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Article ; Online: Human Mesenchymal Stem/Stromal Cells in Immune Regulation and Therapy.

Mezey, Éva

2022 Volume 11, Issue 2, Page(s) 114–134

Abstract: Studies of mesenchymal stem (or stromal) cells (MSCs) have moved from bedside to bench and back again. The stromal cells or fibroblasts are found in all tissues and participate in building the extracellular matrix (ECM). Bone marrow (BM)-derived MSCs ... ...

Abstract	Studies of mesenchymal stem (or stromal) cells (MSCs) have moved from bedside to bench and back again. The stromal cells or fibroblasts are found in all tissues and participate in building the extracellular matrix (ECM). Bone marrow (BM)-derived MSCs have been studied for more than 50 years and have multiple roles. They function as stem cells and give rise to bone, cartilage, and fat in the BM (these are stem cells); support hematopoiesis (pericytes); and participate in sensing environmental changes and balancing pro- and anti-inflammatory conditions. In disease states, they migrate to sites of injury and release cytokines, hormones, nucleic acids depending on the microenvironment they find. Clinicians have begun to exploit these properties of BM, adipose tissue, and umbilical cord MSCs because they are easy to harvest and expand in culture. In this review, I describe the uses to which MSCs have been put, list ongoing clinical trials by organ system, and outline how MSCs are thought to regulate the innate and adaptive immune systems. I will discuss some of the reasons why clinical applications are still lacking. Much more work will have to be done to find the sources, doses, and culture conditions needed to exploit MSCs optimally and learn their healing potential. They are worth the effort.
MeSH term(s)	Adipose Tissue ; Bone Marrow Cells ; Cell Differentiation ; Cells, Cultured ; Humans ; Mesenchymal Stem Cells ; Umbilical Cord
Language	English
Publishing date	2022-03-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Review
ZDB-ID	2642270-0
ISSN	2157-6580 ; 2157-6580
ISSN (online)	2157-6580
ISSN	2157-6580
DOI	10.1093/stcltm/szab020
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Article ; Online: The combination of selenium and vitamin E inhibits type I collagen formation in cultured hepatic stellate cells.

Mezey, Esteban / Liu, Xiaopu / Potter, James J

Biological trace element research

2011 Volume 140, Issue 1, Page(s) 82–94

Abstract: This study investigated the effects of sodium selenite (Se) and of vitamin E (D-α-tochopherol ... without Se or vitamin E and with or without transforming growth factor β1 (TGFβ1). The combination of Se and ... vitamin E, but not either alone, protected against hepatic fibrosis by decreasing TGFβ1-mediated collagen ...

Abstract	This study investigated the effects of sodium selenite (Se) and of vitamin E (D-α-tochopherol) on the deposition of type I collagen by human LX-2 stellate cells. The cultured cells were treated with or without Se or vitamin E and with or without transforming growth factor β1 (TGFβ1). The combination of Se and vitamin E, but not either alone, protected against hepatic fibrosis by decreasing TGFβ1-mediated collagen secretion and accumulation by the stellate cells. This protective effect is due to a combination of decreased formation, decreased stability and increased degradation of the collagen. Effects of Se and vitamin E in decreasing α(1)(I) collagen mRNA and increasing apoptosis of stellate cells indicate decreased formation of collagen, while decreases in transglutaminase 2, which catalyze cross-linking of collagen, lead to decreased stability of the secreted collagen. Effects of Se and vitamin E on reducing tissue inhibitor metalloproteinase 1 (TIMP-1) are associated with increased degradation. The combination of Se and vitamin E decreased lipid peroxidation, while Se alone increased the activity of the antioxidant enzyme thioredoxin reductase. In conclusion, the combination of Se and vitamin E protected against TGFβ1-mediated hepatic fibrosis by decreasing TGFβ1-mediated type I collagen accumulation by stellate cells. This effect is due to a combination of decreased formation, decreased stability and increased degradation of the collagen.
MeSH term(s)	Cells, Cultured ; Collagen Type I/antagonists & inhibitors ; Collagen Type I/biosynthesis ; Hepatic Stellate Cells/cytology ; Hepatic Stellate Cells/drug effects ; Hepatic Stellate Cells/metabolism ; Humans ; Procollagen/antagonists & inhibitors ; Procollagen/biosynthesis ; Sodium Selenite/pharmacology ; Structure-Activity Relationship ; Vitamin E/pharmacology
Chemical Substances	Collagen Type I ; Procollagen ; Vitamin E (1406-18-4) ; Sodium Selenite (HIW548RQ3W)
Language	English
Publishing date	2011-04
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	445336-0
ISSN	1559-0720 ; 0163-4984
ISSN (online)	1559-0720
ISSN	0163-4984
DOI	10.1007/s12011-010-8672-7
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Article ; Online: Prevalence of the apolipoprotein E Arg145Cys dyslipidemia at-risk polymorphism in African-derived populations.

