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Article ; Online: Modeling and Predicting the Cell Migration Properties from Scratch Wound Healing Assay on Cisplatin-Resistant Ovarian Cancer Cell Lines Using Artificial Neural Network

Entaz Bahar / Hyonok Yoon

Healthcare, Vol 9, Iss 911, p

2021 Volume 911

Abstract: The study of artificial neural networks (ANN) has undergone a tremendous revolution in recent years, boosted by deep learning tools. The presence of a greater number of learning tools and their applications, in particular, favors this revolution. However, ...

Abstract	The study of artificial neural networks (ANN) has undergone a tremendous revolution in recent years, boosted by deep learning tools. The presence of a greater number of learning tools and their applications, in particular, favors this revolution. However, there is a significant need to deal with the issue of implementing a systematic method during the development phase of the ANN to increase its performance. A multilayer feedforward neural network (FNN) was proposed in this paper to predict the cell migration assay on cisplatin-sensitive and cisplatin-resistant (CisR) ovarian cancer (OC) cell lines via scratch wound healing assay. An FNN training algorithm model was generated using the MATLAB fitting function in a MATLAB script to accomplish this task. The input parameters were types of cell lines, times, and wound area, and outputs were relative wound area, percentage of wound closure, and wound healing speed. In addition, we tested and compared the initial accuracy of various supervised learning classifier and support vector regression (SVR) algorithms. The proposed ANN model achieved good agreement with the experimental data and minimized error between the estimated and experimental values. The conclusions drawn demonstrate that the developed ANN model is a useful, accurate, fast, and inexpensive method to predict cancerous cell migration characteristics evaluated via scratch wound healing assay.
Keywords	artificial neural network ; cell migration assay ; scratch wound healing assay ; ovarian cancer ; cisplatin-resistant ; Medicine ; R
Subject code	006
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Lidocaine

Entaz Bahar / Hyonok Yoon

Medicina, Vol 57, Iss 782, p

A Local Anesthetic, Its Adverse Effects and Management

2021 Volume 782

Abstract: The most widely used medications in dentistry are local anesthetics (LA), especially lidocaine, and the number of recorded adverse allergic responses, particularly of hazardous responses, is quite low. However, allergic reactions can range from moderate ... ...

Abstract	The most widely used medications in dentistry are local anesthetics (LA), especially lidocaine, and the number of recorded adverse allergic responses, particularly of hazardous responses, is quite low. However, allergic reactions can range from moderate to life-threatening, requiring rapid diagnosis and treatment. This article serves as a review to provide information on LA, their adverse reactions, causes, and management.
Keywords	local anesthetics ; lidocaine ; adverse allergic responses ; Medicine (General) ; R5-920
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Establishment of Acquired Cisplatin Resistance in Ovarian Cancer Cell Lines Characterized by Enriched Metastatic Properties with Increased Twist Expression

Entaz Bahar / Ji-Ye Kim / Hyun-Soo Kim / Hyonok Yoon

International Journal of Molecular Sciences, Vol 21, Iss 7613, p

2020 Volume 7613

Abstract: Ovarian cancer (OC) is the most lethal of the gynecologic cancers, and platinum-based treatment is a part of the standard first-line chemotherapy regimen. However, rapid development of acquired cisplatin resistance remains the main cause of treatment ... ...

Abstract	Ovarian cancer (OC) is the most lethal of the gynecologic cancers, and platinum-based treatment is a part of the standard first-line chemotherapy regimen. However, rapid development of acquired cisplatin resistance remains the main cause of treatment failure, and the underlying mechanism of resistance in OC treatment remains poorly understood. Faced with this problem, our aim in this study was to generate cisplatin-resistant (CisR) OC cell models in vitro and investigate the role of epithelial–mesenchymal transition (EMT) transcription factor Twist on acquired cisplatin resistance in OC cell models. To achieve this aim, OC cell lines OV-90 and SKOV-3 were exposed to cisplatin using pulse dosing and stepwise dose escalation methods for a duration of eight months, and a total of four CisR sublines were generated, two for each cell line. The acquired cisplatin resistance was confirmed by determination of 50% inhibitory concentration (IC 50 ) and clonogenic survival assay. Furthermore, the CisR cells were studied to assess their respective characteristics of metastasis, EMT phenotype, DNA repair and endoplasmic reticulum stress-mediated cell death. We found the IC 50 of CisR cells to cisplatin was 3–5 times higher than parental cells. The expression of Twist and metastatic ability of CisR cells were significantly greater than those of sensitive cells. The CisR cells displayed an EMT phenotype with decreased epithelial cell marker E-cadherin and increased mesenchymal proteins N-cadherin and vimentin. We observed that CisR cells showed significantly higher expression of DNA repair proteins, X-ray repair cross-complementing protein 1 (XRCC1) and poly (ADP-ribose) polymerases 1 (PARP1), with significantly reduced endoplasmic reticulum (ER) stress-mediated cell death. Moreover, Twist knockdown reduced metastatic ability of CisR cells by suppressing EMT, DNA repair and inducing ER stress-induced cell death. In conclusion, we highlighted the utilization of an acquired cisplatin resistance model to identify the potential role of Twist as a therapeutic target to reverse acquired cisplatin resistance in OC.
Keywords	ovarian cancer ; cisplatin resistance ; Twist ; metastasis ; epithelial–mesenchymal transition ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Combination of Niraparib, Cisplatin and Twist Knockdown in Cisplatin-Resistant Ovarian Cancer Cells Potentially Enhances Synthetic Lethality through ER-Stress Mediated Mitochondrial Apoptosis Pathway

