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Article ; Online: Uncovering the Effect of SARS-CoV-2 on Liver Metabolism via Genome-Scale Metabolic Modeling for Reprogramming and Therapeutic Strategies.

Sertbas, Mustafa / Ulgen, Kutlu O

ACS omega

2024 Volume 9, Issue 13, Page(s) 15535–15546

Abstract: Genome-scale metabolic models (GEMs) are promising computational tools that contribute to elucidating host-virus interactions at the system level and developing therapeutic strategies against viral infection. In this study, the effect of severe acute ... ...

Abstract	Genome-scale metabolic models (GEMs) are promising computational tools that contribute to elucidating host-virus interactions at the system level and developing therapeutic strategies against viral infection. In this study, the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on liver metabolism was investigated using integrated GEMs of human hepatocytes and SARS-CoV-2. They were generated for uninfected and infected hepatocytes using transcriptome data. Reporter metabolite analysis resulted in significant transcriptional changes around several metabolites involved in xenobiotics, drugs, arachidonic acid, and leukotriene metabolisms due to SARS-CoV-2 infection. Flux balance analysis and minimization of metabolic adjustment approaches unraveled possible virus-induced hepatocellular reprogramming in fatty acid, glycerophospholipid, sphingolipid cholesterol, and folate metabolisms, bile acid biosynthesis, and carnitine shuttle among others. Reaction knockout analysis provided critical reactions in glycolysis, oxidative phosphorylation, purine metabolism, and reactive oxygen species detoxification subsystems. Computational analysis also showed that administration of dopamine, glucosamine, D-xylose, cysteine, and (
Language	English
Publishing date	2024-03-22
Publishing country	United States
Document type	Journal Article
ISSN	2470-1343
ISSN (online)	2470-1343
DOI	10.1021/acsomega.4c00392
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Article ; Online: Evaluation of the correlation between frequency of seborrheic dermatitis and quantitative climate data.

Kutlu, Ömer

International journal of dermatology

2021 Volume 61, Issue 2, Page(s) e65–e67

MeSH term(s)	Antifungal Agents/therapeutic use ; Dermatitis, Seborrheic/drug therapy ; Dermatitis, Seborrheic/epidemiology ; Humans ; Malassezia
Chemical Substances	Antifungal Agents
Language	English
Publishing date	2021-07-09
Publishing country	England
Document type	Letter
ZDB-ID	412254-9
ISSN	1365-4632 ; 0011-9059 ; 1461-1244
ISSN (online)	1365-4632
ISSN	0011-9059 ; 1461-1244
DOI	10.1111/ijd.15783
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Article ; Online: Ultraviolet C Supported Novel Phototherapy Units at the Crossroads of the COVID-19 Pandemic.

Kutlu, Ömer

Photobiomodulation, photomedicine, and laser surgery

2021 Volume 39, Issue 7, Page(s) 437–438

Abstract: The numerous dermatology clinics have decreased or stopped phototherapy sessions due to the increased risk of getting COVID-19 during the current pandemic. In this context, poorly ventilated phototherapy units (PUs) should be redesigned in order to ... ...

Abstract	The numerous dermatology clinics have decreased or stopped phototherapy sessions due to the increased risk of getting COVID-19 during the current pandemic. In this context, poorly ventilated phototherapy units (PUs) should be redesigned in order to continue UV-based therapies and to protect our patients from getting COVID-19. Recently, it has been reported that ultraviolet C (UVC)-related dose and virus concentration may play a decisive role in the virucidal activity. Considering air changes per hour and viral inactivation time, 30 min of 30-W UVC radiation is able to inactivate poorly ventilated PUs of 3-4 m length, 5.5-7 m width, and 2.7-3 m height. Upper-air UVC radiation for 30 min between sessions would allow us to have more treatment options for numerous dermatological diseases in novel PUs during the COVID-19 pandemic and possible future pandemics.
MeSH term(s)	COVID-19/prevention & control ; Equipment Design ; Humans ; Infection Control/methods ; Pandemics ; Phototherapy/instrumentation ; SARS-CoV-2/radiation effects ; Ultraviolet Rays ; Ventilation ; Virus Inactivation/radiation effects
Language	English
Publishing date	2021-07-15
Publishing country	United States
Document type	Letter
ISSN	2578-5478
ISSN (online)	2578-5478
DOI	10.1089/photob.2021.0018
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Article ; Online: Evaluation of quality of life of patients with hirsutism among Turkish women: A single-center cross-sectional study.

