Shi H

References (44)

Title : Smartphone-assisted colorimetric biosensor for the determination of organophosphorus pesticides on the peel of fruits - Li_2024_Food.Chem_443_138459
Author(s) : Li D , Li J , Wu C , Liu H , Zhao M , Shi H , Zhang Y , Wang T
Ref : Food Chem , 443 :138459 , 2024
Abstract : Nowadays, the widespread use of organophosphorus pesticides (OPs) in agricultural production leads to varying degrees of residues in crops, which pose a potential threat to human health. Conventional methods used in national standard for the detection of OPs in fruits and vegetables require expensive instruments or cumbersome sample pretreatment steps for the analysis. To address these challenges, in this work, we took advantage of the peroxidase-like activity of PtCu(3) alloy nanocrystals (NCs) for a colorimetric and smartphone assisted sensitive detection of OPs. With the assist of a smartphone, the concentration of OPs on the peel of fruits could be obtained by comparing the B/RG value (the brightness value of blue divided by those of red and green) of a test strip with a calibration curve. This work not only provides a facile and cost-effective method to detect pesticides but also makes a positive contribution to food safety warning.
ESTHER : Li_2024_Food.Chem_443_138459
PubMedSearch : Li_2024_Food.Chem_443_138459
PubMedID: 38306911

Title : Depletion of ApoA5 aggravates spontaneous and diet-induced nonalcoholic fatty liver disease by reducing hepatic NR1D1 in hamsters - Guo_2024_Theranostics_14_2036
Author(s) : Guo J , Miao G , Zhang W , Shi H , Lai P , Xu Y , Zhang L , Chen G , Han Y , Zhao Y , Liu G , Wang Y , Huang W , Xian X
Ref : Theranostics , 14 :2036 , 2024
Abstract : Background: ApoA5 mainly synthesized and secreted by liver is a key modulator of lipoprotein lipase (LPL) activity and triglyceride-rich lipoproteins (TRLs). Although the role of ApoA5 in extrahepatic triglyceride (TG) metabolism in circulation has been well documented, the relationship between ApoA5 and nonalcoholic fatty liver disease (NAFLD) remains incompletely understood and the underlying molecular mechanism still needs to be elucidated. Methods: We used CRISPR/Cas9 gene editing to delete Apoa5 gene from Syrian golden hamster, a small rodent model replicating human metabolic features. Then, the ApoA5-deficient (ApoA5(-/-)) hamsters were used to investigate NAFLD with or without challenging a high fat diet (HFD). Results: ApoA5(-/-) hamsters exhibited hypertriglyceridemia (HTG) with markedly elevated TG levels at 2300 mg/dL and hepatic steatosis on a regular chow diet, accompanied with an increase in the expression levels of genes regulating lipolysis and small adipocytes in the adipose tissue. An HFD challenge predisposed ApoA5(-/-) hamsters to severe HTG (sHTG) and nonalcoholic steatohepatitis (NASH). Mechanistic studies in vitro and in vivo revealed that targeting ApoA5 disrupted NR1D1 mRNA stability in the HepG2 cells and the liver to reduce both mRNA and protein levels of NR1D1, respectively. Overexpression of human NR1D1 by adeno-associated virus 8 (AAV8) in the livers of ApoA5(-/-) hamsters significantly ameliorated fatty liver without affecting plasma lipid levels. Moreover, restoration of hepatic ApoA5 or activation of UCP1 in brown adipose tissue (BAT) by cold exposure or CL316243 administration could significantly correct sHTG and hepatic steatosis in ApoA5(-/-) hamsters. Conclusions: Our data demonstrate that HTG caused by ApoA5 deficiency in hamsters is sufficient to elicit hepatic steatosis and HFD aggravates NAFLD by reducing hepatic NR1D1 mRNA and protein levels, which provides a mechanistic link between ApoA5 and NAFLD and suggests the new insights into the potential therapeutic approaches for the treatment of HTG and the related disorders due to ApoA5 deficiency in the clinical trials in future.
ESTHER : Guo_2024_Theranostics_14_2036
PubMedSearch : Guo_2024_Theranostics_14_2036
PubMedID: 38505614

Title : Hepatocyte-specific disruption of soluble epoxide hydrolase attenuates abdominal aortic aneurysm formation: novel role of the liver in aneurysm pathogenesis - Kim_2023_bioRxiv__
Author(s) : Kim D , Horimatsu T , Ogbi M , Goo B , Shi H , Veerapaneni P , Chouhaita R , Moses M , Prasad R , Benson TW , Harb R , Aboud G , Seller H , Haigh S , Fulton DJ , Csanyi G , Huo Y , Long X , Coffey P , Lee R , Guha A , Zeldin D , Hwang SH , Hammock BD , Weintraub NL , Kim HW
Ref : Biorxiv , : , 2023
Abstract : INTRODUCTION: Inflammation is a key pathogenic feature of abdominal aortic aneurysm (AAA). Soluble epoxide hydrolase (sEH) is a pro-inflammatory enzyme that converts cytochrome P450-derived epoxides of fatty acids to the corresponding diols, and pharmacological inhibition of sEH prevented AAA formation. Both cytochrome P450 enzymes and sEH are highly expressed in the liver. Here, we investigated the role of hepatic sEH in AAA using a selective pharmacological inhibitor of sEH and hepatocyte-specific Ephx2 (which encodes sEH gene) knockout (KO) mice in two models of AAA [angiotensin II (AngII) infusion and calcium chloride (CaCl (2) ) application]. METHODS AND RESULTS: sEH expression and activity were strikingly higher in mouse liver compared with aorta and further increased the context of AAA, in conjunction with elevated expression of the transcription factor Sp1 and the epigenetic regulator Jarid1b, which have been reported to positively regulate sEH expression. Pharmacological sEH inhibition, or liver-specific sEH disruption, achieved by crossing sEH floxed mice with albumin-cre mice, prevented AAA formation in both models, concomitant with reduced expression of hepatic sEH as well as complement factor 3 (C3) and serum amyloid A (SAA), liver-derived factors linked to AAA formation. Moreover, sEH antagonism markedly reduced C3 and SAA protein accumulation in the aortic wall. Co-incubation of liver ex vivo with aneurysm-prone aorta resulted in induction of sEH in the liver, concomitant with upregulation of Sp1, Jarid1b, C3 and SAA gene expression, suggesting that the aneurysm-prone aorta secretes factors that activate sEH and downstream inflammatory signaling in the liver. Using an unbiased proteomic approach, we identified a number of dysregulated proteins [ e.g., plastin-2, galectin-3 (gal-3), cathepsin S] released by aneurysm-prone aorta as potential candidate mediators of hepatic sEH induction. CONCLUSION: We provide the first direct evidence of the liver's role in orchestrating AAA via the enzyme sEH. These findings not only provide novel insight into AAA pathogenesis, but they have potentially important implications with regard to developing effective medical therapies for AAA.
ESTHER : Kim_2023_bioRxiv__
PubMedSearch : Kim_2023_bioRxiv__
PubMedID: 37503031

Title : Multi-compartmental MOF microreactors derived from Pickering double emulsions for chemo-enzymatic cascade catalysis - Tian_2023_Nat.Commun_14_3226
Author(s) : Tian D , Hao R , Zhang X , Shi H , Wang Y , Liang L , Liu H , Yang H
Ref : Nat Commun , 14 :3226 , 2023
Abstract : Bioinspired multi-compartment architectures are desired in synthetic biology and metabolic engineering, as credited by their cell-like structures and intrinsic ability of assembling catalytic species for spatiotemporal control over cascade reactions like in living systems. Herein, we describe a general Pickering double emulsion-directed interfacial synthesis method for the fabrication of multicompartmental MOF microreactors. This approach employs multiple liquid-liquid interfaces as a controllable platform for the self-completing growth of dense MOF layers, enabling the microreactor with tailor-made inner architectures and selective permeability. Importantly, simultaneous encapsulation of incompatible functionalities, including hydrophilic enzyme and hydrophobic molecular catalyst, can be realized in a single MOF microreactor for operating chemo-enzymatic cascade reactions. As exemplified by the Grubb' catalyst/CALB lipase driven olefin metathesis/ transesterification cascade reaction and glucose oxidase (GOx)/Fe-porphyrin catalyzed oxidation reaction, the multicompartmental microreactor exhibits 2.24-5.81 folds enhancement in cascade reaction efficiency in comparison to the homogeneous counterparts or physical mixture of individual analogues, due to the restrained mutual inactivation and substrate channelling effects. Our study prompts further design of multicompartment systems and the development of artificial cells capable of complex cellular transformations.
ESTHER : Tian_2023_Nat.Commun_14_3226
PubMedSearch : Tian_2023_Nat.Commun_14_3226
PubMedID: 37270555

Title : Artificial Intelligence Aided Lipase Production and Engineering for Enzymatic Performance Improvement - Ge_2023_J.Agric.Food.Chem__
Author(s) : Ge F , Chen G , Qian M , Xu C , Liu J , Cao J , Li X , Hu D , Xu Y , Xin Y , Wang D , Zhou J , Shi H , Tan Z
Ref : Journal of Agricultural and Food Chemistry , : , 2023
Abstract : With the development of artificial intelligence (AI), tailoring methods for enzyme engineering have been widely expanded. Additional protocols based on optimized network models have been used to predict and optimize lipase production as well as properties, namely, catalytic activity, stability, and substrate specificity. Here, different network models and algorithms for the prediction and reforming of lipase, focusing on its modification methods and cases based on AI, are reviewed in terms of both their advantages and disadvantages. Different neural networks coupled with various algorithms are usually applied to predict the maximum yield of lipase by optimizing the external cultivations for lipase production, while one part is used to predict the molecule variations affecting the properties of lipase. However, few studies have directly utilized AI to engineer lipase by affecting the structure of the enzyme, and a set of research gaps needs to be explored. Additionally, future perspectives of AI application in enzymes, including lipase engineering, are deduced to help the redesign of enzymes and the reform of new functional biocatalysts. This review provides a new horizon for developing effective and innovative AI tools for lipase production and engineering and facilitating lipase applications in the food industry and biomass conversion.
ESTHER : Ge_2023_J.Agric.Food.Chem__
PubMedSearch : Ge_2023_J.Agric.Food.Chem__
PubMedID: 37800676

