Effects of Dietary Medlar (Mespilus germanica L.) Extract on Growth Performance, Innate Immune Characteristics, Antioxidant Status, and Responses to Crowding Stress in Rainbow Trout (Oncorhynchus mykiss).

High stocking density is a stress factor that potentially affects physiological and immune responses. In this study, the effects of medlar (Mespilus germanica) extract (ME) supplementation on growth performance, antioxidant, immune status, and stress responses in rainbow trout (Oncorhynchus mykiss) were studied. Six hundred fish (40.19 ± 1.09 g; average fish weight ± standard error) were distributed randomly into five experimental groups (assayed in triplicates). The experimental diets were formulated as follows: 0 (T1, control), 0.5% (T2), 1% (T3), 1.5% (T4), and 2% (T4). After 60 days feeding trial, the fish were confined, and the density increased (60 kg/m3) for further 14 days. Results showed significant increases in final weight (FW), weight gain (WG), specific growth rate, and feed intake in the T4 compared to the control (P < 0.05). The feed conversion ratio (FCR) in T4 significantly decreased compared to the control (P < 0.05). Also, the treated groups showed significant improvements in catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), lysozyme (LYZ), total immunoglobulin (total Ig), respiratory burst activity (RBA), total protein, and phagocytosis (PHA) (P < 0.05). Moreover, compared with the control group, supplementation could significantly decrease glucose (GLU) and cortisol (CORT), alanine transaminase (ALT), lactate dehydrogenase (LDH), aspartate transaminase (AST), and alkaline phosphatase (ALP) (P < 0.05). After the challenge, FW and WG in all treated challenge groups were significantly improved compared to the control group (P < 0.05). FCR showed a significant decrease in all treated challenged groups compared to the control group (P < 0.05). However, malondialdehyde, CAT, GPx, SOD, LYZ, complement activity (C3 and C4), total Ig, RBA, peroxidase, and PHA in challenged treated groups were significantly increased compared to the control group (P < 0.05). All treated challenged groups showed lower ALT, LDH, AST, ALP, GLU, and CORT levels than the control group (P < 0.05). The experiment herein successfully demonstrated that dietary ME stimulated fish growth, antioxidant status, and immune responses in crowding conditions and can be recommended as beneficial feed additives for rainbow trout.

Exploring the impact of miR-128 in inflammatory diseases: A comprehensive study on autoimmune diseases.

microRNAs (miRNAs) play a crucial role in various biological processes, including immune system regulation, such as cell proliferation, tolerance (central and peripheral), and T helper cell development. Dysregulation of miRNA expression and activity can disrupt immune responses and increase susceptibility to neuroimmune disorders. Conversely, miRNAs have been shown to have a protective role in modulating immune responses and preventing autoimmunity. Specifically, reducing the expression of miRNA-128 (miR-128) in an Alzheimer's disease (AD) mouse model has been found to improve cognitive deficits and reduce neuropathology. This comprehensive review focuses on the significance of miR-128 in the pathogenesis of neuroautoimmune disorders, including multiple sclerosis (MS), AD, Parkinson's disease (PD), Huntington's disease (HD), epilepsy, as well as other immune-mediated diseases such as inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). Additionally, we present compelling evidence supporting the potential use of miR-128 as a diagnostic or therapeutic biomarker for neuroimmune disorders. Collectively, the available literature suggests that targeting miR-128 could be a promising strategy to alleviate the behavioral symptoms associated with neuroimmune diseases. Furthermore, further research in this area may uncover new insights into the molecular mechanisms underlying these disorders and potentially lead to the development of novel therapeutic approaches.

Ketoprofen suppresses triple negative breast cancer cell growth by inducing apoptosis and inhibiting autophagy.

BACKGROUND: Triple-negative breast cancer (TNBC) is an invasive phenotype with undesirable clinical features, poor prognosis, and therapy resistance. Ketoprofen is a Non-steroidal anti-inflammatory drug (NSAID) with anti-tumor properties. AIM: To investigate the effects of Ketoprofen on apoptosis and autophagy in TNBC cell line MDA-MB-231. METHODS: The cytotoxic activity of Ketoprofen was assayed by the MTS method. Flowcytometry was utilized to measure the number of apoptotic MDA-MB-231 cells. The expression levels of apoptosis and autophagy markers, JAK2 and STAT3 were determined using quantitative real time-PCR (qRT-PCR) and western blotting methods. RESULTS: Ketoprofen significantly decreased the proliferation of MDA-MB-231 cells compared to control cells. It also considerably induced apoptosis and apoptotic markers in these cells in comparison to controls. Treating the MADA-MB-231 cell line with Ketoprofen had an inhibitory effect on autophagy markers in this cell line. The use of FasL, as a death ligand, and ZB4, as an antibody that blocks the extrinsic pathway of apoptosis, revealed the involvement of the extrinsic pathway in the apoptosis-stimulating effect of Ketoprofen in the MADA-MB-231 cell line. Ketoprofen also hindered the phosphorylation and activation of JAK2 and STAT molecules leading to the inhibition of the JAK/STAT pathway in this TNBC cell line. CONCLUSION: The outcomes of this study uncovered the anti-TNBC activity of Ketoprofen by inducing apoptosis and inhibiting viability and autophagy in MADA-MB-231 cells. Our data also suggested that Ketoprofen impedes apoptosis in TNBC cells by two different mechanisms including the induction of the extrinsic apoptotic pathway and inhibition of the JAK/STAT signaling.

Expression of ZO1, vimentin, pan-cadherin and AGTR1 in tanycyte-like cells of the sulcus medianus organum.

Tanycytes are a specialized ependymal lining of brain ventricles with exceptional features of having long basal processes and junctional complexes between cell bodies. These tanycytes are present at the regions of circumventricular organs (CVOs) which possess common morphological and functional features enabling them to be described as the brain windows where the barrier systems have special properties. Previous studies detailed seven of these CVOs but little information is available regarding another putative site at the rostral part of the median sulcus of the 4th ventricle, or the sulcus medianus organum (SMO). Here we performed a pilot immunohistochemical study to support earlier observations suggesting the SMO as a novel CVO. We labeled rat brain with ZO1, vimentin, pan-cadherin and angiotensin II type 1 receptors markers which showed a morphologically distinct population of cells at the region of the SMO similar to tanycytes present in the median eminence, a known CVO. These cells had basal processes reaching the deeply seated blood vessels while the caudal part of the median sulcus did not show similar long cellular extensions. We concluded that tanycyte-like cells are present in the SMO in a pattern resembling that of other CVOs where the strategic location of the SMO is probably for signal integration between brainstem nuclei and the rostrally located neuronal centers.