69 results on '"Vermeulen, J.L.M."'
Search Results
2. Delayed Tooth Development and the Impaired Differentiation of Stem/Progenitor Cells in Incisors from Type 2 Diabetes Mice.
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Kobayashi, Yoshifumi, Huang, Jia, Barnett, Brandon K., Falcon, Carla Y., Falcon, Paul A., Hirschberg, Craig S., Fine, Daniel H., Ye, Yi, and Shimizu, Emi
- Abstract
Patients with diabetes mellitus (DM) have an increased risk of tooth decay caused by alterations in their tooth development and their oral environment, as well as a tendency to present with pulp infection due to compromised immune response. The present study analyzed the characteristic alterations in tooth development under DM conditions using incisors from db/db type 2 diabetic mouse model (T2DM mice). In micro-CT analyses, T2DM mice showed delayed dentin and enamel formation. Through transcriptomic analyses, pre-ameloblast- and pre-odontoblast-specific genes were found to be significantly decreased in the incisors of T2DM mice, whereas major ameloblast- and mature odontoblast-specific genes were not changed. Stem cell markers were decreased in T2DM mice compared to those from the control mice, suggesting that the stemness of dental pulp cells (DPCs) is attenuated in T2DM mice. In vitro analyses demonstrated that DPCs from T2DM mice have lower colony-forming units (CFU), slower propagation, and diminished differentiation characteristics compared to the control. These data suggest that T2DM conditions could impair the differentiation property of multiple progenitor/stem cells in the tooth, resulting in delayed tooth development in T2DM mice. [ABSTRACT FROM AUTHOR] more...
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- 2024
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3. Exploring the Potential of Epiregulin and Amphiregulin as Prognostic, Predictive, and Therapeutic Targets in Colorectal Cancer.
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Guernsey-Biddle, Cara, High, Peyton, and Carmon, Kendra S.
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EPIDERMAL growth factor receptors ,IMMUNE checkpoint proteins ,COLORECTAL cancer ,PANITUMUMAB ,AMPHIREGULIN ,METASTATIC breast cancer - Abstract
Simple Summary: Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths in the United States, with a 14% five-year survival rate when metastasized. Current treatment options for metastatic CRC (mCRC) include combination chemotherapy regimens, immune checkpoint therapy, and monoclonal antibodies (mAbs), such as those targeting the epidermal growth factor receptor (EGFR). However, efficacy of these therapies is limited. EGFR-targeted mAbs extend survival only in a subset of mCRC patients (10–20%), in part due to drug resistance. Thus, additional biomarkers are required to identify responsive patients and to develop novel targeting strategies that will overcome resistance. This review aims to provide a comprehensive overview of EGFR ligands epiregulin (EREG) and amphiregulin (AREG) as prognostic, predictive, and therapeutic targets in CRC. The epidermal growth factor receptor (EGFR) plays a critical role in regulating essential cellular processes that are frequently hijacked to promote cancer. In colorectal cancer (CRC) in particular, the EGFR signaling pathway is frequently hyperactivated via receptor and/or ligand overexpression and downstream oncogenic mutations. Current EGFR-targeted therapies for metastatic CRC (mCRC) include the mAbs cetuximab and panitumumab. However, intrinsic and acquired resistance to EGFR-targeted mAbs are commonly observed. Thus, additional biomarkers are necessary to better understand patient sensitivity to EGFR-targeted therapies. Furthermore, therapeutic targeting of alternative EGFR pathway components may serve as one mechanism to overcome EGFR-targeted mAb resistance. In this review, we discuss the mounting evidence supporting EGFR ligands epiregulin (EREG) and amphiregulin (AREG), which are overexpressed in CRC with potential key roles in tumor progression, as predictive biomarkers for EGFR-targeted therapy sensitivity, as well as mediators of therapy resistance, though further studies are necessary to validate the prognostic roles and mechanisms by which these ligands contribute to resistance. Additionally, we review recent advances towards therapeutic targeting of EREG and AREG in cancer through the development and use of EREG- and AREG-targeted mAbs as well as antibody–drug conjugates (ADCs). We conclude with a discussion on the roadblocks to clinical implementation of EREG and AREG as biomarkers, as well as approaches to enhance the efficacy of current EREG- and AREG-targeted strategies. [ABSTRACT FROM AUTHOR] more...
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- 2024
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4. Pancreastatin Inhibition Alters the Colonic Epithelial Cells Profile in a Sex-Dependent Manner.
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Tshikudi, Diane M., Hutchison, Hannah, and Ghia, Jean-Eric
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The impaired mucosal barrier is a hallmark of ulcerative colitis (UC), an inflammatory colonic disorder with epidemiological and pathophysiology sex bias. UC Patients overexpress the colonic epithelial cells (CECs)-derived peptide pancreastatin (PST). Pancreastatin inhibitor 8 (PSTi8), an inhibitor of PST, has shown promising anti-inflammatory effects on UC. However, no data exist in the context of CEC barrier function and integrity. We investigated the impact of PSTi8 treatment on CECs in homeostatic and colitic conditions. PSTi8 (2.5 mg/mL/kg, i.r.) or PBS treatment started one day before colitis induction (5% dextran sodium sulfate for five days) in male and female C57BL/6 mice. The disease activity score was assessed daily. Epithelial-associated cytokines, markers specific to differentiation, proliferation, differentiated CECs, stem cells, CECs regulators, and the PSTi8 G-protein coupled receptor 78 (GPR78) signaling pathway, were evaluated using ELISA, immunofluorescence and qRT-PCR. PSTi8 treatment reduced the epithelial-associated cytokines and differentiated CECs while promoting CEC proliferation and self-renewal in females at a steady state through the GRP78 signaling pathway. PSTi8 treatment exacerbated colitis severity and increased CEC differentiation while reducing proliferation in colitic females. Conversely, PSTi8 treatment reduced males' susceptibility to colitis by preserving stem cells and differentiated CECs. PST regulated colonic mucosal maintenance in a sex- and disease-dependent manner. [ABSTRACT FROM AUTHOR] more...
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- 2024
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5. Participation of Semaphorin Family and Plexins in the Clinical Course of Patients with Inflammatory Bowel Disease.
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Fonseca-Camarillo, Gabriela, Furuzawa-Carballeda, Janette, Aguilar-León, Diana, Martínez-Benítez, Braulio, Barreto-Zúñiga, Rafael, and Yamamoto-Furusho, Jesús K.
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INFLAMMATORY bowel diseases ,GENE expression ,ULCERATIVE colitis ,SEMAPHORINS ,PATIENTS' families - Abstract
Semaphorins are an immunoregulatory protein family. Plexins bind semaphorins (SEMAs) and can form receptor complexes that give them chemotactic capacity. The role and expression profile of semaphorins and plexins in inflammatory bowel disease (IBD) is currently unknown. Aim: Characterize the semaphorins and plexins gene and protein expression in intestinal tissue from IBD patients and correlate them with the clinical phenotype. Material and Methods: This comparative and cross-sectional study enrolled 54 diagnosed IBD patients and 20 controls. Gene and protein expression of semaphorins and plexins were determined by RT-PCR and IHQ for the co-localization with neutrophils (myeloperoxidase, MPO) or CD123 plasmacytoid dendritic cells in intestinal tissue from IBD patients. Results: Colonic mucosa from active and remission ulcerative colitis (UC) had a significantly lower SEMA4D and PLXNA1, but higher PLXNB1 gene expression than the control group. The only significant difference between active UC and remission was observed in the higher gene expression of SEMA6D in remission. It was associated with histological remission (p = 0.01, OR = 15, 95% CI: 1.39–16.1). The low expression of PLXNA1 was associated with mild intermittent activity with two relapses per year (p = 0.003, OR = 0.05, CI = 0.006–0.51). Higher SEMA4D+ positive cells were detected in the submucosa, while PLXNC1+/MPO+ in the mucosal and submucosa of active UC patients compared with controls. Conclusions: The increased expression of the semaphorin and plexin family in IBD patients suggests their immunoregulatory function and is associated with remission and clinical phenotype in patients with UC. [ABSTRACT FROM AUTHOR] more...
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- 2024
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6. Adaptation of Conductometric Monoenzyme Biosensor for Rapid Quantitative Analysis of L-arginine in Dietary Supplements.
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Saiapina, Olga Y., Berketa, Kseniia, Sverstiuk, Andrii S., Fayura, Lyubov, Sibirny, Andriy A., Dzyadevych, Sergei, and Soldatkin, Oleksandr O.
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BIOSENSORS ,ARGININE deiminase ,ARGININE ,ION exchange chromatography ,FOOD additives - Abstract
The present study reports on the development, adaptation, and optimization of a novel monoenzyme conductometric biosensor based on a recombinant arginine deiminase (ADI) for the determination of arginine in dietary supplements with a high accuracy of results. Aiming for the highly sensitive determination of arginine in real samples, we studied the effect of parameters of the working buffer solution (its pH, buffer capacity, ionic strength, temperature, and protein concentration) on the sensitivity of the biosensor to arginine. Thus, it was determined that the optimal buffer is a 5 mM phosphate buffer solution with pH 6.2, and the optimal temperature is 39.5 °C. The linear functioning range is 2.5–750 µM of L-arginine with a minimal limit of detection of 2 µM. The concentration of arginine in food additive samples was determined using the developed ADI-based biosensor. Based on the obtained results, the most effective method of biosensor analysis using the method of standard additions was chosen. It was also checked how the reproducibility of the biosensor changes during the analysis of pharmaceutical samples. The results of the determination of arginine in real samples using a conductometric biosensor based on ADI clearly correlated with the data obtained using the method of ion-exchange chromatography and enzymatic spectrophotometric analysis. We concluded that the developed biosensor would be effective for the accurate and selective determination of arginine in dietary supplements intended for the prevention and/or elimination of arginine deficiency. [ABSTRACT FROM AUTHOR] more...
