BACKGROUND Hepatocellular carcinoma(HCC)surveillance is crucial for patients with compensated cirrhosis(CC)and decompensated cirrhosis(DC).Increasing evidence has revealed a connection between thyroid hormone(TH)and H...BACKGROUND Hepatocellular carcinoma(HCC)surveillance is crucial for patients with compensated cirrhosis(CC)and decompensated cirrhosis(DC).Increasing evidence has revealed a connection between thyroid hormone(TH)and HCC,although this relationship remains contentious.Complements and immunoglobulin(Ig),which serve as surrogates of cirrhosis-associated immune dysfunc-tion,are associated with the severity and outcomes of liver cirrhosis(LC).To date,there is a lack of evidence supporting the recommendation of TH,Ig,and com-plement tests in patients at high risk of HCC.AIM To assess the predictive value of TH,Ig,and complements for HCC development.METHODS Data from 142 patients,comprising 72 patients with CC and 70 patients with DC,were analysed as a training set.Among them,100 patients who underwent complement and Ig tests were considered for internal validation.Logistic regression was employed to identify independent risk factors for HCC development.RESULTS The median follow-up duration was 32(24-37 months)months.The incidence of HCC was significantly higher in the DC group(16/70,22.9%)compared to the CC group(3/72,4.2%)(χ^(2)=10.698,P<0.01).Patients with DC exhibited lower total tetraiodothyronine(TT4),total triiodothyronine(TT3),free triiodothyronine,complement C3,and C4(all P<0.01),and higher IgA and IgG(both P<0.01).In both CC and DC patients,TT3 and TT4 positively correlated with alanine transaminase(ALT),aspartate transaminase(AST),and gamma-glutamyl transpeptidase(GGT).IgG positively correlated with IgM,IgA,ALT,and AST,while it negatively correlated with C3 and C4.Multivariable analysis indicated that age,DC status,and GGT were independent risk factors for HCC development.CONCLUSION The predictive value of TH,Ig,and complements for HCC development is suboptimal.Age,DC,and GGT emerge as more significant factors during HCC surveillance in hepatitis B virus-related LC.展开更多
Enantiomer identification is of paramount industrial value and physiological significance.Construction of sensitive chiral sensors with high enantiomeric discrimination ability is highly desirable.In this work,a chira...Enantiomer identification is of paramount industrial value and physiological significance.Construction of sensitive chiral sensors with high enantiomeric discrimination ability is highly desirable.In this work,a chiral covalent organic framework/anodic aluminum oxide(c-COF/AAO)membrane was prepared for electrochemical enantioselective recognition and sensing.Benefiting from the remarkable asymmetry,the asprepared nanofluidic c-COF/AAO presents a distinct ion current rectification(ICR)characteristic,enabling sensitive bioanalysis.In addition,owing to the large surface area,high chemical stability and perfect ion selectivity of chiral COF,the prepared c-COF/AAO membrane presents exceptionally selective mass transport and thereby enables excellent chiral discrimination for S-/R-Naproxen(S-/R-Npx)enantiomers.It is especially noteworthy that the detection limit is achieved as low as 3.88 pmol/L.These results raise the possibility for a facile,stable and low-cost method to carry out sensitive enantioselective recognition and detection.展开更多
Thermal diodes,based on the thermal rectification effect,have demonstrated great promise for advanced thermal management.In previous studies,almost all thermal diodes were discussed under the condition of steady state...Thermal diodes,based on the thermal rectification effect,have demonstrated great promise for advanced thermal management.In previous studies,almost all thermal diodes were discussed under the condition of steady states,while the heat source of a practical thermal system often operates under dynamically fluctuating temperatures.Therefore,in this work,we employ finite element simulation to investigate transient thermal rectification behaviors in a well-built heterojunction which exhibits intrinsic thermal rectification effect under steady state.Unidirectional energy transport in the heterojunction system,decoupled from the steady-state temperature bias,is observed under a time-dependent fluctuating heat source.This phenomenon enables straightforward realization of both giant thermal rectification and negative thermal transport.Furthermore,a series of novel thermal regulation strategies are unveiled by adjusting the average temperature,frequency,and phase of the heat source.Our work not only deepens fundamental understanding of thermal regulation in time-dependent oscillating temperature systems but also uncovers many unexplored energy-saving thermal management strategies.展开更多
Synaptic pruning is a crucial process in synaptic refinement,eliminating unstable synaptic connections in neural circuits.This process is triggered and regulated primarily by spontaneous neural activity and experience...Synaptic pruning is a crucial process in synaptic refinement,eliminating unstable synaptic connections in neural circuits.This process is triggered and regulated primarily by spontaneous neural activity and experience-dependent mechanisms.The pruning process involves multiple molecular signals and a series of regulatory activities governing the“eat me”and“don't eat me”states.Under physiological conditions,the interaction between glial cells and neurons results in the clearance of unnecessary synapses,maintaining normal neural circuit functionality via synaptic pruning.Alterations in genetic and environmental factors can lead to imbalanced synaptic pruning,thus promoting the occurrence and development of autism spectrum disorder,schizophrenia,Alzheimer's disease,and other neurological disorders.In this review,we investigated the molecular mechanisms responsible for synaptic pruning during neural development.We focus on how synaptic pruning can regulate neural circuits and its association with neurological disorders.Furthermore,we discuss the application of emerging optical and imaging technologies to observe synaptic structure and function,as well as their potential for clinical translation.Our aim was to enhance our understanding of synaptic pruning during neural development,including the molecular basis underlying the regulation of synaptic function and the dynamic changes in synaptic density,and to investigate the potential role of these mechanisms in the pathophysiology of neurological diseases,thus providing a theoretical foundation for the treatment of neurological disorders.展开更多
BACKGROUND Complement-mediated thrombotic microangiopathy(TMA)is a rare endothelial injury syndrome caused by dysregulated activation of the alternative complement pathway,often linked to genetic abnormalities in comp...BACKGROUND Complement-mediated thrombotic microangiopathy(TMA)is a rare endothelial injury syndrome caused by dysregulated activation of the alternative complement pathway,often linked to genetic abnormalities in complement factor H(CFH),complement factor I,or complement factor H-related(CFHR)proteins.Both renal transplantation and pregnancy are independent triggers for recurrence.This case highlights a genetically high-risk patient who achieved a successful term pregnancy after renal transplantation without complement inhibition,emphasizing individualized risk stratification,close surveillance,and multidisciplinary management for favourable maternal and graft outcomes.CASE SUMMARY A 32-year-old woman with end-stage renal disease secondary to genetically confirmed complement-mediated TMA—homozygous CFH exon 17 deletion and CFHR3-CFHR1 duplication—was maintained on dialysis for 2.5 years before undergoing a successful live-donor kidney transplant from her mother.Post-transplant immunosuppression included tacrolimus,mycophenolate mofetil,and prednisolone,later modified to azathioprine during pregnancy planning.One-year post-transplant,she conceived spontaneously.Pregnancy was complicated by transient gestational hypertension,controlled with nifedipine,labetalol,and amlodipine.Proteinuria remained<150 mg/day;white blood cell counts 5.8-7.2×109/L without cytopenia.Serum creatinine ranged 0.9-1.1 mg/dL,and tacrolimus trough levels 5-7 ng/mL.At 36 weeks,she delivered a healthy 3 kg infant by elective caesarean section.Postpartum follow-up at three months confirmed stable maternal and graft function.CONCLUSION High-risk complement-mediated TMA patients can achieve successful pregnancy post-transplant through individualized care without mandatory complement blockade.展开更多
