-dimensional printing-assisted anterior debridement and artificial vertebral body replacement, his preoperative symptoms of neck pain and stiffness had been alleviated. Also, his symptoms of numbness in both upper limbs had disappeared completely. At the last follow-up examination, he had recovered well and the tuberculosis focus had been completely cured. CONCLUSION: To the best of our knowledge, we have reported the first clinical application of 3-dimensional printing-assisted cervical anterior bilateral pedicle screw fixation of an artificial vertebral body. We accomplished ultrashort segment fixation, with excellent clinical outcomes obtained, which were maintained at the recent 2-year follow-up examination.

16.
World Neurosurg ; 127: e1237-e1241, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31009781

RESUMO

OBJECTIVE: We tested the hypothesis that low hemoglobin levels are associated with acute seizures after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Patients with ruptured intracranial aneurysms were enrolled in the observational cohort study that prospectively collected age, sex, symptom onset, history of diabetes and hypertension, history of coronary artery disease, temperature, Hunt-Hess grade, Fisher grade, aneurysm location, hemoglobin, hematocrit, serum potassium, sodium, calcium, phosphorus, iron, and modified Rankin Scale. Acute seizures were determined as seizures within 1 week after aSAH. RESULTS: We included 554 patients with requisite data for analysis in the prospective study. Incidence of acute seizures following aSAH was 3.61%. In the univariate analysis, significant differences were detected in admission Hunt-Hess grade, Fisher grade, hemoglobin, and serum iron between epilepsy and nonepilepsy groups. Furthermore, acute seizures were associated with higher modified Rankin Scale score and poor outcome (P = 0.004). Serum hemoglobin levels were 114.30 ± 20.08 g/L in the epilepsy group, which were lower than those in the nonepilepsy group (128.64 ± 17.94 mmol/L, P = 0.001). Serum iron levels were 8.89 ± 5.03 g/L in the epilepsy group, which were also lower than those in the nonepilepsy group (13.71 ± 6.70 mmol/L, P = 0.002). The hemoglobin level was positively correlated with serum iron on admission (ρ = 0.321, P = 0.000). In the multivariate logistic regression model, lower hemoglobin was considered as an independent risk factor of acute seizures (odds ratio 4.286, 95% confidence interval 1.492-12.315, P = 0.007). The optimal cutoff value for hemoglobin level as a predictor for acute epilepsy after aSAH was determined as 119 g/L in the receiver operating characteristic curve (sensitivity was 75.00%, and specificity was 69.48%). CONCLUSIONS: These data support the hypothesis that hemoglobin was inversely associated with acute seizures following aSAH.

17.
Dalton Trans ; 48(26): 9676-9683, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-30924816

RESUMO

The reactions of a three-coordinate cobalt(i) complex [(IAdMes)(PPh3)CoCl] (1) (IAdMes = 1-mesityl-3-adamantyl-4,5-dimethylimidazol-2-ylidene) with LiCH3, LiCH2SiMe3 and NaCp gave ligand-based C(sp3)-H bond activation products [(IAd'Mes)Co(η6-C6H5PPh2)] (2), [(IAdMes')(PPh3)Co(CH2SiMe3)] (4) and [(IAd'Mes)Co(η5-Cp)] (5), respectively (IAd'Mes and IAdMes' denote adamantyl- and mesityl-cyclometallated N-heterocyclic carbene (NHC) ligands, respectively). All the cobalt-NHC complexes have been characterized by various spectroscopic methods, and their structures have been established by single-crystal X-ray diffraction studies. These cyclometallation reactions are among the rare examples of C(sp3)-H bond activation reactions observed in structurally well-defined low-valent cobalt complexes. Different cyclometallated NHC ligands ([IAd'Mes]1-versus [IAdMes']1-) and different oxidation states of the metal center (cobalt(i) versus cobalt(ii)) in the resultant cobalt complexes hint at different mechanisms for these cobalt-mediated C(sp3)-H bond activation reactions.

