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Article ; Online: Naringenin Orchestrates and Regulates the Reactive Oxygen Species-Mediated Pathways and Proinflammatory Signaling: Targeting Hallmarks of Aging-Associated Disorders.

Deepika / Dakal, Tikam Chand / Sharma, Narendra Kumar / Ranga, Vipin / Maurya, Pawan Kumar

2024 Volume 27, Issue 1, Page(s) 3–16

Abstract: The therapeutic application of flavonoids in the management of infectious diseases, cancers, chronic wounds, aging, and neurodegenerative disorders has been well documented in scientific literature. The citric flavonoid naringenin comes under the ... ...

Abstract	The therapeutic application of flavonoids in the management of infectious diseases, cancers, chronic wounds, aging, and neurodegenerative disorders has been well documented in scientific literature. The citric flavonoid naringenin comes under the category of flavanone and exhibits a plethora of health benefits. Very few flavonoids such as curcumin, resveratrol, catechin, quercetin, and kaempferol have been studied to exert their anti-aging properties in humans. The effect of naringenin in the context of age-associated disorders in detail has not been elucidated yet. The databases used for the literature search were Science Direct, Google Scholar, and PubMed. More emphasis has been put on the recent literature on "naringenin" and its effect on "age-associated disorders." Almost all chronic degenerative disorders are characterized by oxidative stress and inflammatory response. The study aims at highlighting the reactive oxygen species-mediated activity of naringenin and the underlying molecular mechanism leading to the prevention of various age-associated disorders. Altogether, the review presents a systematic comprehension of the pharmaceutical and clinicopathological benefits of naringenin in age-associated disorders.
MeSH term(s)	Humans ; Reactive Oxygen Species ; Flavanones/pharmacology ; Flavonoids ; Aging
Chemical Substances	naringenin (HN5425SBF2) ; Reactive Oxygen Species ; Flavanones ; Flavonoids
Language	English
Publishing date	2024-02-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2150779-X
ISSN	1557-8577 ; 1549-1684
ISSN (online)	1557-8577
ISSN	1549-1684
DOI	10.1089/rej.2023.0065
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Article ; Online: Assessment of MMP14, CAV2, CLU and SPARCL1 expression profiles in endometriosis.

Pant, Anuja / Dakal, Tikam Chand / Moar, Kareena / Dhabhai, Bhanupriya / Arora, Taruna K / Sharma, Narendra Kumar / Ranga, Vipin / Maurya, Pawan Kumar

Pathology, research and practice

2023 Volume 251, Page(s) 154892

Abstract: Endometriotic cells exhibit a notable degree of invasiveness and some characteristics of tissue remodeling underlying lesion formation. In this regard, do matrix metalloproteinases 14 (MMP14) and other related genes such as SPARC-like protein 1 (SPARCL1), ...

Abstract	Endometriotic cells exhibit a notable degree of invasiveness and some characteristics of tissue remodeling underlying lesion formation. In this regard, do matrix metalloproteinases 14 (MMP14) and other related genes such as SPARC-like protein 1 (SPARCL1), caveolin 2 (CAV2), and clusterin (CLU) exert any significant influence in the processes of endometriosis development and pathophysiology is not apparent. We aim to assess whether these genes could serve as potential diagnostic biomarkers in endometriosis. Microarray-based gene expression analysis was performed on total RNA extracted from endometriotic tissue samples treated with and without gonadotropin-releasing hormone agonist (GnRHa). The GnRHa untreated patients were considered the control group. The validation of genes was performed using quantitative real-time polymerase chain reaction (qRT-PCR). qRT-PCR analysis showed significant downregulation in the expression of MMP14 (p = 0.024), CAV2 (p = 0.017), and upregulation of CLU (p = 0.005) in endometriosis patients treated with GnRHa. SPARCL1 did not show any significant (p = 0.30) change in the expression compared to the control group. These data have the potential to contribute to the comprehension of the molecular pathways implicated in the remodeling of the extracellular matrix, which is a vital step for the physiology of the endometrium. Based on the result, it is concluded that changes in the expression of MMP14, CAV2, and CLU post-treatment imply their role in the pathophysiology of endometriosis and may serve as a potential diagnostic biomarker of endometriosis in response to GnRHa treatment in patients with ovarian endometrioma.
MeSH term(s)	Female ; Humans ; Endometriosis/pathology ; Clusterin/genetics ; Clusterin/metabolism ; Caveolin 2/metabolism ; Matrix Metalloproteinase 14/genetics ; Matrix Metalloproteinase 14/metabolism ; Endometrium/pathology ; Calcium-Binding Proteins/metabolism ; Extracellular Matrix Proteins/genetics
Chemical Substances	Clusterin ; Caveolin 2 ; Matrix Metalloproteinase 14 (EC 3.4.24.80) ; MMP14 protein, human (EC 3.4.24.80) ; CLU protein, human ; SPARCL1 protein, human ; Calcium-Binding Proteins ; Extracellular Matrix Proteins
Language	English
Publishing date	2023-10-14
Publishing country	Germany
Document type	Journal Article
ZDB-ID	391889-0
ISSN	1618-0631 ; 0344-0338
ISSN (online)	1618-0631
ISSN	0344-0338
DOI	10.1016/j.prp.2023.154892
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Article: Immunogenic SARS-CoV-2 Epitopes: In Silico Study Towards Better Understanding of COVID-19 Disease-Paving the Way for Vaccine Development.

