Rivers are important habitats for wintering waterbirds.However,they are easily influenced by natural and human activities.An important approach for waterbirds to adapt to habitats is adjusting the activity time and en...Rivers are important habitats for wintering waterbirds.However,they are easily influenced by natural and human activities.An important approach for waterbirds to adapt to habitats is adjusting the activity time and energy expenditure allocation of diurnal behavior.The compensatory foraging hypothesis predicts that increased energy expenditure leads to longer foraging time,which in turn increases food intake and helps maintain a constant energy balance.However,it is unclear whether human-disturbed habitats result in increased energy expenditure related to safety or foraging.In this study,the scan sample method was used to observe the diurnal behavior of the wintering Spot-billed Duck(Anas poecilorhyncha) in two rivers in the Xin’an River Basin from October 2021 to March 2022.The allocation of time and energy expenditure for activity in both normal and disturbed environments was calculated.The results showed that foraging accounted for the highest percentage of time and energy expenditure.Additionally,foraging decreased in the disturbed environment than that in the normal environment.Resting behavior showed the opposite trend,while other behaviors were similar in both environments.The total diurnal energy expenditure of ducks in the disturbed environment was greater than that in the normal environment,with decreased foraging and resting time percentage and increased behaviors related to immediate safety(swimming and alert) and comfort.These results oppose the compensatory foraging hypothesis in favor of increased security.The optimal diurnal energy expenditure model included river width and water depth,which had a positive relationship;an increase in either of these two factors resulted in an increase in energy expenditure.This study provides a better understanding of energy allocation strategies underlying the superficial time allocation of wintering waterbirds according to environmental conditions.Exploring these changes can help understand the maximum fitness of wintering waterbirds in response to nature and human influences.展开更多
Activity data and emission factors are critical for estimating greenhouse gas emissions and devising effective climate change mitigation strategies. This study developed the activity data and emission factor in the Fo...Activity data and emission factors are critical for estimating greenhouse gas emissions and devising effective climate change mitigation strategies. This study developed the activity data and emission factor in the Forestry and Other Land Use Change (FOLU) subsector in Malawi. The results indicate that “forestland to cropland,” and “wetland to cropland,” were the major land use changes from the year 2000 to the year 2022. The forestland steadily declined at a rate of 13,591 ha (0.5%) per annum. Similarly, grassland declined at the rate of 1651 ha (0.5%) per annum. On the other hand, cropland, wetland, and settlements steadily increased at the rate of 8228 ha (0.14%);5257 ha (0.17%);and 1941 ha (8.1%) per annum, respectively. Furthermore, the results indicate that the “grassland to forestland” changes were higher than the “forestland to grassland” changes, suggesting that forest regrowth was occurring. On the emission factor, the results interestingly indicate that there was a significant increase in carbon sequestration in the FOLU subsector from the year 2011 to 2022. Carbon sequestration increased annually by 13.66 ± 0.17 tCO<sub>2</sub> e/ha/yr (4.6%), with an uncertainty of 2.44%. Therefore, it can be concluded that there is potential for a Carbon market in Malawi.展开更多
BACKGROUND Patients with ankylosing spondylitis(AS)frequently suffer from comorbid sleep disorders,exacerbating the burden of the disease and affecting their quality of life.AIM To investigate the clinical significanc...BACKGROUND Patients with ankylosing spondylitis(AS)frequently suffer from comorbid sleep disorders,exacerbating the burden of the disease and affecting their quality of life.AIM To investigate the clinical significance of serum inflammatory factors,health index and disease activity scores in patients with AS complicated by sleep disorders.METHODS A total of 106 AS patients with comorbid sleep disorders were included in the study.The patients were grouped into the desirable and undesirable prognosis groups in accordance with their clinical outcomes.The serum levels of inflammatory factors,including C-reactive protein,erythrocyte sedimentation rate,interleukin(IL)-6,tumour necrosis factor-αand IL-1β,were measured.Disease activity scores,such as the Bath AS functional index,Bath AS disease activity index,Bath AS metrology index and AS disease activity score,were assessed.The health index was obtained through the Short Form-36 questionnaire.RESULTS The study found significant associations amongst serum inflammatory factors,health index and disease activity scores in AS patients with comorbid sleep disorders.Positive correlations were found between serum inflammatory factors and disease activity scores,indicating the influence of heightened systemic inflammation on disease severity and functional impairment.Conversely,negative correlations were found between disease activity scores and health index parameters,highlighting the effect of disease activity on various aspects of healthrelated quality of life.Logistic regression analysis further confirmed the predictive value of these factors on patient outcomes,underscoring their potential utility in risk assessment and prognostication.CONCLUSION The findings demonstrate the intricate interplay amongst disease activity,systemic inflammation and patientreported health outcomes in AS patients complicated by sleep disorders.The results emphasise the need for comprehensive care strategies that address the diverse needs and challenges faced by these patients and underscore the potential relevance of serum inflammatory factors,health index and disease activity scores as prognostic markers in this patient population.展开更多
Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease(NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with...Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease(NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with fatty liver display features of metabolic syndrome(Met S), like insulin resistance(IR), glucose intolerance, hypertension and dyslipidemia. Recently, epidemiological studies have linked obesity, Met S, and NAFLD to decreased bone mineral density and osteoporosis, highlighting an intricate interplay among bone, adipose tissue, and liver. Osteoprotegerin(OPG), an important symbol of the receptor activator of nuclear factor-B ligand/receptor activator of nuclear factor kappa B/OPG system activation, typically considered for its role in bone metabolism, may also play critical roles in the initiation and perpetuation of obesityrelated comorbidities. Clinical data have indicated that OPG concentrations are associated with hypertension, left ventricular hypertrophy, vascular calcification, endothelial dysfunction, and severity of liver damage in chronic hepatitis C. Nonetheless, the relationship between circulating OPG and IR as a key feature of Met S as well as between OPG and NAFLD remains uncertain. Thus, the aims of the present review are to provide the existent knowledge on these associations and to discuss briefly the underlying mechanisms linking OPG and NAFLD.展开更多
