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Medical Microbiology Commons

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Articles 751 - 780 of 2008

Full-Text Articles in Medical Microbiology

Realistic And Critical Review Of The State Of Systemic Anti-Microbial Peptides, Guangshun Wang, Abraham F. Mechesso Jan 2022

Realistic And Critical Review Of The State Of Systemic Anti-Microbial Peptides, Guangshun Wang, Abraham F. Mechesso

Journal Articles: Pathology and Microbiology

Antimicrobial peptide research remains active not only because of the growing antibiotic resistance problem but also our desire to understand the role of innate immune peptides in host defense. While numerous peptides are currently under active development for topical use, this article highlights peptides with systemic efficacy. The scaffolds of these peptides range from linear to cyclic forms. The neutropenic mouse model is well established to illustrate antimicrobial efficacy from direct killing. The majority of tests, however, are conducted using normal mice so that both direct antimicrobial and immune regulatory effects can be characterized. These systemic examples underscore the possibility …


Insect Cell Expression And Purification Of Recombinant Sars-Cov-2 Spike Proteins That Demonstrate Ace2 Binding, Lucas R. Struble, Audrey L. Smith, William E. Lutz, Gabrielle Grubbs, Satish Sagar, Kenneth W. Bayles, Prakash Radhakrishnan, Surender Khurana, Dalia El-Gamal, Gloria E. O. Borgstahl Jan 2022

Insect Cell Expression And Purification Of Recombinant Sars-Cov-2 Spike Proteins That Demonstrate Ace2 Binding, Lucas R. Struble, Audrey L. Smith, William E. Lutz, Gabrielle Grubbs, Satish Sagar, Kenneth W. Bayles, Prakash Radhakrishnan, Surender Khurana, Dalia El-Gamal, Gloria E. O. Borgstahl

Journal Articles: Pathology and Microbiology

The COVID-19 pandemic caused by SARS-CoV-2 infection has led to socio-economic shutdowns and the loss of over 5 million lives worldwide. There is a need for the identification of therapeutic targets to treat COVID-19. SARS-CoV-2 spike is a target of interest for the development of therapeutic targets. We developed a robust SARS-CoV-2 S spike expression and purification protocol from insect cells and studied four recombinant SARS-CoV-2 spike protein constructs based on the original SARS-CoV-2 sequence using a baculovirus expression system: a spike protein receptor-binding domain that includes the SD1 domain (RBD) coupled to a fluorescent tag (S-RBD-eGFP), spike ectodomain coupled …


Type I Ifn Signaling Protects Mice From Lethal Sars-Cov-2 Neuroinvasion., Md Bashir Uddin, Yuejin Liang, Shengjun Shao, Sunil Palani, Michael Mckelvey, Scott C. Weaver, Keer Sun Jan 2022

Type I Ifn Signaling Protects Mice From Lethal Sars-Cov-2 Neuroinvasion., Md Bashir Uddin, Yuejin Liang, Shengjun Shao, Sunil Palani, Michael Mckelvey, Scott C. Weaver, Keer Sun

Journal Articles: Pathology and Microbiology

Multiple organ damage is common in patients with severe COVID-19, even though the underlying pathogenic mechanisms remain unclear. Acute viral infection typically activates type I IFN (IFN-I) signaling. The antiviral role of IFN-I is well characterized in vitro. However, our understanding of how IFN-I regulates host immune response to SARS-CoV-2 infection in vivo is incomplete. Using a human ACE2-transgenic mouse model, we show in the present study that IFN-I receptor signaling is essential for protection against the acute lethality of SARS-CoV-2 in mice. Interestingly, although IFN-I signaling limits viral replication in the lung, the primary infection site, it is dispensable …


Clinical Laboratory Testing Practices In Diffuse Gliomas Prior To Publication Of 2021 World Health Organization Classification Of Central Nervous System Tumors, Shakti H. Ramkissoon, Helen Fernandes, Dolores H. Lopez-Terrada, Meera R. Hameed, Dimitri G. Trembath, Julia A. Bridge, Neal I. Lindeman, Rhona J. Souers, Patricia Vasalos, Daniel J Brat, Joel T. Moncur Jan 2022

Clinical Laboratory Testing Practices In Diffuse Gliomas Prior To Publication Of 2021 World Health Organization Classification Of Central Nervous System Tumors, Shakti H. Ramkissoon, Helen Fernandes, Dolores H. Lopez-Terrada, Meera R. Hameed, Dimitri G. Trembath, Julia A. Bridge, Neal I. Lindeman, Rhona J. Souers, Patricia Vasalos, Daniel J Brat, Joel T. Moncur

Journal Articles: Pathology and Microbiology

CONTEXT.—: Integration of molecular data into glioma classification supports diagnostic, prognostic, and therapeutic decision-making; however, testing practices for these informative biomarkers in clinical laboratories remain unclear.

OBJECTIVE.—: To examine the prevalence of molecular testing for clinically relevant biomarkers in adult and pediatric gliomas through review of a College of American Pathologists proficiency testing survey prior to the release of the 2021 World Health Organization Classification of Central Nervous System Tumors.

