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Biomedicine & Pharmacotherapy =... Jun 2024Vitamin K2 (VK2) is an effective compound for anti-ferroptosis and anti-osteoporosis, and Semen sojae praeparatum (Dandouchi in Chinese) is the main source of VK2....
Vitamin K2 (VK2) is an effective compound for anti-ferroptosis and anti-osteoporosis, and Semen sojae praeparatum (Dandouchi in Chinese) is the main source of VK2. Chondrocyte ferroptosis and extracellular matrix (ECM) degradation playing a role in the pathogenesis of osteoarthritis (OA). Glutathione peroxidase 4 (GPX4) is the intersection of two mechanisms in regulating OA progression. But no studies have elucidated the therapeutic effects and mechanisms of VK2 on OA. This study utilized an in vivo rat OA model created via anterior cruciate ligament transection (ACLT) and an in vitro chondrocyte oxidative damage model induced by TBHP to investigate the protective effects and mechanisms of action of VK2 in OA. Knee joint pain in mice was evaluated using the Von Frey test. Micro-CT and Safranin O-Fast Green staining were employed to observe the extent of damage to the tibial cartilage and subchondral bone, while immunohistochemistry and PCR were used to examine GPX4 levels in joint cartilage. The effects of VK2 on rat chondrocyte viability were assessed using CCK-8 and flow cytometry assays, and chondrocyte morphology was observed with toluidine blue and alcian blue staining. The impact of VK2 on intracellular ferroptosis-related markers was observed using fluorescent staining and flow cytometry. Protein expression changes were detected by immunofluorescence and Western blot analysis. Furthermore, specific protein inhibitors were applied to confirm the dual-regulatory effects of VK2 on GPX4. VK2 can increase bone mass and cartilage thickness in the subchondral bone of the tibia, and reduce pain and the OARSI score induced by OA. Immunohistochemistry results indicate that VK2 exerts its anti-OA effects by regulating GPX4 to delay ECM degradation. VK2 can inhibit the activation of the MAPK/NFκB signaling pathway caused by reduced expression of intracellular GPX4, thereby decreasing ECM degradation. Additionally, VK2 can reverse the inhibitory effect of RSL3 on GPX4, increase intracellular GSH content and the GSH/GSSG ratio, reduce MDA content, and rescue chondrocyte ferroptosis. The protective mechanism of VK2 may involve its dual-target regulation of GPX4, reducing chondrocyte ferroptosis and inhibiting the MAPK/NFκB signaling pathway to decelerate the degradation of the chondrocyte extracellular matrix.
Topics: Animals; Ferroptosis; Extracellular Matrix; Chondrocytes; Male; Osteoarthritis; Rats, Sprague-Dawley; Rats; Phospholipid Hydroperoxide Glutathione Peroxidase; Mice; Vitamin K 2; Mice, Inbred C57BL; Cartilage, Articular; Disease Models, Animal; Signal Transduction; Cells, Cultured
PubMed: 38759289
DOI: 10.1016/j.biopha.2024.116697 -
Medicine May 2024Amniotic fluid embolism (AFE) is a fatal obstetric condition that often rapidly leads to severe respiratory and circulatory failure. It is complicated by obstetric... (Review)
Review
RATIONALE
Amniotic fluid embolism (AFE) is a fatal obstetric condition that often rapidly leads to severe respiratory and circulatory failure. It is complicated by obstetric disseminated intravascular coagulation (DIC) with bleeding tendency; therefore, the introduction of venoarterial extracorporeal membrane oxygenation (VA-ECMO) is challenging. We report the case of a patient with AFE requiring massive blood transfusion, rescued using VA-ECMO without initial anticoagulation.
PATIENTS CONCERNS
A 39-year-old pregnant patient was admitted with a complaint of abdominal pain. An emergency cesarean section was performed because a sudden decrease in fetal heart rate was detected in addition to DIC with hyperfibrinolysis. Intra- and post-operatively, the patient had a bleeding tendency and required massive blood transfusions. After surgery, the patient developed lethal respiratory and circulatory failure, and VA-ECMO was introduced.
