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8-Epi-xanthatin induces the apoptosis of DU145 prostate carcinoma cells through signal transducer and activator of transcription 3 inhibition and reactive oxygen species generation
No full textSignal transducer and activator of transcription 3 (STAT3) is aberrantly activated in many human cancers. We tried to find STAT3 inhibitors from natural sources and found that Xanthium fruit extracts decreased phosphorylation of STAT3-Y705. 8-Epi-xanthatin (EXT) was isolated from the extracts. When DU145 cancer cells were treated with EXT, p-STAT3-Y705 was decreased with an IC50 of 3.2 μM. EXT decreased the expression of STAT3 target genes, such as cyclin A, cyclin D1, and BCL-2, and induced PARP cleavage, indicating apoptotic cell death. Downregulation of EXT-induced p-STAT3-Y705 was rescued by pretreating DU145 cells with antioxidants, such as N-acetyl-L-cysteine (NAC), indicating that reactive oxygen species (ROS) were involved in the EXT-induced inhibition of STAT3 activation. Furthermore, we proved the association of EXT with STAT3 protein by using a drug affinity responsive target stability (DARTS) assay and a cellular thermal shift assay (CETSA). EXT inhibited proliferation of DU145 cells with a GI50 of 6 μM and reduced tumor growth in mice xenografted with DU145 cells. Immunoblotting showed that phosphorylation of STAT3-Y705 was lower in EXT-treated tumor tissue than in control tissues. Collectively, we found that EXT binds to, and inhibits, STAT3 activation and could be a lead compound for anticancer therapy.
A study of genes that regulate development of both lateral organs and seeds in soybean
No full text콩 측기관과 종자 발달을 조절하는 유전자의 연구OGM512201
N-adamantyl phthalimidine: a new thalidomide-like drug that lacks cereblon binding and mitigates neuronal and synaptic loss, neuroinflammation, and behavioral deficits in traumatic brain injury and LPS challenge
No full textNeuroinflammation contributes to delayed secondary cell death following traumatic brain injury (TBI), has the potential to chronically exacerbate the initial insult, and represents a therapeutic target that has largely failed to translate into human efficacy. Thalidomide-like drugs have effectively mitigated neuroinflammation across cellular and animal models of TBI and neurodegeneration but are complicated by adverse actions in humans. We hence developed N-adamantyl phthalimidine (NAP) as a new thalidomide-like drug to mitigate inflammation without binding to cereblon, a key target associated with the antiproliferative, antiangiogenic, and teratogenic actions seen in this drug class. We utilized a phenotypic drug discovery approach that employed multiple cellular and animal models and ultimately examined immunohistochemical, biochemical, and behavioral measures following controlled cortical impact (CCI) TBI in mice. NAP mitigated LPS-induced inflammation across cellular and rodent models and reduced oligomeric α-synuclein and amyloid-β mediated inflammation. Following CCI TBI, NAP mitigated neuronal and synaptic loss, neuroinflammation, and behavioral deficits, and is unencumbered by cereblon binding, a key protein underpinning the teratogenic and adverse actions of thalidomide-like drugs in humans. In summary, NAP represents a new class of thalidomide-like drugs with anti-inflammatory actions for promising efficacy in the treatment of TBI and potentially longer-term neurodegenerative disorders.
