T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue ...T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue damage by T-2 toxin.Twenty-four male Sprague-Dawley rats were orally administered T-2 toxin through gavage for 12 weeks at the dose of 0,10,and 100 nanograms per gram body weight per day(ng/(g·day)),respectively.Morphological,pathological,and ultrastructural alterations in cardiac tissue were meticulously examined.Non-targeted metabolomics analysis was employed to analyze alterations in cardiac metabolites.The expression of the Sirt3/FoxO3α/MnSOD signaling pathway and the level of oxidative stress markers were detected.The results showed that exposure to T-2 toxin elicited myocardial tissue disorders,interstitial hemorrhage,capillary dilation,and fibrotic damage.Mitochondria were markedly impaired,including swelling,fusion,matrix degradation,and membrane damage.Metabonomics analysis unveiled that T-2 toxin could cause alterations in cardiacmetabolic profiles as well as in the Sirt3/FoxO3α/MnSOD signaling pathway.T-2 toxin could inhibit the expressions of the signaling pathway and elevate the level of oxidative stress.In conclusion,the T-2 toxin probably induces cardiac fibrotic impairment by affecting amino acid and choline metabolism as well as up-regulating oxidative stress mediated by the Sirt3/FoxO3α/MnSOD signaling pathway.This study is expected to provide targets for preventing and treating T-2 toxin-induced cardiac fibrotic injury.展开更多
Objective To investigate the effect on the structure of reestablished cartilage in vitro and CD44 expression on chondrocytes and compare the inducing effect on the reestablished cartilage in vitro between cor...Objective To investigate the effect on the structure of reestablished cartilage in vitro and CD44 expression on chondrocytes and compare the inducing effect on the reestablished cartilage in vitro between cortical bone matrix gelatin and cancellous bone matrix gelatin. Methods To plant human fetal chondrocytes on the BMG, the damage of the cultured chondrocytes was observed by the optical microscope (HE staining). The immunohistochemistry of CD44 was quantitative analysis by the image collection and analysis system. Results With the increasing concentration of T 2 toxin, the damage of chondroytes was more and more evident and CD44 expression was lowered. After adding selenium, the damage was relieved and CD44 expression increased. The density of chondrocytes on the cortical bone matrix gelatin was much higher than that on the cancellous bone matrix gelatin. Conclusion T 2 toxin can lower the CD44 expression on the chondrocytes and adding selenium can relieve the damage caused by T 2toxin and increased CD44 expression. The inducing effect on reestablished cartilage in vitro of cortical bone matrix gelatin was much higher than that of cancellous bone matrix gelatin.展开更多
[Objective] This study aimed to establish a real-time PCR method for de- tecting stx2 gene in Shiga toxin-producing E. coli （STEC）. [Method] According to the known STEC stx2 gene sequences published in GenBank, PCR ...[Objective] This study aimed to establish a real-time PCR method for de- tecting stx2 gene in Shiga toxin-producing E. coli （STEC）. [Method] According to the known STEC stx2 gene sequences published in GenBank, PCR primers and probes were designed based on the conserved region to construct recombinant plasmid as a positive template, thus optimizing the reaction conditions and establishing the real- time PCR method. [Result] A standard curve was established based on the opti- mized real-time PCR system, indicting a good linear correlation between the initial template concentration and Ct value, with the correlation coefficient F^e of above 0.995. The established method had a good specificity, without non-specific amplifica- tion for 10 non-STEC intestinal bacterial strains; the detection limit of initial template was 1.0x102 copies/μI, indicating a high sensitivity; furthermore, the coefficients of variation within and among batches were lower than 1% and 5% respectively, sug- gesting a good repeatability. [Conclusion] In this study, a real-time PCR method was successfully established for detecting STEC stx2 gene, which provided technical means for rapid detection of STEC in samples.展开更多
Objective:To investigate the effects of T-2 toxin on expressions of Fas,p53,Bcl-xL,Bcl-2,Bax and caspase-3 on human chondrocytes.Methods:Human chondrocytes were treated with T-2 toxin(1～20 ng/ml)for 5 d.Fas,p53 and o...Objective:To investigate the effects of T-2 toxin on expressions of Fas,p53,Bcl-xL,Bcl-2,Bax and caspase-3 on human chondrocytes.Methods:Human chondrocytes were treated with T-2 toxin(1～20 ng/ml)for 5 d.Fas,p53 and other apoptosis-related proteins such as Bax,Bcl-2,Bcl-xL,caspase-3 were determined by Western blot analysis and their mRNA expressions were determined by reverse transcriptase-polymerase chain reaction(RT-PCR).Results:Increases in Fas,p53 and the pro-apoptotic factor Bax protein and mRNA expressions and a decrease of the anti-apoptotic factor Bcl-xL were observed in a dose-dependent manner after exposures to 1～20 ng/ml T-2 toxin,while the expression of the anti-apoptotic factor Bcl-2 was unchanged.Meanwhile,T-2 toxin could also up-regulate the expressions of both pro-caspase-3 and caspase-3 in a dose-dependent manner.Conclusion:These data suggest a possible underlying molecular mechanism for T-2 toxin to induce the apoptosis sig- naling pathway in human chondrocytes by regulation of apoptosis-related proteins.展开更多
