Browsing by Subject "Inflammation"

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    A human antithrombin isoform dampens inflammatory responses and protects from organ damage during bacterial infection
    (Nature Research, 2019) Papareddy, Praveen; Rossnagel, Madlen; Hollwedel, Femke; Kilic, Gülcan; Veerla, Srinivas; Naudin, Clément; Smeds, Emanuel; Westman, Johannes; Martínez-Martínez, Irene; Egesten, Arne; Morena-Barrio, María Eugenia de la; Corral, Javier; Linder, Adam; Artoni, Andrea; Abbattista, Maria; Novembrino, Cristina; Brakebusch, Cord Hebert; Martinelli, Ida; Kasetty, Gopinath; Herwarld, Heiko; Medicina
    Severe infectious diseases are often characterized by an overwhelming and unbalanced systemic immune response to microbial infections. Human antithrombin (hAT) is a crucial coagulation inhibitor with anti-inflammatory activities. Here we identify three hAT-binding proteins (CD13, CD300f and LRP-1) on human monocytes that are involved in blocking the activity of nuclear factor-κB. We found that the modulating effect is primarily restricted to the less abundant β-isoform (hβAT) of hAT that lacks N-glycosylation at position 135. Individuals with a mutation at this position have increased production of hβAT and analysis of their blood, which was stimulated ex vivo with lipopolysaccharide, showed a decreased inflammatory response. Similar findings were recorded when heterozygotic mice expressing hAT or hβAT were challenged with lipopolysaccharide or infected with Escherichia coli bacteria. Our results finally demonstrate that in a lethal E. coli infection model, survival rates increased when mice were treated with hβAT one hour and five hours after infection. The treatment also resulted in a reduction of the inflammatory response and less severe organ damage.
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    A novel CD14high CD16high subset of peritoneal macrophages from cirrhotic patients is associated to an increased response to LPS
    (Elsevier, 2016-03-01) Fernández-Fernández, María Dolores; Tristán-Manzano, María; Sánchez-Velasco, Eduardo; Miras-López, Manuel; García-Penarrubia, Pilar; Hernández Caselles, Trinidad; Martínez-Esparza Alvargonzález, María Concepción; Ruiz Alcaraz, Antonio José; Tapia Abellán, Ana; Bioquímica y Biología Molecular B e Inmunología
    The aim of this study was to characterize monocyte-derived macrophages (M-DM) from blood and ascites of cirrhotic patients comparatively with those obtained from blood of healthy controls. The phenotypic profile based on CD14/CD16 expression was analyzed by flow cytometry. Cells were isolated and stimulated in vitro with LPS and heat killed Candida albicans. Phosphorylation of ERK, c-Jun, p38 MAPK, and PKB/Akt was analyzed by Western blotting. A novel CD14(high)CD16(high) M-DM subpopulation is present in ascites (∼33%). The CD14(++)CD16(+) intermediate subset is increased in the blood of cirrhotic patients (∼from 4% to 11%) and is predominant in ascites (49%), while the classical CD14(++)CD16(-) subpopulation is notably reduced in ascites (18%). Basal hyperactivation of ERK and JNK/c-Jun pathways observed in ascites M-DM correlates with CD14/CD16 high expressing subsets, while PI3K/PKB does it with the CD16 low expressing cells. In vitro LPS treatment highly increases ERK1/2, PKB/Akt and c-Jun phosphorylation, while that of p38 MAPK is decreased in M-DM from ascites compared to control blood M-DM. Stimulation of healthy blood M-DM with LPS and C. albicans induced higher phosphorylation levels of p38 than those from ascites. Regarding cytokines secretion, in vitro activated M-DM from ascites of cirrhotic patients produced significantly higher amounts of IL-6, IL-10 and TNF-α, and lower levels of IL-1β and IL-12 than control blood M-DM. In conclusion, a new subpopulation of CD14(high)CD16(high) peritoneal M-DM has been identified in ascites of cirrhotic patients, which is very sensitive to LPS stimulation.
