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
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
(±)-Penicithrones A–D(1a/1b–4a/4b),four novel pairs of anthrone–cyclopentenone heterodimers characterized by a distinctive bridged 6/6/6−5 tetracyclic core skeleton,together with three previously identified co...(±)-Penicithrones A–D(1a/1b–4a/4b),four novel pairs of anthrone–cyclopentenone heterodimers characterized by a distinctive bridged 6/6/6−5 tetracyclic core skeleton,together with three previously identified compounds(5–7),were isolated from the crude extract of the mangrove-derived fungus Penicillium sp.,guided by heteronuclear single quantum correlation(HSQC)-based small molecule accurate recognition technology(SMART 2.0)and liquid chromatography-tandem mass spectrometry(LC-MS/MS)-based molecular networking.The structural elucidation of new compounds was accomplished through comprehensive spectroscopic analysis,and their absolute configurations were determined using DP4+^(13)C nuclear magnetic resonance(NMR)calculations and electronic circular dichroism(ECD)calculations.Compounds 1a/1b–4a/4b demonstrated moderate cytotoxicity against three human cancer cell lines HeLa,HCT116 and MCF-7 with half maximal inhibitory concentration(IC50)values ranging from 15.95±1.64 to 28.56±2.59μmol·L–1.展开更多
Ostreopsis cf.ovata is a marine benthic dinoflagellate in tropical and temperate seas and can produce potent toxic compounds.The existence of O.cf.ovata has been found in the Chinese coastal areas,but studies on its t...Ostreopsis cf.ovata is a marine benthic dinoflagellate in tropical and temperate seas and can produce potent toxic compounds.The existence of O.cf.ovata has been found in the Chinese coastal areas,but studies on its toxicity are very few.This study investigated the toxicity of the O.cf.ovata(TIO991)isolated from Weizhou Island in the South China Sea by using methanol and chloroform to extract toxic compounds from the algal cells cultured indoor.Experiments on mouse acute toxicity showed that the crude methanol extract(CME)of O.cf.ovata caused the death of mice in 16–18 min.Furthermore,CME inhibited the cell reproduction of human neuroblastoma cells(BE(2)-M17 cells)by Cell Counting Kit-8 with a dose-and time-effect relationship and caused cell death in the form of cell necrosis.We found that CME had strong hemolytic activity and was significantly inhibited by ouabain,indicating that CME might contain palytoxins.By contrast,the crude chloroform extract of O.cf.ovata was relatively weak in toxicity as obtained in our experiments on mouse acute toxicity,cytotoxicity,and hemolytic activity.This suggests that the algae may raise the potential threat to marine ecosystems and public health.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
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
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
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
Plasma electrolytic oxidation is a well-known technique for surface modification of biomedical magnesium alloys,with good corrosion protection and the ability to produce biocompatible and bioactive coatings.In this st...Plasma electrolytic oxidation is a well-known technique for surface modification of biomedical magnesium alloys,with good corrosion protection and the ability to produce biocompatible and bioactive coatings.In this study,calcium-phosphate coatings were produced on WE43 magnesium alloy for use,as orthopedic implants.Coating formation was prepared using different oxidation parameters with various duty ratios(DR)of 15,25 and 50%and current ratios(R)-2 or 1.6.Application of R with excess cathodic current(R>1)in processes with DR≥25%allowed attaining the soft-sparking regime(SSR)that resulted in thicker oxide coatings with higher degree of crystallinity compared to the films obtained without SSR.The results of the corrosion tests contributed to a noticeable improvement in the corrosion resistance of the magnesium alloy.Optimization of the oxidation parameters allowed the selection of the variants with the most favorable degradation behavior over the tested immersion period,indicating a successful modification of the magnesium alloy surface to obtain an implant biomaterial capable of providing controlled degradation.Furthermore,biological evaluation of the produced coatings showed that the proposed surface modifications significantly reduced the cytotoxic effects observed in direct contact with the material while still maintaining the cell proliferation-promoting effects of the material eluents.展开更多
