Fumarate Research Articles

The effects of ambient temperature exposure on feline fecal metabolome.

The fecal metabolome provides insight into overall gastrointestinal and microbial health. Methods for fecal sample storage in metabolomics research vary, however, making comparisons within current literature difficult. This study investigated the effect of ambient temperature exposure on microbial-derived metabolites of feline fecal samples. Fecal samples were collected from 11 healthy cats from a local boarding facility. Samples were manually homogenized and aliquoted. The first aliquot was frozen at -80°C within 1 hour of defecation, and remaining samples were exposed to ambient temperature for 2, 4, 6, 8, 12, and 24 h prior to freezing at -80°C. Fecal metabolites were quantified using 1H NMR spectroscopy. Fifty metabolites were grouped into six categories (27 amino acids, 8 fatty acids, 5 sugars, 3 alcohols, 2 nitrogenous bases, 5 miscellaneous). Concentrations of 20 out of 50 metabolites significantly differed due to ambient temperature exposure (7 amino acids, 6 fatty acids, 2 alcohols, 1 nitrogenous base, 4 miscellaneous). The earliest detected changes occurred 6 h post-defecation for cadaverine and fumaric acid. This study shows ambient temperature exposure alters the composition of the feline fecal metabolome, but short-term (up to 4 h) exposure prior to storage in the freezer seems to be acceptable.

Dimethyl fumarate possesses antiplatelet and antithrombotic properties

BackgroundDimethyl fumarate (DMF) is a methyl ester of fumaric acid and has been approved for treating multiple sclerosis (MS) and psoriasis due to anti-inflammatory effect. There is a close association between platelets and the pathogenesis of MS. Whether DMF affects platelet function remains unclear. Our study intends to evaluate DMF’s effect on platelet function. MethodsWashed human platelets were treated with different concentrations of DMF (0, 50, 100 and 200 μM) at 37 °C for 1 h followed by analysis of platelet aggregation, granules release, receptors expression, spreading and clot retraction. In addition, mice received intraperitoneal injection of DMF (15 mg/kg) to assess tail bleeding time, arterial and venous thrombosis. ResultsDMF significantly inhibited platelet aggregation and the release of dense/alpha granules in response to collagen-related peptide (CRP) or thrombin stimulation dose-dependently without altering the expression of platelet receptors αIIbβ3, GPIbα, and GPVI. In addition, DMF-treated platelets presented significantly reduced spreading on collagen or fibrinogen and thrombin-mediated clot retraction along with the decreased phosphorylation of c-Src and PLCγ2. Moreover, administration of DMF into mice significantly prolonged the tail bleeding time and impaired arterial and venous thrombus formation. Furthermore, DMF reduced the generation of intracellular reactive oxygen species and calcium mobilization, and inhibited NF-κB activation and the phosphorylation of ERK1/2, p38 and AKT. ConclusionDMF inhibits platelet function and arterial/venous thrombus formation. Considering the presence of thrombotic events in MS, our study indicates that DMF treatment for patients with MS might obtain both anti-inflammatory and anti-thrombotic benefits.

Differentiation of obese and healthy mice by analyzing the carboxylic acids in the TCA cycle in their feces

The tricarboxylic acid cycle is an important metabolic route in almost all living bodies, yet current analytical methods for the detection of the relevant tricarboxylic acids (TCAs) in biological samples are still unsatisfactory due to their complex matrix and physicochemical properties. In this work, a sample method based on solid phase extraction (SPE) in conjunction with liquid chromatography-mass spectrometry (LC-MS) analysis has been developed for the simultaneous determination of 7 TCAs, including α-ketoglutaric acid, malic acid, malonic acid, aconitic acid, citric acid, succinic acid and fumaric acid, in mice faeces. By treatment with macroporous styrene chelate resin and solid phase extraction, the matrix in mice feces was selectively and efficiently removed. Under optimized parameters, the limit of quantitation for the TCAs was in the range of 1-50 ng/mL, and the content of the TCAs in mice feces was determined with a recovery range of 76.2 % to 128.4 %. Interestingly, the content of malic acid, malonic acid, succinic acid and fumaric acid in the normal mice's feces was found to be 2-10 times higher than that of obese mice, indicating a new potential method for the diagnosis of obesity.

