A maternal low-protein (LP) diet during gestation and/or lactation results in metabolic syndrome in their offspring. Here, we investigated the effect of maternal LP diet during puberty and adulthood on the metabolic homeostasis of glucose and lipids in offspring. Female mice were fed with normal-protein (NP) diet or a LP diet for 11 weeks. Male offspring were then fed with a high-fat diet (NP-HFD and LP-HFD groups) or standard chow diet (NP-Chow and LP-Chow groups) for 4 months. Results showed that maternal LP diet during puberty and adulthood did not alter the insulin sensitivity and hepatic lipid homeostasis of their offspring under chow diet, but aggravated insulin resistance, hepatic steatosis, and hypercholesterolemia of offspring in response to a post-weaning HFD. Accordingly, transcriptomics study with offspring's liver indicated that several genes related to glucose and lipid metabolism, including lipoprotein lipase (Lpl), long-chain acyl-CoA synthetase 1 (Acsl1), Apoprotein A1 (Apoa1), major urinary protein 19 (Mup19), cholesterol 7alpha hydroxylase (Cyp7a1) and fibroblast growth factor 1 (Fgf1), were changed by maternal LP diet. Taken together, maternal LP diet during puberty and adulthood could disarrange the expression of metabolic genes in the liver of offspring and aggravate insulin resistance and hepatic steatosis in offspring fed a HFD.
Title: A versatile biomimetic multienzyme cascade nanoplatform based on boronic acid-modified metal-organic framework for colorimetric biosensing Shen H, Shi H, Feng B, Ding C, Yu S Ref: J Mater Chem B, :, 2022 : PubMed
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.
Title: In situ and real-time insight into Rhizopus chinensis lipase under high pressure and temperature: Conformational traits and biobehavioural analysis Chen G, Zhang Q, Chen H, Lu Q, Miao M, Campanella OH, Feng B Ref: Int J Biol Macromol, 154:1314, 2020 : PubMed
An in situ and real-time investigation was performed using an optical cell system and in-silico analysis to reveal the impacts of pressure and temperature on the conformational state and behaviours of Rhizopus chinensis lipase (RCL). The fluorescence intensity (FI) of RCL increased remarkably under high pressure, and part of this increase was recovered after depressurization. This result displayed the partially reversible conformational change of RCL, which may be associated with the local change of Trp224 near the catalytic centre. High temperature caused a significant loss of secondary structure, whereas the alpha-helical segments including the lid were preserved by high pressure even at temperatures over 60 degreesC. The parameters of enzymatic reaction monitored by UV showed that the hydrolysis rate was remarkably enhanced by the pressure of 200 MPa. In the pressure range of 0.1-200 MPa, the active volume measured by the in situ system decreased from -2.85 to -6.73 mL/mol with the temperature increasing from 20 degreesC to 40 degreesC. The high catalytic capacity of the lipase under high pressure and high temperature was primarily attributed to pressure protection on RCL.
Title: Protection effect of polyols on Rhizopus chinensis lipase counteracting the deactivation from high pressure and high temperature treatment Chen G, Zhang Q, Lu Q, Feng B Ref: Int J Biol Macromol, 127:555, 2019 : PubMed
The influence of polyols on Rhizopus chinensis lipase (RCL) was investigated under high pressure. The poor stability of RCL was observed at 500MPa at 60 degrees C without polyols which protected RCL against the loss of activity. The lipase is more stable in phosphate buffer than in tris buffer despite the protection of polyols. The activity was maintained 63% by the sorbitol of 2mol/L in Tris-HCl buffer but 73% in phosphate buffer after the treatment at 500MPa and 60 degrees C for 25min. The same protective effects could be observed at 1mol/L of sorbitol, erythritol, xylitol, and mannitol. However, further increase of hydroxyl group number could not significantly improve the enzyme stability. The protection of polyols on RCL appears to depend on both of the polyol nature and the hydroxyl group number. Together with fluorescence spectra, circular dichroism spectra indicated that the chaotic conformation of RCL under high pressure became more ordered with 1mol/L sorbitol. The results showed that sorbitol effectively stabilized the lipase conformation including the hydrophobic core under extreme conditions. It might be attributed to the interaction of polyols with RCL surface to modify intra-/intermolecular hydrogen bonds, maintaining the hydrophobic interactions within RCL.
