Plasma Factor Research Articles

Factor VIIa - antithrombin complexes are increased in asthma: relation to the exacerbation-prone asthma phenotype.

Asthma is associated with a prothrombotic state. Plasma factor VIIa-antithrombin complex concentrations (FVIIa-AT) indirectly reflect the interaction of tissue factor (TF) with FVII. Since TF is a key initiator of coagulation in vivo, we hypothesized that FVIIa-AT are higher in asthma. In 159 clinically stable adult asthma patients and 62 controls, we determined FVIIa-AT in plasma and analyzed their relation to circulating inflammatory and prothrombotic markers together with the total plasma potential for fibrinolysis (clot lysis time, CLT) and thrombin generation. We recorded clinical outcomes, including asthma exacerbations, during 3-year follow-up. Asthma patients were characterized by 38.5% higher FVIIa-AT (p<0.001), related to bronchial obstruction (FEV1: r=-0.397, p<0.001), asthma severity (r=0.221, p=0.005) and duration (r=0.194, p=0.015) compared to controls. FVIIa-AT showed weak positive associations with C-reactive protein (r=0.208, p=0.009), fibrinogen (r=0.215, p=0.007), and CLT (r=0.303, p<0.001) but not with thrombin generation parameters. In the follow-up (data obtained from 151 patients), we documented 151 severe asthma exacerbations in 51 (33.8%) patients, including 33 (21.9%) with ≥2 such events. Exacerbation-prone asthma phenotype was related to 13.1% higher FVIIa-AT (p=0.012), along with asthma severity and control (p<0.003, both). High FVIIa-AT (that is ≥ 100.1 pmol/l), defined on receiver operating characteristic curves, was linked to exacerbation-prone asthma phenotype (odds ratio 1.85; 95%CI: 1.23-2.80, p=0.003) and shorter time to first exacerbation (p=0.023). This study is the first to show that FVIIa-AT are higher in asthma in relation to its severity and may help identify individuals at risk of the exacerbation-prone asthma phenotype.

Transfusion of Fresh Frozen Plasma and Coagulation Factors - Indications, Practice and Complications

After severe trauma, but also perioperatively, massive bleeding is associated with increased morbidity and mortality. In severely injured patients, hemorrhagic shock remains to be the main cause of death in addition to traumatic brain hemorrhage. In non-cardiac surgery, a surgical bleeding complication increases perioperative morbidity (intensive care length of stay, acute renal failure, infections, thromboembolic complications) by a factor of three to four and mortality by a factor of six. In cardiac surgery, postoperative bleeding requiring surgical revision is associated with a 50% increase in mortality. One possible therapeutic approach is the transfusion of erythrocytes to plasma in a fixed ratio. This practice of untargeted coagulation therapy is mainly used in the USA and some Scandinavian countries. Mortality is significantly worse in the USA than in central Europe, particularly in the case of severe injuries. There is increasing evidence that targeted coagulation therapy with coagulation factor concentrates based on the results of point-of-care coagulation diagnostics is more effective and associated with fewer transfusion- and bleeding-related complications.

Numerical studies of the voltage amplitude effect on plasma characteristics in atmospheric pressure driven by dual LF-RF frequency discharge

Abstract Dielectric barrier discharges (DBDs) are primarily utilized as efficient sources of large-volume diffuse plasmas. However, the synergistic interaction of certain key plasma factors limits their broader application. In the present study, we report on numerical investigations of the effects of voltage amplitude in dual-frequency excitation on atmospheric DBDs using a 50 kHz/5 MHz frequency combination. Our results indicate that varying the voltages for LF and RF significantly influences the electron dynamics during discharge, resulting in distinct spatiotemporal distributions of electron and metastable particle densities. These findings contribute to the regulation of discharges under atmospheric pressure conditions and facilitate the attainment of non-equilibrium and nonlinear plasma parameters.

Comparison of Corneal Epitheliotrophic Factors of Undiluted Autologous Platelet-Rich Plasma and Autologous Serum Eye Drops for Dry Eye Disease.

