| 51. |
- Sabri, Farideh, et al.
(författare)
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Soluble factors released by virus specific activated cytotoxicT-lymphocytes induce apoptotic death of astroglioma cell lines
- 2003
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Ingår i: Brain Pathology. - : Wiley. - 1015-6305 .- 1750-3639. ; 13:2, s. 165-175
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Tidskriftsartikel (refereegranskat)abstract
- Astrocytomas and astrogliomas represent the most common types of primary tumors in human central nervous system and are associated with high mortality due to the absence of efficient therapy. Here we demonstrate that, upon antigen-specific activation, cytotoxic T-lymphocytes (CTLs) secrete products that inhibit proliferation and induce apoptosis in a significant proportion of astroglioma cell lines. This effect is tumor specific in that normal cultured astrocytes do not develop apoptotic changes upon exposure to supernatant of activated CTLs. Experiments with purified lymphokines and lymphokine specific blocking antibodies indicate that synergistic activities of tumor necrosis factor (TNF)-alpha and interferon (INF)-gamma are required for the apoptosis inducing effect on some astroglioma cell lines. However, this effect appears to be dependent on additional factors produced by activated CTLs. Our results suggest that local application of factors released by activated CTLs or induction of CTL migration and activation in the tumor site may have a therapeutic effect in patients with astrogliomas.
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| 52. |
- Tahmasian, Masoud, et al.
(författare)
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ENIGMA-Sleep : Challenges, opportunities, and the road map
- 2021
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Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 30:6
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Forskningsöversikt (refereegranskat)abstract
- Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across individual sites. Recently, we have launched the ENIGMA-Sleep working group with the collaboration of several institutes from 15 countries to perform large-scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population-based healthy individuals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA-Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine.
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| 53. |
- Wang, Chaojie, et al.
(författare)
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FBI-1 mRNA in normal mucosa is an independent prognostic factor in colorectal cancer patients
- 2018
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Ingår i: International Journal of Clinical and Experimental Pathology. - : E-CENTURY PUBLISHING CORP. - 1936-2625. ; 11:2, s. 642-649
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Tidskriftsartikel (refereegranskat)abstract
- Although several studies provide evidence that FBI-1 is an important gene regulator in colorectal cancer (CRC), it is noteworthy that, to our knowledge, no analysis of the correlation between FBI-1 expression and prognosis in CRC has been reported. Using real-time RT-PCR, we detected FBI-1 mRNA in 161 CRC patients (primary tumor, along with the corresponding normal mucosa), 36 liver metastases, and analyzed the relationship of its expression with clinicopathological features. Colon cancer cell lines were used to study FBI-1 function. Our study found that FBI-1 was significant up-regulated in tumor tissue (2.621 +/- 0.157) compared with the corresponding normal mucosa (1.620 +/- 0.165, P amp;lt; 0.0001). FBI-1 in normal mucosa was a prognostic factor (P = 0.039, RR 0.431, 95% CI 0.194-0.958), independent of gender, age, stage, and differentiation. High levels of FBI-1 mRNA were related with good survival. Patients with complications had a higher primary tumor FBI-1 expression than those without complications (3.400 +/- 0.332 vs. 2.516 +/- 0.241, P = 0.032). Suppression of FBI-1 in colon cancer cell lines could repress proliferation of cancer cells. In conclusion, FBI-1 mRNA is overexpressed in CRC, and takes part in the development of CRC. FBI-1 mRNA in normal mucosa is an independent prognostic factor. Our findings give further support to the concept of "field cancerization", and hint that when we study a biomarker, we should not only focus on the tumor tissue but also the corresponding normal mucosa.
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| 54. |
- Wang, Chao-Jie, et al.
