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1.
Artigo em Inglês | MEDLINE | ID: mdl-33121882

RESUMO

BACKGROUND: This study aimed to investigate the potential of drug-eluting bead transarterial chemoembolization (DEB-TACE) as downstaging therapy for subsequent radical treatment in patients with hepatocellular carcinoma (HCC). METHODS: Totally, 32 patients with unresectable HCC were enrolled, then they received DEB-TACE for down-staging therapy followed by radical treatments (surgery, radiofrequency ablation or microwave ablation). The rate of successful down-staging, treatment response (after DEB-TACE and radical therapy), alpha-fetoprotein (AFP), progression-free survival (PFS) and overall survival (OS) were assessed. RESULTS: After down-staging therapy with DEB-TACE, successful down-staging rate was 59.4%. With the followed radical treatment, the complete response was 81.3%. Subsequent analysis indicated that CNLC stage (IIb vs. IIa) was an independent risk factor for successful down-staging. Furthermore, AFP level presented a declined trend throughout the time points (before DEB-TACE, after DEB-TACE, and after radical treatment). Additionally, 1-year, 2-year and 3-year accumulating PFS were 68.8%, 40.6% and 31.3%, respectively; 1-year, 2-year and 3-year accumulating OS were 84.4%, 71.9% and 53.1%, respectively. Kaplan-Meier curves exhibited that successful down-staging was correlated with longer PFS and OS, then further Cox's regression analysis verified that successful down-staging was an independent factor for predicting increased OS but not PFS. Besides, child-Pugh stage (B vs. A), CNLC stage (IIb vs. IIa) and AFP abnormal after radical treatment were independent factors for decreased PFS or OS. CONCLUSIONS: DEB-TACE has potential as an additionally effective down-staging therapy for radical treatments, and successful down-staging treatment by DEB-TACE associates with favorable survival profiles in patients with unresectable HCC.

2.
Med Sci Monit ; 26: e926392, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044948

RESUMO

BACKGROUND Acute heart failure (AHF) usually requires urgent therapy. Myocardial damage, oxidative stress, and inflammation are major components in the pathology of AHF. This study was designed to investigate the effects of chrysophanol on AHF. MATERIAL AND METHODS Sprague-Dawley rats were injected with isoprenaline hydrochloride to construct AHF rat models. AHF rats were treated with normal saline (negative control), chrysophanol, the combination of chrysophanol and SP600125, or benazepril (positive control) using sham rats as blank controls. Echocardiography, histological staining, and enzyme activity analysis were performed to assess the heart functions and myocardial damage. Effects on apoptosis, oxidative stress (OS), and inflammation were evaluated by biochemical analysis, TUNEL staining, and ELISA. RESULTS Chrysophanol improved the parameters of cardiac functions and alleviated the myocardial damage accompanied by the reduction of creatine kinase and lactate dehydrogenase activity. Meanwhile, chrysophanol inhibited the myocardial apoptosis along with the upregulation of Bcl-2 and downregulation of Bax and cleaved caspase-3. AHF-induced abnormal changes of OS parameters (MDA, GPx, CAT, SOD) and inflammatory markers (IL-6, IL-1ß, TNF-alpha, IFN-γ) were alleviated by chrysophanol. Benazepril treatment showed similar results with chrysophanol, while the addition of SP600125 enhanced the chrysophanol-mediated protection effects in AHF rats. Western blot analysis demonstrated that chrysophanol inhibited the phosphorylation of JNK1/2 and its upstream/downstream factors. CONCLUSIONS Chrysophanol improved cardiac functions and protected against myocardial damage, apoptosis, OS, and inflammation by inhibiting activation of the JNK1/2 pathway in AHF rat models. These finding indicate that chrysophanol may be a promising approach for treatment of AHF.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32880804

