Monomeric Compounds Research Articles

Role of Episamarcandin in Promoting the Apoptosis of Human Colon Cancer HCT116 Cells through the PI3K-Akt Signaling Pathway.

This study identifies the active ingredients of Ferula sinkiangensis and investigates the role and mechanism of episamarcandin in colon cancer cells. The silica gel column chromatography was utilized to separate the chemical components of Ferula sinkiangensis. Sephadex LH-20 and semipreparative HPLC were adopted for further separation and purification. The compound episamarcandin showed good anticolon cancer activity among the 13 monomeric compounds obtained. Its effects on the apoptosis, cell cycle, and invasion and migration of colon cancer HCT 116 cells and PI3K-Akt signaling pathway were further investigated. The results showed that, similar to positive control cisplatin, episamarcandin inhibited the proliferation, promoted the apoptosis, arrested cells at G0/G1 phase, and suppressed migration and invasion of HCT 116 cells. A large number of apoptotic HCT 116 cells were observed under a transmission electron microscope. Fluorescence real-time quantitative PCR and western blot analysis showed that episamarcandin increased the expression of PTEN, p53, and Bax and decreased the expression of P-Akt, Akt, mTOR, Bcl-xl, and Bcl-2. Conclusively, episamarcandin may inhibit cell proliferation, migration, and invasion and promote the apoptosis of human colon cancer HCT 116 cells possibly through the PI3K-Akt signaling pathway.

Ginsenoside Rh2 stimulates the production of mitochondrial reactive oxygen species and induces apoptosis of cervical cancer cells by inhibiting mitochondrial electron transfer chain complex.

Ginsenoside Rh2 (G-Rh2) is a monomeric compound that extracted from ginseng and possesses anti-cancer activities both in vitro and in vivo. Previously, we reported that G-Rh2 induces apoptosis in HeLa cervical cancer cells and that the process was related to reactive oxygen species (ROS) accumulation and mitochondrial dysfunction. However, the upstream mechanisms of G-Rh2, along with its cellular targets, remain to be elucidated. In the present study, the Cell Counting Kit-8 assay, flow cytometry and Hoechst staining revealed that G-Rh2 significantly inhibited cell viability and induced apoptosis of cervical cancer cells. However, G-Rh2 was demonstrated to be non-toxic to End1/e6e7 cells. JC-1, rhodamine 123 staining, oxidative phosphorylation and glycolysis capacity assays demonstrated that G-Rh2 exposure caused an immediate decrease in mitochondrial transmembrane potential due to its inhibition of mitochondrial oxidative phosphorylation, as well as glycolysis, both of which reduced cellular ATP production. Western blotting and electron transport chain (ETC) activity assays revealed that G-Rh2 significantly inhibited the activity of ETC complexes I, III and V. Overexpression of ETC complex III partially significantly restored mitochondrial ROS and inhibited the apoptosis of cervical cancer cells induced by G-Rh2. The predicted results of binding energy in molecular docking, confirmed that G-Rh2 was highly likely to induce mitochondrial ROS production and promote cell apoptosis by targeting the ETC complex, especially for ETC complex III. Taken together, the present results revealed the potential anti-cervical cancer activity of G-Rh2 and provide direct evidence for the contribution of impaired ETC complex activity to cervical cancer cell death.

Phloretin potentiates polymyxin E activity against gram-negative bacteria

AimsThe spread of plasmid-mediated polymyxin resistance has jeopardized the use of polymyxin, the last defender that combats infections caused by multidrug-resistant (MDR) gram-negative pathogens. Main methodsIn this study, phloretin, as a monomeric compound extracted from natural plants, showed a good synergistic effect with polymyxin E against gram-negative bacteria, as evaluated by minimal inhibit concentration (MIC) assay and a series of assays, including growth curve, time-killing, and Western blot assays. A model of mice infected by Salmonella sp. stain HYM2 was established to further identify the synergistic effect of phloretin with polymyxin E. Key findingsThe results suggested that phloretin had the potential ability to recover the antibacterial sensitivity of polymyxin E from 64 μg/mL to no more than 2 μg/mL in E. coli ZJ478 or in Salmonella sp. stain HYM2 with a 32-fold decrease. A series of strains, including mcr-1-positive and mcr-1-negative strains, were treated with a combination of phloretin and polymyxin E, and the fractional inhibitory concentration (FIC) values were all found to be below 0.5. However, the combination of phloretin and polymyxin E did not lead to bacterial resistance. In vivo, the survival rate of infected mice reached nearly 80% with the combination treatment, and the cecal colony value also decreased significantly. SignificanceAll the above results indicated that phloretin is a potential polymyxin potentiator to combat gram-negative stains.

