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1.
RNA Biol ; : 1-11, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34570675

RESUMO

5-Methylcytosine (m5C) is a type of RNA modification that exists in tRNAs and rRNAs and was recently found in mRNA. Although mRNA m5C modification has been reported to regulate diverse biological process, its function in adipogenesis remains unknown. Here, we demonstrated that knockdown of NOL1/NOP2/Sun domain family member 2 (NSUN2), a m5C methyltransferase, increased lipid accumulation of 3T3-L1 preadipocytes through accelerating cell cycle progression during mitotic clonal expansion (MCE) at the early stage of adipogenesis. Mechanistically, we proved that NSUN2 directly targeted cyclin-dependent kinase inhibitor 1A (CDKN1A) mRNA, a key inhibitory regulator of cell cycle progression, and upregulated its protein expression in an m5C-dependent manner. Further study identified that CDKN1A was the target of Aly/REF export factor (ALYREF), a reader of m5C modified mRNA. Upon NSUN2 deficiency, the recognition of CDKN1A mRNA by ALYREF was suppressed, resulting in the decrease of CDKN1A mRNA shuttling from nucleus to cytoplasm. Thereby, the translation of CDKN1A was reduced, leading to the acceleration of cell cycle and the promotion of adipogenesis. Together, these findings unveiled an important function and mechanism of the m5C modification on adipogenesis by controlling cell cycle progression, providing a potential therapeutic target to prevent obesity.

2.
Org Biomol Chem ; 19(38): 8352-8366, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34528053

RESUMO

Histone deacetylase 8 (HDAC8) has been used as a therapeutic target for many cancers as it is highly expressed in neuroblastoma cells and breast cancer cells. HDAC8-selective fluorescent probes need to be urgently developed. Herein, two novel fluorescent probes, namely NP-C6-PCI and AM-C6-PCI, based on the conjugation of 1,8-naphthalimide with a highly selective inhibitor of HDAC8 (PCI-34051) were reported. Compared with PCI-34051 (KD = 6.25 × 10-5 M), NP-C6-PCI (KD = 8.05 × 10-6 M) and AM-C6-PCI (KD = 7.42 × 10-6 M) showed great selectivity toward HDAC8. Two fluorescent probes exhibited high fluorescence intensity under λex = 450 nm and a large Stokes shift (100 nm). NP-C6-PCI was selected for cell and tissue imaging due to the similarity in the bioactivity of NP-C6-PCI with PCI-34051. The ability of NP-C6-PCI to target imaging HDAC8 in SH-SY5Y and MDA-MB-231 tumor cells was demonstrated. Furthermore, NP-C6-PCI was applied to imaging SH-SY5Y tumor tissue slices to indicate the relative expression level of HDAC8. Therefore, this HDAC8-selective fluorescent probe can be expected for applications in HDAC8-targeted drug screening as well as in pathologic diagnoses.

3.
Int J Mol Sci ; 22(16)2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34445242

RESUMO

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and usually lethal lung disease and it has been widely accepted that fibroblast proliferation is one of the key characteristics of IPF. Long noncoding RNAs (lncRNAs) play vital roles in the pathogenesis of many diseases. In this study, we investigated the role of lncRNA FENDRR on fibroblast proliferation. Human lung fibroblasts stably overexpressing FENDRR showed a reduced cell proliferation compared to those expressing the control vector. On the other hand, FENDRR silencing increased fibroblast proliferation. FENDRR bound serine-arginine rich splicing factor 9 (SRSF9) and inhibited the phosphorylation of p70 ribosomal S6 kinase 1 (PS6K), a downstream protein of the mammalian target of rapamycin (mTOR) signaling. Silencing SRSF9 reduced fibroblast proliferation. FENDRR reduced ß-catenin protein, but not mRNA levels. The reduction of ß-catenin protein levels in lung fibroblasts by gene silencing or chemical inhibitor decreased fibroblast proliferation. Adenovirus-mediated FENDRR transfer to the lungs of mice reduced asbestos-induced fibrotic lesions and collagen deposition. RNA sequencing of lung tissues identified 7 cell proliferation-related genes that were up-regulated by asbestos but reversed by FENDRR. In conclusion, FENDRR inhibits fibroblast proliferation and functions as an anti-fibrotic lncRNA.


