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The Asian water plantain, Alisma orientale (Sam.) Juzep, is a traditional Chinese medicinal plant. The dried tubers of the Alisma orientale, commonly referred to as Alismatis rhizome (AR), have long been used in traditional Chinese medicine to treat a variety of diseases. Soil properties and the soil microbial composition are known to affect the quality and bioactivity of plants. Here, we sought to identify variations in soil fungal communities and soil properties to determine which would be optimal for cultivation of A. orietale. Soil properties, heavy metal content, and pesticide residues were determined from soils derived from four different agricultural regions around Shaowu City, Fujian, China, that had previously been cultivated with various crops, namely, Shui Dao Tu (SDT, rice), Guo Shu Tu (GST, pecan), Cha Shu Tu (CST, tea trees), and Sang Shen Tu (SST, mulberry). As fungi can either positively or negatively impact plant growth, the fungal communities in the different soils were characterized using long-read PacBio sequencing. Finally, we examined the quality of A. orientale grown in the different soils. Our results show that fungal community diversity of the GST soil was the highest with saprotrophs the main functional modes in these and SDT soils. Our data show that GST and SDT soils were most suitable for A. orientale growth, with the quality of the AR tubers harvested from GST soil being the highest. These data provide a systematic approach at soil properties of agricultural lands in need of replacement and/or rotating crops. Based on our findings, GST was identified as the optimal soil for planting A. orientale, providing a new resource for local farmers.
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Electroacupuncture (EA) and induced pluripotent stem cell (iPSC)-derived small extracellular vesicles (iPSC-EVs) have substantial beneficial effects on ischemic stroke. However, the detailed mechanisms remain unclear. Here, we explored the mechanisms underlying the regulation of EA and iPSC-EVs in the microbiome-gut-brain axis (MGBA) after ischemic stroke. Ischemic stroke mice (C57BL/6) were subjected to middle cerebral artery occlusion (MCAO) or Sham surgery. EA and iPSC-EVs treatments significantly improved neurological function and neuronal and intestinal tract injury, downregulated the levels of IL-17 expression and upregulated IL-10 levels in brain and colon tissue after cerebral ischemia-reperfusion. EA and iPSC-EVs treatments also modulated the microbiota composition and diversity as well as the differential distribution of species in the intestines of the mice after cerebral ischemia-reperfusion. Our results demonstrated that EA and iPSC-EVs treatments regulated intestinal immunity through MGBA regulation of intestinal microbes, reducing brain and colon damage following cerebral ischemia and positively impacting the outcomes of ischemic stroke. Our findings provide new insights into the application of EA combined with iPSC-EVs as a treatment for ischemic stroke.
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Isquemia Encefálica , Eletroacupuntura , Microbioma Gastrointestinal , Células-Tronco Pluripotentes Induzidas , AVC Isquêmico , Animais , Humanos , Camundongos , Isquemia Encefálica/terapia , Isquemia Encefálica/metabolismo , Eixo Encéfalo-Intestino , Eletroacupuntura/métodos , Células-Tronco Pluripotentes Induzidas/metabolismo , Infarto da Artéria Cerebral Média/terapia , AVC Isquêmico/terapia , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Deficits in event-related potential (ERP) including duration mismatch negativity (MMN) and P3a have been demonstrated widely in chronic schizophrenia (SZ) but inconsistent findings were reported in first-episode patients. Psychotropic medications and diagnosis might contribute to different findings on MMN/P3a ERP in first-episode patients. The present study examined MMN and P3a in first episode drug naïve SZ and bipolar disorder (BPD) patients and explored the relationships among ERPs, neurocognition and global functioning. METHODS: Twenty SZ, 24 BPD and 49 age and sex-matched healthy controls were enrolled in this study. Data of clinical symptoms [Positive and Negative Symptoms Scale (PANSS), Young Manic Rating Scale (YMRS), Hamilton Depression Rating Scale (HAMD)], neurocognition [Wechsler Adult Intelligence Scale (WAIS), Cattell's Culture Fair Intelligence Test (CCFT), Delay Matching to Sample (DMS), Rapid Visual Information Processing (RVP)], and functioning [Functioning Assessment Short Test (FAST)] were collected. P3a and MMN were elicited using a passive auditory oddball paradigm. RESULTS: Significant MMN and P3a deficits and impaired neurocognition were found in both SZ and BPD patients. In SZ, MMN was significantly correlated with FAST (r = 0.48) and CCFT (r = -0.31). In BPD, MMN was significantly correlated with DMS (r = -0.54). For P3a, RVP and FAST scores were significant predictors in SZ, whereas RVP, WAIS and FAST were significant predictors in BPD. CONCLUSIONS: The present study found deficits in MMN, P3a, neurocognition in drug naïve SZ and BPD patients. These deficits appeared to link with levels of higher-order cognition and functioning.