Effects of residual phenolic compounds on xylanase-assisted ClO2 bleaching of hardwood kraft pulp

In both pulping and bleaching processes, lignin in the pulp fiber is degraded into smaller molecules that need to be rinsed away. However, despite the installation of automatic washing equipment, the small phenolic compounds among other lignin degradation products can hardly be completely removed from the brownstock. Among the myriad of small phenolic compounds degrading from lignin, some are water-soluble and highly reactive with bleaching reagents. To understand the impact of residual phenolic compounds from black liquor on pulp bleaching, six monomeric phenolic model compounds were tested in this study. Catechol and vanillin showed inhibitory effects on xylanase activity, while catechol, vanillin, and guaiacol interfered with the delignification reaction in the chlorine dioxide (D) and alkaline extraction (E) stages of the bleaching sequence, thereby preserving the integrity of cellulose in the pulp. Because the efficiency of xylanase and bleaching reagents is hindered by the presence of these phenolic compounds, higher operational cost and more bleaching reagents are needed, which are incompatible with modern environmental policies in the world. Nonetheless, the presence of remaining soluble phenolic compounds in the brownstock can improve the bleaching selectivity important for the production of high-quality pulp with less-degraded cellulose chains.

Chance and Necessity in the Evolution of Matter to Life: A Comprehensive Hypothesis

Specialists in several branches of life sciences are trying to solve, piece by piece, the immensely complex puzzle of the origin of life. Some parts of the puzzle seem to appear with a rather high degree of clarity, while others remain totally obscure. We cannot be sure that life emerged only on our Earth, but we believe that the presence of large amounts of water in its liquid state is absolutely essential for the emergence and evolution of living matter. We can also assume that the latter exploits everywhere the same light elements, mainly C, H, O, N, S, and P, and somehow manipulates the same simple monomeric and polymeric organic compounds, such as alpha-amino acids, carbohydrates, nucleic bases, and surface-active carboxylic acids. The author contributes to the field by stating that all fundamental particles of our matter are “homochiral” and predominantly produce in an absolute asymmetric synthesis amino acids of L-configuration and carbohydrates of D-series. Another important point is that free atmospheric oxygen mainly stems from the photolysis of water molecules by cosmic irradiation and is not necessarily bound to living organisms on the planet.

Discovery of Dimeric Arylsulfonamides as Potent ADAM8 Inhibitors.

The metalloproteinase ADAM8 is upregulated in several cancers but has a dispensable function under physiological conditions. In tumor cells, ADAM8 is involved in invasion, migration, and angiogenesis. The use of bivalent inhibitors could impair migration and invasion through the double binding to a homodimeric form of ADAM8 located on the cell surface of tumor cells. Herein we report the rational design and synthesis of the first dimeric ADAM8 inhibitors selective over ADAM10 and matrix metalloproteinases. Bivalent derivatives have been obtained by dimerizing the structure of a previously described ADAM17 inhibitor, JG26. In particular, derivative 2 was shown to inhibit ADAM8 proteolytic activity in vitro and in cell-based assays at nanomolar concentration. Moreover, it was more effective than the parent monomeric compound in blocking invasiveness in the breast cancer MDA-MB-231 cell line, thus supporting our hypothesis about the importance of inhibiting the active homodimer of ADAM8.

