| 1. |
- Altay, Özlem, et al.
(författare)
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Current Status of COVID-19 Therapies and Drug Repositioning Applications
- 2020
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Ingår i: Iscience. - : Elsevier BV. - 2589-0042. ; 23:7
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Tidskriftsartikel (refereegranskat)abstract
- The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Drug repositioning is an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. In addition, we describe computational approaches to be used in drug repurposing and highlight examples of in silico studies of drug development efforts against SARS-CoV-2.
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| 2. |
- Arslan, M. E., et al.
(författare)
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In vitro neuroprotective effects of farnesene sesquiterpene on alzheimer’s disease model of differentiated neuroblastoma cell line
- 2020
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Ingår i: International Journal of Neuroscience. - : Taylor and Francis Ltd. - 0020-7454 .- 1563-5279 .- 1543-5245.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate neuroprotective properties of the farnesene sesquiterpene on the experimental Alzheimer’s disease model in vitro. Methods: Human neuroblastoma cell line (SHSY-5Y) was differentiated into neuron-like cells by using retinoic acid to constitute the in vitro Alzheimer’s Disease model. β-amyloid 1-42 protein was applied to the transformed cells for 24 and 48 hours in a wide dose ranges (3.125-200 μM) to establish AD cytotoxicity. Then, farnesene was applied to cell cultures in a wide spectrum dose interval (1.625-100 μg/ml) to investigate neuroprotective effect against β-amyloid for 24 and 48 hours. 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release tests were executed to determine cytotoxicity in the Alzheimer model. Nuclear DNA integrity of cells was examined under the fluorescent microscope using the Hoechst 33258 staining method. Furthermore, acetylcholinesterase (AChE) activity, total antioxidant capacity (TAC) and total oxidative status (TOS) levels were analyzed to understand the protection mechanism of the farnesene application on the cell culture model. Finally, flow cytometry analysis was used to find out the cell death mechanism after beta-amyloid and farnesene application to the cell culture. Results: Cell viability tests revealed significant neuroprotection against β-amyloid toxicity in both 24 and 48 hours and the Hoechst 33258 fluorescence staining method showed a significant decrease in necrotic deaths after farnesene application in the cell cultures. Finally, flow cytometry analysis put forth that farnesene could decrease necrotic cell death up to 3-fold resulted from beta-amyloid exposure. Conclusion: According to the investigations, farnesene can potentially be a safe, anti-necrotic and neuroprotective agents against Alzheimer’s disease.
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| 3. |
- Küçükdoğru, R., et al.
(författare)
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Neuroprotective effects of boron nitride nanoparticles in the experimental Parkinson’s disease model against MPP+ induced apoptosis
- 2020
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Ingår i: Metabolic brain disease. - : Springer. - 0885-7490 .- 1573-7365.
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson’s disease (PD) is one of the most aggressive neurodegenerative diseases and characterized by the loss of dopamine-sensitive neurons in the substantia nigra region of the brain. There is no any definitive treatment to completely cure PD and existing treatments can only ease the symptoms of the disease. Boron nitride nanoparticles have been extensively studied in nano-biological studies and researches showed that it can be a promising candidate for PD treatment with its biologically active unique properties. In the present study, it was aimed to investigate ameliorative effects of hexagonal boron nitride nanoparticles (hBNs) against toxicity of 1-methyl-4-phenylpyridinium (MPP+) in experimental PD model. Experimental PD model was constituted by application of MPP+ to differentiated pluripotent human embryonal carcinoma cell (Ntera-2, NT-2) culture in wide range of concentrations (0.62 to 2 mM). Neuroprotective activity of hBNs against MPP+ toxicity was determined by cell viability assays including MTT and LDH release. Oxidative alterations by hBNs application in PD cell culture model were investigated using total antioxidant capacity (TAC) and total oxidant status (TOS) tests. The impacts of hBNs and MPP+ on nuclear integrity were analyzed by Hoechst 33258 fluorescent staining method. Acetylcholinesterase (AChE) enzyme activities were determined by a colorimetric assay towards to hBNs treatment. Cell death mechanisms caused by hBNs and MPP+ exposure was investigated by flow cytometry analysis. Experimental results showed that application of hBNs increased cell viability in PD model against MPP+ application. TAS and TOS analysis were determined that antioxidant capacity elevated after hBNs applications while oxidant levels were reduced. Furthermore, flow cytometric analysis executed that MPP+ induced apoptosis was prevented significantly (p < 0.05) after application with hBNs. In a conclusion, the obtained results indicated that hBNs have a huge potential against MPP+ toxicity and can be used in PD treatment as novel neuroprotective agent and drug delivery system.
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| 4. |
- Lam, S., et al.
(författare)
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A systems biology approach for studying neurodegenerative diseases
- 2020
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 25:7, s. 1146-1159
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Tidskriftsartikel (refereegranskat)abstract
- Neurodegenerative diseases (NDDs), such as Alzheimer's (AD) and Parkinson's (PD), are among the leading causes of lost years of healthy life and exert a great strain on public healthcare systems. Despite being first described more than a century ago, no effective cure exists for AD or PD. Although extensively characterised at the molecular level, traditional neurodegeneration research remains marred by narrow-sense approaches surrounding amyloid beta (A beta), tau, and alpha-synuclein (alpha-syn). A systems biology approach enables the integration of multi-omics data and informs discovery of biomarkers, drug targets, and treatment strategies. Here, we present a comprehensive timeline of high-throughput data collection, and associated biotechnological advancements and computational analysis related to AD and PD. We hereby propose that a philosophical change in the definitions of AD and PD is now needed.