(författare)
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FBI-1 mRNA in normal mucosa is an independent prognostic factor in colorectal cancer patients
- 2018
-
Ingår i: International Journal of Clinical and Experimental Pathology. - : e-Century Publishing. - 1936-2625. ; 11:2, s. 642-649
-
Tidskriftsartikel (refereegranskat)abstract
- Although several studies provide evidence that FBI-1 is an important gene regulator in colorectal cancer (CRC), it is noteworthy that, to our knowledge, no analysis of the correlation between FBI-1 expression and prognosis in CRC has been reported. Using real-time RT-PCR, we detected FBI-1 mRNA in 161 CRC patients (primary tumor, along with the corresponding normal mucosa), 36 liver metastases, and analyzed the relationship of its expression with clinicopathological features. Colon cancer cell lines were used to study FBI-1 function. Our study found that FBI-1 was significant up-regulated in tumor tissue (2.621 +/- 0.157) compared with the corresponding normal mucosa (1.620 +/- 0.165, P < 0.0001). FBI-1 in normal mucosa was a prognostic factor (P = 0.039, RR 0.431, 95% CI 0.194-0.958), independent of gender, age, stage, and differentiation. High levels of FBI-1 mRNA were related with good survival. Patients with complications had a higher primary tumor FBI-1 expression than those without complications (3.400 +/- 0.332 vs. 2.516 +/- 0.241, P = 0.032). Suppression of FBI-1 in colon cancer cell lines could repress proliferation of cancer cells. In conclusion, FBI-1 mRNA is overexpressed in CRC, and takes part in the development of CRC. FBI-1 mRNA in normal mucosa is an independent prognostic factor. Our findings give further support to the concept of "field cancerization", and hint that when we study a biomarker, we should not only focus on the tumor tissue but also the corresponding normal mucosa.
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| 55. |
- Wang, Yu-Cheng, et al.
(författare)
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Porous Carbon Membrane-Supported Atomically Dispersed Pyrrole-Type Fe-N-4 as Active Sites for Electrochemical Hydrazine Oxidation Reaction
- 2020
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Ingår i: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 16:31
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Tidskriftsartikel (refereegranskat)abstract
- The rational design of catalytically active sites in porous materials is essential in electrocatalysis. Herein, atomically dispersed Fe-N-x sites supported by hierarchically porous carbon membranes are designed to electrocatalyze the hydrazine oxidation reaction (HzOR), one of the key techniques in electrochemical nitrogen transformation. The high intrinsic catalytic activity of the Fe-N-x single-atom catalyst together with the uniquely mixed micro-/macroporous membrane support positions such an electrode among the best-known heteroatom-based carbon anodes for hydrazine fuel cells. Combined with advanced characterization techniques, electrochemical probe experiments, and density functional theory calculation, the pyrrole-type Fe-N-4 structure is identified as the real catalytic site in HzOR.
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| 56. |
- Wei, Cheng-Hong
(författare)
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Regulation of T cell activation and death by the affinity of TCR for peptide/MHC complexes
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this study is to investigate the role of the affinity of peptide:MHC/TCR interaction in the regulation of T cell activation, death and repertoire selection. Three aspects pertinent for our understanding of this issue have been analyzed. First, we analyzed the effect of partially agonistic peptides on the activation and survival of CTL clones specific for a highly immunogenic HLA A11-restricted peptide epitope derived from the EBV nuclear Ag 4(EBNA 4), IVTDFSVIK (designated IVT). Several analogues with substitutions of TCR contact residues were able to trigger cytotoxic activity without induction of IL-2 mRNA and protein or T cell proliferation. Triggering with these partial agonists in the absence of exogenous IL-2 resulted in down-regulation of the cytotoxic potential of the specific CTLs. One analogue selectively triggered apoptosis as efficiently as the original epitope, subdividing the partial agonists into apoptosis-inducing and non-inducing ligands. Analysis of early T cell activation events did not reveal significant differences between the two types of analogue peptides. These results demonstrate that some partial agonists can dissociate the induction of CTL death from CTL activation. Then, we characterized the apoptotic programs induced by the immunogenic peptide and its partially agonistic analogues in the IVT-specific CTL clones. Our major finding is that CTL triggering with partially agonistic peptide ligands can initiate death receptor dependent and independent apoptotic programs in the effector cells. In contrast to classical AICD, death receptors are not essential for the elimination of CTLs activated with partially agonistic peptides. In addition, death receptor independent apoptosis requires caspases other than caspase 3 and 8. Induction of anti-apoptotic BCl-2 and BCl-XL expression is associated with resistance to this form of apoptosis. Also, IL-2 enhances classical and inhibits death receptor independent AICD. We concluded that TCR triggering not accompanied by IL-2 production may result in elimination of T-lymphocytes in death receptor independent manner. Our data demonstrated that engagement of TCR by MHC-peptide complexes can trigger diverse apoptotic programs of AICD and that the choice between these programs is determined by the agonistic potency of MHC- peptide ligand. Second, the