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Article ; Online: Synthesis and characterization of molybdenum disulfide nanoparticles in Shewanella oneidensis MR-1 biofilms.

Rees, James D / Gorby, Yuri A / Sawyer, Shayla M

2020 Volume 15, Issue 4, Page(s) 41006

Abstract: ... of molybdenum disulfide nanomaterials at the site of S. oneidensis biofilms grown in the presence of molybdenum ... for molybdenum sulfide, the use of S. oneidensis offers the advantage of significantly reduced heat and chemical ...

Abstract	Shewanella oneidensis MR-1 is a dissimilatory metal-reducing bacterium capable of reducing various metal and sulfur compounds and precipitating them in nanoparticulate form. Here, we report the synthesis of molybdenum disulfide nanomaterials at the site of S. oneidensis biofilms grown in the presence of molybdenum trioxide and sodium thiosulfate. Samples from the growth medium were imaged using scanning electron microscopy and characterized using transmission electron microscopy, energy-dispersive x-ray spectroscopy, absorbance spectroscopy, and x-ray diffraction. These methods revealed the presence of molybdenum disulfide nanoparticle aggregates 50-300 nm in diameter with both hexagonal and rhombohedral polytypes. As a biosynthesis method for molybdenum sulfide, the use of S. oneidensis offers the advantage of significantly reduced heat and chemical solvent input compared to conventional methods of synthesizing molybdenum disulfide nanoparticles.
MeSH term(s)	Biofilms/growth & development ; Disulfides/chemistry ; Green Chemistry Technology ; Metal Nanoparticles/chemistry ; Microscopy, Electron, Scanning ; Molybdenum/chemistry ; Oxides/chemistry ; Particle Size ; Shewanella/chemistry ; Shewanella/physiology ; Spectrometry, X-Ray Emission ; Thiosulfates/chemistry
Chemical Substances	Disulfides ; Oxides ; Thiosulfates ; molybdenum trioxide (22FQ3F03YS) ; Molybdenum (81AH48963U) ; sodium thiosulfate (HX1032V43M) ; molybdenum disulfide (ZC8B4P503V)
Language	English
Publishing date	2020-07-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2234510-3
ISSN	1559-4106 ; 1934-8630
ISSN (online)	1559-4106
ISSN	1934-8630
DOI	10.1116/6.0000199
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: A Plant-Based Dietary Supplement Improves Measures of Metabolic Detoxification and the Quality of Life: A Phase II Multicenter Randomized, Blinded, Placebo-Controlled Clinical Trial.

El-Khodor, Bassem F / Zang, Wei / Gorby, Heather / Dominique, Ashley / Hamrock, Meghan / Metzer, Brandon / Pecorelli, Alessandra / Varadharaj, Saradhadevi / Valacchi, Giuseppe

Integrative medicine (Encinitas, Calif.)

2023 Volume 22, Issue 5, Page(s) 28–39

Abstract: Background: Persistent accumulation and hindered clearance of toxins from tissues over time may promote the development and exacerbation of several diseases. Hepatic metabolic detoxification is a key physiological process responsible for the clearance ... ...

Abstract	Background: Persistent accumulation and hindered clearance of toxins from tissues over time may promote the development and exacerbation of several diseases. Hepatic metabolic detoxification is a key physiological process responsible for the clearance of toxic substances from the body. A healthy diet with nutritional dietary supplementation may support metabolic detoxification and help mitigate the negative effects of toxin burden. Methods: A multicenter, randomized, single-blind, controlled trial was conducted to test the effects of a dietary detoxification product (detox; n = 20) versus an active dietary control product (active control; n = 20) on selected biomarkers of metabolic detoxification, general health, and well-being following 28 days of dietary supplementation. Study participants displayed multiple symptoms commonly associated with elevated toxin burden, but otherwise healthy. Results: The detox group displayed significantly decreased levels of red blood cell total toxic metals, decreased urine total porphyrins, and decreased urine mutagenicity potency compared with baseline. Both the detox and active control groups showed improvements in the symptoms attributed to elevated toxin burden. Fatigue and sleep disruption scores were significantly reduced in the detox group compared with baseline. No significant differences in anthropometric measures and vital signs, and no adverse events or side effects were detected in either group over the study period. Conclusions: This study demonstrates the benefit of nutritional intervention for supporting metabolic detoxification, evidenced by significant changes in multiple detoxification biomarkers and improvement in questionnaire scores related to quality of life, general health, and well-being.
Language	English
Publishing date	2023-12-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2100529-1
ISSN	1945-7081 ; 1546-993X
ISSN (online)	1945-7081
ISSN	1546-993X
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Article: Lipoprotein apheresis for lipoprotein(a) and cardiovascular disease.

