ABSTRACT
Rhabdoviruses with rich species lead a variety of high lethality and rapid transmission diseases to plants and animals around the globe. Vaccination is one of the most effective approaches to prevent and control virus disease. However, the key antigenic epitopes of glycoprotein being used for vaccine development are unclear. In this study, fish-derived Abs are employed for a Micropterus salmoides rhabdovirus (MSRV) vaccine design by phage display and bioinformatics analysis. We constructed an anti-MSRV phage Ab library to screen Abs for glycoprotein segment 2 (G2) (G129-266). Four M13-phage-displayed Abs (Ab-5, Ab-7, Ab-8 and Ab-30) exhibited strong specificity to target Ag, and Ab-7 had the highest affinity with MSRV. Ab-7 (300 µg/ml) significantly increased grass carp ovary cell viability to 83.40% and significantly decreased the titer of MSRV. Molecular docking results showed that the key region of Ag-Ab interaction was located in 10ESQEFTTLTSH20 of G2. G2Ser11 and G2Gln12 were replaced with alanine, respectively, and molecular docking results showed that the Ag-Ab was nonbinding (ΔG > 0). Then, the peptide vaccine KLH-G210-20 was immunized to M. salmoides via i.p. injection. ELISA result showed that the serum Ab potency level increased significantly (p < 0.01). More importantly, the challenge test demonstrated that the peptide vaccine elicited robust protection against MSRV invasion, and the relative percentage survival reached 62.07%. Overall, this study proposed an approach for screening key epitope by combining phage display technology and bioinformatics tools to provide a reliable theoretical reference for the prevention and control of viral diseases.
Subject(s)
Bass , Rhabdoviridae , Vaccines , Animals , Female , Molecular Docking Simulation , Epitopes , Glycoproteins , Vaccine DevelopmentABSTRACT
Globally, streptococcal disease caused by Streptococcus agalactiae is known for its high mortality rate, which severely limits the development of the tilapia breeding industry. As a third-generation vaccine, DNA vaccines have shown great application prospects in the prevention and control of aquatic diseases, but their low immunogenicity limits their development. The combination of DNA vaccines and molecular adjuvants proved to be an effective method for inducing protective immunity. This study constructed recombinant plasmids encoding tilapia HSP70 and IL-1ß genes (pcHSP70 and pcIL-1ß) to verify their effectiveness as molecular adjuvants for S. agalactiae DNA vaccine (pcSIP) in the immunized tilapia model. The results revealed that serum-specific IgM production, enzyme activities, and immune-related gene expression in tilapia immunized with pcSIP plus pcHSP70 or pcIL-1ß were significantly higher than those in tilapia immunized with pcSIP alone. It is worth noting that combination with molecular adjuvants improved the immune protection of DNA vaccines, with a relative percentage survival (RPS) of 51.72% (pcSIP plus pcHSP70) and 44.83% (pcSIP plus pcIL-1ß), respectively, compared with that of pcSIP alone (24.14%). Thus, our study indicated that HSP70 and IL-1ß in tilapia are promising molecular adjuvants of the DNA vaccine in controlling S. agalactiae infection.
ABSTRACT
Late anti-toxin-B humoral immunity acquired after treatment is important for preventing recurrent Clostridioides difficile infection. We prospectively-measured anti-toxin-B IgG and neutralization titers at diagnosis as potential early predictors of recurrence. High anti-toxin-B-IgG/neutralizing antibodies were associated with short-lasting protection within 6-weeks, however, no difference in recurrence risk was observed by 90-days post-infection.
Subject(s)
Antibodies, Bacterial , Bacterial Toxins , Clostridioides difficile , Clostridium Infections , Immunoglobulin G , Recurrence , Clostridium Infections/immunology , Clostridium Infections/prevention & control , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Bacterial Toxins/immunology , Clostridioides difficile/immunology , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Male , Middle Aged , Female , Aged , Bacterial Proteins/immunology , Prospective Studies , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Adult , Aged, 80 and overABSTRACT
We proposed a "Ni sacrifice" method to fabricate Al-based highly reflective p-electrode in the ultraviolet spectral region for AlGaN-based deep-ultraviolet light-emitting diodes (DUV-LEDs). The "Ni sacrifice" p-electrode could have a high optical reflectivity of around 90% at the DUV spectral region below 300â nm. Compared to Ni/Au, indium tin oxide (ITO), and Pd p-contacts, the "Ni sacrifice" led to a higher resistivity of p-contacts and a slightly higher operated voltage of the DUV-LEDs (within 0.6â V at 20â mA). Although the electrical performance was degraded slightly, the light output power and external quantum efficiency of the DUV-LEDs could be improved by utilizing the "Ni sacrifice" p-electrode. Besides, we introduced a grid of vias in the device mesa and reduced the diameter of the vias to achieve an enhanced peak external quantum efficiency (EQE) up to 1.73%. And the wall-plug efficiency (WPE) of DUV-LEDs with a "Ni sacrifice" p-electrode was higher than that of Ni/Au p-electrode DUV-LEDs at low currents. These results highlight the great potential of the proposed "Ni sacrifice" reflective p-electrode for use in DUV-LEDs.