molecular basis of different outcomes of CTLs stimulation with. immunogenic and partially agoistic peptide ligands was analyzed. The role of MHC:peptide/TCR affinity in the regulation of T cell activation was characterized using tetramer technology. Our results demonstrated that the All complexes assembled with the partial agonist dissociated from the surface of IVT-specific CTLs with a faster kinetics as compared with complexes containing the immunogenic peptide. We also showed that the efficiency of CTL recognition correlates with the stability of interaction between the specific TCR and MHC:peptide complex. Tetramer binding and secretion of INFgamma were shown to be compatible with T-cell activation by partially agonistic peptides. In conclusion, our results indicate that the affinity of TCR/MHC:peptide interaction determines the strength of TCR signalling, extent of CTL activation as well as the apoptosis pathway that operates in CTLs in the course of AICD. The third aim of our study was to investigate the influence of the affinity of TCR/MHC interaction on the selection and maintenance of TCR repertoire of peptide specific CTLs. Using tetramer technology, we investigated the restriction of TCR usage among CTL responses against a subdominat EBNA 4 derived peptide referred to as AWF. In agreement with the earlier findings, ex vivo analysis of AVF-specific CTLs using AVF-containing HLA All tetramers revealed the same degree of conservation of the AVF-specific response both in healthy virus carriers and in the course of primary EBV infection. Tetramer binding and dissociation experiments performed with AVF-specific: CTLs or CTLs expressing a very diverse set of TCRs and specific to another immunodominant A 11-restricted EBV-derived peptide epitope did not support a model of affinity driven selection of restricted TCR repertoires. Characterization of individuals that fail to mount responses to the immunodominant A11-restricted CTL epitope but efficiently respond to the AVF-peptide argued against interclonal competition as the reason for the observed TCR conservation. Collectively, our data confirm the existence of naturally induced peptide-specific CTL responses with highly restricted TCR usage. Our data do not support a major role for affinity of MHC:TCR interaction in the selection of structurally conserved TCR-repertoires and suggest that such conservations may be due to structural constrains in MHC:peptide/TCR interactions or endogenous pre-selection of certain clonotypes.
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| 57. |
- Wheeler, Eleanor, et al.
(författare)
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Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations : A transethnic genome-wide meta-analysis
- 2017
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Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.Methods & findings: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 x 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI0.55-0.74) of African American adults with T2Dto remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.Conclusions: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.
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| 58. |
- You, Xiaohu, et al.
(författare)
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Towards 6G wireless communication networks: vision, enabling technologies, and new paradigm shifts
- 2021
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Ingår i: Science China Information Sciences. - : Science Press. - 1674-733X .- 1869-1919. ; 64:1
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Forskningsöversikt (refereegranskat)abstract
- The fifth generation (5G) wireless communication networks are being deployed worldwide from 2020 and more capabilities are in the process of being standardized, such as mass connectivity, ultra-reliability, and guaranteed low latency. However, 5G will not meet all requirements of the future in 2030 and beyond, and sixth generation (6G) wireless communication networks are expected to provide global coverage, enhanced spectral/energy/cost efficiency, better intelligence level and security, etc. To meet these requirements, 6G networks will rely on new enabling technologies, i.e., air interface and transmission technologies and novel network architecture, such as waveform design, multiple access, channel coding schemes, multi-antenna technologies, network slicing, cell-free architecture, and cloud/fog/edge computing. Our vision on 6G is that it will have four new paradigm shifts. First, to satisfy the requirement of global coverage, 6G will not be limited to terrestrial communication networks, which will need to be complemented with non-terrestrial networks such as satellite and unmanned aerial vehicle (UAV) communication networks, thus achieving a space-air-ground-sea integrated communication network. Second, all spectra will be fully explored to further increase data rates and connection density, including the sub-6 GHz, millimeter wave (mmWave), terahertz (THz), and optical frequency bands. Third, facing the big datasets generated by the use of extremely heterogeneous networks, diverse communication scenarios, large numbers of antennas, wide bandwidths, and new service requirements, 6G networks will enable a new range of smart applications with the aid of artificial intelligence (AI) and big data technologies. Fourth, network security will have to be strengthened when developing 6G networks. This article provides a comprehensive survey of recent advances and future trends in these four aspects. Clearly, 6G with additional technical requirements beyond those of 5G will enable faster and further communications to the extent that the boundary between physical and cyber worlds disappears.
