Scientific Papers by burak berber
Gene Therapy, 2020
The novel coronavirus pneumonia (COVID-19) is a highly infectious acute respiratory disease cause... more The novel coronavirus pneumonia (COVID-19) is a highly infectious acute respiratory disease caused by Severe Acute Respiratory Syndrome-Related Coronavirus (SARS-CoV-2) (Prec Clin Med 2020;3:9-13, Lancet 2020;395:497-506, N. Engl J Med 2020a;382:1199-207, Nature 2020;579:270-3). SARS-CoV-2 surveillance is essential to controlling widespread transmission. However, there are several challenges associated with the diagnostic of the COVID-19 during the current outbreak (Liu and Li (2019), Nature 2020;579:265-9, N. Engl J Med 2020;382:727-33). Firstly, the high number of cases overwhelms diagnostic test capacity and proposes the need for a rapid solution for sample processing (Science 2018;360:444-8). Secondly, SARS-CoV-2 is closely related to other important coronavirus species and subspecies, so detection assays can give false-positive results if they are not efficiently specific to SARS-CoV-2. Thirdly, patients with suspected SARS-CoV-2 infection sometimes have a different respiratory viral infection or co-infections with SARS-CoV-2 and other respiratory viruses (MedRxiv 2020a;1-18). Confirmation of the COVID-19 is performed mainly by virus isolation followed by RT-PCR and sequencing (N. Engl J Med 2020;382:727-33, MedRxiv 2020a, Turkish J Biol 2020;44:192-202). The emergence and outbreak of the novel coronavirus highlighted the urgent need for new therapeutic technologies that are fast, precise, stable, easy to manufacture, and target-specific for surveillance and treatment. Molecular biology tools that include gene-editing approaches such as CRISPR-Cas12/13-based SHERLOCK, DETECTR, CARVER and PAC-MAN, antisense oligonucleotides, antisense peptide nucleic acids, ribozymes, aptamers, and RNAi silencing approaches produced with cutting-edge scientific advances compared to conventional diagnostic or treatment methods could be vital in COVID-19 and other future outbreaks. Thus, in this review, we will discuss potent the molecular biology approaches that can revolutionize diagnostic of viral infections and therapies to fight COVID-19 in a highly specific, stable, and efficient way. Highlights • SARS-CoV-2 is an RNA virus that could be targeted and diagnosed with novel CRISPR approaches. • ASO therapy targeting transcript encoding a viral protein or genomic RNA itself could be developed as a response to the SARS-CoV-2 pandemic.
Papers by burak berber
Physiology
Current evidence suggests that cerebrovascular dysfunction including compromised BBB integrity an... more Current evidence suggests that cerebrovascular dysfunction including compromised BBB integrity and decreased CBF are early findings before the development of neuronal pathologies and cognitive deficits in VCID. Hyperphosphorylated tau (p-tau) is historically associated with the neurofibrillary tangles in AD but not in VCID. Notably, our recent study demonstrated that accumulation of non-fibrillar hyperphosphorylated tau (p-tau) is detectable in the brain microvasculature of VCID patients and contributes to the pathogenesis of dementia. Indeed, recent findings support that tau, being a microtubule-binding protein, is highly expressed in microvascular endothelial cells and its hyperphosphorylation leads to microtubule breakdown and disruption of barrier function. There is growing awareness that increased consumption of a high-fat diet (HFD) is believed to increase the risk for the development and progression of VCID, but the underlying mechanisms of how HFD leads to cognitive impairme...
Stroke
Increased consumption of a high-fat diet (HFD) is believed to increase the risk for the developme... more Increased consumption of a high-fat diet (HFD) is believed to increase the risk for the development and progression of VCID, but the underlying mechanisms of how HFD leads to cognitive impairment are unclear, partly due to the use of different HFD models in preclinical studies. Palmitic acid (PA), the most common form of saturated fatty acid, found in the human cerebrospinal fluid in obesity, promotes disruption of BBB integrity. We hypothesized that a PA-rich diet mediates early disruption of blood brain barrier (BBB) integrity which leads to progressive neurovascular pathologies and cognitive impairment in VCID. Methods: Experimental design for in vivo studies is depicted in Fig 1. In vitro studies included assessment of endothelial integrity by trans-endothelial electrical resistance (TEER) and FITC measurements, cell viability, and expression levels of tight junction proteins and cell stress markers (Hsp70, Occludin1, Claudin 5, and Carnitine Palmitoyl transferase 1A -CTP1A) in ...
