Objective Numerous studies have described both motor defects and cognitive impairments in several strains of rodents following 3-nitropropionic acid （3-NP） intoxication. In the present study, we investigated spatial...Objective Numerous studies have described both motor defects and cognitive impairments in several strains of rodents following 3-nitropropionic acid （3-NP） intoxication. In the present study, we investigated spatial recognition memory in Kunming mice that just recovered from motor defects induced by 3-NP. Methods Mouse model was made by systemic subacute 3-NP treatment, and spatial recognition memory was measured through the Y-maze Test, a simple two-trial recognition test. Results （1） On day 15 following 3-NP treatment, affected Kunming mice did not show motor defects in the Rotarod test and presented normal gait again. （2） In the following Y-maze test after lh interval, the percentage （90.0%） of mice showing novel ann preference in 3-NP treatment group was significantly higher than the random chance level （50%）, although it was only slightly higher than that （83.3%） in control group. On day 45 after 3-NP treatment, mice failed to choose unfamiliar novel arm as first choice, and the same occured in the control group. （3） For both post-intoxicated （on day 15 and day 45 following 3-NP treatment） and control groups, the duration in the novel ann and the frequency of entering it, were longer and higher compared with familiar start and other arms. For these mice that recently recovered from motor defects following 3-NP intoxication, no spatial memory deficits were observed through Y-maze Test. Conclusion Kunming mice used in our assays might possess resistance to cognitive impairment induced by 3-NP, which is consistent with previous findings in Swiss EPM-M1 mice.展开更多
Objective Striatum may be involved in depressive disorders according to the neuroimaging analysis and clinical data. However, no animal model at present supported the possible role of striatum in the pathogenesis of d...Objective Striatum may be involved in depressive disorders according to the neuroimaging analysis and clinical data. However, no animal model at present supported the possible role of striatum in the pathogenesis of depression. In the present study, we have investigated the depressive-like behavior in mice recently intoxicated with 3-nitropropionic acid （3- NP）, a widely known toxin that selectively damages the striatum in the brain. Methods Mouse model was made with subacute systemic 3-NP treatment, and the depressive-like behavior was measured using the duration of immobility during forced swimming test （FST）. Results When the mice at day 15 post-intoxication just totally recovered from motor deficits, the duration of immobility in FST was significantly longer than that in controls. The depressive-like behavior was not due to the fatigue or general sickness following 3-NP intoxication and could be reversed by the antidepressant, desipramine hydrochloride. In two successive FST in 24 h interval, the depressive-like behavior could be observed again in subsequent FST （at day 16 post-intoxication）, and the mice presented a normal ＂learned helplessness＂. Conclusion A novel depression animal model could be established in mice during the initial period of recovery from 3-NP intoxication. The depression-like behavior might occur independently without involvement of cognitive defects, and the striatal lesions may underlie the depression-like behavior attributable to 3-NP intoxication.展开更多
Summary： To examine the changes in erythropoietin （Epo） protein and its mRNA expression in rat brain subjected to focal ischemia and possible mechanism of the preconditioning of mitochondrial toxin 3-nitropropionic...Summary： To examine the changes in erythropoietin （Epo） protein and its mRNA expression in rat brain subjected to focal ischemia and possible mechanism of the preconditioning of mitochondrial toxin 3-nitropropionic acid （3-NPA）, rats were administrated either vehicle or 3-NPA at a dose of 20 mg/kg, intraperitoneally （ip）, 3 days prior to a 2-h middle cerebral artery occlusion followed by 24- h reperfusion. Infarct volumes were measured by using 2, 3, 5 triphenylte trazolinm chloride （TTC） staining, and Epo protein and its mRNA levels were assessed by immunohistochemistry and reverse transcriptase polymerase chain reaction （RT-PCR）, respectively. Our results showed that after reperfusion, Epo was found to be expressed extensively in the rat brain. It was most apparent in the basal nuclei and hippocampus, and was, to some extent, present in cortex. Preconditioning with 3-NPA caused a reduction in infarct volume. The expression of both Epo protein and mRNA increased significantly in the different brain areas in the 3-NPA pretreated group as compared with the non-pretreated ischemia model group. These results suggested that preconditioning with low dose 3-NPA could induce ischemic tolerance and neuro-protective effects by increasing the Epo expression in the ischemic and ischemia-related areas.展开更多
Objective The aim of the present study was to determine the changes in the mRNA levels of neurotrophins and their receptors in the striatal tissue of mice treated with 3-nitropropionic acid （3-NP）. Methods At 1 and ...Objective The aim of the present study was to determine the changes in the mRNA levels of neurotrophins and their receptors in the striatal tissue of mice treated with 3-nitropropionic acid （3-NP）. Methods At 1 and 48 h after the last drug administration, the mRNA expression of nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4/5 as well as their receptors p75, TrkA, TrkB and TrkC, was evaluated using semi-quantitative （semi- Q） and real-time RT-PCR. β-actin mRNA and ribosomal 18S （18S rRNA） were tested as internal controls. Results 3-NP treatment did not affect mRNA expression of all neurotrophins and their respective receptors equally. Also, differences in neurotrophin and receptor mRNA expression were observed between semi-Q and real-time RT-PCR. Real-time RT-PCR was more accurate in evaluating the mRNA expression of the neurotrophins than semi-Q, and 18S rRNA was more reliable than β-actin as an internal control. Conclusion Neurotrophins and their receptors expression is differentially affected by neuronal damage produced by inhibition of mitochondrial respiration with 3-NP treatment in low, sub-chronic doses in vivo.展开更多
The involvement of apoptosis in mitochondrial toxin 3 nitropropionic acid (3 NPA) induced ischemic tolerance to transient focal cerebral ischemia in rats and the mechanism was investigated. 3 NPA at a dose of 20 m...The involvement of apoptosis in mitochondrial toxin 3 nitropropionic acid (3 NPA) induced ischemic tolerance to transient focal cerebral ischemia in rats and the mechanism was investigated. 3 NPA at a dose of 20 mg/kg or vehicle control was intraperitoneally into the rats. Three days later, rats were exposed to 2 h of middle cerebral artery occlusion followed by 24 h of reperfusion. Infarct volumes were assessed by 2,3,5 triphenyltetrazolinm chloride (TTC) staining 24 h after reperfusion. Neural cell apoptosis in cerebral ischemic penumbra was detected by terminal deoxynucleotidyl transferase mediated dUTP biotin in situ nick end labeling (TUNEL) and flow cytometry methods (FCM). The results showed that as compared to the vehicle treated group, pretreatment with 3 NPA could reduce the infarct volume by 23.3 % and decrease the number of TUNEL positive neural cells and apoptotic percentage by 47 % ( P< 0.05) and 44.9 % ( P< 0 01), respectively. It was concluded that the development of 3 NPA induced ischemic tolerance in brain might be related to the decreases in neural cell apoptosis.展开更多
