232,138 results match your criteria human pancreatic

A structure-specific small molecule inhibits a miRNA-200 family member precursor and reverses a type 2 diabetes phenotype.

Cell Chem Biol 2021 Jul 26. Epub 2021 Jul 26.

The Scripps Research Institute, Department of Chemistry, 130 Scripps Way, Jupiter, FL 33458, USA. Electronic address:

MicroRNA families are ubiquitous in the human transcriptome, yet targeting of individual members is challenging because of sequence homology. Many secondary structures of the precursors to these miRNAs (pri- and pre-miRNAs), however, are quite different. Here, we demonstrate both in vitro and in cellulis that design of structure-specific small molecules can inhibit a particular miRNA family member to modulate a disease pathway. Read More

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DEPTOR inhibits lung tumorigenesis by inactivating the EGFR-mTOR signals.

Cancer Lett 2021 Jul 25. Epub 2021 Jul 25.

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China; Cancer Center, Zhejiang University, Hangzhou, China. Electronic address:

DEPTOR plays vital roles in the regulation of cell proliferation and survival by directly modulating the activity of mTORC1/2. However, the physiological role of DEPTOR in lung tumorigenesis, as well as its clinical significance, remains elusive. In this study, we revealed that decreased DEPTOR expression correlated with increased tumor size, poor differentiation, and worse survival in patients with lung cancer. Read More

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Caveolin-1 increases glycolysis in pancreatic cancer cells and triggers cachectic states.

FASEB J 2021 Aug;35(8):e21826

The Laboratory of Acute Abdomen Disease Associated Organ Injury and Repair, Nankai Hospital Affiliated to Nankai University, Tianjin, China.

In pancreatic cancer, autocrine insulin-like growth factor-1 (IGF-1) and paracrine insulin stimulate both IGF-1 receptor (IGF1R) and insulin receptor (IR) to increase tumor growth and glycolysis. In pancreatic cancer patients, cancer-induced glycolysis increases hepatic gluconeogenesis, skeletal muscle proteolysis, and fat lipolysis and, thereby, causes cancer cachexia. As a protein coexisting with IGF1R and IR, caveolin-1 (cav-1) may be involved in pancreatic cancer-induced cachexia. Read More

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Analysis of pancreatic extracellular matrix protein post-translational modifications electrostatic repulsion-hydrophilic interaction chromatography coupled with mass spectrometry.

Mol Omics 2021 Jul 27. Epub 2021 Jul 27.

Department of Chemistry, University of Wisconsin-Madison, 777 Highland Ave., Madison, WI 53706, USA. and School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705, USA.

The pancreas is a vital organ with digestive and endocrine roles, and diseases of the pancreas affect millions of people yearly. A better understanding of the pancreas proteome and its dynamic post-translational modifications (PTMs) is necessary to engineer higher fidelity tissue analogues for use in transplantation. The extracellular matrix (ECM) has major roles in binding and signaling essential to the viability of insulin-producing islets of Langerhans. Read More

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Novel humanized mesothelin-expressing genetically engineered mouse models underscore challenges in delivery of complex therapeutics to pancreatic cancers.

Mol Cancer Ther 2021 Jul 26. Epub 2021 Jul 26.

Laboratory of Molecular Biology, NIH- National Cancer Institute Center for Cancer Research

Antibody-based therapies designed for human use frequently fail to cross-react with the murine isoform of their target. Due to this problem, pre-clinical studies of antibody-based mesothelin-targeted therapeutics in immune competent systems have been limited by the lack of suitable mouse models. Here, we describe two immune-competent humanized mesothelin transgenic mouse lines that can act as tolerant hosts for C57Bl/6-syngeneic cell lines expressing the human isoform of mesothelin. Read More

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HELLS serves as a poor prognostic biomarker and its downregulation reserves the malignant phenotype in pancreatic cancer.

BMC Med Genomics 2021 Jul 27;14(1):189. Epub 2021 Jul 27.

Department of Integrative Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China.

Background: SMARCAs, belonged to SWI/SNF2 subfamilies, are critical to cellular processes due to their modulation of chromatin remodeling processes. Although SMARCAs are implicated in the tumor progression of various cancer types, our understanding of how those members affect pancreatic carcinogenesis is quite limited and improving this requires bioinformatics analysis and biology approaches.

