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1.
Integr Cancer Ther ; 23: 15347354241258961, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38899834

RESUMEN

CONTEXT: Salvia miltiorrhiza (SM) is a commonly used herb in traditional Chinese medicine (TCM) and has been used in the treatment of pancreatic cancer to relieve the symptom of "blood stasis and toxin accumulation." Tanshinones (Tan), the main lipophilic constituents extracted from the roots and rhizomes of SM, have been reported to possess anticancer functions in several cancers. But the mechanism of how the active components work in pancreatic cancer still need to be clarified. OBJECTIVE: In this study, we aimed to investigate the therapeutic potential of Tan in pancreatic cancer and elucidate the underlying mechanisms. MATERIALS AND METHODS: The viabilities of PANC-1 and Bxpc-3 cells were determined by MTT assay, after treatment with various concentrations of Tan. The apoptotic cells were quantified by annexin V-FITC/PI staining and DAPI staining assays. The expression of relative proteins was used western blotting. Tumor growth was assessed by subcutaneously inoculating cells into C57BL/6 mice. RESULTS: Our experiments discovered that Tan effectively suppressed pancreatic cancer cell proliferation and promoted apoptosis. Mechanistically, we propose that Tan enhances intracellular ROS levels by activating the AKT/FOXO3/SOD2 signaling pathway, ultimately leading to apoptosis in pancreatic cancer cells. In vivo assay showed the antitumor effect of Tan. CONCLUSION: Tan, a natural compound from Salvia miltiorrhiza, was found to effectively suppress pancreatic cancer cell proliferation and promote apoptosis both in vitro and in vivo. Mechanistically, we propose a positive feedback loop mechanism. These findings provide valuable insights into the molecular pathways driving pancreatic cancer progression.


Asunto(s)
Abietanos , Apoptosis , Proteína Forkhead Box O3 , Neoplasias Pancreáticas , Proteínas Proto-Oncogénicas c-akt , Especies Reactivas de Oxígeno , Salvia miltiorrhiza , Transducción de Señal , Neoplasias Pancreáticas/tratamiento farmacológico , Salvia miltiorrhiza/química , Abietanos/farmacología , Apoptosis/efectos de los fármacos , Animales , Humanos , Proteína Forkhead Box O3/metabolismo , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Extractos Vegetales/farmacología , Ratones Endogámicos C57BL , Proliferación Celular/efectos de los fármacos
2.
Bioeng Transl Med ; 9(2): e10624, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38435820

RESUMEN

Cisplatin-containing combination chemotherapy has been used as the standard treatment for bladder cancer patients at advanced stage. However, nearly 50% of patients are nonresponders. To guide the selection of more effective chemotherapeutic agents, a bladder cancer spheroids microfluidic drug sensitivity analysis system was established in this study. Bladder cancer spheroids were established and successfully cultured in a customized microfluidic device to assess their response to different chemotherapeutic agents. The in vitro drug sensitivity results were also compared to patient-derived xenograft (PDX) models and clinical responses of patients. As a result, bladder cancer spheroids faithfully recapitulate the histopathological and genetic features of their corresponding parental tumors. Furthermore, the in vitro drug sensitivity outcomes of spheroids (n = 8) demonstrated a high level of correlation with the PDX (n = 2) and clinical response in patients (n = 2). Our study highlights the potential of combining bladder cancer spheroids and microfluidic devices as an efficient and accurate platform for personalized selection of chemotherapeutic agents.

3.
ACS Appl Mater Interfaces ; 16(6): 6789-6798, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38297999

RESUMEN

Magnetic biomolecule-based bionic magnetic field sensors are anticipated to open up novel pathways for magnetic field detection. The detection range and accuracy of current bionic magnetic field sensors are limited, and little work is based on the capacitive response principle. We successfully developed a biochemical interface with an extralarge target-receptor size ratio, which can be manufactured in a single step for weak magnetic field detection across a wide frequency range, and we used electrochemical capacitance as a magnetic field change conduction strategy. The thickness-controllable nanoscale bovine serum albumin/graphene layer on an indium tin oxide working electrode combines with the one-step preparation method to immobilize the MagR/Cry4 complex. This capacitive bionic magnetic sensor can achieve the detection range of 0-120 mT. This biointerface design strategy obtains the further improvement of the performance of this bionic magnetic field sensor. Furthermore, the biointerface construction and optimization methodology in this proposal has potential applications in the design of other medical biosensors.


