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1. Critical assessment of variant prioritization methods for rare disease diagnosis within the rare genomes project

Author

Stenton, Sarah L., O’Leary, Melanie C., Lemire, Gabrielle, VanNoy, Grace E., DiTroia, Stephanie, Ganesh, Vijay S., Groopman, Emily, O’Heir, Emily, Mangilog, Brian, Osei-Owusu, Ikeoluwa, Pais, Lynn S., Serrano, Jillian, Singer-Berk, Moriel, Weisburd, Ben, Wilson, Michael W., Austin-Tse, Christina, Abdelhakim, Marwa, Althagafi, Azza, Babbi, Giulia, Bellazzi, Riccardo, Bovo, Samuele, Carta, Maria Giulia, Casadio, Rita, Coenen, Pieter-Jan, De Paoli, Federica, Floris, Matteo, Gajapathy, Manavalan, Hoehndorf, Robert, Jacobsen, Julius O. B., Joseph, Thomas, Kamandula, Akash, Katsonis, Panagiotis, Kint, Cyrielle, Lichtarge, Olivier, Limongelli, Ivan, Lu, Yulan, Magni, Paolo, Mamidi, Tarun Karthik Kumar, Martelli, Pier Luigi, Mulargia, Marta, Nicora, Giovanna, Nykamp, Keith, Pejaver, Vikas, Peng, Yisu, Pham, Thi Hong Cam, Podda, Maurizio S., Rao, Aditya, Rizzo, Ettore, Saipradeep, Vangala G., Savojardo, Castrense, Schols, Peter, Shen, Yang, Sivadasan, Naveen, Smedley, Damian, Soru, Dorian, Srinivasan, Rajgopal, Sun, Yuanfei, Sunderam, Uma, Tan, Wuwei, Tiwari, Naina, Wang, Xiao, Wang, Yaqiong, Williams, Amanda, Worthey, Elizabeth A., Yin, Rujie, You, Yuning, Zeiberg, Daniel, Zucca, Susanna, Bakolitsa, Constantina, Brenner, Steven E., Fullerton, Stephanie M., Radivojac, Predrag, Rehm, Heidi L., and O’Donnell-Luria, Anne

Published
2024
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7. A global database of dissolved organic matter (DOM) concentration measurements in coastal waters (CoastDOM v1)