Abou Ziki, Maen D / Strulovici-Barel, Yael / Hackett, Neil R / Rodriguez-Flores, Juan L / Mezey, Jason G / Salit, Jacqueline / Radisch, Sharon / Hollmann, Charleen / Chouchane, Lotfi / Malek, Joel / Zirie, Mahmoud A / Jayyuosi, Amin / Gotto, Antonio M / Crystal, Ronald G

The American journal of cardiology

2013 Volume 113, Issue 2, Page(s) 302–308

Abstract: Apolipoprotein E, a protein component of blood lipid particles, plays an important role in lipid ... transport. Different mutations in the apolipoprotein E gene have been associated with various clinical ... Saharan Africans are apolipoprotein E R145C. In conclusion, although larger epidemiologic studies are ...

Abstract	Apolipoprotein E, a protein component of blood lipid particles, plays an important role in lipid transport. Different mutations in the apolipoprotein E gene have been associated with various clinical phenotypes. In an initiated study of Qataris, we observed that 17% of the African-derived genetic subgroup were heterozygotes for a rare Arg145Cys (R145C) variant that functions as a dominant trait with incomplete penetrance associated with type III hyperlipoproteinemia. On the basis of this observation, we hypothesized that the R145C polymorphism might be common in African-derived populations. The prevalence of the R145C variant was assessed worldwide in the "1000 Genomes Project" and in 1,012 whites and 1,226 African-Americans in New York, New York. The 1000 Genomes Project data demonstrated that the R145C polymorphism is rare in non-African-derived populations but present in 5% to 12% of Sub-Saharan African-derived populations. The R145C polymorphism was also rare in New York whites (1 of 1,012, 0.1%); however, strikingly, 53 of the 1,226 New York African-Americans (4.3%) were R145C heterozygotes. The lipid profiles of the Qatari and New York R145C heterozygotes were compared with those of controls. The Qatari R145C subjects had higher triglyceride levels than the Qatari controls (p <0.007) and the New York African-American R145C subjects had an average of 52% greater fasting triglyceride levels than the New York African-American controls (p <0.002). From these observations, likely millions of people worldwide derived from Sub-Saharan Africans are apolipoprotein E R145C. In conclusion, although larger epidemiologic studies are necessary to determine the long-term consequences of this polymorphism, the available evidence suggests it is a common cause of a mild triglyceride dyslipidemia.
MeSH term(s)	African Americans ; Alleles ; Apolipoproteins E/blood ; Apolipoproteins E/genetics ; DNA/genetics ; Dyslipidemias/blood ; Dyslipidemias/ethnology ; Dyslipidemias/genetics ; Genetic Predisposition to Disease ; Genotype ; Humans ; New York/epidemiology ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Prevalence ; Risk Factors
Chemical Substances	Apolipoproteins E ; DNA (9007-49-2)
Language	English
Publishing date	2013-10-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80014-4
ISSN	1879-1913 ; 0002-9149
ISSN (online)	1879-1913
ISSN	0002-9149
DOI	10.1016/j.amjcard.2013.09.021
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Article: The Combination of Selenium and Vitamin E Inhibits Type I Collagen Formation in Cultured Hepatic Stellate Cells

