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1.
Plant Physiol ; 195(3): 2016-2031, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38502062

RESUMO

Leguminosae exhibits a wide diversity of legume forms with varying degrees of spiral morphologies, serving as an ideal clade for studying the growth and development of spiral organs. While soybean (Glycine max) develops straight pods, the pod of the model legume Medicago truncatula is a helix structure. Despite the fascinating structures and intensive description of the pods in legumes, little is known regarding the genetic mechanism underlying the highly varied spirality of the legume pods. In this study, we found that KINASE-INDUCIBLE DOMAIN INTERACTING 8 (MtKIX8) plays a key role in regulating the pod structure and spirality in M. truncatula. Unlike the coiled and barrel-shaped helix pods of the wild type, the pods of the mtkix8 mutant are loose and deformed and lose the topologic structure as observed in the wild-type pods. In the pods of the mtkix8 mutant, the cells proliferate more actively and overly expand, particularly in the ventral suture, resulting in uncoordinated growth along the dorsal and ventral sutures of pods. The core cell cycle genes CYCLIN D3s are upregulated in the mtkix8 pods, leading to the prolonged growth of the ventral suture region of the pods. Our study revealed the key role of MtKIX8 in regulating seed pod development in M. truncatula and demonstrates a genetic regulatory model underlying the establishment of the helical pod in legumes.


Assuntos
Regulação da Expressão Gênica de Plantas , Medicago truncatula , Proteínas de Plantas , Medicago truncatula/genética , Medicago truncatula/crescimento & desenvolvimento , Medicago truncatula/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mutação/genética , Sementes/genética , Sementes/crescimento & desenvolvimento
2.
J Mol Cell Cardiol ; 186: 94-106, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38000204

RESUMO

Myocardial ischemia-reperfusion injury (MIRI) is closely related to the final infarct size in acute myocardial infarction (AMI). Therefore, reducing MIRI can effectively improve the prognosis of AMI patients. At the same time, the healing process after AMI is closely related to the local inflammatory microenvironment. Regulatory T cells (Tregs) can regulate various physiological and pathological immune inflammatory responses and play an important role in regulating the immune inflammatory response after AMI. However, different subtypes of Tregs have different effects on MIRI, and the same subtype of Tregs may also have different effects at different stages of MIRI. This article systematically reviews the classification and function of Tregs, as well as the role of various subtypes of Tregs in MIRI. A comprehensive understanding of the role of each subtype of Tregs can help design effective methods to control immune reactions, reduce MIRI, and provide new potential therapeutic options for AMI.


Assuntos
Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Humanos , Traumatismo por Reperfusão Miocárdica/patologia , Linfócitos T Reguladores , Infarto do Miocárdio/terapia
3.
Acta Neuropathol ; 147(1): 62, 2024 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526799

RESUMO

TMEM106B, a gene encoding a lysosome membrane protein, is tightly associated with brain aging, hypomyelinating leukodystrophy, and multiple neurodegenerative diseases, including frontotemporal lobar degeneration with TDP-43 aggregates (FTLD-TDP). Recently, TMEM106B polymorphisms have been associated with tauopathy in chronic traumatic encephalopathy (CTE) and FTLD-TDP patients. However, how TMEM106B influences Tau pathology and its associated neurodegeneration, is unclear. Here we show that loss of TMEM106B enhances the accumulation of pathological Tau, especially in the neuronal soma in the hippocampus, resulting in severe neuronal loss in the PS19 Tau transgenic mice. Moreover, Tmem106b-/- PS19 mice develop significantly increased abnormalities in the neuronal cytoskeleton, autophagy-lysosome activities, as well as glial activation, compared with PS19 and Tmem106b-/- mice. Together, our findings demonstrate that loss of TMEM106B drastically exacerbates Tau pathology and its associated disease phenotypes, and provide new insights into the roles of TMEM106B in neurodegenerative diseases.


