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1.
J Diabetes ; 2023 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-36682739

RESUMO

BACKGROUND: Bile acids (BAs) are closely related to nutrient supply and modified by gut microbiota. Gut microbiota perturbations shape BA composition, which further affects host metabolism. METHODS: We investigated BA profiles in plasma, feces, and liver of mice fed ad libitum, fasted for 24 h, fasted for 24 h and then refed for 24 h using ultraperformance liquid chromatography coupled to tandem mass spectrometry. Gut microbiota was measured by 16S rRNA gene sequencing. Expressions of BA biosynthesis-related genes in the liver and BA reabsorption-related genes in the ileum were analyzed. FINDINGS: Compared with the controls, unconjugated primary BAs (PBAs) and unconjugated secondary BAs (SBAs) in plasma were decreased whereas conjugated SBAs in plasma, unconjugated PBAs, unconjugated SBAs and conjugated SBAs in feces, and unconjugated SBAs in liver were increased in the fasting mice. The expression of BA biosynthesis-related genes in the liver and BA reabsorption-related genes in the ileum were decreased in the fasting mice compared with the controls. Compared with the controls, Akkermansia, Parabacteroides, Muribaculum, Eubacterium_coprostanoligenes and Muribaculaceae were increased in the fasting mice whereas Lactobacillus and Bifidobacterium were decreased. All these changes in BAs and gut microbiota were recovered under refeeding. Akkermansia was negatively correlated with plasma levels of unconjugated PBAs, unconjugated SBAs and glucose, whereas it was positively correlated with plasma conjugated SBAs, fecal unconjugated PBAs, and fecal unconjugated SBAs. CONCLUSIONS: We characterized the BA profiles, gut microbiota, and gene expression responsible for BA biosynthesis and intestinal reabsorption to explore their rapid changes in response to food availability. Our study highlighted the rapid effect of nutrient supply on BAs and gut microbiota.

2.
J Agric Food Chem ; 71(3): 1391-1404, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36625777

RESUMO

Fusarium head blight is one of the most serious diseases caused by Fusarium graminearum in wheat. Here, we developed a new way to prevent and control Fusarium head blight by introducing the resistance genes Fhb1 and Fhb7 into the endophytic fungus Phomopsis liquidambaris, named PL-Fhb1 and PL-Fhb7, respectively, which could colonize wheat. The wheat seedlings were preinoculated with PL-Fhb1 and PL-Fhb7 to enhance the resistance against deoxynivalenol (DON) and PL-Fhb1 and PL-Fhb7 inhibited the growth of F. graminearum by 73% and 49%, respectively. The incidence rate of diseased spikes decreased to 35.2% and 45.4%, and the corresponding DON levels for wheat grains decreased from 13.2 to 1.79 µg/g and from 13.2 µg/g to 0.39 µg/g when the leaves were preinoculated with PL-Fhb1 and PL-Fhb7 after overwintering, respectively. The incidence rates of diseased spikes decreased to 25.7% and 34.7%, and the DON levels for wheat grains decreased from 17.48 µg/g to 1.23 µg/g and from 17.48 µg/g to 0 µg/g when the wheat flowers were inoculated with PL-Fhb1 and PL-Fhb7, and the wheat flowers were subsequently infected with F. graminearum, respectively. It was confirmed that DON was transformed into DON-glutathione (GSH) by PL-Fhb7 using high-performance liquid chromatography-mass spectrometry (HPLC-MS). However, PL-Fhb1 may have increased plant immunity and enhanced the resistance to F. graminearum. This study indicates that engineered endophytes can improve the resistance to Fusarium head blight and presents a new method for the biological control of Fusarium head blight.


Assuntos
Ascomicetos , Fusarium , Triticum/microbiologia , Doenças das Plantas/microbiologia
3.
Carbohydr Polym ; 302: 120419, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36604081

RESUMO

In this work, an innovative PLA/CNF nanocomposite foam with a bimodal cell structure is prepared by a simple one-step depressurization foaming process using only supercritical carbon dioxide (ScCO2) as the foaming agent. Only at a specific foaming temperature, PLA/CNF nanocomposites foam with a bimodal cell structure could be obtained. According to the different crystallization kinetics and nucleation efficiency of samples, it was inferred that the crystallization rate and phase interface would affect the cell structure. The prepared PLA/CNF nanocomposite foam with a bimodal cell structure had an expansion ratio as high as 20 times and thermal conductivity of 0.041 w m-1 k-1, which exhibited low density and excellent thermal-insulation property. Meanwhile, the PLA/CNF nanocomposite foam exhibited excellent compression performance due to the presence of CNFs, which showed promising application in packaging and construction materials.


