-
Bioprocess and Biosystems Engineering Jul 2024Menaquinone-7 (MK-7), a vital vitamin with numerous health benefits, is synthesized and secreted extracellularly by the formation of biofilm, dominantly in Bacillus...
Menaquinone-7 (MK-7), a vital vitamin with numerous health benefits, is synthesized and secreted extracellularly by the formation of biofilm, dominantly in Bacillus strains. Our team developed an innovative biofilm reactor utilizing Bacillus subtilis natto cells to foster biofilm growth on plastic composite supports to produce MK-7. Continuous fermentation in biofilm reactors offers a promising strategy for achieving sustainable and efficient production of Menaquinone-7 (MK-7). Unlike conventional batch fermentation, continuous biofilm reactors maintain a steady state of operation, which reduces resource consumption and waste generation, contributing to sustainability. By optimizing fermentation conditions, MK-7 production was significantly enhanced in this study, demonstrating the potential for sustainable industrial-scale production. To determine the optimal operational parameters, various dilution rates were tested. These rates were selected based on their potential to enhance nutrient supply and biofilm stability, thereby improving MK-7 production. By carefully considering the fermentation conditions and systematically varying the dilution rates, MK-7 production was significantly enhanced during continuous fermentation. The MK-7 productivity was found to increase from 0.12 mg/L/h to 0.33 mg/L/h with a dilution rate increment from 0.007 to 0.042 h). This range was chosen to explore the impact of various nutrient supply rates on MK-7 production and to identify the optimal conditions for maximizing productivity. However, a further increase in the dilution rate to 0.084 h led to reduced productivity at approximately 0.16 mg/L/h, likely due to insufficient retention time for effective biofilm formation. Consequently, a dilution rate of 0.042 h exhibited the highest productivity of 0.33 mg/L/h, outperforming all investigated dilution rates and demonstrating the critical balance between nutrient supply and retention time in continuous fermentation. These findings validate the feasibility of operating continuous fermentation at a 0.084 h dilution rate, corresponding to a 48 h retention time, to achieve the highest MK-7 productivity compared to conventional batch fermentation. The significant advancements achieved in enhancing Menaquinone-7 (MK-7) productivity through continuous fermentation at optimal dilution rates in the present work indicate promising prospects for even greater efficiency and sustainability in MK-7 production through future developments.
Topics: Biofilms; Vitamin K 2; Bioreactors; Bacillus subtilis; Fermentation
PubMed: 38864863
DOI: 10.1007/s00449-024-03040-1 -
Cytokine Aug 2024Host proteins released by the activated endothelial cells during SARS-CoV-2 infection are implicated to be involved in coagulation and endothelial dysfunction. However,...
Host proteins released by the activated endothelial cells during SARS-CoV-2 infection are implicated to be involved in coagulation and endothelial dysfunction. However, the underlying mechanism that governs the vascular dysfunction and disease severity in COVID-19 remains obscure. The study evaluated the serum levels of Bradykinin, Kallikrein, SERPIN A, and IL-18 in COVID-19 (N-42 with 20 moderate and 22 severe) patients compared to healthy controls (HC: N-10) using ELISA at the day of admission (DOA) and day 7 post-admission. The efficacy of the protein levels in predicting disease severity was further determined using machine learning models. The levels of bradykinins and SERPIN A were higher (P ≤ 0.001) in both severe and moderate cases on day 7 post-admission compared to DOA. All the soluble proteins studied were found to elevated (P ≤ 0.01) in severe compared to moderate in day 7 and were positively correlated (P ≤ 0.001) with D-dimer, a marker for coagulation. ROC analysis identified that SERPIN A, IL-18, and bradykinin could predict the clinical condition of COVID-19 with AUC values of 1, 0.979, and 1, respectively. Among the models trained using univariate model analysis, SERPIN A emerged as a strong prognostic biomarker for COVID-19 disease severity. The serum levels of SERPIN A in conjunction with the coagulation marker D-dimer, serve as a predictive indicator for COVID-19 clinical outcomes. However, studies are required to ascertain the role of these markers in disease virulence.