Moriarty, Patrick M / Gray, Jessica V / Gorby, Lauryn K

Journal of clinical lipidology

2019 Volume 13, Issue 6, Page(s) 894–900

Abstract: ... Conclusion: The treatment of CVD patients with an elevated Lp(a) and near normal LDL-C with LA in a U.S ...

Abstract	Background: Elevated lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease (CVD). In the United States, lipoprotein apheresis (LA) therapy is approved for patients with familial hypercholesterolemia. Germany uses LA therapy for patients with an Lp(a) > 60 mg/dL, normal low-density lipoprotein cholesterol (LDL-C) levels, and CVD. LA therapy in this population demonstrated a >70% reduction in CVD events. In the United States, LA is only approved for patients with elevated LDL-C levels, regardless of Lp(a) level. Objective: The objective of the study was to evaluate clinical significance of Lp(a) reduction with LA therapy in the United States. Methods: A retrospective cohort study at one LA site in the United States evaluated 14 CVD patients with elevated Lp(a) and near normal LDL-C levels. Patient data was analyzed to demonstrate possible clinical benefit in reducing Lp(a) levels with LA to mitigate risk of major adverse cardiovascular events. Results: Pre-LA patients' mean LDL-C and Lp(a) were 80 mg/dL and 138 mg/dL, respectively. LA therapy demonstrated a reduction of mean LDL-C to 29 mg/dL and Lp(a) to 51 mg/dL. These represent a percent reduction of 64% and 63% for LDL-C and Lp(a), respectively. There was a 94% reduction in major adverse cardiovascular events over a mean treatment period of 48 months. Conclusion: The treatment of CVD patients with an elevated Lp(a) and near normal LDL-C with LA in a U.S. treatment center demonstrated a significant reduction in future CVD events. LA should be considered for patients in the United States suffering from an elevated Lp(a) and progressive CVD.
MeSH term(s)	Adolescent ; Adult ; Blood Component Removal/methods ; Cardiovascular Diseases/blood ; Cardiovascular Diseases/therapy ; Child ; Cholesterol, LDL/blood ; Female ; Humans ; Lipoprotein(a)/blood ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; Young Adult
Chemical Substances	Cholesterol, LDL ; Lipoprotein(a)
Language	English
Publishing date	2019-09-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2365061-8
ISSN	1876-4789 ; 1933-2874
ISSN (online)	1876-4789
ISSN	1933-2874
DOI	10.1016/j.jacl.2019.09.010
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Article ; Online: Effect of Lipoprotein Apheresis on Progression of Carotid Intima-Media Thickness in Patients with Severe Hypercholesterolemia.

Safarova, Maya S / Nugent, Anne K / Gorby, Lauryn / Dutton, Julie-Ann / Thompson, W Jake / Moriarty, Patrick M

The American journal of cardiology

2022 Volume 177, Page(s) 22–27

Abstract: The extent of intervention effects on carotid intima-media thickness (CIMT) can predict the degree of atherosclerotic cardiovascular risk-reduction. We hypothesized that regular lipoprotein apheresis over the course of 10 years might slow down ... ...

