Acute Phase Protein Response Research Articles

The Effect of Enterococcus faecium AL41 on the Acute Phase Proteins and Selected Mucosal Immune Molecules in Broiler Chickens.

Probiotic bacteria, including the Enterococcus faecium strain, can improve intestinal mucosal health by several mechanisms, including modulation of the immune response, as well as by improving the protective function of the epithelial barrier. In this study, we tested the effect of Enterococcus faecium AL41 on the acute phase proteins response (blood), gene expression of selected molecules of mucosal immunity (immunoglobulin A, mucin-2, insulin-like growth factor 2) and mucus production (all parts of the small intestine) in broilers. Eighty broiler chicks were divided into two groups: a control and E. faecium AL41 (birds were inoculated with AL41 for 7 days) group. The whole experiment lasted 11 days. Our results revealed that the administration of E. faecium AL41 had no substantial effect on the concentrations of acute phase proteins, but we recorded a significant increase in β- and γ-globulin fractions at the end of the experiment, which may indicate an improvement in the immune status. A significant prolonged stimulatory effect of E. faecium AL41 on the relative expression of molecules (immunoglobulin A, mucin-2) as well as on the dynamic of mucus production in the chicken intestine was observed. In addition, AL41 significantly reduced the total number of enterococci in the cecum and faeces.

Acute phase protein response and changes in lipoprotein particle size in dogs with systemic inflammatory response syndrome

BackgroundImproved methodology to measure acute phase proteins and determination of lipoprotein particle‐size distribution (PSD) could be clinically useful in dogs with systemic inflammatory processes.ObjectivesEvaluate an immunoturbidometric assay for serum amyloid A (SAA) and lipoprotein PSD in dogs with sepsis, nonseptic systemic inflammation, and in healthy controls. Correlate dyslipidemic changes with SAA and C‐reactive protein (CRP) concentrations.AnimalsTwenty‐five dogs with sepsis, 15 dogs with nonseptic systemic inflammation, and 22 healthy controls.MethodsProspective, case‐control study. Variables included SAA, CRP, and electrophoretic subfractionation of high‐ and low‐density lipoproteins (HDL, LDL). Continuous variables were compared using ANOVA or Kruskal‐Wallis tests with linear regression or Spearman's rank correlation used to assess relationships between variables.ResultsMedian SAA and CRP concentrations were greater in dogs with sepsis (SAA 460 mg/L, interquartile range [IQR] 886 mg/L; CRP 133.2 mg/L, IQR 91.6 mg/L) and nonseptic inflammation (SAA 201 mg/L, IQR 436 mg/L; CRP 91.1 mg/L, IQR 88.6 mg/L) compared to healthy dogs (SAA 0.0 mg/L, IQR 0.0 mg/L; CRP 4.9 mg/L, IQR 0.0 mg/L) P < .0001. A cutoff of >677.5 mg/L SAA was 43.2% sensitive and 92.3% specific for sepsis. Low‐density lipoprotein was higher in dogs with sepsis 29.6%, (mean, SD 14.6) compared to 14.4% (mean, SD 5.6) of all lipoproteins in healthy controls (P = .005). High‐density lipoprotein was not associated with CRP but was negatively correlated with SAA (r s −0.47, P < .0001). Subfractions of LDL and HDL differed between groups (all P < .05).Conclusions and Clinical ImportanceMeasurement of SAA using the immunoturbidometric assay evaluated in this study and lipoprotein PSD in dogs with inflammation might help distinguish septic from nonseptic causes of inflammation.

Lipopolysaccharide challenge following intravenous amino acid infusion in postpartum dairy cows: II. Clinical and inflammatory responses