Broomcorn millet (Panicum miliaceum L.) is the most water-efficient cereal and one of the earliest domesticated plants. Here we report its high-quality, chromosome-scale genome assembly using a combination of short-read sequencing, single-molecule real-time sequencing, Hi-C, and a high-density genetic map. Phylogenetic analyses reveal two sets of homologous chromosomes that may have merged ~5.6 million years ago, both of which exhibit strong synteny with other grass species. Broomcorn millet contains 55,930 protein-coding genes and 339 microRNA genes. We find Paniceae-specific expansion in several subfamilies of the BTB (broad complex/tramtrack/bric-a-brac) subunit of ubiquitin E3 ligases, suggesting enhanced regulation of protein dynamics may have contributed to the evolution of broomcorn millet. In addition, we identify the coexistence of all three C4 subtypes of carbon fixation candidate genes. The genome sequence is a valuable resource for breeders and will provide the foundation for studying the exceptional stress tolerance as well as C4 biology.
Title: Elucidation of pressure-induced lid movement and catalysis behavior of Rhizopus chinensis lipase Chen G, Tang J, Miao M, Jiang B, Jin J, Feng B Ref: Int J Biol Macromol, 103:360, 2017 : PubMed
The changes of lid movement and catalysis behavior of Rhizopus chinensis lipase under high hydrostatic pressure treatment was studied. Molecular dynamics simulation showed that the lipase lid under pressure was partially opened at below 200MPa but got more closed at over 400MPa. The interfacial activation changed little at pressure below 400MPa but became marginal with the pressure increased to 500MPa. The lipase hydrolysis ability by high pressure treatment underwent a course of initial increasing then reducing with maximum activity obtained at 200MPa and 40 degrees C. At moderate given pressure, the pressure treatment lowered the volume between the reactants and the transition state. Km decreased from 0.592 to 0.441mmol/L with pressure increasing from 0.1 to 200MPa. Meanwhile, vmax and Kcat increased 24.2% and 20% respectively. The change trend of reaction kinetic parameters under 400-500MPa was contrary to that under 0.1-200MPa.
Title: Sarsasapogenin reverses depressive-like behaviors and nicotinic acetylcholine receptors induced by olfactory bulbectomy Feng B, Zhao XY, Song YZ, Liang WN, Liu JL Ref: Neuroscience Letters, 639:173, 2017 : PubMed
Cholinergic signalling in the hippocampus may contribute to the aetiology of mood regulation. Antidepressants can reverse the increase in acetylcholinesterase (AChE) activity induced by olfactory bulbectomy. The activation of nicotinic acetylcholine receptors (nAChRs) also alleviates the symptoms of depression. This study advances the development of sarsasapogenin, which interacts with cholinergic signalling and has a favourable antidepressant profile in olfactory bulbectomised (OB) rats. We examined OB-induced changes in cholinergic signalling, as well as AChE, alpha4-nAChR, and alpha7-nAChR expression in the hippocampus. The results indicate that abnormal cholinergic signalling in the hippocampus contributes to the development of depression in the OB rat model. This depression may be alleviated following treatment with sarsasapogenin.