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    Albiflorin relieves cerebral ischemia-reperfusion injury by activating Nrf2/HO-1 pathway
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Zhu, Fei; Xiong, Jianzhong; Yi, Fei; Luo, Ermin; Huang, Chun; Li, Runying
    Our work aims to investigate the functions of a natural compound, Albiflorin (AF) in cerebral ischemia-reperfusion (IR) injury. The cerebral IR models were established by OGD/R in PC12 cells and MCAO/IR in rats. The cells in a glucose-free medium were placed in an anaerobic chamber containing 95% N2 and 5% CO2 for 3h at 37°C, returned to a normal medium, and incubated for 24h to accomplish OGD/R. Focal cerebral ischemia was conducted by thread occlusion of the right middle cerebral artery for 2h followed by 24h reperfusion in rats. CCK-8 assay indicated that AF had no toxicity to PC12 cells. Flow cytometry, Western blot, or TUNEL showed that AF treatment reduced apoptosis of cells or rat brain tissues. qRT-PCR and ELISA showed that AF decreased IL-1β, IL-6, and TNF-α levels in vitro and in vivo. Elevated levels of MDA, SOD, and ROS induced by IR injury were mitigated by AF in vitro and in vivo. HE and TTC staining revealed that AF ameliorated pathological injury in MCAO/IR rats. Western blot showed that Nrf2, NQO1, and HO-1 expression was activated by AF, and ML385 treatment suppressed the inhibition effects of AF in cerebral IR injury models. Overall, AF alleviates cerebral IR injury via regulating the Nrf2/HO-1 pathway.
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    Aliskiren improves renal morphophysiology and inflammation in Wistar rats with 2K1C renovascular hypertension
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Pereira, Priscila G.; Rabelo, Kíssila; Silva da, Jemima F. R.; Ciambarella, Bianca T.; Argento, Juliana G.C.; Nascimento, Ana L.R.; Vieira, Aline B.; Carvalho de, Jorge J.
    Hypertension is characterized by persistent elevated blood pressure levels, one of the leading causes of death in the world. Renovascular hypertension represents the most common cause of secondary hypertension, and its progress is associated with overactivation of the renin angiotensin aldosterone system (RAAS), causing systemic and local changes. Aliskiren is a renin-inhibiting drug that optimizes RAAS suppression. In this sense, the objective of the present study was to analyze the morphophysiology of the left kidney in Wistar rats with renovascular hypertension after treatment with Aliskiren. Parameters such as systolic blood pressure, urinary creatinine and protein excretion, renal cortex structure and ultrastructure, fibrosis and tissue inflammation were analyzed. Our results showed that the hypertensive animals treated with Aliskiren presented a reestablishment of blood pressure, expression of renin, and renal function, as well as a remodeling of morphological alterations through the reduction of fibrosis. The treatment regulated the laminin expression and decreased pro-inflammatory cytokines, restoring the integrity of the glomerular filtration barrier. Therefore, our findings suggest that Aliskiren has a renoprotective effect acting on the improvement of the morphology, physiology and pathology of the renal cortex of animals with renovascular hypertension
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    Alterations in haemolymph proteome of Mytilus galloprovincialis mussel after an induced injury
    (Elsevier, 2018-01-31) Franco-Martínez, Lorena; Martínez-Subiela, Silvia; Escribano, Damián; Schlosser, Sarah; Nöbauer, Katharina; Razzazi-Fazeli, Ebrahím; Romero, Diego; Cerón, José Joaquín Cerón; Tvarijonaviciute, Asta; Ciencias Sociosanitarias
    A proteomic and biochemical approach was performed to assess the effects of an induced muscle injury on the haemolymph of bivalve molluscs. For this purpose, Mytilus galloprovincialis were exposed to puncture of adductor muscle for three consecutive days, and their haemolymph proteome was then compared to healthy animals using 2-dimensional electrophoresis (2-DE) to identify proteins that differed significantly in abundance. Those proteins were then subjected to tandem mass spectrometry and 6 proteins, namely myosin, tropomyosin, CuZn super-oxide dismutase (SOD), triosephosphate isomerase, EP protein and small heat shock protein were identified. SOD and tropomyosin changes were verified by spectrophotometric measurements and western blotting, respectively. As some of the proteins identified are related to muscular damage and oxidative stress, other biomarkers associated with these processes that can be evaluated by automatic biochemical assays were measured including troponin, creatine kinase (CK), and aspartate aminotransferase (AST) for muscle damage, and SOD, trolox equivalent antioxidant capacity (TEAC) and esterase activity (EA) for oxidative stress. Significantly higher concentrations of troponin, CK, AST, and TEAC were observed in mussels after puncture, being also possible biomarkers of non-specific induced damage.