Nucleophosmin 1 associating with engulfment and cell motility protein 1 regulates hepatocellular carcinoma cell chemotaxis and metastasis.

The chemokine, C-X-C motif chemokine ligand 12 (CXCL12) and its G-protein-coupled receptor (GPCR) and C-X-C chemokine receptor type 4 (CXCR4), are closely associated with promoting hepatocellular carcinoma (HCC) chemotaxis and metastasis. The binding of CXCL12 and CXCR4 depends on the heterotrimeric Gi proteins to regulate actin polymerisation and mobility in HCC. Although the role of GPCR/Gi signalling in carcinogenesis migration has been intensively studied, the detailed mechanism remains largely unknown. In this study, a small interfering RNA technique was used to knock down the Nucleophosmin 1 (NPM1) gene expression. Through the chemotaxis and invasion assays, wound healing, proliferation, filamentous-actin, immunofluorescence, immunohistochemical assays, and co-immunoprecipitation assays, we investigated the specific biological role and underlying mechanisms of the NPM1 in HCC. Additionally, dimethyl fumarate (DMF), a fumaric acid ester, was used to inhibit the HCC cell chemokines and metastasis by regulating ELMO1 and NPM1. Therefore, this study reported that NPM1 gene expression was upregulated in the HCC tissues and cell lines. The NPM1 knockdown significantly inhibited the proliferation, migration, and chemotaxis of the HepG2 cells in vitro. Further mechanistic studies suggested that the NPM1 interacts with ELMO1 and the CXCL12/CXCR4 pathway activates NPM1-dependent regulation of the ELMO1 localisation. Furthermore, the DMF significantly inhibited tumour metastasis induced by the NPM1/ELMO1 signalling pathway, as observed in in vitro cell functional experiments. These data suggested that as a potentially novel therapeutic approach, the simultaneous targeting of NPM1 and ELMO1 could effectively be used to treat HCC.

Solubility Enhancement of Clozapine by Co-crystals

Cocrystallization of drug with coformers is a promising approach to alter the solid state properties of drug substances like solubility and dissolution. The objective of the present work was preparation, formulation and evaluation of the clozapine cocrystal by screening various coformers. Clozapine co-crystals were prepared using different coformers like benzoic acid, fumaric acid, sodium saccharin and sodium acetate. Cocrystals were prepared using solvent evaporation method and solvent drop grinding method. The prepared co-crystals were evaluated for saturation solubility, drug content, dissolution studies, XRD studies and DSC analysis.

Total phenolic and flavonoid contents and antioxidant, antimicrobial and antiproliferative activities of Polycarpontetraphyllum

Plants are organic materials that support a variety of biological processes. The biological activity of the Polycarpon tetraphyllum (L.) L plant was identified in this study. In this case, the Soxhlet apparatus was used to obtain ethanol and methanol extracts of the plant's aerial portions. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) values for the plant were determined using Rel Assay kits. The antioxidant potential of the plant extract was determined by the DPPH test. Antimicrobial activity was determined using the agar dilution test against six bacterial and three fungal strains. The antiproliferative activity of the plant extract against A549 lung cancer cell line was determined by MTT assay. Phenolic compounds in the plant were screened with LC-MS/MS device. As a result of the study, the DPPH activity of the plant was found to be higher in the methanol extract (75.72 ​± ​0.32) at a concentration of 2 ​mg/mL. TAS value of the plant was determined as 8.449 ​± ​0.143 ​mmol/L, TOS value as 12.129 ​± ​0.200 ​μmol/L and OSI value as 0.144 ​± ​0.004. It was determined that the plant extracts showed the highest effect against Acinetobacter baumannii, Candida albicans and C. krusei at 50 ​μg/mL. The ethanol extract of the plant was found to have stronger antiproliferative activity. In addition, the presence of acetohydroxamic acid, catechin hydrate, resveratrol, fumaric acid, 4-hydroxycinnamic acid, 4-gydroxybenzoic acid, oleuropein, ellagic acid, quercetin, butein and luteolin were found in the plant. In this context, it was determined that the plant has important biological activity.

