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Apoptosis

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Full-Text Articles in Medicine and Health Sciences

Acetone Extracts Of Berberis Vulgaris And Cornus Mas L. Induce Apoptosis In Mcf-7 Breast Cancer Cells, Burcu Uslu, Mustafa Yaman, Tuba Özdemi̇r Sanci, Mustafa Güngörmüş, Çağla Zübeyde Köprü, Fatma Esra Güneş Oct 2023

Acetone Extracts Of Berberis Vulgaris And Cornus Mas L. Induce Apoptosis In Mcf-7 Breast Cancer Cells, Burcu Uslu, Mustafa Yaman, Tuba Özdemi̇r Sanci, Mustafa Güngörmüş, Çağla Zübeyde Köprü, Fatma Esra Güneş

Turkish Journal of Medical Sciences

Background/aim: This study aimed to determine the proliferation and apoptotic effects of extracts from Cornus mas L. and Berberis vulgaris fruits on human breast cancer cells (MCF-7). Materials and methods: The Cornus mas L. and Berberis vulgaris fruits, which constitute the herbal material of the study, were turned into 80% acetone extract after washing. The total phenolic content in Berberis vulgaris fruit extracts was determined calorimetrically using Folin-Ciocalteu reagent. The spectrophotometric method was used to determine the total flavonoid amount of the extracts. In order to measure the antioxidant capacity of Cornus mas L. and Berberis vulgaris fruits and extracts, …


Evaluation Of Syringin?S Neuroprotective Effect In A Model Of Neonatal Hypoxic-Ischemic Brain Injury, Ezgi̇ Yangin Ergon, Asli Çeli̇k, Ayşe Gülden Di̇ni̇z Ünlü, Rüya Çolak, Senem Alkan Özdemi̇r, Şebnem Çalkavur, Osman Yilmaz Oct 2023

Evaluation Of Syringin?S Neuroprotective Effect In A Model Of Neonatal Hypoxic-Ischemic Brain Injury, Ezgi̇ Yangin Ergon, Asli Çeli̇k, Ayşe Gülden Di̇ni̇z Ünlü, Rüya Çolak, Senem Alkan Özdemi̇r, Şebnem Çalkavur, Osman Yilmaz

Turkish Journal of Medical Sciences

Background/aim: A significant cause of mortality and morbidity in the neonatal era is hypoxic-ischemic encephalopathy (HIE). This study examined the histopathological analysis and neuroprotective impact of syringin (SYR) in an experimental HIE rat model. Material and methods: On the 7th postnatal day, 24 Wistar albino rats were evaluated in 3 groups using the HIE model under gas anesthesia. In the experiment, Group A received 10 mg/kg SYR plus dimethyl sulfoxide (DMSO), Group B received DMSO only, and Group C served as a sham group. Immunohistochemical techniques were used to assess apoptotic cell measurement and proinflammatory cytokines (TNF-? and IL-1ß primary …


Absence Of Chordin-Like 1 Aids Motor Recovery In A Mouse Model Of Stroke, Eileen Collyer, Bridget R Boyle, Yolanda Gomez-Galvez, Lorraine Iacovitti, Elena Blanco-Suarez Sep 2023

Absence Of Chordin-Like 1 Aids Motor Recovery In A Mouse Model Of Stroke, Eileen Collyer, Bridget R Boyle, Yolanda Gomez-Galvez, Lorraine Iacovitti, Elena Blanco-Suarez

Farber Institute for Neuroscience Faculty Papers

Chordin-like 1 (Chrdl1) is an astrocyte-secreted protein that regulates synaptic maturation, and limits plasticity via GluA2-containing AMPA receptors (AMPARs). It was demonstrated that Chrdl1 expression is very heterogeneous throughout the brain, and it is enriched in astrocytes in cortical layers 2/3, with peak expression in the visual cortex at postnatal day 14. In response to ischemic stroke, Chrdl1 is upregulated during the acute and sub-acute phases in the peri-infarct region, potentially hindering recovery after stroke. Here, we used photothrombosis to model ischemic stroke in the motor cortex of adult male and female mice. In this study, we demonstrate that elimination …


In Vitro Hepatotoxicity Evaluation Of Methotrexate-Loaded Niosome Formulation: Fabrication, Characterization And Cell Culture Studies, Ahmet Doğan Ergi̇n, Çağatay Oltulu, Nebi̇ye Peli̇n Türker, Gülen Meli̇ke Demi̇rbolat Aug 2023

In Vitro Hepatotoxicity Evaluation Of Methotrexate-Loaded Niosome Formulation: Fabrication, Characterization And Cell Culture Studies, Ahmet Doğan Ergi̇n, Çağatay Oltulu, Nebi̇ye Peli̇n Türker, Gülen Meli̇ke Demi̇rbolat