The complement system is a key component of the body's immune system. When abnormally activated, this system can induce inflammation and damage to normal tissues and participate in the development and progression ...The complement system is a key component of the body's immune system. When abnormally activated, this system can induce inflammation and damage to normal tissues and participate in the development and progression of a variety of diseases. In the past, many scholars believed that alcoholic liver disease(ALD) is induced by the stress of ethanol on liver cells, including oxidative stress and dysfunction of mitochondria and protease bodies, causing hepatocyte injury and apoptosis. Recent studies have shown that complement activation is also involved in the genesis and development of ALD. This review focuses on the roles of complement activation in ALD and of therapeutic intervention in complement-activation pathways. We intend to provide new ideas on the diagnosis and treatment of ALD.展开更多
The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the ...The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the pathogen as well as in the generation of the classical inflammatory response through the production of potent proinflammatory molecules. More recently, however, the role of complement in the immune response has been expanded due to observations that link complement activation to adaptive immune responses. It is now appreciated that complement is a functional bridge between innate and adaptive immune responses that allows an integrated host defense to pathogenic challenges. As such, a study of its functions allows insight into the molecular underpinnings of host-pathogen interactions as well as the organization and orchestration of the host immune response. This review attempts to summarize the roles that complement plays in both innate and adaptive immune responses and the consequences of these interactions on host defense.展开更多
The complement pathway is best known for its role in immune surveillance and inflammation. However,its ability of opsonizing and removing not only pathogens,but also necrotic and apoptotic cells,is a phylogenetically ...The complement pathway is best known for its role in immune surveillance and inflammation. However,its ability of opsonizing and removing not only pathogens,but also necrotic and apoptotic cells,is a phylogenetically ancient means of initiating tissue repair. The means and mechanisms of complement-mediated tissue repair are discussed in this review. There is increasing evidence that complement activation contributes to tissue repair at several levels. These range from the chemo-attraction of stem and progenitor cells to areas of complement activation,to increased survival of various cell types in the presence of split products of complement,and to the production of trophic factors by cells activated by the anaphylatoxins C3 a and C5 a. This repair aspect of complement biology has not found sufficient appreciation until recently. The following will examine this aspect of complement biology with an emphasis on the anaphylatoxins C3 a and C5 a.展开更多
The northem pig-tailed macaque (NPM, Macaca leonina) has become a widely used animal model in biomedical research. In this study, we measured serum immunoglobulin IgG, IgM, IgA, complement C3, C4 and CRP levels in 3...The northem pig-tailed macaque (NPM, Macaca leonina) has become a widely used animal model in biomedical research. In this study, we measured serum immunoglobulin IgG, IgM, IgA, complement C3, C4 and CRP levels in 3-11 year old captive northem pig-tailed macaques using HITACHI 7600-20 automated chemistry analyzer in order to determine the influences of age and gender on these items. The results showed that serum IgA, IgM, C3 and C4 levels were not correlated with age (P〉0.05), while serum IgG levels increased progressively with age (r=0.202; P=0.045). Serum IgG, IgA, IgM and C3 levels were higher in females than in males (P〈0.05). Moreover, serum C3 concentration was both positively and strongly correlated with that of C4 (r=0.700; P〈0.0001). This study provides basic serum immunoglobulin and complement data of captive northem pig-tailed macaques, which may prove useful for future breeding efforts and biomedical research.展开更多
The finite element method is used to simulate the rectification process of shield machine, to study the relationship between rectification moment and angle and to explore the influence laws of different soil parameter...The finite element method is used to simulate the rectification process of shield machine, to study the relationship between rectification moment and angle and to explore the influence laws of different soil parameters and buried depth on rectification moment. It is hoped that the reference value of rectification moment can be offered to operator, and theoretical foundation can be laid for future automatic rectification technology. The results show that the rectification moment and angle generally exhibit good linear behavior in clay layers with different soil parameters or buried depths, and then the concept of rectification coefficient, that is, the ratio of rectification angle to rectification moment, is proposed; different soil parameters and buried depths have different influences on rectification coefficient, in which elastic modulus has great influence but others have little influences; the simulations of rectification process are preformed in clay layers with different elastic modulus, and fitting results show that elastic modulus and rectification coefficient present the quadratic function relation.展开更多
By observing two-photon response and anisotropy of the light-induced voltage in Al-Si Schottky barrier potential,it is certified from the experimental and theoretical analysis that the built-in electric field generate...By observing two-photon response and anisotropy of the light-induced voltage in Al-Si Schottky barrier potential,it is certified from the experimental and theoretical analysis that the built-in electric field generated by the Schottky barrier potential will induce the phenomena of optical rectification in Si photodiode.Thus,it is deduced that there must be double-frequency absorption caused by phase-mismatch in the mechanism of two-photon response of Si photodiode.If the intensity of the built-in electric field is strong enough,the double-frequency absorption will be the main factor of the two-photon response,which is different from the conventional opinion that the two-photon response is just the two-photon absorption.展开更多
