The ~ 125 I-UdR-release method is used for evaluation of the cytotoxity of biomaterials. In this method, K562 cells cultured in suspending were used to make a direct contact with materials. The cytotoxity of 14 kinds ...The ~ 125 I-UdR-release method is used for evaluation of the cytotoxity of biomaterials. In this method, K562 cells cultured in suspending were used to make a direct contact with materials. The cytotoxity of 14 kinds of biomaterials has been evaluated using this method. In comparing with other experimental methods for the evaluation of cell cytotoxity, this method shows advantages of the celerity, the simplicity, the objective, the accuracy and the quantitative.展开更多
Two Co(Ⅱ)and Ni(Ⅱ)complexes were synthesized by synergistic coordination of 3,3-diphenylpropionic acid(HDPA)and 2,2′-bipyridylamine(PAm).The structures of complexes[Co(DPA)_(2)(PAm)]·2H_(2)O(1)and[Ni(DPA)_(2)(...Two Co(Ⅱ)and Ni(Ⅱ)complexes were synthesized by synergistic coordination of 3,3-diphenylpropionic acid(HDPA)and 2,2′-bipyridylamine(PAm).The structures of complexes[Co(DPA)_(2)(PAm)]·2H_(2)O(1)and[Ni(DPA)_(2)(PAm)]·2H_(2)O(2)were determined by single-crystal X-ray diffraction,IR spectroscopy,and powder X-ray diffraction.Hirshfeld surface analysis provided quantitative insights into the intermolecular interactions within the complexes,while molecular docking studies elucidated their binding modes and affinities toward urease.Furthermore,the biological activities of both complexes were systematically evaluated through a range of assays,including DNA binding,urease inhibition,antibacterial activity,and in vitro cytotoxicity against cancer cells.Both complexes exhibited binding affinity for DNA and displayed notable urease inhibitory activity.Under in vitro conditions,both complexes showed appreciable cytotoxicity toward HepG2 cells with efficacy comparable to clinically used platinumbased anticancer agents.CCDC:2479943,1;2479944,2.展开更多
Objectives:Drug resistance is the major determinant of chemotherapy failure,leading to relapse and tumor progression,demonstrating the urgent need for novel antineoplastic drugs.This study aimed to evaluate the antica...Objectives:Drug resistance is the major determinant of chemotherapy failure,leading to relapse and tumor progression,demonstrating the urgent need for novel antineoplastic drugs.This study aimed to evaluate the anticancer potential of two novel pyrazole derivatives,P3C.1 and P3C.2,and to elucidate their mechanism of action in cancer cells.Methods:The cytotoxicity of the compounds was evaluated across 27 different cancer cell lines via a nuclear staining assay.Subsequent flow cytometric and biochemical analyses were performed to assess reactive oxygen species(ROS)generation,apoptosis induction,mitochondrial integrity,and cell cycle progression.Additional studies included transcriptome analyses and immunoassays to characterize the molecular mechanisms underlying drug activity.Results:Two novel pyrazole derivatives,P3C.1 and P3C.2,were identified with potent cytotoxicity on a variety of cancer cell lines.Among the adherent cell lines tested,the triple-negative breast cancer(TNBC)cell line MDA-MB-231 exhibited the highest sensitivity to both compounds and was therefore selected for further experimentation.In vitro assays demonstrated that both compounds induced ROS generation,mitochondrial membrane depolarization,cell cycle arrest and apoptosis.Whole-transcriptome sequencing of P3C.1 and P3C.2-treated MDA-MB-231 and two lymphoblastic leukemia cell lines revealed four genes in common associated with cell signaling and membrane dynamics.Connectivity Map(CMAP)database comparisons of shared genes for each cancer subtype revealed a strong similarity between the two compounds with tubulin inhibitors,and subsequent assays confirmed that these compounds act as microtubule-disrupting agents.Moreover,protein phosphorylation analysis indicated that both compounds induced hyperphosphorylation of JNK,and ERK1/2,along with hypophosphorylation of p38 kinases.Conclusions:P3C.1 and P3C.2 emerged as promising anti-breast cancer agents with dual mechanisms of action involving microtubule disruption and altered kinase signaling,leading to induction of apoptosis.展开更多
Atractylodes macrocephala Koidz.(A.macrocephala)is a medicinal and edible plant species belonging to the Compositae family.Its rhizome serves both therapeutic and nutritional purposes in China.This investigation led t...Atractylodes macrocephala Koidz.(A.macrocephala)is a medicinal and edible plant species belonging to the Compositae family.Its rhizome serves both therapeutic and nutritional purposes in China.This investigation led to the isolation of thirteen novel rearranged 9(8→7)-abeo-eudesmane-type sesquiterpenoid dimers(SDs),atramacronins A-M(1-13),three eudesmane-type SDs,atramacronins N-P(14-16),and two previously identified meroterpenoids,atrachinenin G(17)and atrachineninΙ(18),from Atractylodes macrocephala.Structure elucidation was accomplished through comprehensive spectroscopic analysis and single-crystal X-ray diffraction.Compounds 1,4-7,9,and 10 exhibited notable cytotoxicity against Hep3B,HepG2,and Huh7 cell lines,with half maximal inhibitory concentration(IC_(50))values ranging from 3.71 to 13.99μmol·L^(-1).展开更多
Objective Adaptive immune responses play a critical role in the pathogenesis of amyotrophic lateral sclerosis(ALS).In this study,we investigated the functional mechanisms of T cell subtypes and assessed the causal lin...Objective Adaptive immune responses play a critical role in the pathogenesis of amyotrophic lateral sclerosis(ALS).In this study,we investigated the functional mechanisms of T cell subtypes and assessed the causal links between CD4+cytotoxic T cell-related genes and ALS risk.Methods Single-cell RNA sequencing(scRNA-seq)of peripheral blood mononuclear cells(PBMCs)from patients with ALS and healthy controls(HC)was used to identify differentially expressed genes(DEGs)in CD4+cytotoxic T cells.Comprehensive analyses of CD4+cytotoxic T cells,including pseudotemporal trajectory,intercellular communication,and metabolic pathway analysis,were performed.Mendelian randomization(MR)analysis evaluated the causal effects of DEGs on ALS risk,with validation using independent genome-wide association study(GWAS)data.Expression patterns of the causal genes were further verified using scRNA-seq,bulk-seq,and clinical samples.Results CD4+cytotoxic T cells were significantly expanded in patients with ALS.The upregulated genes S100A6,SERPINB6,SMAD7,and TPST2 were positively correlated with ALS susceptibility,whereas DIP2A showed a protective association.Conclusion S100A6,SERPINB6,SMAD7,TPST2,and DIP2A were identified as causal genes and potential therapeutic targets in ALS,implicating CD4+cytotoxic T cells in the disease mechanisms.Further studies targeting these genes and neuroinflammatory pathways are warranted.展开更多