The current study investigates the role of oxidative stress and calcium homeostasis in the development of selective striatal lesions in metabolic impairment model caused by 3-nitropropionic acid (3NP). In this report,...The current study investigates the role of oxidative stress and calcium homeostasis in the development of selective striatal lesions in metabolic impairment model caused by 3-nitropropionic acid (3NP). In this report, we examined the distribution of oxidative stress markers and the production of mitochondrial reactive oxygen species in the presence of 3NP in male Sprague-Dawley rats. Protein oxidation was assessed using 3-nitrotyrosine immunoreactivity, while DNA oxidative damage was evaluated by poly (ADP-ribose) polymerase-1 activity. The Reactive Oxygen Species (ROS) production was determined in isolated mitochondrial from striatum and cerebellum of two age groups following 3NP and variable calcium concentration. The results demonstrate that increased 3-nitro-tyrosine level is the most robust in the striatum and the least evident in the cerebellum following 4 days of 3NP treatment. No significant change in the levels of poly ADP-ribosylated proteins was observed, likely due to a rapid PARP-1 cleavage as detected by the appearance of 50 kDa necrotic fragment. In mitochondrial isolates, there was no immediate increase in mitochondrial ROS following 3NP in either striatum or cerebellum;however, calcium addition resulted in a concentration dependent increase in reactive oxygen species in striatal mitochondria of the older animals. These results suggest that in aging, mitochondria become more susceptible to the generation of ROS in conditions that cause a concurrent compromised in mitochondrial calcium concentration. This finding implicates mitochondria dysfunction as a key cellular target in pathological states that are associated with metabolic impairment. The results also reinforce the notion that mitochondrial function in the striatum and cerebellum respond differently to the aging process, which may explain the variable regional vulnerability in 3NP model.展开更多
Chrysomelina beetlesstore 3-nitropropionic acid in form of a pretoxin,isoxazolin-5-one glucoside-conjugated ester,to protect themselves against predators.Here we identified a cytochrome P450 monooxygenase,CYP347W1,to ...Chrysomelina beetlesstore 3-nitropropionic acid in form of a pretoxin,isoxazolin-5-one glucoside-conjugated ester,to protect themselves against predators.Here we identified a cytochrome P450 monooxygenase,CYP347W1,to be involved in the production of the 3-nitropropionic acid moiety of the isoxazolin-5-one glucoside ester.Knocking down CYP347W1 led to a significant depletion in the concentration of the isoxazolin-5-one glucoside ester and an increase in the concentration of the isoxazolin-5-one glucoside in the larval hemolymph.Enzyme assays with the heterologously expressed CYP347W1 showed freeβ-alanine was not the direct substrate.Homology modeling indicated thatβ-alanine-CoA ester can fit into CYP347W1’s active site.Furthermore,we proved that Phaedon cochleariae eggs are not able to de novo synthesize 3-NPA,although both isoxazolin-5-one glucoside and its 3-NPA-conjugated ester are present in the eggs.These results provide direct evidence for the involvement of CYP347W1 in the biosynthesis of a P.cochleariae chemical defense compound.展开更多
Background:Recent studies have shown glycerolipid metabolism played an essential role in multiple tumors,however,its function in osteosarcoma is unclear.This study aimed to explore the role of glycerolipid metabolism ...Background:Recent studies have shown glycerolipid metabolism played an essential role in multiple tumors,however,its function in osteosarcoma is unclear.This study aimed to explore the role of glycerolipid metabolism in osteosarcoma.Methods:We conducted bioinformatics analysis using data from the Therapeutically Applicable Research to Generate Effective Treatments(TARGET)database and single-cell RNA sequencing.Least Absolute Shrinkage and Selection Operator(LASSO)regression was used to identify the Glycerolipid metabolism-related genes associated with the clinical outcome of osteosarcoma.Tumor-associated macrophages(TAMs)and their interactions with immune cells were examined through single-cell analysis and co-culture experiments.Virtual screening was employed to identify the potential lysophosphatidic acid receptor 6(LPAR6)inhibitors.Results:Glycerolipid metabolism-related genes 1-acylglycerol-3-phosphate O-acyltransferase 3(AGPAT3)and aldehyde dehydrogenase 7 family member A1(ALDH7A1)were identified as key prognostic genes in osteosarcoma,with high AGPAT3 expression correlating with improved survival.Single-cell analysis revealed that AGPAT3 expression is associated with tumor immune microenvironment,particularly with TAMs.Knockdown of AGPAT3 in osteosarcoma cells resulted in elevated lysophosphatidic acid(LPA)levels,which regulated the immune environment,inhibiting cytotoxic T cell function through TAMs’LPAR6 signaling.LPAR6 signaling in TAMs mediates immune regulation through cytokine secretion,including interleukin-6(IL-6)and interleukin-10(IL-10).Further drug virtual screening identified Dutasteride as a potential inhibitor of LPAR6.Conclusion:AGPAT3 is an important gene related to the prognosis of osteosarcoma.Its ability to modulate LPA signaling and TAM activity offers promising therapeutic opportunities for improving osteosarcoma treatment,particularly in immunotherapy contexts.展开更多
In order to reveal the effect of 2-hydroxy-3-naphthyl hydroxamic acid(H205)on the flotation behavior and action mechanism of bastnaesite,single-mineral flotation experiments of bastnaesite were conducted.The flotation...In order to reveal the effect of 2-hydroxy-3-naphthyl hydroxamic acid(H205)on the flotation behavior and action mechanism of bastnaesite,single-mineral flotation experiments of bastnaesite were conducted.The flotation recovery of bastnaesites can be achieved more than 90%when the aeration rate is 40 mL/min,the rotational speed is 200 r/min,the H205 dosage is 120 mg/L,and the pulp pH ranges from 7 to 9.The action mechanism of H205 on the surface of bastnaesite was studied by simultaneous thermogravimetry and differential scanning calorimetry(TG-DSC),Zeta potential measurements,Fourier transform-infrared spectra(FT-IR)and X-ray photoelectron spectroscopy(XPS).These analysis results show that under suitable flotation conditions,H205 has an obvious adsorption phenomenon on the surface of bastnaesite.The adsorption involves electrostatic interactions and chemical interactions,namely H205 has a strong collecting ability of bastnaesite due to the synergism of electrostatic adsorption and chemical adsorption.This study systematically reveals the flotation behavior and adsorption mechanism of H205 on the surface of bastnaesite,and provides useful theoretical guidance for efficient flotation separation of bastnaesite.展开更多