Amino acids (AA) are integral nutrients for a functioning immune system. Postpartum cows experience AA deficits early postpartum that may influence the response to immune activation. This study investigated the clinical and inflammatory responses to a systemic inflammatory stimulus after a 4-d intravenous (IV) AA infusion with a mix of essential and nonessential AA designed to ameliorate the estimated metabolizable protein deficit in early postpartum cows. Our objectives were (1) to describe the clinical and inflammatory response to an acute IV lipopolysaccharide (LPS) challenge in early postpartum cows, and (2) to compare these clinical and inflammatory responses between IV AA-treated and control cows. Cows (n = 14, 4 ± 1 d in milk) were continuously infused IV for 4 d in a matched-pair randomized controlled design and received 0.9% NaCl (CTRL) or IV AA (IVAA) to supply 1 g/kg of BW per day of combined essential and nonessential AA. After infusion ended, cows were challenged with IV LPS (0.0625 µg/kg of BW over 1 h), and serial blood samples were collected for complete blood cell counts and to quantify plasma cytokines and acute-phase proteins. Body temperature, heart rate, and respiratory rate were monitored for 24 h during challenge. During challenge, maximum body temperature was greater in IVAA (41.3 ± 0.20°C) than in CTRL (40.6 ± 0.19°C). In both groups, respiratory rate increased during the first 2 h following challenge, whereas heart rate first decreased over the first 2 h and then increased to reach a maximum at 4 h. Acute leucopenia occurred within 1 h of challenge in both groups before leukocytosis was observed at 24 h, with white blood cell counts returning to baseline values within 72 h. Plasma haptoglobin and serum amyloid A concentrations increased 3-fold and 4-fold in both groups and peaked at 48 and 24 h following challenge, respectively. Plasma concentrations of TNF-α and IL-10 increased within 1 h and peaked at 2 h following the start of challenge. Plasma IL-10 concentrations increased to a greater extent in CTRL compared with IVAA during challenge. Despite differences in IL-10 concentration, previous AA infusion did not alter the acute-phase protein response to LPS challenge. We conclude that AA infusion before systemic inflammatory challenge decreased the anti-inflammatory response but did not alter concentrations of other systemic markers of inflammation.

Clusterin protects against Cr(VI)-induced oxidative stress-associated hepatotoxicity by mediating the Akt-Keap1-Nrf2 signaling pathway.

Hexavalent chromium [Cr(VI)] is a serious environmental pollutant that threatens human life. Cr(VI) is widely used in industrial processes such as metallurgy, leather processing, and electroplating, which can enter the human body through the respiratory or digestive tracts, thus causing a number of human disease, including inflammation and cancer. Although it has been confirmed that oxidative stress is one of the primary mechanism of liver injury caused by Cr(VI) exposure, the related toxic target and effective intervention measures have not been found. Clusterin (CLU) is an acute phase response protein with cytoprotective and apoptosis-delaying effects, and its expression has been confirmed to increase significantly after exposure to Cr(VI). In this study, our data clearly indicates that Cr(VI) is capable of causing hepatocytes damage through the production of large amounts of reactive oxygen species (ROS), causing an increase in aspartate aminotransferase (AST) and alanine aminotransferase (ALT). In contrast, over expression of CLU was able to inhibit ROS production and alleviate Cr(VI)-induced liver injury. The specific mechanisms are that CLU acts on the protein kinase B (PKB/Akt)-Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) signaling pathway to release Nrf2 into the nucleus. This is to initiate the expression of a downstream protein, heme oxygenase 1 (HO-1), thereby attenuating the ubiquitination ability of Keap1 with Nrf2. We also demonstrated that CLU could affect oxidative stress through the Akt/Nrf2 pathway, which reduced the production of ROS induced by Cr(VI) and protected against Cr(VI)-induced oxidative stress-associated hepatotoxicity. This study demonstrates a mechanism of Cr(VI)-induced hepatotoxicity and indicates that CLU as an intervention target of oxidative stress can provide valuable experimental basis for the prevention and treatment of occupational diseases in Cr(VI)-exposed population. Under the state of Cr(VI)-induced oxidative stress, CLU though phosphorylation Akt, leading to Nrf2 dissociation from Keap1. Activated Nrf2 entered the nucleus and formed the next step, thus binding to the structure of the antioxidant response element ARE, which activated HO-1, resulting in the decrease in intracellular ROS.