Abstract	The extent of intervention effects on carotid intima-media thickness (CIMT) can predict the degree of atherosclerotic cardiovascular risk-reduction. We hypothesized that regular lipoprotein apheresis over the course of 10 years might slow down progression of CIMT in patients with severe hypercholesterolemia. This case series describes 10 Caucasian patients (mean age 60 ± 9 years, 70% female, 80% statin intolerant) with a severe hypercholesterolemia phenotype treated with lipoprotein apheresis between 2005 and 2020 (mean duration, 10 ± 4 years). The median pretreatment low-density lipoprotein cholesterol (LDL-C) level was 214 mg/100 ml (95% confidence interval, 145 to 248), lipoprotein(a) (Lp[a]), 26 mg/100 ml (15 to 109; 40% with Lp(a)>60 mg/100 ml). Three patients were diagnosed with a monogenic cause. The baseline mean CIMT was 850 ± 170 µm, and maximum CIMT was 1,040 ± 220 µm across the age range of 46 to 70 years. Acute effects of lipoprotein apheresis determined as a difference before and immediately after the procedure were estimated as a median of 72 ± 8% and 75 ± 7% reduction in the LDL-C and Lp(a) levels, respectively. Using the imputed trajectories, period-specific on-treatment time-weighted averages for LDL-C and Lp(a) were 141 mg/100 ml (interquartile range, 89 to 152; 38% reduction from the baseline) and 24 mg/100 ml (interquartile range, 12 to 119; 19% reduction from baseline), respectively. The number of patients with CIMT above their "vascular age" decreased from 80% to 30% over the treatment course. In conclusion, an increase in CIMT seen with advanced age and severe hypercholesterolemia was halted with lipoprotein apheresis with an estimated annual rate of change in mean common CIMT of -4 µm/y and maximum CIMT of -3 µm/y.
MeSH term(s)	Blood Component Removal/methods ; Carotid Intima-Media Thickness ; Cholesterol, LDL ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Hypercholesterolemia/complications ; Hypercholesterolemia/therapy ; Lipoprotein(a) ; Male
Chemical Substances	Cholesterol, LDL ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Lipoprotein(a)
Language	English
Publishing date	2022-06-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	80014-4
ISSN	1879-1913 ; 0002-9149
ISSN (online)	1879-1913
ISSN	0002-9149
DOI	10.1016/j.amjcard.2022.05.002
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Article ; Online: Lipoprotein(a) and Its Potential Association with Thrombosis and Inflammation in COVID-19: a Testable Hypothesis.

Moriarty, Patrick M / Gorby, Lauryn K / Stroes, Erik S / Kastelein, John P / Davidson, Michael / Tsimikas, Sotirios

Current atherosclerosis reports

2020 Volume 22, Issue 9, Page(s) 48

Abstract: Purpose of review: The COVID-19 pandemic has infected over > 11 million as of today people worldwide and is associated with significant cardiovascular manifestations, particularly in subjects with preexisting comorbidities and cardiovascular risk ... ...

