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Investigation Of Autosegmentation Techniques On T2-Weighted Mri For Off-Line Dose Reconstruction In Mr-Linac Workflow For Head And Neck Cancers, Brigid A Mcdonald, Carlos E Cardenas, Nicolette O'Connell, Sara Ahmed, Mohamed A Naser, Kareem A Wahid, Jiaofeng Xu, Dan Thill, Raed J Zuhour, Shane Mesko, Alexander Augustyn, Samantha M Buszek, Stephen Grant, Bhavana V Chapman, Alexander F Bagley, Renjie He, Abdallah S R Mohamed, John Christodouleas, Kristy K Brock, Clifton D Fuller Jan 2024

Investigation Of Autosegmentation Techniques On T2-Weighted Mri For Off-Line Dose Reconstruction In Mr-Linac Workflow For Head And Neck Cancers, Brigid A Mcdonald, Carlos E Cardenas, Nicolette O'Connell, Sara Ahmed, Mohamed A Naser, Kareem A Wahid, Jiaofeng Xu, Dan Thill, Raed J Zuhour, Shane Mesko, Alexander Augustyn, Samantha M Buszek, Stephen Grant, Bhavana V Chapman, Alexander F Bagley, Renjie He, Abdallah S R Mohamed, John Christodouleas, Kristy K Brock, Clifton D Fuller

Faculty, Staff and Student Publications

Background: In order to accurately accumulate delivered dose for head and neck cancer patients treated with the Adapt to Position workflow on the 1.5T magnetic resonance imaging (MRI)-linear accelerator (MR-linac), the low-resolution T2-weighted MRIs used for daily setup must be segmented to enable reconstruction of the delivered dose at each fraction.

Purpose: In this pilot study, we evaluate various autosegmentation methods for head and neck organs at risk (OARs) on on-board setup MRIs from the MR-linac for off-line reconstruction of delivered dose.

Methods: Seven OARs (parotid glands, submandibular glands, mandible, spinal cord, and brainstem) were contoured on 43 images by …


The Mir-17-92 Cluster In Cardiac Health And Disease, Yuhan Cao, Mingjie Zheng, Maham A Sewani, Jun Wang Jan 2024

The Mir-17-92 Cluster In Cardiac Health And Disease, Yuhan Cao, Mingjie Zheng, Maham A Sewani, Jun Wang

Faculty, Staff and Student Publications

MicroRNAs (miRs) are small noncoding RNAs that play important roles in both physiological and pathological processes through post-transcriptional regulation. The miR-17-92 cluster includes six individual members: miR-17, miR-18a, miR-19a, miR-19b-1, miR-20a, and miR-92a-1. The miR-17-92 cluster has been extensively studied and reported to broadly function in cancer biology, immunology, neurology, pulmonology, and cardiology. This review focuses on its roles in heart development and cardiac diseases. We briefly introduce the nature of the miR-17-92 cluster and its crucial roles in both normal development and the pathogenesis of various diseases. We summarize the recent progress in understanding the versatile roles of miR-17-92 …


Hormone Regulation Of Corticotropin-Releasing Factor Receptor 1 In The Female Mouse Brain, Rose M De Guzman, Jason S Jacobskind, Zachary J Rosinger, Krystyna A Rybka, Katherine E Parra, Aya L Caballero, Massoud S Sharif, Nicholas J Justice, Damian G Zuloaga Jan 2024

Hormone Regulation Of Corticotropin-Releasing Factor Receptor 1 In The Female Mouse Brain, Rose M De Guzman, Jason S Jacobskind, Zachary J Rosinger, Krystyna A Rybka, Katherine E Parra, Aya L Caballero, Massoud S Sharif, Nicholas J Justice, Damian G Zuloaga

Faculty, Staff and Student Publications

Introduction: Corticotropin-releasing factor receptor 1 (CRFR1) is a key regulator of neuroendocrine and behavioral stress responses. Previous studies have demonstrated that CRFR1 in certain hypothalamic and preoptic brain areas is modified by chronic stress and during the postpartum period in female mice, although the potential hormonal contributors to these changes are unknown.

Methods: This study focused on determining the contributions of hormones associated with stress and the maternal period (glucocorticoids, prolactin, estradiol/progesterone) on CRFR1 levels using a CRFR1-GFP reporter mouse line and immunohistochemistry.