DIAGNOSIS
Based on the course of the illness and imaging findings, the patient was diagnosed with AFE.
INTERVENTIONS
By controlling the bleeding tendency with a massive transfusion and tranexamic acid administration, using an antithrombotic ECMO circuit, and delaying the initiation of anticoagulation and anti-DIC medication until the bleeding tendency settled, the patient was managed safely on ECMO without complications.
OUTCOMES
By day 5, both respiration and circulation were stable, and the patient was weaned off VA-ECMO. Mechanical ventilation was discontinued on day 6. Finally, she was discharged home without sequelae.
LESSONS
VA-ECMO may be effective to save the lives of patients who have AFE with lethal circulatory and respiratory failure. For safe management without bleeding complications, it is important to start VA-ECMO without initial anticoagulants and to administer anticoagulants and anti-DIC drugs after the bleeding tendency has resolved.
Topics: Humans; Female; Embolism, Amniotic Fluid; Extracorporeal Membrane Oxygenation; Adult; Pregnancy; Cesarean Section; Blood Transfusion; Tranexamic Acid; Disseminated Intravascular Coagulation; Anticoagulants
PubMed: 38758915
DOI: 10.1097/MD.0000000000038176 -
Medicine May 2024Identifying prognostic factors in elderly patients with severe coronavirus disease 2019 (COVID-19) is crucial for clinical management. Recent evidence suggests... (Observational Study)
Observational Study
Identifying prognostic factors in elderly patients with severe coronavirus disease 2019 (COVID-19) is crucial for clinical management. Recent evidence suggests malnutrition and renal dysfunction are associated with poor outcome. This study aimed to develop a prognostic model incorporating prognostic nutritional index (PNI), estimated glomerular filtration rate (eGFR), and other parameters to predict mortality risk. This retrospective analysis included 155 elderly patients with severe COVID-19. Clinical data and outcomes were collected. Logistic regression analyzed independent mortality predictors. A joint predictor "L" incorporating PNI, eGFR, D-dimer, and lactate dehydrogenase (LDH) was developed and internally validated using bootstrapping. Decreased PNI (OR = 1.103, 95% CI: 0.78-1.169), decreased eGFR (OR = 0.964, 95% CI: 0.937-0.992), elevated D-dimer (OR = 1.001, 95% CI: 1.000-1.004), and LDH (OR = 1.005, 95% CI: 1.001-1.008) were independent mortality risk factors (all P < .05). The joint predictor "L" showed good discrimination (area under the curve [AUC] = 0.863) and calibration. The bootstrapped area under the curve was 0.858, confirming model stability. A combination of PNI, eGFR, D-dimer, and LDH provides useful prognostic information to identify elderly patients with severe COVID-19 at highest mortality risk for early intervention. Further external validation is warranted.
Topics: Humans; COVID-19; Aged; Male; Female; Retrospective Studies; Glomerular Filtration Rate; Prognosis; Nutrition Assessment; SARS-CoV-2; Aged, 80 and over; Fibrin Fibrinogen Degradation Products; Risk Factors; L-Lactate Dehydrogenase; Severity of Illness Index; Malnutrition
PubMed: 38758852
DOI: 10.1097/MD.0000000000038213 -
Zhongguo Xiu Fu Chong Jian Wai Ke Za... May 2024To explore the impact of anemia on the incidence of perioperative lower limb deep vein thrombosis (DVT) in patients undergoing total hip arthroplasty (THA).
OBJECTIVE
To explore the impact of anemia on the incidence of perioperative lower limb deep vein thrombosis (DVT) in patients undergoing total hip arthroplasty (THA).
