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1.
Trauma Surg Acute Care Open ; 6(1): e000608, 2021.
Article in English | MEDLINE | ID: mdl-33490604

ABSTRACT

Recent military conflicts in Iraq and Afghanistan have resulted in the significant increase in blast-related traumatic brain injury (TBI), leading to increased Department of Defense interest in its potential long-term effects ranging from the mildest head injuries termed subconcussive trauma to the most debilitating termed chronic traumatic encephalopathy (CTE). Most patients with mild TBI will recover quickly while others report persistent symptoms called postconcussive syndrome. Repeated concussive and subconcussive head injuries result in neurodegenerative conditions that may hinder the injured for years. Fundamental questions about the nature of these injuries and recovery remain unanswered. Clinically, patients with CTE present with either affective changes or cognitive impairment. Genetically, there have been no clear risk factors identified. The discovery that microglia of the cerebral cortex discharged small extracellular vesicles in the injured and adjacent regions to a TBI may soon shed light on the immediate impact injury mechanisms. The combination of neuroimaging and advanced research techniques may, one day, fill critical knowledge gaps and lead to significant TBI research and treatment advancements.

3.
Proteomics Clin Appl ; 11(9-10)2017 09.
Article in English | MEDLINE | ID: mdl-28544811

ABSTRACT

Traumatic brain injuries (TBI) are among the most misdiagnosed and underreported types of head trauma. The potential long-term impact of undiagnosed or incorrectly identified concussions and other head injuries are potentially devastating, as evidenced by the increasing societal burden exhibited by soldiers returning from combat and athletes in contact sports. Concussions and TBI are notoriously difficult to correctly diagnose and prognosis for these injuries is poorly understood. In order to increase the likelihood of successful diagnosis, treatment, and prediction of outcomes, a definitive differential diagnosis will need to be established. The establishment of a "trauma-specific profile" or a panel of known trauma markers will significantly aid in this goal. Small membrane vesicles called exosomes have been shown to contain proteins and injury-specific biomarkers. In the future it is possible that they could become an important tool, utilized for their diagnostic and therapeutic potential.


Subject(s)
Brain Injuries, Traumatic/metabolism , Brain Injuries, Traumatic/pathology , Exosomes/metabolism , Gene Expression Profiling , Biomarkers/blood , Brain Injuries, Traumatic/blood , Humans
4.
Pancreas ; 45(1): 101-9, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26348467

ABSTRACT

OBJECTIVES: The inhibitor of apoptosis (IAP) proteins are critical modulators of chemotherapeutic resistance in various cancers. To address the alarming emergence of chemotherapeutic resistance in pancreatic cancer, we investigated the efficacy of the turmeric derivative curcumin in reducing IAP protein and mRNA expression resulting in pancreatic cancer cell death. METHODS: The pancreatic adenocarcinoma cell line PANC-1 was used to assess curcumin's effects in pancreatic cancer. Curcumin uptake was measured by spectral analysis and fluorescence microscopy. AlamarBlue and Trypan blue exclusion assays were used to determine PANC-1 cell viability after curcumin treatment. Visualization of PANC-1 cell death was performed using Hoffman Modulation Contrast microscopy. Western blot, and polymerase chain reaction analyses were used to evaluate curcumin's effects on IAP protein and mRNA expression. RESULTS: Curcumin enters PANC-1 cells and is ubiquitously present within the cell after treatment. Furthermore, curcumin reduces cell viability and induces morphological changes characteristic of cell death. Additionally, curcumin decreases IAP protein and mRNA expression in PANC-1 cells. CONCLUSIONS: These data demonstrate that PANC-1 cells are sensitive to curcumin treatment. Futthermore, curcumin is a potential therapeutic tool for overcoming chemotherapeutic resistance mediated by IAPs. Together, this data supports a role for curcumin as part of the therapeutic approach for the treatment of pancreatic cancer.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Carcinoma, Pancreatic Ductal/drug therapy , Curcumin/pharmacology , Inhibitor of Apoptosis Proteins/metabolism , Pancreatic Neoplasms/drug therapy , Antineoplastic Agents, Phytogenic/metabolism , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/pathology , Cell Line, Tumor , Cell Shape/drug effects , Cell Survival/drug effects , Curcumin/metabolism , Dose-Response Relationship, Drug , Gene Expression Regulation, Neoplastic , Humans , Inhibitor of Apoptosis Proteins/genetics , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Signal Transduction/drug effects , Time Factors
5.
Biologics ; 9: 57-67, 2015.
Article in English | MEDLINE | ID: mdl-26185415

ABSTRACT

Survivin is one of the most important members of the inhibitors of apoptosis protein family, as it is expressed in most human cancers but is absent in normal, differentiated tissues. Lending to its importance, survivin has proven associations with apoptosis and cell cycle control, and has more recently been shown to modulate the tumor microenvironment and immune evasion as a result of its extracellular localization. Upregulation of survivin has been found in many cancers including breast, prostate, pancreatic, and hematological malignancies, and it may prove to be associated with the advanced presentation, poorer prognosis, and lower survival rates observed in ethnically diverse populations.

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