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  • MDPI AG  (19)
  • 1
    Online Resource
    Online Resource
    A Novel PDK1/MEK Dual Inhibitor Induces Cytoprotective Autophagy via the PDK1/Akt Signaling Pathway in Non-Small Cell Lung Cancer
    MDPI AG ; 2023
    In:  Pharmaceuticals Vol. 16, No. 2 ( 2023-02-06), p. 244-
    Details
    In: Pharmaceuticals, MDPI AG, Vol. 16, No. 2 ( 2023-02-06), p. 244-
    Abstract: In a preliminary study, we synthesized a series of new PDK1/MEK dual inhibitors. Antitumor activity screening showed that Compound YZT exerts a strong inhibitory action in A549 cells. However, the specific mechanism of YZT against non-small cell lung cancer (NSCLC) is largely unknown. This work confirmed the anti-proliferation and pro-apoptosis effects of YZT in NSCLC cells. Furthermore, YZT promotes autophagy and provokes complete autophagic flux in NSCLC cells. Notably, compared with YZT alone, the combination of YZT with the autophagy inhibitor chloroquine (CQ) or 3-methyladenine (3-MA) markedly strengthened the anti-proliferative and pro-apoptotic actions, suggesting that YZT-induced autophagy is cytoprotective. We further found that YZT-induced autophagy may exert a cytoprotective function by preserving the integrity of mitochondria and decreasing mitochondrial apoptosis. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that PDK1 is an upstream protein of the Akt/mTOR axis and western blotting verified that YZT induces autophagy by the PDK1/Akt/mTOR signaling axis. Finally, YZT plus CQ significantly enhanced the anticancer activities compared to YZT alone in an animal study and immunohistochemistry showed that the level of LC3 was increased by YZT, which is in line with the in vitro results. In short, our study provides reliable experimental basis for developing Compound YZT as a new chemotherapeutic drug candidate and suggests that combined administration of YZT with CQ is a potential therapy against NSCLC.
    Type of Medium: Online Resource
    ISSN: 1424-8247
    URL: Article
    DOI: 10.3390/ph16020244
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2193542-7
    SSG: 15,3
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  • 2
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    Characterization of Different Salt Forms of Chitooligosaccharides and Their Effects on Nitric Oxide Secretion by Macrophages
    MDPI AG ; 2021
    In:  Molecules Vol. 26, No. 9 ( 2021-04-28), p. 2563-
    Details
    In: Molecules, MDPI AG, Vol. 26, No. 9 ( 2021-04-28), p. 2563-
    Abstract: In this paper, chitooligosaccharides in different salt forms, such as chitooligosaccharide lactate, citrate, adipate, etc., were prepared by the microwave method. They were characterized by SEM, FTIR, NMR, etc., and the nitric oxide (NO) expression was determined in RAW 264.7 cells. The results showed that pure chitooligosaccharide was an irregular spherical shape with rough surface, and its different salt type products are amorphous solid with different honeycomb sizes. In addition to the characteristic absorption peaks of chitooligosaccharides, in FTIR, the characteristic absorption of carboxyl group, methylene group, and aromatic group in corresponding acid appeared. The characteristic absorption peaks of carbon in carboxyl group, hydrogen and carbon in methyl, methylene group, and aromatic group in corresponding acid also appeared in NMR. Therefore, the sugar ring structure and linking mode of chitooligosaccharides did not change after salt formation of chitooligosaccharides. Different salt chitooligosaccharides are completely different in promoting NO secretion by macrophages, and pure chitooligosaccharides are the best.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules26092563
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2008644-1
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  • 3
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    WISP1 Polymorphisms Contribute to Platinum-Based Chemotherapy Toxicity in Lung Cancer Patients
    MDPI AG ; 2014
    In:  International Journal of Molecular Sciences Vol. 15, No. 11 ( 2014-11-14), p. 21011-21027
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 15, No. 11 ( 2014-11-14), p. 21011-21027
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms151121011
    Language: English
    Publisher: MDPI AG
    Publication Date: 2014
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 4
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    A Novel Parallel Processing Model for Noise Reduction and Temperature Compensation of MEMS Gyroscope
    MDPI AG ; 2021
    In:  Micromachines Vol. 12, No. 11 ( 2021-10-21), p. 1285-
    Details
    In: Micromachines, MDPI AG, Vol. 12, No. 11 ( 2021-10-21), p. 1285-
    Abstract: To eliminate the noise and temperature drift in an Micro-Electro-Mechanical Systems (MEMS) gyroscope’s output signal for improving measurement accuracy, a parallel processing model based on Multi-objective particle swarm optimization based on variational modal decomposition-time-frequency peak filter (MOVMD–TFPF) and Beetle antennae search algorithm- Elman neural network (BAS–Elman NN) is established. Firstly, variational mode decomposition (VMD) is optimized by multi-objective particle swarm optimization (MOPSO); then, the best decomposition parameters [kbest,abest] can be obtained. Secondly, the gyroscope output signals are decomposed by VMD optimized by MOPSO (MOVMD); then, the intrinsic mode functions (IMFs) obtained after decomposition are classified into a noise segment, mixed segment, and drift segment by sample entropy (SE). According to the idea of a parallel model, the noise segment can be discarded directly, the mixed segment is denoised by time-frequency peak filtering (TFPF), and the drift segment is compensated at the same time. In the compensation part, the beetle antennae search algorithm (BAS) is adopted to optimize the network parameters of the Elman neural network (Elman NN). Subsequently, the double-input/single-output temperature compensation model based on the BAS-Elman NN is established to compensate the drift segment, and these processed segments are reconstructed to form the final gyroscope output signal. Experimental results demonstrate the superiority of this parallel processing model; the angle random walk of the compensated gyroscope output is decreased from 0.531076 to 5.22502 × 10−3°/h/√Hz, and its bias stability is decreased from 32.7364°/h to 0.140403°/h, respectively.
