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Heliyon Jun 2024This study investigated the in vivo embryotoxicity, teratogenic potential, and additional effects of orthodontic acrylic resin as well as its components, utilizing...
OBJECTIVES
This study investigated the in vivo embryotoxicity, teratogenic potential, and additional effects of orthodontic acrylic resin as well as its components, utilizing zebrafish as a model organism. The research focused on morphological, cardiac, behavioral, and cognitive evaluations that were performed on embryos and larval-stage animals subjected to chronic exposure.
MATERIALS AND METHODS
Embryo and larval-stage zebrafish were categorized into five experimental groups, which were further subdivided into five subgroups. These subgroups included three specific doses for each tested substance, a control with the vehicle (0.1 % dimethyl sulfoxide in water), and an absolute control (water). Assessments were performed on day 5 post-fertilization, which included morphological, cardiac, behavioral, and cognitive evaluations. All experiments had a sample size of ten animals and were performed in triplicate. Survival and hatching rates were analyzed using the Kaplan-Meier test, while other measurements were assessed using one-way analysis of variance (ANOVA), followed by the Tukey post hoc test.
RESULTS
Statistically significant differences were observed between the control and treatment groups across all the tested substances for heart rate, cognitive responsiveness, and cellular apoptosis. However, survival, hatching rate, and other parameters exhibited no significant variation, except for the highest dose in the dibutyl phthalate group, which demonstrated a notable difference in survival.
CONCLUSIONS
Chronic exposure to acrylic resin and its components may be associated with decreased cognitive ability and cardiac rhythm, as well as an increase in the level of cellular apoptosis in zebrafish.
PubMed: 38952375
DOI: 10.1016/j.heliyon.2024.e32067 -
Clinical Epigenetics Jun 2024Epigenetic scores (EpiScores), reflecting DNA methylation (DNAm)-based surrogates for complex traits, have been developed for multiple circulating proteins. EpiScores...
BACKGROUND
Epigenetic scores (EpiScores), reflecting DNA methylation (DNAm)-based surrogates for complex traits, have been developed for multiple circulating proteins. EpiScores for pro-inflammatory proteins, such as C-reactive protein (DNAm CRP), are associated with brain health and cognition in adults and with inflammatory comorbidities of preterm birth in neonates. Social disadvantage can become embedded in child development through inflammation, and deprivation is overrepresented in preterm infants. We tested the hypotheses that preterm birth and socioeconomic status (SES) are associated with alterations in a set of EpiScores enriched for inflammation-associated proteins.
RESULTS
In total, 104 protein EpiScores were derived from saliva samples of 332 neonates born at gestational age (GA) 22.14 to 42.14 weeks. Saliva sampling was between 36.57 and 47.14 weeks. Forty-three (41%) EpiScores were associated with low GA at birth (standardised estimates |0.14 to 0.88|, Bonferroni-adjusted p-value < 8.3 × 10). These included EpiScores for chemokines, growth factors, proteins involved in neurogenesis and vascular development, cell membrane proteins and receptors, and other immune proteins. Three EpiScores were associated with SES, or the interaction between birth GA and SES: afamin, intercellular adhesion molecule 5, and hepatocyte growth factor-like protein (standardised estimates |0.06 to 0.13|, Bonferroni-adjusted p-value < 8.3 × 10). In a preterm subgroup (n = 217, median [range] GA 29.29 weeks [22.14 to 33.0 weeks]), SES-EpiScore associations did not remain statistically significant after adjustment for sepsis, bronchopulmonary dysplasia, necrotising enterocolitis, and histological chorioamnionitis.
CONCLUSIONS
Low birth GA is substantially associated with a set of EpiScores. The set was enriched for inflammatory proteins, providing new insights into immune dysregulation in preterm infants. SES had fewer associations with EpiScores; these tended to have small effect sizes and were not statistically significant after adjusting for inflammatory comorbidities. This suggests that inflammation is unlikely to be the primary axis through which SES becomes embedded in the development of preterm infants in the neonatal period.
