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1.
Curr Alzheimer Res ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31894747

RESUMO

BACKGROUND: The specific intravenous immunoglobulin (IVIG) for Alzheimer's disease (AD) is developing, which contains a high level of naturally occurring autoantibodies against amyloid-ß (nAbs-Aß), and the measure of nAbs-Aß content is greatly essential. Though enzyme-linked immunosorbent assay (ELISA) has been widely used in detecting the nAbs-Aß content, the impact of Aß aggregates species chosen as antigen in ELISA on this measure has not been evaluated. OBJECTIVE: To clarify the influence of different Aß40/42 aggregates as antigen during ELISA on the content of nAbs-Aß40/42 measured in IVIG. METHOD: Preparation of various Aß40/42 aggregates was performed by different aggregation solutions and various lengths of time, and analyzed by western blot. Different Aß40/42 aggregates as antigen were adopted to measure the nAbs-Aß40/42 content in IVIG by ELISA, and the control was carried out to reduce interference of nonspecific binding. The Bonferroni and Dunnett's T3 were used for statistical analysis. RESULTS: The duration for the formation of Aß40/42 aggregates had more effect on detecting nAbs-Aß40/42 content in IVIG than the aggregation solution. Higher content of nAbs-Aß40/42 in the same IVIG was displayed when measured with Aß40/42 aggregates at day 3, instead of at day 0.5 and day 7.0. The nAbs-Aß40/42 contents in the same IVIG measured with Aß40/42 aggregates prepared in different solutions were obviously different, but there was no significant regularity among them. CONCLUSION: The nAbs-Aß40/42 content in the same IVIG is significantly different when measured with Aß40/42 aggregated under different conditions. The nAbs-Aß40/42 content in IVIG by antigen-dependent measures, like ELISA, is uncertain.

2.
Genes Dis ; 6(4): 448-454, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31832525

RESUMO

Cerebral ischemia is a major cause of mortality and long-term morbidity worldwide. NDRG4 has been shown to protect against cerebral ischemia, although the underlying mechanisms remain largely unclear. Here we found that NDRG4 expression was decreased in the brain tissues of ischemia/reperfusion (IR) rats, indicating increased apoptosis rates among cerebral cells. NDRG4 restoration via an adenovirus significantly attenuated cerebral infarct sizes and impairments in IR rats. Furthermore, adenovirus-mediated NDRG4 inhibited cell apoptosis in the brains of IR rats and regulated the expression of Bcl-2, Bax, caspase-3, and c-Fos. Moreover, we found that NDRG4 increased expression of BDNF, which is strongly related to cerebral ischemia and cellular apoptosis. Altogether, our findings demonstrate that NDRG4 protects cerebral IR injury by inhibiting cell apoptosis and regulates cerebral cell apoptosis by increasing BDNF expression. These results suggest that NDRG4 may be a therapeutic target for IR treatment.

3.
J Neurosurg Spine ; : 1-6, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31860809

RESUMO

OBJECTIVE: The authors aimed to assess, in a bone-agar experimental setting, the feasibility and accuracy of percutaneous lumbar pedicle screw placements using an intraoperative CT image-based augmented reality (AR)-guided method compared to placements using a radiograph-guided method. They also compared two AR hologram alignment methods. METHODS: Twelve lumbar spine sawbones were completely embedded in hardened opaque agar, and a cubic marker was fixed on each phantom. After intraoperative CT, a 3D model of each phantom was generated, and a specialized application was deployed into an AR headset (Microsoft HoloLens). One hundred twenty pedicle screws, simulated by Kirschner wires (K-wires), were placed by two experienced surgeons, who each placed a total of 60 screws: 20 placed with a radiograph-guided technique, 20 with an AR technique in which the hologram was manually aligned, and 20 with an AR technique in which the hologram was automatically aligned. For each K-wire, the insertion path was expanded to a 6.5-mm diameter to simulate a lumbar pedicle screw. CT imaging of each phantom was performed after all K-wire placements, and the operative time required for each K-wire placement was recorded. An independent radiologist rated all images of K-wire placements. Outcomes were classified as grade I (no pedicle perforation), grade II (screw perforation of the cortex by up to 2 mm), or grade III (screw perforation of the cortex by > 2 mm). In a clinical situation, placements scored as grade I or II would be acceptable and safe for patients. RESULTS: Among all screw placements, 75 (94%) of 80 AR-guided placements and 40 (100%) of 40 radiograph-guided placements were acceptable (i.e., grade I or II; p = 0.106). Radiograph-guided placements had more grade I outcomes than the AR-guided method (p < 0.0001). The accuracy of the two AR alignment methods (p = 0.526) was not statistically significantly different, and neither was it different between the AR and radiograph groups (p < 0.0001). AR-guided placements required less time than the radiograph-guided placements (mean ± standard deviation, 131.76 ± 24.57 vs 181.43 ± 15.82 seconds, p < 0.0001). Placements performed using the automatic-alignment method required less time than those using the manual-alignment method (124.20 ± 23.80 vs 139.33 ± 23.21 seconds, p = 0.0081). CONCLUSIONS: In bone-agar experimental settings, AR-guided percutaneous lumbar pedicle screw placements were acceptable and more efficient than radiograph-guided placements. In a comparison of the two AR-guided placements, the automatic-alignment method was as accurate as the manual method but more efficient. Because of some limitations, the AR-guided system cannot be recommended in a clinical setting until there is significant improvement of this technology.

