RESUMEN
Using proteomics and complexome profiling, we evaluated in a year-long study longitudinal variations in the plasma proteome of kidney failure patients, prior to and after a kidney transplantation. The post-transplant period was complicated by bacterial infections, resulting in dramatic changes in the proteome, attributed to an acute phase response (APR). As positive acute phase proteins (APPs), being elevated upon inflammation, we observed the well-described C-reactive protein and Serum Amyloid A (SAA), but also Fibrinogen, Haptoglobin, Leucine-rich alpha-2-glycoprotein, Lipopolysaccharide-binding protein, Alpha-1-antitrypsin, Alpha-1-antichymotrypsin, S100, and CD14. As negative APPs, being downregulated upon inflammation, we identified the well-documented Serotransferrin and Transthyretin, but added Kallistatin, Heparin cofactor 2, and interalpha-trypsin inhibitor heavy chain H1 and H2 (ITIH1, ITIH2). For the patient with the most severe APR, we performed plasma complexome profiling by SEC-LC-MS on all longitudinal samples. We observed that several plasma proteins displaying alike concentration patterns coelute and form macromolecular complexes. By complexome profiling, we expose how SAA1 and SAA2 become incorporated into high-density lipid particles, replacing largely Apolipoprotein (APO)A1 and APOA4. Overall, our data highlight that the combination of in-depth longitudinal plasma proteome and complexome profiling can shed further light on correlated variations in the abundance of several plasma proteins upon inflammatory events.
Asunto(s)
Proteínas Sanguíneas , Trasplante de Riñón , Proteoma , Humanos , Trasplante de Riñón/efectos adversos , Proteoma/análisis , Proteoma/metabolismo , Estudios Longitudinales , Proteínas Sanguíneas/análisis , Proteínas Sanguíneas/metabolismo , Proteínas de Fase Aguda/metabolismo , Persona de Mediana Edad , Masculino , Proteómica/métodos , Femenino , Insuficiencia Renal/sangre , Reacción de Fase Aguda/sangre , AdultoRESUMEN
BACKGROUND: Reduction of inflammation and early detection of complications after surgical procedures are important objectives for proper veterinary practice. This study aimed to evaluate the differences between shelter and pet female cats in selected acute-phase parameters scheduled to ovariohysterectomy. Postoperative monitoring after ovariohysterectomy with the same laboratory parameters was performed in shelter cats, in which two different types of surgical sutures were used for the entire procedure. The experimental group comprised 40 female cats from animal shelters ('shelter cats,' n = 40). These cats were divided into two subgroups: group A (n = 20) operated on with absorbable sutures and group NA (n = 20) operated on with non-absorbable sutures. In addition, the same parameters were evaluated in pet female cats (n = 19). Blood was collected from shelter cats immediately before surgery (term 0), at 24 and 72 h (terms 1 and 3, respectively), and at 7 and 14 days (terms 7 and 14, respectively) after ovariohysterectomy. Blood samples from the pet cat group were collected only once. RESULT: The mean haptoglobin concentration before ovariohysterectomy in pet cats was significantly lower than that in shelter cats. Fibrinogen concentration was significantly lower in pet cats than in cats from group A. Serum albumin, beta-1, beta-2, and gamma-globulin concentrations were significantly higher in the shelter cats than in the pet cats. Subcutaneous tissue thickening at the site of the postoperative wound was observed in five patients cats (25%) in group A, and two (10%) cats in the NA group. CONCLUSION: These results indicate that ovariohysterectomy leads to local and general inflammatory responses. The majority of cats from animal shelters suffered from subclinical inflammation.