Objective: To identify the relationship between T-2 toxin and Kashin-Beck disease (KBD),the effects of T-2 toxin on aggrecan metabolism in human chondrocytes and cartilage were investigated in vitro. Methods: Chondroc...Objective: To identify the relationship between T-2 toxin and Kashin-Beck disease (KBD),the effects of T-2 toxin on aggrecan metabolism in human chondrocytes and cartilage were investigated in vitro. Methods: Chondrocytes were isolated from human articular cartilage and cultured in vitro. Hyaluronic acid (HA),soluble CD44 (sCD44),IL-1β and TNF-α levels in super-natants were measured by enzyme-linked immunosorbent assay (ELISA). CD44 content in chondrocyte membrane was deter-mined by flow cytometry (FCM). CD44,hyaluronic acid synthetase-2 (HAS-2) and aggrecanases mRNA levels in chondrocytes were determined using reverse transcription polymerase chain reaction (RT-PCR). Immunocytochemical method was used to investigate expressions of BC-13,3-B-3(-) and 2-B-6 epitopes in the cartilage reconstructed in vitro. Results: T-2 toxin inhibited CD44,HAS-2,and aggrecan mRNA expressions,but promoted aggrecanase-2 mRNA expression. Meanwhile,CD44 expression was found to be the lowest in the chondrocytes cultured with T-2 toxin and the highest in control plus selenium group. In addition,ELISA results indicated that there were higher sCD44,IL-1β and TNF-α levels in T-2 toxin group. Similarly,higher HA levels were also observed in T-2 toxin group using radioimmunoprecipitation assay (RIPA). Furthermore,using monoclonal antibodies BC-13,3-B-3 and 2-B-6,strong positive immunostaining was found in the reconstructed cartilage cultured with T-2 toxin,whereas no positive staining or very weak staining was observed in the cartilage cultured without T-2 toxin. Selenium could partly inhibit the effects of T-2 toxin above. Conclusion: T-2 toxin could inhibit aggrecan synthesis,promote aggrecanases and pro-inflammatory cytokines production,and consequently induce aggrecan degradation in chondrocytes. These will perturb metabolism balance between aggrecan synthesis and degradation in cartilage,inducing aggrecan loss in the end,which may be the initiation of the cartilage degradation.展开更多
Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1 mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total relative concentrations of T-2 toxin and HT-2 toxin in the...Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1 mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system（thighbone, knee joints, and costal cartilage） were significantly higher than those in the heart, liver, and kidneys（P 〈 0.05）. The relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system（thighbone and costal cartilage） were also significantly higher than those in the heart, liver, and kidneys. The rats administered T-2 toxin showed rapid metabolism compared with that in rats administered HT-2 toxin, and the metabolic conversion rates in the different tissues were 68.20%-90.70%.展开更多
Objective To investigate chondrocyte apoptosis and the expression of biochemical markers associated with apoptosis in Kashin-Beck disease（KBD） and in an established T-2 toxin-and selenium（Se） deficiency-induced ra...Objective To investigate chondrocyte apoptosis and the expression of biochemical markers associated with apoptosis in Kashin-Beck disease（KBD） and in an established T-2 toxin-and selenium（Se） deficiency-induced rat model. Methods Cartilages were collected from the hand phalanges of five patients with KBD and five healthy children. Sprague-Dawley rats were administered a selenium-deficient diet for 4 weeks prior to T-2 toxin exposure. The apoptotic chondrocytes were observed by terminal deoxynucleotidyl transferase d UTP nick end labeling staining. Caspase-3, p53, Bcl-2, and Bax proteins in the cartilages were visualized by immunohistochemistry, their protein levels were determined by Western blotting, and m RNA levels were determined by real-time reverse transcription polymerase chain reaction. Results Increased chondrocyte apoptosis was observed in the cartilages of children with KBD. Increased apoptotic and caspase-3-stained cells were observed in the cartilages of rats fed with normal and Se-deficient diets plus T-2 toxin exposure compared to those in rats fed with normal and Se-deficient diets. Caspase-3, p53, and Bax proteins and m RNA levels were higher, whereas Bcl-2 levels were lower in rats fed with normal or Se-deficiency diets supplemented with T-2 toxin than the corresponding levels in rats fed with normal diet. Conclusion T-2 toxin under a selenium-deficient nutritional status induces chondrocyte death, which emphasizes the role of chondrocyte apoptosis in cartilage damage and progression of KBD.展开更多