Iron deficiency in the practice of a gynecologist: therapeutic efficacy

Introduction. Iron deficiency (ID) of varying severity is the most common and rather serious extra-gynecological complication of adenomyosis resulting from meno/metrorrhagia of varying intensity, up to abnormal uterine bleeding requiring surgical hemostasis. Taking into account the chronic course of the disease, the complexity of radical therapy as well as a systemic effect ID also particularly affecting reproductive system, an issue of sufficient and timely ID correction in patients with adenomyosis of varying severity remains relevant. Aim: to study an efficacy of ID therapy with drug containing ferrous fumarate and folic acid in patients with adenomyosis. Materials and Methods . An observational study was conducted, which included 90 patients with isolated adenomyosis of varying severity: 30 patients with degree 1 adenomyosis (group 1), 30 patients with degree 2 adenomyosis (group 2), 30 women with degree 3–4 (group 3). All patients received ferrous fumarate plus folic acid for 30 days. To identify an ID variant, the level of serum ferritin, iron, transferrin, total iron-binding capacity of blood serum (TIBC), clinical blood test parameters such as hemoglobin level, erythrocyte count, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC) were measured. Results. A significant increase in ferrokinetic parameters was found in all patient groups. The most significant and clinically important dynamics was noted for serum iron level and TIBC. For instance, after the therapy, the level of serum iron increased in group 1 from 11.0 ± 0.6 μmol/l up to 15.0 ± 1.1 μmol/l, in group 2 – from 9.0 ± 1.6 μmol/l up to 14 .0 ± 0.8 μmol/l, in group 3 from 7.0 ± 1.3 μmol/l up to 12.0 ± 1.3 μmol/l (p < 0.05). In addition, a decreased TIBC was found in group 3: from 68.0 ± 1.8 μmol/l down to 58.0 ± 1.7 μmol/l (p < 0.05); in groups 2 and 3 TIBC level tended to insignificantly decrease. Conclusion . The use of a preparation containing ferrous fumarate along with folic acid can effectively correct background ID of varying severity in patients with adenomyosis of varying intensity. An earlier and longer administration of iron preparations in patients with adenomyosis along with clinical and laboratory parameter monitoring is recommended to achieve more pronounced clinical effect.

Exploration of new solid forms of anti-emetic drug domperidone: Novel salts with enhanced solubility and dissolution

Domperidone (DMP) is an anti-emetic agent used for treatments like dyspepsia, indigestion, epigastric pain, nausea, and vomiting. DMP belongs to BCS class II having poor aqueous solubility and high permeability. In the current work, nine novel salts of DMP with coformers namely acetic acid (ACA), oxalic acid (OXC), Fumaric acid (FMA), Glutaric acid (GLA), Adipic acid (ADA), Saccharin (SAH), Salicylic acid (SAL), 4-Hydroxybenzoic acid (4HBA), and Theophylline-7-acetic acid (THA) have been reported. The crystal structures have been determined by Single-Crystal X-ray Diffraction (SC-XRD). In the SC-XRD study, proton transfer from coformer to piperidine ‘N’ of DMP was observed in all the salts. The prepared salts were further characterized by spectroscopic (FT-IR), thermal (DSC and TGA), and Powder X-ray Diffraction (PXRD) techniques. The solubility study in purified water (pH=6.5) showed 127 and 51-fold enhancement in DMP-GLA and DMP-ACA salts. The salts namely, DMP-ACA, DMP-GLA, and DMP-SAL disintegrate to parent DMP after attaining equilibrium in water medium. In 0.1 N HCl medium, DMP-ACA, DMP-GLA, DMP-ADA, and DMP-4HBA exhibited a two-fold increment in solubility compared to DMP. The in-vitro dissolution study in purified water showed faster drug release in DMP-ACA, DMP-GLA, and DMP-ADA salts.

