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"Sayed, Ramy"
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Main Components of Fish Immunity: An Overview of the Fish Immune System
by
Alesci, Alessio
,
Mokhtar, Doaa
,
Hussein, Manal
in
Adaptive immunity
,
Agricultural research
,
Antibodies
2023
Cellular immune responses consist of innate and adaptive cell-mediated immune mechanisms, where all leukocyte subpopulations are included. Among these are vital processes such as cell-mediated cytotoxicity and phagocytosis. The main cellular constituents of the fish immune system are macrophages, granulocytes, dendritic cells, NK cells, and cytotoxic T cells. This review provides the latest information on cellular defense mechanisms of fish and provides an overview of the function of the mucosal immune system in maintaining the general health of fish. Here, we discuss the fundamental ideas that underpin mucosal immune responses in teleosts, as well as the innate and adaptive immune cells and the molecules that play a role in these immune responses. Moreover, cytokine molecules and pathways in teleosts have been reported to focus on several kinds of associated immunity. Importantly, we also review antigen processing and presentation. The knowledge reported here will enable better understanding, determination, and modulation of the pathways responsible for protective immunity, thus consequently improving the health of the fish in aquaculture.
Journal Article
Immune cell diversity and regenerative markers reveal interactions among macrophages, rodlet cells, and stem cells in the kidney of Poecilia sphenops
2025
The kidneys of molly fish (
Poecilia sphenops
) exhibit complex immune and cellular activities, which are crucial for maintaining renal function and responding to environmental stressors. This study aimed to investigate the histological and immunohistochemical characteristics of immune cells, autophagy, and stem cell activity within the renal tissues of molly fish. Histological analysis revealed the presence of immune cells, including macrophages and granular leukocytes, concentrated around the renal corpuscles (RC) and renal tubules (RT). Additionally, numerous lymphocytes were observed surrounding the RC, and a notable presence of rodlet cells with a thick capsule and rodlet-like inclusions was detected around the RT. Immunohistochemical staining confirmed macrophage activity through CD68 and Iba1 expression, while APG5, an autophagy marker, was observed in macrophages, rodlet cells, and podocytes, indicating active autophagic processes. Polymorphic granulocytes expressed iNOS-2. Inflammatory markers IL-1β and NF-κB were highly expressed in rodlet cells and macrophages, respectively, suggesting their role in immune modulation. The expression of S100 protein in rodlet cells and acetylcholine in macrophages further highlights their specialized functions in immune regulation. Additionally, renal stem cells were identified by expressing Nrf2 and Sox9, indicating a potential role in tissue repair and regeneration. These findings provide critical insights into the kidney’s dual function in immunity and regeneration, contributing to a better understanding of fish renal physiology and potential applications in environmental monitoring and aquaculture health management.
Journal Article
Melatonin protects rats from radiotherapy-induced small intestine toxicity
by
Escames Rosa, Germaine
,
Molina Navarro, Maria Micaela
,
García Verdugo, José Manuel
in
Activation
,
Animals
,
Apoptosis
2017
Radiotherapy-induced gut toxicity is among the most prevalent dose-limiting toxicities following radiotherapy. Prevention of radiation enteropathy requires protection of the small intestine. However, despite the prevalence and burden of this pathology, there are currently no effective treatments for radiotherapy-induced gut toxicity, and this pathology remains unclear. The present study aimed to investigate the changes induced in the rat small intestine after external irradiation of the tongue, and to explore the potential radio-protective effects of melatonin gel. Male Wistar rats were subjected to irradiation of their tongues with an X-Ray YXLON Y.Tu 320-D03 irradiator, receiving a dose of 7.5 Gy/day for 5 days. For 21 days post-irradiation, rats were treated with 45 mg/day melatonin gel or vehicle, by local application into their mouths. Our results showed that mitochondrial oxidative stress, bioenergetic impairment, and subsequent NLRP3 inflammasome activation were involved in the development of radiotherapy-induced gut toxicity. Oral treatment with melatonin gel had a protective effect in the small intestine, which was associated with mitochondrial protection and, consequently, with a reduced inflammatory response, blunting the NF-κB/NLRP3 inflammasome signaling activation. Thus, rats treated with melatonin gel showed reduced intestinal apoptosis, relieving mucosal dysfunction and facilitating intestinal mucosa recovery. Our findings suggest that oral treatment with melatonin gel may be a potential preventive therapy for radiotherapy-induced gut toxicity in cancer patients.