T-2 toxin is one of the most important trichothecene mycotoxins occurring in various agriculture products. The developmental toxicity of T-2 toxin and the exact mechanism of action at early life stages are not underst...T-2 toxin is one of the most important trichothecene mycotoxins occurring in various agriculture products. The developmental toxicity of T-2 toxin and the exact mechanism of action at early life stages are not understood precisely. Zebrafish embryos were exposed to different concentrations of the toxin at 4-6 hours post fertilization （hpf） stage of development, and were observed for different developmental toxic effects at 24, 48, 72, and 144 hpf. Exposure to 0.20 Ixmol/L or higher concentrations of T-2 toxin significantly increased the mortality and malformation rate such as tail deformities, cardiovascular defects and behavioral changes in early developmental stages of zebrafish. T-2 toxin exposure resulted in significant increases in reactive oxygen species （ROS） production and cell apoptosis, mainly in the tall areas, as revealed by Acridine Orange staining at 24 hpf. In addition, T-2 toxin-induced severe tail deformities could be attenuated by co-exposure to reduced glutathione （GSH）. T-2 toxin and GSH co-exposure induced a significant decrease of ROS production in the embryos. The overall results demonstrate that T-2 toxin is able to produce oxidative stress and induce apoptosis, which are involved in the developmental toxicity of T-2 toxin in zebrafish embryos.展开更多
F-2 toxin is an estrogenic mycotoxin that causes reproductive disorders in animals.Betulinic acid(BA)is a natural pentacyclic lupane-structure triterpenoid that has diverse pharmacological activities.In this study,the...F-2 toxin is an estrogenic mycotoxin that causes reproductive disorders in animals.Betulinic acid(BA)is a natural pentacyclic lupane-structure triterpenoid that has diverse pharmacological activities.In this study,the antioxidative and anti-inflammatory effects of BA and its underlying mechanism are explored in F-2 toxin-triggered mouse ovarian damage.We found that BA alleviated the F-2 toxin-induced ovarian impairment by stimulating follicle growth,reducing inflammatory cell infiltration,repairing damaged mitochondria and endoplasmic reticulum.Simultaneously,BA not only reversed F-2 toxin-induced reduction of follicle stimulating hormone(FSH)and luteinizing hormone(LH)levels in the serum,but also restrained the protein expression of the estrogen receptors a(ERa)and ERβ.Moreover,BA restored the balance of F-2 toxin-induced ovarian redox system disorders.Subsequently,we found that 0.25 mg/kg BA played an anti-inflammatory role in the F-2 toxin-induced ovarian impairment by decreasing interleukin-1β(IL-1β).IL-6,and tumor necrosis factor-α(TNF-α)mRNA expression,as well as inhibiting p38 protein expression.These data demonstrated that BA exerts its protective effect on F-2 toxin-induced ovarian oxidative impairment and inflammation by inhibiting p38 expression,which implies a natural product-based medicine to ameliorate F-2 toxin-caused female reproductive toxicity and provides a detoxifying method for food contaminated by mycotoxin.展开更多
T-2 toxin is the most widespread mycotoxin in crops,feed and food,which poses a serious threat to body health.Bone is the main target tissue for T-2 toxin accumulation.Ingestion of food contaminated by T-2 toxin is th...T-2 toxin is the most widespread mycotoxin in crops,feed and food,which poses a serious threat to body health.Bone is the main target tissue for T-2 toxin accumulation.Ingestion of food contaminated by T-2 toxin is the main cause of Kashin-Beck disease.However,the specific mechanism of bone damage caused by T-2 toxin is still unclear.In this study,a total of 40 male C57BL/6N mice were divided into four groups and orally treated with 0,0.5,1.0 and 2.0 mg·kg^(-1) body weight T-2 toxin for 28 days.The results showed that exposure to T-2 toxin led to weight loss,bone mineral density reduction and femoral structural damage of mice.In addition,osteoblast-mediated bone formation was inhibited,and osteoclast-mediated bone resorption was enhanced.Meanwhile,the levels of bone metabolism-related hormones including parathyroid hormone,calcitonin and 1,25-dihydroxyvitamin D3 were reduced.More importantly,it was found that the level of neuropeptide Y(a neurohormone)was decreased.These results provided a new perspetive for understanding the osteotoxicity of T-2 toxin.展开更多
The effects of deoxynlvalenol (DON), T--2 toxin, nivalenol (NIv), hutenolide (BuT).alternariol methyl ether(AME) and monlliformin (cON ) on rabbit articular chondrocytes were observed by using the method of chondrocyt...The effects of deoxynlvalenol (DON), T--2 toxin, nivalenol (NIv), hutenolide (BuT).alternariol methyl ether(AME) and monlliformin (cON ) on rabbit articular chondrocytes were observed by using the method of chondrocyte monolayer culture. The amounts or DNA in chondrocytesand glucuronate in matrix were measured. And the chondrocytes were observed by inversion microscope and transmission electron microscope (TEM). The results showed that the cultured chondrocytes were damaged by all the six mycotoxinsl and the synthesis of DNA and the divided reproductionof chondrocytes were restrained; the damage errect was more evident, esl,ecially in the early stage ofculturel the higher concentration or toxin in the media was used, the lower density of the culturalckondrocytes was observed; the cells were even round damaged and dead, so long as the media contolued toxin. When the six mycotoxins arrected the cultural chondrocytes r.spectively, three dirfereut kinds or ultrastructural changes in ckondrocytes were seen by TEa. The relationship betweenmycotoxiu and KBD was preliminarily discussed, and some problems still need further investigation..展开更多