Assuntos
Demência Frontotemporal , Degeneração Lobar Frontotemporal , Proteínas de Membrana , Proteínas do Tecido Nervoso , Animais , Humanos , Camundongos , Demência Frontotemporal/genética , Degeneração Lobar Frontotemporal/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Proteínas tau/genética
4.
Chem Biodivers ; 21(6): e202400258, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38581076

RESUMO

We presented a strategy utilizing 2D NMR-based metabolomic analysis of crude extracts, categorized by different pharmacological activities, to rapidly identify the primary bioactive components of TCM. It was applied to identify the potential bioactive components from Scutellaria crude extracts that exhibit anti-non-small cell lung cancer (anti-NSCLC) activity. Four Scutellaria species were chosen as the study subjects because of their close phylogenetic relationship, but their crude extracts exhibit significantly different anti-NSCLC activity. Cell proliferation assay was used to assess the anti-NSCLC activity of four species of Scutellaria. 1H-13C HSQC spectra were acquired for the chemical profiling of these crude extracts. Based on the pharmacological classification (PCA, OPLS-DA and univariate hypothesis test) were performed to identify the bioactive constituents in Scutellaria associated with the anti-NSCLC activity. As a result, three compounds, baicalein, wogonin and scutellarin were identified as bioactive compounds. The anti-NSCLC activity of the three potential active compounds were further confirmed via cell proliferation assay. The mechanism of the anti-NSCLC activity by these active constituents was further explored via flow cytometry and western blot analyses. This study demonstrated 2D NMR-based metabolomic analysis of pharmacologically classified crude extracts to be an efficient approach to the identification of active components of herbal medicine.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Espectroscopia de Ressonância Magnética , Metabolômica , Extratos Vegetais , Scutellaria , Scutellaria/química , Humanos , Proliferação de Células/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Apigenina/farmacologia , Apigenina/química , Apigenina/isolamento & purificação , Apigenina/análise , Flavanonas/farmacologia , Flavanonas/química , Flavanonas/isolamento & purificação , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Glucuronatos/farmacologia , Glucuronatos/isolamento & purificação , Glucuronatos/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais
5.
Molecules ; 29(3)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38338362

RESUMO

The recycling and utilization of waste alkaline zinc manganese batteries (S-AZMB) has always been a focus of attention in the fields of environment and energy. However, current research mostly focuses on the recycling of purified materials, while neglecting the direct reuse of waste batteries. Here, we propose a new concept of preparing thermal catalysts by combining unpurified S-AZMB with CeO2 by means of ball milling. A series of characterizations and experiments have confirmed that the combination with S-AZMB not only enhances the thermal catalytic activity of CeO2 but also significantly enhances the concentration of surface oxygen vacancies. In the toluene removal experiment, the temperature (T90) at 90% toluene conversions of CeO2@S-AZMB was 180 °C, lower than the 220 °C for CeO2. More noteworthy is that this S-AZMB-based thermal catalyst can maintain a good structure and thermal catalytic stability in cyclic catalysis.

6.
J Biol Chem ; 298(9): 102348, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35933009

RESUMO

Progranulin (PGRN) is a glycoprotein implicated in several neurodegenerative diseases. It is highly expressed in microglia and macrophages and can be secreted or delivered to the lysosome compartment. PGRN comprises 7.5 granulin repeats and is processed into individual granulin peptides within the lysosome, but the functions of these peptides are largely unknown. Here, we identify CD68, a lysosome membrane protein mainly expressed in hematopoietic cells, as a binding partner of PGRN and PGRN-derived granulin E. Deletion analysis of CD68 showed that this interaction is mediated by the mucin-proline-rich domain of CD68. While CD68 deficiency does not affect the lysosomal localization of PGRN, it results in a specific decrease in the levels of granulin E but no other granulin peptides. On the other hand, the deficiency of PGRN, and its derivative granulin peptides, leads to a significant shift in the molecular weight of CD68, without altering CD68 localization within the cell. Our results support that granulin E and CD68 reciprocally regulate each other's protein homeostasis.


Assuntos
Antígenos CD , Antígenos de Diferenciação Mielomonocítica , Granulinas , Proteínas de Membrana Lisossomal , Proteostase , Granulinas/metabolismo , Proteínas de Membrana Lisossomal/metabolismo , Lisossomos/metabolismo , Mucinas/metabolismo , Progranulinas/metabolismo , Prolina/metabolismo
7.
Mol Biol Evol ; 39(10)2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36181435