Kutlu, Ömer

Journal of cosmetic dermatology

2020 Volume 19, Issue 11, Page(s) 3053–3057

Abstract: Background: Patients with hirsutism have an increased number of psychological diseases including depression, anxiety, and social isolation with decreased quality of life.: Aims: We aimed to investigate changes in the quality of life of patients with ... ...

Abstract	Background: Patients with hirsutism have an increased number of psychological diseases including depression, anxiety, and social isolation with decreased quality of life. Aims: We aimed to investigate changes in the quality of life of patients with hirsutism among Turkish women. Methods: A total of 57 patients diagnosed with hirsutism were included in this study. The patients were investigated in terms of Dermatological Life Quality Index (DLQI) score, concomitant clinical findings, and polycystic ovary syndrome. Modified Ferriman-Gallwey (mFG) was used for the diagnosis of hirsutism. Results: The mean DLQI score of the patients was 9.80 ± 6.50, while the median value of the mFG score was 25 (minimum 8, maximum 34). The mean DLQI score of patients who had an mFG score of four only in one region of the face was statistically higher than women with an mFG score less than four (P = .033). No statistically significant correlation was found between DLQI and mFG scores (P = .254). There was no statistically significant difference in terms of DLQI between women with acne, seborrhea, androgenetic alopecia, menstrual irregularity, or acanthosis nigricans versus those without them (P >.05). The mean DLQI score was statistically significantly higher for patients with PCOS than for those without PCOS (P = .004). Conclusion: As shown by mFG score, quality of life is affected in certain areas for women with hirsutism. The mFG score is not correlated with the quality of life score. Certain areas of excessive hair that lead to stigma may be more important in quality of life for these women. The quality of life seems to be significantly more affected in hirsutism patients with PCOS than those without PCOS. Finally, clinical symptoms and signs appear to have no important role in the quality of life of patients with hirsutism.
MeSH term(s)	Alopecia ; Cross-Sectional Studies ; Female ; Hirsutism/epidemiology ; Humans ; Polycystic Ovary Syndrome/complications ; Quality of Life
Language	English
Publishing date	2020-07-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2280551-5
ISSN	1473-2165 ; 1473-2130
ISSN (online)	1473-2165
ISSN	1473-2130
DOI	10.1111/jocd.13563
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Article ; Online: Dexpanthenol may be a novel treatment for male androgenetic alopecia: Analysis of nine cases.

Kutlu, Ömer

Dermatologic therapy

2020 Volume 33, Issue 3, Page(s) e13381

Abstract: Androgenetic alopecia also known as pattern alopecia, is a disorder characterized by the gradual onset of the conversion of terminal hairs into vellus hairs. Dexpanthenol has an anti-oxidative and anti-inflammatory effect and a cellular repair capability. ...

Abstract	Androgenetic alopecia also known as pattern alopecia, is a disorder characterized by the gradual onset of the conversion of terminal hairs into vellus hairs. Dexpanthenol has an anti-oxidative and anti-inflammatory effect and a cellular repair capability. We present nine male cases who had marked improvement after receiving only systemic dexpanthenol treatment for androgenetic alopecia.
MeSH term(s)	Administration, Cutaneous ; Alopecia/diagnosis ; Alopecia/drug therapy ; Hair ; Humans ; Male ; Pantothenic Acid/analogs & derivatives ; Scalp
Chemical Substances	Pantothenic Acid (19F5HK2737) ; dexpanthenol (1O6C93RI7Z)
Language	English
Publishing date	2020-04-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	1354801-3
ISSN	1529-8019 ; 1396-0296
ISSN (online)	1529-8019
ISSN	1396-0296
DOI	10.1111/dth.13381
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Article ; Online: Analysis of dermatologic conditions in Turkey and Italy by using Google Trends analysis in the era of the COVID-19 pandemic.