Assuntos
Proliferação de Células , Fibroblastos/metabolismo , Pulmão/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais , beta Catenina/metabolismo , Linhagem Celular , Humanos , RNA Longo não Codificante/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Fatores de Processamento de Serina-Arginina/genética , Fatores de Processamento de Serina-Arginina/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , beta Catenina/genética
4.
Commun Biol ; 4(1): 921, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34326461

RESUMO

Retinoic acid-inducible gene I (RIG-I) senses viral RNA and instigates an innate immune signaling cascade to induce type I interferon expression. Currently, the regulatory mechanisms controlling RIG-I activation remain to be fully elucidated. Here we show that the FAK family kinase-interacting protein of 200 kDa (FIP200) facilitates RIG-I activation. FIP200 deficiency impaired RIG-I signaling and increased host susceptibility to RNA virus infection. In vivo studies further demonstrated FIP200 knockout mice were more susceptible to RNA virus infection due to the reduced innate immune response. Mechanistic studies revealed that FIP200 competed with the helicase domain of RIG-I for interaction with the two tandem caspase activation and recruitment domains (2CARD), thereby facilitating the release of 2CARD from the suppression status. Furthermore, FIP200 formed a dimer and facilitated 2CARD oligomerization, thereby promoting RIG-I activation. Taken together, our study defines FIP200 as an innate immune signaling molecule that positively regulates RIG-I activation.

5.
Anal Cell Pathol (Amst) ; 2021: 6615979, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34094815

RESUMO

Liver cancer is a major contributor to cancer-related death with poor survival for sufferers. Meanwhile, Hepatic B virus X protein (HBx) and XB130 are likely to participate in the pathogenesis of liver cancer. However, the detailed mechanism of HBx/XB130 in liver cancer remains to be further investigated. Our study explored the effects of HBx/XB130 on liver cancer progression. HBx and XB130 expression was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot. Overexpression of HBx and XB130 was found in liver cancer tissues and cells. Mechanistic study revealed that HBx could bind to and positively regulate XB130 in HepG2 cells. Subsequently, HBx expression was knocked down, while XB130 was overexpressed in HepG2 cells in order to observe the specific role of HBx/XB130 in liver cancer in vitro. Results of CCK-8, Transwell, wound healing, and colony formation assays suggested that HBx could mediate biological function of HepG2 cells by activating the XB130-mediated PI3K/AKT pathway. In summary, our data illustrate that inhibition of HBx effectively suppressed proliferation and metastasis and induced apoptosis of liver cancer cells, which might be partially reversed by XB130. HBx and XB130 may be potential targets for liver cancer pathogenesis.

6.
Anal Bioanal Chem ; 413(16): 4237-4246, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33948704

RESUMO

Methamphetamine (MA) is a highly addictive and illegal psychostimulant drug and is currently one of the most commonly abused illicit drugs in the world. The on-site rapid detection of trace amounts of MA and screening illicit drugs in clandestine laboratories is important for drug enforcement agencies and the forensic community in general. However, detecting methamphetamine in the presence of nicotine and cigarette smoke by ion mobility spectrometry faces difficulty due to the overlapped spectral peaks of methamphetamine and nicotine. In this work, a new method was developed to detect MA using pyridine as a dopant in the presence of nicotine by a homemade ion mobility spectrometry. The reduced mobilities of MA and nicotine were measured under the temperatures of the drift tube from 40 to 120 °C and doping with pyridine. The result shows that the temperature of 100 °C is beneficial to resolve the two substances. The concentration of doped pyridine is optimized to be 18 ppm. In this doped experiment, the reaction rate of nicotine is higher than that of MA by measuring the instrumental responses of MA and nicotine. No matter how high the nicotine content is, the interference of nicotine can be eliminated in the detection of MA doped with pyridine. This method is also successfully applied for the determination of MA and nicotine simultaneously in real saliva samples. The limit of detection of MA was measured to be about 0.5 ng/µL. The promising results in this work provide an effective method for on-site detection of MA.