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    Analysis of key proinflammatory mechanisms in cardiovascular pathology through stimulation with lipopolysaccharide and urban particulate matter in mouse atrial cardiomyocytes
    (Elsevier, 2025-02-09) Mandaglio-Collados, Darío; Ruiz Alcaraz, Antonio José; Rivera Caravaca, José Miguel; Ramos-Bratos, María Pilar; Marín Ortuño, Francisco; López Gálvez, Raquel; Bioquímica y Biología Molecular B e Inmunología; Facultad de Biología
    Air pollution has emerged as one of the leading causes of mortality, aggravating cardiovascular diseases. Urban-particulate matter (PM) can accumulate in the cardiovascular system and through inflammation, trigger systemic damage. One of the key mechanisms of this process could be related to the activation of the inflammasome through the pre-existence of a low-grade endotoxemia and PM presence in the cells. Herein, we studied the deleterious effects of urban-PM and Lipopolysaccharide (LPS) exposure in a HL-1 mouse cardiomyocyte cell line. Urban-PM induced biological changes, including mRNA expression of pro-inflammatory genes, intracellular reactive oxygen species (ROS) generation and overexpression of inflammasome-related and structural proteins. The results revealed that urban-PM with different ultrastructure, as determined by transmission electron microscopy (TEM), is embedded inside the cardiomyocytes, leading to the recognition and activation of the inflammatory process. The increase of ROS levels and mRNA levels of pro-inflammatory genes were similarly observed in a dose-dependent manner. In addition, components and proteins of the inflammasome such as associated speck-like protein containing a CARD (ASC), caspase-1 and IL-1β were differentially overexpressed in treated HL-1 cells, as well as structural proteins like Connexin 43 (Cx43). These results provide new insights into the mechanisms that mediate innate pro-inflammatory activation in cardiomyocytes in response to air suspension pollutants.
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    Astragaloside IV induces endothelial progenitor cell angiogenesis in deep venous thrombosis through inactivation of PI3K/AKT signaling
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Lyu, Xiaojiang; Yi, Zhigang; He, Yun; Zhang, Chunfeng; Zhu, Ping; Liu, Chonghai
    Background. Deep vein thrombosis (DVT), referred to as venous thromboembolism, is the third most frequent cardiovascular disease. Endothelial progenitor cells (EPCs) contribute to the recanalization of DVT. Astragaloside IV (AS-IV) has been suggested to have angiogenesis-enhancing effects. Here, we investigate the roles and mechanisms of AS-IV in EPCs and DVT. Methods. The experimental DVT model was established by inferior vena cava stenosis in rats. EPCs were collected from patients with DVT. Transwell assays were performed to detect cell migration. Tube formation was determined using Matrigel basement membrane matrix and ImageJ software. The thrombus weight and length were measured. Pathological changes were examined by hematoxylin-eosin staining. The production of proinflammatory cytokines was estimated by ELISA. The level of PI3K/AKT-related proteins was measured by western blotting. Results. AS-IV administration facilitated the migrative and angiogenic functions of human EPCs in vitro. Additionally, AS-IV inhibited thrombosis and repressed the infiltration of leukocytes into the thrombus and the production of proinflammatory cytokines in rats. Mechanistically, AS-IV inactivated PI3K/AKT signaling in rats. Conclusion. AS-IV prevents thrombus in an experimental DVT model by facilitating EPC angiogenesis and decreasing inflammation through inactivation of PI3K/AKT signaling.