Photocatalysis has emerged as an effective approach to sustainably convert biomass into value-added products.CoSe_(2)is a promising nonprecious,efficient cocatalyst for photooxidation,which can facilitate the separati...Photocatalysis has emerged as an effective approach to sustainably convert biomass into value-added products.CoSe_(2)is a promising nonprecious,efficient cocatalyst for photooxidation,which can facilitate the separation of photogenerated electron–holes,increase the reaction rates,and enhance photocatalytic efficiency.In this work,we synthesized a stable and efficient photocatalysis system of CoSe_(2)/g-C_(3)N_(4)through attaching CoSe_(2)on g-C_(3)N_(4)sheets,with a yield of 50.12%for the selective photooxidation of xylose to xylonic acid.Under light illumination,the photogenerated electrons were prone to migrating from g-C_(3)N_(4)to CoSe_(2)due to the higher work function of CoSe_(2),resulting in the accelerated separation of photogenerated electron–holes and the promoted photooxidation.Herein,this study reveals the unique function of CoSe_(2),which can significantly promote oxygen adsorption,work as an electron sink and accelerate the generation of ·O_(2)^(-),thereby improving the selectivity toward xylonic acid over other by-products.This work provides useful insights into the design of selective photocatalysts by engineering g-C_(3)N_(4)for biomass high-value utilization.展开更多
Background:Gallic acid(GA),a plant-derived polyphenol,possesses diverse biological functions such as reducing inflammation and against tumors.Currently,the influence of GA on the resistance of esophageal squamous cell...Background:Gallic acid(GA),a plant-derived polyphenol,possesses diverse biological functions such as reducing inflammation and against tumors.Currently,the influence of GA on the resistance of esophageal squamous cell carcinoma(ESCC)cells to cisplatin(DDP)is not well understood.Methods:Cell counting kit-8 assay examined how GA affected KYSE30 and TE-1 cell viability.5-Ethynyl-2′-deoxyuridine and TdT-mediated dUTP Nick-End labeling staining detected cell proliferation and apoptosis.Clone formation assay,flow cytometry,Carboxyfluorescein diacetate succinimidyl ester fluorescent probes,and Transwell assay determined cell biological properties,and 2′,7′-Dichlorofluorescin diacetate(DCFH-DA)fluorescent probes detected oxidative stress levels.Signal transducer and activator of transcription 3(STAT3)/Notch pathway protein levels after GA and/or Interleukin-6(IL-6)intervention were examined through Western blot.Furthermore,a model for subcutaneous graft tumors was established in nude mice.Results:GA exerted suppressive effects on cell proliferation,and caused apoptosis of KYSE30 and TE-1 cells.IL-6 intervention activated the STAT3/Notch pathway and promoted the malignant biological properties of ESCC cells.In contrast,GA attenuated the effects of IL-6,while STAT3 or Notch inhibitor further enhanced the effects of GA,suggesting that GA inhibited the IL-6/STAT3/Notch pathway.Not only that,GA promoted oxidative stress and enhanced cell sensitivity to DDP both in vitro and in vivo.Conclusion:GA suppresses the malignant progression of ESCC and enhances cell sensitivity to DDP by hindering the IL-6/STAT3/Notch pathway.展开更多
BACKGROUND Gastric cancer(GC)is a type of cancer which causes high cancer-related mortality.Surgical operation and systematic chemical therapies are primary choices for the treatment of GC patients with advanced stage...BACKGROUND Gastric cancer(GC)is a type of cancer which causes high cancer-related mortality.Surgical operation and systematic chemical therapies are primary choices for the treatment of GC patients with advanced stages,however,the 5-year overall survival is only around 30%.AIM To investigate the role of mesenchymal stem cell(MSC)-derived long non-coding RNAs(lncRNA)NKILA in fatty acid oxidation and chemoresistance in GC cells,mediated through the miR-485-5p/STAT3 pathway.METHODS GC cell lines(AGS and MKN45)were co-cultured with human bone marrowderived MSCs were cultured.The MSC identity was confirmed by flow cytometry(CD73,CD90,CD105>95%positive,CD34,CD45 negative).Co-culture of GC cells and MSCs was performed in Transwell plates,where MSCs were placed in the upper chamber and GC cells in the lower chamber for 72 hours.For transfections,pcDNA-NKILA vectors,shSTAT3,and miR-485-5p mimics were utilized.Colony formation,apoptosis assays(Annexin V/PI staining),sphere formation,and flow cytometry were performed to evaluate cell proliferation,stemness,and chemoresistance.qPCR was used to analyze gene expression(Sox2,Oct4,CD133,LIN28,NKILA),and Western blotting assessed protein levels of stemness markers.Luciferase reporter assays were conducted to confirm miR-485-5p/STAT3 interactions,and biotin-labeled RNA pulldown was used to assess RNA-protein binding.Fatty acid oxidation was evaluated using a CPT1 activity assay andβ-oxidation rate detection.ATP levels were measured to assess the energetic status of GC cells.Clinical GC tissue samples were collected from patients at our hospital for validation.RESULTS MSCs were found to enhance the stemness and chemoresistance of GC cells.Co-culturing MKN45 and AGS cells with MSCs significantly increased sphere-forming ability and the expression of key cancer stem cell markers(SOX2,Oct4,LIN28,CD133),indicating that MSCs promote stem-like properties.Flow cytometry confirmed an enrichment of CD44+and CD133+subpopulations in MSC-treated GC cells.Additionally,MSC co-culture reduced chemotherapy-induced apoptosis and enhanced cell proliferation,suggesting a protective role in chemotherapy resistance.MSC-derived lncRNA NKILA further promoted stemness and chemoresistance,enhancing expression of stem cell markers and protecting cells from oxaliplatin and 5-FU-induced apoptosis.MSC co-culture also induced fatty acid oxidation in GC cells,as shown by increased CPT1 activity,β-oxidation rates,and ATP levels.NKILA mediated these effects by upregulating STAT3,which was confirmed to regulate fatty acid oxidation and chemoresistance.NKILA’s interaction with miR-485-5p further promoted STAT3 expression and fatty acid oxidation,reinforcing its role in maintaining stemness and enhancing chemoresistance.CONCLUSION MSCs enhance the stemness and chemoresistance of GC cells by secreting lncRNA NKILA,which promotes fatty acid oxidation through STAT3 activation.NKILA modulates the miR-485-5p/STAT3 axis,thereby increasing energy metabolism and supporting cancer stem cell properties.Targeting NKILA or the miR-485-5p/STAT3 pathway offers potential therapeutic strategies to overcome chemoresistance in GC.展开更多
Reducing the amount of aluminum chloride needed for the catalytic preparation of high quality mesophase and carbon materials is important and we have found that using terephthalic acid(PTA)as a co-catalyst serves this...Reducing the amount of aluminum chloride needed for the catalytic preparation of high quality mesophase and carbon materials is important and we have found that using terephthalic acid(PTA)as a co-catalyst serves this purpose.By adding 3%(mass fraction)AlCl_(3)and 0.9%(mass fraction)PTA to the coal tar pitch,approximately 90%mesophase was synthesized.The product(M-3-0.9)had a high stacking order(L_(c)=3.1 nm,n=10.14)and aromaticity(0.942).By adding PTA,a larger anisotropy content was produced using a smaller amount of AlCl_(3).The PTA participated in the polycondensation reaction through its own benzene ring structure to increase the catalytic activity.However,when its content was higher than 1.5%,the number of oxygen-containing groups in the product increased which was unfavorable for the aromatic lamellar stacking and gave rise to more isotropic structures.The work opens up a new way to prepare mesophase by a catalytic method.展开更多