Assuntos
Estimulantes do Sistema Nervoso Central/análise , Metanfetamina/análise , Nicotina/análise , Saliva/química , Humanos , Drogas Ilícitas/análise , Espectrometria de Mobilidade Iônica/métodos , Limite de Detecção , Piridinas/química , Detecção do Abuso de Substâncias/métodos
7.
Histol Histopathol ; 36(5): 559-566, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33724438

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the most common cancer of the digestive system. However, effective therapeutic targets against CRC have not been found yet. Further, the relationship between the expression of ring finger protein 126 (RNF126) and CRC is not clear. MATERIAL AND METHODS: The expression level of RNF126 in CRC tissues and cell lines was detected by immunohistochemical staining and western blot. Subsequently, endogenous RNF126 expression was inhibited in a CRC cell line using a short hairpin RNA. Next, the effect of RNF126 on the properties of CRC cells was studied through different experimental methods. RESULTS: We found that the RNF126 protein was mainly localized in the cytoplasm. High RNF126 expression was observed to be an independent risk factor for poor prognosis in CRC patients. In vitro studies showed that RNF126 was able to promote the proliferation, migration, and invasion ability of CRC cells. CONCLUSION: RNF126 acts as an oncogene during CRC development, and may serve as a novel target for CRC treatment.

8.
Arch Virol ; 166(2): 363-373, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33206218

RESUMO

Influenza A virus (IAV) infections result in a large number of deaths and substantial economic losses each year. MicroRNAs repress gene expression and are involved in virus-host interactions. miR-29a is known to have anti-tumor and anti-fibrotic effects. However, the role of miR-29a in IAV infection is unclear. In the present study, we investigated the effect of miR-29a on IAV infection and the mechanisms by which it functions. IAV infection was found to cause decreased miR-29a expression in lung epithelial A549 cells and mouse lungs. Overexpression of miR-29a reduced IAV mRNA and protein levels and progeny virus production in HEK293 and A549 cells. Inhibition of IAV infection by miR-29a was observed with different strains of IAV, including A/PR/8/34, A/WSN/1933, and clinical isolates A/OK/3052/09 and A/OK/309/06 H3N2. Knockout of miR-29a using CRISPR/Cas9 resulted in an increase in viral mRNA and protein levels, confirming that miR-29a suppresses IAV infection. A 3' untranslated region (3'-UTR) reporter assay showed that miR-29a had binding sites in the 3'-UTR of the Wnt-Ca2+ signaling receptor frizzled 5 gene, and overexpression of miR-29a reduced the level of the endogenous frizzled 5 protein. Wnt5a treatment of HEK293 and A549 cells enhanced IAV infection. Our results suggest that miR-29a inhibits IAV infection, probably via the frizzled 5 receptor.


Assuntos
Receptores Frizzled/genética , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/genética , Influenza Humana/virologia , MicroRNAs/genética , Regiões 3' não Traduzidas/genética , Células A549 , Animais , Sítios de Ligação/genética , Linhagem Celular , Linhagem Celular Tumoral , Cães , Feminino , Expressão Gênica/genética , Células HEK293 , Humanos , Pulmão/virologia , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos C57BL , Infecções por Orthomyxoviridae/genética , Infecções por Orthomyxoviridae/virologia
9.
Cell Microbiol ; 23(2): e13281, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33099847

RESUMO

Due to the frequent mutations, influenza A virus (IAV) becomes resistant to anti-viral drugs targeting influenza viral proteins. There are increasing interests in anti-viral agents that target host cellular proteins required for virus replication. Tankyrase (TNKS) has poly (ADP-ribose) polymerase activity and is a negative regulator of many host proteins. The objectives of this study are to study the role of TNKS2 in IAV infection, identify the microRNAs targeting TNKS2, and to understand the mechanisms involved. We found that TNKS2 expression was elevated in human lung epithelial cells and mouse lungs during IAV infection. Knock-down of TNKS2 by RNA interference reduced viral replication. Using a computation approach and 3'-untranslation regions (3'-UTR) reporter assay, we identified miR-206 as the microRNA that targeted TNKS2. Overexpression of miR-206 reduced viral protein levels and virus production in cell culture. The effect of miR-206 on IAV replication was strain-independent. miR-206 activated JNK/c-Jun signalling, induced type I interferon expression and enhanced Stat signalling. Finally, the delivery of an adenovirus expressing miR-206 into the lung of mice challenged with IAV increased type I interferon response, suppressed viral load in the lungs and increased survival. Our results indicate that miR-206 has anti-influenza activity by targeting TNKS2 and subsequently activating the anti-viral state.

