Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd

Pivotal Role of Peptides in Gastric Carcinoma: Diagnosis and Therapy

Abstract: Gastric cancer (GC) is still ranked fourth among malignant cancers and remained as the second leading cause of cancer related death. There is mounting evidence that emphasizes on the need for further investigation on the specific receptors overexpression roles in GC progression. Low efficiency and impotence of the common methods for targeting gastric tumorigenesis and related metastases are enough to convince researchers to continue their investigation on new approaches of effective GC targeting. Due to the suitable characteristics of peptides, such as high affinity and specificity, they have great potential for cancer cell targeting. Overexpression of specific targets in GC can facilitate the application of peptide-based pharmaceuticals for effective tumor targeting and therapy and early diagnosis with help of fluorescents or radionuclides. In this review article, we paid particular attention to the characterization of peptide-based pharmaceuticals and radiopharmaceuticals that have been investigated in recent years for GC diagnosis and therapy. Graphic Abstract: Figure not available: see fulltext.. © 2020, Springer Nature B.V

Effects of Peppermint (Mentha piperita L.) Alcoholic Extract on Carbon Tetrachloride-induced Hepatotoxicity in Broiler Chickens Under Heat Stress Condition

In order to investigate the effects of peppermint (Mentha piperita L.) alcoholic extract on liver injury caused by the oxidant carbon tetrachloride (CCl4), an experiment was performed as a completely randomized design in a factorial arrangement (2 × 2) with 4 replications of 10 broilers each. Factors included two levels of peppermint leaf alcoholic extract (0 and 2 mL/Kg body weight) and CCl4 (0 and 1 mL/Kg body weight). Results showed significant (P) interactions for body weight gain (BWG), feed intake (FI) and feed conversion ratio (FCR) on d 42 of the experiment. The alcoholic extract of peppermint leaf did not improve growth performance, whereas CCl4 worsened BWG and FCR (P). The interaction between peppermint extract and CCl4 indicated an ameliorative effect of peppermint extract on BWG and FCR (P). The interaction effects between peppermint extract and CCl4 significantly differed for blood serum concentrations of total protein, albumin, albumin:globulin ratio, glucose, triglyceride, total cholesterol, HDLC, LDLC, LDLC:HDLC ratio, and VLDLC as well as the amount of blood liver enzymes (P). Peppermint extract significantly increased blood serum concentrations of total protein, albumin, triglyceride and HDLC, whilst CCl4 decreased those concentrations (P). Blood serum concentrations of total cholesterol, LDLC, LDLC:HDLC ratio, VLDLC and glucose were decreased by peppermint extract, whereas those concentrations were increased by CCl4 (P). A significantly higher level of liver enzymes was found in blood serum of birds treated by CCl4 than those by peppermint extract (P). A moderate effect on blood serum liver enzymes was observed by the interaction between 2 mL of peppermint extract and 1 mL of CCl4 (P). Generally, this study indicated that in vivo administration of peppermint alcoholic extract ameliorated the adverse effects of CCl4 on growth performance and liver function, therefore it might be useful for the prevention of oxidative stress-induced hepatotoxicity in broilers

Radioprotective effects of montelukast, a selective leukotriene CysLT1 receptor antagonist, against nephrotoxicity induced by gamma radiation in mice

Purpose: In this study, we evaluated the renal protective effects of montelukast (MLK) against ionizing radiation (IR) induced nephrotoxicity in mice. Materials and Methods: Radioprotective effects of MLK were assessed by biochemical analysis including measurements of kidney malondialdehyde (MDA), reduced glutathione (GSH), and serum creatinine and urea levels. Besides, for further evaluation of protective effects of MLK on renal system, 99mTc-dimercaptosuccinic acid (DMSA) has been applied. The total antioxidant capacity of MLK was measured by using 1,1-diphenyl-2-picryl hydrazyl radical reagents and compared with butylated hydroxyl toluene standard antioxidant. Results: The biochemical evaluation revealed that better results have been achieved for the groups administered with MLK than the only radiation group. Besides only IR-treated mice group, those treated with MLK demonstrated a significant decrease in urea and creatinine levels. Statistically, significant differences of MDA and SHG levels (P <.05) were found between the radiation group and MLK plus IR-treated group. Also, 99mTc-DMSA kidney uptake value (ID/g) was observed lower for MLK plus IR-treated mice group than only radiation-treated mice group. Conclusions: According to our findings, MLK has a potential role to be used as a renal protective agent against gamma radiation in radiotherapy. © 2020 Wiley Periodicals, Inc

Folate Receptor Beta for Macrophage Imaging in Rheumatoid Arthritis

Non-invasive imaging modalities constitute an increasingly important tool in diagnostic and therapy response monitoring of patients with autoimmune diseases, including rheumatoid arthritis (RA). In particular, macrophage imaging with positron emission tomography (PET) using novel radiotracers based on differential expression of plasma membrane proteins and functioning of cellular processes may be suited for this. Over the past decade, selective expression of folate receptor β (FRβ), a glycosylphosphatidylinositol-anchored plasma membrane protein, on myeloid cells has emerged as an attractive target for macrophage imaging by exploiting the high binding affinity of folate-based PET tracers. This work discusses molecular, biochemical and functional properties of FRβ, describes the preclinical development of a folate-PET tracer and the evaluation of this tracer in a translational model of arthritis for diagnostics and therapy-response monitoring, and finally the first clinical application of the folate-PET tracer in RA patients with active disease. Consequently, folate-based PET tracers hold great promise for macrophage imaging in a variety of (chronic) inflammatory (autoimmune) diseases beyond RA