Dietary supplementation with plant-derivedα-linolenic acid(ALA)has the potential to alleviate the insufficient intake of global n-3 long-chain polyunsaturated fatty acids(n-3 LCPUFAs),but faces the bottleneck of high...Dietary supplementation with plant-derivedα-linolenic acid(ALA)has the potential to alleviate the insufficient intake of global n-3 long-chain polyunsaturated fatty acids(n-3 LCPUFAs),but faces the bottleneck of highβ-oxidation consumption,oxidative susceptibility,and low conversion efficiency.The current study investigated how flax lignans with different degrees of polymerization and glycosylation affect the conversion of ALA to n-3 LCPUFAs in mice over 35 days of administering sunflower phospholipid-stabilized flaxseed oil nanoemulsions.Results showed that flax lignan macromolecules(FLM)increased hepatic protein expression of elongase of very long chain fatty acid 5(Elovl5,24.2%)and fatty acid desaturase 2(Fads2,44.7%),thereby positively regulating ALA conversion pathways and raising serum eicosapentaenoic acid(EPA)levels(52.7%)via liver lipid re-efflux.Secoisolariciresinol diglucoside(SDG)enhanced ALA desaturation by upregulating hepatic protein expression of Fads1(30.4%)and Fads2(45.6%),increasing serum EPA levels(55.9%)and hepatic docosahexaenoic acid(DHA)levels(10%).Secoisolariciresinol(SECO)elevated hepatic protein expression of Elovl2(30.7%),Elovl5(11.7%),Fads1(37.9%),and Fads2(24.1%),but also increased carnitine palmitoyltransferase 1a(45.2%),leading to decreased ALA,EPA,and DHA levels in serum and liver.Therefore,in comparison,FLM and SDG emerge as the dominant structural units that positively regulate the conversion of ALA.These findings lay a groundwork for designing precise dietary delivery systems to enhance the conversion to n-3 LCPUFAs.展开更多
Patients with glioma have a very high mortality rate,thus improving the poor prognosis of glioma has been the goal in the therapeutic field.Searching for more effective drugs for gliomas from natural compounds is a pr...Patients with glioma have a very high mortality rate,thus improving the poor prognosis of glioma has been the goal in the therapeutic field.Searching for more effective drugs for gliomas from natural compounds is a promising strategy.In this study,both oleanonic acid and oleanolic acid inhibited proliferation of glioma cells and reduced expression of cyclin D1 and E1,but the former has a lower IC_(50)than the latter.Oleanonic acid reduced the expression of p-STAT3 but not p-STAT1 and 5,and also reducing the expression of STAT3 in the nucleus and its transcriptional activity in glioma cells.Furthermore,knockdown of STAT3 expression inhibited proliferation and migration of glioma cells.Next,the expressions of the upstream regulators such as SIRT6 and p-JAK2 but not SIRT1,p-ERK1/2,p300 were increased by oleanonic acid.The overexpression of SIRT6 not only reduced the expression of p-STAT3 and its transcriptional activity but also inhibited the proliferation and migration of glioma cells.In addition,the effects that oleanonic acid reduced the expression of p-STAT3 and its transcriptional activity and inhibited the proliferation and migration were attenuated by the knockdown of SIRT6.Furthermore,oleanonic acid effectively suppressed glioma growth and extended survival in nude mice bearing intracerebral U87 xenografts,but not in nude mice bearing intracerebral SIRT6-knockdown U87xenografts.In conclusion,oleanonic acid upregulates the expression of SIRT6 to inactivates STAT3 and then inhibits glioma growth.展开更多
Background Intestinal oxidative stress serves as an endogenous host defense against the gut microbiota by increas-ing energy expenditure and therefore decreasing feed efficiency(FE).Several systems coordinately regula...Background Intestinal oxidative stress serves as an endogenous host defense against the gut microbiota by increas-ing energy expenditure and therefore decreasing feed efficiency(FE).Several systems coordinately regulate redox bal-ance,including the mitochondrial respiratory chain,nicotinamide adenine dinucleotide phosphate(NADPH)oxidase,and different antioxidants.However,it remains unclear which redox balance compartments in the intestine are crucial for determining FE.Results In this study,we first screened the key targets of different metabolites and redox balance-related gene expression in broiler ceca.We then constructed a mouse colitis model to explore malic acid(MA)ability to allevi-ate intestinal inflammation.We further used controlled release technology to coat MA and investigated its effects on the intestinal redox status and FE in vivo.Finally,we examined the underlying mechanism by which MA modulated redox status using a porcine intestinal epithelial cell jejunum 2(IPEC-J2)cell model in vitro.Our results demonstrated that the MA/malic enzyme 3(ME3)pathway may play an important role in reducing oxidative stress in the broiler cecum.In addition,colon infusion of MA attenuated inflammatory phenotypes in the dextran sulfate sodium salt(DSS)induced mouse colitis model.Then,dietary supplementation with controlled-release MA pellet(MAP)reduced the feed to gain(F/G)ratio and promoted chicken growth,with reduced oxidative stress and increased bacterial diver-sity.Finally,the in vitro IPEC-J2 cell model revealed that ME3 mediated the effect of MA on cellular oxidative stress.Conclusion In summary,our study firstly revealed the important role of the MA/ME3 system in the hindgut of broiler chickens for improving intestinal health and FE,which may also be crucial for the implications of colon inflammation associated diseases.展开更多
Background:The purpose of this report is to summarize the evidence supporting supplementation of n-3 polyunsaturated fatty acids(n-3 PUFAs)in adult cancer patients,and to offer a better understanding of the appropriat...Background:The purpose of this report is to summarize the evidence supporting supplementation of n-3 polyunsaturated fatty acids(n-3 PUFAs)in adult cancer patients,and to offer a better understanding of the appropriate use of n-3 PUFAs in the clinical setting.Methods:Numerous databases were searched for guidelines,clinical decision-making documents,systematic reviews,expert consensus statements,and best evidence summaries about the use of n-3 PUFAs in cancer patients from the inception of the database to December 31,2023.Evidence grading and recommendation rating were conducted.The data extracted included the timing of supplementation,symptom management,disease prevention,cost-effectiveness,route of administration,application scenarios,dosage,and safety.Results:The collected data show that n-3 PUFAs are safe for patients receiving chemotherapy who are at risk of malnutrition and cachexia.Moreover,n-3 PUFA supplementation can alleviate the adverse symptoms associated with chemotherapy,extend survival,and improve the quality of life of patients with cancer.Conclusions:The administration of supplementary n-3 PUFAs should be considered based on the patient’s disease stage,treatment plan,nutritional status,and tolerance,as well as the dosage,route and application scenarios.Promoting the clinical use of n-3 PUFAs may improve the outcomes for patients with cancer.展开更多
基金the Medical Research Foundation of Tongji University, China (No.1509219020).