Dietary Dityrosine Induces Oxidative Stress and Mitochondrial-Lipid Imbalance in Mouse Liver via MiR-144-3p-Mediated Downregulation of Nrf2.

Dityrosine (DT) is a protein oxidation marker present in many high-protein foods, such as dairy and meat products. Chronic dietary intake of DT induces oxidative stress damage in the liver and impairs energy metabolism. This study aims to investigate the mechanisms underlying the effects of DT on disrupted hepatic energy metabolism. The study investigates hepatic lipid accumulation, redox status imbalance, mitochondrial dysfunction, and energy metabolism disorders in 4-week-old C57BL/6J mice after 35 days of DT (420 µgkg-1 body weight) treatment. Transcriptome sequencing and quantitative real-time PCR in HepG2 cells show that DT mainly acted via miR-144-3p. miR-144-3p targets immune responsive gene 1 (IRG1) and decreases the fumaric acid level in the tricarboxylic acid (TCA) cycle, thereby decreasing nuclear factor erythroid 2-related factor 2 (Nrf2) expression and antioxidant activity. Administration of lycopene, a strong antioxidant, alleviates DT-induced damage in mice, confirming the involvement of the Nrf2 pathway in DT-induced abnormal hepatic lipid metabolism and energy homeostasis.

Selective pertraction of dicarboxylic acids from simulated Rhizopus oryzae fermentation broths

Fumaric, malic and succinic acids have been selectively separated by facilitated pertraction with Amberlite LA-2, using n-heptane as liquid membrane. The feed phase consisted on viscous aqueous solution with similar mixture of carboxylic acids and viscosity as those of Rhizopus oryzae fermentation broth. Due to the differences between the acidities and molecule size of these acids, it is possible to selectively recover fumaric acid from the initial solution. The pH-gradient between the feed and stripping phases, as well as carrier concentration in the liquid membrane represent the main process parameters influencing the pertraction selectivity. Among them, Amberlite LA-2 concentration exhibits the most important control on the selectivity factor S, the maximum value of S being reached for carrier concentration of 30 g/l. The increase of feed phase viscosity amplified the magnitude of these influences on pertraction selectivity, due to the hindrance of acids diffusion towards the region where their reaction with Amberlite LA-2 occurs, effect more important for malic acid. Therefore, by modifying the viscosity from 1 to 24 cP, the maximum value of selectivity factor was increased from 12 to 18.8.

Monomethyl fumarate prevents alloimmune rejection in mouse heart transplantation by inducing tolerogenic dendritic cells.

Dendritic cells (DCs) are important targets for eliciting allograft rejection after transplantation. Previous studies have demonstrated that metabolic reprogramming of DCs can transform their immune functions and induce their differentiation into tolerogenic DCs. In this study, we aim to investigate the protective effects and mechanisms of monomethyl fumarate (MMF), a bioactive metabolite of fumaric acid esters, in a mouse model of allogeneic heart transplantation. Bone marrow-derived DCs are harvested and treated with MMF to determine the impact of MMF on the phenotype and immunosuppressive function of DCs by flow cytometry and T-cell proliferation assays. RNA sequencing and Seahorse analyses are performed for mature DCs and MMF-treated DCs (MMF-DCs) to investigate the underlying mechanism. Our results show that MMF prolongs the survival time of heart grafts and inhibits the activation of DCs in vivo. MMF-DCs exhibit a tolerogenic phenotype and function in vitro. RNA sequencing and Seahorse analyses reveal that MMF activates the Nrf2 pathway and mediates metabolic reprogramming. Additionally, MMF-DC infusion prolongs cardiac allograft survival, induces regulatory T cells, and inhibits T-cell activation. MMF prevents allograft rejection in mouse heart transplantation by inducing tolerogenic DCs.

