Journal of Fungi
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2023
·Vol. 9
·期 5
·512
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IF 4.7
Xuan Wang,Xianhao Xu,Jiaheng Liu,Yanfeng Liu,Jianghua Li,Guocheng Du,Xueqin Lv,Long Liu
Retinol, the main active form of vitamin A, plays a role in maintaining vision, immune function, growth, and development. It also inhibits tumor growth and alleviates anemia. Here, we developed aSaccharomyces cerevisiaestrain capable of high retinol production. Firstly, the de novo synthesis pathway of retinol was constructed inS. cerevisiaeto realize the production of retinol. Second, through modular optimization of the metabolic network of retinol, the retinol titer was increased from 3.6 to 153.6 mg/L. Then, we used transporter engineering to regulate and promote the accumulation of the intracellular precursor retinal to improve retinol production. Subsequently, we screened and semi-rationally designed the key enzyme retinol dehydrogenase to further increase the retinol titer to 387.4 mg/L. Lastly, we performed two-phase extraction fermentation using olive oil to obtain a final shaking flask retinol titer of 1.2 g/L, the highest titer reported at the shake flask level. This study laid the foundation for the industrial production of retinol.Keywords:vitamin A;retinol;Saccharomyces cerevisiae;retinol dehydrogenase;olive oil
研究领域:
代谢工程
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生物技术
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微生物生物技术
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DOI
PubMed
高影响因子
Nature Communications
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2023
·Vol. 14
·期 1
·1-18
·
IF 16.6
Wu Yandi,Huang Tongsheng,Li Xinghui,Shen Conghui,Ren Honglin,Wang Haiping,Wu Teng,Fu Xinlu,Deng Shijie,Feng Ziqi,Xiong Shijie,Li Hui,Gao Saifei,Yang Zhenyu,Gao Fei,Dong Lele,Cheng Jianding,Cai Weibin
Diabetic cardiomyopathy is a primary myocardial injury induced by diabetes with complex pathogenesis. In this study, we identify disordered cardiac retinol metabolism in type 2 diabetic male mice and patients characterized by retinol overload, all-trans retinoic acid deficiency. By supplementing type 2 diabetic male mice with retinol or all-trans retinoic acid, we demonstrate that both cardiac retinol overload and all-trans retinoic acid deficiency promote diabetic cardiomyopathy. Mechanistically, by constructing cardiomyocyte-specific conditional retinol dehydrogenase 10-knockout male mice and overexpressing retinol dehydrogenase 10 in male type 2 diabetic mice via adeno-associated virus, we verify that the reduction in cardiac retinol dehydrogenase 10 is the initiating factor for cardiac retinol metabolism disorder and results in diabetic cardiomyopathy through lipotoxicity and ferroptosis. Therefore, we suggest that the reduction of cardiac retinol dehydrogenase 10 and its mediated disorder of cardiac retinol metabolism is a new mechanism underlying diabetic cardiomyopathy.
研究领域:
心脏病学
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内分泌学
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代谢学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
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IF 4.5
Huixian Xu,Qingle Song,Qi Zhou,Bo Yang,Jichuan Zhang,Zhenyuan Wang,Chengyu Wu,Peng Shu,Jiaheng Zhang
Retinol is used to manage epidermal and keratin metabolism, promote collagen formation, erase wrinkles for firmer skin, and restore suppleness and smoothness. Retinol can be difficult to store and use owing to the potential for skin irritation, oxidation, and biological ineffectiveness. The linolenic acid and phosphatidylcholine deep eutectic solvent (DES) had a low melting point, high bioactivity, and integrated capsule technology for retinol encapsulation. Safety evaluation tests revealed that the formulated DES-retinol emulsion was less cytotoxic than free retinol, as well as less irritant toward chicken embryos, pig skin, and human patches. In a keratinocyte inflammatory factor inhibition assay, the DES-retinol emulsion reduced monocyte chemoattractant protein-1 expression, indicating the potential to reduce the inflammatory response of the skin to retinol-induced irritation. The DES-retinol emulsion exhibited pro-permeability, anti-wrinkle, firming, and antioxidant characteristics in cellular, skin, and clinical investigations. The DES-retinol emulsion promoted type I collagen production, suppressed matrix metalloproteinase-1 activity, and reduced the release of reactive oxygen species. Consequently, the quantity, size, and depth of wrinkles were substantially improved, along with an enhanced anti-aging effect, heightened skin hydration, increased collagen intensity and flexibility, and diminished retinol-induced irritation. In conclusion, the retinol-loaded linolenic acid and phosphatidylcholine DES emulsion exhibited improved stability, enhanced transdermal efficiency, and notable therapeutic effects.
