Comprehensive Metabolomics Study of Traditionally Important Rumex Species Found in Western Himalayan Region

Rumex species are traditionally known to cure constipation, pain, inflammation, ulcer and tumor. The biological potential of Rumex nepalens is lies in chemical diversity of its constituents. In the present study, UPLC-DAD-MS method was developed for the concurrent estimation of polyphenols in Rumex species ( R. nepalensis, R. hastatus and R. dentatus) and validated for linearity (r2 > 0.999), limit of quantification and detection, inter and intraday precession, stabilities and recovery. The developed method has also been employed for metabolomic analysis of Rumex species. Qualitative and quantitative variation of polyphenols was observed among the aerial and root parts of Rumex species with highest content of polyphenol detected in aerial part of R. nepalensis. The quantitative data based matrix and HCA plot represents the variation of metabolites among the samples. R. nepalensis being widely used in traditional practices, was incorporated in detail. A total of seven molecules were isolated and characterized among which three compounds viz. 3- O- methyl epicatechin, quercetin-3- O- β-D-glucuronide and β-sitosterol-3- O- β-D-glucoside were isolated for first time from this plant. Eighteen metabolites were profiled in R. nepalensis using UPLC-MS/MS technique. Current comprehensive metabolomics approach will surely help in understanding the chemical diversity, discriminations and quality control analysis of raw materials and furnished products of Rumex.

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ON THE PROCESSING OF HEMATITE RAW MATERIALS AT THE KRYVOROZHSK MINING AND PROCESSING PLANT OF OXIDIZED ORE ON TECHNOLOGY OF DIRECT RECOVERY ITmk3

Metallurgicheskaya i gornorudnaya promyshlennost ◽

10.33101/s005-59768574 ◽

2018 ◽

pp. 32-37

Author(s):

P.I. Loboda ◽

Younes Razaz ◽

S. Grishchenko

Keyword(s):

Magnetic Properties ◽

Cast Iron ◽

Iron Content ◽

Raw Materials ◽

Direct Reduction ◽

Processing Plant ◽

High Iron Content ◽

High Iron ◽

Direct Restoration ◽

First Time

Purpose. To substantiate the efficiency of processing hematite raw materials at the Krivoy Rog Mining and Processing Plant of Oxidized Ores using the direct reduction technology itmk3®. Metodology. Analysis of the results of the itmk3® direct restoration technology developed by Kobe Steel Ltd., Japan and Hares Engineering GmbX, Austria, with a view to using it to process Krivbass hematite ores into granulated iron (so-called “nuggets”). Findings. The involvement in the production of hematite ores (oxidized quartzite) of Krivbass with high iron content, but with low magnetic properties for their processing into granular cast iron is grounded. Originality. The use of itmk3® direct reduction technology from Kobe Steel Ltd., Japan and Hares Engineering GmbH, Austria for the processing of Krivbass hematite ores into granular cast iron is justified for the first time. Practical value. The efficiency of the use of hematite ores (oxidized quartzite) has been substantiated, which can significantly reduce the costs in the mining cycle for the economical production of metallurgical products.

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PERSPECTIVE DEVELOPMENT OF WORLD PRODUCTION OF FEEDS FOR AQUACULTURE: ALTERNATIVE SOURCES OF RAW MATERIALS

VESTNIK OF ASTRAKHAN STATE TECHNICAL UNIVERSITY SERIES FISHING INDUSTRY ◽

10.24143/2073-5529-2017-1-67-78 ◽

2017 ◽

pp. 67-78

Author(s):

Lina Yurievna Lagutkina

Keyword(s):

Raw Materials ◽

Limiting Factors ◽

Current Status ◽

Feed Production ◽

The World ◽

Market Trends ◽

Alternative Sources ◽

World Industry ◽

First Time ◽

A Current

The author of the article discloses the prospects of development of the world feed production for aquaculture based on the analysis of key innovative technological and market trends. The author specifies that shortage, high cost, low ecological compatibility of traditional raw materials - fish flour - are among major limiting factors in the development of production of feeds for aquaculture. This fact, in turn, limits sustainable development of aquaculture both in Russia, and in the world in general. The article presents the overview of a current status of the world industry of feed production in aquaculture, where the regional situation is studied, as well. For the first time, there is given the outlook of innovative technologies in feed production based on the alternative sources of protein (on the example of projects of leading aquabiotechnological companies) which will determine industry’s objectives for the mid-term perspective.