Title : Uncovering the interactions between PME and PMEI at the gene and protein levels: Implications for the design of specific PMEI - Wang_2023_J.Mol.Model_29_286
Author(s) : Wang Y , Zhang D , Huang L , Zhang Z , Shi Q , Hu J , He G , Guo X , Shi H , Liang L
Ref : J Mol Model , 29 :286 , 2023
Abstract : CONTEXT: Pectin methylesterase inhibitor (PMEI) can specifically bind and inhibit the activity of pectin methylesterase (PME), which has been widely used in fruit and vegetable juice processing. However, the limited three-dimensional structure, unclear action mechanism, low thermal stability and biological activity of PMEI severely limited its application. In this work, molecular recognition and conformational changes of PME and PMEI were analyzed by various molecular simulation methods. Then suggestions were proposed for improving thermal stability and affinity maturation of PMEI through semi-rational design. METHODS: Phylogenetic trees of PME and PMEI were established using the Maximum likelihood (ML) method. The results show that PME and PMEI have good sequence and structure conservation in various plants, and the simulated data can be widely adopted. In this work, MD simulations were performed using AMBER20 package and ff14SB force field. Protein interaction analysis indicates that H-bonds, van der Waals forces, and the salt bridge formed of K224 with ID116 are the main driving forces for mutual molecular recognition of PME and PMEI. According to the analyses of free energy landscape (FEL), conformational cluster, and motion, the association with PMEI greatly disrupts PME's dispersed functional motion mode and biological function. By monitoring the changes of residue contact number and binding free energy, (I)G35M/ (I)G35R: (I)T93F and (I)T113W/ (I)T113W: (I)D116W mutations contribute to thermal stability and affinity maturation of the PME-PMEI complex system, respectively. This work reveals the interaction between PME and PMEI at the gene and protein levels and provides options for modifying specific PMEI.
ESTHER : Wang_2023_J.Mol.Model_29_286
PubMedSearch : Wang_2023_J.Mol.Model_29_286
PubMedID: 37610510

Title : Study on the active ingredients of Shenghui decoction inhibiting acetylcholinesterase based on molecular docking and molecular dynamics simulation - Li_2023_Medicine.(Baltimore)_102_e34909
Author(s) : Li Z , Shi H
Ref : Medicine (Baltimore) , 102 :e34909 , 2023
Abstract : We aim to investigate the mechanism and effective components of Shenghui decoction (SHD), which has been shown to inhibit acetylcholinesterase (AChE) through molecular docking (MD) and molecular dynamics simulation (MDS). The effective ingredients in SHD were collected through the TCMSP database and literature review. All components were docked with AChE using CDOCKER. Receptor ligand interaction analysis was performed for the optimal ligand. Two simulation models (model I and II) containing AChE and acetylcholine (ACh) were constructed, in which model II contained the best-docked ligand. Perform 90ns MDS on 2 models. After the simulation, the distance between ACh and AChE peripheral active sites were calculated in both models. The root mean square deviation (RMSD) curve of ligand and receptor, the radius of gyration (Rog) of the receptor, the distance between ligand center and binding site center, and the binding energy of ligand and receptor were calculated in model II. 98 ingredients of SHD were collected, and the best ligand was Tumulosic acid. The residues that form conventional hydrogen bonds between AChE and Tumulosic acid include Tyr132 and Glu201. MDS revealed that ACh could bind to AChE active site in model I. In model II, ACh cannot bind to the binding cavity because the ligand occupies the active site. The RMSD of AChE and Tumulosic acid tends to be stable, the Rog curve of AChE is relatively stable, and the distance between ligand and binding cavity does not fluctuate greatly, indicating that the structure of receptor and ligand is relatively stable. The binding energy of AChE and Tumulosic acid was -24.14 +/- 2.46 kcal/mol. SHD contains many effective ingredients that may inhibit AChE activity. Tumulosic acid can occupy the binding site to prevent ACh from entering the chemical domain, thus exerting AChE inhibitory effect.
ESTHER : Li_2023_Medicine.(Baltimore)_102_e34909
PubMedSearch : Li_2023_Medicine.(Baltimore)_102_e34909
PubMedID: 37746985

Title : A versatile biomimetic multienzyme cascade nanoplatform based on boronic acid-modified metal-organic framework for colorimetric biosensing - Shen_2022_J.Mater.Chem.B__
Author(s) : Shen H , Shi H , Feng B , Ding C , Yu S
Ref : J Mater Chem B , : , 2022
Abstract : The combination of bio- and chemo-catalysts for sequential cascades has received considerable attention in analytical fields because of the regulable catalytic efficiency and selectivity under various physiological conditions. In this paper, a versatile multienzyme cascade nanoplatform with excellent activity for biosensing is demonstrated by combining metal-organic framework (MOF)-based nanozyme with natural enzymes. A boronic acid-modified MOF, MIL-100(Fe)-BA, was obtained via a microwave-assisted metal-ligand-fragment co-assembly strategy. On the one hand, MIL-100(Fe)-BA could serve as a nanozyme with dual oxidase/peroxidase bioactivity to detect glutathione and ascorbic acid with a detection limit of 0.12 microM and 0.09 microM, respectively. On the other hand, the hierarchically porous MIL-100(Fe)-BA possesses adequate recognition sites for immobilizing enzymes with acceptable protein leakage, enabling it to act like a scaffold for the fixation of a single enzyme (sarcosine oxidase) or bi-enzymes (acetylcholinesterase/choline oxidase) and guide a multienzyme cascade reaction system with high efficiency. The cascade nanoplatform has merits of both artificial nanozymes and natural enzymes, providing satisfactory sarcosine/acetylcholine sensing ability with detection limits of 0.26 microM and 1.18 microM. The developed catalytic system not only expands the application of nanozymes in tandem enzymatic bio-catalysis, but provides a facile and efficient multienzyme cascade nanoplatform for biosensing and other applications.
ESTHER : Shen_2022_J.Mater.Chem.B__
PubMedSearch : Shen_2022_J.Mater.Chem.B__
PubMedID: 35394481

Title : Enhancing the methanol tolerance of Candida antarctica lipase B by saturation mutagenesis for biodiesel preparation - Tan_2022_3.Biotech_12_22
Author(s) : Tan Z , Li X , Shi H , Yin X , Zhu X , Bilal M , Onchari MM
Ref : 3 Biotech , 12 :22 , 2022
Abstract : Methanol tolerance of lipase is one of the important factors affecting its esterification ability in biodiesel preparation. By B factor indicated prediction of Candida antarctica lipase B (CalB) surface amino acids, eight sites (Val(139), Ala(146), Leu(147), Pro(218), Val(286), Ala(287), Val(306), and Gly(307)) with high B value indicating more flexibility were chosen to perform saturation mutagenesis. High-methanol-tolerant variants, CalB-P218W and -V306N, created larger haloes on emulsified tributyrin solid plate including 15% (v/v) methanol and showed 19% and 31% higher activity over wild-type CalB (CalB-WT), respectively. By modeling, a newly formed hydrogen bond in CalB-V306N and hydrophobic force in CalB-P218W contributing more stability in protein may have resulted in increased methanol tolerance. CalB-P218W and -V306N transesterified the soybean oil into biodiesel at 30 degreesC by 85% and 89% yield, respectively, over 82% by CalB-WT for 24 h reactions. These results may provide a basis for molecular engineering of CalB and expand its applications in fuel industries. The as-developed semi-rational method could be utilized to enhance the stabilities of many other industrial enzymes.
ESTHER : Tan_2022_3.Biotech_12_22
PubMedSearch : Tan_2022_3.Biotech_12_22
PubMedID: 35036270

Title : Novel pathogenic variant combination in LPL causing familial chylomicronemia syndrome in an Asian family and experimental validation in vitro: a case report - Shi_2022_Transl.Pediatr_11_1717
Author(s) : Shi H , Wang Z
Ref : Transl Pediatr , 11 :1717 , 2022
Abstract : BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder, typically caused by biallelic pathogenic variants in the lipoprotein lipase (LPL) gene. Lipoprotein lipase, encoded by the LPL gene, catalyzes the hydrolysis of triglycerides, and its deficiency or dysfunction can lead to chylomicronemia and potentially fatal recurrent acute pancreatitis. CASE DESCRIPTION: Here, we report an Asian child with FCS due to compound heterozygous LPL variants. The 4-year-old patient presented with splenomegaly and severe hypertriglyceridemia, specifically chylomicronemia which resulted in abnormal coagulation measured by a turbidity-based assay. Based on the clinical features and family history, the diagnosis of FCS was suspected, and confirmed by the identification of compound heterozygous variants in the LPL gene (c.461A>G; p.His154Arg and c.788T>A; p.Leu263Gln) in the patient, inheriting one from each parent. According to the clinical and genetic findings, the patient was diagnosed with FCS. In vitro experimental validation found that the LPL p.H154R variant reduced the expression of lipoprotein lipase and decreased its lipolytic activity, while the LPL p.L263Q variant mainly impaired its lipolytic activity. CONCLUSIONS: FCS was molecularly diagnosed using whole exome sequencing in the case presented. When interpreting abnormal coagulation profiles measured by turbidity-based assay, the possibility of lipemic blood (or chylomicronemia) should be considered and the presence of this phenomenon might indicate the diagnosis of FCS. In vitro experiments showed that the two LPL variants impaired lipoprotein lipase expression and/or function making them likely to be pathogenic.
ESTHER : Shi_2022_Transl.Pediatr_11_1717
PubMedSearch : Shi_2022_Transl.Pediatr_11_1717
PubMedID: 36345447
Gene_locus related to this paper: human-LPL