ABSTRACT
Upon chronic damage to the liver, multiple cytokines stimulate hepatic stellate cells (HSCs), causing the alterations of gene expression profiles and thus leading to HSC activation, a key step in liver fibrogenesis. Activated HSCs are the dominant contributors to liver fibrosis. Bromodomain containing protein 4 (BrD4), an important epigenetic reader, was demonstrated to concentrate on hundreds of enhancers associated with genes involved in multiple profibrotic pathways, thereby directing HSC activation and the fibrotic responses. The present studies were designed to examine the effect of transforming growth factor beta-1 (TGFß1), the most potent pro-fibrotic cytokine, on BrD4 expression in HSCs and, if so, elucidated the underlying mechanisms in vitro and in vivo. The experiments employed the heterogeneous TGFß1 knockout (TGFß1+/- ) mice, gene knockdown in vivo, and a model of thioacetamide (TAA)-induced liver injury. The results revealed that TGFß1 enhanced BrD4 expression in HSCs, which was mediated, at least, by Smad3 signaling and early-immediate gene Egr1 (early growth response-1). TGFß1-induced Smad3 signaling increased Egr1 expression and promoted Egr1 binding to BrD4 promoter at a site around -111 bp, promoting BrD4 expression. Egr1 knockdown reduced BrD4 expression in HSCs in a mouse model of TAA-induced liver injury and lessened liver fibrosis. Double fluorescence staining demonstrated a strong increase in BrD4 expression in activated HSCs in fibrotic areas of the human livers, paralleling the upregulation of p-Smad3 and Egr1. This research suggested novel molecular events underlying the roles of the master pro-fibrotic cytokine TGFß1 in HSC activation and liver fibrogenesis.
Subject(s)
Chemical and Drug Induced Liver Injury, Chronic , Early Growth Response Protein 1 , Hepatic Stellate Cells , Nuclear Proteins , Transcription Factors , Animals , Humans , Mice , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Chemical and Drug Induced Liver Injury, Chronic/metabolism , Early Growth Response Protein 1/genetics , Early Growth Response Protein 1/metabolism , Epigenesis, Genetic , Fibrosis , Hepatic Stellate Cells/metabolism , Liver Cirrhosis/chemically induced , Liver Cirrhosis/genetics , Liver Cirrhosis/metabolism , Nuclear Proteins/metabolism , Smad3 Protein/genetics , Smad3 Protein/metabolism , Thioacetamide/adverse effects , Transcription Factors/metabolism , Transforming Growth Factor beta1/metabolismABSTRACT
The disease caused by Micropterus salmoides rhabdovirus (MSRV) has brought substantial economic losses to the largemouth bass aquaculture industry in China. Vaccination was considered as a potential way to prevent and control this disease. As a kind of sustained and controlled release system, alginate and chitosan microspheres (SA-CS) are widely used in the development of oral vaccination for fish. Here, we prepared a king of alginate-chitosan composite microsphere to encapsulate the second segment of MSRV glycoprotein (G2 protein) and then evaluated the immune effect of the microsphere vaccine on largemouth bass. Largemouth bass were vaccinated via intragastric immunization by different treatments (PBS, SA-CS, G2 and SA-CS-G2). The results showed that a stronger immune response including serum antibody levels, immune-related physiological indexes (acid phosphatase, alkaline phosphatase, superoxide dismutase and total antioxidant capacity) and the expression of immune-related gene (IgMãIL-8ãIL-1ßãCD4ãTGF-ßãTNF-α) can be induced obviously with SA-CS-G2 groups compared with G2 groups when fish were vaccinated. Furthermore, fish were injected with a lethal dose of MSRV after immunization for 28 days, and the highest relative percentage survival (54.8%) was observed in SA-CS-G2 group (40 µg per fish), which is significantly higher than that of G2 group (25.8%). This study showed that alginate-chitosan microspheres as the vaccine carrier can effectively improve the immune effect of oral vaccination and induce better immune protection effect against MSRV infection.
