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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6
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Publication Open Access Multifunctional alginate-based hydrogel with reversible crosslinking for controlled therapeutics delivery(Elsevier, 2020) Ekinci, Duygu; N/A; Department of Chemical and Biological Engineering; Batool, Syeda Rubab; Nazeer, Muhammad Anwaar; Kızılel, Seda; Şahin, Afsun; PhD Student; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; College of Engineering; School of Medicine; N/A; N/A; 28376; 171267Glycan-based alginate hydrogels have great potential in creating new vehicles with responsive behavior and tunable properties for biomedicine. However, precise control and tunability in properties present major barrier for clinical translation of these materials. Here, we report the synthesis of pH responsive anthracene modified glycan-based hydrogels for selective release of therapeutic molecules. Hydrogels were crosslinked through simultaneous photopolymerization of vinyl groups and photodimerization of anthracene. Incorporation of anthracene into these gels leads to reversible control on crosslinking and transition between gel/sol states through dimerization/dedimerization of anthracene groups. Chemotherapeutic drug doxorubicin-loaded hydrogels were then tested in a cancer mimetic microenvironment where 85% of the drug was released from anthracene-conjugated hydrogels at pH 2 for 6 days. Control on gelation with anthracene incorporation was observed through alterations in modulus, where storage modulus was increased two-fold with anthracene conjugation during photopolymerization and photodimerization. Furthermore, cell survival analysis revealed that anthracene conjugation could selectively compromise cancer cell viability without inducing significant toxicity on healthy fibroblasts. This study combines light-induced control of crosslink density due to anthracene and pH-triggered therapeutics delivery with alginate. The approach would be applicable for systems where multiple control is required with high precision.Publication Open Access DNA methylation profiling identifies novel markers of progression in hepatitis B-related chronic liver disease(BioMed Central, 2016) Vatansever, Sezgin; Hardy, Timothy; Sarı, Aysegül Akder; Çakalağaoğlu, Fulya; Avcı, Arzu; Zeybel, Gemma Louise; Bashton, Matthew; Mathers, John C.; Ünsal, Belkis; Mann, Jelena; N/A; Department of Molecular Biology and Genetics; Zeybel, Müjdat; Karahüseyinoğlu, Serçin; Faculty Member; Faculty Member; Department of Molecular Biology and Genetics; School of Medicine; 214694; 110772Background: Chronic hepatitis B infection is characterized by hepatic immune and inflammatory response with considerable variation in the rates of progression to cirrhosis. Genetic variants and environmental cues influence predisposition to the development of chronic liver disease; however, it remains unknown if aberrant DNA methylation is associated with fibrosis progression in chronic hepatitis B. Results: To identify epigenetic marks associated with inflammatory and fibrotic processes of the hepatitis B-induced chronic liver disease, we carried out hepatic genome-wide methylation profiling using Illumina Infinium beadarrays comparing mild and severe fibrotic disease in a discovery cohort of 29 patients. We obtained 310 differentially methylated regions and selected four loci comprising three genes from the top differentially methylated regions: hypermethylation of HOXA2 and HDAC4 along with hypomethylation of PPP1R18 were significantly linked to severe fibrosis. We replicated the prominent methylation marks in an independent cohort of 102 patients by bisulfite modification and pyrosequencing. The timing and causal relationship of epigenetic modifications with disease severity was further investigated using a cohort of patients with serial biopsies. Conclusions: Our findings suggest a linkage of widespread epigenetic dysregulation with disease progression in chronic hepatitis B infection. Cpg methylation at novel genes sheds light on new molecular pathways, which can be potentially exploited as a biomarker or targeted to attenuate inflammation and fibrosis.Publication Open Access TRMU-related transient liver failure of infancy presents with microcephaly and neurodevelopmental delay(Nature Publishing Group (NPG), 2019) N/A; N/A; Azaklı, Hülya; Börklü Yücel, Esra; Arıkan, Çiğdem; Armutlu, Ayşe; Eraslan, Serpil; Kayserili, Hülya; PhD Student; Faculty Member; Teaching Faculty; Researcher; Graduate School of Health Sciences; School of Medicine; N/A; N/A; N/A; N/A; N/A; 7945Publication Open Access Extensive androgen receptor enhancer heterogeneity in primary prostate cancers underlies transcriptional diversity and metastatic potential(Nature Portfolio, 