Abstract	Purpose of review: The COVID-19 pandemic has infected over > 11 million as of today people worldwide and is associated with significant cardiovascular manifestations, particularly in subjects with preexisting comorbidities and cardiovascular risk factors. Recently, a predisposition for arterial and venous thromboses has been reported in COVID-19 infection. We hypothesize that besides conventional risk factors, subjects with elevated lipoprotein(a) (Lp(a)) may have a particularly high risk of developing cardiovascular complications. Recent findings: The Lp(a) molecule has the propensity for inhibiting endogenous fibrinolysis through its apolipoprotein(a) component and for enhancing proinflammatory effects such as through its content of oxidized phospholipids. The LPA gene contains an interleukin-6 (IL-6) response element that may induce an acute phase-type increase in Lp(a) levels following a cytokine storm from COVID-19. Thus, subjects with either baseline elevated Lp(a) or those who have an increase following COVID-19 infection, or both, may be at very high risk of developing thromboses. Elevated Lp(a) may also lead to acute destabilization of preexisting but quiescent atherosclerotic plaques, which might induce acute myocardial infarction and stroke. Ongoing studies with IL-6 antagonists may be informative in understanding this relationship, and registries are being initiated to measure Lp(a) in subjects infected with COVID-19. If indeed an association is suggestive of being causal, consideration can be given to systematic testing of Lp(a) and prophylactic systemic anticoagulation in infected inpatients. Therapeutic lipid apheresis and pharmacotherapy for the reduction of Lp(a) levels may minimize thrombogenic potential and proinflammatory effects. We propose studies to test the hypothesis that Lp(a) may contribute to cardiovascular complications of COVID-19.
MeSH term(s)	Acute-Phase Proteins/analysis ; Acute-Phase Proteins/genetics ; Anticoagulants/therapeutic use ; Apolipoprotein E4/genetics ; Atherosclerosis/etiology ; Betacoronavirus ; Biomarkers/blood ; Biomedical Research ; Blood Component Removal ; COVID-19 ; Coronavirus Infections/blood ; Coronavirus Infections/complications ; Coronavirus Infections/epidemiology ; Genotype ; Humans ; Inflammation/etiology ; Inflammation/prevention & control ; Interleukin-6/antagonists & inhibitors ; Interleukin-6/blood ; Lipoprotein(a)/blood ; Lipoprotein(a)/genetics ; Pandemics ; Pneumonia, Viral/blood ; Pneumonia, Viral/complications ; Pneumonia, Viral/epidemiology ; Race Factors ; Racial Groups/genetics ; Risk Factors ; SARS-CoV-2 ; Severity of Illness Index ; Thrombosis/etiology ; Thrombosis/prevention & control
Chemical Substances	Acute-Phase Proteins ; Anticoagulants ; Apolipoprotein E4 ; Biomarkers ; Interleukin-6 ; Lipoprotein(a)
Keywords	covid19
Language	English
Publishing date	2020-07-25
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2057369-8
ISSN	1534-6242 ; 1523-3804
ISSN (online)	1534-6242
ISSN	1523-3804
DOI	10.1007/s11883-020-00867-3
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Article ; Online: Lipoprotein(a) and Its Potential Association with Thrombosis and Inflammation in COVID-19

Moriarty, Patrick M. / Gorby, Lauryn K. / Stroes, Erik S. / Kastelein, John P. / Davidson, Michael / Tsimikas, Sotirios

Current Atherosclerosis Reports

a Testable Hypothesis

2020 Volume 22, Issue 9

Keywords	Cardiology and Cardiovascular Medicine ; covid19
Language	English
Publisher	Springer Science and Business Media LLC
Publishing country	us
Document type	Article ; Online
ZDB-ID	2057369-8
ISSN	1523-3804
ISSN	1523-3804
DOI	10.1007/s11883-020-00867-3
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Article: Lipoprotein(a) and Its Potential Association with Thrombosis and Inflammation in COVID-19: a Testable Hypothesis

Moriarty, Patrick M / Gorby, Lauryn K / Stroes, Erik S / Kastelein, John P / Davidson, Michael / Tsimikas, Sotirios

Curr Atheroscler Rep

Abstract: PURPOSE OF REVIEW: The COVID-19 pandemic has infected over > 11 million as of today people worldwide and is associated with significant cardiovascular manifestations, particularly in subjects with preexisting comorbidities and cardiovascular risk factors. ...