Results: Administration of dexamethasone, an agonist of the glucocorticoid receptor, elevated CRFR1 in the anteroventral periventricular nucleus …


Generation Of Non-Alloreactive Antiviral Central Memory Cd8 Human Veto T Cells For Cell Therapy, Esther Bachar-Lustig, Assaf Lask, Yaki Eidelstein, Noga Or-Geva, Rotem Gidron-Budovsky, Bar Nathansohn-Levy, Matthias Eyrich, Wei-Hsin Liu, Giang Dang, Karla Castro Miranda, Alejandro Ramirez, Indreshpal Kaur, Katayoun Rezvani, Elizabeth Shpall, Richard E Champlin, Arnon Nagler, Avichai Shimoni, Sivan Barnees-Kagan, Yair Reisner Jan 2024

Generation Of Non-Alloreactive Antiviral Central Memory Cd8 Human Veto T Cells For Cell Therapy, Esther Bachar-Lustig, Assaf Lask, Yaki Eidelstein, Noga Or-Geva, Rotem Gidron-Budovsky, Bar Nathansohn-Levy, Matthias Eyrich, Wei-Hsin Liu, Giang Dang, Karla Castro Miranda, Alejandro Ramirez, Indreshpal Kaur, Katayoun Rezvani, Elizabeth Shpall, Richard E Champlin, Arnon Nagler, Avichai Shimoni, Sivan Barnees-Kagan, Yair Reisner

Faculty, Staff and Student Publications

Previous studies in mice demonstrated that CD8 T cells exhibit marked veto activity enhancing engraftment in several models for T cell-depleted bone marrow (TDBM) allografting. To reduce the risk of graft-versus-host disease (GVHD) associated with allogeneic CD8 veto T cells, these studies made use of naive CD8 T cells stimulated against third-party stimulators under cytokine deprivation and subsequent expansion in the presence of IL-15. More recently, it was shown that mouse CD8 veto T cells can be generated by stimulating CD8 memory T cells from ovalbumin immunized mice under cytokine deprivation, using ovalbumin as a third-party antigen. These cells also …


A Blood-Based Metabolite Signature For Personalized Risk Assessment Of Pancreatic Cancer, Ricardo A León-Letelier, Yihui Chen, Riccardo Ballaro, Ehsan Irajizad, Kim-An Do, Anirban Maitra, Jianjun Zhang, C Max Schmidt, Johannes F Fahrmann Jan 2024

A Blood-Based Metabolite Signature For Personalized Risk Assessment Of Pancreatic Cancer, Ricardo A León-Letelier, Yihui Chen, Riccardo Ballaro, Ehsan Irajizad, Kim-An Do, Anirban Maitra, Jianjun Zhang, C Max Schmidt, Johannes F Fahrmann

Faculty, Staff and Student Publications

No abstract provided.


Emerging Therapeutic Options For Follicular-Derived Thyroid Cancer In The Era Of Immunotherapy, Naimah Turner, Sarah Hamidi, Rim Ouni, Rene Rico, Ying C Henderson, Maria Puche, Sayan Alekseev, Jocelynn G Colunga-Minutti, Mark E Zafereo, Stephen Y Lai, Sang T Kim, Maria E Cabanillas, Roza Nurieva Jan 2024

Emerging Therapeutic Options For Follicular-Derived Thyroid Cancer In The Era Of Immunotherapy, Naimah Turner, Sarah Hamidi, Rim Ouni, Rene Rico, Ying C Henderson, Maria Puche, Sayan Alekseev, Jocelynn G Colunga-Minutti, Mark E Zafereo, Stephen Y Lai, Sang T Kim, Maria E Cabanillas, Roza Nurieva

Faculty, Staff and Student Publications

Although most follicular-derived thyroid cancers are well differentiated and have an overall excellent prognosis following treatment with surgery and radioiodine, management of advanced thyroid cancers, including iodine refractory disease and poorly differentiated/undifferentiated subtypes, is more challenging. Over the past decade, better understanding of the genetic drivers and immune milieu of advanced thyroid cancers has led to significant progress in the management of these patients. Numerous targeted kinase inhibitors are now approved by the U.S Food and Drug administration (FDA) for the treatment of advanced, radioiodine refractory differentiated thyroid cancers (DTC) as well as anaplastic thyroid cancer (ATC). Immunotherapy has also …


Enhancing Efficacy Of The Mek Inhibitor Trametinib With Paclitaxel In Kras-Mutated Colorectal Cancer, Susmita Ghosh, Fan Fan, Reid Powell, Yong Sung Park, Clifford Stephan, E Scott Kopetz, Lee M Ellis, Rajat Bhattacharya Jan 2024

Enhancing Efficacy Of The Mek Inhibitor Trametinib With Paclitaxel In Kras-Mutated Colorectal Cancer, Susmita Ghosh, Fan Fan, Reid Powell, Yong Sung Park, Clifford Stephan, E Scott Kopetz, Lee M Ellis, Rajat Bhattacharya

Faculty, Staff and Student Publications

Background: KRAS is frequently mutated in the tumors of patients with metastatic colorectal cancer (mCRC) and thus represents a valid target for therapy. However, the strategies of targeting KRAS directly and targeting the downstream effector mitogen-activated protein kinase kinase (MEK) via monotherapies have shown limited efficacy. Thus, there is a strong need for novel, effective combination therapies to improve MEK-inhibitor efficacy in patients with KRAS-mutated mCRC.

Objective: Our objective was to identify novel drug combinations that enhance MEK-inhibitor efficacy in patients with KRAS-mutated mCRC.