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    Biomarker-based assessment of somatostatin-6 immunomodulation in gilthead Seabream: From serum proteins to skin mucus enzymes
    (0022-10-20) Jose Carlos Campos Sánchez; Cristóbal Espinosa-Ruiz; Francisco A. Guardiola; Esteban Abad, María de los Ángeles; Guardiola Abellán, Francisco Antonio; Marín Parra, Claudia; Biología Celular e Histología
    This study evaluated the immunomodulatory role of somatostatin-6 (SST6) in gilthead seabream (Sparus aurata) using a validated inflammation model induced by λ-carrageenan and a comprehensive panel of serum and skin mucus biomarkers. SST6 was administered at 1 nM and 2 nM, and its effects were assessed in these matrices. The λ-carrageenan model triggered a local inflammatory response with reduced peroxidase, esterase, and protease activities in skin mucus, consistent with the resolution phase of innate immunity. SST6 at 1 nM enhanced serum complement activity without affecting acute-phase proteins, suggesting reinforcement of basal immune surveillance in the host. When combined with λ-carrageenan, SST6 promoted an increase in serum immunoglobulin levels and a selective shift in proteinogram fractions (α2-globulin), while further decreasing the oxidative and proteolytic activities in skin mucus. Correlation analysis revealed the coordinated regulation of key mucosal enzymes, reinforcing the functional integration of local immune responses. These results indicate that SST6 facilitates an early transition from innate to adaptive immunity while preserving the integrity of the mucosal barrier. Furthermore, this study provides the first evidence of complement activation by SST6 in fish and highlights the value of integrating biomarker-based tools to monitor immunophysiological responses and test bioactive compounds in aquaculture research.
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    Brassica bioactives could ameliorate the chronic inflammatory condition of endometriosis
    (MDPI, 2020-12-10) García-Ibañez, Paula; Yepes-Molina, Lucía; Ruiz Alcaraz, Antonio José; Martínez-Esparza Alvargonzález, María Concepción; Moreno, Diego A.; Carvajal, Micaela; García Peñarrubia, María del Pilar; Bioquímica y Biología Molecular B e Inmunología; Facultad de Biología
    Endometriosis is a chronic, inflammatory, hormone-dependent disease characterized by histological lesions produced by the presence of endometrial tissue outside the uterine cavity. Despite the fact that an estimated 176 million women are affected worldwide by this gynecological disorder, risk factors that cause endometriosis have not been properly defined and current treatments are not efficient. Although the interaction between diet and human health has been the focus of many studies, little information about the correlation of foods and their bioactive derivates with endometriosis is available. In this framework, Brassica crops have emerged as potential candidates for ameliorating the chronic inflammatory condition of endometriosis, due to their abundant content of health-promoting compounds such as glucosinolates and their hydrolysis products, isothiocyanates. Several inflammation-related signaling pathways have been included among the known targets of isothiocyanates, but those involving aquaporin water channels have an important role in endometriosis. Therefore, the aim of this review is to highlight the promising effects of the phytochemicals present in Brassica spp. as major candidates for inclusion in a dietary approach aiming to improve the inflammatory condition of women affected with endometriosis. This review points out the potential roles of glucosinolates and sothiocyanates from Brassicas as anti-inflammatory compounds, which might contribute to a reduction in endometriosis symptoms. In view of these promising results, further investigation of the effect of glucosinolates on chronic inflammatory diseases, either as diet coadjuvants or as therapeutic molecules, should be performed. In addition, we highlight the involvement of aquaporins in the maintenance of immune homeostasis. In brief, glucosinolates and the modulation of cellular water by aquaporins could shed light on new approaches to improve the quality of life for women with endometriosis.
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    Brassica bioactives could ameliorate the chronic inflammatory condition of Endometriosis
    (MDPI, ) García Ibánez, Paula; Yepes Molina, Lucía; Moreno, Diego A.; Carvajal, Micaela; García Peñarrubia, Pilar; Martínez-Esparza Alvargonzález, María Concepción; Ruiz Alcaraz, Antonio José; Bioquímica y Biología Molecular B e Inmunología
    Endometriosis is a chronic, inflammatory, hormone-dependent disease characterized by histological lesions produced by the presence of endometrial tissue outside the uterine cavity. Despite the fact that an estimated 176 million women are a ected worldwide by this gynecological disorder, risk factors that cause endometriosis have not been properly defined and current treatments are not e cient. Although the interaction between diet and human health has been the focus of many studies, little information about the correlation of foods and their bioactive derivates with endometriosis is available. In this framework, Brassica crops have emerged as potential candidates for ameliorating the chronic inflammatory condition of endometriosis, due to their abundant content of health-promoting compounds such as glucosinolates and their hydrolysis products, isothiocyanates. Several inflammation-related signaling pathways have been included among the known targets of isothiocyanates, but those involving aquaporin water channels have an important role in endometriosis. Therefore, the aim of this review is to highlight the promising e ects of the phytochemicals present in Brassica spp. as major candidates for inclusion in a dietary approach aiming to improve the inflammatory condition of women a ected with endometriosis. This review points out the potential roles of glucosinolates and isothiocyanates from Brassicas as anti-inflammatory compounds, which might contribute to a reduction in endometriosis symptoms. In view of these promising results, further investigation of the e ect of glucosinolates on chronic inflammatory diseases, either as diet coadjuvants or as therapeutic molecules, should be performed. In addition, we highlight the involvement of aquaporins in the maintenance of immune homeostasis. In brief, glucosinolates and the modulation of cellular water by aquaporins could shed light on new approaches to improve the quality of life for women with endometriosis.