Evaluation of the Drug-Drug Interaction Potential of Ensitrelvir Fumaric Acid with Cytochrome P450 3A Substrates in Healthy Japanese Adults.

Management of drug-drug interactions (DDIs) for ensitrelvir, a novel 3-chymotrypsin-like protease inhibitor of SARS-CoV-2 infection is crucial. A previous clinical DDI study of ensitrelvir with midazolam, a clinical index cytochrome P450 (CYP) 3A substrate, demonstrated that ensitrelvir given for 5 days orally with a loading/maintenance dose of 750/250 mg acted as a strong CYP3A inhibitor. The objectives of this study were to investigate the effect of ensitrelvir on the pharmacokinetics of CYP3A substrates, dexamethasone, prednisolone and midazolam, and to assess the pharmacokinetics, safety, and tolerability of ensitrelvir following multiple-dose administration of ensitrelvir. This was a Phase 1, multicenter, single-arm, open-label study in healthy Japanese adult participants. The effects of multiple doses of ensitrelvir in the fasted state on the pharmacokinetics of dexamethasone, prednisolone, and midazolam were investigated. Ensitrelvir was administered from Day 1 through Day 5, with a loading/maintenance dose of 750/250 mg for the dexamethasone and prednisolone cohorts whereas 375/125 mg for the midazolam cohort. Either dexamethasone, prednisolone, or midazolam was administered alone (Day -2) or in combination with ensitrelvir (Day 5) in each of the cohorts. Additionally, dexamethasone or prednisolone was administered on Days 9 and 14. The pharmacokinetic parameters of ensitrelvir, dexamethasone, prednisolone, and midazolam were calculated based on their plasma concentration data with non-compartmental analysis. In safety assessments, the nature, frequency, and severity of treatment-emergent adverse events were evaluated and recorded. The area under the concentration-time curve (AUC) ratio of dexamethasone on Day 5 was 3.47-fold compared with the corresponding values for dexamethasone alone on Day -2 and the effect diminished over time after the last dose of ensitrelvir. No clinically meaningful effect was observed for prednisolone. The AUC ratio of midazolam was 6.77-fold with ensitrelvir 375/125 mg suggesting ensitrelvir at 375/125 mg strongly inhibits CYP3A similar to that at 750/250 mg. No new safety signals with ensitrelvir were reported during the study. The inhibitory effect for CYP3A was confirmed after the last dose of ensitrelvir, and the effect diminished over time. In addition, ensitrelvir at 375/125 mg showed CYP3A inhibitory potential similar to that at 750/250 mg. These findings can be used as a clinical recommendation for prescribing ensitrelvir with regard to concomitant medications. Japan Registry of Clinical Trials identifier: jRCT2031210202.

Effect of double bond position and density on properties of UV-induced bio-based polyurethane adhesion-reducing adhesives

In this paper, hydroxyl terminated copolyesters with different double bond position and density were prepared from bio-based dibasic acids. Bio-based unsaturated polyesters with -C=CH2 in side (MPIA), -CH=CH- in main chain (MPFA), and with -C=CH2 in side and -CH=CH- in main chain together (BDIA) were synthesized by using itaconic acid, fumaric acid, cis-2-butene-1,4-diol, and 2-methyl-1,3-propanediol as raw materials. The number molecular weight of MPIA, MPFA and BDIA was controlled almost the same. UV-induced bio-based polyurethane adhesion-reducing adhesives (BPURA) was prepared by bio-based unsaturated polyester, isophorone diisocyanate (IPDI), chain extender and photoinitiator. BPURA produced by MPIA, MPFA and BDIA were named BPURA-1, BPURA-2 and BPURA-3, respectively. The 1800 peel strength before and after UV irradiation of BPURA-1 was 22.07 and 0.17 N/25 mm, while that of BPURA-2 was 8.56 and 0.34 N/25 mm, respectively. It could be found that the contribution of 1800 peel strength of -C=CH2 in side (BPURA-1) was greater than that of -CH=CH- in the main chain (BPURA-2). SEM and 3D laser measurement microscope showed that BPURA-3 had the highest roughness after UV irradiation, which is conducive to the viscosity reduction effect of the adhesive. The 1800 peel strength before and after UV irradiation of BPURA-3 was 21.22 and 0.11 N/25 mm, respectively, which meets the bond strength standard of temporary bonding adhesive during wafer processing.