Topics: Humans; Saliva; Female; Infant, Newborn; Gestational Age; Epigenesis, Genetic; Male; DNA Methylation; Premature Birth; Pregnancy; Infant, Premature; Social Class; Adult; Inflammation
PubMed: 38951914
DOI: 10.1186/s13148-024-01701-2 -
Discover Mental Health Jul 2024Ketamine, a pharmacological agent that acts as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, has garnered considerable interest because of its notable and... (Review)
Review
Ketamine, a pharmacological agent that acts as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, has garnered considerable interest because of its notable and expeditious antidepressant properties observed in individuals diagnosed with major depressive disorder (MDD) who exhibit resistance to conventional therapeutic interventions. A comprehensive and rigorous systematic review was undertaken to evaluate the prevalence of ketamine abuse undergoing ketamine treatment for depressive disorders. A comprehensive search was conducted across the electronic databases to identify pertinent studies published between 2021 and 2023. The present investigation incorporated a comprehensive range of studies encompassing the abuse or misuse of ketamine, including case reports, observational studies, and clinical trials. Data extraction and quality assessment were conducted in accordance with predetermined criteria. The findings of this systematic review demonstrate the importance of monitoring and addressing ketamine abuse in patients receiving ketamine treatment for depressive disorders like MDD. The wide range of reported prevalence rates highlights the need for standardized criteria and measures for defining and assessing ketamine abuse. This study presents a significant contribution to the field by introducing a novel screening questionnaire and assessment algorithm designed to identify and evaluate ketamine misuse among major depressive disorder (MDD) patients undergoing ketamine treatment. This innovative tool holds the potential to enhance clinical practice by providing healthcare professionals with a standardized approach to promptly detect and address ketamine misuse. The integration of this screening tool into routine care protocols can facilitate more effective monitoring and management of ketamine misuse in this population, ultimately leading to improved patient outcomes and safety.
PubMed: 38951348
DOI: 10.1007/s44192-024-00077-2 -
Scientific Reports Jul 2024Chalcones are intermediate products in the biosynthesis of flavonoids, which possess a wide range of biological properties, including antimicrobial and anticancer...
Chalcones are intermediate products in the biosynthesis of flavonoids, which possess a wide range of biological properties, including antimicrobial and anticancer activities. The introduction of a chlorine atom and the glucosyl moiety into their structure may increase their bioavailability, bioactivity, and pharmacological use. The combined chemical and biotechnological methods can be applied to obtain such compounds. Therefore, 2-chloro-2'-hydroxychalcone and 3-chloro-2'-hydroxychalcone were synthesized and biotransformed in cultures of two strains of filamentous fungi, i.e. Isaria fumosorosea KCH J2 and Beauveria bassiana KCH J1.5 to obtain their novel glycosylated derivatives. Pharmacokinetics, drug-likeness, and biological activity of them were predicted using cheminformatics tools. 2-Chloro-2'-hydroxychalcone, 3-chloro-2'-hydroxychalcone, their main glycosylation products, and 2'-hydrochychalcone were screened for antimicrobial activity against several microbial strains. The growth of Escherichia coli 10,536 was completely inhibited by chalcones with a chlorine atom and 3-chlorodihydrochalcone 2'-O-β-D-(4″-O-methyl)-glucopyranoside. The strain Pseudomonas aeruginosa DSM 939 was the most resistant to the action of the tested compounds. However, chalcone aglycones and glycosides with a chlorine atom almost completely inhibited the growth of bacteria Staphylococcus aureus DSM 799 and yeast Candida albicans DSM 1386. The tested compounds had different effects on lactic acid bacteria depending on the tested species. In general, chlorinated chalcones were more effective in the inhibition of the tested microbial strains than their unchlorinated counterparts and aglycones were a little more effective than their glycosides.
Topics: Chalcones; Chlorine; Anti-Infective Agents; Biotransformation; Microbial Sensitivity Tests; Beauveria; Fungi; Escherichia coli
PubMed: 38951205
DOI: 10.1038/s41598-024-65054-9 -
JPMA. the Journal of the Pakistan... Jun 2024To compare the effects of magnesium sulphate on the total dose of intravenous morphine consumption postoperatively following limb amputations along with rescue analgesia... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To compare the effects of magnesium sulphate on the total dose of intravenous morphine consumption postoperatively following limb amputations along with rescue analgesia requirement, pain scores and side effects.
METHODS
This prospective, triple-blinded, randomised controlled study was conducted from October 2021 to May 2022 at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised of patients scheduled for limb amputations. They were randomised into 2 equal groups. The anaesthesia protocol was uniform for all patients. Intervention group A was administered 30mg/kg loading dose and 10mg/kg/hr maintenance dose of magnesium sulphate intravenously, while patients in control group B received the same amount of plain isotonic saline. Morphine consumption, including that used for rescue analgesia and patient-controlled analgesia, was measured for 24 hours postoperatively. Numeric rating scale was used for the evaluation of postoperative pain in both groups at 15min, 1h, 2h, at discharge from the post-anaesthesia care unit and at 12h and 24h in the ward. Data was analysed using SPSS 23.