Asunto(s)
Histerectomía , Ovariectomía , Animales , Gatos/cirugía , Femenino , Histerectomía/veterinaria , Ovariectomía/veterinaria , Suturas/veterinaria , Técnicas de Sutura/veterinaria , Fibrinógeno/análisis , Haptoglobinas/análisis , Periodo PosoperatorioRESUMEN
Mass spectrometry-based secretomics approaches frequently utilize serum-free culture conditions to circumvent serum-induced interference and to increase analytical depth. However, this can negatively affect a wide range of cellular functions and cell viability. These effects become particularly apparent when investigating transcriptionally regulated secretion events and feedback-loops in response to perturbations that require 48 h or more to fully manifest. We present an "interval-based" secretomics workflow, which determines protein secretion rates in short serum-free time windows. Relative quantification using tandem mass tags enables precise monitoring of time-dependent changes. We applied this approach to determine temporal profiles of protein secretion in the hepatocyte model cell lines HepG2 and HepaRG after stimulation of the acute-phase response (APR) by the cytokines IL1b and IL6. While the popular hepatocarcinoma cell line HepG2 showed an incomplete APR, secretion patterns derived from differentiated HepaRG cells recapitulated the expected APR more comprehensively. For several APR response proteins, substantial secretion was only observed after 72 h, a time window at which cell fitness is substantially impaired under serum-free cell culture conditions. The interval-based secretomics approach enabled the first comprehensive analysis of time-dependent secretion of liver cell models in response to these proinflammatory cytokines. The extended time range facilitated the observation of distinct chronological phases and cytokine-dependent secretion phenotypes of the APR. IL1b directed the APR toward pathogen defense over three distinct phases-chemotaxis, effector, clearance-while IL6 directed the APR toward regeneration. Protein shedding on the cell surface was pronounced upon IL1b stimulation, and small molecule inhibition of ADAM and matrix metalloproteases identified induced as well as constitutive shedding events. Inhibition of ADAM proteases with TAPI-0 resulted in reduced shedding of the sorting receptor SORT1, and an attenuated cytokine response suggesting a direct link between cell surface shedding and cytokine secretion rates.
Asunto(s)
Reacción de Fase Aguda , Interleucina-6 , Proteínas de Fase Aguda , Citocinas , Hepatocitos/metabolismo , HumanosRESUMEN
This review is intended to demonstrate that the local production of acute phase proteins (termed local acute phase response (lAPR)) and especially fibrin/fibrinogen (FN) is a defense mechanism of cancer cells to therapy, and inhibition of the lAPR can augment the effectiveness of cancer therapy. Previously we detected a lAPR accompanying tumor cell death during the treatment of triple-negative breast cancer (TNBC) with modulated electro-hyperthermia (mEHT) in mice. We observed a similar lAPR in in hypoxic mouse kidneys. In both models, production of FN chains was predominant among the locally produced acute phase proteins. The production and extracellular release of FN into the tumor microenvironment is a known method of self-defense in tumor cells. We propose that the lAPR is a new, novel cellular defense mechanism like the heat shock response (HSR). In this review, we demonstrate a potential synergism between FN inhibition and mEHT in cancer treatment, suggesting that the effectiveness of mEHT and chemotherapy can be enhanced by inhibiting the HSR and/or the lAPR. Non-anticoagulant inhibition of FN offers potential new therapeutic options for cancer treatment.
Asunto(s)
Hipertermia Inducida , Neoplasias , Animales , Ratones , Fibrinógeno , Proteínas de Fase Aguda , Hipertermia Inducida/métodos , Neoplasias/terapia , Neoplasias/patología , Microambiente TumoralRESUMEN
C-reactive protein (CRP) is a major acute phase protein and inflammatory marker, the expression of which is largely liver specific and highly inducible. Enhancers are regulatory elements critical for the precise activation of gene expression, yet the contributions of enhancers to the expression pattern of CRP have not been well defined. Here, we identify a constitutively active enhancer (E1) located 37.7 kb upstream of the promoter of human CRP in hepatocytes. By using chromatin immunoprecipitation, luciferase reporter assay, in situ genetic manipulation, CRISPRi, and CRISPRa, we show that E1 is enriched in binding sites for transcription factors STAT3 and C/EBP-ß and is essential for the full induction of human CRP during the acute phase. Moreover, we demonstrate that E1 orchestrates with the promoter of CRP to determine its varied expression across tissues and species through surveying activities of E1-promoter hybrids and the associated epigenetic modifications. These results thus suggest an intriguing mode of molecular evolution wherein expression-changing mutations in distal regulatory elements initiate subsequent functional selection involving coupling among distal/proximal regulatory mutations and activity-changing coding mutations.