Development of a cosmetic ingredient containing DHA derivatives for anti-inflammation, anti-wrinkle, and improvement of skin barrier function
No full textIt is very important to control the inflammation of the skin because it can develop into diseases such as atopy as well as scarring and aging. In this work, we recently identified the in vitro synthesis of specialized pro-resolving mediators (SPMs) known to control inflammation in the human body and the applicability of cosmetics. Using recombinant protein of lipoxygenase from Glycine max, we succeeded to prepare mixtures of mono- or di-hydroxy DHA named as S-SPMs and used them for in vitro efficacy test. To investigate anti-inflammatory effect of S-SPMs, mRNA level of TNF-α and IL-6 were analyzed. Under UVB exposed condition, expression of both were decreased by S-SPMs treatment. And we observed reduced production of nitric oxide (NO) by S-SPMs application under the condition with diesel particulate matter (DPM). At the same experimental condition, malondialdehyde (MDA) production was decreased by S-SPMs, indicating the inhibitory effect of S-SPMs in lipid peroxidation. In addition, S-SPMs treatment resulted in reduction of matrix metalloproteinases-1 (MMP-1) expression and elevation of procollagen type I synthesis. Together with this, mRNA level of filaggrin and loricrin were increased by S-SPMs, indicating enhancement of skin barrier function. These results demonstrate that S-SPMs is a good candidate to develop as a cosmetic ingredient for anti-inflammation, anti-wrinkle, and improvement of skin barrier function.
A more accessible, time-saving, and efficient method for in vitro plant regeneration from potato protoplasts
No full textBoth obtaining high-yielding, viable protoplasts and following reliable regeneration protocols are prerequisites for the continuous expansion and development of newly emerging systems involving protoplast utilization. This study determines an efficient process from protoplast isolation to shoot regeneration in vitro. The maximum yield of protoplast extraction, which was 6.36 ± 0.51 × 106 protoplasts/g fresh weight (FW), was approximately 3.7 times higher than that previously reported for potato protoplasts. To obtain data, wounded leaves were used by partially cutting both sides of the midrib, and isolated protoplasts were purified by the sucrose cushion method, with a sucrose concentration of 20%. We confirmed a significant effect on the extraction efficiency by measuring enzymolysis during a 6 h period, with three times more washing buffer than the amount normally used. Protoplasts fixed in alginate lenses with appropriate space were successfully recovered and developed into microcalli 2 weeks after culture. In addition, to induce high efficiency regeneration from protoplasts, calli in which greening occurred for 6 weeks were induced to develop shoots in regeneration medium solidified by Gelrite, and they presented a high regeneration efficiency of 86.24 ± 11.76%.
DGG-100629 inhibits lung cancer growth by suppressing the NFATc1/DDIAS/STAT3 pathway
No full textDNA damage-induced apoptosis suppressor (DDIAS) promotes the progression of lung cancer and hepatocellular carcinoma through the regulation of multiple pathways. We screened a chemical library for anticancer agent(s) capable of inhibiting DDIAS transcription. DGG-100629 was found to suppress lung cancer cell growth through the inhibition of DDIAS expression. DGG-100629 induced c-Jun NH(2)-terminal kinase (JNK) activation and inhibited NFATc1 nuclear translocation. Treatment with SP600125 (a JNK inhibitor) or knockdown of JNK1 restored DDIAS expression and reversed DGG-100629-induced cell death. In addition, DGG-100629 suppressed the signal transducer and activator of transcription (STAT3) signaling pathway. DDIAS or STAT3 overexpression restored lung cancer cell growth in the presence of DGG-100629. In a xenograft assay, DGG-100629 inhibited tumor growth by reducing the level of phosphorylated STAT3 and the expression of STAT3 target genes. Moreover, DGG-100629 inhibited the growth of lung cancer patient-derived gefitinib-resistant cells expressing NFATc1 and DDIAS. Our findings emphasize the potential of DDIAS blockade as a therapeutic approach and suggest a novel strategy for the treatment of gefitinib-resistant lung cancer.