Design: In this study, we performed unbiased high-throughput screening (HTS) to identify drugs that …


Enhanced Tumor Control And Survival In Preclinical Models With Adoptive Cell Therapy Preceded By Low-Dose Radiotherapy, Nahum Puebla-Osorio, Natalie Wall Fowlkes, Hampartsoum B Barsoumian, Kristina Xega, Gitika Srivastava, Claudia Kettlun-Leyton, Sara Nizzero, Tiffany Voss, Thomas S Riad, Christina Wong, Ailing Huang, Yun Hu, Joylise Mitchell, Mingee Kim, Zahid Rafiq, Kewen He, Duygu Sezen, Ethan Hsu, Fatemeh Masrorpour, Aurian Maleki, Carola Leuschner, Maria Angelica Cortez, Philipp Oertle, Marko Loparic, Marija Plodinec, Janet L Markman, James W Welsh Jan 2024

Enhanced Tumor Control And Survival In Preclinical Models With Adoptive Cell Therapy Preceded By Low-Dose Radiotherapy, Nahum Puebla-Osorio, Natalie Wall Fowlkes, Hampartsoum B Barsoumian, Kristina Xega, Gitika Srivastava, Claudia Kettlun-Leyton, Sara Nizzero, Tiffany Voss, Thomas S Riad, Christina Wong, Ailing Huang, Yun Hu, Joylise Mitchell, Mingee Kim, Zahid Rafiq, Kewen He, Duygu Sezen, Ethan Hsu, Fatemeh Masrorpour, Aurian Maleki, Carola Leuschner, Maria Angelica Cortez, Philipp Oertle, Marko Loparic, Marija Plodinec, Janet L Markman, James W Welsh

Faculty, Staff and Student Publications

Introduction: Effective infiltration of chimeric antigen receptor T (CAR-T) cells into solid tumors is critical for achieving a robust antitumor response and improving therapeutic outcomes. While CAR-T cell therapies have succeeded in hematologic malignancies, their efficacy in solid tumors remains limited due to poor tumor penetration and an immunosuppressive tumor microenvironment. This study aimed to evaluate the potential of low-dose radiotherapy (LDRT) administered before T-cell therapy to enhance the antitumor effect by promoting CAR-T cell infiltration. We hypothesized that combining LDRT with T-cell therapy would improve tumor control and survival compared to either treatment alone.

Methods: We investigated this hypothesis …


Generation Of A Wt1 Conditional Deletion, Nuclear Red Fluorescent Protein Reporter Allele In The Mouse, Jace A Aloway, E Cristy Ruteshouser, Vicki Huff, Richard R Behringer Jan 2024

Generation Of A Wt1 Conditional Deletion, Nuclear Red Fluorescent Protein Reporter Allele In The Mouse, Jace A Aloway, E Cristy Ruteshouser, Vicki Huff, Richard R Behringer

Faculty, Staff and Student Publications

A Wt1 conditional deletion, nuclear red fluorescent protein (RFP) reporter allele was generated in the mouse by gene targeting in embryonic stem cells. Upon Cre-mediated recombination, a deletion allele is generated that expresses RFP in a Wt1-specific pattern. RFP expression was detected in embryonic and adult tissues known to express Wt1, including the kidney, mesonephros, and testis. In addition, RFP expression and WT1 co-localization was detected in the adult uterine stroma and myometrium, suggesting a role in uterine function. Crosses with Wnt7a-Cre transgenic mice that express Cre in the Müllerian duct epithelium activate Wt1-directed RFP expression in the epithelium of …


A Goldilocks Computational Protocol For Inhibitor Discovery Targeting Dna Damage Responses Including Replication-Repair Functions, Davide Moiani, John A Tainer Jan 2024

A Goldilocks Computational Protocol For Inhibitor Discovery Targeting Dna Damage Responses Including Replication-Repair Functions, Davide Moiani, John A Tainer

Faculty, Staff and Student Publications

While many researchers can design knockdown and knockout methodologies to remove a gene product, this is mainly untrue for new chemical inhibitor designs that empower multifunctional DNA Damage Response (DDR) networks. Here, we present a robust Goldilocks (GL) computational discovery protocol to efficiently innovate inhibitor tools and preclinical drug candidates for cellular and structural biologists without requiring extensive virtual screen (VS) and chemical synthesis expertise. By computationally targeting DDR replication and repair proteins, we exemplify the identification of DDR target sites and compounds to probe cancer biology. Our GL pipeline integrates experimental and predicted structures to efficiently discover leads, allowing …


Aging-Related Biomarker Discovery In The Era Of Immune Checkpoint Inhibitors For Cancer Patients, Abdullah Al-Danakh, Mohammed Safi, Yuli Jian, Linlin Yang, Xinqing Zhu, Qiwei Chen, Kangkang Yang, Shujing Wang, Jianjun Zhang, Deyong Yang Jan 2024

