Calcium is a critical second messenger molecule in all cells and is vital in neurons for synaptic transmission.Given this importance,calcium ions are tightly controlled by a host of molecular players including ion cha...Calcium is a critical second messenger molecule in all cells and is vital in neurons for synaptic transmission.Given this importance,calcium ions are tightly controlled by a host of molecular players including ion channels,sensors,and buffering proteins.Calcium can act directly by binding to signaling molecules or calcium’s effects can be indirect,for example by altering nuclear histones.展开更多
Scgn is an EF-hand calcium-binding protein occupying a unique position within the family of neuron-specific calcium sensors.As a key participant in calcium signaling,Scgn regulates diverse neural processes through its...Scgn is an EF-hand calcium-binding protein occupying a unique position within the family of neuron-specific calcium sensors.As a key participant in calcium signaling,Scgn regulates diverse neural processes through its six EF-hand domains,including endocrine granule secretion,synaptic vesicle release,and plays crucial roles in neurodevelopment and neurological disorders.This review systematically summarizes Scgn’s structural characteristics,expression patterns,and multifaceted roles within the nervous system,while exploring its potential pathological significance and therapeutic value in neuropsychiatric disorders.Existing studies indicate that Scgn is specifically distributed in brain regions such as the olfactory bulb and hippocampus.It engages in Ca^(2+)-dependent interactions with key synaptic secretion molecules like SNAP-25 and Doc2α,thereby regulating neurotransmission and synaptic plasticity.Furthermore,pathological alterations in Scgn observed in diseases like Alzheimer’s disease,Parkinson’s disease,and epilepsy suggest its potential as an early biomarker and therapeutic target,offering significant prospects for translational research.展开更多
Emerging evidence has suggested global histone H4 acetylation status plays an important role in neural plasticity. For instance, the imbalance of this epigenetic marker has been hypothesized as a key factor for the de...Emerging evidence has suggested global histone H4 acetylation status plays an important role in neural plasticity. For instance, the imbalance of this epigenetic marker has been hypothesized as a key factor for the development and progression of several neurological diseases. Likewise, astrocytic reactivity-a wellknown process that markedly influences the tissue remodeling after a central nervous system injury-is crucial for tissue remodeling after spinal cord injury（SCI）. However, the linkage between the above-mentioned mechanisms after SCI remains poorly understood. We sought to investigate the relation between both glial fibrillary acidic protein（GFAP） and S100 calcium-binding protein B（S100B）（astrocytic reactivity classical markers） and global histone H4 acetylation levels. Sixty-one male Wistar rats（aged ~3 months） were divided into the following groups： sham; 6 hours post-SCI; 24 hours post-SCI; 48 hours post-SCI; 72 hours post-SCI; and 7 days post-SCI. The results suggested that GFAP, but not S100B was associated with global histone H4 acetylation levels. Moreover, global histone H4 acetylation levels exhibited a complex pattern after SCI, encompassing at least three clearly defined phases（first phase： no changes in the 6, 24 and 48 hours post-SCI groups; second phase： increased levels in the 72 hours post-SCI group; and a third phase： return to levels similar to control in the 7 days post-SCI group）. Overall, these findings suggest global H4 acetylation levels exhibit distinct patterns of expression during the first week post-SCI, which may be associated with GFAP levels in the perilesional tissue. Current data encourage studies using H4 acetylation as a possible biomarker for tissue remodeling after spinal cord injury.展开更多
The body surface of crustaceans is covered with a sturdy shell.The growth and development of crustaceans are realized through molting.Neocaridina denticulata sinensis is a suitable candidate for crustacean scientific ...The body surface of crustaceans is covered with a sturdy shell.The growth and development of crustaceans are realized through molting.Neocaridina denticulata sinensis is a suitable candidate for crustacean scientific research.Two calcium-associated cuticular protein genes,named NdCAP-1 and NdCAP-2,were obtained from N.denticulata sinensis.Molecular docking simulated the binding effect of both proteins and calcium ions.Semi-quantitative reverse transcription PCR results show that NdCAP-1 is expressed in D_(2-4) stage,NdCAP-2 expressed in D_(2-4) and A-B stages,and both were significantly expressed in the cephalothorax cuticle and pereiopods.Then,it was revealed that NdCAP-1 and NdCAP-2 are regulated by NdEcR-mediated 20 E signaling pathways.Knockdown of NdCAP-1 and NdCAP-2 was observed to cause surface defects.The recombinant proteins(rNdCAP-1 and rNdCAP-2),obtained by prokaryotic expression,had calcium-binding and chitin-binding ability,inhibited formation of calcium carbonate precipitate.These results show that calcium-associated cuticular proteins play important roles in cuticle formation and calcification.展开更多