研究领域:
药剂学
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皮肤科学
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生物医学工程
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DOI
高影响因子
Applied Materials Today
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2025
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IF 6.9
Huixian Xu,Rui Ye,Ye Zhong,Wanling Chen,Jichuan Zhang,Zhenyuan Wang,Le Du,Fan Hu,Chengyu Wu,Jiaheng Zhang
Although retinol and its derivatives are effective anti-aging substances, they can induce “retinoid dermatitis.” To solve this problem, a novel 4-t-butylcyclohexanol α-lipoic acid ionic liquid (BLA-IL) was prepared and confirmed. Retinol can be directly dissolved into BLA-IL, encapsulated into nanoparticles (NPs) and form retinoid-loaded ionic liquid NPs. In-vivo and ex-vivo studies investigated the developed formulation's safety, transdermal enhancement, and efficacy. Safety assessments revealed that BLA-IL-mediated TRPV1 antagonism was achieved. In particular, IL-NPs increase the amount of retinoid in the skin by 4.3 times compared to the free retinoid and 27 % more than NPs. Based on in vivo and in vitro experiments, BLA-IL synergistically doubled the effect of fibroblast COL-I synthesis, with upregulation to 756.9 %, simultaneously enhancing COL-I, COL3A1, and Elna gene expression and inhibiting MMP-1, reactive oxygen species, and neutrophil aggregation. Clinically, retinoid-loaded IL-NPs significantly improved wrinkles, R2, collagen intensity, ITA°, and l -value compared to free retinoid in volunteers. In conclusion, this study displayed that BLA-IL NPs could promote transdermal delivery and achieve synergistic anti-aging efficacy. It could be a promising technology combining IL and nano-technology in the pharmaceutic and cosmetic transdermal areas.
研究领域:
药剂学
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皮肤科学
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生物材料
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化妆品科学
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产品关联
DOI
高影响因子
ACTA PHYSIOLOGIAE PLANTARUM
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2023
·Vol. 46
·期 2
·1-17
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IF 2.6
Kumari Monika,Singh Hidam Bishworjit,Khan Mohammad Imtiyaj
Betalains are health-promoting plant pigments accumulated in non-anthocyanic plants. Owing to its limited distribution in nature, metabolic trade-offs of inhibiting them are poorly understood. The aim of this study was to investigate the effects of inhibition of betalains in Amaranthus tricolor seedlings to gain insights into the relationship of betalain biosynthesis with other biosynthetic pathways in betalain-accumulating plants. Phenylalanine (Phe; 12.5, 25, and 50 mmol L −1 ) and 3-methyl-2-benzothiazolinone hydrazone (MBTH) (25 mmol L −1 ) were treated to inhibit betalain biosynthesis in ten-day-old A. tricolor (red) seedlings. After two and six days of treatment, target (betalain-related metabolites) and non-target metabolites were analyzed. In two days, Phe content increased by 2.6, 8.5, and 17.4-fold in Phe (12.5, 25, and 50 mmol L −1 )-treated seedlings, respectively, compared to control, indicating the uptake of Phe by the seedlings. Phe treatment led to a 10.1–18% decrease in betacyanins, while MBTH caused an 18.3% decrease in two days. In both treatments, cyclo -DOPA formation, which is essential for betacyanin biosynthesis, seems to be inhibited, albeit through different mechanisms. Betalain biosynthetic precursors and intermediates, viz., tyrosine, L-DOPA, and dopamine decreased differentially. Ascorbic acid, α -tocopherol, and retinol contents increased in both treatments concomitant with the reduction in betalains, total phenols, and antioxidant enzymes. Therefore, Phe treatment is beneficial in enhancing antioxidant metabolites in betalain-accumulating plants. However, the mechanism of increasing ascorbic acid on inhibiting betalains needs further investigation in other betalain-producing plants also to understand if ascorbic acid is involved in regulating betalain biosynthesis.