Turkish Journal of Medical Sciences

Background/aim: Methotrexate (MTX) is a folic acid antagonist that is widely used to treat osteosarcoma, leukemia, breast cancer, and autoimmune and inflammatory diseases. The most important concerns with MTX are its poor solubility and high toxicity, particularly in liver cells. To enhance its solubility and to minimize its toxicity, we encapsulated MTX in niosomes and investigated its hepatotoxicity mechanisms using genetic biomarkers. Materials and methods: Niosomes were successfully prepared using a modified thin film method, and the prepared monodisperse smallsized formulation was subsequently characterized. In vitro cytotoxicity studies were performed both in hepatocarcinoma (HEP3G) and healthy liver (AML12) cell lines. …


The Role Of Curcumin On Apoptosis And Nlrp3 Inflammasome-Dependent Pyroptosis On Colorectal Cancer In Vitro, Zeynep Dal, Başak Aru Aug 2023

The Role Of Curcumin On Apoptosis And Nlrp3 Inflammasome-Dependent Pyroptosis On Colorectal Cancer In Vitro, Zeynep Dal, Başak Aru

Turkish Journal of Medical Sciences

Background/aim: Colorectal cancer (CRC) is one of the most common cancers worldwide. Many factors such as stress, lifestyle, and dietary habits are known to play a role in the initiation and progression of the disease. Herbal therapeutic agents including curcumin can hold a great potential against cancer treatment; however, their efficacy on CRC is still under investigation. Herein, we evaluated the anticancer mechanism of curcumin on four different CRC cell lines. Materials and methods: Cells were treated with curcumin for 24, 48 and 72 h, and IC50 doses for each cell line were calculated. Mechanistic studies were conducted with the …


Mycobacterium Avium Subsp. Paratuberculosis Candidate Vaccine Strains Are Pro-Apoptotic In Raw264.7murinemacrophages, Raul G. Barletta, John P. Bannantine, Judith R. Stabel, Ezhumalai Muthukrishnan, Dirk Anderson, Enakshy Dutta, Vamsi Manthena, Mostafa Hanafy, Denise K. Zinniel Jun 2023

Mycobacterium Avium Subsp. Paratuberculosis Candidate Vaccine Strains Are Pro-Apoptotic In Raw264.7murinemacrophages, Raul G. Barletta, John P. Bannantine, Judith R. Stabel, Ezhumalai Muthukrishnan, Dirk Anderson, Enakshy Dutta, Vamsi Manthena, Mostafa Hanafy, Denise K. Zinniel

School of Veterinary and Biomedical Sciences: Faculty Publications

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of Johne’s disease, a severe gastroenteritis of ruminants. This study developed a model cell culture system to rapidly screen MAP mutants with vaccine potential for apoptosis. Two wild-type strains, a transposon mutant, and two deletion mutant MAP strains (MOI of 10 with 1.2 × 106 CFU) were tested in murine RAW 264.7 macrophages to determine if they induce apoptosis and/or necrosis. Both deletion mutants were previously shown to be attenuated and immunogenic in primary bovine macrophages. All strains had similar growth rates, but cell morphology indicated that both deletion mutants …


Effects Of Recurrent Ketamine Exposure On Brain Histopathology In Juvenile Rats, Ayşe Hande Arpaci, Süheyla Esra Özkoçer, Emel Güneş, Çi̇ğdem Elmas, Berri̇n Işik Jan 2023

Effects Of Recurrent Ketamine Exposure On Brain Histopathology In Juvenile Rats, Ayşe Hande Arpaci, Süheyla Esra Özkoçer, Emel Güneş, Çi̇ğdem Elmas, Berri̇n Işik

Turkish Journal of Medical Sciences

Background/aim: Ketamine (KET) is a commonly used anesthetic agent. However, several previous studies reported that KET leads to neuronal damage in neurodevelopmental stages and has neuroprotective effects. The present experimental study aimed to determine the undesirable histopathological effects of KET in the cerebral cortex, striatum, and hippocampus after recurrent KET administration in juvenile rats. Materials and methods: After ethical approval was obtained, 32 juvenile male Wistar Albino rats were randomized into four groups: 1 mg/kg serum saline intraperitoneally (i.p.), 5 mg/kg KET i.p., 20 mg/kg KET i.p., and 50 mg/kg KET i.p. KET was administered for three consecutive days at …


Chemical Characterization And Biological Evaluation Of Epilobium Parviflorum Extracts In An In Vitro Model Of Human Malignant Melanoma, Sotiris Kyriakou, Venetia Tragkola, Ioannis Paraskevaidis, Mihalis Plioukas, Dimitrios T. Trafalis, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidi Jan 2023