The aim of this work was to explore the physicochemical and structural properties,lipid oxidation and antioxidant capacity of the peptides extracted from Cantonese cured meat and as well as to investigate the effect o...The aim of this work was to explore the physicochemical and structural properties,lipid oxidation and antioxidant capacity of the peptides extracted from Cantonese cured meat and as well as to investigate the effect of drying time on the sarcoplasmic and myofibrillar proteins of Cantonese cured meat.The results suggested that salting out,protein oxidation and heat treatment were closely related to surface hydrophobicity and the secondary structure of peptides was changed by processing.And the peroxide value and the value of tributyltin compounds were different in evaluating the degree of lipid oxidation.Glu and His were the major amino acid.The approximate molecular weights of the sarcoplasmic proteins and myofibrillar proteins ranged from 31 kDa to 50 kDa and 66 kDa,respectively.The results indicated that reducing the levels of protein oxidation and improvement of the antioxidant properties should be of great interest to preserve the nutritional quality of meat products and prolong preservation period.展开更多
Background： Despite its high prevalence, morbidity, and mortality, sepsis-associated encephalopathy （SAE） is still poorly understood. The aim of this prospective and observational study was to investigate the clini...Background： Despite its high prevalence, morbidity, and mortality, sepsis-associated encephalopathy （SAE） is still poorly understood. The aim of this prospective and observational study was to investigate the clinical significance of calcium-binding protein A8 （S 100AS） in serum and tumor necrosis factor receptor-associated factor 6 （TRAF6） in peripheral blood mononuclear cells （PBMCs） in diagnosing SAE and predicting its prognosis. Methods： Data of septic patients were collected within 24 h after Intensive Care Unit admission fi-om July 2014 to March 2015. Healthy medical personnel served as the control group. SAE was defined as cerebral dysfhnction in the presence of sepsis that fulfilled the exclusion criteria. The biochemical indicators, Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation score II, TRAF6 in PBMC, serum S 100A8, S 10013, and neuron-specific enolase were evaluated in SAE patients afresh. TRAF6 and S 100A8 were also measured in the control group. Results： Of the 57 enrolled patients, 29 were diagnosed with SAE. The S 100A8 and TRAF6 concentrations in SAE patients were both significantly higher than that in no-encephalopathy （NE） patients, and higher in NE than that in controls （3.74 ± 3.13 vs. 1.08 ± 0.75 vs. 0.37 ± 0.14 ng/ml, P 〈 0.01 ; 3.18 ± 1.55 vs. 1.02 ± 0.63 vs. 0.47 ± 0.10, P 〈 0.01）. S 100A8 levels of 1.93 ng/ml were diagnostic of SAE with 92.90% specificity and 69.00% sensitivity in the receiver operating characteristic （ROC） curve, and the area under the curve was 0.86 （95% confidence interval [CI]： 0.76-0.95）. TRAF6-relative levels of 1.44 were diagnostic of SAE with 85.70% specificity and 86.20% sensitivity, and the area under the curve was 0.94 （95% CI： 0.88-0.99）. In addition, S 100A8 levels of 2.41 ng/ml predicted 28-day mortality of SAE with 90.00% specificity and 73.70% sensitivity in the ROC curve, and the area under the curve was 0.88. TRAF6 relative levels of 2.94 predicted 28-day mortality of SAE with 80.00% specificity and 68.40% sensitivity, and the area under the curve was 0.77. Compared with TRAF6, the specificity of serum S 100A8 in diagnosing SAE and predicting mortality was higher, although the sensitivity was low. In contrast, the TRAF6 had higher sensitivity for diagnosis. Conclusions： Peripheral blood levels of S 100A8 and TRAF6 in SAE patients were elevated and might be related to the severity of SAE and predict the outcome of SAE. The efficacy and specificity of S 100A8 for SAE diagnosis were superior, despite its weak sensitivity. S100A8 might be a better biomarker for diagnosis of SAE and predicting prognosis.展开更多
Background We investigated the co-expression of calb indin-D28k (CB), calretinin (CR) and parvalbumin (PV, a combination of the three is referred to as CaBPs) with γ-aminobutyric acid (GABA) or glycine in neurons of ...Background We investigated the co-expression of calb indin-D28k (CB), calretinin (CR) and parvalbumin (PV, a combination of the three is referred to as CaBPs) with γ-aminobutyric acid (GABA) or glycine in neurons of the rat medullary dorsal horn (MDH).Methods Immunofluorescence histochemical double-staining for CaBPs and GABA or glycine was performed on the sections from rat MDH. Results CB-, CR-, PV-, GABA- and glycine-like immunoreactive (LI) neurons were differentially observed in all layers of the MDH, but particularly in lamina Ⅱ. Neurons that exhibited immunoreactivity for both CaBPs and GABA or glycine were also observed mainly in lamina Ⅱ. A few of them were found in laminae I and III. The percentages of neurons which co-expressed CB/GABA or CB/glycine out of the total numbers of CB- and GABA-LI neurons or CB- and glycine-LI neurons were 5.3% and 12.1% or 4.1% and 10.0%, respectively. The ratios of CR/GABA or CR/glycine co-existing neurons out of the total numbers of CR- and GABA-LI neurons or CR- and glycine-LI neurons were 5.8% and 7.6% or 4.4% and 7.1%, respectively. The rates of PV/GABA or PV/glycine co-localized neurons out of the total numbers of PV- and GABA-LI neurons or PV- and glycine-LI neurons were 11.1% and 5.1% or 9.9% and 5.1%, respectively. Conclusion The results indicate that some neurons in the MDH contain both CaBPs and GABA or glycine.展开更多