Hemolytic uremic syndrome （HUS） is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and patho-genetic classifications. New findings in genetics and, in ...Hemolytic uremic syndrome （HUS） is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and patho-genetic classifications. New findings in genetics and, in particular, mutations of genes that encode the complement-regulatory proteins have improved our understanding of atypical HUS. Similarly, the comple-ment proteins are clearly involved in all types of thrombotic microangiopathy： typical HUS, atypical HUS and thrombotic thrombocytopenic purpura （TTP）. Fur-thermore, several secondary HUS appear to be related to abnormalities in complement genes in predisposed patients. The authors highlight the therapeutic as-pects of this rare disease, examining both “traditional therapy” （including plasma therapy, kidney and kidney-liver transplantation） and “new therapies”. The latter include anti-Shiga-toxin antibodies and anti-C5 mono-clonal antibody “eculizumab”. Eculizumab has been recently launched for the treatment of the atypical HUS, but it appears to be effective in the treatment of typical HUS and in TTP. Future therapies are in phases Ⅰ and Ⅱ. They include anti-C5 antibodies, which are more purifed, less immunogenic and absorbed orally and, anti-C3 antibodies, which are more powerful, but potentially less safe. Additionally, infusions of recombinant complement-regulatory proteins are a potential future therapy.展开更多
T-2 toxin is one of the most widespread and toxic fungal toxins in food and feed.It can cause gastrointestinal toxicity,hepatotoxicity,immunotoxicity,reproductive toxicity,neurotoxicity,and nephrotoxicity in humans an...T-2 toxin is one of the most widespread and toxic fungal toxins in food and feed.It can cause gastrointestinal toxicity,hepatotoxicity,immunotoxicity,reproductive toxicity,neurotoxicity,and nephrotoxicity in humans and animals.T-2 toxin is physicochemically stable and does not readily degrade during food and feed processing.Therefore,suppressing T-2 toxin-induced organ toxicity through antidotes is an urgent issue.Protective agents against the organ toxicity of T-2 toxin have been recorded widely in the literature,but these protective agents and their molecular mechanisms of detoxification have not been comprehensively summarized.In this review,we provide an overview of the various protective agents to T-2 toxin and the molecular mechanisms underlying the detoxification effects.Targeting appropriate targets to antagonize T-2 toxin toxicity is also an important option.This review will provide essential guidance and strategies for the better application and development of T-2 toxin antidotes specific for organ toxicity in the future.展开更多
T-2 toxin,one of the most dangerous natural pollutants,induces apoptosis through multiple pathways.Amongst,P53 mediated apoptosis pathway,an important collection of molecules,plays a key role in cell vital activity.Re...T-2 toxin,one of the most dangerous natural pollutants,induces apoptosis through multiple pathways.Amongst,P53 mediated apoptosis pathway,an important collection of molecules,plays a key role in cell vital activity.Real-time monitoring of upstream and downstream activation relationships of P53 mRNA,Bax mRNA,and cytochrome c(Cyt c)in signaling pathways is of great significance for understanding the apoptotic machinery in human physiology.In this work,a novel nucleic acid multicolor fluorescent probe,based on silica-coated symmetric gold nanostars(S-AuNSs@SiO_(2)),was developed for highly sensitive in situ real-time imaging of P53 mRNA,Bax mRNA,and Cyt c during T-2 toxin-induced apoptosis.The nucleic acid chains modified with carboxyl groups were modified on the surface of S-AuNSs@SiO_(2)by amide reaction.The complementary chains of targeted mRNA and the aptamer of targeted Cyt c were modified with different fluorophores,respectively,and successfully hybridized on S-AuNSs@SiO_(2)surface.When targets were present,the fluorescent chains bound to the targets and detached from the material,resulting in the quenched fluorescence being revived.The probes based on S-AuNSs showed excellent performance is partly ascribed to the presence of 20 symmetric“hot spots”.Notably,the amide-bonded probe exhibited excellent anti-interference capability against biological agents(nucleases and biothiols).During the real-time fluorescence imaging of T-2 toxin-induced apoptosis,the corresponding fluorescence signals of P53 mRNA,Bax mRNA,and Cyt c were observed sequentially.Therefore,S-AuNSs@SiO_(2)probe not only provides a novel tool for real-time monitoring of apoptosis pathways cascade but also has considerable potential in disease diagnosis and pharmaceutical medical.展开更多
基金supported by the National Natural Science Foundation of China(No.81872567).