RESULTS
Of the 24 patients enrolled, the study was completed by 20(83.33%). There were 10(50%) patients in group A; 8(40%) males and 2(20%) females with mean age 24.8±14.14 years and mean surgery time 130.5±47.86 minutes. There were 10(50%) patients in group B; 8(40%) males and 2(20%) females with mean age 23.2±7.4 years and mean surgery time 117±23.85 minutes (p>0.05). Total morphine used over 24 hours in group A was 16±3.1 mg compared to 29.6±11.2 mg in group B (p<0.05). The time for first use of patient-controlled analgesia after arriving in the postanaesthesia care unit was significantly delayed in group A (72.2±24.95 minutes) compared to that in group B (25±26.68 minutes) (p<0.05). Pain scores were significantly higher in the group B at 15min compared to group A (p<0.05), but not at the rest of the time points (p>0.05).
CONCLUSIONS
Intravenous magnesium sulphate proved to be effective in lowering postoperative opioid requirement following limb amputations.
Topics: Humans; Pain, Postoperative; Magnesium Sulfate; Female; Male; Analgesics, Opioid; Adult; Morphine; Prospective Studies; Amputation, Surgical; Pain Measurement; Middle Aged; Analgesia, Patient-Controlled; Young Adult; Acute Pain
PubMed: 38948969
DOI: 10.47391/JPMA.9022 -
BioRxiv : the Preprint Server For... Jun 2024Conductive hydrogels have gained interest in biomedical applications and soft electronics. To tackle the challenge of ionic hydrogels falling short of desired mechanical...
Conductive hydrogels have gained interest in biomedical applications and soft electronics. To tackle the challenge of ionic hydrogels falling short of desired mechanical properties in previous studies, our investigation aimed to understand the pivotal structural factors that impact the conductivity and mechanical behavior of polyethylene glycol (PEG)-based hydrogels with ionic conductivity. Polyether urethane diacrylamide (PEUDAm), a functionalized long-chain macromer based on PEG, was used to synthesize hydrogels with ionic conductivity conferred by incorporating ions into the liquid phase of hydrogel. The impact of salt concentration, water content, temperature, and gel formation on both mechanical properties and conductivity was characterized to establish parameters for tuning hydrogel properties. To further expand the range of conductivity available in these ionic hydrogels, 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) was incorporated as a single copolymer network or double network configuration. As expected, conductivity in these ionic gels was primarily driven by ion diffusivity and charge density, which was dependent on hydrogel network formation and swelling. Copolymer network structure had minimal effect on the conductivity which was primarily driven by counter-ion equilibrium; however, the mechanical properties and equilibrium swelling was strongly dependent on network structure. The structure-property relationships elucidated here enables the rationale design of this new double network hydrogel to achieve target properties for a broad range of applications.
PubMed: 38948818
DOI: 10.1101/2024.06.17.599239 -
BioRxiv : the Preprint Server For... Jun 2024Transposase genes are ubiquitous in all domains of life and provide a rich reservoir for the evolution of novel protein functions. Here we report deep evolutionary links...
Transposase genes are ubiquitous in all domains of life and provide a rich reservoir for the evolution of novel protein functions. Here we report deep evolutionary links between bacterial IS110 transposases, which catalyze RNA-guided DNA recombination using bridge RNAs, and archaeal/eukaryotic Nop5-family proteins, which promote RNA-guided RNA 2'-O-methylation using C/D-box snoRNAs. Based on conservation in the protein primary sequence, domain architecture, and three-dimensional structure, as well as common architectural features of the non-coding RNA components, we propose that programmable RNA modification emerged via exaptation of components derived from IS110-like transposons. Alongside recent studies highlighting the origins of CRISPR-Cas9 and Cas12 in IS605-family transposons, these findings underscore how recurrent domestication events of transposable elements gave rise to complex RNA-guided biological mechanisms.
PubMed: 38948817
DOI: 10.1101/2024.06.21.599552 -
BioRxiv : the Preprint Server For... Jun 2024Beckwith-Wiedemann Syndrome (BWS) is an epigenetic overgrowth syndrome caused by methylation changes in the human 11p15 chromosomal locus. Patients with BWS exhibit...