DESIGN.—: College of American Pathologists proficiency testing 2020 survey results from 96 laboratories performing molecular testing for diffuse gliomas were used to determine the use of testing for molecular biomarkers …


Ifn-Γ Transforms The Transcriptomic Landscape And Triggers Myeloid Cell Hyperresponsiveness To Cause Lethal Lung Injury, Atul K. Verma, Michael Mckelvey, Md Bashir Uddin, Sunil Palani, Meng Niu, Christopher Bauer, Shengjun Shao, Keer Sun Jan 2022

Ifn-Γ Transforms The Transcriptomic Landscape And Triggers Myeloid Cell Hyperresponsiveness To Cause Lethal Lung Injury, Atul K. Verma, Michael Mckelvey, Md Bashir Uddin, Sunil Palani, Meng Niu, Christopher Bauer, Shengjun Shao, Keer Sun

Journal Articles: Pathology and Microbiology

Acute Respiratory Distress Syndrome (ARDS) is an inflammatory disease that is associated with high mortality but no specific treatment. Our understanding of initial events that trigger ARDS pathogenesis is limited. We have developed a mouse model of inflammatory lung injury by influenza and methicillin-resistant Staphylococcus aureus (MRSA) coinfection plus daily antibiotic therapy. Using this pneumonic ARDS model, here we show that IFN-γ receptor signaling drives inflammatory cytokine storm and lung tissue damage. By single-cell RNA sequencing (scRNA-seq) analysis, we demonstrate that IFN-γ signaling induces a transcriptional shift in airway immune cells, particularly by upregulating macrophage and monocyte expression of genes …


Catabolic Ornithine Carbamoyltransferase Activity Facilitates Growth Of Staphylococcus Aureus In Defined Medium Lacking Glucose And Arginine, Itidal Reslane, Cortney R. Halsey, Amanda Stastny, Barbara J. Cabrera, Jong-Sam Ahn, Dhananjay Shinde, Madeline R. Galac, Margaret F. Sladek, Fareha Razvi, Mckenzie K. Lehman, Kenneth W. Bayles, Vinai Chittezham Thomas, Luke D. Handke, Paul D. Fey Jan 2022

Catabolic Ornithine Carbamoyltransferase Activity Facilitates Growth Of Staphylococcus Aureus In Defined Medium Lacking Glucose And Arginine, Itidal Reslane, Cortney R. Halsey, Amanda Stastny, Barbara J. Cabrera, Jong-Sam Ahn, Dhananjay Shinde, Madeline R. Galac, Margaret F. Sladek, Fareha Razvi, Mckenzie K. Lehman, Kenneth W. Bayles, Vinai Chittezham Thomas, Luke D. Handke, Paul D. Fey

Journal Articles: Pathology and Microbiology

Previous studies have found that arginine biosynthesis in Staphylococcus aureus is repressed via carbon catabolite repression (CcpA), and proline is used as a precursor. Unexpectedly, however, robust growth of S. aureus is not observed in complete defined medium lacking both glucose and arginine (CDM-R). Mutants able to grow on agar-containing defined medium lacking arginine (CDM-R) were selected and found to contain mutations within ahrC, encoding the canonical arginine biosynthesis pathway repressor (AhrC), or single nucleotide polymorphisms (SNPs) upstream of the native arginine deiminase (ADI) operon arcA1B1D1C1. Reverse transcription-PCR (RT-PCR) studies found that mutations within ccpA or ahrC or …


Exploring Epigenetic Reprogramming During Central Nervous System Infection, Zachary Van Roy, Tammy Kielian Jan 2022

Exploring Epigenetic Reprogramming During Central Nervous System Infection, Zachary Van Roy, Tammy Kielian

Journal Articles: Pathology and Microbiology

Epigenetics involves the study of various modes of adaptable transcriptional regulation, contributing to cell identity, characteristics, and function. During central nervous system (CNS) infection, epigenetic mechanisms can exert pronounced control over the maturation and antimicrobial properties of nearly every immune cell type. Epigenetics is a relatively new field, with the first mention of these marks proposed only a half-century ago and a substantial body of immunological epigenetic research emerging only in the last few decades. Here, we review the best-characterized epigenetic marks and their functions as well as illustrate how various immune cell populations responding to CNS infection utilize these …


The Staphylococcus Aureus Cida And Lrga Proteins Are Functional Holins Involved In The Transport Of By-Products Of Carbohydrate Metabolism, Jennifer L. Endres, Sujata S. Chaudhari, Xinyan Zhang, Janani Prahlad, Shu-Qi Wang, Lily A. Foley, Sorin Luca, Jeffrey L. Bose, Vinai C. Thomas, Kenneth W. Bayles Jan 2022

The Staphylococcus Aureus Cida And Lrga Proteins Are Functional Holins Involved In The Transport Of By-Products Of Carbohydrate Metabolism, Jennifer L. Endres, Sujata S. Chaudhari, Xinyan Zhang, Janani Prahlad, Shu-Qi Wang, Lily A. Foley, Sorin Luca, Jeffrey L. Bose, Vinai C. Thomas, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