Surface-modified cerium oxide as a corrosion inhibitor to enhance the performance of epoxy coatings

PurposeThe study aims to investigate the anticorrosion performance of epoxy coatings using modified cerium oxide (CeO2) by terephthalic acid (CeO2-t) and fumaric acid (CeO2-f) as corrosion inhibitors.Design/methodology/approachThe chemical state of CeO2-t, and CeO2-f were analyzed by infrared radiation (IR) and X-ray diffraction (XRD). The effect of different inhibitors on the coating properties was analyzed by neutral salt spray tests (NSST) and electrochemical impedance spectroscopy (EIS).FindingsThe results of IR and XRD illustrate that the modification of CeO2 was successful, and fumaric acid underwent a ring-opening reaction with epoxy resin (EP) in the coatings. The results of NSST and EIS showed that the coatings containing CeO2-f exhibited the best anticorrosion performance.Originality/valueCeO2 is an effective inhibitor of the organic coatings. When surface modified, it is chemically bonded to EP, enhancing the anticorrosion performance of EP.

Screening of Antiglaucoma, Antidiabetic, Anti-Alzheimer, and Antioxidant Activities of Astragalus alopecurus Pall-Analysis of Phenolics Profiles by LC-MS/MS.

Astragalus species are traditionally used for diabetes, ulcers, leukemia, wounds, stomachaches, sore throats, abdominal pain, and toothaches. Although the preventive effects of Astragalus species against diseases are known, there is no record of the therapeutic effects of Astragalus alopecurus. In this study, we aimed to evaluate the in vitro antiglaucoma, antidiabetic, anti-Alzheimer's disease, and antioxidant activities of the methanolic (MEAA) and water (WEAA) extracts of the aerial part of A. alopecurus. Additionally, its phenolic compound profiles were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). MEAA and WEAA were evaluated for their inhibition ability on α-glycosidase, α-amylase, acetylcholinesterase (AChE), and human carbonic anhydrase II (hCA II) enzymes. The phenolic compounds of MEAA were analyzed by LC-MS/MS. Furthermore, total phenolic and flavonoid contents were determined. In this context, the antioxidant activity was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), N,N-dimethyl-p-phenylene diamine (DMPD), ferric reducing antioxidant power (FRAP), cupric ions (Cu2+) reducing antioxidant capacity (CUPRAC), ferric ions (Fe3+) reducing, and ferrous ions (Fe2+) chelating methods. MEAA and WEAA had IC50 values of 9.07 and 2.24 μg/mL for α-glycosidase, 693.15 and 346.58 μg/mL for α-amylase, 1.99 and 2.45 μg/mL for AChE, and 147.7 and 171.7 μg/mL for hCA II. While the total phenolic amounts in MEAA and WEAA were 16.00 and 18.50 μg gallic acid equivalent (GAE)/mg extract, the total flavonoid contents in both extracts were calculated as 66.23 and 33.115 μg quercetin equivalent (QE)/mg, respectively. MEAA and WEAA showed, respectively, variable activities on DPPH radical scavenging (IC50: 99.02 and 115.53 μg/mL), ABTS radical scavenging (IC50: 32.21 and 30.22 µg/mL), DMPD radical scavenging (IC50: 231.05 and 65.22 μg/mL), and Fe2+ chelating (IC50: 46.21 and 33.01 μg/mL). MEAA and WEAA reducing abilities were, respectively, Fe3+ reducing (λ700: 0.308 and 0.284), FRAP (λ593: 0.284 and 0.284), and CUPRAC (λ450: 0.163 and 0.137). A total of 35 phenolics were scanned, and 10 phenolic compounds were determined by LC-MS/MS analysis. LC-MS/MS revealed that MEAA mainly contained isorhamnetin, fumaric acid, and rosmarinic acid derivatives. This is the first report indicating that MEAA and WEAA have α-glycosidase, α-amylase, AChE, hCA II inhibition abilities, and antioxidant activities. These results demonstrate the potential of Astragalus species through antioxidant properties and enzyme inhibitor ability traditionally used in medicine. This work provides the foundation for further research into the establishment of novel therapeutics for diabetes, glaucoma, and Alzheimer's disease.

