Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions...Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 mg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13C5]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.展开更多
A novel water-soluble cystine C60 derivative was synthesized in the presence of the catalyst, tetrabutylammonium hydroxide （TBAH）. The product was characterized by FT-IR, UV, ^1H NMR, ^13C NMR, MS and elemental anal...A novel water-soluble cystine C60 derivative was synthesized in the presence of the catalyst, tetrabutylammonium hydroxide （TBAH）. The product was characterized by FT-IR, UV, ^1H NMR, ^13C NMR, MS and elemental analysis. Furthermore, the scavenging ability to superoxygen anion radical O2^·- and hydroxyl radical ^·OH was studied by chemiluminescence. It was found that cystine C60 derivative showed an excellent efficiency in eliminating superoxygen anion radical and hydroxyl radical. The 50% inhibition concentration （IC50） for superoxygen anion radical and hydroxyl radical were 0.167 and 0.008 mg/mL, respectively.展开更多
Oxidative stress has been considered as a major cause of cellular injuries in a variety of clinical abnormalities,especially prominent in neural diseases.One of the usable ways to prevent the reactive oxygen species(R...Oxidative stress has been considered as a major cause of cellular injuries in a variety of clinical abnormalities,especially prominent in neural diseases.One of the usable ways to prevent the reactive oxygen species(ROS)-mediated cellular injury is dietary or pharmaceutical augmentation of some free radical scavenger.Water-soluble amino-fullerene is a novel compound that behaves as a free radical scavenger with excellent biology consistent.In the present study,we have synthesized and characterized a novel cystine C60 derivative for the first time,and investigated the effects on hydrogen peroxide-induced oxidative stress and apoptotic death in cultured rat pheochromocytoma(PC12)cells.PC12 cells treated with hydrogen peroxide underwent apoptotic death as determined by MTT,PI/Hoechst 33342 staining and flow cytometry analysis.These results suggested that cystine C60 derivative has the potential to prevent oxidative stress-induced cell death and has no evident toxicity.展开更多
Cystine is the primary source material for the synthesis of glutathione.However,the pharmacokinetics and tissue distribution of cystine are largely unknown.A surrogate analyte D_(4)-cystine was employed to generate ca...Cystine is the primary source material for the synthesis of glutathione.However,the pharmacokinetics and tissue distribution of cystine are largely unknown.A surrogate analyte D_(4)-cystine was employed to generate calibration curves for the determination of levels of D_(4)-cystine and endogenous cystine in mice by liquid chromatography-tandem mass spectrometry(LC-MS/MS).Validation assessments proved the sensitivity,specificity and reproducibility of the method with a lower limit of quantification(LLOQ)of 5 ng/mL over 5e5000 ng/mL in plasma.The pharmacokinetics of D_(4)-cystine were evaluated after administering injections and oral solutions,both of which minimally impacted endogenous cystine levels.The absolute bioavailability of cystine was 18.6%,15.1%and 25.6%at doses of 25,50 and 100 mg/kg,respectively.Intravenously injected D_(4)-cystine resulted in dramatically high plasma levels with reduced levels in the brain and liver.Intragastrically administered D_(4)-cystine resulted in high levels in the plasma and stomach with relatively low levels in the lung,kidney,heart and brain.展开更多
An electrochemical quartz crystal impedance system has been applied to monitorgeneration of precipitate and adsorption of the precipitate onto An electrode during electrochmicaloxidation and Fe(CN)_6,3-/Fe(CN),6 4- el...An electrochemical quartz crystal impedance system has been applied to monitorgeneration of precipitate and adsorption of the precipitate onto An electrode during electrochmicaloxidation and Fe(CN)_6,3-/Fe(CN),6 4- electrochemical catalytic oxidation of L-cysteine in phosphateaqueous buffer (pH 7.4). Significant decreases in the resonant frequency and increases in themotional resistance and the static capacitance were found during the precipitate adsorption, and thefrequency shift found in solution was ca. 2 times that in air. Similar responses of quartz crystalimpedance and a white precipitate were obtained during redox titration of L-cysteine solutionusing K_3Fe(CN)_6 solution. FT-IR analysis indicated that the white precipitate is cystine. Theelectrode collection efficiency of the electrogenerated cystine was estimated.展开更多
Objective To evaluate the effectiveness of ESWL for treating patients with cystine calculus. Methods Of 31 patients, 20 were subjected to ESWL only, 6 were subjected to combination therapy of PCNL and ESWL, 2 Pneumati...Objective To evaluate the effectiveness of ESWL for treating patients with cystine calculus. Methods Of 31 patients, 20 were subjected to ESWL only, 6 were subjected to combination therapy of PCNL and ESWL, 2 Pneumatic Lithotriptor-ESWL, 3 Laser lithotripsy-ESWL. Results For 14 renal stones, the fragmentation after ESWL manotherapy was 85. 7% and 14.3% after twice ESWL sessions. For 17 ureter calculus, the fragmentation after ESWL manotherapy was 82.3% and 11.7% after twice ESWL sessions. One patient （ 5.8% ） failed and changed to open surgery. Conclusion ESWL is an effective and reliable method for treating patients with cystine calculus, however, better effects and shorter treatment time could be obtained by the combination of ESWL with other therapy options.展开更多
The cystine/glutamate antiporter SLC7A11(also commonly known as xCT)functions to import cystine for glutathione biosynthesis and antioxidant defense and is overexpressed in multiple human cancers.Recent studies reveal...The cystine/glutamate antiporter SLC7A11(also commonly known as xCT)functions to import cystine for glutathione biosynthesis and antioxidant defense and is overexpressed in multiple human cancers.Recent studies revealed that SLC7A11 overexpression promotes tumor growth partly through suppressing ferroptosis,a form of regulated cell death induced by excessive lipid peroxidation.However,cancer cells with high expression of SLC7A11(SLC7A11^(high))also have to endure the significant cost associated with SLC7A11-mediated metabolic reprogramming,leading to glucose-and glutamine-dependency in SLC7A11^(high) cancer cells,which presents potential metabolic vulnerabilities for therapeutic targeting in SLC7A11^(high) cancer.In this review,we summarize diverse regulatory mechanisms of SLC7A11 in cancer,discuss ferroptosis-dependent and-independent functions of SLC7A11 in promoting tumor development,explore the mechanistic basis of SLC7A11-induced nutrient dependency in cancer cells,and conceptualize therapeutic strategies to target SLC7A11 in cancer treatment.This review will provide the foundation for further understanding SLC7A11 in ferroptosis,nutrient dependency,and tumor biology and for developing novel effective cancer therapies.展开更多