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- 2024
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7. Studying the Effect of the Host Genetic Background of Juvenile Polyposis Development Using Collaborative Cross and Smad4 Knock-Out Mouse Models.
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Zohud, Osayd, Midlej, Kareem, Lone, Iqbal M., Nashef, Aysar, Abu-Elnaaj, Imad, and Iraqi, Fuad A.
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KNOCKOUT mice ,SMAD proteins ,MICE ,K-nearest neighbor classification ,INTESTINAL polyps ,LABORATORY mice ,MACHINE learning ,GENETIC variation - Abstract
Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterized by multiple juvenile polyps in the gastrointestinal tract, often associated with mutations in genes such as Smad4 and BMPR1A. This study explores the impact of Smad4 knock-out on the development of intestinal polyps using collaborative cross (CC) mice, a genetically diverse model. Our results reveal a significant increase in intestinal polyps in Smad4 knock-out mice across the entire population, emphasizing the broad influence of Smad4 on polyposis. Sex-specific analyses demonstrate higher polyp counts in knock-out males and females compared to their WT counterparts, with distinct correlation patterns. Line-specific effects highlight the nuanced response to Smad4 knock-out, underscoring the importance of genetic variability. Multimorbidity heat maps offer insights into complex relationships between polyp counts, locations, and sizes. Heritability analysis reveals a significant genetic basis for polyp counts and sizes, while machine learning models, including k-nearest neighbors and linear regression, identify key predictors, enhancing our understanding of juvenile polyposis genetics. Overall, this study provides new information on understanding the intricate genetic interplay in the context of Smad4 knock-out, offering valuable insights that could inform the identification of potential therapeutic targets for juvenile polyposis and related diseases. [ABSTRACT FROM AUTHOR] more...
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- 2024
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8. National Trends in the Incidence of Sporadic Malignant Colorectal Polyps in Young Patients (20–49 Years): An 18-Year SEER Database Analysis.
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Aloysius, Mark M., Nikumbh, Tejas, Yadukumar, Lekha, Asija, Udit, Shah, Niraj J., Aswath, Ganesh, John, Savio, and Goyal, Hemant
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DATABASES ,COLON polyps ,VIRTUAL colonoscopy ,MEDICAL screening ,COLORECTAL cancer ,EARLY detection of cancer ,PHYSICIANS - Abstract
Background and Objectives: Conflicting guidelines exist for initiating average-risk colorectal cancer screening at the age of 45 years. The United States Preventive Services Task Force (USPSTF) changed its guidelines in 2021 to recommend initiating screening at 45 years due to an increasing incidence of young-onset colorectal cancer. However, the American College of Physicians (ACP) recently recommended not screening average-risk individuals between 45 and 49 years old. We aim to study the national trends in the incidence of sporadic malignant polyps (SMP) in patients from 20 to 49 years old. Materials and Methods: We analyzed the Surveillance, Epidemiology, and End Results database (2000–2017) on patients aged 20–49 years who underwent diagnostic colonoscopy with at least a single malignant sporadic colorectal polyp. Results: Of the 10,742 patients diagnosed with SMP, 42.9% were female. The mean age of incidence was 43.07 years (42.91–43.23, 95% CI). Approximately 50% of malignant polyps were diagnosed between 45 and 49 years of age, followed by 25–30% between 40 and 45. There was an upward trend in malignant polyps, with a decreased incidence of malignant villous adenomas and a rise in malignant adenomas and tubulovillous adenomas. Conclusions: Our findings suggest that almost half of the SMPs under 50 years occurred in individuals under age 45, younger than the current screening threshold recommended by the ACP. There has been an upward trend in malignant polyps in the last two decades. This reflects changes in tumor biology, and necessitates further research and support in the USPSTF guidelines to start screening at the age of 45 years. [ABSTRACT FROM AUTHOR] more...
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- 2024
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9. Role of Epiregulin in Lung Tumorigenesis and Therapeutic Resistance.
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Sunaga, Noriaki, Miura, Yosuke, Masuda, Tomomi, and Sakurai, Reiko
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LUNG physiology ,THERAPEUTIC use of antineoplastic agents ,LUNG cancer ,PROTEINS ,GENETIC mutation ,NEOVASCULARIZATION inhibitors ,GROWTH factors ,CARCINOGENESIS ,EPIDERMAL growth factor ,LUNG tumors ,CELL physiology ,TRANSFERASES ,CELL proliferation ,DRUG resistance in cancer cells ,PHENOTYPES - Abstract
Simple Summary: Epiregulin (EREG) is a member of the ErbB family of ligands that plays multiple roles in cellular processes, including cell proliferation, invasion, and angiogenesis. Accumulating evidence has indicated that EREG is involved in lung tumorigenesis and therapeutic resistance. It is becoming evident that EREG contributes to the epithelial–mesenchymal transition, cancer stemness, immune evasion, and resistance to anticancer drugs in several human cancers, including non-small cell lung cancer. In this review, we summarized the current understanding of EREG as an oncogene and discussed its oncogenic role in lung tumorigenesis and therapeutic resistance. Epidermal growth factor (EGF) signaling regulates multiple cellular processes and plays an essential role in tumorigenesis. Epiregulin (EREG), a member of the EGF family, binds to the epidermal growth factor receptor (EGFR) and ErbB4, and it stimulates EGFR-related downstream pathways. Increasing evidence indicates that both the aberrant expression and oncogenic function of EREG play pivotal roles in tumor development in many human cancers, including non-small cell lung cancer (NSCLC). EREG overexpression is induced by activating mutations in the EGFR, KRAS, and BRAF and contributes to the aggressive phenotypes of NSCLC with oncogenic drivers. Recent studies have elucidated the roles of EREG in a tumor microenvironment, including the epithelial–mesenchymal transition, angiogenesis, immune evasion, and resistance to anticancer therapy. In this review, we summarized the current understanding of EREG as an oncogene and discussed its oncogenic role in lung tumorigenesis and therapeutic resistance. [ABSTRACT FROM AUTHOR] more...
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- 2024
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10. Macrophage Inflammatory Proteins (MIPs) Contribute to Malignant Potential of Colorectal Polyps and Modulate Likelihood of Cancerization Associated with Standard Risk Factors.
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Wierzbicki, Jarosław, Bednarz-Misa, Iwona, Lewandowski, Łukasz, Lipiński, Artur, Kłopot, Anna, Neubauer, Katarzyna, and Krzystek-Korpacka, Małgorzata
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MACROPHAGE inflammatory proteins ,COLON polyps ,ADENOMATOUS polyps ,GENE expression ,MESSENGER RNA ,PROTEIN expression - Abstract
Better understanding of molecular changes leading to neoplastic transformation is prerequisite to optimize risk assessment and chemopreventive and surveillance strategies. Data on macrophage inflammatory proteins (MIPs) in colorectal carcinogenesis are scanty and their clinical relevance remains unknown. Therefore, transcript and protein expression of CCL3, CCL4, CXCL2, and CCL19 were determined in 173 and 62 patients, respectively, using RT-qPCR and immunohistochemistry with reference to polyps' characteristics. The likelihood of malignancy was modeled using probit regression. With the increasing malignancy potential of hyperplastic–tubular–tubulo-villous–villous polyps, the expression of CCL3, CCL4, and CCL19 in lesions decreased. CCL19 expression decreased also in normal mucosa while that of CXCL2 increased. Likewise, lesion CCL3 and lesion and normal mucosa CCL19 decreased and normal CXCL2 increased along the hyperplasia–low–high dysplasia grade. The bigger the lesion, the lower CCL3 and higher CXCL2 in normal mucosa. Singular polyps had higher CCL3, CCL4, and CCL19 levels in normal mucosa. CCL3, CCL4 and CXCL2 modulated the likelihood of malignancy associated with traditional risk factors. There was no correlation between the protein and mRNA expression of CCL3 and CCL19. In summary, the polyp-adjacent mucosa contributes to gaining potential for malignancy by polyps. MIPs may help in specifying cancerization probability estimated based on standard risk factors. [ABSTRACT FROM AUTHOR] more...
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- 2024
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11. Centrosomal Protein 55 (CEP55) Drives Immune Exclusion and Resistance to Immune Checkpoint Inhibitors in Colorectal Cancer.
