Targeting Human Pancreatic Cancer with a Fluorophore-Conjugated Mucin 4 (MUC4) Antibody: Initial Characterization in Orthotopic Cell Line Mouse Models.

Pancreatic cancer is the third leading cause of death related to cancer. The only possible cure presently is complete surgical resection; however, this is limited by difficulty in clearly defining tumor margins. Enhancement of the visualization of pancreatic ductal adenocarcinoma (PDAC) tumor margins using near-infrared dye-conjugated tumor-specific antibodies was pioneered by using anti-CEA, anti-CA19.

Genetic Code Expansion in MR-1 Allows Site-Specific Incorporation of Bioorthogonal Functional Groups into a -Type Cytochrome.

Genetic code expansion has enabled cellular synthesis of proteins containing unique chemical functional groups to allow the understanding and modulation of biological systems and engineer new biotechnology. Here, we report the development of efficient methods for site-specific incorporation of structurally diverse noncanonical amino acids (ncAAs) into proteins expressed in the electroactive bacterium MR-1. We demonstrate that the biosynthetic machinery for ncAA incorporation is compatible and orthogonal to the endogenous pathways of MR-1 for protein synthesis, maturation of -type cytochromes, and protein secretion.

Nonperturbative Fluorogenic Labeling of Immunophilins Enables the Wash-free Detection of Immunosuppressants.

Immunosuppressants are clinically approved drugs to treat the potential rejection of transplanted organs and require frequent monitoring due to their narrow therapeutic window. Immunophilins are small proteins that bind immunosuppressants with high affinity, yet there are no examples of fluorogenic immunophilins and their potential application as optical biosensors for immunosuppressive drugs in clinical biosamples. In the present work, we designed novel diazonium BODIPY salts for the site-specific labeling of tyrosine residues in peptides via solid-phase synthesis as well as for late-stage functionalization of whole recombinant proteins.

Chimeric antibody targeting unique epitope on onco-mucin16 reduces tumor burden in pancreatic and lung malignancies.

Aberrantly expressed onco-mucin 16 (MUC16) and its post-cleavage generated surface tethered carboxy-terminal (MUC16-Cter) domain are strongly associated with poor prognosis and lethality of pancreatic (PC) and non-small cell lung cancer (NSCLC). To date, most anti-MUC16 antibodies are directed towards the extracellular domain of MUC16 (CA125), which is usually cleaved and shed in the circulation hence obscuring antibody accessibility to the cancer cells. Herein, we establish the utility of targeting a post-cleavage generated, surface-tethered oncogenic MUC16 carboxy-terminal (MUC16-Cter) domain by using a novel chimeric antibody in human IgG1 format, ch5E6, whose epitope expression directly correlates with disease severity in both cancers.

Bilateral variation in the branching pattern of the subclavian artery: an unusual finding with clinical implications.

The subclavian artery is a significant branch of the aortic arch. We present a rare case of a bilateral variation in the branching pattern of the subclavian artery, observed in an adult male cadaver aged 70 years. On both the sides of the neck, all the branches of the subclavian artery took their origin from its first part.

Mucins as Potential Biomarkers for Early Detection of Cancer.

Early detection significantly correlates with improved survival in cancer patients. So far, a limited number of biomarkers have been validated to diagnose cancers at an early stage. Considering the leading cancer types that contribute to more than 50% of deaths in the USA, we discuss the ongoing endeavors toward early detection of lung, breast, ovarian, colon, prostate, liver, and pancreatic cancers to highlight the significance of mucin glycoproteins in cancer diagnosis.

Metals in Prebiotic Catalysis: A Possible Evolutionary Pathway for the Emergence of Metalloproteins.

Proteinaceous catalysts found in extant biology are products of life that were potentially derived through prolonged periods of evolution. Given their complexity, it is reasonable to assume that they were not accessible to prebiotic chemistry as such. Nevertheless, the dependence of many enzymes on metal ions or metal-ligand cores suggests that catalysis relevant to biology could also be possible with just the metal centers.