Cystine/glutamate antiporter solute carrier family 7 member 11(SLC7A11;also known as xCT)plays a key role in antioxidant defense by mediating cystine uptake,promoting glutathione synthesis,and maintaining cell surviva...Cystine/glutamate antiporter solute carrier family 7 member 11(SLC7A11;also known as xCT)plays a key role in antioxidant defense by mediating cystine uptake,promoting glutathione synthesis,and maintaining cell survival under oxidative stress conditions.Recent studies showed that,to prevent toxic buildup of highly insoluble cystine inside cells,cancer cells with high expression of SLC7A11(SLC7A11high)are forced to quickly reduce cystine to more soluble cysteine,which requires substantial NADPH supply from the glucose-pentose phosphate pathway(PPP)route,thereby inducing glucose-and PPP-dependency in SLC7A11high cancer cells.Limiting glucose supply to SLC7A11high cancer cells results in significant NADPH“debt”,redox“bankruptcy”,and subsequent cell death.This review summarizes our current understanding of NADPH-generating and-consuming pathways,discusses the opposing role of SLC7A11 in protecting cells from oxidative stresseinduced cell death such as ferroptosis but promoting glucose starvationeinduced cell death,and proposes the concept that SLC7A11-mediated cystine uptake acts as a double-edged sword in cellular redox regulation.A detailed understanding of SLC7A11 in redox biology may identify metabolic vulnerabilities in SLC7A11high cancer for therapeutic targeting.展开更多
The cystine/glutamate exchanger(xCT,SLC7 A11)is a component of the system X_c amino-acid antiporter that is able to export glutamate and import cysteine into cells.The xCT amino acid exchanger has received a lot of at...The cystine/glutamate exchanger(xCT,SLC7 A11)is a component of the system X_c amino-acid antiporter that is able to export glutamate and import cysteine into cells.The xCT amino acid exchanger has received a lot of attention,due to the fact that cysteine is an essential substrate for the synthesis of glutathione(GSH),an endogenous antioxidant in cells.The objective of this research was to clone the full-length cDNA of chicken xCT,and to investigate the gene expression of xCT in different tissues,including intestinal segments of broiler chickens during development.The full-length cDNA of chicken xCT(2,703 bp)was obtained from the jejunum by reverse transcription-PCR and sequenced.Homology tests showed that chicken xCT had 80.4%,80.2%,and 71.2%homology at the nucleotide level with humans,cattle,and rats,respectively.Likewise,amino acid sequence analysis showed that chicken xCT protein is 86.4%,79.3%,and 75.6%homologous with humans,cattle,and rats,respectively.Additionally,phylogenetic analysis indicated that chicken xCT genes share a closer genetic relationship with humans and cattle,than with rats.The chicken xCT protein has 12 transmembrane helixes,6 extracellular loops,and 5 intracellular loops.The mRNA of xCT was detected in all tissues,including intestinal segments,in which the mRNA expression of xCT was significantly higher(P<0.05)within the colon,compared to the jejunum and ileum.During development,a linear pattern of changes regarding the levels of the xCT mRNA was found,indicating that there was an abundance of xCT within the duodenum(P<0.05).Furthermore,there were changes of the xCT mRNA abundance in the colon during development,which displayed linear and cubic patterns(P<0.05).These results indicated that xCT is widely expressed both in intestinal segments,as well as other organs that are not associated with nutrient absorption.Further investigation is needed to characterize the functional relevance of xCT activity in oxidative stress and inflammation in the small intestine of broiler chickens.展开更多
The physicochemical characteristics of nanoparticles are closely related to their drug delivery performances in vitro and in vivo.A well-designed nanocarrier can prolong the drug half-life in the blood circulation,upr...The physicochemical characteristics of nanoparticles are closely related to their drug delivery performances in vitro and in vivo.A well-designed nanocarrier can prolong the drug half-life in the blood circulation,upregulate the drug accumulation at the target site,and enhance the treatment efficacy.To elucidate the impact of physicochemical properties on the fate of nanogel as a nanocarrier of chemotherapeutics,three methoxy poly(ethylene glycol)-poly(L-phenylalanine-co-L-cystine)(mPEG-P(LP-coLC))nanogels with different L-cystine proportions were developed,namely mPEG-P(LP10-co-LC5)(NG10-5),mPEG-P(LP10-coLC10)(NG10-10),and mPEG-P(LP10-co-LC15)(NG10-15).The three nanogels shared similar surface charge and reductionresponsive behavior,but they had distinct diameters and different drug release profiles.Among them,NG10-5,which has the smallest diameter,was preferentially internalized by tumor cells in vitro and showed rapid migration to the tumor site in vivo.Using doxorubicin(DOX)as a model chemotherapeutic agent,NG10-5/DOX had the most prolonged blood circulation period and highest tumor accumulation after intravenous administration.NG10-5/DOX also had the most potent antitumor effect of all three drug-loaded nanogels.Accordingly,adjusting physicochemical characteristics by changing the amino acid composition might improve the therapeutic efficacies of nanogels and enhance their potential for clinical application.展开更多
Recently,various semiconductor/metal composites have been developed to fabricate surfaceenhanced Raman spectroscopy substrates.However,low metal loading on semiconductors is still a challenge.In this study,cystine was...Recently,various semiconductor/metal composites have been developed to fabricate surfaceenhanced Raman spectroscopy substrates.However,low metal loading on semiconductors is still a challenge.In this study,cystine was introduced to increase the accumulation of gold nanoparticles on zinc oxide,owing to the biomineralization_property of_cystine.Morphological analysis revealed that the obtained ZnO/Au/cystine composite not only had a higher metal loading but also formed a porous structure,which is beneficial for Raman performance.Compared with ZnO/Au,the ZnO/Au/cystine substrate displayed a 40-fold enhancement in the Raman signal and a lower limit of detection(10^(-11) mol·L^(-1))in the detection of rhodamine 6G.Moreover,the substrate has favorable homogeneity and stability.Finally,ZnO/Au/cystine displayed excellent performance toward crystal violet and methylene blue in a test based on river water samples.This study provided a promising method to fabricate sensitive semiconductor/noblemetal-based surface-enhanced Ramans spectroscopy substrates for Raman detection.展开更多