Serum amyloid A1 exacerbates hepatic steatosis via TLR4-mediated NF-κB signaling pathway

ObjectiveChronic inflammatory response plays a prominent role in obesity-related nonalcoholic fatty liver disease (NAFLD). However, the intrahepatic triggering mechanism of inflammation remains obscure. This study aimed to elucidate the role of serum amyloid A1 (SAA1), an acute-phase response protein, in the obesity-induced hepatic inflammation and NAFLD. MethodsMale mice were fed a high fat diet (HFD) for 16 weeks, and insulin resistance, hepatic steatosis, and inflammation in mice were monitored. Murine SAA1/2 was genetically manipulated to investigate the role of SAA1 in NAFLD. ResultsWe found that SAA1 was increased in the NAFLD liver in both humans and mice. Knockout of SAA1/2 or knockdown of hepatic SAA1/2 promoted energy expenditure and alleviated HFD-induced metabolic disorder, hepatic steatosis, and inflammation. Endogenous overexpression of SAA1 in hepatocytes by adeno-associated virus 8 (AAV8) transfection aggravated overnutrition-associated gain of body weight, insulin resistance, hepatic lipid accumulation, and liver injury, which were markedly alleviated by knockout of murine toll-like receptor 4 (TLR4). Mechanistically, SAA1 directly bound with TLR4/myeloid differentiation 2 (MD2) to induce TLR4 internalization, leading to the activation of nuclear factor (NF)-κB signaling and production of both SAA1 and other inflammatory cytokines, including interleukin (IL)-6 and C–C chemokine ligand (CCL2) in hepatocytes. Administration of HFD mice with an AAV8-shRNA-SAA1/2 showed a therapeutic effect on hepatic inflammation and NAFLD progression. ConclusionsThese results demonstrate that SAA1 triggers hepatic steatosis and intrahepatic inflammatory response by forming a SAA1/TLR4/NF-κB/SAA1 feedforward regulatory circuit, which, in turn, leads to NAFLD progression. SAA1 may act as a potential target for the disease intervention.

The Neuroinflammatory Acute Phase Response in Parkinsonian-Related Disorders.

Neuroinflammation is implicated in the pathophysiology of Parkinson's disease (PD) and related conditions, yet prior clinical biomarker data report mixed findings. The aim was to measure a panel of neuroinflammatory acute phase response (APR) proteins in the cerebrospinal fluid (CSF) of participants with PD and related disorders. Eleven APR proteins were measured in the CSF of 867 participants from the BioFINDER cohort who were healthy (612) or had a diagnosis of PD (155), multiple system atrophy (MSA) (26), progressive supranuclear palsy (PSP) (22), dementia with Lewy bodies (DLB) (23), or Parkinson's disease with dementia (PDD) (29). CSF APR proteins were mostly unchanged in PD, with only haptoglobin and α1-antitrypsin significantly elevated compared to controls. These proteins were variably increased in the other disorders. Certain protein components yielded unique signatures according to diagnosis: ferritin and transthyretin were selectively elevated in MSA and discriminated these patients from all others. Haptoglobin was selectively increased in PSP, discriminating this disease from MSA when used in combination with ferritin and transthyretin. This panel of proteins did not correlate well with severity of motor impairment in any disease category, but several (particularly ceruloplasmin and ferritin) were associated with memory performance (Mini-Mental State Examination) in patients with DLB and PDD. These findings provide new insights into inflammatory changes in PD and related disorders while also introducing biomarkers of potential clinical diagnostic utility. © 2022 International Parkinson and Movement Disorder Society.

Rapamycin, Acarbose and 17\u03b1-estradiol share common mechanisms regulating the MAPK pathways involved in intracellular signaling and inflammation

BackgroundRapamycin (Rapa), acarbose (ACA), and 17α-estradiol (17aE2, males only) have health benefits that increase lifespan of mice. Little is known about how these three agents alter the network of pathways downstream of insulin/IGF1 signals as well as inflammatory/stress responses.ResultsACA, Rapa, and 17aE2 (in males, but not in females) oppose age-related increases in the MEK1- ERK1/2-MNK1/2 cascade, and thus reduce phosphorylation of eIF4E, a key component of cap-dependent translation. In parallel, these treatments (in both sexes) reduce age-related increases in the MEK3-p38MAPK-MK2 pathway, to decrease levels of the acute phase response proteins involved in inflammation.ConclusionEach of three drugs converges on the regulation of both the ERK1/2 signaling pathway and the p38-MAPK pathway. The changes induced by treatments in ERK1/2 signaling are seen in both sexes, but the 17aE2 effects are male-specific, consistent with the effects on lifespan. However, the inhibition of age-dependent p38MAPK pathways and acute phase responses is triggered in both sexes by all three drugs, suggesting new approaches to prevention or reversal of age-related inflammatory changes in a clinical setting independent of lifespan effects.