Title: Design, Synthesis, and Biological Evaluation of a New Series of Biphenyl/Bibenzyl Derivatives Functioning as Dual Inhibitors of Acetylcholinesterase and Butyrylcholinesterase Wang DM, Feng B, Fu H, Liu AL, Wang L, Du GH, Wu S Ref: Molecules, 22:, 2017 : PubMed
Alzheimer's disease (AD), the most common form of dementia in adults, is a progressive neurodegenerative disorder of the brain characterized by loss of memory and steady deterioration of cognition. Here, a series of symmetrical molecules containing biphenyl/bibenzyl scaffolds (12-36) were designed, synthesized, and evaluated for their ability to inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). A biological evaluation showed that most of these biphenyl derivatives were potent AChE and BuChE inhibitors. Among them, compound 15 displayed the greatest ability to inhibit BuChE (IC50 = 0.74 microM) and was also a good AChE inhibitor (IC50 = 1.18 microM). Compound 19 was not only a potent AChE inhibitor (IC50 = 0.096 microM), but also a mild BuChE inhibitor (IC50 =1.25 microM). Overall, these results suggested that compound 19 may be a promising agent in the treatment of AD.
Title: Surrogate markers of the kidney and liver in the assessment of gestational diabetes mellitus and fetal outcome Liu H, Shao-Gang M, Liang C, Feng B, Wei X Ref: J Clin Diagn Res, 9:OC14, 2015 : PubMed
INTRODUCTION: To investigate whether serum levels of butyrylcho-linesterase activity, cystatin C, and pre-albumin has the potential value as gamma-glutamyl transferase in reflecting gestational diabetes mellitus and its fetal outcome. MATERIALS AND METHODS: Seventy-six gestational diabetes mellitus women and 76 pregnancies with normal glucose tolerance in the second trimester were enrolled. Maternal serum parameters of butyrylcholinesterase activity, gamma-glutamyl transferase, cystatin C, and pre-albumin were detected and evaluated. The pregnant complications and fetal outcome were also evaluated. RESULTS: Levels of butyrylcholinesterase activity, gamma-glutamyl transferase, cystatin C, pre-albumin and glycemic variables were higher in the gestational diabetes mellitus patients than in the controls. Levels of butyrylcholinesterase activity were significantly correlated to the levels of fasting plasma glucose, cystatin C, and gamma- glutamyl transferase (p < 0.05) in the gestational diabetes mellitus group. There were statistical differences in cases of preterm delivery, preeclampsia and postpartum hemorrhage. Higher levels of gamma-glutamyl transferase and pre-albumin were risk markers for gestational diabetes mellitus (p < 0.05). The diagnosis curve demonstrated that gamma-glutamyl transferase had a significant advantage over other markers (p < 0.001) but no significance compared with pre-albumin (p = 0.096). None of the detected markers showed predictive value for fetal outcome. CONCLUSION: Serum levels of butyrylcholinesterase activity, gamma-glutamyl transferase, cystatin C and pre-albumin were correlated with gestational diabetes mellitus status but not with the fetal outcome. Pre-albumin can be equivalent as gamma-glutamyl transferase in reflecting the presence of gestational diabetes mellitus.
The effects of solvents with different log P values, and of lipases on the synthesis of water-soluble plant stanol derivatives were investigated. Results showed that conversion in solvents with log P<0.37 was mainly controlled by the hydrophobicity of the solvent and subsequent complete or partial deactivation of the enzyme. The solubility of substrate was the leading factor for the conversion in solvents with log P>0.37. Lipozyme RM IM and tert-butanol was the most suitable biocatalyst and solvent, respectively. The highest yield (>51%) of plant stanyl sorbitol succinate was obtained under the selected conditions: 50 mol/mL plant stanyl hemisuccinate, 1:3 molar ratio of plant stanyl hemisuccinate to d-sorbitol, 80 mg/mL 3 molecular sieves and 100mg/mL Lipozyme RM IM in tert-butanol, 150 r/min and 55 degreeC. Fourier transform infrared spectroscopy, mass spectroscopy and nuclear magnetic resonance spectroscopy were adopted to determine the structure of product, suggesting that water-soluble plant stanol derivatives were successfully synthesized.
