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ACS Applied Materials & Interfaces Jul 2024The occurrence of cancer is often closely related to multiple tumor markers, so it is important to develop multitarget detection methods. By the proper design of the...
The occurrence of cancer is often closely related to multiple tumor markers, so it is important to develop multitarget detection methods. By the proper design of the input signals and logical operations of DNA logic gates, detection and diagnosis of cancer at different stages can be achieved. For example, in the early stages, specific input signals can be designed to correspond to early specific tumor markers, thereby achieving early cancer detection. In the late stage, logic gates for multitarget detection can be designed to simultaneously detect multiple biomarkers to improve diagnostic accuracy and comprehensiveness. In this work, we constructed a dual-target-triggered DNA logic gate for anchoring DNA tetrahedra, where methylene blue was embedded in the DNA tetrahedra to sensitize ZnO@CdS@Au, achieving ultrasensitive detection of the target substance. We tested the response of AND and OR logic gates to the platform. For AND logic gates, the sensing platform only responds when both miRNAs are present. In the concentration range of 10 aM to 10 nM, the photoelectric signal gradually increases with an increase of the target concentration. Subsequently, we used OR logic gates for miRNA detection. Even if only one target exists, the sensing platform exhibits excellent performance. Similarly, within the concentration range of 10 aM to 10 nM, the photoelectric signal gradually increases with an increase of the target concentration. The minimum detection limit is 1.10 aM. Whether it is the need to detect multiple targets simultaneously or only one of them, we can achieve it by selecting the appropriate logic gate. This strategy holds promising application prospects in fields such as biosensing, medical diagnosis, and environmental monitoring.
PubMed: 38952261
DOI: 10.1021/acsami.4c08276 -
Environmental Microbiology Jul 2024The influence of environmental factors on the interactions between phages and bacteria, particularly single-stranded DNA (ssDNA) phages, has been largely unexplored. In...
The influence of environmental factors on the interactions between phages and bacteria, particularly single-stranded DNA (ssDNA) phages, has been largely unexplored. In this study, we used Finnlakevirus FLiP, the first known ssDNA phage species with a lipid membrane, as our model phage. We examined the infectivity of FLiP with three Flavobacterium host strains, B330, B167 and B114. We discovered that FLiP infection is contingent on the host strain and conditions such as temperature and bacterial growth phase. FLiP can infect its hosts across a wide temperature range, but optimal phage replication varies with each host. We uncovered some unique aspects of phage infectivity: FLiP has limited infectivity in liquid-suspended cells, but it improves when cells are surface-attached. Moreover, FLiP infects stationary phase B167 and B114 cells more rapidly and efficiently than exponentially growing cells, a pattern not observed with the B330 host. We also present the first experimental evidence of endolysin function in ssDNA phages. The activity of FLiP's lytic enzymes was found to be condition-dependent. Our findings underscore the importance of studying phage ecology in contexts that are relevant to the environment, as both the host and the surrounding conditions can significantly alter the outcome of phage-host interactions.
Topics: DNA, Single-Stranded; Bacteriophages; Flavobacterium; Host Microbial Interactions; Endopeptidases; Virus Replication; Temperature
PubMed: 38952172
DOI: 10.1111/1462-2920.16670 -
Current Cancer Drug Targets Jun 2024Epigenetic mechanisms have been shown to play a critical role in the development and progression of gastrointestinal [GI] cancers. These mechanisms involve modifications...
Epigenetic mechanisms have been shown to play a critical role in the development and progression of gastrointestinal [GI] cancers. These mechanisms involve modifications to DNA and histones that can alter gene expression patterns and may contribute to the initiation and progression of cancers. In recent years, epigenetic therapies have emerged as a promising approach to treating GI cancers. These therapies target specific epigenetic modifications, such as DNA methylation and histone acetylation, to restore normal gene expression patterns and inhibit cancer cell growth. Several epigenetic drugs have been approved for the treatment of GI cancers. Moreover, the use of epigenetic therapies in combination with other treatments, such as chemotherapeutic agents, is being studied to improve treatment outcomes. We have provided an overview of the role of epigenetic mechanisms in GI cancer treatment aimed to focus on recent evidence of the use of epigenetic agents in clinical and preclinical GI cancer studies, including gastric, esophageal, hepatic, pancreatic, and colorectal cancers. Overall, the role of epigenetic mechanisms in GI cancer treatments is an active area of research with the potential to improve patients' treatment outcomes and advance cancer treatment strategies.
