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Diabetic nephropathy(DN), a progressive chronic kidney disease(CKD) induced by diabetes mellitus, is the main cause of end-stage renal disease. Renal interstitial fibrosis(RIF) is an irreversible factor in the progression and deterioration of the renal function in DN. Chronic inflammation has become a key link in the pathogenesis of DN-RIF. The NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome is an important inflammatory regulator regulated by a variety of signals. It promotes the production of pro-inflammatory cytokines and induces renal inflammatory cell infiltration to participate in the process of renal fibrosis, demonstrating a complex mechanism of action. In view of the important role of NLRP3 inflammasomes in the prevention and treatment of DN-RIF, a large number of experimental studies have demonstrated that traditional Chinese medicine(TCM) can reduce the inflammation by regulating the pathways involving NLRP3 inflammasome, thereby slowing down the progression of DN-RIF and improving the renal function. This paper reviews the relationship between NLRP3 inflammasomes and DN-RIF, and the research progress in the mechanism of TCM intervention in NLRP3 inflammasomes to alleviate DN-RIF, aiming to provide new ideas for the targeted treatment of DN-RIF.
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Diabetes Mellitus , Nefropatías Diabéticas , Humanos , Inflamasomas/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Medicina Tradicional China , Inflamación/metabolismo , FibrosisRESUMEN
INTRODUCTION: Renowned for its role in traditional Chinese medicine, Panax notoginseng exhibits healing properties including bidirectional regulatory effects on hematological system diseases. However, the presence of nodular structures near the top of the main root, known as nail heads, may impact the quality of the plant's valuable roots. OBJECTIVES: In this paper, we aim to systematically analyze nail heads to identify their potential correlation with P. notoginseng quality. Additionally, we will investigate the molecular mechanisms behind nail head development. METHODS: Morphological characteristics and anatomical features were analyzed to determine the biological properties of nail heads. Active component analysis and MALDI mass spectrometry imaging (MALDI-MSI) were performed to determine the correlation between nail heads and P. notoginseng quality. Phytohormone quantitation, MALDI-MSI, RNA-seq, and Arabidopsis transformation were conducted to elucidate the mechanisms of nail head formation. Finally, protein-nucleic acid and protein-protein interactions were investigated to construct a transcriptional regulatory network of nodule development and quality formation. RESULTS: Our analyses have revealed that nail heads originate from an undeveloped lateral root. The content of ginsenosides was found to be positively associated with the amount of nail heads. Ginsenoside Rb1 specifically accumulated in the cortex of nail heads, while IAA, tZR and JAs also showed highest accumulation in the nodule. RNA-seq analysis identified PnIAA14 and PnCYP735A1 as inhibitors of lateral root development. PnMYB31 and PnMYB78 were found to form binary complexes with PnbHLH31 to synergistically regulate the expression of PnIAA14, PnCYP735A1, PnSS, and PnFPS. CONCLUSION: Our study details the major biological properties of nodular structures in P. notoginseng and outlines their impact on the quality of the herb. It was also determined that PnMYB31- and PnMYB78-PnbHLH31 regulate phytohormones and ginsenosides accumulation, further affecting plant development and quality. This research provides insights for quality evaluation and clinical applications of P. notoginseng.
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PURPOSE: XinJiaCongRongTuSiZiWan (XJCRTSZW) is a traditional Chinese medicine compound for invigorating the kidney, nourishing blood, and promoting blood circulation. This study aimed to explore the effect of XJCRTSZW on triptolide (TP)-induced oxidative stress injury. METHODS: Adult female Sprague-Dawley rats and human ovarian granulosa cell lines were treated with TP and XJCRTSZW. Hematoxylin and eosin staining, enzyme-linked immunosorbent assay, flow cytometry, CCK-8, JC-1 staining, transmission electron microscopy, reverse transcription-quantitative polymerase chain reaction, and Western blotting were performed in this study. RESULTS: XJCRTSZW treatment observably ameliorated the TP-induced pathological symptoms. Furthermore, XJCRTSZW treatment observably enhanced the TP-induced reduction of estradiol, anti-Mullerian hormone, progesterone, superoxide dismutase, ATP content, mitochondrial membrane potential, p62, and Hsp60 mRNA, and protein levels in vivo and in vitro (p < 0.05). However, TP-induced elevation of follicle stimulating hormone and luteinizing hormone concentrations, malondialdehyde levels, reactive oxygen species levels, apoptosis rate, mitophagy, and the mRNA and protein expressions of LC3-II/LC3-I, PTEN-induced kinase 1 (PINK1), and Parkin were decreased (p < 0.05). In addition, XJCRTSZW treatment markedly increased cell viability in vitro (p < 0.05). CONCLUSIONS: XJCRTSZW protects TP-induced rats from oxidative stress injury via the mitophagy-mediated PINK1/Parkin pathway.