METHODS
A retrospective analysis was conducted on clinical data of 1 916 non-fracture patients who underwent THA between September 2015 and December 2021, meeting the selection criteria. Among them, there were 811 male and 1 105 female patients, aged between 18 and 94 years with an average of 59.2 years. Among the patients, 213 were diagnosed with anemia, while 1 703 were not. Preoperative DVT was observed in 55 patients, while 1 861 patients did not have DVT preoperatively (of which 75 patients developed new-onset DVT postoperatively). Univariate analysis was performed on variables including age, gender, body mass index (BMI), diabetes, hypertension, history of tumors, history of thrombosis, history of smoking, revision surgery, preoperative D-dimer positivity (≥0.5 mg/L), presence of anemia, operation time, intraoperative blood loss, transfusion requirement, and pre- and post-operative levels of red blood cells, hemoglobin, hematocrit, and platelets. Furthermore, logistic regression was utilized for multivariate analysis to identify risk factors associated with DVT formation.
RESULTS
Univariate analysis showed that age, gender, hypertension, revision surgery, preoperative levels of red blood cells, preoperative hemoglobin, preoperative D-dimer positivity, and anemia were influencing factors for preoperative DVT ( <0.05). Further logistic regression analysis indicated that age (>60 years old), female, preoperative D-dimer positivity, and anemia were risk factors for preoperative DVT ( <0.05). Univariate analysis also revealed that age, female, revision surgery, preoperative D-dimer positivity, anemia, transfusion requirement, postoperative level of red blood cells, and postoperative hemoglobin level were influencing factors for postoperative new-onset DVT ( <0.05). Further logistic regression analysis indicated that age (>60 years old), female, and revision surgery were risk factors for postoperative new-onset DVT ( <0.05).
CONCLUSION
The incidence of anemia is higher among patients with preoperative DVT for THA, and anemia is an independent risk factor for preoperative DVT occurrence in THA. While anemia may not be an independent risk factor for THA postoperative new-onset DVT, the incidence of anemia is higher among patients with postoperative new-onset DVT.
Topics: Humans; Venous Thrombosis; Arthroplasty, Replacement, Hip; Female; Male; Middle Aged; Retrospective Studies; Aged; Anemia; Incidence; Risk Factors; Lower Extremity; Adult; Postoperative Complications; Aged, 80 and over; Adolescent; Perioperative Period; Young Adult; Fibrin Fibrinogen Degradation Products
PubMed: 38752243
DOI: 10.7507/1002-1892.202401083 -
Scientific Reports May 2024Intravenous application of tranexamic acid (TXA) in posterior lumbar interbody fusion (PLIF) can effectively reduce blood loss without affecting coagulation function....
Intravenous application of tranexamic acid (TXA) in posterior lumbar interbody fusion (PLIF) can effectively reduce blood loss without affecting coagulation function. However, it has not been reported whether preoperative use of anticoagulants may affect the efficacy of TXA in PLIF. The purpose of this study is to observe the effect of preoperative use of anticoagulants on coagulation indicators and blood loss after PLIF receiving intravenous unit dose TXA. A retrospective analysis was conducted on data from 53 patients with PLIF between 2020.11 and 2022.9, who received intravenous application of a unit dose of TXA (1 g/100 mL) 15 min before the skin incision after general anesthesia. Those who used anticoagulants within one week before surgery were recorded as the observation group, while those who did not use anticoagulants were recorded as the control group. The main observation indicators include surgical time, intraoperative blood loss, postoperative drainage volume, blood transfusion, and red blood cell (RBC), hemoglobin (HB), and hematocrit (HCT) measured on the 1st, 4th, 7th, and last-test postoperative days. Secondary observation indicators included postoperative incision healing, deep vein thrombosis of lower limbs, postoperative hospital stay, and activated partial thrombin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (FIB), and platelets (PLT) on the 1st and 4th days after surgery. The operation was successfully completed in both groups, the incision healed well after operation, and no lower limb deep vein thrombosis occurred. There was no significant difference in surgical time, intraoperative blood loss, postoperative drainage volume, and blood transfusion between the two groups (p > 0.05). There was no significant difference in the RBC, HB, and HCT measured on the 1st, 4th, 7th, and last-test postoperative days between the two groups (p > 0.05). There was no statistically significant difference in APTT, PT, TT, FIB and PLT between the two groups on the 1st and 4th postoperative days (p > 0.05). There was no significant difference in postoperative hospital stay between the two groups (p > 0.05). The use of anticoagulants within one week before surgery does not affect the hemostatic effect of intravenous unit dose TXA in PLIF.