Glioblastoma(GBM),the most aggressive and lethal primary brain tumor in adults,continues to resist conventional therapeutic approaches,withmedian survival remaining dismally low.Immune checkpoint inhibitors(ICIs),whic...Glioblastoma(GBM),the most aggressive and lethal primary brain tumor in adults,continues to resist conventional therapeutic approaches,withmedian survival remaining dismally low.Immune checkpoint inhibitors(ICIs),which have revolutionized the treatment of several solid tumors,have shown limited efficacy inGBMowing to the highly immunosuppressive and heterogeneousmicroenvironment of the tumor.The unique immune landscape of the central nervous system(CNS),characterized by low immunogenicity,restricted T-cell infiltration,and an abundance of regulatory and myeloid-derived suppressor cells,poses considerable barriers to effective immune reactivation.This review provides a comprehensive synthesis of the mechanistic barriers undermining ICI efficacy in GBM,including the blood-brain barrier,low tumor mutational burden,adaptive immune resistance,and iatrogenic immunosuppression.It also explores emerging predictive and prognostic biomarkers,such as programmed death-ligand 1(PD-L1)expression,immune gene signatures,tumor-infiltrating lymphocyte profiles,and circulating markers in cerebrospinal fluid and plasma,which hold promise for guiding patient selection and therapeutic monitoring.Importantly,recent breakthroughs in combinatorial immunotherapy strategies are highlighted,including the integration of ICIs with radiotherapy,anti-angiogenic agents,oncolytic viruses,personalized neoantigen vaccines,and tumor microenvironment reprogramming approaches.Innovative delivery platforms,such as nanoparticles,focused ultrasound,and convection-enhanced delivery,are also discussed for their potential to improve drug bioavailability and local immune activation in the CNS.This review hypothesizes that the therapeutic efficacy of ICIs in GBM can be considerably enhanced by disrupting immune exclusion and reversing immunosuppression through integrated,multimodal strategies guided by dynamic biomarker profiling and spatially resolved immunemapping.This hypothesisdriven approach aims to bridge translational gaps and inform next-generation clinical trial designs that may unlock the potential of immunotherapy for GBM.展开更多
Objective:Multiple sclerosis(MS)is a chronic inflammatory demyelinating disease of the central nervous system(CNS).Soluble interleukin-2 receptor alpha(sIL-2Rα)has been implicated inMS pathogenesis,but its mechanisms...Objective:Multiple sclerosis(MS)is a chronic inflammatory demyelinating disease of the central nervous system(CNS).Soluble interleukin-2 receptor alpha(sIL-2Rα)has been implicated inMS pathogenesis,but its mechanisms remain unclear.This study investigates how sIL-2Rαexacerbates MS by modulating microglial activation and antibody-dependent cellular cytotoxicity(ADCC)in an experimental autoimmune encephalomyelitis(EAE)mouse model.Methods:Female C57BL/6J mice were induced with EAE and treated with sIL-2Rα.Clinical symptoms,histopathology,and molecular changes were analyzed.Microglial activation was assessed via immunohistochemistry,Western blot,and RNA sequencing.In vitro,ADCC-mediated oligodendrocyte injury was evaluated using Fc receptor inhibition and PI3K-Akt pathway blockade.Results:sIL-2Rα accelerated EAE onset and severity,increasingmicroglial M1 polarization and CNS inflammation.RNA-seq revealed PI3K-Akt pathway activation,upregulating Fc receptors(FcγR)on microglia,which enhanced ADCC against oligodendrocytes(p<0.001).Inhibiting FcγR or PI3K-Akt reduced oligodendrocyte damage.Conclusion:sIL-2Rαexacerbates MS by activating microglia via the PI3K-Aktaxis,promoting ADCC and demyelination.Targeting this pathway may offer novel therapeutic strategies for MS.展开更多
A chemical investigation of Streptomyces sp.GZWMJZ-662,an endophytic actinomycete isolated from Houttuynia cordata Thunb.,has yielded eleven bohemamine dimers(1-11).Notably,the newly identified dibohemamines I-O(1-7)h...A chemical investigation of Streptomyces sp.GZWMJZ-662,an endophytic actinomycete isolated from Houttuynia cordata Thunb.,has yielded eleven bohemamine dimers(1-11).Notably,the newly identified dibohemamines I-O(1-7)have not been previously reported.Their structures were elucidated through detailed spectroscopic analysis,encompassing high-resolution electrospray ionization mass,nuclear magnetic resonance,infrared radiation,ultraviolet-visible,and electronic circular dichroism spectroscopy.Dibohemamine I(1)exhibited selective cytotoxic effects against the cancer cell lines 786-O and GBC-SD among the 18 cell lines evaluated,with the half-inhibitory concentration values of 3.24±0.20 and 7.36±0.41μM,respectively.展开更多
Phytochemical study of the n-BuOH extract of Ilex asprella resulted in the discovery of ten new pentacyclic triterpenoid glycosides,comprising nine ursane-type glycosides(1-9)and one oleanane-type glycoside(10),along ...Phytochemical study of the n-BuOH extract of Ilex asprella resulted in the discovery of ten new pentacyclic triterpenoid glycosides,comprising nine ursane-type glycosides(1-9)and one oleanane-type glycoside(10),along with seven known compounds(11-17).Compound 1 is the first reported 19,22-epoxy ursane triterpenoid glycoside,whereas 4 and 5 are rare examples of ursane triterpenoid glycosides containing a 28,19-lactone group.The structural characterization of these compounds was achieved using spectroscopic and chemical techniques,as well as single-crystal X-ray analysis.Compounds 7,12,15,and 17 exhibited moderate cytotoxic activities against H1975 and HCC827 cancer cells.展开更多
From the seeds of Peganum harmala L.,three new alkaloids ofβ-carboline were isolated.Among them,peganumiums A(1)and B(2)were dimers with specific new scaffolds,all with long conjugated systems.Peganumium A and peganu...From the seeds of Peganum harmala L.,three new alkaloids ofβ-carboline were isolated.Among them,peganumiums A(1)and B(2)were dimers with specific new scaffolds,all with long conjugated systems.Peganumium A and peganumium C(3)were ionic alkaloid salts and peganumium B was a hexacycliccondensed alkaloid.The biosynthetic pathways of the three compounds above were also speculated.A preliminary cytotoxicity assay revealed that peganumium B had strong in vitro antiproliferative ability against a variety of cancer cells.The analysis of^(1)H nuclear magnetic resonance(NMR)metabolomics suggested that the antiproliferative mechanism of peganumium B could be associated with the biosynthesis of phenylalanine,tyrosine and tryptophan,the metabolism of glycine,serine,and threonine,the metabolism of taurine and hypotaurine,and the metabolism of nicotinate and nicotinamide.In addition,peganumium B could reduce the mitochondrial content of body-wall muscle cells of a Caenorhabditis elegans(C.elegans)strain in vivo.展开更多
Ovarian cancer remains a leading cause of gynecological cancer mortality1,and patients with advanced stage ovarian cancer frequently develop malignant ascites that foster immunosuppressive microenvironments and therap...Ovarian cancer remains a leading cause of gynecological cancer mortality1,and patients with advanced stage ovarian cancer frequently develop malignant ascites that foster immunosuppressive microenvironments and therapeutic resistance2,3.Although ascites have traditionally been considered detrimental,we report a paradoxical role in which they enhance the cytotoxicity ofγδT cells—a unique T cell subset that can be allogenically transferred for cancer treatment4,5—toward ovarian cancer.展开更多
BACKGROUND Severe acute respiratory syndrome coronavirus 2 induced coronavirus disease 2019(COVID-19)has posed a great challenge to public health worldwide and also increased susceptibility to colorectal cancer(CRC).N...BACKGROUND Severe acute respiratory syndrome coronavirus 2 induced coronavirus disease 2019(COVID-19)has posed a great challenge to public health worldwide and also increased susceptibility to colorectal cancer(CRC).Natural killer(NK)cells serve as the first line of defense in the host’s innate immune system,performing natural killing functions and mediating cytotoxicity against tumors and viruses.Therefore,a better understanding of NK cell cytotoxicity may facilitate the development of treatment strategies for CRC-associated with COVID-19.AIM To investigate the cytotoxic killing function of peripheral NK cells in patients with CRC and severe COVID-19(CRC+patients).METHODS The percentages of circulating NK and NKT cells in CRC+and age-matched patients with CRC were analyzed using flow cytometry.NK cell cytotoxic activity(NKCA)and corresponding NK cytotoxic factor(NKCF)activity in peripheral blood mononuclear cells were evaluated using a Real-Time Cell Analyzer.RESULTS The numbers and percentage of peripheral NK and NKT cells in patients with CRC+were lower than those in patients with CRC.Additionally,compared to patients with CRC,those with CRC+had lower levels of NKCA and NKCF activity in lysed K562 cells.Positive correlations were observed between NKCA and NK cell numbers,NKCA and NK cell percentages,NKCF activity,and NK cell percentages in patients with CRC+.Furthermore,a negative correlation was observed between NKCA and the severity of COVID-19 in patients with CRC.The area under the receiver operating characteristic curve for NKCA was greater than those for the other indices.CONCLUSION CRC+is associated with lower levels of peripheral NK cells and impaired natural cytotoxicity,contributing to the immunopathogenesis of severe COVID-19 rather than immune control.展开更多
