Haptoglobin is dispensable for haemoglobin uptake by Trypanosoma brucei.

Haptoglobin is a plasma protein of mammals that plays a crucial role in vascular homeostasis by binding free haemoglobin released from ruptured red blood cells. Trypanosoma brucei can exploit this by internalising haptoglobin-haemoglobin complex to acquire host haem. Here, we investigated the impact of haptoglobin deficiency (Hp-/-) on T. brucei brucei infection and the parasite´s capacity to internalise haemoglobin in a Hp-/- mouse model. The infected Hp-/- mice exhibited normal disease progression, with minimal weight loss and no apparent organ pathology, similarly to control mice. While the proteomic profile of mouse sera significantly changed in response to T. b. brucei, no differences in the infection response markers of blood plasma between Hp-/- and control Black mice were observed. Similarly, very few quantitative differences were observed between the proteomes of parasites harvested from Hp-/- and Black mice, including both endogenous proteins and internalised host proteins. While haptoglobin was indeed absent from parasites isolated from Hp-/-mice, haemoglobin peptides were unexpectedly detected in parasites from both Hp-/- and Black mice. Combined, the data support the dispensability of haptoglobin for haemoglobin internalisation by T. b. brucei during infection in mice. Since the trypanosomes knock-outs for their haptoglobin-haemoglobin receptor (HpHbR) internalised significantly less haemoglobin from Hp-/- mice compared to those isolated from Black mice, it suggests that T. b. brucei employs also an HpHbR-independent haptoglobin-mediated mode for haemoglobin internalisation. Our study reveals a so-far hidden flexibility of haemoglobin acquisition by T. b. brucei and offers novel insights into alternative haemoglobin uptake pathways.

Co-administration of PEGylated Apohemoglobin and Haptoglobin can Limit Vascular Dysfunction in the Microcirculation and Prevent Acute Inflammation.

Unfortunately, during pathological conditions resulting in chronic hemolysis cell-free hemoglobin (Hb) is released into the circulation which releases free heme, resulting in several complications. One approach to prevent these toxicities is administration of supplemental scavenger proteins, haptoglobin (Hp) and hemopexin (Hpx). The goal of this body of work is to objectively measure levels of vascular reactivity and inflammatory profiles after an infusion of acellular hemoglobin in animals that were given a co-administration of PEGylated human apohemoglobin (PEG-apoHb), a hemopexin (Hpx)-mimetic that can scavenge free heme from hemoglobin, together with human plasma-derived Hp that can scavenge dimerized Hb. Utilizing intravital microscopy, Golden Syrian hamsters instrumented with a dorsal window chamber were used to evaluate the in vivo effects of 4 experimental groups that were then challenged with a hypovolemic injection (10% of the animal's blood volume) of human Hb (hHb, 5 g/dL). The four experimental groups consisted of: 1) lactated Ringer's (control), 2) PEG-apoHb only, 3) Hp only, and 4) PEG-apoHb + Hp. The microvascular hemodynamics (diameter and flow) in arterioles and venules were recorded at baseline, 20 minutes after treatment, and 20 minutes after hHb challenge. Systemic parameters (blood pressure and heart rate), blood gases (pH, pCO2, and pO2), blood parameters (Hb concentration and hematocrit), and multiorgan functionality/ inflammation were also measured. Our results suggest that co-administration of PEG-apoHb + Hp as a booster prior to the infusion of acellular hemoglobin significantly prevented vasoconstriction in the microcirculation, significantly increased the number of functional capillaries, and significantly reduced inflammation.

Targeting heme in sickle cell disease: new perspectives on priapism treatment.

Men with sickle cell disease (SCD) frequently experience priapism, defined as prolonged, painful erections occurring without sexual arousal or desire. This urological emergency can lead to penile fibrosis and permanent erectile dysfunction if not treated adequately. Due to its complex pathophysiology, there is currently no effective preventative treatment for this condition. Recent studies have highlighted the dysfunction of the nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) pathway in erectile tissues as a critical mechanism in developing priapism in SCD. Additionally, further research indicates that intravascular hemolysis promotes increased smooth muscle relaxation in the corpus cavernosum and that excess heme may significantly contribute to priapism in SCD. Pharmacological treatments should ideally target the pathophysiological basis of the disease. Agents that reduce excess free heme in the plasma have emerged as potential therapeutic candidates. This review explores the molecular mechanisms underlying the excess of heme in SCD and its contribution to developing priapism. We discuss pharmacological approaches targeting the excess free heme in the plasma, highlighting it as a potential therapeutic target for future interventions in managing priapism.