Breast cancer is a prevalent malignancy worldwide.The majority of breast cancers belong to the estrogen receptor(ER)-positive luminal subtype that can be effectively treated with antiestrogen therapies.However,a signi...Breast cancer is a prevalent malignancy worldwide.The majority of breast cancers belong to the estrogen receptor(ER)-positive luminal subtype that can be effectively treated with antiestrogen therapies.However,a significant portion of such malignancies become hormone-refractory and incurable.Cancer cells often uptake more cystines to increase glutathione(GSH)biosynthesis and reduce reactive oxygen species(ROS),thereby preventing ROS-induced ferroptosis and leading to therapeutic resistance.However,few molecules of these processes are targetable for cancer therapy.However,few therapeutic targets have been established that target these processes.Here,we report that the gene for SLC7A13,a member of the SLC7A13-SLC3A1 cystine transporter,was amplified and overexpressed in 19.7% and 49.7% of breast cancers,respectively.SLC7A13 amplifi cation and overexpression were associated with worse overall survival and disease-free survival in patients with luminal breast cancer.Functionally,SLC7A13 overexpression promoted,while its silencing attenuated,cell survival or proliferation.Molecularly,SLC7A13 silencing reduced cystine uptake and GSH biosynthesis,leading to increased lipid ROS levels.The cryo-EM structure of the human SLC7A13-SLC3A1 complex was determined at 2.64AA,revealing a dimer-of-heterodimers architecture similar to that of other SLC3A1-linked transporters.A specific substrate-binding pocket was identified,containing distinct residues,which suggests a regulatory role in the cystine transporter.These findings suggest that the SLC7A13-SLC3A1 cystine transporter is a therapeutic target for treating luminal breast cancer.They also provide the structural insights for therapeutic development targeting the cystine transporter.展开更多
The iron chelator deferoxamine has been shown to inhibit ferroptosis in spinal cord injury.However,it is unclear whether deferoxamine directly protects neurons from ferroptotic cell death.By comparing the survival rat...The iron chelator deferoxamine has been shown to inhibit ferroptosis in spinal cord injury.However,it is unclear whether deferoxamine directly protects neurons from ferroptotic cell death.By comparing the survival rate and morphology of primary neurons and SH-SY5Y cells exposed to erastin,it was found that these cell types respond differentially to the duration and concentration of erastin treatment.Therefore,we studied the mechanisms of ferroptosis using primary cortical neurons from E16 mouse embryos.After treatment with 50μM erastin for 48 hours,reactive oxygen species levels increased,and the expression of the cystine/glutamate antiporter system light chain and glutathione peroxidase 4 decreased.Pretreatment with deferoxamine for 12 hours inhibited these changes,reduced cell death,and ameliorated cellular morphology.Pretreatment with the apoptosis inhibitor Z-DEVD-FMK or the necroptosis inhibitor necrostain-1 for 12 hours did not protect against erastin-induced ferroptosis.Only deferoxamine protected the primary cortical neurons from ferroptosis induced by erastin,confirming the specificity of the in vitro ferroptosis model.This study was approved by the Animal Ethics Committee at the Institute of Radiation Medicine of the Chinese Academy of Medical Sciences,China(approval No.DWLL-20180913)on September 13,2018.展开更多
DL-3-n-butylphthalide(NBP)-a compound isolated from Apium graveolens seeds-is protective against brain ischemia via various mechanisms in humans and has been approved for treatment of acute ischemic stroke.NBP has sho...DL-3-n-butylphthalide(NBP)-a compound isolated from Apium graveolens seeds-is protective against brain ischemia via various mechanisms in humans and has been approved for treatment of acute ischemic stroke.NBP has shown recent potential as a treatment for Parkinson’s disease.However,the underlying mechanism of action of NBP remains poorly understood.In this study,we established a rat model of Parkinson’s disease by intraperitoneal injection of rotenone for 28 successive days,followed by intragastric injection of NBP for 14-28 days.We found that NBP greatly alleviated rotenone-induced motor disturbance in the rat model of Parkinson’s disease,inhibited loss of dopaminergic neurons and aggregation ofα-synuclein,and reduced iron deposition in the substantia nigra and iron content in serum.These changes were achieved by alterations in the expression of the iron metabolism-related proteins transferrin receptor,ferritin light chain,and transferrin 1.NBP also inhibited oxidative stress in the substantia nigra and protected mitochondria in the rat model of Parkinson’s disease.Our findings suggest that NBP alleviates motor disturbance by inhibition of iron deposition,oxidative stress,and ferroptosis in the substantia nigra.展开更多
A series of alloyed Zn‐Cd‐S solid solutions with a cubic zinc blende structure were fabricated hydrothermally with the assistance of L‐cystine under mild conditions.The products were characterized by XRD,TEM,HRTEM,...A series of alloyed Zn‐Cd‐S solid solutions with a cubic zinc blende structure were fabricated hydrothermally with the assistance of L‐cystine under mild conditions.The products were characterized by XRD,TEM,HRTEM,XPS,UV‐vis,and BET techniques,and the photocatalytic performance for the reduction of water to H2on the solid solutions was evaluated in the presence of S2?/SO32?as hole scavengers under visible light illumination.Among all the samples,the highest photocatalytic activity was achieved over Zn0.9Cd0.1S with a rate of4.4mmol h?1g?1,even without a co‐catalyst,which far exceeded that of CdS.Moreover,Zn0.9Cd0.1S displayed excellent anti‐photocorrosion properties during the photoreduction of water into H2.The enhancement in the photocatalytic performance was mainly attributed to the efficient charge transfer in the Zn0.9Cd0.1alloyed structure and the high surface area.This work provides a simple,cost‐effective and green technique,which can be generalized as a rational preparation route for the large‐scale fabrication of metal sulfide photocatalysts.展开更多
Bone metastasis,a life-threatening complication of advanced breast cancer,is often accompanied by debilitating pain(cancer-induced bone pain,CIBP)that severely impairs life quality and survival.The concurrent treatmen...Bone metastasis,a life-threatening complication of advanced breast cancer,is often accompanied by debilitating pain(cancer-induced bone pain,CIBP)that severely impairs life quality and survival.The concurrent treatment of bone metastases and CIBP remains a clinical challenge because the therapeutic options are limited.In this study,we construct a near-infrared light-activated nano-therapeutic system to meet this conundrum.In detail,sorafenib(SRF)and photosensitizer(chlorin e6,Ce6)are encapsulated into mesoporous hydroxyapatite nanoparticles(HANPs),which are further functionalized with hyaluronic acid(HA)to obtain HA-SRF/Ce6@HANPs system.The designed nanoplatform destroys tumor cells in vitro and in vivo via the synergism of SRF(interrupting the exchange of cystine/glutamate by inhibiting SLC7A11)and photodynamic therapy(PDT,inducing reactive oxygen species generation).The decrease in tumor burden and reduction of extracellular glutamate significantly attenuate CIBP in mice model with developing bone cancer.Moreover,the combination of HA-SRF/Ce6@HANPs and PDT inhibit osteoclasts activation,promote osteoblast differentiation and accelerate bone repair.Overall,the nanoagent with good biocompatibility may provide an effective therapy method for the concurrent treatment of breast cancer bone metastasis and CIBP.展开更多
