In this letter,we have commented on the study by Zhang et al,which utilized bioinformatics and immunohistochemistry to assess the value of fatty acidbinding protein 4(FABP4)as a biomarker for colon adenocarcinoma(COAD...In this letter,we have commented on the study by Zhang et al,which utilized bioinformatics and immunohistochemistry to assess the value of fatty acidbinding protein 4(FABP4)as a biomarker for colon adenocarcinoma(COAD).Their findings improve our understanding of FABP4 in cancer cell adhesion and immune cell infiltration.However,differential expression analysis was insufficient to demonstrate a direct association between FABP4 expression and the occurrence and progression of COAD.Using Mendelian randomization for causal inferences can provide a solid biological foundation for model construction.Furthermore,integrating machine and deep learning approaches may yield more robust and precise prognostic outcomes than using a single Cox regression model.In addition,integrating genome-wide association study data to identify additional pathogenic genes involved in the regulation of fatty acid metabolism may facilitate the development of a multi-target strategy.This approach could potentially mitigate the compensatory effects associated with targeting FABP4 alone,and enhance therapeutic efficacy.Enhancing experimental validation would further improve the reliability of the results.With the continuous advancement of machine learning,multi-omics technologies,and experimental techniques,future studies may systematically integrate diverse sequencing datasets to offer novel insights into the early diagnosis,individualized treatment,and prognostic evaluation of COAD.展开更多
As intracellular fatty acid(FA) carriers,FA-binding proteins(FABPs) widely participate in the absorption,transport,and metabolism of FAs.It is a key protein in insect lipid metabolism and plays an important role in va...As intracellular fatty acid(FA) carriers,FA-binding proteins(FABPs) widely participate in the absorption,transport,and metabolism of FAs.It is a key protein in insect lipid metabolism and plays an important role in various physiological activities of insects.An FABP gene(HvFABP) was cloned from the transcriptional library of Heortia vitessoides Moore(Lepidoptera:Crambidae),and its expression patterns were determined using reverse transcription quantitative PCR(RTqPCR).Stage-and tissue-specific expression profiles indicated that HvFABP highly expressed from prepupal to adult stages and in larval midgut and adult wings.HvFABP expression may be induced through starvation,mRNA expression was downregulated at 24 and 48 h and upregulated at 72 h after starvation.Furthermore,20-hydroxyecdysone can induce the upregulation of its expression.RNA interference-mediated silencing of Hv FABP significantly inhibited HvFABP expression,resulting in delayed development,abnormal molting or lethal phenotypes,and a significantly reduced survival rate.These results indicate that HvFABP plays a key role in the molting of H.vitessoides.展开更多
Suberoylanilide hydroxamic acid(SAHA) is a histone deacetylase inhibitor that shows marked efficacy against many types of cancers and is approved to treat severe metastatic cutaneous T-cell lymphomas. In addition to i...Suberoylanilide hydroxamic acid(SAHA) is a histone deacetylase inhibitor that shows marked efficacy against many types of cancers and is approved to treat severe metastatic cutaneous T-cell lymphomas. In addition to its anticancer activity,SAHA has significant effects on the growth of many viruses. The effect of SAHA on replication of human cytomegalovirus(HCMV) has not, however, been investigated. Here, we showed that the replication of HCMV was significantly suppressed by treatment with SAHA at concentrations that did not show appreciable cytotoxicity. SAHA reduced transcription and protein levels of HCMV immediate early genes, showing that SAHA acts at an early stage in the viral life-cycle. RNAsequencing data mining showed that numerous pathways and molecules were affected by SAHA. Interferon-mediated immunity was one of the most relevant pathways in the RNA-sequencing data, and we confirmed that SAHA inhibits HCMV-induced IFN-mediated immune responses using quantitative Real-time PCR(qRT-PCR). Fatty acid-binding protein 4(FABP4), which plays a role in lipid metabolism, was identified by RNA-sequencing. We found that FABP4 expression was reduced by HCMV infection but increased by treatment with SAHA. We then showed that knockdown of FABP4 partially rescued the effect of SAHA on HCMV replication. Our data suggest that FABP4 contributes to the inhibitory effect of SAHA on HCMV replication.展开更多
[ Objective] The aim of this paper is to provide the basic data for marker-assisted selection of pig breeding using porcine heart fatty acid- binding protein （H-FABP） gene. [Method] According to the related sequence...[ Objective] The aim of this paper is to provide the basic data for marker-assisted selection of pig breeding using porcine heart fatty acid- binding protein （H-FABP） gene. [Method] According to the related sequences of porcine H-FABP gene released in GenBank, specific primers were designed to amplify the intron 3 of porcine H-FABP gene. [ Result] The intron 3 of porcine H-FABP gene was amplified successfully. Its whole sequence was 1 350 bp in length and had been submitted to GenBank （Accession no. ： DQ 002993）. [Condusion] The study lays a theoretical foundation for determination of the major genes affecting intramuscular fat deposition.展开更多