Two-dimensional(2D)Nb_(2)CT_(x)MXene hold great promise for biomedical applications due to their tunable surface chemistry and biocompatibility.However,their practical use requires long-term colloidal and oxidative st...Two-dimensional(2D)Nb_(2)CT_(x)MXene hold great promise for biomedical applications due to their tunable surface chemistry and biocompatibility.However,their practical use requires long-term colloidal and oxidative stability.Here,we propose a tandem-type stabilization strategy combining antioxidant protection and macromolecular surface functionalization.Nb_(2)CT_(x)was first treated with L-ascorbic acid(LA)to suppress oxidation by binding to reactive edges,followed by modification with polyethylene glycol(PEG),poly-L-lysine(PLL),or polydopamine(PDA).This dual approach enhanced stability in biological media—phosphate-buffered saline(PBS)and Dulbecco’s Modified Eagle’s Medium(DMEM)—while preserving non-cytotoxicity toward A375 and HaCaT skin cell lines across 0‒100 mg·L^(-1).Among the tested systems,LA/PEG and LA/PDAmodified MXenes maintained stable zeta potentials(-15 to-12 mV)and particle sizes for 72 h,whereas LA/PLL samples showed aggregation and charge loss.This tandem stabilization effectively prevents oxidation and aggregation without compromising biocompatibility,offering a versatile route for developing oxidation-resistant MXenes for biomedical and nanomedicine applications.展开更多
Hybrid antioxidants cinnamoyldopamine（2a）, p-coumaroyldopamine（2b）, caffeoyldopamine（2c）, feruloyldopamine（2d） and sinapoyldopamine（2e） were synthesized by conjugation of dopamine（DA） and hydroxycinnamic a...Hybrid antioxidants cinnamoyldopamine（2a）, p-coumaroyldopamine（2b）, caffeoyldopamine（2c）, feruloyldopamine（2d） and sinapoyldopamine（2e） were synthesized by conjugation of dopamine（DA） and hydroxycinnamic acids（HCAs）. The stabilities were studied in buffers at p H 1.3, p H 5.0, and p H 7.4 including the human plasma. All the compounds were found highly stable at acidic p H, but underwent hydrolysis at neutral p H. Furthermore, the hydrolysis proceeded much faster in plasma in the following order as indicated by half-life values（t1/2）, 2c（1.21 h）〈2e（1.52 h）〈2d（1.85 h）〈2b（3.38 h）〈2a（3.88 h）, correlating with the number of electron-donating groups. It has been proven by UV spectrum that 2c, 2d, and 2e displayed red shift of more than 50 nm as compared to 2a and 2b, because of the presence of OH and OCH3 groups. In addition, the compounds（2b–e） showed no cytotoxicity on normal HUVEC cells as DA, although 2a displayed a 16% inhibition of proliferation at 40 μM following 48 h incubation. Their free radical-scavenging activities were evaluated using ABTS^＊＋ and superoxide anion assays and the mechanisms were proposed. It was found that they all exhibited higher activities than trolox, a recognized antioxidant. Amazingly, in the case of the hybrids（2a–e）, their activity was higher than that of HCAs while lower or comparable to that of DA, suggesting that there may be a ＂saturation effect＂ with the hybrid molecules in the antioxidant activities.展开更多
To investigate the cytotoxic activity of actinomycete isolated from marine sediment. Methods: In the present study the DNA was isolated and the ITS region of 16s rRNA was amplified by polymerase chain reaction, using ...To investigate the cytotoxic activity of actinomycete isolated from marine sediment. Methods: In the present study the DNA was isolated and the ITS region of 16s rRNA was amplified by polymerase chain reaction, using two universal bacterial primers, 1492R (5′-GGTTACCTTGTTAC GACTT-3′) and Eubac27F (5′-AGAGTTTGATCCTGGCTC AG-3′). The amplified products were purified using TIANgel mini purification kit, ligated to MD18-T simple vector (TaKaRa), and transformed into competent cells of Escherichia coli DH5α. 16S rRNA gene fragment was sequenced using forward primer M13F (-47) and reverse primer M13R (-48). Blast search sequence similarity was found against the existing non-redundant nucleotide sequence database thus, identified as Streptomyces sp SU, Streptomyces rubralavandulae strain SU1, Streptomyces cacaoi strain SU2, Streptomyces cavourensis strain SU3, Streptomyces avidinii strain SU4, Streptomyces globisporus strain SU5, Streptomyces variabilis strain SU6, Streptomycescoelicolor strain SU 7. Among the eight identified isolates, one actinomycete Streptomyces avidinii strain SU4 was selected for further study. Results: Crude extract of the actinomycete isolate exhibited IC50 in 64.5 μg against Hep-2 cell line, 250 μg in VERO cell line. This value is very close to the criteria of cytotoxicity activity for the crude extracts, as established by the American National Cancer Institute (NCI) is in IC50 < 30 μg /mL. The GC MS analysis showed that the active principle might be 1,2-benzenedicarboxylic acid, bis(2-methylpropyl) ester (12.17%), isooctyl phthalate (15.29%) with the retention time 15.642 and 21.612, respectively. Conclusions: This study clearly proves that the marine sediment derived actinomycetes with bioactive metabolites can be expected to provide high quality biological material for high throughout biochemical and anticancer screening programs. These results help us to conclude that the potential of using metabolic engineering and post genomic approaches to isolate more bioactive compounds and make their possible commercial application is not far off.展开更多