    Type of Medium: Online Resource
    ISSN: 2072-666X
    URL: Article
    DOI: 10.3390/mi12111285
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2620864-7
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  • 5
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    Establishing a Prediction Model for the Efficacy of Platinum—Based Chemotherapy in NSCLC Based on a Two Cohorts GWAS Study
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 4 ( 2023-02-07), p. 1318-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 4 ( 2023-02-07), p. 1318-
    Abstract: Platinum drugs combined with other agents have been the first-line treatment for non-small cell lung cancer (NSCLC) in the past decades. To better evaluate the efficacy of platinum–based chemotherapy in NSCLC, we establish a platinum chemotherapy response prediction model. Here, a total of 217 samples from Xiangya Hospital of Central South University were selected as the discovery cohort for a genome-wide association analysis (GWAS) to select SNPs. Another 216 samples were genotyped as a validation cohort. In the discovery cohort, using linkage disequilibrium (LD) pruning, we extract a subset that does not contain correlated SNPs. The SNPs with p 〈 10−3 and p 〈 10−4 are selected for modeling. Subsequently, we validate our model in the validation cohort. Finally, clinical factors are incorporated into the model. The final model includes four SNPs (rs7463048, rs17176196, rs527646, and rs11134542) as well as two clinical factors that contributed to the efficacy of platinum chemotherapy in NSCLC, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.726.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12041318
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 6
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    Anthocyanins Profiling Analysis and RNA-Seq Revealed the Dominating Pigments and Coloring Mechanism in Cyclamen Flowers
    MDPI AG ; 2022
    In:  Biology Vol. 11, No. 12 ( 2022-11-28), p. 1721-
    Details
    In: Biology, MDPI AG, Vol. 11, No. 12 ( 2022-11-28), p. 1721-
    Abstract: Pigments in cyclamen (Cyclamen purpurascens) endows flowers with great ornamental and medicinal values. However, little is known about the biosynthetic pathways of pigments, especially anthocyanins, in cyclamen flowers. Herein, anthocyanins profiling and RNA-Seq were used to decipher the molecular events using cyclamen genotypes of red (HXK) or white (BXK) flowers. We found that red cyclamen petals are rich in cyanidin-3-O-rutinoside, cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, malvidin-3-O-glucoside, peonidin-3-O-rutinoside, quercetin-3-O-glucoside, and ruti. In addition, our transcriptomics data revealed 3589 up-regulated genes and 2788 down-regulated genes comparing the BXK to HXK. Our rich dataset also identified eight putative key genes for anthocyanin synthesis, including four chalcone synthase (CHS, g13809_i0, g12097_i0, g18851_i0, g36714_i0), one chalcone isomerase (CHI, g26337_i0), two flavonoid 3-hydroxylase (F3′H, g14710_i0 and g15005_i0), and one anthocyanidin synthase (ANS, g18981_i0). Importantly, we found a 2.5 order of magnitude higher expression of anthocyanin 3-O-glucosyltransferase (g8206_i0), which encodes a key gene in glycosylation of anthocyanins, in HXK compared to BXK. Taken together, our multiomics approach demonstrated massive changes in gene regulatory networks and anthocyanin metabolism in controlling cyclamen flower color.