Dysregulated inflammation and multi-organ failure are hallmarks of sepsis,a potentially fatal illness for which there are currently no effective treatments.Fatty acid-binding protein(A-FABP)has been identified in rece...Dysregulated inflammation and multi-organ failure are hallmarks of sepsis,a potentially fatal illness for which there are currently no effective treatments.Fatty acid-binding protein(A-FABP)has been identified in recent research as a crucial mediator of the inflammatory pathways underlying sepsis.In this study,we used a murine model of lipopolysaccharide(LPS)-induced endotoxemia to assess the therapeutic potential of 6H2,a monoclonal antibody that targets A-FABP.In comparison to untreated septic mice,6H2 treatment significantly increased survival rates,decreased histopathological damage in the liver,lungs,kidneys,and heart,and reduced systemic inflammation.According to biochemical analyses,6H2 treatment decreased circulating levels of A-FABP,and this was associated with a reduction in inflammatory markers.These results indicate that A-FABP inhibition is a potentially effective treatment approach for sepsis,with 6H2 demonstrating strong therapeutic efficacy.展开更多
Chronic obstructive pulmonary disease(COPD)has become the third-leading cause of death worldwide,which is a severe economic burden to the healthcare system.Chronic bronchitis is the most common condition that contribu...Chronic obstructive pulmonary disease(COPD)has become the third-leading cause of death worldwide,which is a severe economic burden to the healthcare system.Chronic bronchitis is the most common condition that contributes to COPD,both locally and systemically.Neutrophilic inflammation predominates in the COPD airway wall and lumen.Logically,repression of neutrophilia is an essential fashion to COPD treatment.However,currently available anti-neutrophilic therapies provide little benefit in COPD patients and may have serious side effects.Thus,there is an urgent need to explore an effective and safe anti-neutrophilic approach that might delay progression of the disease.Sialic acid-binding immunoglobulin-like lectin(Siglec)-9 is a member of the Siglec cell surface immunoglobulin family.It is noteworthy that Siglec-9 is highly expressed on human neutrophils and monocytes.Ligation of Siglec-9 by chemical compounds or synthetic ligands induced apoptosis and autophagic-like cell death in human neutrophils.Furthermore,administration of antibody to Siglec-E,mouse functional ortholog of Siglec-9,restrained recruitment and activation of neutrophils in mouse models of airway inflammation in vivo.Given the critical role that neutrophils play in chronic bronchitis and emphysema,targeting Siglec-9 could be beneficial for the treatment of COPD,asthma,fibrosis,and related chronic inflammatory lung diseases.展开更多
Objective:This study aims to investigate whether the heart fatty acid-binding protein(HFABP)in the cerebrospinal fluid(CSF)was a potential predictive biomarker for Alzheimer’s disease(AD).Methods:We evaluated the ass...Objective:This study aims to investigate whether the heart fatty acid-binding protein(HFABP)in the cerebrospinal fluid(CSF)was a potential predictive biomarker for Alzheimer’s disease(AD).Methods:We evaluated the associations of CSF HFABP levels with core biomarkers,cognition,and brain structure in a sample population(n=302)from the Alzheimer’s Disease Neuroimaging Initiative(ADNI)database.Multiple linear regression and mixed-effects models were employed in the analyses.AD progression was assessed using the Kaplan–Meier survival analysis.Results:CSF HFABP was higher in patients with mild cognitive impairment and AD than the normal controls(p<0.001)and was particularly higher in those with amyloid-β(Aβ)pathologic features.CSF HFABP was associated with higher baseline CSF t-tau(p<0.001),CSF p-tau(p<0.001),and CSF t-tau/Aβ42 and CSF p-tau/Aβ42(p<0.01).Moreover,CSF HFABP was found to play predictive roles in hippocampal atrophy(p<0.01),cognitive decline(p<0.05),and the risk of AD(p<0.001).Conclusion:Our findings suggest that CSF HFABP can be a predictive biomarker of AD.展开更多
Background:Radiofrequency ablation(RFA)is an efficient treatment with unlimited potential for liver cancer that can effectively reduce patient mortality.Understanding the biological process related with RFA treatment ...Background:Radiofrequency ablation(RFA)is an efficient treatment with unlimited potential for liver cancer that can effectively reduce patient mortality.Understanding the biological process related with RFA treatment is important for improving treatment strategy.This study aimed to identify the critical targets for regulating the efficacy of RFA.Methods:The RFA treatment in hepatocellular carcinoma(HCC)tumor models in vivo,was analyzed by RNA sequencing technology.The heat treatment in vitro for HCC tumor cells was also constructed to explore the mechanism after RFA treatment in tumor cells.Nanoparticles with high affinity to tumor cells were applied as a new therapy to interfere with the expression of maternal embryonic leucine zipper kinase(MELK).Results:It was found that RFA treatment upregulated MELK expression,and MELK inhibition promoted RFA efficacy by immunogenic cell death and the antitumor response,including anti-tumoral macrophage polarization and increased CD8+T cell cytotoxicity in HCC.Mechanically,MELK binds to fatty acid-binding protein 5(FABP5),and affects its ubiquitination through the K48R pathway to increase its stability,thereby activating protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling axis to weaken the RFA-mediated antitumor effect.In addition,the synthesis of arginylglycylaspartic acid(RGD)-lipid nanoparticles(LNPs)targeting tumor cell-intrinsic MELK enhanced RFA efficacy in HCC.Conclusions:MELK is a therapeutic target by regulating RFA efficacy in HCC,and targeting MELK via RGD-LNPs provides new insight into improving RFA efficacy in HCC clinical treatment and combating the malignant progression of liver cancer.展开更多