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Transtorno Bipolar , Esquizofrenia , Adulto , Humanos , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Eletroencefalografia , Potenciais Evocados , Potenciais Evocados P300 , Potenciais Evocados Auditivos , Estimulação AcústicaRESUMO
This paper aimed to explore the roles of the combination of electroacupuncture (EA) and induced pluripotent stem cell-derived small extracellular vesicles (iPSC-EVs) on mice with ischemic stroke and the underlying mechanisms. A focal cerebral ischemia model was established in C57BL/6 mice through middle cerebral artery occlusion (MCAO). After 3 days, neurological impairment and motor function were examined by performing behavioral tests. The infarct volume and neuronal apoptosis were examined using TTC staining and TUNEL assays. Flow cytometry was performed to assess the proliferation of T lymphocytes. The changes in the interleukin (IL)-33/ST2 axis were evaluated by immunofluorescence and Western blotting. The combination of EA and iPSC-EVs treatment ameliorated neurological impairments and reduced the infarct volume and neuronal apoptosis in MCAO mice. EA plus iPSC-EVs suppressed T helper (Th1) and Th17 responses and promoted the regulatory T cell (Treg) response. In addition, EA plus iPSC-EVs exerted neuroprotective effects by regulating the IL-33/ST2 axis and inhibiting the microglia and astrocyte activation. Taken together, the study shows that EA and iPSC-EVs exerted a synergistic neuroprotective effect in MCAO mice, and this treatment may represent a novel potent therapy for ischemic stroke and damage to other tissues.
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Eletroacupuntura , Vesículas Extracelulares , Células-Tronco Pluripotentes Induzidas , AVC Isquêmico , Animais , Humanos , Infarto , Proteína 1 Semelhante a Receptor de Interleucina-1 , AVC Isquêmico/terapia , Camundongos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Extrarenal malignant rhabdoid tumor (EMRT) is a rare and high-mortality malignant tumor, which is more common in infants and rarely seen in adults. We firstly report a case of liver malignant rhabdoid tumor (MRT) with a loss of SMARCB1 gene (alias INI1, SNF5, BAF47) expression in a middle-aged woman, and preliminarily summarize the clinical characteristics and discuss its potential treatment of liver MRT by reviewing 55 cases reported in the past. CASE PRESENTATION: We report a 40-year-old woman who was admitted to our hospital for right epigastric pain. Previously, the patient was treated with liver hematoma in another hospital until she came to our hospital for abdominal pain again. In our hospital, we performed surgical treatment on her and the pathology diagnosed EMRT with negative expression of SMARCB1. After surgery, the patient underwent genetic testing, but failed to screen for sensitive targeted or conventional chemotherapy drugs, and she did not receive further treatment. Due to lack of timely diagnosis and effective chemotherapy drugs, tumor recurrence and metastasis occurred one year after surgery. Then the patient chose traditional Chinese medicine for treatment. And the metastatic tumors had still progressed after one year of treatment, but the patient didn't have obvious discomfort symptoms. CONCLUSIONS: Liver MRT is a highly aggressive tumor with high metastatic potential and poor prognosis. It lacks specific symptoms and signs and is easy to be ignored and misdiagnosed. The mortality rate is extremely high as there is no effective treatment. But most tumors are accompanied by SMARCB1 deficiency, which may offer new research directions for cancer therapeutics. For the present, early detection, early diagnosis and early resection remain the key to improve the prognosis of patients.