Subject(s)
Bass , Chitosan , Fish Diseases , Rhabdoviridae , Acid Phosphatase , Alginates , Alkaline Phosphatase , Animals , Antioxidants , Delayed-Action Preparations , Immunoglobulin M , Interleukin-8 , Microspheres , Superoxide Dismutase , Transforming Growth Factor beta , Tumor Necrosis Factor-alpha , Vaccines, Subunit , Vaccines, SyntheticABSTRACT
BACKGROUND: There is a global focus on illness diagnosis in smear-negative and latent tuberculosis infectious populations (SN-TB and LTBI). CD27 has been suggested to play a direct role in active TB. Little is known about smear-negative individuals. Here, we tried to investigate whether it has a role in smear-negative populations. The expression of CD27 and MTB-specific CD27 in CD4+ T cells ("CD27-CD4+" and "CD27-IFN-γ+CD4+") was evaluated in MTB-unexposed controls (HC), TB contacts (TB-C) and SN-TB individuals by flow cytometry. The sensitivity, specificity and AUC (area under curve) of "CD27-IFN-γ+CD4+" cells to distinguish SN-TBs from HCs and TB-Cs were determined by receiver operating characteristic (ROC) curve analysis. The clinical index was selected from the clinical laboratory and evaluated for correlation with "CD27-IFN-γ+CD4+" cells by Spearman statistical analysis. RESULTS: We observed that the percentages of "CD27-IFN-γ+CD4+" cells were significantly increased in the SN-TB group compared with the HC and TB-C groups (AUC was 0.88, sensitivity was 82.14%, specificity was 80.00%, and P < 0.0001). The percentage of "CD27-IFN-γ+CD4+" cells was negatively correlated with WBC (white blood cell count) (r = - 0.3019, P = 0.0182) and positively correlated with IgE (immunoglobulin E) (r = 0.2805, P = 0.0362). Furthermore, "CD27-IFN-γ+CD4+" cells were significantly decreased, especially in the > 50 years group, after clinical treatment. CONCLUSION: The present results demonstrated that the percentage of "CD27-IFN-γ+CD4+" cells might be a conceivable molecular indicator in the diagnosis of SN-TB and was influenced by its outcome of therapy.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , Latent Tuberculosis/diagnosis , Mycobacterium tuberculosis/physiology , Tuberculosis, Pulmonary/diagnosis , Tumor Necrosis Factor Receptor Superfamily, Member 7/metabolism , Adult , Female , Flow Cytometry , Humans , Interferon-gamma/metabolism , Latent Tuberculosis/therapy , Lymphocyte Count , Male , Middle Aged , ROC Curve , Sensitivity and Specificity , Tuberculosis, Pulmonary/therapyABSTRACT
BACKGROUND: Tuberculosis (TB) and type 2 diabetes mellitus (DM) are global health diseases with high morbidity and mortality. Few studies have focused on platelet indices in TB-DM coinfection patients. The objective of this work was to analyze the platelet indices in TB, DM and TB-DM patients to assess the predictive value of the platelet index for the risk of these diseases. METHODS: In total, 246 patients admitted to our hospital were distributed into three groups (113 TB, 59 DM and 74 TB + DM). A total of 133 individuals were also recruited as healthy controls (HC). Platelet indices, namely, platelet count (PC), mean platelet volume (MPV), plateletcrit (PCT) and platelet distribution width (PDW), were compared among the four groups, and the relationship with inflammatory markers was explored by using statistical software. RESULTS: Our study discovered that MPV and PCT were significantly downregulated in TB + DM patients (9.95 ± 1.25 fL, 0.20 ± 0.05%, P < 0.0001, P = 0.0121, separately) compared with DM individuals (10.92 ± 1.17 fL, 0.22 ± 0.04%). Moreover, the changes in MPV were significantly higher in TB + DM patients (9.95 ± 1.25 fL, P = 0.0041) than in TB patients (9.42 ± 1.01 fL). No differences were found in PLT and PDW among the four groups (P > 0.05). The sensitivity and specificity of MPV in the differential diagnosis of DM patients vs TB + DM patients were 64.9 and 66.1% (P < 0.0001), respectively, and the sensitivity and specificity of MPV between TB patients and TB + DM patients was 60.8 and 66.4%, respectively (P = 0.003). MPV improved the diagnosis sensitivity when it was combined with clinical parameters, such as fasting blood glucose in DM and Mycobacterium tuberculosis culture result in TB (76.3% vs 64.9, 72.6% vs 60.8%, P < 0.0001, P = 0.001, respectively). In addition, the sensitivity and specificity of PCT in the differential diagnosis of DM patients vs TB + DM patients were 69.5 and 59.4%, respectively (P = 0.008). PCT improved the diagnosis sensitivity when combined with fasting blood glucose in DM (72.9% vs 64.9%, P = 0.004). In addition, MPV was linked to CRP (C-reactive protein) and ESR (erythrocyte sedimentation rate) in the TB + DM patients (r = 0.3203, P = 0.0054, r = 0.2504, P = 0.0307) but PCT was not (r = 0.1905, r = 0.008675, P > 0.05, respectively). CONCLUSIONS: Our research shows that MPV and PCT might be good clinical laboratory markers to distinguish TB + DM patients from TB or DM individuals, thus providing support for earlier clinical diagnosis, prevention, and therapy.
