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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 -
Molecules (Basel, Switzerland) Jun 2024Peanut shells' adsorption performance in caffeine and triclosan removal was studied. Peanut shells were analyzed for their chemical composition, morphology, and surface...
Peanut shells' adsorption performance in caffeine and triclosan removal was studied. Peanut shells were analyzed for their chemical composition, morphology, and surface functional groups. Batch adsorption and fixed-bed column experiments were carried out with solutions containing 30 mg/L of caffeine and triclosan. The parameters examined included peanut shell particle size (120-150, 300-600, and 800-2000 µm), adsorbent dose (0.02-60 g/L), contact time (up to 180 min), bed height (4-8 cm), and hydraulic loading rate (2.0 and 4.0 m/m-day). After determining the optimal adsorption conditions, kinetics, isotherm, and breakthrough curve models were applied to analyze the experimental data. Peanut shells showed an irregular surface and consisted mainly of polysaccharides (around 70% lignin, cellulose, and hemicellulose), with a specific surface area of 1.7 m/g and a pore volume of 0.005 cm/g. The highest removal efficiencies for caffeine (85.6 ± 1.4%) and triclosan (89.3 ± 1.5%) were achieved using the smallest particles and 10.0 and 0.1 g/L doses over 180 and 45 min, respectively. Triclosan showed easier removal compared to caffeine due to its higher lipophilic character. The pseudo-second-order kinetics model provided the best fit with the experimental data, suggesting a chemisorption process between caffeine/triclosan and the adsorbent. Equilibrium data were well-described by the Sips model, with maximum adsorption capacities of 3.3 mg/g and 289.3 mg/g for caffeine and triclosan, respectively. In fixed-bed column adsorption tests, particle size significantly influenced efficiency and hydraulic behavior, with 120-150 µm particles exhibiting the highest adsorption capacity for caffeine (0.72 mg/g) and triclosan (143.44 mg/g), albeit with clogging issues. The experimental data also showed good agreement with the Bohart-Adams, Thomas, and Yoon-Nelson models. Therefore, the findings of this study highlight not only the effective capability of peanut shells to remove caffeine and triclosan but also their versatility as a promising option for water treatment and sanitation applications in different contexts.
Topics: Caffeine; Triclosan; Arachis; Adsorption; Kinetics; Water Pollutants, Chemical; Particle Size; Water Purification
PubMed: 38930987
DOI: 10.3390/molecules29122923 -
Medicina (Kaunas, Lithuania) Jun 2024Colorectal cancer is a major global health concern, with a significant increase in morbidity and mortality rates associated with metastatic stages. This study...
Influence of Biomarkers on Mortality among Patients with Hepatic Metastasis of Colorectal Cancer Treated with FOLFOX/CAPOX and FOLFIRI/CAPIRI, Including Anti-EGFR and Anti-VEGF Therapies.
Colorectal cancer is a major global health concern, with a significant increase in morbidity and mortality rates associated with metastatic stages. This study investigates the prognostic significance of various clinical and laboratory parameters in patients with metastatic CRC. A retrospective cohort of 188 CRC patients with hepatic metastasis from the OncoHelp Association in Timisoara was analyzed from January 2016 to March 2023. Data on demographics, clinical characteristics, and biomarkers, such as lymphocyte counts, as well as various inflammation indices, were examined. Statistical analyses included univariate and multivariate logistic regression, Kaplan-Meier survival analysis, and ROC curve assessments. Our findings indicate significant associations between survival outcomes and several biomarkers. Higher BMI and lymphocyte counts were linked with better survival rates, while higher values of Neutrophil-Hemoglobin-Lymphocyte (NHL) score, Neutrophil-Lymphocyte Ratio (NLR), Platelet-Lymphocyte Ratio (PLR), and Systemic Immune-Inflammation Index (SII) were predictors of poorer outcomes. Notably, the presence of hepatic metastasis at diagnosis was a critical factor, significantly reducing overall survival. The study has expanded the current understanding of prognostic factors in CRC, advocating for a multi-dimensional approach to prognostic evaluations. This approach should consider not only the traditional metrics such as tumor stage and histological grading but also incorporate a broader spectrum of biomarkers. Future studies should aim to validate these findings and explore the integration of these biomarkers into routine clinical practice, enhancing the precision of prognostic assessments and ultimately guiding more personalized treatment strategies for CRC patients.