Aging-Related Biomarker Discovery In The Era Of Immune Checkpoint Inhibitors For Cancer Patients, Abdullah Al-Danakh, Mohammed Safi, Yuli Jian, Linlin Yang, Xinqing Zhu, Qiwei Chen, Kangkang Yang, Shujing Wang, Jianjun Zhang, Deyong Yang

Faculty, Staff and Student Publications

Older patients with cancer, particularly those over 75 years of age, often experience poorer clinical outcomes compared to younger patients. This can be attributed to age-related comorbidities, weakened immune function, and reduced tolerance to treatment-related adverse effects. In the immune checkpoint inhibitors (ICI) era, age has emerged as an influential factor impacting the discovery of predictive biomarkers for ICI treatment. These age-linked changes in the immune system can influence the composition and functionality of tumor-infiltrating immune cells (TIICs) that play a crucial role in the cancer response. Older patients may have lower levels of TIICs infiltration due to age-related immune …


Gut Microbiome And Hepatic Transcriptomic Determinants Of Hcc Development In Mice With Metabolic Dysfunction-Associated Steatohepatitis, Lillian I Dolapchiev, Kristyn A Gonzales, Lorenzo R Cruz, Mihai Gagea, Heather L Stevenson, Suet-Ying Kwan, Laura Beretta Jan 2024

Gut Microbiome And Hepatic Transcriptomic Determinants Of Hcc Development In Mice With Metabolic Dysfunction-Associated Steatohepatitis, Lillian I Dolapchiev, Kristyn A Gonzales, Lorenzo R Cruz, Mihai Gagea, Heather L Stevenson, Suet-Ying Kwan, Laura Beretta

Faculty, Staff and Student Publications

Purpose: Hepatocellular carcinoma (HCC) related to metabolic dysfunction-associated steatotic liver disease (MASLD) is often diagnosed at a late stage, and its incidence is increasing. Predictive biomarkers are therefore needed to identify individuals at high risk of HCC. We aimed to characterize the gut microbiome and hepatic transcriptome associated with HCC development in female mice with hepatocyte-deletion of Pten (HepPten -). These mice present with large variations in HCC development, making them a powerful model for biomarker discovery.

Methods & results: Sequencing of stool 16S and hepatic RNA was performed on a first set of mice. Among all liver histology …


Usp22 Overexpression Fails To Augment Tumor Formation In Mmtv-Erbb2 Mice But Loss Of Function Impacts Mmtv Promoter Activity, Xianghong Kuang, Andrew Salinger, Fernando Benavides, William J Muller, Sharon Y R Dent, Evangelia Koutelou Jan 2024

Usp22 Overexpression Fails To Augment Tumor Formation In Mmtv-Erbb2 Mice But Loss Of Function Impacts Mmtv Promoter Activity, Xianghong Kuang, Andrew Salinger, Fernando Benavides, William J Muller, Sharon Y R Dent, Evangelia Koutelou

Faculty, Staff and Student Publications

The Ubiquitin Specific Peptidase 22 (USP22), a component of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) histone modifying complex, is overexpressed in multiple human cancers, but how USP22 impacts tumorigenesis is not clear. We reported previously that Usp22 loss in mice impacts execution of several signaling pathways driven by growth factor receptors such as erythroblastic oncogene B b2 (ERBB2). To determine whether changes in USP22 expression affects ERBB2-driven tumorigenesis, we introduced conditional overexpression or deletion alleles of Usp22 into mice bearing the Mouse mammary tumor virus-Neu-Ires-Cre (MMTV-NIC) transgene, which drives both rat ERBB2/NEU expression and Cre recombinase activity from the MMTV promoter resulting …


Protection Against Fibrosis By A Bacterial Consortium In Metabolic Dysfunction-Associated Steatohepatitis And The Role Of Amino Acid Metabolism, Suet-Ying Kwan, Kristyn A Gonzales, Mohamed A Jamal, Heather L Stevenson, Lin Tan, Philip L Lorenzi, P Andrew Futreal, Ernest T Hawk, Joseph B Mccormick, Susan P Fisher-Hoch, Robert R Jenq, Laura Beretta Jan 2024

Protection Against Fibrosis By A Bacterial Consortium In Metabolic Dysfunction-Associated Steatohepatitis And The Role Of Amino Acid Metabolism, Suet-Ying Kwan, Kristyn A Gonzales, Mohamed A Jamal, Heather L Stevenson, Lin Tan, Philip L Lorenzi, P Andrew Futreal, Ernest T Hawk, Joseph B Mccormick, Susan P Fisher-Hoch, Robert R Jenq, Laura Beretta