Subject(s)
Diabetes Mellitus, Type 2/epidemiology , Mean Platelet Volume , Tuberculosis/epidemiology , Adult , Biomarkers/blood , Blood Platelets/metabolism , Blood Sedimentation , Comorbidity , Humans , Male , Middle Aged , Platelet Count , Predictive Value of Tests , Tuberculosis/blood , Tuberculosis/metabolismABSTRACT
INTRODUCTION: Obese patients are often accompanied by hyperleptinemia and prone to develop liver fibrosis. Accumulating data including those obtained from human studies suggested the promotion role of leptin in liver fibrosis. The remodeling of the DNA methylation is an epigenetic mechanism for regulating gene expression and is essential for hepatic stellate cell (HSC) activation, a key step in liver fibrogenesis. Leptin increases the expression of methionine adenosyltransferase 2A (MAT2A) which is associated with DNA methylation and HSC activation. Curcumin, an active polyphenol of the golden spice turmeric, inhibits leptin-induced HSC activation and liver fibrogenesis. Thus, the present research aimed to investigate the influence of curcumin on the roles of leptin in MAT2A expression in HSCs. METHODS: The in vivo experiments were conducted by using leptin-deficient obese mice. The gene expressions were examined by Western blot, real-time PCR, promoter activity assay, and immunostaining analysis. RESULTS: Curcumin reduced leptin-induced MAT2A expression. JNK signaling contributed to leptin-induced increase in MAT2A level, which could be interrupted by curcumin treatment. Curcumin inhibited leptin-induced MAT2A promoter activity by influencing MAT2A promoter fragments between -2,847 bp and - 2,752 bp and between -2,752 bp and +49 bp. The effect of curcumin on leptin-induced MAT2A expression paralleled the reductions in leptin-induced activated HSCs and liver fibrosis. CONCLUSION: These results might have implications for curcumin inhibition of the liver fibrogenesis in obese patients with hyperleptinemia.
Subject(s)
Curcumin/pharmacology , Hepatic Stellate Cells/drug effects , Leptin/metabolism , Liver Cirrhosis/prevention & control , Animals , Hepatic Stellate Cells/metabolism , Liver Cirrhosis/pathology , MAP Kinase Signaling System/drug effects , Male , Methionine Adenosyltransferase/genetics , Mice , Mice, Inbred C57BL , Mice, Obese , Obesity/complicationsABSTRACT
White spot syndrome virus (WSSV) is a serious pathogen threatening global crustacean aquaculture with no commercially available drugs. Herbal medicines widely used in antiviral research offer a rich reserve for drug discovery. Here, we investigated the inhibitory activity of 13 herbal medicines against WSSV in crayfish Procambarus clarkii and discovered that naringenin (NAR) has potent anti-WSSV activity. In the preliminary screening, the extracts of Typha angustifolia displayed the highest inhibitory activity on WSSV replication (84.62%, 100 mg/kg). Further, NAR, the main active compound of T. angustifolia, showed a much higher inhibition rate (92.85%, 50 mg/kg). NAR repressed WSSV proliferation followed a dose-dependent manner and significantly improved the survival of WSSV-challenged crayfish. Moreover, pre- or post-treatment of NAR displayed a comparable inhibition on the viral loads. NAR decreased the transcriptional levels of vital genes in viral life cycle, particularly for the immediately early-stage gene ie1. Further results showed that NAR could decrease the STAT gene expression to block ie1 transcription. Besides, NAR modulated immune-related gene Hsp70, antioxidant (cMnSOD, mMnSOD, CAT, GST), anti-inflammatory (COX-1, COX-2) and pro-apoptosis-related factors (Bax and BI-1) to inhibit WSSV replication. Overall, these results suggest that NAR may have the potential to be developed as preventive or therapeutic agent against WSSV.
