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1.
Phytomedicine ; 129: 155570, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38579645

RESUMO

BACKGROUND: Energy deficiency and oxidative stress are interconnected during ischemia/reperfusion (I/R) and serve as potential targets for the treatment of cerebral ischemic stroke. Baicalin is a neuroprotective antioxidant, but the underlying mechanisms are not fully revealed. PURPOSE: This study explored whether and how baicalin rescued neurons against ischemia/reperfusion (I/R) attack by focusing on the regulation of neuronal pyruvate dehydrogenase kinase 2 (PDK2)-pyruvate dehydrogenase (PDH) axis implicated with succinate dehydrogenase (SDH)-mediated oxidative stress. STUDY DESIGN: The effect of the tested drug was explored in vitro and in vivo with the model of oxygen-glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion/reperfusion (MCAO/R), respectively. METHODS: Neuronal damage was evaluated according to cell viability, infarct area, and Nissl staining. Protein levels were measured by western blotting and immunofluorescence. Gene expression was investigated by RT-qPCR. Mitochondrial status was also estimated by fluorescence probe labeling. RESULTS: SDH activation-induced excessive production of reactive oxygen species (ROS) changed the protein expression of Lon protease 1 (LonP1) and hypoxia-inducible factor-1ɑ (HIF-1ɑ) in the early stage of I/R, leading to an upregulation of PDK2 and a decrease in PDH activity in neurons and cerebral cortices. Treatment with baicalin prevented these alterations and ameliorated neuronal ATP production and survival. CONCLUSION: Baicalin improves the function of the neuronal PDK2-PDH axis via suppression of SDH-mediated oxidative stress, revealing a new signaling pathway as a promising target under I/R conditions and the potential role of baicalin in the treatment of acute ischemic stroke.


Assuntos
Flavonoides , Neurônios , Fármacos Neuroprotetores , Estresse Oxidativo , Piruvato Desidrogenase Quinase de Transferência de Acetil , Traumatismo por Reperfusão , Flavonoides/farmacologia , Animais , Traumatismo por Reperfusão/tratamento farmacológico , Neurônios/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , Fármacos Neuroprotetores/farmacologia , Succinato Desidrogenase/metabolismo , Masculino , Espécies Reativas de Oxigênio/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Ratos Sprague-Dawley , Sobrevivência Celular/efeitos dos fármacos , Ratos , Antioxidantes/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo
2.
Artigo em Inglês | MEDLINE | ID: mdl-38639616

RESUMO

Objective: Network pharmacology is an emerging discipline that applies computational methods to understand drug actions and interactions with multiple molecular targets. Xiao'ai Jiedu is a valued traditional Chinese medicine preparation for which the mechanism of action is not yet established. This study aims to explore the mechanism of Xiao'ai Jiedu in treating lung cancer through network pharmacology. Methods: First, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) data platform was used to analyze the target treatment results of different medicinal materials in Mr. Zhou's cancer prescriptions. Then, functional enrichment analysis was performed to conduct a secondary analysis of the dissemination of cancer biological and pharmacological information in the human body. The Cancer Genome Atlas (TCGA) was used to obtain several cancer-aggressive target groups, and their transcription RNA was extracted for collection. The CIBERSORT evaluation method was used to conduct a Spearman correlation analysis on the data processing results. Then the matching degree between the experimental cells and the principle of drug treatment was analyzed to improve the statistical analysis. Results: Pharmacology research results showed that the network can accurately eliminate cancer detoxification targeted target correlation set, and through the data interpretation found that four different gene transcription have significant influence on lung cancer. The findings also confirmed that the degree of immune cell infiltration has a key role in lung cancer The study summarizes the active ingredients and their targets and mechanisms of action of the elimination of Xiao'ai Jiedu formula for the treatment of lung cancer. Conclusion: Network pharmacology can carry on the processing of the data, find the key to conform to the goal of research data, and the corresponding results are obtained, and the development of network pharmacology is not limited to, the study of lung cancer.