Methods: To address this issue, we investigated the transcriptional and survival data of SMARCAs in patients with pancreatic cancer using ONCOMINE, GEPIA, Human Protein Atlas, and Kaplan-Meier plotter. Read More

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Pancreatic specific CHRM3 activation causes pancreatitis in mice.

JCI Insight 2021 Jul 27. Epub 2021 Jul 27.

Department of Cancer Biology, Mayo Clinic, Jacksonville, United States of America.

Hyperstimulation of the cholecystokinin receptor (CCK1R), a Gq-protein coupled receptor (GPCR), in pancreatic acinar cells is commonly used to induce pancreatitis in rodents. Human pancreatic acinar cells lack CCK1R but express cholinergic receptor muscarinic 3 (M3R), another GPCR. To test whether M3R activation is involved in pancreatitis, a mutant M3R was conditionally expressed in pancreatic acinar cells in mice. Read More

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Coreceptor therapy has distinct short- and long-term tolerogenic effects intrinsic to autoreactive effector T cells.

JCI Insight 2021 Jul 27. Epub 2021 Jul 27.

Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, United States of America.

Immunotherapies are needed in the clinic that effectively suppress beta cell autoimmunity and reestablish long-term self-tolerance in type 1 diabetes. We previously demonstrated that nondepleting αCD4 and αCD8α antibodies establish rapid and indefinite remission in recent-onset diabetic NOD mice. Diabetes reversal by coreceptor therapy (CoRT) is induced by suppression of pathogenic effector T cells (Teff) and the selective egress of T cells from the pancreatic lymph nodes and islets that remain free of infiltration long-term. Read More

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MicroRNA-1252-5p, regulated by Myb, inhibits invasion and epithelial-mesenchymal transition of pancreatic cancer cells by targeting NEDD9.

Aging (Albany NY) 2021 Jul 27;13(undefined). Epub 2021 Jul 27.

Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, China.

MicroRNAs (miRNAs) are known to be involved in the development and progression of pancreatic cancer (PAC). The expression levels and roles of miR-1252-5p in PAC remain unclear. Quantitative real-time PCR and hybridization were used to detect miR-1252-5p expression in PAC cells and human tissues. Read More

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The power and the promise of circRNAs for cancer precision medicine with functional diagnostics and prognostic prediction.

Carcinogenesis 2021 Jul 27. Epub 2021 Jul 27.

National Engineering Laboratory for Deep Process of Rice and Byproducts, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, Hunan, China.

Circular RNA (circRNA) is a large class of covalently closed circular RNA. As a member of competitive endogenous RNA (ceRNA), it participates in the regulation of circRNA-miRNA-mRNA network and plays an important role in the regulation of physiology and pathology. CircRNA is produced by the reverse splicing of exon, intron or both, forming exon or intron circRNA. Read More

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SARS-CoV2 infects pancreatic beta cells in vivo and induces cellular and subcellular disruptions that reflect beta cell dysfunction.

Res Sq 2021 Jul 20. Epub 2021 Jul 20.

Increasing evidence of new-onset diabetes during the COVID19 pandemic indicates that the SARS-CoV2 virus may drive beta-cell dysfunction leading to diabetes, but it is unclear if it is a primary or secondary effect. Here, we present evidence of SARS-CoV-2 infection of pancreatic beta cells using a robust and reproducible non-human primates model of mild to moderate COVID19 pathogenesis. Pancreas from SARS-CoV-2 infected subjects were positive for the SARS-CoV2 spike protein by immunohistochemistry and structures indicative of viral replication were evident by electron microscopy. Read More

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High-fat diet associated sensitization to metabolic stress in Wfs1 heterozygous mice.

Mol Genet Metab 2021 Jul 13. Epub 2021 Jul 13.

Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, WA, Australia; Perron Institute for Neurological and Translational Science, Perth, WA, Australia.

