RESUMO
Eukaryotic organisms have evolved a set of strategies to safeguard genome integrity, but the underlying mechanisms remain poorly understood. Here, we report that asymmetric leaves1/2 enhancer7 (AE7), an Arabidopsis thaliana gene encoding a protein in the evolutionarily conserved Domain of Unknown Function 59 family, participates in the cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) pathway to maintain genome integrity. The severe ae7-2 allele is embryo lethal, whereas plants with the weak ae7 (ae7-1) allele are viable but exhibit highly accumulated DNA damage that activates the DNA damage response to arrest the cell cycle. AE7 is part of a protein complex with CIA1, NAR1, and MET18, which are highly conserved in eukaryotes and are involved in the biogenesis of cytosolic and nuclear Fe-S proteins. ae7-1 plants have lower activities of the cytosolic [4Fe-4S] enzyme aconitase and the nuclear [4Fe-4S] enzyme DNA glycosylase ROS1. Additionally, mutations in the gene encoding the mitochondrial ATP binding cassette transporter ATM3/ABCB25, which is required for the activity of cytosolic Fe-S enzymes in Arabidopsis, also result in defective genome integrity similar to that of ae7-1. These results indicate that AE7 is a central member of the CIA pathway, linking plant mitochondria to nuclear genome integrity through assembly of Fe-S proteins.
Assuntos
Proteínas de Arabidopsis/fisiologia , Arabidopsis/genética , Proteínas de Ciclo Celular/fisiologia , Genoma de Planta , Proteínas Ferro-Enxofre/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/fisiologia , Alelos , Arabidopsis/enzimologia , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Pontos de Checagem do Ciclo Celular , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Dano ao DNA , Mitocôndrias/metabolismo , Mutação , Leveduras/genéticaRESUMO
Background: Oral cancer is one of the most prevalent malignant tumors worldwide. Silibinin has been reported to exert therapeutic effects in various cancer models. However, its mechanism of action in oral cancer remains unclear. We aimed to examine the molecular processes underlying the effects of silibinin in oral cancer in vitro and in vivo as well as its potential anticancer effects. Next, we investigated the molecular processes underlying both in vitro and in vivo outcomes of silibinin treatment on oral cancer. Methods: To investigate the effects of silibinin on the growth of oral cancer cells, cell proliferation and anchorage-independent colony formation tests were conducted on YD10B and Ca9-22 oral cancer cells. The effects of silibinin on the migration and invasion of oral cancer cells were evaluated using transwell assays. Flow cytometry was used to examine apoptosis, cell cycle distribution, and accumulation of reactive oxygen species (ROS). The molecular mechanism underlying the anticancer effects of silibinin was explored using immunoblotting. The in vivo effects of silibinin were evaluated using a Ca9-22 xenograft mouse model. Results: Silibinin effectively suppressed YD10B and Ca9-22 cell proliferation and colony formation in a dose-dependent manner. Moreover, it induced cell cycle arrest in the G0/G1 phase, apoptosis, and ROS generation in these cells. Furthermore, silibinin inhibited the migration and invasion abilities of YD10B and Ca9-22 cells by regulating the expression of proteins involved in the epithelial-mesenchymal transition. Western blotting revealed that silibinin downregulated SOD1 and SOD2 and triggered the JNK/c-Jun pathway in oral cancer cells. Silibinin significantly inhibited xenograft tumor growth in nude mice, with no obvious toxicity. Conclusions: Silibinin considerably reduced the development of oral cancer cells by inducing apoptosis, G0/G1 arrest, ROS generation, and activation of the JNK/c-Jun pathway. Importantly, silibinin effectively suppressed xenograft tumor growth in nude mice. Our findings indicate that silibinin may be a promising option for the prevention or treatment of oral cancer.