Asunto(s)
Técnicas Biosensibles , Grafito , Biónica , Capacidad Eléctrica , Electrodos
4.
RSC Adv ; 13(45): 31738-31755, 2023 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-37908645

RESUMEN

Thermal management, including heating and cooling, plays an important role in human productive activities and daily life. Nevertheless, in the actual environment, almost all the ambient scenarios come with the challenge that the objects are located in a quite dynamic and variable environment, which includes fluctuations in aspects such as space, time, sunlight, season, and temperature. It is imperative to develop low-energy or even zero-energy thermal-management technologies with renewable and clean energy. In this review, we summarised the latest technological advances and the prospects in this burgeoning field. First, we present the fundamental principles of the daytime passive radiative cooling (PDRC) thermal management device. Next, In the domain of dual-mode systems, they are classified into various types based on the diverse mechanisms of transitioning between cooling and heating states, including electrical responsive, mechanical responsive, temperature responsive, and solution responsive. Furthermore, we conducted an in-depth analysis of the principles and design methodologies associated with these categories, followed by a comparative assessment of their performance in radiative cooling and solar heating applications. Finally, this review presents the challenges and opportunities of dynamic dual mode thermal management, while also identifying future directions.

5.
Sci Rep ; 13(1): 16495, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37779129

RESUMEN

The Polygonatum genus represents a perennial herb with the Liliaceae family, boasting substantial economic and medicinal significance. The majority of Polygonatum plants exhibit notable similarity while lacking distinctive identifying characteristics, thus resulting in the proliferation of adulterated medicinal materials within the market. Within this study, we conducted an in-depth analysis of the complete chloroplast (cp) genomes of four Polygonatum plants and compared them with four closely akin species. The primary objectives were to unveil structural variations, species divergence, and the phylogenetic interrelations among taxa. The cp genomes of the four Polygonatum species were typified by a conventional quadripartite structure, incorporating a large single copy region (LSC), a small single copy region (SSC), and a pair of inverted repeat regions. In total, we annotated a range of 131 to 133 genes, encompassing 84 to 86 protein-coding genes, 38 transfer RNA (tRNA) genes, 8 ribosomal RNA (rRNA) genes, and 0 to 2 pseudogenes (ycf1, infA). Our comparative analyses unequivocally revealed a remarkable consistency in gene order and GC content within the Polygonatum genus. Furthermore, we predicted a potential 59 to 64 RNA editing sites distributed across 22 protein-coding genes, with the ndhB gene exhibiting the most prominent propensity for RNA editing sites, boasting a tally of 15 sites. Notably, six regions of substantial potential variability were ascertained, characterized by elevated Pi values. Noteworthy, molecular markers for species identification, population genetic scrutiny, and phylogenetic investigations within the genus were identified in the form of the psaJ-rpl33 and trnS + trnT-psaD barcodes. The resultant phylogenetic tree unequivocally depicted the formation of a monophyletic clade comprising species within the evolutionary framework of Liliaceae, demonstrating closer evolutionary affinities with Maianthemum, Dracaeneae, and Asparageae. This comprehensive compendium of findings collectively contributes to the advancement of molecular species identification, elucidation of phylogenetic interrelationships, and the establishment of DNA barcodes tailored to the Polygonatum species.


Asunto(s)
Genoma del Cloroplasto , Liliaceae , Polygonatum , Filogenia , Polygonatum/genética , Código de Barras del ADN Taxonómico , Genoma del Cloroplasto/genética , ADN , Cloroplastos/genética
6.
Nat Commun ; 14(1): 5424, 2023 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-37696785

RESUMEN

Magnetic skyrmions, topologically-stabilized spin textures that emerge in magnetic systems, have garnered considerable interest due to a variety of electromagnetic responses that are governed by the topology. The topology that creates a microscopic gyrotropic force also causes detrimental effects, such as the skyrmion Hall effect, which is a well-studied phenomenon highlighting the influence of topology on the deterministic dynamics and drift motion. Furthermore, the gyrotropic force is anticipated to have a substantial impact on stochastic diffusive motion; however, the predicted repercussions have yet to be demonstrated, even qualitatively. Here we demonstrate enhanced thermally-activated diffusive motion of skyrmions in a specifically designed synthetic antiferromagnet. Suppressing the effective gyrotropic force by tuning the angular momentum compensation leads to a more than 10 times enhanced diffusion coefficient compared to that of ferromagnetic skyrmions. Consequently, our findings not only demonstrate the gyro-force dependence of the diffusion coefficient but also enable ultimately energy-efficient unconventional stochastic computing.