Morphometric analysis of the palatine triangle in adult human skulls: a potential aid for anthropologists and intraoral bone grafts.

Morphometrics of the hard palate is an important aspect of forensic anthropology and odontology. Palatine triangle is a triangular area in the hard palate formed by the palatine processes of the maxillae, which can aid intraoral bone grafts. We present the osteological measurements of the palatine triangle (maxillary palate) based on sex, compare it with other hard palate parameters, and establish the correlation between them.

Muc4 loss mitigates epidermal growth factor receptor activity essential for PDAC tumorigenesis.

Mucin4 (MUC4) appears early during pancreatic intraepithelial neoplasia-1 (PanIN1), coinciding with the expression of epidermal growth factor receptor-1 (EGFR). The EGFR signaling is required for the onset of Kras-driven pancreatic ductal adenocarcinoma (PDAC); however, the players and mechanisms involved in sustained EGFR signaling in early PanIN lesions remain elusive. We generated a unique Esai-CRISPR-based Muc4 conditional knockout murine model to evaluate its effect on PDAC pathology.

Regulation of pancreatic cancer therapy resistance by chemokines.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy characterized by high resistance and poor response to chemotherapy. In addition, the poorly immunogenic pancreatic tumors constitute an immunosuppressive tumor microenvironment (TME) that render immunotherapy-based approaches ineffective. Understanding the mechanisms of therapy resistance, identifying new targets, and developing effective strategies to overcome resistance can significantly impact the management of PDAC patients.

Endothelin-axis antagonism enhances tumor perfusion in pancreatic cancer.

Delivery of therapeutic agents in pancreatic cancer (PC) is impaired due to its hypovascular and desmoplastic tumor microenvironment. The Endothelin (ET)-axis is the major regulator of vasomotor tone under physiological conditions and is highly upregulated in multiple cancers. We investigated the effect of dual endothelin receptor antagonist bosentan on perfusion and macromolecular transport in a PC cell-fibroblast co-implantation tumor model using Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI).

Characterization of recombinant β subunit of human MUC4 mucin (rMUC4β).

MUC4 is a transmembrane mucin expressed on various epithelial surfaces, including respiratory and gastrointestinal tracts, and helps in their lubrication and protection. MUC4 is also aberrantly overexpressed in various epithelial malignancies and functionally contributes to cancer development and progression. MUC4 is putatively cleaved at the GDPH site into a mucin-like α-subunit and a membrane-tethered growth factor-like β-subunit.

Morphohistological analysis of the prevalence and distribution of atheroma in the abdominal aorta and its branches: a cadaveric study.

Background: Aneurysms and atheromatous processes are prominent pathological features that are commonly associated with significant morbidity and mortality.

Objectives: This cadaveric study was conducted to evaluate the morphometric and histological aspects of atheromatous plaque formation in abdominal aortas and their branches and their associated morphological variations, if present, characterized by loops, kinking, or tortuosity.

Methods: The study was performed using 30 human cadavers (approx.

Topics of Nicotine-Related Discussions on Twitter: Infoveillance Study.

Background: Cultural trends in the United States, the nicotine consumer marketplace, and tobacco policies are changing.

Objective: The goal of this study was to identify and describe nicotine-related topics of conversation authored by the public and social bots on Twitter, including any misinformation or misconceptions that health education campaigns could potentially correct.

Methods: Twitter posts containing the term "nicotine" were obtained from September 30, 2018 to October 1, 2019.

Modeling pancreatic cancer in mice for experimental therapeutics.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy that is characterized by early metastasis, low resectability, high recurrence, and therapy resistance. The experimental mouse models have played a central role in understanding the pathobiology of PDAC and in the preclinical evaluation of various therapeutic modalities. Different mouse models with targetable pathological hallmarks have been developed and employed to address the unique challenges associated with PDAC progression, metastasis, and stromal heterogeneity.