Subject(s)
Antiviral Agents/pharmacology , Astacoidea/virology , Flavanones/pharmacology , Typhaceae/chemistry , White spot syndrome virus 1/drug effects , Animals , Antiviral Agents/chemistry , Flavanones/chemistry , Virus Replication/drug effects , White spot syndrome virus 1/physiologyABSTRACT
PRIMARY OBJECTIVE: Oxidative stress is the principal factor in traumatic brain injury (TBI) that initiates the events that result in protracted neuronal dysfunction and remodeling. Importantly, antioxidants can protect the brain against oxidative damage and modulate the capacity of the brain to cope with synaptic dysfunction and cognitive impairment. RESEARCH DESIGN: To date, however, no studies have investigated the effects of procyanidins (PC) on cognitive deficits after TBI. METHODS AND PROCEDURES: In the present study, rats with controlled cortical impact (CCI) were used to investigate the protective effects of procyanidins. MAIN OUTCOMES AND RESULTS: The results showed that procyanidins reduced the level of malondialdehyde (MDA) and elevated the level of glutathione (GSH) and the activity of superoxide dismutase (SOD). In addition, treatment with procyanidins, which elevated the levels of brain-derived neurotropic factor (BDNF), phosphorylation-cAMP-response element binding protein (pCREB), total CREB, and cyclic AMP (cAMP), improved cognitive performance in the Morris water maze after TBI. CONCLUSIONS: These results suggest that procyanidins appear to counteract oxidative damage and behavioral dysfunction after TBI through antioxidant activity and the up-regulation of cAMP/CREB signaling.
Subject(s)
Brain Injuries/drug therapy , Brain Injuries/metabolism , Cognition Disorders/drug therapy , Cognition Disorders/metabolism , Oxidative Stress/drug effects , Proanthocyanidins/pharmacology , Animals , Antioxidants/pharmacology , Brain-Derived Neurotrophic Factor/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Glutathione/metabolism , Male , Malondialdehyde/metabolism , Maze Learning/drug effects , Neuronal Plasticity/physiology , Random Allocation , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/metabolismABSTRACT
BACKGROUND: Post-operative volume of subdural fluid is considered to correlate with recurrence in chronic subdural haematoma (CSDH). Information on the applications of computer-assisted volumetric analysis in patients with CSDHs is lacking. OBJECTIVE: To investigate the relationship between haematoma recurrence and longitudinal changes in subdural fluid volume using CT volumetric analysis. METHODS: Fifty-four patients harbouring 64 CSDHs were studied prospectively. The association between recurrence rate and CT findings were investigated. RESULTS: Eleven patients (20.4%) experienced post-operative recurrence. Higher pre-operative (over 120 ml) and/or pre-discharge subdural fluid volumes (over 22 ml) were significantly associated with recurrence; the probability of non-recurrence for values below these thresholds were 92.7% and 95.2%, respectively. CSDHs with larger pre-operative (over 15.1 mm) and/or residual (over 11.7 mm) widths also had significantly increased recurrence rates. Bilateral CSDHs were not found to be more likely to recur in this series. On receiver-operating characteristic curve, the areas under curve for the magnitude of changes in subdural fluid volume were greater than a single time-point measure of either width or volume of the subdural fluid cavity. CONCLUSIONS: Close imaging follow-up is important for CSDH patients for recurrence prediction. Using quantitative CT volumetric analysis, strong evidence was provided that changes in the residual fluid volume during the 'self-resolution' period can be used as significantly radiological predictors of recurrence.
Subject(s)
Decompressive Craniectomy , Hematoma, Subdural, Chronic/diagnostic imaging , Hematoma, Subdural, Chronic/pathology , Tomography, X-Ray Computed , Adolescent , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Hematoma, Subdural, Chronic/prevention & control , Humans , Male , Middle Aged , Pilot Projects , Postoperative Period , Predictive Value of Tests , Prospective Studies , Recurrence , Risk Assessment , Subdural Space/diagnostic imaging , Subdural Space/pathologyABSTRACT
BACKGROUND: Dexamethasone (DEXA) is commonly used to reduce brain swelling during neurosurgical procedures. DEXA, however, has many side-effects that can increase the risks of post-operative complications. In contrast, progesterone (PRO) has fewer side-effects and has been found to be neuroprotective on traumatic brain injury (TBI). Whether PRO may be used as an alternative to DEXA during routine procedures has not been fully explored. OBJECT: To compare the effects of DEXA and PRO on surgical brain injury (SBI). METHODS: Seventy-five adult male Sprague Dawley rats were randomized into five groups: (1) SBI + drug vehicle (peanut oil, 1 ml kg(-1)); (2) SBI + DEXA (1 mg kg(-1)); (3) SBI + low-dose PRO (10 mg kg(-1)); (4) SBI + high-dose PRO (20 mg kg(-1)); and (5) sham SBI + drug vehicle. Magnetic resonance imaging study and assessments of brain water content (BWC), blood-brain barrier (BBB) permeability, cellular inflammatory responses and matrix metalloproteinase 9 (MMP-9) expression were conducted. RESULTS: This model consistently resulted in increased BWC and BBB disruption. PRO reduced astrocyte and microglia responses and attenuated brain oedema with preservation of BBB. A significant down-regulation of MMP-9 expression occurred in the PRO 20 group. CONCLUSIONS: PRO is as effective as DEXA in reducing brain oedema and inflammation following SBI; 10 mg kg(-1) of PRO was demonstrated to be more effective in relieving acute cellular inflammatory responses.