A novel series of compounds combining indolin-2-one and quinazolin-4（3H）-one moiety via a carbon-carbon double bond were synthesized by aldol-condensation of 2-methylquinazolin-4（3H）-one-6-carbaldehyde with variou...A novel series of compounds combining indolin-2-one and quinazolin-4（3H）-one moiety via a carbon-carbon double bond were synthesized by aldol-condensation of 2-methylquinazolin-4（3H）-one-6-carbaldehyde with various indolin-2-ones. The synthesized compounds were evaluated for their cytotoxic activity against five human cancer cell lines, namely, A549, MCF-7, HeLa, HT-29 and HCT-116. We found that compound 5e with two bromine atoms at the 5- and 7-positions of the indolin-2-one ring was most potent, which inhibited proliferation of five cancer cell lines in the range of 32.0%-62.3% at a concentration of 50 p,M. Our results further indicate that the connection of 5,7-dibromoindolin-2-one and 2-methylquinazolin- 4（3H）-one moiety with a carbon-carbon double bond is essential for compound 5e to exert cytotoxicity.展开更多
Rhizoma Coptidis （RC）, a widely used traditional Chinese medicine, is commonly believed to be non-toxic. However, little is known about its cytotoxicity and relevant mechanisms at cellular and genetic levels. The pr...Rhizoma Coptidis （RC）, a widely used traditional Chinese medicine, is commonly believed to be non-toxic. However, little is known about its cytotoxicity and relevant mechanisms at cellular and genetic levels. The present study aimed to explore the cytotoxicity of RC and its possible mechanisms related to cell cycle arrest, DNA damage and reactive oxygen species （ROS） level in L929 murine fibroblast cells. The cells were cultured in vitro and treated with different RC concentrations for 24 h. Cell viability was determined by CCK-8 method, morphological changes were observed with an inverted microscope, cell cycle and ROS level were examined by flow cytometry, and DNA damages were detected by comet assay. Our results showed that cell viability was significantly decreased in a dose-dependent manner when the RC concentration was higher than 1 mg/mL. ARC concentration above 1 mg/mL altered the morphology of L929 cells. Both cells at G2/M phase and the ROS level increased in the 2 mg/mL group. Each DNA damage indicator score increased in the groups with the RC concentration of above 0.05 mg/mL. Taken together, our study suggested that RC at a high dosage exhibited cytotoxicity on L929 cells, which was likely to be the consequences of cell cycle arrest, DNA damage and accumulation of intracellular ROS.展开更多
Ursolic acid(UA) is a pentacyclic triterpene of the ursane type. As a common chemical constituent among species of the family Lamiaceae, UA possesses a broad spectrum of pharmacological properties. This overview focus...Ursolic acid(UA) is a pentacyclic triterpene of the ursane type. As a common chemical constituent among species of the family Lamiaceae, UA possesses a broad spectrum of pharmacological properties. This overview focuses on the anticancer properties of UA against breast cancer(BC) and colorectal cancer(CRC)that are most common among women and men, respectively. In vitro studies have shown that UA inhibited the growth of BC and CRC cell lines through various molecular targets and signaling pathways.There are several in vivo studies on the cytotoxic activity of UA against BC and CRC. UA also inhibits the growth of other types of cancer. Studies on structural modifications of UA have shown that the –OH groups at C3 and at C28 are critical factors influencing the cytotoxic activity of UA and its derivatives.Some needs for future research are suggested. Sources of information were from ScienceDirect, Google Scholar and PubMed.展开更多