Data Independent Acquisition Mass Spectrometry Enhanced Personalized Glycosylation Profiling of Haptoglobin in Hepatocellular Carcinoma.

Aberrant glycosylation has gained significant interest for biomarker discovery. However, low detectability, complex glycan structures, and heterogeneity present challenges in glycoprotein assay development. Using haptoglobin (Hp) as a model, we developed an integrated platform combining functionalized magnetic nanoparticles and zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) for highly specific glycopeptide enrichment, followed by a data-independent acquisition (DIA) strategy to establish a deep cancer-specific Hp-glycosylation profile in hepatitis B virus (HBV, n = 5) and hepatocellular carcinoma (HCC, n = 5) patients. The DIA strategy established one of the deepest Hp-glycosylation landscapes (1029 glycopeptides, 130 glycans) across serum samples, including 54 glycopeptides exclusively detected in HCC patients. Additionally, single-shot DIA searches against a DIA-based spectral library outperformed the DDA approach by 2-3-fold glycopeptide coverage across patients. Among the four N-glycan sites on Hp (N-184, N-207, N-211, N-241), the total glycan type distribution revealed significantly enhanced detection of combined fucosylated-sialylated glycans, which were the most dominant glycoforms identified in HCC patients. Quantitation analysis revealed 48 glycopeptides significantly enriched in HCC (p < 0.05), including a hybrid monosialylated triantennary glycopeptide on the N-184 site with nearly none-to-all elevation to differentiate HCC from the HBV group (HCC/HBV ratio: 2462 ± 766, p < 0.05). In summary, DIA-MS presents an unbiased and comprehensive alternative for targeted glycoproteomics to guide discovery and validation of glyco-biomarkers.

Method for quantifying free hemoglobin, distinct from the hemoglobin-haptoglobin complex, in human serum.

The measurement of free hemoglobin (free Hb) in blood is crucial for assessing the risk of organ damage in patients with hemolytic diseases. However, the colorimetric method, commonly used in clinical practice, does not distinguish between free Hb and the hemoglobin-haptoglobin complex (Hb-Hp) in the blood, instead reflecting the total Hb level. Although size-exclusion high-performance liquid chromatography (SEC-HPLC) can specifically measure free Hb, its clinical use is limited by long assay times. Here, we developed a novel assay method for the rapid quantification of free Hb in serum, distinguishing it from Hb-Hp, using a latex agglutination immunoturbidimetric assay (LATIA). This method could be used to measure free Hb in sera in the range of 1-100 µg/mL in approximately 15 min using an automatic biochemistry analyzer. Using Hb-spiked serum samples from healthy adults, there was a high correlation with Hb levels determined using the newly developed method and SEC-HPLC, indicating a high specificity for free Hb. This novel assay can be used to monitor levels of free Hb in patients with various hemolytic diseases and to design therapeutic strategies based on measured values. However, further studies are required to assess its clinical performance.

Non-specific markers of inflammation in bare-nosed wombats (Vombatus ursinus) with sarcoptic mange.

Sarcoptic mange, caused by epidermal infection with Sarcoptes scabiei, negatively impacts the health, welfare, and local abundance of bare-nosed wombats (Vombatus ursinus) in Australia. Improved understanding of the host immune response to disease and its contribution to pathophysiology could be used to inform management actions for this species in and ex situ. To evaluate the immune response of bare-nosed wombats to sarcoptic mange, we validated three assays (haptoglobin, agarose gel electrophoresis, and micro-erythrocyte sedimentation rate) measuring non-specific markers of inflammation using serum samples from free-living wombats from Tasmania (n = 33). We then analysed correlations between the assay results for each non-specific marker of inflammation and wombat's sarcoptic mange scores, and performed histopathological examinations to investigate association of the acute phase response with systemic amyloidosis. We present evidence that haptoglobin and erythrocyte sedimentation rate increased, and albumin decreased, in association with sarcoptic mange scores. This research demonstrates links between the acute phase response and sarcoptic mange severity in bare-nosed wombats, highlighting the utility of non-specific markers of inflammation for aiding assessment of the systemic effects of mange. Showing the value of agarose gel electrophoresis, we also identified specific acute phase proteins warranting future evaluation and found evidence of an immunoglobulin response in mange-affected wombats, revealed by increasing γ-globulins in association with apparent disease severity. Meanwhile, owing to its relatively low resource requirements and rapidity, the erythrocyte sedimentation rate assay may be useful as a point-of-care test to support therapeutic decisions in the field. Our methods and findings are likely to be applicable to a range of other clinical and population health scenarios in captive and free-living wombats, and species impacted by sarcoptic mange globally.