10.
Front Genet ; 11: 568192, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33133154

RESUMO

Cumulative studies have shown that RNA binding proteins (RBPs) play an important role in numerous malignant tumors and are related to the occurrence and progression of tumors. However, the role of RBPs in kidney renal clear cell carcinoma (KIRC) is not fully understood. In this study, we first downloaded gene expression data and corresponding clinical information of KIRC from the Cancer Genome Atlas (TCGA) database, International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) database, respectively. A total of 137 differentially expressed RBPs (DERBPs) were then identified between normal and tumor tissue, including 38 downregulated and 99 upregulated RBPs. Nine RBPs (EIF4A1, RPL36A, EXOSC5, RPL28, RPL13, RPS19, RPS2, EEF1A2, and OASL) were served as prognostic genes and exploited to construct a prognostic model through survival analysis. Kaplan-Meier curves analysis showed that the low-risk group had a better survival outcome when compared with the high-risk group. The area under the curve (AUC) value of the prognostic model was 0.713 in the TCGA data set (training data set), 0.706 in the ICGC data set, and 0.687 in the GSE29609 data set, respectively, confirming a good prognostic model. The prognostic model was also identified as an independent prognostic factor for KIRC survival by performing cox regression analysis. In addition, we also built a nomogram relying on age and the prognostic model and internal validation in the TCGA data set. The clinical benefit of the prognostic model was revealed by decision curve analysis (DCA). Gene set enrichment analysis revealed several crucial pathways (ERBB signaling pathway, pathways in cancer, MTOR signaling pathway, WNT signaling pathway, and TGF BETA signaling pathway) that may explain the underlying mechanisms of KIRC. Furthermore, potential drugs for KIRC treatment were predicted by the Connectivity Map (Cmap) database based on DERBPs, including several important drugs, such as depudecin and vorinostat, that could reverse KIRC gene expression, which may provide reference for the treatment of KIRC. In summary, we developed and validated a robust nine-RBP signature for KIRC prognosis prediction. A nomogram with risk score and age can be applied to promote the individualized prediction of overall survival in patients with KIRC. Moreover, the two drugs depudecin and vorinostat may contribute to KIRC treatment.

11.
Am J Transl Res ; 12(10): 6537-6548, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194050

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has spread to almost all countries. The currently reported epidemiological statistics show that age, gender, and type of comorbidities may be high-risk factors for critically ill patients with COVID-19. However, there is no comprehensive analysis of these risk factors. In the present study, we systematically explored the prognostic value of the clinical factors (gender, age and comorbidities) in 189 COVID-19 patients from Wuhan, China. We discovered that the gender, age and comorbidities were tightly associated with the survival of COVID-19 patients via performing Kaplan-Meier curve analysis. Compared with the female patients, male patients have a lower survival rate. Similarly, the older patients and those with more comorbidities also tended to have an unfavorable survival outcome. In addition, further stratified analysis of COVID-19 patients according to the three risk factors indicated that some laboratory indicators including CRP, IL-6 and lymphocytes showed significant trends in gender, age and comorbidities groups. Together, these result which may provide a certain reference value for the prevention and treatment of COVID-19.

12.
Sci Rep ; 10(1): 14412, 2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32879362

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma (RCC). Despite the existing extensive research, the molecular and pathogenic mechanisms of ccRCC are elusive. We aimed to identify the immune-related lncRNA signature and molecular subtypes associated with ccRCC. By integrating 4 microarray datasets from Gene Expression Omnibus database, we identified 49 immune-related genes. The corresponding immune-related lncRNAs were further identified in the TCGA dataset. 12-lncRNAs prognostic and independent signature was identified through survival analysis and survival difference between risk groups was further identified based on the risk score. Besides, we identified 3 molecular subtypes and survival analysis result showed that cluster 2 has a better survival outcome. Further, ssGSEA enrichment analysis for the immune-associated gene sets revealed that cluster 1 corresponded to a high immune infiltration level. While cluster 2 and cluster 3 corresponded to low and medium immune infiltration level, respectively. In addition, we validated the 12-lncRNA prognostic signature and molecular subtypes in an external validation dataset from the ICGC database. In summary, we identified a 12-lncRNA prognostic signature which may provide new insights into the molecular mechanisms of ccRCC and the molecular subtypes provided a theoretical basis for personalized treatment by clinicians.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , RNA Longo não Codificante/genética , Biomarcadores Tumorais/imunologia , Carcinoma de Células Renais/classificação , Carcinoma de Células Renais/imunologia , Redes Reguladoras de Genes , Humanos , Neoplasias Renais/classificação , Neoplasias Renais/imunologia , RNA Longo não Codificante/imunologia , Transcriptoma
13.
Environ Pollut ; 265(Pt B): 114628, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32806440

