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Ganoderma lucidum (GL) is a mushroom that has been widely used in Asia for its immunostimulatory and anti-inflammatory capacity, which has been hypothesized to be attributed mainly to the recognition of its cell-surface patterns by cells of the immune system present in the gastrointestinal tract, resulting in a cascade of modulatory events. However, the nutraceutical properties of GL have not been tested in dogs. Forty adult beagles were used in a completely randomized design. The objective of the present study was to evaluate the effects of dietary inclusion of GL on peripheral blood mononuclear cells (PBMC; T cells, B cells, monocytes, and natural killers), vaccine response, nutrient digestibility, fecal fermentative end-products, and skin and coat quality of adult dogs. Dogs were fed a commercial dry extruded complete and balanced diet plus GL top-dressed daily upon feeding time. Four experimental treatments were used: 0% GL supplementation (control), 5 mg/kg BW of GL, 10 mg/kg BW of GL, or 15 mg/kg BW of GL. Following a 7 d adaptation to the control diet, dogs were fed their respective treatment diets for 28 d. They were challenged with vaccination of a modified live virus Canine Distemper, Adenovirus Type 1 (Hepatitis), Adenovirus Type 2, Parainfluenza, and Parvovirus and killed Rabies Virus on day 7 with blood collections on days 0, 14, and 28. The inclusion of GL in all dosages was well-accepted by all dogs, with no detrimental effect on macronutrient apparent total tract digestibility. There was a trend that the percentage of major histocompatibility II (MHC-II) from B cells was greater in dogs fed 15 mg/kg of GL (41.91%) compared to the control group (34.63%). The phagocytosis response tended to have treatment-by-time interaction among treatments; dogs fed 15 mg/kg of GL tended to have greater phagocytosis activity on day 28 than dogs from the control group and dogs fed 5 mg/kg of GL. The vaccine-specific serum immunoglobulin G (IgG) concentrations were higher in the group supplemented with 15 mg/kg of GL compared to treatment control 7 d after the vaccination for rabies. These data suggest that the inclusion of GL had no detrimental effects on any analyzed PBMC. Due to changes in immune parameters among treatments, GL may also exert beneficial immunostimulatory effects in healthy adult dogs when provided at a daily dose of 15 mg/ kg BW.
Ganoderma lucidum (GL) is a fungus from which products have become popular in the human food and health industry over the past decade. Due to this, a growing interest in using GL extracts in animal products has also developed. The current study investigated the nutritional properties of GL supplemented to adult beagles in three different inclusion levels in terms of body weight (BW; 5, 10, and 15 mg/kg BW). The results indicated no impact on the overall health, apparent total tract macronutrient digestibility (ATTD), fecal microbial DNA, and skin and coat health. The highlighted results included increased phagocytic activity and vaccine-specific response in the group of dogs supplemented with 15 mg/kg BW.
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Reishi , Vacinas , Cães , Animais , Digestão , Leucócitos Mononucleares , Fezes , Dieta/veterinária , Suplementos Nutricionais , Ração Animal/análiseRESUMO
Pulsatilla chinensis f. alba D. K. Zang 1993 is a forma of Pulsatilla chinensis (Bge.) Regel, the root of P. chinensis is traditional Chinese medicine called Pulsatillae radix. The biggest difference between P. chinensis f. alba and P. chinensis is that P. chinensis f. alba sepals is white. The complete chloroplast genome of P. chinensis f. alba was sequenced using the Illumina NovaSeq platform for the first time. The lengths of the genome, large single-copy (LSC), small single-copy (SSC), two inverted repeats (IRs), and GC content were 163,654 bp, 82,355 bp, 19,069 bp, 31,115 bp, and 37.2%, respectively. It had 134 genes, including 90 protein-coding genes, 36 tRNA genes, and eight rRNA genes. The maximum-likelihood tree indicated that P. chinensis f. alba had a closer relationship with P. chinensis. This study would provide a theoretical basis for the further study of Pulsatilla plants genetics phylogenetic research.