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    Brazilin attenuates kidney ischemia- reperfusion injury by regulating inflammation, oxidative stress, and mitochondrial dysfunction
    (2026) Lulu Zhang; Fei Mu; Ying Yu; Chen Cui; Meng Tang; Kexin Sun; Yanping Yin; Jingwen Wang; Rui Gong; Jinyi Zhao; Biología Celular e Histología; Universidad de Murcia, Departamento de Biología Celular e Histología
    Brazilin, a natural homoisoflavonoid, is the primary bioactive ingredient derived from the bark and heartwood of Caesalpinia sappan L. It has been proven to exhibit multiple biological activities and therapeutic potential in chronic degenerative diseases, fibrotic disorders, inflammatory diseases, and cancers. However, whether it is involved in regulating the pathological process of acute kidney injury (AKI) is not fully understood. This study aimed to elucidate the role and key pharmacological molecular mechanisms of brazilin in AKI. Our data demonstrated that pretreatment with brazilin can significantly reduce the high expression of serum creatinine (Scr), blood urea nitrogen (BUN), and lipocalin-2 (LCN2) in mice exposed to ischemia/ reperfusion (I/R) and alleviate kidney histopathological damage. Meanwhile, pretreatment with brazilin can alleviate apoptosis, inflammation, and oxidative stress injury in the kidney tissue cells by partially inhibiting the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammatory pathway or activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase‐1 (HO-1) antioxidant pathway. In vitro, pretreatment with brazilin significantly downregulated pro-apoptotic Bax and upregulated anti apoptotic Bcl-2 expression in human renal proximal tubular cells (HK-2) subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Besides, it ameliorated mitochondrial dysfunction by enhancing mitochondrial biogenesis and restoring mitochondrial membrane potential. These effects collectively suppressed oxidative stress injury and NLRP3 inflammasome signaling pathway activation. In summary, brazilin exhibits significant protective effects against I/R-induced AKI by attenuating inflammation, oxidative stress and cell apoptosis, and mitochondrial damage. These findings suggest that brazilin holds promise as a potential therapeutic agent for AKI.
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    C-Reactive protein and embolization during carotid artery stenting. A serological and morphological study
    (F. Hernández y Juan F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología, 2011) Faggioli, G.; Fittipaldi, S.; Pini, R.; Beltrandi, E.; Mauro, R.; Freyrie, A.; Rapezzi, C.; Stella, A.; Pasquinelli, G.
    Introduction. High-sensitivity C-Reactive Protein (hsCRP) levels are correlated with vulnerable carotid plaques, although their impact on the outcome of carotid revascularization is unknown. The aim of our study was to investigate the correlation between hsCRP and embolization during carotid artery stenting (CAS). Methods. Patients with symptomatic carotid stenosis were submitted to CAS with distal protection filters. Serum hsCRP was analysed prior to CAS and patients were divided into two groups: Class I, patients presenting hsCRP<5 mg/l and, Class II, patients presenting hsCRP≥5 mg/l. Plaques were categorised by ultrasound grey scale measurement as homogenous and dishomogenous. Afterwards CAS filters were analyzed microscopically and ultrastructurally to determine the type and the amount of debris present, based on percentage of surface involvement (SI) and pore occluded (PO) by embolic material. Results. Fourteen patients underwent uneventful CAS, with a mean hsCRP of 11.5±18.4 mg/l. Eight patients were in Class I and six in Class II. All filters had microscopic debris. SI was 25.4% in Class I and 33.3% in Class II (p=ns), PO 22.9% and 33.3% respectively (p=0.049). Patients in Class II who also had a dishomogenous plaque showed greater SI and PO compared with patients in Class I with homogenous plaque (35.0% vs. 21.8% and 40.4% vs. 22.7% respectively, p<0.05). Microscopically embolic material was identified as atherosclerotic plaque fragments and platelet aggregates and was similar in both groups. Discussion. High hsCRP levels are associated with significantly greater embolization during CAS in symptomatic patients, particularly in dishomogenous plaque. Although these results need further investigation due to the limited number of enrolled patients, this study suggests that CAS may not be indicated as a method of carotid revascularization in this setting.