Title: Lipase-catalyzed synthesis of conjugated linoleyl beta-sitosterol and its cholesterol-lowering properties in mice Li R, Jia CS, Yue L, Zhang XM, Xia QY, Zhao SL, Feng B, Zhong F, Chen WJ Ref: Journal of Agricultural and Food Chemistry, 58:1898, 2010 : PubMed
Conjugated linoleyl beta-sitosterol (CLS) was prepared from beta-sitosterol and conjugated linoleic acid (CLA) via lipase-catalyzed synthesis in n-hexane in the presence of molecular sieves. Its plasma cholesterol-lowering properties were also studied. The optimal biosynthesis conditions were as follows: beta-sitosterol concentration of 50 micromol/mL, the molar ratio of CLA to beta-sitosterol of 1:1, the lipase concentration of 20 mg/mL, and 4 A molecular sieve concentration of 60 mg/mL in n-hexane at 50 degrees C with vigorous shaking of 150 rpm for 72 h, and the highest yield of CLS reached 72.6%. The isolated CLS mixed with mice feed had good cholesterol-lowering properties. It decreased serum total cholesterol (TC), serum triacylglycerols (TAGs), serum low-density lipoprotein cholesterol (LDL-C), atherogenic index (AI), liver weight (LW), liver index (LI), liver TC, and TAGs of mice, which was shown that CLS could prevent the formation of atherosclerosis and moderate the fat pathologic changes of liver. However, the HDL-C was not decreased, which proved the advantage of CLS over the other cholesterol-lowering products.
An efficient method for enzymatic-selective synthesis of dilauryl mannoses was developed using lipase-catalyzed condensation of D: -mannose and lauric acid in a simultaneous reaction-extraction system. The highest equilibrium conversion of diesters of 51% (1,6-diester: 14%; 3,6-diester: 18%; 4,6-diester: 19%) and the total conversion of mono and dilauryl mannoses of 76% were achieved at the n-hexane/acetonitrile ratio of 1:1, the molar ratio of lauric acid to mannose of 4:1, 60 g/l molecular sieves and 5 g/l lipase at 50 degrees C for 72 h in 15 ml SRE system. The new system will be important for the synthesis of dilauryl mannoses.
Title: Lipase-catalyzed selective synthesis of monolauroyl maltose using continuous stirred tank reactor Liu Q, Jia C, Kim JM, Jiang P, Zhang X, Feng B, Xu S Ref: Biotechnol Lett, 30:497, 2008 : PubMed
Monolauroyl maltose was synthesized by an immobilized lipase that catalyzed condensation of maltose and lauric acid in acetone using a batch reactor or a continuous stirred tank reactor. Mono- and di-lauroyl maltoses were identified by FT-IR, (1)H NMR, (13)C NMR and MS. Monolauroyl maltose was selectively synthesized in a continuous stirred tank reactor and no diester was detected. The highest concentration of monolauroyl maltose at 28 mmol/l was obtained in 250 ml acetone when maltose was added at 4 g/d and the molar ratio of lauric acid to maltose was fixed at 4:1 at a flow rate of 0.15 ml/min for both influx and effluent without supplement of fresh molecular sieve.