Asunto(s)
Proteína C-Reactiva , Elementos de Facilitación Genéticos , Sitios de Unión , Proteína C-Reactiva/genética , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Regulación de la Expresión Génica , Hepatocitos , Humanos , Regiones Promotoras Genéticas , Factor de Transcripción STAT3/metabolismo , Transcripción GenéticaRESUMEN
BACKGROUND: Sepsis-associated encephalopathy (SAE) is a common and severe complication of sepsis. While several studies have reported the proteomic alteration in plasma, urine, heart, etc. of sepsis, few research focused on the brain tissue. This study aims at discovering the differentially abundant proteins in the brains of septic rats to identify biomarkers of SAE. METHODS: The Prague-Dawley rats were randomly divided into sepsis (n = 6) or sham (n = 6) groups, and then the whole brain tissue was dissected at 24 h after surgery for further protein identification by Quantitative iTRAQ LC-MS/MS Proteomics. Ingenuity pathway analysis, Gene ontology knowledgebase, and STRING database are used to explore the biological significance of proteins with altered concentration. RESULTS: Among the total of 3163 proteins identified in the brain tissue, 57 were increased while 38 were decreased in the sepsis group compared to the sham group. Bioinformatic analyses suggest that the differentially abundant proteins are highly related to cellular microtubule metabolism, energy production, nucleic acid metabolism, neurological disease, etc. Additionally, acute phase response signaling was possibly activated and PI3K/AKT signaling was suppressed during sepsis. An interaction network established by IPA revealed that Akt1, Gc-globulin, and ApoA1 were the core proteins. The increase of Gc-globulin and the decrease of Akt1 and ApoA1 were confirmed by Western blot. CONCLUSION: Based on the multifunction of these proteins in several brain diseases, we first propose that Gc-globulin, ApoA1, PI3K/AKT pathway, and acute phase response proteins (hemopexin and cluster of alpha-2-macroglobulin) could be potential candidates for the diagnosis and treatment of SAE. These results may provide new insights into the pathologic mechanism of SAE, yet further research is required to explore the functional implications and clinical applications of the differentially abundant proteins in the brains of sepsis group.
Asunto(s)
Globulinas , Proteómica , Encefalopatía Asociada a la Sepsis , Animales , Ratas , Reacción de Fase Aguda/metabolismo , Biomarcadores/metabolismo , Cromatografía Liquida , Fosfatidilinositol 3-Quinasas/metabolismo , Proteómica/métodos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sepsis/complicaciones , Encefalopatía Asociada a la Sepsis/diagnóstico , Encefalopatía Asociada a la Sepsis/metabolismo , Espectrometría de Masas en TándemRESUMEN
α1 -Acid glycoprotein (AGP) is a prominent acute phase component of blood plasma and extravascular fluids. As a member of the immunocalins, AGP exerts protective effects against Gram-negative bacterial infections but the underlying molecular mechanisms still need to be elucidated. Notably, the chemical structures of phenothiazine, phenoxazine and acridine type ligands of AGP are similar to those of phenazine compounds excreted by the opportunistic human pathogen Pseudomonas aeruginosa and related bacterial species. These molecules, like pyocyanin, act as quorum sensing-associated virulence factors and are important contributors to bacterial biofilm formation and host colonisation. Molecular docking simulations revealed that these agents fit into the multi-lobed cavity of AGP. The binding site is decorated by several aromatic residues which seem to be essential for molecular recognition of the ligands allowing multifold π-π and CH-π interactions. The estimated affinity constants (~105 M-1 ) predict that these secondary metabolites could be trapped inside the ß-barrel of AGP which in turn could reduce their cytotoxic effects and disrupt the microbial QS network, facilitating the eradication of bacterial infections.
Asunto(s)
Biopelículas , Percepción de Quorum , Humanos , Simulación del Acoplamiento Molecular , Orosomucoide/metabolismo , Orosomucoide/farmacología , Ligandos , Antibacterianos/farmacología , Fenazinas , Pseudomonas aeruginosa , Proteínas Bacterianas/metabolismoRESUMEN
Although anemia, thrombocytopenia, and mild lymphopenia have been reported in the acute phase response after zoledronic acid, severe lymphopenia has not been reported. This article describes a case of severe lymphopenia following a 5 mg zoledronic acid infusion administered to treat osteoporosis. Zoledronic acid is used to treat osteoporosis, hypercalcemia, Paget's disease, and solid malignancies, including multiple myeloma, breast cancer, and prostate cancer. An acute phase response can be seen in 42% of patients after zoledronic acid treatment. Acute phase response may be accompanied by short-term spontaneously recovered anemia, thrombocytopenia, and severe lymphopenia.