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Neoplasias Hepáticas , Tumor Rabdoide , Adulto , Biomarcadores Tumorais , Feminino , Humanos , Lactente , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Tumor Rabdoide/genética , Tumor Rabdoide/cirurgiaRESUMO
OBJECTIVE: This study aims to dissect the mechanism of traditional Chinese medicinal herbs against asthma; we chose to first focus on the main chemical components of licorice to investigate their contribution to asthmatic inflammation inhibition. METHODS: Production of cellular nucleotide molecules such as cAMP, cGMP, and cGAMP was examined by using enzyme-linked immunosorbent assay (ELISA). Enzyme-encoding genes were tested in vitro using quantitative real-time PCR and protein level was detected by Western blotting analysis. In addition, co-culturing of murine dendritic cells together with T cells was conducted to examine the expression of cytokine genes and host immune response. RESULTS: We found that one of the components within licorice, named liquiritigenin (LR), could efficiently enhance cAMP production in different cell lines. The augmentation of such molecules was linked to the high expression of cAMP synthesis genes and repressed expression of cAMP breaking down genes. In addition, the downstream immune response was also alleviated by the increase in cAMP levels by LR, suggesting the great potential of this molecule against inflammation. Subsequent immunological tests showed that LR could efficiently inhibit the expression of several cytokines and alter the NF-κB pathway and T cell polarization. CONCLUSION: Altogether, we have identified a promising antiasthmatic agent LR that could exhibit immunosuppressive function by elevating the cAMP level.
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Asma , AMP Cíclico/biossíntese , Células Dendríticas/imunologia , Flavanonas/farmacologia , Pterigotos , Transdução de Sinais/efeitos dos fármacos , Antiasmáticos/farmacologia , Asma/tratamento farmacológico , Asma/imunologia , Asma/patologia , Células Cultivadas , Citocinas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Imunidade Celular/efeitos dos fármacos , Imunidade Celular/genética , Testes Imunológicos/métodos , NF-kappa B/metabolismoRESUMO
Ischemic stroke is a common cause of morbidity, mortality, and disability worldwide. Electroacupuncture (EA) is an effective method for alleviating brain damage after ischemic stroke. However, the underlying mechanism has not been fully elucidated. This study aimed to determine whether endoplasmic reticulum stress (ERS) could contribute to the protective effects of EA in cerebral ischemia/reperfusion injury (CIRI) to provide a rationale for the widespread clinical use of EA. Rats were divided into the sham-operated (sham) group, the CIRI (model) group, and the EA group. Rats in the model group were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by 72 h of reperfusion. Rats with CIRI were treated daily with EA at GV20 and ST36 for a total of 3 days. The Longa scoring system and adhesive removal somatosensory test were applied to evaluate neurological deficits. Then, 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed to measure the infarct volume. Immunofluorescence staining for NeuN and GFAP and terminal deoxynucleotidyl transferase- (TdT-) mediated dUTP nick-end labeling (TUNEL) staining were performed to detect apoptotic cells in brain tissue. Immunohistochemistry, quantitative real-time polymerase chain reaction (qPCR), and western blotting were used to measure the levels of ERS indicators (GRP78, CHOP/GADD153, p-eIF2α, and caspase 12). The results showed that EA significantly reduced the cerebral infarct volume, improved neurological function, and inhibited neuronal apoptosis. In the EA group compared with the model group, the mRNA expression levels of GRP78 were significantly increased, and the expression levels of proapoptotic proteins (CHOP/GADD153, p-eIF2α, and caspase 12) were significantly decreased. These results suggest that the possible mechanism by which EA protects cells against neuronal injury in CIRI may involve inhibiting endoplasmic reticulum stress.