The purpose is to explore the effect of the spatial distribution of ground control points (GCPs) on the accuracy of imagery rectification. Both area-distributed and linearly distributed GCPs were used to rectify a L...The purpose is to explore the effect of the spatial distribution of ground control points (GCPs) on the accuracy of imagery rectification. Both area-distributed and linearly distributed GCPs were used to rectify a Landsat TM image of a coastal zone. Rectification accuracy was checked against 99 independent points over the intertidal mudflats with no ground control. Results indicate that the root-mean-square error of residuals over these areas is several times larger than its GCPs-measured counterpart. If the GCPs are spatially dispersed over an area, residuals fluctuate but increase steadily with distance to the source of control in easting (R^2= 0. 827). in northing they fluctuate around 150 m until 15 km, beyond which they rise steadily at a small range of fluctuation. These residuals are less predictable from distance to the source of control than in easting (R^2= 0.517 ). If the GCPs are distributed along a control line, residuals rise with distance to it linearly and predictably (R^2 = 0. 877) in the direction perpendicular to it. In a direction parallel to it, the distance has little impact on rectification residuals.展开更多
· AIM: To investigate the expression of complement factors in the posterior scleral fibroblasts of guinea pigs with negative lens-defocused myopia.· METHODS: Eighteen guinea pigs were assigned randomly to tw...· AIM: To investigate the expression of complement factors in the posterior scleral fibroblasts of guinea pigs with negative lens-defocused myopia.· METHODS: Eighteen guinea pigs were assigned randomly to two groups: the negative lens-defocused group(NLD group, n =9) and the normal control without treatment group(NC group, n =9). The effect of myopic induction was compared in three subgroups: eyes treated with a-10.00 D negative lens in the NLD group(NL group), eyes treated with a plano(0 D) lens in the NLD group(PL group), and untreated right eyes in the NC group(NC group). The following analyses were conducted at four weeks: examination of the refractive error via retinoscopy, assessment of complement C5b-9expression in the posterior scleral fibroblasts using immunohistochemistry, and measurements of complement C1 q and C3 protein levels in the posterior sclera by Western blot.·RESULTS: After an induction period of four weeks, a significant myopic shift was detected in the eyes of the NL group, relative to that of the PL and NC groups(P 【0.05). Data analysis showed a significant increase in the percentage of C5b-9 immunopositive fibroblasts in the posterior sclera of the NL group eyes, compared to the PL group(q =11.50, P 【0.001). Significantly higher levels of C1q(q =4.94, P =0.01) and C3(q =4.07, P =0.03)protein were detected in the posterior sclera of NL group eyes, compared to the PL group. There were no significant difference between the PL and NC groups for C5b-9(q =2.44, P =0.10), C1q(q =1.55, P =0.53) and C3(q =0.98, P =0.77) in the posterior sclera.·CONCLUSION: The data from present study provide evidence of the up-regulation of C5b-9, C1 q and C3 in the posterior scleral fibroblasts in a NLD myopic animal model. The results suggest that the complement system may be involved in the development of myopia.展开更多
AIM:To evaluate serum complement C4a and its relation to liver fibrosis in children with chronic hepatitis C virus(HCV)infection.METHODS:The study included 30 children with chronic HCV infection before receiving antiv...AIM:To evaluate serum complement C4a and its relation to liver fibrosis in children with chronic hepatitis C virus(HCV)infection.METHODS:The study included 30 children with chronic HCV infection before receiving antiviral therapy.Chronic HCV infection was defined by positive anti-HCV,a positive polymerase chain reaction for HCV-RNA for more than 6 mo with absence of any associated liver disease.A second group of 30 age-and sex-matched healthy children served as controls.Serum C4a levels were measured by enzyme-linked immunosorbent assay.Liver fibrosis stage and inflammatory grade were assessed using Ishak scoring system.Serum C4a levels were compared according to different clinical,laboratory and histopathological parameters.Statistical significance for quantitative data was tested by MannWhitney U non-parametric tests.For qualitative data,significance between groups was tested by 2test.Correlation was tested by Spearman’s test.Results were considered significant if P value≤0.05.RESULTS:The age of the patients ranged from 3.5to 18 years and that of controls ranged from 4 to 17years.C4a mean levels were merely lower in patients(153.67±18.69 mg/L)than that in the controls(157.25±11.40 mg/L)with no statistical significance(P=0.378).It did not differ significantly in patients with elevated vs those with normal transaminases(152.25±16.62 vs 155.36±21.33;P=0.868)or with different HCV viremia(P=0.561).Furthermore,there was no statistical significant difference in serum levels between those with no/mild fibrosis and those with moderate fibrosis(154.65±20.59 vs 152.97±17.72;P=0.786)or minimal and mild activity(155.1±21.93 vs 152.99±17.43;P=0.809).Though statistically not significant,C4a was highest in fibrosis score 0(F0),decreasing in F1 and F2 to be the lowest in F3.When comparing significant fibrosis(Ishak score≥3)vs other stages,C4a was significantly lower in F3 compared to other fibrosis scores(143.55±2.33 mg/L vs 155.26±19.64 mg/L;P=0.047)and at a cutoff value of less than 144.01 mg/L,C4a could discriminate F3 with 76.9%sensitivity and75%specificity from other stages of fibrosis.CONCLUSION:Serum complement C4a did not correlate with any of transaminases,HCV viremia or with the histopathological scores.Although C4a decreased with higher stages of fibrosis,this change was not significant enough to predict individual stages of fibrosis.Yet,it could predict significant fibrosis with acceptable clinical performance.展开更多
The complement system plays a crucial role in the innate immune system of animals. It can be activated by distinct yet overlapping classical, alternative and lectin pathways. In the alternative pathway, complement fac...The complement system plays a crucial role in the innate immune system of animals. It can be activated by distinct yet overlapping classical, alternative and lectin pathways. In the alternative pathway, complement factor B(Bf) serves as the catalytic subunit of complement component 3(C3) convertase, which plays the central role among three activation pathways. In this study, the Bf gene in sea cucumber(Apostichopus japonicus), termed Aj Bf, was obtained by rapid amplification of c DNA ends(RACE). The full-length c DNA of Aj Bf was 3231 bp in length barring the poly(A) tail. It contained an open reading frame(ORF) of 2742 bp encoding 913 amino acids, a 105 bp 5'-UTR(5'-terminal untranslated region) and a 384 bp 3'-UTR. Aj Bf was a mosaic protein with six CCP(complement control protein) domains, a VWA(von Willebrand factor A) domain, and a serine protease domain. The deduced molecular weight of Aj Bf protein was 101 k Da. Quantitative real time PCR(q RT-PCR) analysis indicated that the expression level of Aj Bf in A. japonicus was obviously higher at larval stage than that at embryonic stage. Expression detection in different tissues showed that Aj Bf expressed higher in coelomocytes than in other four tissues. In addation, Aj Bf expression in different tissues was induced significantly after LPS or Poly I:C challenge. These results indicated that Aj Bf plays an important role in immune responses to pathogen infection.展开更多