The purpose of this study was to compare the growth factor concentrations in undiluted autologous platelet-rich plasma (APRP) and autologous serum (AS) eye drops. This was a single-center, prospective trial conducted in a tertiary university hospital in Bangkok, Thailand. Ninety-six patients with moderate-to-severe dry eye disease, who were randomly assigned to receive either 100% APRP or 100% AS, were enrolled in the study. Primary outcome measures were the concentrations of epitheliotrophic factors, including epithelial growth factor (EGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), β-nerve growth factor (β-NGF), platelet-derived growth factor (PDGF)-AA, PDGF-BB, transforming growth factor (TGF)-α, TGF-β1, and vascular endothelial growth factor (VEGF) in 100% APRP and 100% AS. Secondary outcome measures were the correlations between baseline patient characteristics and each growth factor concentration. Undiluted APRP contained more EGF, bFGF, and β-NGF than undiluted AS (P < 0.001, P < 0.001, P = 0.018, respectively). Meanwhile, undiluted AS yielded higher concentrations of HGF, PDGF-AA, PDGF-BB, and VEGF compared with undiluted APRP (P < 0.001 all). There were no significant differences in TGF-α and TGF-β1 concentrations between the two groups. In the 100% APRP group, the platelet concentrations had positive correlations with the concentrations of EGF (P = 0.028) and VEGF (P = 0.020). In the 100% AS group, Sjögren's syndrome negatively correlated with the concentrations of PDGF-BB (P = 0.028) and VEGF (P = 0.023). Diabetes mellitus (DM) showed negative correlations with the concentrations of HGF (P = 0.001), TGF-α (P = 0.001), and VEGF (P = 0.002). With our simple preparation protocols, 100% APRP contains higher concentrations of EGF, bFGF, and β-NGF, whereas 100% AS contains higher concentrations of HGF, PDGF-AA, PDGF-BB, and VEGF. This could allow ophthalmologists to tailor treatments to individual patients by targeting growth factor supply based on their underlying pathophysiology. ClinicalTrials.gov identifier, NCT04683796.

Inclusive, exclusive and hierarchical atlas of NFATc1+/PDGFR-α+ cells in dental and periodontal mesenchyme.

Platelet-derived growth factor receptor alpha (PDGFR-α) activity is crucial in the process of dental and periodontal mesenchyme regeneration facilitated by autologous platelet concentrates (APCs), such as platelet-rich fibrin (PRF), platelet-rich plasma (PRP) and concentrated growth factors (CGF), as well as by recombinant PDGF drugs. However, it is largely unclear about the physiological patterns and cellular fate determinations of PDGFR-α+ cells in the homeostasis maintaining of adult dental and periodontal mesenchyme. We previously identified NFATc1 expressing PDGFR-α+ cells as a subtype of skeletal stem cells (SSCs) in limb bone in mice, but their roles in dental and periodontal remain unexplored. To this end, in the present study we investigated the spatiotemporal atlas of NFATc1+ and PDGFR-α+ cells residing in dental and periodontal mesenchyme in mice, their capacity for progeny cell generation, and their inclusive, exclusive and hierarchical relations in homeostasis. We utilized CRISPR/Cas9-mediated gene editing to generate two dual recombination systems, which were Cre-loxP and Dre-rox combined intersectional and exclusive reporters respectively, to concurrently demonstrate the inclusive, exclusive, and hierarchical distributions of NFATc1+ and PDGFR-α+ cells and their lineage commitment. By employing the state-of-the-art transgenic lineage tracing techniques in cooperating with tissue clearing-based advanced imaging and three-dimensional slices reconstruction, we systematically mapped the distribution atlas of NFATc1+ and PDGFR-α+ cells in dental and periodontal mesenchyme and tracked their in vivo fate trajectories in mice. Our findings extend current understanding of NFATc1+ and PDGFR-α+ cells in dental and periodontal mesenchyme homeostasis, and furthermore enhance our comprehension of their sustained therapeutic impact for future clinical investigations.

Hydroxylated-Benz[a]anthracenes Induce Two Apoptosis-Related Gene Expressions in the Liver of the Nibbler Fish Girella punctata.