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Combined antitumor therapies based on nanomedicines have shown efficacy in various tumor models in recent years, overcoming the disadvantages of inefficiency and undesired toxicity of traditional therapies. Herein, we present a copper sulfide- and doxorubicin-loaded gold nanorods@mesoporous SiO2 multifunctional nanocomposite (AuNR@mSiO2@DOX-CuxS-PEG) to integrate chemotherapy, the photothermal properties of AuNRs, and the photodynamic properties of CuxS into a single nanoplatform based on hydrophobic interaction and electrostatic attraction. Upon near-infrared light irradiation, the AuNR@mSiO2@DOX-CuxS-PEG nanocomposites exhibit a synergistic therapeutic effect and inhibit the in situ tumor growth and lung metastasis in a melanoma model. This occurs because of the high photothermal conversion efficiency, boosted intracellular reactive oxygen species production, and excellent doxorubicin (DOX) release, as well as an induced tumor-specific immune response. The inspired antitumor immunity was confirmed by elevated infiltration of activated T cells in tumor tissues and improved maturation and activation of dendritic cells in tumor-draining lymph nodes. This study highlights the superior antitumor therapeutic effect elicited by a multifunctional nanoplatform for skin with in situ melanoma and lung metastasis inhibition, indicating its satisfactory clinical application prospects.
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Melanoma , Nanotubos , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Humanos , Melanoma/tratamento farmacológico , Fototerapia , Dióxido de SilícioRESUMO
Cytoplasmic male sterility (CMS) plays an important role in the application of heterosis in wheat (Triticum aestivum L.). However, the molecular mechanism underlying CMS remains unknown. This study provides a comprehensive morphological and proteomic analysis of the anthers of a P-type CMS wheat line (P) and its maintainer line, Yanshi 9 hao (Y). Cytological observations indicated that the P-type CMS line shows binucleate microspore abortion. In this line, the tapetum degraded early, leading to anther cuticle defects, which could not provide the nutrition needed for microspore development in a timely manner, thus preventing the development of the microspore to the normal binucleate stage. Proteomic analysis revealed novel proteins involved in P-type CMS. Up to 2576 differentially expressed proteins (DEPs) were quantified in all anthers, and these proteins were significantly enriched in oxidative phosphorylation, glycolysis/gluconeogenesis, citrate cycle (TCA cycle), starch and sucrose metabolism, phenylpropanoid biosynthesis, and pyruvate metabolism pathways. These proteins may comprise a network that regulates male sterility in wheat. Based on the function analysis of DEPs involved in the complex network, we concluded that the P-type CMS line may be due to cellular dysfunction caused by disturbed carbohydrate metabolism, inadequate energy supply, and disturbed protein synthesis. These results provide insights into the molecular mechanism underlying male sterility and serve as a valuable resource for researchers in plant biology, in general, and plant sexual reproduction, in particular.
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Infertilidade das Plantas/fisiologia , Proteínas de Plantas/metabolismo , Pólen/metabolismo , Proteoma/metabolismo , Proteômica/métodos , Triticum/metabolismo , Citoplasma/metabolismo , Flores/genética , Flores/crescimento & desenvolvimento , Flores/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Infertilidade das Plantas/genética , Proteínas de Plantas/genética , Pólen/genética , Pólen/crescimento & desenvolvimento , Proteoma/genética , Triticum/genética , Triticum/crescimento & desenvolvimentoRESUMO
Alisma orientale (Sam.) Juzep (A. orientale) is a traditional herb that is often used to treat disease including edema and hyperlipidemia. However, the molecular mechanism by which Alisma orientale (Sam.) Juzep exerts its hypolipidemic effects remains unclear. In this study, a diabetic rat model was established by feeding a high-fat and high-sugar diet combined with a low-dose streptozotocin injection (HFS). Then the rats were treated with an A. orientale water extract (AOW), an A. orientale ethanolic extract (AOE) or metform (MET). The gut microflora and liver transcriptome were analyzed by high-throughput next-generation sequencing. Ultra-performance liquid chromatography-triple quadrupole-mass spectrometry was employed to analyze the major compounds in the AOE. The results showed that the serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels in rats of the AOE group (2.10 g/kg/day, 14 days) were significantly lower than those in the HFS group (p<0.01). Moreover, AOE treatment altered the gut microecology, particularly modulating the relative abundance of gut microflora involved in lipid metabolism compared with the HFS group. Furthermore, compared with the HFS group, the mRNA expression levels of Fam13a, Mapk7, Mpp7, Chac1, Insig1, Mcpt10, Noct, Greb1l, Fabp12 and Hba-a3 were upregulated after the administration of AOE. In contrast, the mRNA expression levels of Lox, Mybl1, Arrdc3, Cyp4a2, Krt20, Vxn, Ggt1, Nr1d1 and S100a9 were downregulated. Moreover, AOE treatment for two weeks markedly promoted the relative abundance of Lachnospiraceae (p = 0.0013). The triterpenoids contents in AOE were alisol A, alisol A 24-acetate, alisol B, alisol B 23-acetate, alisol C 23-acetate, alisol F, alisol F 24-acetate, and alisol G. Our findings above illustrated that the hypolipidemic effect of the triterpenoids of A. orientale is mediated mainly through alteration of the gut microecology and the regulation of genes involved in cholesterol metabolism, especially Insig1.