The Staphylococcus aureus cidABC and lrgAB operons encode members of a well-conserved family of proteins thought to be involved in programmed cell death (PCD). Based on the structural similarities that CidA and LrgA share with bacteriophage holins, we have hypothesized that these proteins function by forming pores within the cytoplasmic membrane. To test this, we utilized a "lysis cassette" system that demonstrated the abilities of the cidA and lrgA genes to support bacteriophage endolysin-induced cell lysis. Typical of holins, CidA- and LrgA-induced lysis was dependent on the coexpression of endolysin, consistent with the proposed holin-like functions of these proteins. In …


Datasets For The Reporting Of Primary Tumour In Bone: Recommendations From The International Collaboration On Cancer Reporting (Iccr), Judith V. M. G. Bovée, Fleur Webster, Fernanda Amary, Daniel Baumhoer, J. L. Hans Bloem, Julia A. Bridge, Justin M. M. Cates, Enrique De Alava, Angelo Paolo Dei Tos, Kevin B. Jones, Annabelle Mahar, G. Petur Nielsen, Alberto Righi, Andrew J. Wagner, Akihiko Yoshida, Christopher D. M. Fletcher Jan 2022

Datasets For The Reporting Of Primary Tumour In Bone: Recommendations From The International Collaboration On Cancer Reporting (Iccr), Judith V. M. G. Bovée, Fleur Webster, Fernanda Amary, Daniel Baumhoer, J. L. Hans Bloem, Julia A. Bridge, Justin M. M. Cates, Enrique De Alava, Angelo Paolo Dei Tos, Kevin B. Jones, Annabelle Mahar, G. Petur Nielsen, Alberto Righi, Andrew J. Wagner, Akihiko Yoshida, Christopher D. M. Fletcher

Journal Articles: Pathology and Microbiology

BACKGROUND AND OBJECTIVES: Bone tumours are relatively rare and, as a consequence, treatment in a centre with expertise is required. Current treatment guidelines also recommend review by a specialised pathologist. Here we report on international consensus-based datasets for the pathology reporting of biopsy and resection specimens of bone sarcomas. The datasets were produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organisations.

METHODS AND RESULTS: According to the ICCR's process for dataset development, an international expert panel consisting of pathologists, an oncologic orthopaedic surgeon, a medical oncologist, and …


Improved Database Filtering Technology Enables More Efficient Ab Initio Design Of Potent Peptides Against Ebola Viruses, Thomas Ripperda, Yangsheng Yu, Atul Verma, Elizabeth Klug, Michellie Thurman, St. Patrick Reid, Guangshun Wang Jan 2022

Improved Database Filtering Technology Enables More Efficient Ab Initio Design Of Potent Peptides Against Ebola Viruses, Thomas Ripperda, Yangsheng Yu, Atul Verma, Elizabeth Klug, Michellie Thurman, St. Patrick Reid, Guangshun Wang

Journal Articles: Pathology and Microbiology

The rapid mutations of viruses such as SARS-CoV-2 require vaccine updates and the development of novel antiviral drugs. This article presents an improved database filtering technology for a more effective design of novel antiviral agents. Different from the previous approach, where the most probable parameters were obtained stepwise from the antimicrobial peptide database, we found it possible to accelerate the design process by deriving multiple parameters in a single step during the peptide amino acid analysis. The resulting peptide DFTavP1 displays the ability to inhibit Ebola virus. A deviation from the most probable peptide parameters reduces antiviral activity. The designed …


Biofilms: Formation, Research Models, Potential Targets, And Methods For Prevention And Treatment, Yajuan Su, Jaime T. Yrastorza, Mitchell Matis, Jenna Cusick, Siwei Zhao, Guangshun Wang, Jingwei Xie Jan 2022

Biofilms: Formation, Research Models, Potential Targets, And Methods For Prevention And Treatment, Yajuan Su, Jaime T. Yrastorza, Mitchell Matis, Jenna Cusick, Siwei Zhao, Guangshun Wang, Jingwei Xie

Journal Articles: Pathology and Microbiology

Due to the continuous rise in biofilm-related infections, biofilms seriously threaten human health. The formation of biofilms makes conventional antibiotics ineffective and dampens immune clearance. Therefore, it is important to understand the mechanisms of biofilm formation and develop novel strategies to treat biofilms more effectively. This review article begins with an introduction to biofilm formation in various clinical scenarios and their corresponding therapy. Established biofilm models used in research are then summarized. The potential targets which may assist in the development of new strategies for combating biofilms are further discussed. The novel technologies developed recently for the prevention and treatment …


The Challenges Of Combatting Antimicrobial Resistance In The Philippines, Janine Patricia G. Robredo, Michelle Ann B. Eala, Joseph A. Paguio, Maria Sonia S. Salamat, Leo Anthony G. Celi Jan 2022

The Challenges Of Combatting Antimicrobial Resistance In The Philippines, Janine Patricia G. Robredo, Michelle Ann B. Eala, Joseph A. Paguio, Maria Sonia S. Salamat, Leo Anthony G. Celi

Ateneo School of Medicine and Public Health Publications

No abstract provided.