Assuntos
Celulose , Nanocompostos , Celulose/química , Poliésteres/química , Pressão , Ácido Láctico , Nanocompostos/química
4.
Neurosurg Rev ; 46(1): 34, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36622450

RESUMO

Craniopharyngioma (CP) is a mostly benign tumor that is nonetheless one of most formidable skull base lesions. CP tends to recur, and scarce clinical results are available regarding its long-term outcomes. From February 1996 to April 2002, craniopharyngiomas primarily resected by open surgery in a single-center and single-surgeon practice were screened. Medical information regarding patients' baseline, tumor parameters, endocrinological results, complications, and quality of life in those patients with a follow-up longer than 20 years were reviewed. Nineteen out of 187 patients who met the inclusion criteria were eligible, and 78.9% of the patients were admitted due to visual deficits. The transcranial approach was mostly applied for the first attempt of opening resection, with 94.7% gross total resection. The size of the tumor ranged from 25 to 45 mm with a mean maximal diameter of 34.7 mm. Although 7 out of 19 patients received an extra procedure, 6 patients (31.5%) regained fertility, with 3 women bearing a total of 5 children and 3 men fathering a total of 4 children, during the 21.4-year follow-up (range: 20.0-23.3 years). The mean Karnofsky Performance Status (KPS) score was 97.9 (range: 80-100) at the last follow-up, and the physical and mental 36-Item Short Form Health Survey (SF-36) scores were 88.0 and 80.5, respectively. The tumor sizes of the patients who regained fertility were not significantly different from those of the patients who remained infertile (t = 1.29, P > 0.2). The time interval from prior surgery to tumor resection for recurrent cases ranged from 0.3 to 17.4 years (mean, 7.3 years). There was no significant difference in the time until tumor recurrence in the patients who underwent a second surgery, a third surgery, or a fourth surgery. The satisfactory results in the present study revealed favorable long-term outcomes following the transcranial management of CPs, with acceptable endocrinological function and tumor-free survival. A decisive policy of open surgery with the objective of radical tumor removal remains a valid method for the primary treatment of CPs, aiming to avoid retreatment after tumor recurrence involving vital hypothalamic structures or hydrocephalus.


Assuntos
Craniofaringioma , Neoplasias Hipofisárias , Masculino , Criança , Humanos , Feminino , Seguimentos , Craniofaringioma/cirurgia , Craniofaringioma/patologia , Resultado do Tratamento , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/patologia , Qualidade de Vida , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/patologia , Estudos Retrospectivos
5.
Food Res Int ; 163: 112192, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36596130

RESUMO

To achieve the goals of rapid content determination of capsaicin and adulteration detection of pepper powder. The method based on the hand-held near-infrared spectrometer combined with ensemble preprocessing was proposed. DoE-based ensemble preprocessing technique was utilized to develop the partial least squares regression models of red pepper [Capsicum annuum L. var. conoides (Mill.) Irish] powders. The performance of final models was evaluated using coefficient of determination (R2), root mean square error of prediction (RMSEP) and residual predictive deviation (RPD). Model development using selective ensemble preprocessing gave the best prediction of capsaicin in Yanjiao pepper powder (R2 = 0.9800, RPD = 7.090, RMSEP = 0.00689) and Tianying pepper powder (R2 = 0.8935, RPD = 3.017, RMSEP = 0.06154). Moreover, the potential of grey wolf optimizer-support vector machine (GWO-SVM) to detect adulterated pepper powder was investigated. The samples were composed of two authentic products and three different adulterants with different adulteration levels. The results showed that the classification accuracy of GWO-SVM model for Yanjiao peppers was over 90 %, which realized the adulteration detection of Yanjiao pepper. And GWO-SVM showed better performance in detecting adulterated Tianying pepper compared to hierarchical cluster analysis, orthogonal partial least squares discriminant analysis and random forest. In summary, the quality control strategy established in this paper can provide a solution for the adulteration detection and quality evaluation of pepper powder in a rapid and on-site way.