Gallium Ligand Coordinated Group 15 Compounds (LGa−ECp', L=(CHNMe)2CH, E=N − Bi, Cp'=η1‐C5H5): Changeover from Electron‐Sharing to Donor‐Acceptor σ‐Interaction

AbstractWe have analyzed the electronic structure and bonding situation in monomeric compounds of gallium with group 15 elements (LGa−ECp', L=(CHNMe)2CH, E=N (1), P (2), As (3), Sb (4) and Bi (5)) at the M06/def2‐TZVPP//BP86/def2‐SVP level of theory. The compounds 1–5 have a singlet ground state with a polarized Ga−E double bond. The molecular orbital analysis indicates that the Ga−E π‐MO and the lone pair on E are susceptible to nucleophilic reactivity. The nucleophilic reactivity of Ga−E π‐MO increases, and that of lone pair on E reduces when the compound changes from 1 to 5. The EDA‐NOCV analysis indicates that the nitrogen and phosphorous form charge‐separated electron‐sharing σ‐bond with Ga. The apparent switchover between the electron‐sharing σ‐interaction and donor‐acceptor σ‐interaction occurs when the group 15 element is arsenic. On the other hand, antimony and bismuth exhibit donor‐acceptor interaction with the LGa fragment in compounds 4 and 5. The π‐bond in 1–5 is similar and is formed by the donation of the p‐type lone pair on E‐atom (pz) to the empty pz‐orbital of Ga. The bonding analysis also shows that the strength of π‐bonding is reduced on moving towards the heavier elements. A very high first and second proton affinity indicates that group 15 elements in compounds 1–5 act as double Lewis bases.

(Me6TREN)MgOCHPh2][B(C6F5)4]: A Model Complex to Explore the Catalytic Activity of Magnesium Alkoxides in Ketone Hydroboration

AbstractThe sterically hindered monomeric alkoxomagnesium compound [(Me6TREN)MgOCHPh2][B(C6F5)4] (1) has been used to explore the role of magnesium alkoxides in ketone hydroboration. Experiments and DFT calculations are suggestive of a concerted reaction pathway traversing through a six‐membered transition state involving Mg−OCHPh2, B−H, and C=O bonds. Prompted by this hypothesis, we investigated the activity of [Mg(OCHPh2)2] (3), which exhibits turn‐over frequency reaching up to 59,400 h−1 under solvent‐free conditions and stability towards C=C, −OH, −NH2 and −NO2. Due to the non‐existence of a metal hydride intermediate, such catalytic reactions will not get hindered in the presence of additional reactive functional groups.

Antiviral activity of esculin against white spot syndrome virus: A new starting point for prevention and control of white spot disease outbreaks in shrimp seedling culture.

White spot syndrome virus (WSSV) is a pathogenic and threatening virus in shrimp culture for which there is no effective control strategy. Finding antiviral lead compounds for the development of anti-WSSV drugs is urgent and necessary; in this study, esculin from 12 monomeric compounds exhibited an excellent anti-WSSV activity. The results showed that esculin increased the survival rate of WSSV-infected shrimps by 59% and reduced the virus copy number in vivo over 90% at 100μM. In the pre-treatment and post-treatment experiments, esculin could prevent and treat WSSV infection. Compared with the control group, the virus copy number decreased by 30% after 6h of esculin pre-incubation with WSSV particles and inhibited horizontal transmission of WSSV to a certain extent. Considering that the antiviral activity of esculin was stable in the aquacultural water for 2days, we evaluated the dosing pattern of continuous medication changes. Obviously, the survival rate of WSSV-infected shrimps was 0% at 108h when no esculin exchange was made, while at 120h the survival rate was over 40% at continuous medicine changes. In addition, esculin significantly increased the expression of antimicrobial peptides and thus improved the ability of shrimp to resist WSSV. Overall, our findings suggest that esculin has the potential to be developed into an anti-WSSV medicine.

Adsorption and Aggregation Behavior of Mixtures of Quaternary-Ammonium-Salt-Type Amphiphilic Compounds with Fluorinated Counterions and Surfactants.