Halogen substituents play a crucial role in the structural diversity and biological activity of natural products,and the synthesis of halogenated molecules remains an area of significant research interest.This study d...Halogen substituents play a crucial role in the structural diversity and biological activity of natural products,and the synthesis of halogenated molecules remains an area of significant research interest.This study describes the generation of 15 new halogenated angucyclinones through the incorporation of halogen-containing phenylamines into a biosynthetic C-ringcleaved angucyclinone under mild conditions.The newly synthesized compounds feature halogen substituents encompassing all four halogen atoms(F,Cl,Br,I),with some compounds containing multiple halogen types.Structural elucidation was accomplished through ultraviolet(UV),infrared spectroscopy(IR),mass spectrometry(MS),and nuclear magnetic resonance(NMR)spectroscopic analyses,expanding the structural diversity of angucyclinonetype polyketides.Cytotoxicity evaluations revealed that eight compounds demonstrated moderate cytotoxic activities against four human tumor cell lines,with half maximal inhibitory concentration(IC_(50))values ranging from 3.35±0.37 to 16.02±6.60μmol·L-1.These findings highlight the significant potential of combining biosynthetic and chemical approaches in generating bioactive halogenated molecules.展开更多
A[3+4]annulation of α-substituted allenes and Schiff bases is reported.This methodology serves as a conduit for the construction of a series of biologically important benzazepine derivatives in good to excellent yiel...A[3+4]annulation of α-substituted allenes and Schiff bases is reported.This methodology serves as a conduit for the construction of a series of biologically important benzazepine derivatives in good to excellent yields under mild conditions by an unprecedented mode involving β’-carbon of α-substituted allenes and the proposed mechanism is supported by capturing the intermediate.Moreover,this class of benzazepine derivatives exhibited potential ability of cytotoxicity toward cancer cells.展开更多
The luminescence behavior of Eu^(3+)-activated lanthanum tungstate nanophosphors exhibiting intense red emission was systematically explored by modifying their surfaces using various agents,including polyvinylpyrrolid...The luminescence behavior of Eu^(3+)-activated lanthanum tungstate nanophosphors exhibiting intense red emission was systematically explored by modifying their surfaces using various agents,including polyvinylpyrrolidone(PVP),cetyltrimethylammonium bromide(CTAB),trisodium citrate(TC),polyvinyl alcohol(PVA),and ethylene glycol(EG).These nanophosphors were synthesized via a facile hydrothermal-assisted solid-state reaction.X-ray diffraction(XRD)analysis confirmed the orthorhombic crystal structure of all the prepared samples.Morphological and size analyses were performed using scanning electron microscopy(SEM)and particle size distribution profiling.High-resolution transmission electron microscopy(HRTEM)complemented by elemental mapping was used to evaluate the particle dimensions and interplanar spacing of the optimized sample.Fourier-transform infrared spectroscopy(FTIR)was used to identify functional groups and assign corresponding vibrational bands.X-ray photoelectron spectroscopy(XPS)provided insights into the elemental composition and binding energies of the optimized nanophosphors.Notably,the PVA-modified sample doped with 14mol%Eu3+exhibited pronounced red emission at 616 nm,attributed to the ^(5)D_(0)→^(7)F_(2) electric dipole transition of Eu3+ions under ultraviolet(UV)excitation.Detailed excitation and emission spectral analyses were performed,with band assignments corresponding to the relevant electronic transitions.Among the surface-treated variants,the PVA-modified nanophosphors demonstrated exceptional color purity of 99.6%,international commission on illumination(CIE)chromaticity coordinates of(0.6351,0.3644),and a correlated color temperature of 1147 K.These superior optical features are ascribed to the enhanced surface passivation and suppression of nonradiative recombination,facilitated effectively by the PVA surface layer.Lifetime decay analysis across all samples revealed a significantly extended lifetime for the optimized composition,further supporting its superior luminescence efficiency.In addition,evaluation of the biocompatibility of the nano-phosphors highlighted their potential for biomedical applications.Overall,these findings emphasize the efficacy of PVA-modified Eu^(3+)-doped lanthanum tungstate nanophosphors as highly efficient red emitters,suitable for application in white light-emitting diodes(WLEDs)and latent fingerprint detection while offering valuable insights into the role of surface modification in tuning the optical properties of nanophosphors.展开更多
Fifteen novel carbazole alkaloids,euchrestifolines A-O(1-15),were obtained from Murraya euchrestifolia.Their structures were elucidated by spectroscopic analysis,Mosher's ester,calculated ECD,and transition metal ...Fifteen novel carbazole alkaloids,euchrestifolines A-O(1-15),were obtained from Murraya euchrestifolia.Their structures were elucidated by spectroscopic analysis,Mosher's ester,calculated ECD,and transition metal complex ECD methods.Notably,euchrestifolines A-C(1-3)are the first naturally occurring pyrrolidone carbazoles to be identified,while euchrestifolines D-F(4-6)represent rare carbazole alkaloids containing a phenylpropanyl moiety;euchrestifoline G(7)features a unique benzopyranocarbazole skeleton.More importantly,these compounds exhibited significant anti-ferroptotic activity,along with inhibitory effects of nitric oxide(NO)production and notable cytotoxicity.This study marks the first disclosure of carbazole's inhibitory effects against ferroptosis,and the EC_(50) values of some carbazoles ranging from 0.04 to 1 μM,substantially lower than the positive control,ferrostatin-1.In sum,this research not only enhances our understanding of carbazole alkaloids but also opens new avenues for the discovery of ferroptosis-related leading compounds.展开更多
