BACKGROUND The prevalence of metabolic dysfunction-associated fatty liver disease(MAFLD)is rapidly increasing,currently affecting approximately 25%of the global population.Liver fibrosis represents a crucial stage in ...BACKGROUND The prevalence of metabolic dysfunction-associated fatty liver disease(MAFLD)is rapidly increasing,currently affecting approximately 25%of the global population.Liver fibrosis represents a crucial stage in the development of MAFLD,with advanced liver fibrosis elevating the risks of cirrhosis and hepatocellular carcinoma.Simple serum markers are less effective in diagnosing liver fibrosis compared to more complex markers.However,imaging techniques like transient elastography face limitations in clinical application due to equipment and technical constraints.Consequently,it is imperative to identify a straightforward yet effective method for assessing MAFLD-associated liver fibrosis.AIM To investigate the predictive value of angiopoietin-like protein 8(ANGPTL8)in MAFLD and its progression.METHODS We analyzed 160 patients who underwent abdominal ultrasonography in the Endocrinology Department,Xiaogan Central Hospital affiliated to Wuhan University of Science and Technology,during September 2021-July 2022.Using abdominal ultrasonography and MAFLD diagnostic criteria,among the 160 patients,80 patients(50%)were diagnosed with MAFLD.The MAFLD group was divided into the liver fibrosis group(n=23)and non-liver fibrosis group(n=57)by using a cut-off fibrosis-4 index≥1.45.Logistical regression was used to analyze the risk of MAFLD and the risk factors for its progression.Receiver operating characteristic curves were used to evaluate the predictive value of serum ANGPTL8 in MAFLD and its progression.RESULTS Compared with non-MAFLD patients,MAFLD patients had higher serum ANGPTL8 and triglyceride-glucose(TyG)index(both P<0.05).Serum ANGPTL8(r=0.576,P<0.001)and TyG index(r=0.473,P<0.001)were positively correlated with MAFLD.Serum ANGPTL8 was a risk factor for MAFLD[odds ratio(OR):1.123,95%confidence interval(CI):1.066-1.184,P<0.001).Serum ANGPTL8 and ANGPTL8+TyG index predicted MAFLD[area under the curve(AUC):0.832 and 0.886,respectively;both P<0.05].Compared with MAFLD patients without fibrosis,those with fibrosis had higher serum ANGPTL8 and TyG index(both P<0.05),and both parameters were positively correlated with MAFLD-associated fibrosis.Elevated serum ANGPTL8(OR:1.093,95%CI:1.044-1.144,P<0.001)and TyG index(OR:2.383,95%CI:1.199-4.736,P<0.013)were risk factors for MAFLD-associated fibrosis.Serum ANGPTL8 and ANGPTL8+TyG index predicted MAFLD-associated fibrosis(AUC:0.812 and 0.835,respectively;both P<0.05).CONCLUSION The serum levels of ANGPTL8 are elevated and positively correlated with MAFLD.They can serve as predictors for the risk of MAFLD and liver fibrosis,with the ANGPTL8+TyG index potentially exhibiting even higher predictive value.展开更多
AIM:To confirm the role of angiopoietin-like protein 8(Angptl 8) in proliferative diabetic retinopathy(PDR).METHODS:The sera and aqueous humor of 10 PDR patients and 10 non-diabetic retinopathy(NDR) patients(...AIM:To confirm the role of angiopoietin-like protein 8(Angptl 8) in proliferative diabetic retinopathy(PDR).METHODS:The sera and aqueous humor of 10 PDR patients and 10 non-diabetic retinopathy(NDR) patients(idiopathic macular hole patients) were collected and the expression of Angptl 8 was detected by enzyme linked immune-sorbent assay(ELISA).Experimental diabetes mice model was induced with streptozotocin.The expression of glycosylated hemoglobin and Angptl 8 in sera was detected.Recombinant Angptl 8 was re-infused into wild type(WT) diabetic mice and spatial frequency threshold and contrast sensitivity were measured.In vitro retinal pigment epithelium(RPE) were stimulated by recombinant Angptl 8 for 24 h.MMT assay were used to detect cell proliferation.At the same time,q RT-PCR and Western blot was used to measure the expression of proliferation-related factors in PRE cells.RESULTS:The expression of Angptl 8 was markedly increased in the sera and aqueous humor of PDR patients(F=99.02,P〈0.0001 in sera;t=10.42,P〈0.0001 in aqueous).After successfully establishing the diabetic mice model,we found that glycosylated hemoglobin and Angptl 8 expression levels were increased.Re-infusion of recombinant Angptl 8 into WT diabetic mice could further decrease spatial frequency threshold and contrast sensitivity(P〈0.01).In vitro,RPE cells stimulated by recombinant Angptl 8could increase the relative absorbance of MMT assay(1.486±0.042 vs 1.000±0.104,P〈0.05) and proliferating cell nuclear antigen(PCNA) expression(0.55±0.01 vs 0.29±0.03,P〈0.05).The proliferative effect of Angptl 8 is mainly mediated by increasing the expression of proliferation-activating factors cyclin A1(4.973±0.205 vs 2.720±0.197,P〈0.05),cyclin F(5.690±0.219 vs 4.297±0.292,P〈0.05) and E2 F2(2.297±0.102 vs 1.750±0.146,P〈0.05),and reducing the expression of proliferation-inhibiting factors cdkn1(2.370±0.074 vs 3.317±0.135,P〈0.05) and cdkn2(4.793±0.065 vs 5.387±0.149,P〈0.05).CONCLUSION:The expression of Angptl 8 is increased in PDR,and the increased Angptl 8 can promote proliferation and increase proliferation-related factors.展开更多
BACKGROUND Intestinal barrier breakdown,a frequent complication of intestinal ischemiareperfusion(I/R)including dysfunction and the structure changes of the intestine,is characterized by a loss of tight junction and e...BACKGROUND Intestinal barrier breakdown,a frequent complication of intestinal ischemiareperfusion(I/R)including dysfunction and the structure changes of the intestine,is characterized by a loss of tight junction and enhanced permeability of the intestinal barrier and increased mortality.To develop effective and novel therapeutics is important for the improvement of outcome of patients with intestinal barrier deterioration.Recombinant human angiopoietin-like protein 4(rhANGPTL4)is reported to protect the blood-brain barrier when administered exogenously,and endogenous ANGPTL4 deficiency deteriorates radiationinduced intestinal injury.AIM To identify whether rhANGPTL4 may protect intestinal barrier breakdown induced by I/R.METHODS Intestinal I/R injury was elicited through clamping the superior mesenteric artery for 60 min followed by 240 min reperfusion.Intestinal epithelial(Caco-2)cells and human umbilical vein endothelial cells were challenged by hypoxia/reoxygenation to mimic I/R in vitro.RESULTS Indicators including fluorescein isothiocyanate-conjugated dextran(4 kilodaltons;FD-4)clearance,ratio of phosphorylated myosin light chain/total myosin light chain,myosin light chain kinase and loss of zonula occludens-1,claudin-2 and VE-cadherin were significantly increased after intestinal I/R or cell hypoxia/reoxygenation.rhANGPTL4 treatment significantly reversed these indicators,which were associated with inhibiting the inflammatory and oxidative cascade,excessive activation of cellular autophagy and apoptosis and improvement of survival rate.Similar results were observed in vitro when cells were challenged by hypoxia/reoxygenation,whereas rhANGPTL4 reversed the indicators close to normal level in Caco-2 cells and human umbilical vein endothelial cells significantly.CONCLUSION rhANGPTL4 can function as a protective agent against intestinal injury induced by intestinal I/R and improve survival via maintenance of intestinal barrier structure and functions.展开更多
