MOLECULAR PHARMACEUTICS
·
2018
·
IF 4.556
Hui Liu,Yuxiang Han,Jiyuan Li,Ming Qin,Qunfeng Fu,Chunhong Wang,Zhibo Liu
Amino acids derivative are well established molecular probes for diagnosis of a variety of cancer using positron emission tomography (PET). Recently, boramino acid (BAAs) was found as a prospective molecular platform for developing PET tracer. The objective of this study was to develop a 18F-labeled alanine derivative through displacing its carboxylate by trifluoroborate as a selective ASCT2 marker for cancer imaging. 18F-Ala-BF3 was first evaluated in healthy FVB/N mice in vivo, exhibiting rapid renal clearance with almost negligible uptake in stomach (1.53 ± 0.31%ID/g). Notable uptake was observed in thyroid (3.71 ± 0.49%ID/g, 40 min post injection), of which the uptake was significantly inhibited by co-injection with natural L-alanine. In addition, we further established 18F-Ala-BF3 on a human gastric cancer cell (BGC-823) xenografts bearing mouse model. Dynamic PET-CT scan revealed the optimal time window for tumor imaging, it was between 40 and 60 min post injection, when the BGC-823 xenografts uptake was 5.49 ± 1.47%ID/g (n = 4), and the tumor-to-stomach, tumor-to-blood, tumor-to-muscle, and tumor-to-brain ratios were 3.27 ± 1.53, 3.80 ± 1.48, 3.47 ± 1.48, and 6.20 ± 1.47, respectively.
研究领域:
医学影像学
·
肿瘤学
·
分子生物学
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DOI
PubMed
高影响因子
PLANT PHYSIOLOGY
·
2023
·
IF 7.4
Li Yuanyuan,Gao Junping,Wang Ying,Cai Jun,Wu Dousheng,Wang Long,Pu Wenxuan,Yu Feng,Zhu Sirui
Transfer RNA (tRNA) can produce smaller RNA fragments called tRNA-derived fragments (tRFs). tRFs play critical roles in multiple cellular programs, although the functional mechanisms of tRFs remain largely unknown in plants. In this study, we examined the phenotype associated with 5′ tRF-Ala (tRF-Ala, produced from tRNA-Ala) overexpression and knockdown lines (tDR-Ala-OE and tDR-Ala-kd, respectively) and the mechanisms by which tRF-Ala affects mRNA levels in Arabidopsis (Arabidopsis thaliana). We investigated the candidate proteins associated with tRF-Ala by quantitative proteomics and confirmed the direct interaction between tRF-Ala and the splicing factor SERINE-ARGININE RICH PROTEIN 34 (SR34). A transcriptome sequencing analysis showed that 318 genes among all the genes (786) with substantial alternative splicing (AS) variance in tDR-Ala-OE lines are targets of SR34. tRF-Ala diminished the binding affinity between SR34 and its targets by direct competition for interaction with SR34. These findings reveal the critical roles of tRF-Ala in regulating mRNA levels and splicing.
研究领域:
植物生物学
·
分子遗传学
·
RNA生物学
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DOI
PubMed
高影响因子
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
·
2026
·
IF 5.3
Xiaoying Jiang,Meiling Feng,Xiaotian Niu,Shan Wang,Yinyan Sun,Wenchao Chen,Renren Bai
Superficial tumours can be effectively treated with photodynamic therapy (PDT), which is characterised by its targeted approach and enhanced safety profile. 5-aminolevulinic acid (ALA), a precursor to the endogenous photosensitiser PpIX, has been widely utilised in PDT. However, its high hydrophilicity, poor permeability and stability, necessitates structural modifications to improve its drug-like properties and increase the PpIX yield. Hydroxypyridinone (HPO) iron chelators can synergistically enhance PpIX production when administered in conjunction with ALA, as well as inducing tumour cell death through iron chelation. Consequently, this study designed a series of novel ALA-HPO derivatives, functioning as dual prodrugs to elevate intracellular PpIX levels and enhance photodynamic anti-tumour effects. The optimised compound AP-8 displayed the highest phototoxicity and greatest PpIX yield, demonstrating superior photodynamic anti-tumour efficacy compared to ALA in a mouse melanoma model, with a TGI of 84.74%. These findings underscore the potent application potential of ALA-HPO derivatives in PDT.
