-
Expert Opinion on Drug Delivery Jul 2024This review discusses novel hybrid assemblies that are based on liposomal formulations. The focus is on the hybrid constructs that are formed through the integration of... (Review)
Review
INTRODUCTION
This review discusses novel hybrid assemblies that are based on liposomal formulations. The focus is on the hybrid constructs that are formed through the integration of liposomes/vesicles with other nano-objects such as nucleic acid nanostructures and metallic nanoparticles. The aim is to introduce some of the recent, specific examples that bridge different technologies and thus may form a new platform for advanced drug delivery applications.
AREAS COVERED
We present selected examples of liposomal formulations combined with complex nanostructures either based on biomolecules like DNA origami or on metallic materials - metal/metal oxide/magnetic particles and metallic nanostructures, such as metal organic frameworks - together with their applications in drug delivery and beyond.
EXPERT OPINION
Merging the above-mentioned techniques could lead to development of drug delivery vehicles with the most desirable properties; multifunctionality, biocompatibility, high drug loading efficiency/accuracy/capacity, and stimuli-responsiveness. In the near future, we believe that especially the strategies combining dynamic, triggerable and programmable DNA nanostructures and liposomes could be used to create artificial liposome clusters for multiple applications such as examining protein-mediated interactions between lipid bilayers and channeling materials between liposomes for enhanced pharmacokinetic properties in drug delivery.
PubMed: 38962823
DOI: 10.1080/17425247.2024.2375389 -
The Journal of Infectious Diseases Jul 2024Tuberculosis (TB) is amongst the largest infectious causes of death worldwide and there is a need for a time- and resource-effective diagnostic method. In this novel and...
BACKGROUND
Tuberculosis (TB) is amongst the largest infectious causes of death worldwide and there is a need for a time- and resource-effective diagnostic method. In this novel and exploratory study, we show the potential of using buccal swabs to collect human DNA and investigate the DNA methylation (DNAm) signatures as a diagnostic tool for TB.
METHODS
Buccal swabs were collected from pulmonary TB patients (n= 7), TB exposed (n= 7), and controls (n= 9) in Sweden. Using Illumina MethylationEPIC array the DNAm status was determined.
RESULTS
We identified 5644 significant differentially methylated CpG sites between the patients and controls. Performing the analysis on a validation cohort of samples collected in Kenya and Peru (patients, n=26; exposed, n=9; control, n=10) confirmed the DNAm signature. We identified a TB consensus disease module, significantly enriched in TB-associated genes. Lastly, we used machine learning to identify a panel of seven CpG sites discriminative for TB and developed a TB classifier. In the validation cohort the classifier performed with an AUC of 0.94, sensitivity of 0.92, and specificity of 1.
CONCLUSION
In summary, the result from this study shows clinical implications of using DNAm signatures from buccal swabs to explore new diagnostic strategies for TB.
PubMed: 38962817
DOI: 10.1093/infdis/jiae333 -
Neuro-oncology Advances 2024Choroid plexus tumors (CPTs) are rare, potentially aggressive CNS tumors with defined histologic criteria for grading. In recent years, several patients within our...
BACKGROUND
Choroid plexus tumors (CPTs) are rare, potentially aggressive CNS tumors with defined histologic criteria for grading. In recent years, several patients within our practice have demonstrated discordance between the histologic diagnosis and clinical behavior. DNA methylation profiling has emerged as a potential diagnostic adjunct for aiding the clinical approach.
METHODS
We reviewed the clinical and pathologic data of all CPTs diagnosed at Boston Children's Hospital from 1995 to 2023. All cases with available material (38/48) underwent DNA methylation profiling at NIH/NCI, and the classifier results were correlated with the WHO histologic grade and patient outcomes. Survival information was analyzed using Kaplan-Meier curves.
RESULTS
There was good correlation (11/12, 92%) between methylation class and WHO histologic grade for choroid plexus carcinomas (CPC); one histologic CPC grouped with choroid plexus papilloma (CPP) group pediatric (P). Five CPPs grouped with methylation class CPC (5/17, 29%). In the group of atypical CPPs ( = 9), there were two that grouped with methylation class CPC. Survival analysis showed utility of methylation classes in the prediction of biologic behavior.