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Wangmo, Dechen, Gates, Travis J., Zhao, Xianda, Sun, Ruping, and Subramanian, Subbaya
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IMMUNE checkpoint inhibitors ,COLORECTAL cancer ,REGULATORY T cells ,GRANZYMES ,IPILIMUMAB ,TUMOR growth ,THERAPEUTICS - Abstract
Colorectal cancer (CRC) currently ranks as the third most common cancer in the United States, and its incidence is on the rise, especially among younger individuals. Despite the remarkable success of immune checkpoint inhibitors (ICIs) in various cancers, most CRC patients fail to respond due to intrinsic resistance mechanisms. While microsatellite instability-high phenotypes serve as a reliable positive predictive biomarker for ICI treatment, the majority of CRC patients with microsatellite-stable (MSS) tumors remain ineligible for this therapeutic approach. In this study, we investigated the role of centrosomal protein 55 (CEP55) in shaping the tumor immune microenvironment in CRC. CEP55 is overexpressed in multiple cancer types and was shown to promote tumorigenesis by upregulating the PI3K/AKT pathway. Our data revealed that elevated CEP55 expression in CRC was associated with reduced T cell infiltration, contributing to immune exclusion. As CRC tumors progressed, CEP55 expression increased alongside sequential mutations in crucial driver genes (APC, KRAS, TP53, and SMAD4), indicating its involvement in tumor progression. CEP55 knockout significantly impaired tumor growth in vitro and in vivo, suggesting that CEP55 plays a crucial role in tumorigenesis. Furthermore, the CEP55 knockout increased CD8
+ T cell infiltration and granzyme B production, indicating improved anti-tumor immunity. Additionally, we observed reduced regulatory T cell infiltration in CEP55 knockout tumors, suggesting diminished immune suppression. Most significantly, CEP55 knockout tumors demonstrated enhanced responsiveness to immune checkpoint inhibition in a clinically relevant orthotopic CRC model. Treatment with anti-PD1 significantly reduced tumor growth in CEP55 knockout tumors compared to control tumors, suggesting that inhibiting CEP55 could improve the efficacy of ICIs. Collectively, our study underscores the crucial role of CEP55 in driving immune exclusion and resistance to ICIs in CRC. Targeting CEP55 emerges as a promising therapeutic strategy to sensitize CRC to immune checkpoint inhibition, thereby improving survival outcomes for CRC patients. [ABSTRACT FROM AUTHOR] more...- Published
- 2024
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12. Introduction of Androgen Receptor Targeting shRNA Inhibits Tumor Growth in Patient-Derived Prostate Cancer Xenografts.
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Thomas, Patrick B., Alinezhad, Saeid, Joshi, Andre, Sweeney, Katrina, Tse, Brian W. C., Tevz, Gregor, McPherson, Stephen, Nelson, Colleen C., Williams, Elizabeth D., and Vela, Ian
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ANDROGEN receptors ,GENE targeting ,CANCER cell culture ,TUMOR growth ,PROSTATE cancer ,XENOGRAFTS ,REPORTER genes - Abstract
Patient-derived xenograft (PDX) models have been established as important preclinical cancer models, overcoming some of the limitations associated with the use of cancer cell lines. The utility of prostate cancer PDX models has been limited by an inability to genetically manipulate them in vivo and difficulties sustaining PDX-derived cancer cells in culture. Viable, short-term propagation of PDX models would allow in vitro transfection with traceable reporters or manipulation of gene expression relevant to different studies within the prostate cancer field. Here, we report an organoid culture system that supports the growth of prostate cancer PDX cells in vitro and permits genetic manipulation, substantially increasing the scope to use PDXs to study the pathobiology of prostate cancer and define potential therapeutic targets. We have established a short-term PDX-derived in vitro cell culture system which enables genetic manipulation of prostate cancer PDXs LuCaP35 and BM18. Genetically manipulated cells could be re-established as viable xenografts when re-implanted subcutaneously in immunocompromised mice and were able to be serially passaged. Tumor growth of the androgen-dependent LuCaP35 PDX was significantly inhibited following depletion of the androgen receptor (AR) in vivo. Taken together, this system provides a method to generate novel preclinical models to assess the impact of controlled genetic perturbations and allows for targeting specific genes of interest in the complex biological setting of solid tumors. [ABSTRACT FROM AUTHOR] more...
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- 2023
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13. Neuregulin 1 (NRG1) and its receptors in the enteric nervous system and other parts of the gastrointestinal wall.
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Gonkowski S
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- Humans, Animals, ErbB Receptors metabolism, Signal Transduction, Neuregulin-1 metabolism, Enteric Nervous System metabolism, Gastrointestinal Tract innervation, Gastrointestinal Tract metabolism
- Abstract
Neuregulin 1 (NRG1) belonging to the transmembrane growth factors family is widespread in living organisms. It acts through ErbB family receptors and first of all takes part in embryogenesis, as well as in developmental, regenerative and adaptive processes occurring in various internal organs and systems. It is known that NRG1 and its receptors are present in various parts of the gastrointestinal (GI) tract. First of all NRG1 and ErbB receptors have been detected in the enteric nervous system (ENS) localized in the wall of the esophagus, stomach and intestine and regulating the majority of the GI tract functions, but also in the mucosal and muscular layers of the GI tract. The NRG1/ErbB pathway is involved in the development and differentiation of the ENS and regulation of the intestinal epithelium functions. Moreover, dysregulation of this pathway results in a wide range of gastrointestinal diseases. However, till now there are no summarizations of previous studies concerning distribution and functions of NRG1 and its receptors in the GI tract. The present review fills this gap., (©The Author(s) 2024. Open Access. This article is licensed under a Creative Commons CC-BY International License.) more...
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- 2024
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14. Unlocking the Potential of the CA2, CA7, and ITM2C Gene Signatures for the Early Detection of Colorectal Cancer: A Comprehensive Analysis of RNA-Seq Data by Utilizing Machine Learning Algorithms.
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Maurya, Neha Shree, Kushwaha, Sandeep, Vetukuri, Ramesh Raju, and Mani, Ashutosh
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MACHINE learning ,EARLY detection of cancer ,FEATURE selection ,DATA analysis ,SUPPORT vector machines ,GENE expression - Abstract
Colorectal cancer affects the colon or rectum and is a common global health issue, with 1.1 million new cases occurring yearly. The study aimed to identify gene signatures for the early detection of CRC using machine learning (ML) algorithms utilizing gene expression data. The TCGA-CRC and GSE50760 datasets were pre-processed and subjected to feature selection using the LASSO method in combination with five ML algorithms: Adaboost, Random Forest (RF), Logistic Regression (LR), Gaussian Naive Bayes (GNB), and Support Vector Machine (SVM). The important features were further analyzed for gene expression, correlation, and survival analyses. Validation of the external dataset GSE142279 was also performed. The RF model had the best classification accuracy for both datasets. A feature selection process resulted in the identification of 12 candidate genes, which were subsequently reduced to 3 (CA2, CA7, and ITM2C) through gene expression and correlation analyses. These three genes achieved 100% accuracy in an external dataset. The AUC values for these genes were 99.24%, 100%, and 99.5%, respectively. The survival analysis showed a significant logrank p-value of 0.044 for the final gene signatures. The analysis of tumor immunocyte infiltration showed a weak correlation with the expression of the gene signatures. CA2, CA7, and ITM2C can serve as gene signatures for the early detection of CRC and may provide valuable information for prognostic and therapeutic decision making. Further research is needed to fully understand the potential of these genes in the context of CRC. [ABSTRACT FROM AUTHOR] more...
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- 2023
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15. Metabolomics Profile of the Secretome of Space-Flown Oligodendrocytes.
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Vergnes, Laurent, Foucaud, Bernard, Cepeda, Carlos, and Espinosa-Jeffrey, Araceli
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HUMAN space flight ,METABOLOMICS ,SPACE flight ,INTRACRANIAL pressure ,OLIGODENDROGLIA ,MYELIN proteins - Abstract
Intracranial hypertension (ICP) and visual impairment intracranial pressure (VIIP) are some of the sequels of long-term space missions. Here we sought to determine how space microgravity (µG) impacts the metabolomics profile of oligodendrocyte progenitors (OLPs), the myelin-forming cells in the central nervous system. We report increased glutamate and energy metabolism while the OLPs were in space for 26 days. We also show that after space flight, OLPs (SPC OLPs) display significantly increased mitochondrial respiration and glycolysis. These data are in agreement with our previous work using simulated microgravity. In addition, our global metabolomics approach allowed for the discovery of endogenous metabolites secreted by OLPs while in space that are significantly modulated by microgravity. Our results provide, for the first time, relevant information about the energetic state of OLPs while in space and after space flight. The functional and molecular relevance of these specific pathways are promising targets for therapeutic intervention for humans in long-term space missions to the moon, Mars and beyond. [ABSTRACT FROM AUTHOR] more...
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- 2023
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16. The Implications of Cannabinoid-Induced Metabolic Dysregulation for Cellular Differentiation and Growth.
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Podinić, Tina, Werstuck, Geoff, and Raha, Sandeep
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CELL growth ,CANNABINOID receptors ,MITOCHONDRIAL membranes ,CANNABINOIDS ,NERVOUS system ,CELLULAR signal transduction - Abstract
The endocannabinoid system (ECS) governs and coordinates several physiological processes through an integrated signaling network, which is responsible for inducing appropriate intracellular metabolic signaling cascades in response to (endo)cannabinoid stimulation. This intricate cellular system ensures the proper functioning of the immune, reproductive, and nervous systems and is involved in the regulation of appetite, memory, metabolism, and development. Cannabinoid receptors have been observed on both cellular and mitochondrial membranes in several tissues and are stimulated by various classes of cannabinoids, rendering the ECS highly versatile. In the context of growth and development, emerging evidence suggests a crucial role for the ECS in cellular growth and differentiation. Indeed, cannabinoids have the potential to disrupt key energy-sensing metabolic signaling pathways requiring mitochondrial-ER crosstalk, whose functioning is essential for successful cellular growth and differentiation. This review aims to explore the extent of cannabinoid-induced cellular dysregulation and its implications for cellular differentiation. [ABSTRACT FROM AUTHOR] more...