PubMed: 38952157
DOI: 10.2174/0115680096306639240520053736 -
Gerontology Jul 2024It is uncertain whether folic acid (FA) combined with docosahexaenoic acid (DHA) could improve cognitive performance. This study evaluated the effects of a 12-month FA...
Cognitive benefits of folic acid, docosahexaenoic acid and a combination of both nutrients in mild cognitive impairment; possible alterations though mitochondrial function and DNA damage.
INTRODUCTION
It is uncertain whether folic acid (FA) combined with docosahexaenoic acid (DHA) could improve cognitive performance. This study evaluated the effects of a 12-month FA and DHA supplementation, in combination or alone, on cognitive function, DNA oxidative damage, and mitochondrial function in participants with mild cognitive impairment (MCI).
METHODS
This randomized, double-blind, placebo-controlled trial recruited MCI participants aged 60 years and older. Two hundred and eighty participants were randomly divided in equal proportion into four groups: FA+DHA (FA 800μg/d + DHA 800mg/d), FA (800μg/d), DHA (800mg/d), and placebo groups daily orally for 12 months. The primary outcome was cognitive function evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-RC). Cognitive tests and blood mechanism-related biomarkers were determined at baseline and 12 months.
RESULTS
During the 12-month follow, scores of full intelligence quotient (FIQ) (βDHA: 1.302, 95%CI: 0.615, 1.990, p < 0.001; βFA: 1.992, 95%CI: 1.304, 2.679, p < 0.001; βFA+DHA: 2.777, 95%CI: 2.090, 3.465, p < 0.001), verbal intelligence quotient, and some subtests of the WAIS-RC were significantly improved in FA+DHA and single intervention groups compared to the placebo group. Moreover, the FA and DHA intervention combination was superior to either intervention alone (p < 0.001). Meanwhile, FA, DHA and their combined use significantly decreased 8-OHdG level and increased mitochondrial DNA copy number compared to the placebo (p < 0.05).
CONCLUSIONS
Supplementation of FA and DHA, alone or combined, for 12 months can improve cognitive function in MCI participants, possibly through mitigating DNA oxidative damage and enhancing mitochondrial function. Combined supplementation may provide more cognitive benefit than supplementation alone.
TRIAL REGISTRATION
Chinese Clinical Trial Registry, ChiCTR2000034351. Registered 3 July 2020 - Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=53345.
PubMed: 38952108
DOI: 10.1159/000540021 -
Phytochemical Analysis : PCA Jul 2024High-quality nucleic acids are the basis for molecular biology experiments. Traditional RNA extraction methods are not suitable for Eleutherococcus senticosus Maxim.
INTRODUCTION
High-quality nucleic acids are the basis for molecular biology experiments. Traditional RNA extraction methods are not suitable for Eleutherococcus senticosus Maxim.
OBJECTIVE
To find a suitable method to improve the quality of RNA extracted, we modified the RNA extraction methods of Trizol.
METHODOLOGY
Based on the conventional Trizol method, the modified Trizol method 1 and modified Trizol method 2 were used as the control for extraction of RNA from E. senticosus Maxim leaves. The modified Trizol method 1 added β-mercaptoethanol on the conventional Trizol method. After RNA was dissolved, a mixed solution of phenol, chloroform, and isoamyl alcohol was added to denature protein and inhibit the degradation of RNA. The modified Trizol method 2 adds PVPP to grind on the basis of modified Trizol method 1, so as to better remove phenols from leaves, and eliminates the step of incubation at -20°C to reduce extraction time and RNA degradation. Chloroform, CTAB, and CHCOONa were used instead of a phenol, chloroform, and isoamyl alcohol mixed solution to ensure complete separation of nucleic acid from plant tissues and to obtain high-purity RNA.
RESULTS
The research results showed that the quality of RNA extracted by conventional Trizol method, modified Trizol method 1, was incomplete, accompanied with different degrees of contamination of polysaccharides, polyphenols, and DNA. The modified Trizol method 2 could better extract RNA from E. senticosus Maxim leaves. The ratio of A260/A280 was in the range of 1.8-2.0, and the yield of RNA was the highest, which was 1.68 and 1.15 times compared with that by conventional Trizol method and modified Trizol method 1 extraction, respectively. The reverse transcription cDNA was further tested through PCR with the specific primers. The amplified fragments are displayed in clear and bright bands in accordance with the expected size.
