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DALTON TRANSACTIONS · 2024 · IF 3.5

Peroxynitrite scavenger FeTPPS binds with hCT to effectively inhibit its amyloid aggregation

Bin Xiao,Junhao Xiao,Sisi Liu,Xiaoying Xiao,Shengping Dai,Yan Sui,Jinming Wu,Huixian Ye

Human calcitonin (hCT) is an endogenous polypeptide commonly employed in treating bone resorption-related illnesses, but its clinical application is limited due to its high aggregation tendency. Metalloporphyrins are effective in suppressing amyloid fibrillation, positioning them as potential drug candidates for amyloidogenic disorders like Alzheimer's and type 2 diabetes. In this work, we investigated the effects of Fe(III) meso-tetra(4-sulfonatophenyl)porphine chloride (FeTPPS), a highly efficient ONOO− decomposition catalyst, on hCT aggregation. Our findings reveal that FeTPPS effectively precludes hCT fibrillation by stabilizing the monomers and delaying the structural transition from α-helix bundles to β-sheet-rich aggregates. The macrocyclic ring of FeTPPS plays a significant role in disrupting hCT self-associations. Among various porphyrin analogs, those with an iron center and negatively charged peripheral substituents exhibit a stronger inhibitory effect on hCT aggregation. Spectroscopic analyses and computational simulations indicate that FeTPPS binds to hCT's core aggregation region via complexation with His20 in a 1 : 1 molar ratio. Hydrophobic interaction, hydrogen bonding, and π–π stacking with the residues involving Tyr12, Phe19, and Ala26 also contribute to the interactions. Collectively, our study provides a promising approach for developing novel hCT drug formulations and offers theoretical guidance for designing metalloporphyrin-based inhibitors for various amyloidosis conditions.

CAS / MDL: 35218-75-8
研究领域: 药物化学 · 蛋白质聚集 · 药物开发 · 淀粉样变性
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SENSORS AND ACTUATORS B-CHEMICAL · 2019 · IF 6.393

An anti-HCT-interference glucose sensor based on a fiber paper-based screen-printed carbon electrode

XinXin He,Shwu Jen Chang,Kalpana Settu,Ching-Jung Chen,Jen-Tsai Liu

As the number of diabetic patients increases year by year, the demand for a self-monitoring blood glucose test also increases. Additionally, more in-depth studies of blood glucose biosensors have led to increasing accuracy requirements. However, at present, most enzyme glucose sensors have difficulty solving issues related to hematocrit (HCT) interference. Most studies on anti-HCT interference in blood glucose sensing have mainly focused on correction factors, such as glucose correction, and electrical impedance or resistivity characteristics to correct the impact of HCT. In this work, we developed an anti-HCT-interference blood glucose sensor based on a fiber paper-based screen-printed carbon electrode with a mediator (potassium ferricyanide) and glucose oxidase (GOD), which were fixed through inkjet printing. When testing whole blood samples with HCT levels of 20%–70% and a fluid dropping method, the results of a consensus error grid analysis showed that 91% of the data points lied within zones A and B. The glucose sensor was exclusively designed with a 16 μL chamber in the working area of the sensor. When the testing fluid was taken in by capillary sucking, the effect of HCT was further reduced, and 95% of the data points lied within zones A and B in the consensus error grid.

研究领域: 生物传感器 · 糖尿病监测 · 电化学
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INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION · 2018 · IF 2.317

In vitro activities of inulin fermentation products to HCT-116 cells enhanced by the cooperation between exogenous strains and adult faecal microbiota

Dan-Ting Yin,Yu Fu,Xin-Huai Zhao

Inulin was fermented by adult faecal microbiota and 10 exogenous strains for 24 or 48 h. The contents of acetate, propionate, butyrate and lactate were quantified in the fermented products, and the growth-inhibitory and apoptosis-inducing effects on a human colon cell line (HCT-116 cells) were assessed. Most of these strains increased contents of acetate, propionate and butyrate, and promoted lactate conversion. Correlation analysis suggested that butyrate and lactate in the fermentation products were positively and negatively correlated with the measured inhibition ratios (p < .05). The results were mostly consistent with the verification trial results using standard acid solutions. The fermentation products could cause apoptosis via inducing DNA fragmentation and increasing total apoptotic populations in the treated cells. Moreover, the fermentation products with higher growth-inhibitory activities demonstrated the increased apoptosis-inducing properties. In conclusion, these strains could cooperate with adult faecal microbiota to confer inulin fermentation products with higher anti-colon cancer activity.