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    C-reactive protein levels are associated with the progression of atherosclerotic lesions in rabbits
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Yu, Qi; Li, Yafeng; Wang, Yanli; Zhao, Sihai; Yang, Peigang; Chen, Yulong; Fan, Jianglin; Liu, Enqi
    Elevated plasma levels of C-reactive protein (CRP) are associated with increased risk of cardiovascular disease. CRP immunoreactive protein is also detected in the lesions of atherosclerosis. However, it is not known whether the CRP contents of atherosclerotic lesions are associated with the initiation and progression of atherosclerosis. To examine this hypothesis, we investigated different types of atherosclerotic lesions of rabbits fed with a cholesterol-rich diet for 6, 12, 16, and 28 weeks and examined their relationship with CRP. We measured the aortic atherosclerotic area, macrophages, and smooth muscle cells along with CRP contents in the lesions. Atherosclerotic lesions of aortas began to form at 6 weeks and were characterized by accumulation of macrophages in the intima, and lesions became more fibrotic in the advanced stage. Both plasma CRP levels and the lesional CRP contents were associated with the lesion size. Our results suggest that plasma CRP, as well as lesional CRP, associated with the formation and progression of atherosclerotic lesions.
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    CD44: functional relevance to inflammation and malignancy
    (Murcia : F. Hernández, 2002) Yasuda, M.; Nakano, K.; Yasumoto, K.; Tanaka, Y.
    CD44 is a principal cell surface receptor for hyaluronan, a major component of extracellular matrices. Cells are surrounded by and encounter matrix in vivo, which in turn serves a variety of cell functions through the direct adhesion via their receptors. CD44 communicates cell-matrix interactions into the cell via “outside-in signaling” and has an important role in biological activities. The interaction of CD44 with fragmented hyaluronan on rheumatoid synovial cells induces expression of VCAM-1 and Fas on the cells, which leads to Fas-mediated apoptosis of synovial cells by the interaction of T cells bearing FasL. On the other hand, engagement of CD44 on tumor cells derived from lung cancer reduces Fas expression and Fas-mediated apoptosis, resulting in less susceptibility of the cells to CTL-mediated cytotoxicity through Fas-FasL pathway. Thus, although the CD44-mediated signaling differs among cells and circumstances, we here propose the functional role of CD44 in inflammatory processes and tumor susceptibility and the rational design of future therapeutic strategies including the exploitation of CD44-mediated pathway in vivo.
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    Cerebrovascular pathophysiology of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Suzuki, Hidenori; Kanamaru, Hideki; Kawakita, Fumihiro; Asada, Reona; Fujimoto, Masashi; Shiba, Masato
    Aneurysmal subarachnoid hemorrhage (SAH) remains a serious cerebrovascular disease. Even if SAH patients survive the initial insults, delayed cerebral ischemia (DCI) may occur at 4 days or later post-SAH. DCI is characteristics of SAH, and is considered to develop by blood breakdown products and inflammatory reactions, or secondary to early brain injury, acute pathophysiological events that occur in the brain within the first 72 hours of aneurysmal SAH. The pathology underlying DCI may involve large artery vasospasm and/or microcirculatory disturbances by microvasospasm, microthrombosis, dysfunction of venous outflow and compression of microvasculature by vasogenic or cytotoxic tissue edema. Recent clinical evidence has shown that large artery vasospasm is not the only cause of DCI, and that both large artery vasospasm-dependent and -independent cerebral infarction causes poor outcome. Animal studies suggest that mechanisms of vasospasm may differ between large artery and arterioles or capillaries, and that many kinds of cells in the vascular wall and brain parenchyma may be involved in the pathogenesis of microcirculatory disturbances. The impairment of the paravascular and glymphatic systems also may play important roles in the development of DCI. As pathological mediators for DCI, glutamate and several matricellular proteins have been investigated in addition to inflammatory molecules. Glutamate is involved in excitotoxicity contributing to cortical spreading ischemia and epileptic activity-related events. Microvascular dysfunction is an attractive mechanism to explain the cause of poor outcomes independently of large cerebral artery vasospasm, but needs more studies to clarify the pathophysiologies or mechanisms and to develop a novel therapeutic strategy.
