Local Production of Acute Phase Proteins: A Defense Reaction of Cancer Cells to Injury with Focus on Fibrinogen.

This review is intended to demonstrate that the local production of acute phase proteins (termed local acute phase response (lAPR)) and especially fibrin/fibrinogen (FN) is a defense mechanism of cancer cells to therapy, and inhibition of the lAPR can augment the effectiveness of cancer therapy. Previously we detected a lAPR accompanying tumor cell death during the treatment of triple-negative breast cancer (TNBC) with modulated electro-hyperthermia (mEHT) in mice. We observed a similar lAPR in in hypoxic mouse kidneys. In both models, production of FN chains was predominant among the locally produced acute phase proteins. The production and extracellular release of FN into the tumor microenvironment is a known method of self-defense in tumor cells. We propose that the lAPR is a new, novel cellular defense mechanism like the heat shock response (HSR). In this review, we demonstrate a potential synergism between FN inhibition and mEHT in cancer treatment, suggesting that the effectiveness of mEHT and chemotherapy can be enhanced by inhibiting the HSR and/or the lAPR. Non-anticoagulant inhibition of FN offers potential new therapeutic options for cancer treatment.

Association of coagulation markers with the severity of white matter hyperintensities in cerebral small vessel disease.

Background and purpose: This study aimed to explore the correlation and causal relationship between fibrinogen, D-dimer, and the severity of cerebral white matter hyperintensity (MMH). Methods: A retrospective analysis of 120 patients with cerebral small vessel disease (CSVD) confirmed by head MRI attending the Third Affiliated Hospital of Beijing University of Traditional Chinese Medicine from August 2021 to February 2023 was performed. According to the Fazekas scale score, the patients were divided into 42 cases in the mild group, 44 cases in the moderate group, and 34 cases in the severe group. The levels of fibrinogen and D-dimer were compared among the three groups; the correlations between fibrinogen, D-dimer, and WMH severity were further analyzed; and independent risk factors for WMH severity were explored using the multivariate ordered logistic regression analysis. Furthermore, a two-sample Mendelian randomization (MR) analysis was performed to investigate the genetically predicted effect of fibrinogen and D-dimer on WMH. Results: As the severity of WMH increased, the levels of D-dimer and fibrinogen also gradually increased, and the results showed a positive correlational association, with significant differences within the groups (all p < 0.05); the multivariate ordered logistic regression model showed that after adjusting for the relevant covariates, D-dimer (OR = 5.998, 95% CI 2.213-16.252, p < 0.001) and fibrinogen (OR = 9.074, 95% CI 4.054-20.311, p < 0.001) remained independent risk factors for the severity of WMH. In the MR study, the random-effect inverse variance weighted (IVW) model showed that increased levels of genetically predicted D-dimer (OR, 1.01; 95% confidence interval 0.95-1.06; p = 0.81) and fibrinogen (OR, 1.91; 95% confidence interval 0.97-3.78; p = 0.06) were not associated with increased risk of WMH. The authors did not obtain strong evidence of a direct causal relationship between D-dimer, fibrinogen, and WMH. Conclusion: In this retrospective-based study, the authors found possible associations between D-dimer, fibrinogen, and WMH, but there was no obvious causal evidence. Further efforts are still needed to investigate the pathophysiology between D-dimer, fibrinogen, and WMH.

Recombinant tissue-type plasminogen activator (rt-PA) effectively restores neurological function and improves prognosis in acute ischemic stroke.

OBJECTIVE: To evaluate the clinical efficacy of intravenous thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) for acute ischemic stroke. METHODS: A total of 76 patients with acute ischemic stroke admitted to the Encephalopathy Dept. of Zhecheng Hospital of Traditional Chinese Medicine between February 2021 and June 2022 were recruited in this prospective trial (ClinicalTrials.gov, NCT03884410) and patients were randomized 1:1 to receive either aspirin plus clopidogrel (control group) or aspirin plus clopidogrel and rt-PA intravenous thrombolytic therapy (experimental group), with 38 cases in each group. The treatment efficiency, National Institute of Health stroke scale (NIHSS) scores, daily living ability, coagulation function, serum Lipoprotein-associated phospholipaseA2 (Lp-PLA2), homocysteine (HCY), hypersensitive C-reactive protein (hsCRP) levels, adverse events, and prognosis were evaluated and compared between the two groups. RESULTS: Intravenous thrombolysis with rt-PA resulted in a better treatment outcome of patients versus aspirin plus clopidogrel (P<0.05). Patients with rt-PA exhibited better improvement in neurological function than those with aspirin plus clopidogrel, as shown by the lower NIHSS scores (P<0.05). Intravenous thrombolysis with rt-PA resulted in a better quality of life of patients than aspirin plus clopidogrel, indicated by the higher Barthel Index (BI) levels (P<0.05). The lower von Willebrand factor (vWF) and Factor VIII (F) levels indicated better coagulation function of patients with rt-PA versus those with aspirin plus clopidogrel (P<0.05). The lower serum concentrations of Lp-PLA2, HCY, and hsCRP suggested patients with rt-PA had milder inflammatory responses versus those without rt-PA (P<0.05). There was no significant difference in the incidence of adverse events in the two groups (P>0.05). Intravenous thrombolytic therapy with rt-PA better enhanced the prognosis of patients than with aspirin plus clopidogrel (P<0.05). CONCLUSION: Compared with conventional pharmacological regimens, additional rt-PA intravenous thrombolytic therapy improves the clinical outcome of patients with acute ischemic stroke, promotes neurological recovery, and enhances patient prognosis without increasing the risk of patient-related adverse events.