文摘T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue damage by T-2 toxin.Twenty-four male Sprague-Dawley rats were orally administered T-2 toxin through gavage for 12 weeks at the dose of 0,10,and 100 nanograms per gram body weight per day(ng/(g·day)),respectively.Morphological,pathological,and ultrastructural alterations in cardiac tissue were meticulously examined.Non-targeted metabolomics analysis was employed to analyze alterations in cardiac metabolites.The expression of the Sirt3/FoxO3α/MnSOD signaling pathway and the level of oxidative stress markers were detected.The results showed that exposure to T-2 toxin elicited myocardial tissue disorders,interstitial hemorrhage,capillary dilation,and fibrotic damage.Mitochondria were markedly impaired,including swelling,fusion,matrix degradation,and membrane damage.Metabonomics analysis unveiled that T-2 toxin could cause alterations in cardiacmetabolic profiles as well as in the Sirt3/FoxO3α/MnSOD signaling pathway.T-2 toxin could inhibit the expressions of the signaling pathway and elevate the level of oxidative stress.In conclusion,the T-2 toxin probably induces cardiac fibrotic impairment by affecting amino acid and choline metabolism as well as up-regulating oxidative stress mediated by the Sirt3/FoxO3α/MnSOD signaling pathway.This study is expected to provide targets for preventing and treating T-2 toxin-induced cardiac fibrotic injury.
文摘Objective To investigate the effect on the structure of reestablished cartilage in vitro and CD44 expression on chondrocytes and compare the inducing effect on the reestablished cartilage in vitro between cortical bone matrix gelatin and cancellous bone matrix gelatin. Methods To plant human fetal chondrocytes on the BMG, the damage of the cultured chondrocytes was observed by the optical microscope (HE staining). The immunohistochemistry of CD44 was quantitative analysis by the image collection and analysis system. Results With the increasing concentration of T 2 toxin, the damage of chondroytes was more and more evident and CD44 expression was lowered. After adding selenium, the damage was relieved and CD44 expression increased. The density of chondrocytes on the cortical bone matrix gelatin was much higher than that on the cancellous bone matrix gelatin. Conclusion T 2 toxin can lower the CD44 expression on the chondrocytes and adding selenium can relieve the damage caused by T 2toxin and increased CD44 expression. The inducing effect on reestablished cartilage in vitro of cortical bone matrix gelatin was much higher than that of cancellous bone matrix gelatin.
基金Supported by Agricultural Science and Technology Support Program(Social Development)of Jiangsu Province(BE2011771)~~
文摘[Objective] This study aimed to establish a real-time PCR method for de- tecting stx2 gene in Shiga toxin-producing E. coli （STEC）. [Method] According to the known STEC stx2 gene sequences published in GenBank, PCR primers and probes were designed based on the conserved region to construct recombinant plasmid as a positive template, thus optimizing the reaction conditions and establishing the real- time PCR method. [Result] A standard curve was established based on the opti- mized real-time PCR system, indicting a good linear correlation between the initial template concentration and Ct value, with the correlation coefficient F^e of above 0.995. The established method had a good specificity, without non-specific amplifica- tion for 10 non-STEC intestinal bacterial strains; the detection limit of initial template was 1.0x102 copies/μI, indicating a high sensitivity; furthermore, the coefficients of variation within and among batches were lower than 1% and 5% respectively, sug- gesting a good repeatability. [Conclusion] In this study, a real-time PCR method was successfully established for detecting STEC stx2 gene, which provided technical means for rapid detection of STEC in samples.
基金Project(Nos.3063058 and 30471499)supported by the National Natural Science Foundation of China
文摘Objective:To investigate the effects of T-2 toxin on expressions of Fas,p53,Bcl-xL,Bcl-2,Bax and caspase-3 on human chondrocytes.Methods:Human chondrocytes were treated with T-2 toxin(1～20 ng/ml)for 5 d.Fas,p53 and other apoptosis-related proteins such as Bax,Bcl-2,Bcl-xL,caspase-3 were determined by Western blot analysis and their mRNA expressions were determined by reverse transcriptase-polymerase chain reaction(RT-PCR).Results:Increases in Fas,p53 and the pro-apoptotic factor Bax protein and mRNA expressions and a decrease of the anti-apoptotic factor Bcl-xL were observed in a dose-dependent manner after exposures to 1～20 ng/ml T-2 toxin,while the expression of the anti-apoptotic factor Bcl-2 was unchanged.Meanwhile,T-2 toxin could also up-regulate the expressions of both pro-caspase-3 and caspase-3 in a dose-dependent manner.Conclusion:These data suggest a possible underlying molecular mechanism for T-2 toxin to induce the apoptosis sig- naling pathway in human chondrocytes by regulation of apoptosis-related proteins.