Pregnancy toxemia is a metabolic disorder of lipid and glucose. Recent investigations have found that angiopoietin-like protein 3 (ANGPTL3) can contribute to disorder of carbohydrate and lipid metabolism. The presen...Pregnancy toxemia is a metabolic disorder of lipid and glucose. Recent investigations have found that angiopoietin-like protein 3 (ANGPTL3) can contribute to disorder of carbohydrate and lipid metabolism. The present study was conducted to investigate the change of ANGPTL3 expression during pregnancy toxemia, We firstly cloned the full-length cDNA of ANGPTL3 in Liuyang Black goats, revealing that goat ANGPTL3 had the typical structure of the angiopoietin-like family, and its mRNA was exclusively expressed in liver. Pregnancy toxemia of pregnant goat does with twins during late gestation was induced by being fasted for 72 h, and then they were recovered after 5 d ofrefeeding. Hepatic ANGPTL3 gene expression was significantly down-regulated concomitantly with decreased serum glucose concentration, elevated serum β-hydroxybutyrate and free fatty acid levels in pregnant toxemic goats, and these changes were reversed after refeeding. These results suggest ANGPTL3 may play a certain role in the development of pregnancy toxemia in goats.展开更多
Recovery of functional beta cell mass offers a biological cure for type 1 diabetes. However, beta cell mass is difficult to regain once lost since the proliferation rate of beta cells after youth is very low. Angiopoi...Recovery of functional beta cell mass offers a biological cure for type 1 diabetes. However, beta cell mass is difficult to regain once lost since the proliferation rate of beta cells after youth is very low. Angiopoietin like-protein 8 (ANGPTL8), a peptide that has a role in the regulation of lipoprotein lipase activity, was reported to increase beta cell proliferation in mice in 2013. Subsequent studies of human ANGPTL8 for short term (3 to 8 days) in non-diabetic mice showed little or no increase in beta cell proliferation. Here, we examined the effect of ANGPTL8 on glucose homeostasis in models that have not been examined previously. We expressed mouse ANGPTL8 using adenovirus in 2 mouse models of diabetes (streptozotocin and Non-Obese Diabetic (NOD) mice) over 2 weeks. Also, we tested ANGPTL8 in NOD mice deficient in leukocyte 12-lipoxygenase (12LO), an enzyme that contributes to insulitis and loss of beta cell function in NOD, in an effort to determine whether 12LO deficiency alters the response to ANGPTL8. Adenovirus-mediated expression of ANGPTL8 lowered blood glucose levels in streptozotocin treated mice without an increase in beta cell proliferation or serum insulin concentration. While ANGPTL8 did not reverse hyperglycemia in overtly hyperglycemic NOD mice or alter glucose homeostasis of non-diabetic NOD mice, ANGPTL8 reduced blood glucose levels in 12LOKO NOD mice. However, the lower glucose levels in 12LOKO NOD were not associated with higher serum insulin levels or beta cell proliferation. In summary, while mouse ANGPTL8 does not increase beta cell proliferation in NOD mice or streptozotocin treated mice in agreement with studies in non-diabetic mice, it lowers blood glucose levels in multiple low-dose streptozotocin induced diabetes and 12LO deficiency indicating that host factors influence the impact of ANGPTL8 on glucose homeostasis.展开更多
Three members of the angiopoietin-like(ANGPTL) protein family-ANGPTL3, ANGPTL4 and ANGPTL8-are important regulators of plasma lipoproteins. They inhibit the enzyme lipoprotein lipase, which plays a key role in the int...Three members of the angiopoietin-like(ANGPTL) protein family-ANGPTL3, ANGPTL4 and ANGPTL8-are important regulators of plasma lipoproteins. They inhibit the enzyme lipoprotein lipase, which plays a key role in the intravascular lipolysis of triglycerides present in some lipoprotein classes. This review focuses on the role of ANGPTL3 as emerged from the study of genetic variants of Angptl3 gene in mice and humans. Both loss of function genetic variants and inactivation of Angptl3 gene in mice are associated with a marked reduction of plasma levels of triglyceride and cholesterol and an increased activity of lipoprotein lipase and endothelial lipase. In humans with ANGPTL3 deficiency, caused by homozygous loss of function(LOF) variants of Angptl3 gene, the levels of all plasma lipoproteins are greatly reduced. This plasma lipid disorder referred to as familial combined hypolipidemia(FHBL2) does not appear to be associated with distinct pathological manifestations. Heterozygous carriers of LOF variants have reduced plasma levels of total cholesterol and triglycerides and are at lower risk of developing atherosclerotic cardiovascular disease, as compared to non-carriers. These observations have paved the way to the development of strategies to reduce the plasma level of atherogenic lipoproteins in man by the inactivation of ANGPTL3, using either a specific monoclonal antibody or anti-sense oligonucleotides.展开更多
Background:A recent study reported a positive association between elevated serum levels of angiopoietin-like protein 2 (ANGPTL2) and the development of type 2 diabetes in a general population.However,the relationsh...Background:A recent study reported a positive association between elevated serum levels of angiopoietin-like protein 2 (ANGPTL2) and the development of type 2 diabetes in a general population.However,the relationship of serum ANGPTL2 levels with the risk of developing gestational diabetes mellitus (GDM) has not been reported to date.The aim of this study was to investigate the change of maternal serum ANGPTL2 concentrations in the first trimester of pregnancy and to determine whether ANGPTL2 is a biomarker for subsequent GDM development.Methods:We conducted a prospective,nested case-control study in a pregnancy cohort.First-trimester ANGPTL2 levels were measured using a high-resolution assay in 89 women who subsequently developed GDM and in a random sample of 177 women who remained euglycemic throughout the pregnancy.Median ANGPTL2 levels were compared using Mann-Whitney U-test.Logistic regression was used to compute unadjusted and multivariable-adjusted odds ratios for developing GDM among ANGPTL2 quartiles.Results:The serum levels of ANGPTL2 was higher in women with GDM than that in women without GDM (3.06 [2.59,3.65] ng/ml vs.2.46 [2.05,2.96] ng/ml,P =0.003).Fasting blood glucose was higher in women with GDM than that in women without GDM (5.0 ± 0.9 mmol/L vs.4.4 ± 0.6 mmol/L,P 〈 0.001).Glucose challenge test showed that the blood glucose was higher in women with GDM than that in women without GDM (9.1 ± 3.5 mmol/L vs.6.2 ± 1.2 mmol/L,P 〈 0.001).A multivariate model adjusted for baseline characteristics,medical complications,and gestational characteristics revealed that the risk of developing GDM among women in Q4 compared with Q1 was 2.90-fold more likely to develop GDM later in pregnancy.Conclusions:At 1 1-13 weeks in pregnancies that develop GDM,the serum concentration of ANGPTL2 is increased,and it can be combined with maternal factors to provide effective early screening for GDM.展开更多
Recent advances in hematopoietic stem cells(HSCs)expansion by growth factors including angiopoietin-like proteins(Angptls)have opened up the possibility to use HSCs in regenerative medicine.However,the unavailability ...Recent advances in hematopoietic stem cells(HSCs)expansion by growth factors including angiopoietin-like proteins(Angptls)have opened up the possibility to use HSCs in regenerative medicine.However,the unavailability of true in vitro HSCs expansion by these growth factors has limited the understanding of the cellular and molecular mechanism of HSCs expansion.Here,we report the functional role of mouse Angptls 1,2,3,4,6 and 7 and growth factors SCF,TPO,IGF-2 and FGF-1 on purified mouse bone-marrow(BM)Lineage-Sca-1+(Lin-Sca-1+)HSCs.The recombinant retroviral transduced-CHO-S cells that secrete Angptls in serum-free medium were used alone or in combination with growth factors(SCF,TPO,IGF-2 and FGF-1).None of the Angptls stimu-lated HSC proliferation,enhanced or inhibited HSCs colony formation,but they did support the survival of HSCs.By contrast,any of the six Angptls together with saturating levels of growth factors dramatically stimulated a 3-to 4.5-fold net expansion of HSCs compared to stimulation with a combination of those growth factors alone.These findings lead to an understanding of the basic function of Angptls on signaling pathways for the survival as well as expansion of HSCs in the bone marrow niche.展开更多