RESUMO

Thermoprofundales, formerly Marine Benthic Group D (MBG-D), is a ubiquitous archaeal lineage found in sedimentary environments worldwide. However, its taxonomic classification, metabolic pathways, and evolutionary history are largely unexplored because of its uncultivability and limited number of sequenced genomes. In this study, phylogenomic analysis and average amino acid identity values of a collection of 146 Thermoprofundales genomes revealed five Thermoprofundales subgroups (A-E) with distinct habitat preferences. Most of the microorganisms from Subgroups B and D were thermophiles inhabiting hydrothermal vents and hot spring sediments, whereas those from Subgroup E were adapted to surface environments where sunlight is available. H2 production may be featured in Thermoprofundales as evidenced by a gene cluster encoding the ancient membrane-bound hydrogenase (MBH) complex. Interestingly, a unique structure separating the MBH gene cluster into two modular units was observed exclusively in the genomes of Subgroup E, which included a peripheral arm encoding the [NiFe] hydrogenase domain and a membrane arm encoding the Na+/H+ antiporter domain. These two modular structures were confirmed to function independently by detecting the H2-evolving activity in vitro and salt tolerance to 0.2 M NaCl in vivo, respectively. The peripheral arm of Subgroup E resembles the proposed common ancestral respiratory complex of modern respiratory systems, which plays a key role in the early evolution of life. In addition, molecular dating analysis revealed that Thermoprofundales is an early emerging archaeal lineage among the extant MBH-containing microorganisms, indicating new insights into the evolution of this ubiquitous archaea lineage.


Assuntos
Archaea , Hidrogenase , Archaea/genética , Archaea/metabolismo , Hidrogenase/química , Hidrogenase/genética , Hidrogenase/metabolismo , Cloreto de Sódio/metabolismo , Filogenia , Sistema Respiratório/metabolismo , Aminoácidos/genética , Antiporters/genética , Antiporters/metabolismo
8.
Anal Chem ; 95(6): 3195-3203, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36728684

RESUMO

Two-dimensional (2D) 1H-13C heteronuclear single quantum coherence (HSQC) has been increasingly applied to metabolomics studies because it can greatly improve the resolving capability compared with one-dimensional (1D) 1H NMR. However, preprocessing methods such as peak matching and alignment tools for 2D NMR-based metabolomics have lagged behind similar methods for 1D 1H NMR-based metabolomics. Correct matching and alignment of 2D NMR spectral features across multiple samples are particularly important for subsequent multivariate data analysis. Considering different intensity dynamic ranges of a variety of metabolites and the chemical shift variation across the spectra of multiple samples, here, we developed an efficient peak matching and alignment algorithm for 2D 1H-13C HSQC-based metabolomics, called global intensity-guided peak matching and alignment (GIPMA). In GIPMA, peaks identified in all spectra are pooled together and sorted by intensity. Chemical shift of a stronger peak is regarded to be more accurate and reliable than that of a weaker peak. The strongest undesignated peak is chosen as the reference of a new cluster if it is not located within the chemical shift tolerance of any existing peak cluster (PC), or otherwise it is matched to an existing PC and the aligned chemical shift of the PC is updated as the intensity-weighted average of the chemical shifts of all peaks in the cluster. Setting an optimum chemical shift tolerance (Δδo) is critical for the peak matching and alignment across multiple samples. GIPMA dynamically searches for and intelligently selects the Δδo for peak matching to maximize the number of valid peak clusters (vPC), that is, spectral features, among multiple samples. By GIPMA, fully automatic peakwise matching and alignment do not require any spectrum as initial reference, while the chemical shift of each PC is updated as the intensity-weighted average of the chemical shifts of all peaks in the same PC, which is warranted to be statistically more accurate. Accurate chemical shifts for each representative spectral feature will facilitate subsequent peak assignment and are essential for correct metabolite identification and result interpretation. The proposed method was demonstrated successfully on the spectra of six model mixtures consisting of seven typical metabolites, yielding correct matching of all known spectral features. The performance of GIPMA was also demonstrated on 2D 1H-13C HSQC spectra of 87 real extracts of 29 samples of five Dendrobium species. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) of the 87 matched and aligned spectra by GIPMA generates correct classification of the 29 samples into five groups. In summary, the proposed algorithm of GIPMA provided a practical peak matching and alignment method to facilitate 2D NMR-based metabolomics studies.