RESUMO

BACKGROUND: Liver disease is associated with increased bleeding risk. The efficacy and safety of direct oral anticoagulants (DOACs) is a subject of contention in atrial fibrillation (AF) patients with liver disease. METHODS: Electronic databases (PubMed, Embase, and Cochrane Library) were searched to retrieve studies on the efficacy and safety of DOACs versus warfarin in AF patients with liver disease from January 1980 to April 2020. A meta-analysis was conducted using a random-effects model. RESULTS: Six studies involving 41,859 patients were included. Compared with warfarin, DOACs demonstrated significant reduction in ischemic stroke (HR, 0.68; 95% CI (0.54-0.86)), major bleeding (0.74 (0.59-0.92)), and intracranial hemorrhage (ICH) (0.48 (0.40-0.58)), with no significant effect on gastrointestinal bleeding (P = 0.893) in AF patients with liver disease. Similar results were observed in regular-dose, reduced-dose, and active liver disease subgroups, albeit Asian patients had a slight reduction in major bleeding (P = 0.055). Furthermore, the pooled estimates of individual DOAC subgroups indicated that dabigatran and apixaban led to greater safety in major bleeding (P < 0.001), ICH (P < 0.001), and gastrointestinal bleeding (P < 0.005) in these patients. The same trends were observed in AF patients with cirrhosis. CONCLUSIONS: Our findings suggest that DOACs significantly reduce the risk of ischemic stroke, major bleeding, and ICH, with no significant effect on the risk of gastrointestinal bleeding in AF patients with liver disease compared with warfarin.

4.
Biomed Res Int ; 2020: 8163789, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32775443

RESUMO

Background: Neoangiogenesis after cerebral ischemia in mammals is insufficient to restore neurological function, illustrating the need to design better strategies for improving outcomes. Our previous study has suggested that transcutaneous auricular vagus nerve stimulation (ta-VNS) induced angiogenesis and improved neurological functions in a rat model of cerebral ischemia/reperfusion (I/R) injury. However, the mechanisms involved need further exploration. Peroxisome proliferator-activated receptor-γ (PPAR-γ), well known as a ligand-modulated nuclear transcription factor, plays a crucial role in the regulation of cerebrovascular structure and function. Hence, the present study was designed to explore the role of PPAR-γ in ta-VNS-mediated angiogenesis and uncover the possible molecular mechanisms against ischemic stroke. Methods: Adult male Sprague-Dawley rats were transfected with either PPAR-γ small interfering RNA (siRNA) or lentiviral vector without siRNA prior to surgery and subsequently received ta-VNS treatment. The expression and localization of PPAR-γ in the ischemic boundary after ta-VNS treatment were examined. Subsequently, neurological deficit scores, neuronal damage, and infarct volume were all evaluated. Additionally, microvessel density, endothelial cell proliferation condition, and the expression of angiogenesis-related molecules in the peri-infarct cortex were measured. Results: We found that the expression of PPAR-γ in the peri-infarct cortex increased at 14 d and reached normal levels at 28 d after reperfusion. Ta-VNS treatment further upregulated PPAR-γ expression in the ischemic cortex. PPAR-γ was mainly expressed in neurons and astrocytes. Furthermore, ta-VNS-treated I/R rats showed better neurobehavioral recovery, alleviated neuronal injury, reduced infarct volume, and increased angiogenesis, as indicated by the elevated levels of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and phosphorylated endothelial nitric oxide synthase (P-eNOS). Surprisingly, the beneficial effects of ta-VNS were weakened after PPAR-γ silencing. Conclusions: Our results suggest that PPAR-γ is a potential mediator of ta-VNS-induced angiogenesis and neuroprotection against cerebral I/R injury.

5.
Eur Spine J ; 29(10): 2609-2618, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32504265

RESUMO

PURPOSE: This study aimed to evaluate facet joint parameters and osteoarthritis grades, and segmental angular and translational motions among different grades of L5/S1 intervertebral disc (IVD) degeneration. METHODS: This retrospective study analysed kinematic magnetic resonance imaging (kMRI) images of the lumbar spine of 214 patients with low back pain. Degenerations of the L5/S1 IVDs and facet joints osteoarthritis were assessed using the Pfirrmann and Pathria grading scales, respectively. Facet joint parameters included facet joint angle and facet joint space width. Angular and translation segmental motions were measured using MRI Analyzer software. RESULTS: The mean age of the studied patients was 44.1 ± 13.9 years. Patients with L5/S1 disc degeneration were associated with higher odds of facet joint osteoarthritis (odds ratio = 2.28, 95% confidence interval = 1.23-4.23, P = 0.008). There was a positive correlation between L5/S1 disc degeneration grade and the facet joint grade (r = 0.365, P > 0.001). Grade IV facet joint osteoarthritis did not appear in grades I or II disc degeneration (P > 0.001). The average facet joint width decreased significantly with increasing Pfirrmann grading (P = 0.017). The difference in facet joint angle between groups was not statistically significant (P = 0.532). The differences in the angular and translational motions were not statistically significant (P = 0.530, and 0.510, respectively). CONCLUSION: A positive correlation exists between L5/S1 disc degeneration and facet joint osteoarthritis grades. The facet joint space width decreases significantly with increasing grade of disc degeneration.