Two previously undescribed steroidal compounds, 16, 23-epoxy-22, 26-epimino-cholest-22(N), 23, 25(26)-trien-3β-ol-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside(1) and 26-O-β-D-gluc...Two previously undescribed steroidal compounds, 16, 23-epoxy-22, 26-epimino-cholest-22(N), 23, 25(26)-trien-3β-ol-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside(1) and 26-O-β-D-glucopyranosyl-(25 R)-5α-furost-20(22)-en-3β, 26-diol(2), together with 7 known ones including 26-O-β-D-glucopyranosyl-(25 R)-5, 20(22)-dien-furost-3β, 26-diol(3),(25 R)-5-en-spirost-3β-ol-O-β-D-glucopyranosyl-(1→4)-[α-L-rhmanopyranosyl-(1→2)]-β-D-galactopyranoside(4), funkioside D(5), aspidistrin(6), tigogenin-3-O-β-D-lucotrioside(7), desglucolanatigonin II(8), and degalactotigonin(9), were isolated from Solanum lyratum Thunb. Their cytotoxic activities were tested in two cancer cell lines by MTT method. One of the steroidal glycosides(6) showed significant cytotoxic activity against gastric cancer SGC7901 and liver cancer BEL-7402 cells.展开更多
A new compound 8-chloro-5,6,7-trihydroxy-2-（3-hydroxy-4-methoxyphenethyl）-5,6,7,8-tetralaydro-4H-chromen-4-one （1） was isolated from the Chinese eaglewood [Aquilaria sinensis （Lour.） Gilg]. Its structure was elu...A new compound 8-chloro-5,6,7-trihydroxy-2-（3-hydroxy-4-methoxyphenethyl）-5,6,7,8-tetralaydro-4H-chromen-4-one （1） was isolated from the Chinese eaglewood [Aquilaria sinensis （Lour.） Gilg]. Its structure was elucidated on the basis of spectral data. Compound I showed cytotoxicity against human gastric cancer cell line （SGC-7901） in vitro by MTT method with the IC50 value of 14.6 μg/mL.展开更多
ABM: To investigate the cytotoxicity of the cytokine-induced killer (CIK) cells from the post-operation patients with primary hepatocellular carcinoma (HCC) to multidrug-resistant (MDR) cell of HCC both in vitro and i...ABM: To investigate the cytotoxicity of the cytokine-induced killer (CIK) cells from the post-operation patients with primary hepatocellular carcinoma (HCC) to multidrug-resistant (MDR) cell of HCC both in vitro and in vivo. METHODS: A drug-resistant cell line was established by culturing human HCC cell line Bel-7402 in complete RPMI 1640 medium with increasing concentrations of adriamycin from 10 to 2 000 nmol/L. CIK cells were obtained by inducing the peripheral blood mononuclear cells with rhlFN-γ, monoclonal anti-CD3 antibody, rhIL-1α as well as rhIL-2, which were added into the culture. To detect the cytotoxicity of the CIK cells from HCC patients, the Bel-7402/R was taken as target (T) cells and CIK cells as effect (E) cells. Cytotoxic test was performed and measured by MTT. As to in vivo test, CIK cells were transfused into patients with HCC. The tumor specimens of the patients were obtained and immunohistochemistry was carried out to detect CD3, CD45, CD45RO as well as CD68. RESULTS: A MDR 1 HCC cell line Bel-7402/R was established. Its MDR1 mRNA overexpressed which was shown by RT-PCR; the P-glycoprotein expression increased from 1.32% of parent cells to 54%. CIK cells expanded vigorously by more than 70-fold and the CD3+CD56+ increased by more than 600-fold after 3-wk incubation on average. The cytotoxicity of CIK from HCC patients to Bel-7402/R was about 50% and to L-02 below 10% (t = 8.87, P<0.01), the same as that of CIK from normal individuals. Each of the 17 patients received 1-5×1010of CIK cell transfusion. No side effects were observed. After CIK treatment, the tumor tissue nodules formed and a large amount of lymphocytes infiltrated in the liver cancer tissue and CD3, CD45, CD45RO, and CD68 increased greatly which was shown by immunohistochemistry. CONCLUSION: A stable MDR1 HCC cell line has been established which could recover from liquid nitrogen and CIK from HCC patients has strong cytotoxicity to MDR HCC cell. CIK adoptive immunotherapy is safe and has no side effects. Receivers improved their immunity to tumor evidently. CIK treatment may be a better choice for HCC patients after operation to prevent the recurrence, especially when tumors have developed drug resistance.展开更多
The cytotoxicities of single-walled carbon nanotubes （SWNTs） and acid purified single-walled carbon nanotubes （SWNT-COOH） were investigated by spectroscopic analysis. Cell viability and cell apoptosis were applied...The cytotoxicities of single-walled carbon nanotubes （SWNTs） and acid purified single-walled carbon nanotubes （SWNT-COOH） were investigated by spectroscopic analysis. Cell viability and cell apoptosis were applied to assessing the cytotoxicity of SWNT-COOH, cetyltrimethyl ammonium bromide （CTAB） and acid purified carbon nanotubes modified with cetyltrimethyl ammonium bromide （SWNT-COOH/CTAB）. The results indicate that SWNTs are more toxic than SWNT-COOH. Concentration and time-curve analyses indicate that cytotoxicity of SWNT-COOH/CTAB is more related to the toxicity of the surfactant CTAB. The cytotoxicity effect of CTAB and SWNT-COOH/CTAB is acceptable at low concentrations （0.5-25μg/mL）. The cytotoxicity observation suggests that SWNT-COOH/CTAB can safely applied to biomedical field at low concentrations （0.5-25μg/mL）.展开更多
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.