AIM: To provide the expression profile of serine protease SNC19/matriptase and its inhibitor hepatocyte growth factor activator inhibitor type 1 (HAI-1) in normal and malignant tissues of gastrointestinal tract at ...AIM: To provide the expression profile of serine protease SNC19/matriptase and its inhibitor hepatocyte growth factor activator inhibitor type 1 (HAI-1) in normal and malignant tissues of gastrointestinal tract at mRNA level for further study on their correlations with tumor progression and metastasis. METHODS: Total RNAs were prepared from 37 samples of colorectal cancer tissues, 40 samples of gastric cancer tissues, and their adjacent normal tissues. The expression of SNC19/matriptase and HAI-1 in these samples was detected by real-time fluorescent quantitative PCR using glyceraldehyde-3-phosphate dehydrogenase as internal standard, and the clinical significance for the correlation with clinicopathological parameters was evaluated. RESULTS: In gastric cancer tissues the expression of HAI-1 and SNC19/matriptase was significantly lower than that in the corresponding adjacent normal tissues (Z = -3.280, P= 0.006; Z= -4.651, P= 0.000). HAI-1:SNC19/matriptase ratio showed no difference between normal and malignant tissues (P〉0.05). Analysis of clinicopathological parameters showed decreased expression of HAI-1 and HAI-1:SNC19/ matriptase ratio associated with stage Ⅲ/Ⅳ gastric tumors as compared to stage Ⅰ/Ⅱ ones (Z= -2.140, P= 0.031; Z = -2.155, P = 0.031), and with lymph node-positive gastric cancer tissues as compared to lymph node-negative ones (Z = -2.081, P = 0.036; Z= -2.686, P = 0.006). The expression of SNC19/matriptase had no relationship with stages and lymph node metastasis (P〉0.05). The expression of HAI-1 and HAI-1:SNC19/matriptase ratio increased in well-differentiated gastric cancer tissues, but there was no statistical significance (P〉0.05). The difference of SNC19/matriptase expression was not significant in gastric cancer tissues of different histological differentiation status (P〉0.05). In colorectal cancer tissues, the expression of HAI-1 and SNC19/matriptase was also markedly lower than that in their adjacent normal tissues (Z= -3.100, P = 0.002; Z= -2.731, P = 0.006), whereas HAI-1:SNC19/matriptase ratio showed no difference. Decreased expression of HAI-1 was associated with increased invasive depth and lymph node metastasis, but there was no statistical significance (P〉0.05). The difference of SNC19/matriptase expression and HAI-1: SNC19/matriptase ratio was not significant in different stages and different lymph node metastasis status (P〉0.05). The expression of SNC19/matriptase, HAI-1 or HAI-1: SNC19/matriptase ratio showed no difference in colorectal cancer tissues of different histological differentiation status (P〉0.05). CONCLUSION: The expressions of SNC19/matriptase and its inhibitor HAI-1 are decreased in gastrointestinal cancer tissues compared to their normal counterparts, and the decreased expression of HAI-1 may correlate with invasion and lymph node metastasis. The possible mechanisms involved need to be further investigated.展开更多
AIM: To investigate whether DNA-dependent activator of interferon-regulatory factors (DAI) inhibits hepatitis B virus (HBV) replication and what the mechanism is. METHODS: After the human hepatoma cell line Huh7...AIM: To investigate whether DNA-dependent activator of interferon-regulatory factors (DAI) inhibits hepatitis B virus (HBV) replication and what the mechanism is. METHODS: After the human hepatoma cell line Huh7 was cotransfected with DAI and HBV expressing plas- mid, viral protein (HBV surface antigen and HBV e an- tigen) secretion was detected by enzyme-linked immu- nosorbent assay, and HBV RNA was analyzed by real- time polymerase chain reaction and Northern blotting, and viral DNA replicative intermediates were examined by Southern blotting. Interferon regulatory factor 3 (IRF3) phosphorylation and nuclear translocation were analyzed via Western blotting and immunofluorescence staining respectively. Nuclear factor-KB (NF-KB) activity induced by DAI was detected by immunofluorescence staining of P65 and dual luciferase reporter assay. Tran- swell co-culture experiment was performed in order to investigate whether the antiviral effects of DAI were dependent on the secreted cytokines. RESULTS: Viral protein secretion was significantly re- duced by 57% (P 〈 0.05), and the level of total HBV RNA was reduced by 67% (P 〈 0.05). The viral core particle-associated DNA was also dramatically down- regulated in DAI-expressing Huh7 cells. Analysis of involved signaling pathways revealed that activation of NF-KB signaling was essential for DAI to elicit antivi- ral response in Huh7 cells. When the NF-KB signaling pathway was blocked by a NF-KB signaling suppressor (I~:B^-SR), the anti-HBV activity of DAI was remarkably abrogated. The inhibitory effect of DAI was indepen- dent of IRF3 signaling and secreted cytokines. CONCLUSION: This study demonstrates that DAI can inhibit HBV replication and the inhibitory effect is asso- ciated with activation of NF-KB but independent of IRF3 and secreted cytokines.展开更多
Vascular calcifications are commonly observed in patients with chronic kidney disease (CKD) and contri-bute to the excessive cardiovascular morbidity and mortality rates observed in these patients populations. Altho...Vascular calcifications are commonly observed in patients with chronic kidney disease (CKD) and contri-bute to the excessive cardiovascular morbidity and mortality rates observed in these patients populations. Although the pathogenetic mechanisms are not yet fully elucidated, recent evidence suggests a link between bone metabolism and the development and progression of vascular calcifications. Moreover, accumulating data indicate that receptor activator of nuclear factor κB ligand/osteoprotegerin axis which plays essential roles in the regulation of bone metabolism is also involved in extra-osseous bone formation. Further studies are required to establish the prognostic significance of the above biomarkers as predictors of the presence and severity of vascular calcifications in CKD patients and of cardiovascular morbidity and mortality. Moreover, randomized clinical trials are needed to clarify whether inhibition of osteoclast activity will protect from vascular calcifcations.展开更多
Objective The aim of this study was to investigate the prospective association between physical activity(PA),independently or in conjunction with other contributing factors,and osteoporosis(OP)outcomes.Methods The Phy...Objective The aim of this study was to investigate the prospective association between physical activity(PA),independently or in conjunction with other contributing factors,and osteoporosis(OP)outcomes.Methods The Physical Activity in Osteoporosis Outcomes(PAOPO)study was a community-based cohort investigation.A structured questionnaire was used to gather the participants’sociodemographic characteristics.Bone mineral density(BMD)measurements were performed to assess OP outcomes,and the relationship between BMD and OP was evaluated within this cohort.Results From 2013 to 2014,8,471 participants aged 18 years and older were recruited from Tangshan,China’s Jidong community.Based on their PA level,participants were categorized as inactive,moderately active,or very active.Men showed higher physical exercise levels than women across the activity groups.BMD was significantly higher in the very active group than in the moderately active and inactive groups.Individuals aged>50 years are at a higher risk of developing OP and osteopenia.Conclusion The PAOPO study offers promising insights into the relationship between PA and OP outcomes,encouraging the implementation of PA in preventing and managing OP.展开更多
Primary focal and segmental glomerulosclerosis(FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The differ...Primary focal and segmental glomerulosclerosis(FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The different available therapeutic approaches are unsuccessful, in part due to partially deciphered heterogeneous and complex pathophysiological mechanisms. Moreover, the term FSGS, even in its primary form, comprises a histological description shared by a number of different causes with completely different molecular pathways of disease. This review focuses on the latest developments regarding the pathophysiology of primary acquired FSGS caused by soluble factor urokinase type plasminogen activator receptor, a circulating permeability factor involved in proteinuria and edema formation, and describes recent advances with potential success in therapy.展开更多