7.
ACS Biomater Sci Eng ; 9(8): 4893-4906, 2023 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-37523767

RESUMEN

Liver fibrosis is a progressive physiological change that occurs after liver injury and seriously endangers human health. The lack of reliable and physiologically relevant pathological models of liver fibrosis leads to a longer drug development period and sizeable economic investment. The fabrication of a biomimetic liver-on-a-chip is significant for liver disease treatment and drug development. Here, a sandwich chip with a microwell array structure in its bottom layer was fabricated to simulate the Disse space structure of hepatic sinusoids in vitro. By synergistic modulation of the cross-linking degree of gelatin-methacryloyl (GelMA) hydrogels and the induction of transforming growth factor-beta (TGF-ß), the early and late stages of liver fibrosis were designed in the chip. Owing to its three-dimensional-mixed-culture strategy, it was possible to construct a liver sinusoid model in vitro to allow for faithful physiological emulation. The model was further subjected to drug treatment, and it presented a significant difference in treatment response in early and late fibrosis progression. Our system provides a unique method for emulating liver function through a vitro liver fibrosis-on-a-chip, potentially paving the way for investigating human liver fibrosis and related drug development.


Asunto(s)
Hidrogeles , Cirrosis Hepática , Humanos , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/patología , Hidrogeles/química
8.
Cell Prolif ; 56(5): e13473, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37199072

RESUMEN

Cancer cell spheroids have been shown to mimic in vivo tumour microenvironment and are therefore suitable for in vitro drug screening. Microfluidic technology can provide conveniences for spheroid assays such as high-throughput, simplifying manual operation and saving reagent. Here, we propose a concentration gradient generator based on microfluidic technology for cell spheroid culture and assay. The chip consists of upper microchannels and lower microwells. After partitioning HepG2 suspension into the microwells with concave and non-adhesive bottoms, spheroids can spontaneously form. By controlling the fluid replacement and flow in microchannels, the doxorubicin solution is diluted automatically into a series of concentration gradients, which spanning more than one order of magnitude. And then the effect of doxorubicin on spheroids is measured in situ by fluorescent staining. This chip provides a very promising approach to achieve the high-throughput and standardized anti-cancer drug screening in future.


Asunto(s)
Antineoplásicos , Esferoides Celulares , Técnicas de Cultivo de Célula , Evaluación Preclínica de Medicamentos , Doxorrubicina/farmacología
9.
Front Mol Biosci ; 10: 1119356, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36876047

RESUMEN

Rapid development of medical imaging, such as cellular tracking, has increased the demand for "live" contrast agents. This study provides the first experimental evidence demonstrating that transfection of the clMagR/clCry4 gene can impart magnetic resonance imaging (MRI) T2-contrast properties to living prokaryotic Escherichia coli (E. coli) in the presence of Fe3+ through the endogenous formation of iron oxide nanoparticles. The transfected clMagR/clCry4 gene markedly promoted uptake of exogenous iron by E. coli, achieving an intracellular co-precipitation condition and formation of iron oxide nanoparticles. This study will stimulate further exploration of the biological applications of clMagR/clCry4 in imaging studies.

10.
ACS Sens ; 8(2): 793-802, 2023 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-36744464

RESUMEN

Magnetic-sensitive proteins are regarded as key factors in animals' precise perception of the geomagnetic field. Accurate feedback on the response of these tiny proteins to magnetic fields remains a challenge. Here, we first propose a real-time accurate magnetic sensor based on the MagR/Cry4 complex-configured graphene transistor with an integrated on-chip gate. A nanometer-thick denatured bovine serum albumin film was used as the bio-interface of graphene electrolyte-gated transistors (EGTs) to immobilize the MagR/Cry4 complex. With the optimization and characterization of this bionic graphene EGT, it could detect magnetic fields in real time with a sensitivity of 1 mT, which is far lower than in earlier research. It was concluded that our MagR/Cry4 complex-configured graphene EGTs with a side-gate held great promise in terms of geomagnetic field detection. Furthermore, the constructed approach in this paper could also be utilized as a general solution for recording the response of magnetically sensitive biomolecules to magnetic fields in real time.