RESUMO

Volatile organic compounds (VOCs) are important precursors of ozone (O3) and secondary organic aerosols (SOAs). Tracing VOC pollution sources is important for controlling VOC emissions and reducing O3 and SOAs. We built a novel mobile proton transfer reaction mass spectrometry (M-PTR-MS) instrument to image the distribution of VOCs and trace their emission sources in cities and industrial parks. The M-PTR-MS is composed of a vibration-resistant proton transfer reaction mass spectrometry (PTR-MS) with a global positioning system receiver, modified box vehicle, and geographic information system (GIS) software. The PTR-MS, mounted on a vehicle, sends VOC data and vehicle position information to the GIS software. These data are used to image the space distribution of VOCs in real time while the vehicle platform is in motion and the VOC sources are precisely traced using the GIS. The spatial data resolution of the M-PTR-MS is typically 0.8 m. The limits of detection, sensitivity, and repeatability of the M-PTR-MS are 43.5 ppt, 347 counts ppb-1, and 2.4% (RSD, n = 5), respectively. The intensity of reagent ions is stable over 8 h (RSD = 0.45%). Compared with commercial PTR-MS equipment, the M-PTR-MS demonstrated high consistency, with a correlation coefficient of 92.665%. Several field experiments were conducted in China using the M-PTR-MS. In one field experiment, the VOC distribution along three different routes was surveyed; the navigation monitoring lasted 1.8 h over a distance of 26.7 km at an average speed of 15 km h-1. The VOC sources in an industrial park were identified by analyzing the components near different factories. The main species from a VOC source in an underground garage was related to paint. The M-PTR-MS instrument can be used by environmental protection agencies to trace VOC pollution sources in real time, and by researchers to survey VOC emissions in regions of concern.


Assuntos
Compostos Orgânicos Voláteis , China , Cidades , Espectrometria de Massas , Prótons
14.
Sci Rep ; 10(1): 13672, 2020 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-32792604

RESUMO

Macrophages play an essential role in host defense and display remarkable plasticity in switching between classically (pro-inflammatory-M1) and alternatively activated (anti-inflammatory-M2) phenotypes. The molecular mechanisms of macrophage polarization are not fully understood. Long non-coding RNAs (lncRNAs) with a length of > 200 nucleotides have been shown to play diverse roles in biological processes. Aberrant expression of lncRNAs is associated with a variety of pathophysiological conditions such as cancer, diabetes, cardiovascular, pulmonary diseases, and tissue fibrosis. In this study, we investigated the role of lncRNA FENDRR in human and mouse macrophage polarization. Human THP-1 monocytes were activated with phorbol-12-myristate-13-acetate (PMA) and differentiated into M1 macrophages with IFNγ or M2 macrophages with IL4. Real-time PCR analysis revealed that FENDRR was expressed 80-fold higher in M1 macrophages than that in M2 macrophages. Overexpression of FENDRR in PMA-activated THP-1 cells increased the IFNγ-induced expression of M1 markers, including IL1ß and TNFα at both mRNA and protein levels. Knockdown of FENDRR had an opposite effect. Similarly, FENDRR overexpression in primary mouse bone marrow-derived macrophages increased mRNA expression of M1 markers. FENDRR overexpression increased, while FENDRR knock-down decreased, the IFNγ-induced phosphorylation of STAT1 in PMA-activated THP-1 cells. Our studies suggest that FENDRR enhances IFNγ-induced M1 macrophage polarization via the STAT1 pathway.