Topics: Humans; Colorectal Neoplasms; Male; Female; Middle Aged; Liver Neoplasms; Retrospective Studies; Aged; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Leucovorin; Organoplatinum Compounds; Camptothecin; Adult; Biomarkers, Tumor; Prognosis; ErbB Receptors; Kaplan-Meier Estimate
PubMed: 38929620
DOI: 10.3390/medicina60061003 -
Medicina (Kaunas, Lithuania) Jun 2024: Although statins are recommended for secondary prevention of acute ischemic stroke, some population-based studies and clinical evidence suggest that they might be used...
: Although statins are recommended for secondary prevention of acute ischemic stroke, some population-based studies and clinical evidence suggest that they might be used with an increased risk of intracranial hemorrhage. In this nested case-control study, we used Taiwan's nationwide universal health insurance database to investigate the possible association between statin therapy prescribed to acute ischemic stroke patients and their risk of subsequent intracerebral hemorrhage and all-cause mortality in Taiwan. : All data were retrospectively obtained from Taiwan's National Health Insurance Research Database. Acute ischemic stroke patients were divided into a cohort receiving statin pharmacotherapy and a control cohort not receiving statin pharmacotherapy. A 1:1 matching for age, gender, and index day, and propensity score matching was conducted, producing 39,366 cases and 39,366 controls. The primary outcomes were long-term subsequent intracerebral hemorrhage and all-cause mortality. The competing risk between subsequent intracerebral hemorrhage and all-cause mortality was estimated using the Fine and Gray regression hazards model. : Patients receiving statin pharmacotherapy after an acute ischemic stroke had a significantly lower risk of subsequent intracerebral hemorrhage ( < 0.0001) and lower all-cause mortality rates ( < 0.0001). Low, moderate, and high dosages of statin were associated with significantly decreased risks for subsequent intracerebral hemorrhage (adjusted sHRs 0.82, 0.74, 0.53) and all-cause mortality (adjusted sHRs 0.75, 0.74, 0.74), respectively. : Statin pharmacotherapy was found to safely and effectively reduce the risk of subsequent intracerebral hemorrhage and all-cause mortality in acute ischemic stroke patients in Taiwan.
Topics: Humans; Taiwan; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Female; Male; Cerebral Hemorrhage; Aged; Middle Aged; Case-Control Studies; Retrospective Studies; Ischemic Stroke; Big Data; Aged, 80 and over; Data Analysis; Risk Factors; Propensity Score
PubMed: 38929556
DOI: 10.3390/medicina60060939 -
Medicina (Kaunas, Lithuania) May 2024The ongoing concern of the medical profession regarding chronic medication is related to increasing patient adherence and compliance to treatment and reducing...