This study presents a neural network-based model for predicting linear quadratic regulator(LQR)weighting matrices for achieving a target response reduction.Based on the expected weighting matrices,the LQR algorithm is...This study presents a neural network-based model for predicting linear quadratic regulator(LQR)weighting matrices for achieving a target response reduction.Based on the expected weighting matrices,the LQR algorithm is used to determine the various responses of the structure.The responses are determined by numerically analyzing the governing equation of motion using the state-space approach.For training a neural network,four input parameters are considered:the time history of the ground motion,the percentage reduction in lateral displacement,lateral velocity,and lateral acceleration,Output parameters are LQR weighting matrices.To study the effectiveness of an LQR-based neural network(LQRNN),the actual percentage reduction in the responses obtained from using LQRNN is compared with the target percentage reductions.Furthermore,to investigate the efficacy of an active control system using LQRNN,the controlled responses of a system are compared to the corresponding uncontrolled responses.The trained neural network effectively predicts weighting parameters that can provide a percentage reduction in displacement,velocity,and acceleration close to the target percentage reduction.Based on the simulation study,it can be concluded that significant response reductions are observed in the active-controlled system using LQRNN.Moreover,the LQRNN algorithm can replace conventional LQR control with the use of an active control system.展开更多
Objective: This systematic review examines the impact of lifestyle factors on migraine frequency and severity through a comprehensive analysis of lifestyle factors such as diet, physical activity, sleep patterns, stre...Objective: This systematic review examines the impact of lifestyle factors on migraine frequency and severity through a comprehensive analysis of lifestyle factors such as diet, physical activity, sleep patterns, stress, mental health, and environmental influences. Methods: We thoroughly searched Google Scholar, PUBMED, Scopus, and Web of Science databases using keywords related to migraines and lifestyle factors. Keywords incorporated the Boolean operator “and” to narrow search results. Following the PRISMA guidelines, we identified, screened, and evaluated studies for inclusion, resulting in nine studies meeting the eligibility criteria. Results: A total of 4917 records were initially identified from Scopus (2786), PubMed (854), and Web of Science (1277). Following deduplication, 3657 records underwent title screening, with 382 additionally screened by abstract. Ultimately, 88 full-text articles were assessed, resulting in 9 studies meeting eligibility for qualitative synthesis: 7 prospective and 2 retrospective studies. Our findings highlight the multifaceted role of lifestyle factors in migraine pathophysiology and management. Dietary habits, such as high-calorie, high-fat, and gluten-containing diets were linked to migraine triggers. Moderate physical activity showed beneficial effects on migraine management, while intense exercise could exacerbate symptoms. Poor sleep hygiene and insomnia were strongly associated with increased migraine frequency and severity. Chronic stress and poor mental health significantly contributed to migraine exacerbation, with stress management techniques proving beneficial. Environmental factors, including light, sound, weather changes, and allergens, were also identified as significant migraine triggers. Conclusions: Personalized lifestyle modifications, tailored to individual patient profiles, are crucial in managing migraines. Evidence-based recommendations include balanced diets, moderate physical activity, improved sleep hygiene, stress management techniques, and environmental adaptations.展开更多
Objective To study the effect of baicalin on the expression of receptor activator of nuclear factor-κB ligand(RANKL)and osteoprotegerin(OPG)in cultured human periodontal ligament(HPDL)cells.Methods Small interfering ...Objective To study the effect of baicalin on the expression of receptor activator of nuclear factor-κB ligand(RANKL)and osteoprotegerin(OPG)in cultured human periodontal ligament(HPDL)cells.Methods Small interfering RNA(siRNA)eukaryotic expression vector targeted transforming growth factor βⅡ receptor(TGF-β RⅡ)was constructed and transfected into T cells.HPDL cells with T cells transfected with siRNA or not were placed in the culture medium that had been added with lipopolysaccharide(LPS)and baicalin.The obtained solution was divided into six groups according to the components(group Ⅰ:HPDL cells+LPS+T cells transfected with siRNA1+baicalin;group Ⅱ:HPDL cells+LPS+T cells transfected with siRNA1;group Ⅲ:HPDL cells+LPS+T cells+baicalin;group Ⅳ:HPDL cells+LPS+T cells;group Ⅴ:HPDL cells+baicalin;group Ⅵ:HPDL cells)and was cultured for 48 hours.RT-PCR was used to observe the effect of baicalin on the expression of OPG-RANKL in HPDL cells.Results The ratio of RANKL/OPG in group Ⅰ was lower than that in group Ⅱ(P<0.01)and higher than that in group Ⅲ(P<0.01);The ratio of RANKL/OPG in group Ⅲ was lower than that in group Ⅳ(P<0.01);the ratio of RANKL/OPG in group Ⅳ was higher than that in group Ⅵ(P<0.01);the ratio of RANKL/OPG in group Ⅴ was lower than that in group Ⅵ(P<0.05).Conclusion ① Baicalin could decrease the ratio of RANKL/OPG in HPDL cells.② The TGF-β signaling transduction plays an important role in the effect of baicalin on the RANKL/OPG ratio in HPDL cells.③ Baicalin acts not only through TGF-β to regulate RANKL/OPG in HPDL cells,but also through other pathways.展开更多
The effect of triptolide (TP) on the expression of receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) was explored in rat adjuvant induced arthritis (AA). AA was induced in Wista...The effect of triptolide (TP) on the expression of receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) was explored in rat adjuvant induced arthritis (AA). AA was induced in Wistar rats. Arthritis rats were treated with TP and methotrexate (MTX) at the onset (day 9) of arthritis. On the peak of arthritis (day 24), the expression of RANKL and OPG protein in the joints and RANKL mRNA in peripheral blood mononuclear cells (PBMC) was detected. TNF-α and IL-1β levels in peripheral blood were determined. Bone erosion scores were also evaluated. The results showed that bone erosion scores in TP and MTX groups were lower than in AA group (.P〈0.01) ; The expression levels of RANKL in the synovium (P〈0.01) and bone (P〈0.05), and OPG level in synovium (P〈0.05) were lower in TP group than in AA group (P〈0.05). In TP group, the expression levels of RANKL mRNA and TNF-α, IL-1β in PBMC were lower than in AA group (all P〈0.01). It was concluded that TP could inhibit rat adjuvant arthritis bone erosion by suppressing the expression of RANKL.展开更多
Objective To investigate lipopolysaccharide (LPS) induced acute cerebral inflammatory damage and the therapeutic effect of ginkgolide B (BN52021). Methods Thirty Sprague-Dawley rats were randomly divided into 3 gr...Objective To investigate lipopolysaccharide (LPS) induced acute cerebral inflammatory damage and the therapeutic effect of ginkgolide B (BN52021). Methods Thirty Sprague-Dawley rats were randomly divided into 3 groups (n = 10 for each group): Control group, Model group and Treatment group (treated with BN52021). LPS were injected into the fourth ventricle of rat to make a neuroinflammatory murine model. Morris water maze was used to detect the learning and memory ability of rats; changes of synapse number and subcellular ultrastructures were observed under a transmission electron microscope; OX-42 positive microglia in the brain was detected by immunohistochemical method. Results The average escape latency in the Treatment group were significantly shortened than that in the Model group; and the percentage of swimming distance traveled in platform quadrant accounting for total distance increased markedly. The rough endoplasmic reticulum and polyribosomes in the Treatment group were more than that in the Model group, but the number of synapses seemed to have no obvious change. The number of OX-42 positive microglia in the Treatment group decreased markedly than that in the Model group, and the grey density of OX-42-positive cells increased significantly. Conclusion LPS can induce inflammatory damages to the brain, but the damage could be antagonized by BN52021. Platelet activating factor receptor antagonist may offer an effective therapy for neurodegeneration diseases.展开更多
