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Background: Sepsis, which could cause a systemic inflammatory response, is a life-threatening disease with a high morbidity and mortality rate. There is evidence that brain injury may be related to severe systemic infection induced by sepsis. The brain injury caused by sepsis could increase the risk of mortality in septic patients, which seriously affects the septic patient's prognosis of survival. Although there remains a focus on sepsis research, clinical measures to prevent and treat brain injury in sepsis are not yet available, and the high mortality rate is still a big health burden. Therefore, it is necessary to investigate the new molecules or regulated pathways that can effectively inhibit the progress of sepsis. Objective: NLR family pyrin domain-containing 3 (NLRP3) increased in the procession of sepsis and functioned as the key regulator of pyroptosis. Heat shock factor 1 (HSF1) can protect organs from multiorgan dysfunction syndrome induced by lipopolysaccharides in mice, and NLRP3 could be inhibited by HSF1 in many organs. However, whether HSF1 regulated NLRP3 in sepsis-induced brain injury, as well as the detailed mechanism of HSF1 in brain injury, remains unknown in the sepsis model. In this research, we try to explore the relationship between HSF1 and NLRP3 in a sepsis model and try to reveal the mechanism of HSF1 inhibiting the process of brain injury. Methods: In this study, we used wild-type mice and hsf1 -/- mice for in vivo research and PC12 cells for in vitro research. Real-time PCR and Western blot were used to analyze the expression of HSF1, NLRP3, cytokines, and pyrolytic proteins. EthD-III staining was chosen to detect the pyroptosis of the hippocampus and PC12 cells. Results: The results showed that HSF1 is negatively related to pyroptosis. The pyroptosis in cells of brain tissue was significantly increased in the hsf1 -/- mouse model compared to hsf1 +/+ mice. In PC12 cells, hsf1 siRNA can upregulate pyroptosis while HSF1-transfected plasmid could inhibit the pyroptosis. HSF1 could negatively regulate the NLRP3 pathway in PC12 cells, while hsf1 siRNA enhanced the pyroptosis in PC12 cells, which could be reversed by nlrp3 siRNA. Conclusion: These results imply that HSF1 could alleviate sepsis-induced brain injury by inhibiting pyroptosis through the NLRP3-dependent pathway in brain tissue and PC12 cells, suggesting HSF1 as a potential molecular target for treating brain injury in sepsis clinical studies.
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Lesiones Encefálicas , Factores de Transcripción del Choque Térmico , Proteína con Dominio Pirina 3 de la Familia NLR , Sepsis , Animales , Ratones , Ratas , Factores de Transcripción del Choque Térmico/farmacología , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis , ARN Interferente Pequeño , Sepsis/metabolismoRESUMEN
BACKGROUND: Triple negative breast cancer (TNBC) is a molecular subtype of breast cancer, which is a major health burden of females worldwide. Thymoquinone (TQ), a natural compound, has been found to be effective against TNBC cells, and this study identified IL17RD as a novel target of TQ in TNBC cells. METHODS: We have performed chromatin immunoprecipitation Sequence (ChIP-Seq) by MBD1 (methyl-CpG binding domain protein 1) antibody to identify genome-wide methylated sites affected by TQ. ChIP-seq identified 136 genes, including the tumor suppressor IL17RD, as a novel target of TQ, which is epigenetically upregulated by TQ in TNBC cell lines BT-549 and MDA-MB-231. The IL17RD expression and survival outcomes were studied by Kaplan-Meier analysis. RESULTS: TQ treatment inhibited the growth, migration, and invasion of TNBC cells with or without IL17RD overexpression or knockdown, while the combination of IL17RD overexpression and TQ treatment were the most effective against TNBC cells. Moreover, higher expression of IL17RD is associated with longer survival in TNBC patients, indicating potential therapeutic roles of TQ and IL17RD against TNBC. CONCLUSIONS: Our data suggest that IL17RD might be epigenetically upregulated in TNBC cell lines by TQ, and this might be one of the mechanisms by which TQ exerts its anticancer and antimetastatic effects on TNBC cells.