6.
Neurosci Lett ; 730: 135031, 2020 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-32416113

RESUMO

Axonal plasticity is important for neurofunctional recovery after stroke. This study aimed to explore the role of transcutaneous auricular vagus nerve stimulation (ta-VNS) on axonal plasticity and its underlying association with the α7 nicotinic acetylcholine receptor(α7nAchR) after cerebral ischemia/reperfusion (I/R) injury. Adult male Sprague-Dawley rats were pretreated by intraperitoneal injection with either phosphate-buffered saline (PBS) or an α7nAchR antagonist and then subjected to middle cerebral artery occlusion and ta-VNS treatment. α7nAchR expression and localization in the peri-infarct cortex were examined after ta-VNS treatment. Subsequently, neurologic scores were assessed with a battery of tests. Axonal regeneration, indicated by upregulation of growth-associated protein 43 (GAP-43) and neurofilament protein 200 (NF-200), was assessed. Axonal reorganization was examined on the basis of anterograde movement of the neuronal molecular probe biotin dextran amine. Additionally, brain-derived neurotrophic factor (BDNF)-associated signaling was measured 28d after I/R. Our findings showed that ta-VNS treatment enhanced α7nAchR expression in the ischemic cortex. α7nAchR colocalized with DCX and Nestin after reperfusion. Furthermore, ta-VNS-treated I/R rats displayed enhanced neurobehavioral performance and increased axonal plasticity (axonal regeneration and axonal reorganization), as indicated by elevated levels of BDNF/cyclic AMP (cAMP)/protein kinase A (PKA)/phosphorylated cAMP response element-binding protein pathway (p-CREB) pathway members. Strikingly, the beneficial effects of ta-VNS were diminished after α7nAchR blockade. In conclusion, our study is the first to show that α7nAchR is a potential mediator of ta-VNS-induced neuroprotection in the chronic phase of stroke and that its effects may be related to enhanced axonal plasticity through activation of the BDNF/cAMP/PKA/p-CREB pathway.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32340991

RESUMO

Despite the worldwide reemergence of the chikungunya virus (CHIKV) and the high morbidity associated with CHIKV infections, there is no approved vaccine or antiviral treatment available. Here, we aimed to identify the target of a novel class of CHIKV inhibitors, i.e., the CHVB series. CHVB compounds inhibit the in vitro replication of CHIKV isolates with 50% effective concentrations in the low-micromolar range. A CHVB-resistant variant (CHVBres) was selected that carried two mutations in the gene encoding nsP1 (responsible for viral RNA capping), one mutation in nsP2, and one mutation in nsP3. Reverse genetics studies demonstrated that both nsP1 mutations were necessary and sufficient to achieve ∼18-fold resistance, suggesting that CHVB targets viral mRNA capping. Interestingly, CHVBres was cross-resistant to the previously described CHIKV capping inhibitors from the MADTP series, suggesting they share a similar mechanism of action. In enzymatic assays, CHVB inhibited the methyltransferase and guanylyltransferase activities of alphavirus nsP1 proteins. To conclude, we identified a class of CHIKV inhibitors that targets the viral capping machinery. The potent anti-CHIKV activity makes this chemical scaffold a potential candidate for CHIKV drug development.