Asunto(s)
Grafito , Animales , Biónica , Magnetismo , Campos Magnéticos
11.
BMC Genomics ; 23(1): 620, 2022 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-36028808

RESUMEN

BACKGROUND: Tetrastigma hemsleyanum is a valuable traditional Chinese medicinal plant widely distributed in the subtropical areas of China. It belongs to the Cayratieae tribe, family Vitaceae, and exhibited significant anti-tumor and anti-inflammatory activities. However, obvious differences were observed on the quality of T. hemsleyanum root from different regions, requiring the discrimination strategy for the geographical origins. RESULT: This study characterized five complete chloroplast (cp) genomes of T. hemsleynum samples from different regions, and conducted a comparative analysis with other representing species from family Vitaceae to reveal the structural variations, informative markers and phylogenetic relationships. The sequenced cp genomes of T. hemsleyanum exhibited a conserved quadripartite structure with full length ranging from 160,124 bp of Jiangxi Province to 160,618 bp of Zhejiang Province. We identified 112 unique genes (80 protein-coding, 28 tRNA and 4 rRNA genes) in the cp genomes of T. hemsleyanum with highly similar gene order, content and structure. The IR contraction/expansion events occurred on the junctions of ycf1, rps19 and rpl2 genes with different degrees, causing the differences of genome sizes in T. hemsleyanum and Vitaceae plants. The number of SSR markers discovered in T. hemsleyanum was 56-57, exhibiting multiple differences among the five geographic groups. Phylogenetic analysis based on conserved cp genome proteins strongly grouped the five T. hemsleyanum species into one clade, showing a sister relationship with T. planicaule. Comparative analysis of the cp genomes from T. hemsleyanum and Vitaceae revealed five highly variable spacers, including 4 intergenic regions and one protein-coding gene (ycf1). Furthermore, five mutational hotspots were observed among T. hemsleyanum cp genomes from different regions, providing data for designing DNA barcodes trnL and trnN. The combination of molecular markers of trnL and trnN clustered the T. hemsleyanum samples from different regions into four groups, thus successfully separating specimens of Sichuan and Zhejiang from other areas. CONCLUSION: Our study obtained the chloroplast genomes of T. hemsleyanum from different regions, and provided a potential molecular tracing tool for determining the geographical origins of T. hemsleyanum, as well as important insights into the molecular identification approach and and phylogeny in Tetrastigma genus and Vitaceae family.


Asunto(s)
Genoma del Cloroplasto , Vitaceae , Código de Barras del ADN Taxonómico , Estructura Molecular , Filogenia
12.
Mitochondrial DNA B Resour ; 7(5): 783-785, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35558172

RESUMEN

Veronicastrum axillare (Sieb. et Zucc.) Yamazaki is a traditional medical plant with versatile biological activities. Here, we reported the complete chloroplast genome sequence of V. axillare with a total length of 152,691 bp, containing two IR regions of 25,765 bp each, an LSC region of 83,559 bp, and an SSC region of 17,602 bp. The genome encodes 131 genes, including 85 protein-coding genes, 37 tRNAs, eight rRNAs, and one pseudogene (ycf1). The overall GC content is 38.3%, with the highest content of 43.31% in IR region. Comparative analysis revealed 4 potential hotspots among V. axillare and other Veroniceae plants, providing potential markers for population investigations in the tribe Veroniceae. A total of 56 simple sequence repeats were identified in V. axillare. Phylogenetic analysis indicated a sister relationship between V. axillare and V. sibiricum, suggesting a close genetic relationship between the two Veronicastrum species. Our results provide basic genetic resources for investigating the evolutionary status of V. axillare within the tribe Veroniceae.

13.
Analyst ; 147(8): 1722-1729, 2022 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-35343521

RESUMEN

Quantification of tumor cell heterogeneity is critical for clinical diagnostic and therapeutic applications, including evaluation of the cancerous stage of tumors. In this work, we presented a novel method to effectively distinguish the grade of bladder cancer at a single-cell level in both cell line and clinical cell samples. This was achieved by taking advantage of microdroplets and microelectrodes, which can encapsulate and then trap single cells for measuring their impedance in a label-free and non-invasive manner. These findings suggested that this impedance analysis device based on droplet microfluidics is promising in the fields of clinical and point-of-care diagnostics.


