Recent Patents on Anti-Cancer Drug Discovery
·
2021
·Vol. 16
·期 2
·258-272
·
IF 4.169
Zhang Xiangli,Shen Qin,Wang Yi,Zhou Leilei,Weng Qi,Li Qingyong
Background: E2 (Camptothecin - 20 (S) - O- glycine - deoxycholic acid), and G2 (Camptothecin - 20 (S) - O - acetate - deoxycholic acid) are two novel bile acid-derived camptothecin analogues, modified deoxycholic acid at 20-position of CPT(camptothecin) with greater anticancer activity
and lower systematic toxicity in vivo. Objective: We aimed to investigate the metabolism of E2 and G2 by Rat Liver Microsomes (RLM). Methods: Phase I and Phase II metabolism of E2 and G2 in rat liver microsomes were performed, respectively, and the mixed incubation of phase I and
phase II metabolism of E2 and G2 was also processed. Metabolites were identified by liquid chromatographic/mass spectrometry. Results: The results showed that phase I metabolism was the major biotransformation route for both E2 and G2. The isoenzyme involved in their metabolism had some
difference. The intrinsic clearance of G2 was 174.7 mL/min. mg protein, more than three times that of E2 (51.3 mL/min . mg protein), indicating a greater metabolism stability of E2. 10 metabolites of E2 and 14 metabolites of G2 were detected, including phase I metabolites (mainly via hydroxylations
and hydrolysis) and their further glucuronidation products. Conclusion: These findings suggested that E2 and G2 have similar biotransformation pathways except for some differences in the hydrolysis ability of the ester bond and amino bond from the parent compounds, which may result in
the diversity of their metabolism stability and responsible CYPs(Cytochrome P450 proteins).
研究领域:
药理学
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生物化学
·
肿瘤学
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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Hanbing Jiang,Yijie Liu,Chunhua Tang,Zheng Wei,Meilun Chen,Xiaoling Lu,Jie Yang,Peng Yu
This study introduces a novel E2 (17β-estradiol) colorimetric sensor constructed using a truncation optimization strategy of the nucleic acid aptamer. Systematic truncation of the 17β-estradiol nucleic acid aptamer was performed, leading to the design and evaluation of a series of aptamer variants with different lengths to enhance their structural stability and synthesis efficiency. Through a series of experiments, the binding affinities of these truncated aptamer variants with E2 were compared, resulting in the selection of an optimal aptamer, E12. Aptamer E12, chosen through this process, was successfully applied in a gold nanoparticle-based colorimetric assay, enabling susceptible and specific detection of E2. Our research not only presents a simple and cost-effective method for E2 detection but also provides new insights into the truncation optimization strategy of nucleic acid aptamers. The developed E2 colorimetric sensor exhibits outstanding specificity and sensitivity and holds great promise for applications in environmental pollution detection.
研究领域:
生物化学
·
环境科学
·
分析化学
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产品关联
DOI
高影响因子
Journal of Environmental Chemical Engineering
·
2024
·
IF 7.4
Yue Tang,Xiaolin Pi,Huiying Li,Xueni Zhang,Lijun Luo,Fengzhi Jiang
This study presents the synthesis of highly active BiPO 4 /AgI/BC composite photocatalysts via a green, simple, and low-cost ambient temperature precipitation method. The electron transfer rate and visible-light responsiveness can be effectively enhanced by utilizing BiPO 4 compounded with the semiconductor AgI, which has a narrow bandgap and good visible-light responsiveness. Additionally, the introduction of biocarbon (BC) enhances the absorption and separation of photogenerated electrons and holes under visible light. Notably, the synthesized BP-AgI 0.6 -BC 5 % could remove 99.16 % and 99.7 % of EE2 and E2, respectively, at a concentration of 3 mg/L after 40 min of light exposure. The capture experiments and electron paramagnetic resonance spectroscopy reveal that the main active substance in the system is ·O 2 - , with BC playing a crucial role in enhancing the ·O 2 - concentration in the system. The findings from phytotoxicity and antimicrobial tests reveal that BP-AgI 0.6 -BC 5 % can efficiently degrade pollutants, producing degradation products that are substantially less toxic than the original pollutants. Moreover, it can remove more than 99.99 % of E. coli under both dark and light conditions, demonstrating excellent antimicrobial performance. Additionally, the photocatalytic mechanism and degradation pathway were examined in this study. Notably, the composite photocatalysts synthesized in this study achieved efficient degradation of EE2 and E2 under visible light conditions while exhibiting efficient bactericidal function. Furthermore, the room-temperature preparation method is conducive to industrial-scale production, highlighting a better prospect for practical applications.