Podocyte injury is an important cause of proteinuria.Angiopoietin-like protein 4(Angptl4)is a secreted glycoprotein and has a role in proteinuria.However,the exact role of Angptl4 in podocyte injury and its upstream r...Podocyte injury is an important cause of proteinuria.Angiopoietin-like protein 4(Angptl4)is a secreted glycoprotein and has a role in proteinuria.However,the exact role of Angptl4 in podocyte injury and its upstream regulators has not been clarified.In this study,we used lipopolysaccharide(LPS)-induced mice and cultured podocytes as podocyte injury models.Our results indicated that LPS increased the expression of podocyte Angptl4 in vivo and in vitro.Furthermore,we showed that Angptl4 overexpression deteriorated LPS-induced podocyte injury by inducing podocyte cytoskeleton rearrangement,reducing the expression of synaptopodin while Angptl4 knockdown alleviated LPS-induced podocyte injury.In addition,we found that inhibitors and siRNA targeting TLR4/MyD88/NF-κB signaling inhibited the upregulation of Angptl4 in LPS-induced podocytes.Moreover,inhibitors and siRNA targeting calcineurin/NFAT signaling also relieved LPS-induced Angptl4 expression and podocyte injury in vivo and in vitro.Taken together,our study has elucidated that both of the TLR4/MyD88/NF-κB and calcineurin/NFAT signaling mediate the upregulation of Angptl4 in LPS-induced podocytes,which has important implications for further understanding the molecular mechanism of LPS-induced podocyte injury.展开更多
In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the prolifer...In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the proliferation of splenocytes in response to mitogens.The splenocytes and mesenteric lymphocytes activated by T-cell mitogens(Con A and anti-CD3/CD28 antibodies)released high levels of IL-2 but low levels of IFN-γand IL-17A.The release of IL-4 was unaffected by MRJPs.Additionally,splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1βand IL-6,two pro-inflammatory cytokines.The production of IL-1β,IL-6,and IFN-γwas negatively associated with estrogen levels,which were higher in the MRJP-treated animals than in the control group.Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice.Additionally,the LEf Se analysis identified biomarkers in the MRJP-treated mice,including Prevotella,Bacillales,Enterobacteriales,Gammaproteobacteria,Candidatus_Arthromitus,and Shigella.Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.展开更多
The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves t...The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory regions.However,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the disease.The disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized countries.The TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral sclerosis.This review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).展开更多
Bacillus thuringiensis(Bt)cotton production is challenged by two main problems,i.e.,the low concentration of Bt protein at the boll setting stage and the lowest insect resistance in bolls among all the cotton plant’s...Bacillus thuringiensis(Bt)cotton production is challenged by two main problems,i.e.,the low concentration of Bt protein at the boll setting stage and the lowest insect resistance in bolls among all the cotton plant’s organs.Therefore,increasing the Bt protein concentration at the boll stage,especially in bolls,has become the main goal for increasing insect resistance in cotton.In this study,two protein degradation inhibitors(ethylene diamine tetra acetic acid(EDTA)and leupeptin)were sprayed on the bolls,subtending leaves,and whole cotton plants at the peak flowering stage of two Bt cultivars(medium maturation Sikang 1(SK1))and early maturation Zhongmian 425(ZM425)in 2019 and 2020.The Bt protein content and protein degradation metabolism were assessed.The results showed that the Bt protein concentrations were enhanced by 21.3 to 38.8%and 25.0 to 38.6%in the treated bolls of SK1 and ZM425 respectively,while they were decreased in the subtending leaves of these treated bolls.In the treated leaves,the Bt protein concentrations increased by 7.6 to 23.5%and 11.2 to 14.9%in SK1 and ZM425,respectively.The combined application of EDTA and leupeptin to the whole cotton plant increased the Bt protein concentrations in both bolls and subtending leaves.The Bt protein concentrations in bolls were higher,increasing by 22.5 to 31.0%and 19.6 to 32.5%for SK1 and ZM425,respectively.The organs treated with EDTA or/and leupeptin showed reduced free amino acid contents,protease and peptidase activities and significant enhancements in soluble protein contents.These results indicated that inhibiting protein degradation could improve the protein content,thus increasing the Bt protein concentrations in the bolls or/and leaves of cotton plants.Therefore,the increase in the Bt protein concentration without yield reduction suggested that these two protein degradation inhibitors may be applicable for improving insect resistance in cotton production.展开更多
Single-molecule magnetic tweezers(MTs) have revealed multiple transition barriers along the unfolding pathway of several two-state proteins, such as GB1 and Csp. In this study, we utilized MTs to measure the force-dep...Single-molecule magnetic tweezers(MTs) have revealed multiple transition barriers along the unfolding pathway of several two-state proteins, such as GB1 and Csp. In this study, we utilized MTs to measure the force-dependent folding and unfolding rates of both protein L(PLWT) and its Y47W mutant(PLY47W) where the mutation point is not at the force-bearing β-strands. The measurements were conducted within a force range of 3–120 pN. Notably, the unfolding rates of both PLWT and PWY47W exhibit distinct force sensitivities below 50 pN and above 60 pN, implying a two-barrier free energy landscape. Both PLWT and PLY47W share the same force-dependent folding rate and the same transition barriers,but the unfolding rate of PLY47W is faster than that of PLWT. Our finding demonstrates that the residue outside of the force-bearing region will also affect the force-induced unfolding dynamics.展开更多
Essential proteins are inseparable in cell growth and survival. The study of essential proteins is important for understanding cellular functions and biological mechanisms. Therefore, various computable methods have b...Essential proteins are inseparable in cell growth and survival. The study of essential proteins is important for understanding cellular functions and biological mechanisms. Therefore, various computable methods have been proposed to identify essential proteins. Unfortunately, most methods based on network topology only consider the interactions between a protein and its neighboring proteins, and not the interactions with its higher-order distance proteins. In this paper, we propose the DSEP algorithm in which we integrated network topology properties and subcellular localization information in protein–protein interaction(PPI) networks based on four-order distances, and then used random walks to identify the essential proteins. We also propose a method to calculate the finite-order distance of the network, which can greatly reduce the time complexity of our algorithm. We conducted a comprehensive comparison of the DSEP algorithm with 11 existing classical algorithms to identify essential proteins with multiple evaluation methods. The results show that DSEP is superior to these 11 methods.展开更多