Antipalu is a phytomedicinal medicinal beverage that is popular in the District of Abidjan, particularly for the treatment of malaria. However, Antipalu could present potential health effects on patients, and few toxi...Antipalu is a phytomedicinal medicinal beverage that is popular in the District of Abidjan, particularly for the treatment of malaria. However, Antipalu could present potential health effects on patients, and few toxicological studies have been conducted before its use. In order to determine the cytotoxicity of Antipalu, two complementary tests, LDH activity and the MTT cell proliferation assay, were used using Vero cells. Vero cells were exposed to increasing concentrations of Antipalu and incubated for 24, 48 and 72 hours. In addition, forty (40) rats distributed randomly into 4 groups, including 10 animals per group (5 males and 5 females) were used for the potential hepatoxic effects. Animals in group 1 received distilled water and were used as a control group. On the other hand, Lot I, II and III received by gavage a volume of the Antipalu extract corresponding to 1 ml/100 g of body weight at 200 mg/kg, 400 mg/kg, 800 mg/kg, respectively. The extract was administered daily at the same time for 28 days and serum was collected once a week to evaluate hepatic biochemical markers. After 28 days of study, all rats were euthanized by an overdose of ether and the liver of the rats was removed for gross morphological and histopathological analysis. The results of the cell supernatant assay showed an increasing extracellular LDH enzyme activity with lethal concentrations at 10% and 50% (LC10 = 111 µg/mL and LC50 = 555 µg/mL, respectively). In addition, the MTT assay showed a decrease in mitochondrial activity and thus cell proliferation after 24, 48 and 72 H of incubation. Our study showed that Antipalu caused alterations in the plasma membranes of the cells, resulting in the release of lactase dehydrogenase (LDH) into the external environment and a decrease in the mitochondrial activity of the Vero cells. The biochemical parameters ALT, ASAT, ALPs, and GGT showed no significant change (P > 0.05) in the group of treated rats compared to the controls. However, these variations were moderate and transient, with values remaining almost within their standard limits. Microscopic observations of liver tissue sections from rats treated with the Antipalu showed no lesions, edema and necrosis. These results suggest that the Antipalu did not interfere with the functioning or alter the integrity of the liver.展开更多
The global demand for renewable and sustainable non-petroleum-based resources is rapidly increasing.Lignocellulosic biomass is a valuable resource with broad potential for nanocellulose(NC)production.However,limited s...The global demand for renewable and sustainable non-petroleum-based resources is rapidly increasing.Lignocellulosic biomass is a valuable resource with broad potential for nanocellulose(NC)production.However,limited studies are available regarding the potential toxicological impact of NC.We provide an overview of the nanosafety implications associated mainly with nanofibrillated cellulose(CNF)and identify knowledge gaps.For this purpose,we present an analysis of the studies published from 2014 to 2025 in which the authors mention aspects related to toxicity in the context of packaging.We also analyze the main methods used for toxicity evaluations and the main studies about toxicity evaluation using different biomarkers for a broad interpretation.This comprehensive biblio-graphic review highlights the critical need for further research to elucidate the mechanisms fully underlining NC toxicity,mainly due to its nanofibrillar structure.We focus on the cellular responses across different evaluated cell types through in vitro evaluation,always within the context of the dose used,the type of material or its source,and the type of biomarkers used in the assessments.The importance of addressing safety considerations and key knowledge gaps for the responsible use of CNF derived fromlignocellulosic biomass and its bionanocomposites in food packaging is highlighted.展开更多
A key characteristic to be elucidated,to address the harmful health risks of environmental perfluorinated alkyl substances(PFAS),is their binding modes to serum albumin,the most abundant protein in blood.Hexafluoropro...A key characteristic to be elucidated,to address the harmful health risks of environmental perfluorinated alkyl substances(PFAS),is their binding modes to serum albumin,the most abundant protein in blood.Hexafluoropropylene oxide-dimer acid(GenX or HFPO-DA)is a new industrial replacement for the widespread linear long-chain PFAS.However,the detailed interaction of new-generation short-chain PFAS with albumin is still lacking.Herein,the binding characteristics of bovine serum albumin(BSA)to GenX were explored at the molecular and cellular levels.Itwas found that this branched short-chain GenX could bind to BSA with affinity lower than that of legacy linear long-chain perfluorooctanoic acid(PFOA).Site marker competitive study and molecular docking simulation revealed that GenX interacted with subdomain IIIA to form BSA-GenX complex.Consistent with its weaker affinity to albumin protein,the cytotoxicity of branched short-chain GenX was less susceptible to BSA binding compared with that of the linear long-chain PFOA.In contrast to the significant effects of strong BSA-PFOA interaction,the weak affinity of BSA-GenX binding did not influence the structure of protein and the cytotoxicity of GenX.The detailed characterization and direct comparisons of serum albumin interaction with new generation short-chain GenX will provide a better understanding for the toxicological properties of this new alternative.展开更多
Acrylamide(AA)is a harmful substance widely found in infant and child biscuits;however,the health hazards of AA,especially endogenous AA,in the biscuit matrix is poorly understood.This study aimed to determine the eff...Acrylamide(AA)is a harmful substance widely found in infant and child biscuits;however,the health hazards of AA,especially endogenous AA,in the biscuit matrix is poorly understood.This study aimed to determine the effects of endogenous(0.11 mg/(kg bw·day))and exogenous(1.31,5.23,and 10.13 mg/(kg bw·day))AA exposure from biscuit diet on the hematology,hormone levels,immune function,and liver and kidney damage in growing female rat pups.For the hematological indices,a quadratic reduction was observed in percentage of neutrophils(Neu%)and percentage of eosinophils(Eos%)in the leukograms and in mean corpuscular hemoglobin concentration and platelet in the erythrograms in all the AA-exposed groups.In terms of hormones,extremely remarkably elevations in estradiol(E_(2))and growth hormone(GH)levels were associated with exogenous AA,and a significant increase in GH levels was noted in the endogenous AA group.Regarding immune function,endogenous and exogenous AA showed a dose-dependent immunotoxic effect on lysozyme(LYSO),nitric oxide(NO),immunoglobulin(Ig)G,and IgM.In particular,the lactate dehydrogenase(LDH)activity was significantly high in the exogenous medium dose(Exo-M)and exogenous high dose(Exo-H)groups,and the percentage of CD3^(+)T cells in the blood and CD8^(+)expression levels in the spleen were significantly elevated in the Exo-H group.For liver and kidney function,exogenous AA had a dose-dependent effect on alanine aminotransferases(ALT),aspartate transferases(AST),alkaline phosphatase(ALP),urea nitrogen(UREA),and creatinine(CREA-S).In addition to the dose-dependent effect on the pathological changes in the liver and kidneys,the endogenous AA group presented with hepatocellular steatosis,kidney inflammatory infiltrates,and glomerular and tubular atrophy.Overall,our findings suggested the dose-dependent harmful effect of endogenous and exogenous AA.Special attention should be paid to the damage caused by exposure to endogenous AA.Stringent AA intake guidelines and measures are required to minimize AA levels in the food matrix.展开更多
文摘The ~ 125 I-UdR-release method is used for evaluation of the cytotoxity of biomaterials. In this method, K562 cells cultured in suspending were used to make a direct contact with materials. The cytotoxity of 14 kinds of biomaterials has been evaluated using this method. In comparing with other experimental methods for the evaluation of cell cytotoxity, this method shows advantages of the celerity, the simplicity, the objective, the accuracy and the quantitative.