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 National Key Research and Development Program of China(No.2022YFC2303100)the National Natural Science Foundation of China(Nos.32022002 and 21977113).
文摘(±)-Penicithrones A–D(1a/1b–4a/4b),four novel pairs of anthrone–cyclopentenone heterodimers characterized by a distinctive bridged 6/6/6−5 tetracyclic core skeleton,together with three previously identified compounds(5–7),were isolated from the crude extract of the mangrove-derived fungus Penicillium sp.,guided by heteronuclear single quantum correlation(HSQC)-based small molecule accurate recognition technology(SMART 2.0)and liquid chromatography-tandem mass spectrometry(LC-MS/MS)-based molecular networking.The structural elucidation of new compounds was accomplished through comprehensive spectroscopic analysis,and their absolute configurations were determined using DP4+^(13)C nuclear magnetic resonance(NMR)calculations and electronic circular dichroism(ECD)calculations.Compounds 1a/1b–4a/4b demonstrated moderate cytotoxicity against three human cancer cell lines HeLa,HCT116 and MCF-7 with half maximal inhibitory concentration(IC50)values ranging from 15.95±1.64 to 28.56±2.59μmol·L–1.
基金Supported by the Special Research for the Science and Technology Basic Resources Investigation Program of China(No.2018FY100200)the National Natural Science Foundation of China(No.42176206)the Natural Science Foundation of Shandong Province(No.ZR2021MD071)。
文摘Ostreopsis cf.ovata is a marine benthic dinoflagellate in tropical and temperate seas and can produce potent toxic compounds.The existence of O.cf.ovata has been found in the Chinese coastal areas,but studies on its toxicity are very few.This study investigated the toxicity of the O.cf.ovata(TIO991)isolated from Weizhou Island in the South China Sea by using methanol and chloroform to extract toxic compounds from the algal cells cultured indoor.Experiments on mouse acute toxicity showed that the crude methanol extract(CME)of O.cf.ovata caused the death of mice in 16–18 min.Furthermore,CME inhibited the cell reproduction of human neuroblastoma cells(BE(2)-M17 cells)by Cell Counting Kit-8 with a dose-and time-effect relationship and caused cell death in the form of cell necrosis.We found that CME had strong hemolytic activity and was significantly inhibited by ouabain,indicating that CME might contain palytoxins.By contrast,the crude chloroform extract of O.cf.ovata was relatively weak in toxicity as obtained in our experiments on mouse acute toxicity,cytotoxicity,and hemolytic activity.This suggests that the algae may raise the potential threat to marine ecosystems and public health.
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.
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.
基金funded by Silesian University of Technology,no.07/020/BKM24/0104.
文摘Plasma electrolytic oxidation is a well-known technique for surface modification of biomedical magnesium alloys,with good corrosion protection and the ability to produce biocompatible and bioactive coatings.In this study,calcium-phosphate coatings were produced on WE43 magnesium alloy for use,as orthopedic implants.Coating formation was prepared using different oxidation parameters with various duty ratios(DR)of 15,25 and 50%and current ratios(R)-2 or 1.6.Application of R with excess cathodic current(R>1)in processes with DR≥25%allowed attaining the soft-sparking regime(SSR)that resulted in thicker oxide coatings with higher degree of crystallinity compared to the films obtained without SSR.The results of the corrosion tests contributed to a noticeable improvement in the corrosion resistance of the magnesium alloy.Optimization of the oxidation parameters allowed the selection of the variants with the most favorable degradation behavior over the tested immersion period,indicating a successful modification of the magnesium alloy surface to obtain an implant biomaterial capable of providing controlled degradation.Furthermore,biological evaluation of the produced coatings showed that the proposed surface modifications significantly reduced the cytotoxic effects observed in direct contact with the material while still maintaining the cell proliferation-promoting effects of the material eluents.
基金funded by the National Science Centre(NCN)within the framework of the research project‘OPUS-23’(UMO-2022/45/B/ST5/03652)and‘PRELUDIUM 17’(UMO-2019/33/N/ST5/02095)the National Science Centre,within the framework of the research project‘PRELUDIUM-22’(UMO-2023/49/N/ST11/03574)and‘OPUS-18’(UMO-2019/35/B/ST5/02538)+1 种基金the Foundation for Polish Science(FNP,Scholarship START program)ID-UB project(Scholarship Plus program).