Assuntos
Algoritmos , Metabolômica , Metabolômica/métodos , Espectroscopia de Ressonância Magnética/métodos , Análise por Conglomerados
9.
Biomacromolecules ; 24(1): 439-448, 2023 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-36473109

RESUMO

Combining the killing ability of chemotherapy drugs on tumor cells with the inhibiting ability of genetic drugs on tumor cell growth, a dual drug delivery system loaded with therapy drugs and siRNA has gradually received more and more research and extensive attention. In this paper, we designed a DNA nano-assembly based on rolling circle amplification that can co-deliver doxorubicin (Dox) and siRNA simultaneously. In order to fully exploit the potential of the dual loading system in cancer treatment, we selected STAT3 gene as a target and used siRNA to target STAT3 of mRNA and reduce the STAT3 expression in mouse melanoma cell line (B16); meanwhile, Dox as a chemotherapy drug was combined with multivalent aptamers specifically targeting B16 to achieve efficient delivery of siRNA and Dox. The results showed that the synergistic delivery system could achieve high efficiency in targeting and inhibiting proliferation in mouse melanoma cells. In addition, the synergistic effect of the dual delivery system on apoptosis of cancer cells was significantly better than that of single drug delivery systems.


Assuntos
DNA , Doxorrubicina , Sistemas de Liberação de Fármacos por Nanopartículas , Animais , Camundongos , Linhagem Celular Tumoral , DNA/química , Sistemas de Liberação de Medicamentos/métodos , Terapia Genética/métodos , Melanoma/tratamento farmacológico , Melanoma/genética , RNA Interferente Pequeno , Nanopartículas/química , Sistemas de Liberação de Fármacos por Nanopartículas/química
10.
Anal Bioanal Chem ; 415(12): 2217-2226, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36864310

RESUMO

Sensitive detection of cancer cells plays a critical role in early cancer diagnosis. Nucleolin, overexpressed on the surface of cancer cells, is regarded as a candidate biomarker for cancer diagnosis. Thus, cancer cells can be detected through the detection of membrane nucleolin. Herein, we designed a nucleolin-activated polyvalent aptamer nanoprobe (PAN) to detect cancer cells. In brief, a long single-stranded DNA with many repeated sequences was synthesized through rolling circle amplification (RCA). Then the RCA product acted as a scaffold chain to combine with multiple AS1411 sequences, which was doubly modified with fluorophore and quenching group, respectively. The fluorescence of PAN was initially quenched. Upon binding to target protein, the conformation of PAN changed, leading to the recovery of fluorescence. The fluorescence signal of cancer cells treated with PAN was much brighter compared with that of monovalent aptamer nanoprobes (MAN) at the same concentration. Furthermore, the binding affinity of PAN to B16 cells was proved to be 30 times higher than that of MAN by calculating the dissociation constants. The results indicated that PAN could specifically detect target cells, and this design concept has potential to become promising in cancer diagnosis.


Assuntos
Aptâmeros de Nucleotídeos , Neoplasias , Humanos , Fosfoproteínas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Neoplasias/diagnóstico , Aptâmeros de Nucleotídeos/química , DNA de Cadeia Simples , Nucleolina
11.
Int J Mol Sci ; 24(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36614311

RESUMO

3-hydroxybutyrate (3OHB) has been proved to act as a neuroprotective molecule in multiple neurodegenerative diseases. Here, we employed a quantitative proteomics approach to assess the changes of the global protein expression pattern of neural cells upon 3OHB administration. In combination with a disease-related, protein-protein interaction network we pinpointed a hub marker, histone lysine 27 trimethylation, which is one of the key epigenetic markers in multiple neurodegenerative diseases. Integrative analysis of transcriptomic and epigenomic datasets highlighted the involvement of bivalent transcription factors in 3OHB-mediated disease protection and its alteration of neuronal development processes. Transcriptomic profiling revealed that 3OHB impaired the fate decision process of neural precursor cells by repressing differentiation and promoting proliferation. Our study provides a new mechanism of 3OHB's neuroprotective effect, in which chromatin bivalency is sensitive to 3OHB alteration and drives its neuroprotective function both in neurodegenerative diseases and in neural development processes.


Assuntos
Células-Tronco Neurais , Fármacos Neuroprotetores , Cromatina/genética , Ácido 3-Hidroxibutírico , Proteoma , Fármacos Neuroprotetores/farmacologia , Hidroxibutiratos
12.
Chembiochem ; 23(6): e202100548, 2022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-34989090

RESUMO

Isothermal exponential amplification technology has rarely been fabricated as a universal sensing platform for the detection of proteins. To broaden their application, we have developed a strategy, named protein-recognition-initiated exponential amplification reaction (PRIEAR) using protein recognition to induce DNA assembly, which converts protein recognition events into ssDNA amplicons and combines two-stage amplification to achieve exponential amplification. Taking advantage of this principle, diverse biomarkers can be quantified at sub-picomolar concentrations in a homogenous manner, making PRIEAR suitable for clinical settings. Therefore, this strategy can expand the powerful isothermal exponential amplification technology to protein targets and thus provide a new toolbox in clinical and biomedical applications.