Journal Article
Melatonin, clock genes and mitochondria in sepsis
by
Fernández-Ortiz, Marisol
,
Rusanova, Iryna
,
Escames, Germaine
in
Aging (artificial)
,
Animals
,
Antioxidants - pharmacology
2017
After the characterization of the central pacemaker in the suprachiasmatic nucleus, the expression of clock genes was identified in several peripheral tissues including the immune system. The hierarchical control from the central clock to peripheral clocks extends to other functions including endocrine, metabolic, immune, and mitochondrial responses. Increasing evidence links the disruption of the clock genes expression with multiple diseases and aging. Chronodisruption is associated with alterations of the immune system, immunosenescence, impairment of energy metabolism, and reduction of pineal and extrapineal melatonin production. Regarding sepsis, a condition coursing with an exaggerated response of innate immunity, experimental and clinical data showed an alteration of circadian rhythms that reflects the loss of the normal oscillation of the clock. Moreover, recent data point to that some mediators of the immune system affects the normal function of the clock. Under specific conditions, this control disappears reactivating the immune response. So, it seems that clock gene disruption favors the innate immune response, which in turn induces the expression of proinflammatory mediators, causing a further alteration of the clock. Here, the clock control of the mitochondrial function turns off, leading to a bioenergetic decay and formation of reactive oxygen species that, in turn, activate the inflammasome. This arm of the innate immunity is responsible for the huge increase of interleukin-1β and entrance into a vicious cycle that could lead to the death of the patient. The broken clock is recovered by melatonin administration, that is accompanied by the normalization of the innate immunity and mitochondrial homeostasis. Thus, this review emphasizes the connection between clock genes, innate immunity and mitochondria in health and sepsis, and the role of melatonin to maintain clock homeostasis.
Journal Article
The Role of the Tumor Microenvironment (TME) in Advancing Cancer Therapies: Immune System Interactions, Tumor-Infiltrating Lymphocytes (TILs), and the Role of Exosomes and Inflammasomes
by
Fernández-Ortiz, Marisol
,
Sayed, Ramy K. A.
,
Erasha, Atef M.
in
Adaptive immunity
,
Antigens
,
Cancer
2025
Understanding how different contributors within the tumor microenvironment (TME) function and communicate is essential for effective cancer detection and treatment. The TME encompasses all the surroundings of a tumor such as blood vessels, fibroblasts, immune cells, signaling molecules, exosomes, and the extracellular matrix (ECM). Subsequently, effective cancer therapy relies on addressing TME alterations, known drivers of tumor progression, immune evasion, and metastasis. Immune cells and other cell types act differently under cancerous conditions, either driving or hindering cancer progression. For instance, tumor-infiltrating lymphocytes (TILs) include lymphocytes of B and T cell types that can invade malignancies, bringing in and enhancing the ability of immune system to recognize and destroy cancer cells. Therefore, TILs display a promising approach to tackling the TME alterations and have the capability to significantly hinder cancer progression. Similarly, exosomes and inflammasomes exhibit a dual effect, resulting in either tumor progression or inhibition depending on the origin of exosomes, type of inflammasome and tumor. This review will explore how cells function in the presence of a tumor, the communication between cancer cells and immune cells, and the role of TILs, exosomes and inflammasomes within the TME. The efforts in this review are aimed at garnering interest in safer and durable therapies for cancer, in addition to providing a promising avenue for advancing cancer therapy and consequently improving survival rates.