Association of results of the glutaraldehyde coagulation test with plasma acute phase protein concentrations and hematologic findings in hospitalized cows.

Introduction: The glutaraldehyde test (GAT) allows for animal-side semi-quantitative estimation of fibrinogen and gamma-globulin concentrations in blood samples of adult cattle and therefore detection of inflammatory disease conditions. However, the test has potential limitations, especially due to the latency period until sufficiently high fibrinogen and/or gamma-globulin concentrations are reached. The aim of the present study was therefore to assess the association between results of GAT with other inflammatory markers including hematologic variables, fibrinogen, plasma haptoglobin and serum amyloid A (SAA) concentrations. Methods: For the purpose of this prospective observational study, a convenience sample of 202 cows with a broad range of inflammatory and non-inflammatory clinical conditions was included. The GAT was run on EDTA blood, fibrinogen was measured using the Clauss and the heat precipitation method, and commercially available ELISA tests were used for determination of plasma haptoglobin and SAA concentrations. Results: Shortened GAT coagulation times were more closely correlated to serum globulin (rs = -0.72) than to plasma fibrinogen concentrations measured with the heat precipitation (rs = -0.64) and the Clauss method (rs = -0.70). Cows with a markedly (≤3 min) or moderately (4-6 min) shortened coagulation time had higher (p < 0.001) plasma haptoglobin and SAA concentrations than cows with a negative test result. Total leukocyte, monocyte and neutrophil concentrations did not differ significantly between groups. An identified cut-off for the GAT coagulation time of ≤14 min had a sensitivity and specificity of 54.4 and 100%, respectively, for the prediction of an inflammatory state based on clinical findings and/or increased plasma haptoglobin or SAA concentrations. Discussion: In conclusion, this study demonstrates considerable diagnostic agreement between positive GAT results and increased plasma concentrations of haptoglobin and SAA. Despite high specificity, the test lacks sensitivity in case of acute inflammatory conditions indicating that plasma acute phase protein concentrations and hematologic findings can provide additional diagnostic information if the GAT is negative.

Association of Bovine Respiratory Disease during the Pre-Weaning Period with Blood Cell Counts and Circulating Concentration of Metabolites, Minerals, and Acute Phase Proteins in Dairy Calves Transported to a Calf Raising Facility.

Our objective was to investigate the association of bovine respiratory disease (BRD) occurring within the first 56 days of life with blood cell counts and the circulating concentration of metabolites, minerals, and acute phase proteins throughout the pre-weaning period in dairy calves transported to a heifer raising facility within their first week of life. Data from 305 calves transported from dairies in Minnesota to a calf raising facility in New Mexico within their first four days of life were used in this retrospective cohort study. Blood samples were collected at 7, 17, 34, and 56 days of life for the analysis of blood cell counts, biochemistry, and the concentration of acute phase proteins. Blood urea nitrogen, albumin, GLDH, CK, P, Na, K, Cl, Zn, Hp, SAA, and monocyte counts were associated with BRD status throughout or at least at one of the time points evaluated in this study. In conclusion, several hematological variables were associated with BRD status in dairy calves that underwent transportation stress in early life.

Meconium Proteins Involved in Iron Metabolism.