Wolfram syndrome is a rare autosomal recessive disorder caused by mutations in the wolframin ER transmembrane glycoprotein (WFS1) gene and characterized by diabetes mellitus, diabetes insipidus, optic atrophy and deafness. In experimental models the homozygous Wfs1 mutant mice have a full penetrance and clearly expressed phenotype, whereas heterozygous mutants have a less-pronounced phenotype between the wild-type and homozygous mutant mice. Heterozygous WFS1 mutations have been shown to be significant risk factors for diabetes and metabolic disorders in humans. Read More

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A graph centrality-based approach for candidate gene prediction for type 1 diabetes.

Immunol Res 2021 Jul 23. Epub 2021 Jul 23.

School of Physics, University of Hyderabad, Gachibowli, Hyderabad, 500046, Telangana, India.

Type 1 diabetes mellitus (T1DM) or insulin-dependent diabetes is an autoimmune disease that may pose life-threatening situations to individuals. In most cases, cytotoxic T lymphocytes (CTLs) promotes killing of islets of Langerhans in the pancreas, which harbour insulin-producing beta cells. The trigger for autoimmune attack is still unclear; therefore, identifying and targeting candidate genes are imperative to hinder its deleterious effects. Read More

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Identification of a Small-Molecule Glucose Transporter Inhibitor, Glutipyran, That Inhibits Cancer Cell Growth.

ACS Chem Biol 2021 Jul 23. Epub 2021 Jul 23.

Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.

Cancer cells reprogram their metabolism to survive and grow. Small-molecule inhibitors targeting cancer are useful for studying its metabolic pathways and functions and for developing anticancer drugs. Here, we discovered that glutipyran and its derivatives inhibit glycolytic activity and cell growth in human pancreatic cancer cells. Read More

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CircTMC5 promotes gastric cancer progression and metastasis by targeting miR-361-3p/RABL6.

Gastric Cancer 2021 Jul 22. Epub 2021 Jul 22.

Department of General Surgery, The Fourth Affiliated Hospital of Anhui Medical University, No. 100 Huaihai Avenue, Xinzhan District, Hefei City, 230000, Anhui Province, China.

Background: Gastric cancer (GC) is common in East Asia, yet its molecular and pathogenic mechanisms remain unclear. Circular RNAs (circRNAs) are differentially expressed in GC and may be promising biomarkers. Here, we investigated the role and regulatory mechanism of circTMC5 in GC. Read More

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On the causal relationships between hyperinsulinaemia, insulin resistance, obesity and dysglycaemia in type 2 diabetes.

James D Johnson

Diabetologia 2021 Jul 22. Epub 2021 Jul 22.

Diabetes Research Group, Life Sciences Institute, Department of Cellular and Physiological Sciences, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada.

Hundreds of millions of people are affected by hyperinsulinaemia, insulin resistance, obesity and the dysglycaemia that mark a common progression from metabolic health to type 2 diabetes. Although the relative contribution of these features and the order in which they appear may differ between individuals, the common clustering and seemingly progressive nature of type 2 diabetes aetiology has guided research and clinical practice in this area for decades. At the same time, lively debate around the causal relationships between these features has continued, as new data from human trials and highly controlled animal studies are presented. Read More

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Pancreatic Ppy-expressing γ-cells display mixed phenotypic traits and the adaptive plasticity to engage insulin production.

Nat Commun 2021 07 22;12(1):4458. Epub 2021 Jul 22.

Department of Genetic Medicine & Development, iGE3 and Centre facultaire du diabète, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

The cellular identity of pancreatic polypeptide (Ppy)-expressing γ-cells, one of the rarest pancreatic islet cell-type, remains elusive. Within islets, glucagon and somatostatin, released respectively from α- and δ-cells, modulate the secretion of insulin by β-cells. Dysregulation of insulin production raises blood glucose levels, leading to diabetes onset. Read More

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ANGPTL4 accelerates KRAS-Induced acinar to ductal metaplasia and pancreatic carcinogenesis.

Cancer Lett 2021 Jul 23. Epub 2021 Jul 23.