What is the best spectroscopic method for simultaneous analysis of organic acids and (poly)saccharides in biological matrices: Example of Aloe vera extracts?

Several species of (poly)saccharides and organic acids can be found often simultaneously in various biological matrices, e.g., fruits, plant materials, and biological fluids. The analysis of such matrices sometimes represents a challenging task. Using Aloe vera (A. vera) plant materials as an example, the performance of several spectroscopic methods (80 MHz benchtop NMR, NIR, ATR-FTIR and UV–vis) for the simultaneous analysis of quality parameters of this plant material was compared. The determined parameters include (poly)saccharides such as aloverose, fructose and glucose as well as organic acids (malic, lactic, citric, isocitric, acetic, fumaric, benzoic and sorbic acids). 500 MHz NMR and high-performance liquid chromatography (HPLC) were used as the reference methods.UV–vis data can be used only for identification of added preservatives (benzoic and sorbic acids) and drying agent (maltodextrin) and semiquantitative analysis of malic acid. NIR and MIR spectroscopies combined with multivariate regression can deliver more informative overview of A. vera extracts being able to additionally quantify glucose, aloverose, citric, isocitric, malic, lactic acids and fructose. Low-field NMR measurements can be used for the quantification of aloverose, glucose, malic, lactic, acetic, and benzoic acids. The benchtop NMR method was successfully validated in terms of robustness, stability, precision, reproducibility and limit of detection (LOD) and quantification (LOQ), respectively.All spectroscopic techniques are useful for the screening of (poly)saccharides and organic acids in plant extracts and should be applied according to its availability as well as information and confidence required for the specific analytical goal. Benchtop NMR spectroscopy seems to be the most feasible solution for quality control of A. vera products.

A solar-driven adsorbent based on Al-fumarate metal-organic framework coating with high water cycle efficiency

Adsorption bed using pelleted metal-organic frameworks (MOFs) shows high water adsorption capacity, but have low adsorption/desorption rate, which limits the water cycling efficiency. And coating MOFs on the thermal-conductive surface can enhance the water adsorption/desorption rate by promoting heat transfer, furthermore, they can be efficiently driven by green solar light. Based on it, in this work, a novel mixed-solvothermal in-situ synthesis technology of Al-fumarate MOF coating on aluminum foil was developed. The results showed that by respectively adjusting the DMF/H2O ratios, fumaric acid molar contents, and the crystallization temperatures from 5/30–30/5, 2–10 mmol, and 90–120 °C, Al-fumarate MOF with uniform dispersion and controllable thickness (50–620 μm) on aluminum foil could be synthesized directly. The water release properties of different coatings under 1 and 1.2 sunlight (1 kW/m2 and 1.2 kW/m2) were tested. The results showed that the coating with different thicknesses can achieve complete desorption within 8–20 min at a sunlight intensity of 1.2 kW/m2, and the water yield through one cycle can reach 157 g/m2. The coating which displayed a thin strip cauliflower crystal morphology possessed a high adsorption capacity, fast adsorption/desorption rate, low desorption temperature as well as excellent cycle stability.