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- 2023
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17. Prebiotic Supplementation during Lactation Affects Microbial Colonization in Postnatal-Growth-Restricted Mice.
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Marousez, Lucie, Tran, Léa Chantal, Micours, Edwina, Antoine, Matthieu, Gottrand, Frédéric, Lesage, Jean, and Ley, Delphine
- Abstract
Background: An inadequate perinatal nutritional environment can alter the maturation of the intestinal barrier and promote long-term pathologies such as metabolic syndrome or chronic intestinal diseases. The intestinal microbiota seems to play a determining role in the development of the intestinal barrier. In the present study, we investigated the impact of consuming an early postnatal prebiotic fiber (PF) on growth, intestinal morphology and the microbiota at weaning in postnatal-growth-restricted mice (PNGR). Methods: Large litters (15 pups/mother) were generated from FVB/NRj mice to induce PNGR at postnatal day 4 (PN4) and compared to control litters (CTRL, 8 pups/mother). PF (a resistant dextrin) or water was orally administered once daily to the pups from PN8 to PN20 (3.5 g/kg/day). Intestinal morphology was evaluated at weaning (PN21) using the ileum and colon. Microbial colonization and short-chain fatty acid (SCFA) production were investigated using fecal and cecal contents. Results: At weaning, the PNGR mice showed decreased body weight and ileal crypt depth compared to the CTRL. The PNGR microbiota was associated with decreased proportions of the Lachnospiraceae and Oscillospiraceae families and the presence of the Akkermansia family and Enterococcus genus compared to the CTRL pups. The propionate concentrations were also increased with PNGR. While PF supplementation did not impact intestinal morphology in the PNGR pups, the proportions of the Bacteroides and Parabacteroides genera were enriched, but the proportion of the Proteobacteria phylum was reduced. In the CTRL pups, the Akkermansia genus (Verrucomicrobiota phylum) was present in the PF-supplemented CTRL pups compared to the water-supplemented ones. Conclusions: PNGR alters intestinal crypt maturation in the ileum at weaning and gut microbiota colonization. Our data support the notion that PF supplementation might improve gut microbiota establishment during the early postnatal period. [ABSTRACT FROM AUTHOR] more...
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- 2023
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18. Colorectal Cancer—The "Parent" of Low Bowel Obstruction.
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Grigorean, Valentin Titus, Erchid, Anwar, Coman, Ionuţ Simion, and Liţescu, Mircea
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BOWEL obstructions ,COLORECTAL cancer ,SURGICAL emergencies ,POSTOPERATIVE care ,ALIMENTARY canal - Abstract
Introduction: Despite the improvement of early diagnosis methods for multiple pathological entities belonging to the digestive tract, bowel obstruction determined by multiple etiologies represents an important percentage of surgical emergencies. General data: Although sometimes obstructive episodes are possible in the early stages of colorectal cancer, the most commonly installed intestinal obstruction has the significance of an advanced evolutionary stage of neoplastic disease. Development of Obstructive Mechanism: The spontaneous evolution of colorectal cancer is always burdened by complications. The most common complication is low bowel obstruction, found in approximately 20% of the cases of colorectal cancer, and it can occur either relatively abruptly, or is preceded by initially discrete premonitory symptoms, non-specific (until advanced evolutionary stages) and generally neglected or incorrectly interpreted. Success in the complex treatment of a low neoplastic obstruction is conditioned by a complete diagnosis, adequate pre-operative preparation, a surgical act adapted to the case (in one, two or three successive stages), and dynamic postoperative care. The moment of surgery should be chosen with great care and is the result of the experience of the anesthetic-surgical team. The operative act must be adapted to the case and has as its main objective the resolution of intestinal obstruction and only in a secondary way the resolution of the generating disease. Conclusions: The therapeutic measures adopted (medical-surgical) must have a dynamic character in accordance with the particular situation of the patient. Except for certain or probably benign etiologies, the possibility of colorectal neoplasia should always be considered, in low obstructions, regardless of the patient's age. [ABSTRACT FROM AUTHOR] more...
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- 2023
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19. Krüppel-like Factors 4 and 5 in Colorectal Tumorigenesis.
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Lee, Esther, Cheung, Jacky, and Bialkowska, Agnieszka B.
- Subjects
DISEASE progression ,HOMEOSTASIS ,CELL migration ,MICROBIOLOGICAL assay ,COLORECTAL cancer ,CELLULAR signal transduction ,CELL proliferation ,GENE expression profiling ,TRANSCRIPTION factors - Abstract
Simple Summary: Krüppel-like factors (KLFs) are zinc finger-containing transcription factors that play a crucial role in embryogenesis, development, homeostasis, and disease progression by regulating multiple signaling pathways. This review is focused on the role of two members of the KLF family, KLF4 and KLF5, and their intricate roles in colorectal carcinogenesis. Krüppel-like factors (KLFs) are transcription factors regulating various biological processes such as proliferation, differentiation, migration, invasion, and homeostasis. Importantly, they participate in disease development and progression. KLFs are expressed in multiple tissues, and their role is tissue- and context-dependent. KLF4 and KLF5 are two fascinating members of this family that regulate crucial stages of cellular identity from embryogenesis through differentiation and, finally, during tumorigenesis. They maintain homeostasis of various tissues and regulate inflammation, response to injury, regeneration, and development and progression of multiple cancers such as colorectal, breast, ovarian, pancreatic, lung, and prostate, to name a few. Recent studies broaden our understanding of their function and demonstrate their opposing roles in regulating gene expression, cellular function, and tumorigenesis. This review will focus on the roles KLF4 and KLF5 play in colorectal cancer. Understanding the context-dependent functions of KLF4 and KLF5 and the mechanisms through which they exert their effects will be extremely helpful in developing targeted cancer therapy. [ABSTRACT FROM AUTHOR] more...
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- 2023
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20. Human Colonoid–Myofibroblast Coculture for Study of Apical Na + /H + Exchangers of the Lower Cryptal Neck Region.
- Author
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Salari, Azam, Zhou, Kunyan, Nikolovska, Katerina, Seidler, Ursula, and Amiri, Mahdi
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ION transport (Biology) ,NECK ,STEM cells ,EPITHELIAL cells ,MYOFIBROBLASTS - Abstract
Cation and anion transport in the colonocyte apical membrane is highly spatially organized along the cryptal axis. Because of lack of experimental accessibility, information about the functionality of ion transporters in the colonocyte apical membrane in the lower part of the crypt is scarce. The aim of this study was to establish an in vitro model of the colonic lower crypt compartment, which expresses the transit amplifying/progenitor (TA/PE) cells, with accessibility of the apical membrane for functional study of lower crypt-expressed Na
+ /H+ exchangers (NHEs). Colonic crypts and myofibroblasts were isolated from human transverse colonic biopsies, expanded as three-dimensional (3D) colonoids and myofibroblast monolayers, and characterized. Filter-grown colonic myofibroblast–colonic epithelial cell (CM-CE) cocultures (myofibroblasts on the bottom of the transwell and colonocytes on the filter) were established. The expression pattern for ion transport/junctional/stem cell markers of the CM-CE monolayers was compared with that of nondifferentiated (EM) and differentiated (DM) colonoid monolayers. Fluorometric pHi measurements were performed to characterize apical NHEs. CM-CE cocultures displayed a rapid increase in transepithelial electrical resistance (TEER), paralleled by downregulation of claudin-2. They maintained proliferative activity and an expression pattern resembling TA/PE cells. The CM-CE monolayers displayed high apical Na+ /H+ exchange activity, mediated to >80% by NHE2. Human colonoid–myofibroblast cocultures allow the study of ion transporters that are expressed in the apical membrane of the nondifferentiated colonocytes of the cryptal neck region. The NHE2 isoform is the predominant apical Na+ /H+ exchanger in this epithelial compartment. [ABSTRACT FROM AUTHOR] more...- Published
- 2023
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21. Effects of Different-Syllable Aggressive Calls on Food Intake and Gene Expression in Vespertilio sinensis.