Topics: Humans; COVID-19; Biomarkers; Female; Male; Middle Aged; Prognosis; Interleukin-18; SARS-CoV-2; Bradykinin; Adult; Aged; Fibrin Fibrinogen Degradation Products; Severity of Illness Index; Endothelium, Vascular; Kallikreins; alpha 1-Antitrypsin
PubMed: 38857562
DOI: 10.1016/j.cyto.2024.156673 -
Life Sciences Aug 2024Long-term oral anticoagulation is the primary therapy for preventing ischemic stroke in patients with atrial fibrillation (AF). Different types of oral anticoagulant...
AIMS
Long-term oral anticoagulation is the primary therapy for preventing ischemic stroke in patients with atrial fibrillation (AF). Different types of oral anticoagulant drugs can have specific effects on the metabolism of patients. Here we characterize, for the first time, the serum metabolomic and lipoproteomic profiles of AF patients treated with anticoagulants: vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs).
MATERIALS AND METHODS
Serum samples of 167 AF patients (median age 78 years, 62 % males, 70 % on DOACs treatment) were analyzed via high resolution H nuclear magnetic resonance (NMR) spectroscopy. Data on 25 metabolites and 112 lipoprotein-related fractions were quantified and analyzed with multivariate and univariate statistical approaches.
KEY FINDINGS
Our data provide evidence that patients treated with VKAs and DOACs present significant differences in their profiles: lower levels of alanine and lactate (odds ratio: 1.72 and 1.84), free cholesterol VLDL-4 subfraction (OR: 1.75), triglycerides LDL-1 subfraction (OR: 1.80) and 4 IDL cholesterol fractions (ORs ∼ 1.80), as well as higher levels of HDL cholesterol (OR: 0.48), apolipoprotein A1 (OR: 0.42) and 7 HDL cholesterol fractions/subfractions (ORs: 0.40-0.51) are characteristic of serum profile of patients on DOACs' therapy.
SIGNIFICANCE
Our results support the usefulness of NMR-based metabolomics for the description of the effects of oral anticoagulants on AF patient circulating metabolites and lipoproteins. The higher serum levels of HDL cholesterol observed in patients on DOACs could contribute to explaining their reduced cardiovascular risk, suggesting the need of further studies in this direction to fully understand possible clinical implications.
Topics: Humans; Atrial Fibrillation; Male; Female; Aged; Vitamin K; Anticoagulants; Administration, Oral; Aged, 80 and over; Metabolomics; Metabolome; Middle Aged; Magnetic Resonance Spectroscopy
PubMed: 38852797
DOI: 10.1016/j.lfs.2024.122796 -
Journal of Stroke and Cerebrovascular... Dec 2023Early fibrinolysis disorder exists in aneurysmal subarachnoid hemorrhage (aSAH). We aimed to investigate the association of markers of early fibrinolysis disorder with...
Elevated markers of early fibrinolysis disorder as predictors of poor 90-day prognosis in patients with aneurysmal subarachnoid hemorrhage: A large prospective cohort study.
OBJECTIVES
Early fibrinolysis disorder exists in aneurysmal subarachnoid hemorrhage (aSAH). We aimed to investigate the association of markers of early fibrinolysis disorder with poor 90-day prognosis in patients with aSAH.
MATERIALS AND METHODS
A total of 693 consecutive aSAH patients from April 2020 to December 2022 were selected from the Long-term Prognosis of Emergency Aneurysmal Subarachnoid Hemorrhage (LongTEAM) trial. Poor 90-day prognosis was defined as a modified Rankin Scale 3-6 at 90 days after discharge. D-dimer (DD) and Fibrin degradation product (FDP) levels on admission were used to assess fibrinolysis disorder and patients were classified according to their quartiles. Multivariable logistic regression analysis was used to determine the association.