研究领域:
环境科学
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材料科学
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生物学
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DOI
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Yu Zhang,Zhiqing Lin,Qi Yao,Jian He,Haotian Feng,Wenyi Zhang,Zhigang Liu,Tian Yuan,Xuebo Liu,Long Ding
This study aimed to investigate the effect of milk peptides on irritable bowel syndrome (IBS). The mice were intragastrally administered with casein or whey protein hydrolysates at a dose of 1 g/kg body weight/day for 24 days and were subjected to Citrobacter rodentium infection and water avoidance stress from day 7 to 24. Results indicated that casein and whey protein hydrolysates effectively reduced diarrhea, anxiety, and visceral hypersensitivity in IBS mice.. Casein and whey protein hydrolysates regulated gut microbiota composition and increased the abundance of short-chain fatty acid-producing bacteria, such as Alloprevotella and Alistipes . Whey protein hydrolysate significantly increased the mRNA levels of zonula occludens-1 (ZO-1) and claudin-1 in the colon, while casein hydrolysate significantly improved the mRNA levels of occludin. Casein and whey protein hydrolysates both decreased the levels of pro-inflammatory cytokines including interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), while increased the level of anti-inflammatory cytokine interleukin-10 (IL-10). Importantly, casein and whey protein hydrolysates significantly reduced colonic mast cell activation and decreased prostaglandin E2 (PGE2) production. Moreover, three novel casein-derived cyclooxygenase-2 (COX2)-inhibitory peptides RGPF, FPK, and NPW were identified with IC 50 values of 0.36 ± 0.03, 0.64 ± 0.01, and 1.10 ± 0.09 mM, respectively and predicted to form hydrogen bonds and hydrophobic interactions with the residues of the active site of COX2. This study highlighted the potential of milk peptides as bioactive ingredients in functional foods for managing IBS.
研究领域:
营养学
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免疫学
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微生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CLINICAL LABORATORY ANALYSIS
·
2024
·Vol. 38
·期 4
·e25011
·
IF 2.6
Ningning Wang,Qingqing Liu,Feihu Che,Qingyang Sun,Yue Wang,Chunli Yang,Yuzhu Dai,Jun Cheng
Background To establish a chemiluminescence method for detecting anti-E1 and anti-E2 antibodies in the serum of patients with hepatitis C virus (HCV) infection. Methods The microplate was coated with recombinant envelope proteins E1 and E2 by indirect method, respectively, and the kits for detecting anti-E1 and anti-E2 antibodies were prepared. The methodological indexes were evaluated. Results The methodological indexes of the kits were as follows: precision test (the variation coefficient of anti-E1 antibody 6.71%–8.95% for within run and 9.91%–12.16% for between run, the variation coefficient of anti-E2 antibody 6.06%–8.44% for within run and 10.77%–13.98% for between run, respectively). The blank limit and detection limit were 1.18 RLIR and 3.16 RLIR for the anti-E1 antibody, and 1.26 RLIR and 3.32 RLIR for the anti-E2 antibody, respectively. The correlation coefficients ( r ) of anti-E1 and anti-E2 were 0.9963 and 0.9828, the analysis and measurement ranges (AMR) were 1.66–41.28 RLIR and 1.55–19.46 RLIR, and the average recovery was 96.4% and 93.7%, respectively. The rheumatoid factor and other positive serum samples had no interference or cross-reaction to the test, and the kits were stable within 15 months. The positive rates of anti-E1 and anti-E2 antibodies in 45 patients with HCV infection were 35.6% (16/45) and 44.4% (20/45), respectively. Conclusions The kits for detecting anti-E1 and anti-E2 meet the requirements of methodology, and can be used in screening diagnosis, disease monitoring, prognosis evaluation, disease mechanism, and epidemiological studies of HCV infection. The HCV envelope proteins E1 and E2 have an immune response in HCV-infected patients.