Title : Traditional Chinese medicine promotes the control and treatment of dementia - Tao_2022_Front.Pharmacol_13_1015966
Author(s) : Tao P , Xu W , Gu S , Shi H , Wang Q , Xu Y
Ref : Front Pharmacol , 13 :1015966 , 2022
Abstract : Dementia is a syndrome that impairs learning and memory. To date, there is no effective therapy for dementia. Current prescription drugs, such as cholinesterase inhibitors, fail to improve the condition of dementia and are often accompanied by severe adverse effects. In recent years, the number of studies into the use of traditional Chinese medicine (TCM) for dementia treatment has increased, revealing a formula that could significantly improve memory and cognitive dysfunctions in animal models. TCM showed fewer adverse effects, lower costs, and improved suitability for long-term use compared with currently prescribed drugs. Due to the complexity of ingredients and variations in bioactivity of herbal medicines, the multi-target nature of the traditional Chinese formula affected the outcome of dementia therapy. Innovations in TCM will create a platform for the development of new drugs for the prevention and treatment of dementia, further strengthening and enhancing the current influence of TCM.
ESTHER : Tao_2022_Front.Pharmacol_13_1015966
PubMedSearch : Tao_2022_Front.Pharmacol_13_1015966
PubMedID: 36304171

Title : Behavioral, histopathological, genetic, and organism-wide responses to phenanthrene-induced oxidative stress in Eisenia fetida earthworms in natural soil microcosms - He_2022_Environ.Sci.Pollut.Res.Int__
Author(s) : He F , Yu H , Shi H , Li X , Chu S , Huo C , Liu R
Ref : Environ Sci Pollut Res Int , : , 2022
Abstract : Phenanthrene (PHE) contamination not only changes the quality of soil environment but also threatens to the soil organisms. There is lack of focus on the eco-toxicity potential of this contaminant in real soil in the current investigation. Here, we assessed the toxic effects of PHE on earthworms (Eisenia fetida) in natural soil matrix. PHE exhibited a relatively high toxicity to E. fetida in natural soil, with the LC(50) determined to be 56.68 mg kg(-1) after a 14-day exposure. Excessive ROS induced by PHE, leading to oxidative damage to biomacromolecules in E. fetida, including lipid peroxidation, protein carbonylation, and DNA damage. The antioxidant defense system (total antioxidant capacity, glutathione S-transferase, peroxidase, catalase, carboxylesterase, and superoxide dismutase) in E. fetida responded quickly to scavenge excess ROS and free radicals. Exposure to PHE resulted in earthworm avoidance responses (2.5 mg kg(-1)) and habitat function loss (10 mg kg(-1)). Histological observations indicated that the intestine, body wall, and seminal vesicle in E. fetida were severely damaged after exposure to high-dose PHE. Moreover, earthworm growth (weight change) and reproduction (cocoon production and the number of juvenile) were also inhibited after exposure to this pollutant. Furthermore, the integrated toxicity of PHE toward E. fetida at different doses and exposure times was assessed by the integrated biomarker response (IBR), which confirmed that PHE is more toxic to earthworms in the high-dose and long-term exposure groups. Our results showed that PHE exposure induced oxidative stress, disturbed antioxidant defense system, and caused oxidative damage in E. fetida. These effects can trigger behavior changes and damage histological structure, finally cause growth inhibition, genotoxicity, and reproductive toxicity in earthworms. The strength of this study is the comprehensive toxicity evaluation of PHE to earthworms and highlights the need to investigate the eco-toxicity potential of exogenous environmental pollutants in a real soil environment.
ESTHER : He_2022_Environ.Sci.Pollut.Res.Int__
PubMedSearch : He_2022_Environ.Sci.Pollut.Res.Int__
PubMedID: 35113383

Title : Enantioselective Metabolic Mechanism and Metabolism Pathway of Pydiflumetofen in Rat Liver Microsomes: In Vitro and In Silico Study - Wang_2022_J.Agric.Food.Chem_70_2520
Author(s) : Wang Z , Li R , Wu Q , Duan J , Tan Y , Sun X , Chen R , Shi H , Wang M
Ref : Journal of Agricultural and Food Chemistry , 70 :2520 , 2022
Abstract : Pydiflumetofen (PYD) has been used worldwide. However, the enantioselective fate of PYD within mammals is not clear. Thus, the enantioselective metabolism and its potential mechanisms of PYD were explored via in vitro and in silico. Consistent results were observed between metabolism and enzyme kinetics experiments, with S-PYD metabolizing faster than R-PYD in rat liver microsomes. Moreover, CYP3A1 and carboxylesterase 1 were found to be major enzymes participating in the metabolism of PYD. Based on the computational results, S-PYD bound with CYP3A1 and carboxylesterase 1 more tightly with lower binding free energy than R-PYD, explaining the mechanism of enantioselective metabolism. Nine phase I metabolites of PYD were identified, and metabolic pathways of PYD were speculated. This study is the first to clarify the metabolism of PYD in mammals, and further research to evaluate the toxicological implications of these metabolites will help in assessing the risk of PYD.
ESTHER : Wang_2022_J.Agric.Food.Chem_70_2520
PubMedSearch : Wang_2022_J.Agric.Food.Chem_70_2520
PubMedID: 35184556

Title : Digging and identification of novel microorganisms from the soil environments with high methanol-tolerant lipase production for biodiesel preparation - Tan_2022_Environ.Res_212_113570
Author(s) : Tan Z , Chen G , Zhao Y , Shi H , Wang S , Bilal M , Li D , Li X
Ref : Environ Research , 212 :113570 , 2022
Abstract : Converting renewable biomass into carbon-neutral biofuels is one of the most effective strategies to achieve zero carbon emissions and contribute to environmental protection. Microorganisms from the soil were primarily screened on the rhodamine B-plate for highly-active lipase producing strains and re-screened on a tributyrin-methanol plate using crude lipases produced from the initially screened-out strains. The lipase-producing strains with higher methanol-tolerant lipase were identified based on morphological characteristics and 16S rDNA sequencing. The crude lipases with much higher methanol-tolerance from screened top-4 strains, Stenotrophomonas maltophilia D18, Lysinibacillus fusiformis B23, Acinetobacter junii C69, and A. pittii C95 showed temperature optima of 25 degreesC, 35 degreesC, 30 degreesC, and 30 degreesC at pH 7.0, respectively, while their pH optima were 8.0, 7.0, 7.5, and 7.5 at each optimum temperature, respectively. After 24-h incubation, they retained more than 85% of their original activities in 25%, 15%, 20%, and 20% of methanol, respectively. They catalyzed the conversion of soybean oil into biodiesel by yields of 63.1%, 35.4%, 74.6%, and 78.5% after 24-h reactions, respectively. In conclusion, the as-isolated microorganisms producing high methanol-tolerant lipase are considered promising to provide robust biocatalyst for efficient biodiesel preparation and other industrial applications.
ESTHER : Tan_2022_Environ.Res_212_113570
PubMedSearch : Tan_2022_Environ.Res_212_113570
PubMedID: 35671798

Title : Enantioselective disposition and metabolic products of isofenphos-methyl in rats and the hepatotoxic effects - Gao_2020_Environ.Int_143_105940
Author(s) : Gao B , Zhao S , Shi H , Zhang Z , Li L , He Z , Wen Y , Covaci A , Wang M
Ref : Environ Int , 143 :105940 , 2020
Abstract : Isofenphos-methyl (IFP), a chiral organophosphorus pesticide, is one of the main chemicals used to control underground insects and nematodes. Recently, the use of IFP on vegetables and fruits has been prohibited due to its high toxicity. In this study, we investigated the enantioselective distribution and metabolism of IFP and its metabolites, namely, isofenphos-methyl oxon (IFPO) and isocarbophos oxon (ICPO), in male Sprague Dawley (SD) rats. Forty eight hours (48 h) after exposure, ICPO was the main detectable compound in blood (up to 75%) and urine (up to 77%), and we found that (S)-ICPO was significantly more stable than (R)-ICPO (p < 0.05). Therefore, (S)-ICPO was proposed as a suitable candidate biomarker for the biomonitoring of IFP in human urine and blood. After 48 h exposure, 21.2-41.0%, 4.1-15.1%, and 8.6-18.7% of dosed IFP was detected in the liver of racemic, R and S enantiomer-exposed rats, respectively, and R-IFP and R-IFPO showed a faster degradation (p < 0.05). Our results showed that after one week of consecutive exposure to IFP, ICPO was accumulated in the liver of rats in both racemic and enantiopure groups (no difference between the groups, p > 0.05). We found that cytochrome P450 (CYP) (i.e. CYP2C11, CYP2D2 and CYP3A2 enzymes and carboxylesterases) is responsible for the enantioselective metabolism of IFP in liver. In addition, rats exposed to (S)-IFP exhibited hepatic lipid peroxidation, liver inflammation and hepatic fibrosis. This study provides useful information and a reference for the biomonitoring and risk assessment of IFP and organophosphorus pesticide exposure.
ESTHER : Gao_2020_Environ.Int_143_105940
PubMedSearch : Gao_2020_Environ.Int_143_105940
PubMedID: 32663714