Polycyclic aromatic hydrocarbons (PAHs) are known to have toxic effects on fish. In this study, we examined the effects of benz[a]anthracene (BaA), a type of PAH, on fish liver metabolism. Nibbler fish (Girella punctata) were intraperitoneally injected with BaA (10 ng/g body weight) four times over a 10-day period. BaA significantly decreased known bone metabolism-related plasma factors such as calcium and inorganic phosphorus. Moreover, significant reductions were observed in the plasma levels of known liver metabolism-related factors, including ferrous ions, total bile acids, total bilirubin, free bilirubin, aspartate aminotransferase, and alkaline phosphatase. Interestingly, mono-hydroxylated metabolites of BaA, such as 3 hydroxylbenz[a]anthracene (3-OHBaA), were detected in the bile of BaA-injected nibbler fish. This hydroxylated form of BaA was found in its free form, rather than conjugated with glucuronic acid or sulfuric acid. Due to the lack of whole-genome sequence data for the nibbler fish, two nibbler fish-specific apoptosis-related factors (TNF receptor superfamily member 1A: tnfrsf1a and TNF superfamily member 10: tnfsf10) were isolated by De novo RNA sequencing. In a liver tissue culture, 3-OHBaA (10-6 M) significantly upregulated the expression of tnfrsf1a and tnfsf10 in the liver. These results provide the first evidence that 3-OHBaA metabolites exhibit toxic effects on the liver in teleost.

Alzheimer's Disease: In Vitro and In Vivo Evidence of Activation of the Plasma Bradykinin-Forming Cascade and Implications for Therapy.

The plaques associated with Alzheimer's disease are formed as a result of the aggregation of Aβ peptides, which vary in length from 38 to 43 amino acids. The 1-40 peptide is the most abundant, while the 1-42 peptide appears to be the most destructive to neurons and/or glial cells in a variety of assays. We have demonstrated that aggregated Aβ, a state prior to plaque formation, will activate the plasma bradykinin-forming pathway when tested in vitro. Aggregation is zinc-dependent, optimal at 25-50 µM, and the rate of aggregation is paralleled by the rate of activation of the bradykinin-forming pathway as assessed by plasma kallikrein formation. The aggregation of Aβ 1-38, 1-40, and 1-42 is optimal after incubation for 3 days, 3 h, and under 1 min, respectively. The cascade is initiated by the autoactivation of factor XII upon binding to aggregated Aβ; then, prekallikrein is converted to kallikrein, which cleaves high-molecular-weight kininogen (HK) to release bradykinin. Studies by a variety of other researchers have demonstrated the presence of each "activation-step" in either the plasma or spinal fluid of patients with Alzheimer's disease, including activated factor XII, kallikrein, and bradykinin itself. There is also evidence that activation is more prominent as dementia worsens. We now have medications that can block each step of the bradykinin-forming pathway as currently employed for the therapy of hereditary angioedema. Given the current state of therapy for Alzheimer's disease, which includes monoclonal antibodies that retard the rate of progression by 30% at most and have significant side effects, it seems imperative to explore prophylaxis using one of the long-acting agents that target plasma kallikrein or factor XIIa. There is a long-acting bradykinin antagonist in development, and techniques to target kallikrein mRNA to lower levels or knock out the prekallikrein gene are being developed.

Propagation Characteristics of Nonplanar Electron-Acoustic Waves in Non-Thermal Plasma

Abstract Nonplanar electron acoustic waves (NEAWs) having double spectral index distributed hot electrons are studied under two temperature electrons model in a collisionless unmagnetized plasma. Using this model, the Korteweg-de Vries (KdV) equation is derived in nonplanar geometry. On the basis of solutions of KdV equation, alteration of velocity, width and amplitude of acoustic waves having various plasma factors are investigated. Nonlinear and dispersion coefficients obtained rely on double spectral index parameters r and q, and particle density α. Combine influence of these factors significantly alters the features of electron acoustic waves in nonplanar geometry. This study is expected to contribute to the understanding of the nonlinear principles that underlie nonplanar electrostatic waves in laboratory plasmas as well as space.

Grapefruit-Derived Vesicles Loaded with Recombinant HSP70 Activate Antitumor Immunity in Colon Cancer In Vitro and In Vivo.