Journal Article
The potential role of the pseudobranch of molly fish (Poecilia sphenops) in immunity and cell regeneration
2023
The pseudobranch is a gill-like structure that exhibits great variations in structure and function among fish species, and therefore, it has remained a topic of investigation for a long time. This study was conducted on adult Molly fish (
Poecilia sphenops
) to investigate the potential functions of their pseudobranch using histological, histochemical, immunohistochemical analysis, and scanning electron microscopy. The pseudobranch of Molly fish was of embedded type. It comprised many rows of parallel lamellae that were fused completely throughout their length by a thin connective tissue. These lamellae consisted of a central blood capillary, surrounded by large secretory pseudobranch cells (PSCs). Immunohistochemical analysis revealed the expression of PSCs for CD3, CD45, iNOS-2, and NF-κB, confirming their role in immunity. Furthermore, T-lymphocytes-positive CD3, leucocytes-positive CD45, and dendritic cells-positive CD-8 and macrophage- positive APG-5 could be distinguished. Moreover, myogenin and TGF-β-positive PSCs were identified, in addition to nests of stem cells- positive SOX-9 were detected. Melanocytes, telocytes, and GFAP-positive astrocytes were also demonstrated. Scanning electron microscopy revealed that the PSCs were covered by microridges, which may increase the surface area for ionic exchange. In conclusion, pseudobranch is a highly specialized structure that may be involved in immune response, ion transport, acid–base balance, as well as cell proliferation and regeneration.
Journal Article
Aflatoxin detoxification by manganese peroxidase purified from Pleurotus ostreatus
2014
Manganese peroxidase (MnP) was produced from white rot edible mushroom Pleurotus ostreatus on the culture filtrate. The enzyme was purified to homogeneity using (NH4)2SO4 precipitation, DEAE-Sepharose and Sephadex G-100 column chromatography. The final enzyme activity achieved 81 U mL(-1), specific activity 78 U mg(-1) with purification fold of 130 and recovery 1.2% of the crude enzyme. SDS-PAGE indicated that the pure enzyme have a molecular mass of approximately 42 kDa. The optimum pH was between 4-5 and the optimum temperature was 25 °C. The pure MnP activity was enhanced by Mn(2+), Cu(2+), Ca(2+) and K(+) and inhibited by Hg(+2) and Cd(+2). H2O2 at 5 mM enhanced MnP activity while at 10 mM inhibited it significantly. The MnP-cDNA encoding gene was sequenced and determined (GenBank accession no. AB698450.1). The MnP-cDNA was found to consist of 497 bp in an Open Reading Frame (ORF) encoding 165 amino acids. MnP from P. ostreatus could detoxify aflatoxin B1 (AFB1) depending on enzyme concentration and incubation period. The highest detoxification power (90%) was observed after 48 h incubation at 1.5 U mL(-1) enzyme activities.
Journal Article
Morphological and ultrasonographic characterization of the three zones of supratesticular region of testicular artery in Assaf rams
by
Sayed, Ramy K. A
,
Álvarez García, Mercedes
,
Neila Montero, Marta
in
692/4025/1527
,
692/698
,
692/698/690
2022
To fully understand the histological, morphometrical and heamodynamic variations of different supratesticular artery regions, 20 mature and healthy Assaf rams were examined through ultrasound and morphological studies. The testicular artery images of the spermatic cord as shown by B-mode analysis indicated a tortuous pattern along its course toward the testis, although it tends to be less tortuous close to the inguinal ring. Doppler velocimetric values showed a progressive decline in flow velocity, in addition to pulsatility and vessel resistivity when entering the testis, where there were significant differences in the Doppler indices and velocities among the different regions. The peak systolic velocity, pulsatility index and resistive index were higher in the proximal supratesticular artery region, followed by middle and distal ones, while the end diastolic velocity was higher in the distal supratesticular region. The total arterial blood flow and total arterial blood flow rate reported a progressive and significant increase along the testicular cord until entering the testis. Histological examination revealed presence of vasa vasorum in the tunica adventitia, with their diameter is higher in the proximal supratesticular zone than middle and distal ones. Morphometrically, the thickness of the supratesticular artery wall showed a significant decline downward toward the testis; meanwhile, the outer arterial diameter and inner luminal diameter displayed a significant increase distally. The expression of alpha smooth muscle actin and vimentin was higher in the tunica media of the proximal supratesticular artery zone than in middle and distal ones.