8.
Biologicals ; 65: 25-32, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32165080

RESUMO

Immunoglobulin preparations are one of the promising drugs for Alzheimer's disease (AD). Anti-ß-amyloid (Aß) oligomers antibodies in immunoglobulin preparations are considered to be critical for the therapeutic effect against Alzheimer's disease. However, the antibodies content in immunoglobulin preparations varies greatly. In order to determine which factor contributes to the difference of the antibodies content, the content of anti-Aß oligomers antibodies in multiple batches of immunoglobulin preparations from two manufacturers were measured by enzyme-linked immunosorbent assay. The results showed that no significant difference was found in the antibodies content among different bathes of normal immunoglobulin preparations prepared by the same process from the same manufacturer, whereas significant difference was found in the antibodies content between normal immunoglobulin preparations prepared by ethanol fractionation and those by chromatography process from the same manufacturer. In addition, significant variation existed in the antibodies content between normal immunoglobulin preparations and specific immunoglobulin preparations that are produced by plasma pool of immunized donors. Based on analysis of these results, the preparation process and raw plasma could be the main contributing factors affecting the content of anti-Aß oligomers antibodies in immunoglobulin preparations. This finding might help to develop AD-specific immunoglobulin preparation containing higher content of anti-Aß oligomers antibodies.

9.
Acta Biomater ; 108: 223-236, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32165192

RESUMO

The periosteum plays a critical role in bone formation and defect reconstruction. The concept of tissue engineering in the periosteum has been suggested to solve the clinical problems related to bone defect repair. Insertion of polymethyl methacrylate (PMMA) bone cement can induce the autologous generation of a tissue-engineered periosteum and has been considered as a promising strategy for bone defect reconstruction. The PMMA-induced membrane is a crucial element in the reconstruction of bone defects, especially for angiogenesis, but its biological mechanism remains elusive. Here, a PMMA-induced membrane model was established using a femoral critically sized defect in mice. We identified myeloid-derived suppressor cells (MDSCs) as a regulatory component of induced membrane vascularization. The increased number of MDSCs was markedly linked to increased membrane thickness and capillary density. Importantly, the results of an in vitro coculture assay indicated that MDSCs of the induced membrane further facilitated the angiogenic capacity of human umbilical vein endothelial cells (HUVECs) by upregulating the expression of VEGFA, Ang2 and HIF-1α. Furthermore, signaling pathway blockade results suggested that STAT3 activation is involved in the upregulation of VEGFA, Ang2 and HIF-1α expression in induced membrane MDSCs. Our findings provide new insights into the mechanism of angiogenesis in the PMMA-induced membrane and confirm the key signaling molecules of MDSCs in induced membrane angiogenesis. Based on these results, this strategy may become a new therapy for the treatment of large bone defects in the future. STATEMENT OF SIGNIFICANCE: In this study, we established an autologous tissue-engineered periosteum - PMMA-induced membrane, which was formed by the foreign body reaction to PMMA bone cement. The induced membrane establishes a blood supply for the large bone defect healing. After investigation, our study discovered the critical cell type in the formation and angiogenesis processes of the induced membrane, myeloid-derived suppressor cells (MDSCs). We revealed that MDSCs of the induced membrane promote the angiogenesis of endothelial cells through the expression of VEGFA, Ang2 and HIF-1α, which was upregulated by the activation of STAT3 signaling. Our findings clarified the beneficial effect of MDSCs in the angiogenesis of bone repair, and offered an additional target for the study of foreign body reactions to bone repair materials.

10.
Int J Surg ; 76: 136-143, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32165279

RESUMO

BACKGROUND: Percutaneous endoscopic transforaminal lumbar interbody fusion (PETLIF) has been used in the treatment of lumbar degenerative diseases, as a novel minimally invasive technique. OBJECTIVES: To compare the surgical trauma and the medium-short term postoperative outcomes of PETLIF and traditional minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). METHODS: From April to August of 2018, 75 patients with lumbar degenerative diseases received PETLIF (Group PE, 35 cases) or MIS-TLIF (Group MIS, 40 cases) were enrolled in the prospective cohort study. We recorded the serum creatine kinase (CK) and C-reactive protein (CRP), blood loss, visual analog scale (VAS), Oswestry Disability Index (ODI), modified Macnab criteria score, complications, and fusion rates of the 2 groups. RESULTS: There were significant reductions in CRP (P = 0.002) on postoperative day (POD) 3, and CK (P = 0.011) on POD 1 for Group PE than Group MIS. The mean true total blood loss (P < 0.001), intraoperative blood loss (P < 0.001), postoperative drains (P < 0.001), and hidden blood (P = 0.020) in the Group PE were significantly less compared with Group MIS. The VAS score for low-back pain, leg pain and ODI score improved significantly in both groups after surgery (P < 0.05). The VAS of low-back pain on POD 1 was significant less (P < 0.001) for Group PE. There was no statistical difference (P = 0.561) in CT fusion rates between Group PE (85%) and Group MIS (92%). No serious complication was observed in any patients. CONCLUSION: The study indicated that PETLIF had advantages of less surgical trauma, less postoperative low-back pain, less hidden blood loss, and faster recovery, compared with MIS-TLIF. There was no significant difference in medium-short term surgical outcomes between the 2 techniques. However, the indications of PETLIF is relatively limited, and the learning curve of PETLIF is deep, surgeons need to select indications strictly. Further study with big sample size and long-term follow-up is needed.