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Diterpenos , Mitocondrias , Mitofagia , Fenantrenos , Adulto , Ratas , Femenino , Humanos , Animales , Ratas Sprague-Dawley , Estrés Oxidativo , Ubiquitina-Proteína Ligasas , Transducción de Señal , Proteínas Quinasas/metabolismo , Proteínas Quinasas/farmacología , ARN Mensajero/metabolismo , Compuestos EpoxiRESUMEN
BACKGROUND: Anthocyanins are the most important compounds for nutritional quality and economic values of blood orange. However, there are few reports on the pre-harvest treatment accelerating the accumulation of anthocyanins in postharvest blood orange fruit. Here, we performed a comparative transcriptome and metabolomics analysis to elucidate the underlying mechanism involved in seasonal drought (SD) treatment during the fruit expansion stage on anthocyanin accumulation in postharvest 'Tarocco' blood orange fruit. RESULTS: Our results showed that SD treatment slowed down the fruit enlargement and increased the sugar accumulation during the fruit development and maturation period. Obviously, under SD treatment, the accumulation of anthocyanin in blood orange fruit during postharvest storage was significantly accelerated and markedly higher than that in CK. Meanwhile, the total flavonoids and phenols content and antioxidant activity in SD treatment fruits were also sensibly increased during postharvest storage. Based on metabolome analysis, we found that substrates required for anthocyanin biosynthesis, such as amino acids and their derivatives, and phenolic acids, had significantly accumulated and were higher in SD treated mature fruits compared with that of CK. Furthermore, according to the results of the transcriptome data and weighted gene coexpression correlation network analysis (WGCNA) analysis, phenylalanine ammonia-lyase (PAL3) was considered a key structural gene. The qRT-PCR analysis verified that the PAL3 was highly expressed in SD treated postharvest stored fruits, and was significantly positively correlated with the anthocyanin content. Moreover, we found that other structural genes in the anthocyanin biosynthesis pathway were also upregulated under SD treatment, as evidenced by transcriptome data and qRT-PCR analysis. CONCLUSIONS: The findings suggest that SD treatment promotes the accumulation of substrates necessary for anthocyanin biosynthesis during the fruit ripening process, and activates the expression of anthocyanin biosynthesis pathway genes during the postharvest storage period. This is especially true for PAL3, which co-contributed to the rapid accumulation of anthocyanin. The present study provides a theoretical basis for the postharvest quality control and water-saving utilization of blood orange fruit.
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Antocianinas , Frutas , Frutas/metabolismo , Sequías , Antioxidantes/metabolismo , Perfilación de la Expresión GénicaRESUMEN
Drinking water treatment sludge (DWTS) is a by-product of water treatment, and it is difficult to recycle to high value and poses potential environmental risks. Recycling DWTS into cement-based materials is an effective measure to achieve its high-volume utilization and reduce its environmental load. DWTS is rich in silica-alumina phases and has potential pozzolanic activity after drying, grinding and calcination, giving it similar properties to traditional supplementary cementitious materials. Adjusting the sludge production process and coagulant type will change its physical and chemical properties. Adding a small amount of DWTS can generate additional hydration products and refine the pore structure of the cement sample, thus improving the mechanical properties and durability of the sample. However, adding high-volume DWTS to concrete causes microstructural deterioration, but it is feasible to use high-volume DWTS to produce artificial aggregates, lightweight concrete, and sintered bricks. Meanwhile, calcined DWTS has similar compositions to clay, which makes it a potential raw material for cement clinker production. Cement-based materials can effectively solidify heavy metal ions in DWTS, and alkali-activated binders, magnesium-based cement, and carbon curing technology can further reduce the risk of heavy metal leaching. This review provides support for the high-value utilization of DWTS in cement-based materials and the reduction of its potential environmental risks.
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Mineral licks are key ecological components of the Amazon rainforest, providing critical dietary functions for herbivorous and frugivorous mammals and birds, which help maintain the structure and function of the forest itself through seed and nutrient dispersal. One of the most frequent visitors of interior forest mineral licks in the Amazon is the red brocket deer (Mazama americana), a large-bodied ruminant frugivore and seed predator. While several hypotheses for the drivers of geophagy exist, including mineral supplementation, toxin adsorption, and habitat selection, robust data on geophagy for the red brocket deer for large numbers of mineral licks is nonexistent. We used soil data from 83 mineral licks in conjunction with camera trap data from 52 of those mineral licks and a mixed-effects modeling approach to test the three proposed hypotheses of geophagy for the red brocket deer. We found that consumed soils at mineral licks had elevated concentrations of almost all major and minor biologically active minerals measured, including Ca, Na, Mg, K, Cu, Zn, and Mn. Model results suggest that all three hypotheses hold true to some extent for the red brocket deer, with the greatest support for the mineral supplementation hypothesis, in particular with respect to Mg, Ca, Na, Cu, and Zn. This study provides critical information on the feeding ecology of the red brocket deer in the wild, and the first robust analysis of geophagy of an Amazonian mammal involving a large sample size of interior forest mineral licks.