Asunto(s)
Anemia , Conservadores de la Densidad Ósea , Linfopenia , Osteoporosis , Trombocitopenia , Masculino , Humanos , Ácido Zoledrónico/efectos adversos , Difosfonatos , Reacción de Fase Aguda/inducido químicamente , Imidazoles , Infusiones Intravenosas , Osteoporosis/tratamiento farmacológico , Osteoporosis/inducido químicamente , Trombocitopenia/inducido químicamente , Linfopenia/inducido químicamente , Anemia/inducido químicamente , Conservadores de la Densidad Ósea/efectos adversosRESUMEN
AIM: The aim of this work is to assess the safety and efficacy of two oral zoledronate preparations by determining their effects on bone resorption in healthy postmenopausal women. METHODS: The preparations studied were zoledronic acid in enteric-coated capsules or a microparticle preparation of zoledronic acid in these capsules. Bone resorption was measured as ß-C-telopeptideof type I collagen (CTX) in fasting serum. Separate cohorts, each of five women, were recruited and allocated in sequence to single doses of 20 mg, 40 mg, or 60 mg of oral zoledronate. RESULTS: Zoledronate 20 mg enteric capsules were well tolerated, reduced serum CTX by a median 51% at 1 week, but by only 17% at 1 month. Doses of 40 or 60 mg of this preparation produced APR and/or gastrointestinal symptoms in more than half of participants. With these doses, median CTX reduction at 1 week was >80%, ~70% at 1 month, but only ~30% at 6 months. Enteric capsules containing microparticles of zoledronate 20 mg reduced CTX by a median 53% at 1 week, with offset over 3 months. Two or three of these capsules dosed weekly reduced CTX by ~50% at 1 month, and by ~30% at 3 and 6 months. CONCLUSIONS: Oral zoledronate 20 mg circumvents the problem of APR symptoms but, even with multiple doses, the anti-resorptive effect is smaller and less sustained than with intravenous zoledronate. Probably a viable oral regimen of zoledronate dosing at intervals of weeks to months could be developed, but the advantage of infrequent dosing would be lost.
Asunto(s)
Conservadores de la Densidad Ósea , Resorción Ósea , Osteoporosis Posmenopáusica , Femenino , Humanos , Anciano , Ácido Zoledrónico/farmacología , Ácido Zoledrónico/uso terapéutico , Difosfonatos/efectos adversos , Imidazoles/efectos adversos , Densidad Ósea , Remodelación Ósea , Conservadores de la Densidad Ósea/efectos adversos , Osteoporosis Posmenopáusica/tratamiento farmacológico , Osteoporosis Posmenopáusica/inducido químicamente , Administración OralRESUMEN
BACKGROUND: Acute phase response (APR) is characterized by a change in concentration of different proteins, including C-reactive protein and serum amyloid A (SAA) that can be linked to both exposure to metal oxide nanomaterials and risk of cardiovascular diseases. In this study, we intratracheally exposed mice to ZnO, CuO, Al2O3, SnO2 and TiO2 and carbon black (Printex 90) nanomaterials with a wide range in phagolysosomal solubility. We subsequently assessed neutrophil numbers, protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid, Saa3 and Saa1 mRNA levels in lung and liver tissue, respectively, and SAA3 and SAA1/2 in plasma. Endpoints were analyzed 1 and 28 days after exposure, including histopathology of lung and liver tissues. RESULTS: All nanomaterials induced pulmonary inflammation after 1 day, and exposure to ZnO, CuO, SnO2, TiO2 and Printex 90 increased Saa3 mRNA levels in lungs and Saa1 mRNA levels in liver. Additionally, CuO, SnO2, TiO2 and Printex 90 increased plasma levels of SAA3 and SAA1/2. Acute phase response was predicted by deposited surface area for insoluble metal oxides, 1 and 28 days post-exposure. CONCLUSION: Soluble and insoluble metal oxides induced dose-dependent APR with different time dependency. Neutrophil influx, Saa3 mRNA levels in lung tissue and plasma SAA3 levels correlated across all studied nanomaterials, suggesting that these endpoints can be used as biomarkers of acute phase response and cardiovascular disease risk following exposure to soluble and insoluble particles.