Subject(s)
Brain Edema/metabolism , Brain Injuries/metabolism , Dexamethasone/pharmacology , Glucocorticoids/pharmacology , Inflammation/metabolism , Neurosurgical Procedures/adverse effects , Progesterone/pharmacology , Animals , Blood-Brain Barrier/drug effects , Blotting, Western , Brain Edema/drug therapy , Brain Edema/immunology , Brain Injuries/immunology , Brain Injuries/surgery , Disease Models, Animal , Down-Regulation , Inflammation/drug therapy , Male , Matrix Metalloproteinase Inhibitors , Neuroprotective Agents/pharmacology , Rats , Rats, Sprague-Dawley , Treatment OutcomeABSTRACT
Drinking is a risk factor for traumatic brain injury (TBI), and ethanol can aggravate the outcome by promoting brain edema. The mechanism involved is not fully understood. It has been confirmed that aquaporin-4 (AQP4) and vascular endothelial growth factor (VEGF) play pivotal roles in cytotoxic/vasogenic brain edema individually, and both of these proteins are downstream regulatory factors of hypoxia-inducible factor-1α (HIF-1α). In this study, we used a fluid percussion injury (FPI) model in rats to determine the effects of acute ethanol intake on the expression levels of HIF-1α, AQP4, and VEGF prior to FPI. The animals were sacrificed 1, 2, 3, and 4 days post-injury. We found that the expression levels of HIF-1α and AQP4 were significantly upregulated in the ethanol-pretreated groups, whereas the VEGF expression level was not. In addition, there was a positive correlation between HIF-1α and AQP4. The results of this study indicate that cytotoxic brain edema may play an important role in the early stage of FPI in ethanol-pre-treated animals and that HIF-1α and AQP4 might be involved.
Subject(s)
Brain Edema/metabolism , Brain Injuries/metabolism , Ethanol/pharmacology , Animals , Aquaporin 4/metabolism , Brain Edema/chemically induced , Disease Models, Animal , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Male , Rats , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Background: Neuroinflammation is a major cause of secondary brain injury in intracerebral hemorrhage (ICH). To date, the prognostic value of YKL-40 (chitinase-3-like-1 protein), a biomarker of neuroinflammation, in cerebral amyloid angiopathy-related intracerebral hemorrhage (CAA-ICH) remains undiscovered. Objective: To evaluate the relationships between serum YKL-40 and CAA-ICH recurrence. Methods: Clinical and imaging information of 68 first-onset probable CAA-ICH cases and 95 controls were collected at baseline. Serum YKL-40 was measured by Luminex assay. Cox proportional hazards model was used to analyze the associations between YKL-40 level and CAA-ICH recurrence. Results: Serum YKL-40 level was significantly higher in CAA-ICH cases than healthy controls (median [interquartile range, IQR], 46.1 [19.8, 93.4] versus 24.4 [13.9, 59.0] ng/mL, pâ=â0.004). Higher level of YKL-40 predicted increased risk of CAA-ICH recurrence adjusted for age, ICH volume and enlarged perivascular space score (ePVS) (above versus below 115.5âng/ml, adjusted hazard ratios 4.721, 95% confidence intervals 1.829-12.189, pâ=â0.001) within a median follow-up period of 2.4 years. Adding YKL-40 to a model of only MRI imaging markers including ICH volume and ePVS score improved the discriminatory power (concordance index from 0.707 to 0.772, pâ=â0.001) and the reclassification power (net reclassification improvement 28.4%; integrated discrimination index 11.0%). Conclusions: Serum YKL-40 level might be a candidate prognostic biomarker for CAA-ICH recurrence.
