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
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
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
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
To improve the controlled release ability,we prepared attapulgite into microspheres by spray drying.This research began with a thorough thermogravimetric analysis to optimize attapulgite's heat treatment for drug ...To improve the controlled release ability,we prepared attapulgite into microspheres by spray drying.This research began with a thorough thermogravimetric analysis to optimize attapulgite's heat treatment for drug loading.By advanced spray drying,attapulgite was transformed into microspheres,refining its drug release characteristics.Various parameters were examined,achieving optimal particle size and morphology at 25%solid content,2.5%dispersant,and 3% binder.Attapulgite microspheres demonstrated exceptional encapsulation efficiency,exceeding 95% for doxorubicin hydrochloride,highlighting their versatility in drug delivery.FTIR and XRD were used to predict changes in material properties after spray drying.Notably,cytotoxicity tests confirmed the high biocompatibility of attapulgite microspheres,devoid of cell death induction.Attapulgite microsphere loaded with doxorubicin enable sustained drug release and maintain killing ability against tumor cells.This study confirms the viability of spray dried attapulgite microspheres for efficient drug loading and delivery and provides insights for innovative drug delivery systems that utilize the unique properties of attapulgite to advance therapeutics.展开更多
Five novel emestrin-type epipolythiodioxopiperazines(ETPs),prenylemestrins C-G(1-5),along with two known ETPs,prenylemestrin A(6)and prenylemestrin B(7),were obtained from Aspergillus nidulans.Their structures were ch...Five novel emestrin-type epipolythiodioxopiperazines(ETPs),prenylemestrins C-G(1-5),along with two known ETPs,prenylemestrin A(6)and prenylemestrin B(7),were obtained from Aspergillus nidulans.Their structures were characterized by spectroscopic data,X-ray crystallographic data,ECD comparisons and calculations.Prenylemestrins C-G(1-5)represent a rare class of ETPs,characterized by a 2,5-dithia-7,9-diazabicyclo[4.2.2]decane-8,10-dione core involving a hemiterpene moiety.Notably,compound 6 exhibited moderate cytotoxicity,inducing G2/M cell cycle arrest and apoptosis of L1210 cells by regulating the PI3K/AKT signaling pathway and mitochondrial apoptotic mechanisms.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
Background:Scutellaria root(root of Scutellaria baicalensis),which has potent anti-inflammatory effects,is a component of useful traditional formulaes.Albeit a low frequency,it has been reported to cause severe inters...Background:Scutellaria root(root of Scutellaria baicalensis),which has potent anti-inflammatory effects,is a component of useful traditional formulaes.Albeit a low frequency,it has been reported to cause severe interstitial pneumonia and liver dysfunction.Importantly,the hepatotoxicity induced by Scutellaria root can be controlled by the baicalin content,one of its major constituents.This study aimed to clarify the role of MRP2 in modulating baicalin-induced cytotoxicity in HepG2 cells,providing insights that inform safer use and assessment of baicalin.Methods:Cytotoxicity of HepG2 and MDCK cells was assessed using a cell counting kit-8 assay in the presence and absence of MK571,an MRP2 inhibitor.MRP2 expression levels were confirmed using agarose gel electrophoresis,and intracellular baicalin concentrations were measured using LC/MS.Results:Baicalin exhibited concentration-dependent cytotoxicity,with higher toxicity observed in MRP2-negative MDCK cells than in MRP2-positive HepG2 cells.Pre-treatment with MK571 increased baicalin-induced cytotoxicity in HepG2 cells and doubled the intracellular baicalin concentration.Conclusion:Our results indicated that MRP2 plays an important role in reducing baicalin-induced hepatocyte toxicity by decreasing intracellular baicalin levels.Monitoring MRP2 activity could serve as a critical predictive biomarker to identify individuals at higher risk of baicalin-induced hepatotoxicity,enabling personalized dosing strategies and minimizing adverse effects associated with Scutellaria root-containing formulae.展开更多