4.
Mol Med Rep ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31746390

RESUMO

Intervertebral disc degeneration (IDD) and ligamentum flavum hypertrophy (LFH) are major causes of degenerative spinal disorders. Comparative and proteomic analysis was used to identify differentially expressed proteins (DEPs) in IDD and LFH discs compared with normal discs. Subsequent gene ontology term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the DEPs in human IDD discs or LFH samples were performed to identify the biological processes and signaling pathways involved in IDD and LFH. The PI3K­AKT signaling pathway, advanced glycation endproducts­receptor for advanced glycation endproducts signaling pathway, p53 signaling pathway, and transforming growth factor­b signaling pathway were activated in disc degeneration. This review summarizes the recently identified DEPs, including prolargin, fibronectin 1, cartilage intermediate layer protein, cartilage oligomeric matrix protein, and collagen types I, II and IV, and their pathophysiological roles in degenerative spinal disorders, and may provide a deeper understanding of the pathological processes of human generative spinal disorders. The present review aimed to summarize significantly changed proteins in degenerative spinal disorders and provide a deeper understanding to prevent these diseases.

5.
Pain Physician ; 22(6): E587-E599, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31775412

RESUMO

BACKGROUND: Currently, various retractor systems are widely used for access to the lumbar spine in minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). Nevertheless, studies concerning the comparison of extensible retractor and inextensible tube systems are quite rare. OBJECTIVES: This article was to compare perioperative characteristics, clinical outcomes, and multifidus muscle injury of obconic inextensible tube versus extensible retractor system for single-level MIS-TLIF. STUDY DESIGN: A prospective observational study on 91 patients with a mean follow-up of 20.0 ± 4.1 months. SETTING: This study was conducted by a university-affiliated hospital in a major Chinese city. METHODS: From April 2015 to May 2016, 91 consecutive patients who underwent MIS-TLIF procedure using an obconic inextensible endoscopic tube or extensible retractor system were enrolled in this study. Operation parameters such as incision length, blood loss, postoperative drainage volume, surgical time, analgesic use rate, time to ambulation, and postoperative hospitalization days were evaluated. The concentration of white blood cells, interleukin-6, interleukin-8, tumor necrosis factor alpha, and creatine phosphokinase (CPK)-MM of the enrolled patients were measured for postoperative traumatic stress and muscle injury. Multifidus muscle edema and atrophy were evaluated by T2-weighted magnetic resonance imaging (MRI) at 3 different time points (preoperative, postoperative, and 1-year follow-up). Clinical outcomes such as Visual Analog Scale (VAS) score, Japanese Orthopedic Association (JOA) score, Oswestry Disability Index (ODI) score, fusion rates, and MacNab criteria were assessed for patients' symptoms. RESULTS: In terms of baseline characteristics, the 2 groups were similar regarding sample size, gender, age, symptoms duration, operation level, body mass index, physical examination, and all the clinical outcomes measures (P > 0.05). Perioperative analysis showed that the inextensible group had comparative incision length, blood loss, operation time, time to ambulation, and postoperative hospitalization (P > 0.05). The inextensible tubular group had less postoperative drainage volume and analgesic use rate (P < 0.05). The concentration level of CPK-MM and c-reactive protein (CRP) was lower in the inextensible tubular group compared with the extensible retractor group.No significant difference was found between the 2 groups regarding MRI T2 signal intensity ratio of multifidus muscle at the immediate postoperative period. The MRI T2 signal intensity ratio of multifidus muscle was lower in the inextensible tubular group than the extensible retractor group at the 1-year follow-up period. The VAS scores for low back pain and leg pain improved significantly in both groups after surgery, as did the JOA and ODI scores. However, there were no significant differences between the 2 groups regarding the preoperative and final follow-up VAS, JOA, and ODI scores, fusion rates, and the distribution of the MacNab criteria. LIMITATIONS: This was not a randomized controlled trail, which could provide more evidence-based medicine conclusions. CONCLUSIONS: The obconic inextensible endoscopic tube system via the transforaminal approach for lumbar interbody fusion is a safe and sufficient technique. When compared with the extensible retractor system, it has comparable clinical outcomes, with additional significant benefits of less postoperative drainage volume and analgesic use rate, less multifidus muscle injury in terms of lower CPK-MM levels at immediate postoperative period, less change in CRP, and less change in MRI T2 signal intensity ratio of multifidus muscles at 1-year follow-up. KEY WORDS: Minimally invasive, endoscopic, lumbar interbody fusion, tubular, multifidus muscle.