Background:In plastic surgery,tissue expansion is widely used for repairing skin defects.However,low expansion efficiency and skin rupture caused by thin,expanded skin remain significant challenges in promoting skin r...Background:In plastic surgery,tissue expansion is widely used for repairing skin defects.However,low expansion efficiency and skin rupture caused by thin,expanded skin remain significant challenges in promoting skin regeneration during expansion.S100 calcium-binding protein A9(S100A9)is essential in promoting wound healing;however,its effects on skin regeneration during tissue expansion remain unclear.The aim of the present study was to explore the role of S100A9 in skin regeneration,particularly collagen production to investigate its importance in skin regeneration during tissue expansion.Methods:The expression and distribution of S100A9 and its receptors-toll-like receptor 4(TLR-4)and receptor for advanced glycation end products were studied in expanded skin.These character-istics were investigated in skin samples of rats and patients.Moreover,the expression of S100A9 was investigated in stretched keratinocytes in vitro.The effects of S100A9 on the proliferation and migration of skin fibroblasts were also observed.TAK-242 was used to inhibit the binding of S100A9 to TLR-4;the levels of collagen I(COL I),transforming growth factor beta(TGF-β),TLR-4 and phospho-extracellular signal-related kinase 1/2(p-ERK1/2)in fibroblasts were determined.Furthermore,fibroblasts were co-cultured with stretched S100A9-knockout keratinocytes by siRNA transfection and the levels of COL I,TGF-β,TLR-4 and p-ERK1/2 in fibroblasts were investigated.Additionally,the area of expanded skin,thickness of the dermis,and synthesis of COL I,TGF-β,TLR-4 and p-ERK1/2 were analysed to determine the effects of S100A9 on expanded skin.Results:Increased expression of S100A9 and TLR-4 was associated with decreased extracellular matrix(ECM)in the expanded dermis.Furthermore,S100A9 facilitated the proliferation and migration of human skin fibroblasts as well as the expression of COL I and TGF-βin fibroblasts via the TLR-4/ERK1/2 pathway.We found that mechanical stretch-induced S100A9 expression and secretion of keratinocytes stimulated COL I,TGF-β,TLR-4 and p-ERK1/2 expression in skin fibroblasts.Recombined S100A9 protein aided expanded skin regeneration and rescued dermal thinning in rats in vivo as well as increasing ECM deposition during expansion.Conclusions:These findings demonstrate that mechanical stretch promoted expanded skin regeneration by upregulating S100A9 expression.Our study laid the foundation for clinically improving tissue expansion using S100A9.展开更多
Background:With the increasing risk of nuclear exposure,more attention has been paid to the prevention and treatment of acute radiation syndrome(ARS).Although amino acids are key nutrients involved in hematopoietic re...Background:With the increasing risk of nuclear exposure,more attention has been paid to the prevention and treatment of acute radiation syndrome(ARS).Although amino acids are key nutrients involved in hematopoietic regulation,the impacts of amino acids on bone marrow hematopoiesis following irradiation and the associated mechanisms have not been fully elucidated.Hence,it is of paramount importance to study the changes in amino acid metabolism after irradiation and their effects on hematopoiesis as well as the related mechanisms.Methods:The content of serum amino acids was analyzed using metabolomic sequencing.The survival rate and body weight of the irradiated mice were detected after altering the methionine content in the diet.Extracellular matrix(ECM)protein analysis was performed via proteomics analysis.Inflammatory factors were examined by enzyme-linked immunosorbent assay(ELISA).Flow cytometry,Western blotting,and immunofluorescence were employed to determine the mechanism by which S100 calcium-binding protein A4(S100A4)regulates macrophage polarization.Results:The survival time of irradiated mice was significantly associated with alterations in multiple amino acids,particularly methionine.A high methionine diet promoted irradiation tolerance,especially in the recovery of bone marrow hematopoiesis,yet with dose limitations.Folate metabolism could partially alleviate the dose bottleneck by reducing the accumulation of homocysteine.Mechanistically,high methionine levels maintained the abundance of ECM components,including collagens and glycoproteins,in the bone marrow post-irradiation,among which the level of S100A4 was significantly changed.S100A4 regulated macrophage polarization via the STAT3 pathway,inhibited bone marrow inflammation and facilitated the proliferation and differentiation of hematopoietic stem/progenitor cells.Conclusions:We have demonstrated that an appropriate elevation in dietary methionine enhances irradiation tolerance in mice and explains the mechanism by which methionine regulates bone marrow hematopoiesis after irradiation.展开更多