文摘Two Co(Ⅱ)and Ni(Ⅱ)complexes were synthesized by synergistic coordination of 3,3-diphenylpropionic acid(HDPA)and 2,2′-bipyridylamine(PAm).The structures of complexes[Co(DPA)_(2)(PAm)]·2H_(2)O(1)and[Ni(DPA)_(2)(PAm)]·2H_(2)O(2)were determined by single-crystal X-ray diffraction,IR spectroscopy,and powder X-ray diffraction.Hirshfeld surface analysis provided quantitative insights into the intermolecular interactions within the complexes,while molecular docking studies elucidated their binding modes and affinities toward urease.Furthermore,the biological activities of both complexes were systematically evaluated through a range of assays,including DNA binding,urease inhibition,antibacterial activity,and in vitro cytotoxicity against cancer cells.Both complexes exhibited binding affinity for DNA and displayed notable urease inhibitory activity.Under in vitro conditions,both complexes showed appreciable cytotoxicity toward HepG2 cells with efficacy comparable to clinically used platinumbased anticancer agents.CCDC:2479943,1;2479944,2.
基金supported by NIH grant 1R16GM149379 to Renato J.Aguilerasupported by the core facilities of the BBRC,funded by the Research Centers in Minority Institutions grant 5U54MD007592 from the National Institute on Minority Health and Health Disparities to Robert A.Kirkensupported Denisse A.Gutierrez,Ana P.Betancourt,Elisa Robles-Escajeda and Armando Varela-Ramirez。
文摘Objectives:Drug resistance is the major determinant of chemotherapy failure,leading to relapse and tumor progression,demonstrating the urgent need for novel antineoplastic drugs.This study aimed to evaluate the anticancer potential of two novel pyrazole derivatives,P3C.1 and P3C.2,and to elucidate their mechanism of action in cancer cells.Methods:The cytotoxicity of the compounds was evaluated across 27 different cancer cell lines via a nuclear staining assay.Subsequent flow cytometric and biochemical analyses were performed to assess reactive oxygen species(ROS)generation,apoptosis induction,mitochondrial integrity,and cell cycle progression.Additional studies included transcriptome analyses and immunoassays to characterize the molecular mechanisms underlying drug activity.Results:Two novel pyrazole derivatives,P3C.1 and P3C.2,were identified with potent cytotoxicity on a variety of cancer cell lines.Among the adherent cell lines tested,the triple-negative breast cancer(TNBC)cell line MDA-MB-231 exhibited the highest sensitivity to both compounds and was therefore selected for further experimentation.In vitro assays demonstrated that both compounds induced ROS generation,mitochondrial membrane depolarization,cell cycle arrest and apoptosis.Whole-transcriptome sequencing of P3C.1 and P3C.2-treated MDA-MB-231 and two lymphoblastic leukemia cell lines revealed four genes in common associated with cell signaling and membrane dynamics.Connectivity Map(CMAP)database comparisons of shared genes for each cancer subtype revealed a strong similarity between the two compounds with tubulin inhibitors,and subsequent assays confirmed that these compounds act as microtubule-disrupting agents.Moreover,protein phosphorylation analysis indicated that both compounds induced hyperphosphorylation of JNK,and ERK1/2,along with hypophosphorylation of p38 kinases.Conclusions:P3C.1 and P3C.2 emerged as promising anti-breast cancer agents with dual mechanisms of action involving microtubule disruption and altered kinase signaling,leading to induction of apoptosis.
基金supported by the National Natural Science Foundation of China(Nos.32470414,32100319,and 82104377)the Fundamental Research Funds for the Central Universities,SWU(No.SWU-KR22052)+1 种基金the Natural Science Foundation of Chongqing,China(No.CSTB2022NSCQMSX0878)Chongqing Municipal Training Program of Innovation and Entrepreneurship for Undergraduates(No.S20241063290).
文摘Atractylodes macrocephala Koidz.(A.macrocephala)is a medicinal and edible plant species belonging to the Compositae family.Its rhizome serves both therapeutic and nutritional purposes in China.This investigation led to the isolation of thirteen novel rearranged 9(8→7)-abeo-eudesmane-type sesquiterpenoid dimers(SDs),atramacronins A-M(1-13),three eudesmane-type SDs,atramacronins N-P(14-16),and two previously identified meroterpenoids,atrachinenin G(17)and atrachineninΙ(18),from Atractylodes macrocephala.Structure elucidation was accomplished through comprehensive spectroscopic analysis and single-crystal X-ray diffraction.Compounds 1,4-7,9,and 10 exhibited notable cytotoxicity against Hep3B,HepG2,and Huh7 cell lines,with half maximal inhibitory concentration(IC_(50))values ranging from 3.71 to 13.99μmol·L^(-1).
文摘Objective Adaptive immune responses play a critical role in the pathogenesis of amyotrophic lateral sclerosis(ALS).In this study,we investigated the functional mechanisms of T cell subtypes and assessed the causal links between CD4+cytotoxic T cell-related genes and ALS risk.Methods Single-cell RNA sequencing(scRNA-seq)of peripheral blood mononuclear cells(PBMCs)from patients with ALS and healthy controls(HC)was used to identify differentially expressed genes(DEGs)in CD4+cytotoxic T cells.Comprehensive analyses of CD4+cytotoxic T cells,including pseudotemporal trajectory,intercellular communication,and metabolic pathway analysis,were performed.Mendelian randomization(MR)analysis evaluated the causal effects of DEGs on ALS risk,with validation using independent genome-wide association study(GWAS)data.Expression patterns of the causal genes were further verified using scRNA-seq,bulk-seq,and clinical samples.Results CD4+cytotoxic T cells were significantly expanded in patients with ALS.The upregulated genes S100A6,SERPINB6,SMAD7,and TPST2 were positively correlated with ALS susceptibility,whereas DIP2A showed a protective association.Conclusion S100A6,SERPINB6,SMAD7,TPST2,and DIP2A were identified as causal genes and potential therapeutic targets in ALS,implicating CD4+cytotoxic T cells in the disease mechanisms.Further studies targeting these genes and neuroinflammatory pathways are warranted.