AIM: To systematically review the association between complement factors I (CFI) polymorphisms and age- related macular degeneration (AMD) and to explore whether CFI polymorphisms are associated with AMD, METHODS...AIM: To systematically review the association between complement factors I (CFI) polymorphisms and age- related macular degeneration (AMD) and to explore whether CFI polymorphisms are associated with AMD, METHODS: Meta-analysis of articles published from 1995 to January 2015 of articles involved with AMD and polymorphisms of the CFI gene. Eligible data were pooled in a Meta-analysis, analyzing using STATA software (version 12.0), Review Manager (version 5.2) and different models based on the heterogeneity of effect sizes. Egger's test, Begg's rank correlation methods were used to evaluate for publication bias.~ RESULTS: Thirteen articles were eligible, describing two loci polymorphisms of the CFI gene (of which 12 articles focus on rs10033900T〉C and 3 articles focus on rs2285714C〉T). For rs10033900T〉C, the results of our study revealed that having a mutant allele C, TC, CC and TC+CC was associated with a decreased risk of AMD in all population groups studied (C versus T models, OR=0.84, 95%Ch 0.72-0.99, P=0.04; TC versus TT models OR= 0.89, 95%Ch 0.88-0.99, P=0.04;CC versus "1-1" models, OR=0.76, 95%Ch 0.60-0.98, P=-0.03; TC+CC versus TT models, OR=0.81, 95%Ch0.65-0.99, P=0.04). We found that C allele were related to lower AMD risk in the Caucasian population by subgroup analysis, but there was no association with AMD under the allele and genotypes comparison in Asian studies. For rs2285714 C〉T, the TC, TT genotypes contributed to a higher risk of AMD, compared with the CC carriers and CT+CC (OR=1.34, 95%Ch 1.09-1.63, P=0.004; OR=1.50, 95%Ch 1.25-1.80, P〈0.0001). CONCLUSION: This Meta-analysis suggests that CFI rs10033900T〉C and rs2285714C〉T polymorphisms may contribute to AMD.展开更多
Previous studies have reported age-specific pathological and functional outcomes in young and aged patients suffering spinal cord injury,but the mechanisms remain poorly understood. In this study, we examined mice wit...Previous studies have reported age-specific pathological and functional outcomes in young and aged patients suffering spinal cord injury,but the mechanisms remain poorly understood. In this study, we examined mice with spinal cord injury. Gene expression profiles from the Gene Expression Omnibus database (accession number GSE93561) were used, including spinal cord samples from 3 young injured mice (2–3-months old, induced by Impactor at Th9 level) and 3 control mice (2–3-months old, no treatment), as well as 2 aged injured mice (15–18-months old, induced by Impactor at Th9 level) and 2 control mice (15–18-months old, no treatment). Differentially expressed genes (DEGs) in spinal cord tissue from injured and control mice were identified using the Linear Models for Microarray data method,with a threshold of adjusted P 〈 0.05 and |logFC(fold change)| 〉 1.5. Protein–protein interaction networks were constructed using data from the STRING database, followed by module analysis by Cytoscape software to screen crucial genes. Kyoto encyclopedia of genes and genomes pathway and Gene Ontology enrichment analyses were performed to investigate the underlying functions of DEGs using Database for Annotation, Visualization and Integrated Discovery. Consequently, 1,604 and 1,153 DEGs were identified between injured and normal control mice in spinal cord tissue of aged and young mice, respectively. Furthermore, a Venn diagram showed that 960 DEGs were shared among aged and young mice, while 644 and 193 DEGs were specific to aged and young mice, respectively. Functional enrichment indicates that shared DEGs are involved in osteoclast differentiation, extracellular matrix–receptor interaction, nuclear factor-kappa B signaling pathway, and focal adhesion. Unique genes for aged and young injured groups were involved in the cell cycle (upregulation of PLK1) and complement (upregulation of C3) activation, respectively. These findings were confirmed by functional analysis of genes in modules (common, 4; aged, 2; young, 1) screened from protein–protein interaction networks. Accordingly, cell cycle and complement inhibitors may be specific treatments for spinal cord injury in aged and young mice, respectively.展开更多
AIM: Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world and complement factor H (CFH) polymorphism has been found to associate with the AMD. To investigate whether the Y402...AIM: Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world and complement factor H (CFH) polymorphism has been found to associate with the AMD. To investigate whether the Y402H variant in CFH is associated with AMD in Chinese populations, a systematic review and meta-analysis were performed to estimate the magnitude of the gene effect and the possible mode of action. METHODS: A meta-analysis was performed using data available from ten case-control studies assessing association between the CFH Y402H polymorphism and AMD in Chinese populations involving 1538 AMD. Data extraction and study quality assessment were performed in duplicate. Summary odds ratios (ORs) and 95% confidence intervals (CIs) an allele contrast and genotype contrast were estimated usingfixed- effects models. The Q-statistic test was used to assess heterogeneity, and Funnel plot was used to evaluate publication bias. RESULTS: Seven of ten case-control studies were neovascular AMD, and few studies came from west and north of China. There was strong evidence for association between CFH and AMD in Chinese population, with those having risk allele C 2.35 times more likely to have AMD than subjects with T allele. Evidence of publication bias was not observed in our meta-analysis. CONCLUSION: This meta-analysis summarizes the strong evidence for an association between CFH and AMD in Chinese and indicates each C allele increasing the odds of AMD by 2.33-fold. But more evidences about the relation between CFH polymorphism and different type of Chinese AMD from various district were needed.展开更多
Anti-complement activity guided fractionation led to the isolation of 24 compounds from Commelina communis.Bioassay showed that six compounds inhibited the classical pathway and alternative pathway with CH 50 values o...Anti-complement activity guided fractionation led to the isolation of 24 compounds from Commelina communis.Bioassay showed that six compounds inhibited the classical pathway and alternative pathway with CH 50 values of 0.12-1.44 mM and AP 50 values of 0.28-7.05 mM,respectively.Preliminary mechanism studies demonstrated that quinovic acid acted on C1q,C2,C3,C4,C5 and C9 components of the complement system,β-sitosterol interacted with C3 and C4,(+)-catechin-3-O-β-Dgluco(2-cinnamoyl)-pyranoside,p-cresol and 6-methoxy-3-methylbenzene-1,2,4-triol blocked C1q,C2,C3,C5 and C9.展开更多
Amplified inflammatory reaction has been observed to be involved in cardiometabolic diseases such as obesity,insulin resistance,diabetes,dyslipidemia,and atherosclerosis.The complement system was originally viewed as ...Amplified inflammatory reaction has been observed to be involved in cardiometabolic diseases such as obesity,insulin resistance,diabetes,dyslipidemia,and atherosclerosis.The complement system was originally viewed as a supportive first line of defense against microbial invaders,and research over the past decade has come to appreciate that the functions of the complement system extend beyond the defense and elimination of microbes,involving in such diverse processes as clearance of the immune complexes,complementing T and B cell immune functions,tissue regeneration,and metabolism.The focus of this review is to summarize the role of the activation of complement system and the initiation and progression of metabolic disorders including obesity,insulin resistance and diabetes mellitus.In addition,we briefly describe the interaction of the activation of the complement system with diabetic complications such as diabetic retinopathy,nephropathy and neuropathy,highlighting that targeting complement system therapeutics could be one of possible routes to slow down those aforementioned diabetic complications.展开更多
基金Supported by The Research Foundation of Jiangsu Province Administration of Traditional Chinese Medicine,No.MS2023088The Science and Technology Project of Changzhou,No.CE20225040+1 种基金The Research Foundation of Nanjing Medical University Changzhou Medical Center,No.CMCC202311Leading Talent of Changzhou“The 14th Five-Year Plan”High-Level Health Talents Training Project,No.2022CZLJ021.