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DOI
高影响因子
JOURNAL OF MEDICAL VIROLOGY
·
2024
·Vol. 96
·期 6
·e29723
·
IF 6.8
Dekai Zheng,Changhao Cheng,Yanhua Tang,Zhixin Fang,Xuelian Gao,Yuchuan Chen,Qiuhong You,Kaifeng Wang,Heqi Zhou,Zhixian Lan,Jian Sun
Hepatitis B virus (HBV) can be completely suppressed after antiviral treatment; however, some patients with chronic hepatitis B (CHB) exhibit elevated alanine aminotransferase (ALT) levels and sustained disease progression. This study provides novel insights into the mechanism and potential predictive biomarkers of persistently elevated ALT (PeALT) in patients with CHB after complete viral inhibition. Patients having CHB with undetectable HBV DNA at least 12 months after antiviral treatment were enrolled from a prospective, observational cohort. Patients with PeALT and persistently normal ALT (PnALT) were matched 1:1 using propensity score matching. Correlations between plasma metabolites and the risk of elevated ALT were examined using multivariate logistic regression. A mouse model of carbon tetrachloride-induced liver injury was established to validate the effect of key differential metabolites on liver injury. Of the 1238 patients with CHB who achieved complete viral suppression, 40 (3.23%) had PeALT levels during follow-up (median follow-up: 2.42 years). Additionally, 40 patients with PnALT levels were matched as controls. Ser-Phe-Ala, Lys-Ala-Leu-Glu, 3-methylhippuric acid, 3-methylxanthine, and 7-methylxanthine were identified as critical differential metabolites between the two groups and independently associated with PeALT risk. Ser-Phe-Ala and Lys-Ala-Leu-Glu levels could be used to discriminate patients with PeALT from those with PnALT. Furthermore, N -acetyl- l -methionine (NALM) demonstrated the strongest negative correlation with ALT levels. NALM supplementation alleviated liver injury and hepatic necrosis induced by carbon tetrachloride in mice. Changes in circulating metabolites may contribute to PeALT levels in patients with CHB who have achieved complete viral suppression after antiviral treatment.
研究领域:
肝病学
·
代谢组学
·
药理学
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产品关联
DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2026
·
IF 7.5
Wen-yuan Zhang,Qian-qian Wei,Tao Zhang,Chunmei Geng,Hai-yan Wu,Chang-shui Wang,Jing Chen,Lei Feng,Pei Jiang
Background and Purpose Despite breakthroughs in immunotherapy and targeted therapies, chemotherapy remains indispensable in oncology. Experimental Approach This study seeks to pinpoint key pathways in doxorubicin (DOX)-treated mouse hippocampus, utilising comprehensive transcriptomic and metabolomic analyses, and validating the mechanisms in vitro and in vivo. Key Results Our multi-omics investigation revealed that sustained DOX exposure induced significant down-regulation of 5-aminolevulinate synthase 2 (ALAS2) and its catalytic product 5-aminolevulinic acid (5-ALA) in the hippocampal region. ALAS2 deficiency was specific to hippocampal neurons, which were more sensitive to oxidative damage than astrocytes or microglia. In vivo and in vitro studies demonstrated that 5-ALA administration or ALAS2 overexpression protected the brain from DOX-induced neurotoxicity. ALAS2 catalyses the condensation of glycine and succinyl-CoA to form 5-ALA, the key precursor of haem. Beyond its role in erythropoiesis, haem is a metabolite that modulates cellular redox homeostasis through interactions with the BACH1 (BTB and CNC homology 1)/NRF2 (nuclear factor erythroid 2 like 2) pathway. We found that DOX suppressed the ALAS2/5-ALA axis, thereby enhancing BACH1 stability. This stabilised BACH1 competes with NRF2 for binding to antioxidant response elements (AREs) in target gene promoters. Conversely, reinforcing the ALAS2/5-ALA axis elevated intracellular haem levels, promoting BACH1 degradation and enhancing NRF2 activity. Using a zebrafish model, we further highlighted the antioxidant and neuroprotective role of 5-ALA against DOX-induced neurotoxicity. Conclusions and Implications In conclusion, this study elucidates a novel endogenous neuroprotective mechanism wherein the ALAS2/5-ALA axis modulates the BACH1/NRF2 pathway. 5-ALA shows promise for repurposing to mitigate chemotherapy-associated neurotoxicity. Graphical
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DOI
PubMed
高影响因子
PLANT CELL TISSUE AND ORGAN CULTURE
·
2018
·Vol. 134
·期 2
·319-330
·
IF 2.004
Zheng Jie,An Yuyan,Wang Liangju