- Author
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Li, Xin, Zhou, Ruizhu, Feng, Lei, Wang, Hui, Feng, Jiang, and Wu, Hui
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GENE expression ,BAT diseases ,INGESTION ,FOOD consumption ,WHITE noise ,COLONIES (Biology) ,ENERGY metabolism - Abstract
Simple Summary: Most social animals have to face the social stress caused by territorial conflicts. To save costs, social animals use acoustic signals instead of physical fights to solve conflicts. Bats live in clusters and frequently produce aggressive calls of different syllables, but little is known about the effects of social stress represented by different types of aggressive calls on the physiology of bats. Here, we conducted playback experiments to investigate the effects of two types of aggressive calls representing different competitive intentions on food intake, body mass, hormone levels, and gene expression in Asian particolored bats (Vespertilio sinensis). Our results showed that different types of aggressive calls exerted different physiological effects on social animals. Interestingly, we found that more aggressive calls do not have a greater impact on bats. Social animals enjoy colony benefits but are also exposed to social stress, which affects their physiology in many ways, including alterations to their energy intake, metabolism, and even gene expression. Aggressive calls are defined as calls emitted during aggressive conflicts between individuals of the same species over resources, such as territory, food, or mates. Aggressive calls produced by animals in different aggressive states indicate different levels of competitive intentions. However, whether aggressive calls produced in different aggressive states exert different physiological effects on animals has yet to be determined. Importantly, bats live in clusters and frequently produce aggressive calls of different syllables, thus providing an ideal model for investigating this question. Here, we conducted playback experiments to investigate the effects of two types of aggressive calls representing different competitive intentions on food intake, body mass, corticosterone (CORT) concentration, and gene expression in Vespertilio sinensis. We found that the playback of both aggressive calls resulted in a significant decrease in food intake and body mass, and bats in the tonal-syllable aggressive-calls (tonal calls) playback group exhibited a more significant decrease when compared to the noisy-syllable aggressive-calls (noisy calls) playback group. Surprisingly, the weight and food intake in the white-noise group decreased the most when compared to before playback. Transcriptome results showed that, when compared to the control and white-noise groups, differentially expressed genes (DEGs) involved in energy and metabolism were detected in the noisy-calls playback group, and DEGs involved in immunity and disease were detected in the tonal-calls playback group. These results suggested that the playback of the two types of aggressive calls differentially affected body mass, food intake, and gene expression in bats. Notably, bat responses to external-noise playback (synthetic white noise) were more pronounced than the playback of the two aggressive calls, suggesting that bats have somewhat adapted to internal aggressive calls. Comparative transcriptome analysis suggested that the playback of the two syllabic aggressive calls disrupted the immune system and increased the risk of disease in bats. This study provides new insight into how animals differ in response to different social stressors and anthropogenic noise. [ABSTRACT FROM AUTHOR] more...
- Published
- 2023
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22. Exploration of the Gut–Brain Axis through Metabolomics Identifies Serum Propionic Acid Associated with Higher Cognitive Decline in Older Persons.
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Neuffer, Jeanne, González-Domínguez, Raúl, Lefèvre-Arbogast, Sophie, Low, Dorrain Y., Driollet, Bénédicte, Helmer, Catherine, Du Preez, Andrea, de Lucia, Chiara, Ruigrok, Silvie R., Altendorfer, Barbara, Aigner, Ludwig, Lucassen, Paul J., Korosi, Aniko, Thuret, Sandrine, Manach, Claudine, Pallàs, Mercè, Urpi-Sardà, Mireia, Sánchez-Pla, Alex, Andres-Lacueva, Cristina, and Samieri, Cécilia more...
- Abstract
The gut microbiome is involved in nutrient metabolism and produces metabolites that, via the gut–brain axis, signal to the brain and influence cognition. Human studies have so far had limited success in identifying early metabolic alterations linked to cognitive aging, likely due to limitations in metabolite coverage or follow-ups. Older persons from the Three-City population-based cohort who had not been diagnosed with dementia at the time of blood sampling were included, and repeated measures of cognition over 12 subsequent years were collected. Using a targeted metabolomics platform, we identified 72 circulating gut-derived metabolites in a case–control study on cognitive decline, nested within the cohort (discovery n = 418; validation n = 420). Higher serum levels of propionic acid, a short-chain fatty acid, were associated with increased odds of cognitive decline (OR for 1 SD = 1.40 (95% CI 1.11, 1.75) for discovery and 1.26 (1.02, 1.55) for validation). Additional analyses suggested mediation by hypercholesterolemia and diabetes. Propionic acid strongly correlated with blood glucose (r = 0.79) and with intakes of meat and cheese (r > 0.15), but not fiber (r = 0.04), suggesting a minor role of prebiotic foods per se, but a possible link to processed foods, in which propionic acid is a common preservative. The adverse impact of propionic acid on metabolism and cognition deserves further investigation. [ABSTRACT FROM AUTHOR] more...
- Published
- 2022
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23. Sequential Accumulation of 'Driver' Pathway Mutations Induces the Upregulation of Hydrogen-Sulfide-Producing Enzymes in Human Colonic Epithelial Cell Organoids.
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Ascenção, Kelly, Dilek, Nahzli, Zuhra, Karim, Módis, Katalin, Sato, Toshiro, and Szabo, Csaba
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BIOENERGETICS ,GLYCOLYSIS ,EPITHELIAL cells ,TUMOR suppressor genes ,ENZYMES ,DIOXYGENASES ,ORGANOIDS ,COLON cancer - Abstract
Recently, a CRISPR-Cas9 genome-editing system was developed with introduced sequential 'driver' mutations in the WNT, MAPK, TGF-β, TP53 and PI3K pathways into organoids derived from normal human intestinal epithelial cells. Prior studies have demonstrated that isogenic organoids harboring mutations in the tumor suppressor genes APC, SMAD4 and TP53, as well as the oncogene KRAS, assumed more proliferative and invasive properties in vitro and in vivo. A separate body of studies implicates the role of various hydrogen sulfide (H
2 S)-producing enzymes in the pathogenesis of colon cancer. The current study was designed to determine if the sequential mutations in the above pathway affect the expression of various H2 S producing enzymes. Western blotting was used to detect the expression of the H2 S-producing enzymes cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST), as well as several key enzymes involved in H2 S degradation such as thiosulfate sulfurtransferase/rhodanese (TST), ethylmalonic encephalopathy 1 protein/persulfide dioxygenase (ETHE1) and sulfide-quinone oxidoreductase (SQR). H2 S levels were detected by live-cell imaging using a fluorescent H2 S probe. Bioenergetic parameters were assessed by Extracellular Flux Analysis; markers of epithelial-mesenchymal transition (EMT) were assessed by Western blotting. The results show that the consecutive mutations produced gradual upregulations in CBS expression—in particular in its truncated (45 kDa) form—as well as in CSE and 3-MST expression. In more advanced organoids, when the upregulation of H2 S-producing enzymes coincided with the downregulation of the H2 S-degrading enzyme SQR, increased H2 S generation was also detected. This effect coincided with the upregulation of cellular bioenergetics (mitochondrial respiration and/or glycolysis) and an upregulation of the Wnt/β-catenin pathway, a key effector of EMT. Thus sequential mutations in colon epithelial cells according to the Vogelstein sequence are associated with a gradual upregulation of multiple H2 S generating pathways, which, in turn, translates into functional changes in cellular bioenergetics and dedifferentiation, producing more aggressive and more invasive colon cancer phenotypes. [ABSTRACT FROM AUTHOR] more...- Published
- 2022
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24. Molecular Characterization and Nutrition Regulation of the Glutamine Synthetase Gene in Triploid Crucian Carp.
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Zhou, Xiaomei, Zhao, Dafang, Chen, Yuan, Xiao, Yangbo, Mao, Zhuangwen, Cao, Shenping, Qu, Fufa, Li, Yutong, Jin, Junyan, Liu, Zhen, Li, Jianzhong, and He, Zhimin
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CRUCIAN carp ,GLUTAMINE synthetase ,MEAT flavor & odor ,CARP ,FISH meal - Abstract
Glutamine synthetase (GS) is a key enzyme that catalyzes the synthesis of glutamine from glutamate, which plays a role in the promotion of muscle cell growth and in improving the flavor of meats. In this study, a GS gene encoding 371 amino acids was cloned from triploid crucian carp and showed the highest level of similarity with the GS gene found in Cyprinus carpio. Meanwhile, GS was differentially expressed in different tissues, and its day–night expression changes showed obvious oscillation. Additionally, the effects of glutamate and glutamine on GS expression in muscle cells were investigated in vitro and in vivo. We found that its expression was obviously increased due to high levels of glutamate (2 mg/mL) but decreased by glutamine in vitro. However, it was significantly promoted by glutamate and glutamine in vivo, with an optimal concentration of 2%. Furthermore, the use of lysine–glutamate dipeptides as feed additives also had a positive influence on GS expression (the optimal concentration is 0.8%). Finally, we explored the effects of different protein levels and sources on the expression of GS, and the results demonstrated that GS had the highest expression at the 35% protein level, but no significant differences were observed in the different protein sources between the fish meal diet (FM) and the mixed diet comprising soybean meal and rapeseed meal (SM). This study sheds new light on the regulation of GS in teleost fish and provides new perceptions and strategies for the formulation of high-quality feed for triploid crucian carp. [ABSTRACT FROM AUTHOR] more...
- Published
- 2022
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25. Neonatal Rat Glia Cultured in Physiological Normoxia for Modeling Neuropathological Conditions In Vitro.