CAS / MDL:
研究领域:
医学检验
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病毒学
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产品关联
DOI
PubMed
高影响因子
Journal of Water Process Engineering
·
2024
·
IF 6.3
Xiaolin Pi,Xueni Zhang,Yue Tang,Changjiang He,Lijun Luo,Siping Ji,Fengzhi Jiang
Biochar (BC) composite photocatalysts have attracted much attention by virtue of their high efficiency in removing endocrine disruptors (EDCs). However, there has been a lack of systematic research on the mechanism and constitutive relationship of BC on photocatalysts, which has seriously impeded the development process in this field. In this study, Bi 2 WO 6 –BC 2% composite photocatalysts were prepared by microwave-assisted hydrothermal method and used for degradation of 17α-ethinylestradiol (EE2) and 17β-estradiol (E2) in conjunction with persulfate synergy (PS). The removal rate of EE2 and E2 by Bi 2 WO 6 –BC 2% was as high as 99.41 % (12 min) and 97.84 % (15 min), respectively. Systematic studies have shown that BC enhances the catalytic activity mainly through the following ways, increasing the specific surface area of the photocatalytic system, enriching the types of functional groups, enhancing the separation ability of photogenerated electron–hole pairs, and promoting the concentration of active free radicals. The results of the phytotoxicity experiments showed that compared to the EE2 or E2 pollutant solutions, the stem and root lengths of V. radiata increased by 93.63 % and 389.58 % in EE2 metabolites, and by 117.35 % and 160.38 % in E2 metabolites. Similarly, the stem and root lengths of P. vulgaris increased by 80.08 % and 174.91 % in EE2 metabolites, and by 188.92 % and 345.75 % in E2 metabolites. This work not only fills the gap in the study of the mechanism of action of BC, but also provides a green catalyst with very excellent photocatalytic efficiency and detoxification properties.
研究领域:
环境科学
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光催化技术
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毒理学
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产品关联
DOI
高影响因子
Biomaterials Research
·
2025
·
IF 9.6
Min Zhou,Ruyue Han,Wenjie Xu,Xinyan Hao,Yanjin Peng,Yucheng Tang,Pengcheng Sun,Tiantian Tang,Junyong Wu,Daxiong Xiang
Cancer continues to pose remarkable medical challenges worldwide. While current cancer therapies can lead to initial clinical improvement, they are often followed by recurrence, metastasis, and drug resistance, underscoring the urgent need for innovative treatment strategies. Atorvastatin calcium (AC), a widely used lipid-lowering and anti-inflammation drug in the clinic, has shown antitumor potential. To further improve the antitumor efficacy, we developed self-assembled AC and polydopamine (PDA) nanoparticles whose surface was coated with macrophage membranes (CM) as a biomimetic drug delivery system [AC@PDA@CM (APM)]. APM showed high drug-loading capacity, excellent stability, excellent bioavailability, and tumor-targeting ability, ultimately achieving photothermal synergistic cancer immunotherapy. Our findings indicate that APM efficiently delivers AC to tumor sites while leveraging photothermal therapy (PTT) to enhance local tumor ablation and antitumor immune effect. Notably, APM mitigates tumor immunosuppression triggered by PTT through AC, suppressing the COX-2/PGE2 pathway and immune evasion signal CD47. Furthermore, APM notably reduced nonspecific distribution and side effects, which is conducive to ensuring the safety level of medication. This integrated approach boosts therapeutic efficacy and highlights the potential of APM as a multifunctional agent for cancer therapy, paving the way for future clinical applications.
研究领域:
癌症研究
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药学
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纳米医学
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免疫治疗
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产品关联
DOI
PubMed
高影响因子
Frontiers in Aging Neuroscience
·
2020
·
IF 4.364
Feng Chenxi,Bao Xiaoming,Shan Ling,Ling Yunxiang,Ding Yanfei,Wang Jia,Cao Yanzi,Wang Qinwen,Cui Wei,Xu Shujun
Calcium-sensing receptor (CaSR) is a G protein-coupled receptor (GPCRs). Soluble β-amyloid peptide (Aβ) is one of the orthosteric modulators of CaSR, while, the role and underlying mechanism of CaSR in cognitive decline in Alzheimer’s disease (AD) is unclear. In this study, molecular technology such as live-cell imaging combined with behavioral tests were used to explore the role and the underlying mechanism of CaSR in the cognitive deficits in AD mice. The expression levels of CaSR were increased both in AD mice and Aβ1–42 (β-amyloid protein)-treated primary cultured neurons. Pharmacological inhibition of CaSR ameliorated recognitive and spatial memory deficits of Aβ1–42-oligomer-treated mice in a dose-dependent manner. Pharmacological inhibition of CaSR or down-regulation of the expression of CaSR by CaSR-shRNA-lentivirus prevented the impairment of filopodia, and the synapse induced by oligomeric Aβ1–42. The contents of cytosolic phospholipase A2 (cPLA2) and prostaglandin E2 (PGE2) in hippocampal neurons and tissue were increased after treatment with Aβ1–42 oligomers. Inhibition or down-regulation of CaSR mediates Aβ-induced synapse formation and cognitive deficits partially, through the activation of the cPLA2/PGE2 pathway. This study provides novel insights on CaSR, which is a promising therapeutic target for AD.