Mezey, Esteban / Liu, Xiaopu / Potter, James J

Biological trace element research.. 2011 Apr., v. 140, no. 1

2011

Abstract	This study investigated the effects of sodium selenite (Se) and of vitamin E (D-α-tochopherol) on the deposition of type I collagen by human LX-2 stellate cells. The cultured cells were treated with or without Se or vitamin E and with or without transforming growth factor β1 (TGFβ1). The combination of Se and vitamin E, but not either alone, protected against hepatic fibrosis by decreasing TGFβ1-mediated collagen secretion and accumulation by the stellate cells. This protective effect is due to a combination of decreased formation, decreased stability and increased degradation of the collagen. Effects of Se and vitamin E in decreasing α1(I) collagen mRNA and increasing apoptosis of stellate cells indicate decreased formation of collagen, while decreases in transglutaminase 2, which catalyze cross-linking of collagen, lead to decreased stability of the secreted collagen. Effects of Se and vitamin E on reducing tissue inhibitor metalloproteinase 1 (TIMP-1) are associated with increased degradation. The combination of Se and vitamin E decreased lipid peroxidation, while Se alone increased the activity of the antioxidant enzyme thioredoxin reductase. In conclusion, the combination of Se and vitamin E protected against TGFβ1-mediated hepatic fibrosis by decreasing TGFβ1-mediated type I collagen accumulation by stellate cells. This effect is due to a combination of decreased formation, decreased stability and increased degradation of the collagen.
Keywords	antioxidant activity ; apoptosis ; collagen ; crosslinking ; cultured cells ; fibrosis ; humans ; lead ; lipid peroxidation ; messenger RNA ; protective effect ; protein-glutamine gamma-glutamyltransferase ; secretion ; selenium ; sodium selenite ; transforming growth factors ; vitamin E
Language	English
Dates of publication	2011-04
Size	p. 82-94.
Publishing place	Springer-Verlag
Document type	Article
ZDB-ID	445336-0
ISSN	1559-0720 ; 0163-4984
ISSN (online)	1559-0720
ISSN	0163-4984
DOI	10.1007/s12011-010-8672-7
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Article ; Online: Differential expression of vitamin E and selenium-responsive genes by disease severity in chronic obstructive pulmonary disease.

Agler, Anne H / Crystal, Ronald G / Mezey, Jason G / Fuller, Jennifer / Gao, Chuan / Hansen, Joyanna G / Cassano, Patricia A

COPD

2013 Volume 10, Issue 4, Page(s) 450–458

Abstract: ... in a similar pattern. Lung tissue samples from patients with COPD were assayed for vitamin E and ... gene expression. Selenium and vitamin E were assayed in corresponding plasma samples. Discovery based genome-wide ... for vitamin E-responsive and selenium-responsive genes. GOLD II-IV COPD patients had 30% lower lung tissue ...