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Alisma/química , Diabetes Mellitus Experimental/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Fígado/metabolismo , Animais , Colestenonas/farmacologia , Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Transcriptoma/efeitos dos fármacos , Triterpenos/química , Triterpenos/farmacologiaRESUMO
The limited capacity of central nerve regeneration after cerebral ischemia has been the focus of attention in the field. Electroacupuncture (EA) is an effective therapy for functional rehabilitation after cerebral stroke. However, the underlying mechanism is still unclear. This study explored whether EA can improve the inhibitory microenvironment, attenuate RhoA/ROCK-mediated neurite regrowth inhibitory pathways, andpromote the expression of neuroplasticity proteins, thus exerting a protective role in cerebral ischemia/reperfusion (I/R) injury. Rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by 7 days of reperfusion, and they received EA or fasudil once daily for 7 days. The Garcia JH score, 2,3,5-triphenyltetrazolium chloride (TTC) staining, and transmission electron microscopy (TEM) were used to assess neural injury. The protein and mRNA levels of myelin-associated inhibitors (MAIs), RhoA/ROCK pathway-related molecules and neuroplasticity-related proteins were examined to explore the effect of EA on rats with cerebral I/R injury. We found that EA significantly decreased the infarct size and improved neurological function and hippocampal ultrastructure in the rats with cerebral ischemia/reperfusion (I/R) injury. EA ameliorates the inhibition of axonal regrowth and provides a protective role in functional rehabilitation after cerebral stroke by downregulating the MAI-induced RhoA/ROCK signaling pathway and by promoting the expression of GAP43 and BDNF to protect against cerebral I/R injury. Our findings provide a better understanding of the molecular mechanism underlying EA as an effective therapy for ischemic stroke.
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Encéfalo/metabolismo , Bainha de Mielina/metabolismo , Crescimento Neuronal/fisiologia , Traumatismo por Reperfusão/terapia , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Animais , Encéfalo/fisiopatologia , Eletroacupuntura , Masculino , Medição da Dor , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Transdução de Sinais/fisiologiaRESUMO
OBJECTIVE: The aim of this study was to investigate the effects of acupuncture on urinary retention and provide treatment suggestions. METHODS: A total of 113 hospitalized patients with urinary retention were included in this study. The GV20, CV6, CV4, CV3, ST28, SP6, and SP9 points were selected as the main acupoints. Acupuncture therapy was conducted for 30 minutes per session. The total number of treatment sessions was determined by the symptoms and the length of hospital stay. Bladder postvoid residual urine volume (PVR) was measured pretreatment and posttreatment by ultrasonic. Efficacy defined as spontaneous urination and a residual urine volume <50 mL was measured. RESULTS: The median number of acupuncture treatment sessions was 3 (range, 1-12 times). Acupuncture treatment significantly reduced the PVR (545.1 ± 23.9 mL vs 67.4 ± 10.7 mL; p < 0.001). Among the 113 patients, 99 (87.6%) patients were cured and 8 (7.1%) patients were improved of their urinary retention. The remaining 6 (5.3%) patients' urinary retention did not improve. The effective rate was 94.7%. There was significant difference in the efficacy rate between patients with one urinary catheterization and with two or more. Acupuncture treatment was not associated with side effects. CONCLUSION: Acupuncture is an effective and safe treatment option for urinary retention. Early application of acupuncture treatment should be considered in clinic, and repeated urinary catheter insertion and removal should be avoided. Our study suggests that a randomized controlled study with a large sample size to verify the efficacy of acupuncture for the treatment of urinary retention is warranted.