2022) Kneppers, J.; Severson, T.M.; Siefert, J.C.; Schol, P.; Joosten, S.E.P.; Yu, I.P.L.; Huang, C.F.; Morova, T.; Giambartolomei, C.; Seo, J.H.; Baca, S.C.; Carneiro, I.; Emberly, E.; Pasaniuc, B.; Jerónimo, C.; Henrique, R.; Freedman, M.L.; Wessels, L.F.A.; Bergman, A.M.; Zwart, W.; N/A; Lack, Nathan Alan; Altıntaş, Umut Berkay; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Sciences and Engineering; 120842; N/AAndrogen receptor (AR) drives prostate cancer (PCa) development and progression. AR chromatin binding profiles are highly plastic and form recurrent programmatic changes that differentiate disease stages, subtypes and patient outcomes. While prior studies focused on concordance between patient subgroups, inter-tumor heterogeneity of AR enhancer selectivity remains unexplored. Here we report high levels of AR chromatin binding heterogeneity in human primary prostate tumors, that overlap with heterogeneity observed in healthy prostate epithelium. Such heterogeneity has functional consequences, as somatic mutations converge on commonly-shared AR sites in primary over metastatic tissues. In contrast, less-frequently shared AR sites associate strongly with AR-driven gene expression, while such heterogeneous AR enhancer usage also distinguishes patients’ outcome. These findings indicate that epigenetic heterogeneity in primary disease is directly informative for risk of biochemical relapse. Cumulatively, our results illustrate a high level of AR enhancer heterogeneity in primary PCa driving differential expression and clinical impact.Publication Open Access Treating chronic hepatitis delta: the need for surrogate markers of treatment efficacy(Elsevier, 2019) Abbas, Zaigham; Buti, Maria; Cornberg, Markus; Esteban, Rafael; Etzion, Ohad; Ganes, Edward J.; Gish, Robert G.; Glenn, Jeffrey S.; Hamids, Saeed; Heller, Theo; Koh, Christopher; Lampertico, Pietro; Lurie, Yoav; Manns, Michael; Parana, Raymundo; Rizzetto, Mario; Urban, Stephan; Wedemeyer, Heiner; Wranke, A.; Borzacov, Pinheiro L. M.; Lobato, C.; Hamid, S.; Ceausu, E.; Dalekos, G. N.; Turcanu, A.; Niro, G. A.; Lubna, F.; Abbas, M.; Ingiliz, P.; Ferenci, P.; Vanwolleghem, T.; Hayden, T.; Dashdorj, N.; Motoc, A.; Hardtke, S.; N/A; Yurtaydın, Süleyman Cihan; Faculty Member; School of MedicineChronic hepatitis delta represents the most severe form of chronic viral hepatitis. The current treatment of hepatitis delta virus (HDV) infection consists of the use of interferons and is largely unsatisfactory. Several new compounds are currently in development for the treatment of HDV infection. However, surrogate markers that can be used to develop clinical endpoints in HDV infection are not well defined. In the current manuscript, we aimed to evaluate the existing data on treatment of HDV infection and to suggest treatment goals (possible "trial endpoints") that could be used across different clinical trials.Publication Open Access Influence of multidrug resistant organisms on the outcome of diabetic foot infection(Elsevier, 2018) Saltoğlu, Neşe; Tülek, Necla; Yemisen, Mücahit; Kadanalı, Ayten; Karagöz, Gül; Batırel, Ayşe; Ak, Öznür; Sönmezer, Cağla; Eraksoy, Haluk; Cağatay, Atahan; Sürme, Serkan; Nemli, Salih A.; Demirdal, Tuna; Coşkun, Ömer; Öztürk, Derya; Ceran, Nurgül; Pehlivanoğlu, Filiz; Şengoz, Gönül; Aslan, Turan; Akkoyunlu, Yasemin; Öncül, Oral; Ay, Hakan; Mülazımoğlu, Lütfiye; Ertürk, Buket; Yılmaz, Fatma; Yörük, Gülşen; Uzun, Nuray; Şimşek, Funda; Yıldırmak, Taner; Yaşar, Kadriye Kart; Sönmezoğlu, Meral; Küçükkardalı, Yaşar; Tuna, Nazan; Karabay, Oğuz; Özgüneş, Nail; Sargın, Fatma; N/A; Ergönül, Önder; Faculty Member; School of Medicine; 110398Objectives: We described the clinical outcomes of the diabetic patients who had foot infections with multidrug resistant organisms. Methods: We included the patients with diabetic foot infections (DFI) from 19 centers, between May 2011 and December 2015. Infection was defined according to IDSA DFI guidelines. Patients with severe infection, complicated moderate infection were hospitalized. The patients were followed-up for 6 months after discharge. Results: In total, 791 patients with DFI were included, 531(67%) were male, median age was 62 (19-90). Severe infection was diagnosed in 85 (11%) patients. Osteomyelitis was diagnosed in 291(36.8%) patients. 536 microorganisms were isolated, the most common microorganisms were S. aureus (20%), P. aeruginosa (19%) and E. coli (12%). Methicillin resistance (MR) rate among Staphylococcus aureus isolates was 31%. Multidrug resistant bacteria were detected in 21% of P. aeruginosa isolates. ESBL (+) Gram negative bacteria (GNB) was detected in 38% of E. coli and Klebsiella isolates. Sixty three patients (8%) were rehospitalized. Of the 791 patiens, 127 (16%) had major amputation, and 24 (3%) patients died. In multivariate analysis, significant predictors for fatality were; dialysis (OR: 8.3, Cl: 1.82-38.15, p = 0.006), isolation of Klebsiella spp. (OR:7.7, Cl: 1.24-47.96, p = 0.028), and chronic heart failure (OR: 3, Cl: 1.01-9.04, p = 0.05). MR Staphylococcus was detected in 