RESULTS
Of 693 patients included, 131 (18.9%) had poor 90-day prognosis. Patients in the highest quartile of DD and FDP levels had higher risk of poor 90-day prognosis than those in the first quartile (DD: adjusted odds ratio [aOR]=2.22, 95% confidence interval [CI], 1.13-4.36, p = 0.021; FDP: aOR=2.87, 95% CI, 1.48-5.58, p = 0.002), after adjusting for potential risk factors. Meanwhile, a linear dose-response relationship between DD and FDP and poor 90-day prognosis was found. Subgroup analysis showed that DD and FDP were consistently associated with poor 90-day prognosis across subgroups, and no intergroup interaction was found. Interestingly, the associations of DD and FDP with poor 90-day prognosis were more significant in low-grade aSAH patients.
CONCLUSIONS
Elevated markers of early fibrinolysis disorder, including DD and FDP on admission, were associated with poor 90-day prognosis in aSAH patients.
Topics: Humans; Subarachnoid Hemorrhage; Male; Female; Middle Aged; Biomarkers; Prognosis; Fibrin Fibrinogen Degradation Products; Prospective Studies; Time Factors; Fibrinolysis; Risk Factors; Aged; Predictive Value of Tests; Risk Assessment; Adult; Up-Regulation; Disability Evaluation
PubMed: 38847809
DOI: 10.1016/j.jstrokecerebrovasdis.2023.107433 -
The Journal of Dermatological Treatment Dec 2024This study aimed to evaluate the efficacy of tranexamic acid (TXA) in treating melasma through a meta-analysis and systematic review of randomized controlled trials... (Meta-Analysis)
Meta-Analysis Review
This study aimed to evaluate the efficacy of tranexamic acid (TXA) in treating melasma through a meta-analysis and systematic review of randomized controlled trials (RCTs). The study focused on identifying associated adverse effects and comparing TXA's effectiveness with other melasma treatments. Following PROSPERO and PRISMA guidelines, an extensive electronic search was conducted across four databases for RCTs on TXA use in melasma. Inclusion criteria encompassed full-text English articles with specific outcome measures, while studies with high bias risk or non-English publications were excluded. Data were extracted from 22 relevant studies and analyzed using the RevMan software, with heterogeneity identified using I² statistics and forest plots. A total of 22 studies with 1280 patients were included. TXA was administered orally, topically, or via injection, with treatment durations ranging from 8 weeks to nearly 2 years. TXA significantly reduced melasma severity, evidenced by reductions in MASI, mMASI, MI, and hemi-MASI scores. Oral TXA showed the most substantial decrease in MASI scores, followed by injections and topical applications. However, studies exhibited high heterogeneity, particularly in combined treatments. Adverse effects included gastrointestinal discomfort, skin irritation, and menstrual irregularities. TXA is effective in treating melasma, either alone or combined with other treatments. Despite significant reductions in melasma severity, further research is necessary to standardize TXA administration methods and address long-term effects. The high heterogeneity observed suggests a need for more consistent treatment protocols.
Topics: Melanosis; Humans; Tranexamic Acid; Randomized Controlled Trials as Topic; Treatment Outcome; Administration, Oral; Antifibrinolytic Agents; Severity of Illness Index; Administration, Cutaneous
PubMed: 38843906
DOI: 10.1080/09546634.2024.2361106 -
Scientific Reports Jun 2024This study aims to observe the hemostatic and anti-inflammatory effects of intravenous administration of tranexamic acid (TXA) in dual segment posterior lumbar interbody...