Hepatoprotective effect of bone marrow-derived mesenchymal stromal cells in CCl-induced liver cirrhosis.

Bone marrow mesenchymal stromal cells (BM-MSCs) are multipotent stem cells which are ideal candidates for use in regenerative medicine. The objectives of this study were to evaluate the hepatoprotective effect of BM-MSC and its combination treatment with silymarin in carbon tetrachloride (CCl)-induced liver cirrhosis animal model and to investigate whether tail vein or portal vein infusion was the ideal route for BM-MSC transplantation. 36 female Wistar rats were randomly divided into six groups ( = 6): Group 1 (normal control), Group 2 (received only CCl, disease model), Group 3 (CCl + BM-MSCs through tail vein), Group 4 (CCl + BM-MSCs through portal vein), Group 5 (CCl + silymarin), Group 6 (CCl + BM-MSCs + silymarin).

Proteo-Genomic Analysis of SARS-CoV-2: A Clinical Landscape of Single-Nucleotide Polymorphisms, COVID-19 Proteome, and Host Responses.

A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and continues to be a global health challenge. To understand viral disease biology, we have carried out proteo-genomic analysis using next-generation sequencing (NGS) and mass spectrometry on nasopharyngeal swabs of COVID-19 patients to examine the clinical genome and proteome. Our study confirms the mutability of SARS-CoV-2 showing multiple single-nucleotide polymorphisms.

The Current Landscape of Antibody-based Therapies in Solid Malignancies.

Over the past three decades, monoclonal antibodies (mAbs) have revolutionized the landscape of cancer therapy. Still, this benefit remains restricted to a small proportion of patients due to moderate response rates and resistance emergence. The field has started to embrace better mAb-based formats with advancements in molecular and protein engineering technologies.

Polyanhydride nanoparticles stabilize pancreatic cancer antigen MUC4β.

Pancreatic cancer (PC) is one of the most lethal malignancies and represents an increasing and challenging threat, especially with an aging population. The identification of immunogenic PC-specific upregulated antigens and an enhanced understanding of the immunosuppressive tumor microenvironment have provided opportunities to enable the immune system to recognize cancer cells. Due to its differential upregulation and functional role in PC, the transmembrane mucin MUC4 is an attractive target for immunotherapy.

Circulation of Asian-I and Cosmopolitan genotypes of Dengue-2 virus in northeast India, 2016-2017.

Background & Objectives: Dengue is a major public health problem in northeast India where the majority of the cases go unreported and undiagnosed. Even though all four dengue serotypes are reported, there is a dearth of information on genetic diversity. The present cross-sectional study was undertaken during 2016-17 to determine the genetic variance of dengue virus serotype 2 (DENV-2) based on the envelope (E) glycoprotein gene.

Double-bellied superior rectus muscle.

Congenital variations of extraocular muscles are rare. We report a double-bellied superior rectus muscle, observed in an adult male cadaver aged 70 years. The superior rectus muscle had two equal-sized bellies, which took separate origins from the common tendinous ring and united to form a common belly 1 cm before the insertion.

Unusual duplication and vulnerable intrapancreatic course of the left gastroepiploic artery: a rare anatomical variation.

The left gastroepiploic artery (LGEA) is the least described artery in the medical literature. Unusual variations of this artery might lead to vascular injuries, causing intraoperative bleeding after surgery. We observed rare vascular variations in an adult male cadaver.

Cancer-associated mucins: role in immune modulation and metastasis.

Mucins (MUC) protect epithelial barriers from environmental insult to maintain homeostasis. However, their aberrant overexpression and glycosylation in various malignancies facilitate oncogenic events from inception to metastasis. Mucin-associated sialyl-Tn (sTn) antigens bind to various receptors present on the dendritic cells (DCs), macrophages, and natural killer (NK) cells, resulting in overall immunosuppression by either receptor masking or inhibition of cytolytic activity.