Objective To observe the activating effect of ciliary neurotrophic factor (CNTF) on astrocyte in vitro. Methods Astrocytes cultured purely from newborn rats. Cerebral cortex was raised in normal and serum deprivatio...Objective To observe the activating effect of ciliary neurotrophic factor (CNTF) on astrocyte in vitro. Methods Astrocytes cultured purely from newborn rats. Cerebral cortex was raised in normal and serum deprivation condition with different concentrations (in ng/ml: 0, 2, 20, or 200) of CNTF. After cultured for 24 h, the shape and the cell cycle of astrocytes were examined by immunocytochemistry and flow cytometer, respectively. Results The immunoactivity of glial fibrillary acidic protein (GFAP) and the nuclear size of astrocytes were increased when CNTF was applied, whether cells were cultured in medium with or without serum. CNTF promoted astrocytes to enter the cell cycle in medium with serum, but had no this effect in medium without serum. Conclusion In medium without serum, astrocytes could differentiate into activated state ceils with CNTF application, but could not proliferate; in medium with serum, astrocytes could proliferate with aid of CNTF.展开更多
Hypoxia(low oxygen level) is an important feature during infections and affects the host defence mechanisms. The host has evolved specific responses to address hypoxia, which are strongly dependent on the activation...Hypoxia(low oxygen level) is an important feature during infections and affects the host defence mechanisms. The host has evolved specific responses to address hypoxia, which are strongly dependent on the activation of hypoxia-inducible factor 1(HIF-1).Hypoxia interferes degradation of HIF-1 alpha subunit(HIF-1α), leading to stabilisation of HIF-1α, heterodimerization with HIF-1 beta subunit(HIF-1β) and subsequent activation of HIF-1 pathway. Apical periodontitis(periapical lesion) is a consequence of endodontic infection and ultimately results in destruction of tooth-supporting tissue, including alveolar bone. Thus far, the role of HIF-1 in periapical lesions has not been systematically examined. In the present study, we determined the role of HIF-1 in a wellcharacterised mouse periapical lesion model using two HIF-1α-activating strategies, dimethyloxalylglycine(DMOG) and adenovirusinduced constitutively active HIF-1α(CA-HIF1 A). Both DMOG and CA-HIF1 A attenuated periapical inflammation and tissue destruction. The attenuation in vivo was associated with downregulation of nuclear factor-κappa B(NF-κB) and osteoclastic gene expressions. These two agents also suppressed NF-κB activation and subsequent production of proinflammatory cytokines by macrophages. Furthermore, activation of HIF-1α by DMOG specifically suppressed lipopolysaccharide-stimulated macrophage differentiation into M1 cells, increasing the ratio of M2 macrophages against M1 cells. Taken together, our data indicated that activation of HIF-1 plays a protective role in the development of apical periodontitis via downregulation of NF-κB, proinflammatory cytokines, M1 macrophages and osteoclastogenesis.展开更多
INTRODUCTIONDendritic cells (DCs) play a key regulatory role inantitumor immunity,especially in its immuneaccessory role via MHC-Ⅰ molecules.We haverecently reported that DCs were able to enhance thekilling activity ...INTRODUCTIONDendritic cells (DCs) play a key regulatory role inantitumor immunity,especially in its immuneaccessory role via MHC-Ⅰ molecules.We haverecently reported that DCs were able to enhance thekilling activity of Lymphokine and PHA activatedkiller (LPAK) cells in vitro.In the presentstudy,we evaluated the effects of GM-CSF andTNF upon antitumor activities of freshly展开更多
AIM To define signaling events initiating healing after intestinal epithelial injury, activation of mitogen activated protein kinase (MAPK) pathways was assessed after wounding using an in vitro model. METHODS P...AIM To define signaling events initiating healing after intestinal epithelial injury, activation of mitogen activated protein kinase (MAPK) pathways was assessed after wounding using an in vitro model. METHODS Proteins isolated from wounded monolayers of nontransformed intestinal epithelial cells (IEC 6) were analyzed for tyrosine phosphorylation and MAPK expression by Western blot. Extracellular signal regulated kinase (ERK) 1, ERK2, and Raf 1 activities were assessed by immune complex kinase assays. RESULTS Tyrosine phosphorylation of several proteins including ERK1 was substantially increased 5 minutes after injury. Another MAPK, c Jun N terminal protein kinase (JNK), was also activated after wounding. Conditioned medium from wounded but not intact IEC 6 monolayers resulted in increased activity of ERK1, ERK2, and Raf 1 kinase. Wound conditioned medium stimulated proliferation of subconfluent IEC 6 cells compared with conditioned medium from intact IEC 6 cultures and contained higher amounts of transforming growth factor (TGF) α than supernatants of confluent IEC 6 cultures. Activation of ERK1 and ERK2 was partially inhibited by neutralizing anti TGF α. CONCLUSION Wounding of intestinal epithelial cells results in activation of Raf 1, ERK1, ERK2, and JNK1 MAPKs and subsequent cell proliferation in vitro. Activation of ERK1 and ERK2 is mediated in part by TGF α.展开更多
Objective The mechanism through which platelet activating factor (PAF) induces cardiac electrical activity and arrhythmia is not well understood and previous studies have suggested a potential involvement of ion cha...Objective The mechanism through which platelet activating factor (PAF) induces cardiac electrical activity and arrhythmia is not well understood and previous studies have suggested a potential involvement of ion channels in its action. The present study was aimed to clarify the role of PAF in fatal arrhythmias following acute myocardia infarction (AMI) and the underlying mechanism. Methods (1) Blood PAF levels were measured among 72 AMI patients at the time of diagnosis with AMI and 48 h later, and their electrocardiogram (ECG) was recorded continuously. (2) Ischemia simulation and surface electrocardiogram were conducted in 20 pigs and their PAF levels were measured. (3) PAF perfusion and standard microelectrode recording were performed on guinea pig papillarymuscles. Results In both humans and pigs, elevated PAF levels were detected in AMI and simulated ischemia, respectively, and even higher PAF levels were found when fatal arrhythmias occurred. In guinea pig myocardium, PAF induced a shortening of action potential duration at 90% level of repolarization (APD 90 )under non-ischemic conditions and a more pronounced shortening under early simulated ischemic conditions. Conclusion AMI and ischemia are associated with increased PAF levels in humans and pigs, which are further raised when fatal arrhythmia follows. The effects of PAF on the myocardium may be mediated by multiple ion channels.展开更多