Assuntos
Técnicas Biossensoriais , Técnicas de Amplificação de Ácido Nucleico , DNA , Proteínas
13.
Langmuir ; 38(38): 11778-11786, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36102591

RESUMO

DNA nanotechnology is beginning to yield unique advantages in the area of drug delivery. For the dual-targeting and proliferation suppression of cancer cells, a "willow branch" DNA assembly based on rolling circle amplification (RCA) was built. Three single-stranded DNAs, including antibody modified cDNAs, aptamer cDNAs, and simple cDNAs, were employed in the DNA self-assembly, along with the RCA scaffolds (every 63 bases is a repeat unit). "Willow branch" DNA (WB DNA) assembly successfully linked multiple antibodies and aptamers together to achieve dual targeting of cancer cells. Binding of CD44 antibodies and S2.2 aptamers to receptors on the cell membrane inhibits both pathways, ß-catenin signaling and nuclear factor-kappa B-specific transcription activity, through feedback regulation. Results demonstrated that WB DNA assembly could effectively exert multivalency clustering cell-surface receptors, modulating signal pathways and inhibiting proliferation. This study proposes a new approach for cancer dual-target and proliferation inhibition by clustering multivalent receptors.


Assuntos
Aptâmeros de Nucleotídeos , Neoplasias , Salix , Anticorpos , Aptâmeros de Nucleotídeos/metabolismo , Aptâmeros de Nucleotídeos/farmacologia , Proliferação de Células , DNA/genética , DNA/metabolismo , DNA de Cadeia Simples , Humanos , Oligonucleotídeos , Salix/metabolismo , beta Catenina/metabolismo
14.
J Nat Prod ; 85(1): 15-24, 2022 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-35000392

RESUMO

Bakuchiol, a prenylated phenolic monoterpene derived from the fruit of Psoralen corylifolia L. (Buguzhi), is widely used to treat tumors, viruses, inflammation, and bacterial infections. In this study, we designed and synthesized 30 bakuchiol derivatives to identify new anti-inflammatory drugs. The anti-inflammatory activities of the derivatives were screened using lipopolysaccharide-induced RAW264.7 cells. To evaluate the anti-inflammatory activity of the compounds, we measured nitric oxide (NO), interleukin-6, and tumor necrosis factor-α production. Based on the screening results, compound 7a displayed more pronounced activity than bakuchiol and celecoxib. Furthermore, the mechanistic studies indicated that 7a inhibited pro-inflammatory cytokine release, which was correlated with activation of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway and blockade of the nuclear factor-κB/mitogen-activated protein kinase signaling pathway. The in vivo anti-inflammatory activity in zebrafish indicated that 7a inhibited NO and reactive oxygen species production in a dose-dependent manner. These results indicate that 7a is a potential candidate for development as an anti-inflammatory agent.


Assuntos
Anti-Inflamatórios/farmacologia , Fenóis/síntese química , Fenóis/farmacologia , Animais , Citocinas/metabolismo , Heme Oxigenase-1/metabolismo , Técnicas In Vitro , Mediadores da Inflamação/metabolismo , Camundongos , Estrutura Molecular , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Fenóis/química , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
15.
Environ Res ; 212(Pt B): 113300, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35427591

RESUMO

The resource utilization of spent alkaline Zn-Mn batteries (S-AZMB) has always been a hot issue in the field of energy regeneration and environmental protection. The cumbersome and complicated purification process is the reason for their limited recycling. Not long ago, we proved that unpurified S-AZMB can be used directly: construct a Z-scheme photocatalytic system by combining with commercial TiO2 through high-temperature calcination. In order for this finding to be truly adopted by the application market, the high energy consumption calcination process needs to be improved urgently. In this work, we explore the temperature dependence of performance for the composite photocatalyst (TiO2@S-AZMB). A series of experimental results confirm that lowering the calcination temperature not only conducive to improving the separation efficiency of photogenerated electron-hole pairs, but also can significantly improve the environmental adaptability of the catalyst. Specifically, the catalyst synthesized by calcination temperature at 200 °C exhibits higher toluene removal efficiency than that at 500 °C under different initial concentration of pollutants, relative humidity, light intensity and oxygen content. This study not only further improves the photocatalytic performance of the composite catalyst, but also accords with the idea of energy saving and emission reduction, which provides more space for the possibility of recycling S-AZMB.