Heart fatty acid-binding protein (H-FABP) is supposed to be the most sensitive biomarker of early acute myocardial infarction (AMI). To evaluate the diagnostic value of H-FABP for AMI in the early stage, the plasma le...Heart fatty acid-binding protein (H-FABP) is supposed to be the most sensitive biomarker of early acute myocardial infarction (AMI). To evaluate the diagnostic value of H-FABP for AMI in the early stage, the plasma levels of H-FABP were measured by sandwich ELISA in 93 patients with suspected AMI at admission within 6 h after onset of chest pain and 69 normal healthy subjects. The plasma concentrations of cardiac troponin-I (cTnI), creatine kinase-MB (CK-MB) and myoglobin (Mb) were assayed at the same time by using corpuscle chemiluminescence for those patients. The patients were classified as AMI group (n=32) and non-AMI group (n=61) retrospectively. The diagnostic validity was evaluated in terms of sensitivity, specificity and receiver operating characteristic (ROC) curve analysis. The results showed the cutoff value of H-FABP for AMI was 16.8 ng/ml, and its diagnostic sensitivity for AMI was 64.29 % within 3 h and 84.38 % within 6 h after onset of chest pain, and the diagnostic specificity for non-AMI was 100 % within 3 h and 91.8 % within 6 h. H-FABP had higher sensitivity than that of cTnI and CK-MB at all time points (P<0.05), whereas there was no significant difference in specificity among the four markers. But the area under the ROC curve of H-FABP was significantly greater than that of cTnI, CK-MB and Mb within 3 h. These results revealed that H-FABP possessed high diagnostic sensitivity and specificity for AMI in early stage, especially within 3 h after onset of persistent angina pectoris. In conclusion, H-FABP can be used as a sensitive marker for AMI in the early stage.展开更多
To assess the prevalence of a panel of serologic markers that reflect gut barrier dysfunction in a mixed cohort of pediatric and adult primary sclerosing cholangitis(PSC)patients.METHODSSera of 67 PSC patients[median ...To assess the prevalence of a panel of serologic markers that reflect gut barrier dysfunction in a mixed cohort of pediatric and adult primary sclerosing cholangitis(PSC)patients.METHODSSera of 67 PSC patients[median age(range):32(5-79)years,concomitant IBD:67%and cirrhosis:20%]were assayed for the presence of antibodies against to F-actin(AAA IgA/IgG)and gliadin(AGA IgA/IgG)]and for serum level of intestinal fatty acid-binding protein(I-FABP)by ELISA.Markers of lipopolysaccharide(LPS)exposure[LPS binding protein(LBP)]and various anti-microbial antibodies[anti-OMP Plus IgA and endotoxin core IgA antibody(EndoCAb)]were also determined.Poor disease outcome was defined as orthotopic liver transplantation and/or liver-related death during the follow-up[median:99(14-106)mo].One hundred and fifty-three healthy subjects(HCONT)and 172 ulcerative colitis(UC)patients were the controls.RESULTSA total of 28.4%,28.0%,9%and 20.9%of PSC patients were positive for AAA IgA,AAA IgG,AGA IgA and AGA IgG,respectively.Frequencies of AAA IgA and AAA IgG(P<0.001,for both)and AGA IgG(P=0.01,for both)but not AGA IgA were significantly higher compared to both of the HCONT and the UC groups.In survival analysis,AAA IgA-positivity was revealed as an independent predictor of poor disease outcome after adjusting either for the presence of cirrhosis[HR=5.15(1.27-20.86),P=0.022 or for the Mayo risk score(HR=4.24(0.99-18.21),P=0.052].AAA IgA-positivity was significantly associated with higher frequency of anti-microbial antibodies(P<0.001 for EndoCab IgA and P=0.012 for anti-OMP Plus IgA)and higher level of the enterocyte damage marker(median I-FABP<sub>AAA IgA pos</sub><sub>vs</sub><sub>neg</sub>:365 vs 166 pg/mL,P=0.011),but not with serum LBP level.CONCLUSIONPresence of IgA type AAA identified PSC patients with progressive disease.Moreover,it is associated with enhanced mucosal immune response to various microbial antigens and enterocyte damage further highlighting the importance of the gut-liver interaction in PSC.展开更多
Objective:To investigate the relationship between the fatty acid-binding protein 4(FABP4)and colorectal cancer(CRC).Methods:Using an enzyme-linked immunosorbent assay(ELISA),we measured the expression of FABP4 in plas...Objective:To investigate the relationship between the fatty acid-binding protein 4(FABP4)and colorectal cancer(CRC).Methods:Using an enzyme-linked immunosorbent assay(ELISA),we measured the expression of FABP4 in plasma of50 patients who underwent surgery for CRC from October 2017 to May 2018 and 50 healthy controls.The content of the visceral fat area(VFA)as seen with abdominal computed tomography(CT)scanning was measured by ImageJ software.The expression levels of FABP4,E-cadherin,and Snail proteins in CRC and adjacent tissues were determined by immunohistochemistry.Results:The mean concentration of plasma FABP4 of CRC patients was higher than that of the control group(22.46 vs.9.82 ng/m L;P<0.05).The concentration of plasma FABP4 was related to the tumor,node,metastatis(TNM)stage and lymph node metastasis and was independent of age,body mass index(BMI),tumor size and location,and the degree of differentiation of CRC.The concentration of plasma FABP4 was positively correlated with high VFA and lipoprotein-a(LPA)(P<0.05);but it was not correlated with total cholesterol(TG),total triglyceride(TC),low-density lipoprotein(LDL),high-density lipoprotein(HDL),or apolipoprotein AI(Apo-AI).The expression of FABP4 protein in CRC tissues was positively correlated with the degree of CRC differentiation,tumor stage,and lymph node metastasis.The level of FABP4 protein was negatively correlated with E-cadherin protein(r=-0.3292,P=0.0196)and positively correlated with Snail protein(r=0.5856,P<0.0001).Conclusions:High LPA and VFA were risk factors for increased plasma FABP4 in CRC patients.FABP4 protein was highly expressed in CRC tissues and associated with TNM stage,differentiation,and lymph node metastasis of CRC.The level of FABP4 in CRC tissue was correlated with E-cadherin and Snail expression,suggesting that FABP4 may promote CRC progression related to epithelial-mesenchymal transition(EMT).展开更多