研究领域: 微生物学 · 癌症研究 · 胃肠病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Current Research in Food Science · 2022 · IF 6.269

Activities of the soluble and non-digestible longan (Dimocarpus longan Lour.) polysaccharides against HCT-116 cells as affected by a chemical selenylation

Ya-Hui Yu,Li Wang,Qiang Zhang,Xiao-Nan Zhang,Xin-Huai Zhao

The soluble and non-digestible longan ( Dimocarpus longan Lour . ) polysaccharides (LP) with Se content less than 0.01 g/kg were extracted and selenylated chemically with the HNO 3 –Na 2 SeO 3 system, to prepare two selenylated products namely SeLP1 and SeLP2 with enhanced Se contents of 1.46 and 4.79 g/kg, respectively. LP, SeLP1, and SeLP2 were then measured and compared for their saccharide features and bioactivity in human colon carcinoma HCT-116 cells. Compared with LP, both SeLP1 and SeLP2 contained more neutral saccharides, but showed reduced uronic acid content and undetectable sulfate. Moreover, SeLP1 and especially SeLP2 in the cells showed higher activities than LP, reflected by their enhanced capacity to inhibit cell growth, alter cell morphology, and suppress cell colony formation. Compared with LP, SeLP1 and especially SeLP2 were also more capable of promoting intracellular reactive oxygen species and Ca 2+ levels, causing mitochondrial membrane potential loss, or inducing cell apoptosis via up- and down-regulating the eight apoptosis-related genes and proteins. Overall, the performed chemical selenylation of LP resulted in obvious changes in these saccharide features and simultaneously enhanced the anti-cancer activity of the selenylated products against the cells clearly, while a higher selenylation extent of the selenylated products consistently caused higher activity towards the cells. The results of this study thus highlighted that this chemical selenylation is applicable when aiming to enhance the bioactivities of natural polysaccharides.

研究领域: 药理学 · 癌症研究 · 生物化学 · 细胞生物学
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MOLECULAR AND CELLULAR BIOCHEMISTRY · 2020 ·Vol. 476 ·期 2 ·513-523 · IF 2.795

Inhibitory effect of bound polyphenol from foxtail millet bran on miR-149 methylation increases the chemosensitivity of human colorectal cancer HCT-8/Fu cells

Shan Shuhua,Lu Yang,Zhang Xiaoli,Shi Jiangying,Li Hanqing,Li Zhuoyu

Nature polyphenols widely present in plants and foods are promising candidates in cancer chemotherapy. Emerging evidence has shown that plant polyphenols regulate the expression of miRNAs to exert the anti-Multidrug resistance (MDR) activity, which partly attributes to their regulation on miRNAs methylation. Our previous study found that bound polyphenol from foxtail millet bran (BPIS) had potential as an anti-MDR agent for colorectal cancer (CRC), but its mechanism remains unclear. The present findings demonstrated that BPIS upregulated the expression of miR-149 by reducing the methylation of its CpG islands, which subsequently induced the cell cycle arrest in G2/M phase, resulting in enhancing the chemo-sensitivity of HCT-8/Fu cells. Mechanically, BPIS and its active components (FA and p-CA) reduced miR-149 methylation by inhibiting the expression levels of DNA methyltransferases, promoting a remarkable increase of miR-149 expression. Further, the increased miR-149 induced cell cycle arrest in G 2 /M phase by inhibiting the expression of Akt, Cyclin B1 and CDK1, thus increasing the chemosensitivity of HCT-8/Fu cells. Additionally, a strong inducer of DNA de-methylation (5-aza-dc) treatment markedly increased the chemosensitivity of CRC through elevating miR-149 expression, which indicates the hypermethylation of miR-149 may be the key cause of drug resistance in CRC. The study indicates that the enhanced chemosensitivity of BPIS on CRC is mainly attributed to the increase of miR-149 expression induced by methylation inhibition.