The surface adsorption and aggregation behavior of a mixture of quaternary-ammonium-salt-type amphiphilic monomeric compounds (C4 FSA, C8 FSA, and C4 NTf2) or gemini compounds (C10-2-C4 FSA) and various surfactants (nonionic hexaoxyethylene dodecyl ether (C12EO6), anionic sodium dodecyl sulfate (SDS), cationic dodecyltrimethylammonium bromide (C12TAB), and zwitterionic N-dodecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (C12Sb)) was investigated. Both types of compounds contained alkyl chains of nonidentical lengths that used bis(fluorosulfonyl)imide (FSA-) or bis(trifluoromethanesulfonyl)imide (NTf2-) as counterions. The mixtures were analyzed for surface tension, viscosity, electrical conductivity, and pyrene fluorescence, in addition to evaluation by cryogenic transmission electron microscopy, small-angle X-ray scattering, and dynamic light scattering. Our results showed that the surface tension depended on the surfactant structure. For the mixture of C8 FSA and SDS, as the SDS concentration increased, the surface tension first decreased and became constant at the critical micelle concentration (CMC). In this concentration range, C8 FSA and SDS were approximately equimolar (2.5 mmol dm-3), the mixture adsorbed efficiently at the air-water interface, and vesicles and linear-type micelles were formed in the solution owing to the decreased electrostatic repulsion between the hydrophilic groups. As the SDS concentration further increased, the surface tension increased and reached another constant value. The C8 FSA at the interface was replaced by SDS and the aggregates transformed into spherical micelles. The surface tension plot of the mixture of the amphiphilic compounds and C12Sb showed a minimum at the CMC. The lowest CMC and surface tension were observed for C10-2-C4 FSA, indicating that the gemini compounds offer excellent adsorption and orientation at the air-water interface. It was revealed that the quaternary-ammonium-salt-type amphiphilic compounds in this study acted as ionic liquids on their own and as surfactants in aqueous solution. Further, they could improve the surface activity of conventional ionic surfactants.

Role of F124 in the inhibition of Bacillus firmus K-1 Xyn11A by monomeric aromatic phenolic compounds

This study aimed to investigate the inhibitory effect of monomeric aromatic phenolic compounds on Xyn11A and its F124A mutant. The inhibitory assay showed gallic acid as the most potent inhibitor for the WT. Conversely, gallic acid completely lost its inhibitory effect and resistance to the other compounds increased significantly in the F124A mutant. Molecular docking revealed that phenolic compounds inhibited WT by simultaneously binding to E78, R112, and F124. The pi-pi stacking of F124 and aromatic rings of phenolic compounds mediated the hydrogen bonds formed between phenolic inhibitors and E78. Gallic acid's strongest inhibitory effects in WT may be due to the high number of hydroxyl groups. However, in F124A, the phenolic compounds bound tyrosine residues sitting far from the catalytic site. Gallic acid's binding to Y69, which is furthest away from the catalytic site and highest specific binding energy, may have contributed to gallic acid's loss of inhibitory effects in F124A.

Thermal Conversion of Flax Shives in Sub- and Supercritical Ethanol in the Presence of Ru/C Catalyst

Thermal conversion of flax shives was studied in sub- and supercritical ethanol medium at 225 and 250 °C in the presence of the bifunctional catalyst 3% Ru/C. The use of 3% Ru/C catalyst in the process of thermal conversion of flax shives in supercritical ethanol was found to increase the conversion of the shives by 27% and the yield of liquid products by 10%. The use of 3% Ru/C catalyst in sub- and supercritical ethanol led to the destruction of both lignin and cellulose. The degree of delignification in the non-catalytic thermal conversion increased upon transition from subcritical (225 °C) to supercritical (250 °C) conditions. Main monomeric products of the thermal conversion process were guaiacylpropene or guaiacylpropane depending on the process temperature. In the presence of Ru/C catalyst, the molecular weight distribution was shifted towards an increase in the content of monomeric compounds in the liquid products.

Traditional Uses, Phytochemical Constituents and Pharmacological Properties of Averrhoa carambola L.: A Review.