Activated carbon supported palladium catalyst was prepared by excessive impregnation method.The performance of catalyst was evaluat-ed by selective dechlorination of 2.3.6-richlopridine to 23-dichloropyridine.The inlu...Activated carbon supported palladium catalyst was prepared by excessive impregnation method.The performance of catalyst was evaluat-ed by selective dechlorination of 2.3.6-richlopridine to 23-dichloropyridine.The inluence of palladium loading.reaction temperature and acid-binding agent on the eatalyst activity was invetigated.Resuls showed that the palladium load of 0.5%6(w),under the condition of the reaction temperature 140℃,the cornverion of 2.3.6 trichloropyridine was 100%and the sletivrity of 2.3-dichlropridine was more than 71%.Adding ti-ethylamine in solvent methanol can efectively improve the target product selectivity,and under the optimal conditions,the Belectivity of 23-dichlopyridine can reach to 80%.展开更多
Background and Aims:Hepatocellular carcinoma(HCC)remains challenging to treat in advanced stages,primarily due to the development of resistance to sorafenib.There is an urgent need for novel therapeutic strategies to ...Background and Aims:Hepatocellular carcinoma(HCC)remains challenging to treat in advanced stages,primarily due to the development of resistance to sorafenib.There is an urgent need for novel therapeutic strategies to overcome this resistance.This study aimed to investigate the potential of oleanolic acid(OA),a natural hepatoprotective compound,in mitigating sorafenib resistance and elucidate its underlying molecular mechanisms.Methods:Sorafenib-resistant Huh7 and HepG2 cell lines were established to mimic the resistant phenotype.The effects of OA on these cells were evaluated by assessing cell invasion,migration,and sensitivity to sorafenib.Gene expression analysis was conducted to identify molecular changes induced by OA treatment,with a focus on fabp3 expression.Results:Oleanolic acid significantly inhibited the invasive and migratory capabilities of sorafenib-resistant Huh7 and HepG2 cells(p<0.01).Furthermore,OA treatment downregulated fabp3 expression and restored the cells’sensitivity to sorafenib.Conclusions:Oleanolic acid shows promise as an adjunct therapy for overcoming sorafenib resistance in HCC.By reducing cell aggressiveness and restoring drug sensitivity,OA may enhance the therapeutic efficacy of current treatments for advanced HCC.展开更多
The overexpression of sialic acids on glycans,called hypersialylation,is a common alteration found in cancer cells.Sialylated glycans can enhance immune evasion by interacting with sialic acid-binding immunoglobulin-l...The overexpression of sialic acids on glycans,called hypersialylation,is a common alteration found in cancer cells.Sialylated glycans can enhance immune evasion by interacting with sialic acid-binding immunoglobulin-like lectin(Siglec)receptors on tumorinfiltrating immune cells.Here,we investigated the effect of sialylated glycans and their interaction with Siglec receptors on myeloid-derived suppressor cells(MDSCs).We found that MDSCs derived from the blood of lung cancer patients and tumor-bearing mice strongly express inhibitory Siglec receptors and are highly sialylated.In murine cancer models of emergency myelopoiesis,Siglec-E knockout in myeloid cells resulted in prolonged survival and increased tumor infiltration of activated T cells.Targeting suppressive myeloid cells by blocking Siglec receptors or desialylation strongly reduced their suppressive potential.We further identified CCL2 as a mediator involved in T-cell suppression upon interaction between sialoglycans and Siglec receptors on MDSCs.Our results demonstrated that sialylated glycans inhibit anticancer immunity by modulating CCL2 expression.展开更多
文摘In this letter,we have commented on the study by Zhang et al,which utilized bioinformatics and immunohistochemistry to assess the value of fatty acidbinding protein 4(FABP4)as a biomarker for colon adenocarcinoma(COAD).Their findings improve our understanding of FABP4 in cancer cell adhesion and immune cell infiltration.However,differential expression analysis was insufficient to demonstrate a direct association between FABP4 expression and the occurrence and progression of COAD.Using Mendelian randomization for causal inferences can provide a solid biological foundation for model construction.Furthermore,integrating machine and deep learning approaches may yield more robust and precise prognostic outcomes than using a single Cox regression model.In addition,integrating genome-wide association study data to identify additional pathogenic genes involved in the regulation of fatty acid metabolism may facilitate the development of a multi-target strategy.This approach could potentially mitigate the compensatory effects associated with targeting FABP4 alone,and enhance therapeutic efficacy.Enhancing experimental validation would further improve the reliability of the results.With the continuous advancement of machine learning,multi-omics technologies,and experimental techniques,future studies may systematically integrate diverse sequencing datasets to offer novel insights into the early diagnosis,individualized treatment,and prognostic evaluation of COAD.