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The great structural and functional diversity supports polysaccharides as favorable candidates for new drug development. Previously we reported that a drug candidate pectin-like natural polysaccharide, RN1 might target galectin-3 (Gal-3) to impede pancreatic cancer cell growth in vivo. However, the quality control of polysaccharide-based drug research faces great challenges due to the heterogeneity. A potential solution is to synthesize structurally identified subfragments of this polysaccharide as alternatives. In this work, we took RN1 as an example, and synthesized five subfragments derived from the putative repeating units of RN1. Among them, pentasaccharide 4 showed an approximative binding affinity to Gal-3 in vitro, as well as an antiproliferative activity against pancreatic BxPC-3 cells comparable to that of RN1. Further, we scaled up pentasaccharide 4 to gram-scale in an efficient synthetic route with a 6.9 % yield from D-galactose. Importantly, pentasaccharide 4 significantly suppressed the growth of pancreatic tumor in vivo. Based on the mechanism complementarity of galactin-3 inhibitor and docetaxel, the combination administration of pentasaccharide 4 and docetaxel afforded better result. The result suggested pentasaccharide 4 was one of the functional structural domains of polysaccharide RN1 and might be a leading compound for anti-pancreatic cancer new drug development.
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Carcinoma , Neoplasias Pancreáticas , Humanos , Pectinas/química , Docetaxel , Polissacarídeos/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Oligossacarídeos , Galectina 3/metabolismoRESUMO
The efficient extraction of phthalic acid esters (PAEs) is challenging due to their extremely low concentration, complicated matrices and hydrophilicity. Herein, hollow microspheres, as an ideal coating, possess significant potential for solid-phase microextraction (SPME) due to their fascinating properties. In this study, multiwalled carbon nanotube hollow microspheres (MWCNT-HMs) were utilized as a fiber coating for the SPME of PAEs from tea beverages. MWCNT-HMs were obtained by dissolving the polystyrene (PS) cores with organic solvents. Interestingly, MWCNT-HMs well maintain the morphology of the MWCNTs@PS precursors. The layer-by-layer (LBL) assembly of MWCNTs on PS microsphere templates was achieved through electrostatic interactions. Six PAEs, di-ethyl phthalate (DEP), di-iso-butyl phthalate (DIBP), di-n-butyl phthalate (DBP), benzyl butyl phthalate (BBP), di-2-ethylhexyl phthalate (DEHP) and di-n-octyl phthalate (DOP), were selected as target analytes for assessing the efficiency of the coating for SPME. The stirring rate, sample solution pH and extraction time were optimized by using the Box-Behnken design. Under optimal working conditions, the proposed MWCNT-HMs/SPME was coupled with gas chromatography-tandem mass spectrometry (GC-MS/MS) to achieve high enrichment factors (118-2137), wide linearity (0.0004-10 µg L-1), low limits of detection (0.00011-0.0026 µg L-1) and acceptable recovery (80.2-108.5%) for the detection of PAEs. Therefore, the MWCNT-HM coated fibers are promising alternatives in the SPME method for the sensitive detection of PAEs at trace levels in tea beverages.
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Nanotubos de Carbono , Ácidos Ftálicos , Microextração em Fase Sólida/métodos , Microesferas , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Massas em Tandem , Ácidos Ftálicos/análise , Ácidos Ftálicos/química , Bebidas/análise , CháRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Taohong Siwu decoction (TSD) is a classic traditional Chinese medicine (TCM) prescription used to promote the blood circulation and alleviate blood stasis. TSD consists of Paeonia lactiflora Pall., Conioselinum anthriscoides (H. Boissieu) Pimenov & Kljuykov, Rehmannia glutinosa (Gaertn.) DC., Prunus persica (L.) Batsch, Angelica sinensis (Oliv.) Diels, and Carthamus creticus L. in the ratio of 3:2:4:3:3:2. Studies on the effects of TSD on myocardial ischemia-reperfusion injury (MIRI) from the perspective of autophagy and pyroptosis have not been reported. AIM OF THE STUDY: Investigate the effect of TSD on MIRI and explore the underlying mechanisms. MATERIALS AND METHODS: We searched the main components and corresponding potential targets of TSD on The Pharmacology of Traditional Chinese Medicine Systems database for target prediction. We identified targets for MIRI on Online Mendelian Inheritance in Man and GeneCards databases. The intersection of the compound target and disease target was obtained and a protein-protein interaction network constructed. We undertook enrichment analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. The results of network pharmacology were verified by in vivo experiments in mice. RESULTS: In mice, TSD significantly reduced the volume of the myocardial infarct, significantly reduced serum levels of cardiac troponin-nI (CTnI), creatine kinase-myocardial band (CK-MB), malonaldehyde (MDA), interleukin (IL)-6, increased the activity of superoxide dismutase (SOD) and IL-10 level, reduced the level of pyroptosis in myocardial tissue, increased the number of autophagosomes, and significantly reduced the fluorescence intensity of apoptosis-associated speck-like protein (ASC), Nod-like receptor protein 3 (NLRP3), and caspase-1. TSD administration increased the protein expression of microtubule-associated protein light chain 3 (LC3), but reduced the protein expression of p62, NLRP3, ASC, caspase-1, cleaved caspase-1, pro-caspase-1, gasdermin D (GSDMD), GSDMD-N-terminal, IL-18, and IL-1ß. Administration of 3-Methyladenin could reverse the effect of TSD in inhibiting inflammation and the release of proinflammatory factors. CONCLUSION: TSD treatment alleviated MIRI by promoting autophagy to suppress activation of the NLRP3 inflammasome and reducing the release of proinflammatory factors.