Department of Medicine, College of Medicine, and Program in Biomedical Sciences & Engineering, Inha University, 366, Seohae-daero, Jung-gu, Incheon, 22332, Republic of Korea. Electronic address:

Oncogenic KRAS induces neoplastic transformation of pancreatic acinar cells through acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN), and drives pancreatic ductal adenocarcinoma (PDAC). Angiopoietin-like 4 (ANGPTL4) is known to be involved in the regulation of cancer growth and metastasis. However, whether ANGPTL4 affects KRAS-mediated ADM and early PDAC intervention remains unknown. Read More

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DDIT4 S-Nitrosylation Aids p38-MAPK Signaling Complex Assembly to Promote Hepatic Reactive Oxygen Species Production.

Adv Sci (Weinh) 2021 Jul 26:e2101957. Epub 2021 Jul 26.

Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Translational Medicine, Nanjing Medical University, Nanjing, 211166, China.

Mitogen-activated protein kinase (MAPK) signaling plays a significant role in reactive oxygen species (ROS) production. The authors have previously shown that Brahma-related gene 1 (BRG1), a chromatin remodeling protein, contributes to hepatic ROS accumulation in multiple animal and cellular models of liver injury. Here it is reported that DNA damage-induced transcript 4 (DDIT4) is identified as a direct transcriptional target for BRG1. Read More

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The Evolving Story of Incretins (GIP and GLP-1) in Metabolic and Cardiovascular Disease: A Pathophysiological Update.

Diabetes Obes Metab 2021 Jul 26. Epub 2021 Jul 26.

Charité - Universitätsmedizin Berlin, Klinik für Endokrinologie, Stoffwechsel- und Ernährungsmedizin, Berlin, Germany.

The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have their main physiological role in augmenting insulin secretion after their nutrient-induced secretion from the gut. A functioning entero-insular (gut-endocrine pancreas) axis is essential for the maintenance of a normal glucose tolerance. This is exemplified by the incretin effect (greater insulin secretory response to oral as compared to "isoglycaemic" intravenous glucose administration due to the secretion and action of incretin hormones). Read More

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A Preclinical Human-Derived Autologous Gastric Cancer Organoid/Immune Cell Co-Culture Model to Predict the Efficacy of Targeted Therapies.

J Vis Exp 2021 Jul 6(173). Epub 2021 Jul 6.

Department of Cellular and Molecular Medicine, University of Arizona, Tucson;

Tumors expressing programmed cell death-ligand 1 (PD-L1) interact with programmed cell death protein 1 (PD-1) on CD8+ cytotoxic T lymphocytes (CTLs) to evade immune surveillance leading to the inhibition of CTL proliferation, survival, and effector function, and subsequently cancer persistence. Approximately 40% of gastric cancers express PD-L1, yet the response rate to immunotherapy is only 30%. We present the use of human-derived autologous gastric cancer organoid/immune cell co-culture as a preclinical model that may predict the efficacy of targeted therapies to improve the outcome of cancer patients. Read More

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LOC100996425 acts as a promoter in prostate cancer by mediating hepatocyte nuclear factor 4A and the AMPK/mTOR pathway.

J Cell Mol Med 2021 Jul 26. Epub 2021 Jul 26.

Department of Urology, The Second Hospital of Jilin University, Changchun, China.

The involvement of long non-coding RNAs (lncRNAs), differentially expressed genes and signals in prostate cancer (PCa) continues to be a subject of investigation. This study determined effects of LOC100996425 on human PCa by targeting hepatocyte nuclear factor 4A (HNF4A) via the AMPK/mTOR pathway. PCa and adjacent normal tissues were obtained to characterize expression pattern of LOC100996425, HNF4A and the AMPK/mTOR pathway-related genes. Read More

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ATF3 induces RAB7 to govern autodegradation in paligenosis, a conserved cell plasticity program.

EMBO Rep 2021 Jul 26:e51806. Epub 2021 Jul 26.

Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Differentiated cells across multiple species and organs can re-enter the cell cycle to aid in injury-induced tissue regeneration by a cellular program called paligenosis. Here, we show that activating transcription factor 3 (ATF3) is induced early during paligenosis in multiple cellular contexts, transcriptionally activating the lysosomal trafficking gene Rab7b. ATF3 and RAB7B are upregulated in gastric and pancreatic digestive-enzyme-secreting cells at the onset of paligenosis Stage 1, when cells massively induce autophagic and lysosomal machinery to dismantle differentiated cell morphological features. Read More

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A microfluidic system for monitoring glucagon secretion from human pancreatic islets of Langerhans.

