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Ghana Medical Journal Mar 2024To assess the performance of the Sex Hormone-Binding Globulin (SHBG) assay as a diagnostic indicator of Gestational Diabetes Mellitus (GDM) in the study population.
OBJECTIVE
To assess the performance of the Sex Hormone-Binding Globulin (SHBG) assay as a diagnostic indicator of Gestational Diabetes Mellitus (GDM) in the study population.
DESIGN
Analytical cross-sectional study.
SETTING
Hospital-based, Benue State University Teaching Hospital (BSUTH), Makurdi, Nigeria.
PARTICIPANTS
Women with singleton pregnancies at 24 to 28 weeks gestational age attending Antenatal care at BSUTH, Makurdi.
INTERVENTION
Serum SHBG levels were assayed by ELISA during a diagnostic 75-gram Oral Glucose Tolerance Test (OGTT) for assessment of GDM in the cohort of consecutively selected participants who met the inclusion criteria.
MAIN OUTCOME MEASURES
Serum levels of SHBG and presence of GDM in the participants.
RESULT
Serum SHBG was significantly negatively correlated (rpb = - 0.534, p-value < 0.001) with the presence of GDM. It had an area under the ROC curve of 0.897 (95% Confidence Interval = 0.858-0.935; p-value < 0.001). A cut-off value of 452.0 nmol/L indicative of GDM had a diagnostic odds ratio of 21.4 in the study population.
CONCLUSION
SHBG is a valuable diagnostic indicator for GDM in the study population.
FUNDING
None declared.
Topics: Humans; Female; Diabetes, Gestational; Pregnancy; Sex Hormone-Binding Globulin; Cross-Sectional Studies; Adult; Glucose Tolerance Test; Nigeria; ROC Curve; Young Adult; Biomarkers; Enzyme-Linked Immunosorbent Assay
PubMed: 38957276
DOI: 10.4314/gmj.v58i1.8 -
Journal of Orthopaedic Translation Jul 2024Over-activated osteoclast (OC) is a major cause of diseases related to bone loss and bone metabolism. Both bone resorption inhibition and apoptosis induction of...
BACKGROUND
Over-activated osteoclast (OC) is a major cause of diseases related to bone loss and bone metabolism. Both bone resorption inhibition and apoptosis induction of osteoclast are crucial in treating these diseases. is an important interferon-stimulated and apoptotic gene. However, how regulates bone formation and remodeling is unknown.
METHODS
We generate global and chimeric knockout mouse models and utilize these models to explore the function and mechanism of in regulating bone formation and remodeling and .
RESULTS
We show that depletion enhances osteoclast generation . knockout increases osteoclast number and bone resorption, thereby exacerbating bone loss in both OVX and osteolysis models. Activation of XAF1 with BV6 (a potent XIAP inhibitor) suppresses osteoclast formation. Mechanistically, deletion decreases osteoclast apoptosis by facilitating the interaction between XIAP and caspase-3/7.
CONCLUSIONS
Our data illustrates an essential role of in controlling osteoclastogenesis in both osteoporosis and osteolysis mouse models and highlights its underlying mechanism, indicating a potential role in clinical treatment.The translational potential of this article: The translation potential of this article is that we first indicated that osteoclast apoptosis induced by XAF1 contribute to the progression of osteoporosis and osteolysis, which provides a novel strategy in the prevention of osteoporosis and osteolysis.
PubMed: 38957269
DOI: 10.1016/j.jot.2024.05.001 -
Critical Care Explorations Jul 2024Ventilator-associated pneumonia (VAP) frequently occurs in patients with cardiac arrest. Diagnosis of VAP after cardiac arrest remains challenging, while the use of... (Randomized Controlled Trial)
Randomized Controlled Trial
Can Biomarkers Correctly Predict Ventilator-associated Pneumonia in Patients Treated With Targeted Temperature Management After Cardiac Arrest? An Exploratory Study of the Multicenter Randomized Antibiotic (ANTHARTIC) Study.