文摘Glioblastoma(GBM),the most aggressive and lethal primary brain tumor in adults,continues to resist conventional therapeutic approaches,withmedian survival remaining dismally low.Immune checkpoint inhibitors(ICIs),which have revolutionized the treatment of several solid tumors,have shown limited efficacy inGBMowing to the highly immunosuppressive and heterogeneousmicroenvironment of the tumor.The unique immune landscape of the central nervous system(CNS),characterized by low immunogenicity,restricted T-cell infiltration,and an abundance of regulatory and myeloid-derived suppressor cells,poses considerable barriers to effective immune reactivation.This review provides a comprehensive synthesis of the mechanistic barriers undermining ICI efficacy in GBM,including the blood-brain barrier,low tumor mutational burden,adaptive immune resistance,and iatrogenic immunosuppression.It also explores emerging predictive and prognostic biomarkers,such as programmed death-ligand 1(PD-L1)expression,immune gene signatures,tumor-infiltrating lymphocyte profiles,and circulating markers in cerebrospinal fluid and plasma,which hold promise for guiding patient selection and therapeutic monitoring.Importantly,recent breakthroughs in combinatorial immunotherapy strategies are highlighted,including the integration of ICIs with radiotherapy,anti-angiogenic agents,oncolytic viruses,personalized neoantigen vaccines,and tumor microenvironment reprogramming approaches.Innovative delivery platforms,such as nanoparticles,focused ultrasound,and convection-enhanced delivery,are also discussed for their potential to improve drug bioavailability and local immune activation in the CNS.This review hypothesizes that the therapeutic efficacy of ICIs in GBM can be considerably enhanced by disrupting immune exclusion and reversing immunosuppression through integrated,multimodal strategies guided by dynamic biomarker profiling and spatially resolved immunemapping.This hypothesisdriven approach aims to bridge translational gaps and inform next-generation clinical trial designs that may unlock the potential of immunotherapy for GBM.
基金supported by the National Natural Science Foundation of China[82201489,2022].
文摘Objective:Multiple sclerosis(MS)is a chronic inflammatory demyelinating disease of the central nervous system(CNS).Soluble interleukin-2 receptor alpha(sIL-2Rα)has been implicated inMS pathogenesis,but its mechanisms remain unclear.This study investigates how sIL-2Rαexacerbates MS by modulating microglial activation and antibody-dependent cellular cytotoxicity(ADCC)in an experimental autoimmune encephalomyelitis(EAE)mouse model.Methods:Female C57BL/6J mice were induced with EAE and treated with sIL-2Rα.Clinical symptoms,histopathology,and molecular changes were analyzed.Microglial activation was assessed via immunohistochemistry,Western blot,and RNA sequencing.In vitro,ADCC-mediated oligodendrocyte injury was evaluated using Fc receptor inhibition and PI3K-Akt pathway blockade.Results:sIL-2Rα accelerated EAE onset and severity,increasingmicroglial M1 polarization and CNS inflammation.RNA-seq revealed PI3K-Akt pathway activation,upregulating Fc receptors(FcγR)on microglia,which enhanced ADCC against oligodendrocytes(p<0.001).Inhibiting FcγR or PI3K-Akt reduced oligodendrocyte damage.Conclusion:sIL-2Rαexacerbates MS by activating microglia via the PI3K-Aktaxis,promoting ADCC and demyelination.Targeting this pathway may offer novel therapeutic strategies for MS.
基金The National Natural Science Foundation of China,82460684,Li-Ping WangWest Light Foundation,Chinese Academy of Sciences,RZ[2022]4,Li-Ping Wang+3 种基金Research Foundation for Advanced Talents(D.Wang),TCZJZ[2022]02,Dong-Yang WangProject of State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University,QJJ[2022]419,Peng FuCultivation project of National Natural Science Foundation of Guizhou Medical University,20NSP065,Li-Ping Wangthe 100 Leading Talents of Guizhou Province,W.Zhu,Wei-Ming Zhu.
文摘A chemical investigation of Streptomyces sp.GZWMJZ-662,an endophytic actinomycete isolated from Houttuynia cordata Thunb.,has yielded eleven bohemamine dimers(1-11).Notably,the newly identified dibohemamines I-O(1-7)have not been previously reported.Their structures were elucidated through detailed spectroscopic analysis,encompassing high-resolution electrospray ionization mass,nuclear magnetic resonance,infrared radiation,ultraviolet-visible,and electronic circular dichroism spectroscopy.Dibohemamine I(1)exhibited selective cytotoxic effects against the cancer cell lines 786-O and GBC-SD among the 18 cell lines evaluated,with the half-inhibitory concentration values of 3.24±0.20 and 7.36±0.41μM,respectively.
基金supported by the Qi-Huang Chief Scientist Project of the National Administration of Traditional Chinese Medicine(2020).
文摘Phytochemical study of the n-BuOH extract of Ilex asprella resulted in the discovery of ten new pentacyclic triterpenoid glycosides,comprising nine ursane-type glycosides(1-9)and one oleanane-type glycoside(10),along with seven known compounds(11-17).Compound 1 is the first reported 19,22-epoxy ursane triterpenoid glycoside,whereas 4 and 5 are rare examples of ursane triterpenoid glycosides containing a 28,19-lactone group.The structural characterization of these compounds was achieved using spectroscopic and chemical techniques,as well as single-crystal X-ray analysis.Compounds 7,12,15,and 17 exhibited moderate cytotoxic activities against H1975 and HCC827 cancer cells.
基金Financial support from Beijing Natural Science Foundation(No.7232283)。
文摘From the seeds of Peganum harmala L.,three new alkaloids ofβ-carboline were isolated.Among them,peganumiums A(1)and B(2)were dimers with specific new scaffolds,all with long conjugated systems.Peganumium A and peganumium C(3)were ionic alkaloid salts and peganumium B was a hexacycliccondensed alkaloid.The biosynthetic pathways of the three compounds above were also speculated.A preliminary cytotoxicity assay revealed that peganumium B had strong in vitro antiproliferative ability against a variety of cancer cells.The analysis of^(1)H nuclear magnetic resonance(NMR)metabolomics suggested that the antiproliferative mechanism of peganumium B could be associated with the biosynthesis of phenylalanine,tyrosine and tryptophan,the metabolism of glycine,serine,and threonine,the metabolism of taurine and hypotaurine,and the metabolism of nicotinate and nicotinamide.In addition,peganumium B could reduce the mitochondrial content of body-wall muscle cells of a Caenorhabditis elegans(C.elegans)strain in vivo.
基金supported by the National Natural Science Foundation of China(Grant No.82274034)the Peking University Medicine plus X Pilot Program-Platform Construction Project(Grant No.2024YXXLHPT004).
文摘Ovarian cancer remains a leading cause of gynecological cancer mortality1,and patients with advanced stage ovarian cancer frequently develop malignant ascites that foster immunosuppressive microenvironments and therapeutic resistance2,3.Although ascites have traditionally been considered detrimental,we report a paradoxical role in which they enhance the cytotoxicity ofγδT cells—a unique T cell subset that can be allogenically transferred for cancer treatment4,5—toward ovarian cancer.