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Safety assessment of biological raw materials in the system of medicines quality assurance

10.33920/med-06-2002-05 ◽

2020 ◽

pp. 63-72

Author(s):

Yu. Olefir ◽

E. Sakanyan ◽

I. Osipova ◽

V. Dobrynin ◽

M. Smirnova ◽

...

Keyword(s):

Raw Materials ◽

State Level ◽

The State ◽

Spongiform Encephalopathy ◽

Safety Standards ◽

Wide Range ◽

The Russian Federation ◽

Key Aspects ◽

First Time ◽

Medicines Quality

The entry of a wide range of biotechnological products into the pharmaceutical market calls for rein-forcement of the quality, efficacy and safety standards at the state level. The following general monographs have been elaborated for the first time to be included into the State Pharmacopoeia of the Russian Federation, XIV edition: "Viral safety" and "Reduction of the risk of transmitting animal spongiform encephalopathy via medicinal products". These general monographs were elaborated taking into account the requirements of foreign pharmacopoeias and the WHO recommendations. The present paper summarises the key aspects of the monographs.

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Antimutagenic, Antiproliferative and Antioxidant Properties of Sea Grape Leaf Extract Fractions (Coccoloba uvifera L.)

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621999210104201242 ◽

2021 ◽

Vol 21 ◽

Author(s):

Jorge A. Ramos-Hernández ◽

Montserrat Calderón-Santoyo ◽

Armando Burgos-Hernández ◽

Joel S. García- Romo ◽

Arturo Navarro-Ocaña ◽

...

Keyword(s):

Antioxidant Properties ◽

In Vitro Tests ◽

Antimutagenic Activity ◽

Hexane Extraction ◽

Biological Potential ◽

Hct 116 ◽

Pharmaceutical Industries ◽

Grape Leaf ◽

First Time

Background: Cancer is a disease characterized by the invasion and uncontrolled growth of cells. One of the best ways to minimize the harmful effects of mutagens is through the use of natural antimutagens. In this regard, the search for new antimutagens that act in the chemoprevention could represent a promising field in this area. Objective: In this study biological potential of 11 fractions from Coccoloba uvifera L. leaf hexane extract was evaluated by several in vitro tests. Methods: Leaves were lyophilized and hexane extraction was performed. The extract was fractionated by column chromatography with hexane, ethyl acetate, and methanol. The antimutagenic (Ames test), antiproliferative (MTT test), and antioxidant capacity (DPPH, ABTS, and ferrous ion chelation) of the fractions were evaluated. Results: Fractions 4, 6, 8, and 9 have antimutagenic activity (against sodium azide in strain TA100), fraction 11 showed antiproliferative capacity (IC50 of 24 ± 9 μg/mL in cells of HCT 116). The fractions with the highest activity were analyzed by HPLC-MS and lupeol, acacetin, and β-sitosterol were identified. Conclusion: This study demonstrates, for the first time, the bioactivity of C. uvifera leaf as a new source of high biological value compounds (HBVC), which can be of interest to the food and pharmaceutical industries.

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Feasibility and Evaluation of Automated Methods for Radiolabeling of Radiopharmaceutical Kits with Gallium-68

Current Radiopharmaceuticals ◽

10.2174/1874471012666190110170623 ◽

2019 ◽

Vol 12 (3) ◽

pp. 229-237 ◽

Cited By ~ 3

Author(s):

Alban Revy ◽

François Hallouard ◽

Sandrine Joyeux-Klamber ◽

Andrea Skanjeti ◽

Catherine Rioufol ◽

...