Chemical Characterization And Biological Evaluation Of Epilobium Parviflorum Extracts In An In Vitro Model Of Human Malignant Melanoma, Sotiris Kyriakou, Venetia Tragkola, Ioannis Paraskevaidis, Mihalis Plioukas, Dimitrios T. Trafalis, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidi

School of Veterinary and Biomedical Sciences: Faculty Publications

Malignant melanoma is an aggressive type of skin cancer characterised by high metastatic capacity and mortality rate. On the other hand, Epilobium parviflorum is known for its medicinal properties, including its anticancer potency. In this context, we aimed to (i) isolate various extracts of E. parviflorum, (ii) characterize their phytochemical content, and (iii) determine their cytotoxic potential in an in vitro model of human malignant melanoma. To these ends, we utilized various spectrophotometric and chromatographic (UPLC-MS/MS) approaches to document the higher content of the methanolic extract in polyphenols, soluble sugars, proteins, condensed tannins, and chlorophylls -a and -b as …


Curcumin Promotes Skin Wound Healing By Activating Nrf2 Signaling Pathways And Inducing Apoptosis In Mice, Junli Wu, Li Deng, Ling Yin, Zhirong Mao, Xiaoqing Gao Jan 2023

Curcumin Promotes Skin Wound Healing By Activating Nrf2 Signaling Pathways And Inducing Apoptosis In Mice, Junli Wu, Li Deng, Ling Yin, Zhirong Mao, Xiaoqing Gao

Turkish Journal of Medical Sciences

Background/aim: Curcumin may have potential as a therapy for wound healing, but the underlying mechanism remains unclear. It is not known whether curcumin can promote wound healing by activating Nrf2 signaling pathway and inducing apoptosis. This study determined the role of Nrf2 signaling pathway and apoptosis in curcumin-promoting skin wound healing. Materials and methods: The full-thickness skin defect model of mice was made and randomly divided into a control group and a curcumin group. The mice in the curcumin group and in the control group received respectively a daily topical treatment of Vaseline cream with or without 5 mg curcumin. …


High Energy Blue Light Induces Oxidative Stress And Retinal Cell Apoptosis, Jessica Malinsky Jan 2023

High Energy Blue Light Induces Oxidative Stress And Retinal Cell Apoptosis, Jessica Malinsky

Capstone Showcase

Blue light (BL) is a high energy, short wavelength spanning 400 to 500 nm. Found in technological and environmental forms, BL has been shown to induce photochemical damage of the retina by reactive oxygen species (ROS) production. Excess ROS leads to oxidative stress, which disrupts retinal mitochondrial structure and function. As mitochondria amply occupy photoreceptors, they also contribute to oxidative stress due to their selectively significant absorption of BL at 400 to 500 nm. ROS generation that induces oxidative stress subsequently promotes retinal mitochondrial apoptosis. BL filtering and preventative mechanisms have been suggested to improve or repair BL-induced retinal damage, …


Investigating The P53 Tumor-Suppressive Network And The Dynamics/Mechanism Of P53 Loss Of Heterozygosity, Jun Wang Jan 2023

Investigating The P53 Tumor-Suppressive Network And The Dynamics/Mechanism Of P53 Loss Of Heterozygosity, Jun Wang

All ETDs from UAB

Tumor suppressor gene TP53 is the most frequently mutated gene across human cancers (~50%). Patients with Li-Fraumeni syndrome (LFS) who carry germline p53 mutations exhibit a diverse spectrum of childhood- and adult-onset malignancies. Despite over 40 years of dedicated studies to understand the role of p53 in tumor prevention, there are still many unanswered questions regarding the underlying mechanisms of p53. Previous studies have supported the notion that p53 exerts its tumor-suppressive function through its transcriptional activities. Therefore, strategies to enhance p53’s functions in tumor suppression via manipulating of downstream target gene activities in cancers show promising. To better investigate …


Expression Of St6gal1 Imparts Stem-Like Cell Behaviors, Thereby Promoting Neoplasia, Sejal Sanjay Shinde Jan 2023

Expression Of St6gal1 Imparts Stem-Like Cell Behaviors, Thereby Promoting Neoplasia, Sejal Sanjay Shinde

All ETDs from UAB

Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most lethal malignancies with a five-year survival of ~10%. Recent studies in the US population suggest PDAC as the fourth leading cause of cancer-related deaths in 2022. ST6 β-galactoside α2,6-sialyltransferase (ST6GAL1) is a glycosyltransferase which is known to be upregulated in cancer. It acts as a master regulator of a cell by being the predominant sialyltransferase catalyzing the addition of a bulky negatively charged sialic acid to the galactose sugar in an α2,6-linkage. Due to this, the sialic acid changes the structure and function of cell surface receptor proteins and regulates signal …


Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal Dec 2022

Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal

Electronic Theses and Dissertations

Human Immunodeficiency Virus (HIV) infection initiates major metabolic and cell- survival complications. Anti-retroviral therapy (ART) is the current approach to suppress active HIV replication to a level of undetected viral load, but it is not a curative approach. Newer and sophisticated gene editing technologies could indeed be a potent antiviral therapy to achieve a clinical sterilization/cure of HIV infection. Chronic HIV patients, even under a successful ART regimen, exhibit a low-grade inflammation, immune senescence, premature aging, telomeric DNA attrition, T cell apoptosis, and cellular homeostasis. In this dissertation, we investigated CD4 T cell homeostasis, degree of T cell apoptosis, an …


Modeling The Role Of Cyclin C In Connecting Stress-Induced Mitochondrial Fission To Apoptosis, Steven J. Doyle, Randy Strich May 2022

Modeling The Role Of Cyclin C In Connecting Stress-Induced Mitochondrial Fission To Apoptosis, Steven J. Doyle, Randy Strich

Rowan-Virtua Research Day

For normal cell function, exogenous signals must be correctly interpreted, and the proper response executed. The mitochondria are key regulatory nodes of cellular fate. For example, mitochondria undergo fission and fusion cycles depending on the energetic needs of the cell. Additionally, regulated cell death pathways also function at the mitochondria. Cyclin C is a transcriptional regulator of stress response and growth control genes. Following stress, a portion of cyclin C translocates to the cytoplasm, where it interacts with both the mitochondrial fission and apoptotic machinery. Based on these findings, we hypothesize that Cyclin C represents a key mediator linking transcription …


Viridiflorol Induces Anti-Neoplastic Effects On Breast, Lung, And Brain Cancer Cells Through Apoptosis, Maaged A. Akiel, Ohoud Y. Alshehri, Shokran A. Aljihani, Amani Almuaysib, Ammar Bader, Ahmed I. Al‐Asmari, Hassan S. Alamri, Bahauddeen M. Alrfaei, Majed A. Halwani Jan 2022

Viridiflorol Induces Anti-Neoplastic Effects On Breast, Lung, And Brain Cancer Cells Through Apoptosis, Maaged A. Akiel, Ohoud Y. Alshehri, Shokran A. Aljihani, Amani Almuaysib, Ammar Bader, Ahmed I. Al‐Asmari, Hassan S. Alamri, Bahauddeen M. Alrfaei, Majed A. Halwani

Human and Molecular Genetics Publications

All active natural molecules are not fully exploited as therapeutic agents, causing delays in the advancement of anticancer drug discovery. Viridiflorol is a natural volatile element that may work as anti-cancer compound. We tested the anticancer properties of viridiflorol at different concentrations ranging from 0.03 to 300 μM in vitro on three cancer cells including breast (MCF-7), lung (A549) and brain (Daoy). The cancer cells responses were documented after treatment using MTT and Annexin V assays. Viridiflorol showed cytotoxic effects against all tested cell lines, reducing cell viability in a concentration-dependent manner with variable IC50 values. Daoy and A549 cell …


Sorafenib, Rapamycin, And Venetoclax Attenuate Doxorubicin-Induced Senescence And Promote Apoptosis In Hct116 Cells, Homood M. As Sobeai, Munirah Alohaydib, Ali R. Alhoshani, Khalid Alhazzani, Mashal M. Almutairi, Tareq Saleh, David A. Gewirtz, Moureq R. Alotiabi Jan 2022

Sorafenib, Rapamycin, And Venetoclax Attenuate Doxorubicin-Induced Senescence And Promote Apoptosis In Hct116 Cells, Homood M. As Sobeai, Munirah Alohaydib, Ali R. Alhoshani, Khalid Alhazzani, Mashal M. Almutairi, Tareq Saleh, David A. Gewirtz, Moureq R. Alotiabi

Pharmacology and Toxicology Publications

Emerging evidence has shown that the therapy-induced senescent growth arrest in cancer cells is of durable nature whereby a subset of cells can reinstate proliferative capacity. Promising new drugs named senolytics selectively target senescent cells and commit them into apoptosis. Accordingly, senolytics have been proposed as adjuvant cancer treatment to cull senescent tumor cells, and thus, screening for agents that exhibit senolytic properties is highly warranted. Our study aimed to investigate three agents, sorafenib, rapamycin, and venetoclax for their senolytic potential in doxorubicin-induced senescence in HCT116 cells. HCT116 cells were treated with one of the three agents, sorafenib …