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Traumatismo por Reperfusão Miocárdica , Humanos , Camundongos , Animais , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Inflamassomos/metabolismo , Autofagia , Interleucina-6 , CaspasesRESUMO
Ellagic acid is one of the most representative natural antioxidants, and is rich in pomegranate peel. In this study, a consecutive countercurrent chromatographic (CCC) separation method was established to improve the preparative efficiency of ellagic acid from pomegranate peel. By optimizing the solvent system, sample size and flow rate, 280 mg of ellagic acid was obtained from 5 g of crude sample from pomegranate peel by CCC after six consecutive injections. Moreover, the values of EC50 for ellagic acid in scavenging ABTS·+ and DPPH· were 4.59 ± 0.07 and 10.54 ± 0.07 µg/ml, respectively, indicating a strong antioxidant activity. This study not only established a high-throughput method for the preparation of ellagic acid, but also provided a successful example for the development of and research on other natural antioxidants.
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Lythraceae , Punica granatum , Antioxidantes/análise , Ácido Elágico/análise , Ácido Elágico/química , Lythraceae/química , Extratos Vegetais/químicaRESUMO
Context: The intestinal microbiota and their metabolites play an important role in acute ischemic stroke (AIS) and modulate brain functions directly or indirectly through immune, endocrine, vagal, and other humoral pathways. However, relatively few investigations have evaluated the gut microbiome and its levels of inflammatory factors or the potential associations of those factors with stroke outcomes in patients who have had acute ischemic stroke (AIS), with different stroke severities. Objective: The study intended to determine if AIS patients would have different gut microbiota and inflammatory-factor levels than healthy individuals and if those levels would be associated with the stroke's severity and the patient's prognosis. Design: The research team performed a prospective observational study. Setting: The study took place in the Department of Rehabilitation at the General Hospital of Wanbei Coal and Electricity Group, which is the Third Affiliated Hospital of Bengbu Medical College in Suzhou, Anhui, China. Participants: Participants were 90 patients who had received a diagnosis and treatment of AIS within 48 hours of the stroke's onset at the hospital, between October 2021 and March 2022. Groups: The research team performed multiple comparisons of the baseline demographic and clinical characteristics, the gut microbiota, and levels of inflammatory factors of a number of groups: (1) the AIS patients, the AIS group, to the healthy controls, the control group; (2) the AIS participants who had had a mild or moderate stroke, the mild-moderate group, and those who had had a severe stroke, the severe group; (3) the AIS participants who had had a good primary outcome, the good outcome group, and those who had had a poor primary outcome, the poor outcome group; (4) the mild-moderate and severe groups to the control group; and (5) the good outcome and poor outcome groups to the control group. Outcome Measures: The research team: (1) obtained participants' fecal samples within 72 hours of admission; (2) collected baseline data for the included AIS patients and controls; (3) used 16S rRNA gene sequencing and an enzyme-linked immunosorbent assay (ELISA) to compare the fecal microbial compositions, lipopolysaccharide (LPS) contents, and inflammatory-factor levels between groups; and (4) evaluated the associations of the fecal microbial compositions with severity of stroke and 90-day functional outcomes, using logistic-regression models. Results: The gut microflora distinguished AIS patients from healthy controls. The LPS and inflammatory-factor levels were associated with an increased risk of poor functional outcomes at day 90. Conclusions: Dysbiosis of gut microbiota and LPS and inflammatory-factor levels can increase AIS patients' subsequent risks for poor functional outcomes, indicating that the dysbiosis and levels could be potential prognostic markers and therapeutic targets for stroke.