研究领域:
植物学
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代谢生物学
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DOI
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2023
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IF 5.2
Yuyan Yang,Shaowei Yan,Bin Yu,Chang Gao,Kuan Chang,Jing Wang
Emulsion systems are widely used as carriers for diverse actives processing moisturizing, anti-aging, whitening and other functions. Recently, emulsions containing lamellar gel phase have been attracting more and more research interests since it improves the physical stability of degradable actives. In the present work, o/w emulsions containing lamellar gel phase composed of ceteareth-20 (O-20) and mixed fatty alcohols (FA) were developed for retinyl propionate (RP) stabilization and transdermal delivery . The lamellar gel phase was confirmed by XRD combined with cryo-SEM, and main factors for lamellar gel phase formation were investigated and discussed. Moreover, effects of carrier oil on the emulsion properties were studied and the result showed that introduction of carrier oil benefits RP retention, rheological and transdermal properties. This study proves that O-20/FA based lamellar phase emulsion is promising system for RP stabilization and utilization in cosmetic formulations.
研究领域:
化妆品科学
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药物递送系统
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材料科学
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产品关联
DOI
高影响因子
MICROBIOLOGICAL RESEARCH
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2025
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IF 6.9
Jing Xu,Haoming Xu,Jianhong Li,Wenqi Huang,Yingfei Li,Xue Guo,Minzheng Zhu,Yao Peng,Youlian Zhou,Yuqiang Nie
Gut microbiota and their metabolites play a significant role in inflammatory bowel disease. Here, we attempted to determine the anti-inflammatory role of the probiotic Clostridium. butyricum (CB) in inflammatory bowel disease and identify the exact immune mechanism. The clinical significance of Clostridiales and CB was explored in patients with ulcerative colitis. The inflammation-suppressive role of CB was evaluated in mice with DSS-induced colitis. 16S rRNA sequencing was performed to assess changes in the gut microbiota. Altered transcription levels were detected by RNA sequencing. Flow cytometry was performed to assess the frequency of IgA responses to gut microbiota. Clostridiales and CB were depleted in ulcerative colitis. Oral gavage with CB significantly suppressed weight loss and colon shortening in the dextran sulfate sodium-induced colitis mouse model. Intestinal barrier injury was reversed and the gut microbiota was restored upon treatment with CB administration. The mucosal immune response to gut microbiota was reversed upon treatment with CB. CB conditional medium was more effective than heat-killed CB in alleviating inflammation. Mechanistically, retinol metabolism and retinoic acid levels were higher in groups treated with CB and butyrate. CB and the metabolite butyrate exerted a suppressive role on the abundance of Immunoglobulin A-coated gut microbiota by inhibiting retinoic acid synthesis. In summary, CB protects against inflammation and intestinal barrier injury by producing anti-inflammatory metabolites that can regulate the mucosal immune response to gut microbiota by increasing retinoic acid levels in the colon.
研究领域:
微生物学
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免疫学
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肠道疾病研究
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DOI
PubMed
高影响因子
BMC BIOLOGY
·
2021
·Vol. 19
·期 1
·1-18
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IF 7.431
Yuan Dongjuan,Li Song,Shang Ziyu,Wan Muchun,Lin Yu,Zhang Yanhua,Feng Yaoyu,Xu Lian,Xiao Lihua
Background Nematodes are a widespread and diverse group comprising free-living and parasitic species, some of which have major detrimental effects on crops, animals, and human health. Genomic comparisons of nematodes may help reveal the genetic bases for the evolution of parasitic lifestyles. Fatty acid and retinol-binding proteins (FARs) are thought to be unique to nematodes and play essential roles in their development, reproduction, infection, and possibly parasitism through promoting the uptake, transport, and distribution of lipid and retinol. However, the evolution of FAR family proteins across the phylum Nematoda remains elusive.Results We report here the evolutionary relationship of the FAR gene family across nematodes. No FAR was found in Trichocephalida species and Romanomermis culicivorax from Clade I, and FAR could be found in species from Clades III, IV, and V. FAR proteins are conserved in Clade III species and separated into three clusters. Tandem duplications and high divergence events lead to variable richness and low homology of FARs in Steinernema of Clade IVa, Strongyloides of Clade IVb, and intestinal parasitic nematodes from Clades Vc and Ve. Moreover, different richness and sequence variations of FARs in pine wood, root-knot, stem, and cyst nematodes might be determined by reproduction mode or parasitism. However, murine lungworm Angiostrongylus and bovine lungworm Dictyocaulus viviparus from Clade Vd have only 3–4 orthologs of FAR. RNA-seq data showed that far genes, especially far-1 and far-2, were highly expressed in most nematodes. Angiostrongylus cantonensis FAR-1 and FAR-3 have low sequence homology and distinct ligand-binding properties, leading to differences in the cavity volume of proteins. These data indicate that FAR proteins diverged early and experienced low selective pressure to form genus-level diversity. The far genes are present in endophyte or root-colonized bacteria of Streptomyces, Kitasatospora sp., Bacillus subtilis, and Lysobacter, suggesting that bacterial far genes might be derived from plant-parasitic nematodes by horizontal gene transfer.Conclusion sData from these comparative analyses have provided insights into genus-level diversity of FAR proteins in the phylum Nematoda. FAR diversification provides a glimpse into the complicated evolution history across free-living and parasitic nematodes.