FTIR-ATR technique with second-order derivative measurement was used for assessing the amount of oxidation products of cystine present on the plasma-treated wool fabric surface. In this paper, three non-polymerising g...FTIR-ATR technique with second-order derivative measurement was used for assessing the amount of oxidation products of cystine present on the plasma-treated wool fabric surface. In this paper, three non-polymerising gases namely oxygen, nitrogen and 25% hydrogen/75% nitrogen gas mixture were used for the plasma treatment of wool fabric. The oxidation products of cystine studied included S-sulphonate, cysteic acid, cystine monoxide and cystine dioxide. The variations of the amount of these products as a function of treatment time were studied. Experimental results showed that the oxygen plasma could produce a large amount of oxidation products of cystine on the wool fabric surface followed by nitrogen plasma and gas mixture plasma.展开更多
Objective:To observe the clinical effect of Banxia Atractylodes macrocephala Tianma decoction in the treatment of hypertension.Methods:A total of 100 patients with hypertension were selected from our hospital(April 20...Objective:To observe the clinical effect of Banxia Atractylodes macrocephala Tianma decoction in the treatment of hypertension.Methods:A total of 100 patients with hypertension were selected from our hospital(April 2016 to July 2019)and divided into 2 groups by random digital method.The control group was given routine symptomatic treatment of western medicine,and the observation group was given Banxia Atractylodes Gastrodia decoction on the basis of the control group.the levels of syndrome score and adiponectin(apn),cysc(cysc),uric acid(ua),c-reactive protein(crp),superoxide dismutase(sod),malondialdehyde(mda),8-hydroxydeoxyguanylic acid(8-ohdg)were recorded before and after treatment in group 2,and the total effective rate of clinical treatment was counted in group 2.Results:After treatment,the total effective rate(92.00%)in the observation group was higher than that in the control group(74.00%),and the difference was statistically significant(P<0.05).The APN、SOD level of the observation group was higher than that of the control group after treatment,and the CysC、UA、CRP、MDA、8-OHdG level and TCM symptom score were lower than those of the control group(P<0.05).Conclusion:Rhizoma Pinelliae and Rhizoma Gastrodiae decoction for treating hypertension can relieve oxidative stress injury,adjust the expression level of APN,CysC,CRP and UA,and improve the symptoms and improve the curative effect.展开更多
There are at least three conserved protein folds shared by ion channel-targeted neurotoxins and antimicrobial defensins,including cysteine-stabilizedα-helix andβ-sheet fold(CSαβ),inhibitor cystine knot fold(ICK)an...There are at least three conserved protein folds shared by ion channel-targeted neurotoxins and antimicrobial defensins,including cysteine-stabilizedα-helix andβ-sheet fold(CSαβ),inhibitor cystine knot fold(ICK)andβ-defensin fold(BDF).Based on a combined data of sequences,structures and functions,it has been proposed that these neurotoxins could originate from related ancient antimicrobial defensins by neofunctionalization.This provides an ideal system to study how a novel function emerged from a conserved structural scaffold during evolution.The elucidation of functional novelty of proteins not only has great significance in evolutionary biology but also will be helpful in guiding rational molecular design.This review describes recent progresses in origin of neurotoxins,focusing on the three conserved protein scaffolds.展开更多
The metabolic pathway of sulfur-containing amino acids in organisms begins with methionine,which is metabolized to produce important sulfur-containing biomolecules such as adenosylmethionine,adenosylhomocysteine,homoc...The metabolic pathway of sulfur-containing amino acids in organisms begins with methionine,which is metabolized to produce important sulfur-containing biomolecules such as adenosylmethionine,adenosylhomocysteine,homocysteine,cystine,and hydrogen sulfide(H2S).These sulfur-containing biomolecules play a wide range of physiological roles in the body,including antiinflammation,antioxidant stress,DNA methylation,protein synthesis,etc.,which are essential for maintaining cellular function and overall health.In contrast,dysregulation of the metabolic pathway of sulfur-containing amino acids leads to abnormal levels of sulfur-containing biomolecules,which produce a range of pathological consequences in multiple systems of the body,such as neurodegenerative diseases,cardiovascular diseases,and cancer.This review traces the milestones in the development of these sulfur-containing biomolecules from their initial discovery to their clinical applications and describes in detail the structure,physiochemical properties,metabolism,sulfide signaling pathway,physiopathological functions,and assays of sulfur-containing biomolecules.In addition,the paper also explores the regulatory role and mechanism of sulfur-containing biomolecules on cardiovascular diseases,liver diseases,neurological diseases,metabolic diseases and tumors.The focus is placed on donors of sulfur-containing biological macromolecule metabolites,small-molecule drug screening targeting H2S-producing enzymes,and the latest advancements in preclinical and clinical research related to hydrogen sulfide,including clinical trials and FDA-approved drugs.Additionally,an overview of future research directions in this field is provided.The aim is to enhance the understanding of the complex physiological and pathological roles of sulfur-containing biomolecules and to offer insights into developing effective therapeutic strategies for diseases associated with dysregulated sulfur-containing amino acid metabolism.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant NOs.:82272935,91957120 and 21974114)the Postdoctoral Fellowship Program of CPSF(Program No.:GZC20240901)+5 种基金the Xiamen Medical Industry Combined Guidance Project,China(Project No.:3502Z20244ZD2022)the Scientific Research Foundation for Advanced Talents,Xiang'an Hospital of Xiamen University,China(Grant No.:PM20180917008)the Fundamental Research Funds for the Central Universities,China(Grant No.:20720210001)Major Science and Technology Special Project of Fujian Province,China(Project No.:2022YZ036012)Joint Laboratory of School of Medicine,Xiamen University-Shanghai Jiangxia Blood Technology Co.,Ltd.,China(Grant No.:XDHT2020010C)Joint Research Center of School of Medicine,Xiamen University-Jiangsu Charity Biotech Co.,Ltd.,China(Grant No.:20233160C0002).