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    Changes in salivary proteins can reflect beneficial physiological effects of ejaculation in the dog
    (2021-01-28) Muñoz-Prieto, Alberto; Escribano, Damián; Horvatić, Anita; Contreras-Aguilar, María Dolores; Bernal, Luis; Rubić, Ivana; Cerón, Jose Joaquín; Dabrowski, Roman; Mrljak, Vladimir; Medicina y Cirugía Animal
    The objective of this study was to study the changes in salivary proteins that occur in the dog after the ejaculation process. Saliva samples from eight dogs before and after induced ejaculation were analyzed by proteomic using Tandem Mass Tag (TMT) labeling and LC-MS/MS analysis. A total of 33 salivary proteins showed significant changes after the ejaculation process. The up-regulated proteins that showed changes of higher magnitude were mucin-7 (MUC-7), peroxiredoxin-4 (PRDX4) and galectin-3 (LEGALS3) whereas proteins such as alpha-1-acid glycoprotein (A1G1) and alpha-1B-glycoprotein (A1BG) were the most down-regulated. MUC-7 and PRDX4 expression in saliva after ejaculation could be associated with the protective “environment” created by the organism to exert pr 3o-fertility activities and antioxidants benefits in spermatozoa. Also LEGALS3 increment could be associated with an improvement of wellbeing and could contribute to a positive global effect in the body. Down-regulations of A1G1 and A1GB proteins found in saliva after ejaculation could be associated with a reduction in systemic inflammation. Overall it can be concluded that, changes in proteins in saliva that are produced after ejaculation can reflect a state of increase immune defenses, improvement of antioxidant status and low inflammation.
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    Changes of inflammatory and oxidative stress biomarkers in dogs with different stages of heart failure
    (BioMed Central (BMC), 2020-11-10) Peres Rubio, Camila; Saril, A.; Kocaturk, M.; Tanaka, R.; Koch, J.; Cerón, J.J.; Yilmaz, Z.; Medicina y Cirugía Animal
    Background: Heart failure (HF) is associated with changes in inflammatory and oxidative stress biomarkers. This study aimed to evaluate the changes of a panel of inflammatory and oxidative stress biomarkers in dogs with different stages of HF and its relation with the severity of the disease and echocardiographic changes. A total of 29 dogs with HF as a result of myxomatous mitral valve degeneration or dilated cardiomyopathy were included and classified as stage-A (healthy), B (asymptomatic dogs), C (symptomatic dogs) and D (dogs with end-stage HF) according to the ACVIM staging system. In these dogs an ecnhocardiographic examination was performed and cytokines, and inflammatory and oxidative stress markers were evaluated in serum. Results: KC-like was significantly increased in dogs of stage-C (P<0.01) and -D (P < 0.05) compared with stage-A and -B. Stage-D dogs showed significantly higher serum CRP and Hp (P < 0.05) but lower serum antioxidant capacity (PON1, TEAC, CUPRAC, and thiol) compared to stage-A and -B (P < 0.05). After the treatment, serum levels of CRP, Hp and KClike decreased and serum antioxidant levels increased compared to their pre-treatment values. Left ventricular dimension and LA/Ao ratio correlated positively with CRP, MCP-1, and KC-like but negatively with PON1, GM-CSF, IL-7 and antioxidant biomarkers (P < 0.01). Conclusion: Our results showed that dogs with advanced HF show increases in positive acute-phase proteins and selected inflammatory cytokines such as KC-like, and decreases in antioxidant biomarkers, indicating that inflammation and oxidative stress act as collaborative partners in the pathogenesis of HF. Some of these biomarkers of inflammation and oxidative stress could have the potential to be biomarkers to monitor the severity of the disease and the effect of treatment.
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    Characterization of inflammatory reaction in upper airways of cystic fibrosis patients
    (Murcia : F. Hernández, 2000) Lesprit, E.; Escudier, E.; Roger, G.; Pruliere, V.; Lenoir, G.; Reinert, Ph.; Coste, A.
