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Nutrients Jun 2024Choline is an essential nutrient, with high requirements during fetal and postnatal growth. Tissue concentrations of total choline are tightly regulated, requiring an... (Review)
Review
Choline is an essential nutrient, with high requirements during fetal and postnatal growth. Tissue concentrations of total choline are tightly regulated, requiring an increase in its pool size proportional to growth. Phosphatidylcholine and sphingomyelin, containing a choline headgroup, are constitutive membrane phospholipids, accounting for >85% of total choline, indicating that choline requirements are particularly high during growth. Daily phosphatidylcholine secretion via bile for lipid digestion and very low-density lipoproteins for plasma transport of arachidonic and docosahexaenoic acid to other organs exceed 50% of its hepatic pool. Moreover, phosphatidylcholine is required for converting pro-apoptotic ceramides to sphingomyelin, while choline is the source of betaine as a methyl donor for creatine synthesis, DNA methylation/repair and kidney function. Interrupted choline supply, as during current total parenteral nutrition (TPN), causes a rapid drop in plasma choline concentration and accumulating deficit. The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) defined choline as critical to all infants requiring TPN, claiming its inclusion in parenteral feeding regimes. We performed a systematic literature search in Pubmed with the terms "choline" and "parenteral nutrition", resulting in 47 relevant publications. Their results, together with cross-references, are discussed. While studies on parenteral choline administration in neonates and older children are lacking, preclinical and observational studies, as well as small randomized controlled trials in adults, suggest choline deficiency as a major contributor to acute and chronic TPN-associated liver disease, and the safety and efficacy of parenteral choline administration for its prevention. Hence, we call for choline formulations suitable to be added to TPN solutions and clinical trials to study their efficacy, particularly in growing children including preterm infants.
Topics: Choline; Humans; Dietary Supplements; Parenteral Nutrition; Infant, Newborn; Infant; Choline Deficiency; Child; Parenteral Nutrition, Total; Child, Preschool
PubMed: 38931230
DOI: 10.3390/nu16121873 -
Nutrients Jun 2024Patients with chronic kidney disease (CKD) suffer disproportionately from a high burden of cardiovascular disease, which, despite recent scientific advances, remains... (Review)
Review
Patients with chronic kidney disease (CKD) suffer disproportionately from a high burden of cardiovascular disease, which, despite recent scientific advances, remains partly understood. Vascular calcification (VC) is the result of an ongoing process of misplaced calcium in the inner and medial layers of the arteries, which has emerged as a critical contributor to cardiovascular events in CKD. Beyond its established role in blood clotting and bone health, vitamin K appears crucial in regulating VC via vitamin K-dependent proteins (VKDPs). Among these, the matrix Gla protein (MGP) serves as both a potent inhibitor of VC and a valuable biomarker (in its inactive form) for reflecting circulating vitamin K levels. CKD patients, especially in advanced stages, often present with vitamin K deficiency due to dietary restrictions, medications, and impaired intestinal absorption in the uremic environment. Epidemiological studies confirm a strong association between vitamin K levels, inactive MGP, and increased CVD risk across CKD stages. Based on the promising results of pre-clinical data, an increasing number of clinical trials have investigated the potential benefits of vitamin K supplementation to prevent, delay, or even reverse VC, but the results have remained inconsistent.
Topics: Humans; Vascular Calcification; Vitamin K; Renal Insufficiency, Chronic; Matrix Gla Protein; Vitamin K Deficiency; Extracellular Matrix Proteins; Calcium-Binding Proteins; Dietary Supplements; Cardiovascular Diseases; Biomarkers
PubMed: 38931153
DOI: 10.3390/nu16121798 -
Molecules (Basel, Switzerland) Jun 2024Type 2 diabetes mellitus (T2DM), a multifactorial and complicated metabolic disorder, is a growing public health problem. Numerous studies have indicated that bioactive... (Review)
Review
Type 2 diabetes mellitus (T2DM), a multifactorial and complicated metabolic disorder, is a growing public health problem. Numerous studies have indicated that bioactive compounds from herbal medicine have beneficial effects on T2DM prevention and treatment, owing to their numerous biological properties. Curcumin, the major curcuminoid of turmeric, is one of the most studied bioactive components of herbal supplements, and has a variety of biological activities. Clinical trials and preclinical research have recently produced compelling data to demonstrate the crucial functions of curcumin against T2DM via several routes. Accordingly, this review systematically summarizes the antidiabetic activity of curcumin, along with various mechanisms. Results showed that effectiveness of curcumin on T2DM is due to it being anti-inflammatory, anti-oxidant, antihyperglycemic, anti-apoptotic, and antihyperlipidemic, among other activities. In light of these results, curcumin may be a promising prevention/treatment choice for T2DM.