This study aims to observe the hemostatic and anti-inflammatory effects of intravenous administration of tranexamic acid (TXA) in dual segment posterior lumbar interbody fusion (PLIF). The data of 53 patients with lumbar disease treated with double-segment PLIF were included in this study. The observation group was received a single-dose intravenous of TXA (1 g/100 mL) 15 min before skin incision after general anesthesia. The control group was not received TXA. The observation indicators included postoperative activated partial prothrombin time (APTT), thrombin time (PT), thrombin time (TT), fibrinogen (FIB), platelets (PLT), and postoperative deep vein thrombosis in the lower limbs, surgical time, intraoperative bleeding volume, postoperative drainage volume, transfusion rate, postoperative hospital stay, red blood cell (RBC), hemoglobin (HB), hematocrit (HCT), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) on the 1st, 4th, 7th, and last tested day after surgery. All patients successfully completed the operation, and there was no deep vein thrombosis after operation. There was no statistically significant difference in postoperative APTT, PT, TT, FIB, PLT, surgical time, and postoperative hospital stay between the two groups (p > 0.05). The intraoperative bleeding volume, postoperative drainage volume, and transfusion rate in the observation group were lower than those in the control group, and the differences were statistically significant (p < 0.05). There was no statistically significant difference in RBC, HB, HCT, CRP, and ESR between the two groups on the 1st, 4th, 7th, and last tested day after surgery (p > 0.05). Intravenous administration of TXA in dual segment PLIF does not affect coagulation function and can reduce bleeding volume, postoperative drainage volume, and transfusion rate. Moreover, it does not affect the postoperative inflammatory response.
Topics: Humans; Tranexamic Acid; Female; Male; Middle Aged; Spinal Fusion; Case-Control Studies; Aged; Lumbar Vertebrae; Administration, Intravenous; Anti-Inflammatory Agents; Hemostatics; Adult; Blood Loss, Surgical; Antifibrinolytic Agents
PubMed: 38834591
DOI: 10.1038/s41598-024-62823-4 -
International Journal of Systematic and... Jun 2024During a study on the diversity of culturable actinobacteria from coastal halophytes in Thailand, strain LSe6-5 was isolated from leaves of sea purslane ( L.), and a...
During a study on the diversity of culturable actinobacteria from coastal halophytes in Thailand, strain LSe6-5 was isolated from leaves of sea purslane ( L.), and a polyphasic approach was employed to determine its taxonomic position. The 16S rRNA gene sequences analysis indicated that the strain was most closely related to Tu 6233 (99.2 %), YIM M13156 (99.1 %), and PB261 (98.7 %). The genome of strain LSe6-5 was estimated to be 4.33 Mbp in size, with DNA G+C contents of 74.3%. A phylogenomic tree based on whole-genome sequences revealed that strain LSe6-5 formed a clade with DSM 45722, indicating their close relationship. However, the average nucleotide identity (ANI)-blast, ANI-MUMmer, and dDDH values between strain LSe6-5 with DSM 45722 (87.1, 88.9, and 33.0 %) were below the thresholds of 95-96 % ANI and 70 % dDDH for identifying a novel species. Furthermore, strain LSe6-5 showed morphological and chemotaxonomic characteristics of the genus . Cells were motile, rod-shaped, and Gram-stain-positive. Optimal growth of strain LSe6-5 occurred at 28 °C, pH 7.0, and 0-3 % NaCl. The whole-cell hydrolysates contained -diaminopimelic acid as the diagnostic diamino acid, with galactose, glucose, mannose, and ribose as whole-cell sugars. The predominant menaquinones were MK-9(H) and MK-9(H). The polar lipid profile was composed of diphosphatidylglycerol, hydroxyphosphatidylethanolamine, phosphatidylinositol, glycophosphatidylinositol, an unidentified phospholipid, and an unidentified lipid. Major cellular fatty acids were -C, -C, and -C. From the distinct phylogenetic position and combination of genotypic and phenotypic characteristics, it is supported that strain LSe6-5 represents a novel species of the genus , for which the name sp. nov. is proposed. The type strain is strain LSe6-5 (=TBRC 16417= NBRC 115929).