文摘Objective Numerous studies have described both motor defects and cognitive impairments in several strains of rodents following 3-nitropropionic acid （3-NP） intoxication. In the present study, we investigated spatial recognition memory in Kunming mice that just recovered from motor defects induced by 3-NP. Methods Mouse model was made by systemic subacute 3-NP treatment, and spatial recognition memory was measured through the Y-maze Test, a simple two-trial recognition test. Results （1） On day 15 following 3-NP treatment, affected Kunming mice did not show motor defects in the Rotarod test and presented normal gait again. （2） In the following Y-maze test after lh interval, the percentage （90.0%） of mice showing novel ann preference in 3-NP treatment group was significantly higher than the random chance level （50%）, although it was only slightly higher than that （83.3%） in control group. On day 45 after 3-NP treatment, mice failed to choose unfamiliar novel arm as first choice, and the same occured in the control group. （3） For both post-intoxicated （on day 15 and day 45 following 3-NP treatment） and control groups, the duration in the novel ann and the frequency of entering it, were longer and higher compared with familiar start and other arms. For these mice that recently recovered from motor defects following 3-NP intoxication, no spatial memory deficits were observed through Y-maze Test. Conclusion Kunming mice used in our assays might possess resistance to cognitive impairment induced by 3-NP, which is consistent with previous findings in Swiss EPM-M1 mice.
文摘Objective Striatum may be involved in depressive disorders according to the neuroimaging analysis and clinical data. However, no animal model at present supported the possible role of striatum in the pathogenesis of depression. In the present study, we have investigated the depressive-like behavior in mice recently intoxicated with 3-nitropropionic acid （3- NP）, a widely known toxin that selectively damages the striatum in the brain. Methods Mouse model was made with subacute systemic 3-NP treatment, and the depressive-like behavior was measured using the duration of immobility during forced swimming test （FST）. Results When the mice at day 15 post-intoxication just totally recovered from motor deficits, the duration of immobility in FST was significantly longer than that in controls. The depressive-like behavior was not due to the fatigue or general sickness following 3-NP intoxication and could be reversed by the antidepressant, desipramine hydrochloride. In two successive FST in 24 h interval, the depressive-like behavior could be observed again in subsequent FST （at day 16 post-intoxication）, and the mice presented a normal ＂learned helplessness＂. Conclusion A novel depression animal model could be established in mice during the initial period of recovery from 3-NP intoxication. The depression-like behavior might occur independently without involvement of cognitive defects, and the striatal lesions may underlie the depression-like behavior attributable to 3-NP intoxication.
基金This project was supported by scientific research Funds of Zhengzhou Municipal Government, China (No. 04BA60AB YD08)
文摘Summary： To examine the changes in erythropoietin （Epo） protein and its mRNA expression in rat brain subjected to focal ischemia and possible mechanism of the preconditioning of mitochondrial toxin 3-nitropropionic acid （3-NPA）, rats were administrated either vehicle or 3-NPA at a dose of 20 mg/kg, intraperitoneally （ip）, 3 days prior to a 2-h middle cerebral artery occlusion followed by 24- h reperfusion. Infarct volumes were measured by using 2, 3, 5 triphenylte trazolinm chloride （TTC） staining, and Epo protein and its mRNA levels were assessed by immunohistochemistry and reverse transcriptase polymerase chain reaction （RT-PCR）, respectively. Our results showed that after reperfusion, Epo was found to be expressed extensively in the rat brain. It was most apparent in the basal nuclei and hippocampus, and was, to some extent, present in cortex. Preconditioning with 3-NPA caused a reduction in infarct volume. The expression of both Epo protein and mRNA increased significantly in the different brain areas in the 3-NPA pretreated group as compared with the non-pretreated ischemia model group. These results suggested that preconditioning with low dose 3-NPA could induce ischemic tolerance and neuro-protective effects by increasing the Epo expression in the ischemic and ischemia-related areas.
基金supported by the Consejo Nacional de Ciencia y Tecnología (Grant No. 42598)
文摘Objective The aim of the present study was to determine the changes in the mRNA levels of neurotrophins and their receptors in the striatal tissue of mice treated with 3-nitropropionic acid （3-NP）. Methods At 1 and 48 h after the last drug administration, the mRNA expression of nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4/5 as well as their receptors p75, TrkA, TrkB and TrkC, was evaluated using semi-quantitative （semi- Q） and real-time RT-PCR. β-actin mRNA and ribosomal 18S （18S rRNA） were tested as internal controls. Results 3-NP treatment did not affect mRNA expression of all neurotrophins and their respective receptors equally. Also, differences in neurotrophin and receptor mRNA expression were observed between semi-Q and real-time RT-PCR. Real-time RT-PCR was more accurate in evaluating the mRNA expression of the neurotrophins than semi-Q, and 18S rRNA was more reliable than β-actin as an internal control. Conclusion Neurotrophins and their receptors expression is differentially affected by neuronal damage produced by inhibition of mitochondrial respiration with 3-NP treatment in low, sub-chronic doses in vivo.
基金ThisprojectwassupportedbyagrantfrominitiativeFoundationofNatioualEducationMinistryforscholarscomingbackfromothercountries (No .2 0 0 1 345)
文摘The involvement of apoptosis in mitochondrial toxin 3 nitropropionic acid (3 NPA) induced ischemic tolerance to transient focal cerebral ischemia in rats and the mechanism was investigated. 3 NPA at a dose of 20 mg/kg or vehicle control was intraperitoneally into the rats. Three days later, rats were exposed to 2 h of middle cerebral artery occlusion followed by 24 h of reperfusion. Infarct volumes were assessed by 2,3,5 triphenyltetrazolinm chloride (TTC) staining 24 h after reperfusion. Neural cell apoptosis in cerebral ischemic penumbra was detected by terminal deoxynucleotidyl transferase mediated dUTP biotin in situ nick end labeling (TUNEL) and flow cytometry methods (FCM). The results showed that as compared to the vehicle treated group, pretreatment with 3 NPA could reduce the infarct volume by 23.3 % and decrease the number of TUNEL positive neural cells and apoptotic percentage by 47 % ( P< 0.05) and 44.9 % ( P< 0 01), respectively. It was concluded that the development of 3 NPA induced ischemic tolerance in brain might be related to the decreases in neural cell apoptosis.