Topics: Humans; Tranexamic Acid; Female; Male; Middle Aged; Retrospective Studies; Case-Control Studies; Anticoagulants; Blood Loss, Surgical; Aged; Administration, Intravenous; Spinal Fusion; Preoperative Care; Antifibrinolytic Agents; Blood Coagulation
PubMed: 38744855
DOI: 10.1038/s41598-024-60440-9 -
Lipids in Health and Disease May 2024Skin barrier alterations play a crucial function in melasma development. Past researches have demonstrated variations in lipid content between the epidermis of melasma... (Comparative Study)
Comparative Study
BACKGROUND
Skin barrier alterations play a crucial function in melasma development. Past researches have demonstrated variations in lipid content between the epidermis of melasma lesions and normal tissues, along with the varied expression of lipid-related genes in melasma. This study aimed to analyze the lipidome profiles of skin surface lipids (SSL) in patients with melasma before and after treatment to understand associated abnormalities.
METHODS
Melasma was treated with tranexamic acid orally and hydroquinone cream topically. Disease was assessed using the Melasma Area and Severity Index (MASI), and the impact to life was evaluated with Melasma Quality of Life (MELASQoL) score. Epidermal melanin particles were observed using reflection confocal microscopy (RCM), whereas epidermal pigment and blood vessel morphology were observed using dermoscopy, and SSL samples were collected. Specific information regarding alterations in lipid composition was obtained through multivariate analysis of the liquid chromatography-mass spectrometry data.
RESULTS
After treatment, patients with melasma exhibited decreased MASI and MELASQoL scores (P < 0.001); RCM revealed reduced melanin content in the lesions, and dermoscopy revealed fewer blood vessels. Fifteen lipid subclasses and 382 lipid molecules were identified using lipidomic assays. The expression levels of total lipids, phosphatidylcholine, and phosphatidylethanolamine in the melasma lesions decreased after treatment (P < 0.05).
CONCLUSION
This study revealed alterations in the SSL composition after effective melasma treatment, suggesting a compensatory role for lipids in melasma barrier function. The mechanism involving SSL and the lipid barrier, which influences melasma's occurrence, needs further elucidation.
Topics: Humans; Melanosis; Female; Adult; Lipidomics; Quality of Life; Hydroquinones; Tranexamic Acid; Middle Aged; Melanins; Male; Lipids; Epidermis; Phosphatidylethanolamines; Phosphatidylcholines; Skin; Lipid Metabolism
PubMed: 38734619
DOI: 10.1186/s12944-024-02130-z -
Nutrients Apr 2024The available evidence on vitamin K status in cystic fibrosis (CF) is scarce, lacking data on vitamin K2 (menaquinones-MK). Therefore, we assessed vitamin K1, MK-4 and...
The available evidence on vitamin K status in cystic fibrosis (CF) is scarce, lacking data on vitamin K2 (menaquinones-MK). Therefore, we assessed vitamin K1, MK-4 and MK-7 concentrations (LC-MS/MS) in 63 pancreatic insufficient and modulator naïve CF patients, and compared to 61 healthy subjects (HS). Vitamin K1 levels did not differ between studied groups. MK-4 concentrations were higher (median <1st-3rd quartile>: 0.778 <0.589-1.086> vs. 0.349 <0.256-0.469>, < 0.0001) and MK-7 levels lower (0.150 <0.094-0.259> vs. 0.231 <0.191-0.315>, = 0.0007) in CF patients than in HS. MK-7 concentrations were higher in CF patients receiving K1 and MK-7 supplementation than in those receiving vitamin K1 alone or no supplementation. Moreover, vitamin K1 concentrations depended on the supplementation regime. Based on multivariate logistic regression analysis, we have found that MK-7 supplementation dose has been the only predictive factor for MK-7 levels. In conclusion, vitamin K1 levels in CF are low if not currently supplemented. MK-4 concentrations in CF patients supplemented with large doses of vitamin K1 are higher than in HS. MK-7 levels in CF subjects not receiving MK-7 supplementation, with no regard to vitamin K1 supplementation, are low. There do not seem to be any good clinical predictive factors for vitamin K status.