IMPORTANCE
Ventilator-associated pneumonia (VAP) frequently occurs in patients with cardiac arrest. Diagnosis of VAP after cardiac arrest remains challenging, while the use of current biomarkers such as C-reactive protein (CRP) or procalcitonin (PCT) is debated.
OBJECTIVES
To evaluate biomarkers' impact in helping VAP diagnosis after cardiac arrest.
DESIGN SETTING AND PARTICIPANTS
This is a prospective ancillary study of the randomized, multicenter, double-blind placebo-controlled ANtibiotherapy during Therapeutic HypothermiA to pRevenT Infectious Complications (ANTHARTIC) trial evaluating the impact of antibiotic prophylaxis to prevent VAP in out-of-hospital patients with cardiac arrest secondary to shockable rhythm and treated with therapeutic hypothermia. An adjudication committee blindly evaluated VAP according to predefined clinical, radiologic, and microbiological criteria. All patients with available biomarker(s), sample(s), and consent approval were included.
MAIN OUTCOMES AND MEASURES
The main endpoint was to evaluate the ability of biomarkers to correctly diagnose and predict VAP within 48 hours after sampling. The secondary endpoint was to study the combination of two biomarkers in discriminating VAP. Blood samples were collected at baseline on day 3. Routine and exploratory panel of inflammatory biomarkers measurements were blindly performed. Analyses were adjusted on the randomization group.
RESULTS
Among 161 patients of the ANTHARTIC trial with available biological sample(s), patients with VAP ( = 33) had higher body mass index and Acute Physiology and Chronic Health Evaluation II score, more unwitnessed cardiac arrest, more catecholamines, and experienced more prolonged therapeutic hypothermia duration than patients without VAP ( = 121). In univariate analyses, biomarkers significantly associated with VAP and showing an area under the curve (AUC) greater than 0.70 were CRP (AUC = 0.76), interleukin (IL) 17A and 17C (IL17C) (0.74), macrophage colony-stimulating factor 1 (0.73), PCT (0.72), and vascular endothelial growth factor A (VEGF-A) (0.71). Multivariate analysis combining novel biomarkers revealed several pairs with value of less than 0.001 and odds ratio greater than 1: VEGF-A + IL12 subunit beta (IL12B), Fms-related tyrosine kinase 3 ligands (Flt3L) + C-C chemokine 20 (CCL20), Flt3L + IL17A, Flt3L + IL6, STAM-binding protein (STAMBP) + CCL20, STAMBP + IL6, CCL20 + 4EBP1, CCL20 + caspase-8 (CASP8), IL6 + 4EBP1, and IL6 + CASP8. Best AUCs were observed for CRP + IL6 (0.79), CRP + CCL20 (0.78), CRP + IL17A, and CRP + IL17C.
CONCLUSIONS AND RELEVANCE
Our exploratory study shows that specific biomarkers, especially CRP combined with IL6, could help to better diagnose or predict early VAP occurrence in cardiac arrest patients.
Topics: Humans; Biomarkers; Pneumonia, Ventilator-Associated; Male; Female; Hypothermia, Induced; Middle Aged; Aged; Prospective Studies; Procalcitonin; Double-Blind Method; Anti-Bacterial Agents; C-Reactive Protein; Heart Arrest; Predictive Value of Tests
PubMed: 38957212
DOI: 10.1097/CCE.0000000000001104 -
International Journal of Nanomedicine 2024Salidroside (SAL) is the most effective component of , a traditional Chinese medicine. Cryptotanshinone (CT) is the main fat-soluble extract of , exhibiting considerable...
BACKGROUND
Salidroside (SAL) is the most effective component of , a traditional Chinese medicine. Cryptotanshinone (CT) is the main fat-soluble extract of , exhibiting considerable potential for application in osteogenesis. Herein, a polycaprolactone/gelatin nanofiber membrane loaded with CT and SAL (PSGC membrane) was successfully fabricated via coaxial electrospinning and characterized.