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Neoplasias de la Mama Triple Negativas , Benzoquinonas/farmacología , Línea Celular Tumoral , Femenino , Humanos , Procesos Neoplásicos , Receptores de Interleucina/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/metabolismoRESUMEN
Cancer is one of the major health burdens worldwide, and genetic polymorphisms in individuals are closely associated with cancer susceptibility. Like in many other developing countries, the risk of cancer is increasing among Bangladeshi population. Genetic polymorphisms in xenobiotic metabolic enzymes (CYP1A1, CYP2A6, CYP3A4, CYP3A5, NAT2, SULT1A), cell cycle regulatory proteins (TP53, HER2, MDM2, miR-218-2, TGFB), cell signaling protein (CDH1), DNA repair proteins (BRCA1, BRCA2, EXO1, RAD51, XRCC2, ECCR1, ERCC4, XPC, ERCC2), and others (HLA-DRB1, INSIG2, GCNT1P5) have been found to be associated with various cancers like cancers of breast, bladder, cervix, colon, lung, prostate, etc. in different studies with Bangladeshi population. In this review article, we have discussed these gene polymorphisms associated with cancers in the Bangladeshi population, and also made a comparison with other ethnic groups. This will probably be helpful in understanding drug effects, drug resistance, and personalized medicine in the population of this region.
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Arilamina N-Acetiltransferasa , MicroARNs , Neoplasias , Arilamina N-Acetiltransferasa/genética , Bangladesh/epidemiología , Estudios de Casos y Controles , Citocromo P-450 CYP1A1/genética , Proteínas de Unión al ADN/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Neoplasias/genética , Polimorfismo Genético/genética , Proteína de la Xerodermia Pigmentosa del Grupo D/genéticaRESUMEN
Thymoquinone, a well-known phytoconstituent derived from the seeds of Nigella sativa, exhibits unique pharmacological activities However, despite the various medicinal properties of thymoquinone, its administration in vivo remains challenging due to poor aqueous solubility, bioavailability, and stability. Therefore, an advanced drugdelivery system is required to improve the therapeutic outcome of thymoquinone by enhancing its solubility and stability in biological systems. Therefore, this study is mainly focused on preparing thymoquinone-loaded liposomes to improve its physicochemical stability in gastric media and its performance in different cancer cell line studies. Liposomes were prepared using phospholipid extracted from egg yolk. The liposomal nano preparations were evaluated in terms of hydrodynamic diameter, zeta potential, microscopic analysis, and entrapment efficiency. Cell-viability measurements were conducted using breast and cervical cancer cell lines. Optimized liposomal preparation exhibited polygonal, globule-like shape with a hydrodynamic diameter of less than 260 nm, PDI of 0.6, and zeta potential values of -23.0 mV. Solid-state characterizations performed using DSC and XRPD showed that the freeze-dried liposomal preparations were amorphous in nature. Gastric pH stability data showed no physical changes (precipitation, degradation) or significant growth in the average size of blank and thymoquinone-loaded liposomes after 24 h. Cell line studies exhibited better performance for thymoquinone-loaded liposomal drug delivery system compared with the thymoquinone-only solution; this finding can play a critical role in improving breast and cervical cancer treatment management.
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Neoplasias de la Mama , Neoplasias del Cuello Uterino , Benzoquinonas , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Liposomas/química , Tamaño de la Partícula , Fosfolípidos , Neoplasias del Cuello Uterino/tratamiento farmacológicoRESUMEN
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related deaths in women worldwide. In this study, a large Chinese pedigree with breast cancer including a proband and two female patients was recruited and a familial history of breast cancer was collected by questionnaire. Clinicopathological assessments and neoadjuvant therapy-related information were obtained for the proband. Blood samples were taken, and gDNA was extracted. The BRCA1/2 and PALB2 genes were screened using next-generation sequencing by a targeted gene panel. We have successfully identified a novel, germline heterozygous, missense mutation of the gene BRCA2: c.7007G>T, p.R2336L, which is likely to be pathogenic in the proband and her elder sister who both had breast cancer. Furthermore, the risk factors for developing breast cancer in this family are discussed. Thus, genetic counselling and long-term follow-up should be provided for this family of breast cancer patients as well as carriers carrying a germline variant of BRCA2: c.7007G>T (p.R2336L).