Cytosine base editor-mediated multiplex genome editing to accelerate discovery of novel antibiotics in Bacillus subtilis and Paenibacillus polymyxa
No full textGenome-based identification of new antibiotics is emerging as an alternative to traditional methods. However, uncovering hidden antibiotics under the background of known antibiotics remains a challenge. To over this problem using a quick and effective genetic approach, we developed a multiplex genome editing system using a cytosine base editor (CBE). The CBE system achieved simultaneous double, triple, quadruple, and quintuple gene editing with efficiencies of 100, 100, 83, and 75%, respectively, as well as the 100% editing efficiency of single targets in Bacillus subtilis. Whole-genome sequencing of the edited strains showed that they had an average of 8.5 off-target single-nucleotide variants at gRNA-independent positions. The CBE system was used to simultaneously knockout five known antibiotic biosynthetic gene clusters to leave only an uncharacterized polyketide biosynthetic gene cluster in Paenibacillus polymyxa E681. The polyketide showed antimicrobial activities against gram-positive bacteria, but not gram-negative bacteria and fungi. Therefore, our findings suggested that the CBE system might serve as a powerful tool for multiplex genome editing and greatly accelerating the unraveling of hidden antibiotics in Bacillus and Paenibacillus species.
The human TOR signaling regulator is the key indicator of liver cancer patients' overall survival: TIPRL/LC3/CD133/CD44 as potential biomarkers for early liver cancers
No full textRecently, we reported the involvement of TIPRL/LC3/CD133 in liver cancer aggressive-ness. This study assessed the human TOR signaling regulator (TIPRL)/microtubule-associated light chain 3 (LC3)/prominin-1 (CD133)/cluster of differentiation 44 (CD44) as potential diagnostic and prognostic biomarkers for early liver cancer. For the assessment, we stained tissues of human liver disease/cancer with antibodies against TIPRL/LC3/CD133/CD44/CD46, followed by con-focal observation. The roles of TIPRL/LC3/CD133/CD44/CD46 in liver normal and cancer cell lines were determined by in vitro studies. We analyzed the prognostic and diagnostic potentials of TIPRL/LC3/CD133/CD44/CD46 using the receiver-operating characteristic curve, a Kaplan？Meier and uni-/multi-Cox analyses. TIPRL and LC3 were upregulated in tissues of HCCs and adult hepatocytes-derived liver diseases while downregulated in iCCA. Intriguingly, TIPRL levels were found to be critically associated with liver cancer patients’ survivability, and TIPRL is the key player in liver cancer cell proliferation and viability via stemness and self-renewal induction. Further-more, we demonstrate that TIPRL/LC3/CD133 have shown prominent efficiency for diagnosing patients with grade 1 iCCA. TIPRL/LC3/CD133/CD44 have also provided excellent potential for prognosticating patients with grade 1 iCCA and grade 1 HCCs, together with demonstrating that TIPRL/LC3/CD133/CD44 are, either individually or in conjunction, potential biomarkers for early liver cancer. ⓒ 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Comparison between MGI and Illumina sequencing platforms for whole genome sequencing
No full textBackground: Illumina next generation sequencing (NGS) systems are the major sequencing platform in worldwide next-generation sequencing market. On the other hand, MGI Tech launched a series of new NGS equipment that promises to deliver high-quality sequencing data faster and at lower prices than Illumina's sequencing instruments.
Objective: In this study, we compared the performance of the two platform's major sequencing instruments-Illumina's NovaSeq 6000 and MGI's MGISEQ-2000 and DNBSEQ-T7-to test whether the MGISEQ-2000 and DNBSEQ-T7 sequencing instruments are also suitable for whole genome sequencing.
Methods: We sequenced two pairs of normal and tumor tissues from Korean lung cancer patients using the three platforms. Then, we called single nucleotide variants (SNVs) and insertion and deletion (indels) for somatic and germline variants to compare the performance among the three platforms.
Results: In quality control analysis, all of the three platforms showed high-quality scores and deep coverages. Comparison among the three platforms revealed that MGISEQ-2000 is most concordant with NovaSeq 6000 for germline SNVs and indels, and DNBSEQ-T7 is most concordant with NovaSeq 6000 for somatic SNVs and indels.
Conclusions: These results suggest that the performances of the MGISEQ-2000 and DNBSEQ-T7 platforms are comparable to that of the Illumina NovaSeq 6000 platform and support the potential applicability of the MGISEQ-2000 and DNBSEQ-T7 platforms in actual genome analysis fields.