Xue-Jie-San prevents the early development of colitis-associated intestinal fibrosis by blocking Notch1 and FGL1 signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Xue-Jie-San (XJS), as a traditional Chinese herb prescription, has satisfactory effects on improving clinical symptoms and facilitating the healing of intestinal ulcers in patients with Crohn's disease (CD). This motivates the application of XJS on CD-associated complications. AIM OF THE STUDY: Intestinal fibrosis is a debilitating complication of CD. Currently, there is no effective medication available for preventing or reversing CD-related intestinal fibrosis. This study aimed to assess the efficacy and underlying mechanisms of XJS in the treatment of colitis-associated intestinal fibrosis. MATERIALS AND METHODS: A rat model of CD-related intestinal fibrosis was induced by 2,4,6-trinitrobenzene sulfonic acid administration and treated with XJS. The pathological changes of intestinal fibrosis were evaluated using Masson staining. Collagen deposition and epithelial-to-mesenchymal transition (EMT) were verified by immunohistochemical staining and Western blot analysis. Endothelial-to-mesenchymal transition (EndoMT) was assessed with immunofluorescence and immunohistochemical staining as well as Western blot analysis. Transmission electron microscopy was utilized to observe autophagosomes. The levels of autophagy-related proteins were detected via immunofluorescence staining and Western blot. Finally, the mTOR/ULK1 signaling pathway regulated by Notch1 or FGL1 was analyzed by Western blot. RESULTS: The results found that XJS ameliorated intestinal fibrosis through reducing the deposition of collagens such as Collagen 1 and Collagen 3. XJS inhibited the EMT process by increasing E-cadherin levels and decreasing the expressions of N-cadherin, Vimentin and Snail, which played a crucial role in collagen secretion and intestinal fibrosis. In addition, XJS also repressed the EndoMT process as reflected by the upregulation of CD31 and VE-cadherin levels and the downregulation of FSP1 and α-SMA expressions. Autophagy was activated following XJS treatment via suppression of the mTOR/ULK1 signaling pathway. Furthermore, XJS acted as an inhibitor of Notch1 and FGL1 signals, both of which regulated the mTOR signaling. CONCLUSIONS: Our findings validated that XJS prevented the early development of CD-related intestinal fibrosis by blocking the Notch1 and FGL1 signaling pathways to activate autophagy and thereby inhibit EMT and EndoMT.

Systematic mapping of the conformational landscape and dynamism of soluble fibrinogen.

BACKGROUND: Fibrinogen is a soluble, multisubunit, and multidomain dimeric protein, which, upon its proteolytic cleavage by thrombin, is converted to insoluble fibrin, initiating polymerization that substantially contributes to clot growth. Fibrinogen contains numerous, transiently accessible "cryptic" epitopes for hemostatic and immunologic proteins, suggesting that fibrinogen exhibits conformational flexibility, which may play functional roles in its temporal and spatial interactions. Hitherto, there have been limited integrative approaches characterizing the solution structure and internal flexibility of fibrinogen. METHODS: Here, utilizing a multipronged, biophysical approach involving 2 solution-based techniques, temperature-dependent hydrogen-deuterium exchange mass spectrometry and small angle X-ray scattering, corroborated by negative stain electron microscopy, we present a holistic, conformationally dynamic model of human fibrinogen in solution. RESULTS: Our data reveal 4 major and distinct conformations of fibrinogen accommodated by a high degree of internal protein flexibility along its central scaffold. We propose that the fibrinogen structure in the solution consists of a complex, conformational landscape with multiple local minima. This is further supported by the location of numerous point mutations that are linked to dysfibrinogenemia and posttranslational modifications, residing near the identified fibrinogen flexions. CONCLUSION: This work provides a molecular basis for the structural "dynamism" of fibrinogen that is expected to influence the broad swath of its functionally diverse macromolecular interactions and fine-tune the structural and mechanical properties of blood clots.