Assuntos
Degeneração do Disco Intervertebral , Procedimentos Cirúrgicos Minimamente Invasivos , Fusão Vertebral , Adulto , Perda Sanguínea Cirúrgica , Procedimentos Cirúrgicos de Citorredução , Endoscopia , Feminino , Humanos , Degeneração do Disco Intervertebral/cirurgia , Complicações Intraoperatórias , Dor Lombar , Vértebras Lombares/cirurgia , Região Lombossacral/cirurgia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Período Pós-Operatório , Estudos Prospectivos , Fusão Vertebral/métodos , Centros de Atenção Terciária , Resultado do Tratamento , Escala Visual Analógica
11.
Life Sci ; 248: 117444, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32084433

RESUMO

AIMS: Nonhuman primates have been used to investigate pathogenic mechanisms and evaluate immune responses following Chlamydia trachomatis inoculation. This study aimed to systemically profile antibody responses to C. trachomatis infection in nonhuman primates. MATERIALS AND METHODS: Sera were obtained from 4 pig-tailed and 8 long-tailed macaques which were intravaginally or ocularly infected with live C. trachomatis organisms, and analyzed by C. trachomatis proteome array of antigens. KEY FINDINGS: The sera from 12 macaques recognized total 172 C. trachomatis antigens. While 84 antigens were recognized by pig-tailed macaques intravaginally infected with serovar D strain, 125 antigens were recognized by long-tailed macaques ocularly infected with serovar A, and 37 antigens were recognized by both. Ocular inoculation with virulent A2497 strain induced antibodies to more antigens. Among the antigens uniquely recognized by A2497 strain infected macaques, outer membrane complex B antigen (OmcB) induced robust antibody response. Although macaques infected by less virulent A/HAR-13 strain failed to develop antibodies to OmcB, reinfection by A2497 strain induced high levels of antibodies to OmcB. SIGNIFICANCE: Proteome array has revealed a correlation of chlamydial infection invasiveness with chlamydial antigen immunogenicity, and identified antibody responses to OmcB potentially as biomarkers for invasive infection with C. trachomatis.


Assuntos
Anticorpos Antibacterianos/biossíntese , Antígenos de Bactérias/sangue , Infecções por Chlamydia/imunologia , Chlamydia trachomatis/imunologia , Infecções do Sistema Genital/imunologia , Tracoma/imunologia , Animais , Anticorpos Antibacterianos/classificação , Antígenos de Bactérias/classificação , Proteínas da Membrana Bacteriana Externa/sangue , Infecções por Chlamydia/sangue , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/patogenicidade , Olho/imunologia , Olho/microbiologia , Feminino , Soros Imunes/química , Macaca fascicularis , Macaca nemestrina , Masculino , Análise Serial de Proteínas , Proteoma/química , Proteoma/imunologia , Infecções do Sistema Genital/sangue , Infecções do Sistema Genital/microbiologia , Tracoma/sangue , Tracoma/microbiologia , Vagina/imunologia , Vagina/microbiologia
12.
J Photochem Photobiol B ; 204: 111782, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32062389