研究领域:
神经科学
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药理学
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分子生物学
·
神经退行性疾病
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DOI
PubMed
高影响因子
npj Clean Water
·
2025
·
IF 11.4
Lv Shiyu,Yuan Tian,Zhang Xueyan,Yang Pu,Fu Kerong,Yao Xia,Fu Weilin,Zhang Qiuxian,Luo Yanli,Wang Feng
Herein, LaFeO 3 photocatalysts (HX-LFO and SX-LFO) were synthesized using hydrothermal and sol–gel methods, respectively, for removing β-E2 from dairy cattle breeding wastewater. A combination of flocculation pretreatment and photocatalytic Fenton oxidation was used to achieve efficient β-E2 degradation. Results revealed that HX-LFO had high defect concentrations and achieved better photocatalytic Fenton oxidation efficiency for β-E2 than SX-LFO. The H0.7-LFO/H 2 O 2 /visible (Vis) system completely degraded 2 mg/L of β-E2 within 2 h and achieved a total organic carbon (TOC) mineralization rate of 99.7%. The intermediate products, degradation pathways, and ecological toxicity of β-E2 degradation were analyzed. The H0.7-LFO/H 2 O 2 /Vis system exhibited stable degradation performance when humic acid and multiple anions coexisted in the reaction solution. The developed system increased the β-E2 degradation rate to 83.38%–100%. Characterizations and density functional theory calculations revealed that the La-defect formation energy in La/O dual-defect LaFeO 3 was lower than that in LaFeO 3 containing only La defects. Moreover, O defects facilitated the formation of La defects that lowered the energy barrier for free-radical desorption, making it easier for free radicals to form and diffuse into the reaction solution. La/O dual-defect LaFeO 3 exhibited lower binding energy for β-E2, accelerating charge transfer within itself and from itself to β-E2.
研究领域:
环境催化
·
水污染控制
·
材料化学
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环境功能材料
·
污染物降解机制
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DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2021
·
IF 6.986
Weiya Wang,Yuan Peng,Jin Wu,Man Zhang,Qiaofeng Li,Zunquan Zhao,Mingzhu Liu,Jiu Wang,Gaofang Cao,Jialei Bai,Zhixian Gao
17β-Estradiol (E2) can cause an adverse effect on the human endocrine system even at the nanomolar level. Measurements of very low levels of E2 remain a critical challenge due to insufficient sensitivity. In this study, a multistep isothermal amplification fluorescence strategy was constructed, which could realize the exponential amplification of target E2. Specifically, strand displacement reaction (SDA), rolling circle amplification (RCA), and multiprimed rolling circle amplification (MRCA) were combined in a series to quantify trace complementary strand of E2 (cDNA). The E2 aptamer and cDNA were hybridized and modified on the magnetic beads. E2 could bind to its aptamer and cause the release of the cDNA. Then, cDNA would combine with the template DNA, initiating the SDA–RCA–MRCA. The molecular beacons, possessing low background signal, whose fluorescence was quenched in the state of chain folding, could be specifically recognized by the long single-stranded DNA (L-ssDNA) generated by the multistep isothermal amplification triggered by cDNA, and then the fluorescence of the molecular beacons could be restored. Therefore, the E2 could be quantitatively detected by the recovery fluorescence intensity. The fluorescence value showed a good linear relationship with the concentration of E2 in the range of 0.001836–183.6 nM, and the limit of detection (LOD) was as low as 63.09 fM. In addition, the recovery rates of this method spiked in milk and water were 80.8–107.0%, respectively. This method has the advantage of multistep isothermal amplification to obtain abundant fluorescence signals, which may provide a new possibility for highly sensitive detection of other small-molecule targets.