Factors Associated With Hpv16 Cervical Precancerous Stage : Microbiome/Virome And Hpv16 E1, Thanayod Sasivimolrattana Jan 2022

Factors Associated With Hpv16 Cervical Precancerous Stage : Microbiome/Virome And Hpv16 E1, Thanayod Sasivimolrattana

Chulalongkorn University Theses and Dissertations (Chula ETD)

The human papillomavirus type 16 (HPV16) and/or high-risk (Hr-) HPV are the main causes of cervical cancer. The viral factors, such as the E6 and E7 oncogenes, have been recognized as the major factors of carcinogenesis. However, it is currently unknown how other HPV genes, particularly E1, contribute to the development of cancer. Beside HPV, another element that may contribute to the development of cervical cancer is the microbiota in the cervix. Cervical bacteriome and mycobiome have been the focus of numerous investigations; less is known about cervical virome, particularly when HPV is present. No study has investigated the entire …


Predicting Cancer Immunotherapy Response From Gut Microbiomes Using Machine Learning Models, Hai Liang, Jay-Hyun Jo, Zhiwei Zhang, Margaret A Macgibeny, Jungmin Han, Diana M Proctor, Monica E Taylor, You Che, Paul Juneau, Andrea B Apolo, John A Mcculloch, Diwakar Davar, Hassane M Zarour, Amiran K Dzutsev, Isaac Brownell, Giorgio Trinchieri, James L Gulley, Heidi H Kong Jan 2022

Predicting Cancer Immunotherapy Response From Gut Microbiomes Using Machine Learning Models, Hai Liang, Jay-Hyun Jo, Zhiwei Zhang, Margaret A Macgibeny, Jungmin Han, Diana M Proctor, Monica E Taylor, You Che, Paul Juneau, Andrea B Apolo, John A Mcculloch, Diwakar Davar, Hassane M Zarour, Amiran K Dzutsev, Isaac Brownell, Giorgio Trinchieri, James L Gulley, Heidi H Kong

Faculty, Staff and Student Publications

Cancer immunotherapy has significantly improved patient survival. Yet, half of patients do not respond to immunotherapy. Gut microbiomes have been linked to clinical responsiveness of melanoma patients on immunotherapies; however, different taxa have been associated with response status with implicated taxa inconsistent between studies. We used a tumor-agnostic approach to find common gut microbiome features of response among immunotherapy patients with different advanced stage cancers. A combined meta-analysis of 16S rRNA gene sequencing data from our mixed tumor cohort and three published immunotherapy gut microbiome datasets from different melanoma patient cohorts found certain gut bacterial taxa correlated with immunotherapy response …


Effects Of Different Serum Supplements On Piggybac Cd19 Chimeric Antigen Receptor T Cells, Mulita Sanyanusin Jan 2022

Effects Of Different Serum Supplements On Piggybac Cd19 Chimeric Antigen Receptor T Cells, Mulita Sanyanusin

Chulalongkorn University Theses and Dissertations (Chula ETD)

Chimeric Antigen Receptor (CAR) T cell is a novel therapy for relapse and refractory hematologic malignancy. Characteristics of CAR T cells is associated with clinical efficacy and toxicity. Type of serum supplements used during cultivation affect the immunophenotype and function of viral-based CAR T cells. This study explores the effect of serum supplements on non-viral piggyBac transposon CAR T cell production. PiggyBac CD19 CAR T cells were expanded in cultured conditions containing either fetal bovine serum, human AB serum, human platelet lysate or xeno-free serum replacement. Then, the effect of different serum supplements on cell expansion, transfection efficiency, immunophenotypes and …


Functional Analysis Of Laminin Subunit Beta-3 (Lamb3) In Hpv16 Positive Cervical Cancer Cell Lines, Warattaya Wattanathavorn Jan 2022

Functional Analysis Of Laminin Subunit Beta-3 (Lamb3) In Hpv16 Positive Cervical Cancer Cell Lines, Warattaya Wattanathavorn

Chulalongkorn University Theses and Dissertations (Chula ETD)

Nearly 100% cervical cancer cases are infected with high-risk (HR) HPV types, in which HR-HPV16 is found in >50%. The mechanism of cervical cell transformation is related to the powerful activity of viral E6 and E7 oncoproteins. The aim of this study is to identify key genes and their associated pathways through comprehensive bioinformatics analysis as well as to explore the effects of a significant gene in cervical cancer carcinogenesis. In this study, the transcriptome sequencing (RNA-seq) of HPV16 positive cervical cancer cell lines (SiHa and CaSki) was compared to HPV negative cervical cancer cell lines (C33A) to identify significant …


Effects Of Gaba On Inflammation And Intestinal Barrier Disruption, Tyrel W. Long Jan 2022