Background:Colorectal cancer(CRC)is one of the most frequently diagnosed cancers.In many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluoro...Background:Colorectal cancer(CRC)is one of the most frequently diagnosed cancers.In many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil(5-FU).The epithelial-to-mesenchymal transition(EMT)and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many cancers.This study looked into the effect of 5-FU dose escalation on EMT and protein methylation in CRC.Materials and Methods:HCT-116,Caco-2,and DLD-1 CRC cell lines were exposed to dose escalation treatment of 5-FU.The motility and invasive potentials of the cells before and after treatment with 5-FU were investigated through wound healing and invasion assays.This was followed by aWestern blot which analyzed the protein expressions of the epithelial marker E-cadherin,mesenchymal marker vimentin,and the EMT transcription factor(EMTTF),the snail family transcriptional repressor 1(Snail)in the parental and desensitized cells.Western blotting was also conducted to study the protein expressions of the protein methyltransferases(PMTs),Euchromatic histone lysine methyltransferase 2(EHMT2/G9A),protein arginine methyltransferase(PRMT5),and SET domain containing 7/9(SETD7/9)along with the global lysine and arginine methylation profiles.Results:The dose escalation method generated 5-FU desensitized CRC cells with distinct morphological features and increased tolerance to high doses of 5-FU.The 5-FU desensitized cells experienced a decrease in migration and invasion when compared to the parental cells.This was reflected in the observed reduction in E-cadherin,vimentin,and Snail in the desensitized cell lines.Additionally,the protein expressions of EHMT2/G9A,PRMT5,and SETD7/9 also decreased in the desensitized cells and global protein lysine and arginine methylation became dysregulated with 5-FU treatment.Conclusion:This study showed that continuous,dose-escalation treatment of 5-FU in CRC cells generated 5-FU desensitized cancer cells that seemed to be less aggressive than parental cells.展开更多
Cowpea (Vigna unguiculata L. Walp) is a multi-purpose legume with high quality protein for human consumption and livestock. The objective of this work was to develop near-infrared spectroscopy (NIRS) prediction models...Cowpea (Vigna unguiculata L. Walp) is a multi-purpose legume with high quality protein for human consumption and livestock. The objective of this work was to develop near-infrared spectroscopy (NIRS) prediction models to estimate protein content in cowpea. A total of 116 cowpea breeding lines with a wide range of protein contents (19.28 % to 32.04%) were selected to build the model using whole seed and ground seed samples. Partial least-squares discriminant analysis (PLS-DA) regression technique with different pre-treatments (derivatives, standard normal variate, and multiplicative scatter correction) were carried out to develop the protein prediction model. Results showed: 1) spectral plots of both the whole seed and ground seed showed higher spectral scatter at higher wavelengths (>1450 nm), 2) data pre-processing affects prediction accuracy for bot whole seed and ground seed samples, 3) prediction using ground seed samples (0.64 R<sup>2</sup> 0.85) is better than the whole seed (0.33 R<sup>2</sup> 0.78), and 4) the data pre-processing second derivative with standard normal variate has the best prediction (R<sup>2</sup>_whole seed = 0.78, R<sup>2</sup>_ground seed = 0.85). The results will be of interest in cowpea breeding programs aimed at improving total seed protein content.展开更多
Globally,the prevalence of anxiety and depression has reached epidemic proportions.Food-derived protein hydrolysates and peptides delivered through dietary supplementation can avoid the negative risks associated with ...Globally,the prevalence of anxiety and depression has reached epidemic proportions.Food-derived protein hydrolysates and peptides delivered through dietary supplementation can avoid the negative risks associated with traditional pharmaceuticals while delivering superior anxiolytic and antidepressant effects.This review summarizes current research on food-derived anxiolytic and antidepressant protein hydrolysates and peptides,and subsequently analyses their physicochemical characteristics and elaborates on their mechanisms.The aim of this work is to contribute to the in-depth study and provide a theoretical foundation for the development of related products to better serve patients with anxiety and depression.展开更多
Background: Preeclampsia is reported to complicate 2% - 8% of pregnancies globally and is an important cause of maternal and perinatal morbidity and mortality. The aetiology and pathogenesis are still poorly understoo...Background: Preeclampsia is reported to complicate 2% - 8% of pregnancies globally and is an important cause of maternal and perinatal morbidity and mortality. The aetiology and pathogenesis are still poorly understood and substantial improvement has not been made in the prediction, prevention and treatment of the disease. Objective: To compare the frequency of activated protein C resistance (APC-R) in patients with pre-eclampsia to that of normotensive pregnant women and to determine the correlation between activated protein ratio (APC-ratio) and the severity of pre-eclampsia. Methodology: A cross-sectional study was carried out in 100 pre-eclamptic patients and 100 normotensive pregnant controls. The APC-ratio was determined using the modified activated partial thromboplastin time. Study participants with APC-ratio of less than 2.0 were defined as having APC-R. Data was analyzed using SPSS version 22.0. Results: Mean APC-ratio was significantly lower in pre-eclamptics (2.89 ± 1.70) compared to normotensive pregnant women (3.57 ± 1.06) (p = 0.0008) and the levels were also higher in mild (2.95 ± 1.15) compared to severe pre-eclamptics (2.62 ± 1.14). The frequency of APC-R was 26% among women with pre-eclampsia compared to 4% among normotensive controls (p = 0.000). Among 100 pre-eclamptic women 7 (21.2%) out of 33 with mild pre–eclampsia had APC-R, while 19 (28.4%) out of 67 with severe pre-eclampsia had APC-R. APC-ratio had a significant negative correlation with mean arterial blood pressure (r = −0.324;p = 0.000) and proteinuria (r = −0.379;p = 0.000) among study participants. Conclusion: The frequency of activated protein c resistance is significantly higher in pre-eclamptics compared to normotensive pregnant women and this is more pronounced in those with severe pre-eclampsia compared with those with mild disease. APC-R may therefore be used as a marker of severity in the disease.展开更多
Plant height influences plant architecture,lodging resistance,and yield performance.It is modulated by gibberellic acid(GA)metabolism and signaling.DELLA proteins,acting as central repressors of GA signaling,integrate...Plant height influences plant architecture,lodging resistance,and yield performance.It is modulated by gibberellic acid(GA)metabolism and signaling.DELLA proteins,acting as central repressors of GA signaling,integrate various environmental and hormonal signals to regulate plant growth and development in Arabidopsis.We examined the role of two DELLA proteins,GmRGAa and GmRGAb,in soybean plant height control.Knockout of these proteins led to longer internodes and increased plant height,primarily by increasing cell elongation.GmRGAs functioned under different light conditions,including red,blue,and far-red light,to repress plant height.Interaction studies revealed that GmRGAs interacted with the blue light receptor GmCRY1b.Consistent with this,GmCRY1b partially regulated plant height via GmRGAs.Additionally,DELLA proteins were found to stabilize the protein GmSTF1/2,a key positive regulator of photomorphogenesis.This stabilization led to increased transcription of GmGA2ox-7b and subsequent reduction in plant height.This study enhances our understanding of DELLA-mediated plant height control,offering Gmrgaab mutants for soybean structure and yield optimization.展开更多