基金supported by the National Natural Science Foundation of China (32070012)。
文摘As intracellular fatty acid(FA) carriers,FA-binding proteins(FABPs) widely participate in the absorption,transport,and metabolism of FAs.It is a key protein in insect lipid metabolism and plays an important role in various physiological activities of insects.An FABP gene(HvFABP) was cloned from the transcriptional library of Heortia vitessoides Moore(Lepidoptera:Crambidae),and its expression patterns were determined using reverse transcription quantitative PCR(RTqPCR).Stage-and tissue-specific expression profiles indicated that HvFABP highly expressed from prepupal to adult stages and in larval midgut and adult wings.HvFABP expression may be induced through starvation,mRNA expression was downregulated at 24 and 48 h and upregulated at 72 h after starvation.Furthermore,20-hydroxyecdysone can induce the upregulation of its expression.RNA interference-mediated silencing of Hv FABP significantly inhibited HvFABP expression,resulting in delayed development,abnormal molting or lethal phenotypes,and a significantly reduced survival rate.These results indicate that HvFABP plays a key role in the molting of H.vitessoides.
基金This research was supported by National Key R&D Program of China Grant(2016YFA0502101)National Natural Science Foundation of China(grants 81371826 and 81572002 to Z.Q.,grants 31300148 and 31570169)。
文摘Suberoylanilide hydroxamic acid(SAHA) is a histone deacetylase inhibitor that shows marked efficacy against many types of cancers and is approved to treat severe metastatic cutaneous T-cell lymphomas. In addition to its anticancer activity,SAHA has significant effects on the growth of many viruses. The effect of SAHA on replication of human cytomegalovirus(HCMV) has not, however, been investigated. Here, we showed that the replication of HCMV was significantly suppressed by treatment with SAHA at concentrations that did not show appreciable cytotoxicity. SAHA reduced transcription and protein levels of HCMV immediate early genes, showing that SAHA acts at an early stage in the viral life-cycle. RNAsequencing data mining showed that numerous pathways and molecules were affected by SAHA. Interferon-mediated immunity was one of the most relevant pathways in the RNA-sequencing data, and we confirmed that SAHA inhibits HCMV-induced IFN-mediated immune responses using quantitative Real-time PCR(qRT-PCR). Fatty acid-binding protein 4(FABP4), which plays a role in lipid metabolism, was identified by RNA-sequencing. We found that FABP4 expression was reduced by HCMV infection but increased by treatment with SAHA. We then showed that knockdown of FABP4 partially rescued the effect of SAHA on HCMV replication. Our data suggest that FABP4 contributes to the inhibitory effect of SAHA on HCMV replication.
基金funded by the Research Project of Hebei United University ( 07101168)
文摘[ Objective] The aim of this paper is to provide the basic data for marker-assisted selection of pig breeding using porcine heart fatty acid- binding protein （H-FABP） gene. [Method] According to the related sequences of porcine H-FABP gene released in GenBank, specific primers were designed to amplify the intron 3 of porcine H-FABP gene. [ Result] The intron 3 of porcine H-FABP gene was amplified successfully. Its whole sequence was 1 350 bp in length and had been submitted to GenBank （Accession no. ： DQ 002993）. [Condusion] The study lays a theoretical foundation for determination of the major genes affecting intramuscular fat deposition.
文摘Dysregulated inflammation and multi-organ failure are hallmarks of sepsis,a potentially fatal illness for which there are currently no effective treatments.Fatty acid-binding protein(A-FABP)has been identified in recent research as a crucial mediator of the inflammatory pathways underlying sepsis.In this study,we used a murine model of lipopolysaccharide(LPS)-induced endotoxemia to assess the therapeutic potential of 6H2,a monoclonal antibody that targets A-FABP.In comparison to untreated septic mice,6H2 treatment significantly increased survival rates,decreased histopathological damage in the liver,lungs,kidneys,and heart,and reduced systemic inflammation.According to biochemical analyses,6H2 treatment decreased circulating levels of A-FABP,and this was associated with a reduction in inflammatory markers.These results indicate that A-FABP inhibition is a potentially effective treatment approach for sepsis,with 6H2 demonstrating strong therapeutic efficacy.
