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Heliyon Jun 2024Gastrointestinal cancer poses a considerable global health risk, encompassing a heterogeneous spectrum of malignancies that afflict the gastrointestinal tract. It is...
BACKGROUND
Gastrointestinal cancer poses a considerable global health risk, encompassing a heterogeneous spectrum of malignancies that afflict the gastrointestinal tract. It is significant to develop efficacious therapeutic agents, as they are indispensable for both the treatment and prevention of this formidable disease.
METHODS
In this study, we synthesized a novel thiophene derivative, designated as compound 1312. An assessment was performed to investigate its anti-proliferative activity in several cancer cell lines (GES-1, EC9706, SGC7901, and HT-29). Furthermore, we performed molecular biology techniques to investigate the inhibitory impact of compound 1312 on gastrointestinal cell lines SGC-7901 and HT-29.
RESULTS
Our findings reveal that compound 1312 exhibits significant efficacy in suppressing colony formation of cancer cells. Notably, it triggers cell cycle arrest at the G2/M phase in gastrointestinal cell lines SGC7901 and HT-29. Compound 1312 was confirmed to exert inhibitory effects on cell migration and invasion in SGC7901. Additionally, the compound elicits apoptotic cell death through the activation of the DNA repair enzyme poly (ADP-ribose) polymerase (PARP) and the caspase signaling cascade. Furthermore, experiments revealed that compound 1312 effectively suppresses both the β-tubulin cytoskeletal network and the Wnt/β-catenin signaling pathway. These multifaceted anti-cancer activities highlight the potential of compound 1312 as a promising therapeutic agent for the treatment of gastrointestinal malignancies.
CONCLUSION
This study indicates the promising potential of compound 1312 as a prospective candidate agent for gastrointestinal cancer treatment. Further comprehensive investigations are needed to explore its therapeutic efficacy in greater detail.
PubMed: 38912446
DOI: 10.1016/j.heliyon.2024.e32241 -
Innovation (Cambridge (Mass.)) Jul 2024Stony corals, the primary architects of coral reef ecosystems, are largely underrepresented in omics studies despite their importance. The presence of endosymbiotic... (Review)
Review
Stony corals, the primary architects of coral reef ecosystems, are largely underrepresented in omics studies despite their importance. The presence of endosymbiotic Symbiodiniaceae algae complicates the extraction of pure coral DNA, posing a challenge for genomic research. Here, we devised a comprehensive methodological framework that incorporates various experimental treatments to achieve 99% purity in coral DNA extraction and a robust bioinformatics pipeline to guarantee the assembly of high-quality, contamination-free coral genomes. Validation of our framework using samples demonstrated its efficacy and superiority in obtaining high-quality pure coral genomes using easily accessible adult colony. This integrated framework serves as a critical foundation for large-scale genome-enabled research on stony corals, providing insight into coral evolution and conservation.
PubMed: 38912429
DOI: 10.1016/j.xinn.2024.100643 -
ISME Communications Jan 2024Shotgun metagenomic sequencing provides valuable insights into microbial communities, but the high cost of library preparation with standard kits and protocols is a...
Shotgun metagenomic sequencing provides valuable insights into microbial communities, but the high cost of library preparation with standard kits and protocols is a barrier for many. New methods such as Hackflex use diluted commercially available reagents to greatly reduce library preparation costs. However, these methods have not been systematically validated for metagenomic sequencing. Here, we evaluate Hackflex performance by sequencing metagenomic libraries from known mock communities as well as mouse fecal samples prepared by Hackflex, Illumina DNA Prep, and Illumina TruSeq methods. Hackflex successfully recovered all members of the Zymo mock community, performing best for samples with DNA concentrations <1 ng/μL. Furthermore, Hackflex was able to delineate microbiota of individual inbred mice from the same breeding stock at the same mouse facility, and statistical modeling indicated that mouse ID explained a greater fraction of the variance in metagenomic composition than did library preparation method. These results show that Hackflex is suitable for generating inventories of bacterial communities through metagenomic sequencing.