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| 5. |
- Li, Xiangyu, et al.
(författare)
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Classification of clear cell renal cell carcinoma based on PKM alternative splicing
- 2020
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Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Clear cell renal cell carcinoma (ccRCC) accounts for 70-80% of kidney cancer diagnoses and displays high molecular and histologic heterogeneity. Hence, it is necessary to reveal the underlying molecular mechanisms involved in progression of ccRCC to better stratify the patients and design effective treatment strategies. Here, we analyzed the survival outcome of ccRCC patients as a consequence of the differential expression of four transcript isoforms of the pyruvate kinase muscle type (PKM). We first extracted a classification biomarker consisting of eight gene pairs whose within-sample relative expression orderings (REOs) could be used to robustly classify the patients into two groups with distinct molecular characteristics and survival outcomes. Next, we validated our findings in a validation cohort and an independent Japanese ccRCC cohort. We finally performed drug repositioning analysis based on transcriptomic expression profiles of drug-perturbed cancer cell lines and proposed that paracetamol, nizatidine, dimethadione and conessine can be repurposed to treat the patients in one of the subtype of ccRCC whereas chenodeoxycholic acid, fenoterol and hexylcaine can be repurposed to treat the patients in the other subtype.
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| 6. |
- Ozcan, Mehmet, et al.
(författare)
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Improvement in the Current Therapies for Hepatocellular Carcinoma Using a Systems Medicine Approach
- 2020
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Ingår i: Advanced Biosystems. - : Wiley. - 2366-7478. ; 4:6
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Tidskriftsartikel (refereegranskat)abstract
- Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death primarily due to the lack of effective targeted therapies. Despite the distinct morphological and phenotypic patterns of HCC, treatment strategies are restricted to relatively homogeneous therapies, including multitargeted tyrosine kinase inhibitors and immune checkpoint inhibitors. Therefore, more effective therapy options are needed to target dysregulated metabolic and molecular pathways in HCC. Integrative genomic profiling of HCC patients provides insight into the most frequently mutated genes and molecular targets, including telomerase reverse transcriptase, the TP53 gene, and the Wnt/β-catenin signaling pathway oncogene (CTNNB1). Moreover, emerging techniques, such as genome-scale metabolic models may elucidate the underlying cancer-specific metabolism, which allows for the discovery of potential drug targets and identification of biomarkers. De novo lipogenesis has been revealed as consistently upregulated since it is required for cell proliferation in all HCC patients. The metabolic network-driven stratification of HCC patients in terms of redox responses, utilization of metabolites, and subtype-specific pathways may have clinical implications to drive the development of personalized medicine. In this review, the current and emerging therapeutic targets in light of molecular approaches and metabolic network-based strategies are summarized, prompting effective treatment of HCC patients. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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| 7. |
- Pagoni, A., et al.
(författare)
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Novel anti-Alzheimer phenol-lipoyl hybrids : Synthesis, physico-chemical characterization, and biological evaluation
- 2020
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier Masson SAS. - 0223-5234 .- 1768-3254. ; 186
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Tidskriftsartikel (refereegranskat)abstract
- To date, drugs that hit a single target are inadequate for the treatment of neurodegenerative diseases, such as Alzheimer's or Parkinson's diseases. The development of multitarget ligands, able to interact with the different pathways involved in the progession of these disorders, represents a great challenge for medicinal chemists. In this context, we report here the synthesis and biological evaluation of phenol-lipoyl hybrids (SV1-13), obtained via a linking strategy, to take advantage of the synergistic effect due to the antioxidant portions and anti-amyloid properties of the single constituents present in the hybrid molecule. Biological results showed that SV5 and SV10 possessed the best protective activity against Aβ1-42 induced neurotoxicity in differentiated SH-SY5Y cells. SV9 and SV10 showed remarkable antioxidant properties due to their ability to counteract the damage caused by H2O2 in SHSY-5Y-treated cells. Hovewer, SV5, showing moderate antioxidant and good neuroprotective activities, resulted the best candidate for further experiments since it also resulted stable both simulated and plasma fluids.
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| 8. |
- Özdemir, O., et al.
(författare)
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Anticancer effects of novel NSAIDs derivatives on cultured human glioblastoma cells
- 2020
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Ingår i: Zeitschrift für Naturforschung C - A Journal of Biosciences. - : Walter de Gruyter GmbH. - 0939-5075 .- 1865-7125.
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Tidskriftsartikel (refereegranskat)abstract
- Several epidemiologic, clinical and experimental reports indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) could have a potential as anticancer agents. The aim of this study was the evaluation of cytotoxic potential in human glioblastoma cells of novel synthesized NSAID derivatives, obtained by linking, through a spacer, α-lipoic acid (ALA) to anti-inflammatory drugs, such as naproxen (AL-3, 11 and 17), flurbiprofen (AL-6, 13 and 19) and ibuprofen (AL-9, 15 and 21). The effects on the level of gene expression were also determined using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. According to our results, NSAID derivatives exhibited concentration dependent cytotoxic effects on U87-MG cell line when compared with the control group. Moreover, treatment of the most active compounds (AL-3, AL-6 and AL-9) caused upregulation of tumor suppressor gene PTEN and downregulation of some oncogenes such as AKT1, RAF1 and EGFR. In conclusion, our results revealed that AL-3, AL-6 and AL-9 could be suitable candidates for further investigation to develop new pharmacological strategies for the prevention of cancer.
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