文摘The current study investigates the role of oxidative stress and calcium homeostasis in the development of selective striatal lesions in metabolic impairment model caused by 3-nitropropionic acid (3NP). In this report, we examined the distribution of oxidative stress markers and the production of mitochondrial reactive oxygen species in the presence of 3NP in male Sprague-Dawley rats. Protein oxidation was assessed using 3-nitrotyrosine immunoreactivity, while DNA oxidative damage was evaluated by poly (ADP-ribose) polymerase-1 activity. The Reactive Oxygen Species (ROS) production was determined in isolated mitochondrial from striatum and cerebellum of two age groups following 3NP and variable calcium concentration. The results demonstrate that increased 3-nitro-tyrosine level is the most robust in the striatum and the least evident in the cerebellum following 4 days of 3NP treatment. No significant change in the levels of poly ADP-ribosylated proteins was observed, likely due to a rapid PARP-1 cleavage as detected by the appearance of 50 kDa necrotic fragment. In mitochondrial isolates, there was no immediate increase in mitochondrial ROS following 3NP in either striatum or cerebellum;however, calcium addition resulted in a concentration dependent increase in reactive oxygen species in striatal mitochondria of the older animals. These results suggest that in aging, mitochondria become more susceptible to the generation of ROS in conditions that cause a concurrent compromised in mitochondrial calcium concentration. This finding implicates mitochondria dysfunction as a key cellular target in pathological states that are associated with metabolic impairment. The results also reinforce the notion that mitochondrial function in the striatum and cerebellum respond differently to the aging process, which may explain the variable regional vulnerability in 3NP model.
基金supported by the Max Planck Society and the China Scholarship Council(grant number 201406300098).
文摘Chrysomelina beetlesstore 3-nitropropionic acid in form of a pretoxin,isoxazolin-5-one glucoside-conjugated ester,to protect themselves against predators.Here we identified a cytochrome P450 monooxygenase,CYP347W1,to be involved in the production of the 3-nitropropionic acid moiety of the isoxazolin-5-one glucoside ester.Knocking down CYP347W1 led to a significant depletion in the concentration of the isoxazolin-5-one glucoside ester and an increase in the concentration of the isoxazolin-5-one glucoside in the larval hemolymph.Enzyme assays with the heterologously expressed CYP347W1 showed freeβ-alanine was not the direct substrate.Homology modeling indicated thatβ-alanine-CoA ester can fit into CYP347W1’s active site.Furthermore,we proved that Phaedon cochleariae eggs are not able to de novo synthesize 3-NPA,although both isoxazolin-5-one glucoside and its 3-NPA-conjugated ester are present in the eggs.These results provide direct evidence for the involvement of CYP347W1 in the biosynthesis of a P.cochleariae chemical defense compound.
基金supported by the National Natural Science Foundation of China(grant number 82460425)Jiangxi Provincial Health Technology Project(grant number 202510141).
文摘Background:Recent studies have shown glycerolipid metabolism played an essential role in multiple tumors,however,its function in osteosarcoma is unclear.This study aimed to explore the role of glycerolipid metabolism in osteosarcoma.Methods:We conducted bioinformatics analysis using data from the Therapeutically Applicable Research to Generate Effective Treatments(TARGET)database and single-cell RNA sequencing.Least Absolute Shrinkage and Selection Operator(LASSO)regression was used to identify the Glycerolipid metabolism-related genes associated with the clinical outcome of osteosarcoma.Tumor-associated macrophages(TAMs)and their interactions with immune cells were examined through single-cell analysis and co-culture experiments.Virtual screening was employed to identify the potential lysophosphatidic acid receptor 6(LPAR6)inhibitors.Results:Glycerolipid metabolism-related genes 1-acylglycerol-3-phosphate O-acyltransferase 3(AGPAT3)and aldehyde dehydrogenase 7 family member A1(ALDH7A1)were identified as key prognostic genes in osteosarcoma,with high AGPAT3 expression correlating with improved survival.Single-cell analysis revealed that AGPAT3 expression is associated with tumor immune microenvironment,particularly with TAMs.Knockdown of AGPAT3 in osteosarcoma cells resulted in elevated lysophosphatidic acid(LPA)levels,which regulated the immune environment,inhibiting cytotoxic T cell function through TAMs’LPAR6 signaling.LPAR6 signaling in TAMs mediates immune regulation through cytokine secretion,including interleukin-6(IL-6)and interleukin-10(IL-10).Further drug virtual screening identified Dutasteride as a potential inhibitor of LPAR6.Conclusion:AGPAT3 is an important gene related to the prognosis of osteosarcoma.Its ability to modulate LPA signaling and TAM activity offers promising therapeutic opportunities for improving osteosarcoma treatment,particularly in immunotherapy contexts.
基金Project supported by the Natural Science Foundation Innovation Group Project of Hubei Province(2023AFA044)the National Natural Science Foundation of China(52222405)+1 种基金the Science and Technology Research Project of Education Department of Hubei Province(Q20221505)the China Postdoctoral Science(2023M731041)。
文摘In order to reveal the effect of 2-hydroxy-3-naphthyl hydroxamic acid(H205)on the flotation behavior and action mechanism of bastnaesite,single-mineral flotation experiments of bastnaesite were conducted.The flotation recovery of bastnaesites can be achieved more than 90%when the aeration rate is 40 mL/min,the rotational speed is 200 r/min,the H205 dosage is 120 mg/L,and the pulp pH ranges from 7 to 9.The action mechanism of H205 on the surface of bastnaesite was studied by simultaneous thermogravimetry and differential scanning calorimetry(TG-DSC),Zeta potential measurements,Fourier transform-infrared spectra(FT-IR)and X-ray photoelectron spectroscopy(XPS).These analysis results show that under suitable flotation conditions,H205 has an obvious adsorption phenomenon on the surface of bastnaesite.The adsorption involves electrostatic interactions and chemical interactions,namely H205 has a strong collecting ability of bastnaesite due to the synergism of electrostatic adsorption and chemical adsorption.This study systematically reveals the flotation behavior and adsorption mechanism of H205 on the surface of bastnaesite,and provides useful theoretical guidance for efficient flotation separation of bastnaesite.
基金financial support by National Key Research and Development Project(Grant No.2023YFE0109600)Guangzhou Key Research and Development Program(Grant No.2023B03J1330)+5 种基金National Program for Support of Topnotch Young Professionals(Grant No.x2qsA4210090)Guangzhou Basic and Applied Basic Research Foundation(Grant No.2024A04J3413)National Natural Science Foundation of China(Grant No.32201499)State Key Laboratory of Pulp and Paper Engineering(Grant Nos.2023PY01 and 202215)Guangdong Basic and Applied Basic Research Foundation(Grant Nos.2023A1515012519 and 2023B1515040013)China Postdoctoral Science Foundation(Grant No.2023M732021).