基金Project supported by the National Natural Science Foundation of China (Nos. 30471499 and 30170831)the Ministry of Education of China (No.Key 03152)the Science Foundation of Shaanxi Province of China (No.2004KW-20)
文摘Objective: To identify the relationship between T-2 toxin and Kashin-Beck disease (KBD),the effects of T-2 toxin on aggrecan metabolism in human chondrocytes and cartilage were investigated in vitro. Methods: Chondrocytes were isolated from human articular cartilage and cultured in vitro. Hyaluronic acid (HA),soluble CD44 (sCD44),IL-1β and TNF-α levels in super-natants were measured by enzyme-linked immunosorbent assay (ELISA). CD44 content in chondrocyte membrane was deter-mined by flow cytometry (FCM). CD44,hyaluronic acid synthetase-2 (HAS-2) and aggrecanases mRNA levels in chondrocytes were determined using reverse transcription polymerase chain reaction (RT-PCR). Immunocytochemical method was used to investigate expressions of BC-13,3-B-3(-) and 2-B-6 epitopes in the cartilage reconstructed in vitro. Results: T-2 toxin inhibited CD44,HAS-2,and aggrecan mRNA expressions,but promoted aggrecanase-2 mRNA expression. Meanwhile,CD44 expression was found to be the lowest in the chondrocytes cultured with T-2 toxin and the highest in control plus selenium group. In addition,ELISA results indicated that there were higher sCD44,IL-1β and TNF-α levels in T-2 toxin group. Similarly,higher HA levels were also observed in T-2 toxin group using radioimmunoprecipitation assay (RIPA). Furthermore,using monoclonal antibodies BC-13,3-B-3 and 2-B-6,strong positive immunostaining was found in the reconstructed cartilage cultured with T-2 toxin,whereas no positive staining or very weak staining was observed in the cartilage cultured without T-2 toxin. Selenium could partly inhibit the effects of T-2 toxin above. Conclusion: T-2 toxin could inhibit aggrecan synthesis,promote aggrecanases and pro-inflammatory cytokines production,and consequently induce aggrecan degradation in chondrocytes. These will perturb metabolism balance between aggrecan synthesis and degradation in cartilage,inducing aggrecan loss in the end,which may be the initiation of the cartilage degradation.
基金partially supported by National Natural Scientific Foundation of China[81620108026,81302393]
文摘Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1 mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system（thighbone, knee joints, and costal cartilage） were significantly higher than those in the heart, liver, and kidneys（P 〈 0.05）. The relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system（thighbone and costal cartilage） were also significantly higher than those in the heart, liver, and kidneys. The rats administered T-2 toxin showed rapid metabolism compared with that in rats administered HT-2 toxin, and the metabolic conversion rates in the different tissues were 68.20%-90.70%.
基金supported by the National Natural Science Foundation of China(No.81573102 and No.81273006)the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry(11-01)
文摘Objective To investigate chondrocyte apoptosis and the expression of biochemical markers associated with apoptosis in Kashin-Beck disease（KBD） and in an established T-2 toxin-and selenium（Se） deficiency-induced rat model. Methods Cartilages were collected from the hand phalanges of five patients with KBD and five healthy children. Sprague-Dawley rats were administered a selenium-deficient diet for 4 weeks prior to T-2 toxin exposure. The apoptotic chondrocytes were observed by terminal deoxynucleotidyl transferase d UTP nick end labeling staining. Caspase-3, p53, Bcl-2, and Bax proteins in the cartilages were visualized by immunohistochemistry, their protein levels were determined by Western blotting, and m RNA levels were determined by real-time reverse transcription polymerase chain reaction. Results Increased chondrocyte apoptosis was observed in the cartilages of children with KBD. Increased apoptotic and caspase-3-stained cells were observed in the cartilages of rats fed with normal and Se-deficient diets plus T-2 toxin exposure compared to those in rats fed with normal and Se-deficient diets. Caspase-3, p53, and Bax proteins and m RNA levels were higher, whereas Bcl-2 levels were lower in rats fed with normal or Se-deficiency diets supplemented with T-2 toxin than the corresponding levels in rats fed with normal diet. Conclusion T-2 toxin under a selenium-deficient nutritional status induces chondrocyte death, which emphasizes the role of chondrocyte apoptosis in cartilage damage and progression of KBD.