21% of the rehospitalized patients, as the most common microorganism (p < 0.001). Conclusion: Among rehospitalized patients, methicillin resistant Staphylococcus infections was detected as the most common agent, and Klebsiella spp. infections were found to be significantly associated with fatality.Publication Open Access The effect of metabolic syndrome on cardiovascular disease and cumulative organ damage in Takayasu's arteritis(BMJ Publishing Group, 2019) Tahra, Sema Kaymaz; Yazıcı, Ayten; Çefle, Ayşe; Kara, Mete; Yarkan-Tuğsal, Handan; Gerçik, Önay; Akar, Servet; Önen, Fatoş; Aksu, Kenan; Keser, Gökhan; Bes, Cemal; Kamalı, Sevil; Alibaz-Öner, Fatma; Direskeneli, Haner; N/A; Kanıtez, Nilüfer Alpay; Faculty Member; School of Medicine; 239432Publication Open Access Plasmon-coupled photocapacitor neuromodulators(American Chemical Society (ACS), 2020) Ülgüt, Burak; Çetin, Arif E.; N/A; N/A; Department of Molecular Biology and Genetics; Department of Electrical and Electronics Engineering; Department of Chemical and Biological Engineering; Melikov, Rustamzhon; Srivastava, Shashi Bhushan; Karatüm, Onuralp; Doğru-Yüksel, Itır Bakış; Jalali, Houman Bahmani; Sadeghi, Sadra; Dikbaş, Uğur Meriç; Kavaklı, İbrahim Halil; Nizamoğlu, Sedat; PhD Student; Researcher; PhD Student; PhD Student; Master Student; Faculty Member; Faculty Member; Department of Molecular Biology and Genetics; Department of Electrical and Electronics Engineering; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of Sciences; College of Engineering; N/A; N/A; N/A; N/A; N/A; N/A; N/A; 40319; 130295Efficient transduction of optical energy to bioelectrical stimuli is an important goal for effective communication with biological systems. For that, plasmonics has a significant potential via boosting the light-matter interactions. However, plasmonics has been primarily used for heat-induced cell stimulation due to membrane capacitance change (i.e., optocapacitance). Instead, here, we demonstrate that plasmonic coupling to photocapacitor biointerfaces improves safe and efficacious neuromodulating displacement charges for an average of 185% in the entire visible spectrum while maintaining the faradic currents below 1%. Hot-electron injection dominantly leads the enhancement of displacement current in the blue spectral window, and the nanoantenna effect is mainly responsible for the improvement in the red spectral region. The plasmonic photocapacitor facilitates wireless modulation of single cells at three orders of magnitude below the maximum retinal intensity levels, corresponding to one of the most sensitive optoelectronic neural interfaces. This study introduces a new way of using plasmonics for safe and effective photostimulation of neurons and paves the way toward ultrasensitive plasmon-assisted neurostimulation devices.Publication Open Access HotRegion: a database of predicted hot spot clusters(Oxford University Press (OUP), 2012) N/A; Department of Computer Engineering; Department of Chemical and Biological Engineering; Çukuroğlu, Engin; Gürsoy, Attila; Keskin, Özlem; PhD Student; Faculty Member; Department of Computer Engineering; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; 8745; 26605Hot spots are energetically important residues at protein interfaces and they are not randomly distributed across the interface but rather clustered. These clustered hot spots form hot regions. Hot regions are important for the stability of protein complexes, as well as providing specificity to binding sites. We propose a database called HotRegion, which provides the hot region information of the interfaces by using predicted hot spot residues, and structural properties of these interface residues such as pair potentials of interface residues, accessible surface area (ASA) and relative ASA values of interface residues of both monomer and complex forms of proteins. Also, the 3D visualization of the interface and interactions among hot spot residues are provided.Publication Open Access Development of highly luminescent and cytocompatible near-IR-emitting aqueous Ag2S quantum dots(Royal Society of Chemistry (RSC), 2012) Çizmeciyan, M. Natali; Erdem, Rengin; Özen, Can; Kurt, Adnan; N/A; Department of Physics; Department of Chemistry; Hocaoğlu, İbrahim; Sennaroğlu, Alphan; Acar, Havva Funda Yağcı; PhD Student; Faculty Member; Department of Physics; Department of Chemistry; Graduate School of Sciences and Engineering; College of Sciences; N/A; 23851; 178902Colloidally stable and highly luminescent near-IR emitting Ag2S quantum dots (NIRQDs) were prepared by a very simple aqueous method using 2-mercaptopropionic acid (2MPA) as a coating. Emission of Ag2S-2MPA NIRQDs can be tuned between 780 and 950 nm. These NIRQDs have photoluminescence quantum yields (PLQY) around 7–39% and exhibit excellent cytocompatibility even at 600 mg mL 1 in NIH/3T3 cells. With such improved properties, Ag2S-2MPA NIRQDs have a great potential in practical bio-applications.