Primary Budd-Chiari syndrome (BCS) is a spontaneously fatal disease characterized by an obstruction of the hepatic venous outflow tract due to thrombosis or a primary disease of the venous wall. The primary form of BC...Primary Budd-Chiari syndrome (BCS) is a spontaneously fatal disease characterized by an obstruction of the hepatic venous outflow tract due to thrombosis or a primary disease of the venous wall. The primary form of BCS is extremely rare. This is a disease mainly affecting young adults of both sexes. Clinical manifestations are variable;they can be asymptomatic, acute, or subacute but mostly chronic. Several causes have been identified, such as myeloproliferative syndrome, antiphospholipid syndrome, paroxysmal nocturnal hemoglobinuria, and inherited thrombotic disorders. Data on primary BCS in Sub-Saharan Africa is rare as most publications available are case reports. In these reports, the causes are unknown with poor prognosis in most cases often leading to patient death. We herein present a case report of a male patient diagnosed with a primary BCS at Yaoundé General Hospital (Cameroon) caused by a Protein C deficiency who presented with ascites decompensating liver cirrhosis. Treatment was based on anticoagulants, diuretics and laxatives administration. Two years after the diagnosis, the patient is alive with clinical and paraclinical improvement.展开更多
基金Supported by Youth Talents Project of Joint Fund of Hubei Health Commission,No.WJ2019H170and Xiaogan Natural Science Project,No.XGKJ2020010033。
文摘BACKGROUND The prevalence of metabolic dysfunction-associated fatty liver disease(MAFLD)is rapidly increasing,currently affecting approximately 25%of the global population.Liver fibrosis represents a crucial stage in the development of MAFLD,with advanced liver fibrosis elevating the risks of cirrhosis and hepatocellular carcinoma.Simple serum markers are less effective in diagnosing liver fibrosis compared to more complex markers.However,imaging techniques like transient elastography face limitations in clinical application due to equipment and technical constraints.Consequently,it is imperative to identify a straightforward yet effective method for assessing MAFLD-associated liver fibrosis.AIM To investigate the predictive value of angiopoietin-like protein 8(ANGPTL8)in MAFLD and its progression.METHODS We analyzed 160 patients who underwent abdominal ultrasonography in the Endocrinology Department,Xiaogan Central Hospital affiliated to Wuhan University of Science and Technology,during September 2021-July 2022.Using abdominal ultrasonography and MAFLD diagnostic criteria,among the 160 patients,80 patients(50%)were diagnosed with MAFLD.The MAFLD group was divided into the liver fibrosis group(n=23)and non-liver fibrosis group(n=57)by using a cut-off fibrosis-4 index≥1.45.Logistical regression was used to analyze the risk of MAFLD and the risk factors for its progression.Receiver operating characteristic curves were used to evaluate the predictive value of serum ANGPTL8 in MAFLD and its progression.RESULTS Compared with non-MAFLD patients,MAFLD patients had higher serum ANGPTL8 and triglyceride-glucose(TyG)index(both P<0.05).Serum ANGPTL8(r=0.576,P<0.001)and TyG index(r=0.473,P<0.001)were positively correlated with MAFLD.Serum ANGPTL8 was a risk factor for MAFLD[odds ratio(OR):1.123,95%confidence interval(CI):1.066-1.184,P<0.001).Serum ANGPTL8 and ANGPTL8+TyG index predicted MAFLD[area under the curve(AUC):0.832 and 0.886,respectively;both P<0.05].Compared with MAFLD patients without fibrosis,those with fibrosis had higher serum ANGPTL8 and TyG index(both P<0.05),and both parameters were positively correlated with MAFLD-associated fibrosis.Elevated serum ANGPTL8(OR:1.093,95%CI:1.044-1.144,P<0.001)and TyG index(OR:2.383,95%CI:1.199-4.736,P<0.013)were risk factors for MAFLD-associated fibrosis.Serum ANGPTL8 and ANGPTL8+TyG index predicted MAFLD-associated fibrosis(AUC:0.812 and 0.835,respectively;both P<0.05).CONCLUSION The serum levels of ANGPTL8 are elevated and positively correlated with MAFLD.They can serve as predictors for the risk of MAFLD and liver fibrosis,with the ANGPTL8+TyG index potentially exhibiting even higher predictive value.
文摘AIM:To confirm the role of angiopoietin-like protein 8(Angptl 8) in proliferative diabetic retinopathy(PDR).METHODS:The sera and aqueous humor of 10 PDR patients and 10 non-diabetic retinopathy(NDR) patients(idiopathic macular hole patients) were collected and the expression of Angptl 8 was detected by enzyme linked immune-sorbent assay(ELISA).Experimental diabetes mice model was induced with streptozotocin.The expression of glycosylated hemoglobin and Angptl 8 in sera was detected.Recombinant Angptl 8 was re-infused into wild type(WT) diabetic mice and spatial frequency threshold and contrast sensitivity were measured.In vitro retinal pigment epithelium(RPE) were stimulated by recombinant Angptl 8 for 24 h.MMT assay were used to detect cell proliferation.At the same time,q RT-PCR and Western blot was used to measure the expression of proliferation-related factors in PRE cells.RESULTS:The expression of Angptl 8 was markedly increased in the sera and aqueous humor of PDR patients(F=99.02,P〈0.0001 in sera;t=10.42,P〈0.0001 in aqueous).After successfully establishing the diabetic mice model,we found that glycosylated hemoglobin and Angptl 8 expression levels were increased.Re-infusion of recombinant Angptl 8 into WT diabetic mice could further decrease spatial frequency threshold and contrast sensitivity(P〈0.01).In vitro,RPE cells stimulated by recombinant Angptl 8could increase the relative absorbance of MMT assay(1.486±0.042 vs 1.000±0.104,P〈0.05) and proliferating cell nuclear antigen(PCNA) expression(0.55±0.01 vs 0.29±0.03,P〈0.05).The proliferative effect of Angptl 8 is mainly mediated by increasing the expression of proliferation-activating factors cyclin A1(4.973±0.205 vs 2.720±0.197,P〈0.05),cyclin F(5.690±0.219 vs 4.297±0.292,P〈0.05) and E2 F2(2.297±0.102 vs 1.750±0.146,P〈0.05),and reducing the expression of proliferation-inhibiting factors cdkn1(2.370±0.074 vs 3.317±0.135,P〈0.05) and cdkn2(4.793±0.065 vs 5.387±0.149,P〈0.05).CONCLUSION:The expression of Angptl 8 is increased in PDR,and the increased Angptl 8 can promote proliferation and increase proliferation-related factors.
基金the National Natural Science Foundation of China,No.81600446the Science and Technology of Traditional Chinese Medicine Foundation in Qingdao,No.2021-zyyz03the Science and technology development of Medicine and health Foundation in Shandong Province,China,No.202004010508.
文摘BACKGROUND Intestinal barrier breakdown,a frequent complication of intestinal ischemiareperfusion(I/R)including dysfunction and the structure changes of the intestine,is characterized by a loss of tight junction and enhanced permeability of the intestinal barrier and increased mortality.To develop effective and novel therapeutics is important for the improvement of outcome of patients with intestinal barrier deterioration.Recombinant human angiopoietin-like protein 4(rhANGPTL4)is reported to protect the blood-brain barrier when administered exogenously,and endogenous ANGPTL4 deficiency deteriorates radiationinduced intestinal injury.AIM To identify whether rhANGPTL4 may protect intestinal barrier breakdown induced by I/R.METHODS Intestinal I/R injury was elicited through clamping the superior mesenteric artery for 60 min followed by 240 min reperfusion.Intestinal epithelial(Caco-2)cells and human umbilical vein endothelial cells were challenged by hypoxia/reoxygenation to mimic I/R in vitro.RESULTS Indicators including fluorescein isothiocyanate-conjugated dextran(4 kilodaltons;FD-4)clearance,ratio of phosphorylated myosin light chain/total myosin light chain,myosin light chain kinase and loss of zonula occludens-1,claudin-2 and VE-cadherin were significantly increased after intestinal I/R or cell hypoxia/reoxygenation.rhANGPTL4 treatment significantly reversed these indicators,which were associated with inhibiting the inflammatory and oxidative cascade,excessive activation of cellular autophagy and apoptosis and improvement of survival rate.Similar results were observed in vitro when cells were challenged by hypoxia/reoxygenation,whereas rhANGPTL4 reversed the indicators close to normal level in Caco-2 cells and human umbilical vein endothelial cells significantly.CONCLUSION rhANGPTL4 can function as a protective agent against intestinal injury induced by intestinal I/R and improve survival via maintenance of intestinal barrier structure and functions.