Topics: Humans; Cystic Fibrosis; Female; Male; Vitamin K 2; Cross-Sectional Studies; Prothrombin; Adolescent; Adult; Vitamin K 1; Young Adult; Nutritional Status; Dietary Supplements; Vitamin K Deficiency; Vitamin K
PubMed: 38732584
DOI: 10.3390/nu16091337 -
International Journal of Molecular... May 2024Colorectal cancer (CRC) is one of the most common neoplasms in developed countries, with increasing incidence and mortality, even in young people. A variety of serum...
Colorectal cancer (CRC) is one of the most common neoplasms in developed countries, with increasing incidence and mortality, even in young people. A variety of serum markers have been associated with CRC (CEA, CA 19-9), but neither should be used as a screening tool for the diagnosis or evolution staging of CRC. The sensitivity and specificity of these markers are not as good as is required, so new ones need to be found. Matrix Gla protein and PIVKA II are involved in carcinogenesis, but few studies have evaluated their usefulness in predicting the presence and severity of CRC. Two hundred patients were divided into three groups: 80 patients were included in the control group; 80 with CRC and without hepatic metastasis were included in Group 1; 40 patients with CRC and hepatic metastasis were included in Group 2. Vitamin K-dependent proteins (VKDPs) levels in plasma were determined. Patients with CRC without methastasis (Group 1) and CRC patients with methastasis (Group 2) presented significantly higher values of CEA, CA 19-9, PIVKA II (310.05 ± 38.22 vs. 430.13 ± 122.13 vs. 20.23 ± 10.90), and ucMGP (14,300.00 ± 2387.02 vs. 13,410.52 ± 2243.16 vs. 1780.31 ± 864.70) compared to control group (Group 0). Interestingly, Group 1 presented the greatest PIVKA II values. Out of all the markers, significant differences between the histological subgroups were found only for ucMGP, but only in non-metastatic CRC. Studying the discrimination capacity between the patients with CRC vs. those without, no significant differences were found between the classical tumor markers and the VKDP AUROC curves (PIVKA II and ucMGP AUROCs = 1). For the metastatic stage, the sensitivity and specificity of the VKDPs were lower in comparison with those of CA 19-9 and CEA, respectively (PIVKA II AUROC = 0.789, ucMGP AUROC = 0.608). The serum levels of these VKDPs are significantly altered in patients with colorectal carcinoma; it is possible to find additional value of these in the early stages of the disease.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Biomarkers; Biomarkers, Tumor; CA-19-9 Antigen; Calcium-Binding Proteins; Carcinoembryonic Antigen; Colorectal Neoplasms; Extracellular Matrix Proteins; Liver Neoplasms; Matrix Gla Protein; Protein Precursors; Prothrombin; ROC Curve; Vitamin K
PubMed: 38732222
DOI: 10.3390/ijms25094997 -
Medicine May 2024Warfarin, a widely utilized anticoagulant, is paramount for preventing thromboembolic events in patients with mechanical heart valve replacements. However, its narrow...