Exploring the Fibrin(ogen)olytic, Anticoagulant, and Antithrombotic Activities of Natural Cysteine Protease (Ficin) with the κ-Carrageenan-Induced Rat Tail Thrombosis Model.

Although fibrinolytic enzymes and thrombolytic agents help in cardiovascular disease treatment, those currently available have several side effects. This warrants the search for safer alternatives. Several natural cysteine protease preparations are used in traditional medicine to improve platelet aggregation and thrombosis-related diseases. Hence, this study aimed to investigate the effect of ficin, a natural cysteine protease, on fibrin(ogen) and blood coagulation. The optimal pH (pH 7) and temperature (37 °C) for proteolytic activity were determined using the azocasein method. Fibrinogen action and fibrinolytic activity were measured both electrophoretically and by the fibrin plate assay. The effect of ficin on blood coagulation was studied by conventional coagulation tests: prothrombin time (PT), activated partial thromboplastin time (aPTT), blood clot lysis assay, and the κ-carrageenan thrombosis model. The Aα, Bß, and γ bands of fibrinogen are readily cleaved by ficin, and we also observed a significant increase in PT and aPTT. Further, the mean length of the infarcted regions in the tails of Sprague-Dawley rats was shorter in rats administered 10 U/mL of ficin than in control rats. These findings suggest that natural cysteine protease, ficin contains novel fibrin and fibrinogenolytic enzymes and can be used for preventing and/or treating thrombosis-associated cardiovascular disorders.

Fibrin deposition associates with cartilage degeneration in arthritis.

BACKGROUND: Cartilage damage in inflammatory arthritis is attributed to inflammatory cytokines and pannus infiltration. Activation of the coagulation system is a well known feature of arthritis, especially in rheumatoid arthritis (RA). Here we describe mechanisms by which fibrin directly mediates cartilage degeneration. METHODS: Fibrin deposits were stained on cartilage and synovial tissue of RA and osteoarthritis (OA) patients and in murine adjuvant-induced arthritis (AIA) in wild-type or fibrinogen deficient mice. Fibrinogen expression and procoagulant activity in chondrocytes were evaluated using qRT-PCR analysis and turbidimetry. Chondro-synovial adhesion was studied in co-cultures of human RA cartilage and synoviocytes, and in the AIA model. Calcific deposits were stained in human RA and OA cartilage and in vitro in fibrinogen-stimulated chondrocytes. FINDINGS: Fibrin deposits on cartilage correlated with the severity of cartilage damage in human RA explants and in AIA in wild-type mice, whilst fibrinogen deficient mice were protected. Fibrin upregulated Adamts5 and Mmp13 in chondrocytes. Chondro-synovial adhesion only occurred in fibrin-rich cartilage areas and correlated with cartilage damage. In vitro, autologous human synoviocytes, cultured on RA cartilage explants, adhered exclusively to fibrin-rich areas. Fibrin co-localized with calcification in human RA cartilage and triggered chondrocyte mineralization by inducing pro-calcification genes (Anx5, Pit1, Pc1) and the IL-6 cytokine. Similar fibrin-mediated mechanisms were observed in OA models, but to a lesser extent and without pseudo-membranes formation. INTERPRETATION: In arthritis, fibrin plaques directly impair cartilage integrity via a triad of catabolism, adhesion, and calcification. FUNDING: None.

Laser Needle Knife's Effects on Rabbits Cervical Spondylopathy of Vertebral Artery, Fibrinogen, and Blood Viscosity.

Objective: To determine the effect of laser needle-knife on vertebroarterial morphology, fibrinogen and blood viscosity in a rabbit model of cervical spondylotic arteriopathy (CSA) and the mechanism of action involved. Methods: A number of 40 healthy common grade rabbits were divided into four groups: normal control, model, acupuncture, and laser needle knife group. The normal control group does not establish a CSA rabbit model, and the other groups all establish a CSA rabbit model, but they are treated in different ways. CSA model rabbits were treated with acupuncture and moxibustion at "fengchi" and "cervical Jiaji" points, rabbits in the laser needle knife group were treated with "Jiaji" points, and the acupuncture points were punctured with the laser needle knife. The location of the acupuncture points is determined according to the acupoint map of the experimental map. The right vertebroarterial morphology before and after the treatment was analyzed by scanning electron microscope, and FIB concentration and blood viscosity were determined using the coagulation method. Results: After the treatment, the capillary and micropore hyperplasia in the laser needle knife group were more evident than that in the model group. Acupuncture and laser needle knife therapy can reduce whole blood viscosity (1/s, 5/s), and that the distinction between the two treatments is not statistically evident. Conclusion: Acupuncture and laser needle knife can regulate the coagulation and fibrinolysis system in CSA, stimulate capillary and micropore hyperplasia, reduce blood viscosity, and improve blood circulation, which may be one of the therapeutic mechanisms behind the laser needle knife treatment of CSA.