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BACKGROUND: Nitrogen (N) metabolism-related key genes and conserved amino acid sites in key enzymes play a crucial role in improving N use efficiency (NUE) under N stress. However, it is not clearly known about the molecular mechanism of N deficiency-induced improvement of NUE in the N-sensitive rhizomatous medicinal plant Panax notoginseng (Burk.) F. H. Chen. To explore the potential regulatory mechanism, the transcriptome and proteome were analyzed and the three-dimensional (3D) information and molecular docking models of key genes were compared in the roots of P. notoginseng grown under N regimes. RESULTS: Total N uptake and the proportion of N distribution to roots were significantly reduced, but the NUE, N use efficiency in biomass production (NUEb), the recovery of N fertilizer (RNF) and the proportion of N distribution to shoot were increased in the N0-treated (without N addition) plants. The expression of N uptake- and transport-related genes NPF1.2, NRT2.4, NPF8.1, NPF4.6, AVP, proteins AMT and NRT2 were obviously up-regulated in the N0-grown plants. Meanwhile, the expression of CIPK23, PLC2, NLP6, TCP20, and BT1 related to the nitrate signal-sensing and transduction were up-regulated under the N0 condition. Glutamine synthetase (GS) activity was decreased in the N-deficient plants, while the activity of glutamate dehydrogenase (GDH) increased. The expression of genes GS1-1 and GDH1, and proteins GDH1 and GDH2 were up-regulated in the N0-grown plants, there was a significantly positive correlation between the expression of protein GDH1 and of gene GDH1. Glu192, Glu199 and Glu400 in PnGS1 and PnGDH1were the key amino acid residues that affect the NUE and lead to the differences in GDH enzyme activity. The 3D structure, docking model, and residues of Solanum tuberosum and P. notoginseng was similar. CONCLUSIONS: N deficiency might promote the expression of key genes for N uptake (genes NPF8.1, NPF4.6, AMT, AVP and NRT2), transport (NPF1.2 and NRT2.4), assimilation (proteins GS1 and GDH1), signaling and transduction (genes CIPK23, PLC2, NLP6, TCP20, and BT1) to enhance NUE in the rhizomatous species. N deficiency might induce Glu192, Glu199 and Glu400 to improve the biological activity of GS1 and GDH, this has been hypothesized to be the main reason for the enhanced ability of N assimilation in N-deficient rhizomatous species. The key genes and residues involved in improving NUE provide excellent candidates for the breeding of medicinal plants.
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Panax notoginseng , Plantas Medicinales , Nitrógeno/metabolismo , Plantas Medicinales/genética , Plantas Medicinales/metabolismo , Panax notoginseng/genética , Panax notoginseng/metabolismo , Simulación del Acoplamiento Molecular , Fitomejoramiento , Aminoácidos/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Contaminants such as microplastics (MPs) and heavy metals are commonly found in soils, both of which are extremely difficult to degrade and can easily form compound contamination, altering the physicochemical properties of the soil and thus potentially changing the growth and physiological and ecological characteristics of plants. In order to study the effects of the combined contamination of soil MPs and heavy metals on soil properties and plant growth, polystyrene microplastics (PS-MPs) with a particle size of 3 µm and the heavy metal cadmium were selected in the study. The changes in the physicochemical properties of soil and their effects on lettuce (Lactuca sativa) seed germination and seedling growth were studied at various exposure concentrations of PS-MPs (0, 10, 50, 100, 200, and 400 mg·kg-1) and combined with different Cd contamination concentrations (0, 1.2, and 6.0 mg·kg-1), respectively. The results showed that soil organic matter (SOM), available phosphorus (AP), alkali-hydrolysable nitrogen (AHN), and available kalium (AK) showed significant decreases as the intensity of PS-MPs combined with Cd contamination increased. Simultaneously, PS-MPs combined with Cd contamination also significantly reduced the germination rate of lettuce seeds, but low concentrations of PS-MPs slowed down the effect of Cd (6.0 mg·kg-1) contamination on lettuce seeds, and high concentrations of PS-MPs enhanced the effect of Cd (6.0 mg·kg-1). The fresh weight, dry weight, and plant height of lettuce seedlings showed an increasing and then decreasing trend with increasing exposure to PS-MPs. Chlorophyll content, superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) showed a decreasing trend, whereas malondialdehyde (MDA) content showed an overall increasing trend under different Cd concentrations. The main physicochemical indicators of the soil were negatively correlated with MDA of lettuce seedlings, whereas other indicators of the seedlings were positively correlated. The combined contamination of PS-MPs and Cd could affect the germination of plant seeds and the physiological and ecological characteristics of seedlings by changing the physicochemical properties of the soil. Both exposure to single PS-MPs contaminants and the combination of PS-MPs with Cd inhibited the germination of lettuce seeds and affected the physiological activities of their seedlings, and the inhibition was significantly increased with increasing exposure. Low exposure to PS-MPs or the combination of PS-MPs with Cd contamination exhibited a promotive effect on lettuce seedling growth. High exposure to PS-MPs combined with Cd contamination exhibited significant ecological effects on lettuce seedlings, and high exposure to PS-MPs exacerbated the ecotoxicological effects of Cd contaminants on lettuce seedlings, and PS-MPs and Cd exhibited synergistic effects. The results can provide some reference for assessing the ecological effects of MPs and heavy metal pollution in soil-plant systems.