Traditional Palestinian medicine uses Thymus capitatus (T. capitatus), a plant recognized for its therapeutic properties due to its high concentration of essential oils such as thymol and carvacrol, to treat skin dise...Traditional Palestinian medicine uses Thymus capitatus (T. capitatus), a plant recognized for its therapeutic properties due to its high concentration of essential oils such as thymol and carvacrol, to treat skin diseases, gastrointestinal disorders, and respiratory infections. The present study was conducted to evaluate the antioxidant and anticancer activities of T. capitatus essential oil (EO). Moreover, this study employed computational methods including ADMET analysis and molecular docking. Using Gas chromatography-mass spectrometry (GC-MS) analysis, the phytochemical composition of T. capitatus essential oil was identified. The DPPH scavenging method was used to assess antioxidant activity. The Michigan Cancer Foundation-7 (MCF-7) and human colorectal carcinoma (HCT-116) cell lines were used to test for cytotoxic and cytostatic effects. The results of GC/MS analysis revealed 21 chemicals, accounting for 95.82% of their content, with carvacrol (61.23%), p-Cymene (9.49%) and γ-Terpinene (9.4%) being the most abundant. With an IC50 value of 0.27 ± 0.009 mg/mL, the DPPH assay demonstrated a robust scavenging capacity when compared to the IC50 value of butylated hydroxytoluene (BHT), which was 0.37 ± 0.007 mg/mL. T. capitatus EO showed potent anticancer activity on HCT-116 and MCF cell lines. The ADMET in-silico investigations revealed satisfying physicochemical and pharmacokinetics profiles, justified by good human intestinal absorption (HIA exceeding 93%), good permeabilities to the blood-brain barrier (BBB) and central nervous system (CNS), without any inhibition effect on 1A2, 2C9, 2C19, 2D6, and 3A4 cytochromes. Furthermore, all ligands were determined to be non-toxic, with no Ames mutagenicity detected based on toxicity predictions, making them ideal candidates for further drug development.展开更多
The interest in using the Datura stramonium plant is due to its natural products,which are used in many pharmaceutical industries.The objective of the current study was to assess the therapeutic and cytotoxic effects ...The interest in using the Datura stramonium plant is due to its natural products,which are used in many pharmaceutical industries.The objective of the current study was to assess the therapeutic and cytotoxic effects of the D.stramonium plant on two types of human cancer cell models(MCF7 and HT29)in vitro.A soxhlet apparatus was used to obtain methanolic extract from dried plant leaves.The recovered crude,after the solvent had evaporated,was then dispersed at varied concentrations of extract 100,50,20,and 0.0µg/mL and tested to see how the cells responded.Also,the cancer-testis antigen(CTA)gene transcription in the two cell types exposed to the plant extract was examined using a semi-quantitative real-time polymerase chain reaction.Gas chromatography–mass spectrometry(GC-MS)results produced the significant main metabolites Nonanoic acid,Tropine N-Oxide,3,6-Ditigloyloxy-7-hydroxytropane,Hexadecanoic acid,2-Pentadecanone,6,10,14-trimethyl-,Carvenone,methyl ester,Phytol,Aposcopolamine,Hyoscyamine,4,8,12,16-Tetramethylheptadecan-4-olide,Scopolamine,Alpha.-Tocospiro A,1,2-Cycloheptanedione,3,3,7,7-tetramethyl-,dihydrazone,Campesterol,Stigmasterol,Gamma-Sitosterol and dl-.alpha.-Tocopherol.The results showed that the two types of cell lines impacted by D.stramonium extract,through untreated type 1 cells(MCF7)gave a highly significant transcription according to all applicable genes.All implemented analyses cleared the strong genetic impacts of Datura extract on cancer cells’genomes.TGIF2LY and C2orf63 transcript accumulation were also significantly elevated when exposed to plant extract at a level of 50µg/mL in cell line type 2(HT29),but TGIF2LY and P53 had the lowest relative expression at a level of 100µg/mL when treated the same cell line type.展开更多