Color is a key factor for fruit commercial value. 5-Aminolevulinic acid (5-ALA), as an eco-friendly plant growth regulator, shows an attractively promotive effect on plant secondary metabolism, especially for fruit coloration. Brassinosteroids (BRs) can also improve plant flavonoid biosynthesis. No information is now available on the relationship between 5-ALA and BR. Here, we found that 1.5 mg L −1 24-epibrassinolide (24-EBL) promoted 50 mg L −1 5-ALA-induced anthocyanin accumulation, while, brassinazole (Brz) significantly inhibited the 5-ALA-induced flavonoid accumulation. HPLC analysis further showed that the inductive effects of 5-ALA on the accumulation of cyanidin-3-galactoside, quercetin-3-galactoside, quercetin and kaempferol were elevated by 24-EBL, but impaired by Brz. These results suggest that brassinolide biosynthesis might involve in 5-ALA-induced flavonoid accumulation. Gene expression analysis showed that 5-ALA and 5-ALA + 24-EBL induced the expression of regulatory genes MdMYB10, MdMYB9, MdbHLH3 and MdbHLH33 . These two treatments also up-regulated the structural gene expressions of anthocyanin biosynthesis and transportation, including MdCHS, MdF3′H, MdDFR, MdANS, MdUFGT, MdGST and MdMATE , as well as flavonol biosynthetic gene MdFLS . But Brz decreased 5-ALA-induced up-regulation of these genes. In addition, 5-ALA also induced the expression of MdBRI1, MdBAK1 and MdBZR1 , which are involved in brassinolide signal transduction. These results indicate that 24-EBL enhances 5-ALA-promoted expression of genes related to flavonoid biosynthesis and brassinolide signal transduction, while Brz exhibits the opposite effects. Taken together, we propose that 24-EBL is involved in 5-ALA-induced anthocyanin and flavonol accumulation in calli of apples. Our results provide new insights into 5-ALA-induced fruit coloration.
研究领域:
植物生理学
·
分子生物学
·
园艺学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Bin Wang,Jin Zhou,Xiang-Yang Zhang,Yu-Shun Yang,Chang-Hong Liu,Hai-Liang Zhu,Qing-Cai Jiao
Enzyme reaction has been accepted widely in numerous applications owing to the high efficiency and stereo-selectivity, as well as simple preparation by gene engineering. However, the fragility and complex purification process of the enzyme are long-standing problems which limit the large-scale application. One possible solution may be the enzyme immobilization. As one type of porous material with high loading capacity and designable functionality, Metal-Organic Frameworks (MOFs) are ideal choices for the immobilization of enzyme with a considerable interest in recent years. In this study, d -amino acid transaminase ( DAT ), an important enzyme for industrial synthesis of d -Ala, was covalently immobilized on the surface of a star MOFs material, UiO-66-NH 2. Interestingly, we found that the nanoscale hybrid enzyme UiO-66-NH 2 -Gd- DAT not only maintained the high catalytic efficiency but also got rid of the interference of polluting enzymes, which meant that we could obtain efficient and stereo-selective immobilized enzyme without complex purification process. In general, our findings demonstrated that using UiO-66-NH 2 might be a promising strategy to immobilize enzyme and produce effective biocatalyst with high activity and stereo-selectivity.
研究领域:
生物化学
·
生物技术
·
催化
·
材料科学
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DOI
PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Qian Zhou,Dankui Liao,Yongfang Xu,Lei Wang,Lixia Sun,Jianhua Sun,Xiongdiao Lan,Zhangfa Tong,Guangzhi Zhou
From the perspective of functional food development, an in-depth study of the interaction between food-derived angiotensin-converting enzyme inhibitory peptides (ACEIPs) and serum albumin is crucial for understanding their physicochemical stability after absorption within the body. Thus, this study explored the interaction mechanisms of bovine serum albumin (BSA) with bonito sauce-derived ACEIP Ala-Gly-Pro (AGP) using biosafety, biophysics, and computational biology. The results indicated that AGP demonstrated good biosafety, and competitively inhibited ACE activity (500 ± 24 μmol/L). Multi-spectroscopic and isothermal titration calorimetry analysis proved that AGP could spontaneously insert in the site I of BSA and form a non-covalent complex, clearly changing the structure and microenvironment of BSA. Molecular docking and molecular dynamics simulations successfully revealed the dynamic conformational changes and non-covalent interactions in the BSA–AGP complex. These findings provide valuable data on food-derived ACEIP AGP, serving as a reference and model for studying similar peptides in developing antihypertensive functional foods.