文摘Two-dimensional(2D)Nb_(2)CT_(x)MXene hold great promise for biomedical applications due to their tunable surface chemistry and biocompatibility.However,their practical use requires long-term colloidal and oxidative stability.Here,we propose a tandem-type stabilization strategy combining antioxidant protection and macromolecular surface functionalization.Nb_(2)CT_(x)was first treated with L-ascorbic acid(LA)to suppress oxidation by binding to reactive edges,followed by modification with polyethylene glycol(PEG),poly-L-lysine(PLL),or polydopamine(PDA).This dual approach enhanced stability in biological media—phosphate-buffered saline(PBS)and Dulbecco’s Modified Eagle’s Medium(DMEM)—while preserving non-cytotoxicity toward A375 and HaCaT skin cell lines across 0‒100 mg·L^(-1).Among the tested systems,LA/PEG and LA/PDAmodified MXenes maintained stable zeta potentials(-15 to-12 mV)and particle sizes for 72 h,whereas LA/PLL samples showed aggregation and charge loss.This tandem stabilization effectively prevents oxidation and aggregation without compromising biocompatibility,offering a versatile route for developing oxidation-resistant MXenes for biomedical and nanomedicine applications.
基金The National Natural Science Foundation of China(Grant No.21302079)the Fundamental Research Funds for the Central Universities(Grant No.lzujbky-2014-151)
文摘Hybrid antioxidants cinnamoyldopamine（2a）, p-coumaroyldopamine（2b）, caffeoyldopamine（2c）, feruloyldopamine（2d） and sinapoyldopamine（2e） were synthesized by conjugation of dopamine（DA） and hydroxycinnamic acids（HCAs）. The stabilities were studied in buffers at p H 1.3, p H 5.0, and p H 7.4 including the human plasma. All the compounds were found highly stable at acidic p H, but underwent hydrolysis at neutral p H. Furthermore, the hydrolysis proceeded much faster in plasma in the following order as indicated by half-life values（t1/2）, 2c（1.21 h）〈2e（1.52 h）〈2d（1.85 h）〈2b（3.38 h）〈2a（3.88 h）, correlating with the number of electron-donating groups. It has been proven by UV spectrum that 2c, 2d, and 2e displayed red shift of more than 50 nm as compared to 2a and 2b, because of the presence of OH and OCH3 groups. In addition, the compounds（2b–e） showed no cytotoxicity on normal HUVEC cells as DA, although 2a displayed a 16% inhibition of proliferation at 40 μM following 48 h incubation. Their free radical-scavenging activities were evaluated using ABTS^＊＋ and superoxide anion assays and the mechanisms were proposed. It was found that they all exhibited higher activities than trolox, a recognized antioxidant. Amazingly, in the case of the hybrids（2a–e）, their activity was higher than that of HCAs while lower or comparable to that of DA, suggesting that there may be a ＂saturation effect＂ with the hybrid molecules in the antioxidant activities.
文摘To investigate the cytotoxic activity of actinomycete isolated from marine sediment. Methods: In the present study the DNA was isolated and the ITS region of 16s rRNA was amplified by polymerase chain reaction, using two universal bacterial primers, 1492R (5′-GGTTACCTTGTTAC GACTT-3′) and Eubac27F (5′-AGAGTTTGATCCTGGCTC AG-3′). The amplified products were purified using TIANgel mini purification kit, ligated to MD18-T simple vector (TaKaRa), and transformed into competent cells of Escherichia coli DH5α. 16S rRNA gene fragment was sequenced using forward primer M13F (-47) and reverse primer M13R (-48). Blast search sequence similarity was found against the existing non-redundant nucleotide sequence database thus, identified as Streptomyces sp SU, Streptomyces rubralavandulae strain SU1, Streptomyces cacaoi strain SU2, Streptomyces cavourensis strain SU3, Streptomyces avidinii strain SU4, Streptomyces globisporus strain SU5, Streptomyces variabilis strain SU6, Streptomycescoelicolor strain SU 7. Among the eight identified isolates, one actinomycete Streptomyces avidinii strain SU4 was selected for further study. Results: Crude extract of the actinomycete isolate exhibited IC50 in 64.5 μg against Hep-2 cell line, 250 μg in VERO cell line. This value is very close to the criteria of cytotoxicity activity for the crude extracts, as established by the American National Cancer Institute (NCI) is in IC50 < 30 μg /mL. The GC MS analysis showed that the active principle might be 1,2-benzenedicarboxylic acid, bis(2-methylpropyl) ester (12.17%), isooctyl phthalate (15.29%) with the retention time 15.642 and 21.612, respectively. Conclusions: This study clearly proves that the marine sediment derived actinomycetes with bioactive metabolites can be expected to provide high quality biological material for high throughout biochemical and anticancer screening programs. These results help us to conclude that the potential of using metabolic engineering and post genomic approaches to isolate more bioactive compounds and make their possible commercial application is not far off.
