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Article ; Online: Systolic aortic regurgitation predicts all-cause mortality and hospitalization in outpatients with heart failure and preserved ejection fraction

İsmail Bolat / Murat Biteker

İstanbul Kuzey Klinikleri, Vol 7, Iss 4, Pp 335-

2020 Volume 340

Abstract: OBJECTIVE: Systolic aortic regurgitation (SAR) is considered to be a specific sign of heart failure (HF). However, the prevalence and importance of SAR in patients with HF and preserved ejection fraction (HFpEF) are unknown. Therefore, we sought to ... ...

Abstract	OBJECTIVE: Systolic aortic regurgitation (SAR) is considered to be a specific sign of heart failure (HF). However, the prevalence and importance of SAR in patients with HF and preserved ejection fraction (HFpEF) are unknown. Therefore, we sought to examine the prevalence of SAR in HFpEF outpatients and its association with all-cause mortality and/or cardiovascular hospitalizations during a 1-year follow-up. METHODS: We enrolled 301 consecutive outpatients with HFpEF (mean age of 67.3+-9.6 years, 53.5% women) and prospectively followed up for one year. Demographic, clinical, echocardiographic, and laboratory data were obtained at study entry. The composite endpoint of this study was all-cause mortality or HF-related hospitalizations in one year. RESULTS: SAR was noted in 30 (9.9%) of the patients, and 38 patients (12.6%) reached the primary endpoint. The primary composite endpoint in one year was higher for the patients with SAR (26.3%) compared to the patients without SAR (7.6%, p<0.001). After adjusting for important covariates, SAR remained independently associated with primary outcome (OR 2.315; 95% CI 1.188–5.477; p=0.008). CONCLUSION: To our knowledge, this is the first study to demonstrate that the presence of SAR is associated with adverse events in patients with HFpEF.
Keywords	echocardiography ; heart failure and preserved ejection fraction ; outcome ; prognosis ; systolic aortic regurgitation ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	KARE Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Carnosic Acid Ameliorates Indomethacin-Induced Gastric Ulceration in Rats by Alleviating Oxidative Stress and Inflammation

Betul Danisman / Betul Cicek / Serkan Yildirim / Ismail Bolat / Deniz Kantar / Kirill S. Golokhvast / Dragana Nikitovic / Aristidis Tsatsakis / Ali Taghizadehghalehjoughi

Biomedicines, Vol 11, Iss 829, p

2023 Volume 829

Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and indomethacin (IND) are the most commonly prescribed for inflammation or pain. However, widespread use causes several adverse effects, such as gastric ulcers, upper gastric system bleeding, ...

Abstract	Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and indomethacin (IND) are the most commonly prescribed for inflammation or pain. However, widespread use causes several adverse effects, such as gastric ulcers, upper gastric system bleeding, and erosions. Carnosic acid (CA) is an important natural antioxidant found in rosemary (Rosmarinus essentials) and exhibits a protective effect by suppressing oxidative stress and inflammation. This study aimed to investigate the impact of CA on IND-induced gastric ulceration. Wistar male rats received CA (100 mg/kg) or esomeprazole (ESP) (20 mg/kg, standard drug) by oral gavage for 14 days, after that gastric ulceration was induced by oral administration of 100 mg/kg IND. CA pretreatment attenuated both gross morphological lesions and histopathological alterations. CA strongly reduced IND-induced oxidative stress, verified by a decrease in MDA ( p < 0.001) and TOS levels ( p < 0.05). Furthermore, an IND-dependent increase in CAT ( p < 0.001) and GPx ( p < 0.01) activities, as well as a reduction in GSH levels ( p < 0.01), were ameliorated by CA pretreatment. CA also attenuated inflammatory damage by suppressing IL-1β ( p < 0.01), IL-6 ( p < 0.01), and TNFα ( p < 0.001) production and increasing Nrf2/HO-1 ( p < 0.05) expressions. In conclusion, CA shows a gastroprotective effect by reducing oxidative stress and attenuating inflammation.
Keywords	indomethacin ; gastric ulcer ; carnosic acid ; inflammation ; oxidative stress ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Investigation of Neurotoxicity Oxidative Stress and Oxidative DNA Damage in Cadmium-Induced Brain Injury in Rats

İsmail BOLAT / Serkan YILDIRIM / Nesrin CEYLAN / Yavuz Selim SAĞLAM / Ferit Kansu ÖRNEK / Merve BOLAT / Metin KILIÇOĞLU

Veterinary Sciences and Practices, Vol 18, Iss 1, Pp 19-

2023 Volume 24

Keywords	Veterinary medicine ; SF600-1100
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	AVES
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Protective Effect of Betulinic Acid Administration on Kidney Damage in Acetaminophen-Induced Nephrotoxicity Model

Eda Dokumacioglu / Hatice İskender / Armagan Hayirli / Guler Yenice / Kubra Asena Terim Kapakin / Ismail Bolat / Esra Manavoglu Kirman

Makara Journal of Health Research, Vol 27, Iss 1, Pp 59-

2023 Volume 67

Abstract: Background: Acetaminophen (APAP) is the most widely used analgesic drug worldwide, but it may induce renal toxicity. Betulinic acid (BA) ameliorates the oxidative stress and inflammatory response to renal damage. The present study aimed to investigate ... ...