Author

Lønborg, Christian, Carreira, Cátia, Abril, Gwenaël, Agustí, Susana, Amaral, Valentina, Andersson, Agneta, Arístegui, Javier, Bhadury, Punyasloke, Bif, Mariana B., Borges, Alberto V., Bouillon, Steven, Calleja, Maria Ll., Cotovicz Jr., Luiz C., Cozzi, Stefano, Doval, Maryló, Duarte, Carlos M., Eyre, Bradley, Fichot, Cédric G., García-Martín, E. Elena, Garzon-Garcia, Alexandra, Giani, Michele, Gonçalves-Araujo, Rafael, Gruber, Renee, Hansell, Dennis A., Hashihama, Fuminori, He, Ding, Holding, Johnna M., Hunter, William R., Ibánhez, J. Severino P., Ibello, Valeria, Jiang, Shan, Kim, Guebuem, Klun, Katja, Kowalczuk, Piotr, Kubo, Atsushi, Lee, Choon-Weng, Lopes, Cláudia B., Maggioni, Federica, Magni, Paolo, Marrase, Celia, Martin, Patrick, McCallister, S. Leigh, McCallum, Roisin, Medeiros, Patricia M., Morán, Xosé Anxelu G., Muller-Karger, Frank E., Myers-Pigg, Allison, Norli, Marit, Oakes, Joanne M., Osterholz, Helena, Park, Hyukyung, Lund Paulsen, Maria, Rosentreter, Judith A., Ross, Jeff D., Rueda-Roa, Digna, Santinelli, Chiara, Shen, Yuan, Teira, Eva, Tinta, Tinkara, Uher, Guenther, Wakita, Masahide, Ward, Nicholas, Watanabe, Kenta, Xin, Yu, Yamashita, Youhei, Yang, Liyang, Yeo, Jacob, Yuan, Huamao, Zheng, Qiang, Álvarez-Salgado, Xosé Antón, Lønborg, Christian, Carreira, Cátia, Abril, Gwenaël, Agustí, Susana, Amaral, Valentina, Andersson, Agneta, Arístegui, Javier, Bhadury, Punyasloke, Bif, Mariana B., Borges, Alberto V., Bouillon, Steven, Calleja, Maria Ll., Cotovicz Jr., Luiz C., Cozzi, Stefano, Doval, Maryló, Duarte, Carlos M., Eyre, Bradley, Fichot, Cédric G., García-Martín, E. Elena, Garzon-Garcia, Alexandra, Giani, Michele, Gonçalves-Araujo, Rafael, Gruber, Renee, Hansell, Dennis A., Hashihama, Fuminori, He, Ding, Holding, Johnna M., Hunter, William R., Ibánhez, J. Severino P., Ibello, Valeria, Jiang, Shan, Kim, Guebuem, Klun, Katja, Kowalczuk, Piotr, Kubo, Atsushi, Lee, Choon-Weng, Lopes, Cláudia B., Maggioni, Federica, Magni, Paolo, Marrase, Celia, Martin, Patrick, McCallister, S. Leigh, McCallum, Roisin, Medeiros, Patricia M., Morán, Xosé Anxelu G., Muller-Karger, Frank E., Myers-Pigg, Allison, Norli, Marit, Oakes, Joanne M., Osterholz, Helena, Park, Hyukyung, Lund Paulsen, Maria, Rosentreter, Judith A., Ross, Jeff D., Rueda-Roa, Digna, Santinelli, Chiara, Shen, Yuan, Teira, Eva, Tinta, Tinkara, Uher, Guenther, Wakita, Masahide, Ward, Nicholas, Watanabe, Kenta, Xin, Yu, Yamashita, Youhei, Yang, Liyang, Yeo, Jacob, Yuan, Huamao, Zheng, Qiang, and Álvarez-Salgado, Xosé Antón

Abstract

Measurements of dissolved organic carbon (DOC), nitrogen (DON), and phosphorus (DOP) concentrations are used to characterize the dissolved organic matter (DOM) pool and are important components of biogeochemical cycling in the coastal ocean. Here, we present the first edition of a global database (CoastDOM v1; available at https://doi.org/10.1594/PANGAEA.964012, Lønborg et al., 2023) compiling previously published and unpublished measurements of DOC, DON, and DOP in coastal waters. These data are complemented by hydrographic data such as temperature and salinity and, to the extent possible, other biogeochemical variables (e.g. chlorophyll a, inorganic nutrients) and the inorganic carbon system (e.g. dissolved inorganic carbon and total alkalinity). Overall, CoastDOM v1 includes observations of concentrations from all continents. However, most data were collected in the Northern Hemisphere, with a clear gap in DOM measurements from the Southern Hemisphere. The data included were collected from 1978 to 2022 and consist of 62 338 data points for DOC, 20 356 for DON, and 13 533 for DOP. The number of measurements decreases progressively in the sequence DOC > DON > DOP, reflecting both differences in the maturity of the analytical methods and the greater focus on carbon cycling by the aquatic science community. The global database shows that the average DOC concentration in coastal waters (average ± standard deviation (SD): 182±314 µmol C L−1; median: 103 µmol C L−1) is 13-fold higher than the average coastal DON concentration (13.6±30.4 µmol N L−1; median: 8.0 µmol N L−1), which is itself 39-fold higher than the average coastal DOP concentration (0.34±1.11 µmol P L−1; median: 0.18 µmol P L−1). This dataset will be useful for identifying global spatial and temporal patterns in DOM and will help facilitate the reuse of DOC, DON, and DOP data in studies aimed at better characterizing local biogeochemic