CONCLUSION
The modified Trizol method 2 could better extract RNA from E. senticosus Maxim leaves. High-quality RNA has more advantages in molecular biology study of E. senticosus Maxim.
PubMed: 38952075
DOI: 10.1002/pca.3404 -
International Journal of Stem Cells Jul 2024Histone H2B monoubiquitination (H2Bub1) is a dynamic posttranslational modification which are linked to DNA damage and plays a key role in a wide variety of regulatory...
Histone H2B monoubiquitination (H2Bub1) is a dynamic posttranslational modification which are linked to DNA damage and plays a key role in a wide variety of regulatory transcriptional programs. Cancer cells exhibit a variety of epigenetic changes, particularly any aberrant H2Bub1 has frequently been associated with the development of tumors. Nevertheless, our understanding of the mechanisms governing the histone H2B deubiquitination and their associated functions during stem cell differentiation remain only partially understood. In this study, we wished to investigate the role of deubiquitinating enzymes (DUBs) on H2Bub1 regulation during stem cell differentiation. In a search for potential DUBs for H2B monoubiquitination, we identified Usp7, a ubiquitin-specific protease that acts as a negative regulator of H2B ubiquitination during the neuronal differentiation of mouse embryonic carcinoma cells. Loss of function of the gene by a CRISPR/Cas9 system during retinoic acid-mediated cell differentiation contributes to the increase in H2Bub1. Furthermore, knockout of the gene particularly elevated the expression of neuronal differentiation related genes including astryocyte-specific markers and oligodendrocyte-specific markers. In particular, glial lineage cell-specific transcription factors including oligodendrocyte transcription factor 2, glial fibrillary acidic protein, and SRY-box transcription factor 10 was significantly upregulated during neuronal differentiation. Thus, our findings suggest a novel role of Usp7 in gliogenesis in mouse embryonic carcinoma cells.
PubMed: 38952059
DOI: 10.15283/ijsc23202 -
Annals of Transplantation Jul 2024BACKGROUND The relationship between clonal hematopoiesis (CH)-associated gene mutations and allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been...
BACKGROUND The relationship between clonal hematopoiesis (CH)-associated gene mutations and allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been extensively studied since next-generation sequencing (NGS) technology became widely available. However, research has mainly focused on the relationship between donor CH mutations and transplant prognosis, and research into the relationship between CH mutations in the recipient and acute graft-versus-host disease (aGVHD) is lacking. MATERIAL AND METHODS We analyzed NGS results and their correlation with aGVHD and prognosis in 196 AML patients undergoing allo-HSCT. RESULTS A total of 93 (47.4%) patients had CH mutations. The most frequently mutated genes were DNMT3A (28 of 196; 14.3%), TET2 (22 of 196; 11.2%), IDH1 (15 of 196; 7.7%), IDH2 (14 of 196; 7.1%), and ASXL1 (13 of 196; 6.6%). The incidence of aGVHD was higher in patients older than 45 years old with DTA mutations (DNMT3A, TET2 or ASXL1). DNMT3A mutation but not with TET2 or ASXL1 mutation was an independent risk factor for aGVHD in patients receiving allo-HSCT older than 45 years old. With a median follow-up of 42.7 months, CH mutations were not associated with overall survival and leukemia-free survival. CONCLUSIONS DNMT3A mutation, but not TET2 or ASXL1 mutation, was associated with higher incidence of aGVHD.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Male; Female; Graft vs Host Disease; Middle Aged; Adult; Leukemia, Myeloid, Acute; Mutation; Clonal Hematopoiesis; Young Adult; Adolescent; DNA Methyltransferase 3A; Dioxygenases; DNA (Cytosine-5-)-Methyltransferases; Aged; Prognosis; Transplantation, Homologous; High-Throughput Nucleotide Sequencing; DNA-Binding Proteins; Repressor Proteins
PubMed: 38952007
DOI: 10.12659/AOT.943688 -
Journal of Clinical Neurology (Seoul,... Jul 2024Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inherited disorder of fatty acid oxidation that causes lipid storage myopathy (LSM). This is the first report on...