Title : Effects of ammonia exposure on antioxidant function, immune response and NF-kappaB pathway in Chinese Strip-necked Turtle (Mauremys sinensis) - Liang_2020_Aquat.Toxicol__105621
Author(s) : Liang L , Huang Z , Li N , Wang D , Ding L , Shi H , Hong M
Ref : Aquat Toxicol , :105621 , 2020
Abstract : As one of the main toxic substances in aquaculture water, ammonia causes seriously physiological harm to aquatic animals. In order to investigate the effects of ammonia exposure on the antioxidant defense, immune response, and NF-kappaB signaling pathway in Chinese Strip-necked Turtle (Mauremys sinensis), we designed two experimental groups (control and 6.45 mM ammonia), and sampled at 6 h, 24 h, 48 h, re 24 h (recover 24 h), and re 48 h. The results showed that the blood ammonia (BA) content was significantly increased when the turtles were subjected to ammonia, and the activities of cholinesterase (CHE) and aspartate aminotransferase (AST) in the serum also showed a significant upward trend. The malondialdehyde (MDA) content continuously increased during ammonia exposure, and more than doubled at 48 h compared with the control group. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) and their corresponding relative mRNA expression levels in the liver during ammonia exposure were obviously increased when compared to the control group, but most decreased to the normal levels at re 48 h. In addition, the relative mRNA and protein expression levels of NF-E2 related factor 2 (Nrf2) showed similar up-regulation patterns to antioxidase during ammonia exposed periods; whereas kelch-like ECH-binding protein 1 (Keap1), as Nrf2 negative regulator, showed opposite patterns. Moreover, the relative mRNA expression levels of heat shock proteins (HSP70, HSP90) significantly elevated upon the exposure of ammonia. Furthermore, ammonia increased the relative mRNA and protein expression levels of p50 and p65 at different exposed times. The reative mRNA expression levels of immune cytokines (BAFF and IL-6) were upregulated during ammonia exposured time, while there was a decline but did not return to normal levels, in the recovery periods. Taken together, these results indicated that antioxidation, immunity, and NF-kappaB signaling played a certain protective role for Mauremys sinensis under ammonia exposure. Our results will be helpful to understand the mechanism of aquatic toxicology induced by ammonia in turtles.
ESTHER : Liang_2020_Aquat.Toxicol__105621
PubMedSearch : Liang_2020_Aquat.Toxicol__105621
PubMedID: 33129562

Title : Western diet induces severe nonalcoholic steatohepatitis, ductular reaction, and hepatic fibrosis in liver CGI-58 knockout mice - Yang_2020_Sci.Rep_10_4701
Author(s) : Yang P , Wang Y , Tang W , Sun W , Ma Y , Lin S , Jing J , Jiang L , Shi H , Song Z , Yu L
Ref : Sci Rep , 10 :4701 , 2020
Abstract : Humans and rodents with Comparative Gene Identification-58 (CGI-58) mutations manifest nonalcoholic fatty liver disease (NAFLD). Here we show that liver CGI-58 knockout (LivKO) mice fed a Western diet rapidly develop advanced NAFLD, including nonalcoholic steatohepatitis (NASH) and hepatic fibrosis. After 14 weeks of diet challenge, starting at 6 weeks of age, LivKO mice showed increased inflammatory cell infiltration and proinflammatory gene expression in the liver, which was associated with elevated plasma levels of aminotransferases. Hepatic ductular reactions, pericellular fibrosis, and bridging fibrosis were observed only in the LivKO mice. Consistently, the KO mice had a significant increase in hepatic mRNAs for fibrogenic genes. In addition, LivKO mice displayed massive accumulation of lipid droplets (LDs) in hepatocytes. LDs were also observed in the cholangiocytes of the LivKO mice, but not the floxed controls. Four of the five LD coat proteins, including perilipins 2, 3, 4, and 5, were increased in the CGI-58 KO liver. CRISPR/Cas9-mediated knockout of CGI-58 in Huh7 human hepatoma cells induced LD deposition and perilipin expression, suggesting a cell autonomous effect. Our findings establish the Western diet-fed LivKO mice as an animal model of NASH and hepatic fibrosis. These animals may facilitate preclinical screening of therapeutic agents that counter against NAFLD progression.
ESTHER : Yang_2020_Sci.Rep_10_4701
PubMedSearch : Yang_2020_Sci.Rep_10_4701
PubMedID: 32170127
Gene_locus related to this paper: human-ABHD5 , mouse-abhd5

Title : A potential biomarker of isofenphos-methyl in humans: A chiral view - Gao_2019_Environ.Int_127_694
Author(s) : Gao B , Zhao S , Zhang Z , Li L , Hu K , Kaziem AE , He Z , Hua X , Shi H , Wang M
Ref : Environ Int , 127 :694 , 2019
Abstract : Isofenphos-methyl (IFP) is a very active and persistent chiral insecticide. However, IFP has lower activity against acetylcholinesterases (AChEs). Previously, it was confirmed that phosphorothioate organophosphorus pesticides with N-alkyl (POPN) require activation by oxidative desulfuration and N-dealkylation. In this work, we demonstrated that IFP could be metabolized in human liver microsomes to isofenphos-methyl oxon (IFPO, 52.7%), isocarbophos (ICP, 14.2%) and isocarbophos oxon (ICPO, 11.2%). It was found that (R)-IFP was preferentially degraded compared to the (S)-enantiomer, and the enantiomeric fraction (EF) value reached 0.61 at 60min. However, (S)-enantiomers of the three metabolites, were degraded preferentially, and the EF values ranged from 0.34 to 0.45. Cytochrome P450 (CYP) isoforms CYP3A4, CYP2E1, and CYP1A2 and carboxylesterase enzyme have an essential role in the enantioselective metabolism of IFP; but, the enzymes that participate in the degradation of IFP metabolites are different. The AChE inhibition bioassay indicated that ICPO is the only effective inhibitor of AChE. The covalent molecular docking has proposed that the metabolites of IFP and its analogs after N-dealkylation and oxidative desulfuration will possess the highest inhibitory activity against AChE. This study is the first to demonstrate that ICPO can be regarded as a potential biomarker for the biomonitoring of IFP and ICP exposure in humans.
ESTHER : Gao_2019_Environ.Int_127_694
PubMedSearch : Gao_2019_Environ.Int_127_694
PubMedID: 30991225

Title : Proteomic and metabolomic responses in hepatopancreas of whiteleg shrimp Litopenaeus vannamei infected by microsporidian Enterocytozoon hepatopenaei - Ning_2019_Fish.Shellfish.Immunol_87_534
Author(s) : Ning M , Wei P , Shen H , Wan X , Jin M , Li X , Shi H , Qiao Y , Jiang G , Gu W , Wang W , Wang L , Meng Q
Ref : Fish Shellfish Immunol , 87 :534 , 2019
Abstract : Enterocytozoon hepatopenaei (EHP) causes hepatopancreatic microsporidiosis (HPM) in shrimp. HPM is not normally associated with shrimp mortality, but is associated with significant growth retardation. In this study, the responses induced by EHP were investigated in hepatopancreas of shrimp Litopenaeus vannamei using proteomics and metabolomics. Among differential proteins identified, several (e.g., peritrophin-44-like protein, alpha2 macroglobulin isoform 2, prophenoloxidase-activating enzymes, ferritin, Rab11A and cathepsin C) were related to pathogen infection and host immunity. Other proteomic biomarkers (i.e., farnesoic acid o-methyltransferase, juvenile hormone esterase-like carboxylesterase 1 and ecdysteroid-regulated protein) resulted in a growth hormone disorder that prevented the shrimp from molting. Both proteomic KEGG pathway (e.g., "Glycolysis/gluconeogenesis" and "Glyoxylate and dicarboxylate metabolism") and metabolomic KEGG pathway (e.g., "Galactose metabolism" and "Biosynthesis of unsaturated fatty acids") data indicated that energy metabolism pathway was down-regulated in the hepatopancreas when infected by EHP. More importantly, the changes of hormone regulation and energy metabolism could provide much-needed insight into the underlying mechanisms of stunted growth in shrimp after EHP infection. Altogether, this study demonstrated that proteomics and metabolomics could provide an insightful view into the effects of microsporidial infection in the shrimp L. vannamei.
ESTHER : Ning_2019_Fish.Shellfish.Immunol_87_534
PubMedSearch : Ning_2019_Fish.Shellfish.Immunol_87_534
PubMedID: 30721776

Title : Loss of Abhd5 Promotes Colorectal Tumor Development and Progression by Inducing Aerobic Glycolysis and Epithelial-Mesenchymal Transition -
Author(s) : Ou J , Miao H , Ma Y , Guo F , Deng J , Wei X , Zhou J , Xie G , Shi H , Xue B , Liang H , Yu L
Ref : Cell Rep , 24 :2795 , 2018
PubMedID: 30184511
Gene_locus related to this paper: human-ABHD5