Abstract	PURPOSE OF REVIEW: The COVID-19 pandemic has infected over > 11 million as of today people worldwide and is associated with significant cardiovascular manifestations, particularly in subjects with preexisting comorbidities and cardiovascular risk factors. Recently, a predisposition for arterial and venous thromboses has been reported in COVID-19 infection. We hypothesize that besides conventional risk factors, subjects with elevated lipoprotein(a) (Lp(a)) may have a particularly high risk of developing cardiovascular complications. RECENT FINDINGS: The Lp(a) molecule has the propensity for inhibiting endogenous fibrinolysis through its apolipoprotein(a) component and for enhancing proinflammatory effects such as through its content of oxidized phospholipids. The LPA gene contains an interleukin-6 (IL-6) response element that may induce an acute phase-type increase in Lp(a) levels following a cytokine storm from COVID-19. Thus, subjects with either baseline elevated Lp(a) or those who have an increase following COVID-19 infection, or both, may be at very high risk of developing thromboses. Elevated Lp(a) may also lead to acute destabilization of preexisting but quiescent atherosclerotic plaques, which might induce acute myocardial infarction and stroke. Ongoing studies with IL-6 antagonists may be informative in understanding this relationship, and registries are being initiated to measure Lp(a) in subjects infected with COVID-19. If indeed an association is suggestive of being causal, consideration can be given to systematic testing of Lp(a) and prophylactic systemic anticoagulation in infected inpatients. Therapeutic lipid apheresis and pharmacotherapy for the reduction of Lp(a) levels may minimize thrombogenic potential and proinflammatory effects. We propose studies to test the hypothesis that Lp(a) may contribute to cardiovascular complications of COVID-19.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #671154
Database	COVID19

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Article ; Online: MTG16 regulates colonic epithelial differentiation, colitis, and tumorigenesis by repressing E protein transcription factors.

JCI insight

2022 Volume 7, Issue 10

Abstract: Aberrant epithelial differentiation and regeneration contribute to colon pathologies, including inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Myeloid translocation gene 16 (MTG16, also known as CBFA2T3) is a transcriptional ... ...

Abstract	Aberrant epithelial differentiation and regeneration contribute to colon pathologies, including inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Myeloid translocation gene 16 (MTG16, also known as CBFA2T3) is a transcriptional corepressor expressed in the colonic epithelium. MTG16 deficiency in mice exacerbates colitis and increases tumor burden in CAC, though the underlying mechanisms remain unclear. Here, we identified MTG16 as a central mediator of epithelial differentiation, promoting goblet and restraining enteroendocrine cell development in homeostasis and enabling regeneration following dextran sulfate sodium-induced (DSS-induced) colitis. Transcriptomic analyses implicated increased Ephrussi box-binding transcription factor (E protein) activity in MTG16-deficient colon crypts. Using a mouse model with a point mutation that attenuates MTG16:E protein interactions (Mtg16P209T), we showed that MTG16 exerts control over colonic epithelial differentiation and regeneration by repressing E protein-mediated transcription. Mimicking murine colitis, MTG16 expression was increased in biopsies from patients with active IBD compared with unaffected controls. Finally, uncoupling MTG16:E protein interactions partially phenocopied the enhanced tumorigenicity of Mtg16-/- colon in the azoxymethane/DSS-induced model of CAC, indicating that MTG16 protects from tumorigenesis through additional mechanisms. Collectively, our results demonstrate that MTG16, via its repression of E protein targets, is a key regulator of cell fate decisions during colon homeostasis, colitis, and cancer.
MeSH term(s)	Animals ; Carcinogenesis/genetics ; Carcinogenesis/metabolism ; Cell Transformation, Neoplastic/genetics ; Colitis/chemically induced ; Colitis/genetics ; Colitis/metabolism ; Dextran Sulfate/toxicity ; Humans ; Inflammatory Bowel Diseases/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Transcription Factors/genetics
Chemical Substances	Transcription Factors ; Dextran Sulfate (9042-14-2)
Language	English
Publishing date	2022-05-23
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.153045
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Article ; Online: Improved soluble expression and use of recombinant human renalase.

Morrison, Clifford S / Paskaleva, Elena E / Rios, Marvin A / Beusse, Thomas R / Blair, Elaina M / Lin, Lucy Q / Hu, James R / Gorby, Aidan H / Dodds, David R / Armiger, William B / Dordick, Jonathan S / Koffas, Mattheos A G

PloS one

2020 Volume 15, Issue 11, Page(s) e0242109

Abstract: Electrochemical bioreactor systems have enjoyed significant attention in the past few decades, particularly because of their applications to biobatteries, artificial photosynthetic systems, and microbial electrosynthesis. A key opportunity with ... ...