The lack of specific biological materials and biomarkers limits our knowledge of the mechanisms underlying intrauterine regulation of iron supply to the fetus. Determining the meconium content of proteins commonly used in the laboratory to assess the transport, storage, and distribution of iron in the body may elucidate their roles in fetal development. Ferritin, transferrin, haptoglobin, ceruloplasmin, lactoferrin, myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), and calprotectin were determined by ELISA in meconium samples obtained from 122 neonates. There were strong correlations between the meconium concentrations of haptoglobin, transferrin, and NGAL (p < 0.05). Meconium concentrations of ferritin were several-fold higher than the concentrations of the other proteins, with the exception of calprotectin whose concentration was approximately three-fold higher than that of ferritin. Meconium ceruloplasmin concentration significantly correlated with the concentrations of MPO, NGAL, lactoferrin, and calprotectin. Correlations between the meconium concentrations of haptoglobin, transferrin, and NGAL may reflect their collaborative involvement in the storage and transport of iron in the intrauterine environment in line with their recognized biological properties. High meconium concentrations of ferritin may provide information about the demand for iron and its utilization by the fetus. The associations between ceruloplasmin and neutrophil proteins may indicate the involvement of ceruloplasmin in the regulation of neutrophil activity in the intrauterine environment.

A Randomised Controlled Trial of SFX-01 After Subarachnoid Haemorrhage - The SAS Study.

SFX-01 is a novel drug for clinical delivery of sulforaphane (SFN). SFN is a potent nuclear factor erythroid 2-related factor 2 activator that reduces inflammation and oxidation, improving outcomes after subarachnoid haemorrhage (SAH) in animal models. This was a multi-centre, double-blind, placebo-controlled, parallel-group randomised clinical trial to evaluate the safety, pharmacokinetics and efficacy of 28 days of SFX-01 300 mg BD in patients aged 18-80 with spontaneous SAH and high blood load on CT. Primary outcomes were (1) safety, (2) plasma and CSF SFN and metabolite levels and (3) vasospasm on transcranial doppler ultrasound. Secondary outcomes included CSF haptoglobin and malondialdehyde and clinical outcome on the modified Rankin Scale (mRS) and SAH outcome tool (SAHOT). A total of 105 patients were randomised (54 SFX-01, 51 placebo). There were no differences in adverse events other than nausea (9 SFX-01 (16.7%), 1 placebo (2.0%)). SFN, SFN-glutathione and SFN-N-acetyl-cysteine AUClast were 16.2, 277 and 415 h × ng/ml. Plasma SFN was higher in GSTT1 null individuals (t = 2.40, p = 0.023). CSF levels were low with many samples below the lower limit of quantification and predicted by the CSF/serum albumin ratio (R2 = 0.182, p = 0.039). There was no difference in CSF haptoglobin (1.981 95%CI 0.992-3.786, p = 0.052) or malondialdehyde (1.12 95%CI 0.7477-1.687, p = 0.572) or middle cerebral artery flow velocity (1.04 95%CI 0.903-1.211, p = 0.545) or functional outcome (mRS 1.647 95%CI 0.721-3.821, p = 0.237, SAHOT 1.082 95%CI 0.464-2.525, p = 0.855). SFX-01 is safe and effective for the delivery of SFN in acutely unwell patients. SFN penetrated CSF less than expected and did not reduce large vessel vasospasm or improve outcome. Trial registration: NCT02614742 clinicaltrials.gov.

Diet supplementation with Saccharomyces cerevisiae influences the electrophoretic parameters in blood in young Charolaise bulls.

Introduction: The objective of the research was to investigate the effect of Saccharomyces cerevisiae supplementation on some acute-phase proteins, haptoglobin and all electrophoretic parameters in young Charolaise bulls. Material and Methods: Sixty bulls were divided into two equal groups: the control group (CG) receiving the base diet without yeast supplementation and the diet supplementation group (YG) receiving the base diet with 5g of Saccharomyces cerevisiae supplementation. The base diet was total mixed ration allocated at 11.85 kg per animal per day. Blood samples were collected from all bulls on day 0 before the start of the diet supplementation, and on days 20 and 40 after the start. Total proteins, albumin, globulin fraction (α1-, α2-, ß1-, ß2- and γ-globulins), albumin: globulin ratio (A: G) and haptoglobin were determined. Results: Two-way analysis of variance showed a significant effect of the yeast feeding time on all studied parameters except α2-globulins in both groups. The YG showed a higher average concentration of total proteins, albumin and A: G and a lower average concentration of γ-globulins and haptoglobin than the CG. Conclusion: These results indicated the beneficial effect of the Saccharomyces cerevisiae on the inflammatory status of the young bulls, which showed an adequate response in serum levels of the acute-phase proteins tested.