CONCLUSIONS
Results indicated that methylation profiling may serve as a valuable tool in the clinical decision-making process for patients with CPTs, providing additional prognostic information compared to WHO histologic grade alone. The value of methylation array analysis is particularly important given the lack of consensus on treatment regimens for CPTs.
PubMed: 38962753
DOI: 10.1093/noajnl/vdae097 -
Neuro-oncology Advances 2024pathogenic variants (PV) have been recently identified as the most frequent variants predisposing to Sonic Hedgehog (SHH) medulloblastomas (MB); however, guidelines are...
BACKGROUND
pathogenic variants (PV) have been recently identified as the most frequent variants predisposing to Sonic Hedgehog (SHH) medulloblastomas (MB); however, guidelines are still lacking for genetic counseling in this new syndrome.
METHODS
We retrospectively reviewed clinical and genetic data of a French series of 29 -mutated MB.
RESULTS
All patients developed SHH-MB, with a biallelic inactivation of found in 24 tumors. Other recurrent alterations encompassed the pathway and activation of signaling. The median age at diagnosis was 7.3 years (range: 3-14). -mutated MB behave as sporadic cases, with similar distribution within clinical and molecular risk groups and similar outcomes (5 y - OS = 86%); no unusual side effect of treatments was noticed. Remarkably, a germline PV was identified in all patients with available constitutional DNA ( = 26); moreover, all tested familial trio ( = 11) revealed that the PVs were inherited. Two of the 26 index cases from the French series had a family history of MB; pedigrees from these patients and from 1 additional Dutch family suggested a weak penetrance. Apart from MB, no cancer was associated with PVs; second tumors reported in 4 patients occurred within the irradiation fields, in the usual time-lapse for expected radiotherapy-induced neoplasms.
CONCLUSIONS
The low penetrance, the "at risk' age window limited to childhood and the narrow tumor spectrum, question the actual benefit of genetic screening in these patients and their family. Our results suggest restricting germline sequencing to patients with SHH-MB, depending on the parents" request.
PubMed: 38962751
DOI: 10.1093/noajnl/vdae075 -
Case Reports in Oncological Medicine 2024Primary mandibular telangiectatic osteosarcomas are very rare lesions, with only nine cases reported. Histologically, these lesions show multiple cystic blood-filled...
Primary mandibular telangiectatic osteosarcomas are very rare lesions, with only nine cases reported. Histologically, these lesions show multiple cystic blood-filled cavities traversed by neoplastic bone in septa lined by high-grade malignant cells. Here, we report an 81-year-old woman who presented with a mandibular mass, which was surgically resected and analyzed by histologic examination and whole exome DNA sequencing. A diagnosis of telangiectatic osteosarcoma was given. Comparative sequencing data analysis of paired benign and tumor DNA revealed 1577 variants unique to the tumor DNA, which clustered into several gene families, including those regulating DNA repair and apoptosis. Comparison of benign and tumor DNA revealed many shared gene polymorphisms associated with an increased cancer risk. These included polymorphisms in the ATM, p53, BRCA1, and BRCA2 and many other genes. Interestingly, the patient's family history showed an unusually high cancer incidence, likely related to these cancer risk-associated polymorphisms. To our knowledge, this is the first-time sequencing applied to a mandibular telangiectatic osteosarcoma. Our findings may shed light on the molecular origins of these rare tumors and how they may relate to other tumors in related kindreds.
PubMed: 38962713
DOI: 10.1155/2024/2418888 -
Frontiers in Veterinary Science 2024()-infected livestock and wildlife have been epidemiologically linked to human Q fever outbreaks. Despite this growing zoonotic threat, knowledge of coxiellosis in wild...
INTRODUCTION
()-infected livestock and wildlife have been epidemiologically linked to human Q fever outbreaks. Despite this growing zoonotic threat, knowledge of coxiellosis in wild animals remains limited, and studies to understand their epidemiologic role are needed. In -endemic areas, ticks have been reported to harbor and spread and may serve as indicators of risk of infection in wild animal habitats. Therefore, the aim of this study was to compare molecular techniques for detecting DNA in ticks.
