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1.
Mol Cell ; 72(1): 48-59.e4, 2018 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-30220562

RESUMO

The signaling of prostaglandin D2 (PGD2) through G-protein-coupled receptor (GPCR) CRTH2 is a major pathway in type 2 inflammation. Compelling evidence suggests the therapeutic benefits of blocking CRTH2 signaling in many inflammatory disorders. Currently, a number of CRTH2 antagonists are under clinical investigation, and one compound, fevipiprant, has advanced to phase 3 clinical trials for asthma. Here, we present the crystal structures of human CRTH2 with two antagonists, fevipiprant and CAY10471. The structures, together with docking and ligand-binding data, reveal a semi-occluded pocket covered by a well-structured amino terminus and different binding modes of chemically diverse CRTH2 antagonists. Structural analysis suggests a ligand entry port and a binding process that is facilitated by opposite charge attraction for PGD2, which differs significantly from the binding pose and binding environment of lysophospholipids and endocannabinoids, revealing a new mechanism for lipid recognition by GPCRs.


Assuntos
Prostaglandina D2/química , Receptores Acoplados a Proteínas G/química , Receptores Imunológicos/química , Receptores de Prostaglandina/química , Carbazóis/química , Humanos , Ácidos Indolacéticos/química , Ligantes , Simulação de Acoplamento Molecular , Prostaglandina D2/genética , Ligação Proteica , Piridinas/química , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/genética , Receptores Imunológicos/antagonistas & inibidores , Receptores Imunológicos/genética , Receptores de Prostaglandina/antagonistas & inibidores , Receptores de Prostaglandina/genética , Transdução de Sinais , Sulfonamidas/química
2.
Environ Microbiol ; 25(11): 2592-2603, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37349980

RESUMO

Soil arsenic (As) pollution not only decreases plant productivity but also soil quality, in turn hampering sustainable agricultural development. Despite the negative effects of As contamination on rice yield and quality being reported widely, the responses of microbial communities and co-occurrence networks in paddy soil to As pollution have not been explored. Here, based on high-throughput sequencing technologies, we investigated bacterial abundance and diversity in paddy soils with different levels of As contamination, and constructed associated microbial co-occurrence networks. As pollution reduced soil bacterial diversity significantly (p < 0.001). In addition, bioavailable As concentrations were negatively correlated with Actinobacteria and Acidobacteria relative abundance (p < 0.05). Conversely, As pollution had a positive relationship with Chloroflexi, Betaproteobacteria, and Bacteroidetes relative abundance (p < 0.05). Firmicutes relative abundance decreased with an increase in total As concentration. The ecological clusters and key groups in bacterial co-occurrence networks exhibited distinct trends with an increase in As pollution. Notably, Acidobacteria play an important role in maintaining microbial networks in As contaminated soils. Overall, we provide empirical evidence that As contamination influences soil microbial community structure, posing a threat to soil ecosystem health and sustainable agriculture.


Assuntos
Arsênio , Microbiota , Poluentes do Solo , Humanos , Arsênio/toxicidade , Solo/química , Bactérias/genética , Microbiota/genética , Acidobacteria , Atividades Humanas , Microbiologia do Solo , RNA Ribossômico 16S
3.
Biochem Biophys Res Commun ; 645: 55-60, 2023 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-36680937

RESUMO

Chronic pain is frequently reported in clinical practice. Therefore, it is important to identify effective therapy to relieve pain. In this work, we selected Forsythoside B (FB), a phenylethanoid glycoside isolated from Forsythia suspensa (Thunb.) Vahl, to evaluate its effect in modulating inflammatory pain induced by complete Freund's adjuvant (CFA) and the involved mechanisms. We discovered that FB could attenuate inflammatory pain triggered by CFA injection and exert anti-anxiety effects. In detail, proinflammatory cytokines, consisting of IL-6 and TNF-α, were decreased after FB administration in the CFA-injected mice. Furthermore, the FB application ameliorated the activation of ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP), the microglia and astrocytes markers respectively. Therefore, our findings indicate that FB could be a promising treatment for chronic inflammatory pain.