The ongoing concern of the medical profession regarding chronic medication is related to increasing patient adherence and compliance to treatment and reducing medication side effects. In this respect, drugs represented by fixed-dose combinations of active substances within the same tablet have emerged. Such a principle can be extrapolated by following the potential beneficial effects that a chronic medication can have on chronic pathologies affecting different systems. The study included 48 female Albino Wistar rats, aged 16-18 months, which were divided into two groups: ovariectomized and non-ovariectomized rats. One batch of 12 non-ovariectomized rats received no treatment, becoming a control batch (NOVX-M). The ovariectomized (OVX) group was divided into 3 batches of 12 rats each: no treatment, control (OVX-M), fenofibrate-treated (OVX-F) and statin-treated (OVX-S) rats. At 12 weeks after ovariectomy, a femoral fracture occurred in the right hind limb of all animals included in the experiment To reveal the changes, at intervals of 2, 4, 6 and 8 weeks post-fracture, the proximal part of the femur was evaluated by NMR diffusiometry, which allows random motion of proton molecules expressed by self-diffusion coefficients, , thus allowing analysis of the size and complexity of microscopic order cavities within biological structures, such as pores inside bones. The effects of hypolipidemic medication in the absence of estrogen were evidenced, proving the beneficial effect that fenofibrate can have in preserving healthy tissue exposed to osteoporotic risk during the menopausal period. The effects of lipid-lowering medication are also influenced by the duration of administration. Osteoporosis and heart disease are two chronic pathologies that affect mainly female population in the second half of life, and proving the dual therapeutic potential of lipid-lowering medication may also have positive effects by increasing adherence and compliance to treatment.
Topics: Animals; Rats, Wistar; Female; Rats; Ovariectomy; Hypolipidemic Agents; Magnetic Resonance Spectroscopy; Fenofibrate; Disease Models, Animal; Femur; Bone and Bones
PubMed: 38929535
DOI: 10.3390/medicina60060918 -
Medicina (Kaunas, Lithuania) May 2024: Gemcitabine has been used to treat various solid cancers, including, since 1997, metastatic pancreatic cancer. Here, we developed an HPLC-UV method to determine serum...
: Gemcitabine has been used to treat various solid cancers, including, since 1997, metastatic pancreatic cancer. Here, we developed an HPLC-UV method to determine serum gemcitabine levels and use it in pharmacokinetic studies. : The analysis was performed after a single protein precipitation step on a reversed-phase column, isocratically eluted with sodium phosphate buffer and methanol. For the pharmacokinetic study, NOD/SCID mice received a single dose of gemcitabine at 100 mg/kg by either subcutaneous (SC) or intraperitoneal (IP) administration. Blood samples were collected at 5, 15, and 30 min and 1, 2, 4, and 6 h after the administration of gemcitabine for further analysis. : The duration of the analysis was ~12.5 min. The calibration curve was linear (r = 0.999) over the range of 1-400 μM. The mean recovery of GEM was 96.53% and the limit of detection was 0.166 μΜ. T, Tmax, Cmax, AUC, and clearance were 64.49 min, 5.00 min, 264.88 μmol/L, 9351.95 μmol/L*min, and 0.0103(mg)/(μmol/L)/min, respectively, for the SC administration. The corresponding values for the IP administration were 59.34 min, 5.00 min, 300.73 μmol/L, 8981.35 μmol/L*min and 0.0108(mg)/(μmol/L)/min (not statistically different from the SC administration). : A simple, valid, sensitive, and inexpensive method for the measurement of gemcitabine in serum has been developed. This method may be useful for monitoring gemcitabine levels in cancer patients as part of therapeutic drug monitoring.
Topics: Deoxycytidine; Gemcitabine; Chromatography, High Pressure Liquid; Animals; Mice; Reproducibility of Results; Mice, SCID; Antimetabolites, Antineoplastic; Mice, Inbred NOD
PubMed: 38929481
DOI: 10.3390/medicina60060864 -
International Journal of Molecular... Jun 2024Etiological factors involved in myelodysplastic syndrome (MDS) include immunologic, oxidative stress and inflammatory factors, among others, and these are targets for...