基金National Key Research and Development Program of China(No.2018YFC1313602)Major International(Regional)Joint Research Project(No.81820108001)+4 种基金National Natural Science Foundation of China(Nos.81670029 and 82000038)Jiangsu Key Principal Investigator of Medicine(No.ZDRCA2016018)Project 333 for Cultivation of Young and Middle-aged Leading Talents(No.BRA2019078)Jiangsu Key Program of Social Development(No.BE2015651)Nanjing Key Project of Science and Technology((No.2019060002)(to L.Zhou),and NIH P01HL107151(to Z.Zhu))。
文摘Chronic obstructive pulmonary disease(COPD)has become the third-leading cause of death worldwide,which is a severe economic burden to the healthcare system.Chronic bronchitis is the most common condition that contributes to COPD,both locally and systemically.Neutrophilic inflammation predominates in the COPD airway wall and lumen.Logically,repression of neutrophilia is an essential fashion to COPD treatment.However,currently available anti-neutrophilic therapies provide little benefit in COPD patients and may have serious side effects.Thus,there is an urgent need to explore an effective and safe anti-neutrophilic approach that might delay progression of the disease.Sialic acid-binding immunoglobulin-like lectin(Siglec)-9 is a member of the Siglec cell surface immunoglobulin family.It is noteworthy that Siglec-9 is highly expressed on human neutrophils and monocytes.Ligation of Siglec-9 by chemical compounds or synthetic ligands induced apoptosis and autophagic-like cell death in human neutrophils.Furthermore,administration of antibody to Siglec-E,mouse functional ortholog of Siglec-9,restrained recruitment and activation of neutrophils in mouse models of airway inflammation in vivo.Given the critical role that neutrophils play in chronic bronchitis and emphysema,targeting Siglec-9 could be beneficial for the treatment of COPD,asthma,fibrosis,and related chronic inflammatory lung diseases.
基金funded by the Alzheimer’s Disease Neuroimaging Initiative(ADNI)(National Institutes of Health Grant U01 AG024904)DOD ADNI(Department of Defense award number W81XWH-12-2-0012)funded by the National Institute on Aging,the National Institute of Biomedical Imaging and Bioengineering
文摘Objective:This study aims to investigate whether the heart fatty acid-binding protein(HFABP)in the cerebrospinal fluid(CSF)was a potential predictive biomarker for Alzheimer’s disease(AD).Methods:We evaluated the associations of CSF HFABP levels with core biomarkers,cognition,and brain structure in a sample population(n=302)from the Alzheimer’s Disease Neuroimaging Initiative(ADNI)database.Multiple linear regression and mixed-effects models were employed in the analyses.AD progression was assessed using the Kaplan–Meier survival analysis.Results:CSF HFABP was higher in patients with mild cognitive impairment and AD than the normal controls(p<0.001)and was particularly higher in those with amyloid-β(Aβ)pathologic features.CSF HFABP was associated with higher baseline CSF t-tau(p<0.001),CSF p-tau(p<0.001),and CSF t-tau/Aβ42 and CSF p-tau/Aβ42(p<0.01).Moreover,CSF HFABP was found to play predictive roles in hippocampal atrophy(p<0.01),cognitive decline(p<0.05),and the risk of AD(p<0.001).Conclusion:Our findings suggest that CSF HFABP can be a predictive biomarker of AD.
基金supported by the National Natural Science Foundation of China(82072025,82072026,82102162,and 82303886)the“Leading Goose”Research and Development Program of Zhejiang Province(2023C03062)+1 种基金the National Natural Science Foundation of Zhejiang Province(LY22H160040 and LQ22H180010)the Key Research and Development Project of Lishui City(2022ZDYF12,2022ZDYF20,and 2022ZDYF20).
文摘Background:Radiofrequency ablation(RFA)is an efficient treatment with unlimited potential for liver cancer that can effectively reduce patient mortality.Understanding the biological process related with RFA treatment is important for improving treatment strategy.This study aimed to identify the critical targets for regulating the efficacy of RFA.Methods:The RFA treatment in hepatocellular carcinoma(HCC)tumor models in vivo,was analyzed by RNA sequencing technology.The heat treatment in vitro for HCC tumor cells was also constructed to explore the mechanism after RFA treatment in tumor cells.Nanoparticles with high affinity to tumor cells were applied as a new therapy to interfere with the expression of maternal embryonic leucine zipper kinase(MELK).Results:It was found that RFA treatment upregulated MELK expression,and MELK inhibition promoted RFA efficacy by immunogenic cell death and the antitumor response,including anti-tumoral macrophage polarization and increased CD8+T cell cytotoxicity in HCC.Mechanically,MELK binds to fatty acid-binding protein 5(FABP5),and affects its ubiquitination through the K48R pathway to increase its stability,thereby activating protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling axis to weaken the RFA-mediated antitumor effect.In addition,the synthesis of arginylglycylaspartic acid(RGD)-lipid nanoparticles(LNPs)targeting tumor cell-intrinsic MELK enhanced RFA efficacy in HCC.Conclusions:MELK is a therapeutic target by regulating RFA efficacy in HCC,and targeting MELK via RGD-LNPs provides new insight into improving RFA efficacy in HCC clinical treatment and combating the malignant progression of liver cancer.