文摘BACKGROUND Severe acute respiratory syndrome coronavirus 2 induced coronavirus disease 2019(COVID-19)has posed a great challenge to public health worldwide and also increased susceptibility to colorectal cancer(CRC).Natural killer(NK)cells serve as the first line of defense in the host’s innate immune system,performing natural killing functions and mediating cytotoxicity against tumors and viruses.Therefore,a better understanding of NK cell cytotoxicity may facilitate the development of treatment strategies for CRC-associated with COVID-19.AIM To investigate the cytotoxic killing function of peripheral NK cells in patients with CRC and severe COVID-19(CRC+patients).METHODS The percentages of circulating NK and NKT cells in CRC+and age-matched patients with CRC were analyzed using flow cytometry.NK cell cytotoxic activity(NKCA)and corresponding NK cytotoxic factor(NKCF)activity in peripheral blood mononuclear cells were evaluated using a Real-Time Cell Analyzer.RESULTS The numbers and percentage of peripheral NK and NKT cells in patients with CRC+were lower than those in patients with CRC.Additionally,compared to patients with CRC,those with CRC+had lower levels of NKCA and NKCF activity in lysed K562 cells.Positive correlations were observed between NKCA and NK cell numbers,NKCA and NK cell percentages,NKCF activity,and NK cell percentages in patients with CRC+.Furthermore,a negative correlation was observed between NKCA and the severity of COVID-19 in patients with CRC.The area under the receiver operating characteristic curve for NKCA was greater than those for the other indices.CONCLUSION CRC+is associated with lower levels of peripheral NK cells and impaired natural cytotoxicity,contributing to the immunopathogenesis of severe COVID-19 rather than immune control.
基金supported by the National Key Research and Development Program of China(Nos.2023YFC3503900,2023YFA0914102)National Natural Science Foundation of China(Nos.82325046,82273829,92357305,22377004,22077007)the key project at central government level:the ability establishment of sustainable use for valuable Chinese medicine resources(No.2060302-2201-17)。
文摘Halogen substituents play a crucial role in the structural diversity and biological activity of natural products,and the synthesis of halogenated molecules remains an area of significant research interest.This study describes the generation of 15 new halogenated angucyclinones through the incorporation of halogen-containing phenylamines into a biosynthetic C-ringcleaved angucyclinone under mild conditions.The newly synthesized compounds feature halogen substituents encompassing all four halogen atoms(F,Cl,Br,I),with some compounds containing multiple halogen types.Structural elucidation was accomplished through ultraviolet(UV),infrared spectroscopy(IR),mass spectrometry(MS),and nuclear magnetic resonance(NMR)spectroscopic analyses,expanding the structural diversity of angucyclinonetype polyketides.Cytotoxicity evaluations revealed that eight compounds demonstrated moderate cytotoxic activities against four human tumor cell lines,with half maximal inhibitory concentration(IC_(50))values ranging from 3.35±0.37 to 16.02±6.60μmol·L-1.These findings highlight the significant potential of combining biosynthetic and chemical approaches in generating bioactive halogenated molecules.
基金financially supported by the National Natural Science Foundation of China(No.21572271).
文摘A[3+4]annulation of α-substituted allenes and Schiff bases is reported.This methodology serves as a conduit for the construction of a series of biologically important benzazepine derivatives in good to excellent yields under mild conditions by an unprecedented mode involving β’-carbon of α-substituted allenes and the proposed mechanism is supported by capturing the intermediate.Moreover,this class of benzazepine derivatives exhibited potential ability of cytotoxicity toward cancer cells.
基金financial support provided by the National Research Foundation of Korea(NRF)through the Basic Science Research Program,funded by the Ministry of Education(Nos.2021R1A6A1A03039493 and 2022R1A2C1009389)the authors extend their appreciation to the Researchers Supporting Project(No.RSPD2025R956)。
文摘The luminescence behavior of Eu^(3+)-activated lanthanum tungstate nanophosphors exhibiting intense red emission was systematically explored by modifying their surfaces using various agents,including polyvinylpyrrolidone(PVP),cetyltrimethylammonium bromide(CTAB),trisodium citrate(TC),polyvinyl alcohol(PVA),and ethylene glycol(EG).These nanophosphors were synthesized via a facile hydrothermal-assisted solid-state reaction.X-ray diffraction(XRD)analysis confirmed the orthorhombic crystal structure of all the prepared samples.Morphological and size analyses were performed using scanning electron microscopy(SEM)and particle size distribution profiling.High-resolution transmission electron microscopy(HRTEM)complemented by elemental mapping was used to evaluate the particle dimensions and interplanar spacing of the optimized sample.Fourier-transform infrared spectroscopy(FTIR)was used to identify functional groups and assign corresponding vibrational bands.X-ray photoelectron spectroscopy(XPS)provided insights into the elemental composition and binding energies of the optimized nanophosphors.Notably,the PVA-modified sample doped with 14mol%Eu3+exhibited pronounced red emission at 616 nm,attributed to the ^(5)D_(0)→^(7)F_(2) electric dipole transition of Eu3+ions under ultraviolet(UV)excitation.Detailed excitation and emission spectral analyses were performed,with band assignments corresponding to the relevant electronic transitions.Among the surface-treated variants,the PVA-modified nanophosphors demonstrated exceptional color purity of 99.6%,international commission on illumination(CIE)chromaticity coordinates of(0.6351,0.3644),and a correlated color temperature of 1147 K.These superior optical features are ascribed to the enhanced surface passivation and suppression of nonradiative recombination,facilitated effectively by the PVA surface layer.Lifetime decay analysis across all samples revealed a significantly extended lifetime for the optimized composition,further supporting its superior luminescence efficiency.In addition,evaluation of the biocompatibility of the nano-phosphors highlighted their potential for biomedical applications.Overall,these findings emphasize the efficacy of PVA-modified Eu^(3+)-doped lanthanum tungstate nanophosphors as highly efficient red emitters,suitable for application in white light-emitting diodes(WLEDs)and latent fingerprint detection while offering valuable insights into the role of surface modification in tuning the optical properties of nanophosphors.
基金the National Natural Science Foundation of China(NSFC)for their financial support through grant numbers 81973199,82173949,U23A20514,81773864,and 81473106the funding provided by the Key Research and Development Project of Shandong Province(2021CXGC010507).
文摘Fifteen novel carbazole alkaloids,euchrestifolines A-O(1-15),were obtained from Murraya euchrestifolia.Their structures were elucidated by spectroscopic analysis,Mosher's ester,calculated ECD,and transition metal complex ECD methods.Notably,euchrestifolines A-C(1-3)are the first naturally occurring pyrrolidone carbazoles to be identified,while euchrestifolines D-F(4-6)represent rare carbazole alkaloids containing a phenylpropanyl moiety;euchrestifoline G(7)features a unique benzopyranocarbazole skeleton.More importantly,these compounds exhibited significant anti-ferroptotic activity,along with inhibitory effects of nitric oxide(NO)production and notable cytotoxicity.This study marks the first disclosure of carbazole's inhibitory effects against ferroptosis,and the EC_(50) values of some carbazoles ranging from 0.04 to 1 μM,substantially lower than the positive control,ferrostatin-1.In sum,this research not only enhances our understanding of carbazole alkaloids but also opens new avenues for the discovery of ferroptosis-related leading compounds.