基金National Natural Science Foundation of China (Grant No.20972099,31130017)Beijing Municipal Commission of Education (Grant No.KZ201210028035)+1 种基金Scientific Research Base Development Program of the Beijing Municipal Commission of Educationthe 973 Project (Grant No.2013CB911000)
文摘A novel series of compounds combining indolin-2-one and quinazolin-4（3H）-one moiety via a carbon-carbon double bond were synthesized by aldol-condensation of 2-methylquinazolin-4（3H）-one-6-carbaldehyde with various indolin-2-ones. The synthesized compounds were evaluated for their cytotoxic activity against five human cancer cell lines, namely, A549, MCF-7, HeLa, HT-29 and HCT-116. We found that compound 5e with two bromine atoms at the 5- and 7-positions of the indolin-2-one ring was most potent, which inhibited proliferation of five cancer cell lines in the range of 32.0%-62.3% at a concentration of 50 p,M. Our results further indicate that the connection of 5,7-dibromoindolin-2-one and 2-methylquinazolin- 4（3H）-one moiety with a carbon-carbon double bond is essential for compound 5e to exert cytotoxicity.
基金National Natural Science Foundation of China(Grant No.31172358)
文摘Rhizoma Coptidis （RC）, a widely used traditional Chinese medicine, is commonly believed to be non-toxic. However, little is known about its cytotoxicity and relevant mechanisms at cellular and genetic levels. The present study aimed to explore the cytotoxicity of RC and its possible mechanisms related to cell cycle arrest, DNA damage and reactive oxygen species （ROS） level in L929 murine fibroblast cells. The cells were cultured in vitro and treated with different RC concentrations for 24 h. Cell viability was determined by CCK-8 method, morphological changes were observed with an inverted microscope, cell cycle and ROS level were examined by flow cytometry, and DNA damages were detected by comet assay. Our results showed that cell viability was significantly decreased in a dose-dependent manner when the RC concentration was higher than 1 mg/mL. ARC concentration above 1 mg/mL altered the morphology of L929 cells. Both cells at G2/M phase and the ROS level increased in the 2 mg/mL group. Each DNA damage indicator score increased in the groups with the RC concentration of above 0.05 mg/mL. Taken together, our study suggested that RC at a high dosage exhibited cytotoxicity on L929 cells, which was likely to be the consequences of cell cycle arrest, DNA damage and accumulation of intracellular ROS.
基金funding from UCSI University (Proj-In-FAS-049 Proj-In-FAS-052)+1 种基金the Ministry of Higher Education (MOHE),Malaysia (FRGS/2/2014/SG01/UCSI/02/2 FRGS/1/2018/TK10/UCSI/02/1) for supporting our research group
文摘Ursolic acid(UA) is a pentacyclic triterpene of the ursane type. As a common chemical constituent among species of the family Lamiaceae, UA possesses a broad spectrum of pharmacological properties. This overview focuses on the anticancer properties of UA against breast cancer(BC) and colorectal cancer(CRC)that are most common among women and men, respectively. In vitro studies have shown that UA inhibited the growth of BC and CRC cell lines through various molecular targets and signaling pathways.There are several in vivo studies on the cytotoxic activity of UA against BC and CRC. UA also inhibits the growth of other types of cancer. Studies on structural modifications of UA have shown that the –OH groups at C3 and at C28 are critical factors influencing the cytotoxic activity of UA and its derivatives.Some needs for future research are suggested. Sources of information were from ScienceDirect, Google Scholar and PubMed.
基金supported by the Science and Technology Department Plan of Jilin Province(Nos.20160101341JC and 20160622010JC)
文摘Two previously undescribed steroidal compounds, 16, 23-epoxy-22, 26-epimino-cholest-22(N), 23, 25(26)-trien-3β-ol-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside(1) and 26-O-β-D-glucopyranosyl-(25 R)-5α-furost-20(22)-en-3β, 26-diol(2), together with 7 known ones including 26-O-β-D-glucopyranosyl-(25 R)-5, 20(22)-dien-furost-3β, 26-diol(3),(25 R)-5-en-spirost-3β-ol-O-β-D-glucopyranosyl-(1→4)-[α-L-rhmanopyranosyl-(1→2)]-β-D-galactopyranoside(4), funkioside D(5), aspidistrin(6), tigogenin-3-O-β-D-lucotrioside(7), desglucolanatigonin II(8), and degalactotigonin(9), were isolated from Solanum lyratum Thunb. Their cytotoxic activities were tested in two cancer cell lines by MTT method. One of the steroidal glycosides(6) showed significant cytotoxic activity against gastric cancer SGC7901 and liver cancer BEL-7402 cells.