16.
Planta Med ; 88(11): 933-949, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34521131

RESUMO

The dried stem bark of Berberis kansuensis is a commonly used Tibetan herbal medicine for the treatment of diabetes. Its main chemical components are alkaloids, such as berberine, magnoflorine and jatrorrhizine. However, the role of gut microbiota in the in vivo metabolism of these chemical components has not been fully elucidated. In this study, an ultra-high performance liquid chromatography method coupled with Orbitrap mass spectrometry (UHPLC-Orbitrap-MS) technology was applied to detect and identify prototype components and metabolites in rat intestinal contents and serum samples after oral administration of a B. kansuensis extract. A total of 16 prototype components and 40 metabolites were identified. The primary metabolic pathways of the chemical components from B. kansuensis extract were demethylation, desaturation, deglycosylation, reduction, hydroxylation, and other conjugation reactions including sulfation, glucuronidation, glycosidation, and methylation. By comparing the differences of metabolites between diabetic and pseudo-germ-free diabetic rats, we found that the metabolic transformation of some chemical components in B. kansuensis extract such as bufotenin, ferulic acid 4-O-ß-D-glucopyranoside, magnoflorine, and 8-oxyberberine, was affected by the gut microbiota. The results revealed that the gut microbiota can affect the metabolic transformation of chemical constituents in B. kansuensis extract. These findings can enhance our understanding of the active ingredients of B. kansuensis extract and the key role of the gut microbiota on them.


Assuntos
Berberis , Diabetes Mellitus Experimental , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Animais , Berberis/química , Cromatografia Líquida de Alta Pressão/métodos , Diabetes Mellitus Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Ratos
17.
Neoplasma ; 69(2): 303-310, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35068161

RESUMO

The release of circulating tumor cells (CTCs) into vasculature is an early event in the metastatic process and the detection of CTCs has been widely used clinically. In addition, cancer stem cells (CSCs) are the source of distant metastasis. However, the relationship between CTCs and CSCs in nasopharyngeal carcinoma (NPC) patients was largely unknown. A total of 93 NPC patients were enrolled in this study. The CTCs in the peripheral blood were detected. The expression of ALDH1A1 in the tumor tissues of the corresponding patients was detected using immunohistochemistry (IHC). The prognostic value of CTCs level and the correlation with the expression of ALDH1A1 was evaluated. Data showed that the detection of CTCs was positively correlated with metastasis (p<0.001). The positive detection of CTCs was also associated with poor overall survival (p=0.025). CTCs ≥2 demonstrated good specificity and sensitivity in predicting distant metastasis, while CTCs ≥8 demonstrated better specificity and sensitivity in predicting prognosis than CTCs ≥2. Furthermore, we found that there was a positive relationship between the detection of CTCs and the expression of ALDH1A1 (p=0.001). The prognosis analysis also demonstrated that high ALDH1A1 expression was correlated with poor overall survival (p=0.006). Our study demonstrated a positive correlation between the CTCs and the expression of CSCs, both were positively correlated with metastasis and poor prognosis. These results indicated that the CTCs might indirectly reflect the expression of CSCs.


Assuntos
Neoplasias Nasofaríngeas , Células Neoplásicas Circulantes , Biomarcadores Tumorais/metabolismo , Humanos , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/patologia , Células Neoplásicas Circulantes/metabolismo , Células-Tronco Neoplásicas/patologia , Prognóstico
18.
Molecules ; 27(15)2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35897871

RESUMO

Scrophulariae Radix (SR) is one of the oldest and most frequently used Chinese herbs for oriental medicine in China. Before clinical use, the SR should be processed using different methods after harvest, such as steaming, "sweating", and traditional fire-drying. In order to investigate the difference in chemical constituents using different processing methods, the two-dimensional (2D) 1H-13C heteronuclear single quantum correlation (1H-13C HSQC)-based metabolomics approach was applied to extensively characterize the difference in the chemical components in the extracts of SR processed using different processing methods. In total, 20 compounds were identified as potential chemical markers that changed significantly with different steaming durations. Seven compounds can be used as potential chemical markers to differentiate processing by sweating, hot-air drying, and steaming for 4 h. These findings could elucidate the change of chemical constituents of the processed SR and provide a guide for the processing. In addition, our protocol may represent a general approach to characterizing chemical compounds of traditional Chinese medicine (TCM) and therefore might be considered as a promising approach to exploring the scientific basis of traditional processing of TCM.