Acute phase proteins in veterinary medicine: A review

The acute phase proteins (APPs) are a group of blood proteins that contribute to restoring homeostasis and limiting microbial growth in an antibody-independent manner in animals which are exposed to different pathological conditions like infection, inflammation, surgical trauma and stress. In the last two decades, many advances have been made in monitoring APPs in both farm and companion animals for clinical and experimental purposes. Also, the mechanism of the APPs response is receiving attention in veterinary science in connection with the innate immune systems of animals. This review describes the many of new results of research and role APPs in farm animal, with special reference to their functions, types, induction and regulatory expression, some of biological functions, and their current and future applications to veterinary diagnosis and animal production.

Associations between a protective lifestyle behaviour score and biomarkers of chronic low-grade inflammation: a cross-sectional analysis in middle-to-older aged adults.

Certain lifestyle behaviours may have a protective effect against low-grade systemic inflammation, which is linked to chronic disease. Our objective was to examine associations between a five-component protective lifestyle behaviour (PLB) score and a range of pro-inflammatory cytokines, adipocytokines, acute-phase response proteins, coagulation factors and white blood cells. This was a cross-sectional study of 2045 middle-to-older aged men and women. Low-risk behaviours included never smoking, moderate alcohol intake, moderate-to-vigorous physical activity, a high-quality diet (upper 40% Dietary Approaches to Stop Hypertension score) and a normal body mass index (BMI) (18.5-24.9 kg/m2). Linear and logistic regression analyses tested individual protective behaviour and PLB score associations with biomarkers. Analysis of individual low-risk behaviours revealed varied associations depending on the biomarker, with normal BMI showing the most consistent associations. Examination of the PLB score showed that compared to subjects with 4-5 protective behaviours, those with 0-1 protective behaviours had 1.4-3.8 increased odds of having a less favourable inflammatory profile. Following adjustment for BMI, significant trend relationships were observed between the number of protective behaviours and complement component 3 (P < 0.001), c-reactive protein (P < 0.001), interleukin 6 (P < 0.001), tumour necrosis factor alpha (P < 0.001) and white blood cell count (P < 0.001) concentrations. These results suggest a cumulative protective effect of healthy lifestyle behaviours against systemic inflammation in middle-to-older aged adults which is independent of having a healthy body weight.

197 Awardee Talk: Novel Management Strategies to Enhance Growth and Development of Feedlot Receiving Cattle

Abstract Feedlot receiving is one of the most critical phases within the beef production cycle, when cattle are exposed to several stress and health challenges that impact their welfare and productivity. These stressors include weaning, road transport, and commingling with different animals, which elicit adrenocortical and acute-phase protein responses known to impair cattle immunocompetence and growth. Accordingly, incidence of bovine respiratory disease (BRD) is elevated during feedlot receiving, despite efforts to minimize stress and vaccination protocols against BRD pathogens. With increased restrictions regarding the use of feed-grade antimicrobials in livestock systems, our research group has focused on developing management systems that minimize stress and enhance performance and immunity of receiving cattle. By providing all vaccines against BRD pathogens prior to feedlot entry, our group reported increased (P ≤ 0.05) vaccine efficacy, body weight (BW) gain, feed efficiency, and reduced BRD incidence during the receiving period compared to on-arrival or delayed vaccination. Reducing the number of cattle sources within receiving pens, as a manner to alleviate commingling stress, reduced (P = 0.04) the number of antimicrobials needed for cattle diagnosed with BRD to regain health. Administration of a bovine appeasing substance (BAS) to beef cattle at weaning alleviated (P ≤ 0.05) the resultant acute-phase protein response, enhanced humoral immunity against BRD pathogens, and improved BW gain during a 6-wk postweaning period. Likewise, BAS administration to steers upon feedlot arrival facilitated (P ≤ 0.05) early detection of BRD signs and lessened the BRD recurrence upon first antimicrobial treatment, resulting in improved (P ≤ 0.05) BW gain and feed efficiency during a 45-d receiving period. Collective, vaccinating cattle against BRD prior to feedlot arrival, reducing the number of cattle sources within receiving pens, and the use of BAS during stressful events are favorable strategies to enhance performance and immunity of feedlot cattle.