基金supported by the National Basic Re-search Program(973)of China(No.2011CB503803)the National Key Project on Drug Development from the Ministry of Science and Technology of China(No.2009ZX09501-034)China Postdoctoral Science Foundation(No.20110491865)
文摘T-2 toxin is one of the most important trichothecene mycotoxins occurring in various agriculture products. The developmental toxicity of T-2 toxin and the exact mechanism of action at early life stages are not understood precisely. Zebrafish embryos were exposed to different concentrations of the toxin at 4-6 hours post fertilization （hpf） stage of development, and were observed for different developmental toxic effects at 24, 48, 72, and 144 hpf. Exposure to 0.20 Ixmol/L or higher concentrations of T-2 toxin significantly increased the mortality and malformation rate such as tail deformities, cardiovascular defects and behavioral changes in early developmental stages of zebrafish. T-2 toxin exposure resulted in significant increases in reactive oxygen species （ROS） production and cell apoptosis, mainly in the tall areas, as revealed by Acridine Orange staining at 24 hpf. In addition, T-2 toxin-induced severe tail deformities could be attenuated by co-exposure to reduced glutathione （GSH）. T-2 toxin and GSH co-exposure induced a significant decrease of ROS production in the embryos. The overall results demonstrate that T-2 toxin is able to produce oxidative stress and induce apoptosis, which are involved in the developmental toxicity of T-2 toxin in zebrafish embryos.
基金supported by the National Natural Science Foundation of China (32273084)the Special Funds for Construction of Innovative Provinces in Hunan Province,China (2020NK2032)+2 种基金the Natural Science Foundation of Hunan Province,China (2020JJ4368)Innovation Foundation for Postgraduate of Hunan Province,China (CX20220670)Innovation Foundation for Postgraduate of Hunan Agricultural University,China (2022XC010)。
文摘F-2 toxin is an estrogenic mycotoxin that causes reproductive disorders in animals.Betulinic acid(BA)is a natural pentacyclic lupane-structure triterpenoid that has diverse pharmacological activities.In this study,the antioxidative and anti-inflammatory effects of BA and its underlying mechanism are explored in F-2 toxin-triggered mouse ovarian damage.We found that BA alleviated the F-2 toxin-induced ovarian impairment by stimulating follicle growth,reducing inflammatory cell infiltration,repairing damaged mitochondria and endoplasmic reticulum.Simultaneously,BA not only reversed F-2 toxin-induced reduction of follicle stimulating hormone(FSH)and luteinizing hormone(LH)levels in the serum,but also restrained the protein expression of the estrogen receptors a(ERa)and ERβ.Moreover,BA restored the balance of F-2 toxin-induced ovarian redox system disorders.Subsequently,we found that 0.25 mg/kg BA played an anti-inflammatory role in the F-2 toxin-induced ovarian impairment by decreasing interleukin-1β(IL-1β).IL-6,and tumor necrosis factor-α(TNF-α)mRNA expression,as well as inhibiting p38 protein expression.These data demonstrated that BA exerts its protective effect on F-2 toxin-induced ovarian oxidative impairment and inflammation by inhibiting p38 expression,which implies a natural product-based medicine to ameliorate F-2 toxin-caused female reproductive toxicity and provides a detoxifying method for food contaminated by mycotoxin.
基金Supported by the National Natural Science Foundation of China(31872530)。
文摘T-2 toxin is the most widespread mycotoxin in crops,feed and food,which poses a serious threat to body health.Bone is the main target tissue for T-2 toxin accumulation.Ingestion of food contaminated by T-2 toxin is the main cause of Kashin-Beck disease.However,the specific mechanism of bone damage caused by T-2 toxin is still unclear.In this study,a total of 40 male C57BL/6N mice were divided into four groups and orally treated with 0,0.5,1.0 and 2.0 mg·kg^(-1) body weight T-2 toxin for 28 days.The results showed that exposure to T-2 toxin led to weight loss,bone mineral density reduction and femoral structural damage of mice.In addition,osteoblast-mediated bone formation was inhibited,and osteoclast-mediated bone resorption was enhanced.Meanwhile,the levels of bone metabolism-related hormones including parathyroid hormone,calcitonin and 1,25-dihydroxyvitamin D3 were reduced.More importantly,it was found that the level of neuropeptide Y(a neurohormone)was decreased.These results provided a new perspetive for understanding the osteotoxicity of T-2 toxin.