Favorable Efficacy Of Adalimumab Treatment In Experimental Acute Pancreatitis Model, Başak Çakir Güney, Alpaslan Tanoğlu, Murat Yeni̇çeri̇, Zafer Çirak, Ayşe Gökçen Sade, Yeşi̇m Önal Taştan, Zeli̇ha Seri̇ndağ, Mustafa Kaplan Jan 2022

Favorable Efficacy Of Adalimumab Treatment In Experimental Acute Pancreatitis Model, Başak Çakir Güney, Alpaslan Tanoğlu, Murat Yeni̇çeri̇, Zafer Çirak, Ayşe Gökçen Sade, Yeşi̇m Önal Taştan, Zeli̇ha Seri̇ndağ, Mustafa Kaplan

Turkish Journal of Medical Sciences

Background/aim: Acute pancreatitis is a clinical picture with a wide range of symptoms from mild inflammation to multiorgan failure and death. The aim of this study is to investigate the effects of Adalimumab (ADA) on inflammation and apoptosis in a cerulein-induced acute pancreatitis model in rats. Material and methods: Experimental cerulein-induced acute pancreatitis model was created by applying 4 intraperitoneal cerulein injections at 1-h intervals. A total of 40 rats, 8 in each group, were randomly distributed into five groups. In the groups that ADA treatment was given, two different doses of ADA were administered 5 mg/kg and 20 mg/kg …


Targeting The Cdk6 Dependence Of Ph+ Acute Lymphoblastic Leukemia, Patrizia Porazzi, Marco De Dominici, Joseph Salvino, Bruno Calabretta Sep 2021

Targeting The Cdk6 Dependence Of Ph+ Acute Lymphoblastic Leukemia, Patrizia Porazzi, Marco De Dominici, Joseph Salvino, Bruno Calabretta

Department of Cancer Biology Faculty Papers

Ph+ ALL is a poor-prognosis leukemia subtype driven by the BCR-ABL1 oncogene, either the p190-or the p210-BCR/ABL isoform in a 70:30 ratio. Tyrosine Kinase inhibitors (TKIs) are the drugs of choice in the therapy of Ph+ ALL. In combination with standard chemotherapy, TKIs have markedly improved the outcome of Ph+ ALL, in particular if this treatment is followed by bone marrow transplantation. However, resistance to TKIs develops with high frequency, causing leukemia relapse that results in


Multiple Autonomous Cell Death Suppression Strategies Ensure Cytomegalovirus Fitness, Pratyusha Mandal, Lynsey Nagrani, Liliana Hernandez, Anita Louise Mccormick, Christopher Dillon, Heather Koehler, Linda Roback, Emad S Alnemri, Douglas Green, Edward Mocarski Aug 2021

Multiple Autonomous Cell Death Suppression Strategies Ensure Cytomegalovirus Fitness, Pratyusha Mandal, Lynsey Nagrani, Liliana Hernandez, Anita Louise Mccormick, Christopher Dillon, Heather Koehler, Linda Roback, Emad S Alnemri, Douglas Green, Edward Mocarski

Department of Biochemistry and Molecular Biology Faculty Papers

Programmed cell death pathways eliminate infected cells and regulate infection-associated inflammation during pathogen invasion. Cytomegaloviruses encode several distinct suppressors that block intrinsic apoptosis, extrinsic apoptosis, and necroptosis, pathways that impact pathogenesis of this ubiquitous herpesvirus. Here, we expanded the understanding of three cell autonomous suppression mechanisms on which murine cytomegalovirus relies: (i) M38.5-encoded viral mitochon-drial inhibitor of apoptosis (vMIA), a BAX suppressor that functions in concert with M41.1-encoded viral inhibitor of BAK oligomerization (vIBO), (ii) M36-encoded viral inhibitor of caspase-8 activation (vICA), and (iii) M45-encoded viral inhibitor of RIP/RHIM activation (vIRA). Following infection of bone marrow-derived macrophages, the virus initially …


Distinct Mechanisms Control Genome Recognition By P53 At Its Target Genes Linked To Different Cell Fates., Marina Farkas, Hideharu Hashimoto, Yingtao Bi, Ramana V Davuluri, Lois Resnick-Silverman, James J. Manfredi, Erik W. Debler, Steven B. Mcmahon Jan 2021

Distinct Mechanisms Control Genome Recognition By P53 At Its Target Genes Linked To Different Cell Fates., Marina Farkas, Hideharu Hashimoto, Yingtao Bi, Ramana V Davuluri, Lois Resnick-Silverman, James J. Manfredi, Erik W. Debler, Steven B. Mcmahon