Keyword(s):

The European Union ◽

Preparation Time ◽

Limit Of Quantification ◽

Manual Method ◽

Personnel Costs ◽

Automated Method ◽

Gallium 68 ◽

The Right ◽

First Time ◽

Automated Methods

Objective: Recent gallium-68 labeled peptides are of increasing interest in PET imaging in nuclear medicine. Somakit TOC® is a radiopharmaceutical kit registered in the European Union for the preparation of [68Ga]Ga-DOTA-TOC used for the diagnosis of neuroendocrine tumors. Development of a labeling process using a synthesizer is particularly interesting for the quality and reproducibility of the final product although only manual processes are described in the Summary of Product (SmPC) of the registered product. The aim of the present study was therefore to evaluate the feasibility and value of using an automated synthesizer for the preparation of [68Ga]Ga-DOTA-TOC according to the SmPC of the Somakit TOC®. Methods: Three methods of preparation were compared; each followed the SmPC of the Somakit TOC®. Over time, overheads, and overexposure were evaluated for each method. Results: Mean±SD preparation time was 26.2±0.3 minutes for the manual method, 28±0.5 minutes for the semi-automated, and 40.3±0.2 minutes for the automated method. Overcost of the semi-automated method is 0.25€ per preparation for consumables and from 0.58€ to 0.92€ for personnel costs according to the operator (respectively, technician or pharmacist). For the automated method, overcost is 70€ for consumables and from 4.06€ to 6.44€ for personnel. For the manual method, extremity exposure was 0.425mSv for the right finger, and 0.350mSv for the left finger; for both the semi-automated and automated method extremity exposure were below the limit of quantification. Conclusion: The present study reports for the first time both the feasibility of using a [68Ga]- radiopharmaceutical kit with a synthesizer and the limits for the development of a fully automated process.

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Analysis of Pembrolizumab in Human Plasma by LC-MS/HRMS. Method Validation and Comparison with Elisa

Biomedicines ◽

10.3390/biomedicines9060621 ◽

2021 ◽

Vol 9 (6) ◽

pp. 621

Author(s):

Aurélien Millet ◽

Nihel Khoudour ◽

Jérôme Guitton ◽

Dorothée Lebert ◽

François Goldwasser ◽

...

Keyword(s):

Mass Spectrometry ◽

Human Plasma ◽

High Resolution Mass Spectrometry ◽

Internal Standard ◽

Therapeutic Drug ◽

Limit Of Quantification ◽

Immunoglobulin G4 ◽

Positive Mode ◽

Surrogate Peptide ◽

First Time

Pembrolizumab is a humanized immunoglobulin G4-kappa anti-PD1 antibody used in the treatment of different solid tumors or haematological malignancies. A liquid chromatography coupled with a high resolution mass spectrometry (orbitrap technology) method was fully developed, optimized, and validated for quantitative analysis of pembrolizumab in human plasma. A mass spectrometry assay was used for the first time a full-length stable isotope-labelled pembrolizumab-like (Arginine 13C6-15N4 and Lysine 13C6-15N2) as an internal standard; the sample preparation was based on albumin depletion and trypsin digestion and, finally, one surrogate peptide was quantified in positive mode. The assay showed good linearity over the range of 1–100 μg/mL, a limit of quantification at 1 μg/mL, excellent accuracy from 4.4% to 5.1%, and also a between-day precision below 20% at the limit of quantification. In parallel, an in-house ELISA was developed with a linearity range from 2.5 to 50 µg/mL. Then, results were obtained from 70 plasma samples of cancer patients that were treated with pembrolizumab and quantified with both methods were compared using the Passing-Bablok regression analysis and Bland-Altman plotting. The LC-MS/HRMS method is easy to implement in the laboratory for use in the context of PK/PD studies, clinical trials, or therapeutic drug monitoring.

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Bufadienolides from the Skin Secretions of the Neotropical Toad Rhinella alata (Anura: Bufonidae): Antiprotozoal Activity against Trypanosoma cruzi

Molecules ◽

10.3390/molecules26144217 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4217

Author(s):

Candelario Rodriguez ◽

Roberto Ibáñez ◽

Luis Mojica ◽

Michelle Ng ◽

Carmenza Spadafora ◽

...

