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1.
Chem Biodivers ; : e202401984, 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39441614

RESUMO

Wuzi Yanzong decoction (WZYZD) belongs to the traditional formula for treating male infertility caused by oligoasthenozoospermia (OLI). This research aims to elucidate the therapeutic substance basis and potential pharmacological mechanisms of WZYZD in treating OLI. A total of 52 chemical ingredients were identified from WZYZD. HE and TUNEL staining demonstrated that WZYZD can markedly alleviate OLI. Immunofluorescence analysis showed that WZYZD can significantly increase the expression levels of DNMT3A, PIWIL1, SETDB1, and PRMT5. Methyl capture sequencing proved that WZYZD can markedly upregulate the methylated level of Spata, Bcl, and Pik3 series genes. Network pharmacology analysis proved that WZYZD can ameliorate OLI through BCL-2 and PI3K-AKT signaling pathways. The immunofluorescence assay of BCL-2 and SPATA18 proved the aforementioned results. The potential mechanism of WZYZD in treating OLI mainly involved recruiting methyltransferase DNMT3A, PIWIL1, PRMT5, and SETDB1 and increasing the methylation degree of Spata, Bcl, and Pik3 series genes.

2.
J Sci Food Agric ; 103(14): 7260-7272, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37357594

RESUMO

BACKGROUND: Portulaca oleracea has served as food and folk medicine in many parts of the world for thousands of years. Portulaca oleracea extract (POE) was prepared from fresh plants. This study aims to evaluate the antibacterial diarrhea effect and explore the possible mechanism. RESULTS: POE was effective in reducing diarrhea rate, improving intestinal tissue, and reducing cytokines concentrations of interleukin (IL)-6, IL-10, IL-12 p40 and TNF-α in blood. Besides, the result of histological observation showed that the mucus layer thickness and crypt length in the POE-treated group was higher than that in the model group. The POE could significantly upregulate the protein expression of MUC2, occludin and ZO-1. 16S rRNA sequencing analysis showed that Parabacteroides, Clostridium and Muribaculaceae may be the key functional microflora of POE. The non-targeted metabolomics also suggested that the antibacterial diarrheal effects of P. oleracea may be attributed to the regulation of amino acid metabolism and composition of the gut microbiota. CONCLUSION: Portulaca oleracea has definite clinical efficacy against bacterial diarrhea and anti-inflammatory effects. Its regulation of gut microbiota and fecal metabolism may account for its antibacterial diarrhea and anti-inflammatory effects. © 2023 Society of Chemical Industry.


Assuntos
Microbioma Gastrointestinal , Portulaca , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Portulaca/química , RNA Ribossômico 16S , Interleucina-6 , Anti-Inflamatórios , Diarreia/tratamento farmacológico , Antibacterianos/farmacologia
3.
Biotechnol Lett ; 43(6): 1221-1228, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33666816

RESUMO

OBJECTIVE: To enhance biotin production in Escherichia coli by engineering a heterologous biotin synthetic pathway. RESULTS: Biotin operon genes from Pseudomonas putida, which consisted of a bioBFHCD cluster and a bioA gene, was engineered into Escherichia coli for biotin production. The introduction of bioW gene from Bacillus subtilis, encoding pimeloyl-CoA synthetase and sam2 gene from Saccharomyces cerevisiae, encoding S-adenosyl-L-methionine (SAM) synthetase contributed to the heterologous production of biotin in recombinant E. coli. Furthermore, biotin production was efficiently enhanced by optimization of the fermentation compositions, especially pimelic acid and L-methionine, the precursor related to the pimeloyl-CoA and SAM synthesis, respectively. The combination of overexpression of the heterologous biotin operon genes and enhanced supply of key intermediate pimeloyl-CoA and SAM increased biotin production in E. coli by more than 121-fold. With bioprocess engineering efforts, biotin was produced at a final titer of 92.6 mg/L in a shake flask and 208.7 mg/L in a fed-batch fermenter. CONCLUSION: Through introduction of heterologous biotin synthetic pathway, increasing the supply of precursor pimeloyl-CoA and cofactor SAM can significantly enhance biotin production in E. coli.