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| 59. |
- Zhang, Bin, et al.
(författare)
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Dampness and mould in Chinese homes and sick building syndrome (SBS) symptoms - Associations with climate, family size, cleaning and ventilation
- 2023
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Ingår i: Building and Environment. - : Elsevier. - 0360-1323 .- 1873-684X. ; 245
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Tidskriftsartikel (refereegranskat)abstract
- We investigated associations between dampness in Chinese homes and sick building syndrome (SBS) symptoms and studied the role of climate, family size, cleaning and ventilation for dampness, mould and SBS. A questionnaire survey was done in 2019-2020 among adults in five cities (32349 participants) and data on outdoor climate was collected. Multilevel logistic regression was used to calculate adjusted odds ratios (ORs). In total, 2.2% had rhinitis, 1.8% eye, 1.6% throat and 2.9% skin symptoms, 2.1% headache and 8.7% fatigue (weekly symptoms). Overall, 12.1% reported indoor mould, 5.7% damp bedding, 5.3% mould odour and 33.8% humid air in current home. Mould was associated with all symptoms (ORs 1.86-2.15 for minor mold growth and 1.65-3.45 for major mould growth). Damp bedding was associated with all symptoms (ORs 2.18-2.80 for minor dampness and 2.51-8.03 for major dampness). Mould odour was associated with all symptoms (ORs 1.84-2.77 for sometimes odour and ORs 3.78-7.80 for weekly odour). Perception of humid air was associated with all symptoms. ORs increased by number of dampness signs. Precipitation, outdoor relative air humidity and temperature increased dampness, mould and SBS symptoms. Large family size increased dermal symptoms. Daily floor cleaning, airing in winter, putting bedding to sunshine and mechanical ventilation in the bathroom reduced dampness, mould and SBS symptoms. In conclusion, mould and dampness in Chinese homes can increase rhinitis and SBS-symptoms in a dose-response manner. A warmer and more humid climate can increase, and cleaning and ventilation in the home can decrease dampness, mould and SBS symptoms.
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| 60. |
- Zhang, Cheng, et al.
(författare)
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Discovery of therapeutic agents targeting PKLR for NAFLD using drug repositioning
- 2022
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Ingår i: eBioMedicine. - : Elsevier BV. - 2352-3964. ; 83
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Tidskriftsartikel (refereegranskat)abstract
- Background Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver pathologies. However, no medical treatment has been approved for the treatment of NAFLD. In our previous study, we found that PKLR could be a potential target for treatment of NALFD. Here, we investigated the effect of PKLR in in vivo model and performed drug repositioning to identify a drug candidate for treatment of NAFLD. Methods Tissue samples from liver, muscle, white adipose and heart were obtained from control and PKLR knock-out mice fed with chow and high sucrose diets. Lipidomics as well as transcriptomics analyses were conducted using these tissue samples. In addition, a computational drug repositioning analysis was performed and drug candidates were identified. The drug candidates were both tested in in vitro and in vivo models to evaluate their toxicity and efficacy. Findings The Pklr KO reversed the increased hepatic triglyceride level in mice fed with high sucrose diet and partly recovered the transcriptomic changes in the liver as well as in other three tissues. Both liver and white adipose tissues exhibited dysregulated circadian transcriptomic profiles, and these dysregulations were reversed by hepatic knockout of Pklr. In addition, 10 small molecule drug candidates were identified as potential inhibitor of PKLR using our drug repositioning pipeline, and two of them significantly inhibited both the PKLR expression and triglyceride level in in vitro model. Finally, the two selected small molecule drugs were evaluated in in vivo rat models and we found that these drugs attenuate the hepatic steatosis without side effect on other tissues. Interpretation In conclusion, our study provided biological insights about the critical role of PKLR in NAFLD progression and proposed a treatment strategy for NAFLD patients, which has been validated in preclinical studies. Copyright (C) 2022 The Authors. Published by Elsevier B.V.