研究领域:
生物化学
·
分子生物学
·
食品科学
·
药理学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Yu-Qiao Wang,Yi-Tong Han,Jia-Nan Yan,Yi-Nan Du,Xin-Yu Jiang,Hai-Tao Wu
Gel properties of hydrogel-forming by Ala-Lys dipeptide (AK) and iota-carrageenan (ι-C) were investigated by rheological behavior, fourier transform infrared analysis, cryo-scanning electron microscopy, low field-NMR relaxometry and magnetic resonance imaging. Iota-carrageenan was changed from a liquid to a gel with the addition of AK, and the existence of AK significantly increased the storage modulus ( G' ) of ι-C from 590.4 to 1077.8 Pa. In the ι-C/AK gel, the blue-shift of O H stretching and water deformation were observed, meanwhile, the presence of amide I band at 1682 cm −1 was observed. The network of ι-C/AK gel showed a dense honeycomb structure with flocculating continuous phase and rough entanglement morphology. After adding AK, the water free in the pores of ι-C entered the ι-C/AK gel matrix, and the binding capacity of bound water was enhanced. These scenarios proved that the AK as the cationic dipeptide could control the conversion of negatively charged ι-C from an original random structure to a helical structure due to electrostatic interactions and hydrogen bonds. This study provides a new opportunity for the peptides into carbohydrate-based gel matrices, which could provide insights for the further application of ι-C/AK gels in the fields of food industry, tissue engineering and drug delivery.
研究领域:
食品科学
·
材料科学
·
生物医学工程
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DOI
PubMed
高影响因子
WEED SCIENCE
·
2023
·Vol. 71
·期 3
·224-232
·
IF 2.5
Zhi Tang,Zilu Wang,Mali Wang,Fan Yin,Min Liao,Haiqun Cao,Ning Zhao
Shortawn foxtail (Alopecurus aequalis Sobol.) is an obligate wetland plant that is widely distributed throughout Europe, temperate Asia, and North America. In China, it is widespread in the middle and lower reaches of the Yangtze River as a noxious weed in winter cropping fields with a rice (Oryza sativa L.) rotation. The acetolactate synthase (ALS)-inhibiting herbicide mesosulfuron-methyl has been widely used to control annual grass and broadleaf weeds, including A. aequalis, in wheat (Triticum aestivum L.) fields, leading to the selection of herbicide-resistant weeds. In this study, an A. aequalis population, AHFT-4, that survived mesosulfuron-methyl at the field-recommended rate (9 g ai ha−1) was collected in Anhui Province. Single-dose testing confirmed that the suspected resistant AHFT-4 had evolved resistance to mesosulfuron-methyl. Target gene sequencing revealed a resistance mutation of Pro-197-Ala in ALS1 of the resistant plants, and a derived cleaved amplified polymorphic sequence marker was developed to specifically detect the mutation. A relative expression assay showed no significant difference in ALS expression between AHFT-4 and a susceptible population without or with mesosulfuron-methyl treatment. Whole-plant dose–response bioassays indicated that AHFT-4 had evolved broad-spectrum cross-resistance to ALS-inhibiting herbicides of all five chemical families tested, with GR50 resistance index (RI) values ranging from 21 to 206. However, it remained susceptible to the photosystem II inhibitor isoproturon. Pretreatment with the cytochrome P450 inhibitor malathion or the glutathione S-transferase inhibitor 4-chloro-7-nitrobenzoxadiazole had no significant effects on the resistance of AHFT-4 to mesosulfuron-methyl. To our knowledge, this study reports for the first time the ALS gene Pro-197-Ala substitution conferring broad-spectrum cross-resistance to ALS-inhibiting herbicides in A. aequalis.