文摘Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 mg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13C5]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.
基金The project supported by the National Natural Science Foundation of China(No.20474020).
文摘A novel water-soluble cystine C60 derivative was synthesized in the presence of the catalyst, tetrabutylammonium hydroxide （TBAH）. The product was characterized by FT-IR, UV, ^1H NMR, ^13C NMR, MS and elemental analysis. Furthermore, the scavenging ability to superoxygen anion radical O2^·- and hydroxyl radical ^·OH was studied by chemiluminescence. It was found that cystine C60 derivative showed an excellent efficiency in eliminating superoxygen anion radical and hydroxyl radical. The 50% inhibition concentration （IC50） for superoxygen anion radical and hydroxyl radical were 0.167 and 0.008 mg/mL, respectively.
文摘Oxidative stress has been considered as a major cause of cellular injuries in a variety of clinical abnormalities,especially prominent in neural diseases.One of the usable ways to prevent the reactive oxygen species(ROS)-mediated cellular injury is dietary or pharmaceutical augmentation of some free radical scavenger.Water-soluble amino-fullerene is a novel compound that behaves as a free radical scavenger with excellent biology consistent.In the present study,we have synthesized and characterized a novel cystine C60 derivative for the first time,and investigated the effects on hydrogen peroxide-induced oxidative stress and apoptotic death in cultured rat pheochromocytoma(PC12)cells.PC12 cells treated with hydrogen peroxide underwent apoptotic death as determined by MTT,PI/Hoechst 33342 staining and flow cytometry analysis.These results suggested that cystine C60 derivative has the potential to prevent oxidative stress-induced cell death and has no evident toxicity.
基金This study was financially supported by the National Natural Science Foundation of the People's Republic of China(Grant Nos.:81773814 and 81530098)the National Key Special Project of Science and Technology for Innovation Drugs of China(Project No.:2017ZX09301013)the National Key Research and Development Program(Grant No.:2018YFC0807403).
文摘Cystine is the primary source material for the synthesis of glutathione.However,the pharmacokinetics and tissue distribution of cystine are largely unknown.A surrogate analyte D_(4)-cystine was employed to generate calibration curves for the determination of levels of D_(4)-cystine and endogenous cystine in mice by liquid chromatography-tandem mass spectrometry(LC-MS/MS).Validation assessments proved the sensitivity,specificity and reproducibility of the method with a lower limit of quantification(LLOQ)of 5 ng/mL over 5e5000 ng/mL in plasma.The pharmacokinetics of D_(4)-cystine were evaluated after administering injections and oral solutions,both of which minimally impacted endogenous cystine levels.The absolute bioavailability of cystine was 18.6%,15.1%and 25.6%at doses of 25,50 and 100 mg/kg,respectively.Intravenously injected D_(4)-cystine resulted in dramatically high plasma levels with reduced levels in the brain and liver.Intragastrically administered D_(4)-cystine resulted in high levels in the plasma and stomach with relatively low levels in the lung,kidney,heart and brain.
文摘An electrochemical quartz crystal impedance system has been applied to monitorgeneration of precipitate and adsorption of the precipitate onto An electrode during electrochmicaloxidation and Fe(CN)_6,3-/Fe(CN),6 4- electrochemical catalytic oxidation of L-cysteine in phosphateaqueous buffer (pH 7.4). Significant decreases in the resonant frequency and increases in themotional resistance and the static capacitance were found during the precipitate adsorption, and thefrequency shift found in solution was ca. 2 times that in air. Similar responses of quartz crystalimpedance and a white precipitate were obtained during redox titration of L-cysteine solutionusing K_3Fe(CN)_6 solution. FT-IR analysis indicated that the white precipitate is cystine. Theelectrode collection efficiency of the electrogenerated cystine was estimated.
文摘Objective To evaluate the effectiveness of ESWL for treating patients with cystine calculus. Methods Of 31 patients, 20 were subjected to ESWL only, 6 were subjected to combination therapy of PCNL and ESWL, 2 Pneumatic Lithotriptor-ESWL, 3 Laser lithotripsy-ESWL. Results For 14 renal stones, the fragmentation after ESWL manotherapy was 85. 7% and 14.3% after twice ESWL sessions. For 17 ureter calculus, the fragmentation after ESWL manotherapy was 82.3% and 11.7% after twice ESWL sessions. One patient （ 5.8% ） failed and changed to open surgery. Conclusion ESWL is an effective and reliable method for treating patients with cystine calculus, however, better effects and shorter treatment time could be obtained by the combination of ESWL with other therapy options.
基金The research in authors'lab has been supported by The University of Texas MD Anderson Cancer Center,KC180131 from Department of Defense Kidney Cancer Research Program,R01CA181196,R01CA190370,R01CA244144 from the National Institutes of Health(to BG)CPRIT Research Training Grant(RP170067)Dr.John J.Kopchick Research Award from The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences(to PK).
文摘The cystine/glutamate antiporter SLC7A11(also commonly known as xCT)functions to import cystine for glutathione biosynthesis and antioxidant defense and is overexpressed in multiple human cancers.Recent studies revealed that SLC7A11 overexpression promotes tumor growth partly through suppressing ferroptosis,a form of regulated cell death induced by excessive lipid peroxidation.However,cancer cells with high expression of SLC7A11(SLC7A11^(high))also have to endure the significant cost associated with SLC7A11-mediated metabolic reprogramming,leading to glucose-and glutamine-dependency in SLC7A11^(high) cancer cells,which presents potential metabolic vulnerabilities for therapeutic targeting in SLC7A11^(high) cancer.In this review,we summarize diverse regulatory mechanisms of SLC7A11 in cancer,discuss ferroptosis-dependent and-independent functions of SLC7A11 in promoting tumor development,explore the mechanistic basis of SLC7A11-induced nutrient dependency in cancer cells,and conceptualize therapeutic strategies to target SLC7A11 in cancer treatment.This review will provide the foundation for further understanding SLC7A11 in ferroptosis,nutrient dependency,and tumor biology and for developing novel effective cancer therapies.