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Pueblo Asiatico/genética , Neoplasias de la Mama/genética , Genes BRCA2 , Mutación de Línea Germinal/genética , Adulto , Proteína BRCA2/química , Proteína BRCA2/genética , Secuencia de Bases , Carcinoma Ductal de Mama/genética , Secuencia Conservada , Femenino , Humanos , Masculino , Persona de Mediana Edad , LinajeRESUMEN
Unfortunately, as for the second institute name of first author Baixu Zhou, "Department of Gynecology and Obstetrics, Guangzhou Women and Children's Hospital, Guangzhou, Guangdong, China", should be "Department of Gynecology and Obstetrics, Guangdong Women and Children Hospital, Guangzhou, Guangdong, China".
RESUMEN
In this study, we have analyzed 23 Y-chromosomal short tandem repeats (Y-STRs) (DYS576, DYS389I, DYS389II, DYS448, DYS19, DYS391, DYS481, DYS549, DYS533, DYS438, DYS437, DYS570, DYS635, DYS390, DYS439, DYS392, DYS643, DYS393, DYS458, DYS460, DYS385ab, DYS456 and Y-GATA-H4) in 175 father-son sample pairs using a Microreader™ 24Y Direct ID system. Sixteen repeat mutations of father-son pairs at 10 loci, including three mutations at DYS570, 2 mutations at DYS549, DYS460, DYS458, and DYS576, and 1 mutation at other five loci, were revealed. Furthermore, all of the observed repeat mutations were single repeat changes with 5 (31.25%) repeat insertions and 11 (68.75%) repeat deletions. The deletion rate is more than two fold higher than of insertions (11:5 = 2.2-fold). Locus-specific mutation rates estimated varied between 5.71 × 10-3 (CI from 0.1 × 10-3 to 31.4 × 10-3) and 1.71 × 10-2 (CI from 3.6 × 10-3 to 49.3 × 10-3) for the 23 Y-STRs. An average mutation rate across all 23 Y-STR markers was estimated as 3.97 × 10-3 (CI 2.3 × 10-3 to 6.4 × 10-3). Thus, locus-specific mutation rates in DYS460, DYS458, and DYS438, estimated are much higher than previously published comprehensive data, but an average mutation rate across all 23 Y-STR markers is similar to previous reports (3.97 × 10-3 vs 4.34 × 10-3). These results by characterizing Y-STR mutations will not only provided new information for Y-STR mutations but also might be important for paternal lineage identification, kinship analysis, and family relationship reconstruction in our forensic Y-STR analysis.
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Pueblo Asiatico/genética , Cromosomas Humanos Y/genética , Repeticiones de Microsatélite , Mutación , China , Padre , Humanos , MasculinoRESUMEN
Targeting on the IKKß to discover anti-inflammatory drugs has been launched for ten years, due to its predominant role in canonical NF-κB signaling. In the current study, we identified a novel IKKß inhibitor, ellipticine (ELL), an alkaloid isolated from Ochrosia elliptica and Rauvolfia sandwicensis. We found that ELL reduced the secretion and mRNA expression of TNF-α and IL-6 and decreased the protein expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in bone marrow derived macrophages (BMDMs) stimulated with LPS. In coincided with the results, ELL suppressed PGE2 and NO production in BMDMs. Underlying mechanistic study showed that ELL inhibited IκBα phosphorylation and degradation as well as NF-κB nuclear translocation, which was attributed to suppression of IKKα/ß activation. Furthermore, kinase assay and binding assay results indicated that ELL inhibited IKKß activity via directly binding to IKKß and in turn resulted in suppression of NF-κB signaling. To identify the binding sites of ELL on IKKß, IKKßC46A plasmid was prepared and the kinase assay was performed. The results demonstrated that the inhibitory effect of ELL on IKKß activity was impaired in the mutation, implying that anti-inflammatory effect of ELL was partially attributed to binding on cysteine 46. Furthermore, ELL up-regulated LC3 II expression and reduced p62 expression, suggesting that autophagy induction contributed to the anti-inflammatory effect of ELL as well. In coincided with the in vitro results, ELL increased the survival and antagonized the hypothermia in the mice with LPS-induced septic shock. Consistently, ELL reduced TNF-α and IL-6 production in the serum of the mice treated with LPS. Collectively, our study provides evidence that ELL is an IKKß inhibitor and has potential to be developed as a lead compound for treatment inflammatory diseases in the future.