Published
2024

8. Metabolic Engineering of Bacillus subtilis for the Production of Poly-γ-Glutamic Acid from Glycerol Feedstock.

Author

Pasotti, Lorenzo, Massaiu, Ilaria, Magni, Paolo, and Calvio, Cinzia

Subjects
BACILLUS subtilis, GLUTAMIC acid, OPERONS, SUSTAINABILITY, MICROBIOLOGICAL synthesis, GLYCERIN, BIOCHEMICAL engineering
Abstract

Poly-γ-glutamic acid (γ-PGA) is an attractive biopolymer for medical, agri-food, and environmental applications. Although microbial synthesis by Bacilli fed on waste streams has been widely adopted, the obtainment of efficient sustainable production processes is still under investigation by bioprocess and metabolic engineering approaches. The abundant glycerol-rich waste generated in the biodiesel industry can be used as a carbon source for γ-PGA production. Here, we studied fermentation performance in different engineered Bacillus subtilis strains in glycerol-based media, considering a swrA+ degU32Hy mutant as the initial producer strain and glucose-based media for comparison. Modifications included engineering the biosynthetic pgs operon regulation (replacing its native promoter with Physpank), precursor accumulation (sucCD or odhAB deletion), and enhanced glutamate racemization (racE overexpression), predicted as crucial reactions by genome-scale model simulations. All interventions increased productivity in glucose-based media, with Physpank-pgs ∆sucCD showing the highest γ-PGA titer (52 g/L). Weaker effects were observed in glycerol-based media: ∆sucCD and Physpank-pgs led to slight improvements under low- and high-glutamate conditions, respectively, reaching ~22 g/L γ-PGA (26% increase). No performance decrease was detected by replacing pure glycerol with crude glycerol waste from a biodiesel plant, and by a 30-fold scale-up. These results may be relevant for improving industrial γ-PGA production efficiency and process sustainability using waste feedstock. The performance differences observed between glucose and glycerol media also motivate additional computational and experimental studies to design metabolically optimized strains. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Insulin-like Growth Factor 1, Growth Hormone, and Anti-Müllerian Hormone Receptors Are Differentially Expressed during GnRH Neuron Development

Author

Paganoni, Alyssa J. J., primary, Cannarella, Rossella, additional, Oleari, Roberto, additional, Amoruso, Federica, additional, Antal, Renata, additional, Ruzza, Marco, additional, Olivieri, Chiara, additional, Condorelli, Rosita A., additional, La Vignera, Sandro, additional, Tolaj, Fationa, additional, Cariboni, Anna, additional, Calogero, Aldo E., additional, and Magni, Paolo, additional

Published
2023
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15. Perspective: Improving Nutritional Guidelines for Sustainable Health Policies: Current Status and Perspectives

Author

Magni, Paolo, Bier, Dennis M, Pecorelli, Sergio, Agostoni, Carlo, Astrup, Arne, Brighenti, Furio, Cook, Robert, Folco, Emanuela, Fontana, Luigi, Gibson, Robert A, Guerra, Ranieri, Guyatt, Gordon H, Ioannidis, John PA, Jackson, Ann S, Klurfeld, David M, Makrides, Maria, Mathioudakis, Basil, Monaco, Alessandro, Patel, Chirag J, Racagni, Giorgio, Schünemann, Holger J, Shamir, Raanan, Zmora, Niv, and Peracino, Andrea

Published
2017
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22. Model‐based prediction of effective target exposure for MEN1611 in combination with trastuzumab in HER2‐positive advanced or metastatic breast cancer patients.