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Microbioma Gastrointestinal , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/complicações , Lipopolissacarídeos , Disbiose/complicações , RNA Ribossômico 16S/genética , Acidente Vascular Cerebral/complicaçõesRESUMO
The use of various hemp-derived products has been rapidly growing in the human nutrition industry and has sparked great interest in using these ingredients for companion animals as well. Thorough research is needed to determine the ingredient and safety standards required for AAFCO approval of hemp ingredients. In order to be effectively incorporated into pet food products, we must determine the nutrient content, quality, and utility of these ingredients in pet species. The objective of this study was to evaluate the nutrient composition of seeds from four different varieties of hemp, NWG 452, NWG 331, NWG 2730, X-59, and determine protein quality and true metabolizable energy using a cecectomized rooster model. The seeds were similar in macronutrient composition, with small variations in acid hydrolyzed fat, crude protein, total dietary fiber and gross energy content, as well as amino acid and long-chain fatty acid profiles. All essential amino acids were present in concentrations that exceeded the NRC (2006) recommended allowances for adult dogs and cats at maintenance with the exception of tryptophan. The long-chain fatty acid profile presented a favorable ratio of omega-6 to omega-3 fatty acids of close to 3.5:1. The results of the cecectomized rooster assay indicated no significant difference in the standardized amino acid digestibility of the indispensable amino acids among the seed varieties (P > 0.05). A significant difference in the true metabolizable energy corrected for nitrogen was observed among the seeds (P < 0.05), following the pattern of higher acid hydrolyzed fat and lower total dietary fiber content resulting in higher metabolizable energy. An adapted calculation of digestible indispensable amino acid score was made to determine protein quality of the hemp seeds using AAFCO nutrient profiles and NRC recommended allowances for adult dogs and cats at maintenance as reference points. The resulting scores determined tryptophan to be the first limiting amino acid and indicate that hemp seeds alone do not meet all the amino acid requirements for adult dogs and cats at maintenance, and would need a complimentary protein source for practical use in companion animal diets. The data from this study suggest that hemp seeds may provide a beneficial source of fat, protein, and dietary fiber, with consideration to differences in nutrient profile among seed varieties. However, further investigation in vivo is needed to determine the safety and efficacy of utilizing hemp in the diets of both canines and felines.
Hemp products have become popular in the human food and health industry over the past few years. Due to this, a growing interest in using hemp ingredients in animal products has developed as well. There is a need to investigate the nutritional properties and potential utility of hemp seeds in food products for companion animals in order for them to be consumed safely and effectively. Four different varieties of hemp seed were evaluated and found to have similar fat, fiber, and protein content as well as protein quality. The results indicate that hemp seeds may be an advantageous ingredient in the development of pet food products, but a more in depth evaluation using pet species is necessary to confirm this.
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Cannabis , Doenças do Gato , Doenças do Cão , Gatos , Animais , Cães , Masculino , Humanos , Aminoácidos/metabolismo , Cannabis/química , Cannabis/metabolismo , Galinhas/metabolismo , Triptofano/metabolismo , Digestão , Dieta/veterinária , Nutrientes/metabolismo , Proteínas/metabolismo , Fibras na Dieta/metabolismo , Ácidos Graxos/metabolismo , Ração Animal/análise , Sementes/químicaRESUMO
Arming activatable mild-photothermal therapy (PTT) with the property of relieving tumor thermotolerance holds great promise for overcoming traditional mild PTT limitations such as thermoresistance, insufficient therapeutic effect, and off-target heating. Herein, a mitochondria-targeting, defect-engineered AFCT nanozyme with enhanced multi-enzymatic activity was elaborately designed as a tumor microenvironment (TME)-activatable phototheranostic agent to achieve remarkable anti-tumor therapy via "electron transport chain (ETC) interference and synergistic adjuvant therapy". Density functional theory calculations revealed that the synergistic effect among multi-enzyme active centers endows the AFCT nanozymes with excellent catalytic activity. In TME, open sources of H2O2 can be achieved by superoxide dismutase-mimicking AFCT nanozymes. In response to the dual stimuli of H2O2 and mild acidity, the peroxidase-mimicking activity of AFCT nanozymes not only catalyzes the accumulation of H2O2 to generate ·OH but also converts the loaded 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) into its oxidized form with strong near-infrared absorption, specifically unlocking its photothermal and photoacoustic imaging properties. Intriguingly, the undesired thermoresistance of tumor cells can be greatly alleviated owing to the reduced expression of heat shock proteins enabled by NADH POD-mimicking AFCT-mediated NADH depletion and consequent restriction of ATP supply. Meanwhile, the accumulated ·OH can facilitate both apoptosis and ferroptosis in tumor cells, resulting in synergistic therapeutic outcomes in combination with TME-activated mild PTT.