研究领域: 肿瘤学 · 药理学 · 分子生物学 · 表观遗传学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2018 · IF 3.412

Reversal Effects of Bound Polyphenol from Foxtail Millet Bran on Multidrug Resistance in Human HCT-8/Fu Colorectal Cancer Cell

Yang Lu,Shuhua Shan,Hanqing Li,Jiangying Shi,Xiaoli Zhang,Zhuoyu Li

Foxtail millet is the second-most widely planted species of millet and the most important cereal food in China. Our previous study showed that bound polyphenol of inner shell (BPIS) from foxtail millet bran displayed effective antitumor activities in vitro and in vivo. The present research further implied that BPIS has the ability to reverse the multidrug resistance of colorectal cancer in human HCT-8/Fu cells, the IC50 values of 5-fluorouracil (5-Fu), oxaliplatin (L–OHP), and vincristine (VCR) were decreased form 6593 ± 53.8, 799 ± 48.9, and 247 ± 10.3 μM to 5350 ± 22.3 (3261 ± 56.9), 416 ± 16.6 (252 ± 15.6), and 144 ± 8.30 (83.8 ± 5.60) μM when HCT-8/Fu cells were pretreated with 0.5 (1.0) mg/mL BPIS for 12 h. The 12 phenolic acid compounds of BPIS were identified by ultraperformance liquid chromatography-triple-time of flight/mass spectrometry (UPLC-Triple-TOF/MS) method. Especially, the fraction of molecular weight (MW) < 200 of BPIS reversed the multidrug resistance in HCT-8/Fu cells, and ferulic acid and p-coumaric acid were the main active components, the IC50 values were 1.23 ± 0.195 and 2.68 ± 0.163 mg/mL, respectively. The present data implied that BPIS significantly enhanced the sensitivity of chemotherapeutic drugs through inhibiting cell proliferation, promoting cell apoptosis, and increasing the accumulation of rhodamine-123 (Rh-123) in HCT-8/Fu cells. Real-time polymerase chain reaction (RT-PCR) and Western blot data indicated that BPIS also decreased the expression levels of multidrug resistance protein 1 (MRP1), P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP). Collectively, these results show that BPIS has potential ability to be used as a new drug-resistance reversal agent in colorectal cancer.

研究领域: 药理学 · 肿瘤学 · 生物化学 · 癌症研究 · 植物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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STAR Protocols · 2024 · IF 1.3

Protocol for the cryopreservation of Cryptosporidium isolates using enteroids

Miner Deng,Yanting Wei,Na Li,Lihua Xiao,Yaoyu Feng,Yaqiong Guo

Summary A major bottleneck in the progress of Cryptosporidium research is the lack of accessible cryopreservation of Cryptosporidium oocysts. Here, we present a protocol for the cryopreservation of Cryptosporidium isolates using enteroids. We describe the steps for the establishment of enteroid cultures and cryopreservation of C. parvum -infected HCT-8 cultures. We then detail procedures for the recovery and propagation of frozen parasites using enteroids. For complete details on the use and execution of this protocol, please refer to Deng et al. 1

CAS / MDL: 145-42-6
研究领域: 微生物学 · 寄生虫学 · 细胞生物学
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Foods · 2022 ·Vol. 11 ·期 23 ·3748 · IF 5.561

Monosaccharide Composition and In Vitro Activity to HCT-116 Cells of Purslane Polysaccharides after a Covalent Chemical Selenylation

Ling-Yu Li,Qing-Yun Guan,Ya-Ru Lin,Jun-Ren Zhao,Li Wang,Qiang Zhang,Hong-Fang Liu,Xin-Huai Zhao

The anti-cancer effects of selenylated plant polysaccharides are a focus of research. As a natural plant with extensive biological effects, there have been few studies related to edible purslane (Portulaca oleraceaL.). Thus, in this study, solubleP. oleraceapolysaccharides (PPS) were extracted from the driedP. oleraceaand then selenylated chemically using the HNO3-Na2SeO3method to obtain two selenylated products, namely, SePPS1 and SePPS2. Compared with the extracted PPS, SePPS1 and SePPS2 had much higher Se contents (840.3 and 1770.5 versus 66.0 mg/kg) while also showing lower contents in three saccharides—arabinose, fucose, and ribose—and higher contents in seven saccharides including galactose, glucose, fructose, mannose, rhamnose, galacturonic acid, and glucuronic acid, but a stable xylose content demonstrated that the performed chemical selenylation of PPS led to changes in monosaccharide composition. Moreover, SePPS1 and SePPS2 shared similar features with respect to monosaccharide composition and possessed higher bioactivity than PPS in human colon cancer HCT-116 cells. Generally, SePPS1 and SePPS2 were more active than PPS with respect to cell growth inhibition, the alteration of cell morphology, disruption of mitochondrial membrane potential, intracellular reactive oxygen species (ROS) generation, the induction of cell apoptosis, and upregulation or downregulation of five apoptosis-related genes and proteins such as Bax, Bcl-2, caspases-3/-9, and cytochrome C, that cause cell apoptosis and growth suppression via the ROS-mediated mitochondrial pathway. SePPS2 consistently showed the highest capacity to exert these observed effects on the targeted cells, suggesting that the performed chemical selenylation of PPS (in particular when higher degrees of selenylation are reached) resulted in an increase in activity in the cells. It can thus be concluded that the performed selenylation of PPS was able to incorporate inorganic Se into the final PPS products, changing their monosaccharide composition and endowing them with enhanced nutraceutical and anti-cancer effects in the colon.Keywords:purslane;polysaccharide;selenylation;monosaccharide composition;HCT-116 cells;nutraceutical effect