Beckwith-Wiedemann Syndrome (BWS) is an epigenetic overgrowth syndrome caused by methylation changes in the human 11p15 chromosomal locus. Patients with BWS exhibit tissue overgrowth, as well as an increased risk of childhood neoplasms in the liver and kidney. To understand the impact of these 11p15 changes, specifically in the liver, we performed single-nucleus RNA sequencing (snRNA-seq) and single-nucleus assay for transposase-accessible chromatin with sequencing (snATAC-seq) to generate paired, cell-type-specific transcriptional and chromatin accessibility profiles of both BWS-liver and nonBWS-liver nontumorous tissue. Our integrated RNA+ATACseq multiomic approach uncovered hepatocyte-specific enrichment and activation of the peroxisome proliferator-activated receptor α (PPARA) - a liver metabolic regulator. To confirm our findings, we utilized a BWS-induced pluripotent stem cell (iPSC) model, where cells were differentiated into hepatocytes. Our data demonstrates the dysregulation of lipid metabolism in BWS-liver, which coincided with observed upregulation of PPARA during hepatocyte differentiation. BWS liver cells exhibited decreased neutral lipids and increased fatty acid β-oxidation, relative to controls. We also observed increased reactive oxygen species (ROS) byproducts in the form of peroxidated lipids in BWS hepatocytes, which coincided with increased oxidative DNA damage. This study proposes a putative mechanism for overgrowth and cancer predisposition in BWS liver due to perturbed metabolism.
PubMed: 38948745
DOI: 10.1101/2024.06.14.599077 -
BioRxiv : the Preprint Server For... Jun 2024Primary hypertension in childhood tracks into adulthood and may be associated with increased cardiovascular risk. Studies conducted in children and adolescents provide...
BACKGROUND
Primary hypertension in childhood tracks into adulthood and may be associated with increased cardiovascular risk. Studies conducted in children and adolescents provide an opportunity to explore the early cardiovascular target organ injury (CV-TOI) in a population free from many of the co-morbid cardiovascular disease risk factors that confound studies in adults.
METHODS
Youths (n=132, mean age 15.8 years) were stratified by blood pressure (BP) as low, elevated, and high-BP and by left ventricular mass index (LVMI) as low- and high-LVMI. Systemic circulating RNA, miRNA, and methylation profiles in peripheral blood mononuclear cells and deep proteome profiles in serum were determined using high-throughput sequencing techniques.
RESULTS
gene expression was elevated in youths with high-BP with and without high-LVMI. expression levels positively correlated with systolic BP (r=0.3143, p=0.0034). The expression of hsa-miR-335-5p, one of the predicted miRNAs, was downregulated in high-BP with high-LVMI youths and was inversely correlated with systolic BP (r=-0.1891, p=0.0489). hypermethylation, circulating PROZ upregulation (log FC=0.61, p=0.0049 and log FC=0.62, p=0.0064), and SOD3 downregulation (log FC=-0.70, p=0.0042 and log FC=-0.64, p=0.010) were observed in youths with elevated BP and high-BP with high-LVMI. Comparing the transcriptomic and proteomic profiles revealed elevated levels in youths displaying high-BP and high-LVMI.
CONCLUSIONS
The findings are compatible with a novel blood pressure-associated mechanism that may occur through impaired angiogenesis and extracellular matrix degradation through dysregulation of Vasohibin-1 and Hyaluronidase1 was identified as a possible mediator of CV-TOI in youth with high-BP and suggests strategies for ameliorating TOI in adult-onset primary hypertension.
PubMed: 38948714
DOI: 10.1101/2024.06.17.599125 -
Metabolic Engineering Communications Jun 2024Squalene is a highly sought-after triterpene compound in growing demand, and its production offers a promising avenue for circular economy practices. In this study, we...
Squalene is a highly sought-after triterpene compound in growing demand, and its production offers a promising avenue for circular economy practices. In this study, we applied metabolic engineering principles to enhance squalene production in the nonconventional yeast , using waste cooking oil as a substrate. By overexpressing key enzymes in the mevalonate pathway - specifically ERG9 encoding squalene synthase, ERG20 encoding farnesyl diphosphate synthase, and HMGR encoding hydroxy-methyl-glutaryl-CoA reductase - we achieved a yield of 779.9 mg/L of squalene. Further co-overexpression of DGA1, encoding diacylglycerol acyltransferase, and CAT2, encoding carnitine acetyltransferase, in combination with prior metabolic enhancements, boosted squalene production to 1381.4 mg/L in the engineered strain Po1g17. To enhance the supply of the precursor acetyl-CoA and inhibit downstream squalene conversion, we supplemented with 6 g/L pyruvic acid and 0.7 mg/L terbinafine, resulting in an overall squalene titer of 2594.1 mg/L. These advancements underscore the potential for sustainable, large-scale squalene production using cell factories, contributing to circular economy initiatives by valorizing waste materials.
PubMed: 38948667
DOI: 10.1016/j.mec.2024.e00240