基金National Basic Research Program of China(No.2007CB 116306)the Science and Technology Foundation of Chinese Academy of Agricultural Sciences(Nos.RKY0726 and RKY0442).
文摘A new compound 8-chloro-5,6,7-trihydroxy-2-（3-hydroxy-4-methoxyphenethyl）-5,6,7,8-tetralaydro-4H-chromen-4-one （1） was isolated from the Chinese eaglewood [Aquilaria sinensis （Lour.） Gilg]. Its structure was elucidated on the basis of spectral data. Compound I showed cytotoxicity against human gastric cancer cell line （SGC-7901） in vitro by MTT method with the IC50 value of 14.6 μg/mL.
文摘ABM: To investigate the cytotoxicity of the cytokine-induced killer (CIK) cells from the post-operation patients with primary hepatocellular carcinoma (HCC) to multidrug-resistant (MDR) cell of HCC both in vitro and in vivo. METHODS: A drug-resistant cell line was established by culturing human HCC cell line Bel-7402 in complete RPMI 1640 medium with increasing concentrations of adriamycin from 10 to 2 000 nmol/L. CIK cells were obtained by inducing the peripheral blood mononuclear cells with rhlFN-γ, monoclonal anti-CD3 antibody, rhIL-1α as well as rhIL-2, which were added into the culture. To detect the cytotoxicity of the CIK cells from HCC patients, the Bel-7402/R was taken as target (T) cells and CIK cells as effect (E) cells. Cytotoxic test was performed and measured by MTT. As to in vivo test, CIK cells were transfused into patients with HCC. The tumor specimens of the patients were obtained and immunohistochemistry was carried out to detect CD3, CD45, CD45RO as well as CD68. RESULTS: A MDR 1 HCC cell line Bel-7402/R was established. Its MDR1 mRNA overexpressed which was shown by RT-PCR; the P-glycoprotein expression increased from 1.32% of parent cells to 54%. CIK cells expanded vigorously by more than 70-fold and the CD3+CD56+ increased by more than 600-fold after 3-wk incubation on average. The cytotoxicity of CIK from HCC patients to Bel-7402/R was about 50% and to L-02 below 10% (t = 8.87, P<0.01), the same as that of CIK from normal individuals. Each of the 17 patients received 1-5×1010of CIK cell transfusion. No side effects were observed. After CIK treatment, the tumor tissue nodules formed and a large amount of lymphocytes infiltrated in the liver cancer tissue and CD3, CD45, CD45RO, and CD68 increased greatly which was shown by immunohistochemistry. CONCLUSION: A stable MDR1 HCC cell line has been established which could recover from liquid nitrogen and CIK from HCC patients has strong cytotoxicity to MDR HCC cell. CIK adoptive immunotherapy is safe and has no side effects. Receivers improved their immunity to tumor evidently. CIK treatment may be a better choice for HCC patients after operation to prevent the recurrence, especially when tumors have developed drug resistance.
基金Project(81172546)supported by the National Natural Science Foundation of ChinaProject(20120162110078)supported by Doctoral Fund of Ministry of Education of China+1 种基金Project(2011ssxp198)supported by the Graduate Degree Thesis Innovation Foundation of Central South University,ChinaProject(13JJ2015)supported by Hunan Provincial Natural Science Foundation of China
文摘The cytotoxicities of single-walled carbon nanotubes （SWNTs） and acid purified single-walled carbon nanotubes （SWNT-COOH） were investigated by spectroscopic analysis. Cell viability and cell apoptosis were applied to assessing the cytotoxicity of SWNT-COOH, cetyltrimethyl ammonium bromide （CTAB） and acid purified carbon nanotubes modified with cetyltrimethyl ammonium bromide （SWNT-COOH/CTAB）. The results indicate that SWNTs are more toxic than SWNT-COOH. Concentration and time-curve analyses indicate that cytotoxicity of SWNT-COOH/CTAB is more related to the toxicity of the surfactant CTAB. The cytotoxicity effect of CTAB and SWNT-COOH/CTAB is acceptable at low concentrations （0.5-25μg/mL）. The cytotoxicity observation suggests that SWNT-COOH/CTAB can safely applied to biomedical field at low concentrations （0.5-25μg/mL）.
