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Article ; Online: Effects of MBOAT7 polymorphism and steatosis on liver function assessed by methacetin breath test.

Di Ciaula, Agostino / Bonfrate, Leonilde / Shanmugam, Harshitha / Weber, Susanne N / Krawczyk, Marcin / Portincasa, Piero

European journal of clinical investigation

2023 Volume 53, Issue 8, Page(s) e14003

Abstract: Background: MBOAT7 rs641738 variant is a risk factor for nonalcoholic fatty liver disease (NAFLD) and liver fibrosis, but the relationship between this polymorphism and early liver dysfunction remains uncertain.: Methods: Eighty outpatients underwent ...

Abstract	Background: MBOAT7 rs641738 variant is a risk factor for nonalcoholic fatty liver disease (NAFLD) and liver fibrosis, but the relationship between this polymorphism and early liver dysfunction remains uncertain. Methods: Eighty outpatients underwent blood analyses, liver imaging by ultrasound and acoustic radiation force impulse shear wave elastography and were genotyped for MBOAT7 (wild-type [WT], rs641738 heterozygous or homozygous) polymorphism using TaqMan assays. Results: NAFLD was confirmed in 53 patients. Portal uptake and hepatocyte microsomal metabolization of ( Conclusions: The homozygous MBOAT7 rs641738 polymorphism per se is associated with a reduced extraction efficiency of (
MeSH term(s)	Humans ; Non-alcoholic Fatty Liver Disease ; Polymorphism, Single Nucleotide ; Acyltransferases/genetics ; Liver/diagnostic imaging ; Liver/pathology ; Liver Cirrhosis/complications ; Membrane Proteins/genetics
Chemical Substances	methacetin (13E468TFHP) ; Acyltransferases (EC 2.3.-) ; MBOAT7 protein, human (EC 2.3.-) ; Membrane Proteins
Language	English
Publishing date	2023-04-17
Publishing country	England
Document type	Journal Article
ZDB-ID	186196-7
ISSN	1365-2362 ; 0014-2972 ; 0960-135X
ISSN (online)	1365-2362
ISSN	0014-2972 ; 0960-135X
DOI	10.1111/eci.14003
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Article ; Online: Exploring Liver Mitochondrial Function by

Molina-Molina, Emilio / Shanmugam, Harshitha / Di Palo, Domenica / Grattagliano, Ignazio / Portincasa, Piero

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2310, Page(s) 179–199

Abstract: The liver is at the crossroad of key metabolic processes, which include detoxification, glycolipidic storage and export, and protein synthesis. The gut-liver axis, moreover, provides hepatocytes with a series of bacterial products and metabolites, which ... ...

Abstract	The liver is at the crossroad of key metabolic processes, which include detoxification, glycolipidic storage and export, and protein synthesis. The gut-liver axis, moreover, provides hepatocytes with a series of bacterial products and metabolites, which contribute to maintain liver function in health and disease. Breath tests (BTs) are developed as diagnostic tools for indirect, rapid, noninvasive assessment of several metabolic processes in the liver. BTs monitor the appearance of CO
MeSH term(s)	Biomarkers/metabolism ; Breath Tests ; Carbon Dioxide/metabolism ; Carbon Isotopes/metabolism ; Humans ; Liver Diseases/diagnosis ; Liver Diseases/metabolism ; Liver Function Tests ; Mitochondria, Liver/metabolism ; Predictive Value of Tests
Chemical Substances	Biomarkers ; Carbon Isotopes ; Carbon Dioxide (142M471B3J)
Language	English
Publishing date	2021-06-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1433-4_11
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Article ; Online: Post-Vaccination Sero-Monitoring of Peste des Petits Ruminants in Sheep and Goats in Karnataka: Progress towards PPR Eradication in India.

Balamurugan, Vinayagamurthy / Ojha, Rakshit / Kumar, Kirubakaran Vinod / Asha, Anand / Ashraf, Suhail / Dsouza, Annett Helcita / Pal, Archana / Bokade, Prajakta Prashant / Harshitha, Shakuntala Krishnaiah / Deshpande, Ramchandra / Swathi, Mahadevappa / Suresh, Kuralayanapalya Puttahonnappa / Govindaraj, GurrappaNaidu / Hasnadka, Subramanya Prasad / ChandraSekar, Shanmugam / Hemadri, Divakar / Guha, Anirban / Felix, Njeumi / Parida, Satya /

Gulati, Baldev Raj

Viruses

2024 Volume 16, Issue 3

Abstract: Peste des petits ruminants (PPR) presents economic challenges in enzootic countries impacting small ruminant productivity. The state of Karnataka, India, implemented a mass vaccination campaign in alignment with the PPR-Global Eradication Programme (GEP) ...