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Nanopartículas , Neoplasias , Humanos , Terapia Fototérmica , Fototerapia/métodos , Peróxido de Hidrogênio , Transporte de Elétrons , NAD , Nanopartículas/uso terapêutico , Neoplasias/terapia , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
The inter-provincial transboundary area of the Taihu Lake Basin is characterized by a complex river network and reciprocating flow. Frequent environmental pollution events in recent years have become a major safety hazard for the water quality in the Taihu Lake Basin. There are few early warning systems for environmental pollution events in China, the ability to simulate risk is insufficient, and systematic research on technology, development, and application is lacking. Thus, water management requirements are not met in the inter-provincial transboundary area of the Taihu Lake Basin. This paper proposes a cross-border risk management plan for pollution sources in the transboundary areas of the Taihu Lake Basin and an early warning and emergency response system for water pollution events using modern information technology. We used this system to assess and classify 2713 risk sources for nitrogen and phosphorus pollution into 5 categories. We simulated the discharge of a pollutant into a tributary and the early warning and emergency response for the transboundary region. The results indicate that the proposed early warning and emergency response system substantially improved the transboundary water environment and lowered the risk of pollution in the Taihu Lake watershed.
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Lagos , Poluentes Químicos da Água , Monitoramento Ambiental/métodos , Qualidade da Água , Poluição da Água/prevenção & controle , Rios , China , Fósforo/análise , Poluentes Químicos da Água/análiseRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Artiri La Li Honey Pill (ALLHP) is a traditional medicinal formula that is widely used in Xinjiang, China, for the treatment of vitiligo. Since the cause of vitiligo has not been determined, no satisfactory treatment is available. Clinical interventions include pharmacological treatment with psoralen, usually in conjunction with ultraviolet A (UVA) radiation, but toxic side effects limit this application. Studies on the activity and mechanisms of ALLHP are scarce. AIM OF THE STUDY: To verify the therapeutic effect of ALLHP on vitiligo and determine its effectiveness as a theoretical and experimental basis for the development of innovative drugs with independent intellectual property rights and the effective use of local resources. MATERIALS AND METHODS: The experimental animal model of vitiligo was established by chemical decoloring. Rats were treated with gradient doses of ALLHP. The therapeutic effect was judged by gross observation. The contents of TYR, MAO, AchE and MDA in serum and skin tissue, the number of hair follicles containing melanin in skin tissue, the distribution of epidermal melanin, and the weight index of immune organs were detected, and the therapeutic effect of ALLHP on vitiligo was evaluated. In addition, certain monomer components in ALLHP were used to intervene in the zebrafish juvenile melanin suppression model, and the melanin-activating activities of some monomer components in ALLHP were screened by counting the melanin area ratio. RESULTS: ALLHP increased the number of melanin-containing hair follicles and the epidermal melanin content in the skin of experimental vitiligo animals, repaired the skin cell morphology to a certain extent, increased the content of TYR in serum and skin, and reduced the content of MDA, AchE and MAO. Carvone, Luteolin, Psoralen and Psoraleae phenol and Bakuchiol could increase the melanin area of experimental melanin inhibition in zebrafish. CONCLUSION: According to the results of this study, ALLHP can increase the number of melanin-containing hair follicles and the epidermal melanin content in the skin of vitiligo animals and restore skin cell morphology to a certain extent by reducing oxidative stress in epidermal tissue. A wide range of active ingredients may promote melanogenesis with ALLHP.