Department of Biochemistry and Molecular Biology Faculty Papers

The tumor suppressor p53 integrates stress response pathways by selectively engaging one of several potential transcriptomes, thereby triggering cell fate decisions (e.g., cell cycle arrest, apoptosis). Foundational to this process is the binding of tetrameric p53 to 20-bp response elements (REs) in the genome (RRRCWWGYYYN0-13RRRCWWGYYY). In general, REs at cell cycle arrest targets (e.g. p21) are of higher affinity than those at apoptosis targets (e.g., BAX). However, the RE sequence code underlying selectivity remains undeciphered. Here, we identify molecular mechanisms mediating p53 binding to high- and low-affinity REs by showing that key determinants of the code are embedded …


Repurposing Niclosamide For Targeting Pancreatic Cancer By Inhibiting Hh/Gli Non-Canonical Axis Of Gsk3Β, Jyoti B. Kaushal, Rakesh Bhatia, Ranjana K. Kanchan, Pratima Raut, Surya Mallapragada, Quan P. Ly, Surinder K. Batra, Satyanarayana Rachagani Jan 2021

Repurposing Niclosamide For Targeting Pancreatic Cancer By Inhibiting Hh/Gli Non-Canonical Axis Of Gsk3Β, Jyoti B. Kaushal, Rakesh Bhatia, Ranjana K. Kanchan, Pratima Raut, Surya Mallapragada, Quan P. Ly, Surinder K. Batra, Satyanarayana Rachagani

Journal Articles: Biochemistry & Molecular Biology

Niclosamide (Nic), an FDA-approved anthelmintic drug, is reported to have anti-cancer efficacy and is being assessed in clinical trials for various solid tumors. Based on its ability to target multiple signaling pathways, in the present study, we evaluated the therapeutic efficacy of Nic on pancreatic cancer (PC) in vitro. We observed an anti-cancerous effect of this drug as shown by the G0/G1 phase cell cycle arrest, inhibition of PC cell viability, colony formation, and migration. Our results revealed the involvement of mitochondrial stress and mTORC1-dependent autophagy as the predominant players of Nic-induced PC cell death. Significant reduction of Nic-induced reactive …


What Is The Restorative Effect Of Vegf Inhibitor Bevacuzimab Against Subarachnoidhemorrhage In An Experimental Model?, Adnan Yalçin Demi̇rci̇, Yahya Güvenç, Ersi̇n Özeren, Çeti̇n Akyol, Pinar Bayram, Deni̇z Bi̇llur, Sevi̇m Aydin, Hakan Seçki̇n, Kazim Yi̇ği̇tkanli Jan 2021

What Is The Restorative Effect Of Vegf Inhibitor Bevacuzimab Against Subarachnoidhemorrhage In An Experimental Model?, Adnan Yalçin Demi̇rci̇, Yahya Güvenç, Ersi̇n Özeren, Çeti̇n Akyol, Pinar Bayram, Deni̇z Bi̇llur, Sevi̇m Aydin, Hakan Seçki̇n, Kazim Yi̇ği̇tkanli

Turkish Journal of Medical Sciences

Background/aim: This study investigated the effect of vascular endothelial growth factor (VEGF) inhibitor bevacuzimab (BVZ) on the rabbit basilar artery using an experimental subarachnoid hemorrhage (SAH) model. Materials and methods: Eighteen adult male New-Zealand white rabbits were randomly divided into three groups: a control group (n = 6), SAH group (n = 6), and SAH+BVZ group (n = 6). Experimental SAH was created by injecting autologous arterial blood into the cisterna magna. In the treatment group, the subjects were administered a daily dose of 10 mg/kg, intravenous BVZ for 2 days after the SAH. Basilar artery diameters were measured with …


The Protective Effects Of Anakinra In A Neonatal Rat Model Of Necrotizing Enterocolitis, Hati̇ce Güneş, Sevcan İpek, Sadik Yurttutan, Tuncay Kuloğlu, Fatma İnanç Tolun, Ülkü Kazanci, Adem Doğaner Jan 2021

The Protective Effects Of Anakinra In A Neonatal Rat Model Of Necrotizing Enterocolitis, Hati̇ce Güneş, Sevcan İpek, Sadik Yurttutan, Tuncay Kuloğlu, Fatma İnanç Tolun, Ülkü Kazanci, Adem Doğaner