Ranga, Vipin / Niemelä, Erik / Tamirat, Mahlet Z / Eriksson, John E / Airenne, Tomi T / Johnson, Mark S

Vaccines

2020 Volume 8, Issue 3

Abstract: The emergence of the COVID-19 outbreak at the end of 2019, caused by the novel coronavirus SARS-CoV-2, has, to date, led to over 13.6 million infections and nearly 600,000 deaths. Consequently, there is an urgent need to better understand the molecular ... ...

Abstract	The emergence of the COVID-19 outbreak at the end of 2019, caused by the novel coronavirus SARS-CoV-2, has, to date, led to over 13.6 million infections and nearly 600,000 deaths. Consequently, there is an urgent need to better understand the molecular factors triggering immune defense against the virus and to develop countermeasures to hinder its spread. Using in silico analyses, we showed that human major histocompatibility complex (MHC) class I cell-surface molecules vary in their capacity for binding different SARS-CoV-2-derived epitopes, i.e., short sequences of 8-11 amino acids, and pinpointed five specific SARS-CoV-2 epitopes that are likely to be presented to cytotoxic T-cells and hence activate immune responses. The identified epitopes, each one of nine amino acids, have high sequence similarity to the equivalent epitopes of SARS-CoV virus, which are known to elicit an effective T cell response in vitro. Moreover, we give a structural explanation for the binding of SARS-CoV-2-epitopes to MHC molecules. Our data can help us to better understand the differences in outcomes of COVID-19 patients and may aid the development of vaccines against SARS-CoV-2 and possible future outbreaks of novel coronaviruses.
Keywords	covid19
Language	English
Publishing date	2020-07-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines8030408
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Article ; Online: Immunogenic SARS-CoV-2 Epitopes

Vipin Ranga / Erik Niemelä / Mahlet Z. Tamirat / John E. Eriksson / Tomi T. Airenne / Mark S. Johnson

Vaccines, Vol 8, Iss 408, p

In Silico Study Towards Better Understanding of COVID-19 Disease—Paving the Way for Vaccine Development

2020 Volume 408

Abstract	The emergence of the COVID-19 outbreak at the end of 2019, caused by the novel coronavirus SARS-CoV-2, has, to date, led to over 13.6 million infections and nearly 600,000 deaths. Consequently, there is an urgent need to better understand the molecular factors triggering immune defense against the virus and to develop countermeasures to hinder its spread. Using in silico analyses, we showed that human major histocompatibility complex (MHC) class I cell-surface molecules vary in their capacity for binding different SARS-CoV-2-derived epitopes, i.e., short sequences of 8-11 amino acids, and pinpointed five specific SARS-CoV-2 epitopes that are likely to be presented to cytotoxic T-cells and hence activate immune responses. The identified epitopes, each one of nine amino acids, have high sequence similarity to the equivalent epitopes of SARS-CoV virus, which are known to elicit an effective T cell response in vitro. Moreover, we give a structural explanation for the binding of SARS-CoV-2-epitopes to MHC molecules. Our data can help us to better understand the differences in outcomes of COVID-19 patients and may aid the development of vaccines against SARS-CoV-2 and possible future outbreaks of novel coronaviruses.
Keywords	SARS-CoV-2 ; COVID-19 ; SARS-CoV ; in silico analysis ; MHC class I epitopes ; HLA ; Medicine ; R
Subject code	570
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Immunogenic SARS-CoV-2 epitopes: In silico study towards better understanding of COVID-19 disease—paving the way for vaccine development

Ranga, Vipin / Niemelä, Erik / Tamirat, Mahlet Z. / Eriksson, John E. / Airenne, Tomi T. / Johnson, Mark S.