基金the National Natural Science Foundation of China (31072167)the Key Project of Hunan Provincial Science & Technology Department, China(2009FJ1005)Innovation Project of Hunan Provincial Education Department (CX2009B153), China
文摘Pregnancy toxemia is a metabolic disorder of lipid and glucose. Recent investigations have found that angiopoietin-like protein 3 (ANGPTL3) can contribute to disorder of carbohydrate and lipid metabolism. The present study was conducted to investigate the change of ANGPTL3 expression during pregnancy toxemia, We firstly cloned the full-length cDNA of ANGPTL3 in Liuyang Black goats, revealing that goat ANGPTL3 had the typical structure of the angiopoietin-like family, and its mRNA was exclusively expressed in liver. Pregnancy toxemia of pregnant goat does with twins during late gestation was induced by being fasted for 72 h, and then they were recovered after 5 d ofrefeeding. Hepatic ANGPTL3 gene expression was significantly down-regulated concomitantly with decreased serum glucose concentration, elevated serum β-hydroxybutyrate and free fatty acid levels in pregnant toxemic goats, and these changes were reversed after refeeding. These results suggest ANGPTL3 may play a certain role in the development of pregnancy toxemia in goats.
文摘Recovery of functional beta cell mass offers a biological cure for type 1 diabetes. However, beta cell mass is difficult to regain once lost since the proliferation rate of beta cells after youth is very low. Angiopoietin like-protein 8 (ANGPTL8), a peptide that has a role in the regulation of lipoprotein lipase activity, was reported to increase beta cell proliferation in mice in 2013. Subsequent studies of human ANGPTL8 for short term (3 to 8 days) in non-diabetic mice showed little or no increase in beta cell proliferation. Here, we examined the effect of ANGPTL8 on glucose homeostasis in models that have not been examined previously. We expressed mouse ANGPTL8 using adenovirus in 2 mouse models of diabetes (streptozotocin and Non-Obese Diabetic (NOD) mice) over 2 weeks. Also, we tested ANGPTL8 in NOD mice deficient in leukocyte 12-lipoxygenase (12LO), an enzyme that contributes to insulitis and loss of beta cell function in NOD, in an effort to determine whether 12LO deficiency alters the response to ANGPTL8. Adenovirus-mediated expression of ANGPTL8 lowered blood glucose levels in streptozotocin treated mice without an increase in beta cell proliferation or serum insulin concentration. While ANGPTL8 did not reverse hyperglycemia in overtly hyperglycemic NOD mice or alter glucose homeostasis of non-diabetic NOD mice, ANGPTL8 reduced blood glucose levels in 12LOKO NOD mice. However, the lower glucose levels in 12LOKO NOD were not associated with higher serum insulin levels or beta cell proliferation. In summary, while mouse ANGPTL8 does not increase beta cell proliferation in NOD mice or streptozotocin treated mice in agreement with studies in non-diabetic mice, it lowers blood glucose levels in multiple low-dose streptozotocin induced diabetes and 12LO deficiency indicating that host factors influence the impact of ANGPTL8 on glucose homeostasis.
文摘Three members of the angiopoietin-like(ANGPTL) protein family-ANGPTL3, ANGPTL4 and ANGPTL8-are important regulators of plasma lipoproteins. They inhibit the enzyme lipoprotein lipase, which plays a key role in the intravascular lipolysis of triglycerides present in some lipoprotein classes. This review focuses on the role of ANGPTL3 as emerged from the study of genetic variants of Angptl3 gene in mice and humans. Both loss of function genetic variants and inactivation of Angptl3 gene in mice are associated with a marked reduction of plasma levels of triglyceride and cholesterol and an increased activity of lipoprotein lipase and endothelial lipase. In humans with ANGPTL3 deficiency, caused by homozygous loss of function(LOF) variants of Angptl3 gene, the levels of all plasma lipoproteins are greatly reduced. This plasma lipid disorder referred to as familial combined hypolipidemia(FHBL2) does not appear to be associated with distinct pathological manifestations. Heterozygous carriers of LOF variants have reduced plasma levels of total cholesterol and triglycerides and are at lower risk of developing atherosclerotic cardiovascular disease, as compared to non-carriers. These observations have paved the way to the development of strategies to reduce the plasma level of atherogenic lipoproteins in man by the inactivation of ANGPTL3, using either a specific monoclonal antibody or anti-sense oligonucleotides.
基金This study was supported by the grant of the National Natural Science Foundation of China (No. 81471427).
文摘Background:A recent study reported a positive association between elevated serum levels of angiopoietin-like protein 2 (ANGPTL2) and the development of type 2 diabetes in a general population.However,the relationship of serum ANGPTL2 levels with the risk of developing gestational diabetes mellitus (GDM) has not been reported to date.The aim of this study was to investigate the change of maternal serum ANGPTL2 concentrations in the first trimester of pregnancy and to determine whether ANGPTL2 is a biomarker for subsequent GDM development.Methods:We conducted a prospective,nested case-control study in a pregnancy cohort.First-trimester ANGPTL2 levels were measured using a high-resolution assay in 89 women who subsequently developed GDM and in a random sample of 177 women who remained euglycemic throughout the pregnancy.Median ANGPTL2 levels were compared using Mann-Whitney U-test.Logistic regression was used to compute unadjusted and multivariable-adjusted odds ratios for developing GDM among ANGPTL2 quartiles.Results:The serum levels of ANGPTL2 was higher in women with GDM than that in women without GDM (3.06 [2.59,3.65] ng/ml vs.2.46 [2.05,2.96] ng/ml,P =0.003).Fasting blood glucose was higher in women with GDM than that in women without GDM (5.0 ± 0.9 mmol/L vs.4.4 ± 0.6 mmol/L,P 〈 0.001).Glucose challenge test showed that the blood glucose was higher in women with GDM than that in women without GDM (9.1 ± 3.5 mmol/L vs.6.2 ± 1.2 mmol/L,P 〈 0.001).A multivariate model adjusted for baseline characteristics,medical complications,and gestational characteristics revealed that the risk of developing GDM among women in Q4 compared with Q1 was 2.90-fold more likely to develop GDM later in pregnancy.Conclusions:At 1 1-13 weeks in pregnancies that develop GDM,the serum concentration of ANGPTL2 is increased,and it can be combined with maternal factors to provide effective early screening for GDM.
基金supported by Technology Development Program for Agriculture and Forestry No.610002-3,Ministry for Food,Agriculture,Forestry and Fisheries,Republic of Korea。
文摘Recent advances in hematopoietic stem cells(HSCs)expansion by growth factors including angiopoietin-like proteins(Angptls)have opened up the possibility to use HSCs in regenerative medicine.However,the unavailability of true in vitro HSCs expansion by these growth factors has limited the understanding of the cellular and molecular mechanism of HSCs expansion.Here,we report the functional role of mouse Angptls 1,2,3,4,6 and 7 and growth factors SCF,TPO,IGF-2 and FGF-1 on purified mouse bone-marrow(BM)Lineage-Sca-1+(Lin-Sca-1+)HSCs.The recombinant retroviral transduced-CHO-S cells that secrete Angptls in serum-free medium were used alone or in combination with growth factors(SCF,TPO,IGF-2 and FGF-1).None of the Angptls stimu-lated HSC proliferation,enhanced or inhibited HSCs colony formation,but they did support the survival of HSCs.By contrast,any of the six Angptls together with saturating levels of growth factors dramatically stimulated a 3-to 4.5-fold net expansion of HSCs compared to stimulation with a combination of those growth factors alone.These findings lead to an understanding of the basic function of Angptls on signaling pathways for the survival as well as expansion of HSCs in the bone marrow niche.