Objective The pathogenesis and progression of heart failure(HF)are governed by complex,interconnected biological pathways,with dysregulated immune responses and maladaptive cardiac remodeling playing central roles.Alt...Objective The pathogenesis and progression of heart failure(HF)are governed by complex,interconnected biological pathways,with dysregulated immune responses and maladaptive cardiac remodeling playing central roles.Although specific inflammatory mediators have been implicated in modulating critical features of cardiac remodeling—such as cardiomyocyte hypertrophy and extracellular matrix fibrosis—the precise molecular mechanisms driving these processes remain incompletely characterized.Methods Integrated bioinformatics analysis of HF and hypertrophic cardiomyopathy(HCM)transcriptomic datasets identified pathologically relevant candidate genes.A protein-protein interaction(PPI)network was constructed from these candidates using the STRING database,followed by module analysis.Serum S100 calcium-binding protein A9(S100A9)protein expression in HF patients was quantified by Western blotting under reducing conditions.The functional relevance of prioritized genes was subsequently validated through:(i)in vitro cyclic mechanical stretch in primary neonatal rat cardiomyocytes,and(ii)in vivo pressure overload modeling via transverse aortic constriction(TAC)in mice.Results Bioinformatics analysis of HF and HCM datasets revealed a significant association between immune function and cardiac remodeling.Using CytoNCA,we identified core genes,among which the top 25 included multiple inflammatory pathway-related factors,such as S100A9 and Toll-like receptor 2(TLR2).Notably,S100A9 levels were significantly elevated in the serum of HF patients and in mechanically stretched cardiomyocytes.This increase correlated with upregulated expression of hypertrophy-related markers,including atrial natriuretic peptide(ANP).Furthermore,mechanical stretch-induced S100A9 upregulation markedly enhanced TLR2 expression in cardiomyocytes.Importantly,TLR2 inhibition substantially attenuated the mechanical stretch-induced upregulation of S100A9 mRNA expression,as well as the subsequent hypertrophic and inflammatory responses in cardiomyocytes.Conclusion The inflammatory mediators S100A9 and TLR2 engage in reciprocal activation that amplifies the hypertrophic response in mechanically stretched cardiomyocytes.This pathogenic cross-talk exacerbates maladaptive remodeling and likely accelerates HF progression.展开更多
BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignancies in elderly populations,and chemotherapy resistance remains a critical clinical challenge.Emerging evidence highlights the interplay between ...BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignancies in elderly populations,and chemotherapy resistance remains a critical clinical challenge.Emerging evidence highlights the interplay between chronic inflammation,gut microbiome dysbiosis,and CRC progression.Proinflammatory cytokines[e.g.,interleukin(IL)-6,tumor necrosis factor-alpha(TNF-α)]and mediators like S100 calcium-binding protein A12(S100A12)/soluble receptor for advanced glycation end products(sRAGE)are implicated in tumorigenesis,while gut microbial imbalances may exacerbate inflammatory microenvironments conducive to che-motherapy resistance.However,the triad relationship between S100A12/sRAGE,gut microbiota profiles,and chemotherapy efficacy in elderly patients with CRC remains unexplored,limiting biomarker-driven therapeutic strategies.AIM To analyze the correlation between serum levels of S100A12,sRAGE,gut microbiome dysbiosis,and systemic inflammation in elderly patients with CRC and to assess their predictive value for chemotherapy efficacy.METHODS A retrospective analysis was conducted on the clinical data of 120 elderly patients with advanced-stage CRC who visited our hospital from August 2023 to May 2024.These patients were enrolled in the study group.Additionally,120 healthy individuals undergoing routine health check-ups during the same period were selected as the control group.Serum S100A12,sRAGE,IL-6,and TNF-αlevels were measured by ELISA,and fresh stool samples were collected before chemotherapy to analyze gut microbiome composition in the study group.Follow-up observations were conducted after chemotherapy.Pearson correlation analysis was used to explore the relationship between serum S100A12,sRAGE levels,and gut microbiome dysbiosis in patients with CRC.The predictive diagnostic value of pre-chemotherapy serum S100A12 and sRAGE levels for chemotherapy efficacy was assessed using receiver operating characteristic curves.RESULTS Pre-chemotherapy serum S100A12,sRAGE,IL-6,and TNF-αlevels were significantly elevated in patients with CRC vs controls(all P<0.05).These biomarkers progressively increased with microbiota dysbiosis severity(severe vs mild dysbiosis:S100A12:340.26±52.39μg/L vs 302.53±56.97μg/L;sRAGE:525.64±37.32 ng/L vs 441.38±48.73 ng/L,P<0.05)and correlated strongly with IL-6(r=0.712)and TNF-α(r=0.698).Post-chemotherapy,biomarker levels decreased(P<0.05),coinciding with beneficial microbiota recovery(Bifidobacterium 176%,Lactobacillus 153%)and pathogenic taxa reduction(Escherichia coli 62%).The combined S100A12/sRAGE model predicted chemotherapy resistance with an area under the curve of 0.914(sensitivity=86.07%,specificity=88.89%),outper-forming individual biomarkers.CONCLUSION Elevated serum S100A12 and sRAGE in elderly patients with CRC reflected gut microbiome dysbiosis and systemic inflammation,driven by IL-6/TNF-αsignaling.Their post-chemotherapy decline parallels microbiota restoration,supporting a microbiome-inflammation-biomarker axis.The combined biomarker model offers robust clinical utility for chemotherapy efficacy prediction and personalized therapeutic strategies.展开更多
文摘Calcium is a critical second messenger molecule in all cells and is vital in neurons for synaptic transmission.Given this importance,calcium ions are tightly controlled by a host of molecular players including ion channels,sensors,and buffering proteins.Calcium can act directly by binding to signaling molecules or calcium’s effects can be indirect,for example by altering nuclear histones.