Assuntos
Capsaicina , Capsicum , Pós/análise , Alimentos , Análise dos Mínimos Quadrados
6.
Environ Toxicol ; 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36602409

RESUMO

Environmental pollutants are recognized as one of the major concerns for public health. The free-living nematode Caenorhabditis elegans are widely used to evaluate the toxicity of environmental contaminants in biomonitoring researches. In the present study, a new transgenic strain, rps-30-/- ;RFP-RPS-30UbL was generated, with constitutively active rps-30 promoter used to control the expression of RFP-RPS-30UbL fusion protein. We found RFP-RPS-30UbL would accumulate to form 'rod-like' structures, when worms were exposed to environmental contaminants, including Cd, Hg, Pb, As, Paraquat and Dichlorvos. The number of the 'rod-like' structures was induced by environmental contaminants in a concentration- and time-dependent manner. The 'rod-like' structure formation could be detectable in response to the concentration of each contaminant as low as 24-h LC50 × 10-7 , and the detectable time could be within 2 h. Detecting the transcription and expression levels of RFP-RPS-30UbL in worms exposed to different kinds of environmental contaminants showed that the expression level of RFP-RPS-30UbL was not regulated by environmental contaminants, and the number differences of 'rod-like' structures were just due to the morphological change of RFP-RPS-30UbL from dispersion to accumulation induced by environmental contaminants. In addition, this transgenic strain was developed in rps-30-/- homozygous worm, which was a longevity strain. Detection of lifespan and brood size showed that rps-30-/- ;RFP-RPS-30UbL transgenic worm was more suitable to be cultured and used further than N2;GFP-RPS-30UbL , for expressing RPS-30UbL in wild type N2 worms shortened the lifespan and deceased the brood size. Therefore, rps-30-/- ;RFP-RPS-30UbL transgenic worm might play a potential role in versatile environmental biomonitoring, with the advantage of not only the convenient and quick fluorescence-based reporter assay, but also the quantificational evaluation of the toxicities of environmental contaminants using 'rod-like' structures with high sensitivity, off-limited the expression level of the reporter protein.

7.
Nat Commun ; 14(1): 290, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36653415

RESUMO

Weed species are detrimental to crop yield. An understanding of how weeds originate and adapt to field environments is needed for successful crop management and reduction of herbicide use. Although early flowering is one of the weed trait syndromes that enable ruderal weeds to overcome frequent disturbances, the underlying genetic basis is poorly understood. Here, we establish Cardamine occulta as a model to study weed ruderality. By genome assembly and QTL mapping, we identify impairment of the vernalization response regulator gene FLC and a subsequent dominant mutation in the blue-light receptor gene CRY2 as genetic drivers for the establishment of short life cycle in ruderal weeds. Population genomics study further suggests that the mutations in these two genes enable individuals to overcome human disturbances through early deposition of seeds into the soil seed bank and quickly dominate local populations, thereby facilitating their spread in East China. Notably, functionally equivalent dominant mutations in CRY2 are shared by another weed species, Rorippa palustris, suggesting a common evolutionary trajectory of early flowering in ruderal weeds in Brassicaceae.


Assuntos
Brassicaceae , Herbicidas , Humanos , Animais , Brassicaceae/genética , Plantas Daninhas/genética , Solo , Estágios do Ciclo de Vida
8.
Int J Mol Sci ; 24(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36674552

RESUMO

Platelets are the second most abundant blood component after red blood cells and can participate in a variety of physiological and pathological functions. Beyond its traditional role in hemostasis and thrombosis, it also plays an indispensable role in inflammatory diseases. However, thrombocytopenia is a common hematologic problem in the clinic, and it presents a proportional relationship with the fatality of many diseases. Therefore, the prevention and treatment of thrombocytopenia is of great importance. The expression of Toll-like receptors (TLRs) is one of the most relevant characteristics of thrombopoiesis and the platelet inflammatory function. We know that the TLR family is found on the surface or inside almost all cells, where they perform many immune functions. Of those, TLR2 and TLR4 are the main stress-inducing members and play an integral role in inflammatory diseases and platelet production and function. Therefore, the aim of this review is to present and discuss the relationship between platelets, inflammation and the TLR family and extend recent research on the influence of the TLR2 and TLR4 pathways and the regulation of platelet production and function. Reviewing the interaction between TLRs and platelets in inflammation may be a research direction or program for the treatment of thrombocytopenia-related and inflammatory-related diseases.