Author

Tosca, Elena M., Borella, Elisa, Piana, Chiara, Bouchene, Salim, Merlino, Giuseppe, Fiascarelli, Alessio, Mazzei, Paolo, and Magni, Paolo

Subjects
METASTATIC breast cancer, TRASTUZUMAB, CANCER patients, CONCENTRATION functions, TUMOR growth
Abstract

MEN1611 is a novel orally bioavailable PI3K inhibitor currently in clinical development for patients with HER2‐positive (HER2+) PI3KCA mutated advanced/metastatic breast cancer (BC) in combination with trastuzumab (TZB). In this work, a translational model‐based approach to determine the minimum target exposure of MEN1611 in combination with TZB was applied. First, pharmacokinetic (PK) models for MEN1611 and TZB in mice were developed. Then, in vivo tumor growth inhibition (TGI) data from seven combination studies in mice xenograft models representative of the human HER2+ BC non‐responsive to TZB (alterations of the PI3K/AkT/mTOR pathway) were analyzed using a PK‐pharmacodynamic (PD) TGI model for co‐administration of MEN1611 and TZB. The established PK‐PD relationship was used to quantify the minimum effective MEN1611 concentration, as a function of TZB concentration, needed for tumor eradication in xenograft mice. Finally, a range of minimum effective exposures for MEN1611 were extrapolated to patients with BC, considering the typical steady‐state TZB plasma levels in patients with BC following three alternative regimens (i.v. 4 mg/kg loading dose +2 mg/kg q1w, i.v. 8 mg/kg loading dose +6 mg/kg q3w or s.c. 600 mg q3w). A threshold of about 2000 ng·h/ml for MEN1611 exposure associated with a high likelihood of effective antitumor activity in a large majority of patients was identified for the 3‐weekly and the weekly i.v. schedule for TZB. A slightly lower exposure (i.e., 25% lower) was found for the 3‐weekly s.c. schedule. This important outcome confirmed the adequacy of the therapeutic dose administered in the ongoing phase 1b B‐PRECISE‐01 study in patients with HER2+ PI3KCA mutated advanced/metastatic BC. [ABSTRACT FROM AUTHOR]

Published
2023
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23. Anti-Inflammatory, Antioxidant Activities, and Phytochemical Characterization of Edible Plants Exerting Synergistic Effects in Human Gastric Epithelial Cells

Author

Atchan, Achille Parfait Nwakiban, primary, Monthe, Orissa Charlène, additional, Tchamgoue, Armelle Deutou, additional, Singh, Yeshvanthi, additional, Shivashankara, Shilpa Talkad, additional, Selvi, Moorthy Karthika, additional, Agbor, Gabriel Agbor, additional, Magni, Paolo, additional, Piazza, Stefano, additional, Manjappara, Uma Venkateswaran, additional, Kuiate, Jules-Roger, additional, and Dell’Agli, Mario, additional

Published
2023
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26. Macrobenthos of the Tortolì Lagoon: A Peculiar Case of High Benthic Biodiversity among Mediterranean Lagoons.

Author

Giampaoletti, Jacopo, Sbrana, Alice, Magni, Paolo, and Gravina, Maria Flavia

Subjects
LAGOONS, BIODIVERSITY, SPECIES distribution, OYSTER culture, PONDS, INTERTIDAL zonation
Abstract

Coastal lagoons and brackish ponds are extremely dynamic and temporary ecosystems that follow natural changes throughout their geological history. The correct management of the lagoons ensures their integrity and proper functioning. For this reason, their ecological status should be surveyed for assessing the most appropriate strategies of use. In the present study, historical datasets collected in 2003–2004 are used to investigate the spatiotemporal variation in the species composition and community structure of the macrobenthos of the Tortolì Lagoon (Sardinia, Italy) and to assess their relationship with key environmental variables. Owing to the presence of a riverine runoff at a site and confined areas at some distance from the sea inlet, we hypothesize the marked spatiotemporal changes of the macrobenthic community consistent with the high environmental variability typical of coastal lagoons. The results show a surprisingly high benthic biodiversity for a medium-sized lagoon (250 ha), with 101 species unevenly distributed across the lagoon. The environmental variables did not explain the zonation of the macrobenthic community as that typically found along a lagoonal gradient, due to a marked marine influence. The sampling sites were in fact discriminated by the species distribution according to their ecological affinity; in particular, the most distinctive characteristics of the Tortolì Lagoon emerged from the strictly marine species that represented the most abundant group, consistently with the high marinization of the lagoon. Our results show that the Tortolì Lagoon constitutes a peculiar ecosystem within Mediterranean lagoons, departing from the classic confinement theory. [ABSTRACT FROM AUTHOR]