Asunto(s)
Nanoestructuras , Óxido de Zinc , Ratones , Animales , Reacción de Fase Aguda/inducido químicamente , Óxido de Zinc/toxicidad , Óxido de Zinc/metabolismo , Pulmón/metabolismo , Nanoestructuras/toxicidad , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Endotoxemia and sepsis induce neuroinflammation and increase the risk of neurodegenerative disorders although the mechanism by which peripheral infection leads to brain inflammation is not well understood. While circulating serum lipoproteins are known immunometabolites with the potential to modulate the acute phase response and cross the blood brain barrier, their contribution to neuroinflammation during systemic infection is unknown. The objective of this study was to elucidate the mechanisms by which lipoprotein subclasses modulate lipopolysaccharide (LPS)-induced neuroinflammation. Adult C57BL/6 mice were divided into 6 treatment groups, including a sterile saline vehicle control group (n = 9), an LPS group (n = 11), a premixed LPS + HDL group (n = 6), a premixed LPS + LDL group (n = 5), a HDL only group (n = 6) and an LDL only group (n = 3). In all cases injections were administered intraperitoneally. LPS was administered at 0.5 mg/kg, and lipoproteins were administered at 20 mg/kg. Behavioural testing and tissue collection was performed 6 h post-injection. The magnitude of peripheral and central inflammation was determined by qPCR of pro-inflammatory genes in fresh liver and brain. Metabolite profiles of liver, plasma and brain were determined by 1H NMR. Endotoxin concentration in the brain was measured by the Limulus Amoebocyte Lysate (LAL) assay. Co-administration of LPS + HDL exacerbated both peripheral and central inflammation, whilst LPS + LDL attenuated this inflammation. Metabolomic analysis identified several metabolites significantly associated with LPS-induced inflammation, which were partially rescued by LDL, but not HDL. Endotoxin was detected at significantly greater concentrations in the brains of animals that received LPS + HDL compared to LPS + saline, but not those that received LPS + LDL. These results suggest that HDL may promote neuroinflammation through direct shuttling of endotoxin to the brain. In contrast, LDL was shown to have anti-neuroinflammatory properties in this study. Our results indicate that lipoproteins may be useful targets in neuroinflammation and neurodegeneration associated with endotoxemia and sepsis.
Asunto(s)
Encefalitis , Endotoxemia , Sepsis , Ratones , Animales , Lipopolisacáridos/farmacología , Enfermedades Neuroinflamatorias , Ratones Endogámicos C57BL , Lipoproteínas , Inflamación/inducido químicamente , Endotoxinas/efectos adversosRESUMEN
Photodynamic therapy (PDT) is a medical treatment with the use of a photosensitizing agent (PS), which, when activated by light, results in selective tissue damage with a cytotoxic effect on tumor cells. PDT leads to the induction of an acute-phase response, which results in the involvement of adrenal glucocorticoid (GC) hormones. PDT, by activating the hormonal response, affects the treatment of cancer. GC release is observed due to adrenal activity, which is driven by changes in the hypothalamic pituitary-adrenal axis triggered by stress signals emanating from the PDT treated tumor. The hormones released in this process in the context of the PDT-induced acute-phase response perform many important functions during anticancer therapy. They lead, among other things, to the systemic mobilization of neutrophils and the production of acute-phase reagents, and also control the production of immunoregulatory proteins and proteins that modulate inflammation. GCs can radically affect the activity of various inflammatory and immune cells, including the apoptosis of cancer cells. A better understanding of the modulation of GC activity could improve the outcomes of cancer patients treated with PDT.
RESUMEN
Ferritin is an acute phase response protein, which may not rise as expected in acute bacterial infections. This could be due to the time required for its production or to a lack of response of ferritin to the bacterial inflammatory process. Medical records of hospitalized patients with acute hyper inflammation were retrieved and studied, looking closely at two acute phase proteins: C-reactive protein (CRP) and ferritin. The estimated time between symptom onset and the procurement of blood tests was also measured. 225 patients had a median ferritin level of 109.9 ng/mL [IQR 85.1, 131.7] and a median CRP level of 248.4 mg/L [IQR 221, 277.5]. An infectious inflammatory process was identified in 195 patients. Ferritin levels were relatively low in comparison with the CRP in each group, divided according to time from symptom onset until the procurement of blood tests. The discrepancy between high CRP and low ferritin suggests that these two acute phase response proteins utilize different pathways, resulting in a failure to increase ferritin concentrations in a documented state of hyperinflammation. A new entity of normoferremic inflammation accounts for a significant percentage of patients with acute bacterial infections, which enables bacteria to better survive the inflammation and serves as a new "inflammatory stamp".