Topics: Curcumin; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Animals; Antioxidants; Anti-Inflammatory Agents
PubMed: 38930998
DOI: 10.3390/molecules29122934 -
Molecules (Basel, Switzerland) Jun 2024The epidermal growth factor receptor (EGFR) is a pivotal target in cancer therapy due to its significance within the tyrosine kinase family. EGFR inhibitors like AG-1478...
The epidermal growth factor receptor (EGFR) is a pivotal target in cancer therapy due to its significance within the tyrosine kinase family. EGFR inhibitors like AG-1478 and PD153035, featuring a 4-anilinoquinazoline moiety, have garnered global attention for their potent therapeutic activities. While pre-clinical studies have highlighted the significant impact of halogen substitution at the C3'-anilino position on drug potency, the underlying mechanism remains unclear. This study investigates the influence of halogen substitution (X = H, F, Cl, Br, I) on the structure, properties, and spectroscopy of halogen-substituted 4-anilinoquinazoline tyrosine kinase inhibitors (TKIs) using time-dependent density functional methods (TD-DFT) with the B3LYP functional. Our calculations revealed that halogen substitution did not induce significant changes in the three-dimensional conformation of the TKIs but led to noticeable alterations in electronic properties, such as dipole moment and spatial extent, impacting interactions at the EGFR binding site. The UV-visible spectra show that more potent TKI-X compounds typically have shorter wavelengths, with bromine's peak wavelength at 326.71 nm and hydrogen, with the lowest IC50 nM, shifting its lambda max to 333.17 nm, indicating a correlation between potency and spectral characteristics. Further analysis of the four lowest-lying conformers of each TKI-X, along with their crystal structures from the EGFR database, confirms that the most potent conformer is often not the global minimum structure but one of the low-lying conformers. The more potent TKI-Cl and TKI-Br exhibit larger deviations (RMSD > 0.65 Å) from their global minimum structures compared to other TKI-X (RMSD < 0.15 Å), indicating that potency is associated with greater flexibility. Dipole moments of TKI-X correlate with drug potency (ln(IC50 nM)), with TKI-Cl and TKI-Br showing significantly higher dipole moments (>8.0 Debye) in both their global minimum and crystal structures. Additionally, optical spectral shifts correlate with potency, as TKI-Cl and TKI-Br exhibit blue shifts from their global minimum structures, in contrast to other TKI-X. This suggests that optical reporting can effectively probe drug potency and conformation changes.
Topics: ErbB Receptors; Quinazolines; Protein Kinase Inhibitors; Halogens; Aniline Compounds; Humans; Binding Sites; Models, Molecular; Structure-Activity Relationship
PubMed: 38930865
DOI: 10.3390/molecules29122800 -
Molecules (Basel, Switzerland) Jun 2024Our hypothesis that controlled ozone applications interfere with the redox balance of a biological organism (first published in 1998 with a preclinical trial on... (Review)
Review
Our hypothesis that controlled ozone applications interfere with the redox balance of a biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl intoxication) has been verified over the past two decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes and type 2 diabetes, and in the prevention of intoxications. Low-dose ozone acts as a redox bioregulator: the restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase in the antioxidant repair markers, here mainly shown as a glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, and relevant data are displayed, evaluated and comprehensively discussed: the repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone-treated groups and depending on the indication, the stress markers are simultaneously reduced, and the redox system regains its balance.