Serum Amyloid A and Haptoglobin concentrations in calves at first event of respiratory disease were not associated with subsequent risk of respiratory disease during the preweaning period.

Bovine respiratory disease (BRD) causes decreased welfare and production losses and is a major reason for use of antimicrobials in dairy calves. Inflammatory markers released into the blood stream during BRD include acute phase proteins such as Serum Amyloid A (SAA) and Haptoglobin (Hp). This longitudinal observational study aimed to investigate whether the serum concentrations of SAA and Hp measured on the day of a detected mild clinical event of BRD, were associated the odds of developing recurrent BRD events requiring additional treatments in up to a 46-day follow-up period after the first event. A total of 65 preweaned dairy calves were observed for 46 days each in one Danish dairy herd. They were enrolled in this study in the age between 17 and 24 days of age and were followed for the following 46 days in total in which the calves potentially could develop an event of BRD. The calves were clinically assessed every other day using a Visual Analogue Scale (VAS), where a mild BRD event was defined as a calf that deviated from a normal and non-affected calf. The clinical signs included that the calf was less interested in its surroundings, slightly depressed, less bright, alert, and responsive with less clear eyes and using longer time to get up. The calf could have scruffy hair coat and drooping ears. Blood samples were collected on the day of the first mild BRD event that was only treated with a non-steroidal anti-inflammatory drug. A logistic regression model was performed to detect associations between having recurrent events of BRD and VAS, serum SAA and Hp concentrations at the day of the first BRD event and the follow-up period after the BRD event. Only the follow-up period after the first BRD event had a significant association with the odds ratio of having recurrent events of BRD of 2.3 for a 10-day difference in follow-up time after the BRD event.

Investigating the importance of selected surface-exposed loops in HpuB for hemoglobin binding and utilization by Neisseria gonorrhoeae.

Neisseria gonorrhoeae is the etiological agent of the sexually transmitted infection gonorrhea. The pathogen is a global health challenge since no protective immunity results from infection, and far fewer treatment options are available with increasing antimicrobial resistance. With no efficacious vaccines, researchers are exploring new targets for vaccine development and innovative therapeutics. The outer membrane TonB-dependent transporters (TdTs) produced by N. gonorrhoeae are considered promising vaccine antigens as they are highly conserved and play crucial roles in overcoming nutritional immunity. One of these TdTs is part of the hemoglobin transport system comprised of HpuA and HpuB. This system allows N. gonorrhoeae to acquire iron from hemoglobin (hHb). In the current study, mutations in the hpuB gene were generated to better understand the structure-function relationships in HpuB. This study is one of the first to demonstrate that N. gonorrhoeae can bind to and utilize hemoglobin produced by animals other than humans. This study also determined that when HpuA is absent, mutations targeting extracellular loop 7 of HpuB led to defective hHb binding and utilization. However, when the lipoprotein HpuA is present, these loop 7 mutants recovered their ability to bind hHb, although the growth phenotype remained significantly impaired. Interestingly, loop 7 contains putative heme-binding motifs and a hypothetical α-helical region, both of which may be important for the use of hHb. Taken together, these results highlight the importance of loop 7 in the functionality of HpuB in binding hHb and extracting and internalizing iron.

Puzzling undetectable haptoglobin in a transfused pregnant patient.

BACKGROUND-AIM: Pregnancy induces physiological changes that can affect serologic and immunologic markers, potentially resulting in lower or undetectable haptoglobin values compared to non-pregnant counterparts. Such variations may lead to inaccurate diagnosis of hemolysis. METHODS: We report a case of a patient in second trimester of pregnancy receiving induction chemotherapy due to B-cell acute lymphocytic leukemia with undetectable haptoglobin levels in a routine laboratory sample collected less than 12 h posttransfusion of red cell unit. Despite undetectable haptoglobin, lactate dehydrogenase (LD) was within reference intervals (RI). The patient was evaluated for acute hemolytic transfusion reaction (AHTR) and followed up. Haptoglobin levels showed an upward trend during follow-up visits, reaching 15 mg/dL, and within RI in the third trimester. RESULTS: The patient did not meet the Center for Disease Control (CDC) criteria for AHTR. Alternative explanations for the observed laboratory findings were explored. Undetectable haptoglobin levels were attributed to various factors, including recent RBC transfusion, pregnancy-related physiological changes, and potential hyperhydration treatment plan due to chemotherapy. CONCLUSION: This case underscores the importance of cautious interpretation of laboratory results in pregnant patients, necessitating trimester-specific reference intervals for haptoglobin. A multidisciplinary approach to patient care is crucial for accurate diagnosis and management.