Gene Therapy, 2020
The novel coronavirus pneumonia (COVID-19) is a highly infectious acute respiratory disease cause... more The novel coronavirus pneumonia (COVID-19) is a highly infectious acute respiratory disease caused by Severe Acute Respiratory Syndrome-Related Coronavirus (SARS-CoV-2) (
Journal of Virological Methods, 2021
While the whole genomic sequence of SARS-CoV-2 had been revealed, it was also demonstrated that t... more While the whole genomic sequence of SARS-CoV-2 had been revealed, it was also demonstrated that the genome of SARS-CoV-2 exhibits identity with the genome of SARS-CoV and MERS-CoV with ratios of 80 % and 50 % respectively. In the light of SARS-CoV-2 infection and mortality data, diagnosis and treatment of COVID-19 came into prominence around the world. As such many RT-PCR kits have been developed by biotechnology scientists. However viruses are fast mutating organisms and in order to increase accuracy, feasibility in long term and avoid the off target results of RT-PCR assays, regions of viral genome with low mutation rate and designing of primers targeting these regions are quite important. In this scope, we are presenting a novel algorithm that could be used for finding low mutation rate regions of SARS-CoV-2 and primers that were designed according to findings from our algorithm in this study.
Klinik calismalarda, rejenerasyon yetersizlikleri genelde anormal bir karaciger yapisi olusmasi d... more Klinik calismalarda, rejenerasyon yetersizlikleri genelde anormal bir karaciger yapisi olusmasi durumunda veya normal karaciger yenilenmesinin ciddi sekilde etkilenmesi durumunda ortaya cikar. Anormal rejeneratif yanitlari anlamak ve “normal saglikli rejenerasyon”dan farkliliklari gostermek, yeni tedavi stratejilerini belirlemek acisindan kritik olacaktir. Ornegin asiri fibroz, anormal duktal yanitlar, karaciger bozukluklarindan kaynaklanan bagisiklik bozuklugu gibi hastaliklarin tedavisi icin karaciger rejenerasyonu hedef olabilir. Hayvan modellerinden elde edilen veriler, klinik ortamda karaciger rejenerasyonunu tesvik etmek ya da karaciger yenilenmesi sirasinda olusan komplikasyonlari onlemek icin yeni tedavilerin gelistirilmesine yardimci olabilmektedir. Bu derlemede karaciger rejenerasyonunun olusum sureci ve mammalian target of rapamycin (mTOR) sinyal yolaginin karaciger rejenerasyonu uzerindeki etkisi arastirilmistir.
Briefings in Bioinformatics, 2021
Dihydroorotate dehydrogenase (DHODH) is a key enzyme required for de novo pyrimidine synthesis an... more Dihydroorotate dehydrogenase (DHODH) is a key enzyme required for de novo pyrimidine synthesis and it is suggested as a target for COVID19 treatment due to high pyrimidine demand by the virus replication in the infected host cells as well as its proven effect of blocking of cytokine release by the immune cells to prevent inflammation leading to acute respiratory distress. There are a number of clinical trials underway for COVID19 treatment using DHODH inhibitors; however, there are only a small number of known DHODH antagonists available for testing. Here, we have applied a methodology to identify DHODH antagonist candidates, and compared them using in silico target prediction tools. A large set of 7900 FDA-approved and clinical stage drugs obtained from DrugBank were docked against 20 different structures DHODH available in PDB. Drugs were eliminated according to their predicted affinities by Autodock Vina. About 28 FDA-approved and 79 clinical trial ongoing drugs remained. The mod...