The phyto-compounds Fumaric acid, di(1-adamantylmethyl) ester and 2-Pentamethyldisilanyloxypentane Borne from Physalis longifolia Against Various Medical and Agronomic Pests

Objectives: To identify the major phytocompounds of Physalis longifolia leaf methanol extract and assess the ovicidal and larvicidal toxicity of target medical and agronomic pests of Aedes aegypti, Culex quinquefasciatus, Spodoptera litura and Helicoverpa armigera eggs and larvae. Methods: In this study, the phyto-compounds identification was made by GC-MS analysis. The selected phyto-compounds were applied towards eggs were tested various concentrations 4-16mg/ml and larvae were tested various concentrations 2- 200mg/ml of medical and agronomic pests. Overall mortality was examined using probit analysis to calculate LC50/LC90. Findings: The most common an Indian medicinal flora, Physalis longifolia leaf methanol extract and its derived major phyto-bioactive constituents Fumaric acid, di(1-adamantylmethyl) ester and 2-Pentamethyldisilanyloxypentane were authentically isolated by GCMS analysis. By phyto-chemical screening, more numbers of bio-active phytochemicals were occupied in high polar leaf extract. P. longifolia leaf methanol extract and its derived major phyto-bioactive constituents Fumaric acid, di(1-adamantylmethyl) ester and 2-Pentamethyldisilanyloxypentane were showed topper eggs toxicity above 90% which reached nearly 100% and the larval toxicity of LC50/ LC90 values were 11.01/18.73, 10.56/ 17.90, 14.19/ 26.59, 14.88/ 27.80 mg/ml and 10.91/ 18.75, 10.70/ 18.26, 15.77/ 29.29 and 14.86/26.55 mg/ml against the medical and agronomic pests of Ae. aegypti, Cx. quinquefasciatus, S. litura and H. armigera, respectively. Novelty: The biotoxicity of selected P. longifolia leaf methanol extract and its derived major phyto-bioactive constituents were well effective, environmental friendlier and produced least toxicity on non-target organisms. The medicinal flora, P. longifolia originated phyto-products could be a valuable farmer and ecofriendly bio-toxic weapon on medical and agronomic pests which promotelesser susceptible on non-target organisms. Keywords: Phytoproducts; Ecotoxicity; Physalis longifolia; Medical pest; Agronomic pest

The real-world effectiveness and persistence of acitretin, ciclosporin, fumaric acid esters and methotrexate for treating moderate-to-severe psoriasis

The real-world effectiveness and persistence of acitretin, ciclosporin, fumaric acid esters and methotrexate for treating moderate-to-severe psoriasis

Exogenous leucine alleviates heat stress and improves saponin synthesis in Panax notoginseng by improving antioxidant capacity and maintaining metabolic homeostasis.

Panax notoginseng saponins (PNSs) are used as industrial raw materials to produce many drugs to treat cardio-cerebrovascular diseases. However, it is a heat-sensitive plant, and its large-scale artificial cultivation is impeded by high temperature stress, leading to decreases in productivity and PNSs yield. Here, we examined exogenous foliar leucine to alleviate heat stress and explored the underlying mechanism using metabolomics. The results indicated that 3 and 5 mM exogenous foliar leucine significantly alleviated heat stress in one-year- and two-year-old P. notoginseng in pots and field trials. Exogenous foliar leucine enhanced the antioxidant capacity by increasing the activities of antioxidant enzymes (POD, SOD) and the contents of antioxidant metabolites (amino acids). Moreover, exogenous foliar leucine enhanced carbohydrate metabolism, including sugars (sucrose, maltose) and TCA cycle metabolites (citric acid, aconitic acid, succinic acid and fumaric acid), in P. notoginseng leaves, stems, and fibrous roots to improve the energy supply of plants and further alleviate heat stress. Field experiments further verified that exogenous foliar leucine increased the productivity and PNSs accumulation in P. notoginseng. These results suggest that leucine application is beneficial for improving the growth and quality of P. notoginseng under heat stress. It is therefore possible to develop plant growth regulators based on leucine to improve the heat resistance of P. notoginseng and other crops.