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Antiinflamatorios/uso terapéutico , Elipticinas/uso terapéutico , Quinasa I-kappa B/antagonistas & inhibidores , Inflamación/tratamiento farmacológico , Choque Séptico/tratamiento farmacológico , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Células Cultivadas , Descubrimiento de Drogas , Elipticinas/química , Elipticinas/farmacología , Femenino , Humanos , Quinasa I-kappa B/inmunología , Inflamación/inmunología , Ratones , Ochrosia/química , Choque Séptico/inmunologíaRESUMEN
This study aimed to clone and characterize novel isoforms of the human SPATA3 gene. The isoforms of SPATA3 gene was cloned into pGMT vector using human testis cDNA as template, and Sanger sequencing was performed. Their characterizations and tissue-specific expression profiles were analyzed. The two novel isoforms were successfully cloned and deposited into GenBank as MG029442 (AYP71042) and MG029443 (AYP71043) respectively. Isoforms SPATA3-I1 and SPATA3-I2 were found with higher identity, where only 7 amino acids missed at N-terminus in SPATA3-I2, whereas SPATA3-I3 and SPATA3-I4 had more C-terminus deletion but in SPATA3-I3 no amino acid missed at N-terminus. Importantly, we found the characterization of QQPSPESTP domain with two repeats for isoforms SPATA3-I1 and SPATA3-I4, whereas three repeats for isoforms SPATA3-I1 and SPATA3-I2. The SPATA3 family of genes is orthologous conserved; the similar core PEST domain was also revealed with variable repeats, indicating that this domain may pay roles in the spermatogenesis and male development differently. Furthermore, RNA-seq data indicated that the SPATA3 gene is only expressed in testis. This further suggests that SPATA3 plays potential roles only in male development, spermatogenesis or spermatogenesis cell apoptosis. Thus, in this study we cloned the two novel isoforms of SPATA3, SPATA3-I3 and SPATA3-I4, and found interesting characteristic PEST domain (QQPSPESTP) conserved in different isoforms as well as in different species. SPATA3 is an essential gene and may functions in male reproductive system, specifically in spermatogenesis.