Asunto(s)
Infecciones Bacterianas , Proteína C-Reactiva , Ferritinas , Inflamación , Humanos , Proteínas de Fase Aguda/metabolismo , Reacción de Fase Aguda , Bacterias/metabolismo , Infecciones Bacterianas/complicaciones , Biomarcadores , Proteína C-Reactiva/metabolismo , Ferritinas/sangre , Inflamación/sangre , Inflamación/complicacionesRESUMEN
Serum amyloid A (SAA) is a family of proteins, the plasma levels of which may increase >1000-fold in acute inflammatory states. We investigated the role of SAA in sepsis using mice deficient in all three acute-phase SAA isoforms (SAA-TKO). SAA deficiency significantly increased mortality rates in the three experimental sepsis mouse models: cecal ligation and puncture (CLP), cecal slurry (CS) injection, and lipopolysaccharide (LPS) treatments. SAA-TKO mice had exacerbated lung pathology compared to wild-type (WT) mice after CLP. A bulk RNA sequencing performed on lung tissues excised 24 h after CLP indicated significant enrichment in the expression of genes associated with chemokine production, chemokine and cytokine-mediated signaling, neutrophil chemotaxis, and neutrophil migration in SAA-TKO compared to WT mice. Consistently, myeloperoxidase activity and neutrophil counts were significantly increased in the lungs of septic SAA-TKO mice compared to WT mice. The in vitro treatment of HL-60, neutrophil-like cells, with SAA or SAA bound to a high-density lipoprotein (SAA-HDL), significantly decreased cellular transmigration through laminin-coated membranes compared to untreated cells. Thus, SAA potentially prevents neutrophil transmigration into injured lungs, thus reducing exacerbated tissue injury and mortality. In conclusion, we demonstrate for the first time that endogenous SAA plays a protective role in sepsis, including ameliorating lung injury.
Asunto(s)
Lesión Pulmonar , Sepsis , Animales , Ratones , Lesión Pulmonar/patología , Proteína Amiloide A Sérica/genética , Sepsis/patología , Pulmón/patología , Quimiocinas , Ratones Endogámicos C57BL , Modelos Animales de EnfermedadRESUMEN
α1-Antitrypsin (AAT), an acute-phase reactant not unsimilar to C-reactive protein (CRP), is a serine protease inhibitor that harbors tissue-protective and immunomodulatory attributes. Its concentrations appropriately increase during conditions of extensive tissue injury, and it induces immune tolerance, in part, by inhibiting the enzymatic activity of the inflammatory serine protease, proteinase 3 (PR3). Typically administered to patients with genetic AAT deficiency, AAT treatment was recently shown to improve outcomes in patients with steroid-refractory graft-versus-host disease (GVHD). GVHD represents a grave outcome of allogeneic hematopoietic stem cell transplantation (HSCT), a potentially curative intervention for hematological diseases. The procedure requires radio/chemotherapy conditioning of the prospective marrow recipient, a cytotoxic process that causes vast tissue injury and, in some formats, interferes with liver production of AAT. To date, changes in the functional profile of AAT during allogeneic HSCT, and during the cytotoxic intervention that precedes HSCT, are unknown. The present study followed 53 patients scheduled for allogeneic HSCT (trial registration NCT03188601). Serum samples were tested before and after HSCT for AAT and CRP levels and for intrinsic anti-proteolytic activity. The ex vivo response to clinical-grade AAT was tested on circulating patient leukocytes and on a human epithelial cell line treated with patient sera in a gap closure assay. According to the ex vivo experiments, circulating leukocytes responded to AAT with a favorable immune-regulated profile, and epithelial gap closure was enhanced by AAT in sera from GVHD-free patients but not in sera from patients who developed GVHD. According to serum collected prior to HSCT, non-relapse mortality was reliably predicted by combining three components: AAT and CRP levels and serum anti-proteolytic activity. Taken together, HSCT outcomes are significantly affected by the anti-proteolytic function of circulating AAT, supporting early AAT augmentation therapy for allogeneic HSCT patients.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Estudios Prospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Serina Proteasas , Serina Endopeptidasas , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & controlRESUMEN
Ticks have saliva rich in immunoregulatory molecules that interfere with the host's physiology in order to feed. This study aimed to evaluate the concentration of acute phase proteins and circulating oxidative stress in response to infestation by Amblyomma sculptum and Dermacentor nitens in two breed horses, Mangalarga Marchador and Breton Postier, to define resistance or susceptibility to ticks. Among the oxidative stress markers, we observed lower malondialdehyde and nitric oxide in horses with tick infestation, consequently not altering the antioxidant enzymes. Breton Postier with tick infestation showed a reduction in the ferric reducing ability of plasma (FRAP), which may be due to lower feeding of the host due to the stress caused by the infestation or even to sequestration of components induced by the tick during blood feeding. The alpha-1-antitrypsin, an acute phase protein, showed an increase in Mangalarga Marchador with tick infestation; curiously it is related to a protective action against tissue damage, pathogens and parasites. We could assume that Mangalarga Marchador showed a better response to ticks when compared to Breton Postier. However, it is still early to define the resistance or susceptibility to ticks, as we did not observe significant changes in most of the analyzed variables. Further studies are needed to understand the compounds and mechanisms of action of the tick saliva in the acute phase proteins and the possible relationships of oxidative stress in the host and the tick during blood feeding.
