In this paper, a small series of novel quinoline sulfonamide derivatives was synthesized, and their structure of the target compounds were confirmed by 1H NMR and MS. The screening of the news target ...compounds' in vitro cytotoxic activities against tumor cell lines by the MTT method was performed. Among them, compound
(N-(4-methoxybenzyl)-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-6-sulfonamide exhibited the strongest inhibitory effect on the proliferation of HeLa (IC
: 1.34 μM), and this value correlated well with the inhibitory activities of the compound against tubulin polymerization (IC
: 6.74 μM). In summary, a new type of quinoline-sulfonamide derivative with tubulin polymerization inhibitory activity was discovered, and it can be used as a lead compound for further modification.
Tetrazoles represent a class of five-membered heterocyclic compounds with polynitrogen electron-rich planar structural features. This special structure makes tetrazole derivatives useful drugs, ...explosives, and other functional materials with a wide range of applications in many fields of medicine, agriculture, material science, etc. Based on our research works on azoles and other references in recent years, this review covers reported work on the synthesis and biological activities of tetrazole derivatives.
ABSTRACT
Lignin is a major component of plant cell walls and is essential for plant growth and development. Lignin biosynthesis is controlled by a hierarchical regulatory network involving multiple ...transcription factors. In this study, we showed that the gene encoding an APETALA 2/ethylene‐responsive element binding factor (AP2/ERF) transcription factor, PagERF81, from poplar 84 K (Populus alba × P. glandulosa) is highly expressed in expanding secondary xylem cells. Two independent homozygous Pagerf81 mutant lines created by gene editing, produced significantly more but smaller vessel cells and longer fiber cells with more lignin in cell walls, while PagERF81 overexpression lines had less lignin, compared to non‐transgenic controls. Transcriptome and reverse transcription quantitative PCR data revealed that multiple lignin biosynthesis genes including Cinnamoyl CoA reductase 1 (PagCCR1), Cinnamyl alcohol dehydrogenase 6 (PagCAD6), and 4‐Coumarate‐CoA ligase‐like 9 (Pag4CLL9) were up‐regulated in Pagerf81 mutants, but down‐regulated in PagERF81 overexpression lines. In addition, a transient transactivation assay revealed that PagERF81 repressed the transcription of these three genes. Furthermore, yeast one hybrid and electrophoretic mobility shift assays showed that PagERF81 directly bound to a GCC sequence in the PagCCR1 promoter. No known vessel or fiber cell differentiation related genes were differentially expressed, so the smaller vessel cells and longer fiber cells observed in the Pagerf81 lines might be caused by abnormal lignin deposition in the secondary cell walls. This study provides insight into the regulation of lignin biosynthesis, and a molecular tool to engineer wood with high lignin content, which would contribute to the lignin‐related chemical industry and carbon sequestration.
The APETALA 2/ethylene‐responsive element binding factor (AP2/ERF) transcription factor PagERF81 plays an important role in lignin biosynthesis and xylem cell differentiation in poplar and the monolignol biosynthesis gene PagCCR1 is a direct target of PagERF81.
Temporal lobe epilepsy (TLE) is the most common form of adult localization-related epilepsy that is accompanied by progressive etiopathology and high incidences of drug resistance. Circular RNAs ...(circRNAs) play important roles in fine-tuning gene expression, however, the expression profile and clinical significance of circRNAs in TLE remains unknown.
Circular RNA microarray was conducted to identify TLE-related circRNAs. CCK8 assays and flow cytometric assays were conducted to clarify the role of circRNA in TLE in vitro. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in TLE cell.
586 differentially expressed circRNAs were identified between TLE and the control tissues. The expression of circRNA-0067835 was significantly down-regulated in tissues and plasma from TLE patients. Lower circRNA-0067835 correlated to increased seizure frequency, HS, and higher Engel's score. Overexpression of circRNA-0067835 observably decreased SH-SY5Y cell proliferation by causing G1 arrest and promoting apoptosis. Bioinformatics online programs predicted that circRNA-0067835 acted as miR-155 sponge to regulate FOXO3a expression, which was validated using luciferase reporter assay.
Our experiments showed that circRNA-0067835 regulated refractory epilepsy progression by acting as a sponge of miR-155 to promote FOXO3a expression, indicating that circRNA-0067835 may serve as a potential therapeutic target for patients with TLE.