Abstract	Antioxidant nutritional status is hypothesized to influence chronic obstructive pulmonary disease (COPD) susceptibility and progression. Although past studies relate antioxidants to gene expression, there are no data in patients with COPD. This study investigated the hypothesis that antioxidant status is compromised in patients with COPD, and antioxidant-responsive genes differentially express in a similar pattern. Lung tissue samples from patients with COPD were assayed for vitamin E and gene expression. Selenium and vitamin E were assayed in corresponding plasma samples. Discovery based genome-wide expression analysis compared moderate, severe, and very severe COPD (GOLD II-IV) patients to mild and at-risk/normal (GOLD 0-I). Hypotheses-driven analyses assessed differential gene expression by disease severity for vitamin E-responsive and selenium-responsive genes. GOLD II-IV COPD patients had 30% lower lung tissue vitamin E levels compared to GOLD 0-I participants (p = 0.0082). No statistically significant genome-wide differences in expression by disease severity were identified. Hypothesis-driven analyses of 109 genes found 16 genes differentially expressed (padjusted < 0.05) by disease severity including 6 selenium-responsive genes (range in fold-change -1.39 to 2.25), 6 vitamin E-responsive genes (fold-change -2.30 to 1.51), and 4 COPD-associated genes. Lung tissue vitamin E in patients with COPD was associated with disease severity and vitamin E-responsive genes were differentially expressed by disease severity. Although nutritional status is hypothesized to contribute to COPD risk, and is of therapeutic interest, evidence to date is mainly observational. The findings reported herein are novel, and support a role of vitamin E in COPD progression.
MeSH term(s)	Aged ; Aged, 80 and over ; Antioxidants/analysis ; Antioxidants/metabolism ; Female ; Gene Expression ; Gene Expression Profiling ; Humans ; Lung/chemistry ; Male ; Middle Aged ; Nutritional Status ; Oligonucleotide Array Sequence Analysis ; Pulmonary Disease, Chronic Obstructive/blood ; Pulmonary Disease, Chronic Obstructive/genetics ; Pulmonary Disease, Chronic Obstructive/physiopathology ; RNA/analysis ; Selenium/blood ; Severity of Illness Index ; alpha-Tocopherol/analysis ; alpha-Tocopherol/blood
Chemical Substances	Antioxidants ; RNA (63231-63-0) ; alpha-Tocopherol (H4N855PNZ1) ; Selenium (H6241UJ22B)
Language	English
Publishing date	2013-07-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2171107-0
ISSN	1541-2563 ; 1541-2555
ISSN (online)	1541-2563
ISSN	1541-2555
DOI	10.3109/15412555.2012.761958
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Article: A randomized placebo controlled trial of vitamin E for alcoholic hepatitis.

Mezey, Esteban / Potter, James J / Rennie-Tankersley, Lynda / Caballeria, Juan / Pares, Albert

Journal of hepatology

2003 Volume 40, Issue 1, Page(s) 40–46

Abstract: Background/aims: The effect of vitamin E administration on clinical and laboratory parameters ... 1000 I.U. of vitamin E per day, while 26 patients received placebo for 3 months. The patients were ... followed for 1 year after entry into the trial.: Results: Vitamin E did not result in significant ...

Abstract	Background/aims: The effect of vitamin E administration on clinical and laboratory parameters of liver function and on markers of fibrogenesis was assessed in patients with mild to moderate alcoholic hepatitis in a double blind placebo controlled randomized trial. Methods: Twenty-five patients received 1000 I.U. of vitamin E per day, while 26 patients received placebo for 3 months. The patients were followed for 1 year after entry into the trial. Results: Vitamin E did not result in significant greater decreases in serum aminotransferases and serum bilirubin or in greater increases in serum albumin as compared with placebo. Prothrombin time did not change, while serum creatinine remained in the normal range. Monocyte nuclear nuclear factor-kappa B binding activity decreased in patients who remained abstinent, regardless of whether they received vitamin E. As regards markers of hepatic fibrogenesis, vitamin E treatment decreased serum hyaluronic acid (P<0.05) while serum aminoterminal peptide of type III procollagen did not change in either group. Four patients in the treatment group and five in the placebo group died during the 1-year study. Conclusions: Vitamin E treatment improves serum hyaluronic acid but has no beneficial effects on tests of liver function in patients with mild to moderate alcoholic hepatitis.
MeSH term(s)	Antioxidants/therapeutic use ; Bilirubin/blood ; Double-Blind Method ; Female ; Hepatitis, Alcoholic/blood ; Hepatitis, Alcoholic/drug therapy ; Hepatitis, Alcoholic/mortality ; Hepatitis, Alcoholic/physiopathology ; Humans ; Hyaluronic Acid/blood ; Liver Function Tests ; Male ; Middle Aged ; Monocytes/metabolism ; NF-kappa B/blood ; Peptide Fragments/blood ; Procollagen/blood ; Prothrombin Time ; Serum Albumin/analysis ; Transaminases/blood ; Treatment Failure ; Vitamin E/therapeutic use
Chemical Substances	Antioxidants ; NF-kappa B ; Peptide Fragments ; Procollagen ; Serum Albumin ; procollagen Type III-N-terminal peptide ; Vitamin E (1406-18-4) ; Hyaluronic Acid (9004-61-9) ; Transaminases (EC 2.6.1.-) ; Bilirubin (RFM9X3LJ49)
Language	English
Publishing date	2003-11-20
Publishing country	Netherlands
Document type	Clinical Trial ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	605953-3
ISSN	1600-0641 ; 0168-8278
ISSN (online)	1600-0641
ISSN	0168-8278
DOI	10.1016/s0168-8278(03)00476-8
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Article ; Online: Effect of osteoarthritis and its surgical treatment on patients' quality of life: a longitudinal study.