6.
Eur J Radiol ; 120: 108686, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31586850

RESUMO

PURPOSE: To determine whether imaging parameters derived from intravoxel incoherent motion (IVIM) diffusion weighted imaging (DWI) vary according to tumor-stroma ratio(TSR) or dominant stroma type of breast cancer. METHODS: We prospectively enrolled 77 patients with breast cancer who underwent IVIM DWI on a 3.0 T MR scanner. The values of IVIM parameters (D, D* and f) were measured. After surgery, TSR or dominant stroma type was evaluated. The relationship between imaging parameters and tumor stroma characteristics was analyzed. RESULTS: The mean D and f values were lower in stroma-poor tumor than in stroma-rich tumor (P = 0.012, 0.015). The mean D value was lower in the collagen-dominant type than in fibroblast-dominant or lymphocyte-dominant type (P = 0.032, 0.043). According to multivariate linear regression analyses, tumor size (P = 0.007), TSR (P = 0.008), dominant stroma type (collagen dominant, P = 0.012), and histological grade (P = 0.031) were independently correlated with D value; and tumor size (P = 0.011), TSR (P = 0.021) and histological grade (P = 0.037) were independently correlated with f value. CONCLUSION: In breast cancer, D and f values show significant differences according to TSR, and D value is lower in collagen dominant type than in fibroblast dominant or lymphocyte dominant types.

7.
Nano Lett ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31576756

RESUMO

Low temporal resolution and limited photocontrollable fluorescent protein probes have restricted the widespread application of single-molecule localization microscopy (SMLM). In the current study, we developed a new photoconvertible fluorescent protein (PCFP), pcStar, and quick single molecule-guided Bayesian localization microscopy (Quick-SIMBA). The combination of pcStar and Quick-SIMBA achieved the highest temporal resolution (0.1-0.25 s) with large field-of-view (76 × 9.4 µm2 -76 × 31.4 µm2) among the SMLM methods, which enabled the dynamic movements of the endoplasmic reticulum dense tubular matrix to be resolved. Moreover, pcStar extended the application of SMLM to imaging the immediate early nanostructures in Drosophila embryos and revealed a specific "parallel three-pillar" structure in the neuronal-glial cell junction, helping to elucidate glial cell "locking" and support of neurons during Drosophila embryogenesis.