Vaccines

Abstract	The emergence of the COVID-19 outbreak at the end of 2019, caused by the novel coronavirus SARS-CoV-2, has, to date, led to over 13.6 million infections and nearly 600,000 deaths. Consequently, there is an urgent need to better understand the molecular factors triggering immune defense against the virus and to develop countermeasures to hinder its spread. Using in silico analyses, we showed that human major histocompatibility complex (MHC) class I cell-surface molecules vary in their capacity for binding different SARS-CoV-2-derived epitopes, i.e., short sequences of 8-11 amino acids, and pinpointed five specific SARS-CoV-2 epitopes that are likely to be presented to cytotoxic T-cells and hence activate immune responses. The identified epitopes, each one of nine amino acids, have high sequence similarity to the equivalent epitopes of SARS-CoV virus, which are known to elicit an effective T cell response in vitro. Moreover, we give a structural explanation for the binding of SARS-CoV-2-epitopes to MHC molecules. Our data can help us to better understand the differences in outcomes of COVID-19 patients and may aid the development of vaccines against SARS-CoV-2 and possible future outbreaks of novel coronaviruses.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #671396
Database	COVID19

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Article ; Online: DUX4

Vuoristo, Sanna / Bhagat, Shruti / Hydén-Granskog, Christel / Yoshihara, Masahito / Gawriyski, Lisa / Jouhilahti, Eeva-Mari / Ranga, Vipin / Tamirat, Mahlet / Huhtala, Mikko / Kirjanov, Ida / Nykänen, Sonja / Krjutškov, Kaarel / Damdimopoulos, Anastassius / Weltner, Jere / Hashimoto, Kosuke / Recher, Gaëlle / Ezer, Sini / Paluoja, Priit / Paloviita, Pauliina /

Takegami, Yujiro / Kanemaru, Ai / Lundin, Karolina / Airenne, Tomi T / Otonkoski, Timo / Tapanainen, Juha S / Kawaji, Hideya / Murakawa, Yasuhiro / Bürglin, Thomas R / Varjosalo, Markku / Johnson, Mark S / Tuuri, Timo / Katayama, Shintaro / Kere, Juha

iScience

2022 Volume 25, Issue 4, Page(s) 104137

Abstract: Double homeobox 4 ( ...

Abstract	Double homeobox 4 (
Language	English
Publishing date	2022-03-22
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.104137
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Article ; Online: Phylogenetic and mutational analyses of human LEUTX, a homeobox gene implicated in embryogenesis.

Katayama, Shintaro / Ranga, Vipin / Jouhilahti, Eeva-Mari / Airenne, Tomi T / Johnson, Mark S / Mukherjee, Krishanu / Bürglin, Thomas R / Kere, Juha

Scientific reports

2018 Volume 8, Issue 1, Page(s) 17421

Abstract: Recently, human PAIRED-LIKE homeobox transcription factor (TF) genes were discovered whose expression is limited to the period of embryo genome activation up to the 8-cell stage. One of these TFs is LEUTX, but its importance for human embryogenesis is ... ...