文摘BACKGROUND Hepatocellular carcinoma(HCC)surveillance is crucial for patients with compensated cirrhosis(CC)and decompensated cirrhosis(DC).Increasing evidence has revealed a connection between thyroid hormone(TH)and HCC,although this relationship remains contentious.Complements and immunoglobulin(Ig),which serve as surrogates of cirrhosis-associated immune dysfunc-tion,are associated with the severity and outcomes of liver cirrhosis(LC).To date,there is a lack of evidence supporting the recommendation of TH,Ig,and com-plement tests in patients at high risk of HCC.AIM To assess the predictive value of TH,Ig,and complements for HCC development.METHODS Data from 142 patients,comprising 72 patients with CC and 70 patients with DC,were analysed as a training set.Among them,100 patients who underwent complement and Ig tests were considered for internal validation.Logistic regression was employed to identify independent risk factors for HCC development.RESULTS The median follow-up duration was 32(24-37 months)months.The incidence of HCC was significantly higher in the DC group(16/70,22.9%)compared to the CC group(3/72,4.2%)(χ^(2)=10.698,P<0.01).Patients with DC exhibited lower total tetraiodothyronine(TT4),total triiodothyronine(TT3),free triiodothyronine,complement C3,and C4(all P<0.01),and higher IgA and IgG(both P<0.01).In both CC and DC patients,TT3 and TT4 positively correlated with alanine transaminase(ALT),aspartate transaminase(AST),and gamma-glutamyl transpeptidase(GGT).IgG positively correlated with IgM,IgA,ALT,and AST,while it negatively correlated with C3 and C4.Multivariable analysis indicated that age,DC status,and GGT were independent risk factors for HCC development.CONCLUSION The predictive value of TH,Ig,and complements for HCC development is suboptimal.Age,DC,and GGT emerge as more significant factors during HCC surveillance in hepatitis B virus-related LC.
基金supported by grants from the National Natural Science Foundation of China(Nos.22274076,22304084)the Primary Research&Development Plan of Jiangsu Province(No.BE2022793)+1 种基金the Natural Science Foundation of Jiangsu Province of China(No.BK20230377)Jiangsu Provincial Department of Education(No.211090B52303)。
文摘Enantiomer identification is of paramount industrial value and physiological significance.Construction of sensitive chiral sensors with high enantiomeric discrimination ability is highly desirable.In this work,a chiral covalent organic framework/anodic aluminum oxide(c-COF/AAO)membrane was prepared for electrochemical enantioselective recognition and sensing.Benefiting from the remarkable asymmetry,the asprepared nanofluidic c-COF/AAO presents a distinct ion current rectification(ICR)characteristic,enabling sensitive bioanalysis.In addition,owing to the large surface area,high chemical stability and perfect ion selectivity of chiral COF,the prepared c-COF/AAO membrane presents exceptionally selective mass transport and thereby enables excellent chiral discrimination for S-/R-Naproxen(S-/R-Npx)enantiomers.It is especially noteworthy that the detection limit is achieved as low as 3.88 pmol/L.These results raise the possibility for a facile,stable and low-cost method to carry out sensitive enantioselective recognition and detection.
基金supported by the National Key Research and Development Program of China(Grant No.2023YFA1407001)Department of Science and Technology of Jiangsu Province(Grant No.BK20220032)。
文摘Thermal diodes,based on the thermal rectification effect,have demonstrated great promise for advanced thermal management.In previous studies,almost all thermal diodes were discussed under the condition of steady states,while the heat source of a practical thermal system often operates under dynamically fluctuating temperatures.Therefore,in this work,we employ finite element simulation to investigate transient thermal rectification behaviors in a well-built heterojunction which exhibits intrinsic thermal rectification effect under steady state.Unidirectional energy transport in the heterojunction system,decoupled from the steady-state temperature bias,is observed under a time-dependent fluctuating heat source.This phenomenon enables straightforward realization of both giant thermal rectification and negative thermal transport.Furthermore,a series of novel thermal regulation strategies are unveiled by adjusting the average temperature,frequency,and phase of the heat source.Our work not only deepens fundamental understanding of thermal regulation in time-dependent oscillating temperature systems but also uncovers many unexplored energy-saving thermal management strategies.
基金supported by the National Natural Science Foundation of China,No.31760290,82160688the Key Development Areas Project of Ganzhou Science and Technology,No.2022B-SF9554(all to XL)。
文摘Synaptic pruning is a crucial process in synaptic refinement,eliminating unstable synaptic connections in neural circuits.This process is triggered and regulated primarily by spontaneous neural activity and experience-dependent mechanisms.The pruning process involves multiple molecular signals and a series of regulatory activities governing the“eat me”and“don't eat me”states.Under physiological conditions,the interaction between glial cells and neurons results in the clearance of unnecessary synapses,maintaining normal neural circuit functionality via synaptic pruning.Alterations in genetic and environmental factors can lead to imbalanced synaptic pruning,thus promoting the occurrence and development of autism spectrum disorder,schizophrenia,Alzheimer's disease,and other neurological disorders.In this review,we investigated the molecular mechanisms responsible for synaptic pruning during neural development.We focus on how synaptic pruning can regulate neural circuits and its association with neurological disorders.Furthermore,we discuss the application of emerging optical and imaging technologies to observe synaptic structure and function,as well as their potential for clinical translation.Our aim was to enhance our understanding of synaptic pruning during neural development,including the molecular basis underlying the regulation of synaptic function and the dynamic changes in synaptic density,and to investigate the potential role of these mechanisms in the pathophysiology of neurological diseases,thus providing a theoretical foundation for the treatment of neurological disorders.