Subject(s)
Biomarkers , Cerebral Amyloid Angiopathy , Cerebral Hemorrhage , Chitinase-3-Like Protein 1 , Recurrence , Humans , Chitinase-3-Like Protein 1/blood , Male , Female , Aged , Cerebral Amyloid Angiopathy/blood , Cerebral Amyloid Angiopathy/complications , Cerebral Amyloid Angiopathy/diagnostic imaging , Biomarkers/blood , Cerebral Hemorrhage/blood , Cerebral Hemorrhage/diagnostic imaging , Middle Aged , Aged, 80 and over , Magnetic Resonance ImagingABSTRACT
OBJECTIVE: Our study aims to prospectively compare an autologous duraplasty in situ technique (IS group) with the synthetic dural graft duraplasty (SDG group) to clarify the effectiveness and superiority of the former in the treatment of patients with Chiari malformation type 1 (CM-I). METHOD: 29 patients with CM-I were randomly assigned to either IS or SDG group. In both groups, a dissection from the occipital bone was performed. All procedures were performed by the same surgeon. The two duraplasty methods were compared in terms of surgical factors and complications. Data analysis was done for the baseline material, the neurological outcome and MRI-documented syrinx size at the 6 month follow-up. RESULT: 29 patients were enrolled in this study, 14 in the IS group and 15 in the SDG group. The results showed no significant difference in operation time (P = 0.916), amount of bleeding (P = 0.120), operation complications, hospitalization time (P = 0.854) and prognosis between the two groups. The hospitalization cost of IS group was 15,125 yuan less than that of SDG group (P < 0.05). CONCLUSION: The autogenous duraplasty in situ technique is a novel, simple, effective and economical surgical management for patients with CM-I.
Subject(s)
Arnold-Chiari Malformation , Dura Mater , Humans , Arnold-Chiari Malformation/surgery , Arnold-Chiari Malformation/diagnostic imaging , Male , Female , Adult , Dura Mater/surgery , Dura Mater/diagnostic imaging , Prospective Studies , Middle Aged , Treatment Outcome , Young Adult , Transplantation, Autologous/methods , Adolescent , Neurosurgical Procedures/methods , Magnetic Resonance ImagingABSTRACT
Entamoeba histolytica, the causative agent of amebiasis, is one of the top three parasitic causes of mortality worldwide. However, no vaccine exists against amebiasis. Using a lead candidate vaccine containing the LecA fragment of Gal-lectin and GLA-3M-052 liposome adjuvant, we immunized rhesus macaques via intranasal or intramuscular routes. The vaccine elicited high-avidity functional humoral responses as seen by the inhibition of amebic attachment to mammalian target cells by plasma and stool antibodies. Importantly, antigen-specific IFN-γ-secreting peripheral blood mononuclear cells (PBMCs) and IgG/IgA memory B cells (BMEM) were detected in immunized animals. Furthermore, antigen-specific antibody and cellular responses were maintained for at least 8 months after the final immunization as observed by robust LecA-specific BMEM as well as IFN-γ+ PBMC responses. Overall, both intranasal and intramuscular immunizations elicited a durable and functional response in systemic and mucosal compartments, which supports advancing the LecA+GLA-3M-052 liposome vaccine candidate to clinical testing.
Subject(s)
Administration, Intranasal , Antibodies, Protozoan , Entamoeba histolytica , Entamoebiasis , Interferon-gamma , Leukocytes, Mononuclear , Liposomes , Macaca mulatta , Protozoan Vaccines , Animals , Entamoeba histolytica/immunology , Liposomes/immunology , Liposomes/administration & dosage , Protozoan Vaccines/immunology , Protozoan Vaccines/administration & dosage , Antibodies, Protozoan/blood , Antibodies, Protozoan/immunology , Leukocytes, Mononuclear/immunology , Entamoebiasis/prevention & control , Entamoebiasis/immunology , Interferon-gamma/immunology , Interferon-gamma/metabolism , Injections, Intramuscular , Immunogenicity, Vaccine , Adjuvants, Vaccine/administration & dosage , Adjuvants, Immunologic/administration & dosage , B-Lymphocytes/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin A/immunology , Immunoglobulin A/blood , Antigens, Protozoan/immunology , Immunity, Humoral , Immunologic Memory , Protozoan Proteins/immunologyABSTRACT
Central nervous system hemangiopericytoma (HPC) is a malignant vascularized mesenchymal tumor with a high rate of recurrence. Because of its rarity, few clinical characteristics and prognostic analysis information regarding recurrent HPC exist for doctors to pursue optimal outcomes. Forty-six recurrent HPC cases treated at our hospital between 2004 and 2012 were compiled into a single database based on a retrospective review of patient records, which were used to summarize the clinical characteristics. The mean survival of the recurrent HPC patients in our cohort was 41.6 ± 4.4 months, with 1-, 2-, 3-, and 4-year survival rates of 80.4, 65.2, 59.2, and 53.8 %, respectively. Thirty patients (65.2 %) suffered their first tumor recurrence, with a mean survival of 36.9 ± 4.1 months. Sixteen patients (34.8 %) suffered a second or further tumor recurrence, with a mean survival of 39.7 ± 7.0 months. Eighteen patients (39.1 %) died of all causes during the follow-up period, with a mean survival of 14.2 ± 5.6 months. Univariate and multivariate regression analyses showed that factors associated with good prognosis included recurrence age over 35 years, an interval between the first and second recurrence of more than 1 year and a clear boundary of the recurrent tumor. Gross total resection with adjuvant external beam radiotherapy could independently delay tumor recurrence of the second or more times and prolong the postoperative survival; thus, this strategy should be pursued as the initial treatment.