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Metales Pesados , Contaminantes del Suelo , Cadmio/toxicidad , Cadmio/metabolismo , Microplásticos , Lactuca , Plásticos , Poliestirenos , Suelo , Metales Pesados/metabolismo , Plantones , Contaminantes del Suelo/análisisRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and arthritic pain. Sinomenine (SIN), derived from the rhizome of Chinese medical herb Qing Teng (scientific name: Sinomenium acutum (Thunb.) Rehd. Et Wils), has a longstanding use in Chinese traditional medicine for treating rheumatoid arthritis. It has been shown to possess anti-inflammatory, analgesic, and immunosuppressive effects with minimal side-effects clinically. However, the mechanisms governing its effects in treatment of joint pathology, especially on fibroblast-like synoviocytes (FLSs) dysfunction, and arthritic pain remains unclear. AIM: This study aimed to investigate the effect and underlying mechanism of SIN on arthritic joint inflammation and joint FLSs dysfunctions. MATERIALS AND METHODS: Collagen-induced arthritis (CIA) was induced in rats and the therapeutic effects of SIN on joint pathology were evaluated histopathologically. Next, we conducted a series of experiments using LPS-induced FLSs, which were divided into five groups (Naïve, LPS, SIN 10, 20, 50 µg/ml). The expression of inflammatory factors was measured by qPCR and ELISA. The invasive ability of cells was detected by modified Transwell assay and qPCR. Transwell migration and cell scratch assays were used to assess the migration ability of cells. The distribution and content of relevant proteins were observed by immunofluorescence and laser confocal microscopy, as well as Western Blot and qPCR. FLSs were transfected with plasmids (CRMP2 T514A/D) to directly modulate the post-translational modification of CRMP2 protein and downstream effects on FLSs function was monitored. RESULTS: SIN alleviated joint inflammation in rats with CIA, as evidenced by improvement of synovial hyperplasia, inflammatory cell infiltration and cartilage damage, as well as inhibition of pro-inflammatory cytokines release from FLSs induced by LPS. In vitro studies revealed a concentration-dependent suppression of SIN on the invasion and migration of FLSs induced by LPS. In addition, SIN downregulated the expression of cellular CRMP2 that was induced by LPS in FLSs, but increased its phosphorylation at residue T514. Moreover, regulation of pCRMP2 T514 by plasmids transfection (CRMP2 T514A/D) significantly influenced the migration and invasion of FLSs. Finally, SIN promoted nuclear translocation of pCRMP2 T514 in FLSs. CONCLUSIONS: SIN may exert its anti-inflammatory and analgesic effects by modulating CRMP2 T514 phosphorylation and its nuclear translocation of FLSs, inhibiting pro-inflammatory cytokine release, and suppressing abnormal invasion and migration. Phosphorylation of CRMP2 at the T514 site in FLSs may present a new therapeutic target for treating inflammatory joint's destruction and arthritic pain in RA.