Effects Of Gaba On Inflammation And Intestinal Barrier Disruption, Tyrel W. Long

EWU Masters Thesis Collection

Gut dysbiosis and intestinal barrier disruption have been linked to multiple sclerosis (MS). Our previous works show that experimental autoimmune encephalomyelitis (EAE) induction modifies the gut's microbiota composition, reducing frequencies of gamma-aminobutyric acid (GABA)-producing bacteria. GABA levels are reduced in the brains and circulation of MS patients. We engineered Lactococcus lactis with extra copies of gadB (glutamic acid decarboxylase) and gadC (glutamate/GABA antiporter) to increase GABA levels produced by the bacterium (GAD-L. lactis). EAE studies showed that the treatment with GAD-L. lactis and not with a L. lactis control expressing an empty plasmid (P-L. lactis) reduced the severity of the …


Regenerative Medicine Technologies Applied To Transplant Medicine An Update, Astgik Petrosyan, Filippo Montali, Andrea Peloso, Antonio Citro, Lori N Byers, Catherine La Pointe, Mara Suleiman, Alice Marchetti, Eoin P Mcneill, Allison L Speer, Wai Hoe Ng, Xi Ren, Benedetta Bussolati, Laura Perin, Paolo Di Nardo, Vincenzo Cardinale, Jerome Duisit, Alexandra Rose Monetti, John Richard Savino, Amish Asthana, Giuseppe Orlando Jan 2022

Regenerative Medicine Technologies Applied To Transplant Medicine An Update, Astgik Petrosyan, Filippo Montali, Andrea Peloso, Antonio Citro, Lori N Byers, Catherine La Pointe, Mara Suleiman, Alice Marchetti, Eoin P Mcneill, Allison L Speer, Wai Hoe Ng, Xi Ren, Benedetta Bussolati, Laura Perin, Paolo Di Nardo, Vincenzo Cardinale, Jerome Duisit, Alexandra Rose Monetti, John Richard Savino, Amish Asthana, Giuseppe Orlando

Faculty, Staff and Student Publications

Regenerative medicine (RM) is changing how we think and practice transplant medicine. In regenerative medicine, the aim is to develop and employ methods to regenerate, restore or replace damaged/diseased tissues or organs. Regenerative medicine investigates using tools such as novel technologies or techniques, extracellular vesicles, cell-based therapies, and tissue-engineered constructs to design effective patient-specific treatments. This review illustrates current advancements in regenerative medicine that may pertain to transplant medicine. We highlight progress made and various tools designed and employed specifically for each tissue or organ, such as the kidney, heart, liver, lung, vasculature, gastrointestinal tract, and pancreas. By combing both …


Critical Analysis Of Laboratory Requisition Forms Received In A Cytopathology Laboratory Of A Tertiary Care Centre: An Audit And Review Of Literature, Shivali Sehgal, Sujata Jetley, Zeeba S Jairajpuri, Sabina Khan Jan 2022

Critical Analysis Of Laboratory Requisition Forms Received In A Cytopathology Laboratory Of A Tertiary Care Centre: An Audit And Review Of Literature, Shivali Sehgal, Sujata Jetley, Zeeba S Jairajpuri, Sabina Khan

Faculty, Staff and Student Publications

BACKGROUND: A laboratory requisition form (LRF) is the main communication link between the laboratories and the clinicians. In a cytopathology laboratory, incomplete forms with inadequate information significantly impact the quality of the results and waste precious time of the lab.

AIMS: The aim of this study was to audit the LRFs for adequacy of demographic and clinical data and to analyze the reasons for the same.

SETTINGS AND DESIGN: A retrospective study was conducted in the cytopathology laboratory of a tertiary care center.

MATERIALS AND METHODS: All the original LRFs received for Pap smears and FNACs of 1-month duration were …


Radiofrequency Ablation In Combination With Cd73 Inhibitor Ab680 Reduces Tumor Growth And Enhances Anti-Tumor Immunity In A Syngeneic Model Of Pancreatic Ductal Adenocarcinoma, Erika Y Faraoni, Lincoln N Strickland, Baylee J O'Brien, Joseph F Barraza, Nirav C Thosani, Curtis J Wray, Tingting W Mills, Jennifer M Bailey-Lundberg Jan 2022

Radiofrequency Ablation In Combination With Cd73 Inhibitor Ab680 Reduces Tumor Growth And Enhances Anti-Tumor Immunity In A Syngeneic Model Of Pancreatic Ductal Adenocarcinoma, Erika Y Faraoni, Lincoln N Strickland, Baylee J O'Brien, Joseph F Barraza, Nirav C Thosani, Curtis J Wray, Tingting W Mills, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma presents a 5-year overall survival rate of 11%, placing an imperative need for the discovery and application of innovative treatments. Radiofrequency ablation represents a promising therapy for PDA, as studies show it induces coagulative necrosis and a host adaptive immune response. In this work we evaluated the effects of RFA treatment in vivo by establishing a syngeneic mouse model of PDA and performing tumor ablation in one flank. Our studies revealed RFA acutely impaired PDA tumor growth; however, such effects were not sustained one week after treatment. Adenosine (ADO) pathway represents a strong immunosuppressive mechanism that was …