Title : Characterization of two novel thermostable esterases from Thermoanaerobacterium thermosaccharolyticum - Li_2018_Protein.Expr.Purif_152_64
Author(s) : Li W , Shi H , Ding H , Wang L , Zhang Y , Li X , Wang F
Ref : Protein Expr Purif , 152 :64 , 2018
Abstract : This paper first describes characterization of two thermostable esterases (ThLip1 and ThLip2) from the thermophilic bacterium Thermoanaerobacterium thermosaccharolyticum DSM 571. The recombinant esterase ThLip1 was active at 80 degrees C, pH 6.5 and maintained approx. 85% of original activity after 2h incubation at 75 degrees C. Kinetic parameters, Km, Vmax and kcat/Km for 4-Nitrophenyl caprylate (pNPC) were 3.52+/-0.47mM, 191.18+/-1.82mumolmin(-1) mg(-1) and 20.80+/-0.07mM(-1)s(-1), respectively. The purified recombinant esterase ThLip2 was optimally active at pH 6.5 and 75 degrees C and it was stable against a pH range of 6.0-8.0 possessing 2h half-life at 80 degrees C. Kinetic experiments at 75 degrees C with pNPC as a substrate gave a Km of 3.37mM, Vmax of 578.14mumolmin(-1) mg(-1)and kcat of 231.2 s(-1). The hydrolysis of linalyl acetate were carried out using ThLip1 and ThLip2 as catalyst, affording linalool yields over 140mg/l in 10h.
ESTHER : Li_2018_Protein.Expr.Purif_152_64
PubMedSearch : Li_2018_Protein.Expr.Purif_152_64
PubMedID: 29684442

Title : In Vitro and in Vivo Evaluation of (11)C-Labeled Azetidinecarboxylates for Imaging Monoacylglycerol Lipase by PET Imaging Studies - Cheng_2018_J.Med.Chem_61_2278
Author(s) : Cheng R , Mori W , Ma L , Alhouayek M , Hatori A , Zhang Y , Ogasawara D , Yuan G , Chen Z , Zhang X , Shi H , Yamasaki T , Xie L , Kumata K , Fujinaga M , Nagai Y , Minamimoto T , Svensson M , Wang L , Du Y , Ondrechen MJ , Vasdev N , Cravatt BF , Fowler C , Zhang MR , Liang SH
Ref : Journal of Medicinal Chemistry , 61 :2278 , 2018
Abstract : Monoacylglycerol lipase (MAGL) is the principle enzyme for metabolizing endogenous cannabinoid ligand 2-arachidonoyglycerol (2-AG). Blockade of MAGL increases 2-AG levels, resulting in subsequent activation of the endocannabinoid system, and has emerged as a novel therapeutic strategy to treat drug addiction, inflammation, and neurodegenerative diseases. Herein we report a new series of MAGL inhibitors, which were radiolabeled by site-specific labeling technologies, including (11)C-carbonylation and spirocyclic iodonium ylide (SCIDY) radiofluorination. The lead compound [(11)C]10 (MAGL-0519) demonstrated high specific binding and selectivity in vitro and in vivo. We also observed unexpected washout kinetics with these irreversible radiotracers, in which in vivo evidence for turnover of the covalent residue was unveiled between MAGL and azetidine carboxylates. This work may lead to new directions for drug discovery and PET tracer development based on azetidine carboxylate inhibitor scaffold.
ESTHER : Cheng_2018_J.Med.Chem_61_2278
PubMedSearch : Cheng_2018_J.Med.Chem_61_2278
PubMedID: 29481079

Title : Heat shock transcription factor 3 regulates plant immune response through modulation of salicylic acid accumulation and signalling in cassava - Wei_2018_Mol.Plant.Pathol_19_2209
Author(s) : Wei Y , Liu G , Chang Y , He C , Shi H
Ref : Mol Plant Pathol , 19 :2209 , 2018
Abstract : As the terminal components of signal transduction, heat stress transcription factors (Hsfs) mediate the activation of multiple genes responsive to various stresses. However, the information and functional analysis are very limited in non-model plants, especially in cassava (Manihot esculenta), one of the most important crops in tropical areas. In this study, 32 MeHsfs were identified from the cassava genome; the evolutionary tree, gene structures and motifs were also analysed. Gene expression analysis found that MeHsfs were commonly regulated by Xanthomonas axonopodis pv. manihotis (Xam). Amongst these MeHsfs, MeHsf3 was specifically located in the cell nucleus and showed transcriptionally activated activity on heat stress elements (HSEs). Through transient expression in Nicotiana benthamiana leaves and virus-induced gene silencing (VIGS) in cassava, we identified the essential role of MeHsf3 in plant disease resistance, by regulating the transcripts of Enhanced Disease Susceptibility 1 (EDS1) and pathogen-related gene 4 (PR4). Notably, as regulators of defence susceptibility, MeEDS1 and MePR4 were identified as direct targets of MeHsf3. Moreover, the disease sensitivity of MeHsf3- and MeEDS1-silenced plants could be restored by exogenous salicylic acid (SA) treatment. Taken together, this study highlights the involvement of MeHsf3 in defence resistance through the transcriptional activation of MeEDS1 and MePR4.
ESTHER : Wei_2018_Mol.Plant.Pathol_19_2209
PubMedSearch : Wei_2018_Mol.Plant.Pathol_19_2209
PubMedID: 29660238

Title : Lipolysis in Brown Adipocytes Is Not Essential for Cold-Induced Thermogenesis in Mice - Shin_2017_Cell.Metab_26_764
Author(s) : Shin H , Ma Y , Chanturiya T , Cao Q , Wang Y , Kadegowda AKG , Jackson R , Rumore D , Xue B , Shi H , Gavrilova O , Yu L
Ref : Cell Metab , 26 :764 , 2017
Abstract : Lipid droplet (LD) lipolysis in brown adipose tissue (BAT) is generally considered to be required for cold-induced nonshivering thermogenesis. Here, we show that mice lacking BAT Comparative Gene Identification-58 (CGI-58), a lipolytic activator essential for the stimulated LD lipolysis, have normal thermogenic capacity and are not cold sensitive. Relative to littermate controls, these animals had higher body temperatures when they were provided food during cold exposure. The increase in body temperature in the fed, cold-exposed knockout mice was associated with increased energy expenditure and with increased sympathetic innervation and browning of white adipose tissue (WAT). Mice lacking CGI-58 in both BAT and WAT were cold sensitive, but only in the fasted state. Thus, LD lipolysis in BAT is not essential for cold-induced nonshivering thermogenesis in vivo. Rather, CGI-58-dependent LD lipolysis in BAT regulates WAT thermogenesis, and our data uncover an essential role of WAT lipolysis in fueling thermogenesis during fasting.
ESTHER : Shin_2017_Cell.Metab_26_764
PubMedSearch : Shin_2017_Cell.Metab_26_764
PubMedID: 28988822

Title : Bioaccumulation mechanism of organophosphate esters in adult zebrafish (Danio rerio) - Wang_2017_Environ.Pollut_229_177
Author(s) : Wang G , Shi H , Du Z , Chen H , Peng J , Gao S
Ref : Environ Pollut , 229 :177 , 2017
Abstract : Although organophosphate esters (OPEs) have been detected with growing frequency in water ecosystems, the underlying accumulation mechanisms of these compounds in fish are still unknown. Here, we investigated the tissue-specific accumulation and depuration of seven OPEs in adult zebrafish at three levels (0, 1/150 LC50 (environmentally relevant level), and 1/30 LC50 per OPE congener) in laboratory after 19 days exposure and 3 days depuration. The bioaccumulation of OPEs varied among tissues. Muscle contained the lowest level of OPEs and liver had the highest level of two (TPP and TCEP) of the seven OPEs at steady state. The high levels and slow depuration rates of TDCIPP, TPHP, and TCP observed in roe indicated that the accumulated OPEs were potentially stored in roe and transferred to the next generation. After examination of the major metabolites (organophosphate diesters) in selected tissues, a physiologically based toxicokinetic (PBTK) model used in fish was adopted to explore the key factors affecting the bioaccumulation of OPEs in zebrafish. Biotransformation of OPEs with polychlorinated alkyl moieties (i.e. TDCIPP) and aryl moieties (i.e. TPHP and TCP) has more significant impacts on the accumulation than those of OPEs with alkyl or short chain chlorinated alkyl moieties. Furthermore, the partition process between tissues and blood was also investigated, and was demonstrated to be the dominant process for OPEs accumulation in zebrafish. This study provides critical information on the bioaccumulation, tissue distribution, and metabolization of OPEs in relation with OPE structures in fish, as well as the underlying bioaccumulation mechanisms/pathways of OPEs in aquatic life.
ESTHER : Wang_2017_Environ.Pollut_229_177
PubMedSearch : Wang_2017_Environ.Pollut_229_177
PubMedID: 28599202

Title : Macrophage ABHD5 promotes colorectal cancer growth by suppressing spermidine production by SRM - Miao_2016_Nat.Commun_7_11716
Author(s) : Miao H , Ou J , Peng Y , Zhang X , Chen Y , Hao L , Xie G , Wang Z , Pang X , Ruan Z , Li J , Yu L , Xue B , Shi H , Shi C , Liang H
Ref : Nat Commun , 7 :11716 , 2016
Abstract : Metabolic reprogramming in stromal cells plays an essential role in regulating tumour growth. The metabolic activities of tumour-associated macrophages (TAMs) in colorectal cancer (CRC) are incompletely characterized. Here, we identify TAM-derived factors and their roles in the development of CRC. We demonstrate that ABHD5, a lipolytic co-activator, is ectopically expressed in CRC-associated macrophages. We demonstrate in vitro and in mouse models that macrophage ABHD5 potentiates growth of CRC cells. Mechanistically, ABHD5 suppresses spermidine synthase (SRM)-dependent spermidine production in macrophages by inhibiting the reactive oxygen species-dependent expression of C/EBPvarepsilon, which activates transcription of the srm gene. Notably, macrophage-specific ABHD5 transgene-induced CRC growth in mice can be prevented by an additional SRM transgene in macrophages. Altogether, our results show that the lipolytic factor ABHD5 suppresses SRM-dependent spermidine production in TAMs and potentiates the growth of CRC. The ABHD5/SRM/spermidine axis in TAMs might represent a potential target for therapy.
ESTHER : Miao_2016_Nat.Commun_7_11716
PubMedSearch : Miao_2016_Nat.Commun_7_11716
PubMedID: 27189574