Nine novel compounds,comprising seven tetrahydroanthraquinones(auxarthrolones A−G,1−7),aγ-butenolide glycoside(malfilamentoside E,26),and aγ-butenolide(auxarthrolide A,27),together with eighteen known compounds(8−25...Nine novel compounds,comprising seven tetrahydroanthraquinones(auxarthrolones A−G,1−7),aγ-butenolide glycoside(malfilamentoside E,26),and aγ-butenolide(auxarthrolide A,27),together with eighteen known compounds(8−25)were isolated from rice-based solid culture of Auxarthron umbrinum(A.umbrinum)DSM3193 using the one strain many compounds(OSMAC)approach.The structural elucidation of these compounds was accomplished through nuclear magnetic resonance(NMR),mass spectrometry(MS),and NMR calculation combined with DP4+analysis or MAEΔΔδparameter,while the absolute configurations of new compounds were established through single-crystal X-ray diffraction,electronic circular dichroism(ECD)spectroscopic data analysis and/or chemical derivatization.Austrocortilutein(10)and auxarthrol H(14)demonstrated moderate cytotoxicity against U87 and U251[half maximal inhibitory concentration(IC_(50))3.5−12.1μmol·L^(−1)].Additionally,auxarthrolone A(1),auxarthrol H(14),eupolyphagin B(15),and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone(17)exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid,thus demonstrating fibroblast proliferation-promoting activity.展开更多
Maternal consumption of a high-fat diet has been linked to increased risks of obesity and impaired glucose metabolism in offspring.However,the precise epigenetic mechanisms governing these intergenerational effects,pa...Maternal consumption of a high-fat diet has been linked to increased risks of obesity and impaired glucose metabolism in offspring.However,the precise epigenetic mechanisms governing these intergenerational effects,particularly during the early stages of offspring development,remain poorly understood.In this study,female C57BL/6J mice were randomly assigned to either a high-fat diet or normal chow diet throughout gestation and lactation.Methylated DNA immunoprecipitation(MeDIP)coupled with microarray analysis was employed to identify differentially methylated genes in the livers of offspring at weaning age.We found that maternal high-fat diet feeding predisposes offspring to obesity and impaired glucose metabolism as early as the weaning period.DNA methylation profile analysis unveiled a significant enrichment of differentially methylated genes within the natural killer(NK)cell-mediated cytotoxicity pathway.MeDIP-PCR validated reduced methylation levels of specific genes within this pathway,including tumour necrosis factorα(TNF-α),phosphoinositide 3-kinase(PI3K),and SHC adaptor protein 1(SHC1).Consistently,the expressions of TNF-α,PI3K,and SHC1 were significantly upregulated,accompanied by elevated serum TNF-αand interleukin-6(IL-6)levels in offspring from dams fed with high-fat diet.Moreover,we assessed the expressions of genes associated with NK cell activities,uncovering a notable rise in hepatic granzyme B levels and a trend towards increased CD107a expression in offspring from dams fed a high-fat diet.In addition,methylation levels of TNF-α,PI3K,and SHC1 promoters were inversely correlated with glucose response during glucose tolerance testing.In conclusion,our findings underscore the critical role of the NK cell-mediated cytotoxicity signaling pathway in mediating DNA methylation patterns,thereby contributing to the programming effects of maternal high-fat diet consumption on offspring glucose metabolism as early as the weaning period.展开更多
K−Na co-doped δ-MnO_(2)(KNMOH)nanoflowers were synthesized,and their cytotoxic effects against HeLa cervical cancer cells were evaluated.The KNMOH exhibited significant dose-and time-dependent cytotoxicity at concent...K−Na co-doped δ-MnO_(2)(KNMOH)nanoflowers were synthesized,and their cytotoxic effects against HeLa cervical cancer cells were evaluated.The KNMOH exhibited significant dose-and time-dependent cytotoxicity at concentrations of 50 and 100μg/mL.After 24 h of incubation treatment,cell viability decreased to(36.8±6.5)% and(33.4±6.4)%at 50 and 100μg/mL,respectively.With extended exposure to 48 h,cell viability was(45.2±2.3)%and(32.3±2.8)%at the same concentrations.Phase-contrast microscopy revealed characteristic morphological changes including cell shrinkage and membrane blebbing formation,indicative of cell death.These findings demonstrate the potential of KNMOH nanoflowers as a cytotoxic agent for cervical cancer applications and provide a foundation for further mechanistic studies.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.