基金This work was supported by the Andrew Sabin Family Fellow Award from The University of Texas MD Anderson Cancer Center,KC180131 fromDepartment of Defense Kidney Cancer Research Program,R01CA181196 and R01CA244144 from the National Institutes of Health(to B.G.).
文摘Cystine/glutamate antiporter solute carrier family 7 member 11(SLC7A11;also known as xCT)plays a key role in antioxidant defense by mediating cystine uptake,promoting glutathione synthesis,and maintaining cell survival under oxidative stress conditions.Recent studies showed that,to prevent toxic buildup of highly insoluble cystine inside cells,cancer cells with high expression of SLC7A11(SLC7A11high)are forced to quickly reduce cystine to more soluble cysteine,which requires substantial NADPH supply from the glucose-pentose phosphate pathway(PPP)route,thereby inducing glucose-and PPP-dependency in SLC7A11high cancer cells.Limiting glucose supply to SLC7A11high cancer cells results in significant NADPH“debt”,redox“bankruptcy”,and subsequent cell death.This review summarizes our current understanding of NADPH-generating and-consuming pathways,discusses the opposing role of SLC7A11 in protecting cells from oxidative stresseinduced cell death such as ferroptosis but promoting glucose starvationeinduced cell death,and proposes the concept that SLC7A11-mediated cystine uptake acts as a double-edged sword in cellular redox regulation.A detailed understanding of SLC7A11 in redox biology may identify metabolic vulnerabilities in SLC7A11high cancer for therapeutic targeting.
基金funded by the University of Manitoba Start-Up Grant(C.Yang,46561)the Manitoba Graduate Scholarship from the University of Manitoba.
文摘The cystine/glutamate exchanger(xCT,SLC7 A11)is a component of the system X_c amino-acid antiporter that is able to export glutamate and import cysteine into cells.The xCT amino acid exchanger has received a lot of attention,due to the fact that cysteine is an essential substrate for the synthesis of glutathione(GSH),an endogenous antioxidant in cells.The objective of this research was to clone the full-length cDNA of chicken xCT,and to investigate the gene expression of xCT in different tissues,including intestinal segments of broiler chickens during development.The full-length cDNA of chicken xCT(2,703 bp)was obtained from the jejunum by reverse transcription-PCR and sequenced.Homology tests showed that chicken xCT had 80.4%,80.2%,and 71.2%homology at the nucleotide level with humans,cattle,and rats,respectively.Likewise,amino acid sequence analysis showed that chicken xCT protein is 86.4%,79.3%,and 75.6%homologous with humans,cattle,and rats,respectively.Additionally,phylogenetic analysis indicated that chicken xCT genes share a closer genetic relationship with humans and cattle,than with rats.The chicken xCT protein has 12 transmembrane helixes,6 extracellular loops,and 5 intracellular loops.The mRNA of xCT was detected in all tissues,including intestinal segments,in which the mRNA expression of xCT was significantly higher(P<0.05)within the colon,compared to the jejunum and ileum.During development,a linear pattern of changes regarding the levels of the xCT mRNA was found,indicating that there was an abundance of xCT within the duodenum(P<0.05).Furthermore,there were changes of the xCT mRNA abundance in the colon during development,which displayed linear and cubic patterns(P<0.05).These results indicated that xCT is widely expressed both in intestinal segments,as well as other organs that are not associated with nutrient absorption.Further investigation is needed to characterize the functional relevance of xCT activity in oxidative stress and inflammation in the small intestine of broiler chickens.
基金the National Natural Science Foundation of China(52022095,51973216,51873207,51803006,51833010,51673190,51603204)the Science and Technology Development Program of Jilin Province(20200404182YY)+1 种基金the Youth Talents Promotion Project of Jilin Province(181909)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2019230)。
文摘The physicochemical characteristics of nanoparticles are closely related to their drug delivery performances in vitro and in vivo.A well-designed nanocarrier can prolong the drug half-life in the blood circulation,upregulate the drug accumulation at the target site,and enhance the treatment efficacy.To elucidate the impact of physicochemical properties on the fate of nanogel as a nanocarrier of chemotherapeutics,three methoxy poly(ethylene glycol)-poly(L-phenylalanine-co-L-cystine)(mPEG-P(LP-coLC))nanogels with different L-cystine proportions were developed,namely mPEG-P(LP10-co-LC5)(NG10-5),mPEG-P(LP10-coLC10)(NG10-10),and mPEG-P(LP10-co-LC15)(NG10-15).The three nanogels shared similar surface charge and reductionresponsive behavior,but they had distinct diameters and different drug release profiles.Among them,NG10-5,which has the smallest diameter,was preferentially internalized by tumor cells in vitro and showed rapid migration to the tumor site in vivo.Using doxorubicin(DOX)as a model chemotherapeutic agent,NG10-5/DOX had the most prolonged blood circulation period and highest tumor accumulation after intravenous administration.NG10-5/DOX also had the most potent antitumor effect of all three drug-loaded nanogels.Accordingly,adjusting physicochemical characteristics by changing the amino acid composition might improve the therapeutic efficacies of nanogels and enhance their potential for clinical application.
基金the National Natural Science Foundation of China(Grant Nos.21621004 and 22178260)the Tianjin Development Program for Innovation and Entrepreneurship(2018)the Cooperative Program of Technical Center of Gongbei Customs District of China(Grant No.2020GKF-0281).
文摘Recently,various semiconductor/metal composites have been developed to fabricate surfaceenhanced Raman spectroscopy substrates.However,low metal loading on semiconductors is still a challenge.In this study,cystine was introduced to increase the accumulation of gold nanoparticles on zinc oxide,owing to the biomineralization_property of_cystine.Morphological analysis revealed that the obtained ZnO/Au/cystine composite not only had a higher metal loading but also formed a porous structure,which is beneficial for Raman performance.Compared with ZnO/Au,the ZnO/Au/cystine substrate displayed a 40-fold enhancement in the Raman signal and a lower limit of detection(10^(-11) mol·L^(-1))in the detection of rhodamine 6G.Moreover,the substrate has favorable homogeneity and stability.Finally,ZnO/Au/cystine displayed excellent performance toward crystal violet and methylene blue in a test based on river water samples.This study provided a promising method to fabricate sensitive semiconductor/noblemetal-based surface-enhanced Ramans spectroscopy substrates for Raman detection.