研究领域:
分子生物学
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遗传学
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进化生物学
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DOI
PubMed
高影响因子
Food Science and Human Wellness
·
2022
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IF 8.022
Zhixian Li,Zhuqing Dai,Enjuan Shi,Peng Wan,Guijie Chen,Zhongyuan Zhang,Yayuan Xu,Ruichang Gao,Xiaoxiong Zeng,Dajing Li
β -Carotene, a typical non-oxygenated carotenoid, is the most efficient source of retinol (VA). The low bio-availability of β -carotene lead to large accumulation in colon; however, the relationship between β -carotene and gut microflora remains unclear. This study intends to explore the interaction between β -carotene and gut microflora using an in vitro fermentation model. After 24 h fermentation, the degradation rate of β -carotene was (64.28 ± 6.23)%, which was 1.46 times that of the group without gut microflora. Meanwhile, the production of VA was nearly 2 times that of the group without gut microflora, indicating that the gut microflora can metabolize β -carotene into VA. β -Carotene also influences the production of short-chain fatty acids (SCFAs), the production of total SCFAs in 0.5 mg/mL β -carotene (BCM) group was (44.00 ± 1.16) mmol/L, which was 2.26 times that of the blank control (BLK) group. Among them, the production of acetic acid in BCM group was (19.06 ± 0.82) mmol/L, which was 2.64 time that of the BLK group. Furthermore, β -carotene significantly affected the structure and composition of gut microflora, increasing the abundance of Roseburia , Parasutterella and Lachnospiraceae, and decreasing the abundance of Dialister , Collinsella and Enterobacter ( P < 0.05). This study provides a new way to understand how β -carotene works in human body with gut microflora.
研究领域:
营养学
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微生物学
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胃肠病学
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DOI
高影响因子
PLoS Neglected Tropical Diseases
·
2025
·Vol. 19
·期 1
·e0012769
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IF 3.4
Wenmin Qi,Fei Shen,Chuyue Wang,Juan Wen,Xi Pan,Zhongying Zhao,Lihua Xiao,Yaoyu Feng,Dongjuan Yuan
Fatty acid and retinol binding proteins (FARs) are lipid-binding protein that may be associated with modulating nematode pathogenicity to their hosts. However, the functional mechanism of FARs remains elusive. We attempt to study the function of a certain FAR that may be important in the development of Nippostrongylus brasiliensis . Nb -FAR-1 was highly expressed throughout developmental stages by RNA-seq data and qPCR analyses, and Nb -FAR-1 was a secretory protein and abundant in the excretory-secretory products. Nb -FAR-1 could bind fatty acids and retinol. Fatty acid pattern of parasitic adults was more similar to rat intestine than to free-living L3s, indicating that N . brasiliensis may be dependent on the host to obtain fatty acids. Lentivirus-mediated RNAi was performed on L3s, resulting in a reduction in the expression of Nb - far-1 gene. Furthermore, these RNAi effects could be maintained in several generations. The offspring L3s in Nb - far-1 RNAi group had a reduction in lipid droplets within the subcuticle and the swelling of the perioral epidermis, accompanied with down-regulated expression of enzymes in amino acid and glycerolipid metabolism and glycometabolism for growth by RNA-seq data. Adults in Nb - far-1 RNAi group had the crumpled epidermis loosely attached to the basal membrane of body surface and the breakage of mouth epidermis, accompanied with a decrease in adult egg-shedding and an appearance of abnormal eggs. In vitro culture of eggs showed decreased efficiency of egg hatchability and larval development in the Nb - far-1 RNAi group. Transcriptomic analysis showed that interference with Nb - far-1 expression induced downregulated expression of major sperm protein and serpin for reproduction, and collagen for epidermis formation in adults, most of which were relatively high expression in adults but low expression in L3s in the WT group. Thus, Nb -FAR-1 may affect the reproduction, growth, and development of N . brasiliensis by regulating the level of lipids.
