Exploring the Anti-Inflammatory Potential of a Peptide Mimetic of Sialic Acid(\(\alpha\)2,3) Galactose | Chapter 9 | Recent Developments in Chemistry and Biochemistry Research Vol. 5

 

A tetravalent peptide with the functional sequence NPSHPLSG designated svH1C, binds with high avidity to lectin-type receptors specific for structures that contain sialic acid (5-acetylneuraminic acid, Neu5Ac). Among the sialic acid-binding immunoglobulin-like lectins (the Siglec family of receptors), the peptide binds preferentially to those that bind Neu5Ac(\(\alpha\)2,3)Gal and Neu5Ac(\(\alpha\)2,8) Neu5Ac(\(\alpha\)2,3)Gal sequences and the larger sialyl Lewisx (sLex) structure.  svH1C has a flexible structure that enables binding with high avidity in the glycan binding site in an ‘induced-fit’ conformation.  Peritoneal populations of cells in C57BL/6 mice that constitute the innate immune system were increased 2- to 6-fold after three alternate-day subcutaneous injections. Incubation of neuraminidase-treated, human peripheral blood mononuclear cells with biotin-tagged svH1C resulted in substantial binding of the peptide to a subset of the CD14+ monocyte population. Nanomolar concentrations of svH1C induced phagocytic activity of adherent cells (monocytes and macrophages) from PBMC cultures. Predictions by molecular modeling suggest that the peptide binds to P- and E-selectins, which are receptors that facilitate the migration of neutrophils and T cells through endothelial tissues, and to siglecs on macrophages with avidities that are expected to mitigate neutrophil-driven inflammation. The therapeutic value of these anti-inflammatory activities was demonstrated by the resolution of severe lipopolysaccharide-induced inflammation in the skin of mice in two weeks by daily subcutaneous injections of 1 nmol/g body weight. These results support the conclusion that svH1C mimics Neu5Ac(\(\alpha\)2,3) Gal sequences and interacts with glycan binding sites of specific receptors with avidities sufficient to promote repair and restoration of damaged tissues.

 

Author(s) Details

Laura L. Eggink
Wild Boar Biosciences, LLC. 1615 W. University Drive, Suite 132, Tempe, AZ -85281-3257, USA.

J. Kenneth Hoober
Wild Boar Biosciences, LLC. 1615 W. University Drive, Suite 132, Tempe, AZ -85281-3257, USA.

 

Please see the book here:- https://doi.org/10.9734/bpi/rdcbr/v5/1744

Neutrophils in Rectal Cancer: The Sarandria Score - a New Clinical Prognostic and Predictive Score and Further Proof of Identifying Rectal Cancer as a Separate Clinical and Pathological Entity from Colon Cancer | Chapter 07 | New Horizons in Medicine and Medical Research Vol. 7

 This study aims to provide fresh insight on neutrophils' role in rectal cancer while also emphasising the differences between rectal and colon cancer, as well as strengthen and emphasise a new clinical prognostic and predictive scoring system (Sarandria Score). This research offers a new scoring method for patients with stage III rectal cancer that may be used as an inclusion criterion as well as a predictive and prognostic scoring system.

Background: Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second most commonly diagnosed cancer in women, making it a serious public health concern. Various studies have discovered significant disparities in adjuvant therapy responsiveness and prognosis dependent on the primary site of CRC (right-sided colon, left-sided colon, rectum). A larger density of tumor-associated neutrophils (TANs) has previously been linked to a better response to 5-FU-based treatment in stage III CRC patients.

Results: This chapter assesses the current state of knowledge on neutrophil participation in colorectal cancer, including a novel finding on the role of neutrophils in rectal cancer discovered by Dr. Nicola Sarandria. When chemotherapeutic drugs are present, it covers a number of variables that point to neutrophils playing an anti-tumor role in rectal cancer (such as 5-fluorouracil). The clinical significance of TANs was studied, as well as if it altered depending on the location of the primary CRC (right-sided colon, left-sided colon, rectum).

Conclusions: This chapter introduces the Sarandria Score, a new clinical prognostic and predictive scoring system for rectal cancer patients with intratumoral neutrophilic infiltration, as well as the possibility of a new inclusion criteria for Stage III rectal cancer patients receiving 5-FU therapy based on this infiltrate. Higher TANs densities were connected to greater disease-free survival (DFS) in rectal cancer patients treated with 5-FU, according to the author's medical degree thesis (while it was inversely related in patients without 5-FU therapy). This adds to the growing body of data showing colorectal cancer can be separated into two types: colon and rectal cancer.

Author(S) Details

Nicola Sarandria
University of Padova, Padova, Italy.

View Book:- https://stm.bookpi.org/NHMMR-V7/article/view/6665

COVID-19, Immune System and Hi-D FACS: A Review | Chapter 15 | Emerging Trends in Disease and Health Research Vol. 3

 Hi-D immunophenotyping of COVID-19 patients' peripheral blood indicated a considerable shift in immune cell ratios, particularly between mature and immature neutrophils, which was linked to severity. Absolute numbers of lymphocyte subsets were also reduced differently in COVID-19 individuals depending on clinical severity, according to Hi-D FACS. Using Hi-D FACS to study immune responses in the context of clinical severity is a basis for overcoming the lack of an efficient antiviral immune response in COVID-19 patients with severe disease, and it can serve as a predictive biomarker for disease outcome and control.

Author(S) Details

K. Heydari
Stanford Medicine, Cell Therapy Facility, Stanford Health Care, USA.

View Book:- https://stm.bookpi.org/ETDHR-V3/article/view/5892