Assuntos
Trombocitopenia , Trombopoese , Humanos , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Receptores Toll-Like , Trombocitopenia/metabolismo , Inflamação
9.
Phytomedicine ; 110: 154637, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36610353

RESUMO

BACKGROUND: Non-peptide thrombopoietin receptor (TPOR) agonists are promising therapies for the mitigation and treatment of thrombocytopenia. However, only few agents are available as safe and effective for stimulating platelet production for thrombocytopenic patients in the clinic. PURPOSE: This study aimed to develop a novel small molecule TPOR agonist and investigate its underlying regulation of function in megakaryocytes (MKs) differentiation and thrombopoiesis. METHODS: A potential active compound that promotes MKs differentiation and thrombopoiesis was obtained by machine learning (ML). Meanwhile, the effect was verified in zebrafish model, HEL and Meg-01 cells. Next, the key regulatory target was identified by Drug Affinity Responsive Target Stabilization Assay (DARTS), Cellular Thermal Shift Assay (CETSA), and molecular simulation experiments. After that, RNA-sequencing (RNA-seq) was used to further confirm the associated pathways and evaluate the gene expression induced during MK differentiation. In vivo, irradiation (IR) mice, C57BL/6N-TPORem1cyagen (Tpor-/-) mice were constructed by CRISPR/Cas9 technology to examine the therapeutic effect of TMEA on thrombocytopenia. RESULTS: A natural chemical-structure small molecule TMEA was predicted to be a potential active compound based on ML. Obvious phenotypes of MKs differentiation were observed by TMEA induction in zebrafish model and TMEA could increase co-expression of CD41/CD42b, DNA content, and promote polyploidization and maturation of MKs in HEL and Meg-01 cells. Mechanically, TMEA could bind with TPOR protein and further regulate the PI3K/AKT/mTOR/P70S6K and MEK/ERK signal pathways. In vivo, TMEA evidently promoted platelet regeneration in mice with radiation-induced thrombocytopenia but had no effect on Tpor-/- and C57BL/6 (WT) mice. CONCLUSION: TMEA could serve as a novel TPOR agonist to promote MKs differentiation and thrombopoiesis via mTOR and ERK signaling and could potentially be created as a promising new drug to treat thrombocytopenia.


Assuntos
Trombocitopenia , Trombopoese , Camundongos , Animais , Megacariócitos , Peixe-Zebra/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos Endogâmicos C57BL , Transdução de Sinais , Trombocitopenia/tratamento farmacológico , Trombocitopenia/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Diferenciação Celular
10.
Org Biomol Chem ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36655817

RESUMO

Trisindolylmethanes (TIMs) exist in many bioactive natural products and are frequently applied in medicinal chemistry and materials science. Herein, a simple and efficient protocol promoted by B(C6F5)3·H2O for the synthesis of their fluoroalkylated analogues, fluoroalkylated 3,3',3''-TIMs, is reported for the first time. Easily accessible fluorocarboxylic acids are utilized as the fluoroalkyl sources, exhibiting an obvious fluorine effect. This convenient and green process features mild and metal-free conditions, easy scale-up, and an environmentally friendly byproduct.

11.
Plant Cell Environ ; 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609800

RESUMO

Plants live in fixed locations and have evolved adaptation mechanisms that integrate multiple responses to various environmental signals. Among the different components of these response pathways, receptors/sensors represent nodes that recognise environmental signals. Additionally, RNA metabolism plays an essential role in the regulation of gene expression and protein synthesis. With the development of RNA biotechnology, recent advances have been made in determining the roles of RNA metabolism in response to different environmental signals-especially the roles of alternative splicing and translation. In this review, we discuss recent progress in research on how the environmental adaptation mechanisms in plants are affected at the posttranscriptional level. These findings improve our understanding of the mechanism through which plants adapt to environmental changes by regulating the posttranscriptional level and are conducive for breeding stress-tolerant plants to cope with dynamic and rapidly changing environments.