Topics: Oxidative Stress; Ozone; Oxidation-Reduction; Humans; Mitochondria; Reactive Oxygen Species; Animals; Antioxidants; Biomarkers
PubMed: 38930804
DOI: 10.3390/molecules29122738 -
Microorganisms Jun 2024The second leading cause of death in children under five years old is diarrheal disease. Probiotics, specifically bifidobacteria, have been associated with a reduction... (Review)
Review
The second leading cause of death in children under five years old is diarrheal disease. Probiotics, specifically bifidobacteria, have been associated with a reduction in the number of diarrhea episodes and their severity in babies. In this paper, we summarize the preclinical and clinical evidence of the efficacy of subsp. IM1 against various gastrointestinal pathogens using in vitro models, animal models, and clinical studies carried out in our laboratory. The preclinical data demonstrate that IM1 effectively inhibits rotavirus replication (by up to 36.05%) in MA-104 and HT-29 cells and from infection (up to 48.50%) through the production of an 11-amino-acid peptide. IM1 displays the capability to displace pathogens from enterocytes, particularly and , and to reduce the adhesion to the HT29 cells of and . In animal models, the IM1 strain exhibits in vivo protection against rotavirus and improves the clinical symptomatology of bacterial gastroenteritis. A clinical study involving infants under 3 months of age revealed that IM1 reduced episodes of diarrhea, proving to be safe, well tolerated, and associated with a lower prevalence of constipation. IM1 emerges as an effective probiotic, diminishing episodes of diarrhea caused by gastrointestinal pathogens.
PubMed: 38930565
DOI: 10.3390/microorganisms12061183 -
Microorganisms Jun 2024Glucocorticoids may be given prior to major orthopedic surgery to decrease postoperative nausea, vomiting, and pain. Additionally, many orthopedic patients may be on...
Glucocorticoids may be given prior to major orthopedic surgery to decrease postoperative nausea, vomiting, and pain. Additionally, many orthopedic patients may be on chronic glucocorticoid therapy. The aim of our study was to investigate whether glucocorticoid administration influences Orthopedic-Device-Related Infection (ODRI) in a rat model. Screws colonized with were implanted in the tibia of skeletally mature female Wistar rats. The treated groups received either a single shot of dexamethasone in a short-term risk study, or a daily dose of dexamethasone in a longer-term interference study. In both phases, bone changes in the vicinity of the implant were monitored with microCT. There were no statistically significant differences in bacteriological outcome with or without dexamethasone. In the interference study, new bone formation was statistically higher in the dexamethasone-treated group ( = 0.0005) as revealed by CT and histopathological analysis, although with relatively low direct osseointegration of the implant. In conclusion, dexamethasone does not increase the risk of developing periprosthetic osteolysis or infection in a pre-clinical model of ODRI. Long-term administration of dexamethasone seemed to offer a benefit in terms of new bone formation around the implant, but with low osseointegration.
PubMed: 38930516
DOI: 10.3390/microorganisms12061134 -
Materials (Basel, Switzerland) Jun 2024In this study, the potential of silk fibroin biomaterials for enhancing wound healing is explored, focusing on their integration into a human 3D ex vivo wound model...
In this study, the potential of silk fibroin biomaterials for enhancing wound healing is explored, focusing on their integration into a human 3D ex vivo wound model derived from abdominoplasties. For this purpose, cast silk fibroin membranes and electrospun nonwoven matrices from silk cocoons were compared to untreated controls over 20 days. Keratinocyte behavior and wound healing were analyzed qualitatively and quantitatively by histomorphometric and immune histochemical methods (HE, Ki67, TUNEL). Findings reveal rapid keratinocyte proliferation on both silk fibroin membrane and nonwoven matrices, along with enhanced infiltration in the matrix, suggesting improved early wound closure. Silk fibroin membranes exhibited a significantly improved early regeneration, followed by nonwoven matrices ( < 0.05) compared to untreated wounds, resulting in the formation of multi-layered epidermal structures with complete regeneration. Overall, the materials demonstrated excellent biocompatibility, supporting cell activity with no signs of increased apoptosis or early degradation. These results underscore silk fibroin's potential in clinical wound care, particularly in tissue integration and re-epithelialization, offering valuable insights for advanced and-as a result of the electrospinning technique-individual wound care development. Furthermore, the use of an ex vivo wound model appears to be a viable option for pre-clinical testing.