Published
2023
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28. Oral Porphyromonas gingivalis and Fusobacterium nucleatum Abundance in Subjects in Primary and Secondary Cardiovascular Prevention, with or without Heterozygous Familial Hypercholesterolemia

Author

Curia, Maria Cristina, primary, Pignatelli, Pamela, additional, D’Antonio, Domenica Lucia, additional, D’Ardes, Damiano, additional, Olmastroni, Elena, additional, Scorpiglione, Luca, additional, Cipollone, Francesco, additional, Catapano, Alberico Luigi, additional, Piattelli, Adriano, additional, Bucci, Marco, additional, and Magni, Paolo, additional

Published
2022
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31. Testing strategy for new ocean sensors

Author

Barton, John, Salat, Jordi, García-Ladona, Emilio, Piera, Jaume, Salvador, Joaquín, Fernández Gallego, Pedro, Antognarelli, Fabio, Satta, Andrea, Magni, Paolo, Ribotti, Alberto, Barton, John, Salat, Jordi, García-Ladona, Emilio, Piera, Jaume, Salvador, Joaquín, Fernández Gallego, Pedro, Antognarelli, Fabio, Satta, Andrea, Magni, Paolo, and Ribotti, Alberto

Abstract

The definition of a sensor monitoring strategy is based on the location for water monitoring, sensor performances, data storage and transmission. For any new sensor, available instruments currently used in oceanographic studies are identified to perform comparisons. Suitable transmission technology is selected according to the test conditions: open sea, coastal areas, remote locations, etc. Sensitivity and stress tests are designed to establish confidence limits under different environmental situations, so that the results obtained in planned testing exercises are enabled to certify the performance of the new instruments. In this paper, we will address three key phases to test and certify the performance of new sensors: (1) RD basis for cost-effective sensor development, (2) sensor development, sensor web platform and integration, and (3) field testing

Published
2022

34. Polyphenol-Rich Extracts of Xylopia and Aframomum Species Show Metabolic Benefits by Lowering Hepatic Lipid Accumulation in Diet-Induced Obese Mice

Author

Nwakiban Atchan, Achille Parfait, primary, Shivashankara, Shilpa Talkad, additional, Piazza, Stefano, additional, Tchamgoue, Armelle Deutou, additional, Beretta, Giangiacomo, additional, Dell’Agli, Mario, additional, Magni, Paolo, additional, Agbor, Gabriel Agbor, additional, Kuiaté, Jules-Roger, additional, and Manjappara, Uma Venkateswaran, additional

Published
2022
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39. Hydroethanolic Extract of Prunus domestica L.: Metabolite Profiling and In Vitro Modulation of Molecular Mechanisms Associated to Cardiometabolic Diseases

Author

Ullah, Hammad, primary, Sommella, Eduardo, additional, Santarcangelo, Cristina, additional, D’Avino, Danilo, additional, Rossi, Antonietta, additional, Dacrema, Marco, additional, Minno, Alessandro Di, additional, Di Matteo, Giacomo, additional, Mannina, Luisa, additional, Campiglia, Pietro, additional, Magni, Paolo, additional, and Daglia, Maria, additional

Published
2022
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41. Cameroonian Spice Extracts Modulate Molecular Mechanisms Relevant to Cardiometabolic Diseases in SW 872 Human Liposarcoma Cells

Author

Atchan Nwakiban, Achille Parfait, Passarelli, Anna, Da Dalt, Lorenzo, Olivieri, Chiara, Demirci, Tugba Nur, Piazza, Stefano, Sangiovanni, Enrico, Carpentier-Maguire, Eugénie, Martinelli, Giulia, Shivashankara, Shilpa Talkad, Manjappara, Uma Venkateswaran, Tchamgoue, Armelle Deutou, Agbor, Gabriel Agbor, Kuiate, Jules-Roger, Daglia, Maria, Dell’Agli, Mario, and Magni, Paolo

