The human gut hosts a diverse community of bacteria referred to as the gut microbiome. We investigated the association between the relative abundance of gastric microbiota and gastric cancer (GC) ...risk in a Korean population. The study participants included 268 GC patients and 288 controls. DNA was extracted from gastric biopsies, and 16S rRNA gene analysis was performed. Unconditional logistic regression models were used to observe the associations. Of the participants, those who had the highest level (highest tertile) of relative Helicobacter pylori and Propionibacterium acnes abundances showed a significantly higher risk for GC after adjusting for potential confounding variables (odds ratio (OR) = 1.86, 95% confidence interval (CI) = 1.17-2.97, p for trend = 0.017 and OR = 4.77, 95% CI = 2.94-7.74, p for trend <0.001, respectively). Subjects who carried Prevotella copri had a significantly higher risk of GC than noncarriers (OR = 2.54, 95% CI = 1.42-4.55, p for trend = 0.002). There was a lower risk of GC in subjects carrying Lactococcus lactis than in noncarriers (OR = 0.21, 95% CI = 0.10-0.44, p for trend <0.001). H. pylori, P. acnes and P. copri are strong risk factors, whereas L. lactis is a protective factor, for GC development in Koreans. Further microbiome studies are warranted to verify the findings of the current study.
Characterizing the microbial communities inhabiting specimens is one of the primary objectives of microbiome studies. A short-read sequencing platform for reading partial regions of the 16S rRNA gene ...is most commonly used by reducing the cost burden of next-generation sequencing (NGS), but misclassification at the species level due to its length being too short to consider sequence similarity remains a challenge. Loop Genomics recently proposed a new 16S full-length-based synthetic long-read sequencing technology (sFL16S). We compared a 16S full-length-based synthetic long-read (sFL16S) and V3-V4 short-read (V3V4) methods using 24 human GUT microbiota samples. Our comparison analyses of sFL16S and V3V4 sequencing data showed that they were highly similar at all classification resolutions except the species level. At the species level, we confirmed that sFL16S showed better resolutions than V3V4 in analyses of alpha-diversity, relative abundance frequency and identification accuracy. Furthermore, we demonstrated that sFL16S could overcome the microbial misidentification caused by different sequence similarity in each 16S variable region through comparison the identification accuracy of Bifidobacterium, Bacteroides, and Alistipes strains classified from both methods. Therefore, this study suggests that the new sFL16S method is a suitable tool to overcome the weakness of the V3V4 method.
Silver nanoparticles (AgNPs) have gained attention for use in cancer therapy. In this study, AgNPs were biosynthesized using naringenin. We investigated the anti-colon cancer activities of biogenic ...AgNPs through transcriptome analysis using RNA sequencing, and the mechanisms of AgNPs in regulating colon cancer cell growth. The synthesized AgNPs were characterized using UV⁻visible spectroscopy (UV⁻vis), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). The AgNPs were spherical with sizes of 2⁻10 nm. Cytotoxicity assays indicated that the AgNPs in HCT116 colorectal cancer cells were very effective at low concentrations. The viability and proliferation of colon cancer cells treated with 5 µg/mL biogenic AgNPs were reduced by 50%. Increased lactate dehydrogenase leakage (LDH), reactive oxygen species (ROS) generation, malondialdehyde (MDA), and decreased dead-cell protease activity and ATP generation were observed. This impaired mitochondrial function and DNA damage led to cell death. The AgNPs upregulated and downregulated the most highly ranked biological processes of oxidation⁻reduction and cell-cycle regulation, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that AgNPs upregulated
in the p53 pathway. Thus, the AgNP tumor suppressive effects were mediated by cell apoptosis following DNA damage, as well as by mitochondrial dysfunction and cell-cycle arrest following aberrant regulation of p53 effector proteins. It is of interest to mention that, to the best of our knowledge, this study is the first report demonstrating cellular responses and molecular pathways analysis of AgNPs in HCT116 colorectal cancer cells.
The rapid development of nanotechnology has led to the use of silver nanoparticles (AgNPs) in biomedical applications, including antibacterial, antiviral, anti-inflammatory, and anticancer therapies. ...The molecular mechanism of AgNPs-induced cytotoxicity has not been studied thoroughly using a combination of cellular assays and RNA sequencing (RNA-Seq) analysis. In this study, we prepared AgNPs using myricetin, an anti-oxidant polyphenol, and studied their effects on NIH3T3 mouse embryonic fibroblasts as an in vitro model system to explore the potential biomedical applications of AgNPs. AgNPs induced loss of cell viability and cell proliferation in a dose-dependent manner, as evident by increased leakage of lactate dehydrogenase (LDH) from cells. Reactive oxygen species (ROS) were a potential source of cytotoxicity. AgNPs also incrementally increased oxidative stress and the level of malondialdehyde, depleted glutathione and superoxide dismutase, reduced mitochondrial membrane potential and adenosine triphosphate (ATP), and caused DNA damage by increasing the level of 8-hydroxy-2'-deoxyguanosine and the expressions of the
and
genes in NIH3T3 cells. Thus, activation of oxidative stress may be crucial for NIH3T3 cytotoxicity. Interestingly, gene ontology (GO) term analysis revealed alterations in epigenetics-related biological processes including nucleosome assembly and DNA methylation due to AgNPs exposure. This study is the first demonstration that AgNPs can alter bulk histone gene expression. Therefore, our genome-scale study suggests that the apoptosis observed in NIH3T3 cells treated with AgNPs is mediated by the repression of genes required for cell survival and the aberrant enhancement of nucleosome assembly components to induce apoptosis.