Journal Article
Structural and Functional Aspects of the Spleen in Molly Fish Poecilia sphenops (Valenciennes, 1846): Synergistic Interactions of Stem Cells, Neurons, and Immune Cells
by
Sayed, Ramy K. A.
,
Albano, Marco
,
Capillo, Gioele
in
Antigen-antibody complexes
,
Apoptosis
,
Blood vessels
2022
In fish, the spleen is the prime secondary lymphoid organ. It has a role in the induction of adaptive immune responses, in addition to its significance in the elimination of immune complexes. This study was conducted on 18 randomly obtained adult molly fish (Poecilia sphenops) of both sexes using histological, immunohistochemical, and ultrastructural studies to highlight the cellular components of the spleen and their potential role in the immune system. The spleen of molly fish was characterized by the presence of well-distinct melanomacrophage centers, and other basic structures present in higher vertebrates including red and white pulps, blood vessels, and ellipsoids. Some mitotic cells could also be identified in the red pulp. Mast cells with characteristic metachromatic granules could be seen among the splenic cells. Rodlet cells were randomly distributed in the spleen and were also observed around the ellipsoids. The white pulp of the spleen expressed APG5. The expressions were well distinct in the melanomacrophages, leukocytes, and macrophages. Myostatin was expressed in leukocytes and epithelial reticular cells. IL-1β showed immunoreactivity in monocytes and macrophages around the ellipsoids. NF-κB and TGF-β were expressed in macrophages and epithelial reticular cells. Nrf2 expression was detected in stem cells and rodlet cells. Sox-9 had a higher expression in epithelial reticular cells and stem cells. The high frequency of immune cells in the spleen confirmed its role in the regulation of both innate and adaptive immunity, cell proliferation, and apoptosis.
Journal Article
Zebrafish as a Human Muscle Model for Studying Age-Dependent Sarcopenia and Frailty
by
Escames, Germaine
,
Sayed, Ramy K. A.
,
Fernández-Martínez, José
in
Aging
,
Aging - physiology
,
Animals
2024
Currently, there is an increase in the aging of the population, which represents a risk factor for many diseases, including sarcopenia. Sarcopenia involves progressive loss of mass, strength, and function of the skeletal muscle. Some mechanisms include alterations in muscle structure, reduced regenerative capacity, oxidative stress, mitochondrial dysfunction, and inflammation. The zebrafish has emerged as a new model for studying skeletal muscle aging because of its numerous advantages, including histological and molecular similarity to human skeletal muscle. In this study, we used fish of 2, 10, 30, and 60 months of age. The older fish showed a higher frailty index with a value of 0.250 ± 0.000 because of reduced locomotor activity and alterations in biometric measurements. We observed changes in muscle structure with a decreased number of myocytes (0.031 myocytes/μm2 ± 0.004 at 60 months) and an increase in collagen with aging up to 15% ± 1.639 in the 60-month group, corresponding to alterations in the synthesis, degradation, and differentiation pathways. These changes were accompanied by mitochondrial alterations, such as a nearly 50% reduction in the number of intermyofibrillar mitochondria, 100% mitochondrial damage, and reduced mitochondrial dynamics. Overall, we demonstrated a similarity in the aging processes of muscle aging between zebrafish and mammals.
Journal Article