Assuntos
Bacillus subtilis/enzimologia , Vias Biossintéticas , Biotina/biossíntese , Escherichia coli/crescimento & desenvolvimento , Pseudomonas putida/enzimologia , Saccharomyces cerevisiae/enzimologia , Bacillus subtilis/genética , Técnicas de Cultura Celular por Lotes , Clonagem Molecular , Escherichia coli/genética , Fermentação , Engenharia Metabólica/métodos , Metionina/química , Óperon , Ácidos Pimélicos/química , Pseudomonas putida/genética , Saccharomyces cerevisiae/genética
4.
Planta Med ; 86(13-14): 967-975, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31766070

RESUMO

The endophytic microbiome in medicinal plants is rich and diverse, but few studies have followed the endophytic microbiome of medicinal plants in different tissues with their growth. In this study, we examined the endophytic bacterial and fungal community structures associated with both the stem and root compartments of Dendrobium huoshanense at different growth years via high-throughput sequencing of 16S rRNA genes and nrDNA fragments of internal transcribed spacer regions. Results indicated that more diverse prokaryotic and fungal operational taxonomic units were detected in roots than in stems, and the alpha diversity of endophytic prokaryotic significantly differed among the 1-, 2-, and 3-year-old roots. The dominant bacterial phyla Proteobacteria Firmicutes, Actinobacteria, Bacteroidetes, and Acidobacteria, and fungal phyla Ascomycota, Basidiomycota, and Ascomycota were detected in the stems and roots with 3 growth years. Moreover, linear discriminant effect size analysis revealed 138 differentially abundant taxonomic clades in the bacterial level, and 197 in the fungal level in six groups. Our results provide evidence for endophytic microbiota communities depending on the tissues and growth years of D. huoshanense. The results from this study should be useful to better understand medicinal plant-microbe interactions.


Assuntos
Dendrobium , Microbiota , Endófitos/genética , Filogenia , Raízes de Plantas , RNA Ribossômico 16S/genética
5.
Physiol Mol Biol Plants ; 26(7): 1425-1435, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32647459

RESUMO

Nitrogen-containing compounds especially alkaloids are important medicinal ingredients in caulis dendrobii plants. Using solid-phase extraction coupled with liquid chromatography tandem mass spectrometry and multivariate data analysis methods, metabolic profiling of the nitrogen-containing compounds was established to distinguish Dendrobium huoshanense and Dendrobium officinale. Hundreds of nitrogen-containing compounds from the two caulis dendrobii were purified by the MCX cartridges. Some compounds were identified by high-resolution tandem mass spectrometry technology. Together with multivariate data analysis methods, comparative analysis of the metabolic profiling from two caulis dendrobii was conducted. A total of 133 nitrogen-containing compounds were identified, including amino acids, pyrrolidines, tropanes, pyrimidines, purines, indoles, piperidines, guanidines, quinolines, isoquinolines and terpenoids. Metabolic profiling analysis showed that the composition and contents of these chemical components were significantly different between D. huoshanense and D. officinale. Moreover, some components were species-specific, distributed in the two caulis dendrobii, such as pilosine, ternatusine, etc. Because alkaloids are mainly derived from amino acids via multistep biochemical reactions, the correlation analysis suggested that amino acids were partially associated with several types of components and significantly correlated with certain alkaloids. Arginine was extremely correlated with guanidines. Pyrimidines, purines and niacin-nicotinamide metabolic intermediates were associated with three independent networks. The results further enriched the chemical components currently identified from caulis dendrobii and provided a technical reference for detecting nitrogen-containing compounds in other medicinal plants.