3.
Nat Commun ; 15(1): 2089, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38453961

RESUMO

Hyperthermic intraperitoneal chemotherapy's role in ovarian cancer remains controversial, hindered by limited understanding of hyperthermia-induced tumor cellular changes. This limits developing potent combinatory strategies anchored in hyperthermic intraperitoneal therapy (HIPET). Here, we perform a comprehensive multi-omics study on ovarian cancer cells under hyperthermia, unveiling a distinct molecular panorama, primarily characterized by rapid protein phosphorylation changes. Based on the phospho-signature, we pinpoint CDK1 kinase is hyperactivated during hyperthermia, influencing the global signaling landscape. We observe dynamic, reversible CDK1 activity, causing replication arrest and early mitotic entry post-hyperthermia. Subsequent drug screening shows WEE1 inhibition synergistically destroys cancer cells with hyperthermia. An in-house developed miniaturized device confirms hyperthermia and WEE1 inhibitor combination significantly reduces tumors in vivo. These findings offer additional insights into HIPET, detailing molecular mechanisms of hyperthermia and identifying precise drug combinations for targeted treatment. This research propels the concept of precise hyperthermic intraperitoneal therapy, highlighting its potential against ovarian cancer.


Assuntos
Hipertermia Induzida , Neoplasias Ovarianas , Feminino , Humanos , Proteína Quinase CDC2/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas Tirosina Quinases/metabolismo , Multiômica , Mitose , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/patologia
4.
J Ethnopharmacol ; 322: 117547, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38135231

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Maimendong and Qianjinweijing Tang (Jin formula) is a traditional Chinese medicine formula that has been proven effective in the treatment of lung cancer in long-term clinical practice. AIM OF THE STUDY: To evaluate the anti-tumor effects of Jin formula combined with cisplatin (JIN + DDP) in vivo and in vitro, as well as to explore the role of long non-coding RNA (lncRNA) in the anti-lung cancer mechanism of its action. MATERIALS AND METHODS: A Lewis lung cancer model was established in C57 BL/6 mice to study the in vivo anti-tumor effect of Jin formula combined with cisplatin. TUNEL staining and western blot were applied to study the effects of Jin formula combined cisplatin on apoptosis. The in vitro anti-cancer function of Jin formula combined with cisplatin was explored by cell viability assay, flow cytometry, wound healing assay and transwell assay. The changes in lncRNA expression profiles were determined by lncRNA microarray, and the differentially expressed lncRNA-p21 was verified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis. The expression differences of lncRNA-p21 in tumor and normal tissues were analyzed by bioinformatics, and the expression differences of lncRNA-p21 in tumor cells and normal cells were detected by qRT-PCR. The role of lncRNA-p21 in the anti-cancer effect of Jin formula combined cisplatin was investigated by knockdown or overexpression of lncRNA-p21 and a series of cell experiments. The expression of MAPK pathway-related proteins was analyzed by western blot. RESULTS: Jin formula combined with cisplatin (JIN + DDP) can suppress tumor growth and promote apoptosis in Lewis lung cancer mouse model. LncRNA-p21 was significantly up-regulated in the JIN and JIN + DDP groups, and the expression of lncRNA-p21 in lung cancer tissues and cells was lower than that in normal tissues and cells. In vitro, JIN + DDP significantly induced apoptosis and inhibited the proliferation, migration, and invasion of H460 and H1650 lung cancer cells. The above effects can be enhanced by the overexpression of lncRNA-p21 and eliminated by knock-down of lncRNA-p21. Further studies revealed that JIN + DDP inhibited the expression of mitogen-activated protein kinase (MAPK) pathway-related proteins, whereas knock-down of lncRNA-p21 abrogated the inhibition of the MAPK signaling pathway. CONCLUSIONS: This study showed that Jin formula combined with cisplatin could effectively inhibit the progression of lung cancer partially through targeting lncRNA-p21.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Animais , Camundongos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Cisplatino/farmacologia , Cisplatino/uso terapêutico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular Tumoral , Proliferação de Células , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Apoptose , MicroRNAs/genética
5.
Mol Pharm ; 20(11): 5800-5810, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37822062

RESUMO

Nanoscale structures have been developed to serve various functions in cancer therapy, encompassing areas such as diagnosis, biomedical visualization, tissue regeneration, and drug delivery. Based on biocompatible chitosan oligosaccharides (COS) and gold nanorods (GNRs), we designed the drug delivery systems (GNR@polyacrylic acid-Mn@COS Janus nanoparticles (JNPs)), which achieved paclitaxel (PTX) loaded on the side of GNRs, and the PAA-Mn domain served as magnetic resonance imaging contrast agents. This system was found to be effectively delivered to tumor sites through the enhanced permeability and retention (EPR) effect and the active target of the COS. The uniform JNPs selectively targeted cancer cells instead of normal cells through interacting with the COS on the surface of tumor cells, and the pH/NIR-responsive drug release behavior further enhanced their therapeutic effects. The in vivo effects of JNPs against tumors were evaluated using subcutaneous and orthotopic lung metastasis models, yielding promising outcomes for both tumor diagnosis and cancer treatment. In conclusion, the obtained JNPs hold great promise as a theranostic nanoplatform with synergistic chemotherapeutic and photothermal effects.