Single-Cell Rna Sequencing Reveals Intratumoral Heterogeneity And Potential Mechanisms Of Malignant Progression In Prostate Cancer With Perineural Invasion, Bao Zhang, Shenghan Wang, Zhichao Fu, Qiang Gao, Lin Yang, Zhentao Lei, Yuqiang Shi, Kai Le, Jie Xiong, Siyao Liu, Jiali Zhang, Junyan Su, Jing Chen, Mengyuan Liu, Beifang Niu Jan 2022

Single-Cell Rna Sequencing Reveals Intratumoral Heterogeneity And Potential Mechanisms Of Malignant Progression In Prostate Cancer With Perineural Invasion, Bao Zhang, Shenghan Wang, Zhichao Fu, Qiang Gao, Lin Yang, Zhentao Lei, Yuqiang Shi, Kai Le, Jie Xiong, Siyao Liu, Jiali Zhang, Junyan Su, Jing Chen, Mengyuan Liu, Beifang Niu

Faculty, Staff and Student Publications

Background: Prostate cancer (PCa) is the second most common cancer among men worldwide. Perineural invasion (PNI) was a prominent characteristic of PCa, which was recognized as a key factor in promoting PCa progression. As a complex and heterogeneous disease, its true condition is difficult to explain thoroughly with conventional bulk RNA sequencing. Thus, an improved understanding of PNI-PCa progression at the single-cell level is needed.

Methods: In this study, we performed scRNAseq on tumor tissues of three PNI-PCa patients. Principal component analysis (PCA) and Uniform manifold approximation and projection (UMAP) were used to reduce dimensionality and visualize the cellular composition …


Oscillations Of The Circadian Clock Protein, Bmal-1, Align To Daily Cycles Of Mechanical Stimuli: A Novel Means To Integrate Biological Time Within Predictive In Vitro Model Systems, Hannah K Heywood, Laurence Gardner, Martin M Knight, David A Lee Jan 2022

Oscillations Of The Circadian Clock Protein, Bmal-1, Align To Daily Cycles Of Mechanical Stimuli: A Novel Means To Integrate Biological Time Within Predictive In Vitro Model Systems, Hannah K Heywood, Laurence Gardner, Martin M Knight, David A Lee

Faculty, Staff and Student Publications

PURPOSE: In vivo, the circadian clock drives 24-h rhythms in human physiology. Isolated cells in vitro retain a functional clockwork but lack necessary timing cues resulting in the rapid loss of tissue-level circadian rhythms. This study tests the hypothesis that repeated daily mechanical stimulation acts as a timing cue for the circadian clockwork. The delineation and integration of circadian timing cues into predictive in vitro model systems, including organ-on-a-chip (OOAC) devices, represent a novel concept that introduces a key component of in vivo physiology into predictive in vitro model systems.

METHODS: Quiescent bovine chondrocytes were entrained for 3 days by …


Small Bowel Stomas Are Associated With Higher Risk Of Circulating Food-Specific-Igg Than Patients With Organic Gastrointestinal Conditions And Colostomies, Walker K. Carson, Joseph L. Baumert, Jennifer Clarke, Jacques Izard Jan 2022

Small Bowel Stomas Are Associated With Higher Risk Of Circulating Food-Specific-Igg Than Patients With Organic Gastrointestinal Conditions And Colostomies, Walker K. Carson, Joseph L. Baumert, Jennifer Clarke, Jacques Izard

Department of Food Science and Technology: Faculty Publications

Objective The effects of food sensitivity can easily be masked by other digestive symptoms in ostomates and are unknown. We investigated food-specific-IgG presence in ostomates relative to participants affected by other digestive diseases.

Design Food-specific-IgG was evaluated for 198 participants with a panel of 109 foods. Immunocompetency status was also tested. Jejunostomates, ileostomates, and colostomates were compared with individuals with digestive tract diseases with inflammatory components (periodontitis, eosinophilic esophagitis, duodenitis, ulcerative colitis, Crohn’s disease, and appendicitis), as well as food malabsorption due to intolerance. A logistic regression model with covariates was used to estimate the effect of the experimental data …


Embryonic Hypotaurine Levels Contribute To Strain-Dependent Susceptibility In Mouse Models Of Valproate-Induced Neural Tube Defects, John W Steele, Ying Linda Lin, Nellie Chen, Bogdan J Wlodarczyk, Qiuying Chen, Nabeel Attarwala, Madhu Venkatesalu, Robert M Cabrera, Steven S Gross, Richard H Finnell Jan 2022

Embryonic Hypotaurine Levels Contribute To Strain-Dependent Susceptibility In Mouse Models Of Valproate-Induced Neural Tube Defects, John W Steele, Ying Linda Lin, Nellie Chen, Bogdan J Wlodarczyk, Qiuying Chen, Nabeel Attarwala, Madhu Venkatesalu, Robert M Cabrera, Steven S Gross, Richard H Finnell