Assuntos
Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Medicina Tradicional Chinesa , Metabolômica/métodos , Raízes de Plantas/química
19.
Oncologist ; 26(12): e2130-e2135, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34423518

RESUMO

LESSONS LEARNED: The combination of anlotinib and S-1 exhibited good antitumor activity in third- or later-line treatment for stage IV non-small cell lung cancer (NSCLC). Combination therapy of anlotinib with S-1 has manageable toxicities in patients with NSCLC. BACKGROUND: This study aimed to evaluate the efficacy and safety of anlotinib combined with S-1 as a third- or later-line treatment for patients with stage IV non-small cell lung cancer (NSCLC). Anlotinib was approved in 2018 by the Chinese Food and Drug Administration (FDA) as a third-line treatment for patients with refractory advanced NSCLC and is under study in the U.S. and Europe. METHODS: Simon's phase II clinical trial design with an α error of 5% and a power ß of 80% was used, anticipating a 10% objective response rate (ORR) of anlotinib and a 30% ORR of anlotinib combined with S-1; the required sample size was 29. A total of 29 patients were enrolled in the clinical trial. Patients were treated with anlotinib plus S-1 over a 21-day treatment course until disease progression or unacceptable toxic effects. If the efficacy was assessed as stable disease, partial response, or complete response after six cycles, anlotinib was maintained until disease progression or death. The primary endpoint was the objective response rate. Somatic mutations were not required for study enrollment. RESULTS: The median follow-up time was 11.1 months. Objective responses were observed in 11 of 29 (37.9%) patients making up the intention-to-treat population, which reached the target primary endpoint of 30% ORR. The median overall and progression-free survival were 16.7 and 5.8 months, respectively. The most common grade 3 adverse events (AEs) were gastrointestinal, including nausea, vomiting and diarrhea, fatigue, and hypertension. No grade 4 treatment-related AEs or treatment-related deaths occurred. CONCLUSION: The combination of anlotinib with S-1 in the third- or later-line treatment of stage IV NSCLC shows promising antitumor activity and manageable toxicity in patients with NSCLC; phase III trials will be planned in the future.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Terapia Combinada , Humanos , Indóis , Neoplasias Pulmonares/tratamento farmacológico , Intervalo Livre de Progressão , Quinolinas , Estados Unidos
20.
Plant Physiol ; 183(2): 780-792, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32220965

RESUMO

The rhizosheath is a layer of soil around the root that provides a favorable environment for soil microbe enrichment and root growth. Rice (Oryza sativa) roots form rhizosheaths under moderate soil drying (MSD) conditions, but how the rhizosheath forms associations with microbes is unclear. To investigate rice rhizosheath formation under MSD, we employed a multiphasic approach, integrating data from high-throughput sequencing and root-bacteria interactions. Rice roots formed a pronounced rhizosheath under MSD, but not under continuous flooding regimens. Plant growth-promoting rhizobacteria of the Enterobacteriaceae were enriched in rhizosheaths of two different rice varieties, 'Gaoshan 1' (drought tolerant) and 'Nipponbare' (drought sensitive). RNA-sequencing analysis revealed that the ethylene pathway was induced in the rhizosheath-root system under MSD. Enterobacter aerogenes, a bacterium isolated from the rhizosheath, degrades the ethylene precursor 1-aminocyclopropane-1-carboxylate, thereby increasing rhizosheath formation. Furthermore, a 1-aminocyclopropane-1-carboxylate deaminase-deficient mutant of E. aerogenes failed to enhance rice rhizosheath formation. Our results suggest that root-bacteria associations substantially contribute to rhizosheath formation in rice under MSD conditions by mechanisms that involve the ethylene response. These data inform strategies to reduce water consumption in rice production, one of the most water-intensive human activities.


Assuntos
Bactérias/metabolismo , Etilenos/metabolismo , Raízes de Plantas/metabolismo , Secas , Oryza/metabolismo , Oryza/microbiologia , Raízes de Plantas/genética , Raízes de Plantas/microbiologia , Solo
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