Hypofibrinogenaemia and hypocalcaemia in adult trauma patients receiving pre-hospital packed red blood cell transfusions: Potential for supplementary pre-hospital therapeutic interventions.

OBJECTIVE: To report the arrival ionised calcium (iCa) and fibrinogen concentrations in trauma patients treated with packed red blood cells by the road-based high-acuity response units of a metropolitan ambulance service. METHODS: A retrospective review of trauma patients treated with packed red blood cells by high-acuity response units between January 2012 and December 2016. Patients were identified from databases at southeast Queensland adult trauma centres, Pathology Queensland Central Transfusion Laboratory, Gold Coast University Hospital blood bank and the Queensland Ambulance Service. Patient characteristics, results of laboratory tests within 30 min of ED arrival were analysed. RESULTS: A total of 164 cases were analysed. The median injury severity score was 33.5 (interquartile range 22-41), with blunt trauma the commonest mechanism of injury (n = 128, 78.0%). Fifty-eight of the 117 patients (24.4%) with fibrinogen measured had a fibrinogen concentration ≤1.5 g/L; 79 of the 123 patients (64.2%) with an international normalised ratio (INR) measurement had an INR >1.2; 97 of 148 patients (63.8%) with an iCa measured, had an iCa below the Pathology Queensland reference range of 1.15-1.32 mmol/L. Arrival fibrinogen concentration ≤1.5 g/L and arrival iCa ≤1.00 were associated with in-hospital mortality with odds ratio 11.90 (95% confidence interval 4.50-31.65) and odds ratio 4.97 (95% confidence interval 1.42-17.47), respectively. CONCLUSIONS: Hypocalcaemia and hypofibrinogenaemia on ED arrival were common in this cohort. Future work should evaluate whether outcomes improve by correction of these deficits during the pre-hospital phase of trauma care.

The Effectiveness of 3 Combined Therapeutic Regimens in Egyptian Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease: A Randomized Double-Blind Prospective Pilot Study.

BACKGROUND: There are differences of opinion about both the most effective combined therapeutic strategy and the clinical benefit of inhaled corticosteroids in nonasthmatic patients with chronic obstructive pulmonary disease. Furthermore, many inflammatory cytokines are reportedly correlated with severity of the disease. OBJECTIVES: To compare the effectiveness of long acting ß-agonist + long-acting muscarinic antagonist (LABA + LAMA) versus LABA + inhaled corticosteroid and LAMA + inhaled corticosteroid in nonasthmatic patients with moderate-to-severe chronic obstructive pulmonary disease. To assess the changes that occurred in plasma concentrations of tumor necrosis factor α, fibrinogen, and interleukin 6, and correlate these with disease activity. METHODS: In this pilot study, 45 nonasthmatic patients with moderate to severe chronic obstructive pulmonary disease were randomized into 3 groups with 15 patients in each group. Group I (LABA + inhaled corticosteroid) received formoterol/budesonide, group II (LAMA + inhaled corticosteroid) received tiotropium/budesonide and group III (LABA + LAMA) received formoterol/tiotropium for 12 weeks. Patients were assessed initially and then at 4 and 12 weeks by measuring the changes that occurred in forced expiratory volume in 1 second as a percent of predicted and in the modified Medical Research Council dyspnea scale. Plasma concentrations of tumor necrosis factor α, fibrinogen, and interleukin 6 were simultaneously measured. RESULTS: The 3 study groups were statistically similar with respect to their demographic data and disease characteristics. All therapeutic options produced an improvement in forced expiratory volume in 1 second as a percent of predicted and in the modified Medical Research Council dyspnea scale as well as a reduction in plasma concentrations of the inflammatory markers. The effects produced by the three therapeutic combinations on forced expiratory volume in 1 second as a percent of predicted, plasma tumor necrosis factor α, interleukin 6, and fibrinogen concentrations were statistically similar after 4 and 12 weeks (4 weeks after treatment: P = 0.358, P = 0.284, P = 0.155, and P = 0.155, respectively, and 12 weeks after treatment: P = 0.710, P = 0.773, P = 0.240, and P = 0.076, respectively). CONCLUSIONS: In nonasthmatic patients with moderate to severe chronic obstructive pulmonary disease, the 3 therapeutic combinations showed similar effectiveness. The results of this pilot study also suggest that inflammatory markers can be used to track disease activity. Clinicaltrials.gov identifier: NCT04520230. (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX).