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Isoformas de Proteínas/genética , Proteínas/genética , Espermatogénesis/genética , Clonación Molecular , ADN Complementario/genética , Humanos , Masculino , Dominios Proteicos/genética , Isoformas de Proteínas/metabolismo , RNA-Seq , Análisis de Secuencia de ADN , Testículo/metabolismoRESUMEN
Prostate cancer (PCa) is the most common cancer diagnosed and the second most common cause of cancer-related death in men worldwide. The current androgen deprivation therapy for PCa cannot fully cure this disease. Moreover, androgen receptor gene amplification and mutation are associated with PCa to develop castration-resistant prostate cancer (CRPC). This review focuses on the deubiquitinases (DUBs) involved in PCa development and progression. For PCa development and progression, several cellular pathways are regulated by specific DUBs which are also highlighted in here. The ubiquitin-specific proteases (USPs), a family member of DUBs mostly involved in the regulation of cellular pathways for PCa development, and the ubiquitin C-terminal hydrolases (UCHs), another family member of DUBs, are responsible for PCa metastasis. Small molecular inhibitors against DUBs can inhibit or reduce the level of specific DUBs through the regulation of cellular pathway to treat this disease. Some small molecular inhibitors are already identified against some of the DUBs, but very few of them are clinically proved in PCa. So, to find out other DUBs involving in the regulation of PCa-related pathways and to develop more effective small molecule inhibitors with greater potency would be a great idea to target PCa cells for future therapeutics and drug development with or without the combination of other anticancer drugs. SIGNIFICANCE OF THE STUDY: This review is targeting DUB proteins which are responsible for PCa induction, proliferation, and metastasis by highlighting their signalling pathway so that the readers can get information about other mechanisms for PCa besides androgen receptor pathway and helps to find other oncogenic DUBs involving in these signalling pathways. This review also hopes to find other oncogenic DUBs involving in PCa-related signalling pathways or to find the DUBs that can regulate multiple oncogenic signalling pathways which might be a good target for PCa therapeutics. In addition, there are some small molecule inhibitors that can inhibit the oncogenic DUBs and thus able to control the oncogenic pathways which would be a novel strategy to treat CRPC by using DUB inhibitor combined with or without other anticancer drugs.
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Antineoplásicos/farmacología , Enzimas Desubicuitinizantes/antagonistas & inhibidores , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/farmacología , Enzimas Desubicuitinizantes/metabolismo , Humanos , Masculino , Neoplasias de la Próstata Resistentes a la Castración/metabolismoRESUMEN
BACKGROUND: Biochar amendment is a promising tool to improve the soil quality and, consequently, higher crop yield has received more attention during last decades. The positive effects of biochar have been attracting more attention especially in the areas with low precipitation rates, such as the Middle East, due to low soil organic carbon content, higher drought intensity, and increasing demands for food production. However, biochar can lead to lower herbicide efficacy, resulting in higher consumption of herbicides. In this study, the impact of two biochars on soil properties, plant growth, and fomesafen efficacy under rain-fed condition was investigated. RESULTS: Biochar amendment at the rate of 5 t ha-1 improved soil quality and plant growth by 40-200% and 46-57%, respectively, compared to the control. The increase of biochar application rate from 5 t ha-1 to 15 t ha-1 showed small additional positive effects on soil and lentil as the tested crop plant, whereas the growth of weeds elevated by 200% in this case. CONCLUSION: Albeit biochar application could be an effective way to improve the soil fertility, the potential risk of weed outbreak in the long term should be evaluated carefully before the use of biochar amendment at field scale. © 2017 Society of Chemical Industry.
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Carbón Orgánico/química , Lens (Planta)/crecimiento & desarrollo , Malezas/crecimiento & desarrollo , Agricultura , Producción de Cultivos , Herbicidas/farmacología , Cinética , Lens (Planta)/efectos de los fármacos , Malezas/efectos de los fármacos , Suelo/químicaRESUMEN
Cervical cancer is one of the most common gynecological malignant tumors worldwide, for which chemotherapeutic strategies are limited due to their non-specific cytotoxicity and drug resistance. The natural product thymoquinone (TQ) has been reported to target a vast number of signaling pathways in carcinogenesis in different cancers, and hence is regarded as a promising anticancer molecule. Inhibition of epithelial to mesenchymal transition (EMT) regulators is an important approach in anticancer research. In this study, TQ was used to treat the cervical cancer cell lines SiHa and CaSki to investigate its effects on EMT-regulatory proteins and cancer metastasis. Our results showed that TQ has time-dependent and dose-dependent cytotoxic effects, and it also inhibits the migration and invasion processes in different cervical cancer cells. At the molecular level, TQ treatment inhibited the expression of Twist1, Zeb1 expression, and increased E-Cadherin expression. Luciferase reporter assay showed that TQ decreases the Twist1 and Zeb1 promoter activities respectively, indicating that Twist1 and Zeb1 might be the direct target of TQ. TQ also increased cellular apoptosis in some extent, but apoptotic genes/proteins we tested were not significant affected. We conclude that TQ inhibits the migration and invasion of cervical cancer cells, probably via Twist1/E-Cadherin/EMT or/and Zeb1/E-Cadherin/EMT, among other signaling pathways.