METHODS AND RESULTS
This membrane capable of sustained and controlled drug release was employed in this study. Co-culturing the membrane with bone marrow mesenchymal stem cells and human umbilical vein endothelial cells revealed excellent biocompatibility and demonstrated osteogenic and angiogenic capabilities. Furthermore, drug release from the PSGC membrane activated the Wnt/β-catenin signaling pathway and promoted osteogenic differentiation and vascularization. Evaluation of the membrane's vascularization and osteogenic capacities involved transplantation onto a rat's subcutaneous area and assessing rat cranium defects for bone regeneration, respectively. Microcomputed tomography, histological tests, immunohistochemistry, and immunofluorescence staining confirmed the membrane's outstanding angiogenic capacity two weeks post-operation, with a higher incidence of osteogenesis observed in rat cranial defects eight weeks post-surgery.
CONCLUSION
Overall, the SAL- and CT-loaded coaxial electrospun nanofiber membrane synergistically enhances bone repair and regeneration.
Topics: Osteogenesis; Animals; Nanofibers; Gelatin; Polyesters; Glucosides; Phenols; Phenanthrenes; Humans; Neovascularization, Physiologic; Human Umbilical Vein Endothelial Cells; Mesenchymal Stem Cells; Rats, Sprague-Dawley; Rats; Male; Bone Regeneration; Membranes, Artificial; Coculture Techniques; Drug Liberation; Cell Differentiation
PubMed: 38957181
DOI: 10.2147/IJN.S461141 -
JOR Spine Sep 2024Pre-clinical animal experiment.
STUDY DESIGN
Pre-clinical animal experiment.
OBJECTIVE
In this study, we investigated therapeutic effects of silibinin in a spinal cord injury (SCI) model. In SCI, loss of cells due to secondary damage mechanisms exceeds that caused by primary damage. Ferroptosis, which is iron-dependent non-apoptotic cell death, is shown to be influential in the pathogenesis of SCI.
METHODS
The study was conducted as an in vivo experiment using a total of 78 adult male/female Sprague Dawley rats. Groups were as follows: Sham, SCI, deferoxamine (DFO) treatment, and silibinin treatment. There were subgroups with follow-up periods of 24 h, 72 h, and 6 weeks in all groups. Malondialdehyde (MDA), glutathione (GSH), and Fe levels were measured by spectrophotometry. Glutathione peroxidase-4 (GPX4), ferroportin (FPN), transferrin receptor (TfR1), and 4-hydroxynonenal (4-HNE)-modified protein levels were assessed by Western blotting. Functional recovery was assessed using Basso-Beattie-Bresnahan test.
RESULTS
Silibinin achieved significant suppression in MDA and 4-HNE levels compared to the SCI both in 72-h and 6 weeks group ( < 0.05). GSH, GPX4, and FNP levels were found to be significantly higher in the silibinin 24 h, 72 h, and 6 weeks group compared to corresponding SCI groups ( < 0.05). Significant reduction in iron levels was observed in silibinin treated rats in 72 h and 6 weeks group ( < 0.05). Silibinin substantially suppressed TfR1 levels in 24 h and 72 h groups ( < 0.05). Significant difference among recovery capacities was observed as follows: Silibinin > DFO > SCI ( < 0.05).
CONCLUSION
Impact of silibinin on iron metabolism and lipid peroxidation, both of which are features of ferroptosis, may contribute to therapeutic activity. Within this context, our findings posit silibinin as a potential therapeutic candidate possessing antiferroptotic properties in SCI model. Therapeutic agents capable of effectively and safely mitigating ferroptotic cell death hold the potential to be critical points of future clinical investigations.
PubMed: 38957164
DOI: 10.1002/jsp2.1344 -
Journal of the American Chemical Society Jul 2024The binding affinity determination of protein-ligand complexes is a cornerstone of drug design. State-of-the-art techniques are limited by lengthy and expensive...