基金This study was supported by the National Natural Science Foundation of China(No.81400716)the Zhejiang Provincial Natural Science Foundation of China(No.LY20H050007,LY19H050005)Medical Health Science and Technology Project of Zhejiang Provincial Health Commission(No.2020383770).
文摘Podocyte injury is an important cause of proteinuria.Angiopoietin-like protein 4(Angptl4)is a secreted glycoprotein and has a role in proteinuria.However,the exact role of Angptl4 in podocyte injury and its upstream regulators has not been clarified.In this study,we used lipopolysaccharide(LPS)-induced mice and cultured podocytes as podocyte injury models.Our results indicated that LPS increased the expression of podocyte Angptl4 in vivo and in vitro.Furthermore,we showed that Angptl4 overexpression deteriorated LPS-induced podocyte injury by inducing podocyte cytoskeleton rearrangement,reducing the expression of synaptopodin while Angptl4 knockdown alleviated LPS-induced podocyte injury.In addition,we found that inhibitors and siRNA targeting TLR4/MyD88/NF-κB signaling inhibited the upregulation of Angptl4 in LPS-induced podocytes.Moreover,inhibitors and siRNA targeting calcineurin/NFAT signaling also relieved LPS-induced Angptl4 expression and podocyte injury in vivo and in vitro.Taken together,our study has elucidated that both of the TLR4/MyD88/NF-κB and calcineurin/NFAT signaling mediate the upregulation of Angptl4 in LPS-induced podocytes,which has important implications for further understanding the molecular mechanism of LPS-induced podocyte injury.
基金financially supported by the National Natural Science Foundation of China(U2004104)the Natural Science Foundation of Henan Province(202300410080)+2 种基金the Key Project of Henan Education Committee(21A310005)the Internal Fund of Hebei University of Economics and Business(2020ZD10)the Postgraduate“Talent Program”of Henan University(SYL20060187 and SYL20060189)。
文摘In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the proliferation of splenocytes in response to mitogens.The splenocytes and mesenteric lymphocytes activated by T-cell mitogens(Con A and anti-CD3/CD28 antibodies)released high levels of IL-2 but low levels of IFN-γand IL-17A.The release of IL-4 was unaffected by MRJPs.Additionally,splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1βand IL-6,two pro-inflammatory cytokines.The production of IL-1β,IL-6,and IFN-γwas negatively associated with estrogen levels,which were higher in the MRJP-treated animals than in the control group.Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice.Additionally,the LEf Se analysis identified biomarkers in the MRJP-treated mice,including Prevotella,Bacillales,Enterobacteriales,Gammaproteobacteria,Candidatus_Arthromitus,and Shigella.Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.
基金in part supported by the National Natural Science Foundation of China,Nos.30560042,81160161,81360198,and 82160255Education Department of Jiangxi Province,Nos.GJJ13198 and GJJ170021+1 种基金Jiangxi Provincial Department of Science and Technology,No.20192BAB205043Health and Family Planning Commission of Jiangxi Province,Nos.20181019 and 202210002(all to RX)。
文摘The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory regions.However,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the disease.The disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized countries.The TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral sclerosis.This review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).
基金supported by the National Natural Science Foundation of China (31901462 and 31671613).
文摘Bacillus thuringiensis(Bt)cotton production is challenged by two main problems,i.e.,the low concentration of Bt protein at the boll setting stage and the lowest insect resistance in bolls among all the cotton plant’s organs.Therefore,increasing the Bt protein concentration at the boll stage,especially in bolls,has become the main goal for increasing insect resistance in cotton.In this study,two protein degradation inhibitors(ethylene diamine tetra acetic acid(EDTA)and leupeptin)were sprayed on the bolls,subtending leaves,and whole cotton plants at the peak flowering stage of two Bt cultivars(medium maturation Sikang 1(SK1))and early maturation Zhongmian 425(ZM425)in 2019 and 2020.The Bt protein content and protein degradation metabolism were assessed.The results showed that the Bt protein concentrations were enhanced by 21.3 to 38.8%and 25.0 to 38.6%in the treated bolls of SK1 and ZM425 respectively,while they were decreased in the subtending leaves of these treated bolls.In the treated leaves,the Bt protein concentrations increased by 7.6 to 23.5%and 11.2 to 14.9%in SK1 and ZM425,respectively.The combined application of EDTA and leupeptin to the whole cotton plant increased the Bt protein concentrations in both bolls and subtending leaves.The Bt protein concentrations in bolls were higher,increasing by 22.5 to 31.0%and 19.6 to 32.5%for SK1 and ZM425,respectively.The organs treated with EDTA or/and leupeptin showed reduced free amino acid contents,protease and peptidase activities and significant enhancements in soluble protein contents.These results indicated that inhibiting protein degradation could improve the protein content,thus increasing the Bt protein concentrations in the bolls or/and leaves of cotton plants.Therefore,the increase in the Bt protein concentration without yield reduction suggested that these two protein degradation inhibitors may be applicable for improving insect resistance in cotton production.
基金supported by the National Natural Science Foundation of China(Grant Nos.12174322 to HC and 12204124 to ZG)111 Project(Grant No.B16029)+1 种基金the Graduate Scientific Research Foundation of Wenzhou University(Grant No.3162023003034 to JH)research grant from Wenzhou Institute。
文摘Single-molecule magnetic tweezers(MTs) have revealed multiple transition barriers along the unfolding pathway of several two-state proteins, such as GB1 and Csp. In this study, we utilized MTs to measure the force-dependent folding and unfolding rates of both protein L(PLWT) and its Y47W mutant(PLY47W) where the mutation point is not at the force-bearing β-strands. The measurements were conducted within a force range of 3–120 pN. Notably, the unfolding rates of both PLWT and PWY47W exhibit distinct force sensitivities below 50 pN and above 60 pN, implying a two-barrier free energy landscape. Both PLWT and PLY47W share the same force-dependent folding rate and the same transition barriers,but the unfolding rate of PLY47W is faster than that of PLWT. Our finding demonstrates that the residue outside of the force-bearing region will also affect the force-induced unfolding dynamics.
基金Project supported by the Gansu Province Industrial Support Plan (Grant No.2023CYZC-25)the Natural Science Foundation of Gansu Province (Grant No.23JRRA770)the National Natural Science Foundation of China (Grant No.62162040)。
文摘Essential proteins are inseparable in cell growth and survival. The study of essential proteins is important for understanding cellular functions and biological mechanisms. Therefore, various computable methods have been proposed to identify essential proteins. Unfortunately, most methods based on network topology only consider the interactions between a protein and its neighboring proteins, and not the interactions with its higher-order distance proteins. In this paper, we propose the DSEP algorithm in which we integrated network topology properties and subcellular localization information in protein–protein interaction(PPI) networks based on four-order distances, and then used random walks to identify the essential proteins. We also propose a method to calculate the finite-order distance of the network, which can greatly reduce the time complexity of our algorithm. We conducted a comprehensive comparison of the DSEP algorithm with 11 existing classical algorithms to identify essential proteins with multiple evaluation methods. The results show that DSEP is superior to these 11 methods.
基金supported through the Faculty of Medicine and Surgery Award 2021 University of Malta(awarded to K.F).