Background/Objectives: Stress protein HSP70 administered exogenously has demonstrated high potential as an efficient adjuvant in antitumor immune response. To enhance the antigen-presenting activity, bioavailability, and stability of exogenous recombinant human HSP70, we propose incorporating it into plant extracellular vesicles. Earlier, we found that grapefruit-derived extracellular vesicles (GEV) were able to store the protein with no loss of its major function, chaperone activity. Methods: In this study, we tested whether HSP70 loaded into GEV (GEV-HSP70) could elicit an antitumor immune response in cellular and animal models of colorectal cancer. Results: To test the hypothesis in vitro, human and mouse colorectal cancer cell lines were used. We have shown that the addition of HSP70, either in free form or as part of GEVs, increases the sensitivity of human (HCT-116, DLD1) or mouse (CT-26) colon cancer cells to mouse cytotoxic lymphocytes and human NK-92 cells. Moreover, the amount of protein in the form of GEV-HSP70 required to cause the same activation of antitumor immunity was 20 times less than when HSP70 was added in free form. In a colon carcinoma model in vivo, GEV-HSP70 were inoculated subcutaneously into BALB/c mice together with CT-26 cells to form a tumor node. As compared with the control groups, we observed an increase in the lifespan of animals and a decrease in the tumor size, as well as a decrease in the level of TGFB1 IL-10 factors in the blood plasma. In vitro analysis of the immunomodulatory activity of GEV-HSP70 showed that antitumor response in GEV-HSP70-treated mice was associated with the accumulation of CD8+ cells. Conclusions: These results demonstrate the high feasibility and efficacy of the new technique based on HSP70 encapsulated in plant vesicles in activation of the specific response to colon tumors.

Age Is Just a Number: Ontogenetic Conservation in Activation of Blood Clotting Factors VII, X, and XII by Caucasus Blunt-Nosed Viper (Macrovipera lebetina obtusa) Venoms.

This study examined the pathophysiological effects of venoms from neonate and adult specimens of the viperid snake Macrovipera lebetina obtusa, focusing on their ability to activate various blood clotting factors in human plasma. All venoms exhibited strong procoagulant properties. In concentration-response tests, the clotting potency of the neonate venoms fell within the range of their parents' maximum clotting velocities and areas under the curve. Intriguingly, females were more potent than males within each age group, but this requires a larger sample size to confirm. Antivenom neutralization efficacy was equipotent across age groups. The venoms potently activated Factor X (FX) robustly, consistent with previous knowledge of this genus. For the first time, the ability to activate Factors VII (FVII) and XII (FXII) was identified in this genus, with FXII exhibiting particularly strong activation. The study found no significant ontogenetic variation in procoagulant venom potency on human plasma, convergent with the Daboia genus, the other large-bodied lineage within the Palearctic viperid clade. However, the activation of FXII and FVII reveals previously undocumented pathways in the procoagulant activity of these venoms, contributing to the broader understanding of venom evolution and its clinical impacts. These findings have implications for venom biodiscovery and the development of antivenoms, highlighting the complexity of clotting factor activation beyond traditional investigations that have myopically focused upon FX and prothrombin pathways, thereby underscoring the importance of exploring additional clotting factors.

The physicochemical properties of lipopolysaccharide chemotypes regulate activation of the contact pathway of blood coagulation.

Lipopolysaccharide (LPS) is the primary pathogenic factor in Gram-negative sepsis. While the presence of LPS in the bloodstream during infection is associated with disseminated intravascular coagulation, the mechanistic link between LPS and blood coagulation activation remains ill-defined. The contact pathway of coagulation-a series of biochemical reactions that initiates blood clotting when plasma factors XII (FXII) and XI (FXI), prekallikrein (PK) and high molecular weight kininogen (HK) interact with anionic surfaces-has been shown to be activated in Gram-negative septic patients. In this study, using an in vivo baboon model of Gram-negative Escherichia coli sepsis, we observed activation of the contact pathway including FXII, FXI and PK. We examined whether E.coli LPS molecules could binding and activate contact pathway members by quantifying the interaction and activation of either FXII, FXI, or PK with each of three chemotypes of LPS: O111:B4, O26:B6, or Rd2. The LPS chemotypes exhibited distinct physicochemical properties as aggregates and formed complexes with FXII, FXI and PK. The LPS chemotype O26:B6 uniquely promoted the autoactivation of FXII to FXIIa, and in complex with FXIIa, promoted the cleavage of FXI and prekallikrein to generate FXIa and plasma kallikrein, respectively. Furthermore, in complex with the active forms of FXI or prekallikrein, LPS chemotypes were able to regulate the catalytic activity of FXIa and plasma kallikrein, respectively, despite the inability to promote the autoactivation of either zymogen. These data suggest that the procoagulant phenotype of E.coli is influenced by bacterial strain and the physicochemical properties of the LPS chemotypes.