197 Awardee Talk: Novel Management Strategies to Enhance Growth and Development of Feedlot Receiving Cattle

Abstract Feedlot receiving is one of the most critical phases within the beef production cycle, when cattle are exposed to several stress and health challenges that impact their welfare and productivity. These stressors include weaning, road transport, and commingling with different animals, which elicit adrenocortical and acute-phase protein responses known to impair cattle immunocompetence and growth. Accordingly, incidence of bovine respiratory disease (BRD) is elevated during feedlot receiving, despite efforts to minimize stress and vaccination protocols against BRD pathogens. With increased restrictions regarding the use of feed-grade antimicrobials in livestock systems, our research group has focused on developing management systems that minimize stress and enhance performance and immunity of receiving cattle. By providing all vaccines against BRD pathogens prior to feedlot entry, our group reported increased (P ≤ 0.05) vaccine efficacy, body weight (BW) gain, feed efficiency, and reduced BRD incidence during the receiving period compared to on-arrival or delayed vaccination. Reducing the number of cattle sources within receiving pens, as a manner to alleviate commingling stress, reduced (P = 0.04) the number of antimicrobials needed for cattle diagnosed with BRD to regain health. Administration of a bovine appeasing substance (BAS) to beef cattle at weaning alleviated (P ≤ 0.05) the resultant acute-phase protein response, enhanced humoral immunity against BRD pathogens, and improved BW gain during a 6-wk postweaning period. Likewise, BAS administration to steers upon feedlot arrival facilitated (P ≤ 0.05) early detection of BRD signs and lessened the BRD recurrence upon first antimicrobial treatment, resulting in improved (P ≤ 0.05) BW gain and feed efficiency during a 45-d receiving period. Collective, vaccinating cattle against BRD prior to feedlot arrival, reducing the number of cattle sources within receiving pens, and the use of BAS during stressful events are favorable strategies to enhance performance and immunity of feedlot cattle.

Therapeutic plasma exchange in patients with COVID-19 pneumonia in intensive care unit: Cases series

IntroductionCOVID 19 pneumonia can lead to an inappropriate inflammatory response, and can be complicated by acute respiratory distress syndrome, multivisceral failure with a high mortality rate. ObjectiveTo observe the effect of therapeutic plasma exchange on the excessive inflammatory response. Materials and methodsIn this study, we included 7 confirmed cases of COVID-19 in the intensive care unit (ICU) department of the university hospital of Oujda. COVID-19 cases were confirmed by RT PCR (reverse transcription‐polymerase chain) and CT (computerized tomography) imaging according to WHO guidelines. Therapeutic plasma exchange was performed decrease cytokine storm-induced ARDS (Acute respiratory distress syndrome). Inflammation marker assays were performed before and after therapeutic plasma exchange to assess its efficacy. ResultsLevels of inflammatory cytokines (IL-6) and acute phase response proteins, including ferritin and CRP, were elevated before therapeutic plasma exchange.After therapeutic plasma exchange, levels of acute phase reactants, inflammatory mediators, were significantly reduced (p < 0.05). ConclusionOur data suggest that therapeutic plasma exchange reduces the inflammatory response in patients with severe COVID-19 not undergoing mechanical ventilation. Further studies are needed to explore the efficacy of therapeutic plasma exchange in patients with COVID-19.

Dietary zinc concentration and lipopolysaccharide injection affect circulating trace minerals, acute phase protein response, and behavior as evaluated by an ear-tag-based accelerometer in beef steers.