Assuntos
Neoplasias da Mama , Nanopartículas , Humanos , Feminino , Neoplasias da Mama/patologia , Terapia Fototérmica , Medicina de Precisão , Nanopartículas/química , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Fototerapia/métodos , Nanomedicina Teranóstica , Linhagem Celular Tumoral , Doxorrubicina/uso terapêutico
6.
Poult Sci ; 102(10): 102935, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37562133

RESUMO

The reproductive performance of breeder roosters has significant economic importance in the poultry industry. Breeder roosters have severely reduced semen quality with age and will be at risk of culling in the following years. In order to extend the use of breeder roosters, we drew on the induced molting model of hens and selected 35 Houdan roosters aged 50 wk for induced molting. By comparing the body weight, testicular weight, semen quality, and reproductive performance before and after induced molting, we found that induced molting could restore the body weight and testicular weight to the levels before molting (P > 0.05). At the same time, it significantly improved sperm motility (P < 0.05) and also improved reproductive performance such as fertilization rate and hatching rate. To further reveal the mechanism underlying the effects of induced molting on semen quality and reproductive performance in aged Houdan roosters, we collected testes from 3 periods: 1 d before fasting (F0), 15 d after fasting (F15), and 32 d after recovery feeding (R32) for transcriptome sequencing analysis. A total of 5,671 genes were detected in F0, F15, and R32, and trend analysis of the 5,671 differential genes showed 2 significant trends (profile 5 and profile 2). KEGG enrichment analysis of the genes in the 2 profiles, revealed significantly enriched pathway regulation of actin cytoskeleton. In the regulation of actin cytoskeleton pathway, we found a protein kinase gene (SRC) and a senescence gene (ROCK2). SRC was highly expressed at F15, leading to the phosphorylation of key substrates, which in turn disrupted the Sertoli cell spermatid connection and the spermiogenesis process, resulting in no mature spermatozoa produced from F15, SRC expression was inhibited at R32, the expression level was reduced, and mature spermatozoa reappeared. The senescence gene ROCK2 was highly expressed at F15 compared to F0 and R32, which may have been responsible for inducing senescence atrophy in the testes.


Assuntos
Galinhas , Análise do Sêmen , Animais , Masculino , Feminino , Análise do Sêmen/veterinária , Galinhas/genética , Suplementos Nutricionais/análise , Muda , Transcriptoma , Motilidade dos Espermatozoides , Espermatozoides/fisiologia , Peso Corporal , Sêmen/fisiologia
7.
Phytomedicine ; 118: 154937, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37393831

RESUMO

BACKGROUND: Polygala japonica Houtt. (PJ) has been demonstrated with several biological potentials such as lipid-lowering and anti-inflammatory effects. However, the effects and mechanisms of PJ on nonalcoholic steatohepatitis (NASH) remain unclear. PURPOSE: The aim of this study was to evaluate the effects of PJ on NASH and illustrate the mechanism based on modulating gut microbiota and host metabolism. MATERIALS AND METHODS: NASH mouse model was induced using methionine and choline deficient (MCD) diet and orally treated with PJ. The therapeutic, anti-inflammatory, and anti-oxidative effects of PJ on mice with NASH were firstly assessed. Then, the gut microbiota of mice was analyzed using 16S rRNA sequencing to assess the changes. Finally, the effects of PJ on the metabolites in liver and feces were explored by untargeted metabolomics. RESULTS: The results indicated that PJ could improve hepatic steatosis, liver injury, inflammatory response, and oxidative stress in NASH mice. PJ treatment also affected the diversity of gut microbiota and changed the relative abundances of Faecalibaculum. Lactobacillus, Muribaculaceae, Dubosiella, Akkermansia, Lachnospiraceae_NK4A136_group, and Turicibacter in NASH mice. In addition, PJ treatment modulated 59 metabolites both in liver and feces. Metabolites involved in histidine, and tryptophan metabolism pathways were identified as the key metabolites according to the correlation analysis between differential gut microbiota and metabolites. CONCLUSION: Our study demonstrated the therapeutic, anti-inflammatory and anti-oxidative potentials of PJ on NASH. The mechanisms of PJ treatment were related to the improvement of gut microbiota dysbiosis and the regulation of histidine and tryptophan metabolism.


Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Polygala , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Polygala/genética , RNA Ribossômico 16S , Histidina/metabolismo , Histidina/farmacologia , Histidina/uso terapêutico , Triptofano/metabolismo , Triptofano/farmacologia , Triptofano/uso terapêutico , Fígado , Fezes , Camundongos Endogâmicos C57BL
8.
Mol Pharm ; 20(8): 4007-4020, 2023 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-37427910

RESUMO

Distant metastasis of malignant tumors is considered to be the main culprit for the failure of current antitumor treatments. Conventional single treatments often exhibit limited efficacy in inhibiting tumor metastasis. Therefore, there is a growing interest in developing collaborative antitumor strategies based on photothermal therapy (PTT) and free-radical-generated photodynamic therapy (PDT), especially utilizing oxygen-independent nanoplatforms, to address this challenge. Such antitumor strategies can enhance the therapeutic outcomes by ensuring the cytotoxicity of free radicals even in the hypoxic tumor microenvironment, thereby improving the effective suppression of primary tumors. Additionally, these approaches can stimulate the production of tumor-associated antigens and amplify the immunogenic cell death (ICD) effects, potentially feasible for enhancing the therapeutic outcomes of immunotherapy. Herein, we fabricated a functional nanosystem that co-loads IR780 and 2,2'-azobis[2-(2-imidazolin-2-yl)propane]-dihydrochloride (AIPH) to realize PTT-triggered thermodynamic combination therapy via the oxygen-independent pathway for the elimination of primary tumors. Furthermore, the nanocomposites were surface-decorated with a predesigned complex peptide (PLGVRGC-anti-PD-L1 peptide, MMP-sensitive), which facilitated the immunotherapy targeting distant tumors. Through the specific recognition of matrix metalloproteinase (MMP), the sensitive segment on the obtained aNC@IR780A was cleaved. As a result, the freed anti-PD-L1 peptide effectively blocked immune checkpoints, leading to the infiltration and activation of T cells (CTLs). This nanosystem was proven to be effective at inhibiting both primary tumors and distant tumors, providing a promising combination strategy for tumor PTT/TDT/immunotherapy.


Assuntos
Nanopartículas , Fototerapia , Linhagem Celular Tumoral , Imunoterapia , Oxigênio , Peptídeos , Polímeros , Termodinâmica , Microambiente Tumoral , Humanos
9.
Chromatographia ; 86(6): 483-495, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37255950

RESUMO

Polar plant growth regulators, used alone or doped in fertilizers, are most effective and widely utilized plant growth regulators (PGRs) in agriculture, which play important roles in mediating the yield and quality of crops and foodstuffs. The application scope has been extended to herbal medicines in the past 2 decades and relevant study is inadequate. The aim of this study is to establish a QuPPe-based extraction method containing low-temperature and d-SPE cleanup procedure followed by the detection on a selective multiresidue ultrahigh-performance liquid chromatography - triple quadrupole tandem mass spectrometry (UHPLC-QqQ-MS/MS) in three herbal matrices. This simple, accurate, versatile and robust method was verified according to the validation criteria of the SANTE/12682/2019 guideline document. The analytical range was from 2.5 to 200 µg/L, and the average recoveries were in the range of 64.6-117.8% (n = 6). The optimized method was applied to 135 herbal medicines thereof. Result showed that the detection frequency of chlormequat was the highest in the investigated PGRs, with the positive rate of 15.6%. Improvement of the detection method for polar PGRs will enrich the coverage of PGRs, which is conducive to safeguard public health and ensure drug safety. Supplementary Information: The online version contains supplementary material available at 10.1007/s10337-023-04254-3.