6.
Zhonghua Nan Ke Xue ; 26(2): 160-166, 2020 Feb.
Artigo em Zh | MEDLINE | ID: mdl-33346421

RESUMO

OBJECTIVE: To investigate the protective effect of Jinkui Shenqi Pills (JSP) against cyclophosphamide-induced testis injury (TI) and its anti-oxidation mechanism in mice. METHODS: Thirty male mice were equally divided into a blank control, a TI model control and a JSP treatment group. The mice in the JSP treatment group were treated intragastrically with JSP and the blank controls with normal saline at 1.2 g/kg qd for 7 days, and then the animals in both the TI model control and JSP treatment groups were injected intraperitoneally with cyclophosphamide at 50 mg/kg, once a week, for 35 days, to induce testis injury. After modeling, all the mice were weighed and sacrificed, followed by detection of the serum T content, measurement of the testis weight, examination of semen parameters in the caudad epididymis, and determination of the levels of super oxide dismutase (SOD) and malondialdehyde (MDA) in the testis tissue and the expressions of relevant genes by qRT-PCR. RESULTS: The mice of the TI model control group, compared with the blank controls, showed significant decreases in the body weight (ï¼»34.63 ± 1.92ï¼½ vs ï¼»48.32 ± 1.64ï¼½ g, P<0.05), testis weight (ï¼»80.00 ± 3.90ï¼½ vs ï¼»140.00 ± 6.10ï¼½ mg, P<0.05), testicular organ coefficient (ï¼»0.22 ± 0.01ï¼½ vs ï¼»0.31 ±0.03ï¼½%, P<0.05), sperm motility (ï¼»48.66 ± 8.08ï¼½% vs ï¼»89.33 ± 4.04ï¼½%, P<0.05), sperm concentration (ï¼»28.42 ± 5.26ï¼½ vs ï¼»77.67 ± 8.73ï¼½ ×106/ml, P<0.05), and levels of serum T (ï¼»8.75 ± 0.96ï¼½ vs ï¼»21.75 ± 1.71ï¼½ pg/ml, P<0.05) and SOD (ï¼»140.82 ± 10.08ï¼½ vs ï¼»358.52 ± 40.41ï¼½ U/mg prot, P<0.05), but remarkable increases in the sperm deformity rate (ï¼»37.33 ± 2.08ï¼½ vs ï¼»15.33±1.53ï¼½%, P<0.05) and MDA level (ï¼»54.89±6.09ï¼½ vs ï¼»30.21±2.17ï¼½ nmol/ng prot, P<0.05). The mice of the JSP treatment group, in comparison with the TI model controls, exhibited markedly increased body weight (ï¼»39.80±2.89ï¼½ vs ï¼»34.63±1.92ï¼½g, P<0.05), testis weight (ï¼»130.00 ± 11.00ï¼½ vs ï¼»80.00 ± 3.90ï¼½ mg, P<0.05), testicular organ coefficient (ï¼»0.28 ± 0.01ï¼½ vs ï¼»0.22 ± 0.01ï¼½%, P<0.05), sperm motility (ï¼»76.00 ± 5.29ï¼½% vs ï¼»48.66 ± 8.08ï¼½%, P<0.05), sperm concentration (ï¼»56.08 ± 4.29ï¼½ vs ï¼»28.42 ± 5.26ï¼½ ×106/ml, P<0.05), and levels of serum T (ï¼»15.50 ± 1.29ï¼½ vs ï¼»8.75 ± 0.96ï¼½ pg/ml, P<0.05) and SOD (ï¼»206.59 ± 16.38ï¼½ vs ï¼»140.82 ± 10.08ï¼½ U/mg prot, P<0.05), but decreased sperm deformity rate (ï¼»25.01 ± 2.99ï¼½% vs ï¼»37.33 ± 2.08ï¼½%, P<0.05) and MDA level (ï¼»35.84 ± 3.61ï¼½ vs ï¼»54.89 ± 6.09ï¼½ nmol/ng prot, P<0.05). The mRNA expressions of NOQ-1, Nrf2 and HO-1 in the testis tissue were significantly lower and that of Caspase-3 remarkably higher in the TI model control than in the blank control group (P<0.05), while those of Nrf2 and HO-1 significantly higher and that of Caspase-3 markedly lower in the JSP treatment group than in the TI model controls (P<0.05). Histopathological images displayed reduced layers of spermatogenic cells in the seminiferous tubules, complete exfoliation of the spermatogenic cells in some of the tubules and decreased number of sperm cells in the TI model controls, which were all found normal in the JSP treatment group. CONCLUSIONS: Jinkui Shenqi Pills can effectively inhibit cyclophosphamide-induced testis injury, which may be related to its effect of regulating the gene expression of the Nrf2 signaling pathway and enhancing the activity of antioxidant enzymes.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Motilidade dos Espermatozoides , Testículo/metabolismo , Animais , Ciclofosfamida , Expressão Gênica , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/genética , Transdução de Sinais , Contagem de Espermatozoides , Espermatozoides , Testículo/efeitos dos fármacos
7.
Zhongguo Zhong Yao Za Zhi ; 44(6): 1145-1150, 2019 Mar.
Artigo em Zh | MEDLINE | ID: mdl-30989976