Abstract	Peste des petits ruminants (PPR) presents economic challenges in enzootic countries impacting small ruminant productivity. The state of Karnataka, India, implemented a mass vaccination campaign in alignment with the PPR-Global Eradication Programme (GEP) and the National Strategic Plan for PPR eradication. This study was conducted from January to March 2023 to assess seroconversion in post-vaccinated goats and sheep at the epidemiological unit (epi-unit) level, aligning with the World Organisation for Animal Health (WOAH) and the Food and Agriculture Organization (FAO) guidelines in the PPR Global Control and Eradication Strategy (GCES). Before vaccination, 3466 random serum samples were collected from small ruminants of three age groups (6-12 months, 1-2 years, and >2 years) across 116 epi-units, spanning 82 taluks in 28 districts. Post-vaccination sero-monitoring included 1102 serum samples collected from small ruminants of the 6-12-month age group only, across 111 epi-units covering 64 taluks in 23 districts. The PPRV antibody status was determined using an indigenous hemagglutinin (H) protein monoclonal antibody-based competitive ELISA kit. Pre-vaccination, the PPR seropositivity rates were 55%, 62%, and 66% in the age groups of 6-12 months, 1-2 years, and >2 years, respectively, with a 61% PPRV antibody prevalence across all the age groups. Notably, 41% of the epi-units exhibited antibody prevalence rates of ≥70%, indicating a substantial population immunity, possibly attributed to the previous vaccination program in the state since 2011. In contrast, only 17% of the epi-units had below 30% seroprevalence rates, emphasizing the need for intensified vaccination. Statistical analysis of the data revealed significant correlations (
MeSH term(s)	Sheep ; Animals ; Peste-des-Petits-Ruminants/epidemiology ; Peste-des-Petits-Ruminants/prevention & control ; Peste-des-petits-ruminants virus ; Goats ; Seroepidemiologic Studies ; India/epidemiology ; Goat Diseases/epidemiology ; Goat Diseases/prevention & control ; Sheep Diseases/epidemiology ; Sheep Diseases/prevention & control ; Vaccination/veterinary ; Antibodies, Viral ; Enzyme-Linked Immunosorbent Assay/veterinary
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2024-02-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v16030333
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Article ; Online: The Potential of the Mediterranean Diet to Improve Mitochondrial Function in Experimental Models of Obesity and Metabolic Syndrome.

Khalil, Mohamad / Shanmugam, Harshitha / Abdallah, Hala / John Britto, Jerlin Stephy / Galerati, Ilaria / Gómez-Ambrosi, Javier / Frühbeck, Gema / Portincasa, Piero

Nutrients

2022 Volume 14, Issue 15

Abstract: The abnormal expansion of body fat paves the way for several metabolic abnormalities including overweight, obesity, and diabetes, which ultimately cluster under the umbrella of metabolic syndrome (MetS). Patients with MetS are at an increased risk of ... ...

Abstract	The abnormal expansion of body fat paves the way for several metabolic abnormalities including overweight, obesity, and diabetes, which ultimately cluster under the umbrella of metabolic syndrome (MetS). Patients with MetS are at an increased risk of cardiovascular disease, morbidity, and mortality. The coexistence of distinct metabolic abnormalities is associated with the release of pro-inflammatory adipocytokines, as components of low-to-medium grade systemic inflammation and increased oxidative stress. Adopting healthy lifestyles, by using appropriate dietary regimens, contributes to the prevention and treatment of MetS. Metabolic abnormalities can influence the function and energetic capacity of mitochondria, as observed in many obesity-related cardio-metabolic disorders. There are preclinical studies both in cellular and animal models, as well as clinical studies, dealing with distinct nutrients of the Mediterranean diet (MD) and dysfunctional mitochondria in obesity and MetS. The term "
MeSH term(s)	Animals ; Diet, Mediterranean ; Metabolic Syndrome/prevention & control ; Mitochondria/metabolism ; Models, Theoretical ; Obesity ; Polyphenols/pharmacology
Chemical Substances	Polyphenols
Language	English
Publishing date	2022-07-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu14153112
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Article ; Online: Liver fat accumulation more than fibrosis causes early liver dynamic dysfunction in patients with non-alcoholic fatty liver disease.