    Type of Medium: Online Resource
    ISSN: 2079-7737
    URL: Article
    DOI: 10.3390/biology11121721
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2661517-4
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  • 7
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    Efficacy of a Chitin-Based Water-Soluble Derivative in Inducing Purpureocillium lilacinum against Nematode Disease (Meloidogyne incognita)
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 13 ( 2021-06-26), p. 6870-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 13 ( 2021-06-26), p. 6870-
    Abstract: Plant-parasitic nematodes cause severe economic losses annually which has been a persistent problem worldwide. As current nematicides are highly toxic, prone to drug resistance, and have poor stability, there is an urgent need to develop safe, efficient, and green strategies. Natural active polysaccharides such as chitin and chitosan with good biocompatibility and biodegradability and inducing plant disease resistance have attracted much attention, but their application is limited due to their poor solubility. Here, we prepared 6-oxychitin with good water solubility by introducing carboxylic acid groups based on retaining the original skeleton of chitin and evaluated its potential for nematode control. The results showed that 6-oxychitin is a better promoter of the nematicidal potential of Purpureocillium lilacinum than other water-soluble chitin derivatives. After treatment, the movement of J2s and egg hatching were obviously inhibited. Further plant experiments found that it can destroy the accumulation and invasion of nematodes, and has a growth-promoting effect. Therefore, 6-oxychitin has great application potential in the nematode control area.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22136870
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
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  • 8
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    A Protective Role of Phenylalanine Ammonia-Lyase from Astragalus membranaceus against Saline-Alkali Stress
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 24 ( 2022-12-10), p. 15686-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 24 ( 2022-12-10), p. 15686-
    Abstract: Phenylalanine ammonia-lyase (PAL, E.C.4.3.1.5) catalyzes the benzene propane metabolism and is the most extensively studied enzyme of the phenylpropanoid pathway. However, the role of PAL genes in Astragalus membranaceus, a non-model plant showing high capability toward abiotic stress, is less studied. Here, we cloned AmPAL and found that it encodes a protein that resides in the cytoplasmic membrane. The mRNA of AmPAL was strongly induced by NaCl or NaHCO3 treatment, especially in the root. Overexpressing AmPAL in Nicotiana tabacum resulted in higher PAL enzyme activities, lower levels of malondialdehyde (MDA), and better root elongation in the seedlings under stress treatment compared to the control plants. The protective role of AmPAL under saline-alkali stress was also observed in 30-day soil-grown plants, which showed higher levels of superoxide dismutase (SOD), proline, and chlorophyll compared to wild-type N. Tabacum. Collectively, we provide evidence that AmPAL is responsive to multiple abiotic stresses and that manipulating the expression of AmPAL can be used to increase the tolerance to adverse environmental factors in plants.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232415686
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
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  • 9
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    Fluoroalkenyl-Grafted Chitosan Oligosaccharide Derivative: An Exploration for Control Nematode Meloidogyne Incognita
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 4 ( 2022-02-14), p. 2080-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 4 ( 2022-02-14), p. 2080-
    Abstract: The exploration of novel, environmentally friendly, and efficient nematicides is essential, and modifying natural biomacromolecules is one feasible approach. In this study, 6-O-(trifluorobutenyl-oxadiazol)-chitosan oligosaccharide derivative was synthesized and characterized by FTIR, NMR, and TG/DTG. Its bioactivity and action mode against root-knot nematode M. incognita were estimated. The results show that the derivative shows high nematicidal activity against J2s, and egg hatching inhibitory activity at 1 mg/mL. The derivative may affect nematode ROS metabolism and further damage intestinal tissue to kill nematode. Meanwhile, by synergism with improving crop resistance, the derivative performed a high control effect on the nematode with low phytotoxicity. These findings suggested that chitosan oligosaccharide derivatives bearing fluoroalkenyl groups are promising green nematicides.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23042080
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
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  • 10
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    Chitosan Oligosaccharide Fluorinated Derivative Control Root-Knot Nematode (Meloidogyne incognita) Disease Based on the Multi-Efficacy Strategy
    MDPI AG ; 2020
    In:  Marine Drugs Vol. 18, No. 5 ( 2020-05-22), p. 273-
    Details
    In: Marine Drugs, MDPI AG, Vol. 18, No. 5 ( 2020-05-22), p. 273-
    Abstract: Plant root-knot nematode disease is a great agricultural problem and commercially available nematicides have the disadvantages of high toxicity and limited usage; thus, it is urgent to develop new nematicides derived from nature substances. In this study, a novel fluorinated derivative was synthesized by modifying chitosan oligosaccharide (COS) using the strategy of multiple functions. The derivatives were characterized by FTIR, NMR, elemental analysis, and TG/DTG. The activity assays show that the derivatives can effectively kill the second instar larvae of Meloidogyne incognita in vitro, among them, chitosan-thiadiazole-trifluorobutene (COSSZFB) perform high eggs hatching inhibitory activity. The derivatives can regulate plant growth (photosynthetic pigment), improve immunity (chitinase and β-1,3-glucanase), and show low cytotoxicity and phytotoxicity. According to the multi-functional activity, the derivatives exhibit a good control effect on plant root-knot nematode disease in vivo. The results demonstrate that the COS derivatives (especially fluorinated derivative) perform multiple activities and show the potential to be further evaluated as nematicides.
    Type of Medium: Online Resource
    ISSN: 1660-3397
    URL: Article
    DOI: 10.3390/md18050273
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2175190-0
    SSG: 15,3
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