To assess plasma trace mineral (TM) concentrations, the acute phase protein response, and behavior in response to a lipopolysaccharide (LPS) challenge, 96 Angus cross steers (average initial body weight [BW]: 285 ± 14.4 kg) were sorted into two groups by BW (heavy and light; n = 48/group), fitted with an ear-tag–based accelerometer (CowManager SensOor; Agis, Harmelen, Netherlands), and stagger started 14 d apart. Consecutive day BW was recorded to start the 24-d trial (days −1 and 0). Dietary treatments began on day 0: common diet with either 30 (Zn30) or 100 (Zn100) mg supplemental Zn/kg DM (ZnSO4). On day 17, steers received one of the following injection treatments intravenously to complete the 2 × 3 factorial: 1) SALINE (~2–3 mL of physiological saline), 2) LOWLPS: 0.25 µg LPS/kg BW, or 3) HIGHLPS: 0.375 µg LPS/kg BW. Blood, rectal temperature (RT), and BW were recorded on day 16 (−24 h relative to injection), and BW was used to assign injection treatment. Approximately 6, 24 (day 18), and 48 (day 19) h after treatment, BW, RT, and blood were collected, and final BW recorded on day 24. Data were analyzed in Proc Mixed of SAS with fixed effects of diet, injection, diet × injection; for BW, RT, dry matter intake (DMI), plasma TM, and haptoglobin-repeated measures analysis were used to evaluate effects over time. Area under the curve analysis determined by GraphPad Prism was used for analysis of accelerometer data. Body weight was unaffected by diet or injection (P ≥ 0.16), but there was an injection × time effect for DMI and RT (P < 0.05), where DMI decreased in both LPS treatments on day 16, but recovered by day 17, and RT was increased in LPS treatments 6 h post-injection. Steers receiving LPS spent less time highly active and eating than SALINE (P < 0.01). Steers in HIGHLPS spent lesser time ruminating, followed by LOWLPS and then SALINE (P < 0.001). An injection × time effect (P < 0.001) for plasma Zn showed decreased concentrations within 6 h of injection and remained decreased through 24 h before recovering by 48 h. A tendency for a diet × time effect (P = 0.06) on plasma Zn suggests plasma Zn repletion occurred at a greater rate in Zn100 compared to Zn30. These results suggest that increased supplemental Zn may alter the rate of recovery of Zn status from an acute inflammatory event. Additionally, ear-tag–based accelerometers used in this study were effective at detecting sickness behavior in feedlot steers, and rumination may be more sensitive than other variables.

Burn Injury Induces Proinflammatory Plasma Extracellular Vesicles That Associate with Length of Hospital Stay in Women: CRP and SAA1 as Potential Prognostic Indicators.

Severe burn injury is a devastating form of trauma that results in persistent immune dysfunction with associated morbidity and mortality. The underlying drivers of this immune dysfunction remain elusive, and there are no prognostic markers to identify at-risk patients. Extracellular vesicles (EVs) are emerging as drivers of immune dysfunction as well as biomarkers. We investigated if EVs after burn injury promote macrophage activation and assessed if EV contents can predict length of hospital stay. EVs isolated early from mice that received a 20% total body surface area (TBSA) burn promoted proinflammatory responses in cultured splenic macrophages. Unbiased LC-MS/MS proteomic analysis of early EVs (<72 h post-injury) from mice and humans showed some similarities including enrichment of acute phase response proteins such as CRP and SAA1. Semi-unbiased assessment of early human burn patient EVs found alterations consistent with increased proinflammatory signaling and loss of inhibition of CRP expression. In a sample of 50 patients with large burn injury, EV SAA1 and CRP were correlated with TBSA injury in both sexes and were correlated with length of hospital stay in women. These findings suggest that EVs are drivers of immune responses after burn injury and their content may predict hospital course.

Out of Control: The Role of the Ubiquitin Proteasome System in Skeletal Muscle during Inflammation.

The majority of critically ill intensive care unit (ICU) patients with severe sepsis develop ICU-acquired weakness (ICUAW) characterized by loss of muscle mass, reduction in myofiber size and decreased muscle strength leading to persisting physical impairment. This phenotype results from a dysregulated protein homeostasis with increased protein degradation and decreased protein synthesis, eventually causing a decrease in muscle structural proteins. The ubiquitin proteasome system (UPS) is the predominant protein-degrading system in muscle that is activated during diverse muscle atrophy conditions, e.g., inflammation. The specificity of UPS-mediated protein degradation is assured by E3 ubiquitin ligases, such as atrogin-1 and MuRF1, which target structural and contractile proteins, proteins involved in energy metabolism and transcription factors for UPS-dependent degradation. Although the regulation of activity and function of E3 ubiquitin ligases in inflammation-induced muscle atrophy is well perceived, the contribution of the proteasome to muscle atrophy during inflammation is still elusive. During inflammation, a shift from standard- to immunoproteasome was described; however, to which extent this contributes to muscle wasting and whether this changes targeting of specific muscular proteins is not well described. This review summarizes the function of the main proinflammatory cytokines and acute phase response proteins and their signaling pathways in inflammation-induced muscle atrophy with a focus on UPS-mediated protein degradation in muscle during sepsis. The regulation and target-specificity of the main E3 ubiquitin ligases in muscle atrophy and their mode of action on myofibrillar proteins will be reported. The function of the standard- and immunoproteasome in inflammation-induced muscle atrophy will be described and the effects of proteasome-inhibitors as treatment strategies will be discussed.