研究领域:
生物化学
·
分子生物学
·
分析化学
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产品关联
DOI
PubMed
高影响因子
NEURON
·
2026
·
IF 16.9
Lei Wang,Yini Yang,Fei Deng,Yuqi Yan,Huan Wang,Bohan Li,Jinxia Wan,Yulong Li
Prostaglandin E2 (PGE2) is an important lipid signaling molecule that regulates a wide range of physiological and pathological processes. However, its dynamics during these processes are largely unknown due to the lack of tools to directly visualize PGE2 with high spatiotemporal resolution. Here, we developed and characterized a genetically encoded G-protein-coupled receptor (GPCR) activation-based (GRAB) PGE2 sensor, which we call GRAB PGE2-1.0 (PGE2-1.0), that has high specificity for PGE2, nanomolar affinity, rapid kinetics, and high spatial resolution when expressed both in vitro and in vivo . Using fiber-photometry recordings, we found that PGE2-1.0 can reliably monitor endogenous PGE2 dynamics in the preoptic area in the brain during acute inflammation. Wide-field in vivo imaging with PGE2-1.0 reveals spatial heterogeneity in cortex-wide PGE2 dynamics during acute inflammation and seizure. Thus, our PGE2-1.0 sensor can be used to detect endogenous PGE2 dynamics with high spatiotemporal resolution, providing a robust tool for studying PGE2 under specific physiological and pathological conditions.
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DOI
PubMed
高影响因子
PLoS Pathogens
·
2026
·Vol. 22
·期 7
·e1014453
·
IF 4.9
Xiangshu Qiu,Rongguang Lu,Jiaxin Tian,He Zhang,Jiyong Zhou,Mengsi Sun,Xinyu Cao,Xiangyu Zhu,Bocheng Liu,Qihui Yu,Yuanyuan Li,Hualei Wang,Ningyi Jin,Huijun Lu,Ning Shi
Getah virus (GETV), a mosquito-borne alphavirus, poses an emerging threat to public health with its increasingly broad host spectrum. While glycosaminoglycans (GAGs) serve as critical attachment factors for many alphaviruses and the low-density lipoprotein receptor (LDLR) facilitates the cellular entry of several members, the precise viral determinants governing these interactions and their implications for viral virulence remain poorly defined. Here, we introduced an H86Y substitution, a potential adaptive mutation site, within the E2 glycoprotein of GETV using reverse genetics. The H86Y mutant replicated more efficiently in mosquito C6/36 cells but was consistently attenuated across several mammalian cell lines. In susceptible mouse models, H86Y infection led to reduced viral loads, milder histopathology, and lower inflammatory responses compared with the parental virus, yet still elicited robust protective immunity in adult mice. Mechanistically, a series of functional assays, including infection in GAG-deficient cells, decoy inhibition, co-immunoprecipitation, receptor overexpression and knockdown, and biolayer interferometry, demonstrated that the residue 86 in E2 glycoprotein is a critical determinant for GETV binding to both GAGs and LDLR. The H86Y mutation concurrently reduces these interactions, contributing the impairment of virus attachment and entry into mammalian cells. Furthermore, the GAG-binding site functionally overlaps with the LDLR interaction interface. In LDLR-deficient suckling mice, the impaired replication of H86Y persisted in examined tissues. However, pre-treatment with heparinase nearly completely eliminated this attenuation phenotype, further confirming that LDLR and GAG are the key host factors mediating attenuation phenotype for H86Y. In summary, the residue 86 of the GETV E2 glycoprotein represents a determinant of viral virulence, and an H86Y mutation attenuates GAGs and LDLR-dependent infection, providing mechanistic insights into alphavirus-host interactions and a potential target for antiviral and vaccine development.
Getah virus is an emerging mosquito-borne alphavirus. We investigated a naturally occurring substitution in the viral E2 glycoprotein, where histidine at position 86 is replaced by tyrosine. This single change, which we call H86Y, weakened the virus in mammalian cells and mice but unexpectedly enhanced its ability to infect mosquito cells. This host-specific switch may explain why the mutation persists in nature despite reducing disease severity in animals. Mechanistically, the attenuation was linked to impaired viral attachment and entry, resulting from a specific reduction in binding affinity for two critical host molecules, the attachment factor GAGs and the cellular entry receptor LDLR. Also, the GAG-binding site functionally overlaps with the LDLR interaction interface. Multiple mouse models supported that LDLR and GAGs are the key host factors mediating attenuation phenotype for H86Y. Despite being weakened, the mutant virus still triggered strong protective immunity, making it a promising vaccine candidate. Together, our findings identify E2 residue 86 as a key virulence determinant that modulates receptor usage, offering a precise target for antiviral and vaccine development against alphaviruses.
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PubMed
高影响因子
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