RESUMO

In order to explore endophytes diversity and difference in Dendrobium huoshanense,in this paper,the metagenomics method was used to analyze the endophytic bacteria and fungi community of 5 groups include 30 samples in different growth years. The results indicate that 3 540 bacterial OTUs were identified from D. huoshanense,and there are 138 OTUs in 5 groups simultaneously;2 168 fungal OTUs were identified,and 143 OTUs exist in 5 groups simultaneously. The dominate endophytic bacteria community are Sphingomonas sp.,Acinetobacter sp.,Burkholderia sp.,Methylobacterium sp.,Enterococcus sp.,Bacillus sp.,the difference endophytic bacteria community are Oceanobacillusd sp.,Actinomycetospora sp.,Paenibacillus sp.. The dominate endophytic fungi community are Zasmidium sp.,Zymoseptoria sp.,Alternaria sp.,Cladosporium sp.,Fusarium sp.,the difference endophytic fungi community are Cyphellophore sp.,Fusarium sp.. The results of clustering revealed that both the endophytic bacteria and the endophytic fungi,ⅢY2 and ⅢY3 are complete clustered,and ⅡY1 and ⅢY1 are also cluster completely. These enriched the species and resources of endophytic bacteria and fungi in D. huoshanense,and provided a theoretical reference for the reasonable harvest of D. huoshanense.


Assuntos
Ascomicetos , Dendrobium , Fusarium , Bactérias , Endófitos , Fungos , Filogenia
8.
Phytomedicine ; 129: 155713, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38735196

RESUMO

BACKGROUND: Oligoasthenozoospermia is the most common type of semen abnormality in male infertile patients. Betaine (BET) has been proved to have pharmacological effects on improving semen quality. BET also belongs to endogenous physiological active substances in the testis. However, the physiological function of BET in rat testis and its pharmacological mechanism against oligoasthenozoospermia remain unclear. PURPOSE: This research aims to prove the therapeutic effect and potential mechanism of BET on oligoasthenozoospermia rat model induced by Tripterygium wilfordii glycosides (TWGs). METHODS: The oligoasthenozoospermia rat model was established by a continuous gavage of TWGs (60 mg/kg) for 28 days. Negative control group, oligoasthenozoospermia group, positive drug group (levocarnitine, 300 mg/kg), and 200 mg/kg, 400 mg/kg, and 800 mg/kg BET groups were created for exploring the therapeutic effect of BET on the oligoasthenozoospermia rat model. The therapeutic effect was evaluated by HE and TUNEL staining. Immunofluorescence assay of DNMT3A, PIWIL1, PRMT5, SETDB1, BHMT2, and METTL3, methylation capture sequencing, Pi-RNA sequencing, and molecular docking were used to elucidate potential pharmacological mechanisms. RESULTS: It is proved that BET can significantly restore testicular pathological damage induced by TWGs, which also can significantly reverse the apoptosis of spermatogenic cells. The spermatogenic cell protein expression levels of DNMT3A, PIWIL1, PRMT5, SETDB1, BHMT2, and METTL3 significantly decreased in oligoasthenozoospermia group. 400 mg/kg and 800 mg/kg BET groups can significantly increase expression level of the above-mentioned proteins. Methylation capture sequencing showed that BET can significantly increase the 5mC methylation level of Spata, Spag, and Specc spermatogenesis-related genes. Pi-RNA sequencing proved that the above-mentioned genes produce a large number of Pi-RNA under BET intervention. Pi-RNA can form complexes with PIWI proteins to participate in DNA methylation of target genes. Molecular docking indicated that BET may not directly act as substrate for methyltransferase and instead participates in DNA methylation by promoting the methionine cycle and increasing S-adenosylmethionine synthesis. CONCLUSION: BET has a significant therapeutic effect on oligoasthenozoospermia rat model induced by TWPs. The mechanism mainly involves that BET can increase the methylation level of Spata, Specc, and Spag target genes through the PIWI/Pi-RNA pathway and up-regulation of methyltransferases (including DNA methyltransferases and histone methyltransferases).