Kutlu, Ömer

Dermatologic therapy

2020 Volume 33, Issue 6, Page(s) e13949

Abstract: Many areas of life including patterns of dermatological diseases that patients attend to the hospital were tremendously affected by implementing stay-at-home orders during the COVID-19 pandemic. We aimed to identify the dermatologic interest of the ... ...

Abstract	Many areas of life including patterns of dermatological diseases that patients attend to the hospital were tremendously affected by implementing stay-at-home orders during the COVID-19 pandemic. We aimed to identify the dermatologic interest of the public during the COVID-19 pandemic by using Google Trends. The terms "acne", "hair loss", "eczema", "genital warts", "molluscum contagiosum", "botox", "skin cancer", and "sunscreen" were analyzed on April 1, May 1, June1, 2020, and the corresponding period of the previous year in Turkey and Italy by using Google Trends. The searching spectrum was between March 31, 2019 and June 1, 2020. The relative change of search term "acne" was +10, +29, +13/-1, +17,+33, "hair loss" was +14, +40, +16/+3, +16, +15, and "eczema" was +2, +34, -4/ +3, +25, +18, on the other hand, the relative change of the "genital warts" was -15, -48, +10/-44, -30, +18 and "molluscum contagiosum" was -12, -2, -4/-4, -1, -12 while "botox" was, -10, -43, -8/-41, -31, +4, "skin cancer" was -27, -38, -38/-22,+33, -7 and sunscreen was -6, -25, -71/-13, 0, -45 in Turkey/Italy on April 1, May 1, and June 1, 2020, respectively. A statistically significant positive correlation was found between the number of COVID-19 cases in Turkey and search terms of the general dermatology group during the COVID-19 pandemic (P < 0.05). The search terms including "acne", "eczema", "hair loss" appears to be increasing while "molluscum contagiosum", "genital warts" "botox", "skin cancer", and "sunscreen" decreasing in the era of the COVID-19 pandemic. Understanding the trends and impacts of dermatologic diseases on public perceptions during the COVID-19 pandemic will allow for better preparation of dermatologists.
MeSH term(s)	COVID-19/diagnosis ; COVID-19/epidemiology ; Consumer Health Information/trends ; Dermatology/trends ; Humans ; Information Seeking Behavior ; Italy/epidemiology ; Search Engine/trends ; Skin Diseases/diagnosis ; Skin Diseases/epidemiology ; Time Factors ; Turkey/epidemiology
Keywords	covid19
Language	English
Publishing date	2020-07-27
Publishing country	United States
Document type	Journal Article ; Observational Study
ZDB-ID	1354801-3
ISSN	1529-8019 ; 1396-0296
ISSN (online)	1529-8019
ISSN	1396-0296
DOI	10.1111/dth.13949
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Article ; Online: Can Tenofovir diphosphate be a candidate drug for Sars-Cov2? First clinical perspective.

Kutlu, Ömer

International journal of clinical practice

2020 Volume 75, Issue 1, Page(s) e13792

Keywords	covid19
Language	English
Publishing date	2020-10-27
Publishing country	India
Document type	Letter
ZDB-ID	1386246-7
ISSN	1742-1241 ; 1368-5031
ISSN (online)	1742-1241
ISSN	1368-5031
DOI	10.1111/ijcp.13792
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Article: Neuroinflammation, Energy and Sphingolipid Metabolism Biomarkers Are Revealed by Metabolic Modeling of Autistic Brains.

Esvap, Elif / Ulgen, Kutlu O

Biomedicines

2023 Volume 11, Issue 2

Abstract: Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders generally characterized by repetitive behaviors and difficulties in communication and social behavior. Despite its heterogeneous nature, several metabolic ... ...