文摘Background:Colorectal cancer(CRC)is one of the most frequently diagnosed cancers.In many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil(5-FU).The epithelial-to-mesenchymal transition(EMT)and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many cancers.This study looked into the effect of 5-FU dose escalation on EMT and protein methylation in CRC.Materials and Methods:HCT-116,Caco-2,and DLD-1 CRC cell lines were exposed to dose escalation treatment of 5-FU.The motility and invasive potentials of the cells before and after treatment with 5-FU were investigated through wound healing and invasion assays.This was followed by aWestern blot which analyzed the protein expressions of the epithelial marker E-cadherin,mesenchymal marker vimentin,and the EMT transcription factor(EMTTF),the snail family transcriptional repressor 1(Snail)in the parental and desensitized cells.Western blotting was also conducted to study the protein expressions of the protein methyltransferases(PMTs),Euchromatic histone lysine methyltransferase 2(EHMT2/G9A),protein arginine methyltransferase(PRMT5),and SET domain containing 7/9(SETD7/9)along with the global lysine and arginine methylation profiles.Results:The dose escalation method generated 5-FU desensitized CRC cells with distinct morphological features and increased tolerance to high doses of 5-FU.The 5-FU desensitized cells experienced a decrease in migration and invasion when compared to the parental cells.This was reflected in the observed reduction in E-cadherin,vimentin,and Snail in the desensitized cell lines.Additionally,the protein expressions of EHMT2/G9A,PRMT5,and SETD7/9 also decreased in the desensitized cells and global protein lysine and arginine methylation became dysregulated with 5-FU treatment.Conclusion:This study showed that continuous,dose-escalation treatment of 5-FU in CRC cells generated 5-FU desensitized cancer cells that seemed to be less aggressive than parental cells.
文摘Cowpea (Vigna unguiculata L. Walp) is a multi-purpose legume with high quality protein for human consumption and livestock. The objective of this work was to develop near-infrared spectroscopy (NIRS) prediction models to estimate protein content in cowpea. A total of 116 cowpea breeding lines with a wide range of protein contents (19.28 % to 32.04%) were selected to build the model using whole seed and ground seed samples. Partial least-squares discriminant analysis (PLS-DA) regression technique with different pre-treatments (derivatives, standard normal variate, and multiplicative scatter correction) were carried out to develop the protein prediction model. Results showed: 1) spectral plots of both the whole seed and ground seed showed higher spectral scatter at higher wavelengths (>1450 nm), 2) data pre-processing affects prediction accuracy for bot whole seed and ground seed samples, 3) prediction using ground seed samples (0.64 R<sup>2</sup> 0.85) is better than the whole seed (0.33 R<sup>2</sup> 0.78), and 4) the data pre-processing second derivative with standard normal variate has the best prediction (R<sup>2</sup>_whole seed = 0.78, R<sup>2</sup>_ground seed = 0.85). The results will be of interest in cowpea breeding programs aimed at improving total seed protein content.
基金supported by the National Key Research and Development Program of China (2021YFD2100402)the National Natural Science Foundation of China (81903275)the Fund of the Cultivation Project of Double First-Class Disciplines of Food Science and Engineering,Beijing Technology&Business University (BTBUYXTD202203)。
文摘Globally,the prevalence of anxiety and depression has reached epidemic proportions.Food-derived protein hydrolysates and peptides delivered through dietary supplementation can avoid the negative risks associated with traditional pharmaceuticals while delivering superior anxiolytic and antidepressant effects.This review summarizes current research on food-derived anxiolytic and antidepressant protein hydrolysates and peptides,and subsequently analyses their physicochemical characteristics and elaborates on their mechanisms.The aim of this work is to contribute to the in-depth study and provide a theoretical foundation for the development of related products to better serve patients with anxiety and depression.
文摘Background: Preeclampsia is reported to complicate 2% - 8% of pregnancies globally and is an important cause of maternal and perinatal morbidity and mortality. The aetiology and pathogenesis are still poorly understood and substantial improvement has not been made in the prediction, prevention and treatment of the disease. Objective: To compare the frequency of activated protein C resistance (APC-R) in patients with pre-eclampsia to that of normotensive pregnant women and to determine the correlation between activated protein ratio (APC-ratio) and the severity of pre-eclampsia. Methodology: A cross-sectional study was carried out in 100 pre-eclamptic patients and 100 normotensive pregnant controls. The APC-ratio was determined using the modified activated partial thromboplastin time. Study participants with APC-ratio of less than 2.0 were defined as having APC-R. Data was analyzed using SPSS version 22.0. Results: Mean APC-ratio was significantly lower in pre-eclamptics (2.89 ± 1.70) compared to normotensive pregnant women (3.57 ± 1.06) (p = 0.0008) and the levels were also higher in mild (2.95 ± 1.15) compared to severe pre-eclamptics (2.62 ± 1.14). The frequency of APC-R was 26% among women with pre-eclampsia compared to 4% among normotensive controls (p = 0.000). Among 100 pre-eclamptic women 7 (21.2%) out of 33 with mild pre–eclampsia had APC-R, while 19 (28.4%) out of 67 with severe pre-eclampsia had APC-R. APC-ratio had a significant negative correlation with mean arterial blood pressure (r = −0.324;p = 0.000) and proteinuria (r = −0.379;p = 0.000) among study participants. Conclusion: The frequency of activated protein c resistance is significantly higher in pre-eclamptics compared to normotensive pregnant women and this is more pronounced in those with severe pre-eclampsia compared with those with mild disease. APC-R may therefore be used as a marker of severity in the disease.
基金supported by the Sci-Tech Innovation 2030(2022ZD0400701-2)Agricultural Science and Technology Innovation Program of CAAS+1 种基金the National Natural Science Foundation of China(31871705)the Central Public-Interest Scientific Institution Basal Research Fund。
文摘Plant height influences plant architecture,lodging resistance,and yield performance.It is modulated by gibberellic acid(GA)metabolism and signaling.DELLA proteins,acting as central repressors of GA signaling,integrate various environmental and hormonal signals to regulate plant growth and development in Arabidopsis.We examined the role of two DELLA proteins,GmRGAa and GmRGAb,in soybean plant height control.Knockout of these proteins led to longer internodes and increased plant height,primarily by increasing cell elongation.GmRGAs functioned under different light conditions,including red,blue,and far-red light,to repress plant height.Interaction studies revealed that GmRGAs interacted with the blue light receptor GmCRY1b.Consistent with this,GmCRY1b partially regulated plant height via GmRGAs.Additionally,DELLA proteins were found to stabilize the protein GmSTF1/2,a key positive regulator of photomorphogenesis.This stabilization led to increased transcription of GmGA2ox-7b and subsequent reduction in plant height.This study enhances our understanding of DELLA-mediated plant height control,offering Gmrgaab mutants for soybean structure and yield optimization.
文摘Primary Budd-Chiari syndrome (BCS) is a spontaneously fatal disease characterized by an obstruction of the hepatic venous outflow tract due to thrombosis or a primary disease of the venous wall. The primary form of BCS is extremely rare. This is a disease mainly affecting young adults of both sexes. Clinical manifestations are variable;they can be asymptomatic, acute, or subacute but mostly chronic. Several causes have been identified, such as myeloproliferative syndrome, antiphospholipid syndrome, paroxysmal nocturnal hemoglobinuria, and inherited thrombotic disorders. Data on primary BCS in Sub-Saharan Africa is rare as most publications available are case reports. In these reports, the causes are unknown with poor prognosis in most cases often leading to patient death. We herein present a case report of a male patient diagnosed with a primary BCS at Yaoundé General Hospital (Cameroon) caused by a Protein C deficiency who presented with ascites decompensating liver cirrhosis. Treatment was based on anticoagulants, diuretics and laxatives administration. Two years after the diagnosis, the patient is alive with clinical and paraclinical improvement.