Di Ciaula, Agostino / Shanmugam, Harshitha / Ribeiro, Rogério / Pina, Ana / Andrade, Rita / Bonfrate, Leonilde / Raposo, João F / Macedo, M Paula / Portincasa, Piero

European journal of internal medicine

2022

Abstract: Introduction: In Non-Alcoholic Fatty Liver Disease (NAFLD), events driving early hepatic dysfunction with respect to specific metabolic pathways are still poorly known.: Methods: We enrolled 84 subjects with obesity and/or type 2 diabetes (T2D). ... ...

Abstract	Introduction: In Non-Alcoholic Fatty Liver Disease (NAFLD), events driving early hepatic dysfunction with respect to specific metabolic pathways are still poorly known. Methods: We enrolled 84 subjects with obesity and/or type 2 diabetes (T2D). FibroScan® served to assess NAFLD by controlled attenuation parameter (CAP), and fibrosis by liver stiffness (LS). Patients with LS above 7 kPa were excluded. APRI and FIB-4 were used as additional serum biomarkers of fibrosis. The stable-isotope dynamic breath test was used to assess the hepatic efficiency of portal extraction (as DOB Results: NAFLD occurred in 45%, 65.9%, and 91.3% of normal weight, overweight, and obese subjects, respectively. Biomarkers of liver fibrosis were comparable across subgroups, and LS was higher in obese, than in normal weight subjects. DOB Conclusions: Overweight, obesity and liver fat accumulation manifest with deranged portal extraction efficiency of methacetin into the steatotic hepatocyte. This functional alteration occurs early, and irrespective of significant fibrosis and presence of T2D.
Language	English
Publishing date	2022-11-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1038679-8
ISSN	1879-0828 ; 0953-6205
ISSN (online)	1879-0828
ISSN	0953-6205
DOI	10.1016/j.ejim.2022.10.024
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Article ; Online: p-Aminobenzoic acid as an alternative chemical biopsy agent for human hepatic UDP-glucose.

Barosa, Cristina / Shanmugam, Harshitha / Cabral, Fernando / Jones, John G

Analytical biochemistry

2019 Volume 590, Page(s) 113511

Abstract: p-Aminobenzoic acid (PABA) was evaluated for noninvasive sampling of UDP-glucose in the liver. Six healthy subjects ingested 550 mg PABA during a breakfast meal. Urine was collected 0-2 and 2-4 h after PABA ingestion. N-acetyl PABA glucuronide (NAPG) was ...

Abstract	p-Aminobenzoic acid (PABA) was evaluated for noninvasive sampling of UDP-glucose in the liver. Six healthy subjects ingested 550 mg PABA during a breakfast meal. Urine was collected 0-2 and 2-4 h after PABA ingestion. N-acetyl PABA glucuronide (NAPG) was identified with 522 ± 212 μmol recovered in the 2-4 h urines. One of the subjects ingested 2 g of 98% [U-
MeSH term(s)	4-Aminobenzoic Acid/urine ; Adult ; Biopsy/methods ; Female ; Healthy Volunteers ; Humans ; Liver/metabolism ; Liver/pathology ; Male ; Middle Aged ; Uridine Diphosphate Glucose/metabolism ; Young Adult
Chemical Substances	4-Aminobenzoic Acid (TL2TJE8QTX) ; Uridine Diphosphate Glucose (V50K1D7P4Y)
Language	English
Publishing date	2019-11-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1110-1
ISSN	1096-0309 ; 0003-2697
ISSN (online)	1096-0309
ISSN	0003-2697
DOI	10.1016/j.ab.2019.113511
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Article ; Online: Genetic and clinical features of familial mediterranean fever (FMF) in a homogeneous cohort of patients from South-Eastern Italy.