Faculty, Staff and Student Publications

The gut microbiota drives progression to liver fibrosis, the main determinant of mortality in metabolic dysfunction-associated steatohepatitis (MASH). In this study, we aimed to identify bacterial species associated with protection against liver fibrosis in a high-risk population, and test their potential to protect against liver fibrosis in vivo. Based on stool shotgun metagenomic sequencing of 340 subjects from a population cohort disproportionally affected by MASH, we identified bacterial species from the Bacteroidales and Clostridiales orders associated with reduced risk of liver fibrosis. A bacterial consortium was subsequently tested in a mouse model of MASH, which demonstrated protective effects against …


Usp22 Overexpression Fails To Augment Tumor Formation In Mmtv-Erbb2 Mice But Loss Of Function Impacts Mmtv Promoter Activity, Xianghong Kuang, Andrew Salinger, Fernando Benavides, William J Muller, Sharon Y R Dent, Evangelia Koutelou Jan 2024

Usp22 Overexpression Fails To Augment Tumor Formation In Mmtv-Erbb2 Mice But Loss Of Function Impacts Mmtv Promoter Activity, Xianghong Kuang, Andrew Salinger, Fernando Benavides, William J Muller, Sharon Y R Dent, Evangelia Koutelou

Faculty, Staff and Student Publications

The Ubiquitin Specific Peptidase 22 (USP22), a component of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) histone modifying complex, is overexpressed in multiple human cancers, but how USP22 impacts tumorigenesis is not clear. We reported previously that Usp22 loss in mice impacts execution of several signaling pathways driven by growth factor receptors such as erythroblastic oncogene B b2 (ERBB2). To determine whether changes in USP22 expression affects ERBB2-driven tumorigenesis, we introduced conditional overexpression or deletion alleles of Usp22 into mice bearing the Mouse mammary tumor virus-Neu-Ires-Cre (MMTV-NIC) transgene, which drives both rat ERBB2/NEU expression and Cre recombinase activity from the MMTV promoter resulting …


Interleukin-1beta And Inflammasome Expression In Spinal Cord Following Chronic Constriction Injury In Male And Female Rats, Suzanne M Green-Fulgham, Jayson B Ball, Andrew J Kwilasz, Michael E Harland, Matthew G Frank, Joseph M Dragavon, Peter M Grace, Linda R Watkins Jan 2024

Interleukin-1beta And Inflammasome Expression In Spinal Cord Following Chronic Constriction Injury In Male And Female Rats, Suzanne M Green-Fulgham, Jayson B Ball, Andrew J Kwilasz, Michael E Harland, Matthew G Frank, Joseph M Dragavon, Peter M Grace, Linda R Watkins

Faculty, Staff and Student Publications

Females represent a majority of chronic pain patients and show greater inflammatory immune responses in human chronic pain patient populations as well as in animal models of neuropathic pain. Recent discoveries in chronic pain research have revealed sex differences in inflammatory signaling, a key component of sensory pathology in chronic neuropathic pain, inviting more research into the nuances of these sex differences. Here we use the chronic constriction injury (CCI) model to explore similarities and differences in expression and production of Inflammatory cytokine IL-1beta in the lumbar spinal cord, as well as its role in chronic pain. We have discovered …


Dissecting The Shared Genetic Architecture Between Alzheimer’S Disease And Frailty: A Cross-Trait Meta-Analyses Of Genome-Wide Association Studies, Nitesh Enduru, Brisa S Fernandes, Zhongming Zhao Jan 2024

Dissecting The Shared Genetic Architecture Between Alzheimer’S Disease And Frailty: A Cross-Trait Meta-Analyses Of Genome-Wide Association Studies, Nitesh Enduru, Brisa S Fernandes, Zhongming Zhao

Faculty, Staff and Student Publications

Introduction: Frailty is the most common medical condition affecting the aging population, and its prevalence increases in the population aged 65 or more. Frailty is commonly diagnosed using the frailty index (FI) or frailty phenotype (FP) assessments. Observational studies have indicated the association of frailty with Alzheimer's disease (AD). However, the shared genetic and biological mechanism of these comorbidity has not been studied.

Methods: To assess the genetic relationship between AD and frailty, we examined it at single nucleotide polymorphism (SNP), gene, and pathway levels.

Results: Overall, 16 genome-wide significant loci (15 unique loci) (p meta-analysis < 5 × 10-8) and 22 genes (21 unique genes) were identified between AD and frailty using cross-trait meta-analysis. The 8 shared loci implicated 11 genes: CLRN1-AS1, CRHR1 …


The Association Of Mirnas As Biomarkers For Severe Liver Dysfunction In Severe Dengue Infection, Napat Pas-Arj Jan 2024

The Association Of Mirnas As Biomarkers For Severe Liver Dysfunction In Severe Dengue Infection, Napat Pas-Arj

Chulalongkorn University Theses and Dissertations (Chula ETD)

Identification early biomarkers for severe liver dysfunction in severe dengue patients is essential. Currently, there is no any data on circulating miRNAs to predict this important complication, Therefore, this study aimed to explore the role of circulating miRNAs in severe liver dysfunction in dengue infection. On the initial day of admission, serum samples were gathered from patients with dengue infection. These patients were monitored for 14 days post-admission to ascertain their final diagnosis. Following the WHO 2009 criteria, participants were categorized into severe liver dysfunction and non-severe liver dysfunction group. To conduct a transcriptomic analysis of circulating miRNAs used the …