Assuntos
Regulação para Baixo , Interferon gama/farmacologia , Monócitos/citologia , RNA Longo não Codificante/genética , Animais , Polaridade Celular , Regulação para Baixo/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Ativação de Macrófagos , Camundongos , Monócitos/metabolismo , Fator de Transcrição STAT1/metabolismo , Células THP-1
15.
Fish Shellfish Immunol ; 106: 21-27, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32693157

RESUMO

Monogenean Gyrodactylus cichlidarum can cause severe mortality of Nile tilapia (Oreochromis niloticus) fry. To date, reports about mucosal immunity of O. niloticus against this parasite have been rare. In order to explore the mucosal immunity of Nile tilapia against G. cichlidarum infection, the expressions of six adaptive immune-related genes and the contents of specific immunoglobulin IgM and IgT in the skin-associated lymphoid tissues (SALT) were dynamically analyzed after primary and secondary infections. The abundances of G. cichlidarum on the hosts after secondary infection were lower than those after primary parasite infection, which implied that hosts could initiate immune protection against G. cichlidarum reinfection to some degree. The transcription levels of TCR-ß and CD4 genes in the skin tissue were significantly up-regulated after primary G. cichlidarum infection, while genes pIgR and IgT were only detected with significant up-regulations during secondary infection. With the exception of pIgR, which had remarkably higher expression in the fish with low parasite loads, all other genes studied tended to have higher mRNA level in the fish with higher parasite loads. The specific IgM content in the skin mucus increased significantly on the 2nd day after the primary exposure, higher than the corresponding value during the secondary exposure, and had significantly positive correlation with the parasite loads during the first parasite infection. These results manifested that acquired immune responses in the SALT of Nile tilapia participated in the resistance against G. cichlidarum infection, underscoring the involvement of mucosal immunity in fish against monogenean infection, and suggesting potential prophylactic treatment of gyrodactylid disease of tilapia.


Assuntos
Ciclídeos , Doenças dos Peixes/imunologia , Imunidade nas Mucosas , Trematódeos/fisiologia , Infecções por Trematódeos/veterinária , Animais , Doenças dos Peixes/parasitologia , Infecções por Trematódeos/imunologia , Infecções por Trematódeos/parasitologia
16.
Oncol Lett ; 20(1): 817-827, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32566009

RESUMO

Salvianolic acid B (Sal-B) is widely used in China for the treatment of numerous diseases. Currently, Salvia miltiorrhiza Bunge is the main source of this compound, but Salvia bowleyana Dunn, a surrogate of S. miltiorrhiza Bge, may provide a novel source for obtaining more Sal-B. In the present study, a simple method for separation and purification of phenolic compounds from S. bowleyana Dunn roots was employed. Sal-B was subsequently purified and its inhibitory effect on the gastric cancer HGC-27 and AGS cell lines was investigated. Sal-B extracted from S. bowleyana Dunn displayed significant antitumor activity in proliferation and apoptosis assays. Overall, it was found that S. bowleyana Dunn has a higher Sal-B content than S. miltiorrhiza Bge and may be used as a novel source of this potential anti-gastric cancer compound.

17.
Anal Bioanal Chem ; 412(22): 5397-5408, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32564118

RESUMO

In order to find out cancer markers in human breath, in vitro cell culture is often used to study the characteristic volatile organic compounds (VOCs). In the cell culture process, disposable vessels are frequently adopted. However, these vessels are normally made of plastic, and they have the possibility to release some VOCs, which may interfere with the cell-specific volatiles and even can result in an incorrect conclusion. In this study, by using glass cell culture flasks as control, the headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS) analyses of the VOCs in plastic cell culture flasks were systematically carried out for the first time. A total of 35 VOCs were detected in five brands of flasks. In each flask, there were between 13 and 25 volatile compounds. Furthermore, the components and packaging bag of each flask were also sampled and analyzed by HS-SPME-GC-MS. The results show that the flask cap, septum, flask body, and packaging bag exhibit respectively different volatile behaviors. The former two parts release the most volatiles which have obvious contributions to the headspace gases in the flasks, while the flask body mainly liberates styrene. For different flasks packed within the same bag, the headspace analyses show that their residual VOCs are inconsistent with each other. Moreover, the residual VOCs in the same flask are variable in three consecutive days. These results indicate that the multiple flasks in parallel cell culture experiments, or the same flask with different cell culture durations, will produce an indelible disturbance to the cell-specific VOCs. In addition, among the 35 VOCs detectable in five brands of empty plastic flasks, 15 VOCs were previously reported as characteristic VOCs from lung cancer, melanoma, cervical cancer cells, or normal cells. This is an alert that, when using plastic flasks, it must be careful to treat the possible interference from the background VOCs in the flasks. This study demonstrates that the cell culture tool needs to be standardized, and the clean glass or metal vessels are strongly recommended for usage when studying cell volatile biomarkers. Graphical abstract.