The Effects of Prunus spinosa L. Flower Extracts, Model Polyphenols and Phenolic Metabolites on Oxidative/Nitrative Modifications of Human Plasma Components with Particular Emphasis on Fibrinogen In Vitro.

Oxidative post-translational modifications of fibrinogen (a multifunctional blood plasma protein essential for hemostasis) are associated with the pathogenesis of cardiovascular disorders (CVDs). Prunus spinosa flower is a herbal medicine used in an adjuvant treatment of CVDs and rich in polyphenolic antioxidants. In the present study, phytochemically standardized P. spinosa flower extracts, their primary native polyphenols and potential phenolic metabolites were evaluated in vitro for their protective effects on fibrinogen (isolated and in the human plasma matrix) using a panel of complementary methods (SDS-PAGE, western blot, C-ELISA, fluorometry, FRAP, TBARS). The results revealed that the tested analytes at in vivo relevant levels (1-5 µg/mL) considerably reduced the structural changes in the fibrinogen molecule under the oxidative stress conditions induced by peroxynitrite. In particular, they diminished the oxidation and/or nitration of amino acid residues, including tyrosine and tryptophan, as well as the formation of high molecular weight aggregates. The decrease in the levels of 3-nitrotyrosine was about 13.5-33.0% and 58.3-97.1% at 1 µg/mL and 50 µg/mL, respectively. The study indicated that low molecular weight polyphenols were crucial for the protective activity of the extracts toward fibrinogen and other human plasma components. The investigated model compounds effectively protected total plasma proteins and lipids against oxidative damage (by reducing the levels of 3-nitrotyrosine and thiobarbituric acid-reactive substances and normalizing/enhancing the non-enzymatic antioxidant capacity of plasma). The work provides insight into the role of native and metabolized polyphenols as contributory factors to the systemic activity of blackthorn flower extracts within the circulatory system.

Pathogen reduction of whole blood: Supplementing fibrinogen partly corrects clot formation in a massive transfusion model.

BACKGROUND: The use of whole blood (WB) to treat trauma patients is becoming more common. Similar to the treatment of individual components, pathogen inactivation (PI) technologies are available to treat WB. The impact of PI on WB function is not well understood. This study investigated the impact of PI of WB with riboflavin/ultraviolet (UV) light on its hemostatic function by modeling transfusion scenarios for trauma patients and assessing transfusion efficacy by rotational thromboelastometry (ROTEM). As fibrinogen is affected by PI of WB, the effect of fibrinogen supplementation commonly used in trauma patients was also analyzed in this model. STUDY DESIGN AND METHODS: Trauma transfusion scenarios were simulated by mixing untreated WB or WB treated with the Mirasol PI technology (riboflavin/UV) in different ratios with hemodiluted blood, and the thromboelasticity was monitored by ROTEM. The impact of supplementation with the fibrinogen concentrate RiaSTAP was investigated in this model. RESULTS: Pathogen-inactivated WB (PI-WB) showed decreased activity in the hemostatic profile compared to the untreated control. Hemodiluted blood at a hematocrit (hct) of 20%, which was reconstituted with PI-WB or untreated WB, exhibited increased alpha values, maximum clot firmness, and clot formation time. Simulating transfusion scenarios by blood replacement with PI-WB resulted in a significant difference in ROTEM parameters between reconstituted PI-treated and -untreated WB (p ≥ .05). The effect of PI treatment waned when PI-WB was enriched with fibrinogen. CONCLUSION: ROTEM investigations suggest that PI treatment has a negative impact on WB clot formation unless fibrinogen supplementation is used.

