Microbial Cell Factories
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2026
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IF 5.8
Lin Menghui,Zheng Miao,Chen Kaiyi,Xu Xinyu,Chen Li,Guo Xiaogang,Le Thanh Ninh,Zhao Minjie,Feng Yanru,Cai Haiying
Heat stress is prevalent in industrial biomanufacturing processes including Baijiu brewing and bioethanol production. It disrupts the membrane structure and lipid homeostasis of Saccharomyces cerevisiae , interferes with genome-wide gene transcription and retards cell growth, thereby greatly lowering fermentation efficiency and product yields. There is an urgent demand for food-safe additives to alleviate heat-induced damage to industrial yeast. Although vitamin D₂ (VD₂) shares a similar sterol structure with endogenous yeast ergosterol, its regulatory effects on yeast under heat stress remain poorly understood. Here, we adopted an integrated strategy combining phenotypic characterization, lipidomics, transcriptomics and molecular docking to explore the protective effects and regulatory pathways of exogenous VD₂ against heat stress in S. cerevisiae . Phenotypic assays showed that VD₂ supplementation effectively alleviated heat-induced growth retardation, elevated intracellular glutathione peroxidase activity and reduced membrane injury. Lipidomic analysis revealed that VD₂ remodelled cellular lipid profiles by increasing triglyceride levels, decreasing phosphatidylcholine content and promoting sphingolipid synthesis. Transcriptomic results further demonstrated significant upregulation of key genes involved in the S-adenosylmethionine (SAM) metabolic axis. Integrated multi-omics data and molecular docking prediction support a tentative mechanistic hypothesis: VD₂ may interact with Opi3p and potentially interfere with its catalytic function, which could further drive downstream metabolic reprogramming. In conclusion, this study reveals that VD₂ alleviates heat-triggered growth suppression by remodelling the SAM-dependent lipid metabolic network. As a food-grade additive, VD₂ possesses promising potential to alleviate heat-induced growth retardation of yeast starters in industrial fermentation. Our findings provide a theoretical basis for developing natural additives to mitigate yeast heat damage and optimizing high-temperature fermentation bioprocesses.
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高影响因子
Journal of Translational Medicine
·
2022
·Vol. 20
·期 1
·1-10
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IF 8.44
Huang Kun,Wang Dan-Dan,Hu Wen-Bao,Zeng Wei-Qian,Xu Xia,Li Qiu-Xiang,Bi Fang-Fang,Yang Huan,Qiu Jian
Background Myotonic dystrophy type 1 (DM1), one of the most common forms of adult-onset muscular dystrophy, is caused by abnormally expanded CTG repeats in the 3′ untranslated region of the DMPK gene. The CUG repeats transcribed from the expanded CTG repeats sequestrate a splicing factor, MBNL1, causing the clinical symptoms in DM1. Nowadays, only symptomatic treatments are available for DM1, and no rational therapy is available. Recently, upregulation of MBNL1 expression has been found to be one of the promising therapies for DM1.Methods All experiments were conducted in the C2C12 myoblasts and HSALR mice, a DM1 mouse model. Real-time PCR and western blot were used to detect the mRNA and protein level, respectively. The rotarod exercise, grip strength and hanging time were used to evaluate the muscle strength of mice.Results In this study, we demonstrated that calcitriol, an active form of vitamin D3, increased MBNL1 in C2C12 mouse myoblasts as well as in HSALR mice model for DM1. In HSALR mice model, calcitriol improved muscle strength, and corrected aberrant splicing in skeletal muscle. Besides, calcitriol reduced the number of central nuclei, and improved muscle histopathology in HSALR mice. In addition, we identified that calcitriol upregulated MBNL1 expression via activating the promoter of Mbnl1 in C2C12 myogenic cells.Conclusion Our study suggests that calcitriol is a potential pharmacological strategy for DM1 that enhances MBNL1 expression.
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PubMed
高影响因子
Natural Product Communications
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2020
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IF 0.468
Ling-Li Zheng,Guan Wen,Yun-Xin Yao,Xiao-Huan Li,Feng Gao
Based on the strong activity dependence of paclitaxel (PTX; Taxol) or docetaxel (Taxotere) on the C-13 side chain, a small library of dehydroepiandrosterone, cholesterol, vitamin D2, and alkaloids talatisamine and songorine-PTX hybrids have been synthesized and evaluated for in vitro anticancer activity by MTT assay against human breast (MCF-7), colon (HCT116), lung carcinoma (A549), and renal adenocarcinoma (786-0) cancer cell lines. Most hybrids (11b, 12b, 13b, 15b, and 18b) reduced the growth of MCF-7 and 786-0 cells with low PTX sensitivity in vitro. Among the synthesized compounds, hybrid 11b was better in inhibiting the growth of the 4 cells than PTX. A relatively low IC50 value of compound 11b (8.16 ± 0.04 μM) was also examined after exposure for 48 hours. Hybrid 11b showed a proapoptotic effect in HCT116 cells evaluated by Annexin V/propidium iodide binding assay. The level of hybrid 11b leading to protective cell death in HCT116 cells was detected using western blot and not easily observed in our basic examinations.