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Artritis Experimental , Artritis Reumatoide , Morfinanos , Sinoviocitos , Ratas , Animales , Fosforilación , Lipopolisacáridos/farmacología , Movimiento Celular , Artritis Reumatoide/patología , Inflamación/tratamiento farmacológico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antiinflamatorios/metabolismo , Citocinas/metabolismo , Antiinflamatorios no Esteroideos/farmacología , Artritis Experimental/inducido químicamente , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/metabolismo , Fibroblastos , Dolor/tratamiento farmacológico , Células Cultivadas , Proliferación CelularRESUMEN
BACKGROUND: Atrial fibrillation (AF) increases risk of embolic stroke, and in postoperative patients, increases cost of care. Consequently, ECG screening for AF in high-risk patients is important but labor-intensive. Artificial intelligence (AI) may reduce AF detection workload, but AI development presents challenges. METHODS AND RESULTS: We used a novel approach to AI development for AF detection using both surface ECG recordings and atrial epicardial electrograms obtained in postoperative cardiac patients. Atrial electrograms were used only to facilitate establishing true AF for AI development; this permitted the establishment of an AI-based tool for subsequent AF detection using ECG records alone. A total of 5 million 30-second epochs from 329 patients were annotated as AF or non-AF by expert ECG readers for AI training and validation, while 5 million 30-second epochs from 330 different patients were used for AI testing. AI performance was assessed at the epoch level as well as AF burden at the patient level. AI achieved an area under the receiver operating characteristic curve of 0.932 on validation and 0.953 on testing. At the epoch level, testing results showed means of AF detection sensitivity, specificity, negative predictive value, positive predictive value, and F1 (harmonic mean of positive predictive value and sensitivity) as 0.970, 0.814, 0.976, 0.776, and 0.862, respectively, while the intraclass correlation coefficient for AF burden detection was 0.952. At the patient level, AF burden sensitivity and positive predictivity were 96.2% and 94.5%, respectively. CONCLUSIONS: Use of both atrial electrograms and surface ECG permitted development of a robust AI-based approach to postoperative AF recognition and AF burden assessment. This novel tool may enhance detection and management of AF, particularly in patients following operative cardiac surgery.
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Fibrilación Atrial , Humanos , Fibrilación Atrial/diagnóstico , Inteligencia Artificial , Técnicas Electrofisiológicas Cardíacas , Electrocardiografía/métodos , HospitalesRESUMEN
BACKGROUND AND AIM: Fecal microbiota transplantation (FMT) has been shown to positively affect the treatment of inflammatory bowel disease (IBD). However, the safety and efficacy of FMT may depend on the route of microbiota delivery. This study investigates the acceptance, satisfaction, and selection preference of a new delivery route, transendoscopic enteral tubing (TET), for treating IBD. METHODS: A survey was conducted among patients with IBD from five medical centers across China. The objective was to assess their acceptance, subjective feelings, and major concerns regarding two types of TET: colonic TET and mid-gut TET. In addition, the survey also analyzed the factors affecting the selection of TET and TET types among these patients. RESULTS: The final analysis included 351 questionnaires. Up to 76.6% of patients were willing to accept TET and preferred to choose colonic TET when they first learned about TET. Patients with longer disease duration, history of enema therapy, or enteral nutrition were more open to considering TET among IBD patients. After treatment, 95.6% of patients were satisfied with TET, including colonic TET (95.9%) and mid-gut TET (95.1%). Patients with a history of enema therapy and ulcerative colitis preferred colonic TET. In contrast, those with a history of enteral nutrition and Crohn's disease were willing to choose mid-gut TET. However, some patients hesitated to accept TET due to concerns about efficacy, safety, and cost. CONCLUSIONS: TET was highly accepted and satisfied patients with IBD. Disease type and combination therapy influenced the choice of colonic or mid-gut TET.
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Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Trasplante de Microbiota Fecal/efectos adversos , Enfermedades Inflamatorias del Intestino/terapia , Enfermedades Inflamatorias del Intestino/etiología , Enfermedad de Crohn/terapia , Enfermedad de Crohn/etiología , Colitis Ulcerosa/terapia , Satisfacción PersonalRESUMEN
Purpose: XinJiaCongRongTuSiZiWan (XJCRTSZW) is a traditional Chinese medicine compound for invigorating the kidney, nourishing blood, and promoting blood circulation. This study aimed to explore the effect of XJCRTSZW on triptolide (TP)-induced oxidative stress injury. Methods: Adult female Sprague-Dawley rats and human ovarian granulosa cell lines were treated with TP and XJCRTSZW. Hematoxylin and eosin staining, enzyme-linked immunosorbent assay, flow cytometry, CCK-8, JC-1 staining, transmission electron microscopy, reverse transcription-quantitative polymerase chain reaction, and Western blotting were performed in this study. Results: XJCRTSZW treatment observably ameliorated the TP-induced pathological symptoms. Furthermore, XJCRTSZW treatment observably enhanced the TP-induced reduction of estradiol, anti-Mullerian hormone, progesterone, superoxide dismutase, ATP content, mitochondrial membrane potential, p62, and Hsp60 mRNA, and protein levels in vivo and in vitro (p < 0.05). However, TP-induced elevation of follicle stimulating hormone and luteinizing hormone concentrations, malondialdehyde levels, reactive oxygen species levels, apoptosis rate, mitophagy, and the mRNA and protein expressions of LC3-II/LC3-I, PTEN-induced kinase 1 (PINK1), and Parkin were decreased (p < 0.05). In addition, XJCRTSZW treatment markedly increased cell viability in vitro (p < 0.05). Conclusions: XJCRTSZW protects TP-induced rats from oxidative stress injury via the mitophagy-mediated PINK1/Parkin pathway.