文摘Photocatalysis has emerged as an effective approach to sustainably convert biomass into value-added products.CoSe_(2)is a promising nonprecious,efficient cocatalyst for photooxidation,which can facilitate the separation of photogenerated electron–holes,increase the reaction rates,and enhance photocatalytic efficiency.In this work,we synthesized a stable and efficient photocatalysis system of CoSe_(2)/g-C_(3)N_(4)through attaching CoSe_(2)on g-C_(3)N_(4)sheets,with a yield of 50.12%for the selective photooxidation of xylose to xylonic acid.Under light illumination,the photogenerated electrons were prone to migrating from g-C_(3)N_(4)to CoSe_(2)due to the higher work function of CoSe_(2),resulting in the accelerated separation of photogenerated electron–holes and the promoted photooxidation.Herein,this study reveals the unique function of CoSe_(2),which can significantly promote oxygen adsorption,work as an electron sink and accelerate the generation of ·O_(2)^(-),thereby improving the selectivity toward xylonic acid over other by-products.This work provides useful insights into the design of selective photocatalysts by engineering g-C_(3)N_(4)for biomass high-value utilization.
基金Mechanistic Investigation into the Extraction,Purification,and Anti-Esophageal Cancer Effects of Gallic Acid Derived from Rhodiola crenulata(YLUKLM2023001).
文摘Background:Gallic acid(GA),a plant-derived polyphenol,possesses diverse biological functions such as reducing inflammation and against tumors.Currently,the influence of GA on the resistance of esophageal squamous cell carcinoma(ESCC)cells to cisplatin(DDP)is not well understood.Methods:Cell counting kit-8 assay examined how GA affected KYSE30 and TE-1 cell viability.5-Ethynyl-2′-deoxyuridine and TdT-mediated dUTP Nick-End labeling staining detected cell proliferation and apoptosis.Clone formation assay,flow cytometry,Carboxyfluorescein diacetate succinimidyl ester fluorescent probes,and Transwell assay determined cell biological properties,and 2′,7′-Dichlorofluorescin diacetate(DCFH-DA)fluorescent probes detected oxidative stress levels.Signal transducer and activator of transcription 3(STAT3)/Notch pathway protein levels after GA and/or Interleukin-6(IL-6)intervention were examined through Western blot.Furthermore,a model for subcutaneous graft tumors was established in nude mice.Results:GA exerted suppressive effects on cell proliferation,and caused apoptosis of KYSE30 and TE-1 cells.IL-6 intervention activated the STAT3/Notch pathway and promoted the malignant biological properties of ESCC cells.In contrast,GA attenuated the effects of IL-6,while STAT3 or Notch inhibitor further enhanced the effects of GA,suggesting that GA inhibited the IL-6/STAT3/Notch pathway.Not only that,GA promoted oxidative stress and enhanced cell sensitivity to DDP both in vitro and in vivo.Conclusion:GA suppresses the malignant progression of ESCC and enhances cell sensitivity to DDP by hindering the IL-6/STAT3/Notch pathway.
文摘BACKGROUND Gastric cancer(GC)is a type of cancer which causes high cancer-related mortality.Surgical operation and systematic chemical therapies are primary choices for the treatment of GC patients with advanced stages,however,the 5-year overall survival is only around 30%.AIM To investigate the role of mesenchymal stem cell(MSC)-derived long non-coding RNAs(lncRNA)NKILA in fatty acid oxidation and chemoresistance in GC cells,mediated through the miR-485-5p/STAT3 pathway.METHODS GC cell lines(AGS and MKN45)were co-cultured with human bone marrowderived MSCs were cultured.The MSC identity was confirmed by flow cytometry(CD73,CD90,CD105>95%positive,CD34,CD45 negative).Co-culture of GC cells and MSCs was performed in Transwell plates,where MSCs were placed in the upper chamber and GC cells in the lower chamber for 72 hours.For transfections,pcDNA-NKILA vectors,shSTAT3,and miR-485-5p mimics were utilized.Colony formation,apoptosis assays(Annexin V/PI staining),sphere formation,and flow cytometry were performed to evaluate cell proliferation,stemness,and chemoresistance.qPCR was used to analyze gene expression(Sox2,Oct4,CD133,LIN28,NKILA),and Western blotting assessed protein levels of stemness markers.Luciferase reporter assays were conducted to confirm miR-485-5p/STAT3 interactions,and biotin-labeled RNA pulldown was used to assess RNA-protein binding.Fatty acid oxidation was evaluated using a CPT1 activity assay andβ-oxidation rate detection.ATP levels were measured to assess the energetic status of GC cells.Clinical GC tissue samples were collected from patients at our hospital for validation.RESULTS MSCs were found to enhance the stemness and chemoresistance of GC cells.Co-culturing MKN45 and AGS cells with MSCs significantly increased sphere-forming ability and the expression of key cancer stem cell markers(SOX2,Oct4,LIN28,CD133),indicating that MSCs promote stem-like properties.Flow cytometry confirmed an enrichment of CD44+and CD133+subpopulations in MSC-treated GC cells.Additionally,MSC co-culture reduced chemotherapy-induced apoptosis and enhanced cell proliferation,suggesting a protective role in chemotherapy resistance.MSC-derived lncRNA NKILA further promoted stemness and chemoresistance,enhancing expression of stem cell markers and protecting cells from oxaliplatin and 5-FU-induced apoptosis.MSC co-culture also induced fatty acid oxidation in GC cells,as shown by increased CPT1 activity,β-oxidation rates,and ATP levels.NKILA mediated these effects by upregulating STAT3,which was confirmed to regulate fatty acid oxidation and chemoresistance.NKILA’s interaction with miR-485-5p further promoted STAT3 expression and fatty acid oxidation,reinforcing its role in maintaining stemness and enhancing chemoresistance.CONCLUSION MSCs enhance the stemness and chemoresistance of GC cells by secreting lncRNA NKILA,which promotes fatty acid oxidation through STAT3 activation.NKILA modulates the miR-485-5p/STAT3 axis,thereby increasing energy metabolism and supporting cancer stem cell properties.Targeting NKILA or the miR-485-5p/STAT3 pathway offers potential therapeutic strategies to overcome chemoresistance in GC.
文摘Reducing the amount of aluminum chloride needed for the catalytic preparation of high quality mesophase and carbon materials is important and we have found that using terephthalic acid(PTA)as a co-catalyst serves this purpose.By adding 3%(mass fraction)AlCl_(3)and 0.9%(mass fraction)PTA to the coal tar pitch,approximately 90%mesophase was synthesized.The product(M-3-0.9)had a high stacking order(L_(c)=3.1 nm,n=10.14)and aromaticity(0.942).By adding PTA,a larger anisotropy content was produced using a smaller amount of AlCl_(3).The PTA participated in the polycondensation reaction through its own benzene ring structure to increase the catalytic activity.However,when its content was higher than 1.5%,the number of oxygen-containing groups in the product increased which was unfavorable for the aromatic lamellar stacking and gave rise to more isotropic structures.The work opens up a new way to prepare mesophase by a catalytic method.