RESUMO
To comprehensively study the ginsenosides distribution in the various tissues of American ginseng, the qualitative and quantitative-targeted and nontargeted mass spectroscopic methods were established using the high-performance liquid chromatography coupled with Qtrap triple quadrupole mass spectrometry (HPLC-QtrapQQQ-MS). The total ginsenosides of the root, stem, and leaf of American ginseng were determined by a colorimetric method, and the contents showed the order from high to low root, stem, and leaf. Eighty-two kinds of ginsenosides were detected in the different parts of American ginseng by enhanced mass scan-information-dependent data acquisition (IDA)-enhanced product ion (EPI) scan mode, including 69 from the root, 62 from the stem, and 48 from the leaf. An HPLC-multiple reaction monitoring (MRM) method was established, and 28 representative ginsenosides were further quantified in the three parts. Nearly all ginsenosides had the highest contents in the root and the lowest content in the leaf. Three types of ginsenosides (protopanaxadiol [PPD]-, protopanaxatiol [PPT]-, and oleanolic acid [OA]-types) were analyzed by precursor ion-IDA-EPI and MRM-IDA-EPI scan modes. Root had the most abundant ginsenosides in PPD- and PPT-type ginsenosides. Meanwhile, the OA-type ginsenosides are significantly enriched in the stem and leaf of American ginseng. The results provided a supplement to the quality assessment of American ginseng. PRACTICAL APPLICATION: The distribution profile of ginsenosides in the parts of American ginseng is different. Except for the root, the stem, and leaf of American ginseng have the most abundant ginsenosides in oleanolic acid type. The results reported herein can help the manufacturers choose appropriate materials to extract the ginsenosides.
Assuntos
Ginsenosídeos , Ácido Oleanólico , Panax , Espectrometria de Massas em Tandem/métodos , Panax/química , Cromatografia Líquida de Alta Pressão/métodosRESUMO
Since the rapid development of network technology, the rise of live-streaming shopping platforms has followed. Some streamers influence consumers' preferences for products through their gender role attributes, thus generating great commercial value. Based on attachment theory and using an experimental approach, this study explored the impact of streamers' gender roles (single gender/androgyny) on consumers' preferences through 2 studies. Study 1 shows the androgynous streamer elicits a higher product preference than the single-gender (masculine and feminine) streamer. Study 2 demonstrates the moderating effect of gender stereotypes through 2 experiments to construct clear boundary conditions for the main effect and the results show that regardless of whether the streamer is male or female when individuals have a high gender stereotype, the single-gender streamer leads to a higher product preference than the androgynous streamer. When individuals have a low gender stereotype, the androgynous streamer promotes a higher product preference than the single-gender streamer.
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Epidemiological and clinical characteristics of patients with COVID-19 have been reported in the last two years. A few studies reported clinical course of illness of median 22 days, including viral shedding of median 20 days, but there are several cases with a longer time of viral shedding. In this study, we included four cases with a longer illness course of more than 40 days who had been discharged or still in hospital by March 15, 2020. Demographic, clinical treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records. We described the epidemiological and clinical characteristics and the course of viral shedding. Two patients had comorbidity, one with hypertension and the other with diabetes. We found smoking was not an independent risk factor. D-dimer maybe related to the severity of illness but not to the course of the illness. Nucleic acid detection suggested that maybe more sampling sites represented more virus replication sites and longer course of illness. In this study we found some non-critical severe relatively young patients whose character was different from former studies described to provide a basis for reference to assess the risk of transmission and the isolation duration of patients.
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BACKGROUND: 20(S)-Ginsenoside Rh2 (G-Rh2) has demonstrated therapeutic effects in many types of cancers. We aimed to investigate the potential anticancer activity and underlying mechanisms of G-Rh2 in oral cancer cells. MATERIALS AND METHODS: The antigrowth effect of G-Rh2 in oral cancer cells was stimulated by cell proliferation, soft agar colony formation, and migration and invasion assay. The cell cycle and apoptosis were detected by flow cytometry. The underlying mechanism of G-Rh2 in oral cancer cells was explored by immunoblotting. RESULTS: G-Rh2 significantly inhibited oral cancer cell growth by inducing apoptosis and cell cycle G0/G1-phase arrest. G-Rh2 inhibited oral cancer cell migration and invasion through regulation of epithelial-mesenchymal transition (EMT)-related proteins. G-Rh2 inhibited the Src/Raf/ERK signaling pathway in YD10B and Ca9-22 cells. CONCLUSION: G-Rh2 exerted anticancer activity in vitro by inhibiting the Src/Raf/ERK signaling pathway in oral cancer. G-Rh2 is a potential therapeutic drug for oral cancer treatment.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Ginsenosídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Quinases raf/metabolismo , Quinases da Família src/metabolismo , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citometria de Fluxo , Ginsenosídeos/química , Humanos , Neoplasias Bucais/metabolismoRESUMO
BACKGROUND/AIM: [6]-Gingerol, a compound extracted from ginger, has been studied for its therapeutic potential in various types of cancers. However, its effects on oral cancer remain largely unknown. Here, we aimed to investigate the potential anticancer activity and underlying mechanisms of [6]-gingerol in oral cancer cells. MATERIALS AND METHODS: We analyzed the antigrowth effects of [6]-gingerol in oral cancer cell lines by cell proliferation, colony formation, migration, and invasion assays. We detected cell cycle and apoptosis with flow cytometry and further explored the mechanisms of action by immunoblotting. RESULTS: [6]-Gingerol significantly inhibited oral cancer cell growth by inducing apoptosis and cell cycle G2/M phase arrest. [6]-Gingerol also inhibited oral cancer cell migration and invasion by up-regulating E-cadherin and down-regulating N-cadherin and vimentin. Moreover, [6]-gingerol induced the activation of AMPK and suppressed the AKT/mTOR signaling pathway in YD10B and Ca9-22 cells. CONCLUSION: [6]-Gingerol exerts anticancer activity by activating AMPK and suppressing the AKT/mTOR signaling pathway in oral cancer cells. Our findings highlight the potential of [6]-gingerol as a therapeutic drug for oral cancer treatment.