Recent studies have demonstrated the generation of midbrain-like organoids (MOs) from human pluripotent stem cells. However, the low efficiency of MO generation and the relatively immature and ...heterogeneous structures of the MOs hinder the translation of these organoids from the bench to the clinic. Here we describe the robust generation of MOs with homogeneous distribution of midbrain dopaminergic (mDA) neurons. Our MOs contain not only mDA neurons but also other neuronal subtypes as well as functional glial cells, including astrocytes and oligodendrocytes. Furthermore, our MOs exhibit mDA neuron-specific cell death upon treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, indicating that MOs could be a proper human model system for studying the in vivo pathology of Parkinson's disease (PD). Our optimized conditions for producing homogeneous and mature MOs might provide an advanced patient-specific platform for in vitro disease modeling as well as for drug screening for PD.
Recently, Chait et al. proposed a new aggregate signature scheme under the RSA setting (IEEE Access, 2023). In this paper, we show that Chait et al.'s aggregate signature scheme is insecure when two ...signers collude with their own secret keys, by presenting an attack algorithm that forges aggregate signatures of aggregator or individual signatures of all other (non-colluding) users. More concretely, our attack algorithm consists of three sub-algorithms: The first sub-algorithm computes a multiple of <inline-formula> <tex-math notation="LaTeX">\phi (N) </tex-math></inline-formula> from secret keys of two users where <inline-formula> <tex-math notation="LaTeX">N </tex-math></inline-formula> is the RSA modulus that is included in the public parameter of the system and <inline-formula> <tex-math notation="LaTeX">\phi </tex-math></inline-formula> is the Euler totient function. The second sub-algorithm recovers an equivalent secret key of a target user that is congruent to his/her original secret key modulo <inline-formula> <tex-math notation="LaTeX">\phi (N) </tex-math></inline-formula> from his/her public key and the multiple of <inline-formula> <tex-math notation="LaTeX">\phi (N) </tex-math></inline-formula> which is the output of the first sub-algorithm. Finally, with the equivalent secret key obtained by the second sub-algorithm, the last sub-algorithm generates valid aggregate/individual signatures of the target user. Our attack algorithm always succeeds in forging aggregate/individual signatures. Furthermore, it is lightweight in the sense that it requires several integer operations, gcd computations, and an execution of aggregate/individual signing algorithm only. For example, when the pubic parameter and secret keys of all users, except the target user, are provided, our experimental results demonstrate that the proposed attack algorithm takes less than 1 second only in total to forge an aggregate signature of 29 individual signatures including that of the target user, where <inline-formula> <tex-math notation="LaTeX">N </tex-math></inline-formula> is 3,072 bits for 128-bit security.
Progesterone (P
) is required for the preparation of the endometrium for a successful pregnancy. P
resistance is a leading cause of the pathogenesis of endometrial disorders like endometriosis, often ...leading to infertility; however, the underlying epigenetic cause remains unclear. Here we demonstrate that CFP1, a regulator of H3K4me3, is required for maintaining epigenetic landscapes of P
-progesterone receptor (PGR) signaling networks in the mouse uterus. Cfp1
;Pgr-Cre (Cfp1
) mice showed impaired P
responses, leading to complete failure of embryo implantation. mRNA and chromatin immunoprecipitation sequencing analyses showed that CFP1 regulates uterine mRNA profiles not only in H3K4me3-dependent but also in H3K4me3-independent manners. CFP1 directly regulates important P
response genes, including Gata2, Sox17, and Ihh, which activate smoothened signaling pathway in the uterus. In a mouse model of endometriosis, Cfp1
ectopic lesions showed P
resistance, which was rescued by a smoothened agonist. In human endometriosis, CFP1 was significantly downregulated, and expression levels between CFP1 and these P
targets are positively related regardless of PGR levels. In brief, our study provides that CFP1 intervenes in the P
-epigenome-transcriptome networks for uterine receptivity for embryo implantation and the pathogenesis of endometriosis.
Precise regulation of the cell cycle of embryonic stem cells (ESCs) is critical for their self-maintenance and differentiation. The cell cycle of ESCs differs from that of somatic cells and is ...different depending on the cell culture conditions. However, the cell cycle regulation in ESCs via epigenetic mechanisms remains unclear. Here, we showed that the ATP-dependent chromatin remodeler Ino80 regulates the cell cycle genes in ESCs under primed conditions. Ino80 loss led to a significantly extended length of the G1-phase in ESCs grown under primed culture conditions. Ino80 directly bound to the transcription start site and regulated the expression of cell cycle-related genes. Furthermore, Ino80 loss induced cell apoptosis. However, the regulatory mechanism of Ino80 in differentiating ESC cycle slightly differed; an extended S-phase was detected in differentiating inducible Ino80 knockout ESCs. RNA-seq analysis of differentiating ESCs revealed that the expression of genes associated with organ development cell cycle is persistently altered in Ino80 knockout cells, suggesting that cell cycle regulation by Ino80 is not limited to undifferentiated ESCs. Therefore, our study establishes the function of Ino80 in ESC cycle via transcriptional regulation, at least partly. Moreover, this Ino80 function may be universal to other cell types.
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