Subjects
Metabolic Syndrome, Plant Extracts, Cameroonian spice extracts, Nutrition. Foods and food supply, Interleukins, SW 872 adipocytes, Liposarcoma, pro-inflammatory cytokines, Article, glucose uptake, Glucose, Cell Line, Tumor, Dietary Supplements, Adipocytes, Humans, oxidative stress, TX341-641, Spices, Reactive Oxygen Species, triglyceride accumulation, Triglycerides
Abstract

The molecular pathophysiology of cardiometabolic diseases is known to be influenced by dysfunctional ectopic adipose tissue. In addition to lifestyle improvements, these conditions may be managed by novel nutraceutical products. This study evaluatedthe effects of 11 Cameroonian medicinal spice extracts on triglyceride accumulation, glucose uptake, reactive oxygen species (ROS) production and interleukin secretion in SW 872 human adipocytes after differentiation with 100 µM oleic acid. Triglyceride content was significantly reduced by all spice extracts. Glucose uptake was significantly increased by Tetrapleura tetraptera, Aframomum melegueta and Zanthoxylum leprieurii. Moreover, Xylopia parviflora, Echinops giganteus and Dichrostachys glomerata significantly reduced the production of ROS. Concerning pro-inflammatory cytokine secretion, we observed that Tetrapleura tetraptera, Echinops giganteus, Dichrostachys glomerata and Aframomum melegueta reduced IL-6 secretion. In addition, Xylopia parviflora, Monodora myristica, Zanthoxylum leprieurii, and Xylopia aethiopica reduced IL-8 secretion, while Dichrostachys glomerata and Aframomum citratum increased it. These findings highlight some interesting properties of these Cameroonian spice extracts in the modulation of cellular parameters relevant to cardiometabolic diseases, which may be further exploited, aiming to develop novel treatment options for these conditions based on nutraceutical products.

Published
2021

47. Nutraceutical approach for the management of cardiovascular risk – a combination containing the probiotic Bifidobacterium longum BB536 and red yeast rice extract: results from a randomized, double-blind, placebo-controlled study

Author

Ruscica, Massimiliano, Pavanello, Chiara, Gandini, Sara, Macchi, Chiara, Botta, Margherita, Dall’Orto, Daria, Del Puppo, Marina, Bertolotti, Marco, Bosisio, Raffaella, Mombelli, Giuliana, Sirtori, Cesare R., Calabresi, Laura, Magni, Paolo, Ruscica, M, Pavanello, C, Gandini, S, Macchi, C, Botta, M, Dall'Orto, D, Del Puppo, M, Bertolotti, M, Bosisio, R, Mombelli, G, Sirtori, C, Calabresi, L, and Magni, P

Subjects
Adult, Male, Cardiovascular risk, Hypercholesterolemia, LDL-cholesterol, Monacolin K, Non-HDL cholesterol, Nutraceutical, Probiotic, Ubiquinone, lcsh:TX341-641, Niacin, Placebos, Double-Blind Method, Risk Factors, Humans, lcsh:RC620-627, Biological Products, Research, Probiotics, Correction, Middle Aged, Bifidobacterium longum, lcsh:Nutritional diseases. Deficiency diseases, Cardiovascular Diseases, Dietary Supplements, Female, lipids (amino acids, peptides, and proteins), lcsh:Nutrition. Foods and food supply
Abstract