PubMed: 38930373
DOI: 10.3390/ma17123004 -
Journal of Clinical Medicine Jun 2024: Congenital diaphragmatic hernia (CDH) is defined as organ protrusion from the abdominal to the thoracic cavity. The Hadlock formula is the most commonly used tool for...
: Congenital diaphragmatic hernia (CDH) is defined as organ protrusion from the abdominal to the thoracic cavity. The Hadlock formula is the most commonly used tool for calculating estimated fetal weight (EFW). The anatomical nature of CDH usually leads to underestimation of the abdominal circumference, resulting in underestimation of fetal weight. Accurate weight estimation is essential before birth for counselling, preparation before surgery and ECMO. The research is made to compare the accuracy of Hadlock's formula and Faschingbauer's formula for fetal weight estimation in CDH fetuses population. : In our study, we investigated differences between EFW and actual birthweight in 42 fetuses with CDH as compared to 80 healthy matched controls. EFW was calculated using the Hadlock formula and a recently introduced formula described by Faschingbauer et al., which was tailored for fetuses with CDH. Additionally, both of the formulas were adjusted for the interval between the ultrasound and delivery for both of the groups. : The majority of hernias were left-sided (92.8% vs. 7.2%). EFW adjusted for the interval between the ultrasound and delivery had the highest correlation with the actual birthweight in both, study group and controls. We compared the results for both tools and found the Hadlock formula to predict birthweight in CDH children with a 7.8 ± 5.5% error as compared to 7.9 ± 6.5% error for the Faschingbauer's formula. : The Hadlock formula adjusted for the interval between the ultrasound and delivery is a more precise method of calculating EFW in fetuses with CDH. Routine biometry scan using Hadlock's formula remains reliable for predicting birthweight.
PubMed: 38929920
DOI: 10.3390/jcm13123392 -
Journal of Personalized Medicine Jun 2024In this study, we evaluated the discharge status of patients with type 2 diabetes mellitus and SARS-CoV-2 infection, focusing on the inflammatory profile through...
In this study, we evaluated the discharge status of patients with type 2 diabetes mellitus and SARS-CoV-2 infection, focusing on the inflammatory profile through biomarkers such as procalcitonin, CRP, LDH, fibrinogen, ESR, and ferritin, as well as electrolyte levels and the prior diagnosis of diabetes or its identification at the time of hospitalization. We assessed parameters at discharge for 45 patients admitted to the Clinical Hospital "Gavril Curteanu" Oradea between 21 October 2021, and 31 December 2021, randomly selected, having as the main inclusion criteria the positive RT-PCR rapid antigen test for viral infection and the diagnosis of type 2 diabetes. At discharge, patients with type 2 diabetes registered significantly lower mean procalcitonin levels among those who survived compared to those who died from COVID-19. In our study, ferritin and hemoglobin values in individuals with type 2 diabetes were outside the reference range at discharge and correlated with severe or moderate forms of COVID-19 infection. Additionally, elevated ferritin levels at discharge were statistically associated with hypokalemia and elevated levels of ESR at discharge. Another strong statistically significant correlation was identified between high CRP levels at discharge, strongly associated ( < 0.001) with elevated LDH and fibrinogen levels in patients with type 2 diabetes and SARS-CoV-2 viral infection. The increase in CRP was inversely statistically associated with the tendency of serum potassium to decrease at discharge in patients with type 2 diabetes and COVID-19. Identifying type 2 diabetes metabolic pathology at the time of hospitalization for SARS-CoV-2 infection, compared to pre-infection diabetes diagnosis, did not significantly influence the laboratory parameter status at the time of discharge. At the discharge of patients with type 2 diabetes and viral infection with the novel coronavirus, procalcitonin was significantly reduced in those who survived COVID-19 infection, and disease severity was significantly correlated with hyperferritinemia and decreased hemoglobin at discharge. Hyperferritinemia in patients with type 2 diabetes and COVID-19 at discharge was associated with hypokalemia and persistent inflammation (quantified by ESR at discharge). The low number of erythrocytes at discharge is associated with maintaining inflammation at discharge (quantified by the ESR value).
PubMed: 38929867
DOI: 10.3390/jpm14060646