To develop novel anti-inflammatory agents, a series of 5-alkyl-4-oxo-4,5-dihydro-1, 2, 4triazolo4,3-aquinoxaline-1-carboxamide derivatives were designed, synthesised, and evaluated for ...anti-inflammatory effects using RAW264.7 cells. Structures of the synthesised compounds were determined using
1
H NMR,
13
C NMR, and HRMS. All the compounds were screened for anti-inflammatory activity based on their inhibitory effects against LPS-induced NO release. Among them, 5-(3,4,5-trimethoxybenzyl)-4-oxo-4,5-dihydro-1, 2, 4triazolo4,3-aquinoxaline-1-carboxamide (6p) showed the highest anti-inflammatory activity and inhibited NO release more potently than the lead compound D1. Further studies revealed that compound 6p reduced the levels of NO, TNF-α, and IL-6, and that its anti-inflammatory activity involves the inhibition of COX-2 and iNOS and downregulation of the mitogen-activated protein kinases (MAPK) signal pathway. Notably, compound 6p displayed more prominent anti-inflammatory activity than D1 and the positive control ibuprofen in the in vivo acute inflammatory model. Overall, these findings indicate that compound 6p is a therapeutic candidate for the treatment of inflammation.
Organelle genome fragmentation has been found in a wide range of eukaryotic lineages; however, its use in phylogenetic reconstruction has not been demonstrated. We explored the use of mitochondrial ...(mt) genome fragmentation in resolving the controversial suborder-level phylogeny of parasitic lice (order Phthiraptera). There are approximately 5000 species of parasitic lice in four suborders (Amblycera, Ischnocera, Rhynchophthirina, and Anoplura), which infest mammals and birds. The phylogenetic relationships among these suborders are unresolved despite decades of studies. We sequenced the mt genomes of eight species of parasitic lice and compared them with 17 other species of parasitic lice sequenced previously. We found that the typical single-chromosome mt genome is retained in the lice of birds but fragmented into many minichromosomes in the lice of eutherian mammals. The shared derived feature of mt genome fragmentation unites the eutherian mammal lice of Ischnocera (family Trichodectidae) with Anoplura and Rhynchophthirina to the exclusion of the bird lice of Ischnocera (family Philopteridae). The novel clade, namely Mitodivisia, is also supported by phylogenetic analysis of mt genome and cox1 gene sequences. Our results demonstrate, for the first time, that organelle genome fragmentation is informative for resolving controversial high-level phylogenies.
Background. Traditional Chinese medicine has been widely used, in conjunction with conventional Western medicine, in clinical practice around the world to treat breast cancer. The study ...systematically reviewed and summarized the quality of life of breast cancer patients treated with integrated treatment method vs. conventional Western medicine. Methods. Eight databases including PubMed, EMBASE, Web of Science, the Cochrane Library, Chinese National Knowledge Infrastructure, China Biology Medicine Disc, Chinese Scientific Journal Database, and Wanfang Data knowledge service platform were searched in this study. The retrieval period was set from January 1, 2005, to December 31, 2020. Results. Twenty-two high-quality publications were included in this study. The total sample size was 1689 patients including 844 in the intervention group receiving traditional Chinese medicine combined with conventional Western medicine and 845 patients in the control group receiving conventional Western medicine only. Compared with the single-used conventional Western medicine treatment, an integrated approach to treat breast cancer can increase quality of life measured by rating scales (SMD = 1.29, 95% CI (1.07, 1.52) and P=0.01) and ranking scales (RR = 1.53, 95% CI (1.39 1.68) and P=0.02) and also decrease adverse reactions measured by rating scales (Z = 10.89, P<0.05; Group 1: I2 = 9.0%, P=0.258, SMD = 1.03; and Group 2: I2 = 31.6%, P=0.199, SMD = 1.56). For further analysis, chemotherapy with epirubicin exhibited higher quality of life than the chemotherapy without epirubicin among breast cancer patients Z = 19.80, P<0.05; Group 1: I2 = 62.4%, P=0.070, SMD = 1.61; and Group 2: I2 = 9.0%, P=0.359, SMD = 1.04. Despite the heterogeneity, which was due to a portion of relative low-quality literature or other factors, the results were satisfactory. In terms of secondary results, the patients with lower tumor markers (CEA and CA153) had better efficiency in quality of life with a statistically significant difference (SMD = 1.39, 95% CI: 1.10,1.67) for rating scales. In addition, secondary results related to high incidence of gastrointestinal adverse reactions (RR = 1.33, 95% CI (1.20, 1.48)) and the traditional Chinese medicine syndrome (RR = 1.50, 95% CI (1.28, 1.80))showed lower quality of life in the intervention group than the control group for ranking scales. Conclusion. Traditional Chinese medicine, when used in conjunction with the conventional Western medicine, could be an effective way in improving the quality of life and alleviating incidence of associated adverse symptoms such as gastrointestinal adverse reactions, value of tumor markers, and the incidence of traditional Chinese medicine syndrome. Further investigation of larger and methodologically sound trials with longer follow-up periods and appropriate comparison groups is needed.