Protective effect of metformin on the NG-nitro-l-arginine methyl ester (l-NAME)-induced rat models of preeclampsia

BackgroundPreeclampsia (PE) is a complex multi-organ disorder characterized by systemic inflammation, endothelial dysfunction, and vasoconstriction, which manifests as hypertension, with or without proteinuria. Effective preventive strategies for PE are currently lacking in clinical practice, leading to significant morbidity and mortality among mothers and newborns. ObjectiveThis study aims to investigate the impact of metformin (MET) on the l-NAME-induced PE rat model, focusing on the mechanisms through which MET may exert its effects. MethodsThirty pregnant Sprague-Dawley (SD) rats were randomly assigned to three groups: Control, PE, and PE + MET, on gestational day 0 (GD0). Regularly measure blood pressure and 24-h proteinuria, and collect tissue samples on GD20. Enzyme-linked immunosorbent assay (ELISA) was used to analyze inflammatory factors, endothelial function biomarkers, angiogenic factors, and apoptosis-related factors in the rat plasma. Western blot, RT-qPCR, and immunohistochemistry techniques were employed to determine the expression levels of key apoptotic proteins in placental tissue. ResultsThe study findings demonstrate that MET administration improves blood pressure and 24-h proteinuria, alleviates fetal growth restriction, ameliorate inflammation cytokines, and restores the balance of angiogenic factors and endothelial function. Moreover, MET inhibits the expression levels of critical apoptotic proteins in the plasma and placental tissue of PE-like rats. ConclusionThe results suggest that MET shows promise in alleviating symptoms associated with l-NAME-induced PE in rats, preserving endothelial function, enhancing angiogenesis, reducing inflammation, inhibiting placental apoptosis, improving placental function, and promoting fetal growth. These findings highlight MET as a potential therapeutic agent for the prevention and treatment of preeclampsia.

Cytokine profiling of plasma in patients with viral hepatitis C

Chronic hepatitis C (CHC) represents a significant public health concern. In the majority of cases, the infection progresses to a chronic form, which is characterised by the development of fibrosis and cirrhosis of the liver. A plethora of cytokines and chemokines are generated as a consequence of inflammatory processes within the liver. These can exert a dual effect, both protective and damaging, particularly in relation to the death of hepatocytes and the progression of liver fibrosis. Furthermore, a number of growth factors have been identified as playing a role in the pathogenesis of CHC. The objective of the study was a comprehensive evaluation of a wide range of cytokines, chemokines and growth factors in the blood plasma of patients with CHC at varying stages of liver fibrosis. The study cohort comprised 63 patients diagnosed with CHC, who were divided into three groups according to the stage of liver fibrosis. The control group comprised healthy individuals (n = 32). Concentrations of the following cytokines were determined in plasma: Interleukins and some cytokines (IL-1α, IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17A, IL-17-E/IL-25, IL-17F, IL-18, IL-27, IFNα, IFNγ, TNFα, TNFβ); chemokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL7/MCP-3, CCL11/Eotaxin, CCL22/MDC, CXCL1/GROα, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, CX3CL1/Fractalkine) and growth factors (EGF, FGF-2, Flt-3L, G-CSF, M-CSF, PDGF-AA, PDGF-AB/BB, TGF-α, VEGF-A) by multiplex analysis based on xMAP technology. Nonparametric statistics methods were used for statistical analysis. As a result of the study, increased concentrations of cytokines IL-12 (p40), IL-15, IL-17E/IL-25, IL-27, IFNγ, TNFα, chemokines CXCL9/MIG and CXCL-10/IP-10 and growth factors FGF-2 and M-CSF were found at all stages of liver fibrosis. Elevated concentrations of cytokines IL-1α, IL-1β, IL-2, IL-6, IL-9, IL-10, IL-17F, IFNα, TNFβ, chemokines CCL2/MCP-1, CCL11/Eotaxin, CCL22/MDC and growth factors G-CSF, TGF-α, Flt-3L were found in severe liver fibrosis/cirrhosis. Correlation analysis revealed a relationship of high significance between the severity of liver fibrosis and the content of cytokines IL-6, IFNγ, TNFα, IL-7, chemokines CCL2/MCP-1, CCL11/Eotaxin, CXCL9/MIG, CXCL10/IP-10, CXCL1/GROα, growth factors TGF-α, PDGF-AA, PDGF-AB/BB. Thus, a certain profile of cytokines characteristic for CHC was revealed, cytokines, chemokines and growth factors significant for liver fibrosis in CHC were found.