Entaz Bahar / Ji-Ye Kim / Dong Chul Kim / Hyun-Soo Kim / Hyonok Yoon

International Journal of Molecular Sciences, Vol 22, Iss 3916, p

2021 Volume 3916

Abstract: Poly (ADP-ribose) polymerase 1 inhibitors (PARPi) are used to treat recurrent ovarian cancer (OC) patients due to greater survival benefits and minimal side effects, especially in those patients with complete or partial response to platinum-based ... ...

Abstract	Poly (ADP-ribose) polymerase 1 inhibitors (PARPi) are used to treat recurrent ovarian cancer (OC) patients due to greater survival benefits and minimal side effects, especially in those patients with complete or partial response to platinum-based chemotherapy. However, acquired resistance of platinum-based chemotherapy leads to the limited efficacy of PARPi monotherapy in most patients. Twist is recognized as a possible oncogene and contributes to acquired cisplatin resistance in OC cells. In this study, we show how Twist knockdown cisplatin-resistant (CisR) OC cells blocked DNA damage response (DDR) to sensitize these cells to a concurrent treatment of cisplatin as a platinum-based chemotherapy agent and niraparib as a PARPi on in vitro two-dimensional (2D) and three-dimensional (3D) cell culture. To investigate the lethality of PARPi and cisplatin on Twist knockdown CisR OC cells, two CisR cell lines (OV90 and SKOV3) were established using step-wise dose escalation method. In addition, in vitro 3D spheroidal cell model was generated using modified hanging drop and hydrogel scaffolds techniques on poly-2-hydroxylethly methacrylate (poly-HEMA) coated plates. Twist expression was strongly correlated with the expression of DDR proteins, PARP1 and XRCC1 and overexpression of both proteins was associated with cisplatin resistance in OC cells. Moreover, combination of cisplatin (Cis) and niraparib (Nira) produced lethality on Twist-knockdown CisR OC cells, according to combination index (CI). We found that Cis alone, Nira alone, or a combination of Cis+Nira therapy increased cell death by suppressing DDR proteins in 2D monolayer cell culture. Notably, the combination of Nira and Cis was considerably effective against 3D-cultures of Twist knockdown CisR OC cells in which Endoplasmic reticulum (ER) stress is upregulated, leading to initiation of mitochondrial-mediated cell death. In addition, immunohistochemically, Cis alone, Nira alone or Cis+Nira showed lower ki-67 (cell proliferative marker) expression and higher cleaved caspase-3 (apoptotic marker) immuno-reactivity. Hence, lethality of PARPi with the combination of Cis on Twist knockdown CisR OC cells may provide an effective way to expand the therapeutic potential to overcome platinum-based chemotherapy resistance and PARPi cross resistance in OC.
Keywords	n/a ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Quercetin Attenuates Manganese-Induced Neuroinflammation by Alleviating Oxidative Stress through Regulation of Apoptosis, iNOS/NF-κB and HO-1/Nrf2 Pathways

Entaz Bahar / Ji-Ye Kim / Hyonok Yoon

International Journal of Molecular Sciences, Vol 18, Iss 9, p

2017 Volume 1989

Abstract: Manganese (Mn) is an essential trace element required for the development of human body and acts as an enzyme co-factor or activator for various reactions of metabolism. While essential in trace amounts, excessive Mn exposure can result in toxic ... ...