Assuntos
Apoptose , Betaína , Metilação de DNA , Modelos Animais de Doenças , Oligospermia , Ratos Sprague-Dawley , Tripterygium , Masculino , Animais , Apoptose/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Betaína/farmacologia , Ratos , Oligospermia/tratamento farmacológico , Tripterygium/química , Astenozoospermia/tratamento farmacológico , Regulação para Cima/efeitos dos fármacos , Testículo/efeitos dos fármacos , Simulação de Acoplamento Molecular , Espermatogênese/efeitos dos fármacos , Metiltransferases/metabolismo , Espermatozoides/efeitos dos fármacos
9.
Int J Biol Macromol ; 255: 128218, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37992933

RESUMO

Peucedanum praeruptorum Dunn, a traditional Chinese medicine rich in coumarin, belongs to the Apiaceae family. A high-quality assembled genome of P. praeruptorum is lacking, which has posed obstacles to functional identification and molecular evolution studies of genes associated with coumarin production. Here, a chromosome-scale reference genome of P. praeruptorum, an important medicinal and aromatic plant, was first sequenced and assembled using Oxford Nanopore Technologies and Hi-C sequencing. The final assembled genome size was 1.83 Gb, with a contig N50 of 11.12 Mb. The entire BUSCO evaluation and second-generation read comparability rates were 96.0 % and 99.31 %, respectively. Furthermore, 99.91 % of the genome was anchored to 11 pseudochromosomes. The comparative genomic study revealed the presence of 18,593 orthogroups, which included 476 species-specific orthogroups and 1211 expanded gene families. Two whole-genome duplication (WGD) events and one whole-genome triplication (WGT) event occurred in P. praeruptorum. In addition to the γ-WGT shared by core eudicots or most eudicots, the first WGD was shared by Apiales, while the most recent WGD was unique to Apiaceae. Our study demonstrated that WGD events that occurred in Apioideae highlighted the important role of tandem duplication in the biosynthesis of coumarins and terpenes in P. praeruptorum. Additionally, the expansion of the cytochrome P450 monooxygenase, O-methyltransferase, ATP-binding cassette (ABC) transporter, and terpene synthase families may be associated with the abundance of coumarins and terpenoids. Moreover, we identified >170 UDP-glucosyltransferase members that may be involved in the glycosylation post-modification of coumarins. Significant gene expansion was observed in the ABCG, ABCB, and ABCC subgroups of the ABC transporter family, potentially facilitating the transmembrane transport of coumarins after bolting. The P. praeruptorum genome provides valuable insights into the machinery of coumarin biosynthesis and enhances our understanding of Apiaceae evolution.


Assuntos
Apiaceae , Cumarínicos , Cumarínicos/química , Sistema Enzimático do Citocromo P-450/genética , Apiaceae/genética , Apiaceae/química , Metiltransferases/genética , Cromossomos
10.
Front Plant Sci ; 14: 1258533, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37860241

RESUMO

Introduction: KNOX plays a pivotal role in governing plant growth, development, and responses to diverse abiotic and biotic stresses. However, information on the relationship between the KNOX gene family and expression levels under different treatments in Dendrobium is still limited. Methods: To address this problem, we first used bioinformatics methods and revealed the presence of 19 KNOX genes distributed among 13 chromosomes in the Dendrobium huoshanense genome. Through an analysis of phylogenetic relationships, these genes were classified into three distinct clades: class I, class II, and class M. Our investigation included promoter analysis, revealing various cis-acting elements associated with hormones, growth and development, and abiotic stress responses. Additionally, qRT-PCR experiments were conducted to assess the expression patterns of DhKNOX genes under different treatments, including ABA, MeJA, SA, and drought. Results: The results demonstrated differential expression of DhKNOX genes in response to these treatments, thereby highlighting their potential roles in stress adaptation. Discussion: Overall, our results contribute important insights for further investigations into the functional characterization of the Dendrobium KNOX gene family, shedding light on their roles in plant development and stress responses.