基金supported by the National Natural Science Foundation of China(Grant No.32170699,32200560)the Hubei Provincial Natural Science Foundation of China(Grant No.2022CFB906,2025AFA009)。
文摘Scgn is an EF-hand calcium-binding protein occupying a unique position within the family of neuron-specific calcium sensors.As a key participant in calcium signaling,Scgn regulates diverse neural processes through its six EF-hand domains,including endocrine granule secretion,synaptic vesicle release,and plays crucial roles in neurodevelopment and neurological disorders.This review systematically summarizes Scgn’s structural characteristics,expression patterns,and multifaceted roles within the nervous system,while exploring its potential pathological significance and therapeutic value in neuropsychiatric disorders.Existing studies indicate that Scgn is specifically distributed in brain regions such as the olfactory bulb and hippocampus.It engages in Ca^(2+)-dependent interactions with key synaptic secretion molecules like SNAP-25 and Doc2α,thereby regulating neurotransmission and synaptic plasticity.Furthermore,pathological alterations in Scgn observed in diseases like Alzheimer’s disease,Parkinson’s disease,and epilepsy suggest its potential as an early biomarker and therapeutic target,offering significant prospects for translational research.
基金supported by Brazilian funding agencies CNPq,CAPES and FAPERGS
文摘Emerging evidence has suggested global histone H4 acetylation status plays an important role in neural plasticity. For instance, the imbalance of this epigenetic marker has been hypothesized as a key factor for the development and progression of several neurological diseases. Likewise, astrocytic reactivity-a wellknown process that markedly influences the tissue remodeling after a central nervous system injury-is crucial for tissue remodeling after spinal cord injury（SCI）. However, the linkage between the above-mentioned mechanisms after SCI remains poorly understood. We sought to investigate the relation between both glial fibrillary acidic protein（GFAP） and S100 calcium-binding protein B（S100B）（astrocytic reactivity classical markers） and global histone H4 acetylation levels. Sixty-one male Wistar rats（aged ~3 months） were divided into the following groups： sham; 6 hours post-SCI; 24 hours post-SCI; 48 hours post-SCI; 72 hours post-SCI; and 7 days post-SCI. The results suggested that GFAP, but not S100B was associated with global histone H4 acetylation levels. Moreover, global histone H4 acetylation levels exhibited a complex pattern after SCI, encompassing at least three clearly defined phases（first phase： no changes in the 6, 24 and 48 hours post-SCI groups; second phase： increased levels in the 72 hours post-SCI group; and a third phase： return to levels similar to control in the 7 days post-SCI group）. Overall, these findings suggest global H4 acetylation levels exhibit distinct patterns of expression during the first week post-SCI, which may be associated with GFAP levels in the perilesional tissue. Current data encourage studies using H4 acetylation as a possible biomarker for tissue remodeling after spinal cord injury.
基金Supported by the National Natural Science Foundation of China(Nos.32172954,32373121)the Key Research and Development Project of Hebei Province(No.22323201D)+2 种基金the Science and Technology Project of Hebei Education Department(No.ZD 2022093)the Natural Science Foundation of Hebei Province(Nos.D2022201003,D2023201002)the Hangzhou Qianjiang Special Expert fund for Prof.Jiquan ZHANG。
文摘The body surface of crustaceans is covered with a sturdy shell.The growth and development of crustaceans are realized through molting.Neocaridina denticulata sinensis is a suitable candidate for crustacean scientific research.Two calcium-associated cuticular protein genes,named NdCAP-1 and NdCAP-2,were obtained from N.denticulata sinensis.Molecular docking simulated the binding effect of both proteins and calcium ions.Semi-quantitative reverse transcription PCR results show that NdCAP-1 is expressed in D_(2-4) stage,NdCAP-2 expressed in D_(2-4) and A-B stages,and both were significantly expressed in the cephalothorax cuticle and pereiopods.Then,it was revealed that NdCAP-1 and NdCAP-2 are regulated by NdEcR-mediated 20 E signaling pathways.Knockdown of NdCAP-1 and NdCAP-2 was observed to cause surface defects.The recombinant proteins(rNdCAP-1 and rNdCAP-2),obtained by prokaryotic expression,had calcium-binding and chitin-binding ability,inhibited formation of calcium carbonate precipitate.These results show that calcium-associated cuticular proteins play important roles in cuticle formation and calcification.