Asunto(s)
Enfermedades de los Caballos , Infestaciones por Garrapatas , Garrapatas , Animales , Caballos , Infestaciones por Garrapatas/veterinaria , Proteínas de Fase Aguda/metabolismo , Saliva , Estrés OxidativoRESUMEN
The present study was executed to evaluate the effect of photoperiod on serum biochemical parameters (glucose, cortisol, ALT, AST and LDH), electrolytic balance (Sodium and potassium), acute phase response (CRP) and histopathology (liver, kidney and skin) of an endangered high valued catfish, Ompok bimaculatus. Catfish (21.00 ± 1.53 cm and 30.00 ± 2.31 g) from the acclimatized stock were randomly distributed to six 120 × 45 × 60 cm3 FRP tanks (n = 20 fish per tank) and exposed to 1500 lx light intensity under different photoperiods [24:0 light: dark (L: D), 15L: 9D, 12L: 12D, 9L: 15D, 0L: 24D and a natural photoperiod (control)], and fed at a daily rate of 2% of bodyweight, twice a day for 60 days. Serum glucose, cortisol and enzymes including aspartate transaminase (AST), lactate dehydrogenase (LDH), alanine transaminase (ALT), and acute phase reactant, such as C-reactive protein (CRP) increased significantly (P < 0.05) in continuous light (24L: 0D), continuous dark (0L: 24D) and short day (9L: 15D) photoperiods, whereas in 15L: 9D and 12L:12D photoperiods, those were in decreasing trend. Serum electrolytes, i.e. potassium level was elevated and sodium level was declined in 24L: 0D, 0L: 24D and 9L: 15D photoperiod groups. Moreover, significant histological alterations in the liver, kidney and skin tissue were also evidenced in the experimented catfish. Typical polygonal hepatocytes with normal blood vessels in liver and normal organization of kidney were seen in catfish of 15L: 9D group. Histological analysis of other groups displayed nuclear degeneration, karyorrhexis, karyolysis, melanomacrophages, nuclear hypertrophy, sinusoid dilation and vacuolar degeneration in liver and hyaline droplets accumulation, granular degeneration, fragmentation of glomerulus and focal necrosis of epithelial cells in kidney. Additionally, general structure of the skin was observed in control group as well as in 15L: 9D group. Contrarily, in 24L: 0D group increased number of mucous cells and vacuoles was observed in the skin of butter catfish. In 9L: 15D and 0L: 24D photoperiods, O. bimaculatus exhibited ruptured epithelial cells, enlarged alarm cells, fat cells, necrotic cells and vacuoles in the skin tissue. The present study depicted that 15L: 9D photoperiod can induce better health of catfish, O. bimaculatus, which, in turn, can help farmers to increase the production of this high valued catfish in future.
Asunto(s)
Bagres , Fotoperiodo , Animales , Reacción de Fase Aguda , Hidrocortisona , Glucosa , Potasio , SodioRESUMEN
Infectious bronchitis virus (IBV) is one of the major respiratory diseases of broiler causing huge economic losses. The inability to control IBV using different vaccination programs owing to the high mutation rate and recombination ability of the RNA genome generates IBV variants. This study was designed to give a specific perspective of carvacrol effect on early immune response, viral shedding titer, oxidative stress, serum biochemical parameters and clinical consequences in broilers experimentally infected by IBV. One hundred and twenty-one-day old commercial broiler chicks were equally divided into 4 groups. First group was considered as control. Second group was given carvacrol, third group was infected with IBV and fourth group was given carvacrol and infected with IBV. Infection with variant IBV induced significant upregulation of chicken interferon-inducible transmembrane protein 3 (chIFITM3) gene in trachea, elevations in serum levels of Alpha-1 acid glycoprotein (α1-AGP) and Interleukin 6 (IL-6), total leucocytic count (TLC), heterophil/lymphocyte (H/L) ratio and oxidative stress in lung and kidney tissues. Beside, histopathological changes in trachea, lung and kidney induced by IBV, elevation of kidney function tests was detected. The pretreatment with carvacrol significantly reduced viral shedding titer, chIFITM3 gene expression, IL-6 and α1-AGP levels, leucocytic response and H/L ratio with minimization of clinical signs intensity. Also, carvacrol relieved oxidative stress, ameliorated the increased uric acid level and histopathological alterations in kidney and lung caused by viral infection.