8.
Medicine (Baltimore) ; 98(38): e17299, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31568015

RESUMO

China's child population ranked second in the world. However, data on the overall patterns and epidemiologic trends of TULFs among children and adolescents in Chongqing, China are scarce. With development of urbanization, motorization, building industry, the incidence patterns of traumatic upper limb fractures in children and adolescents might be about to change. To investigate the incidence patterns of traumatic upper limb fractures in children and adolescents (≤18 years old) according to age (≤3 years old, 3-6 years old, 6-12 years old, and 12-18 years old), gender, time, and etiology groups in Chongqing, China, we retrospectively reviewed 1078 children and adolescents who had traumatic upper limb fractures and who came to our university-affiliated hospitals from 2001 to 2010. The patients were grouped into different age groups, genders, year of admission range groups, and aetiologies. We used Pearson chi-square tests and independent samples t tests to assess differences of the grouped data and continuous variables, respectively. This study enrolled 1078 patients (849 males, 229 females) aged 11.0 ±â€Š4.7 years old. The most common aetiologies and fracture sites of patients were low falls (705, 65.4%) and humerus (492, 45.6%). A total of 146 (13.5%) patients suffered a nerve injury, 94 (8.7%) patients sustained associated injuries, and 106 (9.8%) patients sustained complications. The proportion of injuries due to motor vehicle collisions increased with increasing age and year of admission. Female patients presented with significantly higher proportion of injuries due to motor vehicle collisions and significantly lower proportion of injuries due to hit by others. The proportion decreased from 63.2% to 33.3% in humeral fracture, increased from 8.8% to 35.5% in radius fracture, increased from 7.4% to 28.9% in ulna fracture with increasing age. Female patients presented with significantly higher proportion of humeral fracture, clavicle fracture and significantly lower proportion of radius fracture, ulna fracture, and hand fracture. Low falls and humerus fractures were the most common aetiologies and fracture sites. The pattern of traumatic upper limb fractures has specific age, gender, time, and etiology differences.


Assuntos
Fraturas do Úmero/epidemiologia , Fraturas do Rádio/epidemiologia , Fraturas da Ulna/epidemiologia , Acidentes por Quedas/estatística & dados numéricos , Adolescente , Fatores Etários , Criança , Pré-Escolar , China/epidemiologia , Clavícula/lesões , Feminino , Traumatismos da Mão/epidemiologia , Traumatismos da Mão/etiologia , Humanos , Fraturas do Úmero/etiologia , Incidência , Lactente , Recém-Nascido , Masculino , Fraturas do Rádio/etiologia , Fatores de Risco , Escápula/lesões , Fatores Sexuais , Fraturas da Ulna/etiologia
9.
Infect Genet Evol ; 78: 104049, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31655225

RESUMO

BACKGROUND: To decipher the molecular epidemiology of the Treponema pallidum subspecies, pallidum, researchers have developed different molecular typing schemes which identify strains type from clinical specimens. However, the results of these studies show remarkable diversity. METHODS: We searched for literature in PubMed, MEDLINE, Web of Sciences, and OVID from January 1998 to January 2019, in order to compare the efficiency of typing schemes using published evidence for systematic reviews and meta-analyses. RESULTS: From the 43 studies included, the overall typing efficiency of Treponema pallidum was 71.4% (95% CI: 63.2-78.9%). Subgroup analyses indicated that the typing efficiency of CDC-typing (CDCT, 68.2%, 95% CI: 53.6-81.2%) was worse than those of enhanced CDC-typing (ECDCT, 72.3%, 95% CI: 60-83.1%), CDC-rspA (81.6%, 95% CI: 76.1-86.6%), multi-locus sequence typing (MLST, 67.1%, 95% CI: 61.1-72.7), and sequencing-based molecular typing (SBMT, 71.6%, 95% CI: 50-89.2%). A limitation of this review is that the studies included employed different criteria to collect and investigate samples of Treponema pallidum, which could contribute to heterogeneity. CONCLUSIONS: This analysis suggests that CDCT is an inferior scheme in molecular typing, the discriminatory power was very similar for ECDCT and SBMT. Other factors contributing to the heterogeneity between typing studies warrants further study.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31518449

RESUMO

BACKGROUND AND AIM: The effect of real-time analysis of needle-based confocal laser endomicroscopy (nCLE) for gastric subepithelial lesions (SELs) on the diagnostic value is unclear. The study aimed to investigate the diagnostic efficacy of real-time nCLE for gastric SELs and to assess the technical aspects and safety of real-time nCLE. METHODS: Consecutive patients with gastric SELs ≥ 1 cm were prospectively investigated by endoscopic ultrasound (EUS), followed by nCLE. During EUS-nCLE, real-time nCLE diagnosis was made by an expert endoscopist. The procedure-relative adverse events were assessed and recorded. One-month washout period later, nCLE videos were reviewed off-line by the same endoscopist. The nCLE diagnoses were compared with corresponding pathological results. Additionally, image quality and interobserver agreements for the criteria were evaluated by three experienced endomicroscopists. RESULTS: Except for one failing to be punctured, 60 patients completed EUS-nCLE procedures successfully. Real-time nCLE had high diagnostic accuracies of ≥ 88.3% for gastric SELs. There were no significant differences between real-time and off-line nCLE diagnoses for gastric SELs (P > 0.05). The overall accuracy of real-time nCLE for diagnosis of gastric SELs was 86.7%. There were no procedure-relative adverse events occurred. In addition, the mean image quality score was 3.6 (1 = poor and 5 = excellent). The interobserver agreement was "almost perfect" for ectopic pancreas and "substantial" for gastrointestinal stromal tumor, leiomyoma, and carcinoma. CONCLUSIONS: Endoscopic ultrasound-nCLE could provide in vivo real-time diagnostic imaging with a high diagnostic accuracy. Meanwhile, real-time nCLE was feasible and had a satisfactory safety profile.