Di Ciaula, Agostino / Iacoviello, Matteo / Bonfrate, Leonilde / Khalil, Mohamad / Shanmugam, Harshitha / Lopalco, Giuseppe / Bagnulo, Rosanna / Garganese, Antonella / Iannone, Florenzo / Resta, Nicoletta / Portincasa, Piero / Stella, Alessandro

European journal of internal medicine

2023 Volume 115, Page(s) 79–87

Abstract: Familial Mediterranean Fever (FMF) is linked with the MEFV gene and is the commonest among monogenic autoinflammatory diseases, with high prevalence in the Mediterranean basin. Although the clinical presentation of FMF has a major role in diagnosis, ... ...

Abstract	Familial Mediterranean Fever (FMF) is linked with the MEFV gene and is the commonest among monogenic autoinflammatory diseases, with high prevalence in the Mediterranean basin. Although the clinical presentation of FMF has a major role in diagnosis, genotype/phenotype correlations and the role of "benign" gene variants (as R202Q) appear highly variable and incompletely clear, making difficult to select the most effective strategy in the management of patients. Aim of the present study was to investigate the clinical presentation and the genetic background in a homogenous cohort of patients from Apulia (south eastern Italy). We investigated 217 patients with a clinical suspect of autoinflammatory diseases, who were characterized for the occurrence of specific symptoms and with next generation sequencing by a 4-gene panel including MEFV, MVK, NLRP3 and TNFRSF1A. A genetic change was identified in 122 (53.7%) patients, with 161 different MEFV variants recorded in 100 individuals, 10 variants in NLRP3, and 6 each in TNFRSF1A and MVK. The benign variant R202Q was largely prevalent (41.6% of all MEFV variants). When patients were selected according the number of pathogenic MEFV variants (0, 1, or 2 pathogenic variants), results failed to show significant links between the frequency of symptoms and the number of pathogenic variants. Only family history and Pras score (indicative for severity of disease) predicted the presence of pathogenic variants, as compared with carriers of variants considered of uncertain significance or benign. Fever >38 °C and arthralgias appeared more frequently in R202Q-positive patients than in non-R202Q carriers. These two subgroups showed comparable duration of fever, occurrence of myalgia, abdominal and chest pain, Pras, and IFFS scores. In conclusion, results confirm that FMF manifests in mild form in non-middle eastern patients. This possibility partly affects the reliability of clinical criteria/scores. Furthermore, the presence of the R202Q variant might not be completely neutral in selected groups of patients.
MeSH term(s)	Humans ; Familial Mediterranean Fever/diagnosis ; Familial Mediterranean Fever/epidemiology ; Familial Mediterranean Fever/genetics ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics ; Reproducibility of Results ; Pyrin/genetics ; Genetic Association Studies ; Fever ; Mutation
Chemical Substances	NLR Family, Pyrin Domain-Containing 3 Protein ; Pyrin ; MEFV protein, human
Language	English
Publishing date	2023-05-13
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1038679-8
ISSN	1879-0828 ; 0953-6205
ISSN (online)	1879-0828
ISSN	0953-6205
DOI	10.1016/j.ejim.2023.05.015
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Article: p-Aminobenzoic acid as an alternative chemical biopsy agent for human hepatic UDP-glucose

Barosa, Cristina / Shanmugam, Harshitha / Cabral, Fernando / Jones, John G

Analytical biochemistry. 2020 Feb. 01, v. 590

2020

Abstract: p-Aminobenzoic acid (PABA) was evaluated for noninvasive sampling of UDP-glucose in the liver. Six healthy subjects ingested 550 mg PABA during a breakfast meal. Urine was collected 0–2 and 2–4 h after PABA ingestion. N-acetyl PABA glucuronide (NAPG) was ...