Differential acute-phase protein responses in dogs seropositive or seronegative for Neospora caninum.

Neospora caninum is one of the most prevalent Apicomplexa parasites that causes abortion in cattle, as it infects dogs as its definitive host, causing subclinical disease or active neosporosis, marked by meningoencephalitis, and myopathies with muscle and neuromuscular signs of disease. This study aimed to evaluate the acute phase protein response in dogs seropositive and seronegative for N. caninum. Serum samples of 72 dogs were tested by an immunofluorescence antibody test using N. caninum NC-1 strain, and the study population was divided into four groups: symptomatic - muscular and/or neuromuscular signs - and seropositive (n = 16); symptomatic and seronegative (n = 9); asymptomatic and seropositive (n = 34); and asymptomatic and seronegative (n = 13). C-reactive protein (CRP) was measured via immunoturbidimetric assay and serum haptoglobin (Hp) via hemoglobin-binding capacity assay. In the symptomatic groups, seropositive dogs had higher levels of Hp, but not CRP, while seronegative dogs had higher CRP levels. There was no difference in CRP concentration in asymptomatic dogs. Dogs with neuromuscular signs had higher concentrations for Hp in the group seropositive. Hp concentration did not differ between dogs seropositive and seronegative dogs for each group. Serum Hp and CRP could not sufficiently alone flag subclinical infections. Measurement of CRP and Hp concentrations could be clinically valuable to the diagnosis of neurological diseases, and their relative change may indicate the stage of the infection, although their sole use is not able to support the diagnosis of canine neosporosis. Further studies are encouraged to evaluate the specific dynamics of acute phase proteins in canine neosporosis. Serum samples of 72 dogs were tested by an immunofluorescence antibody test using N. caninum NC-1 strain, and the study population was divided into four groups: (1) dogs with muscular and/or neuromuscular signs and seropositive for N. caninum; (2) dogs with muscular and/or neuromuscular signs and seronegative for N. caninum; (3) dogs seropositive for N. caninum with no neuromuscular signs; and (4) healthy dogs and seronegative for N. caninum. The study evaluated if N. caninum infection could have pathophysiological changes activating the acute phase response and an increase in the concentration of acute phase proteins in serum.

Different expression pattern of thrombospondin gene in the presence and absence of β-glucan fed Penaeus monodon challenged with white spot syndrome virus

Thrombospondins (TSPs) are extracellular, calcium-binding glycoproteins that play an essential role in cell homeostasis and development, wound-healing, angiogenesis, connective tissue organization, immune response etc. and it conserves from sea sponges to mammals. However, their role in shrimp immunity is poorly understood. In the present study, the differential expression profiling of TSP transcripts in Penaeus monodon tissues such as gills, lymphoid organs, hepatopancreas, and hemolymph challenged with white spot syndrome virus (WSSV), were studied by quantitative real-time PCR. Further, shrimps fed with the immunostimulant (β-glucan) when challenged with WSSV showed significant upregulation of TSP expression in gills, hepatopancreas, and lymphoid organ at the early phase of WSSV infection. The results suggest that TSP may be an inducible acute phase response protein to WSSV infection. The possibility of differences in mRNA expression pattern seen in immunostimmulated shrimp after the viral challenge, possibility due to altered immune mechanisms getting triggered during immunostimulant administration and virus infections in the host.