12.
Artigo em Inglês | MEDLINE | ID: mdl-36622590

RESUMO

In this study, the content of chromium (Cr) in three main edible tissues (dorsal muscle, ventral muscle, and head) of 14 different fish species was determined. As expected, Cr level in fish head is generally higher than that in fish muscle. To elucidate the deposition of Cr in the fish head, bighead carp (Hypophthalmichthys nobilis) was chosen as the model fish and a 14-day-exposure experiment of 1 mg/L Cr was subsequently conducted. The fish head was divided into 7 parts, and the results showed that, in different parts of the head, Cr was significantly accumulated in the brain, the muscle after gills, and the muscle of others, and the bone after the fish was exposed to 1-mg/L Cr for 14 days. Additionally, the health risk assessment showed that there was no potential non-carcinogenic risk of consuming the dorsal muscle, the ventral muscle, and the head of the 14 fish species to children, teenagers, and adults as the THQ values were less than 1. However, there was potential carcinogenic risk of consuming the fish head for adults in the 14 fish species. It is worth noting that, in the exposure experiment, the consuming of the lips and the bone of fish head also posed potential carcinogenic risk to adults while there was no potential risk of consuming the total fish head. Overall, compared to the fish muscle, the fish head usually had a high accumulation of Cr, and the Cr was mainly deposited in the position of the bone, which may pose potential carcinogenic risk to adults. Thus, the potential health risk of consuming the fish head is mainly associated with the content of the bone in the head, and, in the health risk assessment, the influence of the bone in the head should be considered, which may overstate the risks as fish head bone is usually not to be eaten.

13.
Artigo em Inglês | MEDLINE | ID: mdl-36637749

RESUMO

PURPOSE: Accurate quantification of pulmonary nodules helps physicians to accurately diagnose and treat lung cancer. We try to improve the segmentation efficiency of irregular nodules while maintaining the segmentation accuracy of simple types of nodules. METHODS: In this paper, we obtain the unique edge part of pulmonary nodules and process it as a single branch stream, i.e., border stream, to explicitly model the nodule edge information. We propose a multi-scale dense selective network based on border modeling (BorDenNet). Its overall framework consists of a dual-branch encoder-decoder, which achieves parallel processing of classical image stream and border stream. We design a dense attention module to facilitate a strongly coupled status of feature images to focus on key regions of pulmonary nodules. Then, during the process of model decoding, the multi-scale selective attention module is proposed to establish long-range correlation relationships between different scale features, which further achieves finer feature discrimination and spatial recovery. We introduce border context enhancement module to mutually fuse and enhance the edge-related voxel features contained in the image stream and border stream and finally achieve the accurate segmentation of pulmonary nodules. RESULTS: We evaluate the BorDenNet rigorously on the lung public dataset LIDC-IDRI. For the segmentation of the target nodules, the average Dice score is 92.78[Formula: see text], the average sensitivity is 91.37[Formula: see text], and the average Hausdorff distance is 3.06 mm. We further test on a private dataset from Shanxi Provincial People's Hospital, which verifies the excellent generalization of BorDenNet. Our BorDenNet relatively improves the segmentation efficiency for multi-type nodules such as adherent pulmonary nodules and ground-glass pulmonary nodules. CONCLUSION: Accurate segmentation of irregular pulmonary nodules can obtain important clinical parameters, which can be used as a guide for clinicians and improve clinical efficiency.

14.
J Org Chem ; 88(1): 647-652, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36480338

RESUMO

A visible-light-induced tandem radical brominative addition/spiro-cyclization/1,2-ester migration of activated alkynes with CBr4 is developed. This protocol features good functional group tolerance, operational simplicity, and mild reaction conditions without the use of catalysts and external additives, providing easy access to valuable 3-bromocoumarins in generally high yields.

15.
ACS Macro Lett ; 12(1): 71-76, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36576724

RESUMO

Surface anchored polymer brushes prepared by surface-initiated controlled radical polymerization (SI-CRP) have raised considerable interest in biomaterials and bioengineering. However, undesired residues of noxious transition metal catalysts critically restrain their widespread biomedical applications. Herein, we present a robust and biocompatible surface-initiated controlled radical polymerization catalyzed by a Sn(0) sheet (SI-Sn0CRP) under ambient conditions. Through this approach, microliter volumes of vinyl monomers with diverse functions (heterocyclic, ionic, hydrophilic, and hydrophobic) could be efficiently converted to homogeneous polymer brushes. The excellent controllability of SI-Sn0CRP strategy is further demonstrated by the exquisite fabrication of predetermined block and patterned polymer brushes through chain extension and photolithography, respectively. Additionally, in virtue of intrinsic biocompatibility of Sn, the resultant polymer brushes present transcendent affinity toward blood and cell, in marked contrast to those of copper-based approaches. This strategy could provide an avenue for the controllable fabrication of biocompatible polymer brushes toward biological applications.