Title : Targeting of cancerassociated fibroblasts enhances the efficacy of cancer chemotherapy by regulating the tumor microenvironment - Li_2016_Mol.Med.Rep_13_2476
Author(s) : Li M , Yin T , Shi H , Wen Y , Zhang B , Chen M , Xu G , Ren K , Wei Y
Ref : Mol Med Rep , 13 :2476 , 2016
Abstract : Cancerassociated fibroblasts (CAFs), key components of the tumor stroma, can regulate tumorigenesis by altering the tumor microenvironment in variety of ways to promote angiogenesis, recruit inflammatory immune cells and remodel the extracellular matrix. Using a murine xenograft model of colon carcinoma, the present study observed that oxaliplatin increased the accumulation of CAFs and stimulated the production of cytokines associated with CAFs. When oxaliplatin was combined with the smallmolecule dipeptidyl peptidase inhibitor PT100, which inhibits CAFs by targeting fibroblast activation protein (FAP), the accumulation of CAFs was markedly reduced, xenograft tumor growth was significantly suppressed and the survival of the mice increased, compared to those of mice treated with oxaliplatin or PT100 alone. Furthermore, the xenograft tumor tissues of mice treated with oxaliplatin and PT100 contained lower numbers of tumorassociated macrophages and dendritic cells, expressed lower levels of cytokines associated with CAFs and had a lower density of CD31+ endothelial cells. The present study demonstrated that pharmacological inhibition of CAFs improved the response to chemotherapy, reduced the recruitment of immune tumorpromoting cells and inhibited angiogenesis. Combining chemotherapy with agents which target CAFs may represent a novel strategy for improving the efficacy of chemotherapy and reducing chemoresistance.
ESTHER : Li_2016_Mol.Med.Rep_13_2476
PubMedSearch : Li_2016_Mol.Med.Rep_13_2476
PubMedID: 26846566

Title : Effects of harmine, an acetylcholinesterase inhibitor, on spatial learning and memory of APP\/PS1 transgenic mice and scopolamine-induced memory impairment mice - He_2015_Eur.J.Pharmacol_768_96
Author(s) : He D , Wu H , Wei Y , Liu W , Huang F , Shi H , Zhang B , Wu X , Wang C
Ref : European Journal of Pharmacology , 768 :96 , 2015
Abstract : Harmine, a beta-carboline alkaloid present in Peganum harmala with a wide spectrum of pharmacological activities, has been shown to exert strong inhibition against acetylcholinesterase in vitro. However, whether it can rescue the impaired cognition has not been elucidated yet. In current study, we examined its effects on scopolamine-induced memory impairment mice and APP/PS1 transgenic mice, one of the models for Alzheimer's disease, using Morris Water Maze test. In addition, whether harmine could penetrate blood brain barrier, interact with and inhibit acetylcholinesterase, and activate downstream signaling network was also investigated. Our results showed that harmine (20mg/kg) administered by oral gavage for 2 weeks could effectively enhance the spatial cognition of C57BL/6 mice impaired by intraperitoneal injection of scopolamine (1mg/kg). Meanwhile, long-term consumption of harmine (20mg/kg) for 10 weeks also slightly benefited the impaired memory of APP/PS1 mice. Furthermore, harmine could pass through blood brain barrier, penetrate into the brain parenchyma shortly after oral administration, and modulate the expression of Egr-1, c-Jun and c-Fos. Molecular docking assay disclosed that harmine molecule could directly dock into the catalytic active site of acetylcholinesterase, which was partially confirmed by its in vivo inhibitory activity on acetylcholinesterase. Taken together, all these results suggested that harmine could ameliorate impaired memory by enhancement of cholinergic neurotransmission via inhibiting the activity of acetylcholinesterase, which may contribute to its clinical use in the therapy of neurological diseases characterized with acetylcholinesterase deficiency.
ESTHER : He_2015_Eur.J.Pharmacol_768_96
PubMedSearch : He_2015_Eur.J.Pharmacol_768_96
PubMedID: 26526348

Title : Muscle-specific deletion of comparative gene identification-58 (CGI-58) causes muscle steatosis but improves insulin sensitivity in male mice - Xie_2015_Endocrinology_156_1648
Author(s) : Xie P , Kadegowda AK , Ma Y , Guo F , Han X , Wang M , Groban L , Xue B , Shi H , Li H , Yu L
Ref : Endocrinology , 156 :1648 , 2015
Abstract : Intramyocellular accumulation of lipids is often associated with insulin resistance. Deficiency of comparative gene identification-58 (CGI-58) causes cytosolic deposition of triglyceride (TG)-rich lipid droplets in most cell types, including muscle due to defective TG hydrolysis. It was unclear, however, whether CGI-58 deficiency-induced lipid accumulation in muscle influences insulin sensitivity. Here we show that muscle-specific CGI-58 knockout mice relative to their controls have increased glucose tolerance and insulin sensitivity on a Western-type high-fat diet, despite TG accumulation in both heart and oxidative skeletal muscle and cholesterol deposition in heart. Although the intracardiomyocellular lipid deposition results in cardiac ventricular fibrosis and systolic dysfunction, muscle-specific CGI-58 knockout mice show increased glucose uptake in heart and soleus muscle, improved insulin signaling in insulin-sensitive tissues, and reduced plasma concentrations of glucose, insulin, and cholesterol. Hepatic contents of TG and cholesterol are also decreased in these animals. Cardiac steatosis is attributable, at least in part, to decreases in cardiac TG hydrolase activity and peroxisome proliferator-activated receptor-alpha/peroxisome proliferator-activated receptor-gamma coactivator-1-dependent mitochondrial fatty acid oxidation. In conclusion, muscle CGI-58 deficiency causes cardiac dysfunction and fat deposition in oxidative muscles but induces a series of favorable metabolic changes in mice fed a high-fat diet.
ESTHER : Xie_2015_Endocrinology_156_1648
PubMedSearch : Xie_2015_Endocrinology_156_1648
PubMedID: 25751639

Title : Macrophage CGI-58 deficiency promotes IL-1beta transcription by activating the SOCS3-FOXO1 pathway - Miao_2015_Clin.Sci.(Lond)_128_493
Author(s) : Miao H , Ou J , Zhang X , Chen Y , Xue B , Shi H , Gan L , Yu L , Liang H
Ref : Clinical Science (Lond) , 128 :493 , 2015
Abstract : Over-nutrition induces low-grade inflammation that dampens insulin sensitivity, but the underlying molecular mediators are not fully understood. Comparative gene identification-58 (CGI-58) is an intracellular lipolytic activator. In the present study, we show that in mouse visceral fat-derived macrophages or human peripheral blood monocytes, CGI-58 negatively and interleukin (IL)-1beta positively correlate with obesity. Saturated non-esterified fatty acid (NEFA) suppresses CGI-58 expression in macrophages and this suppression activates FOXO1 (forkhead box-containing protein O subfamily-1) through inhibition of FOXO1 phosphorylation. Activated FOXO1 binds to an insulin-responsive element in IL-1beta promoter region to potentiate IL-1beta transcription. Gain- and loss-of-function studies demonstrate that NEFA-induced CGI-58 suppression activates FOXO1 to augment IL-1beta transcription by dampening insulin signalling through induction of SOCS3 (suppressor of cytokine signalling 3) expression. CGI-58 deficiency-induced SOCS3 expression is NLRP3 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3) inflammasome-dependent. Our data thus identified a vicious cycle (IL-1beta-SOCS3-FOXO1-IL-1beta) that amplifies IL-1beta secretion and is initiated by CGI-58 deficiency-induced activation of the NLRP3 inflammasome in macrophages. We further show that blocking this cycle with a FOXO1 inhibitor, an antioxidant that inhibits FOXO1 or IL-1 receptor antagonist alleviates chronic inflammation and insulin resistance in high-fat diet (HFD)-fed mice. Collectively, our data suggest that obesity-associated factors such as NEFA and lipopolysaccharide (LPS) probably adopt this vicious cycle to promote inflammation and insulin resistance.
ESTHER : Miao_2015_Clin.Sci.(Lond)_128_493
PubMedSearch : Miao_2015_Clin.Sci.(Lond)_128_493
PubMedID: 25431838

Title : Purification and characterization of a hydrolysis-resistant lipase from Aspergillus terreus - Shi_2014_Biotechnol.Appl.Biochem_61_165
Author(s) : Shi H , Meng Y , Yang M , Zhang Q
Ref : Biotechnol Appl Biochem , 61 :165 , 2014
Abstract : Lipase from Aspergillus terreus was purified to homogeneity using ammonium sulfate precipitation and chromatographies with Q-Sepharose and Sephacryl S-200. It showed a single band on SDS-PAGE and IEF-PAGE with a relative molecular mass of 37.2 kDa and pI of 3.2. Its glycoprotein nature was confirmed with the percentage of saccharides of 5.02% and 3.88% determined by the phenol/sulfuric acid and anthrone/ sulfuric acid methods, respectively. The lipase hydrolyzed both plant oils and animal oils, with the K(m) value for substrate p-NPP of 16.42 mM at pH 6.0, 50 degrees C. The enzyme was tolerant in a wide range of pH (pH 3-12) with optimum activity at pH 4.0. It remained stable under the highest temperature of 65 degrees C, with maximal activity at 50 degrees C. Ca(2)(+), Co(2)(+), Mn(2)(+), and Ni(2)(+) stimulated enzyme activity, but Hg(2)(+) caused inhibition. Detected detergents had no obvious effect on enzyme activity, except SDS, which stimulated the activity at lower concentrations but inhibited the activity at higher concentrations. The inhibitory effect on enzyme activity of phenylmethanesulfonyl fluoride revealed that the Ser was involved in catalysis. Saccharides had no obvious effect on enzyme activity but could enhance its thermostability. Furthermore, the enzyme was resistant to trypsin digestion.
ESTHER : Shi_2014_Biotechnol.Appl.Biochem_61_165
PubMedSearch : Shi_2014_Biotechnol.Appl.Biochem_61_165
PubMedID: 23855368