Topics: Phylogeny; Base Composition; RNA, Ribosomal, 16S; Fatty Acids; Plant Leaves; Thailand; Salt-Tolerant Plants; DNA, Bacterial; Bacterial Typing Techniques; Sequence Analysis, DNA; Vitamin K 2; Phospholipids; Whole Genome Sequencing; Genome, Bacterial
PubMed: 38832855
DOI: 10.1099/ijsem.0.006410 -
Clinical and Applied... 2024The purpose of the study was to investigate baseline inflammatory, hemostatic indicators and new-onset deep vein thrombosis (DVT) with the risk of mortality in COVID-19...
The purpose of the study was to investigate baseline inflammatory, hemostatic indicators and new-onset deep vein thrombosis (DVT) with the risk of mortality in COVID-19 inpatients. In this single-center study, a total of 401 COVID-19 patients hospitalized in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine were enrolled from December 1, 2022 to January 31, 2023. The basic information, first laboratory examination results, imaging examination, and outcome-related indicators were compared between patients in the moderate and severe subgroups. We found that baseline D-dimer and baseline absolute neutrophil count (ANC) levels were associated with new-onset DVT and death in severe hospitalized patients with COVID-19. The odds ratio (OR) of baseline D-dimer and baseline ANC with mortality was 1.18 (95% confidence interval [CI], 1.08-1.28; < .001) and 1.13 (95% CI, 1.06-1.21; < .001). Baseline ANC was associated with the risk of death in severe hospitalized COVID-19 patients, irrespective of the DVT status. In addition, a significantly higher serum neutrophil activity was observed in severe COVID-19 inpatients with DVT or those deceased during hospital stay. New-onset DVT partially mediated the association between baseline D-dimer (indirect effect: 0.011, estimated mediating proportion: 67.0%), baseline ANC (indirect effect: 0.006, estimated mediating proportion: 48.7%), and mortality in severe hospitalized patients with COVID-19. In summary, baseline D-dimer and baseline absolute neutrophil count (ANC) levels were associated with the mortality in severe hospitalized patients with COVID-19, especially DVT inpatients. New-onset DVT partially mediated the association between baseline D-dimer, baseline ANC, and mortality in severe hospitalized patients with COVID-19.
Topics: Humans; COVID-19; Male; Female; Retrospective Studies; Middle Aged; Fibrin Fibrinogen Degradation Products; Aged; SARS-CoV-2; Neutrophils; Venous Thrombosis; Inflammation; Risk Factors; Severity of Illness Index; Hemostasis; Inpatients; Leukocyte Count; Adult; China
PubMed: 38831596
DOI: 10.1177/10760296241255959 -
BMJ Open Jun 2024Tranexamic acid (TXA) is an inexpensive and widely available medication that reduces blood loss and red blood cell (RBC) transfusion in cardiac and orthopaedic... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Tranexamic acid (TXA) is an inexpensive and widely available medication that reduces blood loss and red blood cell (RBC) transfusion in cardiac and orthopaedic surgeries. While the use of TXA in these surgeries is routine, its efficacy and safety in other surgeries, including oncologic surgeries, with comparable rates of transfusion are uncertain. Our primary objective is to evaluate whether a hospital-level policy implementation of routine TXA use in patients undergoing major non-cardiac surgery reduces RBC transfusion without increasing thrombotic risk.
METHODS AND ANALYSIS
A pragmatic, registry-based, blinded, cluster-crossover randomised controlled trial at 10 Canadian sites, enrolling patients undergoing non-cardiac surgeries at high risk for RBC transfusion. Sites are randomised in 4-week intervals to a hospital policy of intraoperative TXA or matching placebo. TXA is administered as 1 g at skin incision, followed by an additional 1 g prior to skin closure. Coprimary outcomes are (1) effectiveness, evaluated as the proportion of patients transfused RBCs during hospital admission and (2) safety, evaluated as the proportion of patients diagnosed with venous thromboembolism within 90 days. Secondary outcomes include: (1) transfusion: number of RBC units transfused (both at a hospital and patient level); (2) safety: in-hospital diagnoses of myocardial infarction, stroke, deep vein thrombosis or pulmonary embolism; (3) clinical: hospital length of stay, intensive care unit admission, hospital survival, 90-day survival and the number of days alive and out of hospital to day 30; and (4) compliance: the proportion of enrolled patients who receive a minimum of one dose of the study intervention.