Assuntos
Materiais Biocompatíveis , Polímeros , Polimerização , Polímeros/química , Cobre/química , Engenharia
16.
Mol Plant ; 16(1): 245-259, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36476805

RESUMO

Salicylic acid (SA) plays a pivotal role in plant response to biotic and abiotic stress. Several core SA signaling regulators and key proteins in SA biosynthesis have been well characterized. However, much remains unknown about the origin, evolution, and early diversification of core elements in plant SA signaling and biosynthesis. In this study, we identified 10 core protein families in SA signaling and biosynthesis across green plant lineages. We found that the key SA signaling receptors, the nonexpresser of pathogenesis-related (NPR) proteins, originated in the most recent common ancestor (MRCA) of land plants and formed divergent groups in the ancestor of seed plants. However, key transcription factors for SA signaling, TGACG motif-binding proteins (TGAs), originated in the MRCA of streptophytes, arguing for the stepwise evolution of core SA signaling in plants. Different from the assembly of the core SA signaling pathway in the ancestor of seed plants, SA exists extensively in green plants, including chlorophytes and streptophyte algae. However, the full isochorismate synthase (ICS)-based SA synthesis pathway was first assembled in the MRCA of land plants. We further revealed that the ancient abnormal inflorescence meristem 1 (AIM1)-based ß-oxidation pathway is crucial for the biosynthesis of SA in chlorophyte algae, and this biosynthesis pathway may have facilitated the adaptation of early-diverging green algae to the high-light-intensity environment on land. Taken together, our findings provide significant insights into the early evolution and diversification of plant SA signaling and biosynthesis pathways, highlighting a crucial role of SA in stress tolerance during plant terrestrialization.


Assuntos
Proteínas de Arabidopsis , Embriófitas , Ácido Salicílico/metabolismo , Plantas/genética , Plantas/metabolismo , Transdução de Sinais , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Embriófitas/metabolismo
17.
Plant Sci ; 327: 111565, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36526028

RESUMO

Jasmonic acid (JA), as an important plant hormone, can induce the synthesis of phenolic acids in Salvia miltiorrhiza Bunge, a model medicinal plant, but the specific mechanism remains to be further elucidated. JA-responsive SmMYB111 positively regulates the biosynthesis of salvianolic acid B (SalB), but the molecular mechanism is unclear. Here, we found that SmMYB111 directly binds to the promoters of SmTAT1 and SmCYP98A14 and activates their transcription. Yeast two hybrid and bimolecular fluorescent complementation assay indicated that SmMYB111 interacts with SmJAZ4. Furthermore, we systematically characterized the function of SmJAZ4, which was highly expressed in flowers and roots and located in the nucleus and cell membrane. The contents of phenolic acids in the SmJAZ4-overexpressed transgenic plantlets and SmJAZ4-overexpressed transgenic hairy roots decreased significantly. SmJAZ4 interacts with SmMYC2 or SmMYB111 to repress their transcriptional activation activity on target enzyme genes of the biosynthesis pathway of phenolic acids. Overall, the molecular mechanism of SmJAZ4-SmMYC2/SmMYB111 module participating in JA signaling regulation of SalB biosynthesis was elucidated, which give a clue for the molecular regulation of phenolic acids biosynthesis in S. miltiorrhiza.


Assuntos
Salvia miltiorrhiza , Salvia miltiorrhiza/genética , Salvia miltiorrhiza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Hidroxibenzoatos/metabolismo , Raízes de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
18.
Biomater Res ; 26(1): 74, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36471380