    Inflammatory cell populations have not been yet precisely evaluated in cystic fibrosis (CF) airways. We intended to characterize morphological modifications, inflammatory cell infiltration and cell proliferation in nasal tissues obtained from 15 CF patients and from 6 non-CF patients with nasal polyposis. Morphological analysis showed an intense inflammatory infiltration in CF and non-CF tissues with only few modifications in the epithelium from CF tissues. Inflammatory cell populations characterized by specific immunolabeling were quantified, showing a predominance of macrophages and T- and B-lymphocytes and only moderate numbers of neutrophils in CF tissues; in non-CF polyps, lymphocytes and eosinophils were abundant. Proliferating cell percentages quantified after proliferating cell nuclear antigen immunolabeling were 5.3+4.1% (mean t SD) in CF polyps and 3.1?1.2% in non-CF polyps in epithelium but were very low in lamina propria. Intense inflammation in nasal tissues from CF patients is therefore dominated by macrophages and lymphocytes rather than by neutrophils. While morphology is preserved, proliferation is high in epithelium from CF polyps. These findings should be regarded in the future for a better understanding of inflammation in CF airway disease.
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    Chemoprevention of Experimental Periodontitis in Diabetic Rats with Silk Fibroin Nanoparticles Loaded with Resveratrol
    (MDPI, 2020-01-19) Giménez-Siurana, Ana; Gomez Garcia, Francisco; Pagan Bernabeu, Ana; Lozano-Pérez, Abel; Aznar-Cervantes, Salvador; Cenis, Luis; Lopez Jornet, Pia; Dermatología, Estomatología, Radiología y Medicina Física
    Objective: the objective of the present work is to study the e ectiveness of treatment with silk fibroin nanoparticles loaded with resveratrol in experimental periodontitis in a diabetic rat model. Introduction: Periodontitis is an inflammatory pathology highly related to other diseases, such as type II diabetes. Both diseases have a specific inflammatory condition, with Interleukin (IL)-6, IL-1 and Transforming Grow Factor (TGF)-1 being the most relevant proinflammatory factors. Silk fibroin (SF) nanoparticles loaded with resveratrol (Res-SFN) are a new alternative as a treatment. Methods: 40 diabetic Sprague Dawley male rats were used and periodontitis was induced by ligation. The animals were divided into 5 treatment groups, and 1 mL of treatment was administered once a day for 4 weeks. The groups were: I: Carboxymethyl cellulose (CMC) 0.8%, II: CMC 0.8% + SF 1%, III: CMC 0.8% + RES-SFN 3 mg/mL, IV: CMC 0.8% + SF 1% + RES-SFN 3 mg/mL, V: Water. A peripheral blood sample was taken every week to quantify the inflammatory profile by ELISA (IL-6, IL-1 and TGF-1 ). After 4 weeks the sacrifice was carried out and biopsies of the gum were taken. Results: Treatment with SF and RES-SFN reduced the amount of chemical inflammation mediators (with the exception of IL-1 in comparisons I-IV and II-IV (p > 0.05)), as well as the anatomopathological variables linked to it, in a significant way (p < 0.05). Conclusion: treatment with RES-SFN has reduced local inflammation in this experimental periodontitis model
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    Chloride regulates dynamic NLRP3-dependent ASC oligomerization and inflammasome priming
    (National Academy of Sciences, 2018-09-19) Martín Sánchez, María Rosario Fátima; Pelegrín Vivancos, Pablo; Green, Jack Peter; Yu, Shi; Lopez-Castejon, Gloria; Lawrence, Catherine B.; Brough, David; Farmacología
    The NLRP3 inflammasome is an important regulator of inflammation and immunity. It is a multi-molecular platform formed within cells that facilitates the activation of pro-inflammatory caspases to drive secretion of cytokines such as IL-1β. Knowledge of the mechanisms regulating formation of the NLRP3-inflammasome is incomplete. Here we report Cl- channel dependent formation of dynamic ASC oligomers and inflammasome specks that remain inactive in the absence of K+ efflux. Formed after Cl- efflux exclusively ASC specks are NLRP3 dependent, reversible, and inactive, though they further prime inflammatory responses accelerating and enhancing release of IL-1β in response to a K+ efflux inducing stimulus. NEK7 is a specific K+ sensor and does not associate with NLRP3 under conditions stimulating exclusively Cl- efflux, but does after K+ efflux, activating the complex driving inflammation. Our investigation delivers new mechanistic understanding into inflammasome activation and the regulation of inflammatory responses.