PubMed: 38912052
DOI: 10.1093/ismeco/ycae075 -
PeerJ 2024Polish Konik remains one of the most important horse breeds in Poland. The primitive, native horses with a stocky body and mouse-like coat color are protected by a...
Polish Konik remains one of the most important horse breeds in Poland. The primitive, native horses with a stocky body and mouse-like coat color are protected by a conservation program, while their Polish population consists of about 3,480 individuals, representing 16 dam and six sire lines. To define the population's genetic structure, mitochondrial DNA and Y chromosome sequence variables were identified. The mtDNA whole hypervariable region analysis was carried out using the Sanger sequencing method on 233 Polish Koniks belonging to all dam lines, while the Y chromosome analysis was performed with the competitive allele-specific PCR genotyping method on 36 horses belonging to all sire lines. The analysis of the mtDNA hypervariable region detected 47 SNPs, which assigned all tested horses to 43 haplotypes. Most dam lines presented more than one haplotype; however, five dam lines were represented by only one haplotype. The haplotypes were classified into six (A, B, E, J, G, R) recognized mtDNA haplogroups, with most horses belonging to haplogroup A, common among Asian horse populations. Y chromosome analysis allocated Polish Koniks in the Crown group, condensing all modern horse breeds, and divided them into three haplotypes clustering with coldblood breeds (28 horses), warmblood breeds (two horses), and Duelmener Pony (six horses). The clustering of all Wicek sire line stallions with Duelmener horses may suggest a historical relationship between the breeds. Additionally, both mtDNA and Y chromosome sequence variability results indicate crossbreeding before the studbooks closure or irregularities in the pedigrees occurred before the DNA testing introduction.
Topics: Animals; Horses; DNA, Mitochondrial; Poland; Y Chromosome; Haplotypes; Male; Polymorphism, Single Nucleotide; Female; Breeding
PubMed: 38912049
DOI: 10.7717/peerj.17549 -
PeerJ 2024Determining the genetic diversity and source rookeries of sea turtles collected from feeding grounds can facilitate effective conservation initiatives. To ascertain the...
Determining the genetic diversity and source rookeries of sea turtles collected from feeding grounds can facilitate effective conservation initiatives. To ascertain the genetic composition and source rookery, we examined a partial sequence of the mitochondrial control region (CR, 796 bp) of 40 green turtles () collected from feeding grounds around the Korean Peninsula between 2014 and 2022. We conducted genetic and mixed-stock analyses (MSA) and identified 10 CR haplotypes previously reported in Japanese populations. In the haplotype network, six, three, and one haplotype(s) grouped with the Japan, Indo-Pacific, and Central South Pacific clades, respectively. The primary rookeries of the green turtles were two distantly remote sites, Ogasawara (OGA) and Central Ryukyu Island (CRI), approximately 1,300 km apart from each other. Comparing three parameters (season, maturity, and specific feeding ground), we noted that OGA was mainly associated with summer and the Jeju Sea, whereas CRI was with fall and the East (Japan) Sea ground. The maturity did not show a distinct pattern. Our results indicate that green turtles in the feeding grounds around the Korean Peninsula originate mainly from the Japan MU and have genetic origins in the Japan, Indo-Pacific, and Central South Pacific clades. Our results provide crucial insights into rookeries and MUs, which are the focus of conservation efforts of the Republic of Korea and potential parties to collaborate for green turtle conservation.
Topics: Animals; Turtles; Republic of Korea; Haplotypes; Genetic Variation; DNA, Mitochondrial; Animal Migration; Feeding Behavior; Seasons; Conservation of Natural Resources
PubMed: 38912045
DOI: 10.7717/peerj.17560 -
PeerJ 2024The development of serodiagnostic tests and vaccines for COVID-19 depends on the identification of epitopes from the SARS-CoV-2 genome. An epitope is the specific part...