The binding affinity determination of protein-ligand complexes is a cornerstone of drug design. State-of-the-art techniques are limited by lengthy and expensive processes. Building upon our recently introduced novel screening method utilizing photochemically induced dynamic nuclear polarization (photo-CIDNP) NMR, we provide the methodological framework to determine binding affinities within 5-15 min using 0.1 mg of protein. The accuracy of our method is demonstrated for the affinity constants of peptides binding to a PDZ domain and fragment ligands binding to the protein PIN1. The method can also be extended to measure the affinity of nonphoto-CIDNP-polarizable ligands in competition binding experiments. Finally, we demonstrate a strong correlation between the ligand-reduced signals in photo-CIDNP-based NMR fragment screening and the well-established saturation transfer difference (STD) NMR. Thus, our methodology measures protein-ligand affinities in the micro- to millimolar range in only a few minutes and informs on the binding epitope in a single-scan experiment, opening new avenues for early stage drug discovery approaches.
Topics: Ligands; Nuclear Magnetic Resonance, Biomolecular; Protein Binding; Photochemical Processes; NIMA-Interacting Peptidylprolyl Isomerase; Proteins; Peptides; Magnetic Resonance Spectroscopy; Models, Molecular; PDZ Domains
PubMed: 38957136
DOI: 10.1021/jacs.4c04000 -
Journal of Food Science Jul 2024Previously, we showed that water extract (soymilk, except pH was increased to 8 from 6.5) of whole soybean could be used directly as a raw material for producing edible...
Previously, we showed that water extract (soymilk, except pH was increased to 8 from 6.5) of whole soybean could be used directly as a raw material for producing edible soy films by deposition of the film-forming solution (soy extract with enhancers). However, the strength of such soy films needed improvement because they were weak. The purpose of this study was to investigate how transglutaminase (TG) cross-linking reactions and film enhancers, including pectin (low- and high-methoxyl pectin), whey protein isolate (WPI), and soy protein isolate (SPI), improve the physical properties of soy films. Soy films prepared with TG had tensile strength (TS) of 3.01 MPa and puncture strength (PS) of 0.78 MPa, which were higher by as much as 51% and 30% than that of soy films without TG treatment, respectively. Pectin showed significant effects on the mechanical properties of TG-added soy films in terms of TS, PS, and % elongation. On the other hand, only TS and PS were increased by the addition of WPI or SPI. Heat curing had a significant effect on soy film's physical properties. TG treatment significantly reduced film solubility when soaked in water and various levels of acid (vinegar) and base (baking soda) solutions. Under the experimental conditions of 35 unit TG and 28 min of reaction, the degrees of cross-linking were evidenced by the disappearance of individual protein subunits, except the basic subunit of glycinin, and the reduction of 21% of lysine residues of the proteins. HIGHLIGHTS: Edible soy films were made with transglutaminase and about 21% lysine cross-linked. The mechanical strength of soy films was increased by incorporating film enhancers. Transglutaminase enhanced the mechanical properties of soy films.
Topics: Transglutaminases; Pectins; Soybean Proteins; Tensile Strength; Solubility; Whey Proteins; Food Packaging; Cross-Linking Reagents; Glycine max; Edible Films; Hydrogen-Ion Concentration; Soy Milk
PubMed: 38957134
DOI: 10.1111/1750-3841.17107 -
Journal of Food Science Jul 2024Mushrooms have garnered significant attention for their nutritional composition and potential health benefits, including antioxidant, antihypertensive, and... (Review)
Review
Mushrooms have garnered significant attention for their nutritional composition and potential health benefits, including antioxidant, antihypertensive, and cholesterol-lowering properties. This review explores the nutritional composition of edible mushrooms, including their high protein content, essential amino acids, low fat, cholesterol levels, and bioactive compounds with medicinal value. Moreover, the study analyzes the microbiology of mushroom fermentation, focusing on the diverse microbial ecosystem involved in the transformation of raw mushrooms and the preservation methods employed to extend their shelf life. Special emphasis is placed on lactic acid fermentation as a cost-effective and efficient preservation technique. It involves controlling the growth of lactic acid bacteria to enhance the microbial stability and nutritional quality of mushrooms. Furthermore, the bioactivities of fermented mushrooms are elucidated, which are antioxidant, antimicrobial, anticancer, anti-glycemic, immune modulatory, and other biological activities. The mechanisms underlying these bioactivities are explored, emphasizing the role of fermented mushrooms in suppressing free radicals, enhancing antioxidant defenses, and modulating immune responses. Overall, this review provides comprehensive insights into the nutritional composition, microbiology, bioactivities, and underlying mechanisms of fermented mushrooms, highlighting their potential as functional foods with significant health-promoting properties.