Title : Intestinal Cgi-58 deficiency reduces postprandial lipid absorption - Xie_2014_PLoS.One_9_e91652
Author(s) : Xie P , Guo F , Ma Y , Zhu H , Wang F , Xue B , Shi H , Yang J , Yu L
Ref : PLoS ONE , 9 :e91652 , 2014
Abstract : Comparative Gene Identification-58 (CGI-58), a lipid droplet (LD)-associated protein, promotes intracellular triglyceride (TG) hydrolysis in vitro. Mutations in human CGI-58 cause TG accumulation in numerous tissues including intestine. Enterocytes are thought not to store TG-rich LDs, but a fatty meal does induce temporary cytosolic accumulation of LDs. Accumulated LDs are eventually cleared out, implying existence of TG hydrolytic machinery in enterocytes. However, identities of proteins responsible for LD-TG hydrolysis remain unknown. Here we report that intestine-specific inactivation of CGI-58 in mice significantly reduces postprandial plasma TG concentrations and intestinal TG hydrolase activity, which is associated with a 4-fold increase in intestinal TG content and large cytosolic LD accumulation in absorptive enterocytes during the fasting state. Intestine-specific CGI-58 knockout mice also display mild yet significant decreases in intestinal fatty acid absorption and oxidation. Surprisingly, inactivation of CGI-58 in intestine significantly raises plasma and intestinal cholesterol, and reduces hepatic cholesterol, without altering intestinal cholesterol absorption and fecal neutral sterol excretion. In conclusion, intestinal CGI-58 is required for efficient postprandial lipoprotein-TG secretion and for maintaining hepatic and plasma lipid homeostasis. Our animal model will serve as a valuable tool to further define how intestinal fat metabolism influences the pathogenesis of metabolic disorders, such as obesity and type 2 diabetes.
ESTHER : Xie_2014_PLoS.One_9_e91652
PubMedSearch : Xie_2014_PLoS.One_9_e91652
PubMedID: 24618586

Title : Loss of abhd5 promotes colorectal tumor development and progression by inducing aerobic glycolysis and epithelial-mesenchymal transition - Ou_2014_Cell.Rep_9_1798
Author(s) : Ou J , Miao H , Ma Y , Guo F , Deng J , Wei X , Zhou J , Xie G , Shi H , Xue B , Liang H , Yu L
Ref : Cell Rep , 9 :1798 , 2014
Abstract : How cancer cells shift metabolism to aerobic glycolysis is largely unknown. Here, we show that deficiency of alpha/beta-hydrolase domain-containing 5 (Abhd5), an intracellular lipolytic activator that is also known as comparative gene identification 58 (CGI-58), promotes this metabolic shift and enhances malignancies of colorectal carcinomas (CRCs). Silencing of Abhd5 in normal fibroblasts induces malignant transformation. Intestine-specific knockout of Abhd5 in Apc(Min/+) mice robustly increases tumorigenesis and malignant transformation of adenomatous polyps. In colon cancer cells, Abhd5 deficiency induces epithelial-mesenchymal transition by suppressing the AMPKalpha-p53 pathway, which is attributable to increased aerobic glycolysis. In human CRCs, Abhd5 expression falls substantially and correlates negatively with malignant features. Our findings link Abhd5 to CRC pathogenesis and suggest that cancer cells develop aerobic glycolysis by suppressing Abhd5-mediated intracellular lipolysis.
ESTHER : Ou_2014_Cell.Rep_9_1798
PubMedSearch : Ou_2014_Cell.Rep_9_1798
PubMedID: 25482557
Gene_locus related to this paper: human-ABHD5

Title : Macrophage CGI-58 deficiency activates ROS-inflammasome pathway to promote insulin resistance in mice - Miao_2014_Cell.Rep_7_223
Author(s) : Miao H , Ou J , Ma Y , Guo F , Yang Z , Wiggins M , Liu C , Song W , Han X , Wang M , Cao Q , Chung BH , Yang D , Liang H , Xue B , Shi H , Gan L , Yu L
Ref : Cell Rep , 7 :223 , 2014
Abstract : Overnutrition activates a proinflammatory program in macrophages to induce insulin resistance (IR), but its molecular mechanisms remain incompletely understood. Here, we show that saturated fatty acid and lipopolysaccharide, two factors implicated in high-fat diet (HFD)-induced IR, suppress macrophage CGI-58 expression. Macrophage-specific CGI-58 knockout (MaKO) in mice aggravates HFD-induced glucose intolerance and IR, which is associated with augmented systemic/tissue inflammation and proinflammatory activation of adipose tissue macrophages. CGI-58-deficient macrophages exhibit mitochondrial dysfunction due to defective peroxisome proliferator-activated receptor (PPAR)gamma signaling. Consequently, they overproduce reactive oxygen species (ROS) to potentiate secretion of proinflammatory cytokines by activating NLRP3 inflammasome. Anti-ROS treatment or NLRP3 silencing prevents CGI-58-deficient macrophages from oversecreting proinflammatory cytokines and from inducing proinflammatory signaling and IR in the cocultured fat slices. Anti-ROS treatment also prevents exacerbation of inflammation and IR in HFD-fed MaKO mice. Our data thus establish CGI-58 as a suppressor of overnutrition-induced NLRP3 inflammasome activation in macrophages.
ESTHER : Miao_2014_Cell.Rep_7_223
PubMedSearch : Miao_2014_Cell.Rep_7_223
PubMedID: 24703845

Title : Deficiency of liver Comparative Gene Identification-58 causes steatohepatitis and fibrosis in mice - Guo_2013_J.Lipid.Res_54_2109
Author(s) : Guo F , Ma Y , Kadegowda AK , Betters JL , Xie P , Liu G , Liu X , Miao H , Ou J , Su X , Zheng Z , Xue B , Shi H , Yu L
Ref : J Lipid Res , 54 :2109 , 2013
Abstract : Triglyceride (TG) accumulation in hepatocytes (hepatic steatosis) preludes the development of advanced nonalcoholic fatty liver diseases (NAFLDs) such as steatohepatitis, fibrosis, and cirrhosis. Mutations in human Comparative Gene Identification-58 (CGI-58) cause cytosolic TG-rich lipid droplets to accumulate in almost all cell types including hepatocytes. However, it is unclear if CGI-58 mutation causes hepatic steatosis locally or via altering lipid metabolism in other tissues. To directly address this question, we created liver-specific CGI-58 knockout (LivKO) mice. LivKO mice on standard chow diet displayed microvesicular and macrovesicular panlobular steatosis, and progressed to advanced NAFLD stages over time, including lobular inflammation and centrilobular fibrosis. Compared with CGI-58 floxed control littermates, LivKO mice showed 8-fold and 52-fold increases in hepatic TG content, which was associated with 40% and 58% decreases in hepatic TG hydrolase activity at 16 and 42 weeks, respectively. Hepatic cholesterol also increased significantly in LivKO mice. At 42 weeks, LivKO mice showed increased hepatic oxidative stress, plasma aminotransferases, and hepatic mRNAs for genes involved in fibrosis and inflammation, such as alpha-smooth muscle actin, collagen type 1 alpha1, tumor necrosis factor alpha, and interleukin-1beta. In conclusion, CGI-58 deficiency in the liver directly causes not only hepatic steatosis but also steatohepatitis and fibrosis.
ESTHER : Guo_2013_J.Lipid.Res_54_2109
PubMedSearch : Guo_2013_J.Lipid.Res_54_2109
PubMedID: 23733885

Title : CGI-58 knockdown in mice causes hepatic steatosis but prevents diet-induced obesity and glucose intolerance - Brown_2010_J.Lipid.Res_51_3306
Author(s) : Brown JM , Betters JL , Lord C , Ma Y , Han X , Yang K , Alger HM , Melchior J , Sawyer J , Shah R , Wilson MD , Liu X , Graham MJ , Lee R , Crooke R , Shulman GI , Xue B , Shi H , Yu L
Ref : J Lipid Res , 51 :3306 , 2010
Abstract : Mutations of Comparative Gene Identification-58 (CGI-58) in humans cause triglyceride (TG) accumulation in multiple tissues. Mice genetically lacking CGI-58 die shortly after birth due to a skin barrier defect. To study the role of CGI-58 in integrated lipid and energy metabolism, we utilized antisense oligonucleotides (ASOs) to inhibit CGI-58 expression in adult mice. Treatment with two distinct CGI-58-targeting ASOs resulted in approximately 80-95% knockdown of CGI-58 protein expression in both liver and white adipose tissue. In chow-fed mice, ASO-mediated depletion of CGI-58 did not alter weight gain, plasma TG, or plasma glucose, yet raised hepatic TG levels approximately 4-fold. When challenged with a high-fat diet (HFD), CGI-58 ASO-treated mice were protected against diet-induced obesity, but their hepatic contents of TG, diacylglycerols, and ceramides were all elevated, and intriguingly, their hepatic phosphatidylglycerol content was increased by 10-fold. These hepatic lipid alterations were associated with significant decreases in hepatic TG hydrolase activity, hepatic lipoprotein-TG secretion, and plasma concentrations of ketones, nonesterified fatty acids, and insulin. Additionally, HFD-fed CGI-58 ASO-treated mice were more glucose tolerant and insulin sensitive. Collectively, this work demonstrates that CGI-58 plays a critical role in limiting hepatic steatosis and maintaining hepatic glycerophospholipid homeostasis and has unmasked an unexpected role for CGI-58 in promoting HFD-induced obesity and insulin resistance.
ESTHER : Brown_2010_J.Lipid.Res_51_3306
PubMedSearch : Brown_2010_J.Lipid.Res_51_3306
PubMedID: 20802159
Gene_locus related to this paper: human-ABHD5 , mouse-abhd5