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| 61. |
- Zhao, Cheng-Shou, et al.
(författare)
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Thermal decomposition behaviors of a self-intumescent flame retardant epoxy resin
- 2022
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Ingår i: Journal of Applied Polymer Science. - : John Wiley & Sons. - 0021-8995 .- 1097-4628. ; 139:18
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Tidskriftsartikel (refereegranskat)abstract
- This paper focuses on revealing the thermal decomposition behaviors of a self-intumescent flame retardant (IFR) epoxy (EP) resin (EP/15%APP-Cu2O) employing 12 wt% ammonium polyphosphate (APP) as a halogen-free flame retardant and 3 wt% copper (I) oxide (Cu2O) as char forming rate regulator. Initially, the thermal stability of EP/15%APP-Cu2O was analyzed and compared to virgin EP resin and flame retardant EP (EP/15%APP) containing 15 wt% APP as flame retardant by thermogravimetric analysis test at different heating rates under nitrogen atmosphere. It was shown that the incorporation of APP altered the decomposition pathway of EP and decreased the onset decomposition temperature. Luckily, compared to EP/15%APP, the onset decomposition temperature of EP/15%APP-Cu2O was just slightly reduced from 300.4 to 292.8 degrees C. Then, the thermal degradation kinetics of EP, EP/15%APP and EP/15%APP-Cu2O were further evaluated by Kissinger and Flynn-Wall-Ozawa methods. It was worth noted that the addition of APP or APP-Cu2O enhanced the thermal degradation activation energies of EP, which contributed to the protective effect of the char formation. Particularly, the incorporation of 3 wt% Cu2O significantly decreased the thermal degradation activation energies at the early decomposition stage of EP. This may be the main contribution for intumescent char formation, which resulted in higher fire safety of EP/15%APP-Cu2O compared to EP/15%APP. These information can potentially help to develop alternative IFR systems.
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| 62. |
- Zhou, Meng Tao, et al.
(författare)
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Continuous Regional Arterial Infusion with Fluorouracil and Octreotide Attenuates Severe Acute Pancreatitis in a Canine Model
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To investigate the therapeutic effects of fluorouracil (5-Fu) and octreotide (Oct) continuous regional arterial infusion (CRAI,) alone or in combination, was administered in a canine model of severe acute pancreatitis (SAP). Materials and Methods: The animals were divided into five groups; group A (Sham), group B (SAP), group C (SAP and 5-Fu), group D (SAP and Oct), and group E (SAP and 5-Fu + Oct). Levels of amylase, alpha-tumor necrosis factor (TNF-alpha), blood urea nitrogen (BUN), creatinine, thromboxane B2 and 6-keto-prostaglandin F1 alpha were measured both before and after the induction of SAP. Pathologic examination of the pancreas and kidneys was performed after termination of the study. Results: Pathologic changes noted in the pancreas in SAP significantly improved following CRAI with either single or combined administration of 5-Fu and Oct, where combination therapy demonstrated the lowest injury score. All treatment groups had significantly lower levels of serum TNF-alpha and amylase activity (P<0.05), though only groups D and E had a lower BUN level as compared to group B. The plasma thromboxane B-2 level increased in SAP, but the ratio of thromboxane B-2/6-keto-prostaglandin F-1 alpha decreased in the treatment groups, with the combination therapy (group E) demonstrating the lowest ratio as compared to the other 3 experimental groups (P<0.05). Conclusions: The findings in the present study demonstrate an attenuation of SAP in a canine model following CRAI administration with 5-Fu or Oct, alone or in combination.
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| 63. |
- Niemi, MEK, et al.
(författare)
-
- 2021
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