Hemadsorption to Contain Postoperative Cell-Free Hemoglobin and Haptoglobin Preservation for Extended Cardiopulmonary Bypass Time in Cardiac Surgery for Acute Kidney Injuries Prevention.

INTRODUCTION: Prevention of acute kidney injury during cardiopulmonary bypass (CPB) is still a challenge and has been the object of numerous studies. The incidence of acute kidney injury in the context of CPB is related to a multifactorial etiology. The role of hemadsorption in relation to cell-free hemoglobin and haptoglobin preservation is not well defined in the literature on CPB during cardiac surgery procedures. METHODS: This is a single-center pilot randomized report including 20 patients undergoing elective CPB procedures with an expected time > 120 minutes for each extracorporeal procedure. Patients were randomly allocated to either standard of care (n=10) or Jafron HA380 (n=10) during CPB. The primary outcome measured was the incidence of postoperative acute kidney injuries. RESULTS: The Jafron study group vs. control group reported postoperative values for cell-free hemoglobin at 10 minutes after CPB (mg/L) (11.6 ± 0.6 vs. 29.9 ± 0.3) (P-value 0.021), haptoglobin 10 minutes after CPB (mg/dl) (129.16 ± 1.22 vs. 59.17 ± 1.49) (P-value 0.017), creatinine peak after CPB (mg/dL) (0.92 ± 0.17 vs. 1.32 ± 0.9) (P-value 0.030), and acute kidney injury after 48 hours (number of patients) (one vs. four) (P-value 0.027). CONCLUSION: This pilot study suggested that the use of Hemoperfusion Cartridge HA380 Jafron for extended CPB time for complex cardiac surgery procedures was safe and effective and is associated with a better postoperative preservation of haptoglobin with a reduction of cell-free hemoglobin values and less incidence of acute kidney injury, though larger studies are warranted to confirm our result.

Potential applications of dual haptoglobin expression in the reclassification and treatment of hepatocellular carcinoma.

HCC is a malignancy characterized by high incidence and mortality rates. Traditional classifications of HCC primarily rely on tumor morphology, phenotype, and multicellular molecular levels, which may not accurately capture the cellular heterogeneity within the tumor. This study integrates scRNA-seq and bulk RNA-seq to spotlight HP as a critical gene within a subgroup of HCC malignant cells. HP is highly expressed in HCC malignant cells and lowly expressed in T cells. Within malignant cells, elevated HP expression interacts with C3, promoting Th1-type responses via the C3/C3AR1 axis. In T cells, down-regulating HP expression favors the expression of Th1 cell-associated marker genes, potentially enhancing Th1-type responses. Consequently, we developed a "HP-promoted Th1 response reclassification" gene set, correlating higher activity scores with improved survival rates in HCC patients. Additionally, four predictive models for neoadjuvant treatment based on HP and C3 expression were established: 1) Low HP and C3 expression with high Th2 cell infiltration; 2) High HP and low C3 expression with high Th2 cell infiltration; 3) High HP and C3 expression with high Th1 cell infiltration; 4) Low HP and high C3 expression with high Th1 cell infiltration. In conclusion, the HP gene selected from the HCC malignant cell subgroup (Malignant_Sub 6) might serve as a potential ally against the tumor by promoting Th1-type immune responses. The establishment of the "HP-promoted Th1 response reclassification" gene set offers predictive insights for HCC patient survival prognosis and neoadjuvant treatment efficacy, providing directions for clinical treatments.

How are Trypanosoma brucei receptors protected from host antibody-mediated attack?

Trypanosoma brucei is the causal agent of African Trypanosomiasis in humans and other animals. It maintains a long-term infection through an antigenic variation based population survival strategy. To proliferate in a mammal, T. brucei acquires iron and haem through the receptor mediated uptake of host transferrin and haptoglobin-hemoglobin respectively. The receptors are exposed to host antibodies but this does not lead to clearance of the infection. Here we discuss how the trypanosome avoids this fate in the context of recent findings on the structure and cell biology of the receptors.