Title: Interaction with sigma(1) protein, but not N-methyl-D-aspartate receptor, is involved in the pharmacological activity of donepezil Maurice T, Meunier J, Feng B, Ieni J, Monaghan DT Ref: Journal of Pharmacology & Experimental Therapeutics, 317:606, 2006 : PubMed
In the present study, we examined the interaction of (+/-)-2,3-dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]-methyl]-1H-in den-1-one hydrochloride (donepezil), a potent cholinesterase inhibitor, with two additional therapeutically relevant targets, N-methyl-d-aspartate (NMDA) and sigma(1) receptors. Donepezil blocked the responses of recombinant NMDA receptors expressed in Xenopus oocytes. The blockade was voltage-dependent, suggesting a channel blocker mechanism of action, and was not competitive at either the l-glutamate or glycine binding sites. The low potency of donepezil (IC(50) = 0.7-3 mM) suggests that NMDA receptor blockade does not contribute to the therapeutic actions of donepezil. Of potential therapeutic relevance, donepezil binds to the sigma(1) receptor with high affinity (K(i) = 14.6 nM) in an in vitro preparation (Neurosci Lett 260:5-8, 1999). Thus, we sought to determine whether an interaction with the sigma(1) receptor may occur in vivo under physiologically relevant conditions by evaluating the sigma(1) receptor dependence effects of donepezil in behavioral tasks. Donepezil showed antidepressant-like activity in the mouse-forced swimming test as did the sigma(1) receptor agonist igmesine. This effect was not displayed by the other cholinesterase inhibitors, rivastigmine and tacrine. The donepezil and igmesine effects were blocked by preadministration of the sigma(1) receptor antagonist N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino) ethylamine (BD1047) and an in vivo antisense probe treatment. The memory-enhancing effect of donepezil was also investigated. All cholinesterase inhibitors attenuated dizocilpine-induced learning impairments. However, only the donepezil and igmesine effects were blocked by BD1047 or the antisense treatment. Therefore, donepezil behaved as an effective sigma(1) receptor agonist on these behavioral responses, and an interaction of the drug with the sigma(1) receptor must be considered in its pharmacological actions.
Title: Molecular Cloning and Characterization of WdPKS1, a Gene Involved in Dihydroxynaphthalene Melanin Biosynthesis and Virulence in Wangiella (Exophiala) dermatitidis. Feng B, Wang X, Hauser M, Kaufmann S, Jentsch S, Haase G, Becker JM, Szaniszlo PJ Ref: Infect Immun, 69:1781, 2001 : PubMed
AIM: To compare the efficacy and safety between huperzine-A (Hup) in capsules and tablets for treating patients with Alzheimer disease (AD). METHODS: Using multicenter, prospective, double-blind, double-mimic, parallel, positive controlled and randomized methods, 60 patients meeting with the NINCDS-ARDRA criteria of AD were divided into 2 equal groups. Patients in the capsule group received 4 capsules of Hup (each contains 50 micrograms) and 4 tablets of placebo (lactose and starch inside); while the tablet group received 4 tablets of Hup (each contains 50 micrograms) and 4 capsules of placebo, p.o., twice a day for 60 d. All the patients were evaluated with a lot of related ranting scales, and physiological and laboratory examination. RESULTS: There were significant differences (P < 0.01) on all the psychological evaluations between 'before' and 'after' the 60-d trial of 2 groups, but there was no significant difference between 2 groups by group t test (P > 0.05). The changes of oxygen free radicals in 2 groups showed marked improvement. No severe side effect besides moderate to mild nausea was found in both groups. CONCLUSION: There is equal efficacy and safety between Hup in capsule and tablet for treating patients with AD, and Hup can reduce the pathological changes of the oxygen free radicals in the plasma and erythrocytes of patients with AD.
Title: A color-selectable and site-specific integrative transformation system for gene expression studies in the dematiaceous fungus Wangiella (Exophiala) dermatitidis Ye X, Feng B, Szaniszlo PJ Ref: Curr Genet, 36:241, 1999 : PubMed
To explore potential virulence factors in the dematiaceous (melanized) fungus Wangiella dermatitidis, we established a gene expression system with properties of homologous transformation and color identification. Using a polyketide synthase gene (WdPKS1) fragment for targeting, we found that 52% of transformants became albinos easily distinguishable from nonspecific transformants. Southern analysis confirmed that the integrations were at the WdPKS1 locus, which however did not affect transformant growth. With a heterologous promoter, P-glaA, enhanced expression of lacZ was found at 37 degrees C. Our results indicated that this system allows the efficient production of isogenic strains for gene function analysis in W. dermatitidis.