基金supported by grants from the National Natural Science Foundation of China(32072267)China Agriculture Research System(CARS-14)+1 种基金National Key Research and Development Program of China(2023YFD2100404)the Innovation Group Project of Hubei Province(2023AFA042).
文摘Dietary supplementation with plant-derivedα-linolenic acid(ALA)has the potential to alleviate the insufficient intake of global n-3 long-chain polyunsaturated fatty acids(n-3 LCPUFAs),but faces the bottleneck of highβ-oxidation consumption,oxidative susceptibility,and low conversion efficiency.The current study investigated how flax lignans with different degrees of polymerization and glycosylation affect the conversion of ALA to n-3 LCPUFAs in mice over 35 days of administering sunflower phospholipid-stabilized flaxseed oil nanoemulsions.Results showed that flax lignan macromolecules(FLM)increased hepatic protein expression of elongase of very long chain fatty acid 5(Elovl5,24.2%)and fatty acid desaturase 2(Fads2,44.7%),thereby positively regulating ALA conversion pathways and raising serum eicosapentaenoic acid(EPA)levels(52.7%)via liver lipid re-efflux.Secoisolariciresinol diglucoside(SDG)enhanced ALA desaturation by upregulating hepatic protein expression of Fads1(30.4%)and Fads2(45.6%),increasing serum EPA levels(55.9%)and hepatic docosahexaenoic acid(DHA)levels(10%).Secoisolariciresinol(SECO)elevated hepatic protein expression of Elovl2(30.7%),Elovl5(11.7%),Fads1(37.9%),and Fads2(24.1%),but also increased carnitine palmitoyltransferase 1a(45.2%),leading to decreased ALA,EPA,and DHA levels in serum and liver.Therefore,in comparison,FLM and SDG emerge as the dominant structural units that positively regulate the conversion of ALA.These findings lay a groundwork for designing precise dietary delivery systems to enhance the conversion to n-3 LCPUFAs.
基金supported by the National Natural Science Foundation of China(81560059,81760058,8160042,and 31800891)。
文摘Patients with glioma have a very high mortality rate,thus improving the poor prognosis of glioma has been the goal in the therapeutic field.Searching for more effective drugs for gliomas from natural compounds is a promising strategy.In this study,both oleanonic acid and oleanolic acid inhibited proliferation of glioma cells and reduced expression of cyclin D1 and E1,but the former has a lower IC_(50)than the latter.Oleanonic acid reduced the expression of p-STAT3 but not p-STAT1 and 5,and also reducing the expression of STAT3 in the nucleus and its transcriptional activity in glioma cells.Furthermore,knockdown of STAT3 expression inhibited proliferation and migration of glioma cells.Next,the expressions of the upstream regulators such as SIRT6 and p-JAK2 but not SIRT1,p-ERK1/2,p300 were increased by oleanonic acid.The overexpression of SIRT6 not only reduced the expression of p-STAT3 and its transcriptional activity but also inhibited the proliferation and migration of glioma cells.In addition,the effects that oleanonic acid reduced the expression of p-STAT3 and its transcriptional activity and inhibited the proliferation and migration were attenuated by the knockdown of SIRT6.Furthermore,oleanonic acid effectively suppressed glioma growth and extended survival in nude mice bearing intracerebral U87 xenografts,but not in nude mice bearing intracerebral SIRT6-knockdown U87xenografts.In conclusion,oleanonic acid upregulates the expression of SIRT6 to inactivates STAT3 and then inhibits glioma growth.
基金supported by the local innovative and research teams project of Guangdong province(2019BT02N630)national key research and development program(2022YFD1300401)+2 种基金Double first-class discipline promoting project(2023B10564001)National Natural Science Foundation of China(32272954)Natural Science Foundation of Guangdong Province,China(2024A1515013131).
文摘Background Intestinal oxidative stress serves as an endogenous host defense against the gut microbiota by increas-ing energy expenditure and therefore decreasing feed efficiency(FE).Several systems coordinately regulate redox bal-ance,including the mitochondrial respiratory chain,nicotinamide adenine dinucleotide phosphate(NADPH)oxidase,and different antioxidants.However,it remains unclear which redox balance compartments in the intestine are crucial for determining FE.Results In this study,we first screened the key targets of different metabolites and redox balance-related gene expression in broiler ceca.We then constructed a mouse colitis model to explore malic acid(MA)ability to allevi-ate intestinal inflammation.We further used controlled release technology to coat MA and investigated its effects on the intestinal redox status and FE in vivo.Finally,we examined the underlying mechanism by which MA modulated redox status using a porcine intestinal epithelial cell jejunum 2(IPEC-J2)cell model in vitro.Our results demonstrated that the MA/malic enzyme 3(ME3)pathway may play an important role in reducing oxidative stress in the broiler cecum.In addition,colon infusion of MA attenuated inflammatory phenotypes in the dextran sulfate sodium salt(DSS)induced mouse colitis model.Then,dietary supplementation with controlled-release MA pellet(MAP)reduced the feed to gain(F/G)ratio and promoted chicken growth,with reduced oxidative stress and increased bacterial diver-sity.Finally,the in vitro IPEC-J2 cell model revealed that ME3 mediated the effect of MA on cellular oxidative stress.Conclusion In summary,our study firstly revealed the important role of the MA/ME3 system in the hindgut of broiler chickens for improving intestinal health and FE,which may also be crucial for the implications of colon inflammation associated diseases.
文摘Background:The purpose of this report is to summarize the evidence supporting supplementation of n-3 polyunsaturated fatty acids(n-3 PUFAs)in adult cancer patients,and to offer a better understanding of the appropriate use of n-3 PUFAs in the clinical setting.Methods:Numerous databases were searched for guidelines,clinical decision-making documents,systematic reviews,expert consensus statements,and best evidence summaries about the use of n-3 PUFAs in cancer patients from the inception of the database to December 31,2023.Evidence grading and recommendation rating were conducted.The data extracted included the timing of supplementation,symptom management,disease prevention,cost-effectiveness,route of administration,application scenarios,dosage,and safety.Results:The collected data show that n-3 PUFAs are safe for patients receiving chemotherapy who are at risk of malnutrition and cachexia.Moreover,n-3 PUFA supplementation can alleviate the adverse symptoms associated with chemotherapy,extend survival,and improve the quality of life of patients with cancer.Conclusions:The administration of supplementary n-3 PUFAs should be considered based on the patient’s disease stage,treatment plan,nutritional status,and tolerance,as well as the dosage,route and application scenarios.Promoting the clinical use of n-3 PUFAs may improve the outcomes for patients with cancer.