Anal Methods 2021 Jul 26. Epub 2021 Jul 26.

Department of Chemistry and Biochemistry, Florida State University, 95 Chieftain Way, Tallahassee, FL 32306, USA.

Glucagon is a 29-amino acid peptide released from α-cells within pancreatic islets of Langerhans to help raise blood glucose levels. While a plethora of methodologies have been developed for quantitative measurement of insulin released from islets, such methods are not well developed for glucagon despite its importance in blood sugar regulation. In this work, a simple yet robust microfluidic device was developed for holding human pancreatic islets and perfuse them with glucose. Read More

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ACE2 Chromogenic Immunostaining Protocol Optimized for Formalin-fixed Paraffin Embedded Human Tissue Sections.

STAR Protoc 2021 Jul 21:100696. Epub 2021 Jul 21.

Department of Pathology, Immunology, and Laboratory Medicine, University of Florida Diabetes Institute, College of Medicine, Gainesville, FL 32610, USA.

Angiotensin-converting enzyme 2 (ACE2) is a key cellular entry factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hence, identifying cell types that express ACE2 is important for understanding the pathophysiology of coronavirus disease 2019 (COVID-19). We performed extensive testing of multiple primary antibodies across various human tissue types. Read More

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Functional Genomic Screening During Somatic Cell Reprogramming Identifies DKK3 as a Roadblock of Organ Regeneration.

Adv Sci (Weinh) 2021 07 13;8(14):2100626. Epub 2021 May 13.

Department of Internal Medicine I University Hospital Ulm Albert-Einstein Allee 23 89081 Ulm Germany.

Somatic cell reprogramming and tissue repair share relevant factors and molecular programs. Here, Dickkopf-3 (DKK3) is identified as novel factor for organ regeneration using combined transcription-factor-induced reprogramming and RNA-interference techniques. Loss of enhances the generation of induced pluripotent stem cells but does not affect de novo derivation of embryonic stem cells, three-germ-layer differentiation or colony formation capacity of liver and pancreatic organoids. Read More

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Icariin inhibits oral squamous cell carcinoma cell proliferation and induces apoptosis via inhibiting the NF-κB and PI3K/AKT pathways.

Ling Sun Jing Zhang

Exp Ther Med 2021 Sep 1;22(3):942. Epub 2021 Jul 1.

Department of Hematology, Yancheng No. 1 People's Hospital, Yancheng, Jiangsu 224006, P.R. China.

Oral squamous cell carcinoma (OSCC), one of the most common types of human cancer, has a high mortality rate and a poor prognosis due to its high rates of recurrence and metastasis. In recent years, icariin (ICA) has been reported to play an important role in a variety of malignancies, such as gastric, colorectal, pancreatic and ovarian cancer. However, its role and mechanism in OSCC remains to be elucidated. Read More

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September 2021

Protecting Stem Cell Derived Pancreatic Beta-Like Cells From Diabetogenic T Cell Recognition.

Front Endocrinol (Lausanne) 2021 9;12:707881. Epub 2021 Jul 9.

Barbara-Davis Center for Diabetes, University of Colorado Anschutz, Aurora, CO, United States.

Type 1 diabetes results from an autoimmune attack directed at pancreatic beta cells predominantly mediated by T cells. Transplantation of stem cell derived beta-like cells (sBC) have been shown to rescue diabetes in preclinical animal models. However, how sBC will respond to an inflammatory environment with diabetogenic T cells in a strict human setting has not been determined. Read More

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Specific Targeting of Recombinant Human Pancreatic Ribonuclease 1 using Gonadotropin-Releasing Hormone Targeting Peptide toward Gonadotropin-Releasing Hormone Receptor-Positive Cancer Cells.

Iran J Med Sci 2021 Jul;46(4):281-290

Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Targeted drug delivery is a novel method to specifically deliver anticancer therapeutics to tumor sites. Gonadotropin-releasing hormone (GnRH) is a decapeptide, and its target binding property has attracted attention as a means of targeted drug delivery. Human pancreatic ribonuclease 1 (hpRNase1) has been shown to exert anticancer properties, when fused to a targeting moiety. Read More

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