Abstract	Recently, human PAIRED-LIKE homeobox transcription factor (TF) genes were discovered whose expression is limited to the period of embryo genome activation up to the 8-cell stage. One of these TFs is LEUTX, but its importance for human embryogenesis is still subject to debate. We confirmed that human LEUTX acts as a TAATCC-targeting transcriptional activator, like other K50-type PAIRED-LIKE TFs. Phylogenetic comparisons revealed that Leutx proteins are conserved across Placentalia and comprise two conserved domains, the homeodomain, and a Leutx-specific domain containing putative transcriptional activation motifs (9aaTAD). Examination of human genotype resources revealed 116 allelic variants in LEUTX. Twenty-four variants potentially affect function, but they occur only heterozygously at low frequency. One variant affects a DNA-specificity determining residue, mutationally reachable by a one-base transition. In vitro and in silico experiments showed that this LEUTX mutation (alanine to valine at position 54 in the homeodomain) results in a transactivational loss-of-function to a minimal TAATCC-containing promoter and a 36 bp motif enriched in genes involved in embryo genome activation. A compensatory change in residue 47 restores function. The results support the notion that human LEUTX functions as a transcriptional activator important for human embryogenesis.
MeSH term(s)	Animals ; Conserved Sequence ; Embryonic Development/genetics ; Gene Expression Regulation, Developmental ; HEK293 Cells ; Homeodomain Proteins/chemistry ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Humans ; Mutation ; Phylogeny ; Promoter Regions, Genetic ; Transcriptional Activation
Chemical Substances	Homeodomain Proteins ; LEUTX protein, human
Language	English
Publishing date	2018-11-27
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-35547-5
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Article ; Online: Phylogenetic and mutational analyses of human LEUTX, a homeobox gene implicated in embryogenesis

Shintaro Katayama / Vipin Ranga / Eeva-Mari Jouhilahti / Tomi T. Airenne / Mark S. Johnson / Krishanu Mukherjee / Thomas R. Bürglin / Juha Kere

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 14

Abstract: Abstract Recently, human PAIRED-LIKE homeobox transcription factor (TF) genes were discovered whose expression is limited to the period of embryo genome activation up to the 8-cell stage. One of these TFs is LEUTX, but its importance for human ... ...

Abstract	Abstract Recently, human PAIRED-LIKE homeobox transcription factor (TF) genes were discovered whose expression is limited to the period of embryo genome activation up to the 8-cell stage. One of these TFs is LEUTX, but its importance for human embryogenesis is still subject to debate. We confirmed that human LEUTX acts as a TAATCC-targeting transcriptional activator, like other K50-type PAIRED-LIKE TFs. Phylogenetic comparisons revealed that Leutx proteins are conserved across Placentalia and comprise two conserved domains, the homeodomain, and a Leutx-specific domain containing putative transcriptional activation motifs (9aaTAD). Examination of human genotype resources revealed 116 allelic variants in LEUTX. Twenty-four variants potentially affect function, but they occur only heterozygously at low frequency. One variant affects a DNA-specificity determining residue, mutationally reachable by a one-base transition. In vitro and in silico experiments showed that this LEUTX mutation (alanine to valine at position 54 in the homeodomain) results in a transactivational loss-of-function to a minimal TAATCC-containing promoter and a 36 bp motif enriched in genes involved in embryo genome activation. A compensatory change in residue 47 restores function. The results support the notion that human LEUTX functions as a transcriptional activator important for human embryogenesis.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2018-11-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Central Reading of Ulcerative Colitis Clinical Trial Videos Using Neural Networks.

Gottlieb, Klaus / Requa, James / Karnes, William / Chandra Gudivada, Ranga / Shen, Jie / Rael, Efren / Arora, Vipin / Dao, Tyler / Ninh, Andrew / McGill, James

Gastroenterology

2020 Volume 160, Issue 3, Page(s) 710–719.e2

Abstract: Background and aims: Endoscopic disease activity scoring in ulcerative colitis (UC) is useful in clinical practice but done infrequently. It is required in clinical trials, where it is expensive and slow because human central readers are needed. A ... ...