研究领域:
植物科学
·
杂草科学
·
分子生物学
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产品关联
DOI
高影响因子
Metabolites
·
2024
·Vol. 14
·期 3
·142
·
IF 3.4
Yaxin Wang,Chaolu Tan,Yinghao Li,Fengyan Meng,Youwei Du,Shuyu Zhang,Wenxin Jiang,Naijie Feng,Liming Zhao,Dianfeng Zheng
A large number of dead seedlings can occur in saline soils, which seriously affects the large-scale cultivation of rice. This study investigated the effects of plant growth regulators (PGRs) and nitrogen application on seedling growth and salt tolerance (Oryza sativaL.), which is of great significance for agricultural production practices. A conventional rice variety, “Huang Huazhan”, was selected for this study. Non-salt stress treatments included 0% NaCl (CK treatment), CK + 0.05 g N/pot (N treatment), CK + 40 mg·L−15-aminolevulinic acid (5-ALA) (A treatment), and CK + 30 mg·L−1diethylaminoethyl acetate (DTA-6) (D treatment). Salt stress treatments included 0.3% NaCl (S treatment), N + 0.3% NaCl (NS treatment), A + 0.3% NaCl (AS treatment), and D + 0.3% NaCl (DS treatment). When 3 leaves and 1 heart emerged from the soil, plants were sprayed with DTA-6 and 5-ALA, followed by the application of 0.3% NaCl (w/w) to the soil after 24 h. Seedling morphology and photosynthetic indices, as well as carbohydrate metabolism and key enzyme activities, were determined for each treatment. Our results showed that N, A, and D treatments promoted seedling growth, photosynthesis, carbohydrate levels, and the activities of key enzymes involved in carbon metabolism when compared to the CK treatment. The A treatment had the most significant effect, with increases in aboveground dry weight and net photosynthetic rates (Pn) ranging from 17.74% to 41.02% and 3.61% to 32.60%, respectively. Stomatal limiting values (Ls) significantly decreased from 19.17% to 43.02%. Salt stress significantly inhibited seedling growth. NS, AS, and DS treatments alleviated the morphological and physiological damage of salt stress on seedlings when compared to the S treatment. The AS treatment was the most effective in improving seedling morphology, promoting photosynthesis, increasing carbohydrate levels, and key enzyme activities. After AS treatment, increases in aboveground dry weight, net photosynthetic rate, soluble sugar content, total sucrose synthase, and amylase activities were 17.50% to 50.79%, 11.39% to 98.10%, 20.20% to 80.85%, 21.21% to 33.53%, and 22.17% to 34.19%, respectively, when compared to the S treatment. In summary, foliar sprays of 5-ALA, DTA-6, and additional nitrogen fertilizer enhanced rice seedling growth, increased photosynthesis, lowered Ls values, and improved seedling salt tolerance. Spraying two regulators, 5-ALA and DTA-6, quantitatively increased the effect of nitrogen fertilizer, with comparable effects on NaCl stress regulation. This study provides the basis for efficient agricultural production.
研究领域:
植物生理学
·
农业科学
·
胁迫生物学
·
作物科学
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DOI
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Qi Zhang,Zhe Zheng,Yiting Zhao,Qing Wu,Chu Wu,Xiuli Wang,Xia Wang,Qigang Wang,Peiru Wang
The transformation of O 2 is primarily facilitated by the catalytic action of redox enzymes, which play a pivotal role in sustaining cellular energy metabolism and redox balance. Bioinspired by O 2 distribution and ROS regulation related to cascade biocatalytic process, a D-peptide NapG D F D F D Y engineered hydrogel has been constructed with encapsulated dual-enzyme superoxide (SOD) and chloroperoxidase (CPO) cascade catalytic circuit and co-assembled photosensitizer of 5-aminolevulinic acid molecules (ALA). Multimodal oxygen modulation has been conducted by the concurrent oxygen generation via SOD-catalyzed ⋅O 2 − dismutation and oxygen consumption for 1 O 2 production by CPO and ALA, achieving self-sustaining enzymatic dynamic therapy (EDT)-photodynamic therapy (PDT) (EDT-PDT) synergy. The endogenous cascade-amplified EDT not only enhances the 1 O 2 efficacy in exogenous PDT therapy, but the intermediate O 2 can also alleviate local neuropathic pain caused by hypoxia for safe PDT treatment. This work pioneers enzyme-mediated dynamic control of tumor redox homeostasis, establishing a new therapeutic axis between biocatalytic amplification and photodynamic processes.
研究领域:
肿瘤学
·
生物材料
·
纳米医学
·
分子生物学
·
转化医学
·
氧化还原生物学
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药物递送系统
·
生物催化
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）