Averrhoa carambola L. (star fruit) is an edible fruit that is extensively cultivated in southern China, Southeast Asia, India, and northern South America. It has a sweet and juicy taste and is frequently used in fruit salads and fruit platters, as a garnish in cocktail drinks and beverages, or squeezed into juice and served as a beverage. Traditionally, it has been used for treating diabetes and diabetic nephropathy, arthralgia, vomiting, lithangiuria, coughing, hangovers, and chronic paroxysmal headache for thousands of years. Currently, approximately 132 compounds have been isolated from A. carambola. Among them, flavonoids, benzoquinone, and their glycosides have been considered as biologically active substances, which are responsible for various biological activities. Pharmacological studies have revealed that crude extracts or monomeric compounds from A. carambola exhibit multiple bioactivities, such as anti-oxidant, anti-hyperglycemic, anti-obesity, anti-hyperlipidemic, anti-tumor, anti-inflammatory, hepatoprotective, cardioprotective, anti-hypertensive, neuroprotective, and others. Thus, A. carambola is a valuable treatment in Chinese medicine with therapeutic potential for multiple diseases, especially diabetes and diabetes-related diseases. Even though it is a very promising candidate in the development of functional food and the pharmaceutical industry, reports on its bioactivities have only been conducted in vivo and in vitro and there is a gap in research regarding clinical settings and safety. This review therefore provides a comprehensive and systematic overview of current progress on botany, ethnopharmacology, phytochemistry, pharmacology, and toxicity of A. carambola, providing a valuable reference for further developments and applications of A. carambola in the pharmaceutical industry and functional food.

Syntheses, Magnetic, Spectral and Biological Studies on the Coordination Compounds of N-(2-Hydroxyphenyl)-C-(3′- Carboxy-2′-Hydroxyphenyl) Thiazolidin-4-One

A dry benzene solution of the Schiff base, N-(2-hydroxyphenyl)-3′-carboxy-2′- hydroxybenzylideneimine upon reacting with mercaptoacetic acid undergoes cyclization and forms N- (2-hydroxyphenyl)-C-(3′-carboxy-2′-hydroxyphenyl)thiazolidin-4-one, LH3 (I). A MeOH solution of I reacts with Ni(II) and UO2(VI) ions and forms the monomeric coordination compounds, [Ni(LH)(MeOH)3] and [UO2(LH)(MeOH)]. The coordination compounds have been characterized on the basis of elemental analyses, molar conductance, molecular weight, spectral (IR, reflectance) studies and magnetic susceptibility measurements. I behaves as a dibasic tridentate OOS donor ligand in these compounds. The compounds are non-electrolytes (M = 4.3-6.4 mho cm2 mol-1) in DMF. Octahedral structure for Ni(II) and UO2(VI) compounds are suggested. LH3 (I) and its complexes while testing with E.Coli. (Gram Negative) and S. Aureus (Gram positive) bacteria show antibacterial activities.

Gypenoside LVI improves hepatic LDL uptake by decreasing PCSK9 and upregulating LDLR expression

BackgroundsAtherosclerotic Cardiovascular Disease (ASCVD) is defined as ischemic or endothelial dysfunction-various inflammatory diseases, which is mainly caused by excessive low-density lipoprotein cholesterol (LDL-C) in circulating blood. Gynostemma pentaphyllum is a traditional Chinese medicine, and total Gypenosides are used for the treatment of hyperlipidemia and to reduce circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) level. However, which gypenoside involved in the modulation of PCSK9 expression is still unknown. PurposeThis study aimed to discover effective PCSK9 inhibitors from Gypenosides in accordance with the 2019 ESC/EAS guidelines. MethodsHPLC was employed to determine major six components of Gypenosides. The inhibitory activity on secreted PCSK9 in HepG2 of six major compounds from Gypenosides were screened by ELISA. The level of low-density lipoprotein (LDL) receptor (LDLR) was determined by Flow cytometry and Immunofluorescence. The expression levels of PCSK9, LDLR and Sterol-regulatory element binding proteins-2 (SREBP-2) were analyzed by qPCR and Western blot. DiI-LDL was added to evaluated LDL uptake into HepG2. ResultsThe results suggested that the mRNA and protein levels of PCSK9 were down-regulated by Gypenoside LVI and the LDLR degradation in lysosomes system was inhibited, thereby leading to an increasing in LDL uptake into HepG2 cells. Furthermore, Gypenoside LVI decreased PCSK9 expression induced by stains. Altogether, Gypenoside LVI enhances LDL uptake into HepG2 cells by increased LDLR level on cell-surface and suppressed PCSK9 expression. ConclusionThis indicates that Gypenoside LVI can be used as a useful supplement for statins in the treatment of hypercholesterolemia. This is firstly reported that monomeric compound of G. pentaphyllum planted in Hunan province has the effect of increasing LDL-C uptake in hepatocytes via inhibiting PCSK9 expression.