Tumor necrosis factor α (TNF-α) and interferon-γ (IFN-γ) are cytokines with strong antitumor activities. They were reacted with a photoactive arylazide-4-azidobenzoic acid, resulting in photoactive TNF-α and ...Tumor necrosis factor α (TNF-α) and interferon-γ (IFN-γ) are cytokines with strong antitumor activities. They were reacted with a photoactive arylazide-4-azidobenzoic acid, resulting in photoactive TNF-α and IFN-γ. The infrared (IR) spectra of these products showed the characteristic absorption of an azido group at 2127 cm^-1. By photo-immobilization, this modified TNF-α and IFN-γ were immobilized on polystyrene membranes for cell culture to prepare biomaterials. The micro-morphology of photoactive cytokines was observed with a scanning electron microscope (SEM). The inhibitory effect on growth of Hela cells and inducing apoptosis activity of these two cytokines were analyzed by growth curve, transmission electron microscope (TEM) and fluorescence active cell sorter (FACS). The results showed that co-immobilization of IFN-γ and TNF-α had significant inhibitory effect on growth of Hela cells, inhibitory rate up to 82%, and IFN-γ had obviously synergistic action.展开更多
基金supported by the National Natural Science Foundation of China (Grant No. 32100400)Huangshan University Startup Project of Scientific Research (2020xkjq013)Environment Conservation Research Centre of Xin’an River Basin (kypt202002)。
文摘Rivers are important habitats for wintering waterbirds.However,they are easily influenced by natural and human activities.An important approach for waterbirds to adapt to habitats is adjusting the activity time and energy expenditure allocation of diurnal behavior.The compensatory foraging hypothesis predicts that increased energy expenditure leads to longer foraging time,which in turn increases food intake and helps maintain a constant energy balance.However,it is unclear whether human-disturbed habitats result in increased energy expenditure related to safety or foraging.In this study,the scan sample method was used to observe the diurnal behavior of the wintering Spot-billed Duck(Anas poecilorhyncha) in two rivers in the Xin’an River Basin from October 2021 to March 2022.The allocation of time and energy expenditure for activity in both normal and disturbed environments was calculated.The results showed that foraging accounted for the highest percentage of time and energy expenditure.Additionally,foraging decreased in the disturbed environment than that in the normal environment.Resting behavior showed the opposite trend,while other behaviors were similar in both environments.The total diurnal energy expenditure of ducks in the disturbed environment was greater than that in the normal environment,with decreased foraging and resting time percentage and increased behaviors related to immediate safety(swimming and alert) and comfort.These results oppose the compensatory foraging hypothesis in favor of increased security.The optimal diurnal energy expenditure model included river width and water depth,which had a positive relationship;an increase in either of these two factors resulted in an increase in energy expenditure.This study provides a better understanding of energy allocation strategies underlying the superficial time allocation of wintering waterbirds according to environmental conditions.Exploring these changes can help understand the maximum fitness of wintering waterbirds in response to nature and human influences.
文摘Activity data and emission factors are critical for estimating greenhouse gas emissions and devising effective climate change mitigation strategies. This study developed the activity data and emission factor in the Forestry and Other Land Use Change (FOLU) subsector in Malawi. The results indicate that “forestland to cropland,” and “wetland to cropland,” were the major land use changes from the year 2000 to the year 2022. The forestland steadily declined at a rate of 13,591 ha (0.5%) per annum. Similarly, grassland declined at the rate of 1651 ha (0.5%) per annum. On the other hand, cropland, wetland, and settlements steadily increased at the rate of 8228 ha (0.14%);5257 ha (0.17%);and 1941 ha (8.1%) per annum, respectively. Furthermore, the results indicate that the “grassland to forestland” changes were higher than the “forestland to grassland” changes, suggesting that forest regrowth was occurring. On the emission factor, the results interestingly indicate that there was a significant increase in carbon sequestration in the FOLU subsector from the year 2011 to 2022. Carbon sequestration increased annually by 13.66 ± 0.17 tCO<sub>2</sub> e/ha/yr (4.6%), with an uncertainty of 2.44%. Therefore, it can be concluded that there is potential for a Carbon market in Malawi.
基金Supported by the Immuno Inflammatory Diseases Research Support Project,No.J202301E036.
文摘BACKGROUND Patients with ankylosing spondylitis(AS)frequently suffer from comorbid sleep disorders,exacerbating the burden of the disease and affecting their quality of life.AIM To investigate the clinical significance of serum inflammatory factors,health index and disease activity scores in patients with AS complicated by sleep disorders.METHODS A total of 106 AS patients with comorbid sleep disorders were included in the study.The patients were grouped into the desirable and undesirable prognosis groups in accordance with their clinical outcomes.The serum levels of inflammatory factors,including C-reactive protein,erythrocyte sedimentation rate,interleukin(IL)-6,tumour necrosis factor-αand IL-1β,were measured.Disease activity scores,such as the Bath AS functional index,Bath AS disease activity index,Bath AS metrology index and AS disease activity score,were assessed.The health index was obtained through the Short Form-36 questionnaire.RESULTS The study found significant associations amongst serum inflammatory factors,health index and disease activity scores in AS patients with comorbid sleep disorders.Positive correlations were found between serum inflammatory factors and disease activity scores,indicating the influence of heightened systemic inflammation on disease severity and functional impairment.Conversely,negative correlations were found between disease activity scores and health index parameters,highlighting the effect of disease activity on various aspects of healthrelated quality of life.Logistic regression analysis further confirmed the predictive value of these factors on patient outcomes,underscoring their potential utility in risk assessment and prognostication.CONCLUSION The findings demonstrate the intricate interplay amongst disease activity,systemic inflammation and patientreported health outcomes in AS patients complicated by sleep disorders.The results emphasise the need for comprehensive care strategies that address the diverse needs and challenges faced by these patients and underscore the potential relevance of serum inflammatory factors,health index and disease activity scores as prognostic markers in this patient population.
文摘Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease(NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with fatty liver display features of metabolic syndrome(Met S), like insulin resistance(IR), glucose intolerance, hypertension and dyslipidemia. Recently, epidemiological studies have linked obesity, Met S, and NAFLD to decreased bone mineral density and osteoporosis, highlighting an intricate interplay among bone, adipose tissue, and liver. Osteoprotegerin(OPG), an important symbol of the receptor activator of nuclear factor-B ligand/receptor activator of nuclear factor kappa B/OPG system activation, typically considered for its role in bone metabolism, may also play critical roles in the initiation and perpetuation of obesityrelated comorbidities. Clinical data have indicated that OPG concentrations are associated with hypertension, left ventricular hypertrophy, vascular calcification, endothelial dysfunction, and severity of liver damage in chronic hepatitis C. Nonetheless, the relationship between circulating OPG and IR as a key feature of Met S as well as between OPG and NAFLD remains uncertain. Thus, the aims of the present review are to provide the existent knowledge on these associations and to discuss briefly the underlying mechanisms linking OPG and NAFLD.