Assuntos
Neoplasias Bucais , Proteínas Proto-Oncogênicas c-akt , Proteínas Quinases Ativadas por AMP/genética , Apoptose , Catecóis , Linhagem Celular Tumoral , Proliferação de Células , Álcoois Graxos , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/genéticaRESUMO
A maternal woman was positive for SARS-CoV-2 tested in throat swabs but negative tested in other body fluids, and she had IgG and IgA detected in breast milk. Her infant negative for SARS-CoV-2 at birth had elevated IgG in serum but quickly decayed. These findings suggest that breastfeeding might have the potential benefit to the neonates.
Assuntos
Anticorpos Antivirais/análise , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Leite Humano/imunologia , Pneumonia Viral/imunologia , Complicações Infecciosas na Gravidez/virologia , Adulto , Anticorpos Antivirais/imunologia , COVID-19 , China , Feminino , Humanos , Imunoglobulina A/análise , Imunoglobulina G/análise , Recém-Nascido , Leite Humano/virologia , Pandemias , Gravidez , Complicações Infecciosas na Gravidez/imunologia , SARS-CoV-2RESUMO
Retroperitoneal schwannomas are a rare disease. During the potent antiretroviral therapy era, the incidence of AIDS-defining cancers has decreased, while the incidence of non-AIDS defining cancers has increased; however, the existence of a relationship between benign or malignant schwannomas and AIDS remains unclear. Although a case of ethmoid malignant schwannoma in an AIDS patient was first reported in 1993, no additional reports of schwannomas associated with AIDS have been published since. In the current study, the case of a 30-year-old male AIDS patient with a large benign retroperitoneal schwannoma is presented. The ideal treatment of retroperitoneal schwannomas is complete excision. However, controversy exists over the necessity of negative soft tissue margins, particularly when adjacent tissue or viscera must also be removed. In the current case study, due to the immune dysfunction in AIDS patients, the incidence of malignancy could not be completely excluded prior to surgery and a significant risk of short-term relapse or malignancy following partial tumor resection was present. The patient underwent complete resection with partial superior mesenteric artery excision in order to attain negative margins, and recovered well. A follow-up was performed 1 year after the procedure and the patient was well and a CT scan demonstrated no evidence of recurrence. However, the long term efficacy of this procedure requires continued observation in this patient.
RESUMO
BACKGROUND: We investigated the hypermethylation status in serum of sporadic breast cancer patients. MATERIAL AND METHODS: The hypermethylation status of BRCA1, p16 and 14-3-3sigma in cancerous tissues and the paired serum of 38 sporadic breast cancer patients was examined by methylation-specific PCR (MSP) assay. Normal and benign tissue and serum control DNA were also examined to determine the specificity of hypermethylation. RESULTS: Hypermethylation of 1 or more genes was found in 36/38 (95%) of sporadic breast cancers. BRCA1 was hypermethylated in 14/38 (37%), p16 in 13/38 (34%), and 14- 3-3sigma in 33/38 (87%) of cancerous tissues. 71% of the corresponding serum DNA was positive for hypermethylation, including all histological types, stages and grades. No methylated products of BRCA1, p16 and 14-3-3sigma were observed in serum DNA from healthy women and patients with benign tissue specimens. A gene unmethylated in the tumor DNA was always found to be unmethylated in matched serum DNA. CONCLUSIONS: Hypermethylation of BRCA1, p16 and 14-3-3sigma is present in all histologic types, stages and grades in sporadic breast cancer and can be detected in serum DNA. It signifies that serum-based hypermethylation screening may enhance early detection of sporadic breast cancer.