Asunto(s)
Técnicas Analíticas Microfluídicas , Neoplasias de la Vejiga Urinaria , Línea Celular , Impedancia Eléctrica , Humanos , Microelectrodos , Microfluídica/métodos , Neoplasias de la Vejiga Urinaria/diagnóstico
14.
BMC Genomics ; 22(1): 880, 2021 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-34872502

RESUMEN

BACKGROUND: The Stephania tetrandra S. Moore (S. tetrandra) is a medicinal plant belonging to the family Menispermaceae that has high medicinal value and is well worth doing further exploration. The wild resources of S. tetrandra were widely distributed in tropical and subtropical regions of China, generating potential genetic diversity and unique population structures. The geographical origin of S. tetrandra is an important factor influencing its quality and price in the market. In addition, the species relationship within Stephania genus still remains uncertain due to high morphological similarity and low support values of molecular analysis approach. The complete chloroplast (cp) genome data has become a promising strategy to determine geographical origin and understand species evolution for closely related plant species. Herein, we sequenced the complete cp genome of S. tetrandra from Zhejiang Province and conducted a comparative analysis within Stephania plants to reveal the structural variations, informative markers and phylogenetic relationship of Stephania species. RESULTS: The cp genome of S. tetrandra voucher ZJ was 157,725 bp, consisting of a large single copy region (89,468 bp), a small single copy region (19,685 bp) and a pair of inverted repeat regions (24,286 bp each). A total of 134 genes were identified in the cp genome of S. tetrandra, including 87 protein-coding genes, 8 rRNA genes, 37 tRNA genes and 2 pseudogene copies (ycf1 and rps19). The gene order and GC content were highly consistent in the Stephania species according to the comparative analysis results, with the highest RSCU value in arginine (1.79) and lowest RSCU value in serine of S. tetrandra, respectively. A total of 90 SSRs have been identified in the cp genome of S. tetrandra, where repeats that consisting of A or T bases were much higher than that of G or C bases. In addition, 92 potential RNA editing sites were identified in 25 protein-coding genes, with the most predicted RNA editing sites in ndhB gene. The variations on length and expansion extent to the junction of ycf1 gene were observed between S. tetrandra vouchers from different regions, indicating potential markers for further geographical origin discrimination. Moreover, the values of transition to transversion ratio (Ts/Tv) in the Stephania species were significantly higher than 1 using Pericampylus glaucus as reference. Comparative analysis of the Stephania cp genomes revealed 5 highly variable regions, including 3 intergenic regions (trnH-psbA, trnD-trnY, trnP) and two protein coding genes (rps16 and ndhA). The identified mutational hotspots of Stephania plants exhibited multiple SNP sites and Gaps, as well as different Ka/Ks ratio values. In addition, five pairs of specific primers targeting the divergence regions were accordingly designed, which could be utilized as potential molecular markers for species identification, population genetic and phylogenetic analysis in Stephania species. Phylogenetic tree analysis based on the conserved chloroplast protein coding genes indicated a sister relationship between S. tetrandra and the monophyletic group of S. japonica and S. kwangsiensis with high support values, suggesting a close genetic relationship within Stephania plants. However, two S. tetrandra vouches from different regions failed to cluster into one clade, confirming the occurrences of genetic diversities and requiring further investigation for geographical tracing strategy. CONCLUSIONS: Overall, we provided comprehensive and detailed information on the complete chloroplast genome and identified nucleotide diversity hotspots of Stephania species. The obtained genetic resource of S. tetrandra from Zhejiang Province would facilitate future studies in DNA barcode, species discrimination, the intraspecific and interspecific variability and the phylogenetic relationships of Stephania plants.