- Author
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Gargas, Justyna, Janowska, Justyna, Ziabska, Karolina, Ziemka-Nalecz, Malgorzata, and Sypecka, Joanna
- Subjects
NEUROGLIA ,PHYSIOLOGICAL models ,EXTRACELLULAR matrix ,CELL populations ,RATS ,HOMEOSTASIS ,MIRROR neurons - Abstract
Cell culture conditions were proven to highly affect crucial biological processes like proliferation, differentiation, intercellular crosstalk, and senescence. Oxygen tension is one of the major factors influencing cell metabolism and thus, modulating cellular response to pathophysiological conditions. In this context, the presented study aimed at the development of a protocol for efficient culture of rat neonatal glial cells (microglia, astrocytes, and oligodendrocytes) in oxygen concentrations relevant to the nervous tissue. The protocol allows for obtaining three major cell populations, which play crucial roles in sustaining tissue homeostasis and are known to be activated in response to a wide spectrum of external stimuli. The cells are cultured in media without supplement addition to avoid potential modulation of cell processes. The application of active biomolecules for coating culturing surfaces might be useful for mirroring physiological cell interactions with extracellular matrix components. The cell fractions can be assembled as cocultures to further evaluate investigated mechanisms, intercellular crosstalk, or cell response to tested pharmacological compounds. Applying additional procedures, like transient oxygen and glucose deprivation, allows to mimic in vitro the selected pathophysiological conditions. The presented culture system for neonatal rat glial cells is a highly useful tool for in vitro modeling selected neuropathological conditions. [ABSTRACT FROM AUTHOR] more...
- Published
- 2022
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26. Porcine Intestinal Organoids: Overview of the State of the Art.
- Author
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Ma, Panpan, Fang, Puxian, Ren, Tianze, Fang, Liurong, and Xiao, Shaobo
- Subjects
DRUG discovery ,INTESTINES ,ORGANOIDS ,DRUG metabolism ,GENOME editing - Abstract
The intestinal tract is a crucial part of the body for growth and development, and its dysregulation can cause several diseases. The lack of appropriate in vitro models hampers the development of effective preventions and treatments against these intestinal tract diseases. Intestinal organoids are three-dimensional (3D) polarized structures composed of different types of cells capable of self-organization and self-renewal, resembling their organ of origin in architecture and function. Porcine intestinal organoids (PIOs) have been cultured and are used widely in agricultural, veterinary, and biomedical research. Based on the similarity of the genomic sequence, anatomic morphology, and drug metabolism with humans and the difficulty in obtaining healthy human tissue, PIOs are also considered ideal models relative to rodents. In this review, we summarize the current knowledge on PIOs, emphasizing their culturing, establishment and development, and applications in the study of host–microbe interactions, nutritional development, drug discovery, and gene editing potential. [ABSTRACT FROM AUTHOR] more...
- Published
- 2022
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27. Mechanobiology of Colorectal Cancer.
- Author
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Brás, Maria Manuela, Sousa, Susana R., Carneiro, Fátima, Radmacher, Manfred, and Granja, Pedro L.
- Subjects
BIOCHEMISTRY ,DISEASE progression ,FIBROBLASTS ,PHENOMENOLOGICAL biology ,COLORECTAL cancer ,CELL motility ,CANCER ,BLOOD circulation ,BIOPHYSICS ,EPITHELIAL cells - Abstract
Simple Summary: It is well documented that colorectal cancer (CRC) is the third most common cancer type, responsible for high mortality in developed countries, resulting in a high socio-economic impact. Several biochemical and gene expression pathways explaining the manifestation of this cancer in humans have already been identified. However, explanations for some of the related biophysical mechanisms and their influence on CRC remain elusive. In CRC, biophysics and medical research have already revealed the importance of studying the effects of the stiffness and viscoelasticity of the substrate on cells, as well as the effect of the shear stress of blood and lymphatic vessels on the behavior of cells and tissues. A deeper understanding of the relationship between the biophysical cues and biochemical signals could be advantageous to develop new diagnostic techniques and therapeutic strategies. Being a disease with a high mortality rate, it becomes crucial to dedicate efforts to finding effective, alternative therapeutic strategies. In this review, the mechanobiology of colorectal cancer (CRC) are discussed. Mechanotransduction of CRC is addressed considering the relationship of several biophysical cues and biochemical pathways. Mechanobiology is focused on considering how it may influence epithelial cells in terms of motility, morphometric changes, intravasation, circulation, extravasation, and metastization in CRC development. The roles of the tumor microenvironment, ECM, and stroma are also discussed, taking into account the influence of alterations and surface modifications on mechanical properties and their impact on epithelial cells and CRC progression. The role of cancer-associated fibroblasts and the impact of flow shear stress is addressed in terms of how it affects CRC metastization. Finally, some insights concerning how the knowledge of biophysical mechanisms may contribute to the development of new therapeutic strategies and targeting molecules and how mechanical changes of the microenvironment play a role in CRC disease are presented. [ABSTRACT FROM AUTHOR] more...
- Published
- 2022
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28. Colorectal Cancer: A Review of Carcinogenesis, Global Epidemiology, Current Challenges, Risk Factors, Preventive and Treatment Strategies.
- Author
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Hossain, Md. Sanower, Karuniawati, Hidayah, Jairoun, Ammar Abdulrahman, Urbi, Zannat, Ooi, Der Jiun, John, Akbar, Lim, Ya Chee, Kibria, K. M. Kaderi, Mohiuddin, A.K. M., Ming, Long Chiau, Goh, Khang Wen, and Hadi, Muhammad Abdul more...
- Subjects
CARCINOGENS ,COLORECTAL cancer ,DRUG resistance in cancer cells ,DISEASE risk factors - Abstract
Simple Summary: The high lethality of colorectal cancer (CRC) is anticipated to continue in the following decades. Early-stage CRC is entirely treatable with surgery and adjuvant therapy (chemotherapy/radiotherapy). However, recurrence is common, and cancer drug resistance increases the chances of treatment failure. At the same time, there are many risk factors leading to high prevalence among both genders. Despite significant improvements in treating other cancers, CRC management is not yet at a satisfactory level. In this comprehensive review, we discussed the development of CRC and its associated risk factors, preventive and treatment strategies and proposed some recommendations. Furthermore, besides chemotherapy and targeted therapy, we discussed natural products as therapeutics for CRC. Colorectal cancer (CRC) is the second most deadly cancer. Global incidence and mortality are likely to be increased in the coming decades. Although the deaths associated with CRC are very high in high-income countries, the incidence and fatalities related to CRC are growing in developing countries too. CRC detected early is entirely curable by surgery and subsequent medications. However, the recurrence rate is high, and cancer drug resistance increases the treatment failure rate. Access to early diagnosis and treatment of CRC for survival is somewhat possible in developed countries. However, these facilities are rarely available in developing countries. Highlighting the current status of CRC, its development, risk factors, and management is crucial in creating public awareness. Therefore, in this review, we have comprehensively discussed the current global epidemiology, drug resistance, challenges, risk factors, and preventive and treatment strategies of CRC. Additionally, there is a brief discussion on the CRC development pathways and recommendations for preventing and treating CRC. [ABSTRACT FROM AUTHOR] more...
- Published
- 2022
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29. Longitudinal metabolomic analysis of plasma enables modeling disease progression in Duchenne muscular dystrophy mouse models.
- Author
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Tsonaka, Roula, Signorelli, Mirko, Sabir, Ekrem, Seyer, Alexandre, Hettne, Kristina, Aartsma-Rus, Annemieke, and Spitali, Pietro
- Published
- 2020
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30. Glutamine Synthetase: Localization Dictates Outcome.
- Author
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Castegna, Alessandra and Menga, Alessio
- Subjects
GLUTAMINE synthetase ,NEUROTOXICOLOGY ,HEALTH outcome assessment ,TUMOR microenvironment ,METABOLISM - Abstract
Glutamine synthetase (GS) is the adenosine triphosphate (ATP)-dependent enzyme that catalyses the synthesis of glutamine by condensing ammonium to glutamate. In the circulatory system, glutamine carries ammonia from muscle and brain to the kidney and liver. In brain reduction of GS activity has been suggested as a mechanism mediating neurotoxicity in neurodegenerative disorders. In cancer, the delicate balance between glutamine synthesis and catabolism is a critical event. In vitro evidence, confirmed in vivo in some cases, suggests that reduced GS activity in cancer cells associates with a more invasive and aggressive phenotype. However, GS is known to be highly expressed in cells of the tumor microenvironment, such as fibroblasts, adipocytes and immune cells, and their ability to synthesize glutamine is responsible for the acquisition of protumoral phenotypes. This has opened a new window into the complex scenario of the tumor microenvironment, in which the balance of glutamine consumption versus glutamine synthesis influences cellular function. Since GS expression responds to glutamine starvation, a lower glutamine synthesizing power due to the absence of GS in cancer cells might apply a metabolic pressure on stromal cells. This event might push stroma towards a GS-high/protumoral phenotype. When referred to stromal cells, GS expression might acquire a 'bad' significance to the point that GS inhibition might be considered a conceivable strategy against cancer metastasis. [ABSTRACT FROM AUTHOR] more...
- Published
- 2018
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31. Recent advances in tissue stem cells.
- Author
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Fu X, He Q, Tao Y, Wang M, Wang W, Wang Y, Yu QC, Zhang F, Zhang X, Chen YG, Gao D, Hu P, Hui L, Wang X, and Zeng YA
- Subjects
- Animals, Brain cytology, Forecasting, Humans, Intestines cytology, Liver cytology, Liver physiology, Male, Muscles cytology, Pancreas cytology, Prostate cytology, Regeneration physiology, Rodentia, Stem Cell Research, Stem Cells physiology
- Abstract
Stem cells are undifferentiated cells capable of self-renewal and differentiation, giving rise to specialized functional cells. Stem cells are of pivotal importance for organ and tissue development, homeostasis, and injury and disease repair. Tissue-specific stem cells are a rare population residing in specific tissues and present powerful potential for regeneration when required. They are usually named based on the resident tissue, such as hematopoietic stem cells and germline stem cells. This review discusses the recent advances in stem cells of various tissues, including neural stem cells, muscle stem cells, liver progenitors, pancreatic islet stem/progenitor cells, intestinal stem cells, and prostate stem cells, and the future perspectives for tissue stem cell research., (© 2021. Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature.) more...