11.
Cancer Manag Res ; 11: 7307-7315, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447588

RESUMO

Background/aims: Patients with glioblastoma multiforme (GBM) that is the most common brain cancer in adults have a rather poor prognosis. The accumulation of immune suppressive myeloid-derived suppressor cell (MDSC) is negatively associated with clinical outcomes in various cancers. A recent study identified that lectin-type oxidized LDL receptor 1 (LOX-1) may serve as a specific marker of human polymorphonuclear neutrophil (PMN)-MDSC. Thus, herein we focused on exploring the role of LOX-1+ PMN-MDSC in GBM progression. Methods: LOX-1, IFN-γ, dichlorodihydrofluorescein diacetate (DCFDA), CD15, CD4 and CD8 expression levels were examined by flow cytometry. ARG1 and iNOS expression levels in PMN were examined by quantitative real-time PCR. LOX-1 and CD15 expression levels in tumor tissue were determined by immunofluorescent microscopy. T cell proliferation was determined by 3H-thymidine incorporation. Results: We identified a protumorigenic subset of PMN, which constitutively expressed LOX-1 and accumulated in the peripheral blood of GBM patients. Compared to LOX-1- PMN, the LOX-1+ PMN exhibited a PMN MDSC profile, with a significant increase in the expression of DCFDA, ARG1 and iNOS, and the capacity of inhibiting the CD3+ T cell proliferation in a dependent-ARG1/iNOS way. Additionally, we found that LOX-1+ PMN negatively correlated with effector immune cells in GBM patients, accumulated in GBM tissues, and was related to early recurrence and disease progression tightly. Conclusion: Our study revealed that LOX-1+ PMN-MDSC inhibited the T cell proliferation to enhance immune suppression, which may play a key role in driving the GBM progression.

12.
J Biomed Opt ; 24(8): 1-11, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31429215

RESUMO

X-ray luminescence computed tomography (XLCT) is an emerging hybrid imaging modality which has the potential for achieving both high sensitivity and spatial resolution simultaneously. For the narrow x-ray beam-based XLCT imaging, based on previous work, a spatial resolution of about double the x-ray beam size can be achieved using a translate/rotate scanning scheme, taking step sizes equal to the x-ray beam width. To break the current spatial resolution limit, we propose a scanning strategy achieved by reducing the scanning step size to be smaller than the x-ray beam size. We performed four sets of numerical simulations and a phantom experiment using cylindrical phantoms and have demonstrated that our proposed scanning method can greatly improve the XLCT-reconstructed image quality compared with the traditional scanning approach. In our simulations, by using a fixed x-ray beam size of 0.8 mm, we were able to successfully reconstruct six embedded targets as small as 0.5 mm in diameter and with the same edge-to-edge distances by using a scanning step as small as 0.2 mm which is a 1.6 times improvement in the spatial resolution compared with the traditional approach. Lastly, the phantom experiment further demonstrated the efficacy of our proposed method in improving the XLCT image quality, with all image quality metrics improving as the step size decreased.

13.
Brain Res Bull ; 153: 15-23, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31400495

RESUMO

Recent animal studies on heterochronic parabiosis (a technique combining the blood circulation of two animals) have revealed that young blood has a powerful rejuvenating effect on brain aging. Circulating factors, especially growth differentiation factor 11 (GDF11) and C-C motif chemokine 11 (CCL11), may play a key role in this effect, which inspires hope for novel approaches to treating age-related cerebral diseases in humans, such as neurodegenerative and neurovascular diseases. Recently, attempts have begun to translate these astonishing and exciting findings from mice to humans and from bench to bedside. However, increasing reports have shown contradictory data, questioning the capacity of these circulating factors to reverse age-related brain dysfunction. In this review, we summarize the current research on the role of young blood, as well as the circulating factors GDF11 and CCL11, in the aging brain and age-related cerebral diseases. We highlight recent controversies, discuss related challenges and provide a future outlook.