Asunto(s)
Infecciones por Coronavirus , Virus de la Bronquitis Infecciosa , Enfermedades de las Aves de Corral , Vacunas Virales , Reacción de Fase Aguda , Animales , Pollos , Infecciones por Coronavirus/veterinaria , Cimenos , Esparcimiento de VirusRESUMEN
INTRODUCTION: To devise a precise and efficient tool for predicting the individualized risk of acute-phase response (APR) in bisphosphonate (BP)-naive osteoporotic (OP) patients, receiving their first intravenous dose of zoledronate (ZOL). METHODS: The baseline clinical and laboratory data of 475 consecutive BP-naive OP patients, who received their first intravenous dose of ZOL between March 2016 and March 2021 in the Affiliated Kunshan Hospital of Jiangsu University, were chosen for analysis. Univariate and multivariable logistic regression models were generated to establish candidate predictors of APR fever risk, using three distinct fever thresholds, namely, 37.3 °C (model A), 38.0 °C (model B), and 38.5 °C (model C). Next, using predictor regression coefficients, three fever-threshold nomograms were developed. Discrimination, calibration, and clinical usefulness of each predicting models were then assessed using the area under the curve (AUC), calibration curve (CC), and decision curve analysis (DCA). The internal and external model validations were then performed. RESULTS: The stable predictors were age, serum 25-hydroxy vitamin D, serum total calcium, and peripheral blood erythrocytes count. These were negatively associated with the APR fever risk. The AUCs of models A, B, and C were 0.828 (95% confidence intervals [CI], 0.782 to 0.874), 0.825 (95% CI, 0.767 to 0.883), and 0.879 (95% CI, 0.824 to 0.934), respectively. Good agreement was observed between the predictions and observations in the CCs of all three nomograms. CONCLUSIONS: This study developed and validated nomogram prediction models that can predict APR fever risk in BP-naive OP patients receiving their first infusion of ZOL.
Asunto(s)
Reacción de Fase Aguda , Difosfonatos , Reacción de Fase Aguda/inducido químicamente , Calcio , Difosfonatos/efectos adversos , Humanos , Estudios Retrospectivos , Vitamina D , Ácido ZoledrónicoRESUMEN
Airway exposure to eg particulate matter is associated with cardiovascular disease including atherosclerosis. Acute phase genes, especially Serum Amyloid A3 (Saa3), are highly expressed in the lung following pulmonary exposure to particles. We aimed to investigate whether the human acute phase protein SAA (a homolog to mouse SAA3) accelerated atherosclerotic plaque progression in Apolipoprotein E knockout (ApoE-/- ) mice. Mice were intratracheally (i.t.) instilled with vehicle (phosphate buffered saline) or 2 µg human SAA once a week for 10 weeks. Plaque progression was assessed in the aorta using noninvasive ultrasound imaging of the aorta arch as well as by en face analysis. Additionally, lipid peroxidation, SAA3, and cholesterol were measured in plasma, inflammation was determined in lung, and mRNA levels of the acute phase genes Saa1 and Saa3 were measured in the liver and lung, respectively. Repeated i.t. instillation with SAA caused a significant progression in the atherosclerotic plaques in the aorta (1.5-fold). Concomitantly, SAA caused a statistically significant increase in neutrophils in bronchoalveolar lavage fluid (625-fold), in pulmonary Saa3 (196-fold), in systemic SAA3 (1.8-fold) and malondialdehyde levels (1.14-fold), indicating acute phase response (APR), inflammation and oxidative stress. Finally, pulmonary exposure to SAA significantly decreased the plasma levels of very low-density lipoproteins - low-density lipoproteins and total cholesterol, possibly due to lipids being sequestered in macrophages or foam cells in the arterial wall. Combined these results indicate the importance of the pulmonary APR and SAA3 for plaque progression.