基金Supported by the National Natural Science Foundation of China,No. 30271450the Natural Science Foundation of Zhejiang Province,No. 300466
文摘AIM: To provide the expression profile of serine protease SNC19/matriptase and its inhibitor hepatocyte growth factor activator inhibitor type 1 (HAI-1) in normal and malignant tissues of gastrointestinal tract at mRNA level for further study on their correlations with tumor progression and metastasis. METHODS: Total RNAs were prepared from 37 samples of colorectal cancer tissues, 40 samples of gastric cancer tissues, and their adjacent normal tissues. The expression of SNC19/matriptase and HAI-1 in these samples was detected by real-time fluorescent quantitative PCR using glyceraldehyde-3-phosphate dehydrogenase as internal standard, and the clinical significance for the correlation with clinicopathological parameters was evaluated. RESULTS: In gastric cancer tissues the expression of HAI-1 and SNC19/matriptase was significantly lower than that in the corresponding adjacent normal tissues (Z = -3.280, P= 0.006; Z= -4.651, P= 0.000). HAI-1:SNC19/matriptase ratio showed no difference between normal and malignant tissues (P〉0.05). Analysis of clinicopathological parameters showed decreased expression of HAI-1 and HAI-1:SNC19/ matriptase ratio associated with stage Ⅲ/Ⅳ gastric tumors as compared to stage Ⅰ/Ⅱ ones (Z= -2.140, P= 0.031; Z = -2.155, P = 0.031), and with lymph node-positive gastric cancer tissues as compared to lymph node-negative ones (Z = -2.081, P = 0.036; Z= -2.686, P = 0.006). The expression of SNC19/matriptase had no relationship with stages and lymph node metastasis (P〉0.05). The expression of HAI-1 and HAI-1:SNC19/matriptase ratio increased in well-differentiated gastric cancer tissues, but there was no statistical significance (P〉0.05). The difference of SNC19/matriptase expression was not significant in gastric cancer tissues of different histological differentiation status (P〉0.05). In colorectal cancer tissues, the expression of HAI-1 and SNC19/matriptase was also markedly lower than that in their adjacent normal tissues (Z= -3.100, P = 0.002; Z= -2.731, P = 0.006), whereas HAI-1:SNC19/matriptase ratio showed no difference. Decreased expression of HAI-1 was associated with increased invasive depth and lymph node metastasis, but there was no statistical significance (P〉0.05). The difference of SNC19/matriptase expression and HAI-1: SNC19/matriptase ratio was not significant in different stages and different lymph node metastasis status (P〉0.05). The expression of SNC19/matriptase, HAI-1 or HAI-1: SNC19/matriptase ratio showed no difference in colorectal cancer tissues of different histological differentiation status (P〉0.05). CONCLUSION: The expressions of SNC19/matriptase and its inhibitor HAI-1 are decreased in gastrointestinal cancer tissues compared to their normal counterparts, and the decreased expression of HAI-1 may correlate with invasion and lymph node metastasis. The possible mechanisms involved need to be further investigated.
基金Supported by Grants of The Chinese State Basic Research, No.2009CB522504National Mega Projects for Infectious Diseases, No. 2008ZX10203
文摘AIM: To investigate whether DNA-dependent activator of interferon-regulatory factors (DAI) inhibits hepatitis B virus (HBV) replication and what the mechanism is. METHODS: After the human hepatoma cell line Huh7 was cotransfected with DAI and HBV expressing plas- mid, viral protein (HBV surface antigen and HBV e an- tigen) secretion was detected by enzyme-linked immu- nosorbent assay, and HBV RNA was analyzed by real- time polymerase chain reaction and Northern blotting, and viral DNA replicative intermediates were examined by Southern blotting. Interferon regulatory factor 3 (IRF3) phosphorylation and nuclear translocation were analyzed via Western blotting and immunofluorescence staining respectively. Nuclear factor-KB (NF-KB) activity induced by DAI was detected by immunofluorescence staining of P65 and dual luciferase reporter assay. Tran- swell co-culture experiment was performed in order to investigate whether the antiviral effects of DAI were dependent on the secreted cytokines. RESULTS: Viral protein secretion was significantly re- duced by 57% (P 〈 0.05), and the level of total HBV RNA was reduced by 67% (P 〈 0.05). The viral core particle-associated DNA was also dramatically down- regulated in DAI-expressing Huh7 cells. Analysis of involved signaling pathways revealed that activation of NF-KB signaling was essential for DAI to elicit antivi- ral response in Huh7 cells. When the NF-KB signaling pathway was blocked by a NF-KB signaling suppressor (I~:B^-SR), the anti-HBV activity of DAI was remarkably abrogated. The inhibitory effect of DAI was indepen- dent of IRF3 signaling and secreted cytokines. CONCLUSION: This study demonstrates that DAI can inhibit HBV replication and the inhibitory effect is asso- ciated with activation of NF-KB but independent of IRF3 and secreted cytokines.
文摘Vascular calcifications are commonly observed in patients with chronic kidney disease (CKD) and contri-bute to the excessive cardiovascular morbidity and mortality rates observed in these patients populations. Although the pathogenetic mechanisms are not yet fully elucidated, recent evidence suggests a link between bone metabolism and the development and progression of vascular calcifications. Moreover, accumulating data indicate that receptor activator of nuclear factor κB ligand/osteoprotegerin axis which plays essential roles in the regulation of bone metabolism is also involved in extra-osseous bone formation. Further studies are required to establish the prognostic significance of the above biomarkers as predictors of the presence and severity of vascular calcifications in CKD patients and of cardiovascular morbidity and mortality. Moreover, randomized clinical trials are needed to clarify whether inhibition of osteoclast activity will protect from vascular calcifcations.
基金supported by the Integrated Project of Major Research Plan of the National Natural Science Foundation of China(No.92249303)National Natural Science Foundation of China(Nos.82371603,82230071,82102217)+3 种基金Shanghai Committee of Science and Technology Laboratory Animal Research Project(No.23141900600)Science and Technology Commission of Shanghai Municipality(21YF1413100)Shanghai Hospital Development Center(SHDC2023CRT013)Baoshan District Health Commission Talents(Excellent Academic Leaders)Program(BSWSYX-2024-05).
文摘Objective The aim of this study was to investigate the prospective association between physical activity(PA),independently or in conjunction with other contributing factors,and osteoporosis(OP)outcomes.Methods The Physical Activity in Osteoporosis Outcomes(PAOPO)study was a community-based cohort investigation.A structured questionnaire was used to gather the participants’sociodemographic characteristics.Bone mineral density(BMD)measurements were performed to assess OP outcomes,and the relationship between BMD and OP was evaluated within this cohort.Results From 2013 to 2014,8,471 participants aged 18 years and older were recruited from Tangshan,China’s Jidong community.Based on their PA level,participants were categorized as inactive,moderately active,or very active.Men showed higher physical exercise levels than women across the activity groups.BMD was significantly higher in the very active group than in the moderately active and inactive groups.Individuals aged>50 years are at a higher risk of developing OP and osteopenia.Conclusion The PAOPO study offers promising insights into the relationship between PA and OP outcomes,encouraging the implementation of PA in preventing and managing OP.
