| 1. |
- Cinici, Emine, et al.
(author)
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Targeted Gene Candidates for Treatment and Early Diagnosis of Age-Related Macular Degeneration
- 2021
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In: BioMed Research International. - : Hindawi Limited. - 2314-6133 .- 2314-6141. ; 2021
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Journal article (peer-reviewed)abstract
- Age-related macular degeneration (AMD) is an eye disease that impairs the sharp and central vision need for daily activities. Recent advances in molecular biology research not only lead to a better understanding of the genetics and pathophysiology of AMD but also to the development of applications based on targeted gene expressions to treat the disease. Clarification of molecular pathways that causing to development and progression in dry and wet types of AMD needs comprehensive and comparative investigations in particular precious biopsies involving peripheral blood samples from the patients. Therefore, in this investigation, dry and wet types of AMD patients and healthy individuals were aimed at investigating in regard to targeted gene candidates by using gene expression analysis for the first time. 13 most potent candidate genes involved in neurodegeneration were selected via in silico approach and investigated through gene expression analysis to suggest new targets for disease therapy. For the analyses, 30 individuals (10 dry and 10 wet types AMD patients and 10 healthy people) were involved in the study. SYBR-Green based Real-Time PCR analysis was performed on isolated peripheral blood mononuclear cells (PBMCs) to analyze differentially expressed genes related to these cases. According to the investigations, only the CRP gene was found to be upregulated for both dry and wet disease types. When the downregulated genes were analyzed, it was found that 11 genes were commonly decreased for both dry and wet types in the aspect of expression pattern. From these genes, CFH, CX3CR1, FLT1, and TIMP3 were found to have the most downregulated gene expression properties for both diseases. From these results, it might be concluded that these common upregulated and downregulated genes could be used as targets for early diagnosis and treatment for AMD.
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| 2. |
- Turkez, Hasan, et al.
(author)
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Promising potential of boron compounds against Glioblastoma : In Vitro antioxidant, anti-inflammatory and anticancer studies
- 2021
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In: Neurochemistry International. - : Elsevier BV. - 0197-0186 .- 1872-9754. ; 149
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Journal article (peer-reviewed)abstract
- Glioblastoma (GB) is the most common and aggressive primary malignant astrocytoma correlated with poor patient survival. There are no curative treatments for GB, and it becomes resistant to chemotherapy, radiation therapy, and immunotherapy. Resistance in GB cells is closely related to their states of redox imbalance, and the role of reactive oxygen species and its impact on cancer cell survival is still far from elucidation. Boron-containing compounds, especially boric acid (BA) and borax (BX) exhibited interesting biological effects involving antibacterial, antiviral, anti-cancerogenic, anti-mutagenic, anti-inflammatory as well as anti-oxidative features. Recent studies indicated that certain boron compounds could be cytotoxic on human GB. Nevertheless, there is gap of knowledge in the literature on exploring the underlying mechanisms of anti-GB action by boron compounds. Here, we identified and compared the potential anti-GB effect of both BA and BX, and revealed their underlying anti-GB mechanism. We performed cell viability, oxidative alterations, oxidative DNA damage po-tential assays, and explored the inflammatory responses and gene expression changes by real-time PCR using U-87MG cells. We found that BA and BX led to a remarkable reduction in U-87MG cell viability in a concentration-dependent manner. We also found that boron compounds increased the total oxidative status and MDA levels along with the SOD and CAT enzyme activities and decreased total antioxidant capacity and GSH levels in U-87MG cells without inducing DNA damage. The cytokine levels of cancer cells were also altered. We verified the selectivity of the compounds using a normal cell line, HaCaT and found an exact opposite condition after treating HaCaT cells with BA and BX. BA applications were more effective than BX on U-87MG cell line in terms of increasing MDA levels, SOD and CAT enzyme activities, and decreasing Interleukin-1 alpha, Interleukin-6 and Tumor necrosis factor-alpha (TNF-alpha) levels. We finally observed that anticancer effect of BA and BX were associated with the BRAF/MAPK, PTEN and PI3K/AKT signaling pathways in respect of downregulatory manner. Especially, BA application was found more favorable because of its inhibitory effect on PIK3CA, PIK3R1, PTEN and RAF1 genes. In conclusion, our analysis indicated that boron compounds may be safe and promising for effective treatment of GB.
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| 3. |
- Turkez, Hasan, et al.
(author)
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Safety and Efficacy Assessments to Take Antioxidants in Glioblastoma Therapy : From In Vitro Experiences to Animal and Clinical Studies
- 2021
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In: Neurochemistry International. - : Elsevier BV. - 0197-0186 .- 1872-9754. ; 150
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Journal article (peer-reviewed)abstract
- Glioblastoma (GBM) is considered one of the most common malignant brain tumors, occurring as over 15% of all primary central nervous system and brain neoplasms. The unique and standard treatment option towards GBM involves the combination of surgical resection followed by radiotherapy (RT) and chemotherapy (CT). However, due to the aggressive nature and heterogeneity of GBMs, they remained difficult to treat. Recent findings from preclinical studies have revealed that disruption of the redox balance via using either oxidative or anti-oxidative agents in GBM presented an effective and promising therapeutic approach. A limited number of clinical trials substantially encouraged their concomitant use with RT or CT. Thus, treatment of GBMs may benefit from natural or synthetic antioxidative compounds as novel therapeutics. Despite the presence of variegated in vitro and in vivo studies focusing on safety and efficacy issues of these promising therapeutics, nowadays their translation to clinics is far from applicability due to several challenges. In this review, we briefly introduce the enzymatic and non-enzymatic antioxidant defense systems as well as potential signaling pathways related to the pathogenesis of GBM with a special interest in antioxidant mechanisms. In addition, we describe the advantages and limitations of antioxidant supplementation in GBM cases or disease models as well as growing challenges for GBM therapies with antioxidants in the future.
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