Abstract	Manganese (Mn) is an essential trace element required for the development of human body and acts as an enzyme co-factor or activator for various reactions of metabolism. While essential in trace amounts, excessive Mn exposure can result in toxic accumulations in human brain tissue and resulting extrapyramidal symptoms called manganism similar to idiopathic Parkinson’s disease (PD). Quercetin (QCT) has been demonstrated to play an important role in altering the progression of neurodegenerative diseases by protecting against oxidative stress. This study aimed to investigate the protective effect of QCT on Mn-induced neurotoxicity and the underlying mechanism in SK-N-MC human neuroblastoma cell line and Sprague-Dawley (SD) male rat brain. The results showed that Mn treatment significantly decreased the cell viability of SK-N-MC cell and increased the release of lactate dehydrogenase (LDH), which was attenuated by QCT pretreatment at 10 and 20 µg/mL. Compared to the Mn alone group, QCT pretreatment significantly attenuated Mn-induced oxidative stress, mitochondrial dysfunction and apoptosis. Meanwhile, QCT pretreatment markedly downregulated the NF-κB but upregulated the heme oxygenase-1 (HO-1) and Nrf2 proteins, compared to the Mn alone group. Our result showed the beneficial effect of QCT on hematological parameters against Mn in rat brain. QCT decrease reactive oxygen species (ROS) and protein carbonyl levels and increased Cu/Zn-superoxide dismutase (SOD) activity induced in Mn-treated rats. QCT administration caused a significant reduction in the Mn-induced neuroinflammation by inhibiting the expression of inflammatory markers such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). QCT lowered the Mn elevated levels of various downstream apoptotic markers, including Bax, cytochrome c, cleaved caspase-3 and polymerase-1 (PARP-1), while QCT treatment upregulated anti-apoptotic Bcl-2 proteins and prevented Mn-induced ...
Keywords	manganese ; manganism ; quercetin ; oxidative stress ; neuroinflammation ; apoptosis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2017-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: ER Stress-Mediated Signaling

Entaz Bahar / Hyongsuk Kim / Hyonok Yoon

International Journal of Molecular Sciences, Vol 17, Iss 9, p

Action Potential and Ca2+ as Key Players

2016 Volume 1558

Abstract: The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, ...

Abstract	The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca2+) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca2+ regulates cell death both at the early and late stages of apoptosis. Severe Ca2+ dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca2+ (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca2+ and action potential in ER stress-mediated apoptosis.
Keywords	endoplasmic reticulum stress ; unfolded protein response ; calcium ; apoptosis ; action potential ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2016-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Precise Modeling of the Protective Effects of Quercetin against Mycotoxin via System Identification with Neural Networks

Changju Yang / Entaz Bahar / Shyam Prasad Adhikari / Seo-Jeong Kim / Hyongsuk Kim / Hyonok Yoon

International Journal of Molecular Sciences, Vol 20, Iss 7, p

2019 Volume 1725

Abstract: Cell cytotoxicity assays, such as cell viability and lactate dehydrogenase (LDH) activity assays, play an important role in toxicological studies of pharmaceutical compounds. However, precise modeling for cytotoxicity studies is essential for successful ... ...

Abstract	Cell cytotoxicity assays, such as cell viability and lactate dehydrogenase (LDH) activity assays, play an important role in toxicological studies of pharmaceutical compounds. However, precise modeling for cytotoxicity studies is essential for successful drug discovery. The aim of our study was to develop a computational modeling that is capable of performing precise prediction, processing, and data representation of cell cytotoxicity. For this, we investigated protective effect of quercetin against various mycotoxins (MTXs), including citrinin (CTN), patulin (PAT), and zearalenol (ZEAR) in four different human cancer cell lines (HeLa, PC-3, Hep G2, and SK-N-MC) in vitro. In addition, the protective effect of quercetin (QCT) against various MTXs was verified via modeling of their nonlinear protective functions using artificial neural networks. The protective model of QCT is built precisely via learning of sparsely measured experimental data by the artificial neural networks (ANNs). The neuromodel revealed that QCT pretreatment at doses of 7.5 to 20 μg/mL significantly attenuated MTX-induced alteration of the cell viability and the LDH activity on HeLa, PC-3, Hep G2, and SK-N-MC cell lines. It has shown that the neuromodel can be used to predict the protective effect of QCT against MTX-induced cytotoxicity for the measurement of percentage (%) of inhibition, cell viability, and LDH activity of MTXs.
Keywords	cell cytotoxicity ; mycotoxins ; quercetin ; artificial neural networks ; computational modeling ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2019-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Polyphenolic Extract of Euphorbia supina Attenuates Manganese-Induced Neurotoxicity by Enhancing Antioxidant Activity through Regulation of ER Stress and ER Stress-Mediated Apoptosis

Entaz Bahar / Geum-Hwa Lee / Kashi Raj Bhattarai / Hwa-Young Lee / Min-Kyung Choi / Harun-Or Rashid / Ji-Ye Kim / Han-Jung Chae / Hyonok Yoon

International Journal of Molecular Sciences, Vol 18, Iss 2, p

2017 Volume 300

Abstract: Manganese (Mn) is an important trace element present in human body, which acts as an enzyme co-factor or activator in various metabolic reactions. While essential in trace amounts, excess levels of Mn in human brain can produce neurotoxicity, including ... ...