METHODS
In total, 169 ticks from wild animals and cattle in wildlife conservancies in northern Kenya were screened for DNA using a conventional PCR (cPCR) and two field-friendly techniques: Biomeme's qPCR Go-strips (Biomeme) and a new PCR high-resolution melt (PCR-HRM) analysis assay. Results were evaluated, in the absence of a gold standard test, using Bayesian latent class analysis (BLCA) to characterize the proportion of positive ticks and estimate sensitivity (Se) and specificity (Sp) of the three tests.
RESULTS
The final BLCA model included main effects and estimated that PCR-HRM had the highest Se (86%; 95% credible interval: 56-99%), followed by the Biomeme (Se = 57%; 95% credible interval: 34-90%), with the estimated Se of the cPCR being the lowest (24%, 95% credible interval: 10-47%). Specificity estimates for all three assays ranged from 94 to 98%. Based on the model, an estimated 16% of ticks had DNA present.
DISCUSSION
These results reflect the endemicity of in northern Kenya and show the promise of the PCR-HRM assay for surveillance in ticks. Further studies using ticks and wild animal samples will enhance understanding of the epidemiological role of ticks in Q fever.
PubMed: 38962707
DOI: 10.3389/fvets.2024.1396714 -
Neurobiology of Stress Jul 2024Adverse early-life experiences (ELA) affect a majority of the world's children. Whereas the enduring impact of ELA on cognitive and emotional health is established,...
Adverse early-life experiences (ELA) affect a majority of the world's children. Whereas the enduring impact of ELA on cognitive and emotional health is established, there are no tools to predict vulnerability to ELA consequences in an individual child. Epigenetic markers including peripheral-cell DNA-methylation profiles may encode ELA and provide predictive outcome markers, yet the interindividual variance of the human genome and rapid changes in DNA methylation in childhood pose significant challenges. Hoping to mitigate these challenges we examined the relation of several ELA dimensions to DNA methylation changes and outcome using a within-subject longitudinal design and a high methylation-change threshold. DNA methylation was analyzed in buccal swab/saliva samples collected twice (neonatally and at 12 months) in 110 infants. We identified CpGs differentially methylated across time for each child and determined whether they associated with ELA indicators and executive function at age 5. We assessed sex differences and derived a sex-dependent 'impact score' based on sites that most contributed to methylation changes. Changes in methylation between two samples of an individual child reflected age-related trends and correlated with executive function years later. Among tested ELA dimensions and life factors including income to needs ratios, maternal sensitivity, body mass index and infant sex, unpredictability of parental and household signals was the strongest predictor of executive function. In girls, high early-life unpredictability interacted with methylation changes to presage executive function. Thus, longitudinal, within-subject changes in methylation profiles may provide a signature of ELA and a potential predictive marker of individual outcome.
PubMed: 38962694
DOI: 10.1016/j.ynstr.2024.100652 -
Epigenetics Communications 2024Exposure to environmental chemicals such as phthalates, phenols, and polycyclic aromatic hydrocarbons (PAHs) during pregnancy can increase the risk of adverse newborn...
BACKGROUND
Exposure to environmental chemicals such as phthalates, phenols, and polycyclic aromatic hydrocarbons (PAHs) during pregnancy can increase the risk of adverse newborn outcomes. We explored the associations between maternal exposure to select environmental chemicals and DNA methylation in cord blood mononuclear cells (CBMC) and placental tissue (maternal and fetal sides) to identify potential mechanisms underlying these associations.
METHOD
This study included 75 pregnant individuals who planned to give birth at the University of Cincinnati Hospital between 2014 and 2017. Maternal urine samples during the delivery visit were collected and analyzed for 37 biomarkers of phenols (12), phthalates (13), phthalate replacements (4), and PAHs (8). Cord blood and placenta tissue (maternal and fetal sides) were also collected to measure the DNA methylation intensities using the Infinium HumanMethylation450K BeadChip. We used linear regression, adjusting for potential confounders, to assess CpG-specific methylation changes in CBMC ( = 54) and placenta [fetal ( = 67) and maternal ( = 68) sides] associated with gestational chemical exposures (29 of 37 biomarkers measured in this study). To account for multiple testing, we used a false discovery rate q-values < 0.05 and presented results by limiting results with a genomic inflation factor of 1±0.5. Additionally, gene set enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomics pathways.