基金supported by Henan Province’s key R&D and promotion projects(scientific and technological research)projects(222102310587)Key Scientific Research Project Plan of Henan Province(22A310011)+4 种基金Grants from the Henan University(Yellow River Scholar Fund for Shanqing Zheng)the National Natural Science Foundation of China(81872584)Key R&D and Natural Science Foundation of Shenzhen(JCYJ20210324093211030)Medical Scientific Research Foundation of Guangdong Province(A2020490)the Interdisciplinary Research for First-class Discipline Construction Project of Henan University(2019YLXKJC04)。
文摘The aim of this work was to explore the physicochemical and structural properties,lipid oxidation and antioxidant capacity of the peptides extracted from Cantonese cured meat and as well as to investigate the effect of drying time on the sarcoplasmic and myofibrillar proteins of Cantonese cured meat.The results suggested that salting out,protein oxidation and heat treatment were closely related to surface hydrophobicity and the secondary structure of peptides was changed by processing.And the peroxide value and the value of tributyltin compounds were different in evaluating the degree of lipid oxidation.Glu and His were the major amino acid.The approximate molecular weights of the sarcoplasmic proteins and myofibrillar proteins ranged from 31 kDa to 50 kDa and 66 kDa,respectively.The results indicated that reducing the levels of protein oxidation and improvement of the antioxidant properties should be of great interest to preserve the nutritional quality of meat products and prolong preservation period.
文摘Background： Despite its high prevalence, morbidity, and mortality, sepsis-associated encephalopathy （SAE） is still poorly understood. The aim of this prospective and observational study was to investigate the clinical significance of calcium-binding protein A8 （S 100AS） in serum and tumor necrosis factor receptor-associated factor 6 （TRAF6） in peripheral blood mononuclear cells （PBMCs） in diagnosing SAE and predicting its prognosis. Methods： Data of septic patients were collected within 24 h after Intensive Care Unit admission fi-om July 2014 to March 2015. Healthy medical personnel served as the control group. SAE was defined as cerebral dysfhnction in the presence of sepsis that fulfilled the exclusion criteria. The biochemical indicators, Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation score II, TRAF6 in PBMC, serum S 100A8, S 10013, and neuron-specific enolase were evaluated in SAE patients afresh. TRAF6 and S 100A8 were also measured in the control group. Results： Of the 57 enrolled patients, 29 were diagnosed with SAE. The S 100A8 and TRAF6 concentrations in SAE patients were both significantly higher than that in no-encephalopathy （NE） patients, and higher in NE than that in controls （3.74 ± 3.13 vs. 1.08 ± 0.75 vs. 0.37 ± 0.14 ng/ml, P 〈 0.01 ; 3.18 ± 1.55 vs. 1.02 ± 0.63 vs. 0.47 ± 0.10, P 〈 0.01）. S 100A8 levels of 1.93 ng/ml were diagnostic of SAE with 92.90% specificity and 69.00% sensitivity in the receiver operating characteristic （ROC） curve, and the area under the curve was 0.86 （95% confidence interval [CI]： 0.76-0.95）. TRAF6-relative levels of 1.44 were diagnostic of SAE with 85.70% specificity and 86.20% sensitivity, and the area under the curve was 0.94 （95% CI： 0.88-0.99）. In addition, S 100A8 levels of 2.41 ng/ml predicted 28-day mortality of SAE with 90.00% specificity and 73.70% sensitivity in the ROC curve, and the area under the curve was 0.88. TRAF6 relative levels of 2.94 predicted 28-day mortality of SAE with 80.00% specificity and 68.40% sensitivity, and the area under the curve was 0.77. Compared with TRAF6, the specificity of serum S 100A8 in diagnosing SAE and predicting mortality was higher, although the sensitivity was low. In contrast, the TRAF6 had higher sensitivity for diagnosis. Conclusions： Peripheral blood levels of S 100A8 and TRAF6 in SAE patients were elevated and might be related to the severity of SAE and predict the outcome of SAE. The efficacy and specificity of S 100A8 for SAE diagnosis were superior, despite its weak sensitivity. S100A8 might be a better biomarker for diagnosis of SAE and predicting prognosis.
文摘Background We investigated the co-expression of calb indin-D28k (CB), calretinin (CR) and parvalbumin (PV, a combination of the three is referred to as CaBPs) with γ-aminobutyric acid (GABA) or glycine in neurons of the rat medullary dorsal horn (MDH).Methods Immunofluorescence histochemical double-staining for CaBPs and GABA or glycine was performed on the sections from rat MDH. Results CB-, CR-, PV-, GABA- and glycine-like immunoreactive (LI) neurons were differentially observed in all layers of the MDH, but particularly in lamina Ⅱ. Neurons that exhibited immunoreactivity for both CaBPs and GABA or glycine were also observed mainly in lamina Ⅱ. A few of them were found in laminae I and III. The percentages of neurons which co-expressed CB/GABA or CB/glycine out of the total numbers of CB- and GABA-LI neurons or CB- and glycine-LI neurons were 5.3% and 12.1% or 4.1% and 10.0%, respectively. The ratios of CR/GABA or CR/glycine co-existing neurons out of the total numbers of CR- and GABA-LI neurons or CR- and glycine-LI neurons were 5.8% and 7.6% or 4.4% and 7.1%, respectively. The rates of PV/GABA or PV/glycine co-localized neurons out of the total numbers of PV- and GABA-LI neurons or PV- and glycine-LI neurons were 11.1% and 5.1% or 9.9% and 5.1%, respectively. Conclusion The results indicate that some neurons in the MDH contain both CaBPs and GABA or glycine.