Background Probiotics incorporated into dairy products have been shown to reduce total (TC) and LDL cholesterolemia (LDL-C) in subjects with moderate hypercholesterolemia. More specifically, probiotics with high biliary salt hydrolase activity, e.g. Bifidobacterium longum BB536, may decrease TC and LDL-C by lowering intestinal cholesterol reabsorption and, combined with other nutraceuticals, may be useful to manage hypercholesterolemia in subjects with low cardiovascular (CV) risk. This study was conducted to evaluate the efficacy and safety of a nutraceutical combination containing Bifidobacterium longum BB536, red yeast rice (RYR) extract (10 mg/day monacolin K), niacin, coenzyme Q10 (Lactoflorene Colesterolo®). The end-points were changes of lipid CV risk markers (LDL-C, TC, non-HDL-cholesterol (HDL-C), triglycerides (TG), apolipoprotein B (ApoB), HDL-C, apolipoprotein AI (ApoAI), lipoprotein(a) (Lp(a), proprotein convertase subtilisin/kexin type 9 (PCSK9)), and of markers of cholesterol synthesis/absorption. Methods A 12-week randomized, parallel, double-blind, placebo-controlled study. Thirty-three subjects (18–70 years) in primary CV prevention and low CV risk (SCORE: 0–1% in 24 and 2–4% in 9 subjects; LDL-C: 130–200 mg/dL) were randomly allocated to either nutraceutical (N = 16) or placebo (N = 17). Results Twelve-week treatment with the nutraceutical combination, compared to placebo, significantly reduced TC (− 16.7%), LDL-C (− 25.7%), non-HDL-C (− 24%) (all p

Published
2019

50. Interactions of oxysterols with atherosclerosis biomarkers in subjects with moderate hypercholesterolemia and effects of a nutraceutical combination (Bifidobacterium longum BB536, red yeast rice extract) (randomized, double-blind, placebo-controlled study)

Author

Cicolari, Stefania, Pavanello, Chiara, Olmastroni, Elena, Puppo, Marina Del, Bertolotti, Marco, Mombelli, Giuliana, Catapano, Alberico L., Calabresi, Laura, and Magni, Paolo

Subjects
cardiovascular risk, 24-OHC, 25-OHC, 27-OHC, Cardiovascular risk, Cholesterol metabolism, Hypercholesterolemia, Monacolin K, Nutraceutical, Oxysterols, Probiotic, hypercholesterolemia, monacolin K, cholesterol metabolism, oxysterols, nutraceutical, probiotic
Abstract

Background: Oxysterol relationship with cardiovascular (CV) risk factors is poorly explored, especially in moderately hypercholesterolaemic subjects. Moreover, the impact of nutraceuticals controlling hypercholesterolaemia on plasma levels of 24-, 25- and 27-hydroxycholesterol (24-OHC, 25-OHC, 27-OHC) is unknown. Methods: Subjects (n = 33, 18&ndash, 70 years) with moderate hypercholesterolaemia (low-density lipoprotein cholesterol (LDL-C:): 130&ndash, 200 mg/dL), in primary CV prevention as well as low CV risk were studied cross-sectionally. Moreover, they were evaluated after treatment with a nutraceutical combination (Bifidobacterium longum BB536, red yeast rice extract (10 mg/dose monacolin K)), following a double-blind, randomized, placebo-controlled design. We evaluated 24-OHC, 25-OHC and 27-OHC levels by gas chromatography/mass spectrometry analysis. Results: 24-OHC and 25-OHC were significantly correlated, 24-OHC was correlated with apoB. 27-OHC and 27-OHC/total cholesterol (TC) were higher in men (median 209 ng/mL and 77 ng/mg, respectively) vs. women (median 168 ng/mL and 56 ng/mg, respectively), 27-OHC/TC was significantly correlated with abdominal circumference, visceral fat and, negatively, with high-density lipoprotein cholesterol (HDL-C). Triglycerides were significantly correlated with 24-OHC, 25-OHC and 27-OHC and with 24-OHC/TC and 25-OHC/TC. After intervention, 27-OHC levels were significantly reduced by 10.4% in the nutraceutical group Levels of 24-OHC, 24-OHC/TC, 25-OHC, 25-OHC/TC and 27-OHC/TC were unchanged. Conclusions: In this study, conducted in moderate hypercholesterolemic subjects, we observed novel relationships between 24-OHC, 25-OHC and 27-OHC and CV risk biomarkers. In addition, no adverse changes of OHC levels upon nutraceutical treatment were found.

Published
2021

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