RESULTS
Among the 29 chemical biomarkers assessed for differential methylation, maternal concentrations of PAH metabolites (1-hydroxynaphthalene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 1-hydroxypyrene), monocarboxyisononyl phthalate, mono-3-carboxypropyl phthalate, and bisphenol A were associated with altered methylation in placenta (maternal or fetal side). Among exposure biomarkers associated with epigenetic changes, 1-hydroxynaphthalene, and mono-3-carboxypropyl phthalate were consistently associated with differential CpG methylation in the placenta. Gene enrichment analysis indicated that maternal 1-hydroxynaphthalene was associated with lipid metabolism and cellular processes of the placenta. Additionally, mono-3-carboxypropyl phthalate was associated with organismal systems and genetic information processing of the placenta.
CONCLUSION
Among the 29 chemical biomarkers assessed during delivery, 1-hydroxynaphthalene and mono-3-carboxypropyl phthalate were associated with DNA methylation in the placenta.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1186/s43682-024-00027-7.
PubMed: 38962689
DOI: 10.1186/s43682-024-00027-7 -
Frontiers in Bioengineering and... 2024Phosphorus (P) is essential for biological systems, playing a pivotal role in energy metabolism and forming crucial structural components of DNA and RNA. Yet its...
Phosphorus (P) is essential for biological systems, playing a pivotal role in energy metabolism and forming crucial structural components of DNA and RNA. Yet its bioavailable forms are scarce. Phytate, a major form of stored phosphorus in cereals and soils, is poorly bioavailable due to its complex structure. Phytases, enzymes that hydrolyze phytate to release useable phosphorus, are vital in overcoming this limitation and have significant biotechnological applications. This study employed novel method to isolate and characterize bacterial strains capable of metabolizing phytate as the sole carbon and phosphorus source from the Andes mountains soils. Ten strains from the genera and Chryseobacterium were isolated, with sp. CP-77 and CP-84 showing specific activities of 3.5 ± 0.4 nkat/mg and 40.8 ± 5 nkat/mg, respectively. Genomic sequencing revealed significant genetic diversity, suggesting CP-77 may represent a novel species. A fosmid library screening identified several phytase genes, including a 3-phytase in CP-77 and a glucose 1-phosphatase and 3-phytase in CP-84. Phylogenetic analysis confirmed the novelty of these enzymes. These findings highlight the potential of phytase-producing bacteria in sustainable agriculture by enhancing phosphorus bioavailability, reducing reliance on synthetic fertilizers, and contributing to environmental management. This study expands our biotechnological toolkit for microbial phosphorus management and underscores the importance of exploring poorly characterized environments for novel microbial functions. The integration of direct cultivation with metagenomic screening offers robust approaches for discovering microbial biocatalysts, promoting sustainable agricultural practices, and advancing environmental conservation.
PubMed: 38962663
DOI: 10.3389/fbioe.2024.1426208 -
Cureus Jun 2024Introduction Collagen plays a vital role in maintaining the structural integrity of dentin, and its modification with bioactive compounds can enhance its mechanical...
Introduction Collagen plays a vital role in maintaining the structural integrity of dentin, and its modification with bioactive compounds can enhance its mechanical properties and bonding capabilities. Aim This study aimed to evaluate the genotoxic effects of grape seed extract (GSE) and marine collagen peptide (MCP) on dental pulp-derived primary cells. Methodology Human dental pulp stem cells were isolated, cultivated, and then treated with GSE and marine collagen peptides. DNA fragmentation was assessed using DAPI (4',6-diamidino-2-phenylindole) staining. Statistical analysis was performed using SPSS version 20 (IBM Corp., Armonk, NY, USA). Results The results showed that GSE exhibited a minimum level of cell death compared to marine collagen peptides. The viable cell count increased steadily over three days in all groups, with the control group showing the highest number of viable cells. The differences in viable cell count among the groups were statistically significant. Conclusion This study suggests that GSE and marine collagen peptides are highly biocompatible with dental pulp cells and could be considered for further clinical studies.
PubMed: 38962594
DOI: 10.7759/cureus.61605