Asunto(s)
Genoma del Cloroplasto , Menispermaceae , Stephania tetrandra , Estructura Molecular , Filogenia
15.
Artículo en Inglés | MEDLINE | ID: mdl-34778532

RESUMEN

Unlike the other studies on emotional design in multimedia learning, the present study differentiated the two confounding variables of visual interface design and structured content to manipulate the instructional material. Specifically, we investigated how the visual aesthetics of positive emotional interface design influenced learners' cognitive processes, emotional valences, learning outcomes, and subjective experience. Eighty-one college students took part in the experimental study. They were divided into the three experimental groups: a holistic layout of positive emotional design group (HPED), a local layout of positive emotional design group (LPED), and a neutral emotional design group (ND). By using a mixed approach of questionnaires and eye tracking, we further explored the differences among the three groups in cognitive processing, learning outcomes, and subjective experience. Results indicated that the LPED group invested higher cognitive effort, put more attentional focus in the relevant knowledge content module, and achieved better learning performance (i.e., retention and transfer tests) in contrast to the HPED group and the ND group. However, no significant difference in dynamic changes of emotional state among the three groups was detected. The analytical results can provide researchers and practitioners with valuable insights into the positive emotional design of multimedia learning, which allows for the facilitation of mental engagement, learning outcomes and subjective perception.

16.
Genetica ; 149(5-6): 299-311, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34546501

RESUMEN

Rubus hirsutus is a type of tonifying kidney-essence herb that belongs to the Rosaceae family, and has been commonly used to treat multiple diseases, such as polyuria, impotence, and infertility. In this study, we determined the complete chloroplast sequence of R. hirsutus and conduced a comparative analysis within the genus Rubus. The assembled chloroplast (cp.) genome is 156,380 bp in length with a GC content of 37.0% and shares a conserved quadripartite structure within the other cp. genomes in this genus. A total of 132 unique genes were annotated in the cp. genome of R. hirsutus, which contained 87 protein-coding genes, 37 tRNAs, and eight rRNAs. Seventeen duplicated genes were identified in the inverted repeats region. Furthermore, 70 simple sequence repeats and 35 long repeats were detected in total in the R. hirsutus chloroplast genome. Eight mutational hotspots were identified in the cp. genome of this species with higher nucleotide variations in non-coding regions than those of coding regions. Furthermore, the gene order, codon usage, and repeat sequence distribution were highly consistent in Rubus according to the results of a comparative analysis. A phylogenetic analysis indicated that there was a sister relationship between R. hirsutus and R. chingii. Overall, the complete chloroplast genome of R. hirsutus and the comparative analysis will help to further the evolutionary study, conservation, phylogenetic reconstruction, and development of molecular barcodes for the genus Rubus.


Asunto(s)
Cloroplastos/genética , Genoma del Cloroplasto/genética , Rubus/clasificación , Rubus/genética , Filogenia , Rubus/citología
17.
Pharm Biol ; 59(1): 893-903, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34214017

RESUMEN

CONTEXT: A portion of patients with chronic myeloid leukaemia (CML) develop resistance to the Bcr-Abl tyrosine kinase inhibitors (TKIs), limiting the clinical applications. Previous results have demonstrated the synergistic effects between cryptotanshinone (CPT) and imatinib on apoptosis of CML cells in vitro. OBJECTIVE: To determine the antileukemia effects of CPT and TKIs on the resistant CML cells, and further investigate the effect of combined treatment of CPT and imatinib on tumour growth and apoptosis in the xenograft model and clarify its regulatory mechanisms. MATERIALS AND METHODS: The combination effects of CPT and second-generation TKIs were evaluated in resistant CML cells K562-R. CPT and imatinib were orally administered once daily for 21 days on K562-R xenografts in nude mice (6 per group). Tumour proliferation and apoptosis were examined by Ki-67, PCNA and TUNEL staining. The expression levels of apoptotic markers and activities of STAT3 and eIF4E pathways were determined via immunohistochemistry staining and western blotting analysis. RESULTS: CPT significantly enhanced the antiproliferative effects of TKIs, via triggering cleavages of caspase proteins, and inhibiting activities of STAT3 and eIF4E pathways. The administration of CPT and imatinib dramatically inhibited the tumour growth of xenografts and achieved a suppression of 60.2%, which is 2.6-fold higher than that of single imatinib group. Furthermore, CPT and imatinib increased the apoptotic rates and markedly decreased the phosphorylation levels of STAT3 and eIF4E. CONCLUSIONS: Our results demonstrated that CPT could significantly enhance the antileukemia efficacy of TKIs, suggesting the therapeutic potential of CPT to overcome CML resistance.