Turkish Journal of Medical Sciences

Background/aim: Necrotizing enterocolitis (NEC) is a commonly seen life-threatening condition in newborns characterized by ischemic necrosis. This study aimed to investigate anakinra's effects, an interleukin-1 receptor antagonist, on oxidative stress, inflammation, and tissue necrosis in an NEC rat model. Materials and methods: Forty Wistar albino pups were divided into four groups randomly as follows; group 1, control group; group 2, anakinra-treated control group; group 3, NEC group; and group 4, NEC and anakinra treatment group. The rats were given hyperosmolar formula feeding, and they were exposed to hypoxia after cold stress at +4 °C and oxygen in order to create …


Beyond Apoptosis: Insight Into The Complex Intracellular Networks That Govern Cell Fate, Hayley Neal Widden Jan 2021

Beyond Apoptosis: Insight Into The Complex Intracellular Networks That Govern Cell Fate, Hayley Neal Widden

All ETDs from UAB

The determination of cell fate is a dynamic process regulated by hundreds of proteins that converge into complex cell signaling pathways. Upon irreparable intracellular stress, a cell undergoes programmed cell death, a process known as intrinsic apoptosis. Apoptosis is regulated by the Bcl-2 family, a class of proteins that act either as pro-survival or pro-death signaling molecules. Due to the oncogenic upregulation of pro- survival Bcl-2 family proteins across human cancer cell types, a novel class of small molecule inhibitors called ‘BH3-mimetics’ have emerged as promising anti-cancer therapeutics currently under clinical investigation. Here, we highlight the crosstalk between anti-apoptotic Bcl-2 …


The Effect Of Testosterone Replacement Therapy On Bladder Functions, Histology, Apoptosis,And Rho-Kinase Expression In Bladder Outlet Obstruction And Hypogonadism Rat Model, Bariş Saylam, Ozan Efesoy, Rabi̇a Bozdoğan Arpaci, Ruki̇ye Nalan Ti̇fti̇k, Mesut Tek, Kansu Büyükafşar, Murat Bozlu, Selahi̇tti̇n Çayan Jan 2021

The Effect Of Testosterone Replacement Therapy On Bladder Functions, Histology, Apoptosis,And Rho-Kinase Expression In Bladder Outlet Obstruction And Hypogonadism Rat Model, Bariş Saylam, Ozan Efesoy, Rabi̇a Bozdoğan Arpaci, Ruki̇ye Nalan Ti̇fti̇k, Mesut Tek, Kansu Büyükafşar, Murat Bozlu, Selahi̇tti̇n Çayan

Turkish Journal of Medical Sciences

Background/aim: The effect of testosterone replacement therapy was investigated on bladder functions, histology, apoptosis as well as Rho-kinase expression in the rat bladder outlet obstruction (BOO) and hypogonadism models. Materials and methods: 30 mature male rats divided into 4 groups: sham group (n = 8), BOO group (n = 8), BOO + orchiectomy group (n = 7), BOO + orchiectomy + testosterone (T) treatment group (n = 7). Cystometric findings, apoptosis index, Rho-kinase (ROCK-2) expression, and smooth muscle/collagen ratio were compared. Results: BOO did not change ROCK-2 expression level, compared to sham group (P > 0.05). However, when compared to BOO …


Manf Is Neuroprotective Against Ethanol-Induced Neurodegeneration Through Ameliorating Er Stress, Yongchao Wang, Wen Wen, Hui Li, Marco Clementino, Hong Xu, Mei Xu, Murong Ma, Jacqueline A. Frank, Jia Luo Dec 2020

Manf Is Neuroprotective Against Ethanol-Induced Neurodegeneration Through Ameliorating Er Stress, Yongchao Wang, Wen Wen, Hui Li, Marco Clementino, Hong Xu, Mei Xu, Murong Ma, Jacqueline A. Frank, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Fetal alcohol spectrum disorders (FASD) are a spectrum of developmental disorders caused by prenatal alcohol exposure. Neuronal loss or neurodegeneration in the central nervous system (CNS) is one of the most devastating features in FASD. It is imperative to delineate the underlying mechanisms to facilitate the treatment of FASD. Endoplasmic reticulum (ER) stress is a hallmark and an underlying mechanism of many neurodegenerative diseases, including ethanol-induced neurodegeneration. Mesencephalic astrocyte-derived neurotrophic factor (MANF) responds to ER stress and has been identified as a protein upregulated in response to ethanol exposure during the brain development. To investigate the role of MANF in …


Mir-132-3p Priming Enhances The Effects Of Mesenchymal Stromal Cell-Derived Exosomes On Ameliorating Brain Ischemic Injury, Qunwen Pan, Xiaoli Kuang, Shuyun Cai, Xiang Wang, Donghui Du, Jinju Wang, Yan Wang, Yanyu Chen, Ji Chen Bihl, Yanfang Chen, Bin Zhao, Xiaotang Ma Jun 2020