基金supported by the National Natural Science Foundation of China 32371267 and 32422039(R.Y.)Science,Technology and Innovation Commission of Shenzhen Municipality JCYJ20200109141229255(J.T.D.)+2 种基金Science,Technology and Innovation Commission of Shenzhen Municipality 20200925174802001(.T.D.)Natural Science Foundation of Guangdong Province 2024A1515011288(R.Y.)Major Talent Recruitment Program of Guangdong Province 2021QNO2Y167(R.Y.).
文摘Breast cancer is a prevalent malignancy worldwide.The majority of breast cancers belong to the estrogen receptor(ER)-positive luminal subtype that can be effectively treated with antiestrogen therapies.However,a significant portion of such malignancies become hormone-refractory and incurable.Cancer cells often uptake more cystines to increase glutathione(GSH)biosynthesis and reduce reactive oxygen species(ROS),thereby preventing ROS-induced ferroptosis and leading to therapeutic resistance.However,few molecules of these processes are targetable for cancer therapy.However,few therapeutic targets have been established that target these processes.Here,we report that the gene for SLC7A13,a member of the SLC7A13-SLC3A1 cystine transporter,was amplified and overexpressed in 19.7% and 49.7% of breast cancers,respectively.SLC7A13 amplifi cation and overexpression were associated with worse overall survival and disease-free survival in patients with luminal breast cancer.Functionally,SLC7A13 overexpression promoted,while its silencing attenuated,cell survival or proliferation.Molecularly,SLC7A13 silencing reduced cystine uptake and GSH biosynthesis,leading to increased lipid ROS levels.The cryo-EM structure of the human SLC7A13-SLC3A1 complex was determined at 2.64AA,revealing a dimer-of-heterodimers architecture similar to that of other SLC3A1-linked transporters.A specific substrate-binding pocket was identified,containing distinct residues,which suggests a regulatory role in the cystine transporter.These findings suggest that the SLC7A13-SLC3A1 cystine transporter is a therapeutic target for treating luminal breast cancer.They also provide the structural insights for therapeutic development targeting the cystine transporter.
基金supported by the National Natural Science Foundation of China,Nos.81672171(to XY),81620108018(to SQF),81772342(to GZN)the State Key Laboratory of Medicinal Chemical Biology of Nankai University of China,No.2017027(to XY)
文摘The iron chelator deferoxamine has been shown to inhibit ferroptosis in spinal cord injury.However,it is unclear whether deferoxamine directly protects neurons from ferroptotic cell death.By comparing the survival rate and morphology of primary neurons and SH-SY5Y cells exposed to erastin,it was found that these cell types respond differentially to the duration and concentration of erastin treatment.Therefore,we studied the mechanisms of ferroptosis using primary cortical neurons from E16 mouse embryos.After treatment with 50μM erastin for 48 hours,reactive oxygen species levels increased,and the expression of the cystine/glutamate antiporter system light chain and glutathione peroxidase 4 decreased.Pretreatment with deferoxamine for 12 hours inhibited these changes,reduced cell death,and ameliorated cellular morphology.Pretreatment with the apoptosis inhibitor Z-DEVD-FMK or the necroptosis inhibitor necrostain-1 for 12 hours did not protect against erastin-induced ferroptosis.Only deferoxamine protected the primary cortical neurons from ferroptosis induced by erastin,confirming the specificity of the in vitro ferroptosis model.This study was approved by the Animal Ethics Committee at the Institute of Radiation Medicine of the Chinese Academy of Medical Sciences,China(approval No.DWLL-20180913)on September 13,2018.
基金funded by the National Natural Science Foundation of China, No. 81873924 (to QQL), No. 82171190 (to GHW)Nantong Science and Technology Project of China, No. MS22021010 (to LHS)High-level Innovation and Entrepreneurship Talents Introduction Program of Jiangsu Province of China (to QQL)
文摘DL-3-n-butylphthalide(NBP)-a compound isolated from Apium graveolens seeds-is protective against brain ischemia via various mechanisms in humans and has been approved for treatment of acute ischemic stroke.NBP has shown recent potential as a treatment for Parkinson’s disease.However,the underlying mechanism of action of NBP remains poorly understood.In this study,we established a rat model of Parkinson’s disease by intraperitoneal injection of rotenone for 28 successive days,followed by intragastric injection of NBP for 14-28 days.We found that NBP greatly alleviated rotenone-induced motor disturbance in the rat model of Parkinson’s disease,inhibited loss of dopaminergic neurons and aggregation ofα-synuclein,and reduced iron deposition in the substantia nigra and iron content in serum.These changes were achieved by alterations in the expression of the iron metabolism-related proteins transferrin receptor,ferritin light chain,and transferrin 1.NBP also inhibited oxidative stress in the substantia nigra and protected mitochondria in the rat model of Parkinson’s disease.Our findings suggest that NBP alleviates motor disturbance by inhibition of iron deposition,oxidative stress,and ferroptosis in the substantia nigra.
基金supported by the National Natural Science Foundation of China (21573100, 21573099) the Open Project of State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (N-14-04)~~
文摘A series of alloyed Zn‐Cd‐S solid solutions with a cubic zinc blende structure were fabricated hydrothermally with the assistance of L‐cystine under mild conditions.The products were characterized by XRD,TEM,HRTEM,XPS,UV‐vis,and BET techniques,and the photocatalytic performance for the reduction of water to H2on the solid solutions was evaluated in the presence of S2?/SO32?as hole scavengers under visible light illumination.Among all the samples,the highest photocatalytic activity was achieved over Zn0.9Cd0.1S with a rate of4.4mmol h?1g?1,even without a co‐catalyst,which far exceeded that of CdS.Moreover,Zn0.9Cd0.1S displayed excellent anti‐photocorrosion properties during the photoreduction of water into H2.The enhancement in the photocatalytic performance was mainly attributed to the efficient charge transfer in the Zn0.9Cd0.1alloyed structure and the high surface area.This work provides a simple,cost‐effective and green technique,which can be generalized as a rational preparation route for the large‐scale fabrication of metal sulfide photocatalysts.