BACKGROUND AND PURPOSE
Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inherited disorder of fatty acid oxidation that causes lipid storage myopathy (LSM). This is the first report on MADD that describes the phenotypic and genetic features of a Malaysian cohort.
METHODS
Among the >2,500 patients in a local muscle biopsy database, patients with LSM were identified and their genomic DNA were extracted from muscle samples and peripheral blood. All 13 exons of the electron-transfer flavoprotein dehydrogenase gene () were subsequently sequenced. Fifty controls were included to determine the prevalence of identified mutations in the normal population.
RESULTS
Fourteen (82%) of the 17 LSM patients had MADD with mutations. Twelve (86%) were Chinese and two were Malay sisters. Other unrelated patients reported that they had no relevant family history. Nine (64%) were females. The median age at onset was 18.5 years (interquartile range=16-37 years). All 14 demonstrated proximal limb weakness, elevated serum creatine kinase levels, and myopathic changes in electromyography. Three patients experienced a metabolic crisis at their presentation. Sanger sequencing of revealed nine different variants/mutations, one of which was novel: c.998A>G (p.Y333C) in exon 9. Notably, 12 (86%) patients, including the 2 Malay sisters, carried a common c.250G>A (p.A84T) variant, consistent with the hotspot mutation reported in southern China. All of the patients responded well to riboflavin therapy.
CONCLUSIONS
Most of our Malaysian cohort with LSM had late-onset, riboflavin-responsive MADD with mutations, and they demonstrated phenotypic and genetic features similar to those of cases reported in southern China. Furthermore, we report a novel mutation and possibly the first ever MADD patients of Malay descent.
PubMed: 38951975
DOI: 10.3988/jcn.2023.0265 -
Nucleus (Austin, Tex.) Dec 2024The nucleus not only is a repository for DNA but also a center of cellular and nuclear mechanotransduction. From nuclear deformation to the interplay between... (Review)
Review
The nucleus not only is a repository for DNA but also a center of cellular and nuclear mechanotransduction. From nuclear deformation to the interplay between mechanosensing components and genetic control, the nucleus is poised at the nexus of mechanical forces and cellular function. Understanding the stresses acting on the nucleus, its mechanical properties, and their effects on gene expression is therefore crucial to appreciate its mechanosensitive function. In this review, we examine many elements of nuclear mechanotransduction, and discuss the repercussions on the health of cells and states of illness. By describing the processes that underlie nuclear mechanosensation and analyzing its effects on gene regulation, the review endeavors to open new avenues for studying nuclear mechanics in physiology and diseases.
Topics: Mechanotransduction, Cellular; Humans; Cell Nucleus; Animals; Gene Expression Regulation
PubMed: 38951951
DOI: 10.1080/19491034.2024.2374854 -
Journal of Medical Case Reports Jul 2024Pulmonary aspergillosis is a prevalent opportunistic fungal infection that can lead to mortality in pediatric patients with underlying immunosuppression. Appropriate and...
BACKGROUND
Pulmonary aspergillosis is a prevalent opportunistic fungal infection that can lead to mortality in pediatric patients with underlying immunosuppression. Appropriate and timely treatment of pulmonary aspergillosis can play a crucial role in reducing mortality among children admitted with suspected infections.
CASE PRESENTATION
The present study reports three cases of inappropriate treatment of pulmonary aspergillosis caused by Aspergillus flavus in two Iranian pediatric patients under investigation and one Afghan patient. Unfortunately, two of them died. The cases involved patients aged 9, 1.5, and 3 years. They had been diagnosed with pulmonary disorders, presenting nonspecific clinical signs and radiographic images suggestive of pneumonia. The identification of A. flavus was confirmed through DNA sequencing of the calmodulin (CaM) region.
CONCLUSION
A. flavus was the most prevalent cause of pulmonary aspergillosis in pediatric patients. Early diagnosis and accurate antifungal treatment of pulmonary aspergillosis could be crucial in reducing the mortality rate and also have significant potential for preventing other complications among children. Moreover, antifungal prophylaxis seems to be essential for enhancing survival in these patients.
Topics: Humans; Aspergillus flavus; Antifungal Agents; Child; Male; Child, Preschool; Pulmonary Aspergillosis; Infant; Female; Fatal Outcome; Iran
PubMed: 38951939
DOI: 10.1186/s13256-024-04599-9