Abstract	p-Aminobenzoic acid (PABA) was evaluated for noninvasive sampling of UDP-glucose in the liver. Six healthy subjects ingested 550 mg PABA during a breakfast meal. Urine was collected 0–2 and 2–4 h after PABA ingestion. N-acetyl PABA glucuronide (NAPG) was identified with 522 ± 212 μmol recovered in the 2–4 h urines. One of the subjects ingested 2 g of 98% [U–2H7]glucose alongside PABA and the NAPG was analyzed for positional 2H-enrichment by 2H NMR following derivatization to 5-O-acetyl monoacetone glucuronolactone. In conclusion, PABA is an effective agent for the chemical biopsy of hepatic UDP-glucose in humans.
Keywords	biopsy ; breakfast ; derivatization ; glucose ; humans ; ingestion ; lactones ; liver ; nuclear magnetic resonance spectroscopy ; p-aminobenzoic acid ; urine
Language	English
Dates of publication	2020-0201
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1110-1
ISSN	1096-0309 ; 0003-2697
ISSN (online)	1096-0309
ISSN	0003-2697
DOI	10.1016/j.ab.2019.113511
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Nonalcoholic Fatty Liver Disease (NAFLD). Mitochondria as Players and Targets of Therapies?

Agostino Di Ciaula / Salvatore Passarella / Harshitha Shanmugam / Marica Noviello / Leonilde Bonfrate / David Q.-H. Wang / Piero Portincasa

International Journal of Molecular Sciences, Vol 22, Iss 5375, p

2021 Volume 5375

Abstract: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and represents the hepatic expression of several metabolic abnormalities of high epidemiologic relevance. Fat accumulation in the hepatocytes results in cellular fragility ... ...

Abstract	Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and represents the hepatic expression of several metabolic abnormalities of high epidemiologic relevance. Fat accumulation in the hepatocytes results in cellular fragility and risk of progression toward necroinflammation, i.e., nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and eventually hepatocellular carcinoma. Several pathways contribute to fat accumulation and damage in the liver and can also involve the mitochondria, whose functional integrity is essential to maintain liver bioenergetics. In NAFLD/NASH, both structural and functional mitochondrial abnormalities occur and can involve mitochondrial electron transport chain, decreased mitochondrial β-oxidation of free fatty acids, excessive generation of reactive oxygen species, and lipid peroxidation. NASH is a major target of therapy, but there is no established single or combined treatment so far. Notably, translational and clinical studies point to mitochondria as future therapeutic targets in NAFLD since the prevention of mitochondrial damage could improve liver bioenergetics.
Keywords	lipotoxicity ; liver steatosis ; mitochondria ; nitrosative stress ; oxidative stress ; steatohepatitis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Unraveling the beneficial effects of herbal Lebanese mixture “Za’atar”. History, studies, and properties of a potential healthy food ingredient

Khalil, Mohamad / Rita Caponio, Giusy / Diab, Farah / Shanmugam, Harshitha / Di Ciaula, Agostino / Khalifeh, Hala / Vergani, Laura / Calasso, Maria / De Angelis, Maria / Portincasa, Piero

Journal of Functional Foods. 2022 Mar., v. 90 p.104993-

2022

Abstract: Interest in plant-based food has grown in recent years due to their primary prevention potential. Za’atar, an ancient and popular Lebanese herbal mixture, might disclose relevant clinical interest, due to the well-known intrinsic properties of its ... ...

Abstract	Interest in plant-based food has grown in recent years due to their primary prevention potential. Za’atar, an ancient and popular Lebanese herbal mixture, might disclose relevant clinical interest, due to the well-known intrinsic properties of its individual components. Za’atar mixture contain Origanum syriacum (Lebanese thyme), Thymbra spicata (Wild thyme), Rhus coriaria (Sumac), and Sesamum indicum (Sesame). Here we explored the history, composition, general employment, and bio-active aspects of Za’atar through available in vitro, animal, and clinical trials evidence to depict its possible role as an innovative nutraceutical tool. The combined action of Za’atar constituents is able to generate comprehensive beneficial effects on several common pathogenic pathways underlying chronic cardio-metabolic diseases and cancer. However, main available evidence derives from animal and in vitro studies. Thus, further human studies are needed to fully characterize Za’atar as a preventive and curative tool.
Keywords	Origanum syriacum ; Rhus coriaria ; Sesamum indicum ; Thymbra spicata ; dietary supplements ; employment ; food composition ; healthy diet ; humans ; plant-based foods ; thyme ; Lebanon ; Biological activities ; Gut microbiota ; Metabolic syndrome ; Nutraceutical ; Phenolic compounds ; Za’atar
Language	English
Dates of publication	2022-03
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Use and reproduction
ZDB-ID	2511964-3
ISSN	1756-4646
ISSN	1756-4646
DOI	10.1016/j.jff.2022.104993
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