基金financially supported by the National Natural Science Foundation of China(No.82001189)The Project Tackling of Key Scientific and Technical Problems of Henan Provine(No.232102311163).
文摘Bone metastasis,a life-threatening complication of advanced breast cancer,is often accompanied by debilitating pain(cancer-induced bone pain,CIBP)that severely impairs life quality and survival.The concurrent treatment of bone metastases and CIBP remains a clinical challenge because the therapeutic options are limited.In this study,we construct a near-infrared light-activated nano-therapeutic system to meet this conundrum.In detail,sorafenib(SRF)and photosensitizer(chlorin e6,Ce6)are encapsulated into mesoporous hydroxyapatite nanoparticles(HANPs),which are further functionalized with hyaluronic acid(HA)to obtain HA-SRF/Ce6@HANPs system.The designed nanoplatform destroys tumor cells in vitro and in vivo via the synergism of SRF(interrupting the exchange of cystine/glutamate by inhibiting SLC7A11)and photodynamic therapy(PDT,inducing reactive oxygen species generation).The decrease in tumor burden and reduction of extracellular glutamate significantly attenuate CIBP in mice model with developing bone cancer.Moreover,the combination of HA-SRF/Ce6@HANPs and PDT inhibit osteoclasts activation,promote osteoblast differentiation and accelerate bone repair.Overall,the nanoagent with good biocompatibility may provide an effective therapy method for the concurrent treatment of breast cancer bone metastasis and CIBP.
文摘FTIR-ATR technique with second-order derivative measurement was used for assessing the amount of oxidation products of cystine present on the plasma-treated wool fabric surface. In this paper, three non-polymerising gases namely oxygen, nitrogen and 25% hydrogen/75% nitrogen gas mixture were used for the plasma treatment of wool fabric. The oxidation products of cystine studied included S-sulphonate, cysteic acid, cystine monoxide and cystine dioxide. The variations of the amount of these products as a function of treatment time were studied. Experimental results showed that the oxygen plasma could produce a large amount of oxidation products of cystine on the wool fabric surface followed by nitrogen plasma and gas mixture plasma.
基金Fund project:2019 Hainan provincial health industry research project(178)and 2019 provincial key specialty construction project of traditional Chinese medicine(Second Batch).
文摘Objective:To observe the clinical effect of Banxia Atractylodes macrocephala Tianma decoction in the treatment of hypertension.Methods:A total of 100 patients with hypertension were selected from our hospital(April 2016 to July 2019)and divided into 2 groups by random digital method.The control group was given routine symptomatic treatment of western medicine,and the observation group was given Banxia Atractylodes Gastrodia decoction on the basis of the control group.the levels of syndrome score and adiponectin(apn),cysc(cysc),uric acid(ua),c-reactive protein(crp),superoxide dismutase(sod),malondialdehyde(mda),8-hydroxydeoxyguanylic acid(8-ohdg)were recorded before and after treatment in group 2,and the total effective rate of clinical treatment was counted in group 2.Results:After treatment,the total effective rate(92.00%)in the observation group was higher than that in the control group(74.00%),and the difference was statistically significant(P<0.05).The APN、SOD level of the observation group was higher than that of the control group after treatment,and the CysC、UA、CRP、MDA、8-OHdG level and TCM symptom score were lower than those of the control group(P<0.05).Conclusion:Rhizoma Pinelliae and Rhizoma Gastrodiae decoction for treating hypertension can relieve oxidative stress injury,adjust the expression level of APN,CysC,CRP and UA,and improve the symptoms and improve the curative effect.
基金supported by the the National Natural Science Foundation of China(No.31221091)the State Key Laboratory of Integrated Management of Pest Insects and Rodents,China(No.Chinese IPM1307,Chinese IPM405 and Chinese IPM1512)
文摘There are at least three conserved protein folds shared by ion channel-targeted neurotoxins and antimicrobial defensins,including cysteine-stabilizedα-helix andβ-sheet fold(CSαβ),inhibitor cystine knot fold(ICK)andβ-defensin fold(BDF).Based on a combined data of sequences,structures and functions,it has been proposed that these neurotoxins could originate from related ancient antimicrobial defensins by neofunctionalization.This provides an ideal system to study how a novel function emerged from a conserved structural scaffold during evolution.The elucidation of functional novelty of proteins not only has great significance in evolutionary biology but also will be helpful in guiding rational molecular design.This review describes recent progresses in origin of neurotoxins,focusing on the three conserved protein scaffolds.
基金supported by National Natural Science Foundation of China(82170243,81921001,82270428)Beijing Natural Science Foundation(7222188)。
文摘The metabolic pathway of sulfur-containing amino acids in organisms begins with methionine,which is metabolized to produce important sulfur-containing biomolecules such as adenosylmethionine,adenosylhomocysteine,homocysteine,cystine,and hydrogen sulfide(H2S).These sulfur-containing biomolecules play a wide range of physiological roles in the body,including antiinflammation,antioxidant stress,DNA methylation,protein synthesis,etc.,which are essential for maintaining cellular function and overall health.In contrast,dysregulation of the metabolic pathway of sulfur-containing amino acids leads to abnormal levels of sulfur-containing biomolecules,which produce a range of pathological consequences in multiple systems of the body,such as neurodegenerative diseases,cardiovascular diseases,and cancer.This review traces the milestones in the development of these sulfur-containing biomolecules from their initial discovery to their clinical applications and describes in detail the structure,physiochemical properties,metabolism,sulfide signaling pathway,physiopathological functions,and assays of sulfur-containing biomolecules.In addition,the paper also explores the regulatory role and mechanism of sulfur-containing biomolecules on cardiovascular diseases,liver diseases,neurological diseases,metabolic diseases and tumors.The focus is placed on donors of sulfur-containing biological macromolecule metabolites,small-molecule drug screening targeting H2S-producing enzymes,and the latest advancements in preclinical and clinical research related to hydrogen sulfide,including clinical trials and FDA-approved drugs.Additionally,an overview of future research directions in this field is provided.The aim is to enhance the understanding of the complex physiological and pathological roles of sulfur-containing biomolecules and to offer insights into developing effective therapeutic strategies for diseases associated with dysregulated sulfur-containing amino acid metabolism.