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Furocumarinas , Vitiligo , Ratos , Animais , Vitiligo/tratamento farmacológico , Melaninas , Peixe-Zebra , Modelos Teóricos , Furocumarinas/uso terapêutico , MonoaminoxidaseRESUMO
BACKGROUND: Impaired alveolar macrophages phagocytosis can contribute to pathogenesis of acute respiratory distress syndrome (ARDS) and negatively impacts clinical outcomes. Chlorogenic acid (CGA) is a naturally occurring polyphenolic compound with potential anti-inflammatory and antioxidant bioactivities. Studies have shown that CGA plays a protective role in ARDS, however, the precise protective mechanism of CGA against ARDS, is still unclear. PURPOSE: The aim of this study was to investigate whether CGA enhances alveolar macrophages phagocytosis to attenuate lung injury during ARDS. METHODS: RAW264.7 cells were stimulated with lipopolysaccharides (100 µg/ml for 24 h) and treated with CGA (100, 200, and 400 µM CGA for 1 h) to measure pro-inflammatory cytokine levels, GPR37 expression and macrophages phagocytosis. Mouse models of ARDS induced by cecal ligation and perforation (CLP) surgery were treated with CGA (100 or 200 mg/kg) to investigate lung inflammatory injury and alveolar macrophages phagocytosis. Computational modeling was performed to examine potential binding sites of G protein-coupled receptor 37 (GPR37) with CGA, and the results were validated by interfering with the binding sites. RESULT: In vitro, CGA notably ameliorated inflammatory response and increased phagocytosis in lipopolysaccharides-induced RAW264.7 cells. In vivo, CGA administration significantly alleviated lung inflammatory injury, decreased the bacteria load in the lung, promoted alveolar macrophages phagocytosis and improved the survival rate in mice with CLP-induced ARDS. Moreover, CGA markedly upregulated the expression of GPR37 in vivo and in vitro. However, the protective effect of CGA against ARDS were reversed after silencing the expression of GPR37. CONCLUSION: CGA has a protective effect against ARDS and may enhance alveolar macrophages phagocytosis and attenuate lung inflammatory injury by upregulating GPR37 expression.
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Lesão Pulmonar , Síndrome do Desconforto Respiratório , Animais , Antioxidantes/farmacologia , Ácido Clorogênico/farmacologia , Ácido Clorogênico/uso terapêutico , Citocinas/metabolismo , Lipopolissacarídeos/farmacologia , Lesão Pulmonar/tratamento farmacológico , Macrófagos Alveolares/metabolismo , Camundongos , Fagocitose , Receptores Acoplados a Proteínas G/metabolismo , Síndrome do Desconforto Respiratório/tratamento farmacológicoRESUMO
Depression has become an important disease threatening human health. In recent years, the efficacy of Traditional Chinese Medicine (TCM) in treating the disease has become increasingly prominent, so it is meaningful to find new antidepressant TCM. Mahonia fortune (Lindl.) Fedde is a primary drug in traditional formulas for the treatment of depression, and alkaloids are the main components of it. However, the detailed mechanism of Mahonia alkaloids (MA) on depression remains unclear. This study aimed to investigate the effect of MA on gap junction function in depression via the miR-205/Cx43 axis. The antidepressant effects of MA were observed by a rat model of reserpine-induced depression and a model of corticosterone (CORT)-induced astrocytes. The concentrations of neurotransmitters were measured by ELISA, the expression of Connexin 43 (Cx43) protein was measured by Immunohistochemistry and western-blot, brain derived neurotrophic factor (BDNF), cAMP-response element binding protein (CREB) proteins were measured by western-blot, the pathological changes of prefrontal cortex were observed by hematoxylin-eosin (H&E) staining. Luciferase reporter assay was performed to verify the binding of miR-205 and Cx43. The regulation effect of Cx43 on CREB was verified by interference experiment. Gap junction dysfunction was detected by fluorescent yellow staining. The results confirmed that MA remarkably decreased miR-205 expression and increased Cx43, BDNF, CREB expression in depression rat and CORT-induced astrocytes. In addition, after overexpression of miR-205 in vitro, the decreased expression of Cx43, BDNF and CREB could be reversed by MA. Moreover, after interfering with Cx43, the decreased expression of CREB and BDNF could be reversed by MA. Thus, MA may ameliorate depressive behavior through CREB/BDNF pathway regulated by miR-205/Cx43 axis.
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Alcaloides , Conexina 43 , Junções Comunicantes , Mahonia , MicroRNAs , Animais , Ratos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Conexina 43/metabolismo , Corticosterona , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Depressão/metabolismo , Junções Comunicantes/metabolismo , Junções Comunicantes/patologia , Hipocampo/metabolismo , Mahonia/química , MicroRNAs/metabolismo , Reserpina , Alcaloides/farmacologia , Alcaloides/uso terapêuticoRESUMO
Nanozymes with the merits of effective enzyme-mimic activities, tunable catalytic properties, pH/temperature tolerance, and high stability have been consumingly researched for nanocatalytic therapy. Herein, the union nanozymes and a natural enzyme nanoplatform (DMSN@CoFe2O4/GOD-PCM) are elaborately designed by simply depositing an ultrasmall cobalt ferrite (CoFe2O4) bimetallic oxide nanozyme and natural glucose oxidase (GOD) that are loaded into the aperture (â¼12 nm) of dendritic mesoporous silica (DMSN) for near-infrared-II-enhanced tumor therapy. Upon irradiation, the hyperthermia generated by CoFe2O4 nanozymes unlocks the "gate" of phase-change material (PCM) for releasing GOD, which reshapes the specific tumor microenvironment (TME) through the glucose metabolism pathway. The resulting strengthened acid condition and a considerable amount of H2O2 efficiently initiate the cascade catalysis reactions. Moreover, highly toxic hydroxyl radicals are generated with a Co/Fe dual-cycle system of ultrasmall CoFe2O4 nanozymes. The in situ glutathione consumption and hypoxia relief further amplify oxidative stress. In addition, chemotherapeutic effects due to the cytotoxicity of cobalt ions enhance the therapeutic performance. Collectively, this study provides a proof of concept for TME-reshaped natural and artificial nanozyme cascade catalysis for combined reactive oxygen species-based therapy and chemotherapy.