研究领域: 药理学 · 癌症研究 · 生物化学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF NANOBIOTECHNOLOGY · 2023 ·Vol. 21 ·期 1 ·1-14 · IF 10.2

Carbon dots-mediated synthesis of gold nanodendrites with extended absorption into NIR-II window for in vivo photothermal therapy

Liu Guoyong,Wang Shuxian,Wang Shumin,Wu Rongrong,Li Hui,Zha Menglei,Song Jibin,Yin Yuxin,Li Kai,Mu Jing,Shi Yu

Background Photothermal therapy (PTT) in the second near-infrared (NIR-II) window has attracted extensive attention due to the benefits in high maximum permissible exposure and penetration depth. Current photothermal agents generally show a broadband absorption accompanied by a gradual attenuation of absorption in the NIR-II window, leading to poor effect of PTT. It remains a great challenge to gain photothermal agents with strong and characteristic absorption in NIR-II regions. To overcome this problem, based on carbon dots (CDs)-mediated growth strategy, we proposed a simple and feasible approach to prepare plasmonic gold nanodendrites (AuNDs) with NIR-II absorption to enhance the therapeutic effect of PTT. Results By rationally regulating the size and branch length of AuNDs, the AuNDs exhibited a broadband absorption from 300 to 1350 nm, with two characteristic absorption peaks located at 1077 and 1265 nm. The AuNDs demonstrated desired optical photothermal conversion efficiency (38.0%), which was further applied in NIR-II photoacoustic imaging (PAI) and PTT in human colon cancer cells (HCT 116)-tumor-bearing mice model. The tumor cells could be effectively eliminated in vivo under 1064 nm laser irradiation by the guidance of PAI. Conclusions We reported a simple but powerful synthetic method to obtain the unique AuNDs with strong and characteristic absorption peaks in the NIR-II window. This study provides a promising solution to tuning the growth of nanoparticles for bioimaging and phototherapy in the NIR-II window. Graphical Abstract

研究领域: 纳米技术 · 生物医学工程 · 材料科学 · 癌症治疗
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2023 ·Vol. 24 ·期 7 ·6854 · IF 5.6

Delivery of Doxorubicin by Ferric Ion-Modified Mesoporous Polydopamine Nanoparticles and Anticancer Activity against HCT-116 Cells In Vitro

Mengwen Guo,Junhong Ling,Xinyi Xu,Xiaokun Ouyang

In clinical cancer research, photothermal therapy is one of the most effective ways to increase sensitivity to chemotherapy. Here, we present a simple and effective method for developing a nanotherapeutic agent for chemotherapy combined with photothermal therapy. The nanotherapeutic agent mesoporous polydopamine-Fe(III)-doxorubicin-hyaluronic acid (MPDA-Fe(III)-DOX-HA) was composed of mesoporous polydopamine modified by ferric ions and loaded with the anticancer drug doxorubicin (DOX), as well as an outer layer coating of hyaluronic acid. The pore size of the mesoporous polydopamine was larger than that of the common polydopamine nanoparticles, and the particle size of MPDA-Fe(III)-DOX-HA nanoparticles was 179 ± 19 nm. With the presence of ferric ions, the heat generation effect of the MPDA-Fe(III)-DOX-HA nanoparticles in the near-infrared light at 808 nm was enhanced. In addition, the experimental findings revealed that the active targeting of hyaluronic acid to tumor cells mitigated the toxicity of DOX on normal cells. Furthermore, under 808 nm illumination, the MPDA-Fe(III)-DOX-HA nanoparticles demonstrated potent cytotoxicity to HCT-116 cells, indicating a good anti-tumor effect in vitro. Therefore, the system developed in this work merits further investigation as a potential nanotherapeutic platform for photothermal treatment of cancer.Keywords:mesoporous polydopamine;ferric ions;doxorubicin (DOX);hyaluronic acid target modification