Keyword(s):

Vero Cells ◽

Chemical Diversity ◽

Hydroxyl Group ◽

Antitrypanosomal Activity ◽

The Family ◽

Toad Venom ◽

Skin Secretions ◽

Pharmacological Potential ◽

First Time ◽

Mcf 7

Toads in the family Bufonidae contain bufadienolides in their venom, which are characterized by their chemical diversity and high pharmacological potential. American trypanosomiasis is a neglected disease that affects an estimated 8 million people in tropical and subtropical countries. In this research, we investigated the chemical composition and antitrypanosomal activity of toad venom from Rhinella alata collected in Panama. Structural determination using mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy led to the identification of 10 bufadienolides. Compounds identified include the following: 16β-hydroxy-desacetyl-bufotalin-3-adipoyl-arginine ester (1), bufotalin (2), 16β-hydroxy-desacetyl-bufotalin-3-pimeloyl-arginine ester (3), bufotalin-3-pimeloyl-arginine ester (4), 16β-hydroxy-desacetyl-bufotalin-3-suberoyl-arginine ester (5), bufotalin-3-suberoyl-arginine ester (6), cinobufagin-3-adipoyl-arginine ester (7), cinobufagin-3-pimeloyl-arginine ester (8), cinobufagin-3-suberoyl-arginine ester (9), and cinobufagin (10). Among these, three new natural products, 1, 3, and 5, are described, and compounds 1–10 are reported for the first time in R. alata. The antitrypanosomal activity assessed in this study revealed that the presence of an arginyl-diacid attached to C-3, and a hydroxyl group at C-14 in the structure of bufadienolides that is important for their biological activity. Bufadienolides showed cytotoxic activity against epithelial kidney Vero cells; however, bufagins (2 and 10) displayed low mammalian cytotoxicity. Compounds 2 and 10 showed activity against the cancer cell lines MCF-7, NCI-H460, and SF-268.

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Untargeted Metabolomics Approach for the Discovery of Environment-Related Pyran-2-ones Chemodiversity in a Marine-Sourced Penicillium restrictum

Marine Drugs ◽

10.3390/md19070378 ◽

2021 ◽

Vol 19 (7) ◽

pp. 378

Author(s):

Van-Tuyen Le ◽

Samuel Bertrand ◽

Thibaut Robiou du Pont ◽

Fabrice Fleury ◽

Nathalie Caroff ◽

...

Keyword(s):

Culture Medium ◽

Blue Mussel ◽

Culture Media ◽

Principal Component ◽

Chemical Diversity ◽

Untargeted Metabolomics ◽

High Chemical ◽

Medium Mass ◽

Metabolomics Study ◽

Penicillium Restrictum

Very little is known about chemical interactions between fungi and their mollusc host within marine environments. Here, we investigated the metabolome of a Penicillium restrictum MMS417 strain isolated from the blue mussel Mytilus edulis collected on the Loire estuary, France. Following the OSMAC approach with the use of 14 culture media, the effect of salinity and of a mussel-derived medium on the metabolic expression were analysed using HPLC-UV/DAD-HRMS/MS. An untargeted metabolomics study was performed using principal component analysis (PCA), orthogonal projection to latent structure discriminant analysis (O-PLSDA) and molecular networking (MN). It highlighted some compounds belonging to sterols, macrolides and pyran-2-ones, which were specifically induced in marine conditions. In particular, a high chemical diversity of pyran-2-ones was found to be related to the presence of mussel extract in the culture medium. Mass spectrometry (MS)- and UV-guided purification resulted in the isolation of five new natural fungal pyran-2-one derivatives—5,6-dihydro-6S-hydroxymethyl-4-methoxy-2H-pyran-2-one (1), (6S, 1’R, 2’S)-LL-P880β (3), 5,6-dihydro-4-methoxy-6S-(1’S, 2’S-dihydroxy pent-3’(E)-enyl)-2H-pyran-2-one (4), 4-methoxy-6-(1’R, 2’S-dihydroxy pent-3’(E)-enyl)-2H-pyran-2-one (6) and 4-methoxy-2H-pyran-2-one (7)—together with the known (6S, 1’S, 2’S)-LL-P880β (2), (1’R, 2’S)-LL-P880γ (5), 5,6-dihydro-4-methoxy-2H-pyran-2-one (8), (6S, 1’S, 2’R)-LL-P880β (9), (6S, 1’S)-pestalotin (10), 1’R-dehydropestalotin (11) and 6-pentyl-4-methoxy-2H-pyran-2-one (12) from the mussel-derived culture medium extract. The structures of 1-12 were determined by 1D- and 2D-MMR experiments as well as high-resolution tandem MS, ECD and DP4 calculations. Some of these compounds were evaluated for their cytotoxic, antibacterial, antileishmanial and in-silico PTP1B inhibitory activities. These results illustrate the utility in using host-derived media for the discovery of new natural products.