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Alisma orientale (Sam.) Juzep (A. orientale) is an important medicinal plant in traditional Chinese medicine. In this study, de novo RNA-seq of A. orientale was performed based on the cDNA libraries from four different tissues, roots, leaves, scapes and inflorescences. A total of 41,685 unigenes were assembled, 25,024 unigene functional annotations were obtained by searching against the five public sequence databases, and 3,411 simple sequence repeats in A. orientale were reported for the first time. 15,402 differentially expressed genes were analysed. The morphological characteristics showed that compared to the other tissues, the leaves had more chlorophyll, the scapes had more vascular bundles, and the inflorescences contained more starch granules and protein. In addition, the metabolic profiles of eight kinds of alisols metabolite profiling, which were measured by ultra-Performance liquid chromatography-triple quadrupole-mass spectrometry showed that alisol B 23-acetate and alisol B were the major components of the four tissues at amounts of 0.068~0.350 mg/g and 0.046~0.587 mg/g, respectively. In addition, qRT-PCR validated that farnesyl pyrophosphate synthase and 3-hydroxy-3-methylglutaryl-CoA reductase should be considered the critical candidate genes involved in alisol biosynthesis. These transcriptome and metabolic profiles of A. orientale may help clarify the molecular mechanisms underlying the medicinal characteristics of A. orientale.
Assuntos
Alisma/genética , Alisma/metabolismo , Inflorescência/crescimento & desenvolvimento , Metabolômica , Plantas Medicinais/genética , Plantas Medicinais/metabolismo , Transcriptoma/genética , Colestenonas/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Ontologia Genética , Modelos Lineares , Repetições de Microssatélites/genética , Anotação de Sequência Molecular , Folhas de Planta/anatomia & histologia , Folhas de Planta/metabolismo , Raízes de Plantas/anatomia & histologia , Raízes de Plantas/metabolismo , Reprodutibilidade dos Testes , Triterpenos/metabolismoRESUMO
The accumulation of dysfunctional mitochondria induced by the impairment of the autophagy-lysosome pathway (ALP), especially mitophagy is an important cause of cerebral ischemia-reperfusion (I/R) injury. Electroacupuncture (EA) exerts remarkable effects in treating ischemic stroke; however, the detailed mechanism remains unclear. In this study, rats were treated with mitochondrial permeability transition pore (mPTP) opening inhibitor, peroxynitrite (ONOO-) scavenger, or selective inhibitor of mitophagy activation during 2-h middle cerebral artery occlusion (MCAO) followed by 24â¯h of reperfusion in combination with EA treatment. RNA-Seq analysis showed that EA treatment in cerebral I/R was linked to the autophagosome, the PI3K/Akt signaling pathway and metabolic pathways. We found that I/R resulted in significantly mitochondrial function impairments including decreased mitochondrial membrane potential (MMP) and ATP levels, aggregation of damaged mitochondria, excessive nitro/oxidative stress, PI3K/Akt/mTOR-mediated ALP dysfunction and deficiency of Pink1/Parkin-mediated mitophagy clearance. The treatment with EA, cyclosporine-A (CsA, a potent inhibitor of mPTP opening) or FeTMPyP (a type of ONOO- scavenger) could significantly increase MMP and/or ATP levels, improve mitochondrial function and decrease neuronal injury. At the same time, EA also improved ALP dysfunction and the deficiency of mitophagy clearance; however, mitochondrial division inhibitor-1 (Mdivi-1, a selective inhibitor of mitophagy activation) blocked mitophagy clearance and aggravated neuronal injury. Taken together, EA ameliorates nitro/oxidative stress-induced mitochondrial functional damage and decreases the accumulation of damaged mitochondria via Pink1/Parkin-mediated mitophagy clearance to protect cells against neuronal injury in cerebral I/R.