18.
J Cell Biochem ; 2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30746746

RESUMO

OBJECTIVE: We have demonstrated runt-related transcription factor 2 (Runx2) plays important role in atherosclerosis. It has been indicated that atherosclerosis shares the similar histopathology with nonalcoholic steatohepatitis (NASH), a progressive stage of nonalcoholic fatty liver disease (NAFLD), on macrophages infiltration. However, the function of Runx2 in NAFLD is completely unknown. Here, we investigated the underlying mechanism of Runx2 triggering macrophages infiltration in the development of NAFLD. METHODS: Mice were fed with high-fat diet (HFD) for a long time. Histopathologic features, macrophages infiltration, expression of monocyte chemotactic protein 1 (MCP-1), and Runx2 were, respectively, analyzed in vivo. Lentivirus or short interfering RNA were transfected in murine hepatic stellate cells (HSCs) and the transwell assay was performed to verify the contribution of Runx2 for macrophages migration in vitro. RESULTS: Long-term treatment with HFD induced the progression of NAFLD, and NASH was initiated from 8 months on diet. HFD increased the expression of F4/80 upon HFD feeding, indicated HFD promotes hepatic infiltration of macrophages in NAFLD. In addition, HFD upregulated the expression of MCP-1 and Runx2 during NAFLD development. Unexpectedly, Runx2 upregulation is cell-type depended in NAFLD, and only abundantly elevated in activated HSCs. Furthermore, we found that Runx2 could increase or decrease the expression of MCP-1 in HSCs, and regulate macrophages migration by influencing MCP-1 production in vitro. CONCLUSIONS: Our results give evidence that the upregulation of Runx2 specific in activated HSCs promotes hepatic infiltration of macrophages by increasing MCP-1 expression in NAFLD, which reveals a novel mechanism and provides a cell-specific therapeutic target for NAFLD.

19.
Mol Med Rep ; 19(3): 2377-2385, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30664218

RESUMO

Leukemia inhibitory factor (LIF) is a multifunctional cytokine. The present study aimed to determine the expression and effects of LIF on nucleus pulposus generation. Degenerated nucleus pulposus samples were obtained from animal models and patients with lumbar intervertebral disc herniation. Degradation scores of intervertebral discs were evaluated via magnetic resonance imaging (MRI) and histology, and the protein expression levels of LIF were detected. Furthermore, cultured primary human degenerated nucleus pulposus cells (DNPCs) were stimulated with various concentrations of recombinant human LIF protein (rhLIF), and aggrecan and collagen type II α1 (COL2α1) protein expression levels were detected by western blotting. In addition, aggrecan expression was determined by toluidine blue staining. The effects of rhLIF on proliferation and apoptosis of DNPCs were evaluated by Cell Counting Kit­8 and flow cytometry, respectively. The results revealed that the degradation scores of intervertebral discs were significantly associated with modeling time, as determined by MRI and histology. In addition, the protein expression levels of LIF were initially increased in patients with lumbar disc herniation and in rabbit models, particularly in the 2­week modeling group; however, its expression decreased with the progression of disc degeneration. Notably, LIF expression in each modeling group was higher than that in the control and 0 week modeling group. The in vitro study revealed that the protein expression levels of aggrecan and COL2α1 were significantly increased in response to rhLIF, in a dose­dependent manner, and statistical differences were identified between the treatment groups and control group. The results of toluidine blue staining were consistent with this finding. Although rhLIF had no effect on proliferation, it inhibited apoptosis of DNPCs in a concentration­dependent manner. In conclusion, LIF was upregulated during the process of intervertebral disc degeneration, and may promote the expression of extracellular matrix components. It may also be hypothesized that LIF acts as a potential protective factor by inhibiting apoptosis of DNPCs without affecting cell proliferation.