文摘BACKGROUND Complement-mediated thrombotic microangiopathy(TMA)is a rare endothelial injury syndrome caused by dysregulated activation of the alternative complement pathway,often linked to genetic abnormalities in complement factor H(CFH),complement factor I,or complement factor H-related(CFHR)proteins.Both renal transplantation and pregnancy are independent triggers for recurrence.This case highlights a genetically high-risk patient who achieved a successful term pregnancy after renal transplantation without complement inhibition,emphasizing individualized risk stratification,close surveillance,and multidisciplinary management for favourable maternal and graft outcomes.CASE SUMMARY A 32-year-old woman with end-stage renal disease secondary to genetically confirmed complement-mediated TMA—homozygous CFH exon 17 deletion and CFHR3-CFHR1 duplication—was maintained on dialysis for 2.5 years before undergoing a successful live-donor kidney transplant from her mother.Post-transplant immunosuppression included tacrolimus,mycophenolate mofetil,and prednisolone,later modified to azathioprine during pregnancy planning.One-year post-transplant,she conceived spontaneously.Pregnancy was complicated by transient gestational hypertension,controlled with nifedipine,labetalol,and amlodipine.Proteinuria remained<150 mg/day;white blood cell counts 5.8-7.2×109/L without cytopenia.Serum creatinine ranged 0.9-1.1 mg/dL,and tacrolimus trough levels 5-7 ng/mL.At 36 weeks,she delivered a healthy 3 kg infant by elective caesarean section.Postpartum follow-up at three months confirmed stable maternal and graft function.CONCLUSION High-risk complement-mediated TMA patients can achieve successful pregnancy post-transplant through individualized care without mandatory complement blockade.
基金Supported by State Key Program of National Natural Science Foundation of China,No.8143000311National Natural Science Foundation of China,No.81660103 and No.81771674+2 种基金111 Project,No.D17011Guangxi BaGui Scholarsthe Natural Science Foundation of Guangxi Province,No.2015GXNSFFA139004
文摘The complement system is a key component of the body's immune system. When abnormally activated, this system can induce inflammation and damage to normal tissues and participate in the development and progression of a variety of diseases. In the past, many scholars believed that alcoholic liver disease(ALD) is induced by the stress of ethanol on liver cells, including oxidative stress and dysfunction of mitochondria and protease bodies, causing hepatocyte injury and apoptosis. Recent studies have shown that complement activation is also involved in the genesis and development of ALD. This review focuses on the roles of complement activation in ALD and of therapeutic intervention in complement-activation pathways. We intend to provide new ideas on the diagnosis and treatment of ALD.
文摘The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the pathogen as well as in the generation of the classical inflammatory response through the production of potent proinflammatory molecules. More recently, however, the role of complement in the immune response has been expanded due to observations that link complement activation to adaptive immune responses. It is now appreciated that complement is a functional bridge between innate and adaptive immune responses that allows an integrated host defense to pathogenic challenges. As such, a study of its functions allows insight into the molecular underpinnings of host-pathogen interactions as well as the organization and orchestration of the host immune response. This review attempts to summarize the roles that complement plays in both innate and adaptive immune responses and the consequences of these interactions on host defense.
基金Supported by The grants R21 HL094878 and R21AI10950 to IUS and RGD
文摘The complement pathway is best known for its role in immune surveillance and inflammation. However,its ability of opsonizing and removing not only pathogens,but also necrotic and apoptotic cells,is a phylogenetically ancient means of initiating tissue repair. The means and mechanisms of complement-mediated tissue repair are discussed in this review. There is increasing evidence that complement activation contributes to tissue repair at several levels. These range from the chemo-attraction of stem and progenitor cells to areas of complement activation,to increased survival of various cell types in the presence of split products of complement,and to the production of trophic factors by cells activated by the anaphylatoxins C3 a and C5 a. This repair aspect of complement biology has not found sufficient appreciation until recently. The following will examine this aspect of complement biology with an emphasis on the anaphylatoxins C3 a and C5 a.
基金Foundation items: This work was supported by the National Natural Science Foundation of China (81172876, U0832601, 81273251, U1202228) the National Special Science Research Program of China (2012CBA01305) the National Science and Technology Major Project (2013ZX10001-002, 2012ZX10001-007) and the Knowledge Innovation Program of CAS (KSCX2-EW-R-13).
文摘The northem pig-tailed macaque (NPM, Macaca leonina) has become a widely used animal model in biomedical research. In this study, we measured serum immunoglobulin IgG, IgM, IgA, complement C3, C4 and CRP levels in 3-11 year old captive northem pig-tailed macaques using HITACHI 7600-20 automated chemistry analyzer in order to determine the influences of age and gender on these items. The results showed that serum IgA, IgM, C3 and C4 levels were not correlated with age (P〉0.05), while serum IgG levels increased progressively with age (r=0.202; P=0.045). Serum IgG, IgA, IgM and C3 levels were higher in females than in males (P〈0.05). Moreover, serum C3 concentration was both positively and strongly correlated with that of C4 (r=0.700; P〈0.0001). This study provides basic serum immunoglobulin and complement data of captive northem pig-tailed macaques, which may prove useful for future breeding efforts and biomedical research.
基金Project(2007CB714006)supported by the National Basic Research Program of China
文摘The finite element method is used to simulate the rectification process of shield machine, to study the relationship between rectification moment and angle and to explore the influence laws of different soil parameters and buried depth on rectification moment. It is hoped that the reference value of rectification moment can be offered to operator, and theoretical foundation can be laid for future automatic rectification technology. The results show that the rectification moment and angle generally exhibit good linear behavior in clay layers with different soil parameters or buried depths, and then the concept of rectification coefficient, that is, the ratio of rectification angle to rectification moment, is proposed; different soil parameters and buried depths have different influences on rectification coefficient, in which elastic modulus has great influence but others have little influences; the simulations of rectification process are preformed in clay layers with different elastic modulus, and fitting results show that elastic modulus and rectification coefficient present the quadratic function relation.
文摘By observing two-photon response and anisotropy of the light-induced voltage in Al-Si Schottky barrier potential,it is certified from the experimental and theoretical analysis that the built-in electric field generated by the Schottky barrier potential will induce the phenomena of optical rectification in Si photodiode.Thus,it is deduced that there must be double-frequency absorption caused by phase-mismatch in the mechanism of two-photon response of Si photodiode.If the intensity of the built-in electric field is strong enough,the double-frequency absorption will be the main factor of the two-photon response,which is different from the conventional opinion that the two-photon response is just the two-photon absorption.
基金financially supported by a grant from the joint key project of National Natural Science Foundation of China under contract(No.50339010)the National"211"Key Project of China.