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Eletroacupuntura , Infarto da Artéria Cerebral Média/terapia , Neurônios/metabolismo , Proteínas Quinases/metabolismo , Traumatismo por Reperfusão/terapia , Ubiquitina-Proteína Ligases/metabolismo , Animais , Cérebro/metabolismo , Cérebro/patologia , Masculino , Mitocôndrias/metabolismo , Mitofagia , Ratos Sprague-Dawley , Transdução de Sinais/fisiologiaRESUMO
Chemotherapy has been widely used for treatment to malignant cancer, such as hepatocellular carcinoma (HCC). Chemotherapeutic effect was not often efficient to achieve totally tumor ablation due to the poor cellular uptake and drug resistance. To address these problems, a novel nanoplatform was constructed based on nontoxic mesoporous silica nanoparticles (MSNs) for a combined chemo/photothermal therapy to enhance tumor cell accumulation and promote toxicity of chemotherapeutic drugs. Prepared MSNs were consisted of Au nanoshell for photothermal conversion and a first-line anti-HCC drug-sorafenib (SO) for chemotherapy. The SO-Au-MSNs could help SO accumulate more in hepatic cancer cells. Under near infrared irradiation, SO-Au-MSNs exerted a high cell inhibition rate which could be attributed to the enhanced toxicity of SO under hyperthermia and synergistic chemo/photothermal therapy. SO-Au-MSNs showed a good compatibility as well as efficient cell cytotoxicity. Overall, SO-Au-MSNs would be a promising candidate for further enhancing the antitumor effect on HCC.
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Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/terapia , Portadores de Fármacos/química , Hipertermia Induzida/métodos , Neoplasias Hepáticas/terapia , Terapia com Luz de Baixa Intensidade/métodos , Antineoplásicos/farmacocinética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Terapia Combinada/métodos , Composição de Medicamentos , Liberação Controlada de Fármacos/efeitos da radiação , Ouro/química , Humanos , Hipertermia Induzida/instrumentação , Lasers , Neoplasias Hepáticas/patologia , Terapia com Luz de Baixa Intensidade/instrumentação , Nanopartículas Metálicas/química , Porosidade , Dióxido de Silício/química , Sorafenibe/administração & dosagem , Sorafenibe/farmacocinéticaRESUMO
To research the correlation between accumulation of triterpenoids and expression of key enzymes genes in triterpenoid biosynthesis of Alisma orientale,the study utilized UPLC-MS/MS method to detect eight triterpenoids content in the tuber of A. orientale from different growth stages,including alisol A,alisol A 24 acetate,alisol B,alisol B 23 acetate,alisol C 23 acetate,alisol F,alisol F 24 acetate and alisol G,and then the Real time quantitative PCR was used to analyze the expression of key enzymes genes HMGR and FPPS in triterpenoid biosynthesis. Correlation analysis showed that there was a significant positive relation between the total growth of these eight triterpenoids and the average relative expression of HMGR and FPPS(HMGR: r = 0. 998,P<0. 01; FPPS: r = 0. 957,P<0. 05),respectively. Therefore,the study preliminarily determined that HMGR and FPPS genes could regulate the biosynthesis of triterpenoids in A. orientale,which laid a foundation for further research on the biosynthesis and regulation mechanism of triterpenoids in A. orientale.
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Alisma/química , Alisma/genética , Geraniltranstransferase/genética , Triterpenos/análise , Cromatografia Líquida , Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/genética , Compostos Fitoquímicos/análise , Extratos Vegetais , Proteínas de Plantas/genética , Tubérculos/química , Espectrometria de Massas em TandemRESUMO
In plants, pollen grain transfers the haploid male genetic material from anther to stigma, both between flowers (cross-pollination) and within the same flower (self-pollination). In order to better understand chemical hybridizing agent (CHA) SQ-1-induced pollen abortion in wheat, comparative cytological and proteomic analyses were conducted. Results indicated that pollen grains underwent serious structural injury, including cell division abnormality, nutritional deficiencies, pollen wall defect and pollen grain malformations in the CHA-SQ-1-treated plants, resulting in pollen abortion and male sterility. A total of 61 proteins showed statistically significant differences in abundance, among which 18 proteins were highly abundant and 43 proteins were less abundant in CHA-SQ-1 treated plants. 60 proteins were successfully identified using MALDI-TOF/TOF mass spectrometry. These proteins were found to be involved in pollen maturation and showed a change in the abundance of a battery of proteins involved in multiple biological processes, including pollen development, carbohydrate and energy metabolism, stress response, protein metabolism. Interactions between these proteins were predicted using bioinformatics analysis. Gene ontology and pathway analyses revealed that the majority of the identified proteins were involved in carbohydrate and energy metabolism. Accordingly, a protein-protein interaction network involving in pollen abortion was proposed. These results provide information for the molecular events underlying CHA-SQ-1-induced pollen abortion and may serve as an additional guide for practical hybrid breeding.