Mir-132-3p Priming Enhances The Effects Of Mesenchymal Stromal Cell-Derived Exosomes On Ameliorating Brain Ischemic Injury, Qunwen Pan, Xiaoli Kuang, Shuyun Cai, Xiang Wang, Donghui Du, Jinju Wang, Yan Wang, Yanyu Chen, Ji Chen Bihl, Yanfang Chen, Bin Zhao, Xiaotang Ma

Pharmacology and Toxicology Faculty Publications

Backgrounds/aims: Mesenchymal stromal cell-derived exosomes (MSC-EXs) could exert protective effects on recipient cells by transferring the contained microRNAs (miRs), and miR-132-3p is one of angiogenic miRs. However, whether the combination of MSC-EXs and miR-132-3p has better effects in ischemic cerebrovascular disease remains unknown. Methods: Mouse MSCs transfected with scrambler control or miR-132-3p mimics were used to generate MSC-EXs and miR-132-3p-overexpressed MSC-EXs (MSC-EXsmiR-132-3p). The effects of EXs on hypoxia/reoxygenation (H/R)-injured ECs in ROS generation, apoptosis, and barrier function were analyzed. The levels of RASA1, Ras, phosphorylations of PI3K, Akt and endothelial nitric oxide synthesis (eNOS), and tight junction proteins (Claudin-5 and …


Effects Of Alternative Chemotherapeutic Agents On Thyroid Cancer Cell Line Ml-1, Husref Rizvanovic May 2020

Effects Of Alternative Chemotherapeutic Agents On Thyroid Cancer Cell Line Ml-1, Husref Rizvanovic

MSU Graduate Theses

Though differentiated thyroid carcinomas have decent prognosis when detected early, radioactive iodine (RAI) resistant and advanced thyroid cancers are still difficult to treat with existing therapies. Better therapeutic agents are needed. Studies have shown that aggressive thyroid cancers (ML-1) express the extracellular matrix protein, matrix metalloproteinase (MMP-2). MMP-2 has been linked to metastasis and aggressiveness of several cancers and has been shown to play a crucial role in tumor invasion. Chlorotoxin is a selective MMP-2 receptor agonist, and Saporin is a well-known ribosome-inactivating protein used for anti-cancer treatment; however, these two agents have never been studied when conjugated together. I …


Cell-Free Dna Release During Programmed Cell Death In Kidney Ischemia Reperfusion Injury, Alexander Dionne Feb 2020

Cell-Free Dna Release During Programmed Cell Death In Kidney Ischemia Reperfusion Injury, Alexander Dionne

Electronic Thesis and Dissertation Repository

Transplantation is invariably associated with ischemia reperfusion injury (IRI) which causes organ dysfunction. IRI is also directly linked to several forms of programmed cell death including apoptosis and necroptosis, which increase kidney dysfunction, promote inflammation and may contribute to premature graft failure. The contribution of necroptosis and apoptosis following kidney IRI to cell-free DNA (cfDNA) generation and the potential of cfDNA to activate effectors such as NK cells involved in kidney IRI have not been defined. Our data indicate that necroptotic microvascular endothelial cells (MVECs) release considerably more cfDNA than apoptotic MVECs or untreated controls (p


Perivascular Macrophages In The Neonatal Macaque Brain Undergo Massive Necroptosis After Simian Immunodeficiency Virus Infection, Diana G. Bohannon, Yueying Wang, Colin H. Reinhart, Julian B. Hattler, Jiangtao Luo, Hamid R. Okhravi, Jianshui Zhang, Qingsheng Li, Marcelo J. Kuroda, Woong-Ki Kim Jan 2020

Perivascular Macrophages In The Neonatal Macaque Brain Undergo Massive Necroptosis After Simian Immunodeficiency Virus Infection, Diana G. Bohannon, Yueying Wang, Colin H. Reinhart, Julian B. Hattler, Jiangtao Luo, Hamid R. Okhravi, Jianshui Zhang, Qingsheng Li, Marcelo J. Kuroda, Woong-Ki Kim

Nebraska Center for Virology: Faculty Publications

We previously showed that rhesus macaques neonatally infected with simian immunodeficiency virus (SIV) do not develop SIV encephalitis (SIVE) and maintain low brain viral loads despite having similar plasma viral loads compared to SIV-infected adults. We hypothesize that differences in myeloid cell populations that are the known target of SIV and HIV in the brain contribute to the lack of neonatal susceptibility to lentivirus-induced encephalitis. Using immunohistochemistry and immunofluorescence microscopy, we examined the frontal cortices from uninfected and SIV-infected infant and adult macaques (n = 8/ea) as well as adults with SIVE (n = 4) to determine differences in myeloid …