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Programme for Harmonization to the International Scale in Latin America for BCR-ABL1 quantification in CML patients: findings and recommendations

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2019-1283 ◽

2020 ◽

Vol 58 (12) ◽

pp. 2025-2035

Author(s):

María Sol Ruiz ◽

María Belén Sánchez ◽

Yuly Masiel Vera Contreras ◽

Evangelina Agrielo ◽

Marta Alonso ◽

...

Keyword(s):

Latin America ◽

Myeloid Leukemia ◽

World Health ◽

Molecular Response ◽

Limit Of Quantification ◽

International Scale ◽

Deep Molecular Response ◽

Health Organization ◽

First Time

AbstractObjectivesThe quantitation of BCR-ABL1 mRNA is mandatory for chronic myeloid leukemia (CML) patients, and RT-qPCR is the most extensively used method in testing laboratories worldwide. Nevertheless, substantial variation in RT-qPCR results makes inter-laboratory comparability hard. To facilitate inter-laboratory comparative assessment, an international scale (IS) for BCR-ABL1 was proposed.MethodsThe laboratory-specific conversion factor (CF) to the IS can be derived from the World Health Organization (WHO) genetic reference panel; however, this material is limited to the manufacturers to produce and calibrate secondary reference reagents. Therefore, we developed secondary reference calibrators, as lyophilized cellular material, aligned to the IS. Our purpose was both to re-evaluate the CF in 18 previously harmonized laboratories and to propagate the IS to new laboratories.ResultsOur field trial including 30 laboratories across Latin America showed that, after correction of raw BCR-ABL1/ABL1 ratios using CF, the relative mean bias was significantly reduced. We also performed a follow-up of participating laboratories by annually revalidating the process; our results support the need for continuous revalidation of CFs. All participating laboratories also received a calibrator to determine the limit of quantification (LOQ); 90% of them could reproducibly detect BCR-ABL1, indicating that these laboratories can report a consistent deep molecular response. In addition, aiming to investigate the variability of BCR-ABL1 measurements across different RNA inputs, we calculated PCR efficiency for each individual assay by using different amounts of RNA.ConclusionsIn conclusion, for the first time in Latin America, we have successfully organized a harmonization platform for BCR-ABL1 measurement that could be of immediate clinical benefit for monitoring the molecular response of patients in low-resource regions.

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Mineralogy and Geochemistry of Ultramafic Rocks from Rachoni Magnesite Mine, Gerakini (Chalkidiki, Northern Greece)

Minerals ◽

10.3390/min10110934 ◽

2020 ◽

Vol 10 (11) ◽

pp. 934

Author(s):

Evangelos Tzamos ◽

Micol Bussolesi ◽

Giovanni Grieco ◽

Pietro Marescotti ◽

Laura Crispini ◽

...

Keyword(s):

Raw Materials ◽

Mining Area ◽

Ultramafic Rocks ◽

Northern Greece ◽

Icp Ms ◽

Time In Literature ◽

History Of ◽

First Time ◽

The Eu

The importance of magnesite for the EU economy and industry is very high, making the understanding of their genesis for the exploration for new deposits a priority for the raw materials scientific community. In this direction, the study of the magnesite-hosting ultramafic rocks can be proved very useful. For the present study, ultramafic rock samples were collected from the magnesite ore-hosting ophiolite of the Gerakini mining area (Chalkidiki, Greece) to investigate the consecutive alteration events of the rocks which led to the metallogenesis of the significant magnesite ores of the area. All samples were subjected to a series of analytical methods for the determination of their mineralogical and geochemical characteristics: optical microscopy, XRD, SEM, EMPA, ICP–MS/OES and CIPW normalization. The results of these analyses revealed that the ultramafic rocks of the area have not only all been subjected to serpentinization, but these rocks have also undergone carbonation, silification and clay alteration. The latter events are attributed to the circulation of CO2-rich fluids responsible for the formation of the magnesite ores and locally, the further alteration of the serpentinites into listvenites. The current mineralogy of these rocks was found to be linked to one or more alteration event that took place, thus a significant contribution to the metallo- and petrogenetic history of the Gerakini ophiolite has been made. Furthermore, for the first time in literature, Fe inclusions in olivines from Greece were reported.

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