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Infertilidade das Plantas , Pólen/genética , Proteoma/metabolismo , Triticum/genética , Estresse Oxidativo , Pólen/crescimento & desenvolvimento , Pólen/metabolismo , Proteoma/genética , Triticum/fisiologiaRESUMO
Systemic lupus erythematosus (SLE) constitutes an autoimmune disease characterized by the breakdown of tolerance to self-antigens, sustained production of pathogenic autoantibodies, and damage to multiple organs and tissues. Nanoparticle (NP)-based therapeutics have demonstrated efficacy in attenuating the progression of SLE. However, investigations of nano-drugs that address the crucial initiating factor in the pathogenesis of SLE; e.g., inefficient clearance of apoptotic cells by phagocytes and consequent accumulation of self-antigens, have seldom been reported. Here, an apoptotic cell-mimicking gold nanocage (AuNC)-based nano drug carrier capable of correcting the impaired clearance of apoptotic cells in SLE was rationally designed and generated by conjugating phosphatidylserine (PS) on the surface of liposome-coated AuNCs for liver X receptor (LXR) agonist T0901317 delivery. Notably, PS-lipos-AuNC@T0901317 could efficiently enhance apoptotic cell clearance by elevating the expression of Mer, one of the pivotal phagocytosis-associated receptors on macrophages, resulting in decreased production of anti-dsDNA autoantibodies, reduced inflammatory response, and alleviation of kidney damage in lupus model mice. Additionally, PS-lipos-AuNC could be tracked by photoacoustic imaging for nano drug carrier biodistribution. By addressing the crucial pathogenic factor of SLE, the NP-based delivery system in this study is envisioned to provide a promising strategy to treat this complex and challenging disease.
Assuntos
Apoptose , Sistemas de Liberação de Medicamentos , Ouro/administração & dosagem , Hidrocarbonetos Fluorados/administração & dosagem , Receptores X do Fígado/agonistas , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Nanocápsulas/administração & dosagem , Sulfonamidas/administração & dosagem , Animais , Autoanticorpos/análise , Citocinas/metabolismo , Progressão da Doença , Avaliação Pré-Clínica de Medicamentos , Feminino , Ouro/farmacocinética , Hidrocarbonetos Fluorados/uso terapêutico , Hidrocarbonetos Fluorados/toxicidade , Lipossomos/administração & dosagem , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos MRL lpr , Fosfatidilserinas , Sulfonamidas/uso terapêutico , Sulfonamidas/toxicidade , Distribuição Tecidual , c-Mer Tirosina Quinase/biossíntese , c-Mer Tirosina Quinase/genéticaRESUMO
It is well-known that anaerobic treatment has been considered as a utility process to accumulate γ-aminobutyric acid (GABA) in tea leaves. In this article, the nonvolatile differential compounds in picked-tea leaves between filled-N2 treatment and filled-CO2 treatment were compared in metabolic profiles and dynamic changes via ultrahigh performance liquid chromatography linked to a hybrid quadrupole orthogonal time-of-flight mass spectrometer (UPLC-Q-TOF-MS). Multivariate analysis and heat map of hierarchical clustering analysis indicated that filled-N2 treatment resulted in a wider range of metabolic perturbation than filled-CO2 treatment, but GABA accumulates faster and more significantly under filled-CO2 treatment than other treatment. The differential metabolites in anaerobic treatment were mainly reflected in the levels of glucose metabolism and amino acid metabolism, and the main differential pathway included the glyoxylate metabolism pathway, galactose metabolism, and phenylalanine metabolism. These metabolomic analyses were also evaluated to illuminate the physiological adaptive strategies of tea adopted to tolerate certain anaerobic stress types.