BACKGROUND
The development of serodiagnostic tests and vaccines for COVID-19 depends on the identification of epitopes from the SARS-CoV-2 genome. An epitope is the specific part of an antigen that is recognized by the immune system and can elicit an immune response. However, when the genetic variants contained in epitopes are used to develop rapid antigen tests (Ag-RDTs) and DNA or RNA vaccines, test sensitivity and vaccine efficacy can be low.
METHODS
Here, we developed a "variant on epitope (VOE)" software, a new Python script for identifying variants located on an epitope. Variant analysis and sensitivity calculation for seven recommended epitopes were processed by VOE. Variants in 1,011 Omicron SRA reads from two variant databases (BCFtools and SARS-CoV-2-Freebayes) were processed by VOE.
RESULTS
A variant with HIGH or MODERATE impact was found on all epitopes from both variant databases except the epitopes KLNDLCFTNV, RVQPTES, LKPFERD, and ITLCFTLKRK on the S gene and ORF7a gene. All epitope variants from the BCFtools and SARS-CoV-2 Freebayes variant databases showed about 100% sensitivity except epitopes APGQTGK and DSKVGGNYN on the S gene, which showed respective sensitivities of 28.4866% and 6.8249%, and 87.7349% and 71.1177%.
CONCLUSIONS
Therefore, the epitopes KLNDLCFTNV, RVQPTES, LKPFERD, and ITLCFTLKRK may be useful for the development of an epitope-based peptide vaccine and GGDGKMKD on the N gene may be useful for the development of serodiagnostic tests. Moreover, VOE can also be used to analyze other epitopes, and a new variant database for VOE may be further established when a new variant of SARS-CoV-2 emerges.
Topics: Humans; SARS-CoV-2; COVID-19; COVID-19 Vaccines; Epitopes; Software; Sensitivity and Specificity
PubMed: 38912043
DOI: 10.7717/peerj.17504 -
Frontiers in Chemistry 2024DNA gyrase and topoisomerase IV show great potential as targets for antibacterial medicines. In recent decades, various categories of small molecule inhibitors have been...
DNA gyrase and topoisomerase IV show great potential as targets for antibacterial medicines. In recent decades, various categories of small molecule inhibitors have been identified; however, none have been effective in the market. For the first time, we developed a series of disalicylic acid methylene/Schiff bases hybrids () to act as antibacterial agents targeting DNA gyrase and topoisomerase IV. The findings indicated that the new targets exhibited significant antibacterial activity against Gram-positive and Gram-negative bacteria, with efficacy ranging from 75% to 115% of the standard ciprofloxacin levels. Compound demonstrated the greatest efficacy compared to the other compounds tested, with minimum inhibitory concentration (MIC) values of 0.030, 0.065, and 0.060 μg/mL against , , and . had a MIC value of 0.050 μg/mL against , which is five times less potent than ciprofloxacin. The inhibitory efficacy of the most potent antibacterial derivatives , , , and against DNA gyrase was assessed. The tested compounds demonstrated inhibitory effects on DNA gyrase, with IC values ranging from 92 to 112 nM. These results indicate that , , , and are more effective than the reference novobiocin, which had an IC value of 170 nM. Compounds , , , and were subjected to additional assessment against topoisomerase IV. Compounds and , which have the highest efficacy in inhibiting gyrase, also demonstrated promising effects on topoisomerase IV. Compounds and exhibit IC values of 3.50 µM and 5.80 µM, respectively. These results are much lower and more potent than novobiocin's IC value of 11 µM. Docking studies demonstrate the potential of compound as an effective dual inhibitor against DNA gyrase and topoisomerase IV, with ADMET analysis indicating promising pharmacokinetic profiles for antibacterial drug development.