文摘The purpose is to explore the effect of the spatial distribution of ground control points (GCPs) on the accuracy of imagery rectification. Both area-distributed and linearly distributed GCPs were used to rectify a Landsat TM image of a coastal zone. Rectification accuracy was checked against 99 independent points over the intertidal mudflats with no ground control. Results indicate that the root-mean-square error of residuals over these areas is several times larger than its GCPs-measured counterpart. If the GCPs are spatially dispersed over an area, residuals fluctuate but increase steadily with distance to the source of control in easting (R^2= 0. 827). in northing they fluctuate around 150 m until 15 km, beyond which they rise steadily at a small range of fluctuation. These residuals are less predictable from distance to the source of control than in easting (R^2= 0.517 ). If the GCPs are distributed along a control line, residuals rise with distance to it linearly and predictably (R^2 = 0. 877) in the direction perpendicular to it. In a direction parallel to it, the distance has little impact on rectification residuals.
基金Supported by the National Natural Science Foundation of China(No.81070755)
文摘· AIM: To investigate the expression of complement factors in the posterior scleral fibroblasts of guinea pigs with negative lens-defocused myopia.· METHODS: Eighteen guinea pigs were assigned randomly to two groups: the negative lens-defocused group(NLD group, n =9) and the normal control without treatment group(NC group, n =9). The effect of myopic induction was compared in three subgroups: eyes treated with a-10.00 D negative lens in the NLD group(NL group), eyes treated with a plano(0 D) lens in the NLD group(PL group), and untreated right eyes in the NC group(NC group). The following analyses were conducted at four weeks: examination of the refractive error via retinoscopy, assessment of complement C5b-9expression in the posterior scleral fibroblasts using immunohistochemistry, and measurements of complement C1 q and C3 protein levels in the posterior sclera by Western blot.·RESULTS: After an induction period of four weeks, a significant myopic shift was detected in the eyes of the NL group, relative to that of the PL and NC groups(P 【0.05). Data analysis showed a significant increase in the percentage of C5b-9 immunopositive fibroblasts in the posterior sclera of the NL group eyes, compared to the PL group(q =11.50, P 【0.001). Significantly higher levels of C1q(q =4.94, P =0.01) and C3(q =4.07, P =0.03)protein were detected in the posterior sclera of NL group eyes, compared to the PL group. There were no significant difference between the PL and NC groups for C5b-9(q =2.44, P =0.10), C1q(q =1.55, P =0.53) and C3(q =0.98, P =0.77) in the posterior sclera.·CONCLUSION: The data from present study provide evidence of the up-regulation of C5b-9, C1 q and C3 in the posterior scleral fibroblasts in a NLD myopic animal model. The results suggest that the complement system may be involved in the development of myopia.
基金Supported by National Liver Institute,Menofiya University,Egypt
文摘AIM:To evaluate serum complement C4a and its relation to liver fibrosis in children with chronic hepatitis C virus(HCV)infection.METHODS:The study included 30 children with chronic HCV infection before receiving antiviral therapy.Chronic HCV infection was defined by positive anti-HCV,a positive polymerase chain reaction for HCV-RNA for more than 6 mo with absence of any associated liver disease.A second group of 30 age-and sex-matched healthy children served as controls.Serum C4a levels were measured by enzyme-linked immunosorbent assay.Liver fibrosis stage and inflammatory grade were assessed using Ishak scoring system.Serum C4a levels were compared according to different clinical,laboratory and histopathological parameters.Statistical significance for quantitative data was tested by MannWhitney U non-parametric tests.For qualitative data,significance between groups was tested by 2test.Correlation was tested by Spearman’s test.Results were considered significant if P value≤0.05.RESULTS:The age of the patients ranged from 3.5to 18 years and that of controls ranged from 4 to 17years.C4a mean levels were merely lower in patients(153.67±18.69 mg/L)than that in the controls(157.25±11.40 mg/L)with no statistical significance(P=0.378).It did not differ significantly in patients with elevated vs those with normal transaminases(152.25±16.62 vs 155.36±21.33;P=0.868)or with different HCV viremia(P=0.561).Furthermore,there was no statistical significant difference in serum levels between those with no/mild fibrosis and those with moderate fibrosis(154.65±20.59 vs 152.97±17.72;P=0.786)or minimal and mild activity(155.1±21.93 vs 152.99±17.43;P=0.809).Though statistically not significant,C4a was highest in fibrosis score 0(F0),decreasing in F1 and F2 to be the lowest in F3.When comparing significant fibrosis(Ishak score≥3)vs other stages,C4a was significantly lower in F3 compared to other fibrosis scores(143.55±2.33 mg/L vs 155.26±19.64 mg/L;P=0.047)and at a cutoff value of less than 144.01 mg/L,C4a could discriminate F3 with 76.9%sensitivity and75%specificity from other stages of fibrosis.CONCLUSION:Serum complement C4a did not correlate with any of transaminases,HCV viremia or with the histopathological scores.Although C4a decreased with higher stages of fibrosis,this change was not significant enough to predict individual stages of fibrosis.Yet,it could predict significant fibrosis with acceptable clinical performance.
基金supported by the National Natural Science Foundation of China(Nos.31272687 and 30972 272)Science and Technology Project of Liaoning Province(2014203006)+1 种基金Ocean and Fisheries Project of Liaoning Province(201301)Science and Technology Project of Dalian City(2013J21DW025)
文摘The complement system plays a crucial role in the innate immune system of animals. It can be activated by distinct yet overlapping classical, alternative and lectin pathways. In the alternative pathway, complement factor B(Bf) serves as the catalytic subunit of complement component 3(C3) convertase, which plays the central role among three activation pathways. In this study, the Bf gene in sea cucumber(Apostichopus japonicus), termed Aj Bf, was obtained by rapid amplification of c DNA ends(RACE). The full-length c DNA of Aj Bf was 3231 bp in length barring the poly(A) tail. It contained an open reading frame(ORF) of 2742 bp encoding 913 amino acids, a 105 bp 5'-UTR(5'-terminal untranslated region) and a 384 bp 3'-UTR. Aj Bf was a mosaic protein with six CCP(complement control protein) domains, a VWA(von Willebrand factor A) domain, and a serine protease domain. The deduced molecular weight of Aj Bf protein was 101 k Da. Quantitative real time PCR(q RT-PCR) analysis indicated that the expression level of Aj Bf in A. japonicus was obviously higher at larval stage than that at embryonic stage. Expression detection in different tissues showed that Aj Bf expressed higher in coelomocytes than in other four tissues. In addation, Aj Bf expression in different tissues was induced significantly after LPS or Poly I:C challenge. These results indicated that Aj Bf plays an important role in immune responses to pathogen infection.