11.
Curr Pharm Biotechnol ; 24(15): 1964-1971, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37070797

RESUMO

BACKGROUND: Sodium new houttuyfonate (SNH) is an adduct of houttuyfonate, which is the main component of the common Chinese medicinal plant Houttuynia cordata. SNH has been widely used in antibacterial and anti-inflammatory treatments in clinics. However, the exact antimicrobial mechanism of SNH is still unclear, despite its mild direct antimicrobial activity in vitro. Objectives: The aim of this study is to investigate the effect and possible mechanism of SNH on macrophages against bacteria in vitro. METHODS: In this study, we assessed the antibacterial and anti-inflammatory effects of SNH on the RAW264.7 macrophage cell line against Pseudomonas aeruginosa, a major opportunistic pathogen. RESULTS: Firstly, we found that SNH showed minimal toxicity on RAW264.7 macrophages. Secondly, our results indicated that SNH effectively inhibited the inflammatory reaction of macrophages stimulated by P. aeruginosa. We also found that SNH improved the phagocytosis and killing effect of RAW264.7 macrophages against P. aeruginosa in vitro. Furthermore, our results revealed that SNH effectively inhibited the expression of the TLR4/NF-кB pathway in macrophage RAW264.7 co-incubated with P. aeruginosa in vitro. CONCLUSION: Based on our findings, SNH can significantly improve the phagocytosis of macrophages and inhibit the excessive release of inflammatory factors by repressing the TLR4/NF-кB pathway.


Assuntos
NF-kappa B , Receptor 4 Toll-Like , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Antibacterianos/farmacologia , Macrófagos , Fagocitose , Anti-Inflamatórios/farmacologia , Lipopolissacarídeos/farmacologia
12.
Front Plant Sci ; 14: 1169386, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37235024

RESUMO

Introduction: Alkaloids are one of the main medicinal components of Dendrobium species. Dendrobium alkaloids are mainly composed of terpene alkaloids. Jasmonic acid (JA) induce the biosynthesis of such alkaloids, mainly by enhancing the expression of JA-responsive genes to increase plant resistance and increase the content of alkaloids. Many JA-responsive genes are the target genes of bHLH transcription factors (TFs), especially the MYC2 transcription factor. Methods: In this study, the differentially expressed genes involved in the JA signaling pathway were screened out from Dendrobium huoshanense using comparative transcriptomics approaches, revealing the critical roles of basic helix-loop-helix (bHLH) family, particularly the MYC2 subfamily. Results and discussion: Microsynteny-based comparative genomics demonstrated that whole genome duplication (WGD) and segmental duplication events drove bHLH genes expansion and functional divergence. Tandem duplication accelerated the generation of bHLH paralogs. Multiple sequence alignments showed that all bHLH proteins included bHLH-zip and ACT-like conserved domains. The MYC2 subfamily had a typical bHLH-MYC_N domain. The phylogenetic tree revealed the classification and putative roles of bHLHs. The analysis of cis-acting elements revealed that promoter of the majority of bHLH genes contain multiple regulatory elements relevant to light response, hormone responses, and abiotic stresses, and the bHLH genes could be activated by binding these elements. The expression profiling and qRT-PCR results indicated that bHLH subgroups IIIe and IIId may have an antagonistic role in JA-mediated expression of stress-related genes. DhbHLH20 and DhbHLH21 were considered to be the positive regulators in the early response of JA signaling, while DhbHLH24 and DhbHLH25 might be the negative regulators. Our findings may provide a practical reference for the functional study of DhbHLH genes and the regulation of secondary metabolites.

13.
Front Pharmacol ; 13: 829759, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35814226

RESUMO

Abemaciclib is a cyclin-dependent kinases 4/6 (CDK4/6) inhibitor approved for the treatment of metastatic breast cancer. Preclinical studies suggest that abemaciclib has the potential for lung cancer treatment. However, several clinical trials demonstrate that monotherapy with abemaciclib has no obvious superiority than erlotinib to treat lung cancer patients, limiting its therapeutic options for lung cancer treatment. Here, we show that the US Food and Drug Administration (FDA)-approved drug, gilteritinib, enhances the cytotoxicity of abemaciclib through inducing apoptosis and senescence in lung cancer cells. Interestingly, abemaciclib in combination with gilteritinib leads to excessive accumulation of vacuoles in lung cancer cells. Mechanistically, combined abemaciclib and gilteritinib induces complete inactivation of AKT and retinoblastoma (Rb) pathways in lung cancer cells. In addition, RNA-sequencing data demonstrate that combination of abemaciclib and gilteritinib treatment induces G2 phase cell-cycle arrest, inhibits DNA replication, and leads to reduction in homologous recombination associated gene expressions. Of note, abemaciclib-resistant lung cancer cells are more sensitive to gilteritinib treatment. In a mouse xenograft model, combined abemaciclib and gilteritinib is more effective than either drug alone in suppressing tumor growth and appears to be well tolerated. Together, our findings support the combination of abemaciclib with gilteritinib as an effective strategy for the treatment of lung cancer, suggesting further evaluation of their efficacy is needed in a clinical trial.