基金supported by grants from the Natural Science Foundation of China(81971851 and 82172229)the Natural Science Foundation of Shaanxi Province(2022JM-600)the Foundation of Xijing Hospital Grants(XJZT21CM33).
文摘Background:In plastic surgery,tissue expansion is widely used for repairing skin defects.However,low expansion efficiency and skin rupture caused by thin,expanded skin remain significant challenges in promoting skin regeneration during expansion.S100 calcium-binding protein A9(S100A9)is essential in promoting wound healing;however,its effects on skin regeneration during tissue expansion remain unclear.The aim of the present study was to explore the role of S100A9 in skin regeneration,particularly collagen production to investigate its importance in skin regeneration during tissue expansion.Methods:The expression and distribution of S100A9 and its receptors-toll-like receptor 4(TLR-4)and receptor for advanced glycation end products were studied in expanded skin.These character-istics were investigated in skin samples of rats and patients.Moreover,the expression of S100A9 was investigated in stretched keratinocytes in vitro.The effects of S100A9 on the proliferation and migration of skin fibroblasts were also observed.TAK-242 was used to inhibit the binding of S100A9 to TLR-4;the levels of collagen I(COL I),transforming growth factor beta(TGF-β),TLR-4 and phospho-extracellular signal-related kinase 1/2(p-ERK1/2)in fibroblasts were determined.Furthermore,fibroblasts were co-cultured with stretched S100A9-knockout keratinocytes by siRNA transfection and the levels of COL I,TGF-β,TLR-4 and p-ERK1/2 in fibroblasts were investigated.Additionally,the area of expanded skin,thickness of the dermis,and synthesis of COL I,TGF-β,TLR-4 and p-ERK1/2 were analysed to determine the effects of S100A9 on expanded skin.Results:Increased expression of S100A9 and TLR-4 was associated with decreased extracellular matrix(ECM)in the expanded dermis.Furthermore,S100A9 facilitated the proliferation and migration of human skin fibroblasts as well as the expression of COL I and TGF-βin fibroblasts via the TLR-4/ERK1/2 pathway.We found that mechanical stretch-induced S100A9 expression and secretion of keratinocytes stimulated COL I,TGF-β,TLR-4 and p-ERK1/2 expression in skin fibroblasts.Recombined S100A9 protein aided expanded skin regeneration and rescued dermal thinning in rats in vivo as well as increasing ECM deposition during expansion.Conclusions:These findings demonstrate that mechanical stretch promoted expanded skin regeneration by upregulating S100A9 expression.Our study laid the foundation for clinically improving tissue expansion using S100A9.
基金supported by the National Natural Science Foundation of China(82020108025,82022061)the Chongqing Natural Science Foundation(cstc2021jcyj-jqX0004,cstb2022nscq-msx0179)the Clinical Research Funding of the Second Affiliated Hospital of the Army Medical(2023XKRC008,2022YQB010).
文摘Background:With the increasing risk of nuclear exposure,more attention has been paid to the prevention and treatment of acute radiation syndrome(ARS).Although amino acids are key nutrients involved in hematopoietic regulation,the impacts of amino acids on bone marrow hematopoiesis following irradiation and the associated mechanisms have not been fully elucidated.Hence,it is of paramount importance to study the changes in amino acid metabolism after irradiation and their effects on hematopoiesis as well as the related mechanisms.Methods:The content of serum amino acids was analyzed using metabolomic sequencing.The survival rate and body weight of the irradiated mice were detected after altering the methionine content in the diet.Extracellular matrix(ECM)protein analysis was performed via proteomics analysis.Inflammatory factors were examined by enzyme-linked immunosorbent assay(ELISA).Flow cytometry,Western blotting,and immunofluorescence were employed to determine the mechanism by which S100 calcium-binding protein A4(S100A4)regulates macrophage polarization.Results:The survival time of irradiated mice was significantly associated with alterations in multiple amino acids,particularly methionine.A high methionine diet promoted irradiation tolerance,especially in the recovery of bone marrow hematopoiesis,yet with dose limitations.Folate metabolism could partially alleviate the dose bottleneck by reducing the accumulation of homocysteine.Mechanistically,high methionine levels maintained the abundance of ECM components,including collagens and glycoproteins,in the bone marrow post-irradiation,among which the level of S100A4 was significantly changed.S100A4 regulated macrophage polarization via the STAT3 pathway,inhibited bone marrow inflammation and facilitated the proliferation and differentiation of hematopoietic stem/progenitor cells.Conclusions:We have demonstrated that an appropriate elevation in dietary methionine enhances irradiation tolerance in mice and explains the mechanism by which methionine regulates bone marrow hematopoiesis after irradiation.
基金supported by the National Key Research and Development Program of China(No.2023YFC2506504)the National Natural Science Foundation of China(No.82370255,and No.U24A20646)the Shanghai Science and Technology Commission Project(No.23410761200).