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Animales , Ratas , Heridas y Lesiones , Estrés Oxidativo , Mitofagia , Animales de Laboratorio , Medicina Tradicional ChinaRESUMEN
OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Zusanli"(ST36) on intestinal mucosal damage, intestinal mucosal oxidative stress injury and apoptosis induced by 5-fluorouraeil (5-FU) chemotherapy in colorectal cancer-bearing mice. METHODS: Thirty male BALB/c mice were randomly divided into normal control, colorectal cancer (CT26), 5-FU, non-acupoint and ST36 groups, with 6 mice in each group. Except for those of the normal control group, mice of the remaining 4 groups received subcutaneous implantation of colorectal CT26 cell suspension (0.1 mL) in the right armpit for establishing colorectal cancer model. Rats of the 5-FU group, non-acupoint group and ST36 group were given with 5 mg/mL 5-FU solution once every 3 days for a total of 21 days. For mice of the non-acupoint group and ST36 group, EA (2 Hz, 1-2 mA) was applied to bilateral ST36 or non-acupoints (the bilateral sunken spots about 3 mm to the midpoint between the tail root and the anus) for 5 min after each intraperitoneal infusion of 5-FU, once every 3 days, for a total of 21 days. After the intervention, the diarrhea index was assessed. The length of colon (from the endpoint of cecum to the anal orifice) was measured. Histopathological changes of colonic mucosa were observed by H.E. staining, and the length of colonic villi was measured. The content of malondialdehyde (MDA), and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of colonic tissue were detected by thibabituric acid, xanthine oxidase and colorimetric method, respectively. The rate of cell apoptosis in the colonic tissue was measured by TUNEL assay. The positive expressions of Bax and Bcl-2 in colonic tissue were determined by immunohistochemistry. RESULTS: The CT26 model group didn't show any significant changes in the diarrhea index, colon length, colon villus length, MDA content, SOD and GSH-Px activities, colonic cell apoptosis rate, and Bax and Bcl-2 expression levels when compared with the normal group. Compared with the CT26 group, the 5-FU group had a remarkable increase in the diarrhea index, MDA content, colonic cell apoptosis rate and Bax expression level (P<0.01, P<0.05), and a marked decrease in the colon length, colon villus length, SOD and GSH-Px activities and Bcl-2 expression level (P<0.01), suggesting the side effects of administration of 5-FU. Compared with the 5-FU group, the diarrhea index, MDA content, colonic cell apoptosis rate and Bax expression level were markedly decreased (P<0.05, P<0.01) and those of the colon length, colon villus length, SOD and GSH-Px activities and Bcl-2 expression level were obviously increased (P<0.01) in the ST36 group. Compared with the 5-FU group, the non-acupoint group also had an increase in the colon villus length, SOD and GSH-Px activities (P<0.01, P<0.05) and a decrease in the cell apoptosis rate (P<0.01). CONCLUSIONS: EA at ST36 has a positive effect in reducing intestinal mucosal damage induced by 5-FU chemotherapy in cancer-bearing mice, which may be related to its function in relieving oxidative stress injury and inhibiting apoptosis of colonic tissue.
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Neoplasias del Colon , Neoplasias Colorrectales , Electroacupuntura , Ratas , Masculino , Ratones , Animales , Proteína X Asociada a bcl-2/metabolismo , Puntos de Acupuntura , Estrés Oxidativo , Apoptosis , Superóxido Dismutasa/metabolismo , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Diarrea , Fluorouracilo/efectos adversosRESUMEN
Background: Although the level of medical care has been improved in recent years, the probability of patients contracting pathogens has increased greatly, with a rising incidence of invasive fungal infections. Deep-seated fungi have become common pathogens of nosocomial infections. Objective: This study aims to systematically assess the effectiveness, mortality, survival rate, and adverse reactions (ARs) of high-dose (HD) liposomal amphotericin B (L-AMB) for human diseases. Methods: Ten articles (1661 patients) of randomized controlled trials (RCTs; whether randomized, single-blind, or double-blind) from January 1, 1960, to December 31, 2020, of HD-L-AMB treatment of diseases were retrieved from the PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases. The primary outcome measure was the overall therapeutic effect, and the secondary outcome measures were mortality, ≥10-week survival, and ARs. Data were meta-analyzed using RevMan 5.3. Results: Ten RCTs involving 1661 patients were included. HD-L-AMB did not show a significant therapeutic advantage in anti-infection treatment. In addition, HD-L-AMB treatment of invasive Aspergillus infection led to high mortality and low survival (≥10 weeks, OR = 0.57, 95%CI 0.34-0.94, P = .03). According to subgroup analysis, the incidence of ARs and the incidence of renal dysfunction associated with invasive fungal infection treatment were higher with HD-L-AMB than with regular-dose L-AMB. Conclusion: HD-L-AMB had no obvious advantage for the treatment of diseases and was accompanied by increased mortality, reduced long-term survival, and increased ARs (including renal insufficiency). Therefore, the use of HD-L-AMB to control infections is recommended with caution only when the preferred treatment is contraindicated.