Asunto(s)
Mesilato de Imatinib/farmacología , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Fenantrenos/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos , Sinergismo Farmacológico , Factor 4E Eucariótico de Iniciación/metabolismo , Femenino , Humanos , Células K562 , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Ratones , Ratones Desnudos , Fenantrenos/administración & dosificación , Fosforilación/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
18.
Braz J Med Biol Res ; 54(8): e10685, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34037092

RESUMEN

Tanshinone I (Tan I) is one of the main bioactive ingredients derived from Salvia miltiorrhiza Bunge, which has exhibited antitumor activities toward various human cancer cells. However, its effects and underlying mechanisms on human chronic myeloid leukemia (CML) cells still require further investigation. This study determined the effects and mechanisms of anti-proliferative and apoptosis induction activity induced by Tan I against K562 cells. The cytotoxic effect of Tan I at varying concentrations on K562 cells was evaluated via MTT assay. Cell apoptosis was further investigated through DAPI staining and flow cytometry analysis. The expression levels of apoptosis-related proteins and activities of JNK/ATF2 and ERK signaling pathways were analyzed by western blot. Quantitative PCR was performed to further determine mRNA expression levels of JNK1/2 and ERK1/2 after Tan I treatment. The results indicated that Tan I significantly inhibited K562 cell growth and induced apoptosis in a concentration- and time-dependent manner. It induced significant cellular morphological changes and increased apoptosis rates in CML cells. Tan I promoted the cleavages of caspase-related proteins, as well as increased the expression levels of PUMA. Furthermore, Tan I significantly activated JNK and inhibited ATF-2 and ERK signaling pathways. The mRNA expression levels of JNK1/2 and ERK1/2 were up-regulated by Tan I, further confirming its regulatory effects on JNK/ERK signaling pathways. Overall, our results indicated that Tan I suppressed cell viability via JNK- and ERK-mediated apoptotic pathways in K562 cells, suggesting that it might be a promising candidate as a novel anti-leukemia drug.


Asunto(s)
Abietanos , Leucemia Mielógena Crónica BCR-ABL Positiva , Abietanos/farmacología , Apoptosis , Línea Celular Tumoral , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico
19.
Mitochondrial DNA B Resour ; 6(3): 1136-1137, 2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33796767

RESUMEN

Ramie (Boehmeria nivea L. Gaud) is a traditional fiber crop and important medicinal plant belonging to the family Urticaceae. In this study, we determine the complete chloroplast genome sequence of B. nivea. The assembled chloroplast genome is 156065 bp in length and shares the conserved quadripartite structure as other cp genomes in Boehmeria. The genome contains 131 genes, including 84 protein genes, 8 rRNA genes, 37 tRNA genes and 2 pseudo genes. There are 17 duplicated genes in the IR region. The overall GC content of B. nivea is 36.33%, with the highest GC content of 42.72% in IR region. A total of 67 simple sequence repeats are identified in the cp genome of B. nivea. Phylogenetic analysis demonstrated that B. nivea clustered together with B. tomentosa, further forming a monophyletic group with the species of Debregeasia and Pipturus. This work provides basic genetic resources for developing robust markers and investigating the population genetics diversities for B. nivea.

20.
Mitochondrial DNA B Resour ; 6(3): 1138-1140, 2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33796768

RESUMEN

Oxalis corymbosa DC. is an important medicinal and edible perennial herb belonging to the wood-sorrel family Oxalidaceae. In this study, we report the complete chloroplast (cp) genome sequence of O. corymbosa. The assembled chloroplast genome was 151,351 bp in length, containing two inverted repeated (IR) regions of 24,587 bp each, a large single copy (LSC) region of 85,476 bp, and a small single copy (SSC) region of 16,701 bp. The genome encodes 128 genes, consisting of 82 protein-coding genes, 37 tRNA genes, eight rRNA genes, and one pseudogene (ycf1). The 82 protein-coding genes encode 25,751 amino acids in total, most of which use the initiation codon ATG, except rps19 and psbC genes start with GTG. The lengths of the tRNA genes range from 71 bp to 93 bp, with the highest GC content of 62.16% in tRNA-Arg (ACG). The overall GC content of O. corymbosa is 36.47%, with the highest GC content of 42.64% in IR region. In addition, a total of 74 simple sequence repeats were identified in the cp genome of O. corymbosa. Phylogenetic analysis indicated a sister relationship between O. corymbosa and O. drummondii, suggesting a close genetic relationship between the two Oxalis species. This work provides basic genetic resources for investigating the evolutionary status and population genetics diversities for this medicinal species.

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