Assuntos
Dor Crônica , Inflamação , Camundongos , Animais , Adjuvante de Freund , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Dor Crônica/induzido quimicamente , Dor Crônica/tratamento farmacológico , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Hiperalgesia/metabolismo
4.
Neuroimmunomodulation ; 30(1): 315-324, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37899033

RESUMO

INTRODUCTION: Inflammatory pain is a significant global clinical challenge that involves both unpleasant sensory and emotional experiences. The treatment of pain is imminent, and we are committed to seeking new analgesics for pain relief. Transcrocetin meglumine salt (TCMS), a saffron metabolite derived from the crocin apocarotenoids, has exhibited the ability to cross the blood-brain barrier and exert neuroprotective effects. In this study, we aimed to investigate whether TCMS could ameliorate complete Freund's adjuvant (CFA)-induced inflammatory pain in mice and elucidate its underlying mechanisms. METHODS: Here, we established an inflammatory pain model in mice by injecting CFA into the left hind paw. Three days later, we administered intraperitoneal injections of TCMS (10 mg/kg) or saline to the animals. We examined mechanical allodynia, thermal hypersensitivity, and anxiety behavior. Furthermore, the activation of glial cells and proinflammatory cytokines in the spinal cord were detected. RESULTS: Our results showed that TCMS significantly reversed the mechanical allodynia and thermal hypersensitivity in the CFA-injected mice. Furthermore, TCMS administration effectively inhibited the activation of microglia and astrocytes in the spinal cord induced by CFA. Additionally, TCMS suppressed the production and release of spinal proinflammatory cytokines, including TNF-α, IL-1ß, and IL-6, in CFA-injected mice. CONCLUSION: Taken together, our findings demonstrate that TCMS holds promise as an innovative analgesic due to its ability to ameliorate inflammatory reactions.


Assuntos
Citocinas , Hiperalgesia , Camundongos , Animais , Citocinas/metabolismo , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Adjuvante de Freund/toxicidade , Meglumina/efeitos adversos , Dor/tratamento farmacológico , Neuroglia/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Medula Espinal
5.
J Clin Lab Anal ; 34(4): e23130, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31876061

RESUMO

BACKGROUND: Coenzyme Q10 (CoQ10) supplementation can improve cognition in patients with Alzheimer's disease (AD) and AD transgenic model mice. To ameliorate the discomfort that patients with AD suffer after several blood extractions, a non-invasive method for detecting urine CoQ10 levels needs to be established. METHODS: Here, we developed a new technique of fluorescence spectrophotometry with ethyl cyanoacetate (FS-ECA), on the basis of the principle that the chemical derivative obtained from the interaction between CoQ10 and ECA was detected by a fluorescence detector at λex/em  = 450/515 nm. As a standard reference method, the same batches of the clinical samples were analyzed by high-performance liquid chromatography with an ultraviolet detector (HPLC-UV) at 275 nm. RESULTS: The limits of detection (LOD) and limits of quantization (LOQ) (serum: 0.021 and 0.043 mg/L; urine: 0.012 and 0.025 mg/L) determined by the FS-ECA method were similar to that obtained through HPLC-UV (serum: 0.017 and 0.035 mg/L; urine: 0.012 and 0.025 mg/L). More importantly, this new FS-ECA technique as well as the conventional HPLC-UV method could detect a marked difference in urine CoQ10 levels between AD and controls. CONCLUSION: Our findings suggest that this non-invasive method for quantifying urine CoQ10 potentially replaces HPLC to detect blood CoQ10.


Assuntos
Química Clínica/métodos , Ubiquinona/análogos & derivados , Acetatos/química , Idoso , Doença de Alzheimer/sangue , Doença de Alzheimer/urina , Cromatografia Líquida de Alta Pressão , Fluorescência , Humanos , Limite de Detecção , Espectrometria de Fluorescência , Temperatura , Fatores de Tempo , Ubiquinona/sangue , Ubiquinona/urina
6.
Analyst ; 144(22): 6760-6772, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31617507