The accuracy of sixteen commonly used internal reference genes was assessed in skeletal muscle-derived satellite cells of Qinchuan cattle at different stages of proliferation and induction of ...differentiation to determine the most suitable ones. Quantitative real-time PCR and three commonly used algorithmic programs, GeNorm, NormFinder and BestKeeper, were used to evaluate the stability of expression of the candidate internal reference genes (GAPDH, ACTB, PPIA, LRP10, HPRT1, YWHAZ, B2M, TBP, EIF3K , RPS9, UXT, 18S rRNA, RPLP0, MARVELD, EMD and RPS15A) in skeletal muscle-derived satellite cells at 0, 12, 24, 36 and 48 h of growth and after differentiation for 0, 2, 4, 6 and 8 days. The expression of two satellite cell marker genes, CCNA2 and MYF5, was used for validation analysis. The results of the software analyses showed that GAPDH and RPS15A were the most stable reference gene combinations during in vitro proliferation of bovine skeletal muscle-derived satellite cells, RPS15A and RPS9 were the most stable reference gene combinations during in vitro induction of differentiation of the cells, and PPIA was the least stable reference gene during proliferation and differentiation and was not recommended. This study lays the foundation for the selection of reference genes for qRT-PCR during the proliferation and induction of differentiation of bovine skeletal muscle-derived satellite cells.
Lappaconitine (LA), a natural compound with a novel C18-diterpenoid alkaloid skeleton, displayed extensive biological profile. Recent research on LA is focused mainly on its anti-tumor and analgesic ...effects, and therefore we aimed to investigate its anti-inflammatory potential. A series of novel LA derivatives with various substituents on the 20-N position was designed and synthesized. In the initial screening of LA derivatives against NO production, all the target compounds, except compound E2, exhibited excellent inhibitory ability relative to that of LA. Particularly, compound A4 exhibited the most potent inhibition with IC50 of 12.91 μmol/L. The elementary structure–activity relationships (SARs) of NO inhibitory activity indicated that replacement of the benzene ring with an electron donating group could improve the anti-inflammatory efficacy. Furthermore, compound A4 shows an anti-inflammatory mechanism by inhibiting NO, PGE2, and TNF-α generation via the suppression of NF-κB and MAPK signaling pathways. Notably, compound A4 could exert a significant therapeutic effect on LPS-induced acute lung injury (ALI) in vivo. Based on the above research, we further investigated the preliminary pharmacokinetic property of A4 in rats. Therefore, compound A4 could be a promising candidate for the development of anti-inflammatory agents in the future.
Lappaconitine derivative A4 significantly reduced the levels of pro-inflammatory cytokines NO. The anti-inflammatory mechanism of A4 might be associated with the inhibition of NO, TNF-α and PGE2 generation as a result of suppressing NF-κB and MAPK signaling pathway. Notably, A4 showed outstanding anti-inflammatory activity both in vivo and in vitro. Display omitted
In the present study, our bioinformatics analysis first reveals the existence of a conserved guanine-rich sequence within the Zaire ebolavirus L gene. Using various methods, we show that this ...sequence tends to fold into G-quadruplex RNA. TMPyP4 treatment evidently inhibits L gene expression at the RNA level. Moreover, the mini-replicon assay demonstrates that TMPyP4 effectively inhibits the artificial Zaire ebolavirus mini-genome and is a more potent inhibitor than ribavirin. Although TMPyP4 treatment reduced the replication of the mutant mini-genome when G-quadruplex formation was abolished in the L gene, its inhibitory effect was significantly alleviated compared with wild-type. Our findings thus provide the first evidence that G-quadruplex RNA is present in a negative-sense RNA virus. Finally, G-quadruplex RNA stabilization may represent a new therapeutic strategy against Ebola virus disease.
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•A conserved guanine-rich sequence is present in the Zaire ebolavirus L gene•This sequence tends to fold into a G-quadruplex RNA structure•TMPyP4 inhibits intracellular replication of artificial Zaire ebolavirus mini-genome•G-quadruplex RNA stabilization represents a new strategy against Ebola virus disease
Wang et al. describe a small molecule that targets the G-quadruplex RNA structure in a negative-sense RNA virus. G-quadruplex RNA stabilization may represent a new therapeutic strategy against Ebola virus.
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