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.
基金Funded by the Major Special Projects of Technological Innovation of Hubei Province(No.2017ACA168)the Open Fund Project of Sanya Science and Education Innovation Park of Wuhan University of Technology(No.2021KF0012)the Guangdong Basic and Applied Basic Research Foundation(No.2021B1515120091)。
文摘To improve the controlled release ability,we prepared attapulgite into microspheres by spray drying.This research began with a thorough thermogravimetric analysis to optimize attapulgite's heat treatment for drug loading.By advanced spray drying,attapulgite was transformed into microspheres,refining its drug release characteristics.Various parameters were examined,achieving optimal particle size and morphology at 25%solid content,2.5%dispersant,and 3% binder.Attapulgite microspheres demonstrated exceptional encapsulation efficiency,exceeding 95% for doxorubicin hydrochloride,highlighting their versatility in drug delivery.FTIR and XRD were used to predict changes in material properties after spray drying.Notably,cytotoxicity tests confirmed the high biocompatibility of attapulgite microspheres,devoid of cell death induction.Attapulgite microsphere loaded with doxorubicin enable sustained drug release and maintain killing ability against tumor cells.This study confirms the viability of spray dried attapulgite microspheres for efficient drug loading and delivery and provides insights for innovative drug delivery systems that utilize the unique properties of attapulgite to advance therapeutics.
基金National Natural Science Foundation of China(U22A20380,82173706,82104028)Fundamental Research Funds for the Central Universities(2024BRA018)financially supported this project.
文摘Five novel emestrin-type epipolythiodioxopiperazines(ETPs),prenylemestrins C-G(1-5),along with two known ETPs,prenylemestrin A(6)and prenylemestrin B(7),were obtained from Aspergillus nidulans.Their structures were characterized by spectroscopic data,X-ray crystallographic data,ECD comparisons and calculations.Prenylemestrins C-G(1-5)represent a rare class of ETPs,characterized by a 2,5-dithia-7,9-diazabicyclo[4.2.2]decane-8,10-dione core involving a hemiterpene moiety.Notably,compound 6 exhibited moderate cytotoxicity,inducing G2/M cell cycle arrest and apoptosis of L1210 cells by regulating the PI3K/AKT signaling pathway and mitochondrial apoptotic mechanisms.
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supported by the JSPS KAKENHI(Grant Number:JP22K06676)。
文摘Background:Scutellaria root(root of Scutellaria baicalensis),which has potent anti-inflammatory effects,is a component of useful traditional formulaes.Albeit a low frequency,it has been reported to cause severe interstitial pneumonia and liver dysfunction.Importantly,the hepatotoxicity induced by Scutellaria root can be controlled by the baicalin content,one of its major constituents.This study aimed to clarify the role of MRP2 in modulating baicalin-induced cytotoxicity in HepG2 cells,providing insights that inform safer use and assessment of baicalin.Methods:Cytotoxicity of HepG2 and MDCK cells was assessed using a cell counting kit-8 assay in the presence and absence of MK571,an MRP2 inhibitor.MRP2 expression levels were confirmed using agarose gel electrophoresis,and intracellular baicalin concentrations were measured using LC/MS.Results:Baicalin exhibited concentration-dependent cytotoxicity,with higher toxicity observed in MRP2-negative MDCK cells than in MRP2-positive HepG2 cells.Pre-treatment with MK571 increased baicalin-induced cytotoxicity in HepG2 cells and doubled the intracellular baicalin concentration.Conclusion:Our results indicated that MRP2 plays an important role in reducing baicalin-induced hepatocyte toxicity by decreasing intracellular baicalin levels.Monitoring MRP2 activity could serve as a critical predictive biomarker to identify individuals at higher risk of baicalin-induced hepatotoxicity,enabling personalized dosing strategies and minimizing adverse effects associated with Scutellaria root-containing formulae.