Application of platelet GPⅡb/Ⅲa receptor inhibitor (A adjuvant) in the detection of platelet aggregation function / 中国输血杂志

【Objective】 To evaluate the effect of adding platelet GPⅡb/Ⅲa receptor inhibitor (A adjuvant) into the Batroxobin cup (A cup) on the accuracy of the thromboelastogram (TEG) platelet aggregation function test using the functional fibrinogen (function fiber cup) test results as a standard. 【Methods】 From December 2019 to May 2020, 100 (persons) whole blood samples were collected from patients who visited the Department of Neurology, Department of Cardiology, Department of General Affairs and Department of Rehabilitation of our hospital for TEG platelet aggregation function test, and the blood standard samples were divided into MA <25 mm group (n=50) and MA≥25 mm group (n=50) according to the A-cup blood clot intensity (MA) value (mm) measured by TEG, the two groups were subdivided into A cup group (n=50, respectively), A auxiliary group (adding A auxiliary in A cup) (n=50, respectively), and functional fiber cup group (n=50, respectively), each subgroup was tested once again. The linear correlation, platelet inhibition and the consistency of drug efficacy interpretation results in platelet Adenosine diphosphate (ADP) and Arachidonic acid (AA) pathway respectively between the three subgroups were compared. 【Results】 (1) In the MA<25mm group, the inhibition rates of ADP and AA pathway in platelet of A cup, A adjuvant and functional fibrin cup subgroups were (32.00±17.44) % vs (30.19±17.44) % vs (30.07±16.18) %, (24.3±33.53) % vs (22.53±30.9) % vs (22.37±31.2) %, respectively (R2 were all>0.975); (2) In the MA≥25 mm group, the inhibition rates of ADP and AA pathway in platelet of A cup, A adjuvant and functional fibrin cup subgroups were (34.34±33.59) % vs (18.45±24.42) % vs (18.01±24.33) %, (23.19±39.33) % vs (8.48±21.75) % vs (8.31±21.7) % ( R2 between the A cup group and the A adjuvant group were all<0.8, and R2 between the A adjuvant group and the functional fibrinogen cup group were all >0.975); (3)Take the test result of the functional fibrinogen cup as the standard, the correct rates of ADP and AA pathway drug efficacy interpretation were 82% (41/50) vs 100% (50/50) and 84% (42/50) vs 100% (50/50) respectively (P<0.05) between the A-cup group and the A adjuvant group, while the interpretation results of drug efficacy of the two pathway were consistent between the A adjuvant group and the functional fibrin cup group (P>0.05). 【Conclusion】 Adding A adjuvant to TEG platelet aggregation function test can effectively inhibit non-specifically activated platelets in the A cup in the detection of platelet aggregation function, truly reflect the function of fibrinogen and improve the accuracy of platelet inhibition rate.

Inverse association between bone mineral density and fibrinogen in menopausal women.

OBJECTIVE: Inflammatory diseases are risk factors for osteoporosis. We aimed to explore whether fibrinogen, which is linked to chronic inflammation, is associated with bone mineral density (BMD) in menopausal women. METHODS: In this cross-sectional study, we analyzed 339 menopausal women from Zhejiang Province between January 2016 and October 2019. Linear regression analysis was performed to assess the relationship between fibrinogen and BMD. RESULTS: Significant inverse association was observed between the serum fibrinogen level and BMD in menopausal women. The mean BMD in each quartile of fibrinogen level was 0.901, 0.897, 0.892, and 0.855 g/cm2, respectively (p = 0.027). After adjusting for age, body mass index, metabolic profiles, blood inflammatory factors, and serum levels of estradiol, calcium, phosphorus, and alkaline phosphatase, fibrinogen levels remained significantly associated with BMD (regression coefficients for quartiles 1-3 vs. quartile 4 were 0.046, 0.027, and 0.036, respectively; p for trend <0.05). CONCLUSIONS: Higher fibrinogen levels were associated with lower BMD in menopausal women, which was independent of age, body mass index, estradiol, and other factors. Therefore, serum fibrinogen can be used as a new predictor of reduced BMD in menopausal women.

Efficacy of Naoxintong capsule combined with butylphthalide injection on acute cerebral infarction and its effects on inflammatory factors, oxidative stress response and hemorheology / 中国基层医药