- Published
- 2021
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32. Mechanism of Bile Acid-Induced Programmed Cell Death and Drug Discovery against Cancer: A Review.
- Author
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Jang, Jung Yoon, Im, Eunok, Choi, Yung Hyun, and Kim, Nam Deuk
- Subjects
CELL death ,FARNESOID X receptor ,DRUG discovery ,APOPTOSIS ,BILE acids ,PROGRAMMED cell death 1 receptors ,CARCINOGENS ,ACID derivatives - Abstract
Bile acids are major signaling molecules that play a significant role as emulsifiers in the digestion and absorption of dietary lipids. Bile acids are amphiphilic molecules produced by the reaction of enzymes with cholesterol as a substrate, and they are the primary metabolites of cholesterol in the body. Bile acids were initially considered as tumor promoters, but many studies have deemed them to be tumor suppressors. The tumor-suppressive effect of bile acids is associated with programmed cell death. Moreover, based on this fact, several synthetic bile acid derivatives have also been used to induce programmed cell death in several types of human cancers. This review comprehensively summarizes the literature related to bile acid-induced programmed cell death, such as apoptosis, autophagy, and necroptosis, and the status of drug development using synthetic bile acid derivatives against human cancers. We hope that this review will provide a reference for the future research and development of drugs against cancer. [ABSTRACT FROM AUTHOR] more...
- Published
- 2022
- Full Text
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33. Tissue Niches Formed by Intestinal Mesenchymal Stromal Cells in Mucosal Homeostasis and Immunity.
- Author
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Pasztoi, Maria and Ohnmacht, Caspar
- Subjects
STROMAL cells ,INFLAMMATORY bowel diseases ,INTESTINES ,INTESTINAL mucosa ,GASTROINTESTINAL system ,HOMEOSTASIS - Abstract
The gastrointestinal tract is the largest mucosal surface in our body and accommodates the majority of the total lymphocyte population. Being continuously exposed to both harmless antigens and potentially threatening pathogens, the intestinal mucosa requires the integration of multiple signals for balancing immune responses. This integration is certainly supported by tissue-resident intestinal mesenchymal cells (IMCs), yet the molecular mechanisms whereby IMCs contribute to these events remain largely undefined. Recent studies using single-cell profiling technologies indicated a previously unappreciated heterogeneity of IMCs and provided further knowledge which will help to understand dynamic interactions between IMCs and hematopoietic cells of the intestinal mucosa. In this review, we focus on recent findings on the immunological functions of IMCs: On one hand, we discuss the steady-state interactions of IMCs with epithelial cells and hematopoietic cells. On the other hand, we summarize our current knowledge about the contribution of IMCs to the development of intestinal inflammatory conditions, such as infections, inflammatory bowel disease, and fibrosis. By providing a comprehensive list of cytokines and chemokines produced by IMCs under homeostatic and inflammatory conditions, we highlight the significant immunomodulatory and tissue niche forming capacities of IMCs. [ABSTRACT FROM AUTHOR] more...
- Published
- 2022
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34. Altered Gut Structure and Anti-Bacterial Defense in Adult Mice Treated with Antibiotics during Early Life.
- Author
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Martins Garcia, Tânia, van Roest, Manon, Vermeulen, Jacqueline L. M., Meisner, Sander, Koster, Jan, Wildenberg, Manon E., van Elburg, Ruurd M., Muncan, Vanesa, and Renes, Ingrid B.
- Subjects
GENE expression profiling ,HOMEOSTASIS ,SMALL intestine ,ANTIBIOTICS ,MICE - Abstract
The association between prolonged antibiotic (AB) use in neonates and increased incidence of later life diseases is not yet fully understood. AB treatment in early life alters intestinal epithelial cell composition, functioning, and maturation, which could be the basis for later life health effects. Here, we investigated whether AB-induced changes in the neonatal gut persisted up to adulthood and whether early life AB had additional long-term consequences for gut functioning. Mice received AB orally from postnatal day 10 to 20. Intestinal morphology, permeability, and gene and protein expression at 8 weeks were analyzed. Our data showed that the majority of the early life AB-induced gut effects did not persist into adulthood, yet early life AB did impact later life gut functioning. Specifically, the proximal small intestine (SI) of adult mice treated with AB in early life was characterized by hyperproliferative crypts, increased number of Paneth cells, and alterations in enteroendocrine cell-specific gene expression profiles. The distal SI of adult mice displayed a reduced expression of antibacterial defense markers. Together, our results suggest that early life AB leads to structural and physiological changes in the adult gut, which may contribute to disease development when homeostatic conditions are under challenge. [ABSTRACT FROM AUTHOR] more...
- Published
- 2022
- Full Text
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35. Fibre-type composition of rabbit jaw muscles is related to their daily activity.
- Author
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Wessel, T., Langenbach, G. E. J., Korfage, J. A. M., Brugman, P., Kawai, N., Tanaka, E., and Eijden, T. M. G. J.
- Subjects
MUSCLE proteins ,ELECTRODIAGNOSIS ,MYOSIN ,GLOBULINS ,IMMUNOGLOBULINS ,MYOSIN antibodies ,BLOOD proteins ,PLASMA cells ,ELECTROMYOGRAPHY - Abstract
Skeletal muscles contain a mixture of fibres with different contractile properties, such as maximum force, contraction velocity and fatigability. Muscles adapt to altered functional demands, for example, by changing their fibre-type composition. This fibre-type composition can be changed by the frequency, duration and presumably the intensity of activation. The aim of this study was to analyse the relationship between the spontaneous daily muscle activation and fibre-type composition in rabbit jaw muscles. Using radio-telemetry combined with electromyography, the daily activity of five jaw muscles was characterized in terms of the total duration of muscle activity (duty time) and the number of activity bursts. Fibre-type composition of the muscles was classified by analysing the myosin heavy chain content of the fibres. The amount of slow-type fibres was positively correlated to the duty time and the number of bursts only for activations exceeding 20–30% of the maximum activity per day. Furthermore, cross-sectional areas of the slow-type fibres were positively correlated to the duty time for activations exceeding 30% of the maximum activity. The present data indicate that the amount of activation above a threshold (> 30% peak activity) is important for determining the fibre-type composition and cross-sectional area of slow-type fibres of a muscle. Activation above this threshold occurred only around 2% of the time in the jaw muscles, suggesting that contractile properties of muscle fibres are maintained by a relatively small number of powerful contractions per day. [ABSTRACT FROM AUTHOR] more...
- Published
- 2005
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36. Direct capture and cloning of receptor kinase and peroxidase genes from genomic DNA.
- Author
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Cheng, Davis W and Armstrong, Ken C
- Subjects
MOLECULAR cloning ,GENES ,DNA ,PEROXIDASE ,GENETICS - Abstract
A direct DNA capture and cloning procedure with magnetic bead separation was used to isolate receptor kinase like and peroxidase genes from oat (Avena sativa) and wheat (Triticum aestivum L.) genomic DNA, respectively. In this procedure, the digoxigenin-labeled probe DNA and target genomic DNA fragments were mixed, denatured, and hybridized. The double-helix complexes formed were captured with anti-digoxigenin immunoglobulin-coated magnetic beads and then cloned into either the lambdaBlueSTAR or pUC18 vector. The effectiveness of this procedure was demonstrated by using two specific DNA probes to capture receptor-like kinase genes and surrounding sequences from oat genomic DNA and a peroxidase gene from wheat genomic DNA.Key words: magnetic beads, enrichment, oat, wheat, Avena sativa, Triticum aestivum.Une méthode de capture directe et de clonage à l'aide de billes magnétiques a été employé pour isoler des gènes de type récepteur kinase ou codant pour des peroxydases au sein de banques génomiques de l'avoine (Avena sativa) et du blé (Triticum aestivum). Dans cette méthode, une sonde d'ADN marquée à la digoxygénine et les fragments d'ADN génomique sont mélangés, dénaturés et hybridés. Les complexes bicaténaires formés sont capturés à l'aide de billes magnétiques portant un anticorps Ig anti-digoxygénine. Ces complexes sont ensuite clonés dans le vecteur lambdaBlueSTAR ou le vecteur pUC18. L'efficacité de cette méthode a été illustrée en utilisant deux sondes d'ADN spécifiques. Une première sonde a permis de capturer des gènes de type récepteur kinase et les régions génomiques voisines à partir de l'ADN génomique de l'avoine. Une seconde sonde a permis de cloner un gène de peroxydase à partir de l'ADN génomique du blé.Mots clés : billes magnétiques, enrichissement, avoine, blé, Avena sativa, Triticum aestivum.[Traduit par la Rédaction] [ABSTRACT FROM AUTHOR] more...
- Published
- 2002
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37. The formation of the right and left heart ventricles from the ventricular part of the cardiac tube during embryogenesis.