Faculty, Staff and Students Publications

Valproic acid (VPA, valproate, Depakote) is a commonly used anti-seizure medication (ASM) in the treatment of epilepsy and a variety of other neurological disorders. While VPA and other ASMs are efficacious for management of seizures, they also increase the risk for adverse pregnancy outcomes, including neural tube defects (NTDs). Thus, the utility of these drugs during pregnancy and in women of childbearing potential presents a continuing public health challenge. Elucidating the underlying genetic or metabolic risk factors for VPA-affected pregnancies may lead to development of non-teratogenic ASMs, novel prevention strategies, or more targeted methods for managing epileptic pregnancies. To address …


Endometriosis-Associated Angiogenesis And Anti-Angiogenic Therapy For Endometriosis, Monica S Chung, Sang Jun Han Jan 2022

Endometriosis-Associated Angiogenesis And Anti-Angiogenic Therapy For Endometriosis, Monica S Chung, Sang Jun Han

Faculty, Staff and Students Publications

Endometriosis is a known estrogen-dependent inflammatory disease affecting reproductive-aged women. Common symptoms include pelvic pain, dysmenorrhea, dyspareunia, heavy menstrual bleeding, and infertility. The exact etiology of endometriosis is largely unknown, and, thus, the diagnosis and treatment of endometriosis are challenging. A complex interplay of many molecular mechanisms is thought to aid in the progression of endometriosis, most notably angiogenesis. This mini-review examines our current knowledge of the molecular etiology of endometriosis-associated angiogenesis and discusses anti-angiogenic therapy, in the blockade of endometriosis-associated angiogenesis, as potential non-hormonal therapy for the treatment of endometriosis.


Common Genomic Aberrations In Mouse And Human Breast Cancers With Concurrent P53 Deficiency And Activated Pten-Pi3k-Akt Pathway, Jarrod D Martinez, Qianxing Mo, Yixiang Xu, Li Qin, Yi Li, Jianming Xu Jan 2022

Common Genomic Aberrations In Mouse And Human Breast Cancers With Concurrent P53 Deficiency And Activated Pten-Pi3k-Akt Pathway, Jarrod D Martinez, Qianxing Mo, Yixiang Xu, Li Qin, Yi Li, Jianming Xu

Faculty, Staff and Students Publications

Simultaneous P53 loss and activation of the PTEN-restricted PI3K-AKT pathway frequently occur in aggressive breast cancers. P53 loss causes genome instability, while PTEN loss and/or activating mutations of PIK3CA and AKT promote cancer cell proliferation that also increases incidences of genomic aberrations. However, the genomic alterations associated with P53 loss and activated PTEN-PI3K-AKT signaling in breast cancer have not been defined. Spatiotemporally controlled breast cancer models with inactivation of both P53 and Pten in adult mice have not been established for studying genomic alterations. Herein, we deleted both floxed Pten and Tp53 genes in the mammary gland epithelial cells in …


Targeting The Pro-Survival Protein Bcl-2 To Prevent Breast Cancer, Adelaide Young, Wen Bu, Weiyu Jiang, Amy Ku, Jyoti Kapali, Sagar Dhamne, Lan Qin, Susan G Hilsenbeck, Yi-Chieh Nancy Du, Yi Li Jan 2022

Targeting The Pro-Survival Protein Bcl-2 To Prevent Breast Cancer, Adelaide Young, Wen Bu, Weiyu Jiang, Amy Ku, Jyoti Kapali, Sagar Dhamne, Lan Qin, Susan G Hilsenbeck, Yi-Chieh Nancy Du, Yi Li

Faculty, Staff and Students Publications

Current chemopreventive strategies require 3-5 years of continuous treatment and have the concerns of significant side effects; therefore, new chemopreventive agents that require shorter and safer treatments are urgently needed. In this study, we developed a new murine model of breast cancer that mimics human breast cancer initiation and is ideal for testing the efficacy of chemopreventive therapeutics. In this model, introduction of lentivirus carrying a PIK3CA gene mutant commonly found in breast cancers infects a small number of the mammary cells, leading to atypia first and then to ductal carcinomas that are positive for both estrogen receptor and progesterone …


Decidualization Of Human Endometrial Stromal Cells Requires Steroid Receptor Coactivator-3, Vineet K Maurya, Maria M Szwarc, David M Lonard, William E Gibbons, San-Pin Wu, Bert W O'Malley, Francesco J Demayo, John P Lydon Jan 2022

Decidualization Of Human Endometrial Stromal Cells Requires Steroid Receptor Coactivator-3, Vineet K Maurya, Maria M Szwarc, David M Lonard, William E Gibbons, San-Pin Wu, Bert W O'Malley, Francesco J Demayo, John P Lydon