Diminished placental Factor XIIIA1 expression associates with pre-conception antiretroviral treatment and preterm birth in pregnant people living with HIV.

We previously showed a link between maternal vascular malperfusion and pre-term birth (PTB) in pregnant people living with HIV (PPLH) initiating antiretroviral treatment (ART) before pregnancy, indicating poor placental vascularisation. After measuring antenatal plasma angiogenic factors to seek mechanistic insights, low levels of plasma Factor XIIIA1 (FXIIIA1) and vascular-endothelial-growth-factor (VEGF) was significantly associated with PTB at the time closest to delivery (median 34 weeks) in PPLH initiating ART before pregnancy. Knowing that FXIIIA1 is crucial for haemostasis, angiogenesis, implantation and pregnancy maintenance and that expression is found on placental macrophages (Hofbauer cells), we examined placentae at delivery from matching participants who either initiating ART before pregnancy or during gestation. Highest FXIIIA1 expression was on Hofbauer cells but was significantly lower in PTB regardless of HIV infection, but was significantly lower in PPLH in PTB from women who initiated ART before pregnancy. To test the hypothesis that antiretroviral drugs may disrupt vascularisation in the placenta, we used a human umbilical vein endothelial cell (HUVEC) matrigel angiogenesis assay. We identified that addition of pre-treated FXIIIA1-expressing MCSF- and IL-10-induced placenta-like macrophages with physiological concentrations of tenofovir, 3TC, and efavirenz resulted in significantly inhibited angiogenesis; akin to the inhibition observed with titratable concentrations of ZED1301, an inhibitor of FXIIIA1. Overall, an efavirenz-containing ART combination inhibits vasculogenesis without causing toxicity and likely does so through inhibition of a FXIIIA1-mediated-placental macrophage pathway.

Back pain exercise therapy remodels human epigenetic profiles in buccal and human peripheral blood mononuclear cells: an exploratory study in young male participants.

With its high and increasing lifetime prevalence, back pain represents a contemporary challenge for patients and healthcare providers. Monitored exercise therapy is a commonly prescribed treatment to relieve pain and functional limitations. However, the benefits of exercise are often gradual, subtle, and evaluated by subjective self-reported scores. Back pain pathogenesis is interlinked with epigenetically mediated processes that modify gene expression without altering the DNA sequence. Therefore, we hypothesize that therapy effects can be objectively evaluated by measurable epigenetic histone posttranslational modifications and proteome expression. Because epigenetic modifications are dynamic and responsive to environmental exposure, lifestyle choices-such as physical activity-can alter epigenetic profiles, subsequent gene expression, and health traits. Instead of invasive sampling (e.g., muscle biopsy), we collect easily accessible buccal swabs and plasma. The plasma proteome provides a systemic understanding of a person's current health state and is an ideal snapshot of downstream, epigenetically regulated, changes upon therapy. This study investigates how molecular profiles evolve in response to standardized sport therapy and non-controlled lifestyle choices. We report that the therapy improves agility, attenuates back pain, and triggers healthier habits. We find that a subset of participants' histone methylation and acetylation profiles cluster samples according to their therapy status, before or after therapy. Integrating epigenetic reprogramming of both buccal cells and peripheral blood mononuclear cells (PBMCs) reveals that these concomitant changes are concordant with higher levels of self-rated back pain improvement and agility gain. Additionally, epigenetic changes correlate with changes in immune response plasma factors, reflecting their comparable ability to rate therapy effects at the molecular level. We also performed an exploratory analysis to confirm the usability of molecular profiles in (1) mapping lifestyle choices and (2) evaluating the distance of a given participant to an optimal health state. This pre-post cohort study highlights the potential of integrated molecular profiles to score therapy efficiency. Our findings reflect the complex interplay of an individual's background and lifestyle upon therapeutic exposure. Future studies are needed to provide mechanistic insights into back pain pathogenesis and lifestyle-based epigenetic reprogramming upon sport therapy intervention to maintain therapeutic effects in the long run.