Etiological factors involved in myelodysplastic syndrome (MDS) include immunologic, oxidative stress and inflammatory factors, among others, and these are targets for microRNAs (miRNs). Here, we evaluated whether some miRNs may affect tumor development comparing untreated and 5-azacitidine (5-AZA) MDS-treated patients. Peripheral blood samples were collected from 20 controls and 24 MDS patients, and selected miRNs related to redox balance and inflammation (inflamma-miRs), including miR-18a, miR-21, miR-34a and miR-146a, were isolated and measured by quantitative real-time polymerase chain reaction (qRTPCR). A differential expression profile of miRNs was detected in untreated MDS patients and the 5-AZA group. Inflammation increases miRNs and, specifically, miR-18a, miR-21 and miR-34a were significantly overexpressed in untreated MDS, compared to controls. However, we did not observe any miRN profile alteration during the progression of the disease. On the other hand, 5-AZA treatment tends to restore miRN expression levels. Relating to prognostic risk factors, high-risk MDS groups (high Revised International Prognostic Scoring System (IPSS-R), high cytogenetic risk, high molecular risk (HMR) mutations) tended to be related with higher expression levels of miR-18a and miR-34a. Higher miRN expression is correlated with lower glutathione peroxidase activity, while they are related with a higher profile of pro-inflammatory cytokines (IL-2, IL-6, IL-8, TNF-α). Although our study was limited by the low number of MDS patients included, we identified miRN deregulation involved in MDS development that could regulate redox sensors and inflammatory responses. Finally, 5-AZA treatment is related with lower miRN expression levels in MDS patients.
Topics: Humans; Myelodysplastic Syndromes; MicroRNAs; Male; Female; Middle Aged; Aged; Inflammation; Azacitidine; Adult; Aged, 80 and over; Oxidative Stress; Case-Control Studies; Prognosis
PubMed: 38928489
DOI: 10.3390/ijms25126784 -
International Journal of Molecular... Jun 2024Chitosan is a natural polymer with numerous biomedical applications. The cellular activity of chitosan has been studied in various types of cancer, including melanoma,...
Chitosan is a natural polymer with numerous biomedical applications. The cellular activity of chitosan has been studied in various types of cancer, including melanoma, and indicates that these molecules can open new perspectives on antiproliferative action and anticancer therapy. This study analyzes how different chitosan conformations, such as α-chitosan (CH) or β-oligochitosan (CO), with various degrees of deacetylation (DDA) and molar mass (MM), both in different concentrations and in CH-CO mixtures, influence the cellular processes of SK-MEL-28 melanocytes, to estimate the reactivity of these cells to the applied treatments. The in vitro evaluation was carried out, aiming at the cellular metabolism (MTT assay), cellular morphology, and chitinase-like glycoprotein YKL-40 expression. The in vitro effect of the CH-CO mixture application on melanocytes is obvious at low concentrations of α-chitosan/β-oligochitosan (1:2 ratio), with the cell's response supporting the hypothesis that β-oligo-chitosan amplifies the effect. This oligochitosan mixture, favored by the β conformation and its small size, penetrates faster into the cells, being more reactive when interacting with some cellular components. Morphological effects expressed by the loss of cell adhesion and the depletion of YKL-40 synthesis are significant responses of melanocytes. β-oligochitosan (1.5 kDa) induces an extension of cytophysiological effects and limits the cell viability compared to α-chitosan (400-900 kDa). Statistical analysis using multivariate techniques showed differences between the CH samples and CH-CO mixtures.
Topics: Chitosan; Melanocytes; Humans; Chitin; Oligosaccharides; Chitinase-3-Like Protein 1; Cell Survival; Cell Proliferation; Cell Line, Tumor; Melanoma
PubMed: 38928474
DOI: 10.3390/ijms25126768 -
International Journal of Molecular... Jun 2024Long non-coding RNAs (lncRNAs) are nucleotide sequences that participate in different biological processes and are associated with different pathologies, including...