14.
Vet Immunol Immunopathol ; 215: 109913, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31420069

RESUMO

The development of a rapid and efficient system to generate porcine monoclonal antibodies (mAbs) is an important step toward the discovery of critical neutralizing targets for designing rational vaccines against porcine viruses. In this study, we established a platform for producing porcine mAbs based on single cell technologies. First, we singled out an optimal donor from 507 pigs based on serum antibody neutralizing activity against porcine reproductive and respiratory syndrome virus (PRRSV). After identifying the contribution of IgG to the neutralizing activity, single CD45R+IgG+Ag+ B cells were sorted from peripheral blood mononuclear cells (PBMCs). Single B cell RT-PCR was performed using primers designed to cover the germline repertoire of the porcine VH/VL gene segments. Paired VH/VLs were cloned into a eukaryotic expression vector and transfected into 293T cells. We demonstrate that full-length porcine mAbs were produced, and antigen-specific mAbs were obtained after further validation. The approach reported in this study can be applied to generate porcine mAbs against any given antigen and may help with the screening of neutralizing antibodies against porcine pathogens.


Assuntos
Anticorpos Monoclonais/biossíntese , Anticorpos Antivirais/biossíntese , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Suínos/imunologia , Animais , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Neutralizantes/genética , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/genética , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/isolamento & purificação , Especificidade de Anticorpos , Linfócitos B/imunologia , Células HEK293 , Humanos , Região Variável de Imunoglobulina/genética , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Transfecção , Recombinação V(D)J
15.
Artigo em Inglês | MEDLINE | ID: mdl-31403937

RESUMO

BACKGROUND: IVD degeneration is a widespread problem all over the world, which a variety of inflammatory cytokines have been implicated in, while Sphingosine 1-phosphate (S1P) is an important lipid mediator that may play a role in IVD degeneration. OBJECTIVE: To study the expression and role of S1PRs in the intervertebal disc (IVD) degeneration to enhance understanding of disc degeneration. METHODS: Degenerated and normal IVD were harvested from patients through surgery. Expression of S1P receptor subtypes was evaluated using real-time PCR, immunohistochemistry, and western blotting. The effect of S1PR on inflammation induced by interleukin-1ß in nucleus pulposus (NP) cells was also assessed by real time PCR and western blotting. RESULTS: The nucleus pulposus mainly expressed the S1PR1/2/3, and the expression decreased in the severe degenerated nucleus pulposus cells. The ligand, S1P, inhibited the up-regulation of matrix metallopeptidase-3 (MMP-3) and ADAM metallopeptidase with thrombospondin type 1 motif 4 (ADAMTS4) induced by IL-1ß. CONCLUSIONS: The results show that an the expression of S1PRs in degenerative discs is down-regulated as degeneration, and S1P can inhibit the inflammation response induced by IL-1ß in NP cells, implicating that S1P/S1PR may contribute to IVD degeneration.

16.
Am J Chin Med ; 47(5): 1043-1056, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31311299

RESUMO

Baicalein is a natural flavonoid with anti-oxidant activities protecting against ischemia/reperfusion (I/R) injury. Previous studies suggest that oxidative burst early after reperfusion accelerates cell death. We therefore investigated the critical therapeutic window of baicalein by examining the timing of baicalein treatment in relation to its oxidant modulating and cytoprotective effects. Using an established chick cardiomyocyte model of I/R, we administered baicalein at various time points after reperfusion and assessed cell viability and the profiles of reactive oxygen species (ROS), nitric oxide (NO), and Akt phosphorylation. Baicalein administered at the onset of reperfusion resulted in a concentration-dependent reduction of cell death (25 µM 48.2±1.9%, 50µM 43.8±1.5%, 100µM 36.6±2.1%, vs. I/R control 57.3±1.4%, all p<0.05). Baicalein (100µM) timely and effectively scavenged ROS burst and enhanced NO production in the early reperfusion phase. Cotreatment with NO synthase (NOS) inhibitor l-NAME (200µM) partially abrogated the cytoprotective effect. Baicalein (100µM) given after reperfusion lost protective effect in a time-dependent manner with cytoprotection completely lost if >60min. Even with only 15-min delay after reperfusion, the ROS scavenging effect was abolished and the NO enhancing effect markedly reduced. The phosphorylation of Akt, an upstream regulator of eNOS, also diminished as the delay lengthened. In conclusion, baicalein treatment after reperfusion confers cardioprotection in a concentration- and time-dependent manner. The critical therapeutic window lies in the early reperfusion phase, during which ROS scavenging and Akt-eNOS mediated NO signaling are most effective.