Assuntos
Degeneração do Disco Intervertebral/tratamento farmacológico , Fator Inibidor de Leucemia/genética , Núcleo Pulposo/efeitos dos fármacos , Proteínas Recombinantes/administração & dosagem , Agrecanas/genética , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo II/genética , Feminino , Citometria de Fluxo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/metabolismo , Disco Intervertebral/fisiopatologia , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/fisiopatologia , Deslocamento do Disco Intervertebral/tratamento farmacológico , Deslocamento do Disco Intervertebral/genética , Deslocamento do Disco Intervertebral/fisiopatologia , Fator Inibidor de Leucemia/administração & dosagem , Imagem por Ressonância Magnética , Masculino , Núcleo Pulposo/diagnóstico por imagem , Núcleo Pulposo/crescimento & desenvolvimento , Núcleo Pulposo/patologia , Coelhos , Proteínas Recombinantes/genética
20.
Phytomedicine ; 53: 223-233, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30668402

RESUMO

BACKGROUND: Discovering novel compounds with higher activities is a key aim of natural products research. Gardenia jasminoides Ellis is a herb with anti-inflammatory properties. Iridoid glycosides (mainly geniposide) and crocetin derivatives (crocins) are the two major active constituents in this herb and are considered its active ingredients. However, which components are responsible for the anti-inflammatory properties of gardenia have remained to be investigated. PURPOSE: Here, we prepared total iridoid glycocides (TIG) and total crocins (TC) from G. jasminoides Ellis, determined their main chemical constituents, and performed animal studies to evaluate their anti-adjuvant arthritis activities, thus, proposing a reasonable mechenism to explain the anti-inflammatory activities of the active components in this herbal remedy. STUDY DESIGN: TIG and TC were prepared by using HPD-100 macroporous resin, and characterized by UHPLC-DAD-MS and UV-Vis spectrophotometer. Then, freund's complete adjuvant-injected rats underwent drug treatments with TIG (160 mg/kg) and TC (160 mg/kg) for 14 days, and their ankle diameters were measured. Moreover, X-ray radiographs of the adjuvant injected hind paws were evaluated. Finally, histopathological examinations of the ankle joints, spleens and thymus were carried out to evaluate inflammatory reactions, and immunohistochemical measurements were conducted to evaluate TNF-α and TGF-ß1 expression in the ankle joint of the rats. RESULTS: The chemical composition determination of the current study showed that TIG was mainly composed of geniposide and TC was a fraction predominantly with crocin-1, crocin-2 and crocin-3. Calculation of results showed that TIG and TC contained 58.2% total iridoid glycosides and 54.7% total crocins, respectively. Our study suggested TIG and TC treatments markedly decreased paw swelling and ankle diameters of AA rats (both p < 0.05). The radiological analysis showed that administration of TIG and TC ameliorated bone destruction, and reduced the radiological bone destruction scores (TIG p < 0.05, TC p>0.05). Moreover, data from histological assessment demonstrated considerable mitigation of inflammation in the joints (both p < 0.01), spleen and thymus of AA rats treated with TIG and TC. TNF-α and TGF-ß1 protein expression according to immunohistochemistry staining also supported the anti-arthritis activities of TIG and TC (TNF-α: TIG p < 0.01 and TC p < 0.05, TGF-ß1: TIG p < 0.01 and TC p>0.05). CONCLUSION: In the current study, fractionation of gardenia prior to further in vivo investigation has for the first time provided reasonable explanation for the anti-inflammatory activity of this herbal remedy. Our study showed that both TIG and TC from gardenia have anti-inflammatory properties. Overall, these experimental findings suggest that gardenia could be regarded as a potential therapeutic target for arthritis. However, as geniposide has a higher content than crocins in this herbal drug, TIG (mainly geniposide) seems to be primarily responsible for the anti-inflammatory properties of gardenia. Taken together, this maiden attempt demonstrated that TIG (mainly geniposide) is more important in evaluating the anti-inflammatory activity of G. jasminoides Ellis.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Artrite Experimental/tratamento farmacológico , Gardenia/química , Glicosídeos Iridoides/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Carotenoides/análise , Cromatografia Líquida de Alta Pressão/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Adjuvante de Freund/toxicidade , Glicosídeos Iridoides/química , Glicosídeos Iridoides/isolamento & purificação , Iridoides/análise , Masculino , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
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