Mezey, Gyöngyi Anna / Paulik, Edit / Máté, Zsuzsanna

BMC musculoskeletal disorders

2023 Volume 24, Issue 1, Page(s) 537

Abstract: Background: Osteoarthritis (OA) is one of the primary causes of pain and disability worldwide leading to patients having some of the worst health-related quality of life (QOL). The purpose of our study was to investigate the progression of the generic ... ...

Abstract	Background: Osteoarthritis (OA) is one of the primary causes of pain and disability worldwide leading to patients having some of the worst health-related quality of life (QOL). The purpose of our study was to investigate the progression of the generic and disease-specific QOL of osteoarthritic patients going through total hip or knee replacement surgery and the factors that might alter the effect of surgery on QOL. Methods: A longitudinal study was performed based on data collected from 120 OA patients who filled in the short version of the WHO's generic measure of quality of life (WHOQOL-BREF) and the disease-specific Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) before and after surgery. Results: Domains related to physical health status showed relatively lower scores in patients before surgery. Patients reported a significant increase of QOL after surgery in the WHOQOL-BREF physical domain, especially if they were from the younger group (< 65 years, p = 0.022) or had a manual job (p = 0.008). Disease-specific QOL outcome results indicate that overall patients gained significantly better QOL in all domains of the WOMAC score. Patients with hip OA seemed to have the most benefit of their operation as they reported better outcome in WOMAC pain (p = 0.019), stiffness (p = 0.010), physical function domains (p = 0.011) and total score (p = 0.007) compared to knee OA patients. Conclusion: There was a statistically significant improvement in all domains concerning physical functions in the study population. Patients also reported significant improvement in the social relationship domain, which indicates that OA itself as well as its management might have a profound effect on patients' life beyond the reduction of their pain.
MeSH term(s)	Humans ; Quality of Life ; Longitudinal Studies ; Health Status ; Osteoarthritis, Knee/surgery ; Pain
Language	English
Publishing date	2023-06-30
Publishing country	England
Document type	Journal Article
ZDB-ID	2041355-5
ISSN	1471-2474 ; 1471-2474
ISSN (online)	1471-2474
ISSN	1471-2474
DOI	10.1186/s12891-023-06662-w
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Article ; Online: Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production.

Németh, Krisztián / Leelahavanichkul, Asada / Yuen, Peter S T / Mayer, Balázs / Parmelee, Alissa / Doi, Kent / Robey, Pamela G / Leelahavanichkul, Kantima / Koller, Beverly H / Brown, Jared M / Hu, Xuzhen / Jelinek, Ivett / Star, Robert A / Mezey, Eva

Nature medicine

2008 Volume 15, Issue 1, Page(s) 42–49

Abstract: ... alpha) reprogram macrophages by releasing prostaglandin E(2) that acts on the macrophages ...