ETHICS AND DISSEMINATION
Institutional research ethics board approval has been obtained at all sites. At the completion of the trial, a plain language summary of the results will be posted on the trial website and distributed in the lay press. Our trial results will be published in a peer-reviewed scientific journal.
TRIAL REGISTRATION NUMBER
NCT04803747.
Topics: Humans; Tranexamic Acid; Antifibrinolytic Agents; Canada; Blood Loss, Surgical; Cross-Over Studies; Erythrocyte Transfusion; Organizational Policy
PubMed: 38830735
DOI: 10.1136/bmjopen-2024-084847 -
Clinica Chimica Acta; International... Jun 2024The metabolic or proliferative abnormalities that are characteristic of tumor cells can lead to abnormal fibrinolysis or coagulation system activity, with certain tumors...
BACKGROUND
The metabolic or proliferative abnormalities that are characteristic of tumor cells can lead to abnormal fibrinolysis or coagulation system activity, with certain tumors exhibiting hypercoagulability or existing in a fibrinolytic state. However, the utility of biomarkers of coagulation and fibrinolysis when seeking to differentiate between benign gallbladder disease and malignant gallbladder tumors remains uncertain.
METHODS
This study included a total of 81 patients with benign gallbladder polyps and 94 patients with malignant gallbladder tumors. Pre-biopsy or pretreatment levels of PT, APTT, FIB, D-dimer, FDP, PLT, PIC, TAT, TM, and t-PAIC from these patients were compared using Mann-Whitney tests. The baseline data of the patients were analyzed using chi-square tests, and the diagnostic utility of these biomarkers in distinguishing between benign and malignant gallbladder lesions was evaluated using ROC curves, and Spearman correlation analysis was employed to assess the correlation between these indicators and tumor parameters.
RESULTS
The average age of malignant gallbladder tumor group was higher than benign gallbladder polyp group. And the base line analysis showed that there was a statistic difference in age, history of smoking, drinking, biliary tract disease, BMI of over weight between these two groups. In patients with malignant gallbladder tumors, FIB, D-dimer, FDP, PIC, TAT, TM, and t-PAIC levels were significantly elevated relative to those in patients affected by benign gallbladder polyp. The AUC for FIB, D-dimer, and FDP was 0.8469, 0.6514, 0.5950, while for PIC, TAT, TM, t-PAIC and four biomarker combined diagnosed was 0.8455, 0.6554, 0.7130, 0.6806, and 0.8859. Among these, TM was associated with the vascular invasion of tumor patients; TAT and t-PAIC were associated with neural invasion; D-dimer and FDP were related to the maximum tumor diameter; and FDP had a certain correlation with the tumor stage.
CONCLUSIONS
In gallbladder tumor patients, conventional coagulation metrics like FIB, D-dimer, and FDP, as well as newer thrombotic indicators such as PIC, TAT, TM, and t-PAIC, were obviously increased. Correlations with tumor parameters suggested their potential as biomarkers to distinguish benign from malignant gallbladder growths.
Topics: Humans; Gallbladder Neoplasms; Female; Male; Cross-Sectional Studies; Middle Aged; Fibrinolysis; Aged; Blood Coagulation; Adult; Biomarkers, Tumor; Diagnosis, Differential; Biomarkers; Fibrin Fibrinogen Degradation Products
PubMed: 38830523
DOI: 10.1016/j.cca.2024.119751