RESUMO

A biomimetic fluorescent nanosensor based on molecularly imprinted polymers modified with carbon dots (CDs@MIPs) has been prepared for rapid, selective and sensitive detection of alpha-fetoprotein (AFP) in clinical samples. The nanosensor was produced using vinyl-functionalized CDs (V-CDs) as transducer elements and support materials, AFP as the template protein, N-isopropylacrylamide (NIPAM) and 4-vinylphenylbronic acid (VPBA) as the thermo-responsive and pH-responsive monomer, respectively, and ammonium peroxodisulphate (APS) and N,N'-methylene bisacrylamide (MBA) as the initiator and cross-linker, respectively. The newly synthesized nanosensor was characterized by FT-IR, TEM, XRD and elemental analysis, which unambiguously confirmed the successful formation of the nanosensor. The fluorescence quenching degree of CDs@MIPs exhibited a good linear response to AFP in a concentration range of 10 to 100 ng mL-1, the limit of detection (LOD) of 0.474 ng mL-1, and high recoveries at three spiking levels of AFP ranging from 97.05% to 102.00%, with relative standard deviations (RSDs) below 4.2% being obtained. Moreover, the proposed CDs@MIPs were successfully exploited to detect AFP in human serum samples. This study successfully established a novel method for rapid, convenient, and highly sensitive and selective detection of AFP, which provides new ideas for the detection of tumor markers.


Assuntos
Materiais Biomiméticos/química , Corantes Fluorescentes/química , Polímeros/química , Pontos Quânticos/química , alfa-Fetoproteínas/análise , Acrilamidas/química , Ácidos Borônicos/química , Carbono/química , Humanos , Limite de Detecção , Impressão Molecular/métodos , Polimerização , Polímeros/síntese química , Espectrometria de Fluorescência/métodos , Sulfatos/química , Compostos de Vinila/química
7.
Chemistry ; 23(11): 2635-2647, 2017 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-27976827

RESUMO

A series of three conjugated meso-porphyrin dendrimers containing conjugated dendrons featuring 2,7-fluorenyl groups, incorporating overall 8, 12, or 28 fluorenyl units have been synthesized and characterized. The photophysical properties of these new compounds were studied in the context of photodynamic therapy. The relevant linear and nonlinear optical properties were measured in organic media and useful structure-properties relationships were derived.

9.
J Sep Sci ; 40(17): 3522-3534, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28704580

RESUMO

In the scope of stroke treatment, new neuronal nitric oxide synthase-postsynaptic density protein-95 uncouplers from herbal medicines were discovered and captured. To do so, highly selective magnetic molecularly imprinted polymers with a core-shell structure were prepared as artificial antibodies. According to the results of computational simulations, we designed and synthesized various polymers with varying amounts and types of template, functional monomer, cross-linker, and solvent. Characterization and performance tests revealed that the most appropriate artificial antibodies showed uniform spherical morphologies, large adsorption capacities, fast-binding kinetics, high selectivity, and quick separation. These artificial antibodies were then used as sorbents for dispersive magnetic solid-phase extraction coupled with high-performance liquid chromatography and mass spectrometry to capture and identify structural analogs to ZL006 from extracts of Scutellariae radix, Psoraleae fructus, and Trifolium pratense. Furthermore, according to the neuroprotective effect and coimmunoprecipitation test, Baicalein, Neobavaisoflavone, Corylifol A, and Biochanin A can be the potential uncouplers of neuronal nitric oxide synthase-postsynaptic density protein-95. Therefore, this present study contributes valuable information for the discovery of neuronal nitric oxide synthase-postsynaptic density protein-95 uncouplers from herbal medicines.


Assuntos
Impressão Molecular , Proteínas do Tecido Nervoso/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Preparações de Plantas/química , Adsorção , Cromatografia Líquida de Alta Pressão , Medicina Herbária , Polímeros , Extração em Fase Sólida
10.
Med Sci Monit ; 23: 1725-1732, 2017 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-28391288

RESUMO

BACKGROUND Leukemia stem cells (LSC) are involved in the incidence, drug resistance, and relapse of leukemia while LSC-related antigen CD33, CD96, and DAPK expression in AML and its prognosis is still unclear. This study explored LSC-related antigens expression in acute myeloid leukemia (AML) and its prognosis. MATERIAL AND METHODS A total of 156 cases of AML patients were enrolled in the experiment. The expression of CD33, CD96, and DAPK in CD34+CD38-CD123+ LSC were tested by flow cytometry. The survival curve was established using the Kaplan-Meier method. RESULTS Among different subtypes of AML, the positive rate of CD33 was M3> M5> M1> M2> M4; for CD96 it was M5> M4> M2> M3> M1; and for DAPK it was M3> M2> M5> M4> M1. After chemotherapy, the response rate in CD33 and CD96 high expression groups, and DAPK low expression group was significantly lower than the groups with CD33 low expression, CD96 low expression, and DAPK high expression. The median survival time in the CD33 high expression group was markedly lower than the CD33 low expression group (36.5 months). The CD96 high expression group exhibited obviously shorter median survival time than the CD96 low expression group. The DAPK high expression group exhibited longer median survival time than the DAPK low expression group. CONCLUSIONS CD33 and CD96 overexpression, and DAPK downregulation in the LSC of AML patients were associated with poor chemotherapy effect and prognosis, and higher recurrence rate.