Objective:To investigate the effect of Naoxintong capsule combined with butylphthalide injection on inflammatory factors, oxidative stress response and hemorheology in patients with acute cerebral infarction. Methods:Eighty-six patients with acute cerebral infarction who received treatment in Zhuji Hospital of Traditional Chinese Medicine from December 2017 to December 2019 were included in this study. Thrombolysis and thrombectomy were contraindicated in these patients. They were randomly assigned to receive treatment either with butylphthalide injection (control group, n = 43) or butylphthalide injection and Naoxintong capsule (observation group, n = 43) for 2 weeks. Therapeutic effects, Barthel Index, inflammatory factors (C-reactive protein, intercellular adhesion molecule-1 and interleukin-6), oxidative stress response (malondialdehyde and superoxide dismutase) and hemorheology (whole blood viscosity at high and low shear rates, plasma viscosity and fibrinogen) were compared between the two groups. Results:Total effective rate in the observation group was significantly higher than that in the control group (93.02% vs. 72.09%, χ2 = 6.541, P < 0.05). After treatment, Barthel Index in the observation group was significantly higher than that in the control group [(61.51 ± 5.24) points vs. (50.43 ± 4.81) points, t = 10.215, P < 0.05). After treatment, serum levels of C-reactive protein, intercellular adhesion molecule-1, and interleukin-6 in the observation group were (4.42 ± 1.03) mg/L, (84.23 ± 5.05) μg/L and (94.33 ± 10.22) μg/L, respectively, which were significantly lower than those in the control group [(8.32 ± 1.71) mg/L, (103.51 ± 6.35) μg/L, (118.92 ± 13.31) μg/L, t = 12.810, 15.583, 9.609, all P < 0.05]. After treatment, serum malondialdehyde level in the observation group was significantly lower than that in the control group [(3.76 ± 0.78) μmol/L vs. (4.94 ± 0.90) μmol/L, t = 6.497, P < 0.05]. Serum superoxide dismutase level in the observation group was significantly higher than that in the control group [(35.76 ± 2.65) U/L vs. (30.34 ± 2.11) U/L, t = 10.492, P < 0.05]. After treatment, whole blood viscosity at high and low shear rates, plasma viscosity and fibrinogen levels in the observation group were (4.10 ± 0.51) mPa · s, (9.31 ± 1.36) mPa · s, (1.24 ± 0.26) mPa · s and (2.71 ± 0.40) g/L respectively, which were significantly lower than those in the control group [(5.72 ± 0.76) mPa · s, (11.49 ± 1.59) mPa · s, (2.21 ± 0.32) mPa · s and (3.92 ± 0.54) g/L, t = 11.607, 6.832, 15.427 11.807, all P < 0.05). Conclusion:Naoxintong capsule combined with butylphthalide injection is highly effective in the treatment of acute cerebral infarction. It can reduce inflammatory reaction and improve oxidative stress response and hemorheological changes.

Assessment of haemostasis and impact of fibrinogen supplementation on clot properties using global haemostasis assays in patients on chronic dialysis.

BACKGORUND: Multifactorial haemostasis disorders are typical of patients with end-stage renal disease (ESRD) on chronic haemodialysis (HD). Thromboelastometry and impedance aggregometry allow for a comprehensive assessment of clot formation, lysis, and platelet (PLT) function. This study aims to determine the haemostatic profile in a group of patients with ESRD on chronic, interrupted dialysis, especially in terms of PLT function and the impact of in vitro fibrinogen concentrate supplementation on clot properties. METHODS: A total of 22 patients on chronic HD and 22 healthy controls (HC) were enrolled in the prospective study with a control group. Global haemostasis assays (GHA) were used to describe the haemostasis profile and to assess the effect of fibrinogen concentrate supplementation on improving clot quality. RESULTS: Despite the lack of considerable differences in the number of PLTs, there was a significantly lower potential of PLT aggregation in the HD group (922 ±163 AU*min). A higher concentration of fibrinogen was also observed in this group which presented considerably higher maximum clot firmness (MCF) FIBTEM (22 ±5.3 mm). Clotting time (CT) EXTEM was also prolonged (72 ±23 s). No hyperfibrinolysis was reported. In vitro fibrinogen concentrate supplementation resulted in significant improvement in MCF FIBTEM (30 mm vs. 22 mm; P < 0.001). However, it also led to a deterioration in PLT aggregation as assessed by TRAPtest. CONCLUSIONS: The haemostasis profile of ESRD patients demonstrates a limited potential of PLT aggregation, with no improvement after fibrinogen addition.

Magnesium Sulfate Improves Some Risk Factors for Atherosclerosis in Patients Suffering from One or Two Coronary Artery Diseases: A Double-blind Clinical Trial Study.