Anti-Cancer Agents in Medicinal Chemistry, 2019
Background: Cancer is the second leading cause of death globally. Hydrazone and hydrazone derivat... more Background: Cancer is the second leading cause of death globally. Hydrazone and hydrazone derivatives have high activity, and for this reason, these compound are greatly used by researchers to synthesize new anti-cancer drug. The aim of this research work is to synthesize novel anticancer agents. Methods: New hydrazone derivatives were synthesized via a reaction between 3-formylphenyl methyl carbonate and benzhydrazide, 4-methylbenzoic hydrazide, 4-tert-butylbenzoic hydrazide, 4-nitrobenzoic hydrazide and 3- methoxybenzoic hydrazide, and were successfully characterized using elemental analysis, 1H-NMR, 13C-NMR, FT-IR and LC-MS techniques. The synthesized compounds were evaluated for their antimicrobial (some grampositive and -negative bacteria, filamentous fungi and yeasts), anti-proliferative (T47D and HCC1428-breast cancer cells) and anti-angiogenic (HUVEC-endothelial cells) activities. The anti-proliferative activities of the hydrazone compounds R1-R5 were studied on these cell l...
Many studies show that short non-coding sequences are widely conserved among regulatory elements.... more Many studies show that short non-coding sequences are widely conserved among regulatory elements. More and more conserved sequences are being discovered since the development next generation sequencing technology. A common approach to identify conserved sequences with regulatory roles rely on the topological change such as hairpin formation on the DNA or RNA level. However G quadruplexes, a non-canonical nucleic acid topology with little established biological role, is rarely considered for conserved regulatory element discovery. Here we present the use of G-quadruplex prediction algorithm to identify putative G-quadruplex-forming and conserved elements in E.coli genome. Phylogenetic analysis of 52 G-quadruplex forming sequences revealed two conserved G-quadruplex motifs with potential regulatory role.
Journal of Molecular Structure, 2020
Abstract In this study, a Schiff base (2-((4-(dimethylamino)benzylidene)amino)-4-methylphenol; 7S... more Abstract In this study, a Schiff base (2-((4-(dimethylamino)benzylidene)amino)-4-methylphenol; 7S2) has been synthesized and characterized with 1H, 13C-NMR, IR and elemental analysis methods. An electronic transition behaviour of the Schiff base has been investigated in the different eight solvents by UV-Vis. spectroscopy. The stable geometry of 7S2 has been determined by DFT method with Gaussian09 program (B3LYP/6-311G(2d, p)). 7S2 has been analysed for its target region selection using the SwissTarget program. A docking study has been performed against DHODH protein while its pharmacokinetic properties has been evaluated using SwissADME, Osiris and Molinspiration. 7S2 has important pharmacokinetic and drug-likeness properties against other FDA approved DHODH inhibitors. Further, 7S2 has been tested with the neutral red uptake assay and found cytotoxic for several cancer cell lines, having IC50 values ranged between 18-23 µg/mL. According to the pharmacokinetic properties and cytotoxic activities, we suggest that 7S2 may have a potential as an anticancer drug.
Here we discuss the potential of targeting Dihydroorotate dehydrogenase enzyme to help treat Covi... more Here we discuss the potential of targeting Dihydroorotate dehydrogenase enzyme to help treat Covid 19. Next, we present a very large scale of docking analysis using 7900 drug candidates and 20 Dihydroorotate dehydrogenase structures. Our findings not only identify 28-FDA approved candidate molecules, but also show common characteristics among the candidates, especially their association with serotonin-dopamine receptors. In continuation, we discuss the existing clinical trials for Covid 19 treatment of some of the drug candidates we have identified, supporting that the rest are good candidates.
Istanbul Bilim University Florence Nightingale Transplantation Journal
Many studies show that short non-coding sequences are widely conserved among regulatory elements.... more Many studies show that short non-coding sequences are widely conserved among regulatory elements. More and more conserved sequences are being discovered since the development next generation sequencing technology. A common approach to identify conserved sequences with regulatory roles rely on the topological change such as hairpin formation on the DNA or RNA level. However G quadruplexes, a non-canonical nucleic acid topology with little established biological role, is rarely considered for conserved regulatory element discovery. Here we present the use of G-quadruplex prediction algorithm to identify putative G-quadruplex-forming and conserved elements in E.coli genome. Phylogenetic analysis of 52 G-quadruplex forming sequences revealed two conserved G-quadruplex motifs with potential regulatory role.
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Scientific Papers by burak berber
Papers by burak berber