14.
Front Microbiol ; 13: 859206, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35369480

RESUMO

Unhealthy diet, in particular high-fat diet (HFD) intake, can cause the development of several metabolic disorders, including obesity, hyperlipidemia, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and metabolic syndrome (MetS). These popular metabolic diseases reduce the quality of life, and induce premature death worldwide. Evidence is accumulating that the gut microbiota is inextricably associated with HFD-induced metabolic disorders, and dietary intervention of gut microbiota is an effective therapeutic strategy for these metabolic dysfunctions. Polysaccharides are polymeric carbohydrate macromolecules and sources of fermentable dietary fiber that exhibit biological activities in the prevention and treatment of HFD-induced metabolic diseases. Of note, natural polysaccharides are among the most potent modulators of the gut microbiota composition. However, the prebiotics-like effects of polysaccharides in treating HFD-induced metabolic diseases remain elusive. In this review, we introduce the critical role of gut microbiota human health and HFD-induced metabolic disorders. Importantly, we review current knowledge about the role of natural polysaccharides in improving HFD-induced metabolic diseases by regulating gut microbiota.

15.
Mitochondrial DNA B Resour ; 7(7): 1218-1220, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35837498

RESUMO

Paederia foetida L. belonging to Rubiaceae family is a perennial medicinal herb widely distributed in India and China. The first complete chloroplast genome sequence of P. foetida was assembled and characterized in this study. The total chloroplast genome was 153,591 bp in length with 37.74% GC content, composed of a large single-copy (LSC) region of 83,677 bp, a small single-copy (SSC) region of 16,888 bp and a pair of inverted repeat (IR) regions of 26,513 bp. The whole chloroplast genome encoded 133 genes, including 88 protein-coding genes, 37 tRNA genes and 8 rRNA genes. Phylogenetic analysis of 30 chloroplast genomes strongly suggested that P. foetida was closely related to P. scandens.

16.
Mitochondrial DNA B Resour ; 7(6): 1087-1089, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35756430

RESUMO

Rubia yunnanensis Diels, an important medicinal herb, is mainly distributed in Yunnan province, Southwest China. In this study, the complete chloroplast genome of R. yunnanensis was successfully sequenced. The assembled chloroplast genome was 155,108 bp in length with an overall GC content of 36.98%, including a pair of inverted repeat (IR) regions (26,573 bp, each), respectively, a large single-copy (LSC) region (84,848 bp) and a small single-copy (SSC) region (17,114 bp). The genome contained 131 genes, comprising 85 protein-coding genes, 37 tRNA genes, eight rRNA genes, and one pseudogene. The phylogenetic analysis indicated that R. yunnanensis was closely related to R. cordifolia.

17.
Front Plant Sci ; 13: 868874, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35548315

RESUMO

Environmental stress is one of the major restrictions on plant development and foodstuff production. The adaptive response in plants largely occurs through an intricate signaling system, which is crucial for regulating the stress-responsive genes. Myelocytomatosis (MYC) transcription factors are the fundamental regulators of the jasmonate (JA) signaling branch that participates in plant development and multiple stresses. By binding to the cis-acting elements of a large number of stress-responsive genes, JA-responsive transcription factors activate the stress-resistant defense genes. The mechanism of stress responses concerns myriad regulatory processes at the physiological and molecular levels. Discovering stress-related regulatory factors is of great value in disclosing the response mechanisms of plants to biotic or abiotic stress, which could guide the genetic improvement of plant resistance. This review summarizes recent researches in various aspects of MYC2-mediated JA signaling and emphasizes MYC2 involvement in plant growth and stress response.