基金Supported by the Scientific Research Project of Traditional Chinese Medicine of Health and Family Planning Commission of Chongqing (ZY20150243)
文摘AIM: To systematically review the association between complement factors I (CFI) polymorphisms and age- related macular degeneration (AMD) and to explore whether CFI polymorphisms are associated with AMD, METHODS: Meta-analysis of articles published from 1995 to January 2015 of articles involved with AMD and polymorphisms of the CFI gene. Eligible data were pooled in a Meta-analysis, analyzing using STATA software (version 12.0), Review Manager (version 5.2) and different models based on the heterogeneity of effect sizes. Egger's test, Begg's rank correlation methods were used to evaluate for publication bias.~ RESULTS: Thirteen articles were eligible, describing two loci polymorphisms of the CFI gene (of which 12 articles focus on rs10033900T〉C and 3 articles focus on rs2285714C〉T). For rs10033900T〉C, the results of our study revealed that having a mutant allele C, TC, CC and TC+CC was associated with a decreased risk of AMD in all population groups studied (C versus T models, OR=0.84, 95%Ch 0.72-0.99, P=0.04; TC versus TT models OR= 0.89, 95%Ch 0.88-0.99, P=0.04;CC versus "1-1" models, OR=0.76, 95%Ch 0.60-0.98, P=-0.03; TC+CC versus TT models, OR=0.81, 95%Ch0.65-0.99, P=0.04). We found that C allele were related to lower AMD risk in the Caucasian population by subgroup analysis, but there was no association with AMD under the allele and genotypes comparison in Asian studies. For rs2285714 C〉T, the TC, TT genotypes contributed to a higher risk of AMD, compared with the CC carriers and CT+CC (OR=1.34, 95%Ch 1.09-1.63, P=0.004; OR=1.50, 95%Ch 1.25-1.80, P〈0.0001). CONCLUSION: This Meta-analysis suggests that CFI rs10033900T〉C and rs2285714C〉T polymorphisms may contribute to AMD.
基金supported by the National Science Fund for Distinguished Young Scientists of China,No.81601052
文摘Previous studies have reported age-specific pathological and functional outcomes in young and aged patients suffering spinal cord injury,but the mechanisms remain poorly understood. In this study, we examined mice with spinal cord injury. Gene expression profiles from the Gene Expression Omnibus database (accession number GSE93561) were used, including spinal cord samples from 3 young injured mice (2–3-months old, induced by Impactor at Th9 level) and 3 control mice (2–3-months old, no treatment), as well as 2 aged injured mice (15–18-months old, induced by Impactor at Th9 level) and 2 control mice (15–18-months old, no treatment). Differentially expressed genes (DEGs) in spinal cord tissue from injured and control mice were identified using the Linear Models for Microarray data method,with a threshold of adjusted P 〈 0.05 and |logFC(fold change)| 〉 1.5. Protein–protein interaction networks were constructed using data from the STRING database, followed by module analysis by Cytoscape software to screen crucial genes. Kyoto encyclopedia of genes and genomes pathway and Gene Ontology enrichment analyses were performed to investigate the underlying functions of DEGs using Database for Annotation, Visualization and Integrated Discovery. Consequently, 1,604 and 1,153 DEGs were identified between injured and normal control mice in spinal cord tissue of aged and young mice, respectively. Furthermore, a Venn diagram showed that 960 DEGs were shared among aged and young mice, while 644 and 193 DEGs were specific to aged and young mice, respectively. Functional enrichment indicates that shared DEGs are involved in osteoclast differentiation, extracellular matrix–receptor interaction, nuclear factor-kappa B signaling pathway, and focal adhesion. Unique genes for aged and young injured groups were involved in the cell cycle (upregulation of PLK1) and complement (upregulation of C3) activation, respectively. These findings were confirmed by functional analysis of genes in modules (common, 4; aged, 2; young, 1) screened from protein–protein interaction networks. Accordingly, cell cycle and complement inhibitors may be specific treatments for spinal cord injury in aged and young mice, respectively.
文摘AIM: Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world and complement factor H (CFH) polymorphism has been found to associate with the AMD. To investigate whether the Y402H variant in CFH is associated with AMD in Chinese populations, a systematic review and meta-analysis were performed to estimate the magnitude of the gene effect and the possible mode of action. METHODS: A meta-analysis was performed using data available from ten case-control studies assessing association between the CFH Y402H polymorphism and AMD in Chinese populations involving 1538 AMD. Data extraction and study quality assessment were performed in duplicate. Summary odds ratios (ORs) and 95% confidence intervals (CIs) an allele contrast and genotype contrast were estimated usingfixed- effects models. The Q-statistic test was used to assess heterogeneity, and Funnel plot was used to evaluate publication bias. RESULTS: Seven of ten case-control studies were neovascular AMD, and few studies came from west and north of China. There was strong evidence for association between CFH and AMD in Chinese population, with those having risk allele C 2.35 times more likely to have AMD than subjects with T allele. Evidence of publication bias was not observed in our meta-analysis. CONCLUSION: This meta-analysis summarizes the strong evidence for an association between CFH and AMD in Chinese and indicates each C allele increasing the odds of AMD by 2.33-fold. But more evidences about the relation between CFH polymorphism and different type of Chinese AMD from various district were needed.
基金National Natural Science Foundation for ExcellentYouth (Grant No.30925042)State Key Program for the InnovativeDrugs from the Ministry of Science and Technology (Grant No.2009ZX09502-013 and 2009ZX09301-011)
文摘Anti-complement activity guided fractionation led to the isolation of 24 compounds from Commelina communis.Bioassay showed that six compounds inhibited the classical pathway and alternative pathway with CH 50 values of 0.12-1.44 mM and AP 50 values of 0.28-7.05 mM,respectively.Preliminary mechanism studies demonstrated that quinovic acid acted on C1q,C2,C3,C4,C5 and C9 components of the complement system,β-sitosterol interacted with C3 and C4,(+)-catechin-3-O-β-Dgluco(2-cinnamoyl)-pyranoside,p-cresol and 6-methoxy-3-methylbenzene-1,2,4-triol blocked C1q,C2,C3,C5 and C9.
文摘Amplified inflammatory reaction has been observed to be involved in cardiometabolic diseases such as obesity,insulin resistance,diabetes,dyslipidemia,and atherosclerosis.The complement system was originally viewed as a supportive first line of defense against microbial invaders,and research over the past decade has come to appreciate that the functions of the complement system extend beyond the defense and elimination of microbes,involving in such diverse processes as clearance of the immune complexes,complementing T and B cell immune functions,tissue regeneration,and metabolism.The focus of this review is to summarize the role of the activation of complement system and the initiation and progression of metabolic disorders including obesity,insulin resistance and diabetes mellitus.In addition,we briefly describe the interaction of the activation of the complement system with diabetic complications such as diabetic retinopathy,nephropathy and neuropathy,highlighting that targeting complement system therapeutics could be one of possible routes to slow down those aforementioned diabetic complications.