- Author
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Mglinets, V.
- Abstract
It has been generally assumed that the initial rudiment of the heart ventricle is divided by the longitudinal interventricular septum into the right and left ventricles. This paper presents evidence for the hypothesis that the right and the left ventricles are produced during normal development from different sequentially located segments of the cardiac tube. These segments yielding rudiments of the right and left ventricles could be detected even during early embryogenesis. This hypothesis requires a new explanation for the process of the formation of two separate outlets from the heart ventricles. [ABSTRACT FROM AUTHOR] more...
- Published
- 2000
- Full Text
- View/download PDF
38. Insights into the Role of Matrix Metalloproteinases in Precancerous Conditions and in Colorectal Cancer.
- Author
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Pezeshkian, Zahra, Nobili, Stefania, Peyravian, Noshad, Shojaee, Bahador, Nazari, Haniye, Soleimani, Hiva, Asadzadeh-Aghdaei, Hamid, Ashrafian Bonab, Maziar, Nazemalhosseini-Mojarad, Ehsan, and Mini, Enrico more...
- Subjects
COLORECTAL cancer ,MATRIX metalloproteinases ,POLYPS ,PRECANCEROUS conditions - Abstract
Simple Summary: Colorectal cancer (CRC) is one of the most common cancer worldwide. CRC is derived from polyps and many factors, such as Matrix Metalloproteinases (MMPs) can gain the progression of colorectal carcinogenesis. Many investigations have indicated the role of MMPs in CRC development while there is not enough knowledge about the function of MMPs in precancerous conditions. This review summarizes the current information about the role of MMPs in polyps and CRC progression. Colorectal cancer (CRC) is the third and second cancer for incidence and mortality worldwide, respectively, and is becoming prevalent in developing countries. Most CRCs derive from polyps, especially adenomatous polyps, which can gradually transform into CRC. The family of Matrix Metalloproteinases (MMPs) plays a critical role in the initiation and progression of CRC. Prominent MMPs, including MMP-1, MMP-2, MMP-7, MMP-8, MMP-9, MMP-12, MMP-13, MMP-14, and MMP-21, have been detected in CRC patients, and the expression of most of them correlates with a poor prognosis. Moreover, many studies have explored the inhibition of MMPs and targeted therapy for CRC, but there is not enough information about the role of MMPs in polyp malignancy. In this review, we discuss the role of MMPs in colorectal cancer and its pathogenesis [ABSTRACT FROM AUTHOR] more...
- Published
- 2021
- Full Text
- View/download PDF
39. Monocyte Chemotactic Proteins (MCP) in Colorectal Adenomas Are Differently Expressed at the Transcriptional and Protein Levels: Implications for Colorectal Cancer Prevention.
- Author
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Wierzbicki, Jarosław, Lipiński, Artur, Bednarz-Misa, Iwona, Lewandowski, Łukasz, Neubauer, Katarzyna, Lewandowska, Paulina, and Krzystek-Korpacka, Małgorzata
- Subjects
COLORECTAL cancer ,CANCER prevention ,COLON polyps ,ADENOMA ,PROTEINS - Abstract
The expression of monocyte chemotactic proteins (MCPs) in colorectal polyps and their suitability as targets for chemoprevention is unknown, although MCP expression and secretion can be modulated by non-steroidal inflammatory drugs. This study was designed to determine the expression patterns of MCP-1/CCL2, MCP-2/CCL8, and MCP-3/CCL7 at the protein (immunohistochemistry; n = 62) and transcriptional levels (RTqPCR; n = 173) in colorectal polyps with reference to the polyp malignancy potential. All chemokines were significantly upregulated in polyps at the protein level but downregulated at the transcriptional level by 1.4-(CCL2), 1.7-(CCL7), and 2.3-fold (CCL8). There was an inverse relation between the immunoreactivity toward chemokine proteins and the number of corresponding transcripts in polyps (CCL2 and CCL7) or in normal mucosa (CCL8). The downregulation of chemokine transcripts correlated with the presence of multiple polyps (CCL2 and CCL8), a larger polyp size (CCL2, CCL7, and CCL8), predominant villous growth patterns (CCL2, CCL7 and CCL8), and high-grade dysplasia (CCL2 and CCL8). In conclusion, MCP-1/CCL2, MCP-2/CCL8, and MCP-3/CCL7 chemokines are counter-regulated at the protein and transcriptional levels. Chemokine-directed chemopreventive strategies should therefore directly neutralize MCP proteins or target molecular pathways contributing to their enhanced translation or reduced degradation, rather than aiming at CCL2, CCL7 or CCL8 expression. [ABSTRACT FROM AUTHOR] more...
- Published
- 2021
- Full Text
- View/download PDF
40. Putative β4-adrenoceptors in rat ventricle mediate increases in contractile force and cell Ca2+: comparison with atrial receptors and relationship to (−)-[3H]-CGP 12177 binding.
- Author
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Sarsero, Doreen, Molenaar, Peter, Kaumann, Alberto J, and Freestone, Nicholas S
- Published
- 1999
- Full Text
- View/download PDF
41. Determinants of the DNA-Binding Specificity of the Avian Homeodomain Protein, AKR.
- Author
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Tejada, Max L., Jia, Zongchao, May, Donna, and Deeley, Roger G.
- Subjects
CARRIER proteins ,CYTOLOGY - Abstract
AKR (Avian Knotted-Related) was the first example of a vertebrate homeodomain protein with a highly divergent Ile residue at position 50 of the DNA-recognition helix. The protein was cloned from a liver cDNA expression library of a day-9 chick embryo by virtue of its ability to bind to the F site in the proximal promoter of the avian apoVLDLII gene. Expression of the apoVLDLII gene is completely estrogen dependent, and mutation or deletion of the F site decreases estrogen inducibility 5- to 10-fold. Subsequent data indicated that AKR is capable of repressing the hormone responsiveness of the apoVLDLII promoter, specifically through binding to F. Involvement of the F site in the hormone-dependent activation of apoVLDLII gene expression, as well as AKR-mediated repression, strongly suggests that both positive and negative regulatory factors interact with this site. Although several mammalian proteins have now been isolated whose homeodomains share many of the structural features of AKR, including the Ile at position 50, little is known of their functions in vivo or the identities of the genes they regulate. Consequently, the elements through which they exert their effects and the structural determinants of their binding specificities remain largely uncharacterized. In this study, we defined the sequence specificity of binding by AKR using polymerase chain reaction-assisted optimal site selection and determined the affinity with which the protein binds to both the optimized site and the F site. Additionally, we generated a three-dimensional model of the AKR homeodomain binding to its optimized site and probed the validity of the model by examining the consequences of mutating amino acid residues in recognition helix 3 and the N-terminal arm on the binding specificity of the homeodomain. Finally, we present evidence that the F site itself may act as an estrogen response element (ERE) when in the vicinity of imperfect or canonical EREs and that AKR can repress hormone inducibility mediated via this site. [ABSTRACT FROM AUTHOR] more...
- Published
- 1999
- Full Text
- View/download PDF
42. Differential expression of PSA-NCAM and HNK-1 epitopes in the developing cardiac conduction system of the chick.
- Author
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Chuck, Emil Thomas and Watanabe, Michiko
- Published
- 1997
- Full Text
- View/download PDF
43. Expression of homeobox genes Msx-1 (Hox-7) and Msx-2 (Hox-8) during cardiac development in the chick.
- Author
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Chan-Thomas, Penny S., Thompson, Robert P., Robert, Benoît, Yacoub, Magdi H., and Barton, Paul J. R.
- Published
- 1993
- Full Text
- View/download PDF
44. Cardiac expression of polysialylated NCAM in the chicken embryo: Correlation with the ventricular conduction system.
- Author
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Watanabe, Michiko, Timm, Maureen, and Fallah-Najmabadi, Hessam
- Published
- 1992
- Full Text
- View/download PDF
45. Developmental Appearance of Ammonia-Metabolizing Enzymes in Prenatal Murine Liver
- Author
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Notenboom, Robbert G. E., Moorman, Antoon F. M., and Lamers, Wouter H.
- Published
- 1997
46. Dystrophin expression in the developing conduction system of the human heart.
- Author
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Ginjaar, Ieke B., Virágh, Szabolcs, Markman, Marry W. M., Van Ommen, Gert-Jan B., and Moorman, Antoon F. M.
- Published
- 1995
- Full Text
- View/download PDF
47. Confocal microscopy of thick sections from acrylamide gel embedded embryos.
- Author
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Germroth, Patricia G., Gourdie, Robert G., and Thompson, Robert P.
- Published
- 1995
- Full Text
- View/download PDF
48. Section directed cryosectioning of specimens for scanning electron microscopy: A new method to study cardiac development.
- Author
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Seo, Jeong-Wook, Kim, Eul-Kyeong, Brown, Nigel A., and Wessels, Andy
- Published
- 1995
- Full Text
- View/download PDF
49. Author Index, Vol. 130, 1987.
- Published
- 1987
- Full Text
- View/download PDF
50. Function of cis-Acting Elements in Human Alcohol Dehydrogenase 4 ( ADH4) Promoter and Role of C/EBP Proteins in Gene Expression.
- Author
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LI, MEI and EDENBERG, HOWARD J.
- Published
- 1998
- Full Text
- View/download PDF
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