文摘Primary focal and segmental glomerulosclerosis(FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The different available therapeutic approaches are unsuccessful, in part due to partially deciphered heterogeneous and complex pathophysiological mechanisms. Moreover, the term FSGS, even in its primary form, comprises a histological description shared by a number of different causes with completely different molecular pathways of disease. This review focuses on the latest developments regarding the pathophysiology of primary acquired FSGS caused by soluble factor urokinase type plasminogen activator receptor, a circulating permeability factor involved in proteinuria and edema formation, and describes recent advances with potential success in therapy.
基金Dean Research&Consultancy under Grant No.Dean (R&C)/2020-21/1155。
文摘This study presents a neural network-based model for predicting linear quadratic regulator(LQR)weighting matrices for achieving a target response reduction.Based on the expected weighting matrices,the LQR algorithm is used to determine the various responses of the structure.The responses are determined by numerically analyzing the governing equation of motion using the state-space approach.For training a neural network,four input parameters are considered:the time history of the ground motion,the percentage reduction in lateral displacement,lateral velocity,and lateral acceleration,Output parameters are LQR weighting matrices.To study the effectiveness of an LQR-based neural network(LQRNN),the actual percentage reduction in the responses obtained from using LQRNN is compared with the target percentage reductions.Furthermore,to investigate the efficacy of an active control system using LQRNN,the controlled responses of a system are compared to the corresponding uncontrolled responses.The trained neural network effectively predicts weighting parameters that can provide a percentage reduction in displacement,velocity,and acceleration close to the target percentage reduction.Based on the simulation study,it can be concluded that significant response reductions are observed in the active-controlled system using LQRNN.Moreover,the LQRNN algorithm can replace conventional LQR control with the use of an active control system.
文摘Objective: This systematic review examines the impact of lifestyle factors on migraine frequency and severity through a comprehensive analysis of lifestyle factors such as diet, physical activity, sleep patterns, stress, mental health, and environmental influences. Methods: We thoroughly searched Google Scholar, PUBMED, Scopus, and Web of Science databases using keywords related to migraines and lifestyle factors. Keywords incorporated the Boolean operator “and” to narrow search results. Following the PRISMA guidelines, we identified, screened, and evaluated studies for inclusion, resulting in nine studies meeting the eligibility criteria. Results: A total of 4917 records were initially identified from Scopus (2786), PubMed (854), and Web of Science (1277). Following deduplication, 3657 records underwent title screening, with 382 additionally screened by abstract. Ultimately, 88 full-text articles were assessed, resulting in 9 studies meeting eligibility for qualitative synthesis: 7 prospective and 2 retrospective studies. Our findings highlight the multifaceted role of lifestyle factors in migraine pathophysiology and management. Dietary habits, such as high-calorie, high-fat, and gluten-containing diets were linked to migraine triggers. Moderate physical activity showed beneficial effects on migraine management, while intense exercise could exacerbate symptoms. Poor sleep hygiene and insomnia were strongly associated with increased migraine frequency and severity. Chronic stress and poor mental health significantly contributed to migraine exacerbation, with stress management techniques proving beneficial. Environmental factors, including light, sound, weather changes, and allergens, were also identified as significant migraine triggers. Conclusions: Personalized lifestyle modifications, tailored to individual patient profiles, are crucial in managing migraines. Evidence-based recommendations include balanced diets, moderate physical activity, improved sleep hygiene, stress management techniques, and environmental adaptations.
基金supported by the Foundation of Stomatology Hospital,Xi'an Jiaotong University
文摘Objective To study the effect of baicalin on the expression of receptor activator of nuclear factor-κB ligand(RANKL)and osteoprotegerin(OPG)in cultured human periodontal ligament(HPDL)cells.Methods Small interfering RNA(siRNA)eukaryotic expression vector targeted transforming growth factor βⅡ receptor(TGF-β RⅡ)was constructed and transfected into T cells.HPDL cells with T cells transfected with siRNA or not were placed in the culture medium that had been added with lipopolysaccharide(LPS)and baicalin.The obtained solution was divided into six groups according to the components(group Ⅰ:HPDL cells+LPS+T cells transfected with siRNA1+baicalin;group Ⅱ:HPDL cells+LPS+T cells transfected with siRNA1;group Ⅲ:HPDL cells+LPS+T cells+baicalin;group Ⅳ:HPDL cells+LPS+T cells;group Ⅴ:HPDL cells+baicalin;group Ⅵ:HPDL cells)and was cultured for 48 hours.RT-PCR was used to observe the effect of baicalin on the expression of OPG-RANKL in HPDL cells.Results The ratio of RANKL/OPG in group Ⅰ was lower than that in group Ⅱ(P<0.01)and higher than that in group Ⅲ(P<0.01);The ratio of RANKL/OPG in group Ⅲ was lower than that in group Ⅳ(P<0.01);the ratio of RANKL/OPG in group Ⅳ was higher than that in group Ⅵ(P<0.01);the ratio of RANKL/OPG in group Ⅴ was lower than that in group Ⅵ(P<0.05).Conclusion ① Baicalin could decrease the ratio of RANKL/OPG in HPDL cells.② The TGF-β signaling transduction plays an important role in the effect of baicalin on the RANKL/OPG ratio in HPDL cells.③ Baicalin acts not only through TGF-β to regulate RANKL/OPG in HPDL cells,but also through other pathways.
文摘The effect of triptolide (TP) on the expression of receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) was explored in rat adjuvant induced arthritis (AA). AA was induced in Wistar rats. Arthritis rats were treated with TP and methotrexate (MTX) at the onset (day 9) of arthritis. On the peak of arthritis (day 24), the expression of RANKL and OPG protein in the joints and RANKL mRNA in peripheral blood mononuclear cells (PBMC) was detected. TNF-α and IL-1β levels in peripheral blood were determined. Bone erosion scores were also evaluated. The results showed that bone erosion scores in TP and MTX groups were lower than in AA group (.P〈0.01) ; The expression levels of RANKL in the synovium (P〈0.01) and bone (P〈0.05), and OPG level in synovium (P〈0.05) were lower in TP group than in AA group (P〈0.05). In TP group, the expression levels of RANKL mRNA and TNF-α, IL-1β in PBMC were lower than in AA group (all P〈0.01). It was concluded that TP could inhibit rat adjuvant arthritis bone erosion by suppressing the expression of RANKL.
文摘Objective To investigate lipopolysaccharide (LPS) induced acute cerebral inflammatory damage and the therapeutic effect of ginkgolide B (BN52021). Methods Thirty Sprague-Dawley rats were randomly divided into 3 groups (n = 10 for each group): Control group, Model group and Treatment group (treated with BN52021). LPS were injected into the fourth ventricle of rat to make a neuroinflammatory murine model. Morris water maze was used to detect the learning and memory ability of rats; changes of synapse number and subcellular ultrastructures were observed under a transmission electron microscope; OX-42 positive microglia in the brain was detected by immunohistochemical method. Results The average escape latency in the Treatment group were significantly shortened than that in the Model group; and the percentage of swimming distance traveled in platform quadrant accounting for total distance increased markedly. The rough endoplasmic reticulum and polyribosomes in the Treatment group were more than that in the Model group, but the number of synapses seemed to have no obvious change. The number of OX-42 positive microglia in the Treatment group decreased markedly than that in the Model group, and the grey density of OX-42-positive cells increased significantly. Conclusion LPS can induce inflammatory damages to the brain, but the damage could be antagonized by BN52021. Platelet activating factor receptor antagonist may offer an effective therapy for neurodegeneration diseases.