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Benzoquinonas/farmacología , Proteínas Nucleares/metabolismo , Proteína 1 Relacionada con Twist/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Apoptosis/efectos de los fármacos , Western Blotting , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Femenino , Humanos , Proteínas Nucleares/genética , Proteína 1 Relacionada con Twist/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genéticaRESUMEN
Litchi (Litchi chinensis Sonn., L. chinensis), a type of tree growing in most areas of southern China, produces an edible fruit that is also a source of traditional medicine. Genetic identification of litchi species or cultivars using molecular markers is very important. In this study, a total of six litchi samples from Fujian, Hainan, Guangdong, Guangxi and Sichuan province, as well as one wild Dimocarpus confinis (D. confinis) sample from Guangxi province were collected for genetic analysis. The cluster dendrograms were constructed for genetic analysis on the basis of DNA amplification results by RAPD and ISSR. The improved RAPD amplified DNA with consistent and clear banding patterns. A total of 176 bands were found, indicating a 72.7 % polymorphism in L. chinensis DNA samples. Significant genetic distances were found among the different species or cultivars, with an index of similarity coefficient ranging from 0.59 to 0.87. Similar to RAPD results, ISSR analysis of the L. chinensis DNA samples showed a range of 0.70-0.93 similarity coefficients. The genetic distance between Hainan sample and Sichuan samples was the farthest, which is consistent with their geographic distance. Furthermore, the index of similarity coefficient between D. confinis and L. chinensis was 0.35-0.41 by RAPD and 0.38-0.48 by ISSR, indicating that these two species have significant genetic difference. This study reveals the high level of genetic differences between different litchi species or cultivars, and confirms the significance of the improved RAPD method in genetic characterization of organisms. Taken together, the improved RAPD combined with ISSR analysis can be used frequently for the genetic diversity, germplasm resources preservation, molecular-assisted breeding, and genetic characterization of various organisms.
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Litchi/genética , Repeticiones de Microsatélite/genética , Técnica del ADN Polimorfo Amplificado Aleatorio/métodos , China , Análisis por Conglomerados , ADN de Plantas/genética , Marcadores Genéticos , Geografía , Filogenia , Reacción en Cadena de la Polimerasa , Especificidad de la EspecieRESUMEN
Gardenia jasminoides is a common garden medicinal plant known for its anticancer, anti-inflammatory, anti-thrombic, anti-fibrotic, antiviral, hepatoprotective, lung-protective, renal-protective, retina-protective and neuroprotective activities. It is found in several regions of the world, including China, but information about its genetic characteristics is limited. Here, we employed an improved method of random amplified polymorphic DNA (RAPD) analysis (with increased RAMP time) to investigate the genetic link between G. jasminoides samples collected from six different regions of Southern China. Total 26 RAPD primers were selected randomly, among which 23 primers generated reproducible polymorphic amplification bands. A total of 174 bands were obtained, where each primer had amplified 5-13 bands with an average of 7.56 bands per primer. The band size ranged approximately 150-2200 bp. Cluster dendrogram was obtained based on the improved RAPD amplification profiles, which showed that the similarity coefficients among six varieties of G. jasminoides ranged 0.67-0.88. To our knowledge, this is the first report of genetic characterization of G. jasminoides using improved RAPD analysis, which may be useful for the preservation of genetic diversity and identification of Gardenia population.