Abstract	Sepsis causes over 200,000 deaths yearly in the US; better treatments are urgently needed. Administering bone marrow stromal cells (BMSCs -- also known as mesenchymal stem cells) to mice before or shortly after inducing sepsis by cecal ligation and puncture reduced mortality and improved organ function. The beneficial effect of BMSCs was eliminated by macrophage depletion or pretreatment with antibodies specific for interleukin-10 (IL-10) or IL-10 receptor. Monocytes and/or macrophages from septic lungs made more IL-10 when prepared from mice treated with BMSCs versus untreated mice. Lipopolysaccharide (LPS)-stimulated macrophages produced more IL-10 when cultured with BMSCs, but this effect was eliminated if the BMSCs lacked the genes encoding Toll-like receptor 4, myeloid differentiation primary response gene-88, tumor necrosis factor (TNF) receptor-1a or cyclooxygenase-2. Our results suggest that BMSCs (activated by LPS or TNF-alpha) reprogram macrophages by releasing prostaglandin E(2) that acts on the macrophages through the prostaglandin EP2 and EP4 receptors. Because BMSCs have been successfully given to humans and can easily be cultured and might be used without human leukocyte antigen matching, we suggest that cultured, banked human BMSCs may be effective in treating sepsis in high-risk patient groups.
MeSH term(s)	Animals ; Bone Marrow Cells/physiology ; Bone Marrow Transplantation/physiology ; Cecal Diseases/complications ; Cecal Diseases/mortality ; Cecal Diseases/physiopathology ; Cecal Diseases/therapy ; Cecum/injuries ; Cecum/pathology ; Cellular Reprogramming/immunology ; Cellular Reprogramming/physiology ; Dinoprostone/physiology ; Humans ; Interleukin-10/biosynthesis ; Interleukin-10/blood ; Macrophages/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Models, Biological ; Sepsis/etiology ; Sepsis/metabolism ; Sepsis/mortality ; Sepsis/therapy ; Stromal Cells/physiology ; Stromal Cells/transplantation ; Survival Analysis ; Transplantation ; Wounds, Penetrating/complications ; Wounds, Penetrating/mortality ; Wounds, Penetrating/physiopathology ; Wounds, Penetrating/therapy
Chemical Substances	Interleukin-10 (130068-27-8) ; Dinoprostone (K7Q1JQR04M)
Language	English
Publishing date	2008-11-21
Publishing country	United States
Document type	Evaluation Study ; Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/nm.1905
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Article ; Online: Transcriptome Profile of a New Mouse Model of Spinocerebellar Ataxia Type 14 Implies Changes in Cerebellar Development.

Mezey, Szilvia E / Kapfhammer, Josef P / Shimobayashi, Etsuko

Genes

2022 Volume 13, Issue 8

Abstract: The autosomal dominant inherited spinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders characterized by cerebellar atrophy and loss of Purkinje neurons. Spinocerebellar ataxia type 14 (SCA14) is a rare variant of SCAs caused by ... ...

Abstract	The autosomal dominant inherited spinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders characterized by cerebellar atrophy and loss of Purkinje neurons. Spinocerebellar ataxia type 14 (SCA14) is a rare variant of SCAs caused by missense mutations or deletions in the
MeSH term(s)	Animals ; Cerebellum/pathology ; Disease Models, Animal ; Humans ; Mice ; Purkinje Cells/pathology ; Spinocerebellar Ataxias/genetics ; Spinocerebellar Ataxias/pathology ; Transcriptome
Language	English
Publishing date	2022-08-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes13081417
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Article ; Online: On the origin of blood cells--hematopoiesis revisited.

Mezey, Éva

Oral diseases

2016 Volume 22, Issue 4, Page(s) 247–248

MeSH term(s)	Cell Lineage/physiology ; Erythroid Cells/cytology ; Hematopoiesis/physiology ; Humans ; Megakaryocyte Progenitor Cells/cytology ; Megakaryocytes/cytology ; Myeloid Cells/cytology
Language	English
Publishing date	2016-02-15
Publishing country	Denmark
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Comment
ZDB-ID	1290529-x
ISSN	1601-0825 ; 1354-523X
ISSN (online)	1601-0825
ISSN	1354-523X
DOI	10.1111/odi.12445
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