Subject(s)
Brain Neoplasms/diagnosis , Hemangiopericytoma/diagnosis , Neoplasm Recurrence, Local/diagnosis , Adolescent , Adult , Aged , Brain Neoplasms/mortality , Brain Neoplasms/radiotherapy , Child , Child, Preschool , Combined Modality Therapy , Female , Follow-Up Studies , Hemangiopericytoma/mortality , Hemangiopericytoma/radiotherapy , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Radiosurgery , Radiotherapy, Conformal , Retrospective Studies , Survival Rate , Tomography, X-Ray Computed , Young AdultABSTRACT
BACKGROUND: Penetrating orbital injuries constitute a significant threat to ocular and cerebral structures. The incidence of central nervous system damage from orbital injury is related to the orbital anatomy and the characteristics of the penetrating object. Penetrating orbital injuries involving the brain stem are extremely rare. OBJECTIVES: To present an uncommon case of penetrating orbital injury and to discuss surgical management. CASE STUDY: A patient suffered from a penetrating injury by a Bakelite comb which extended from his left orbit through the cavernous sinus to the pons. Complete occlusion of the left cavernous segment of the internal carotid artery was detected and a frontotemporal craniotomy with lateral superior orbitotomy was performed to remove the object. A delayed asymptomatic carotid-cavernous fistula was identified 1 year later. CONCLUSION: Surgical treatment remains the mainstay of intervention for penetrating orbitocranial injuries. The rationale of surgical removal of a foreign body should focus on safe exposure and removal of the object at the earliest without inflicting further injuries. Close follow-up for a delayed carotid-cavernous fistula is necessary.
Subject(s)
Blepharoptosis/physiopathology , Brain Stem/physiopathology , Craniotomy/methods , Foreign Bodies/surgery , Head Injuries, Penetrating/surgery , Orbit/surgery , Plastics , Adult , Blindness , Brain Stem/injuries , Head Injuries, Penetrating/physiopathology , Humans , Male , Orbit/injuries , Treatment OutcomeABSTRACT
Epigenetic reader Bromodomain protein 4 (BrD4) functions as a global genomic regulator to direct hepatic stellate cell (HSC) activation (a key step in liver fibrogenesis) and liver fibrosis. The pivotal pro-fibrotic cytokine transforming growth factor-ß1 (TGFß1) signals through both Smad and Stat3 to elicit a wide array of biological effects. Stat3 is widely acknowledged as a regulator of gene transcription and is involved in fibrosis of multiple tissues. The present study focused on BrD4 function implication in the roles of TGFß1-induced Stat3 signaling in HSC activation and liver fibrosis by using heterozygous TGFß1 knockout mice and HSC culture. Results showed that Stat3 was required for TGFß1-induced BrD4 expression in HSCs. BrD4 expression paralleled Stat3 activation in activated HSCs in human cirrhotic livers. BrD4 was involved in the roles of TGFß1-induced Stat3 in HSC activation and liver fibrogenesis. Smad3 bound to phosphorylated-Stat3 and contributed to TGFß1-induced Stat3 signaling. BrD4 expression induced by Stat3 signaling required the early-immediate gene Egr1. Egr1 had a positive feedback on Stat3 activation. In conclusion, a network consisting of Stat3 signaling, Smad3 signaling, Egr1, and BrD4 was involved in the effects of TGFß1 on liver fibrosis, providing new toxicological mechanisms for TGFß1 in liver fibrogenesis.