Faculty, Staff and Students Publications

Steroid receptor coactivator-3 (SRC-3; also known as NCOA3 or AIB1) is a member of the multifunctional p160/SRC family of coactivators, which also includes SRC-1 and SRC-2. Clinical and cell-based studies as well as investigations on mice have demonstrated pivotal roles for each SRC in numerous physiological and pathophysiological contexts, underscoring their functional pleiotropy. We previously demonstrated the critical involvement of SRC-2 in murine embryo implantation as well as in human endometrial stromal cell (HESC) decidualization, a cellular transformation process required for trophoblast invasion and ultimately placentation. We show here that, like SRC-2, SRC-3 is expressed in the epithelial and stromal …


Socioeconomic, Clinical, And Molecular Features Of Breast Cancer Influence Overall Survival Of Latin American Women, Liz Maria De Almeida, Sandra Cortés, Marta Vilensky, Olivia Valenzuela, Laura Cortes-Sanabria, Mirian De Souza, Rafael Alonso Barbeito, Eliana Abdelhay, Nora Artagaveytia, Adrian Daneri-Navarro, Andrea S Llera, Bettina Müller, Osvaldo L Podhajcer, Carlos Velazquez, Elsa Alcoba, Isabel Alonso, Alicia I Bravo, Natalia Camejo, Dirce Maria Carraro, Mónica Castro, Sandra Cataldi, Alfonso Cayota, Mauricio Cerda, Alicia Colombo, Susanne Crocamo, Alicia Del Toro-Arreola, Raul Delgadillo-Cristerna, Lucia Delgado, Marisa Dreyer Breitenbach, Elmer Fernández, Jorge Fernández, Wanda Fernández, Ramon A Franco-Topete, Fancy Gaete, Jorge Gómez, Leivy P Gonzalez-Ramirez, Marisol Guerrero, Susan A Gutierrez-Rubio, Beatriz Jalfin, Alejandra Lopez-Vazquez, Dora Loria, Silvia Míguez, Andres De J Moran-Mendoza, Gilberto Morgan-Villela, Carina Mussetti, Maria Aparecida Nagai, Antonio Oceguera-Villanueva, Rui M Reis, Javier Retamales, Robinson Rodriguez, Cristina Rosales, Efrain Salas-Gonzalez, Laura Segovia, Juan M Sendoya, Aida A Silva-Garcia, Stella Viña, Livia Zagame, Beth Jones, Moysés Szklo, United States-Latin American Cancer Research Network (Us-Lacrn) Jan 2022

Socioeconomic, Clinical, And Molecular Features Of Breast Cancer Influence Overall Survival Of Latin American Women, Liz Maria De Almeida, Sandra Cortés, Marta Vilensky, Olivia Valenzuela, Laura Cortes-Sanabria, Mirian De Souza, Rafael Alonso Barbeito, Eliana Abdelhay, Nora Artagaveytia, Adrian Daneri-Navarro, Andrea S Llera, Bettina Müller, Osvaldo L Podhajcer, Carlos Velazquez, Elsa Alcoba, Isabel Alonso, Alicia I Bravo, Natalia Camejo, Dirce Maria Carraro, Mónica Castro, Sandra Cataldi, Alfonso Cayota, Mauricio Cerda, Alicia Colombo, Susanne Crocamo, Alicia Del Toro-Arreola, Raul Delgadillo-Cristerna, Lucia Delgado, Marisa Dreyer Breitenbach, Elmer Fernández, Jorge Fernández, Wanda Fernández, Ramon A Franco-Topete, Fancy Gaete, Jorge Gómez, Leivy P Gonzalez-Ramirez, Marisol Guerrero, Susan A Gutierrez-Rubio, Beatriz Jalfin, Alejandra Lopez-Vazquez, Dora Loria, Silvia Míguez, Andres De J Moran-Mendoza, Gilberto Morgan-Villela, Carina Mussetti, Maria Aparecida Nagai, Antonio Oceguera-Villanueva, Rui M Reis, Javier Retamales, Robinson Rodriguez, Cristina Rosales, Efrain Salas-Gonzalez, Laura Segovia, Juan M Sendoya, Aida A Silva-Garcia, Stella Viña, Livia Zagame, Beth Jones, Moysés Szklo, United States-Latin American Cancer Research Network (Us-Lacrn)

Faculty, Staff and Students Publications

Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by …


Tdrd3 Is An Antiviral Restriction Factor That Promotes Ifn Signaling With G3bp1, Matthew Deater, Manasi Tamhankar, Richard E Lloyd Jan 2022

Tdrd3 Is An Antiviral Restriction Factor That Promotes Ifn Signaling With G3bp1, Matthew Deater, Manasi Tamhankar, Richard E Lloyd

Faculty, Staff and Students Publications

Stress granules (SGs) are highly dynamic cytoplasmic foci that form in response to activation of the integrated stress response (ISR) that results in eIF2α phosphorylation and global translation shutdown. Stress granules, which are largely nucleated by G3BP1, serve as hubs for mRNA triage, but there is mounting evidence that they also perform cell signaling functions that are vital to cell survival, particularly during viral infection. We previously showed that SG formation leads to NFκB activation and JNK signaling and that this association may be due in part to G3BP1-dependent recruitment of PKR to SGs. Others have reported close associations between …