RESUMO

BACKGROUND: Ultraviolet (UV) fluorescent lamp (FL) was applied in mainstream riboflavin photochemical method (RPM) to inactivate pathogens in blood components. Low UV irradiance emitted by UV-FL resulted in more time to achieve effective inactivation. MATERIALS AND METHODS: A novel light emitting diode (LED) UV illumination with adjustable irradiance was developed by us. Two strains of drug-resistant bacteria (DRB), pan-drug resistant Acinetobacter baumannii (PDRAB) and methicillin-resistant Staphylococcus aureus (MRSA) were cultured and used for evaluating the inactivation effectiveness of RPM using UV-LED or UV-FL against DRB in plasma or platelets. Three plasma factors and four platelet parameters were measured after treatments. RESULTS: There was a linear relationship between UV-LED irradiance and electric current, the minimum UV irradiance was 24 mW/cm2, and the maximum was 258 mW/cm2. At the same UV dose of 15 J/cm2, inactivation effectiveness of UV-LED with 258 mW/cm2 against PDRAB in plasma or platelets were comparable to that of UV-FL with 16 mW/cm2, both above 98%. UV-FL treatment required 10-15 min, but UV-LED only required 1-2 min. However, MRSA showed a resistance to UV-LED (inactivation effectiveness was around 40%) compared with UV-FL (inactivation effectiveness was above 98%). The retention of fibrinogen, factor V, factor VII in plasma and platelet counts in platelets with UV-LED treatment were significantly higher than UV-FL at the same UV dose. CONCLUSION: The treatment of RPM using UV-LED with high UV irradiance was able to dramatically shorten inactivation time against PDRAB in plasma or platelets and improve retention of blood components compared with UV-FL.


Assuntos
Proteínas Sanguíneas/metabolismo , Riboflavina/química , Raios Ultravioleta , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/efeitos da radiação , Plaquetas/citologia , Plaquetas/efeitos dos fármacos , Plaquetas/efeitos da radiação , Farmacorresistência Bacteriana/efeitos dos fármacos , Fator V/metabolismo , Fibrinogênio/metabolismo , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos da radiação , Contagem de Plaquetas , Riboflavina/farmacologia
13.
Biochem Biophys Res Commun ; 524(3): 756-763, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32035615

RESUMO

Intervertebral disc degeneration (IDD) is typically accompanied by a reduced nutrient supply, which is thought to be a contributor to the apoptosis of nucleus pulposus cells (NPCs). Here, we explored whether Forkhead box O3 (FOXO3), a key transcription factor involved in cellular quality control, could protect NPCs against apoptosis under nutrient deficiency. Firstly, we found that FOXO3 knockdown aggravated nutrient deficiency-induced mitochondrial dysfunction, apoptosis and matrix degradation in NPCs. In addition, the siRNA-mediated downregulation of FOXO3 suppressed mitophagy in starved NPCs. However, when we overexpressed FOXO3 in NPCs by lentivirus transfection, the observed detrimental effects induced by nutrient deprivation were significantly reversed by the FOXO3-activated autophagy. Moreover, by analyzing the human NP samples from different age groups as well as degenerated groups, we found that the FOXO3 protein level decreased with aging and degeneration. Together, our data suggest that FOXO3 plays a vital role in disc degeneration and can be a novel therapeutic target for IDD.


Assuntos
Apoptose , Autofagia , Citoproteção , Proteína Forkhead Box O3/metabolismo , Núcleo Pulposo/citologia , Animais , Matriz Extracelular/metabolismo , Matriz Extracelular/ultraestrutura , Técnicas de Silenciamento de Genes , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Mitofagia , Núcleo Pulposo/ultraestrutura , Ratos , Inanição
14.
Medicine (Baltimore) ; 99(4): e18789, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977870

RESUMO

Clinical features of extremity fractures (EFs) in patients presenting with traumatic spinal fractures (TSFs) and spinal cord injury (SCI) have not been investigated. To investigate the clinical features and risk factors for EFs in patients presenting with TSFs and SCI.Data from 1392 patients presenting with TSFs and SCI in our hospitals between 2001 and 2010 were retrospectively reviewed, among which 165 patients (129 males and 36 females, 37.5 ±â€Š10.6 years old) presented with EFs. The clinical features of EFs have been investigated.The frequencies of upper limb fractures were significantly higher in the motor vehicle collisions (MVCs) group than in the high-fall group (P = .012) and the struck-by-object group (P = .002). The frequencies of lower limb fractures were significantly higher in the struck-by-object group (P = .019) and the high-fall group (P = .011) than the MVCs group. Univariate logistic regression analysis show that being in the 19 to 39 age group (P = .001), having a lumbar spinal fracture (P < .001) and experiencing a high fall (P < .001) were risk factors for EFs. Multivariate logistic regression analysis showed that we should focus on the factors that having a lumbar spinal fracture and experiencing a high fall.High fall and MVCs were the most common aetiologies for EFs. Having a lumbar spinal fracture and experiencing a high fall were significant risk factors for EFs. We should make early diagnoses and initiate timely treatment according to different patterns of extremity fractures in patients with TSFs and SCI.