17.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(7): 801-806, 2019 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-31297995

RESUMO

Objective: To investigate the clinical results and complication prevention of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in the treatment of single-segment severe lumbar spinal stenosis (LSS). Methods: The clinical data of 112 patients with severe LSS treated with MIS-TLIF between January 2010 and January 2017 were retrospectively analyzed. There were 43 males and 69 females, aged 52-81 years, with an average age of 65.3 years. The disease duration ranged from 4 to 126 months, with an average of 10.5 months. Clinical manifestations: 104 cases of low back pain, 91 cases of nervous intermittent claudication of both lower limbs, 21 cases of unilateral nerve root pain and/or numbness, and 5 cases of cauda equina nerve injury. The 112 cases were all severe central spinal stenosis, including 32 cases with lateral recess stenosis, 20 cases with foramen stenosis, 9 cases with ossification of ligamentum flavum, 38 cases with disc herniation; 14 cases with two complications and 5 cases with three. Stenosis segment: L 3, 4 in 6 cases, L 4, 5 in 89 cases, and L 5, S 1 in 17 cases. Surgical methods included bilateral decompression through bilateral approach (60 cases), bilateral decompression through unilateral approach (15 cases), and unilateral decompression (37 cases). The operation time, intraoperative blood loss, visual analogue scale (VAS) score of low back pain and leg pain, Oswestry disability index (ODI) score, fusion rate, and surgical complications were recorded. At last follow-up, the lumbar fusion was evaluated by Bridwell method, grades Ⅰ and Ⅱ were expressed as fusion. Results: The operation time was 83-186 minutes (mean, 126.8 minutes), and the intraoperative blood loss was 65-630 mL (mean, 163.1 mL). All the 112 patients were followed up 25-49 months, with an average of 35.1 months. The VAS score of low back pain and leg pain and ODI score at each time point after operation were significantly improved when compared with preoperative scores ( P<0.05). There was no significant difference between the VAS score of low back pain and leg pain and ODI score at the other time points except 1 month after operation ( P<0.05). At last follow-up, 2 cases of cauda equina nerve injury recovered and 3 cases partially recovered. According to Bridwell classification criteria, 58 cases were grade Ⅰ, 47 cases were grade Ⅱ, and 7 cases were grade Ⅲ. The fusion rate was 93.8%. Perioperative complications included 5 cases of incision complications (superficial infection in 3 cases, hematoma formation in 2 cases), 19 cases of internal fixator complications (intraoperative end plate fracture in 8 cases, fusion cage sinking in 11 cases at last follow-up), and 15 cases of neurological complications (dural sac tear in 10 cases, transient neurological symptoms of lower extremities aggravated in 5 cases). Conclusion: MIS-TLIF treatment of single-level severe LSS can achieve good clinical results, while there is a risk of serious complications. Full understanding of the clinical and imaging features of the disease and reasonable and careful operation are helpful to control the occurrence of cauda equina nerve damage.


Assuntos
Fusão Vertebral , Estenose Espinal , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Estudos Retrospectivos , Estenose Espinal/cirurgia
18.
Neural Regen Res ; 14(11): 1977-1985, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31290456