Gene Expression By Nanostring Rna Profiling Of Monocytic Myeloid-Derived Suppressor Cells In Knee Osteoarthritis, Varote Shotelersuk Jan 2024

Gene Expression By Nanostring Rna Profiling Of Monocytic Myeloid-Derived Suppressor Cells In Knee Osteoarthritis, Varote Shotelersuk

Chulalongkorn University Theses and Dissertations (Chula ETD)

Osteoarthritis (OA) is a widespread degenerative joint disease marked by cartilage destruction. This study investigates the role of monocytic myeloid-derived suppressor cells (M-MDSCs) in OA, focusing on their gene expression profiles and their relationship with body mass index (BMI) in knee OA patients. Previous research has shown a positive correlation between M-MDSCs and BMI in OA. We explored the role of M-MDSCs derived from the infrapatellar fat pad (IPFP) in OA patients.Using NanoString technology, we examined the transcriptional profile of M-MDSCs from the IPFP of knee OA patients undergoing total knee replacement surgery, categorized into different BMI groups. Flow cytometry …


Sugar Composition Of Thai Desserts And Gut Microbiome Profiles In Healthy Volunteers: A Randomized Controlled Trial, Sayamon Senaprom Jan 2024

Sugar Composition Of Thai Desserts And Gut Microbiome Profiles In Healthy Volunteers: A Randomized Controlled Trial, Sayamon Senaprom

Chulalongkorn University Theses and Dissertations (Chula ETD)

The glycemic index (GI) measures the blood glucose-raising potential of carbohydrate-rich foods and is associated with obesity and insulin resistance. In addition, an imbalanced gut microbiota has been linked to elevated postprandial blood glucose levels. However, the relationship between consuming Thai desserts predominantly composed of carbohydrates and gut microbiome profiles remains unclear. This study aimed to evaluate the effects of consuming various Thai desserts with different GI values on the gut microbiomes of healthy volunteers. This open-label, parallel randomized clinical trial involved 30 healthy individuals aged 18 to 45 years. Participants were randomly assigned to one of three groups: Phetchaburi’s …


Development Of 3d Cell Culture Model For Graves’ Ophthalmopathy, Rajit Chompoowong Jan 2024

Development Of 3d Cell Culture Model For Graves’ Ophthalmopathy, Rajit Chompoowong

Chulalongkorn University Theses and Dissertations (Chula ETD)

Orbital tissue fibrosis and remodeling contribute to the development of exophthalmos, a hallmark symptom of Graves’ ophthalmopathy (GO). The central pathogenesis to this process are orbital fibroblasts (GOF), which express autoantigen, thyroid-stimulating hormone receptor (TSHR). However, there are limitations in preclinical models for studying the pathogenesis and drug discovery of GO, which poses challenges for developing effective treatment options. This study aimed to identify markers of GOF, explore epigenetic alteration, and develop a scaffold-free 3D cell culture model for GO. The novel results from immunohistochemical analysis showed that vimentin was uniquely expressed in GO but absent in control samples. Additionally, …


Endoscopic Innovations In Diagnosis And Management Of Pancreatic Cancer: A Narrative Review And Future Directions, Prateek Suresh Harne, Vaishali Harne, Curtis Wray, Nirav Thosani Jan 2024

Endoscopic Innovations In Diagnosis And Management Of Pancreatic Cancer: A Narrative Review And Future Directions, Prateek Suresh Harne, Vaishali Harne, Curtis Wray, Nirav Thosani

Faculty, Staff and Student Publications

Pancreatic cancer serves as the third leading cause of cancer-associated morbidity and mortality in the United States, with a 5-year survival rate of only 12% with an expected increase in incidence and mortality in the coming years. Pancreatic ductal adenocarcinomas constitute most pancreatic malignancies. Certain genetic syndromes, including Lynch syndrome, hereditary breast and ovarian cancer syndrome, hereditary pancreatitis, familial adenomatous polyposis, Peutz-Jeghers syndrome, familial pancreatic cancer mutation, and ataxia telangiectasia, confer a significantly higher risk. Screening for pancreatic malignancies currently targets patients with germline mutations or those with significant family history. Screening the general population is not currently viable owing …


Severe Degranulation Of Mesenteric Mast Cells In An Experimental Rat Mammary Tumor Model, Senem Yavaş, Özkan Yavaş, Semi̇ha Ersoy, Gürsel Sönmez Jan 2024

Severe Degranulation Of Mesenteric Mast Cells In An Experimental Rat Mammary Tumor Model, Senem Yavaş, Özkan Yavaş, Semi̇ha Ersoy, Gürsel Sönmez