Visualization and characterization of complement activation in acetylcholine receptor antibody seropositive myasthenia gravis.

There are no blood biomarkers to monitor treatment effects in myasthenia gravis (MG) or studies visualizing the acetylcholine receptor (AChR) antibody-induced membrane attack complex (MAC) at the human muscle membrane. This study aimed to compare levels of complement activation products and native complement components in MG patients and healthy controls (HCs) and to model the AChR antibody-mediated attacks in human muscle cells. We assessed the complement components and activation product levels with enzyme-linked immunosorbent assay and magnetic bead-based sandwich assays in plasma and sera of 23 MG patients and matched HCs. Receiver operator characteristic (ROC) curve analysis evaluated the diagnostic accuracy. Complement levels were correlated with the myasthenia gravis composite (MGC) scores. AChR+ MG modeling in human muscle cells used sera from nine MG patients and three HCs. MG patients had significantly higher plasma levels of C3a (p < .0001), C5 (p = .0003), and soluble C5b-9 (sC5b-9; p < .0001) than HCs. The ROC curve analysis showed a clear separation between MG patients and HCs for plasma C3a (AUC = 0.9720; p < .0001) and sC5b-9 (AUC = 0.8917, p < .0001). MG patients had higher levels of plasma complement Factor I (FI; p = .0002) and lower properdin levels (p < .0001). The MGC had moderate correlations with plasma Factor B (FB), FI, and Factor H. AChR+ MG patient sera triggered the deposition of MAC and reduced AChRs. We suggest validating plasma C3a and sC5b-9 as blood biomarkers for complement activation in MG. Further, the in vitro study allowed visualization of MAC deposition after applying AChR+ MG sera on human muscle cells.

Prospective Reassessment of the Association Between Pro-Inflammatory Factors and Prognosis After on-Pump Cardiac Surgery.

Elevated levels of pro-inflammatory factors in plasma have been linked to worse prognosis after on-pump cardiac surgery, yet interventions that reduce the levels in patients have failed to improve prognosis. Therefore, we explored whether levels of pro-inflammatory factors are associated with prognosis of patients after valve surgery with cardiopulmonary bypass. 244 patients were prospectively enrolled into observational study. Levels of tumor necrosis factor (TNF) - α, interleukin-8 and neutrophil elastase were measured once before and several times after cardiopulmonary bypass. The levels were compared between patients who experienced in-hospital adverse events or not, and between patients who experienced major adverse cardiac or cerebrovascular events (MACCEs) during three-year follow-up or not. Of the 244 patients enrolled, in-hospital adverse events occurred in 38 (15.6 %); of the 237 patients who completed follow-up, MACCEs occurred in 30 (12.7 %). Surgery led to significant increases in levels of all three pro-inflammatory factors, with levels returning to pre-bypass baseline on arrival in the intensive care unit (TNF-α), 4 h after arrival (interleukin-8) or 20 h after arrival (neutrophil elastase). However, pre- and post-bypass levels of all three factors did not differ significantly between patients who experienced adverse events in-hospital or not, or between patients who experienced MACCEs during follow-up or not. Levels of TNF-α, interleukin-8 and neutrophil elastase may not be associated with poor prognosis after cardiopulmonary bypass. This may help explain why "cytokine clearance" strategies fail to improve clinical outcomes after on-pump cardiac surgery.

The Contrasting Effects of Bothrops lanceolatus and Bothrops atrox Venom on Procoagulant Activity and Thrombus Stability under Blood Flow Conditions.