Assuntos
Células da Medula Óssea/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Adolescente , Adulto , Antígenos CD/genética , Antígenos CD/metabolismo , Biomarcadores Farmacológicos , Células da Medula Óssea/imunologia , Proteínas Quinases Associadas com Morte Celular/genética , Proteínas Quinases Associadas com Morte Celular/metabolismo , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/imunologia , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/metabolismo , Prognóstico , Receptores Acoplados a Proteínas G , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/genética , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , Taxa de Sobrevida
11.
Chemistry ; 22(16): 5583-97, 2016 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-26933931

RESUMO

A new family of conjugated meso-tetraphenylporphyrin-based dendrimers with four (TPP1, TPP2), eight (TPP3, TPP4, TPP5) and up to sixteen (TPP6) fluorenyl groups has been synthesized and fully characterized. These tetraphenylporphyrin-cored dendrimers present peripheral alkynyl π-conjugated dendrons with fluorenyl termini. The meso-aryl rings of these porphyrins are functionalized either in para- (TPP1, TPP2, and TPP3) or meta-positions (TPP4, TPP5, and TPP6). Their detailed luminescence properties are discussed in reference to two porphyrins lacking fluorenyl dendrons (TPP-H1,2,3 and TPP-H4,5,6). A strong dependence of their luminescence quantum yield and lifetime on their structures is stated, their nonlinear optical properties were also discussed.

12.
Pest Manag Sci ; 80(2): 734-743, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37779103

RESUMO

BACKGROUND: Rodent infestation is a global problem. Rodents cause huge harm to agriculture, forestry, and animal husbandry around the world and spread various zoonoses. In this study, we simulated the potentially suitable habitats of Bandicota indica and predicted the impact of future climate change on its distribution under different socio-economic pathway scenarios of CMIP6 using a parameter-optimized maximum entropy (MaxEnt) model. RESULTS: The average area under the receiver operating characteristic curve (AUC) value (0.958 ± 0.006) after ten repetitions proved the high accuracy of the MaxEnt model. Model results show that the annual mean temperature (≥ 15.93 °C), isothermality (28.52-80.49%), annual precipitation (780.13-3863.13 mm), precipitation of the warmest quarter (≥ 204.37 mm), and nighttime light (≥ 3.38) were important limiting environmental variables for the distribution of B. indica. Under current climate conditions, the projected potential suitable habitats for B. indica were mainly in India, China, Myanmar, Thailand, and Vietnam, which cover a total area of 301.70 × 104 km2 . The potentially suitable areas of B. indica in the world will expand under different future climate change scenarios by 1.61-17.65%. CONCLUSIONS: These results validate the potential influence of climate change on the distribution of B. indica and aid in understanding the linkages between B. indica niches and the relevant environment, thereby identifying urgent management areas where interventions may be necessary to develop feasible early warning and prevention strategies to protect against this rodent's spread. © 2023 Society of Chemical Industry.


Assuntos
Mudança Climática , Murinae , Animais , Ecossistema , Agricultura , China
13.
Neurosci Bull ; 40(4): 466-482, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38148427