Abstract	Electrochemical bioreactor systems have enjoyed significant attention in the past few decades, particularly because of their applications to biobatteries, artificial photosynthetic systems, and microbial electrosynthesis. A key opportunity with electrochemical bioreactors is the ability to employ cofactor regeneration strategies critical in oxidative and reductive enzymatic and cell-based biotransformations. Electrochemical cofactor regeneration presents several advantages over other current cofactor regeneration systems, such as chemoenzymatic multi-enzyme reactions, because there is no need for a sacrificial substrate and a recycling enzyme. Additionally, process monitoring is simpler and downstream processing is less costly. However, the direct electrochemical reduction of NAD(P)+ on a cathode may produce adventitious side products, including isomers of NAD(P)H that can act as potent competitive inhibitors to NAD(P)H-requiring enzymes such as dehydrogenases. To overcome this limitation, we examined how nature addresses the adventitious formation of isomers of NAD(P)H. Specifically, renalases are enzymes that catalyze the oxidation of 1,2- and 1,6-NAD(P)H to NAD(P)+, yielding an effective recycling of unproductive NAD(P)H isomers. We designed several mutants of recombinant human renalase isoform 1 (rhRen1), expressed them in E. coli BL21(DE3) to enhance protein solubility, and evaluated the activity profiles of the renalase variants against NAD(P)H isomers. The potential for rhRen1 to be employed in engineering applications was then assessed in view of the enzyme's stability upon immobilization. Finally, comparative modeling was performed to assess the underlying reasons for the enhanced solubility and activity of the mutant enzymes.
MeSH term(s)	Enzyme Stability ; Escherichia coli ; Humans ; Industrial Microbiology/methods ; Monoamine Oxidase/chemistry ; Monoamine Oxidase/genetics ; Monoamine Oxidase/metabolism ; Mutation ; NADP/metabolism ; Protein Domains ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Solubility ; Static Electricity
Chemical Substances	Recombinant Proteins ; NADP (53-59-8) ; Monoamine Oxidase (EC 1.4.3.4) ; renalase (EC 1.4.3.4.)
Language	English
Publishing date	2020-11-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0242109
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Article ; Online: MTG16 regulates colonic epithelial differentiation, colitis, and tumorigenesis by repressing E protein transcription factors

JCI Insight, Vol 7, Iss

2022 Volume 10

Abstract	Aberrant epithelial differentiation and regeneration contribute to colon pathologies, including inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Myeloid translocation gene 16 (MTG16, also known as CBFA2T3) is a transcriptional corepressor expressed in the colonic epithelium. MTG16 deficiency in mice exacerbates colitis and increases tumor burden in CAC, though the underlying mechanisms remain unclear. Here, we identified MTG16 as a central mediator of epithelial differentiation, promoting goblet and restraining enteroendocrine cell development in homeostasis and enabling regeneration following dextran sulfate sodium–induced (DSS-induced) colitis. Transcriptomic analyses implicated increased Ephrussi box–binding transcription factor (E protein) activity in MTG16-deficient colon crypts. Using a mouse model with a point mutation that attenuates MTG16:E protein interactions (Mtg16P209T), we showed that MTG16 exerts control over colonic epithelial differentiation and regeneration by repressing E protein–mediated transcription. Mimicking murine colitis, MTG16 expression was increased in biopsies from patients with active IBD compared with unaffected controls. Finally, uncoupling MTG16:E protein interactions partially phenocopied the enhanced tumorigenicity of Mtg16–/– colon in the azoxymethane/DSS-induced model of CAC, indicating that MTG16 protects from tumorigenesis through additional mechanisms. Collectively, our results demonstrate that MTG16, via its repression of E protein targets, is a key regulator of cell fate decisions during colon homeostasis, colitis, and cancer.
Keywords	Cell biology ; Gastroenterology ; Medicine ; R
Subject code	570
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
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