Turkish Journal of Medical Sciences

Background/aim: Breast cancers are one of the most common cancers in women and are responsible for many deaths worldwide. Mast cells are inflammatory cells. Their role in cancers is controversial, and there is limited data on systemic mast cell activation in cancer cases. This study aimed to evaluate systemic mast cell activation in an experimentally induced rat model of breast cancer. Materials and methods: Sprague Dawley female rats were divided into control (n=6) and mammary tumor (n=12) groups. In the tumor group, 20 mg 12-dimethylbenz[a]anthracene (DMBA) dissolved in 1 ml cottonseed oil was administered intragastrically by gavage, and the rats …


The Role Of Circadian Rhythm Proteins Rev-Erb Α/ And Β In The Development Of Neuronal Injury After Taumatic Brain Injury, Mahmud Pençe, Enes Dogan, Hali̇l Koç, Ci̇gdem Bayraktaroglu, Serdar Altunay, Zeynep Balçikanli, Ertugrul Kiliç, Mustafa Beker Jan 2024

The Role Of Circadian Rhythm Proteins Rev-Erb Α/ And Β In The Development Of Neuronal Injury After Taumatic Brain Injury, Mahmud Pençe, Enes Dogan, Hali̇l Koç, Ci̇gdem Bayraktaroglu, Serdar Altunay, Zeynep Balçikanli, Ertugrul Kiliç, Mustafa Beker

Turkish Journal of Medical Sciences

Background/Aim:Circadian rhythm proteins (CRP) play critical roles in both physiological and pathophysiological conditions, including neurodegenerative disorders. As member of CRP, the nuclear receptors REV-ERBα/β regulates circadian rhythm particularly by inhibiting Bmal1 protein and involved in the neuroinflammation- and cell death processes. However, their roles in the development of neuronal injury after traumatic brain injury (TBI) were largely unexplored, which were investigated in the present study.Materials and Methods: For the induction of TBI, animals were submitted to the cryogenic model of TBI, which is a commonly used animal model and shares essential similarities with cerebral ischemia in terms of pathophysiological cascades. …


In Silico Study Of Bioactive Compounds Derived From Indonesian Marine Invertebrates As Novel Antituberculosis Agent, Ayu Masyita, Eri̇s Septiana, Asep Bayu, Bustanussalam Bustanussalam, Jonathan A. Panggabean, Fi̇rdayani̇ Firdayani, Tuti̇k Murniasih Jan 2024

In Silico Study Of Bioactive Compounds Derived From Indonesian Marine Invertebrates As Novel Antituberculosis Agent, Ayu Masyita, Eri̇s Septiana, Asep Bayu, Bustanussalam Bustanussalam, Jonathan A. Panggabean, Fi̇rdayani̇ Firdayani, Tuti̇k Murniasih

Turkish Journal of Medical Sciences

Background/aim: Tuberculosis has still become the most deadly disease globally. The problem of finding an effective therapeutic is one of the obstacles in the treatment of patients. Marine invertebrates were a treasure since they produced many active compounds. Following up on this issue, screening active compounds is very important. This study will explain the result of anti-tuberculosis screening of compounds derived from marine invertebrates using in silico and confirmed to the in vitro-data.Materials and methods: Three-dimensional (3D) structures of pantothenate kinase (MtPanK type 1, PDB ID: 4BFT), Mycobacterium tuberculosis InhA (MtInhA, PDB ID: 2X23), protein kinase B (PDB ID: 5U94), …


Leaky Gut And Inflammatory Biomarkers In A Medication Overuse Headache Model In Male Rats, Doğa Vuralli, Hale Gök Dağidir, Elif Abbasoğlu Topa, Hayrunnisa Bolay Belen Jan 2024

Leaky Gut And Inflammatory Biomarkers In A Medication Overuse Headache Model In Male Rats, Doğa Vuralli, Hale Gök Dağidir, Elif Abbasoğlu Topa, Hayrunnisa Bolay Belen

Turkish Journal of Medical Sciences

Medication overuse is common among chronic migraine patients and nonsteroidal antiinflammatory drugs (NSAIDs)are the most frequently overused drugs. The pathophysiological mechanisms underlying medication overuse headache (MOH) are notcompletely understood. Intestinal hyperpermeability and leaky gut are reported in patients using NSAIDs. The aim of the study is toinvestigate the role of leaky gut and inflammation in an MOH model MOH model in male rats.Methods: The study was conducted in male Sprague Dawley rats. There were two experimental groups. The first group was the chronicNSAID group in which the rats received mefenamic acid (n = 8) for four weeks intraperitoneally (ip) and …


Effects Of Glutamine And Omega-3 Fatty Acids On Intestinal Neomucosa Formation On Colon Serosa In Rats, Mehmet Köstek, Uygar Demi̇r, Ramazan Uçak, Burak Yasin Avci, Aydın Ünal, Osman Bilgin Gülçi̇çek, Ozan Çalişkan, Bülent Çi̇tgez, Erdinç Seri̇n, Sıtkı Gürkan Yetki̇n, Mehmet Mi̇hmanli, Mehmet Uludağ Jan 2024