文摘Antipalu is a phytomedicinal medicinal beverage that is popular in the District of Abidjan, particularly for the treatment of malaria. However, Antipalu could present potential health effects on patients, and few toxicological studies have been conducted before its use. In order to determine the cytotoxicity of Antipalu, two complementary tests, LDH activity and the MTT cell proliferation assay, were used using Vero cells. Vero cells were exposed to increasing concentrations of Antipalu and incubated for 24, 48 and 72 hours. In addition, forty (40) rats distributed randomly into 4 groups, including 10 animals per group (5 males and 5 females) were used for the potential hepatoxic effects. Animals in group 1 received distilled water and were used as a control group. On the other hand, Lot I, II and III received by gavage a volume of the Antipalu extract corresponding to 1 ml/100 g of body weight at 200 mg/kg, 400 mg/kg, 800 mg/kg, respectively. The extract was administered daily at the same time for 28 days and serum was collected once a week to evaluate hepatic biochemical markers. After 28 days of study, all rats were euthanized by an overdose of ether and the liver of the rats was removed for gross morphological and histopathological analysis. The results of the cell supernatant assay showed an increasing extracellular LDH enzyme activity with lethal concentrations at 10% and 50% (LC10 = 111 µg/mL and LC50 = 555 µg/mL, respectively). In addition, the MTT assay showed a decrease in mitochondrial activity and thus cell proliferation after 24, 48 and 72 H of incubation. Our study showed that Antipalu caused alterations in the plasma membranes of the cells, resulting in the release of lactase dehydrogenase (LDH) into the external environment and a decrease in the mitochondrial activity of the Vero cells. The biochemical parameters ALT, ASAT, ALPs, and GGT showed no significant change (P > 0.05) in the group of treated rats compared to the controls. However, these variations were moderate and transient, with values remaining almost within their standard limits. Microscopic observations of liver tissue sections from rats treated with the Antipalu showed no lesions, edema and necrosis. These results suggest that the Antipalu did not interfere with the functioning or alter the integrity of the liver.
基金funded by General Secretariat of Science and Technology,National University of Misiones(SGCyT-UNaM),grant number:16/Q2384-PI.
文摘The global demand for renewable and sustainable non-petroleum-based resources is rapidly increasing.Lignocellulosic biomass is a valuable resource with broad potential for nanocellulose(NC)production.However,limited studies are available regarding the potential toxicological impact of NC.We provide an overview of the nanosafety implications associated mainly with nanofibrillated cellulose(CNF)and identify knowledge gaps.For this purpose,we present an analysis of the studies published from 2014 to 2025 in which the authors mention aspects related to toxicity in the context of packaging.We also analyze the main methods used for toxicity evaluations and the main studies about toxicity evaluation using different biomarkers for a broad interpretation.This comprehensive biblio-graphic review highlights the critical need for further research to elucidate the mechanisms fully underlining NC toxicity,mainly due to its nanofibrillar structure.We focus on the cellular responses across different evaluated cell types through in vitro evaluation,always within the context of the dose used,the type of material or its source,and the type of biomarkers used in the assessments.The importance of addressing safety considerations and key knowledge gaps for the responsible use of CNF derived fromlignocellulosic biomass and its bionanocomposites in food packaging is highlighted.
基金supported by the National Natural Science Foundation of China(Nos.31960196,31760255,and 82260637)Jiangxi Provincial Natural Science Foundation(No.20212BAB205016).
文摘A key characteristic to be elucidated,to address the harmful health risks of environmental perfluorinated alkyl substances(PFAS),is their binding modes to serum albumin,the most abundant protein in blood.Hexafluoropropylene oxide-dimer acid(GenX or HFPO-DA)is a new industrial replacement for the widespread linear long-chain PFAS.However,the detailed interaction of new-generation short-chain PFAS with albumin is still lacking.Herein,the binding characteristics of bovine serum albumin(BSA)to GenX were explored at the molecular and cellular levels.Itwas found that this branched short-chain GenX could bind to BSA with affinity lower than that of legacy linear long-chain perfluorooctanoic acid(PFOA).Site marker competitive study and molecular docking simulation revealed that GenX interacted with subdomain IIIA to form BSA-GenX complex.Consistent with its weaker affinity to albumin protein,the cytotoxicity of branched short-chain GenX was less susceptible to BSA binding compared with that of the linear long-chain PFOA.In contrast to the significant effects of strong BSA-PFOA interaction,the weak affinity of BSA-GenX binding did not influence the structure of protein and the cytotoxicity of GenX.The detailed characterization and direct comparisons of serum albumin interaction with new generation short-chain GenX will provide a better understanding for the toxicological properties of this new alternative.
文摘Acrylamide(AA)is a harmful substance widely found in infant and child biscuits;however,the health hazards of AA,especially endogenous AA,in the biscuit matrix is poorly understood.This study aimed to determine the effects of endogenous(0.11 mg/(kg bw·day))and exogenous(1.31,5.23,and 10.13 mg/(kg bw·day))AA exposure from biscuit diet on the hematology,hormone levels,immune function,and liver and kidney damage in growing female rat pups.For the hematological indices,a quadratic reduction was observed in percentage of neutrophils(Neu%)and percentage of eosinophils(Eos%)in the leukograms and in mean corpuscular hemoglobin concentration and platelet in the erythrograms in all the AA-exposed groups.In terms of hormones,extremely remarkably elevations in estradiol(E_(2))and growth hormone(GH)levels were associated with exogenous AA,and a significant increase in GH levels was noted in the endogenous AA group.Regarding immune function,endogenous and exogenous AA showed a dose-dependent immunotoxic effect on lysozyme(LYSO),nitric oxide(NO),immunoglobulin(Ig)G,and IgM.In particular,the lactate dehydrogenase(LDH)activity was significantly high in the exogenous medium dose(Exo-M)and exogenous high dose(Exo-H)groups,and the percentage of CD3^(+)T cells in the blood and CD8^(+)expression levels in the spleen were significantly elevated in the Exo-H group.For liver and kidney function,exogenous AA had a dose-dependent effect on alanine aminotransferases(ALT),aspartate transferases(AST),alkaline phosphatase(ALP),urea nitrogen(UREA),and creatinine(CREA-S).In addition to the dose-dependent effect on the pathological changes in the liver and kidneys,the endogenous AA group presented with hepatocellular steatosis,kidney inflammatory infiltrates,and glomerular and tubular atrophy.Overall,our findings suggested the dose-dependent harmful effect of endogenous and exogenous AA.Special attention should be paid to the damage caused by exposure to endogenous AA.Stringent AA intake guidelines and measures are required to minimize AA levels in the food matrix.