Hemopexin as an acute phase protein regulates the inflammatory response against bacterial infection of Nile tilapia (Oreochromis niloticus)

Hemopexin, a high affinity heme-binding protein is widely involved in variety physiological and pathological processes. It is an important acute phase response protein, and is important in regulating the inflammatory response. In this study, the open reading frame of Nile tilapia hemopexin (OnHpx) gene was amplified. The expression pattern of OnHpx in natural and bacterial challenged tilapia tissues were analyzed through RT-qPCR. The results indicated the OnHpx was most abundant in liver, and increased significantly in liver, spleen, head kidney and peripheral blood after bacterial challenge. Furthermore, the OnHpx mRNA was also significantly up-regulated in monocytes/macrophages and hepatocytes under the stimulation of S. agalactiae or A. hydrophila. In addition, the recombinant OnHpx protein could effectively reduce the bacteria proliferation and alleviate the inflammatory reaction caused by bacteria. Moreover, the (r)OnHpx also regulated the respiratory burst of monocytes/macrophages and played an important role in the antioxidant process. To our knowledge, these results provide the first evidence on the antibacterial and anti-inflammatory response mechanism of Hpx in early vertebrates. This brings new insights about the understanding of the evolutionary origins and ancient roles of the Hpx in the innate immune defense.

Quantification of Intact O-Glycopeptides on Haptoglobin in Sera of Patients With Hepatocellular Carcinoma and Liver Cirrhosis.

Haptoglobin (Hp) is one of the acute-phase response proteins secreted by the liver, and its aberrant N-glycosylation was previously reported in hepatocellular carcinoma (HCC). Limited studies on Hp O-glycosylation have been previously reported. In this study, we aimed to discover and confirm its O-glycosylation in HCC based on lectin binding and mass spectrometry (MS) detection. First, serum Hp was purified from patients with liver cirrhosis (LC) and HCC, respectively. Then, five lectins with Gal or GalNAc monosaccharide specificity were chosen to perform lectin blot, and the results showed that Hp in HCC bound to these lectins in a much stronger manner than that in LC. Furthermore, label-free quantification based on MS was performed. A total of 26 intact O-glycopeptides were identified on Hp, and most of them were elevated in HCC as compared to LC. Among them, the intensity of HYEGS 316TVPEK (H1N1S1) on Hp was the highest in HCC patients. Increased HYEGS 316TVPEK (H1N1S1) in HCC was quantified and confirmed using the MS method based on 18O/16O C-terminal labeling and multiple reaction monitoring. This study provided a comprehensive understanding of the glycosylation of Hp in liver diseases.

The acute phase response protein SERPINA3 is increased in tear fluid from the unaffected eyes of patients with unilateral acute anterior uveitis

BackgroundTo identify candidate tear fluid biomarkers in patients with unilateral acute anterior uveitis (AAU) that can aid in the differentiation between these patients and patients with bacterial keratitis or healthy controls.MethodsThirteen patients (40.1 ± 16.2 years of age) with unilateral AAU, seven patients with unilateral bacterial keratitis (40.2 ± 15.3 years of age), and 14 healthy subjects (41.1 ± 11.6 years of age) were included. The tear proteome of affected eyes was compared with that of the unaffected eye or healthy controls. Proteins were identified by liquid chromatography tandem mass spectrometry and enzyme-linked immunosorbent assay.ResultsRelative protein ratios were detected and calculated for 272 unique proteins. Compared with healthy controls and the unaffected eye, the top upregulated proteins in AAU eyes were submaxillary gland androgen regulated protein 3B (SMR3B) and SMR3A. Similarly, the top upregulated proteins in bacterial keratitis were S100 calcium-binding protein A9 and orosomucoid 2. The acute phase response protein Serpin Family A Member 3 (SERPINA3) was increased in the healthy eye of AAU patients (P = 0.019) compared with healthy controls. Laser flare measurements in affected eyes of AAU patients showed positive logarithmic correlation with SERPINA3 in tear samples of the unaffected eye (P = 0.022). The use of SERPINA3 as a tear biomarker yielded a sensitivity of 85% and a specificity of 71% in detecting patients with AAU in the study population.ConclusionsThe acute phase response protein SERPINA3 was increased in tear samples of unaffected eyes of patients with unilateral AAU compared with healthy controls. This study highlights SERPINA3 as a potential biomarker for AAU. Future research should explore the dynamic properties of SERPINA3 in the tear fluid of active and quiescent uveitis eyes.