Abstract	Background: Acetaminophen (APAP) is the most widely used analgesic drug worldwide, but it may induce renal toxicity. Betulinic acid (BA) ameliorates the oxidative stress and inflammatory response to renal damage. The present study aimed to investigate the potential protective effects of BA treatment through an experimental kidney damage rat model administered with APAP. Methods: Sprague–Dawley male rats were randomly divided into four groups: control, BA (25 mg/kg for 15 days), APAP (1 g/kg), and APAP + BA groups. BA was administered via oral gavage at a dose of 25 mg/kg for 15 days. APAP was dissolved in hot saline and administered on the last day to produce nephrotoxicity via a single oral gavage at a dose of 1 g/kg. Kidney tissue samples were analyzed for human cartilage glycoprotein 39 (YKL-40), kidney injury molecule 1 (KIM-1), interleukin 18 (IL-18), superoxide dismutase (SOD), and malondialdehyde (MDA). Data were subjected to one-way analysis of variance and the Wilcoxon rank-sum test Results: Renal tissue YKL-40, KIM-1, IL-18, and MDA levels in the APAP group were significantly higher than those in the control group (p < 0.05). The BA treatment completely restored renal KIM-1, YKL-40, and MDA levels and partially restored renal IL-18 and SOD levels in the rats subjected to renal damage induction (p < 0.05). The intertubular regions of rats administered with APAP had degeneration, necrosis, and infiltration of inflammatory cells and were immunopositive for IL-1 beta and 8-hydroxy-2′-deoxyguanosine. Conclusions: BA can be used in the prevention and replacement treatment of nephrotoxicity due to its inhibitory properties in multiple pathways and powerful antioxidant effects.
Keywords	acetaminophen ; betulinic acid ; interleukin 18 ; kidney injury molecule 1 ; malondialdehyde ; superoxide dismutase ; Medicine ; R
Subject code	616
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Universitas Indonesia
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Discovery of therapeutic agents targeting PKLR for NAFLD using drug repositioning

EBioMedicine, Vol 83, Iss , Pp 104214- (2022)

2022

Abstract: Summary: Background: Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver pathologies. However, no medical treatment has been approved for the treatment of NAFLD. In our previous study, we found that PKLR could be a potential ... ...

Abstract	Summary: Background: Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver pathologies. However, no medical treatment has been approved for the treatment of NAFLD. In our previous study, we found that PKLR could be a potential target for treatment of NALFD. Here, we investigated the effect of PKLR in in vivo model and performed drug repositioning to identify a drug candidate for treatment of NAFLD. Methods: Tissue samples from liver, muscle, white adipose and heart were obtained from control and PKLR knockout mice fed with chow and high sucrose diets. Lipidomics as well as transcriptomics analyses were conducted using these tissue samples. In addition, a computational drug repositioning analysis was performed and drug candidates were identified. The drug candidates were both tested in in vitro and in vivo models to evaluate their toxicity and efficacy. Findings: The Pklr KO reversed the increased hepatic triglyceride level in mice fed with high sucrose diet and partly recovered the transcriptomic changes in the liver as well as in other three tissues. Both liver and white adipose tissues exhibited dysregulated circadian transcriptomic profiles, and these dysregulations were reversed by hepatic knockout of Pklr. In addition, 10 small molecule drug candidates were identified as potential inhibitor of PKLR using our drug repositioning pipeline, and two of them significantly inhibited both the PKLR expression and triglyceride level in in vitro model. Finally, the two selected small molecule drugs were evaluated in in vivo rat models and we found that these drugs attenuate the hepatic steatosis without side effect on other tissues. Interpretation: In conclusion, our study provided biological insights about the critical role of PKLR in NAFLD progression and proposed a treatment strategy for NAFLD patients, which has been validated in preclinical studies. Funding: ScandiEdge Therapeutics and Knut and Alice Wallenberg Foundation.
Keywords	Systems biology ; Drug repositioning ; NAFLD ; PKLR ; Circadian rhythms ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2022-09-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients

Burak Yulug / Ozlem Altay / Xiangyu Li / Lutfu Hanoglu / Seyda Cankaya / Simon Lam / Halil Aziz Velioglu / Hong Yang / Ebru Coskun / Ezgi Idil / Rahim Nogaylar / Ahmet Ozsimsek / Cemil Bayram / Ismail Bolat / Sena Oner / Ozlem Ozdemir Tozlu / Mehmet Enes Arslan / Ahmet Hacimuftuoglu / Serkan Yildirim /

Muhammad Arif / Saeed Shoaie / Cheng Zhang / Jens Nielsen / Hasan Turkez / Jan Borén / Mathias Uhlén / Adil Mardinoglu

Translational Neurodegeneration, Vol 12, Iss 1, Pp 1-

a randomised, double-blinded, placebo-controlled phase-II trial

2023 Volume 23

Abstract: Abstract Background Alzheimer’s disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the ... ...