文摘Objective The pathogenesis and progression of heart failure(HF)are governed by complex,interconnected biological pathways,with dysregulated immune responses and maladaptive cardiac remodeling playing central roles.Although specific inflammatory mediators have been implicated in modulating critical features of cardiac remodeling—such as cardiomyocyte hypertrophy and extracellular matrix fibrosis—the precise molecular mechanisms driving these processes remain incompletely characterized.Methods Integrated bioinformatics analysis of HF and hypertrophic cardiomyopathy(HCM)transcriptomic datasets identified pathologically relevant candidate genes.A protein-protein interaction(PPI)network was constructed from these candidates using the STRING database,followed by module analysis.Serum S100 calcium-binding protein A9(S100A9)protein expression in HF patients was quantified by Western blotting under reducing conditions.The functional relevance of prioritized genes was subsequently validated through:(i)in vitro cyclic mechanical stretch in primary neonatal rat cardiomyocytes,and(ii)in vivo pressure overload modeling via transverse aortic constriction(TAC)in mice.Results Bioinformatics analysis of HF and HCM datasets revealed a significant association between immune function and cardiac remodeling.Using CytoNCA,we identified core genes,among which the top 25 included multiple inflammatory pathway-related factors,such as S100A9 and Toll-like receptor 2(TLR2).Notably,S100A9 levels were significantly elevated in the serum of HF patients and in mechanically stretched cardiomyocytes.This increase correlated with upregulated expression of hypertrophy-related markers,including atrial natriuretic peptide(ANP).Furthermore,mechanical stretch-induced S100A9 upregulation markedly enhanced TLR2 expression in cardiomyocytes.Importantly,TLR2 inhibition substantially attenuated the mechanical stretch-induced upregulation of S100A9 mRNA expression,as well as the subsequent hypertrophic and inflammatory responses in cardiomyocytes.Conclusion The inflammatory mediators S100A9 and TLR2 engage in reciprocal activation that amplifies the hypertrophic response in mechanically stretched cardiomyocytes.This pathogenic cross-talk exacerbates maladaptive remodeling and likely accelerates HF progression.
文摘BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignancies in elderly populations,and chemotherapy resistance remains a critical clinical challenge.Emerging evidence highlights the interplay between chronic inflammation,gut microbiome dysbiosis,and CRC progression.Proinflammatory cytokines[e.g.,interleukin(IL)-6,tumor necrosis factor-alpha(TNF-α)]and mediators like S100 calcium-binding protein A12(S100A12)/soluble receptor for advanced glycation end products(sRAGE)are implicated in tumorigenesis,while gut microbial imbalances may exacerbate inflammatory microenvironments conducive to che-motherapy resistance.However,the triad relationship between S100A12/sRAGE,gut microbiota profiles,and chemotherapy efficacy in elderly patients with CRC remains unexplored,limiting biomarker-driven therapeutic strategies.AIM To analyze the correlation between serum levels of S100A12,sRAGE,gut microbiome dysbiosis,and systemic inflammation in elderly patients with CRC and to assess their predictive value for chemotherapy efficacy.METHODS A retrospective analysis was conducted on the clinical data of 120 elderly patients with advanced-stage CRC who visited our hospital from August 2023 to May 2024.These patients were enrolled in the study group.Additionally,120 healthy individuals undergoing routine health check-ups during the same period were selected as the control group.Serum S100A12,sRAGE,IL-6,and TNF-αlevels were measured by ELISA,and fresh stool samples were collected before chemotherapy to analyze gut microbiome composition in the study group.Follow-up observations were conducted after chemotherapy.Pearson correlation analysis was used to explore the relationship between serum S100A12,sRAGE levels,and gut microbiome dysbiosis in patients with CRC.The predictive diagnostic value of pre-chemotherapy serum S100A12 and sRAGE levels for chemotherapy efficacy was assessed using receiver operating characteristic curves.RESULTS Pre-chemotherapy serum S100A12,sRAGE,IL-6,and TNF-αlevels were significantly elevated in patients with CRC vs controls(all P<0.05).These biomarkers progressively increased with microbiota dysbiosis severity(severe vs mild dysbiosis:S100A12:340.26±52.39μg/L vs 302.53±56.97μg/L;sRAGE:525.64±37.32 ng/L vs 441.38±48.73 ng/L,P<0.05)and correlated strongly with IL-6(r=0.712)and TNF-α(r=0.698).Post-chemotherapy,biomarker levels decreased(P<0.05),coinciding with beneficial microbiota recovery(Bifidobacterium 176%,Lactobacillus 153%)and pathogenic taxa reduction(Escherichia coli 62%).The combined S100A12/sRAGE model predicted chemotherapy resistance with an area under the curve of 0.914(sensitivity=86.07%,specificity=88.89%),outper-forming individual biomarkers.CONCLUSION Elevated serum S100A12 and sRAGE in elderly patients with CRC reflected gut microbiome dysbiosis and systemic inflammation,driven by IL-6/TNF-αsignaling.Their post-chemotherapy decline parallels microbiota restoration,supporting a microbiome-inflammation-biomarker axis.The combined biomarker model offers robust clinical utility for chemotherapy efficacy prediction and personalized therapeutic strategies.