文摘Heart fatty acid-binding protein (H-FABP) is supposed to be the most sensitive biomarker of early acute myocardial infarction (AMI). To evaluate the diagnostic value of H-FABP for AMI in the early stage, the plasma levels of H-FABP were measured by sandwich ELISA in 93 patients with suspected AMI at admission within 6 h after onset of chest pain and 69 normal healthy subjects. The plasma concentrations of cardiac troponin-I (cTnI), creatine kinase-MB (CK-MB) and myoglobin (Mb) were assayed at the same time by using corpuscle chemiluminescence for those patients. The patients were classified as AMI group (n=32) and non-AMI group (n=61) retrospectively. The diagnostic validity was evaluated in terms of sensitivity, specificity and receiver operating characteristic (ROC) curve analysis. The results showed the cutoff value of H-FABP for AMI was 16.8 ng/ml, and its diagnostic sensitivity for AMI was 64.29 % within 3 h and 84.38 % within 6 h after onset of chest pain, and the diagnostic specificity for non-AMI was 100 % within 3 h and 91.8 % within 6 h. H-FABP had higher sensitivity than that of cTnI and CK-MB at all time points (P<0.05), whereas there was no significant difference in specificity among the four markers. But the area under the ROC curve of H-FABP was significantly greater than that of cTnI, CK-MB and Mb within 3 h. These results revealed that H-FABP possessed high diagnostic sensitivity and specificity for AMI in early stage, especially within 3 h after onset of persistent angina pectoris. In conclusion, H-FABP can be used as a sensitive marker for AMI in the early stage.
基金Supported by Research Grant of National Research Development and Innovation Office,No.K115818/2015/1János Bólyai Research Scholarship of Hungarian Academy of Sciences to Papp Mthe New National Excellence Program of the Ministry of Human Capacities,No.úNKP-16-3 to Tornai T
文摘To assess the prevalence of a panel of serologic markers that reflect gut barrier dysfunction in a mixed cohort of pediatric and adult primary sclerosing cholangitis(PSC)patients.METHODSSera of 67 PSC patients[median age(range):32(5-79)years,concomitant IBD:67%and cirrhosis:20%]were assayed for the presence of antibodies against to F-actin(AAA IgA/IgG)and gliadin(AGA IgA/IgG)]and for serum level of intestinal fatty acid-binding protein(I-FABP)by ELISA.Markers of lipopolysaccharide(LPS)exposure[LPS binding protein(LBP)]and various anti-microbial antibodies[anti-OMP Plus IgA and endotoxin core IgA antibody(EndoCAb)]were also determined.Poor disease outcome was defined as orthotopic liver transplantation and/or liver-related death during the follow-up[median:99(14-106)mo].One hundred and fifty-three healthy subjects(HCONT)and 172 ulcerative colitis(UC)patients were the controls.RESULTSA total of 28.4%,28.0%,9%and 20.9%of PSC patients were positive for AAA IgA,AAA IgG,AGA IgA and AGA IgG,respectively.Frequencies of AAA IgA and AAA IgG(P<0.001,for both)and AGA IgG(P=0.01,for both)but not AGA IgA were significantly higher compared to both of the HCONT and the UC groups.In survival analysis,AAA IgA-positivity was revealed as an independent predictor of poor disease outcome after adjusting either for the presence of cirrhosis[HR=5.15(1.27-20.86),P=0.022 or for the Mayo risk score(HR=4.24(0.99-18.21),P=0.052].AAA IgA-positivity was significantly associated with higher frequency of anti-microbial antibodies(P<0.001 for EndoCab IgA and P=0.012 for anti-OMP Plus IgA)and higher level of the enterocyte damage marker(median I-FABP<sub>AAA IgA pos</sub><sub>vs</sub><sub>neg</sub>:365 vs 166 pg/mL,P=0.011),but not with serum LBP level.CONCLUSIONPresence of IgA type AAA identified PSC patients with progressive disease.Moreover,it is associated with enhanced mucosal immune response to various microbial antigens and enterocyte damage further highlighting the importance of the gut-liver interaction in PSC.