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ANALYTICAL SCIENCES
·
2024
·
IF 1.8
Cai Tongji,Chen Meilun,Yang Jie,Tang Chunhua,Lu Xiaoling,Wei Zheng,Jiang Hanbing,Hou Yucui,Zhao Jia,Yu Peng
Abstract Vitamin D 3 (VD 3 ) is the main form of vitamin D and an essential nutrient for maintaining human life. Currently, traditional methods for detecting 25-hydroxyvitamin D3(25(OH)D 3 ) are complex and expensive. In this study, we constructed an accurate, sensitive, simple, and cost-effective label-free biosensor based on an aptamer for the detection of 25(OH)D 3 . The aptamer-modified sulfhydryl adopted self-assembly as a way to stably immobilize at the glassy carbon electrode (GCE) surface modified by gold nanoparticles (AuNPs). Upon 25(OH)D 3 binding to the aptamer, the complexes inhibit electron transfer at the electrode surface, leading to reduced [Fe(CN) 6 ] 3−/4− redox peak current. Consequently, the quantity of 25(OH)D 3 that interacts with the electrode-bound aptamer correlates with the observed electric current response values. The Aptamer/AuNPs/GCE aptasensor achieved direct and highly sensitive detection of 25(OH)D 3 over a wide concentration range (1.0–1000 nM), with a limit of detection of 1.0 nM. At the same time, other molecules with a similar structure, such as 25(OH)D 2 , Vitamin D 3 , and Vitamin D 2 , had lower response interference than 25(OH)D 3 . Therefore, this biosensor has great potential to become a portable diagnostic device for 25(OH)D 3 . Graphic abstract
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高影响因子
Current Molecular Pharmacology
·
2024
·Vol. 17
·期 1
·e18761429267000
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IF 2.4
Fengyan Tang,Bo Zhao,Li Zhang,Faisal Raza,Hajra Zafar,Shao Zhong,Lin Li,Wenhua Zhu,Lingna Fang,Bing Lu,Liwen Shen,Ping Guo,Nengxing Yu,Quanmin Li
Objective: The potential mechanism underlying the protective effect of Astragaloside IV (AS-IV) co-treatment with 1, 25-dihydroxy-vitamin D (Vit-D) on neuropathy in diabetic high-fat rats was investigated. Methods: The rat diabetic hyperlipidemia (DH) model was established via streptozotocin and a high-fat diet (HFD). After co-treatment (of AS-IV and Vit-D at respective doses of 50 mg/kg via oral gavage and 30000 IU/kg via intramuscular injection), blood glucose levels, markers of inflammation and oxidative stress, as well as apoptosis and histopathology were evaluated with appropriate techniques. Results: Co-treatment could effectively reduce blood glucose levels substantially (p< 0.01), improve weight loss, and decrease oral glucose tolerance. Reduced respective sensory and motor nerve conduction velocities in rats were substantially improved (p<0.01) after co-treatment. Also, we observed obvious improvement in DH-induced injured nerve fiber myelin structure and other organ pathologies in co-treated rats. Besides, we observed up-regulated expressions of peroxisomal-proliferator activated receptor-alpha (PPAR-α) and Vit-D receptors (VDR) (p< 0.01) through the western blotting technique. Using the same technique, we also discovered reduced levels of interleukin (IL)1 beta, IL-6, and tumor necrosis factor-alpha, coupled with increased IL-10 and superoxide dismutase levels (p< 0.01). Importantly, co-treatment could effectively exert anti-oxidative and anti-inflammatory effects. Also, co-treatment resulted in the up-regulation of PPAR-α and VDR expressions, inhibition of the renin–angiotensin–aldosterone system, and promotion of β-cell sensitivity to insulin. Conclusion: The combined application of AS-IV and Vit-D exhibited health effects such as anti-oxidation, regulation of inflammatory factors, and promotion of cell repair, which may be considered as the mechanisms underlying treatment of diabetic peripheral neuropathy and improvement in biochemical indicators.
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ACS Catalysis
·
2025
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IF 13.1
Lixin Kang,Haoran Li,Kexin Lin,Shen Hu,Song Liu,Yuben Qiao,Ying Wang,Aitao Li
The biocatalytic production of 25-hydroxyvitamin D3 (25(OH)VD3, calcidiol) represents a superior alternative to traditional chemical synthesis. However, the reported VD3 hydroxylases generally exhibit suboptimal catalytic efficiency, limiting their practical applications. In this study, a cytochrome P450 CYP107Pdh from Pseudonocardia dioxanivorans_CB1190, which displays unique C26 hydroxylation activity on VD3, was identified. Then, structure-guided loop engineering combined with binding pocket reshaping was conducted on CYP107Pdh, leading to the generation of the quintuple variant 89_90insIP/T112A/V161L/G186V (M4). This variant shifted the regioselectivity from 91% C26 in the wild type (WT) to 81% C25 for calcidiol production. In addition, variant M4 showed a remarkable enhancement in catalytic activity, achieving a catalytic efficiency (kcat/Km) that is 75-fold higher than that of the WT. Computational analyses revealed that the regioselectivity shift and activity improvement are primarily attributed to a conformational transition in the substrate-binding pocket from an open to a more closed state, which optimizes substrate binding and facilitates efficient 25-hydroxylation of VD3. Finally, a semipreparative biotransformation yielded 2.64 g of crystalline calcidiol (95% purity) from a 1-L reaction, thereby expanding the enzyme library of VD3 hydroxylases and underscoring its potential for industrial-scale production of calcidiol.
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