文摘Objective To observe the activating effect of ciliary neurotrophic factor (CNTF) on astrocyte in vitro. Methods Astrocytes cultured purely from newborn rats. Cerebral cortex was raised in normal and serum deprivation condition with different concentrations (in ng/ml: 0, 2, 20, or 200) of CNTF. After cultured for 24 h, the shape and the cell cycle of astrocytes were examined by immunocytochemistry and flow cytometer, respectively. Results The immunoactivity of glial fibrillary acidic protein (GFAP) and the nuclear size of astrocytes were increased when CNTF was applied, whether cells were cultured in medium with or without serum. CNTF promoted astrocytes to enter the cell cycle in medium with serum, but had no this effect in medium without serum. Conclusion In medium without serum, astrocytes could differentiate into activated state ceils with CNTF application, but could not proliferate; in medium with serum, astrocytes could proliferate with aid of CNTF.
基金supported by the National Institute of Dental and Craniofacial Research(NIDCR)the National Center for Research Resources(NCRR)of the National Institutes of Health(NIH)under award numbers R21DE023178,R01DE024796,and S10RR027553
文摘Hypoxia(low oxygen level) is an important feature during infections and affects the host defence mechanisms. The host has evolved specific responses to address hypoxia, which are strongly dependent on the activation of hypoxia-inducible factor 1(HIF-1).Hypoxia interferes degradation of HIF-1 alpha subunit(HIF-1α), leading to stabilisation of HIF-1α, heterodimerization with HIF-1 beta subunit(HIF-1β) and subsequent activation of HIF-1 pathway. Apical periodontitis(periapical lesion) is a consequence of endodontic infection and ultimately results in destruction of tooth-supporting tissue, including alveolar bone. Thus far, the role of HIF-1 in periapical lesions has not been systematically examined. In the present study, we determined the role of HIF-1 in a wellcharacterised mouse periapical lesion model using two HIF-1α-activating strategies, dimethyloxalylglycine(DMOG) and adenovirusinduced constitutively active HIF-1α(CA-HIF1 A). Both DMOG and CA-HIF1 A attenuated periapical inflammation and tissue destruction. The attenuation in vivo was associated with downregulation of nuclear factor-κappa B(NF-κB) and osteoclastic gene expressions. These two agents also suppressed NF-κB activation and subsequent production of proinflammatory cytokines by macrophages. Furthermore, activation of HIF-1α by DMOG specifically suppressed lipopolysaccharide-stimulated macrophage differentiation into M1 cells, increasing the ratio of M2 macrophages against M1 cells. Taken together, our data indicated that activation of HIF-1 plays a protective role in the development of apical periodontitis via downregulation of NF-κB, proinflammatory cytokines, M1 macrophages and osteoclastogenesis.
基金Natural Science Foundation of the Higher Education Office of Guangdong Province,No.19952901
文摘INTRODUCTIONDendritic cells (DCs) play a key regulatory role inantitumor immunity,especially in its immuneaccessory role via MHC-Ⅰ molecules.We haverecently reported that DCs were able to enhance thekilling activity of Lymphokine and PHA activatedkiller (LPAK) cells in vitro.In the presentstudy,we evaluated the effects of GM-CSF andTNF upon antitumor activities of freshly
文摘AIM To define signaling events initiating healing after intestinal epithelial injury, activation of mitogen activated protein kinase (MAPK) pathways was assessed after wounding using an in vitro model. METHODS Proteins isolated from wounded monolayers of nontransformed intestinal epithelial cells (IEC 6) were analyzed for tyrosine phosphorylation and MAPK expression by Western blot. Extracellular signal regulated kinase (ERK) 1, ERK2, and Raf 1 activities were assessed by immune complex kinase assays. RESULTS Tyrosine phosphorylation of several proteins including ERK1 was substantially increased 5 minutes after injury. Another MAPK, c Jun N terminal protein kinase (JNK), was also activated after wounding. Conditioned medium from wounded but not intact IEC 6 monolayers resulted in increased activity of ERK1, ERK2, and Raf 1 kinase. Wound conditioned medium stimulated proliferation of subconfluent IEC 6 cells compared with conditioned medium from intact IEC 6 cultures and contained higher amounts of transforming growth factor (TGF) α than supernatants of confluent IEC 6 cultures. Activation of ERK1 and ERK2 was partially inhibited by neutralizing anti TGF α. CONCLUSION Wounding of intestinal epithelial cells results in activation of Raf 1, ERK1, ERK2, and JNK1 MAPKs and subsequent cell proliferation in vitro. Activation of ERK1 and ERK2 is mediated in part by TGF α.
文摘Objective The mechanism through which platelet activating factor (PAF) induces cardiac electrical activity and arrhythmia is not well understood and previous studies have suggested a potential involvement of ion channels in its action. The present study was aimed to clarify the role of PAF in fatal arrhythmias following acute myocardia infarction (AMI) and the underlying mechanism. Methods (1) Blood PAF levels were measured among 72 AMI patients at the time of diagnosis with AMI and 48 h later, and their electrocardiogram (ECG) was recorded continuously. (2) Ischemia simulation and surface electrocardiogram were conducted in 20 pigs and their PAF levels were measured. (3) PAF perfusion and standard microelectrode recording were performed on guinea pig papillarymuscles. Results In both humans and pigs, elevated PAF levels were detected in AMI and simulated ischemia, respectively, and even higher PAF levels were found when fatal arrhythmias occurred. In guinea pig myocardium, PAF induced a shortening of action potential duration at 90% level of repolarization (APD 90 )under non-ischemic conditions and a more pronounced shortening under early simulated ischemic conditions. Conclusion AMI and ischemia are associated with increased PAF levels in humans and pigs, which are further raised when fatal arrhythmia follows. The effects of PAF on the myocardium may be mediated by multiple ion channels.
基金This work was supported by the China Postdoctoral Science Foundation under grant No.2004035588.
文摘Tumor necrosis factor α (TNF-α) and interferon-γ (IFN-γ) are cytokines with strong antitumor activities. They were reacted with a photoactive arylazide-4-azidobenzoic acid, resulting in photoactive TNF-α and IFN-γ. The infrared (IR) spectra of these products showed the characteristic absorption of an azido group at 2127 cm^-1. By photo-immobilization, this modified TNF-α and IFN-γ were immobilized on polystyrene membranes for cell culture to prepare biomaterials. The micro-morphology of photoactive cytokines was observed with a scanning electron microscope (SEM). The inhibitory effect on growth of Hela cells and inducing apoptosis activity of these two cytokines were analyzed by growth curve, transmission electron microscope (TEM) and fluorescence active cell sorter (FACS). The results showed that co-immobilization of IFN-γ and TNF-α had significant inhibitory effect on growth of Hela cells, inhibitory rate up to 82%, and IFN-γ had obviously synergistic action.