Assuntos
Fraturas Ósseas/epidemiologia , Extremidade Inferior/lesões , Fraturas da Coluna Vertebral/epidemiologia , Extremidade Superior/lesões , Acidentes/estatística & dados numéricos , Adulto , Fatores Etários , Feminino , Fraturas Ósseas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fraturas da Coluna Vertebral/etiologia
15.
Biomaterials ; 232: 119701, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31901505

RESUMO

Various design and fabrication strategies of carrier-based drug delivery systems have been quickly established and applied for cancer therapy in recent years. These systems contribute greatly to current cancer treatments but further development needs to be made to eliminate obstacles such as low drug loading capacity and severe side effects. To achieve better drug delivery, we propose an innovative strategy for the construction of easy manufactured drug self-delivery systems based on molecular structures, which can be used for the co-delivery of curcuminoids and all the nitrogen-containing derivatives of camptothecin for better targeted cancer therapy with minimized side effects. The formation mechanism investigation demonstrates that the rigid planar structures of camptothecin derivatives and curcuminoids with relevant leaving hydrogens make it possible for them to be assembled into nanoparticles under suitable conditions. These nanoparticles show stabilized particle sizes (100 nm) under various conditions and tunable surface charges which increase from around -10 mV in a normal physiological condition (pH 7.4) to +40 mV under acidic tumor environments. In addition, in vivo mice experiments have demonstrated that, compared to irinotecan (a derivative of camptothecin) itself, the co-delivered irinotecan curcumin nanoparticles exhibited significantly enhanced lung and gallbladder targeting, improved macrophage-clearance escape and ameliorated colorectal cancer treatment with an eradication of life-threatening diarrhea, bringing hope for better targeted chemotherapy and clinical translation. Lastly, the strategy of structure based design of drug self-delivery systems may inspire more research and discoveries of similar self-delivered nano systems for wider pharmaceutical applications.

16.
J Pharmacol Toxicol Methods ; 102: 106678, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31981619

RESUMO

Polyethylene glycol (PEG) conjugation, i.e. PEGylation, is a successful strategy to improve the pharmacokinetics and pharmacodynamics of biopharmaceuticals. In the past few decades, PEGylation technology has developed tremendously, and >15 PEGylated therapeutics have been brought to market, with more in development. However, the widely accepted assumption that PEG would have no antigenicity or immunogenicity is increasingly challenged with popularization of PEGylation technique. Although PEGylation indeed reduces the immunogenicities of the modified molecules, and even appears to completely eliminate their immunogenicities, yet emerging clinical evidence of anti-PEG antibodies (including both pre-existing and PEGylated therapeutics-treatment induced anti-PEG antibodies) have been attracted more and more attention. Anti-PEG antibodies were detected in not only patients treated with PEGylated therapeutics but also PEGylated drugs treatment-naïve individuals with a prevalence from <1% to 72%. In patients, the existing anti-PEG antibodies may attenuate therapeutic efficacy of PEGylated drugs and increase adverse effects. Although there is no golden standard avenue, several types of methods, including passive hemagglutination, Western Blot, enzyme linked immunosorbent assay, flow cytometry, Meso Scale Discovery technology, Acoustic Membrane Microparticle assay, and surface plasmon resonace technique, were established and used to screen, confirm and quantitatively detect anti-PEG antibodies. Herein, we focused on reviewing the prevalence of anti-PEG antibodies in healthy and PEGylated therapeutics-treated patients, and highlighting the detection methods for pre-screening and quantitative detection of anti-PEG antibodies.


Assuntos
Anticorpos/imunologia , Polietilenoglicóis/química , Animais , Anticorpos/sangue , Humanos
17.
J Back Musculoskelet Rehabil ; 33(2): 255-262, 2020.
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.

18.
Mol Med Rep ; 21(1): 9-19, 2020 Jan.
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.

19.
Infect Genet Evol ; 78: 104049, 2020 03.
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.

20.
Nano Lett ; 20(4): 2197-2208, 2020 04 08.
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.

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