RESUMO

HECT, UBA and WWE domain-containing 1 (Huwe1), an E3 ubiquitin ligase involved in the ubiquitin-proteasome system, is widely expressed in brain tissue. Huwe1 is involved in the turnover of numerous substrates, including p53, Mcl-1, Cdc6 and N-myc, thereby playing a critical role in apoptosis and neurogenesis. However, the role of Huwe1 in brain ischemia and reperfusion injury remains unclear. Therefore, in this study, we investigated the role of Huwe1 in an in vitro model of ischemia and reperfusion injury. At 3 days in vitro, primary cortical neurons were transduced with a control or shRNA-Huwe1 lentiviral vector to silence expression of Huwe1. At 7 days in vitro, the cells were exposed to oxygen-glucose deprivation for 3 hours and reperfusion for 24 hours. To examine the role of the c-Jun N-terminal kinase (JNK)/p38 pathway, cortical neurons were pretreated with a JNK inhibitor (SP600125) or a p38MAPK inhibitor (SB203508) for 30 minutes at 7 days in vitro, followed by ischemia and reperfusion. Neuronal apoptosis was assessed by TUNEL assay. Protein expression levels of JNK and p38MAPK and of apoptosis-related proteins (p53, Gadd45a, cleaved caspase-3, Bax and Bcl-2) were measured by western blot assay. Immunofluorescence labeling for cleaved caspase-3 was performed. We observed a significant increase in neuronal apoptosis and Huwe1 expression after ischemia and reperfusion. Treatment with the shRNA-Huwe1 lentiviral vector markedly decreased Huwe1 levels, and significantly decreased the number of TUNEL-positive cells after ischemia and reperfusion. The silencing vector also downregulated the pro-apoptotic proteins Bax and cleaved caspase-3, and upregulated the anti-apoptotic proteins Gadd45a and Bcl-2. Silencing Huwe1 also significantly reduced p-JNK levels and increased p-p38 levels. Our findings show that downregulating Huwe1 affects the JNK and p38MAPK signaling pathways as well as the expression of apoptosis-related genes to provide neuroprotection during ischemia and reperfusion. All animal experiments and procedures were approved by the Animal Ethics Committee of Sichuan University, China in January 2018 (approval No. 2018013).

19.
Clin Neurol Neurosurg ; 183: 105377, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31279300

RESUMO

OBJECTIVES: To assess the feasibility of cement-augmented fenestrated pedicle screw for patients with spondylolisthesis with osteoporotic spine. PATIENTS AND METHODS: From January 2014 to March 2018, a retrospective study of 88 patients with spondylolisthesis and osteoporosis treated with minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) using the conventional pedicle screw (CPS group, n = 52) and the fenestrated pedicle screw (FPS group, n = 36) was performed with a follow-up of 30 months (range, 10-58 months). Clinical outcomes, overall changes in slip degree, and interbody fusion rates were evaluated via questionnaires and radiographic parameters. RESULTS: The VAS, ODI and JOA scores at 3 months were significantly improved in both groups compared with the preoperative assessment (p < 0.001). No significant differences in scores were found between the two groups at any time. Imaging results at different time points revealed greater postoperative improvement in the Taillard index in the FPS group compared with the CPS group. No significant differences in the interbody fusion speed or rates were found between the two groups. In the FPS group, cement leakage occurred in 22 of 97 screws (22.7%), and symptomatic cement leakage was not found. CONCLUSION: MIS-TLIF combined with fenestrated pedicle screws provided greater reduction than did MIS-TLIF combined with conventional pedicle screws in terms of postoperative slip degree. And the application of fenestrated pedicle screw did not obstruct the interbody fusion. Overall, MIS-TLIF combined with the fenestrated pedicle screws is an effective and safe technique for the treatment of spondylolisthesis with osteoporotic spine.

20.
Stem Cells Int ; 2019: 8404168, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249601

RESUMO

Stem cell therapies for intervertebral disc degeneration have been demonstrated as a promising strategy. Previous studies have shown that human nucleus pulposus cell- (NPC-) derived exosomes can induce the differentiation of mesenchymal stem cells (MSCs) into NP-like cells in vitro. However, the mechanism of MSC differentiation into NP-like cells with the induction of NPC exosomes is still unclear. Here, we verified the induction effects of NPC exosomes on the differentiation of MSCs into NP-like cells. In addition, the Notch1 pathway was downregulated in this process. Then, DAPT and soluble Jagged1 (SJAG) were applied to inhibit or enhance the expression of the Notch1 pathway, respectively, resulting in the upregulation or downregulation of collagen II, aggrecan, and Sox9 in MSCs. Knocking down of Notch1 protein facilitated the effects of NPC exosomes on the differentiation of MSCs into NP-like cells. NPC exosomes were more effective than an indirect coculture system in terms of the differentiation of MSCs into NP-like cells. Inhibition of NPC exosome secretion with Rab27a siRNA prevented the induction effects of an indirect coculture system on the differentiation of MSCs into NP-like cells. Transwell migration assays revealed that NPC exosomes could promote the migration of MSCs. Taken together, the Notch1 pathway was negatively associated with the differentiation of MSCs into NP-like cells with the treatments of NPC exosomes. Inhibition of the Notch1 pathway facilitates NPC exosome-induced differentiation of MSCs into NP-like cells in vitro. NPC exosomes play a key role in the differentiation of MSCs into NP-like cells in an indirect coculture system of NPCs and MSCs.

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