PubMed: 38911996
DOI: 10.3389/fchem.2024.1419242 -
Journal of Inflammation Research 2024Alzheimer's disease (AD) is the most common neurodegenerative illness, characterized by memory loss and cognitive decline, accounting for 60-80% of dementia cases. AD is... (Review)
Review
Alzheimer's disease (AD) is the most common neurodegenerative illness, characterized by memory loss and cognitive decline, accounting for 60-80% of dementia cases. AD is characterized by senile plaques made up of amyloid β (Aβ) protein, intracellular neurofibrillary tangles caused by hyperphosphorylation of tau protein linked with microtubules, and neuronal loss. Currently, therapeutic treatments and nanotechnological developments are effective in treating the symptoms of AD, but a cure for the illness has not yet been found. Recently, the increased study of extracellular vesicles (EVs) has led to a growing awareness of their significant involvement in neurodegenerative disorders, including AD. Exosomes are small extracellular vesicles that transport various components including messenger RNAs, non-coding RNAs, proteins, lipids, DNA, and other bioactive compounds from one cell to another, facilitating information transmission and material movement. There is growing evidence indicating that exosomes have complex functions in AD. Exosomes may have a dual role in Alzheimer's disease by contributing to neuronal death and also helping to alleviate the pathological progression of the disease. Therefore, the primary aim of this review is to outline the updated understandings on exosomes biogenesis and many functions of exosomes in the generation, conveyance, distribution, and elimination of hazardous proteins related to Alzheimer's disease. This review is intended to provide novel insights for understanding the development, specific treatment, and early detection of Alzheimer's disease.
PubMed: 38911990
DOI: 10.2147/JIR.S466821 -
RSC Advances Jun 2024In this study, nickel selenide (NiSe), Ag/CN-NiSe, and CN/Ag-NiSe nanowires (NWs) were synthesized coprecipitation. The prepared NWs were employed for the degradation...
In this study, nickel selenide (NiSe), Ag/CN-NiSe, and CN/Ag-NiSe nanowires (NWs) were synthesized coprecipitation. The prepared NWs were employed for the degradation of the rhodamine B (RhB) dye in the absence of light using sodium borohydride (NaBH), bactericidal activity against pathogenic () and docking study to investigate the d-alanine ligase (DDl) and deoxyribonucleic acid (DNA) gyrase of . NWs demonstrate a catalytic degradation efficiency of 69.58% toward RhB in a basic medium. The percentage efficacy of the synthesized materials was evaluated as 19.12-42.62% at low and 36.61-49.72% at high concentrations against pathogenic . Molecular docking results suggest that both CN/Ag-doped NiSe and Ag/CN-doped NiSe possess inhibitory activities toward DDl and DNA gyrase of , which coincides with the bactericidal activity. Based on the research outcomes, the synthesized NWs show potential as an effective agent for water purification and resistance to microbial contaminants.
PubMed: 38911830
DOI: 10.1039/d4ra01437e -
Bioinformatics Advances 2024Genomic islands (GEIs) are clusters of genes in bacterial genomes that are typically acquired by horizontal gene transfer. GEIs play a crucial role in the evolution of...
MOTIVATION
Genomic islands (GEIs) are clusters of genes in bacterial genomes that are typically acquired by horizontal gene transfer. GEIs play a crucial role in the evolution of bacteria by rapidly introducing genetic diversity and thus helping them adapt to changing environments. Specifically of interest to human health, many GEIs contain pathogenicity and antimicrobial resistance genes. Detecting GEIs is, therefore, an important problem in biomedical and environmental research. There have been many previous studies for computationally identifying GEIs. Still, most of these studies rely on detecting anomalies in the unannotated nucleotide sequences or on a fixed set of known features on annotated nucleotide sequences.
RESULTS
Here, we present TreasureIsland, which uses a new unsupervised representation of DNA sequences to predict GEIs. We developed a high-precision boundary detection method featuring an incremental fine-tuning of GEI borders, and we evaluated the accuracy of this framework using a new comprehensive reference dataset, Benbow. We show that TreasureIsland's accuracy rivals other GEI predictors, enabling efficient and faster identification of GEIs in unannotated bacterial genomes.
AVAILABILITY AND IMPLEMENTATION
TreasureIsland is available under an MIT license at: https://github.com/FriedbergLab/GenomicIslandPrediction.
PubMed: 38911822
DOI: 10.1093/bioadv/vbae089