PURPOSE: Given the beneficial effect of MgSO4 on the cardiovascular system, this study was designed to investigate the effect of MgSO4 administration on suppressing some atherosclerotic risk factors in moderate coronary artery disease patients with one or two atherosclerotic vessels. PATIENTS AND METHODS: In a randomized double-blind placebo-controlled clinical trial study, 64 patients with moderate coronary artery disease (55-69% stenosis) were selected according to angiography findings. Patients were divided into four groups including patients with one or two atherosclerotic vessels treated with MgSO4 (Mg-treated-VR1, Mg-treated-VR2, respectively), placebo treated patients with one or two atherosclerotic vessels (Control-VR1, Control-VR2, respectively). The patients received either placebo or MgSO4 supplement capsule containing 300 mg MgSO4 for six months on a daily basis. ESR, Ca/Mg ratio, urine Mg level, serum Mg, fibrinogen, homocysteine, uric acid, Na, K, Ca, CRP, T3, T4, TSH, BUN, and Cr concentrations were measured at baseline and every three months. RESULTS: Serum T3, Ca, K, homocysteine, CRP, and Mg concentrations were significantly improved in Mg-treated groups compared to placebo groups. CONCLUSION: The results of this study showed that despite the slight change in serum magnesium level, oral administration of MgSO4for six months could slightly reduce the serum levels of some inflammatory and vascular factors in moderate coronary artery disease patients.

Oral exposure of pigs to the mycotoxin deoxynivalenol does not modulate the hepatic albumin synthesis during a LPS-induced acute-phase reaction.

The sensitivity of pigs to deoxynivalenol (DON) might be influenced by systemic inflammation (SI) which impacts liver. Besides following acute-phase proteins, our aim was to investigate both the hepatic fractional albumin (ALB) synthesis rate (FSR) and the ALB concentration as indicators of ALB metabolism in presence and absence of SI induced by LPS via pre- or post-hepatic venous route. Each infusion group was pre-conditioned either with a control diet (CON, 0.12 mg DON/kg diet) or with a DON-contaminated diet (DON, 4.59 mg DON/kg diet) for 4 wk. A depression of ALB FSR was observed 195 min after LPS challenge, independent of feeding group or LPS application route, which was not paralleled by a down-regulated ALB mRNA expression but by a reduced availability of free cysteine. The drop in ALB FSR only partly explained the plasma ALB concentrations which were more depressed in the DON-pre-exposed groups, suggesting that ALB levels are influenced by further mechanisms. The abundances of haptoglobin, C-reactive protein, serum amyloid A, pig major acute-phase protein, fibrinogen and LPS-binding protein mRNA were up-regulated upon LPS stimulation but not accompanied by increases in the plasma concentrations of these proteins, pointing at an imbalance between synthesis and consumption.

Thirty years of translational research in Mobility Medicine: Collection of abstracts of the 2020 Padua Muscle Days.

More than half a century of skeletal muscle research is continuing at Padua University (Italy) under the auspices of the Interdepartmental Research Centre of Myology (CIR-Myo), the European Journal of Translational Myology (EJTM) and recently also with the support of the A&CM-C Foundation for Translational Myology, Padova, Italy. The Volume 30(1), 2020 of the EJTM opens with the collection of abstracts for the conference "2020 Padua Muscle Days: Mobility Medicine 30 years of Translational Research". This is an international conference that will be held between March 18-21, 2020 in Euganei Hills and Padova in Italy. The abstracts are excellent examples of translational research and of the multidimensional approaches that are needed to classify and manage (in both the acute and chronic phases) diseases of Mobility that span from neurologic, metabolic and traumatic syndromes to the biological process of aging. One of the typical aim of Physical Medicine and Rehabilitation is indeed to reduce pain and increase mobility enough to enable impaired persons to walk freely, garden, and drive again. The excellent contents of this Collection of Abstracts reflect the high scientific caliber of researchers and clinicians who are eager to present their results at the PaduaMuscleDays. A series of EJTM Communications will also add to this preliminary evidence.

The Effect of Electroacupuncture on Plasma Fibrinogen Levels in Restraint Stress Wistar Rats.

Objective: Blood is a suspended cellular element that dissolves in plasma. Blood transports oxygen and nutrients to all body cells and carries metabolic waste from the whole body. The nature of blood flowing through vessels is a factor that plays an important role in oxygen delivery and tissue perfusion. In acute stress conditions, various reactions can occur and affect the blood flow in blood vessels. Electroacupuncture (EA) is an additional therapy with minimal side-effects that can improve the quality of blood flow. This study investigated the effect of EA bilaterally at ST 36 (Zusanli) on plasma fibrinogen. Materials and Methods: Eighteen male Wistar rats were divided randomly into 3 groups: (1) a control group (n = 6); (2) a restraint-stress group (n = 6); and (3) a restraint-stress-and-EA group (n = 6). EA was performed in group 3 after the rats were subjected to 3 hours of restraint stress. Results: There were significant mean differences in plasma fibrinogen levels (P = 0.048; 95% confidence interval: 0.5-109.5) between the restraint stress groups and the control group. Conclusion: This study showed that the EA on ST 36 lowered levels of plasma fibrinogen of Wistar rats in restraint stress model.