10.
Cell Rep ; 41(13): 111890, 2022 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-36577369

RESUMO

Ovarian cancer (OC) remains a clinical challenge for its difficulty in early diagnosis and insensitivity to treatments. Gut microbiota modulate multiple carcinoma progression through immunoregulation. The relationship between OC and gut microbiota has not been fully characterized. We find that the feces of patients with OC demonstrate different characteristics from benign controls. After fecal microbiota transplantation (FMT) from patients with OC into OC-bearing mice, the tumor development accelerates. Further, an Akkermansia supplementation with FMT significantly suppresses OC progression in mice. RNA sequencing of tumors shows that T cell activation pathways are upregulated after Akkermansia supplementation with FMT. Moreover, acetate accumulation accompanies Akkermansia abundance elevation, which is associated with enhanced interferon γ (IFNγ) secretion of CD8+ T cells and also its tumor-killing property. This work highlights the importance of protective gut microbiome in immune surveillance of OC, which connects accumulation of acetate and the cytotoxic function of CD8+ T cells by increasing IFNγ secretion.


Assuntos
Transplante de Microbiota Fecal , Neoplasias Ovarianas , Camundongos , Animais , Feminino , Humanos , Akkermansia , Linfócitos T CD8-Positivos , Fezes , Neoplasias Ovarianas/terapia , Suplementos Nutricionais
11.
ACS Nano ; 16(12): 20805-20819, 2022 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-36378717

RESUMO

The emergence of X-ray-induced photodynamic therapy (X-PDT) holds tremendous promise for clinical deep-penetrating cancer therapy. However, the clinical application of X-PDT in cancer treatment is still limited due to the hypoxic property of cancerous tissue, the inherent antioxidant system of tumor cells, and the difficulty in matching the absorption spectra of photosensitizers. Herein, a versatile core-shell radiosensitizer (SCNPs@DMSN@CeOx-PEG, denoted as SSCP) was elaborately designed and constructed to enhance X-PDT by coating tunable mesoporous silica on nanoscintillators, followed by embedding the cerium oxide nanoparticles in situ. The obtained SSCP radiosensitizer demonstrated a distinct blue-shift in the ultraviolet light region, so that it could perfectly absorb the ultraviolet light converted by the SCNPs core, resulting in the formation of photoinduced electron-hole (e--h+) pairs separation to generate reactive oxygen species (ROS). In addition, the cerium oxide exhibits high glutathione consumption to heighten ROS accumulation, and catalase-like activity to alleviate the hypoxia, which further enhances the efficiency of radiotherapy. Benefiting from the abundant Lu and Ce elements, the computed tomography imaging performance of SSCP is about 3.79-fold that of the clinical contrast agent (iohexol), which has great potential in both preclinical imaging and clinical translation.


Assuntos
Cério , Nanopartículas , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Raios X , Espécies Reativas de Oxigênio , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Hipóxia/tratamento farmacológico , Linhagem Celular Tumoral
12.
Front Neurol ; 13: 931412, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35837227

RESUMO

Hemifacial spasm (HFS) and temporomandibular joint (TMJ) pain are common facial diseases which cause depression, anxiety, insomnia, and poor quality of life. However, currently there are still no effective therapies to treat HFS and TMJ. Electroacupuncture (EA) has advantages of safety, rapid work, easy operation and convenience. Here, we reported a case of a 50-year-old woman who presented with irregular spasm of eyelids and facial muscles on the left side, and TMJ pain on the right side. The patient had been treated with carbamazepine (20mg per day) and alternative therapies for a year, but still not much improvement in the symptoms. The scores of the Jankovic Rating Scale (JRS), global rating scale (GRS), and visual analog scale (VAS) were 7, 60, and 7 points, respectively. The EMG test showed that the spastic side had higher R1 amplitude, longer R2 duration, and larger R2 area than the non-spasmodic side, and the occurrence rate of the lateral spread responses (LSR) in the Orbicularis oris and the Orbicularis oculi muscle was 60% and 40%, respectively. We considered this patient had left HFS and right TMJ pain. EA was successfully undertaken for two periods over 30 weeks. After EA, JRS and VAS were reduced sharply, and the symptoms of HFS were stable without recurrence. However, the frequency of the lower eyelid increased gradually during the 6-month follow-up. These findings reveal that EA with the frequency of 2 Hz and intensity of ~ 1-2 mA may be a benefit for alleviating symptoms of HFS and TMJ pain without adverse reaction. The potential mechanisms of EA in HFS and TMJ pain co-morbidity involve brain stem mechanism and DNIC mechanism for distal acupuncture and segmental mechanism for local acupuncture analgesia.