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Hipertermia Induzida , Microambiente Tumoral , Catálise , Linhagem Celular Tumoral , Cobalto , Compostos Férricos , Glucose , Glucose Oxidase , Glutationa , Peróxido de Hidrogênio , Óxidos , Espécies Reativas de Oxigênio/metabolismo , Dióxido de SilícioRESUMO
With the development of cities, urban area source pollution has become more severe and a significant source of water pollution. To study the relationship between urban area source pollution and water environmental quality in a river network, this study uses a city in the Yangtze River Delta, China, as an example. The Storm Water Management Model (SWMM) model and the MIKE11 model were combined into a unified modeling framework and used to simulate dynamic changes in the water quality of a river network under light rain, moderate rain, and heavy rain. In the study period, the annual urban area source input loads of potassium permanganate (CODMn), total phosphorus (TP), and ammonia nitrogen were 29.8, 0.9, and 4.8 t, respectively. The influence of light rain on the water quality of the river network was lagging and temporary, and rainfall area pollution was the primary contributor. Under the scenario of moderate rain, overflow from a pipeline network compounded rainfall runoff, resulting in a longer duration of impact on the water quality in the river. Additionally, the water quality in the river course was worse under moderate rain than under light or heavy rain. Under the scenario of heavy rain, rain mainly served a dilutive function. This research can provide support for urban area source pollution control and management.
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Rios , Poluentes Químicos da Água , China , Monitoramento Ambiental/métodos , Fósforo/análise , Chuva , Movimentos da Água , Poluentes Químicos da Água/análise , Poluição da Água/análise , Qualidade da ÁguaRESUMO
Celastrol (Cel), a compound derived from traditional Chinese medicine Tripterygium wilfordii Hook. F, has attracted considerable attention as an anticancer drug. However, its clinical application is limited due to its low bioavailability and potential toxicity. With the advancement of nanoscale metal organic frameworks (MOF), the nano-delivery of drugs can effectively improve those disadvantages. Nevertheless, hydrophobic drugs apparently cannot be encapsulated by the hydrophilic channels of MOF-based drug delivery systems. To address these issues, a new assembly strategy for hydrophobic Cel was developed by coordinating the deprotonated Cel to zeolitic imidazolate framework-8 (ZIF-8) with the assistance of triethylamine (Cel-ZIF-8). This strategy greatly elevates the assembly efficiency of Cel from less than 1% to ca. 80%. The resulted Cel-ZIF-8 remains stable in the physiological condition while dissociating and releasing Cel after a 45-minute incubation in an acidic tumor microenvironment (pH 5.5). Furthermore, Cel-ZIF-8 is proved to be easily taken up by cancer cells and exhibits a better therapeutic effect on tumor cells than free Cel. Overall, the Cel-ZIF-8 provides a novel assembly strategy for hydrophobic drugs, and the findings are envisaged to facilitate the application of Cel in cancer therapies.
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Dictamnus dasycarpus Turcz. 1842 is a medicinal plant of China. Its dry root bark is called BAIXIANPI, which is a common traditional Chinese medicine. Here, we report the complete chloroplast genome of D. dasycarpus. The length of the genome, large single-copy (LSC), small single-copy (SSC), inverted repeat (IR), and GC content was 157,056 bp, 84,497 bp, 18,487 bp, 27,036 bp, and 38.5%, respectively. A total of 132 genes were annotated, including 87 protein coding, eight rRNA, and 37 tRNA genes. Interestingly, 15 genes contained single intron while two others contained two introns. The phylogenetic tree showed the two D. dasycarpus (D. albus) clustered in a clade, which was sister to clade formed by the species of Melicope, Tetradium, Phellodendron, and Zanthoxylum.