Assuntos
Biomarcadores Tumorais/análise , Plásticos , Compostos Orgânicos Voláteis/análise , Testes Respiratórios , Técnicas de Cultura de Células , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Neoplasias/diagnóstico , Microextração em Fase Sólida/métodos
18.
Exp Ther Med ; 19(6): 3604-3610, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32346424

RESUMO

MicroRNA-454 (miR-454), is involved in the progression of various types of cancers. The present study aimed to evaluate the effect of miR-454 on the progression of gastric cancer. SGC-7901 cells overexpressing or silencing miR454 were constructed via transfection and the survival rate of the cells was determined. The relationship between miR-454 and cylindromatosis (CYLD) was explored and the influence of miR-454 on oxaliplatin resistance was investigated in SGC-7901 cells. It was determined that overexpression of miR-454 increased the number of colonies and reduced apoptosis rate of SGC-7901 cells. The CYLD gene was identified as a direct target of miR-454. miR-454 overexpression downregulated the expression of CYLD, leading to an increase in SGC-7901 cell proliferation. Finally, miR-454 was also demonstrated to induce resistance to oxaliplatin in gastric cancer cells. In conclusion, the present in vitro findings suggested that miR-454 might be a novel therapeutic target for gastric cancer.

19.
Children (Basel) ; 7(4)2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32344542

RESUMO

Depression has become the most prevalent mental health problem in developing countries, and especially among adolescents. Lubans and his colleagues proposed a psychosocial mechanism to understand the trajectory of mental health (i.e., depression). Thus, this study aimed (1) to examine the relations between different doses of physical activity (PA), light PA (LPA), moderate PA (MPA), and vigorous PA (VPA), academic self-efficacy, and depression among adolescents, and (2) to investigate the direct and indirect relations of various doses of PA to depression through academic self-efficacy among middle school adolescents. Participants were 428 (235 boys, Mean age = 13.7) adolescents recruited from two middle schools in China. They completed previously validated questionnaires to measure different intensity levels of PA (LPA, MPA, and VPA), academic self-efficacy, and depression. There were significant associations of academic self-efficacy with three different doses of PA (p < 0.01). Both LPA and MPA were negatively associated with depression but not VPA. Structural equation modeling (SEM) revealed a well-fit model suggesting the psychosocial pathway from different doses of PA to depression through academic self-efficacy. Findings of this study indicated that academic self-efficacy regulates adolescents' depression. Tailoring different intensities of PA benefits adolescents' academic self-efficacy by framing the positive and supportive environment in schools, which can potentially reduce the prevalence of depression during adolescence.

20.
Anal Bioanal Chem ; 412(15): 3663-3671, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32333078

RESUMO

Breath analysis is a promising method for metabolomics studies and clinical diagnosis, as it enables the observation of metabolites in a convenient and noninvasive way. In this work, an atmospheric pressure photoionization (APPI) source was modified for online analysis of exhaled breath by coupling with quadrupole time-of-flight mass spectrometry (QTOFMS). Three parameters, namely, the capillary voltage, the sampling flow and the curtain gas flow of the APPI source, were optimized. Five healthy volunteers, three males and two females, were enrolled to test the performance of modified APPI-QTOFMS by analyzing their exhaled breath. A total of 21 compounds were tentatively identified, and four metabolites, namely, dimethyl selenoxide, δ-valerolactam, hydroxymandelic acid and palmitic amide were detected in the exhaled breath for the first time. The result shows that modified APPI-QTOFMS can be used for the online study of exhaled breath. Graphical abstract.


Assuntos
Testes Respiratórios/instrumentação , Espectrometria de Massas/instrumentação , Pressão Atmosférica , Desenho de Equipamento , Expiração , Feminino , Humanos , Lactamas/análise , Masculino , Metabolômica/instrumentação , Compostos Organosselênicos/análise , Óxidos/análise
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