Title : Suppression of N-myc downstream-regulated gene 2 is associated with induction of Myc in colorectal cancer and correlates closely with differentiation - Shi_2009_Biol.Pharm.Bull_32_968
Author(s) : Shi H , Jin H , Chu D , Wang W , Zhang J , Chen C , Xu C , Fan D , Yao L
Ref : Biol Pharm Bull , 32 :968 , 2009
Abstract : NDRG2, a new member of the N-Myc downstream-regulated gene (NDRG) family, is a focus for study at present. Up to now, its expression and function in carcinoma remain to be elucidated. In this study, using a colorectal cancer tissue array and a series of 213 colorectal cancer samples, the relationship between Ndrg2 and c-MYC expression and tumor differentiation level was investigated. Immunohistochemistry showed that Ndrg2 expression was reduced and that c-Myc was increased in colorectal carcinomas. In addition, Ndrg2 protein levels increased from poorly differentiated to well-differentiated carcinomas (p=0.005). Real-time polymerase chain reaction and Western blots demonstrated quantitatively that NDRG2 mRNA and protein levels were lower in colorectal carcinomas compared to the adjacent tissue and normal tissue from the same individual (p=3x10(-8)). Also, the NDRG2 expression level in adjacent carcinoma tissue was lower than that of normal tissue. However, the expression pattern of c-MYC was the inverse (p=5x10(-8)). Finally, we induced the differentiation of the colorectal carcinoma cell lines HT29, SW480 and SW620 and found that NDRG2 expression increased and that c-MYC expression declined with increasing differentiation. These novel data show a disparity in both the mRNA and protein expression levels of Ndrg2 and c-Myc between colorectal cancers and normal tissues. Taken together, NDRG2 may play a role during the differentiation of colorectal cancer cells, and the function of NDRG2 in the development of colorectal cancer should be further investigated.
ESTHER : Shi_2009_Biol.Pharm.Bull_32_968
PubMedSearch : Shi_2009_Biol.Pharm.Bull_32_968
PubMedID: 19483300

Title : Human differentiation-related gene NDRG1 is a Myc downstream-regulated gene that is repressed by Myc on the core promoter region - Zhang_2008_Gene_417_5
Author(s) : Zhang J , Chen S , Zhang W , Liu X , Shi H , Che H , Wang W , Li F , Yao L
Ref : Gene , 417 :5 , 2008
Abstract : N-Myc downstream-regulated gene 1 (ndrg1) is up-regulated in N-Myc knockout mouse embryos. The human NDRG family consists of 4 highly homologous members and human Ndrg1 exhibits approximately 94% homology with mouse ndrg1. However, the regulatory mechanism of NDRG1 via Myc repression is as yet unknown. We previously identified human NDRG2 and demonstrated that this gene is transcriptionally down-regulated by Myc via Miz-1-dependent interaction with the core promoter region of NDRG2. Here, we provide evidence that human NDRG1 is regulated by Myc in a manner similar to NDRG2. We found that Ndrg1 expression levels were enhanced as Myc expression declined in differentiated cells, but were down-regulated following Myc induction. The data revealed that both N-Myc and c-Myc can repress human NDRG1 at the transcriptional level. We further determined that the core promoter region of human NDRG1 is required for Myc repression, and verified the interaction of Myc with the core promoter region. However, the presence of the protein synthesis inhibitor cycloheximide could reverse the repression of Myc, indicating the indirect repression of human NDRG1 by Myc. Moreover, we found that c-Myc-mediated repression can be inhibited by TSA, an HDACs inhibitor, which suggests the involvement of HDACs in the repression process. Taken together, our results demonstrate that, in common with NDRG2, human NDRG1 can be indirectly transcriptionally down-regulated by Myc via interaction with the NDRG1 core promoter.
ESTHER : Zhang_2008_Gene_417_5
PubMedSearch : Zhang_2008_Gene_417_5
PubMedID: 18455888

Title : Poster: Functional and molecular identification and characterization of cardiac M3 and M4 muscarinic acetylcholine receptors -
Author(s) : Shi H , Wang H , Wang Z
Ref : Life Sciences , 64 :583 , 1999

Title : Poster: Modulation of K+ currents by muscarinic acetylcholine receptor agonists in canine atrial myocytes -
Author(s) : Yang X , Shi H , Wang H , Wang Z
Ref : Life Sciences , 64 :576 , 1999

Title : Poster: Pharmacological and molecular characterization of muscarinic acetylcholine receptor subtypes in human heart -
Author(s) : Wang H , Shi H , Deng X , Wang Z
Ref : Life Sciences , 64 :590 , 1999

Title : Poster: Choline alters cardiac function by activating M3 muscarinic acetylcholine receptors (mAChRs) in cardiac myocytes -
Author(s) : Wang Z , Shi H , Wang H
Ref : Life Sciences , 64 :580 , 1999

Title : In vitro selection of RNA molecules that displace cocaine from the membrane-bound nicotinic acetylcholine receptor - Ulrich_1998_Proc.Natl.Acad.Sci.U.S.A_95_14051
Author(s) : Ulrich H , Ippolito JE , Pagan OR , Eterovic VA , Hann RM , Shi H , Lis JT , Eldefrawi ME , Hess GP
Ref : Proc Natl Acad Sci U S A , 95 :14051 , 1998
Abstract : The nicotinic acetylcholine receptor (AChR) controls signal transmission between cells in the nervous system. Abused drugs such as cocaine inhibit this receptor. Transient kinetic investigations indicate that inhibitors decrease the channel-opening equilibrium constant [Hess, G. P. & Grewer, C. (1998) Methods Enzymol. 291, 443-473]. Can compounds be found that compete with inhibitors for their binding site but do not change the channel-opening equilibrium? The systematic evolution of RNA ligands by exponential enrichment methodology and the AChR in Torpedo californica electroplax membranes were used to find RNAs that can displace inhibitors from the receptor. The selection of RNA ligands was carried out in two consecutive steps: (i) a gel-shift selection of high-affinity ligands bound to the AChR in the electroplax membrane, and (ii) subsequent use of nitrocellulose filters to which both the membrane-bound receptor and RNAs bind strongly, but from which the desired RNA can be displaced from the receptor by a high-affinity AChR inhibitor, phencyclidine. After nine selection rounds, two classes of RNA molecules that bind to the AChR with nanomolar affinities were isolated and sequenced. Both classes of RNA molecules are displaced by phencyclidine and cocaine from their binding site on the AChR. Class I molecules are potent inhibitors of AChR activity in BC3H1 muscle cells, as determined by using the whole-cell current-recording technique. Class II molecules, although competing with AChR inhibitors, do not affect receptor activity in this assay; such compounds or derivatives may be useful for alleviating the toxicity experienced by millions of addicts.
ESTHER : Ulrich_1998_Proc.Natl.Acad.Sci.U.S.A_95_14051
PubMedSearch : Ulrich_1998_Proc.Natl.Acad.Sci.U.S.A_95_14051
PubMedID: 9826651

Title : Engineering lipase at the molecular scale for cleaner biodiesel production - A review - Tan_2023_Mol.Catal_546_113271
Author(s) : Tan Z , Chen G , Chen S , Zhang J , Liu J , Ma X , Liao H , Hu Z , Ge F , Ju F , Shi H , Bilal M
Ref : Molecular Catalysis , 546 :113271
Abstract : Increasing environmental concerns and significant demand for industrial fuels necessitate the development of alternate and sustainable energy sources. Biodiesel is a renewable and environmentally friendly fuel produced by trans-esterifying a variety of feedstocks. Lipases are robust triacylglycerol ester hydrolases that catalyze hydrolysis, esterification, interesterification, transesterification, acylation, acidolysis, alcoholysis, aminolysis, and resolution of racemates. Although the lipase-assisted greener biosynthesis of biodiesel has numerous advantages over the traditional alkali-based process, low catalytic efficiency, marginal stability, and high cost of lipase enzymes limit its widespread industrial processability. Protein engineering methodologies such as directed evolution, semi-rational design, and rational design can effectively tailor or improve the biocatalytic characteristics of lipase enzymes used in biodiesel generation, such as thermostability, solvent tolerance, activity, and substrate specificity. These innovative techniques improved our ability to predict structure-function relationships, engineering qualities, computational tools for designing new biocatalysts, and functional screening to manipulate enzyme traits for application in prevalent industrial bioprocesses. Many recent studies have demonstrated improved lipase performance, such as activity, stability, and specificity via protein engineering. This review spotlights a current overview of lipase engineering at the molecular scale with robust biocatalytic properties for biodiesel synthesis.
ESTHER : Tan_2023_Mol.Catal_546_113271
PubMedSearch : Tan_2023_Mol.Catal_546_113271