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Objectives: To investigate the procedural efficiency, efficacy, and safety of high-power, short-term radiofrequency ablation delivered by the SmartTouch Surround Flow (STSF) catheter for paroxysmal atrial fibrillation (AF). Methods: We retrospectively analyzed a total of 72 patients who were admitted with paroxysmal AF, and who underwent radiofrequency catheter ablation (RFCA) for the first time. Of these patients, 36 cases underwent low-power, long-duration (LPLD, (30-35 W/20-40 s) pulmonary vein isolation (PVI) delivered by an SmartTouch (ST) catheter (control group), and the other 36 cases underwent high-power, short-duration (HPSD, (45-50 W/10-20 s) PVI delivered by a STSF catheter (study group). The baseline data, duration of PVI, procedural time, fluoroscopy time, the rate of first-pass isolation, irrigation perfusion, eschar and steam pop occurrences, intraoperative complications, and the rate of stable sinus rhythm maintenance following a blanking period of three months were analyzed between the two groups. Results: The isolation time of bilateral PVI and procedural time in the study group were markedly less than in controls (p < 0.01). The rate of first-pass isolation in the study group was significantly higher than in the control group (95.8% vs. 84.7%, p = 0.023), while the fluid perfusion in the study group was approximately 20% less than that in the control group (767 ± 171 vs. 966 ± 227 ml, p < 0.001). We observed no severe complications in any patients. The rate of freedom from AF recurrences following a blanking period of three months showed a tendency to be higher than in controls (93.9% vs. 87.1%, p = 0.348). Conclusions: The HPSD strategy delivered by the STSF catheter was superior to conventional LPLD ablation through the ST catheter with respect to efficiency, acute procedural effectiveness, short-term safety, and the risk of heart failure in patients with paroxysmal AF.
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Purpose: To investigate the role and mechanism of N-fucosyltransferase VII (FUT7) in acute lymphoblastic leukemia (ALL). Methods: Bone marrow tissues were collected from patients with ALL and children with immune thrombocytopenic purpura (control) hospitalized in our hospital during the same period. Then, the FUT7 expression in bone marrow tissues was detected by qRT-PCR and western blotting. Human ALL cell strain Jurkat was cultured, and after knockdown or overexpression of FUT7, cell proliferation, apoptosis, adhesion and invasion were examined by MTT assay, flow cytometry, fibronectin adhesion assay and transwell, respectively; the protein expression level of integrin α5, integrin ß1, p-FAK, and p-AKT was tested by western blotting. Results: The FUT7 expression was up-regulated in bone marrow cells of ALL patients. After knockdown of FUT7, the proliferation, adhesion and migration ability of ALL cells were significantly reduced, and apoptosis was increased, while the overexpression of FUT7 obtained the opposite results. Moreover, the overexpression of FUT7 also promoted the protein expression of integrin α5, integrin ß1, p-FAK, p-AKT. Conclusion: FUT7 can promote the adhesion and invasion of ALL cells by activating the integrin/FAK/AKT pathway.
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Mild photothermal therapy (PTT, <45 °C) can prevent tumor metastasis and heat damage to normal tissue, compared with traditional PTT (>50 °C). However, its therapeutic efficacy is limited owing to the hypoxic tumor environment and tumor thermoresistance owing to the overproduction of heat shock proteins (HSPs). Herein, a near-infrared (NIR)-triggered theranostic nanoplatform (GA-PB@MONs@LA) is designed for synergistic mild PTT and enhanced Fenton nanocatalytic therapy against hypoxic tumors. The nanoplatform is fabricated by the confined formation of Prussian blue (PB) nanoparticles in mesoporous organosilica nanoparticles (MONs), followed by the loading of gambogic acid (GA), an HSP90 inhibitor, and coating with thermo-sensitive lauric acid (LA). Upon NIR irradiation, the photothermal effect (44 °C) of PB not only induces apoptosis of tumor cells but also triggers the on-demand release of GA, inhibiting the production of HSP90. Moreover, the delivered heat simultaneously enhances the catalase-like and Fenton activity of PB@MONs@LA in an acidic tumor microenvironment, relieving the tumor hypoxia and promoting the generation of highly toxic â¢OH. In addition, the nanoplatform enables magnetic resonance/photoacoustic dual-modal imaging. Thus, this study describes a distinctive paradigm for the development of NIR-triggered theranostic nanoplatforms for enhanced cancer therapy.