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Gardenia/genética , Técnica del ADN Polimorfo Amplificado Aleatorio/métodos , China , ADN de Plantas/genética , ADN de Plantas/aislamiento & purificación , Electroforesis en Gel de Agar , Gardenia/clasificación , Flujo Génico , Variación Genética , Plantas Medicinales/clasificación , Plantas Medicinales/genética , Aislamiento ReproductivoRESUMEN
Generation of the stable cell lines is a highly efficient tool in functional studies of certain genes or proteins, where the particular genes or proteins are inducibly expressed. The KRAB-associated protein-1 (KAP1) is an important transcription regulatory protein, which is investigated in several molecular biological studies. In this study, we have aimed to generate a stable cell line for inducing KAP1 expression. The recombinant plasmid pcDNA5/FRT/TO-KAP1 was constructed at first, which was then transfected into Flp-In™T-REx™-HEK293 cells to establish an inducible pcDNA5/FRT/TO-KAP1-HEK293 cell line. The Western blot analysis showed that the protein level of KAP1 is over-expressed in the established stable cell line by doxycycline induction, both dose and time dependently. Thus we have successfully established stable pcDNA5/FRT/TO-KAP1-HEK293 cell line, which can express KAP1 inducibly. This inducible cell line might be very useful for KAP1 functional studies.
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Antibacterianos/farmacología , Doxiciclina/farmacología , Expresión Génica/efectos de los fármacos , Proteínas Represoras/biosíntesis , Células HEK293 , Humanos , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Proteínas Represoras/genética , Proteína 28 que Contiene Motivos TripartitoAsunto(s)
Genes Dominantes , Predisposición Genética a la Enfermedad/genética , Mutación , Periferinas/genética , Empalme del ARN/genética , Retinitis Pigmentosa/genética , Pueblo Asiatico/genética , Secuencia de Bases , China , Salud de la Familia , Femenino , Predisposición Genética a la Enfermedad/etnología , Humanos , Masculino , Persona de Mediana Edad , Linaje , Retinitis Pigmentosa/etnología , Retinitis Pigmentosa/patologíaRESUMEN
The epithelial to mesenchymal transition (EMT) is an important step for the developmental process. Recent evidences support that EMT allows the tumor cells to acquire invasive properties and to develop metastatic growth characteristics. Some of the transcription factors, which are actively involved in EMT process, have a significant role in the EMT-metastasis linkage. A number of studies have reported that EMT-inducing transcription factors (EMT-TFs), such as Twist, Snail, Slug, and Zeb, are directly or indirectly involved in cancer cell metastasis through a different signaling cascades, including the Akt, signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase (MAPK) and Wnt pathways, with the ultimate consequence of the downregulation of E-cadherin and upregulation of metastatic proteins, such as N-cadherin, vimentin, matrix metalloproteinase (MMP)-2, etc. This review summarizes the update information on the association of EMT-TFs with cancer metastasis and the possible cancer therapeutics via targeting the EMT-TFs.
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Transición Epitelial-Mesenquimal , Metástasis de la Neoplasia , Factores de Transcripción/fisiología , Proteínas de Homeodominio/fisiología , Humanos , Neoplasias/tratamiento farmacológico , Factores de Transcripción de la Familia Snail , Proteína 1 Relacionada con Twist/fisiología , Homeobox 1 de Unión a la E-Box con Dedos de ZincRESUMEN
OBJECTIVE: Autism, a lifelong neuro-developmental disorder is a uniquely human condition. Animal models are not the perfect tools for the full understanding of human development and behavior, but they can be an important place to start. This review focused on the recent updates of animal model research in autism. METHODS: We have reviewed the publications over the last three decades, which are related to animal model study in autism. RESULTS: Animal models are important because they allow researchers to study the underlying neurobiology in a way that is not possible in humans. Improving the availability of better animal models will help the field to increase the development of medicines that can relieve disabling symptoms. Results from the therapeutic approaches are encouraging remarkably, since some behavioral alterations could be reversed even when treatment was performed on adult mice. Finding an animal model system with similar behavioral tendencies as humans is thus vital for understanding the brain mechanisms, supporting social motivation and attention, and the manner in which these mechanisms break down in autism. The ongoing studies should therefore increase the understanding of the biological alterations associated with autism as well as the development of knowledge-based treatments therapy for those struggling with autism. CONCLUSION: In this review, we have presented recent advances in research based on animal models of autism, raising hope for understanding the disease biology for potential therapeutic intervention to improve the quality of life of autism individuals.