RESUMO

BACKGROUND: Gemcitabine (GEM) is one of the first-line chemotherapies for bladder cancer (BC), but the GEMs cannot recognize cancer cells and have a low long-term response rate and high recurrence rate with side effects during the treatment of BC. Targeted transport of GEMs to mediate cytotoxicity to tumor and avoid the systemic side effects remains a challenge in the treatment of BC. METHODS: Based on a firstly confirmed biomarker in BC-protein tyrosine kinase 7 (PTK7), which is overexpressed on the cell membrane surface in BC cells, a novel targeting system protein tyrosine kinase 7 aptamer-Gemcitabine conjugate (PTK7-GEMs) was designed and synthesized using a specific PTK7 aptamer and GEM through auto-synthesis method to deliver GEM against BC. In addition, the antitumor effects and safety evaluation of PTK7-GEMs was assessed with a series of in vitro and in vivo assays. RESULTS: PTK7-GEMs can specifically bind and enter to BC cells dependent on the expression levels of PTK7 and via the macropinocytosis pathway, which induced cytotoxicity after GEM cleavage from PTK7-GEMs respond to the intracellular phosphatase. Moreover, PTK7-GEMs showed stronger anti-tumor efficacy and excellent biosafety in three types of tumor xenograft mice models. CONCLUSION: These results demonstrated that PTK7-GEMs is a successful targeted aptamer-drug conjugates strategy (APDCs) to treat BC, which will provide new directions for the precision treatment of BC in the field of biomarker-oriented tumor targeted therapy.

19.
Zhongguo Zhong Yao Za Zhi ; 47(19): 5256-5263, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36472032

RESUMO

Because of the complex components, simple content determination can hardly reflect the overall quality of Guizhi Fuling Capsules. Therefore, it is necessary to carry out a multi-component dissolution test. The variability of quality among different batches of products from different manufacturers is a common problem of Chinese medicine solid preparations. To comprehensively control the quality of Guizhi Fuling Capsules, we studied the dissolution behaviors of 7 index components in the capsules under different conditions, and investigated the consistency of dissolution behaviors among different batches of products from the same manufacturer. The basket method of general rule 0931 in Chinese Pharmacopoeia was adopted, and the rotating speeds were set at 50, 75, and 100 r·min~(-1), respectively. The hydrochloric acid solution(pH 1.2), acetate buffer solution(pH 4.0), pure water, and phosphate buffer solution(pH 6.8) were used as the dissolution media. Automatic sampling was carried out at the time points of 5, 10, 20, 30, 45, and 60 min, respectively. The cumulative dissolution of 7 index components was measured through ultra-performance liquid chromatography(UPLC). The difference factor f_1 and similarity factor f_2 were calculated to comprehensively evaluate the similarity of the dissolution curves among 8 batches of Guizhi Fuling Capsules, and a variety of dissolution and release equations were fitted. The results showed that multiple components had faster dissolution rates at higher rotating speed and in hydrochloric acid medium. The 8 batches of Guizhi Fuling capsules showed the average f_1 value lower than 15 and the average f_2 value higher than 50, which indicated that different batches of products had similar dissolution behaviors. Most components had synchronous dissolution behaviors and similar release cha-racteristics. This study provides a reference for the quality consistency evaluation among batches, processing optimization, and dosage form improvement of Guizhi Fuling Capsules.


Assuntos
Medicamentos de Ervas Chinesas , Wolfiporia , Cápsulas , Solubilidade , Ácido Clorídrico , Medicamentos de Ervas Chinesas/química , Cromatografia Líquida de Alta Pressão
20.
Adv Healthc Mater ; : e2202022, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36461102

RESUMO

Tracheal defects lead to devastating problems, and practical clinical substitutes that have complex functional structures and can avoid adverse influences from exogenous bioscaffolds are lacking. Herein, a modular strategy for scaffold-free tracheal engineering was developed. A cartilage sheet (Cart-S) prepared by high-density culture was laminated and reshaped to construct a cartilage tube as the main load-bearing structure in which the chondrocytes exhibited a stable phenotype and secreted considerable cartilage-specific matrix, presenting a native-like grid arrangement. To further build a tracheal epithelial barrier, a temperature-sensitive technique was used to construct the monolayer epithelium sheet (Epi-S), in which the airway epithelial cells presented integrated tight junctions, good transepithelial electrical resistance, and favorable ciliary differentiation capability. Epi-S could be integrally transferred to inner wall of cartilage tube, forming a scaffold-free complex tracheal substitute (SC-trachea). Interestingly, when Epi-S was attached to the cartilage surface, epithelium-specific gene expression was significantly enhanced. SC-trachea established abundant blood supply via heterotopic vascularization and then was pedicle transplanted for tracheal reconstruction, achieving 83.3% survival outcomes in rabbit models. Notably, the scaffold-free engineered trachea simultaneously satisfied sufficient mechanical properties and barrier function due to its matrix-rich cartilage structure and well-differentiated ciliated epithelium, demonstrating great clinical potential for long-segmental tracheal reconstruction. This article is protected by copyright. All rights reserved.

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