Abstract	Background and aims: Endoscopic disease activity scoring in ulcerative colitis (UC) is useful in clinical practice but done infrequently. It is required in clinical trials, where it is expensive and slow because human central readers are needed. A machine learning algorithm automating the process could elevate clinical care and facilitate clinical research. Prior work using single-institution databases and endoscopic still images has been promising. Methods: Seven hundred and ninety-five full-length endoscopy videos were prospectively collected from a phase 2 trial of mirikizumab with 249 patients from 14 countries, totaling 19.5 million image frames. Expert central readers assigned each full-length endoscopy videos 1 endoscopic Mayo score (eMS) and 1 Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score. Initially, video data were cleaned and abnormality features extracted using convolutional neural networks. Subsequently, a recurrent neural network was trained on the features to predict eMS and UCEIS from individual full-length endoscopy videos. Results: The primary metric to assess the performance of the recurrent neural network model was quadratic weighted kappa (QWK) comparing the agreement of the machine-read endoscopy score with the human central reader score. QWK progressively penalizes disagreements that exceed 1 level. The model's agreement metric was excellent, with a QWK of 0.844 (95% confidence interval, 0.787-0.901) for eMS and 0.855 (95% confidence interval, 0.80-0.91) for UCEIS. Conclusions: We found that a deep learning algorithm can be trained to predict levels of UC severity from full-length endoscopy videos. Our data set was prospectively collected in a multinational clinical trial, videos rather than still images were used, UCEIS and eMS were reported, and machine learning algorithm performance metrics met or exceeded those previously published for UC severity scores.
MeSH term(s)	Adolescent ; Adult ; Aged ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antibodies, Monoclonal, Humanized/adverse effects ; Colitis, Ulcerative/diagnosis ; Colitis, Ulcerative/drug therapy ; Colon/diagnostic imaging ; Colon/drug effects ; Colonoscopy/methods ; Deep Learning ; Feasibility Studies ; Female ; Humans ; Image Interpretation, Computer-Assisted/methods ; Intestinal Mucosa/diagnostic imaging ; Intestinal Mucosa/drug effects ; Male ; Middle Aged ; Observer Variation ; Predictive Value of Tests ; Prospective Studies ; Severity of Illness Index ; Treatment Outcome ; Video Recording ; Young Adult
Chemical Substances	Antibodies, Monoclonal, Humanized ; mirikizumab (Z7HVY03PHP)
Language	English
Publishing date	2020-10-21
Publishing country	United States
Document type	Clinical Trial, Phase II ; Comparative Study ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2020.10.024
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Article ; Online: Extracellular citrullination inhibits the function of matrix associated TGF-β.

Sipilä, Kalle H / Ranga, Vipin / Rappu, Pekka / Torittu, Annamari / Pirilä, Laura / Käpylä, Jarmo / Johnson, Mark S / Larjava, Hannu / Heino, Jyrki

Matrix biology : journal of the International Society for Matrix Biology

2016 Volume 55, Page(s) 77–89

Abstract: In inflammatory arthritis peptidyl arginine deiminase (PAD) enzymes can citrullinate arginine residues in extracellular matrix (ECM) proteins, such as collagens and fibronectin. This may lead to the generation of anti-citrullinated protein antibodies, ... ...

Abstract	In inflammatory arthritis peptidyl arginine deiminase (PAD) enzymes can citrullinate arginine residues in extracellular matrix (ECM) proteins, such as collagens and fibronectin. This may lead to the generation of anti-citrullinated protein antibodies, important diagnostic markers in rheumatoid arthritis. In addition, the citrullination may directly affect protein function. Based on structural analysis, we found that most ECM-associated growth factors (GFs) have arginine residues in their receptor recognition sites. Thus, they are potential functional targets of extracellular citrullination. To examine this further, we focused on the citrullination of transforming growth factor-βs (TGF-β), well-known ECM-associated GFs. PAD-treatment of CHO-LTBP1 cell derived matrix, rich with TGF-β, decreased the level of TGF-β activity as detected by HaCaT and MLEC-PAI-1/Lu reporter cells. Additional experiments indicated that PAD-treatment inhibits the integrin-mediated TGF-β activation since PAD-treatment decreased the binding of integrin αVβ6 ectodomain as well as integrin-mediated spreading of MG-63 and HaCaT cells to β1-latency associated peptide (TGF-β1 LAP). The citrullination of the RGD site, an important integrin recognition motif, was confirmed by mass spectrometry. Furthermore, the citrullination of active TGF-β1 inhibited its binding to recombinant TGF-β receptor II, and prevented its ability to activate TGF-β signaling. Thus, extracellular PAD activity can affect the function of ECM-associated growth factors by different mechanisms. Importantly, the citrullination of both latent and active TGF-β has the potency to regulate the inflammatory process.
Language	English
Publishing date	2016-09
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1183793-7
ISSN	1569-1802 ; 0945-053X
ISSN (online)	1569-1802
ISSN	0945-053X
DOI	10.1016/j.matbio.2016.02.008
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