An integrated approach to uncover anti-tumor active materials of Curcumae Rhizoma-Sparganii Rhizoma based on spectrum-effect relationship, molecular docking, and ADME evaluation

Ethnopharmacological relevanceCurcumae Rhizoma-Sparganii Rhizoma (CR-SR), an ancient and classical herbal couple, has been extensively used for tumor treatment in clinic of traditional Chinese medicines (TCMs). Aim of the studyThe study aimed to uncover the anti-tumor active materials of CR-SR water decoction (CR:SR = 1:1) via an integrated approach of spectrum-effect relationship, molecular docking, and ADME evaluation. Materials and methodsThe anti-tumor activities toward A549, HepG2, Hela, BGC-823, and MCF-7 cells of the different polar elution fractions (DPEFs) of CR, SR, and CR-SR were determined by Cell Counting Kit-8 (CCK-8) assay. Likewise, the DPEFs’ combinations of CR and SR were also tested. The chemical fingerprints of these fractions were profiled by HPLC. Meanwhile, HPLC-ESI-Q-TOF-MS/MS was applied for the identification of chemical components. The main effect-related compounds were screened out by spectrum-effect relationship and molecular docking method. The oral bioavailability and druggability of these active components were subsequently evaluated. Finally, five monomeric compounds were validated experimentally using HepG2 cells. ResultsThe 80% ethanol elution fraction of CR, SR, and CR-SR showed strong anti-tumor effects toward five cells. Also, the combinations with the 80% ethanol elution fraction of CR and SR showed stronger tumor inhibition effects among the DPEFs’ combinations of CR and SR. By spectrum-effect relationship, HPLC-MS, and molecular docking analysis, 24 main effect-related compounds seemed to have potential anti-tumor effects. ADME evaluation showed rutin performed low oral bioavailability and druggability. Therefore, we suppose that 23 compounds (including 4 unknown compounds) are the primary anti-tumor active components of CR-SR water decoction. Among them, zederone, curcumol, chlorogenic acid, calycosin, and curcumenol were validated successfully with good tumor inhibition effects. ConclusionsIn summary, this study demonstrated that the multi-components of CR-SR contribute to its anti-tumor effects. It established a rapid and useful strategy to explore the active material basis of traditional Chinese herbal couples with a multi-technology integrated approach in practice, including chromatography, mass spectrometry, machine algorithm models, online databases, and in vitro cell experiments.

Separation of monomeric and dimeric phenolic compounds in lignosulphonate lignin on different stationary phases using ultrahigh-performance supercritical fluid chromatography

Lignin is a promising renewable resource and its valorization could help to reduce our dependency on fossil carbon resources. Especially the production of small molecular weight and economically valuable compounds, such as vanillin, are of interest. A good separation of the sample components is crucial for a confident identification of compounds in complex sample mixtures using for instance mass spectrometry. In this work, the resolving power and selectivity of five different stationary phases for ultrahigh-performance supercritical fluid chromatography were studied for the class separation of lignin monomers (LMs) and dimers (LDs). A separation of LMs and LDs will help to identify such compounds in complex technical lignin samples. It could be shown that stationary phases with both hydrogen-bonding acceptor and donator groups offer high overall resolving power, while π-π-interactions are advantageous for the separation of the two compound classes. An almost complete separation combined with an improved overall resolving power was achieved with the 1-aminoanthracene stationary phase, which offers both hydrogen-bonding interactions and π-π-interactions.