文摘Traditional Palestinian medicine uses Thymus capitatus (T. capitatus), a plant recognized for its therapeutic properties due to its high concentration of essential oils such as thymol and carvacrol, to treat skin diseases, gastrointestinal disorders, and respiratory infections. The present study was conducted to evaluate the antioxidant and anticancer activities of T. capitatus essential oil (EO). Moreover, this study employed computational methods including ADMET analysis and molecular docking. Using Gas chromatography-mass spectrometry (GC-MS) analysis, the phytochemical composition of T. capitatus essential oil was identified. The DPPH scavenging method was used to assess antioxidant activity. The Michigan Cancer Foundation-7 (MCF-7) and human colorectal carcinoma (HCT-116) cell lines were used to test for cytotoxic and cytostatic effects. The results of GC/MS analysis revealed 21 chemicals, accounting for 95.82% of their content, with carvacrol (61.23%), p-Cymene (9.49%) and γ-Terpinene (9.4%) being the most abundant. With an IC50 value of 0.27 ± 0.009 mg/mL, the DPPH assay demonstrated a robust scavenging capacity when compared to the IC50 value of butylated hydroxytoluene (BHT), which was 0.37 ± 0.007 mg/mL. T. capitatus EO showed potent anticancer activity on HCT-116 and MCF cell lines. The ADMET in-silico investigations revealed satisfying physicochemical and pharmacokinetics profiles, justified by good human intestinal absorption (HIA exceeding 93%), good permeabilities to the blood-brain barrier (BBB) and central nervous system (CNS), without any inhibition effect on 1A2, 2C9, 2C19, 2D6, and 3A4 cytochromes. Furthermore, all ligands were determined to be non-toxic, with no Ames mutagenicity detected based on toxicity predictions, making them ideal candidates for further drug development.
文摘The interest in using the Datura stramonium plant is due to its natural products,which are used in many pharmaceutical industries.The objective of the current study was to assess the therapeutic and cytotoxic effects of the D.stramonium plant on two types of human cancer cell models(MCF7 and HT29)in vitro.A soxhlet apparatus was used to obtain methanolic extract from dried plant leaves.The recovered crude,after the solvent had evaporated,was then dispersed at varied concentrations of extract 100,50,20,and 0.0µg/mL and tested to see how the cells responded.Also,the cancer-testis antigen(CTA)gene transcription in the two cell types exposed to the plant extract was examined using a semi-quantitative real-time polymerase chain reaction.Gas chromatography–mass spectrometry(GC-MS)results produced the significant main metabolites Nonanoic acid,Tropine N-Oxide,3,6-Ditigloyloxy-7-hydroxytropane,Hexadecanoic acid,2-Pentadecanone,6,10,14-trimethyl-,Carvenone,methyl ester,Phytol,Aposcopolamine,Hyoscyamine,4,8,12,16-Tetramethylheptadecan-4-olide,Scopolamine,Alpha.-Tocospiro A,1,2-Cycloheptanedione,3,3,7,7-tetramethyl-,dihydrazone,Campesterol,Stigmasterol,Gamma-Sitosterol and dl-.alpha.-Tocopherol.The results showed that the two types of cell lines impacted by D.stramonium extract,through untreated type 1 cells(MCF7)gave a highly significant transcription according to all applicable genes.All implemented analyses cleared the strong genetic impacts of Datura extract on cancer cells’genomes.TGIF2LY and C2orf63 transcript accumulation were also significantly elevated when exposed to plant extract at a level of 50µg/mL in cell line type 2(HT29),but TGIF2LY and P53 had the lowest relative expression at a level of 100µg/mL when treated the same cell line type.
基金supported by the National Key Research and Development Program of China(No.2018YFA0901900)the National Science Fund for Distinguished Young Scholars(No.82225042).