Effects Of Glutamine And Omega-3 Fatty Acids On Intestinal Neomucosa Formation On Colon Serosa In Rats, Mehmet Köstek, Uygar Demi̇r, Ramazan Uçak, Burak Yasin Avci, Aydın Ünal, Osman Bilgin Gülçi̇çek, Ozan Çalişkan, Bülent Çi̇tgez, Erdinç Seri̇n, Sıtkı Gürkan Yetki̇n, Mehmet Mi̇hmanli, Mehmet Uludağ

Turkish Journal of Medical Sciences

Intestinal neomucosa formation is a technique defined for the treatment of short bowel syndrome. This study evaluates the effect of glutamine and omega-3 fatty acids on the growth of intestinal neomucosa on the colonic serosal surface has been evaluated.Materials and methods: Thirty-two adult male Sprague-Dawley rats were randomly divided into 4 groups: sham, control, glutamine, and omega-3. Laparotomy was performed on all groups. For rats other than the sham group, a 1-cm full-thickness incision was made 4 cm proximal to the ileocecal valve, and colonic serosal surface was sutured as a serosal patch over these openings. By using the oral …


Effect Of Humic Acid On Oxidative Stress And Neuroprotection In Traumatic Spinal Cord Injury: An Experimental Study, Burak Kinali, Nail Özdemi̇r, Ali Karadağ, Özge Kaya Korkmaz, Ayşe Gülden Di̇ni̇z, Fatma Demet Arslan Jan 2024

Effect Of Humic Acid On Oxidative Stress And Neuroprotection In Traumatic Spinal Cord Injury: An Experimental Study, Burak Kinali, Nail Özdemi̇r, Ali Karadağ, Özge Kaya Korkmaz, Ayşe Gülden Di̇ni̇z, Fatma Demet Arslan

Turkish Journal of Medical Sciences

Traumatic spinal cord injury (TSCI) is an important health problem, especially in developing countries withadditional socioeconomic loss. Humic acid (HA) usually has antioxidant, antiinflammatory, blood circulating, and antiviral effects.Hence, it was aimed herein to show the effect of HA on neuroprotection in a TSCI model.Materials and method: A TSCI model was used, in which 24 Wistar albino rats were divided into 4 groups: control group: subjectedto only laminectomy; sham group: subjected to laminectomy + TSCI; HA 5 mg/kg group: subjected to laminectomy + TSCI +intraperitoneal (IP) injection of 5 mg/kg of HA; and HA 10 mg/kg group: subjected to laminectomy …


Tracking The Footsteps Of Burkholderia Mallei: Determination Of The Molecular Differences And Potential Resistance Genes, Dilek Dülger, Seda Eki̇ci̇, Mehmet Demi̇rci̇, Akın Yi̇ği̇n, Orkun Babacan Jan 2024

Tracking The Footsteps Of Burkholderia Mallei: Determination Of The Molecular Differences And Potential Resistance Genes, Dilek Dülger, Seda Eki̇ci̇, Mehmet Demi̇rci̇, Akın Yi̇ği̇n, Orkun Babacan

Turkish Journal of Medical Sciences

Chemical biological radiological nuclear threats are at an important point in the agenda of world health today, as theycan cause mass deaths. B. mallei attracts attention as a potential biological warfare agent due to its features such as multidrug resistance,a rapid transmission mechanism via aerosol, the absence of a complete treatment protocol for the infection it causes, and the absence ofan approved vaccine for protection against the bacteria. B. mallei suspect samples must be studied by experienced personnel in biosafetylevel III laboratories. B mallei is a difficult and troublesome pathogen to diagnose and many unknowns about B. mallei today. Therefore,the …


Determination Of The Embryotoxic Effects Of Propofol Injected Into Eggs On The Cerebellum And Spinal Cord Using Histologic Methods: An Animal Study, Murat İzgi̇, Emrah Sur Jan 2024

Determination Of The Embryotoxic Effects Of Propofol Injected Into Eggs On The Cerebellum And Spinal Cord Using Histologic Methods: An Animal Study, Murat İzgi̇, Emrah Sur

Turkish Journal of Medical Sciences

This study aims to determine the possible embryotoxic effects of propofol on the cerebellum and spinal cord using fertile chicken eggs. Materials and methods: A total of 430 fertile eggs were divided into 5 groups: control, saline, 2.5 mg.kg–1, 12.5 mg.kg–1, and 37.5 mg.kg–1 propofol. Injections were made immediately before incubation via the air chamber. On the 15th, 18th, and 21st day of incubation, 6 embryos from each group were evaluated. Serial paraffin sections taken from the cerebellum and spinal cord were stained with hematoxylin–eosin, Kluver–Barrera, toluidine blue, and periodic acid-Schiff ’s reaction. The outer granular layer and total cortex …