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This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 µm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 â, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 µL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 µmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.
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Asteraceae , Medicamentos Herbarios Chinos , Neoplasias Pulmonares , Humanos , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/química , Asteraceae/química , Neoplasias Pulmonares/tratamiento farmacológicoRESUMEN
BACKGROUND: Asperosaponin VI (AVI) is a natural triterpenoid saponin isolated from Dipsacus asper Wall with documented anti-inflammatory and bone protective effects. Our previous work reported that AVI protects the liver of septic mice from acute inflammatory damage. In this paper, we further explored the protective effect and the potential mechanisms of AVI in alcoholic fatty liver disease (AFLD). METHODS: The Lieber-Decarli model was constructed to evaluate the effect of AVI on AFLD in C57BL/6 J mice. Additional in vitro work was performed to investigate HepG2 cells exposed to alcohol, then analyzed the degree of liver injury by detecting the ALT and AST levels both in the liver and serum. H&E staining and Sirius red staining were used to evaluate the histopathology variations in the liver. Further, observe lipid droplets in the cytoplasm by Oil Red O staining. We detected the expression of inflammatory cytokines with qualitative PCR; ROS, MDA, SOD, and GSH-px levels were analyzed to observe oxidative stress. Finally, exploring the activation of AMPK signaling pathway by real-time PCR and Western blotting. RESULTS: Histological examination of liver tissue combined with serum ALT and AST levels showed a significant protective effect of AVI against alcoholic liver injury in AFLD mice. Compared with the model group, AVI evidently improved antioxidant capacity, reduced inflammatory response and lipid accumulation both in vitro and in vivo. For mechanically, it was found that AVI up-regulated phosphorylation level of AMP-activated protein kinase (AMPK) and inhibited the endoplasmic reticulum stress (ER) pathway in AFLD. CONCLUSION: AVI protects mice from alcohol-induced hepatic steatosis and liver injury through activating AMPK signaling and repress ER stress, suggesting that it might be a potential therapeutic agent for AFLD.
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Hígado Graso Alcohólico , Saponinas , Ratones , Animales , Hígado Graso Alcohólico/tratamiento farmacológico , Hígado Graso Alcohólico/patología , Metabolismo de los Lípidos , Proteínas Quinasas Activadas por AMP/metabolismo , Ratones Endogámicos C57BL , Hígado , Saponinas/metabolismo , Estrés Oxidativo , Estrés del Retículo EndoplásmicoRESUMEN
Artemisia absinthium, an important herb of the Artemisia genus, was evaluated in this study for its potential as an alternative to classical antibiotics. The antimicrobial activity of methanol extracts of A. absinthium (MEAA) was evaluated using the broth microdilution method, revealing that A. absinthium exhibited broad-spectrum antibacterial and antifungal activity. Ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS) was used to analyze the chemical profile of the MEAA, with a focus on flavonoids, quinic acids, and glucaric acids. A total of 90 compounds were identified, 69 of which were described for the first time in A. absinthium. Additionally, a new class of caffeoyl methyl glucaric acids was identified. The main active compounds were quantified and screened for antimicrobial activity. A. absinthium was found to be rich in quinic acids and flavonoids. The screening for antimicrobial activity also revealed that salicylic acid, caffeic acid, casticin, and 3,4-dicaffeoylquinic acid had varying degrees of antimicrobial activity. The acute toxicity of MEAA was examined following OECD guidelines. The administration of 5000 mg/kg bw of MEAA did not result in mortality in male and female mice. Furthermore, there were no observed effects on the visceral organs or general behavior of the mice, demonstrating the good safety of MEAA. This study provides new evidence for the use of A. absinthium as an alternative to classical antibiotics in addressing the problem of bacterial resistance.