文摘Nine novel compounds,comprising seven tetrahydroanthraquinones(auxarthrolones A−G,1−7),aγ-butenolide glycoside(malfilamentoside E,26),and aγ-butenolide(auxarthrolide A,27),together with eighteen known compounds(8−25)were isolated from rice-based solid culture of Auxarthron umbrinum(A.umbrinum)DSM3193 using the one strain many compounds(OSMAC)approach.The structural elucidation of these compounds was accomplished through nuclear magnetic resonance(NMR),mass spectrometry(MS),and NMR calculation combined with DP4+analysis or MAEΔΔδparameter,while the absolute configurations of new compounds were established through single-crystal X-ray diffraction,electronic circular dichroism(ECD)spectroscopic data analysis and/or chemical derivatization.Austrocortilutein(10)and auxarthrol H(14)demonstrated moderate cytotoxicity against U87 and U251[half maximal inhibitory concentration(IC_(50))3.5−12.1μmol·L^(−1)].Additionally,auxarthrolone A(1),auxarthrol H(14),eupolyphagin B(15),and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone(17)exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid,thus demonstrating fibroblast proliferation-promoting activity.
基金sponsored by National Natural Science Foundation of China(81800703)Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(GZC20231088)+8 种基金Beijing Nova Program(Z201100006820117 and 20220484181)Beijing Municipal Natural Science Foundation(7184252)the Fundamental Research Funds for the Central Universitiesthe Fundamental Research Funds for the Central Universities(BMU2021MX013)Peking University Clinical Scientist Training Program(BMU2023PYJH022)Peking University Medicine Seed Fund for Interdisciplinary ResearchChina Endocrine and Metabolism Young Scientific Talent Research Project(2022-N-02-01)China Diabetes Young Scientific Talent Research ProjectBethune-Merck Diabetes Research Fund of Bethune Charitable Foundation。
文摘Maternal consumption of a high-fat diet has been linked to increased risks of obesity and impaired glucose metabolism in offspring.However,the precise epigenetic mechanisms governing these intergenerational effects,particularly during the early stages of offspring development,remain poorly understood.In this study,female C57BL/6J mice were randomly assigned to either a high-fat diet or normal chow diet throughout gestation and lactation.Methylated DNA immunoprecipitation(MeDIP)coupled with microarray analysis was employed to identify differentially methylated genes in the livers of offspring at weaning age.We found that maternal high-fat diet feeding predisposes offspring to obesity and impaired glucose metabolism as early as the weaning period.DNA methylation profile analysis unveiled a significant enrichment of differentially methylated genes within the natural killer(NK)cell-mediated cytotoxicity pathway.MeDIP-PCR validated reduced methylation levels of specific genes within this pathway,including tumour necrosis factorα(TNF-α),phosphoinositide 3-kinase(PI3K),and SHC adaptor protein 1(SHC1).Consistently,the expressions of TNF-α,PI3K,and SHC1 were significantly upregulated,accompanied by elevated serum TNF-αand interleukin-6(IL-6)levels in offspring from dams fed with high-fat diet.Moreover,we assessed the expressions of genes associated with NK cell activities,uncovering a notable rise in hepatic granzyme B levels and a trend towards increased CD107a expression in offspring from dams fed a high-fat diet.In addition,methylation levels of TNF-α,PI3K,and SHC1 promoters were inversely correlated with glucose response during glucose tolerance testing.In conclusion,our findings underscore the critical role of the NK cell-mediated cytotoxicity signaling pathway in mediating DNA methylation patterns,thereby contributing to the programming effects of maternal high-fat diet consumption on offspring glucose metabolism as early as the weaning period.
文摘K−Na co-doped δ-MnO_(2)(KNMOH)nanoflowers were synthesized,and their cytotoxic effects against HeLa cervical cancer cells were evaluated.The KNMOH exhibited significant dose-and time-dependent cytotoxicity at concentrations of 50 and 100μg/mL.After 24 h of incubation treatment,cell viability decreased to(36.8±6.5)% and(33.4±6.4)%at 50 and 100μg/mL,respectively.With extended exposure to 48 h,cell viability was(45.2±2.3)%and(32.3±2.8)%at the same concentrations.Phase-contrast microscopy revealed characteristic morphological changes including cell shrinkage and membrane blebbing formation,indicative of cell death.These findings demonstrate the potential of KNMOH nanoflowers as a cytotoxic agent for cervical cancer applications and provide a foundation for further mechanistic studies.