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Trastorno Autístico/terapia , Modelos Animales de Enfermedad , Neurobiología/métodos , Investigación , Experimentación Animal , Animales , Humanos , Ratones , Mutagénesis , RatasRESUMEN
Genetic diversity within a species is a common feature, which plays a vital role in its survival and adaptability, and is important for the identification and authentication of a species. Lonicera japonica is a traditionally used medicinal plant, which have been recently genetically characterized by an improved ran- dom amplified polymorphic DNA (RAPD) analysis. In this study, the molecular markers on the basis of these RAPD fragments have been developed to identify specific L. japonica variety. The DNAs were extracted from fresh young leaves of different samples of L. japonica collected from Shenzhen, Yichang, Leshan, Emei and Loudi, China. The DNA materials were amplified using improved RAPD PCR. Different RAPD bands were excised, cloned and developed for stable sequence-characterized amplified region (SCAR) markers with differ- ent species. Two SCAR markers, JYH3-3 and JYH4-3, have been successfully cloned from improved.RAPD fragments. The SCAR marker JYH3-3 was found specific for all of the L. japonica samples collected from the different regions, and another marker JYH 4-3 was strictly specific to the Shenzhen sample from Guangdong province, which is geographically distant from Hubei, Sichuan and Hunan Provinces (source of other L. japonica samples). The marker JYH3-3 was found as specific molecular marker for the identification of L. japonica, while JYH4-3 was found as molecular marker strictly specific for the Shenzhen sample. The developed SCAR markers might serve as more specific molecular markers for L. japonica variety authentication. The combination of improved RAPD analysis and SCAR marker development have resulted useful tools to study the genetic variety of any organism, which we have successfully applied here in L. japonica.
Asunto(s)
Clonación Molecular/métodos , Lonicera/genética , China , Marcadores Genéticos , Lonicera/clasificación , Reacción en Cadena de la Polimerasa , Técnica del ADN Polimorfo Amplificado AleatorioRESUMEN
Purpose: Adipogenesis is one of the major pathways for generating obesity or overweight that can cause a range of metabolic disorders. Circular RNAs (circRNAs), a specific type of RNAs, have a significant influence on metabolic disorders. This study aims to find differentially expressed circRNAs (DECs) during human subcutaneous adipose tissue (SATs) adipogenesis. Patients and Methods: The human adipose tissue-derived stromal cells (hADSCs) were isolated from human SATs (n = 3), and then induced into adipocytes. Total RNAs were extracted from hADSCs and adipocytes, and he DECs were detected using circRNA microarray. The GO and KEGG pathways of DECs were analyzed by bioinformatic methods, and partial DECs were further validated by quantitative polymerase chain reaction (qPCR). Results: Our study detected a total of 1987 DECs, among which, 1134 were found upregulated and 853 were downregulated. GO analysis showed that the upregulated DECs have catalytic activity in intracellular organelle and cytoplasms, whereas downregulated DECs are enriched in organelle lumen, and are involved in positive regulation of developmental process. In addition, pathway results demonstrated that upregulated DECs are involved in platinum drug resistance and cellular senescence, and downregulated DECs are enriched in proteoglycans in cancer and focal adhesion pathway. Two circRNAs, namely has_circ_0001600 and has_circ_0001947 were validated to be significantly upregulated in adipocytes compared to hADSCs. Conclusion: Our study explored DECs between hADSCs derived from SATs and adipocytes, and report that two circRNAs named has_circ_0001600 and has_circ_0001947 might be important factors involved in human adipogenesis, however, the molecular mechanism should be further explored.