Abstract	Abstract Background Alzheimer’s disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress. Methods Here, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients. One-dose CMA included 12.35 g L-serine (61.75%), 1 g nicotinamide riboside (5%), 2.55 g N-acetyl-L-cysteine (12.75%), and 3.73 g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84. The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients. Results We showed a significant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant decline (P = 0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism were significantly improved after CMA treatment. Conclusion Our results indicate that treatment of AD patients with CMA can lead to ...
Keywords	Alzheimer’s disease ; Combined metabolic activators ; Multi-omics ; Systems biology ; Systems medicine ; Neurology. Diseases of the nervous system ; RC346-429
Subject code	610
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Hipertansif hastalarda N- amino terminal prohormon beyin natriüretik peptid düzeyleri ile ilişkili faktörler

Hamdi Püşüroğlu / Mehmet Erturk / Özgür Akgül / Özgür Surgit / İsmail Bolat / Emre Akkaya / Aydın Yıldırım

Dicle Medical Journal, Vol 41, Iss 2, Pp 303-

2014 Volume 308

Abstract: Objectives: In this study we ınvestigated that which the factors affecting the level of N- amino terminal prohormone brain natriuretic peptid (NT-pro BNP) in hypertensive population. Methods: A total of 309 hypertensive patients (mean age 50.5 ± 10.7, 49. ...

Abstract	Objectives: In this study we ınvestigated that which the factors affecting the level of N- amino terminal prohormone brain natriuretic peptid (NT-pro BNP) in hypertensive population. Methods: A total of 309 hypertensive patients (mean age 50.5 ± 10.7, 49.2% male) were enrolled into the study. Lower group was defined as NT-pro BNP 60 pg/dl or low, high group was defined as NT-pro BNP 60 pg/dl higher. The patients with secondary hypertensive, heart failure, coronary artery disease, valvular diseases, chronic renal failure (serum creatinine >1.5 mg/dl, blood urea nitrogen>30 mg/dl) and chronic obstructive pulmonary disease were excluded from the study. Results: Left ventricular mass index, 24-h systolic blood pressure, day systolic blood pressure, night systolic blood pressure and night diastolic blood pressure higher in high group than lower group. In stepwise linear regression analysis, a significant relation was found between sex, left ventricular mass index, age, night systolic blood pressure and higher NT-pro BNP levels (R²=0.236, ß= -0.258, P<0.001, ß=0.185, P=0.006, ß=0.174, P=0.010, ß=0.160, p=0.015 respectively)., Conclusion: Age, gender, left ventricle mass index and night systolic blood pressure were found as independent predictive factors on NT-pro BNP in hypertensive patients.
Keywords	NT-pro BNP ; hypertension ; Medicine ; R ; Medicine (General) ; R5-920
Language	English
Publishing date	2014-06-01T00:00:00Z
Publisher	Dicle University Medical School
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Gender-related differences in presentation and treatment of patients with non-valvular atrial fibrillation

Volkan Doğan / Özcan Başaran / Osman Beton / Mehmet Tekinalp / Ahmet Çağrı Aykan / Ezgi Kalaycıoğlu / İsmail Bolat / Onur Taşar / Özgen Şafak / Macit Kalçık / Cevat Kırma / Murat Biteker

Türk Kardiyoloji Derneği Arşivi, Vol 45, Iss 1, Pp 16-

results from RAMSES study

2017 Volume 25

Abstract: Objective: Gender is an important feature in the management of atrial fibrillation (AF). This study investigated gender-related differences in patients with AF in Turkey. Methods: As a part of RAMSES (ReAl-life Multicenter Survey Evaluating Stroke ... ...