Abstract	Manganese (Mn) is an important trace element present in human body, which acts as an enzyme co-factor or activator in various metabolic reactions. While essential in trace amounts, excess levels of Mn in human brain can produce neurotoxicity, including idiopathic Parkinson’s disease (PD)-like extrapyramidal manganism symptoms. This study aimed to investigate the protective role of polyphenolic extract of Euphorbia supina (PPEES) on Mn-induced neurotoxicity and the underlying mechanism in human neuroblastoma SKNMC cells and Sprague-Dawley (SD) male rat brain. PPEES possessed significant amount of total phenolic and flavonoid contents. PPEES also showed significant antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and reducing power capacity (RPC) assays. Our results showed that Mn treatment significantly reduced cell viability and increased lactate dehydrogenase (LDH) level, which was attenuated by PPEES pretreatment at 100 and 200 µg/mL. Additionally, PPEES pretreatment markedly attenuated Mn-induced antioxidant status alteration by resolving the ROS, MDA and GSH levels and SOD and CAT activities. PPEES pretreatment also significantly attenuated Mn-induced mitochondrial membrane potential (ΔΨm) and apoptosis. Meanwhile, PPEES pretreatment significantly reversed the Mn-induced alteration in the GRP78, GADD34, XBP-1, CHOP, Bcl-2, Bax and caspase-3 activities. Furthermore, administration of PPEES (100 and 200 mg/kg) to Mn exposed rats showed improvement of histopathological alteration in comparison to Mn-treated rats. Moreover, administration of PPEES to Mn exposed rats showed significant reduction of 8-OHdG and Bax immunoreactivity. The results suggest that PPEES treatment reduces Mn-induced oxidative stress and neuronal cell loss in SKNMC cells and in the rat brain. Therefore, PPEES may be considered as potential treat-ment in Mn-intoxicated patients.
Keywords	manganese ; Euphorbia supina ; neurotoxicity ; antioxidant ; neuroprotection ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: β-Cell protection and antidiabetic activities of Crassocephalum crepidioides (Asteraceae) Benth. S. Moore extract against alloxan-induced oxidative stress via regulation of apoptosis and reactive oxygen species (ROS)

Entaz Bahar / Kazi-Marjahan Akter / Geum-Hwa Lee / Hwa-Young Lee / Harun-Or Rashid / Min-Kyung Choi / Kashi Raj Bhattarai / Mir Mohammad Monir Hossain / Joushan Ara / Kishor Mazumder / Obayed Raihan / Han-Jung Chae / Hyonok Yoon

BMC Complementary and Alternative Medicine, Vol 17, Iss 1, Pp 1-

2017 Volume 12

Abstract: Abstract Background Medicinal plants are becoming more popular in the treatment of various diseases because of the adverse effects of the current therapy, especially antioxidant plant components such as phenols and flavonoids have a protective role ... ...

Abstract	Abstract Background Medicinal plants are becoming more popular in the treatment of various diseases because of the adverse effects of the current therapy, especially antioxidant plant components such as phenols and flavonoids have a protective role against oxidative stress-induced degenerative diseases like diabetes. Thus, the purpose of this study was to investigate β-cell protection and antidiabetic activities of Crassocephalum crepidioides (Asteraceae) Benth. S. Moore. Method The in-vitro study was conducted by the pancreatic β-cell culture and α-amylase inhibition technique which includes two methods, namely starch-iodine method and 3,5-dinitrosalicylic acid (DNSA) method. On the other hand, the in-vivo study was performed by oral glucose tolerance test (OGTT) method and alloxan-induced diabetes method by using Wistar albino rat. At the end pancreatic specimens were removed and processed for histopathological study. Result The plant extract showed significant (p < 0.05, p < 0.01) effect on hyperglycemia as compared to standard (Gliclazide) in OGTT. The plant extract showed efficient protection activity of pancreatic β-cell from cell death in INS-1 cell line by significantly reduced (p < 0.05, *p < 0.01) the levels alloxan-induced apoptosis and intracellular reactive oxygen species (ROS) accumulation. In addition, the plant extract showed a significant (p < 0.05, **p < 0.01) effect on hyperglycemia by increases in percent of β-cells present in each islet (45% – 60%) compared to the diabetic group. Conclusion The result showed that C. crepidioides had β-cell protection and antidiabetic activities in pancreatic β-cell culture and Wistar albino rat.
Keywords	Crassocephalum crepidioides ; β-Cell Protection ; Antidiabetes ; Alloxan ; Apoptosis ; Reactive Oxygen Species ; Other systems of medicine ; RZ201-999
Subject code	580
Language	English
Publishing date	2017-03-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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