Abstract	Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders generally characterized by repetitive behaviors and difficulties in communication and social behavior. Despite its heterogeneous nature, several metabolic dysregulations are prevalent in individuals with ASD. This work aims to understand ASD brain metabolism by constructing an ASD-specific prefrontal cortex genome-scale metabolic model (GEM) using transcriptomics data to decipher novel neuroinflammatory biomarkers. The healthy and ASD-specific models are compared via uniform sampling to identify ASD-exclusive metabolic features. Noticeably, the results of our simulations and those found in the literature are comparable, supporting the accuracy of our reconstructed ASD model. We identified that several oxidative stress, mitochondrial dysfunction, and inflammatory markers are elevated in ASD. While oxidative phosphorylation fluxes were similar for healthy and ASD-specific models, and the fluxes through the pathway were nearly undisturbed, the tricarboxylic acid (TCA) fluxes indicated disruptions in the pathway. Similarly, the secretions of mitochondrial dysfunction markers such as pyruvate are found to be higher, as well as the activities of oxidative stress marker enzymes like alanine and aspartate aminotransferases (ALT and AST) and glutathione-disulfide reductase (GSR). We also detected abnormalities in the sphingolipid metabolism, which has been implicated in many inflammatory and immune processes, but its relationship with ASD has not been thoroughly explored in the existing literature. We suggest that important sphingolipid metabolites, such as sphingosine-1-phosphate (S1P), ceramide, and glucosylceramide, may be promising biomarkers for the diagnosis of ASD and provide an opportunity for the adoption of early intervention for young children.
Language	English
Publishing date	2023-02-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11020583
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Article: Understanding the ADHD-Gut Axis by Metabolic Network Analysis.

Taş, Ezgi / Ülgen, Kutlu O

Metabolites

2023 Volume 13, Issue 5

Abstract: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder diagnosed with hyperactivity, impulsivity, and a lack of attention inconsistent with the patient's development level. The fact that people with ADHD frequently experience ... ...

Abstract	Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder diagnosed with hyperactivity, impulsivity, and a lack of attention inconsistent with the patient's development level. The fact that people with ADHD frequently experience gastrointestinal (GI) dysfunction highlights the possibility that the gut microbiome may play a role in this condition. The proposed research aims to determine a biomarker for ADHD by reconstructing a model of the gut-microbial community. Genome-scale metabolic models (GEM) considering the relationship between gene-protein-reaction associations are used to simulate metabolic activities in organisms of gut. The production rates of dopamine and serotonin precursors and the key short chain fatty acids which affect the health status are determined under three diets (Western, Atkins', Vegan) and compared with those of healthy people. Elasticities are calculated to understand the sensitivity of exchange fluxes to changes in diet and bacterial abundance at the species level. The presence of Bacillota (genus
Language	English
Publishing date	2023-04-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo13050592
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Article ; Online: Identification of Therapeutic Targets for Medulloblastoma by Tissue-Specific Genome-Scale Metabolic Model.

Ozbek, Ilkay Irem / Ulgen, Kutlu O

Molecules (Basel, Switzerland)

2023 Volume 28, Issue 2

Abstract: Medulloblastoma (MB), occurring in the cerebellum, is the most common childhood brain tumor. Because conventional methods decline life quality and endanger children with detrimental side effects, computer models are needed to imitate the characteristics ... ...

Abstract	Medulloblastoma (MB), occurring in the cerebellum, is the most common childhood brain tumor. Because conventional methods decline life quality and endanger children with detrimental side effects, computer models are needed to imitate the characteristics of cancer cells and uncover effective therapeutic targets with minimum toxic effects on healthy cells. In this study, metabolic changes specific to MB were captured by the genome-scale metabolic brain model integrated with transcriptome data. To determine the roles of sphingolipid metabolism in proliferation and metastasis in the cancer cell, 79 reactions were incorporated into the MB model. The pathways employed by MB without a carbon source and the link between metastasis and the Warburg effect were examined in detail. To reveal therapeutic targets for MB, biomass-coupled reactions, the essential genes/gene products, and the antimetabolites, which might deplete the use of metabolites in cells by triggering competitive inhibition, were determined. As a result, interfering with the enzymes associated with fatty acid synthesis (FAs) and the mevalonate pathway in cholesterol synthesis, suppressing cardiolipin production, and tumor-supporting sphingolipid metabolites might be effective therapeutic approaches for MB. Moreover, decreasing the activity of succinate synthesis and GABA-catalyzing enzymes concurrently might be a promising strategy for metastatic MB.
MeSH term(s)	Child ; Humans ; Medulloblastoma/genetics ; Medulloblastoma/pathology ; Brain Neoplasms/pathology ; Cerebellum/metabolism ; Transcriptome ; Cerebellar Neoplasms/genetics ; Cerebellar Neoplasms/pathology ; Cell Line, Tumor
Language	English
Publishing date	2023-01-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules28020779
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