13.
ACS Nano ; 16(6): 8939-8953, 2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35666853

RESUMO

Nanosystem-mediated tumor radiosensitization strategy combining the features of X-ray with infinite penetration depth and high atomic number elements shows considerable application potential in clinical cancer therapy. However, it is difficult to achieve satisfactory anticancer efficacy using clinical radiotherapy for the majority of solid tumors due to the restrictions brought about by the tumor hypoxia, insufficient DNA damage, and rapid DNA repair during and after treatment. Inspired by the complementary advantages of nitric oxide (NO) and X-ray-induced photodynamic therapy, we herein report a two-dimensional nanoplatform by the integration of the NO donor-modified LiYF4:Ce scintillator and graphitic carbon nitride nanosheets for on-demand generation of highly cytotoxic peroxynitrite (ONOO-). By simply adjusting the Ce3+ doping content, the obtained nanoscintillator can realize high radioluminescence, activating photosensitive materials to simultaneously generate NO and superoxide radical for the formation of ONOO- in the tumor. Obtained ONOO- effectively amplifies therapeutic efficacy of radiotherapy by directly inducing mitochondrial and DNA damage, overcoming hypoxia-associated radiation resistance. The level of glutamine synthetase (GS) is downregulated by ONOO-, and the inhibition of GS delays DNA damage repair, further enhancing radiosensitivity. This work establishes a combinatorial strategy of ONOO- to overcome the major limitations of radiotherapy and provides insightful guidance to clinical radiotherapy.


Assuntos
Neoplasias , Ácido Peroxinitroso , Humanos , Óxido Nítrico , Dano ao DNA , Reparo do DNA , Neoplasias/radioterapia
14.
Int J Biol Macromol ; 209(Pt A): 356-366, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35405152

RESUMO

Both tea polysaccharides and selenium have certain remission potential for ulcerative colitis (UC), but few reports focused on natural selenium-containing tea polysaccharides. The purpose of this study was to isolate a selenium-containing tea polysaccharide (ASeTP) and determine its structure and effects on UC. Results showed that ASeTP was primarily composed of three purified, ß-pyranoside-linked, protein-binding polysaccharides (SeTP-1, SeTP-2, and SeTP-3) with SeOC, OSeO, and SeO linkages. Specifically, SeTP-1 was a neutral heteropolysaccharide principally composed of mannose, glucose, galactose, xylose, and arabinose, while SeTP-2 and SeTP-3 were acidic heteropolysaccharides due to the existence of glucuronic acid. ASeTP effectively alleviated the symptoms of weight loss, colon shortens, and disease activity index scores increase in dextran sodium sulfate (DSS)-induced colitis mice. ASeTP attenuated the histological damage and maintained the colonic mucosal barrier via up-regulating the expression of occludin, claudin-1, and zona occludens-1 (ZO-1). ASeTP suppressed the levels of pro-inflammatory cytokines and enhanced the antioxidant capacity of colon tissue. Besides, ASeTP beneficially increased the selenium content of the colon. Furthermore, ASeTP remodeled the gut microbiota by accelerating the proliferation of beneficial bacteria and inhibiting pathogenic microorganisms. Thus, ASeTP has the potential to be a functional food against colitis.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Selênio , Animais , Colite/induzido quimicamente , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/microbiologia , Colo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Polissacarídeos/metabolismo , Selênio/metabolismo , Selênio/farmacologia , Chá/metabolismo
15.
Carbohydr Res ; 512: 108498, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35074663

RESUMO

Selenium polysaccharides have antioxidant, anti-tumor and other activities. Tea selenium polysaccharides and Lentinan selenium polysaccharides, etc. have been studied. Pennycress is a super-rich selenium plant and there are few studies about pennycress selenium-containing polysaccharides. In this study, the following researches were carried out on pennycress selenium polysaccharides: Selenium-containing polysaccharides were extracted from the leaves of pennycress (Thlaspi arvense L.) using an efficient subcritical water extraction (SWE) process. After purification, two fractions (Se-PPS1 and Se-PPS3) were obtained and subjected to structural identification. The results showed that the molecular weights of Se-PPS1 and Se-PPS3 were 4.2 × 104 Da and 4.5 × 104 Da, respectively. Se-PPS1 is mainly comprised of glucose, galactose, and xylose. Se-PPS3 consists of glucuronic acid, rhamnose, galacturonic acid, glucose, galactose, xylose, and arabinose. Fourier transform infrared spectroscopy (FT-IR) analysis showed that the two fractions had absorption spectra typical of selenium esters and spectral characteristics of polysaccharides. The glycosidic linkages were determined by Gas chromatography-mass spectrometry (GC-MS) and Nuclear magnetic resonance (NMR). The two fractions have (1 â†’ 6)-ß-D- Galp and T-α-D- Glcp configurations. Moreover, in vitro antioxidant activity assays showed that Se-PPS1 and Se-PPS3 exhibited effective radical-scavenging abilities, suggesting they have potential applications as natural antioxidants in food and medicine.