Fatty acid and retinol-binding protein 1 (FAR-1) is lipid-binding protein that may be associated with modulation of host immune responses and provide insights into nematode pathogenicity to their hosts. However, the role of FAR-1 protein on parasitic nematodes remains unclear. Nippostrongylus brasiliensis was employed to identify the characteristics of Nb - far-1 gene, its expression patterns, ligand binding properties and the functions associated with it. The secretory Nb -FAR-1 protein was found to be highly expressed in N . brasiliensis ESPs and demonstrated affinity for fatty acids and retinol. Interference with Nb - far-1 gene expression resulted in a reduction in the formation of lipid droplets in L3s, a decrease in a rate of adult egg-shedding, egg hatchability, and larval development. Therefore, we proposed that N . brasiliensis Nb -FAR-1 protein may serve as a causative agent in nematode growth, development, and reproduction by regulating the level of lipids.
研究领域:
寄生虫学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2023
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IF 14
Jinsheng Huang,Huiling Huang,Yiyao Wang,Bin Xu,Minzhao Lin,Shisong Han,Yuanyuan Yuan,Yong Wang,Xintao Shuai
Activated hepatic stellate cell (aHSC) is mainly responsible for deposition of extracellular collagen matrix that causes liver fibrosis. Although several siRNAs adequately inhibited HSC activation in vitro, they were demonstrated poor RNAi efficiency in vivo. Developing HSC-targeting and cytoplasmic delivery nanocarrier is highly essential to acquire a desirable siRNA therapeutic index for anti-liver fibrosis. Here, we developed a unique crosslinking nanopolyplex (called T-C-siRNA) modified by vitamin A (VA) with the well-designed natures, including the negative charge, retinol-binding protein (RBP) hijacking, and cytoplasmic siRNA release in response to ROS and cis diol molecules. The nanopolyplex was given a yolk-shell-like shape, camouflage ability in blood, and HSC-targeting capability by hijacking the endogenous ligand RBP via surface VA. PDGFR- β siRNA (siPDGFR- β ) supplied via T-C-siPDGFR- β nanopolyplex dramatically reduced HSC activation and its production of pro-fibrogenic proteins in vitro and in vivo. Furthermore, T-C-siPDGFR- β nanopolyplex effectively alleviated CCl 4 -induced liver injury, decreased hepatic collagen sediment, and recovered liver function in mice. This study provides a sophisticated method for HSC-targeting cytoplasmic RNA delivery using endogenous ligand hijacking and dual sensitivity of ROS and cis diol compounds.
研究领域:
药学
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分子生物学
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纳米技术
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肝病学
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2023
·
IF 8.8
Lili Yin,Kunpeng Gao,Xiangzhao Mao,Yang Hu
Lipase B from Candida antarctica (CALB) plays a prominent role as a biocatalyst in several industries, especially for biphasic conversion of functional lipids. Herein, an amphiphilic Janus halloysite nanosheet (JHNS) was fabricated and employed simultaneously as a solid surfactant for stabilizing Pickering emulsion and as a carrier for immobilizing CALB, with the aim to realize highly efficient biphasic bioconversion. The obtained JHNS could stabilize Pickering emulsion for at least 7 days. Immobilization of CALB on JHNS improved the substrate affinity, catalytic efficiency, thermal stability, and alkaline tolerance of the enzyme. Moreover, JHNS-based immobilized CALB was exploited as a biocatalytic platform for the conversion of retinyl acetate, with almost twice increase in conversion efficiency. Taken together, the JHNS-based immobilized CALB paves the way for the design of efficient biphasic conversion system for the production of added-value lipids.
研究领域:
生物技术
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化学工程
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材料科学
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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）