Topics: Agaricales; Nutritive Value; Fermentation; Humans; Antioxidants; Fermented Foods; Functional Food
PubMed: 38957107
DOI: 10.1111/1750-3841.17172 -
Journal of Food Science Jul 2024The elucidation of the interaction mechanism between phospholipids and milk proteins within emulsions is pivotal for comprehending the properties of infant formula fat...
The elucidation of the interaction mechanism between phospholipids and milk proteins within emulsions is pivotal for comprehending the properties of infant formula fat globules. In this study, multispectral methods and molecular docking were employed to explore the relationship between phosphatidylcholine (PC) and whey protein isolate (WPI). Observations indicate that the binding constant, alongside thermodynamic parameters, diminishes as temperature ascends, hinting at a predominantly static quenching mechanism. Predominantly, van der Waals forces and hydrogen bonds constitute the core interactions between WPI and PC. This assertion is further substantiated by Fourier transform infrared spectroscopy, which verifies PC's influence on WPI's secondary structure. A detailed assessment of thermodynamic parameters coupled with molecular docking reveals that PC predominantly adheres to specific sites within α-lactalbumin, β-lactoglobulin, and bovine serum albumin, propelled by a synergy of hydrophobic interactions, hydrogen bonding, and van der Waals forces, with binding energies noted at -5.59, -6.71, and -7.85 kcal/mol, respectively. An increment in PC concentration is observed to amplify the emulsification properties of WPI whilst concurrently diminishing the zeta potential. This study establishes a theoretical foundation for applying the PC-WPI interaction mechanism in food.
Topics: Whey Proteins; Phosphatidylcholines; Molecular Docking Simulation; Spectroscopy, Fourier Transform Infrared; Hydrophobic and Hydrophilic Interactions; Thermodynamics; Hydrogen Bonding; Lactoglobulins; Emulsions; Lactalbumin; Serum Albumin, Bovine; Infant Formula
PubMed: 38957103
DOI: 10.1111/1750-3841.17175 -
Journal of Agricultural and Food... Jul 2024This study aimed to investigate the mechanisms by which dark septate endophytes (DSE) regulate salt tolerance and the accumulation of bioactive constituents in licorice....
This study aimed to investigate the mechanisms by which dark septate endophytes (DSE) regulate salt tolerance and the accumulation of bioactive constituents in licorice. First, the salt stress tolerance and resynthesis with the plant effect of isolated DSE from wild licorice were tested. Second, the performance of licorice inoculated with DSE, which had the best salt-tolerant and growth-promoting effects, was examined under salt stress. All isolated DSE showed salt tolerance and promoted plant growth, with D43 being the most effective. Under salt stress, D43 could promote growth, increase antioxidant enzyme activities, enhance glycyrrhizic acid accumulation, improve key enzyme activities in the glycyrrhizic acid synthesis pathway, and induce the expression of the key enzyme gene and salt tolerance gene of licorice. The structural equation model demonstrated that DSE alleviate the negative effects of salt stress through direct and indirect pathways. Variations in key enzyme activities, gene expression, and bioactive constituent concentration can be attributed to the effects of DSE. These results contribute to revealing the value of DSE for cultivating medicinal plants in saline soils.
Topics: Glycyrrhizic Acid; Glycyrrhiza; Endophytes; Salt Stress; Salt Tolerance; Ascomycota; Plant Proteins; Gene Expression Regulation, Plant
PubMed: 38957088
DOI: 10.1021/acs.jafc.4c00700