Recent Progress in the Chemical Upcycling of Plastic Wastes.

The massive generation of plastic wastes without satisfactory treatment has induced severe environmental problems and gained increasing attentions. In this Minireview, recent progresses in the chemical upcycling of plastic wastes by using various methods (mainly in the past three to five years) is summarized. The chemical upcycling of plastic wastes points out a "plastic-based refinery" concept, which is to use the plastic wastes as platform feedstocks to produce highly valuable monomeric or oligomeric compounds, putting the plastic wastes back into a circular economy. The different chemical methods to upcycle plastic wastes, including hydrogenolysis, photocatalysis, pyrolysis, solvolysis, and others, are introduced in each section to valorize diverse plastic feedstocks into value-added chemicals, materials, or fuels. In addition, other emerging technologies as well as the new generation of plastic thermosets are covered.

Production of itaconic acid from alkali pretreated lignin by dynamic two stage bioconversion

Expanding the portfolio of products that can be made from lignin will be critical to enabling a viable bio-based economy. Here, we engineer Pseudomonas putida for high-yield production of the tricarboxylic acid cycle-derived building block chemical, itaconic acid, from model aromatic compounds and aromatics derived from lignin. We develop a nitrogen starvation-detecting biosensor for dynamic two-stage bioproduction in which itaconic acid is produced during a non-growth associated production phase. Through the use of two distinct itaconic acid production pathways, the tuning of TCA cycle gene expression, deletion of competing pathways, and dynamic regulation, we achieve an overall maximum yield of 56% (mol/mol) and titer of 1.3 g/L from p-coumarate, and 1.4 g/L titer from monomeric aromatic compounds produced from alkali-treated lignin. This work illustrates a proof-of-principle that using dynamic metabolic control to reroute carbon after it enters central metabolism enables production of valuable chemicals from lignin at high yields by relieving the burden of constitutively expressing toxic heterologous pathways.

The nephroprotective effects and mechanisms of rehmapicrogenin include ROS inhibition via an oestrogen-like pathway both in vivo and in vitro

BackgroundThe root of Rehmannia glutinosa (R. glutinosa) is commonly used in various traditional Chinese herbal formulae to ameliorate nephropathy; however, little is known about its active component(s) and mechanisms. AimIn the present study, we examined the protective effect and potential mechanism of rehmapicrogenin, a monomeric compound extracted from R. glutinosa, against Adriamycin (ADR)-induced nephropathy (AN) in vivo and in vitro. MethodsIn this study, an ADR-induced kidney injury model was employed to investigate the nephroprotective effects of rehmapicrogenin in mice. In vivo, ELISA kits, flow cytometry, haematoxylin-eosin staining, immunofluorescence techniques, and western blotting were used to evaluate the effect of rehmapicrogenin on kidney injury in mice. In vitro, the effects of rehmapicrogenin on NRK-52E cellular damage induced by ADR were determined using the 3-(4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The mechanism was investigated using ELISA kits, flow cytometry and In-Cell Western™ blotting. ResultsIn vivo, rehmapicrogenin treatment significantly attenuated the pathological changes in the kidney induced by ADR; rescued weight, serum creatinine (Scr), blood urea nitrogen (BUN) and urine albumin (U-ALB) levels; reduced reactive oxygen species (ROS) accumulation; and decreased oxidative stress, the apoptosis rate, and cell survival in ADR-treated mice. Importantly, both in vivo and in vitro experimental results demonstrated that rehmapicrogenin regulates the Nrf2/ARE signalling pathway, the most important pathway for oxidative stress. Rehmapicrogenin attenuated ADR-induced kidney damage by reducing oxidative stress through the oestrogen receptor pathway. Moreover, after treatment with ICI 182780 (the oestrogen receptor-nonspecific antagonist Faslodex), the improvement induced by rehmapicrogenin was significantly reversed. ConclusionsIn conclusion, rehmapicrogenin attenuates kidney damage by reducing inflammatory factor release through the oestrogen signalling pathway.