Long non-coding RNAs (lncRNAs) are nucleotide sequences that participate in different biological processes and are associated with different pathologies, including cancer. Long intergenic non-protein-coding RNA 662 (LINC00662) has been reported to be involved in different cancers, including colorectal, prostate, and breast cancer. However, its role in gallbladder cancer has not yet been described. In this article, we hypothesize that LINC00662 has an important role in the acquisition of aggressiveness traits such as a stem-like phenotype, invasion, and chemoresistance in gallbladder cancer. Here, we show that LINC00662 is associated with larger tumor size and lymph node metastasis in patients with gallbladder cancer. Furthermore, we show that the overexpression of LINC00662 promotes an increase in CD133/CD44 cell populations and the expression of stemness-associated genes. LINC00662 promotes greater invasive capacity and the expression of genes associated with epithelial-mesenchymal transition. In addition, the expression of LINC00662 promotes resistance to cisplatin and 5-fluorouracil, associated with increased expression of chemoresistance-related ATP-binding cassette (ABC) transporters in gallbladder cancer (GBC) cell lines. Finally, we show that the mechanism by which LINC00662 exerts its function is through a decrease in microRNA 335-5p (miR-335-5p) and an increase in octamer-binding transcription factor 4 (OCT4) in GBC cells. Thus, our data allow us to propose LINC00662 as a biomarker of poor prognosis and a potential therapeutic target for patients with GBC.
Topics: Humans; Gallbladder Neoplasms; MicroRNAs; RNA, Long Noncoding; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Octamer Transcription Factor-3; Female; Epithelial-Mesenchymal Transition; Drug Resistance, Neoplasm; Male; Neoplasm Invasiveness; Cisplatin; Middle Aged; Neoplastic Stem Cells; Fluorouracil; Lymphatic Metastasis
PubMed: 38928444
DOI: 10.3390/ijms25126740 -
International Journal of Molecular... Jun 2024Colorectal cancer (CRC) is a global health concern, necessitating adjuvant chemotherapy post-curative surgery to mitigate recurrence and enhance survival, particularly...
Colorectal cancer (CRC) is a global health concern, necessitating adjuvant chemotherapy post-curative surgery to mitigate recurrence and enhance survival, particularly in intermediate-stage patients. However, existing therapeutic disparities highlight the need for biomarker-guided adjuvant chemotherapy to achieve better CRC inhibition. This study explores the molecular mechanisms underlying the inhibition of CRC through a genome-wide association study (GWAS) focused on 5-fluorouracil (5-FU)-based adjuvant therapy in intermediate-stage CRC patients, a domain previously unexplored. We retrospectively included 226 intermediate-stage CRC patients undergoing surgical resection followed by 5-FU-based adjuvant chemotherapy. The exploration cohort comprised 31 patients, and the validation cohort included 195 individuals. Genotyping was carried out using either Axiom Genome-Wide TWB 2.0 Array Plate-based or polymerase chain reaction-based methods on genomic DNA derived from collected tissue samples. Statistical analyses involved descriptive statistics, Kaplan-Meier analyses, and Cox proportional hazard analyses. From the GWAS, potential genetic predictors, -rs62139523 and -rs10786578 genotypes, of 5-FU-based adjuvant therapy following surgery in intermediate-stage CRC patients were identified. Validation in a larger cohort of 195 patients emphasized the predictive significance of -rs62139523 genotypes, especially the "A/G" genotype, for improved overall and progression-free survival. This predictive association remained robust across various subgroups, with exceptions for specific demographic and clinical parameters such as age < 58 years old, CEA ≤ 2.5 ng/mL, tumor diameter > 44.0 mm, and tumor-free margin ≥ 50 mm. This study identifies that the -rs62139523 "A/G" genotype modulates therapeutic outcomes, establishing it as a promising biomarker for predicting favorable responses to 5-FU-based adjuvant chemotherapy in intermediate-stage CRC patients, although further investigations are needed to detail these mechanisms.
Topics: Humans; Colorectal Neoplasms; Fluorouracil; Chemotherapy, Adjuvant; Male; Female; Polymorphism, Single Nucleotide; Middle Aged; Aged; Genome-Wide Association Study; Biomarkers, Tumor; Retrospective Studies; Adult; Genotype; N-Acetylgalactosaminyltransferases; Prognosis; Treatment Outcome
PubMed: 38928347
DOI: 10.3390/ijms25126642