基金supported by the Science Foundation of Wuxi Health and Family Planning Commission(No.Z201713 to Min XIA)the Special Project of Clinical Medicine of Nantong University(No.2019JQ006 to Yan ZHANG),China。
文摘Objective:To investigate the relationship between the fatty acid-binding protein 4(FABP4)and colorectal cancer(CRC).Methods:Using an enzyme-linked immunosorbent assay(ELISA),we measured the expression of FABP4 in plasma of50 patients who underwent surgery for CRC from October 2017 to May 2018 and 50 healthy controls.The content of the visceral fat area(VFA)as seen with abdominal computed tomography(CT)scanning was measured by ImageJ software.The expression levels of FABP4,E-cadherin,and Snail proteins in CRC and adjacent tissues were determined by immunohistochemistry.Results:The mean concentration of plasma FABP4 of CRC patients was higher than that of the control group(22.46 vs.9.82 ng/m L;P<0.05).The concentration of plasma FABP4 was related to the tumor,node,metastatis(TNM)stage and lymph node metastasis and was independent of age,body mass index(BMI),tumor size and location,and the degree of differentiation of CRC.The concentration of plasma FABP4 was positively correlated with high VFA and lipoprotein-a(LPA)(P<0.05);but it was not correlated with total cholesterol(TG),total triglyceride(TC),low-density lipoprotein(LDL),high-density lipoprotein(HDL),or apolipoprotein AI(Apo-AI).The expression of FABP4 protein in CRC tissues was positively correlated with the degree of CRC differentiation,tumor stage,and lymph node metastasis.The level of FABP4 protein was negatively correlated with E-cadherin protein(r=-0.3292,P=0.0196)and positively correlated with Snail protein(r=0.5856,P<0.0001).Conclusions:High LPA and VFA were risk factors for increased plasma FABP4 in CRC patients.FABP4 protein was highly expressed in CRC tissues and associated with TNM stage,differentiation,and lymph node metastasis of CRC.The level of FABP4 in CRC tissue was correlated with E-cadherin and Snail expression,suggesting that FABP4 may promote CRC progression related to epithelial-mesenchymal transition(EMT).
基金Supported by Key Research and Development Plan of Shaanxi Province(2020GY-298)Special Fund for Technology Innovation Guidance of Shaanxi Province(2019CGHJ-04)Innovation Capacity Support Program of Shaanxi Province(2020KJXX-031-2020TD-007).
文摘Activated carbon supported palladium catalyst was prepared by excessive impregnation method.The performance of catalyst was evaluat-ed by selective dechlorination of 2.3.6-richlopridine to 23-dichloropyridine.The inluence of palladium loading.reaction temperature and acid-binding agent on the eatalyst activity was invetigated.Resuls showed that the palladium load of 0.5%6(w),under the condition of the reaction temperature 140℃,the cornverion of 2.3.6 trichloropyridine was 100%and the sletivrity of 2.3-dichlropridine was more than 71%.Adding ti-ethylamine in solvent methanol can efectively improve the target product selectivity,and under the optimal conditions,the Belectivity of 23-dichlopyridine can reach to 80%.
基金supported by the Horizontal Project of Jiangsu Medical College(2021010401)the collaborative innovation project for“Double First-Class”Discipline Heilongjiang Province(LJGXCG2023-089)+2 种基金the Joint Guidance Project of Natural Science Foundation of Heilongjiang Province(LH2022H090,PL2024H002)the Innovation Team of Heilongjiang Provincial Department of Education(2024-KYYWF-0617)the he East-Extreme Discipline Construction Team of Jiamusi University(DJXSTD202404).
文摘Background and Aims:Hepatocellular carcinoma(HCC)remains challenging to treat in advanced stages,primarily due to the development of resistance to sorafenib.There is an urgent need for novel therapeutic strategies to overcome this resistance.This study aimed to investigate the potential of oleanolic acid(OA),a natural hepatoprotective compound,in mitigating sorafenib resistance and elucidate its underlying molecular mechanisms.Methods:Sorafenib-resistant Huh7 and HepG2 cell lines were established to mimic the resistant phenotype.The effects of OA on these cells were evaluated by assessing cell invasion,migration,and sensitivity to sorafenib.Gene expression analysis was conducted to identify molecular changes induced by OA treatment,with a focus on fabp3 expression.Results:Oleanolic acid significantly inhibited the invasive and migratory capabilities of sorafenib-resistant Huh7 and HepG2 cells(p<0.01).Furthermore,OA treatment downregulated fabp3 expression and restored the cells’sensitivity to sorafenib.Conclusions:Oleanolic acid shows promise as an adjunct therapy for overcoming sorafenib resistance in HCC.By reducing cell aggressiveness and restoring drug sensitivity,OA may enhance the therapeutic efficacy of current treatments for advanced HCC.
基金supported by funding from the Swiss National Science Foundation(SNSF Grant No.310030-215237/1)the Schoenmakers-Müller Foundation,a research grant from Ono Pharmaceuticals,and the Cancer League of Basel(KlbB).Open access funding provided by University of Basel.
文摘The overexpression of sialic acids on glycans,called hypersialylation,is a common alteration found in cancer cells.Sialylated glycans can enhance immune evasion by interacting with sialic acid-binding immunoglobulin-like lectin(Siglec)receptors on tumorinfiltrating immune cells.Here,we investigated the effect of sialylated glycans and their interaction with Siglec receptors on myeloid-derived suppressor cells(MDSCs).We found that MDSCs derived from the blood of lung cancer patients and tumor-bearing mice strongly express inhibitory Siglec receptors and are highly sialylated.In murine cancer models of emergency myelopoiesis,Siglec-E knockout in myeloid cells resulted in prolonged survival and increased tumor infiltration of activated T cells.Targeting suppressive myeloid cells by blocking Siglec receptors or desialylation strongly reduced their suppressive potential.We further identified CCL2 as a mediator involved in T-cell suppression upon interaction between sialoglycans and Siglec receptors on MDSCs.Our results demonstrated that sialylated glycans inhibit anticancer immunity by modulating CCL2 expression.