Warfarin, a widely utilized anticoagulant, is paramount for preventing thromboembolic events in patients with mechanical heart valve replacements. However, its narrow therapeutic index can lead to over-anticoagulation and overdose, resulting in serious health risks. This study examines the efficacy of human prothrombin complex concentrate (PCC) in managing warfarin overdose, in comparison with traditional treatments. A retrospective analysis was conducted on 162 adults who presented with warfarin overdose (INR > 5.0) at a tertiary care hospital between 2016 and 2020. Participants were divided into 2 groups-those treated with PCC (n = 57) and those treated with conventional methods (n = 105), including vitamin K and fresh frozen plasma. The primary outcome was the rate of reaching the target (International Normalized Ratio) INR within 24 hours. Secondary outcomes included transfusion requirements, thromboembolic events, adverse reactions, 30-day mortality, and length of hospital stay. PCC demonstrated significant efficacy, with 89.5% of patients achieving the target INR within 24 hours, compared to 64.8% in the control group (P < .05). The PCC group also had reduced transfusion requirements and a shorter average hospital stay. There was no significant difference in thromboembolic events or adverse reactions between the 2 groups, and the reduced 30-day mortality in the PCC group was not statistically significant. Human prothrombin complex concentrate is associated with rapid reaching the target INR, decreased transfusion needs, and shortened hospitalization, making it a promising option for warfarin overdose management. While the results are encouraging, larger, multicenter, randomized controlled trials are necessary to further validate these findings and optimize PCC administration protocols.
Topics: Humans; Warfarin; Blood Coagulation Factors; Female; Male; Retrospective Studies; Anticoagulants; International Normalized Ratio; Middle Aged; Drug Overdose; Aged; Heart Valve Prosthesis Implantation; Thromboembolism; Adult; Treatment Outcome; Blood Transfusion; Length of Stay; Vitamin K
PubMed: 38728459
DOI: 10.1097/MD.0000000000038022 -
International Journal of Systematic and... May 2024Two Gram-stain-negative, rod-shaped bacteria, designated as strains KJ10-1 and KJ40-1, were isolated from marine brown algae. Both strains were catalase-positive,...
Two Gram-stain-negative, rod-shaped bacteria, designated as strains KJ10-1 and KJ40-1, were isolated from marine brown algae. Both strains were catalase-positive, oxidase-positive, and facultative aerobic. Strain KJ10-1 exhibited optimal growth at 25 °C, pH 7.0, and 3 % NaCl, whereas strain KJ40-1 showed optimal growth at 25 °C, pH 7.0, and 2 % NaCl. The respiratory quinones of strain KJ10-1 were ubiquinone-8, ubiquinone-7, menaquinone-7, and methylated menaquinone-7, while the respiratory quinone of strain KJ40-1 was only ubiquinone-8. As major fatty acids, strain KJ10-1 contained C, C ω8, iso-C, and summed feature 3 (C 7 and/or C 6) and strain KJ40-1 contained C and summed features 3 and 8 (C 7 and/or C 6). The major polar lipids in strain KJ10-1 were phosphatidylethanolamine, phosphatidylglycerol, and an unidentified aminolipid, whereas those in strain KJ40-1 were phosphatidylethanolamine, phosphatidylglycerol, and diphosphatidylglycerol. The DNA G+C contents of strains KJ10-1 and KJ40-1 were 42.1 and 40.8 mol%, respectively. Based on 16S rRNA gene sequences, strains KJ10-1 and KJ40-1 exhibited the closest relatedness to MMS16-UL250 (98.6 %) and S-1 (95.4 %), respectively. Phylogenetic analyses, based on both 16S rRNA and 92 housekeeping genes, showed that the strains formed distinct phylogenic lineages within the genera and . Digital DNA-DNA hybridization and orthologous average nucleotide identity values between strain KJ10-1 and other species, as well as between strain KJ40-1 and other species, were below the thresholds commonly accepted for prokaryotic species delineation. Based on the phenotypic, chemotaxonomic, and phylogenetic data, strains KJ10-1 and KJ40-1 represent novel species of the genera and , respectively, for which the names sp. nov. and sp. nov. are proposed, respectively. The type strains of and are KJ10-1 (=KACC 22589=JCM 35409) and KJ40-1 (=KACC 22588=JCM 35410), respectively.
Topics: RNA, Ribosomal, 16S; Base Composition; Phylogeny; Fatty Acids; DNA, Bacterial; Bacterial Typing Techniques; Sequence Analysis, DNA; Vibrio; Ubiquinone; Shewanella; Phaeophyceae; Vitamin K 2; Phospholipids; Nucleic Acid Hybridization; Seawater
PubMed: 38728177
DOI: 10.1099/ijsem.0.006378