Abstract	Objective: Gender is an important feature in the management of atrial fibrillation (AF). This study investigated gender-related differences in patients with AF in Turkey. Methods: As a part of RAMSES (ReAl-life Multicenter Survey Evaluating Stroke prevention strategies in Turkey, NCT02344901) study, information of the patients with AF who successively applied to the hospital was analyzed. This cross-sectional, multicenter, nationwide observational study enrolled 6264 non-valvular AF (NVAF) outpatients (55.9% women) from Turkey. Results: Compared with men, women with NVAF were older (71 years [range: 65–78 years] vs. 70 years [range: 62–77 years]; p<0.001), had lower frequency of coronary artery disease (22.0% vs. 38.3%; p<0.001) and congestive heart failure (18.2% vs. 27.2%; p<0.001). Women had higher median CHA2DS2-VASc score (4 [range: 3–5] vs. 3 [range: 2–4]; p<0.001), but similar HAS-BLED score (2 [range: 1–2] vs. 2 [range: 1–2]; p=0.141) when compared with men. Anticoagulant therapy use was higher in women (74.5% vs. 69.9%; p<0.001). Analysis of anticoagulation therapy use revealed that 68.5% of men and 61.6% of women (p=0.204) who had low risk for stroke (CHA2DS2-VASc score: 0 [male], 1 [female]) received anticoagulation therapy, and 30.5% of the men. Meanwhile, 25.3% of the women (p<0.001) with high risk for stroke (CHA2DS2-VASc score: ≥1 [male], ≥2 [female]) had not received any anticogulant therapy. Conclusion: Although women with NVAF receive better treatment than men, anticoagulation therapy is suboptimal in large proportion of men and women, with underuse in high-risk patients and overuse in low-risk patients. There is an urgent need to improve optimization of anticoagulation in patients with NVAF.
Keywords	gender ; non-valvular atrial fibrillation ; oral anticoagulan therapy ; Medicine ; R ; Internal medicine ; RC31-1245 ; Diseases of the circulatory (Cardiovascular) system ; RC666-701
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	KARE Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Neuroprotective effects of dietary borax in the brain tissue of rainbow trout (Oncorhynchus mykiss) exposed to copper-induced toxicity

Alak, Gonca / Ahmet Topal / Arzu Ucar / Aslı Çilingir Yeltekin / Esra Manavoğlu Kirman / Hasan Türkez / İsmail Bolat / Ismail Hakkı Taş / Muhammed Atamanalp / Mustafa Özkaraca / Selim Çomaklı / Veysel Parlak

Fish physiology and biochemistry. 2018 Oct., v. 44, no. 5

2018

Abstract: We aimed to investigate the modulating effects of dietary borax on the pathways in rainbow trout brain exposed to copper. For this aim, a comprehensive assessment was performed including biochemical (acetylcholinesterase (AChE), malondialdehyde (MDA), ... ...

Abstract	We aimed to investigate the modulating effects of dietary borax on the pathways in rainbow trout brain exposed to copper. For this aim, a comprehensive assessment was performed including biochemical (acetylcholinesterase (AChE), malondialdehyde (MDA), oxidative DNA damage (8-hydroxy-2′-deoxyguanosine (8-OHdG), and caspase-3 levels) and transcriptional parameters (heat shock protein 70 (HSP70) and cytochromes P450 (CYP1A), glutathione peroxidase (gpx), superoxide dismutase (sod), and catalase (cat)) parameters and immunohistochemically staining of 8-OHdG. Special fish feed diets were prepared for the trial. These diets contained different concentrations of borax (1.25, 2.5, and 5 mg/kg) and/or copper (500 and 1000 mg/kg) at the period of pre- and co-treatment strategies for 21 days. At the end of the treatment periods, brain tissue was sampled for each experimental group. As a result, the biochemical parameters were increased and AChE activity decreased in the copper and copper-combined groups in comparison with the control group and also with only borax applications (p < 0.05). We observed an increase or decrease in particular biochemical parameters for the borax group in every application and we established that borax had protective effect against copper toxicity by decreasing and/or increasing the relevant biochemical parameters in brain tissue of fish. The biochemical results of borax and its combinations corresponded to the observations of gene expression data, which similarly concluded that HSP70 and CYP1A genes were strongly induced by copper (p < 0.05). In addition, the expression levels of the sod, cat, and gpx genes in the fish brains exposed to borax and the borax combination groups were significantly higher than the only copper-treated groups. In conclusion, borax supplementation provided significant protection against copper-induced neurotoxicity in trout.
Keywords	acetylcholinesterase ; borax ; brain ; caspase-3 ; catalase ; copper ; cytochrome P-450 ; diet ; DNA damage ; fish feeds ; genes ; glutathione peroxidase ; heat-shock protein 70 ; immunohistochemistry ; malondialdehyde ; neuroprotective effect ; neurotoxicity ; Oncorhynchus mykiss ; staining ; superoxide dismutase ; transcription (genetics) ; trout
Language	English
Dates of publication	2018-10
Size	p. 1409-1420.
Publishing place	Springer Netherlands
Document type	Article
ZDB-ID	292907-7
ISSN	1573-5168 ; 0920-1742
ISSN (online)	1573-5168
ISSN	0920-1742
DOI	10.1007/s10695-018-0530-0
Database	NAL-Catalogue (AGRICOLA)

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