Consumption coagulopathy and hemorrhagic syndrome are the typical features of Bothrops sp. snake envenoming. In contrast, B. lanceolatus envenoming can induce thrombotic complications. Our aim was to test whether crude B. lanceolatus and B. atrox venoms would display procoagulant activity and induce thrombus formation under flow conditions. Fibrin formation in human plasma was observed for B. lanceolatus venom at 250-1000 ng/mL concentrations, which also induced clot formation in purified human fibrinogen, indicating thrombin-like activity. The degradation of fibrinogen confirmed the fibrinogenolytic activity of B. lanceolatus venom. B. lanceolatus venom displayed consistent thrombin-like and kallikrein-like activity increases in plasma conditions. The well-known procoagulant B. atrox venom activated plasmatic coagulation factors in vitro and induced firm thrombus formation under high shear rate conditions. In contrast, B. lanceolatus venom induced the formation of fragile thrombi that could not resist shear stress. Our results suggest that crude B. lanceolatus venom displays amidolytic activity and can activate the coagulation cascade, leading to prothrombin activation. B. lanceolatus venom induces the formation of an unstable thrombus under flow conditions, which can be prevented by the specific monovalent antivenom Bothrofav®.

Prolonged administration of oral phenylbutazone and firocoxib in horses has no impact on selected cytokine and growth factor concentrations in platelet-rich plasma and autologous protein solution.

To determine the effects of prolonged administration of the oral NSAIDs phenylbutazone and firocoxib on concentrations of cytokines and growth factors in platelet-rich plasma (PRP) and autologous protein solution (APS). 6 adult University owned horses. Horses were randomized to receive phenylbutazone (1 g, orally, q 12 h) or firocoxib (57 mg, orally, q 24 h) for 6 days. Blood was obtained and processed for APS (Pro-Stride) and PRP (Restigen) before the administration of NSAIDs and at 7 days (1 day following cessation of NSAIDs). Horses underwent a two-week washout period, during which blood was obtained at 14 days and 21 days. The protocol was repeated with a crossover design. PRP and APS were analyzed for concentrations of platelets, leukocytes, and several cytokines (IL-1β, IL-10, IL-6, IL-8, and tumor necrosis factor-α) and growth factors (PDGF, FGF-2, and TGF-β1) using immunoassays. Plasma was evaluated for drug concentrations. No significant differences existed in concentrations of growth factors and cytokines before or after prolonged administration of NSAIDs. There were significant differences in concentrations of leukocytes and platelets in PRP compared to APS, with higher concentrations of leukocytes at the day 7 time point (T) in APS (phenylbutazone) and in concentrations of platelets in APS at T0 (firocoxib) and in APS at T7 (phenylbutazone). Veterinarians can recommend the administration of these oral NSAIDs prior to obtaining blood for PRP and APS provided a single-day washout period is instituted.

Therapeutic Plasma Exchange in Neurological Conditions: An Observation from the Eastern Part of India.

Therapeutic plasma exchange (TPE) is an extracorporeal process of separation of plasma from the cellular components of blood and its replacement with analogous fluids. This process is effective in treatment of disease conditions from dysregulation of the humoral immune system by removal of various humoral pathogenic substances like antibodies, immune complexes, monoclonal proteins, toxins or cytokine(s) and/or the replenishment of a specific plasma factor. To evaluate major indications of therapeutic plasma exchange in neurological disorders. To identify major complications associated and factors associated with premature cessation of the therapeutic plasma exchange cycle. Materials and Methods: This is a hospital based retrospective study conducted by analyzing medical records of patients, who had undergone therapeutic plasma exchange (TPE) for various neurological disorders at IMS & SUM hospital. Medical records total 118 patients who underwent TPE from January 2016 to December 2021 were analyzed. The demographic data, blood group pattern and indications for TPE were enumerated from the records. Various complications of TPE and reasons for incomplete TPE cycle were documented and analyzed. A total of 508 TPE procedures were performed on 118 patients. In this study 61 patients were male and 57 patients were female. O-blood group was commonest blood group among the patients. GBS is the commonest indication of TPE. 57.6 % of patients could complete all sessions TPE cycle. Blockage of vascular access is the commonest cause of incomplete TPE session. Cramps (33%) and mild transient hypotension (27.1%0 were the commonest complications observed. TPE is a safe and effective treatment option for various immune-mediated neurological disorders and should be considered in managing these disorders.