Assuntos
Selênio , Thlaspi , Antioxidantes/química , Polissacarídeos/química , Selênio/análise , Selênio/química , Espectroscopia de Infravermelho com Transformada de Fourier
16.
Food Chem ; 371: 131201, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598116

RESUMO

Hydrophilic constituents are significant for the taste and nutrition of tea, but their simultaneous quantification remains challenging due to the lack of efficient methods. Based on the hydrophilic interaction chromatography coupled with triple quadrupole-tandem mass spectrometry, this work developed and validated an efficient (8.5 min per run), sensitive (LOQ: 0.002-0.493 µg/mL) and accurate method. This method was successfully used to determine the contents of 45 hydrophilic constituents in Yunnan large-leaf tea. Umami amino acids and umami-enhanced nucleotides generally exhibited higher content in green tea and Pu-erh raw tea. By contrast, a few number of amino acids (e.g., proline and γ-aminobutyric acid) and most alkaloids and nucleosides showed significantly higher contents in black tea or Pu-erh ripen tea. By performing the orthogonal partial least squares discriminant analysis, classification models for distinguishing four types of tea, and green tea from Pu-erh raw tea were established.


Assuntos
Camellia , Espectrometria de Massas em Tandem , China , Cromatografia Líquida de Alta Pressão , Interações Hidrofóbicas e Hidrofílicas , Chá
17.
Molecules ; 26(23)2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34885706

RESUMO

A method for the quality evaluation of Atractylodis Macrocephalae Rhizoma (AMR) based on high-performance liquid chromatography (HPLC) fingerprint, HPLC quantification, and chemical pattern recognition analysis was developed and validated. The fingerprint similarity of the 27 batches of AMR samples was 0.887-0.999, which indicates there was very limited variance between the batches. The 27 batches of samples were divided into two categories according to cluster analysis (CA) and principal component analysis (PCA). A total of six differential components of AMR were identified in the partial least-squares discriminant analysis (PLS-DA), among which atractylenolide I, II, III, and atractylone counted 0.003-0.045%, 0.006-0.023%, 0.001-0.058%, and 0.307-1.175%, respectively. The results indicate that the quality evaluation method could be used for quality control and authentication of AMR.


Assuntos
Atractylodes/química , Medicamentos de Ervas Chinesas/química , Lactonas/química , Rizoma/química , Sesquiterpenos/química , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/análise , Análise de Componente Principal
18.
Phytomedicine ; 93: 153795, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34735905

RESUMO

BACKGROUND: Bao Yuan Capsule (BYC) is a patented Chinese medicinal formula for health promotion but its application for ischemic stroke remains unknown. In this study, we proposed the hypothesis that BYC could promote neurogenesis and neurological functional recovery through promoting mitochondrial function and activating PI3K/Akt signaling pathway. METHODS: We firstly performed chemical identification studies by using QIT-TOF-MS technology. Then, we investigated the effects of BYC (1 g/kg, 2 g/kg, 4 g/kg per day) on improving the recovery of the neurological functions in transient middle cerebral artery occlusion (MCAO) ischemic mice. RESULTS: We tentatively characterized 36 compounds from the BYC extractions. At dosage of 4 g/kg, BYC effectively improved locomotor ability, attenuated anxiety-like behaviors, and enhanced the exploring behaviors, learning and memory capability in the transient MCAO ischemic mice. BYC treatment promoted neural stem cell differentiations in the subventricular zone (SVZ) and subgranular zone (SGZ) of the MCAO mice. BYC also up-regulated the expression of Aconitase 2 (ACO2), Succinate dehydrogenase complex, subunit A (SDHA), phosphorylation of AMP-activated protein kinase (p-AMPK), protein kinase B (p-Akt) and glycogen synthase kinase 3ß (p-GSK3ß) in the hippocampus of the MCAO mice. BYC (200 µg/ml) significantly improved the mitochondrial functions in cultured mouse multipotent neural stem like C17.2 cells. BYC treatment also promoted neuronal differentiations in the C17.2 cells under oxygen-glucose deprivation (OGD) condition. The neurogenetic effects were abolished by co-treatments of ATP synthesis inhibitor oligomycin and PI3K/Akt inhibitor wortmannin. Moreover, Akt phosphorylation was dramatically reduced by oligomycin. CONCLUSION: BYC could promote neurogenesis and neurological functional recovery in post ischemic brains by regulating the mitochondrial functions and Akt signaling pathway.