Variability of haptoglobin beta-chain proteoforms.

Existing knowledge on changes of the haptoglobin (Hp) molecule suggests that it may exist in multiple proteoforms, which obviously exhibit different functions. Using two-dimensional electrophoresis (2DE) in combination with mass spectrometry and immunodetection, we have analyzed blood plasma samples from both healthy donors and patients with primary grade IV glioblastoma (GBM), and obtained a detailed composite 2DE distribution map of ß-chain proteoforms, as well as the full-length form of Hp (zonulin). Although the total level of plasma Hp exceeded normal values in cancer patients (especially patients with GBM), the presence of particuar proteoforms, detected by their position on the 2DE map, was very individual. Variability was found in both zonulin and the Hp ß-chain. The presence of an alkaline form of zonulin in plasma can be considered a conditional, but insufficient, GBM biomarker. In other words, we found that at the level of minor proteoforms of Hp, even in normal conditions, there was a high individual variability. On the one hand, this raises questions about the reasons for such variability, if it is present not only in Hp, but also in other proteins. On the other hand, this may explain the discrepancy between the number of experimentally detected proteoforms and the theoretically possible ones not only in Hp, but also in other proteins.

Effects of Trace Mineral Injections on Measures of Growth and Trace Mineral Status of Primiparous Cows and their Calves.

The objective of this study was to evaluate the effects of injectable trace minerals (ITM) administrations at strategic moments in the beef cattle production cycle. At calving, 50 primiparous cows (Angus × Hereford) and their calves were randomly assigned to 1 of 2 treatments: 1) ITM: cattle assigned to the ITM treatment received an ITM injection at calving and a subsequent administration at breeding (cattle over 2 yr: 1.0 mL/90 kg body weight [BW]; calves: 1.0 mL/45 kg BW); or 2) Control: cattle assigned to the control treatment were administered with saline following the same procedure as the cattle assigned to the ITM treatment. Body weight, blood, and liver samples were collected from dams and calves at multiple time points to evaluate the growth and mineral status of cow-calf pairs. All variables were analyzed using the MIXED procedure of SAS. A treatment effect (P = 0.02) was observed for Cu liver concentration of primiparous cows at breeding. Cows assigned to ITM treatment had greater Cu status than cohorts assigned to Control treatment. No treatment effects were observed for the mineral status or growth of calves. The administration of ITM to primiparous cows enhanced Cu status when grazing Cu forages scarce of Cu.

Proteomics in Patients with Fibromyalgia Syndrome: A Systematic Review of Observational Studies.

PURPOSE OF REVIEW: Fibromyalgia syndrome (FMS) is a disease of unknown pathophysiology, with the diagnosis being based on a set of clinical criteria. Proteomic analysis can provide significant biological information for the pathophysiology of the disease but may also reveal biomarkers for diagnosis or therapeutic targets. The present systematic review aims to synthesize the evidence regarding the proteome of adult patients with FMS using data from observational studies. RECENT FINDINGS: An extensive literature search was conducted in MEDLINE/PubMed, CENTRAL, and clinicaltrials.gov from inception until November 2022. The study protocol was published in OSF. Two independent reviewers evaluated the studies and extracted data. The quality of studies was assessed using the modified Newcastle-Ottawa scale adjusted for proteomic research. Ten studies fulfilled the protocol criteria, identifying 3328 proteins, 145 of which were differentially expressed among patients with FMS against controls. The proteins were identified in plasma, serum, cerebrospinal fluid, and saliva samples. The control groups included healthy individuals and patients with pain (inflammatory and non-inflammatory). The most important proteins identified involved transferrin, α-, ß-, and γ-fibrinogen chains, profilin-1, transaldolase, PGAM1, apolipoprotein-C3, complement C4A and C1QC, immunoglobin parts, and acute phase reactants. Weak correlations were observed between proteins and pain sensation, or quality of life scales, apart from the association of transferrin and a2-macroglobulin with moderate-to-severe pain sensation. The quality of included studies was moderate-to-good. FMS appears to be related to protein dysregulation in the complement and coagulation cascades and the metabolism of iron. Several proteins may be dysregulated due to the excessive oxidative stress response.