文摘The effects of deoxynlvalenol (DON), T--2 toxin, nivalenol (NIv), hutenolide (BuT).alternariol methyl ether(AME) and monlliformin (cON ) on rabbit articular chondrocytes were observed by using the method of chondrocyte monolayer culture. The amounts or DNA in chondrocytesand glucuronate in matrix were measured. And the chondrocytes were observed by inversion microscope and transmission electron microscope (TEM). The results showed that the cultured chondrocytes were damaged by all the six mycotoxinsl and the synthesis of DNA and the divided reproductionof chondrocytes were restrained; the damage errect was more evident, esl,ecially in the early stage ofculturel the higher concentration or toxin in the media was used, the lower density of the culturalckondrocytes was observed; the cells were even round damaged and dead, so long as the media contolued toxin. When the six mycotoxins arrected the cultural chondrocytes r.spectively, three dirfereut kinds or ultrastructural changes in ckondrocytes were seen by TEa. The relationship betweenmycotoxiu and KBD was preliminarily discussed, and some problems still need further investigation..
文摘Hemolytic uremic syndrome （HUS） is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and patho-genetic classifications. New findings in genetics and, in particular, mutations of genes that encode the complement-regulatory proteins have improved our understanding of atypical HUS. Similarly, the comple-ment proteins are clearly involved in all types of thrombotic microangiopathy： typical HUS, atypical HUS and thrombotic thrombocytopenic purpura （TTP）. Fur-thermore, several secondary HUS appear to be related to abnormalities in complement genes in predisposed patients. The authors highlight the therapeutic as-pects of this rare disease, examining both “traditional therapy” （including plasma therapy, kidney and kidney-liver transplantation） and “new therapies”. The latter include anti-Shiga-toxin antibodies and anti-C5 mono-clonal antibody “eculizumab”. Eculizumab has been recently launched for the treatment of the atypical HUS, but it appears to be effective in the treatment of typical HUS and in TTP. Future therapies are in phases Ⅰ and Ⅱ. They include anti-C5 antibodies, which are more purifed, less immunogenic and absorbed orally and, anti-C3 antibodies, which are more powerful, but potentially less safe. Additionally, infusions of recombinant complement-regulatory proteins are a potential future therapy.
基金supported by the Doctoral Initiation Fund Project Grant(BK202315)Medical Research Special Fund(2022YKY17)of Hubei University of Science and TechnologyHubei Provincial Natural Science Foundation Programme(2023AFB537)
文摘T-2 toxin is one of the most widespread and toxic fungal toxins in food and feed.It can cause gastrointestinal toxicity,hepatotoxicity,immunotoxicity,reproductive toxicity,neurotoxicity,and nephrotoxicity in humans and animals.T-2 toxin is physicochemically stable and does not readily degrade during food and feed processing.Therefore,suppressing T-2 toxin-induced organ toxicity through antidotes is an urgent issue.Protective agents against the organ toxicity of T-2 toxin have been recorded widely in the literature,but these protective agents and their molecular mechanisms of detoxification have not been comprehensively summarized.In this review,we provide an overview of the various protective agents to T-2 toxin and the molecular mechanisms underlying the detoxification effects.Targeting appropriate targets to antagonize T-2 toxin toxicity is also an important option.This review will provide essential guidance and strategies for the better application and development of T-2 toxin antidotes specific for organ toxicity in the future.
基金the financial support from the Jiangsu Agriculture Science and Technology Innovation Fund(No.CX(19)2005)the Social Development Fund Project of Wuxi(No.N20201001).
文摘T-2 toxin,one of the most dangerous natural pollutants,induces apoptosis through multiple pathways.Amongst,P53 mediated apoptosis pathway,an important collection of molecules,plays a key role in cell vital activity.Real-time monitoring of upstream and downstream activation relationships of P53 mRNA,Bax mRNA,and cytochrome c(Cyt c)in signaling pathways is of great significance for understanding the apoptotic machinery in human physiology.In this work,a novel nucleic acid multicolor fluorescent probe,based on silica-coated symmetric gold nanostars(S-AuNSs@SiO_(2)),was developed for highly sensitive in situ real-time imaging of P53 mRNA,Bax mRNA,and Cyt c during T-2 toxin-induced apoptosis.The nucleic acid chains modified with carboxyl groups were modified on the surface of S-AuNSs@SiO_(2)by amide reaction.The complementary chains of targeted mRNA and the aptamer of targeted Cyt c were modified with different fluorophores,respectively,and successfully hybridized on S-AuNSs@SiO_(2)surface.When targets were present,the fluorescent chains bound to the targets and detached from the material,resulting in the quenched fluorescence being revived.The probes based on S-AuNSs showed excellent performance is partly ascribed to the presence of 20 symmetric“hot spots”.Notably,the amide-bonded probe exhibited excellent anti-interference capability against biological agents(nucleases and biothiols).During the real-time fluorescence imaging of T-2 toxin-induced apoptosis,the corresponding fluorescence signals of P53 mRNA,Bax mRNA,and Cyt c were observed sequentially.Therefore,S-AuNSs@SiO_(2)probe not only provides a novel tool for real-time monitoring of apoptosis pathways cascade but also has considerable potential in disease diagnosis and pharmaceutical medical.