研究领域: 生物医学工程 · 肿瘤学
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CHEMISTRY & BIODIVERSITY · 2025 · IF 2.5

Exploring the Anticancer Mechanisms of Dendrobium officinale Polysaccharides in Colorectal Cancer: Apoptosis and Autophagy Interactions

Shao-Jun Zheng,Xiao-Han Diao,Xiao-Yan Gao,Nai-Dong Chen

Dendrobium officinale polysaccharides (DOP) exhibit anticancer potential against colorectal cancer (CRC), yet their mechanisms remain unclear. This study investigated DOP's effects on HCT-116 cells. DOP dose- and time-dependently inhibited proliferation and induced apoptosis, evidenced by elevated cleaved caspase-3/-9, poly ADP-ribose polymerase (PARP), Bax, and reduced Bcl-2. Concurrently, DOP activated autophagy (increased LC3-II/I, Beclin-1; decreased p62) via phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) suppression. Combining DOP with the autophagy inhibitor chloroquine enhanced apoptosis (higher cleaved PARP, Bax; lower Bcl-2) and reactivated PI3K/Akt/mTOR signaling. These findings demonstrate DOP inhibits CRC by dual induction of apoptosis and autophagy blockade through PI3K/Akt/mTOR inhibition, with autophagy suppression synergistically augmenting apoptosis. The study highlights DOP's translational potential as a functional food or adjuvant therapy, proposing a novel combinatorial strategy for CRC treatment. Graphical Dendrobium officinale polysaccharides (DOP) inhibit HCT-116 colorectal cancer cell proliferation and induce apoptosis by upregulating cleaved caspase-3/-9, PARP, and Bax while downregulating Bcl-2. DOP activates autophagy via PI3K/Akt/mTOR inhibition. Combining DOP with chloroquine enhances apoptosis, revealing autophagy blockade as a synergistic anticancer mechanism.

CAS / MDL: 67-68-5
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Heliyon · 2022 · IF 3.776

The effect of noisome preparation methods in encapsulating 5-fluorouracil and real time cell assay against HCT-116 colon cancer cell line

Onyinyechi Lydia Ugorji,Ogochukwu Ngozi Chidimma Umeh,Chukwuma Obumneme Agubata,Dickson Adah,Nicholas Chinedu Obitte,Amarauche Chukwu

The formulation of niosomes is influenced by a number of variables, and these variables may eventually affect the formulation’s outcome. One of the elements that can influence the physico-chemical properties of niosomes is the method used in preparation of the formulation. In this study, we established if various methods of preparation have any impact on the prepared vesicles when loaded with 5-fluorouracil. Thereafter, a real-time cell assay (an in vitro cytotoxicity test) against HCT-116 colon cancer cell lines was done on an optimised batch. 5-fluorouracil loaded niosomes were prepared with either Tween 60 or Span 60 by four different methods - namely thin film hydration (TFH), reverse phase evaporation (RPE), evaporation/sonication (EVP/SON), and the ethanol injection method (EIM). In vitro evaluations were done on the formulations, and these included particle size analysis, entrapment efficiency, scanning electron microscopy (SEM), photomicrography, drug release, polydispersity index, and Fourier transform infrared spectroscopy (FTIR). The effects of the preparation method and type of non-ionic surfactants on encapsulation efficiency, particle size, and in vitro drug release of the niosomes at pH 7.4 were evaluated. An in vitro cytotoxicity test (real time cell assay (RTCA)) against HCT-116 cells was carried out using the optimised formulation. Results showed physically stable formulations. The TFH method produced the smallest particle sizes (187 nm and 482 nm), while the EVP/SON method produced the largest particle sizes (4476 nm and 9111 nm). The Tween-based niosomes prepared by TFH or RPE had higher drug entrapment. The FTIR studies of niosomal formulations showed broad peaks at wavenumbers above 3000 cm −1 , indicating strong hydrogen bonds. The RTCA showed 5-fluorouracil-loaded niosomes caused more sustained cell death compared to the pure drug and blank niosomes. The methods of preparation affected the particle size, polydispersity index, entrapment efficiency, and the physical stability of the vesicles. The thin film hydration method was more robust in the entrapped 5-fluorouracil and showed lower particle sizes when compared to all the other methods. RTCA showed sustained cell death in real time.

研究领域: 药剂学 · 肿瘤学 · 药物递送系统 · 细胞生物学 · 药物化学
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