18.
Int J Biol Sci ; 18(7): 2744-2758, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35541906

RESUMO

RNA can be modified by over 170 types of distinct chemical modifications, and the most abundant internal modification of mRNA in eukaryotes is N6-methyladenosine (m6A). The m6A modification accelerates mRNA process, including mRNA splicing, translation, transcript stability, export and decay. m6A RNA modification is installed by methyltransferase-like proteins (writers), and potentially removed by demethylases (erasers), and this process is recognized by m6A-binding proteins (readers). Notably, alterations of m6A-modified proteins (writers, erasers and readers) are involved in the tumorigenesis, progression and metastasis. Importantly, the fate of m6A-methylated mRNA is mediated mostly through m6A readers, and among these readers, insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) are unique RNA-binding proteins (RBPs) that stabilize their targets mRNA via m6A modification. In this review, we update the writers, erasers and readers, and their cross-talks in m6A modification, and briefly discuss the oncogenic role of IGF2BPs in cancer. Most importantly, we mainly review the up-to-date knowledges of IGF2BPs (IGF2BP1/2/3) as m6A readers in an m6A-modified manner in cancer progression.


Assuntos
Proteínas de Transporte , Neoplasias , Carcinogênese , Humanos , Neoplasias/metabolismo , RNA/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
19.
Front Plant Sci ; 13: 874579, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35646023

RESUMO

Salt stress is a constraint on crop growth and productivity. When exposed to high salt stress, metabolic abnormalities that disrupt reactive oxygen species (ROS) homeostasis result in massive oxygen radical deposition. Dendrobium huoshanense is a perennial orchid herb that thrives in semi-shade conditions. Although lots of studies have been undertaken on abiotic stresses (high temperature, chilling, drought, etc.) of model plants, few studies were reported on the mechanism of salt stress in D. huoshanense. Using a label-free protein quantification method, a total of 2,002 differential expressed proteins were identified in D. huoshanense. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment indicated that proteins involved in vitamin B6 metabolism, photosynthesis, spliceosome, arginine biosynthesis, oxidative phosphorylation, and MAPK signaling were considerably enriched. Remarkably, six malate dehydrogenases (MDHs) were identified from deferentially expressed proteins. (NAD+)-dependent MDH may directly participate in the biosynthesis of malate in the nocturnal crassulacean acid metabolism (CAM) pathway. Additionally, peroxidases such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), as well as antioxidant enzymes involved in glutathione biosynthesis and some vitamins biosynthesis were also identified. Taken together, these results provide a solid foundation for the investigation of the mechanism of salt stress in Dendrobium spp.

20.
Genes (Basel) ; 13(5)2022 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-35627316

RESUMO

Saposhnikovia divaricata, a well-known Chinese medicinal herb, is the sole species under the genus Saposhnikovia of the Apiaceae subfamily Apioideae Drude. However, information regarding its genetic diversity and evolution is still limited. In this study, the first complete chloroplast genome (cpDNA) of wild S. divaricata was generated using de novo sequencing technology. Similar to the characteristics of Ledebouriella seseloides, the 147,834 bp-long S. divaricata cpDNA contained a large single copy, a small single copy, and two inverted repeat regions. A total of 85 protein-coding, 8 ribosomal RNA, and 36 transfer RNA genes were identified. Compared with five other species, the non-coding regions in the S. divaricata cpDNA exhibited greater variation than the coding regions. Several repeat sequences were also discovered, namely, 33 forward, 14 reverse, 3 complement, and 49 microsatellite repeats. Furthermore, phylogenetic analysis using 47 cpDNA sequences of Apioideae members revealed that L. seseloides and S. divaricata clustered together with a 100% bootstrap value, thereby supporting the validity of renaming L. seseloides to S. divaricata at the genomic level. Notably, S. divaricata was most closely related to Libanotis buchtormensis, which contradicts previous reports. Therefore, these findings provide a valuable foundation for future studies on the genetic diversity and evolution of S. divaricata.


Assuntos
Apiaceae , Genoma de Cloroplastos , Apiaceae/genética , DNA de Cloroplastos/genética , Genômica , Filogenia
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