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Artemisia absinthium , Artemisia , Masculino , Femenino , Animales , Ratones , Artemisia absinthium/química , Antibacterianos/farmacología , Cromatografía de Gases y Espectrometría de Masas , Artemisia/química , Fenoles/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/química , FlavonoidesRESUMEN
Four new δ- and γ-lactone derivatives, hyperelatolides A-D (1-4, respectively), were discovered from the aerial portions of Hypericum elatoides R. Keller. Their structures were elucidated by analysis of NMR spectra, HRESIMS, quantum chemical calculations of NMR and ECD spectra, and X-ray crystallographic data. Hyperelatolides A (1) and B (2) represent the first examples of δ-lactone derivatives characterized by a (Z)-(5,5-dimethyl-2-(2-oxopropyl)cyclohexylidene)methyl moiety and a benzoyloxy group attached to the ß- and γ-positions of the δ-lactone core, respectively, while hyperelatolides C (3) and D (4) are unprecedented γ-lactone derivatives featuring substituents similar to those of 1 and 2. All compounds were tested for their inhibitory effects on NO production in LPS-activated BV-2 cells. Lactones 1 and 2 exhibited considerable antineuroinflammatory activity, with IC50 values of 5.74 ± 0.27 and 7.35 ± 0.26 µM, respectively. Moreover, the mechanistic study revealed that lactone 1 significantly suppressed nuclear factor kappa B signaling and downregulated the expression of inducible nitric oxide synthase and cyclooxygenase-2 in LPS-induced cells, which may contribute to its antineuroinflammatory activity.
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Hypericum , Hypericum/química , Lipopolisacáridos/farmacología , Espectroscopía de Resonancia Magnética , Lactonas/farmacología , Lactonas/química , Transducción de Señal , Estructura Molecular , Óxido NítricoRESUMEN
OBJECTIVE: This study aimed to examine the effects of mindfulness-based stress reduction (MBSR) in patients with acute myocardial infarction (AMI) after primary percutaneous coronary intervention (PPCI). METHODS: A retrospective study was conducted with data collected from AMI patients who underwent successful PPCI. The study included 61 cases that received 8-week MBSR intervention (MBSR group) and 61 cases that received weekly health education (control group) over the same period. Outcome measures, including hemodynamic parameters, psychosocial characteristics [Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS), Perceived Social Support Scale (PSSS)], health-related quality of life [HRQoL, 7-item Seattle Angina Questionnaire (SAQ-7)], and major adverse cardiovascular events (MACE), were assessed at baseline (T1), post-intervention (T2), 1 month after the post-intervention (T3) and 3 months after the post-intervention (T4). RESULTS: Compared to the control group, the MBSR group showed improvements in blood pressure, specifically in systolic blood pressure (SBP) at T4, and diastolic blood pressure (DBP) at T3 and T4, and mean arterial blood pressure (MABP) at T3 and T4. Additionally, the MBSR group had lower scores of anxiety and perceived stress (HADS, PSS) and higher scores of perceived social support (PSSS) after the intervention. Furthermore, the MBSR group had higher scores on the SAQ-7 at all measurement points. The control group had a significantly higher total MACE rate compared to the MBSR group (26.23% vs. 9.84%). CONCLUSIONS: This study provides support for the potential benefits of MBSR as an adjunctive treatment for AMI patients undergoing PPCI.
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Atención Plena , Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Calidad de Vida/psicología , Estudios Retrospectivos , Estrés Psicológico/diagnóstico , Estrés Psicológico/terapia , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapia , Infarto del Miocardio/psicología , Intervención Coronaria Percutánea/efectos adversos , Resultado del TratamientoRESUMEN
Poria(Fu Ling) is a bulk traditional Chinese medicine(TCM)with a long history and complex varieties. The royal medical records of the Qing Dynasty include multiple medicinal materials of Fu Ling, such as Bai Fu Ling(white Poria), Chi Fu Ling(rubra Poria), and Zhu Fu Ling(Poria processed with cinnabaris). The Palace Museum preserves 6 kinds of specimens including Fu Ling Ge(dried Poria), Bai Fu Ling, Chi Fu Ling, Zhu Fu Ling, Bai Fu Shen(white Poria cum Radix Pini), and Fu Shen Mu(Poria cum Radix Pini). After trait identification and textual research, we found that Fu Ling Ge was an intact sclerotium, which was processed into Fu Ling Pi(Poriae Cutis), Bai Fu Ling and other medicinal materials in the Palace. The Fu Ling in the Qing Dynasty Pa-lace was mainly from the tribute paid of the officials in Yunnan-Guizhou region. The tribute situation was stable in the whole Qing Dynasty, and changed in the late Qing Dynasty. The cultural relics of Fu Ling in the Qing Dynasty Palace confirm with the archival documents such as the royal medical records and herbal medicine books, providing precious historical materials for understanding Fu Ling in the Qing Dynasty and a basis for the restoration of the processing of the Fu Ling in the Qing Dynasty Palace.