Assuntos
Isquemia Encefálica , Proteínas Proto-Oncogênicas c-akt , Animais , Isquemia Encefálica/tratamento farmacológico , Camundongos , Mitocôndrias/metabolismo , Neurogênese , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
19.
Anim Nutr ; 7(4): 1105-1114, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34738041

RESUMO

Clostridium butyricum has been widely considered an antibiotic substitute in recent years. It can promote growth performance, improve the immune response and enhance the intestinal barrier function of the host. In the present study, 1-d-old Arbor Acres (AA) broilers were fed C. butyricum (1 × 109 cfu/kg) for 28 d. The transcriptomic characteristics of epithelial cells of the cecal mucosa were determined by RNA-sequence, and the cecal microbiota composition was explored by 16S ribosomal RNA gene sequencing. The changes in the intestinal mucosa of broilers were then analyzed by tissue staining. Gene Ontology (GO) annotations identified substance transport and processes and pathways that might participate in intestinal development and cell viability. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the differentially expressed genes are involved in numerous pathways related to amino acid and vitamin metabolism and antioxidant and defensive functions, among others. The relative expression of some genes associated with intestinal barrier function (claudins 2, 15, 19, and 23, tight junction proteins 1, 2, and 3 and mucin 1) was significantly increased in the treatment group (P < 0.05 or P < 0.01). Moreover, the proportion of Firmicutes was higher in the C. butyricum-treated group, whereas the proportion of Proteobacteria was higher in the control group. At the genus level, the relative abundances of Butyricicoccus and Lactobacillus, among other bacteria, were increased after C. butyricum supplementation. The tissue staining analysis showed that the cecal mucosa of broilers was significantly ameliorated after the addition of C. butyricum (P < 0.05 or P < 0.01). These results showed that dietary supplementation with C. butyricum can enhance the antioxidant capacity, mucosal barrier function, and stabilize the cecal microbiota, resulting in improving the growth performance.

20.
J Food Sci ; 86(9): 4223-4243, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34383327

RESUMO

Bamboo(Phyllostachys edulis) shoot was reported to be rich in phenolics. In the present study, free phenolics, conjugated phenolics, and insoluble-bound phenolics of oven-drying and freeze-drying bamboo shoot tips were extracted and separated, of which total phenolic content (TPC), total flavonoid content (TFC), and their antioxidant activities were determined. Phenolics of different binding forms were qualitatively analyzed using HPLC-ESI-QqQ-MS. A total of 22, 41, and 28 compounds were confirmed or tentatively identified in free, conjugated, and insoluble-bound phenolic extraction, respectively. The majority of the identified compounds were organic acids and phenolic acids. Oven-drying samples exhibited higher TPC (10.53-24.92 mg GAE/100 g DW) and TFC (5.80-33.27 mg CE/100 g DW) values, and stronger antioxidant activities (DPPH, ABTS, and FRAP) than freeze-drying (TPC: 1.67-15.28 mg GAE/100 g DW, TFC: 1.43-29.05 mg CE/100 g DW). Insoluble-bound phenolics were the major contributor to the total antioxidant activity. The present study investigated the phenolics composition and antioxidant activities of different binding forms in bamboo shoot tip comprehensively, and provided available information for their high-value deep-processing.


Assuntos
Antioxidantes , Manipulação de Alimentos , Liofilização , Fenóis , Extratos Vegetais , Poaceae , Antioxidantes/química , Flavonoides/análise , Manipulação de Alimentos/métodos , Manipulação de Alimentos/normas , Alimentos em Conserva/análise , Fenóis/análise , Fenóis/química , Extratos Vegetais/química , Poaceae/química
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