RESUMO

Microtubule-associated protein Tau is responsible for the stabilization of neuronal microtubules under normal physiological conditions. Much attention has been focused on Tau's contribution to cognition, but little research has explored its role in emotions such as pain, anxiety, and depression. In the current study, we found a significant increase in the levels of p-Tau (Thr231), total Tau, IL-1ß, and brain-derived neurotrophic factor (BDNF) on day 7 after complete Freund's adjuvant (CFA) injection; they were present in the vast majority of neurons in the spinal dorsal horn. Microinjection of Mapt-shRNA recombinant adeno-associated virus into the spinal dorsal cord alleviated CFA-induced inflammatory pain and inhibited CFA-induced IL-1ß and BDNF upregulation. Importantly, Tau overexpression was sufficient to induce hyperalgesia by increasing the expression of IL-1ß and BDNF. Furthermore, the activation of glycogen synthase kinase 3 beta partly contributed to Tau accumulation. These findings suggest that Tau in the dorsal horn could be a promising target for chronic inflammatory pain therapy.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Dor Crônica , Humanos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Regulação para Cima , Inflamação/metabolismo , Hiperalgesia/metabolismo , Medula Espinal/metabolismo , Corno Dorsal da Medula Espinal/metabolismo
14.
Phytomedicine ; 128: 155521, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38489891

RESUMO

BACKGROUND: The ancient Chinese herb Salvia miltiorrhiza Bunge (Danshen), plays the important role in cardiovascular and cerebrovascular disease. Furthermore, Danshen could also be used for curing carcinogenesis. Up to now, the anti-tumor effects of the main active constituents of Danshen have made great progress. However, the bioavailability of the active constituents of Danshen were restricted by their unique physical characteristics, like low oral bioavailability, rapid degradation in vivo and so on. PURPOSE: With the leap development of nano-delivery systems, the shortcomings of the active constituents of Danshen have been greatly ameliorated. This review tried to summarize the recent progress of the active constituents of Danshen based delivery systems used for anti-tumor therapeutics. METHODS: A systematic literature search was conducted using 5 databases (Embase, Google scholar, PubMed, Scopus and Web of Science databases) for the identification of relevant data published before September 2023. The words "Danshen", "Salvia miltiorrhiza", "Tanshinone", "Salvianolic acid", "Rosmarinic acid", "tumor", "delivery", "nanomedicine" and other active ingredients contained in Danshen were searched in the above databases to gather information about pharmaceutical decoration for the active constituents of Danshen used for anti-tumor therapeutics. RESULTS: The main extracts of Danshen could inhibit the proliferation of tumor cells effectively and a great deal of studies were conducted to design drug delivery systems to ameliorate the anti-tumor effect of the active contents of Danshen through different ways, like improving bioavailability, increasing tumor targeting ability, enhancing biological barrier permeability and co-delivering with other active agents. CONCLUSION: This review systematically represented recent progress of pharmaceutical decorations for the active constituents of Danshen used for anti-tumor therapeutics, revealing the diversity of nano-decoration skills and trying to inspire more designs of Danshen based nanodelivery systems, with the hope that bringing the nanomedicine of the active constituents of Danshen for anti-tumor therapeutics from bench to bedside in the near future.


Assuntos
Antineoplásicos Fitogênicos , Medicamentos de Ervas Chinesas , Salvia miltiorrhiza , Salvia miltiorrhiza/química , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Humanos , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Sistemas de Liberação de Medicamentos , Animais , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Fármacos por Nanopartículas/química , Nanopartículas/química
15.
Am J Cardiol ; 211: 209-218, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37984642

RESUMO

To investigate the long-term effects of 2 commonly used low-osmolar contrast media, iohexol and iopromide, on renal function and survival in patients who underwent coronary angiography. A total of 14,141 cardiology patients from 2006 to 2013 were recruited, of whom 1,793 patients (679 patients on iohexol and 1,114 on iopromide) were evaluated for long-term renal impairment and 5,410 patients (1,679 patients on iohexol and 3,731 on iopromide) were admitted for survival analyses spanning as long as 15 years. Univariate and multivariate logistic regression were used to explore the risk factors for long-term renal impairment. Cox proportional hazard regression was used to investigate the risk factors affecting survival. Propensity score matching and inverse probability of treatment weighting were applied to balance the baseline clinical characteristics. Patients receiving iohexol demonstrated a greater occurrence of renal impairment compared with those who received iopromide. Such difference remained consistent both before and after propensity score matching or inverse probability of treatment weighting, with a statistical significance of p <0.05. Among clinical variables, receiving contrast-enhanced contrast tomography/magnetic resonance imaging during follow-up, antihypertensive medication usage, presence of proteinuria, and anemia were identified as risk factors for long-term renal impairment (p = 0.041, 0.049, 0.006, and 0.029, respectively). During survival analyses, the difference was insignificant after propensity score matching and inverse probability of treatment weighting. In conclusion, administration of iohexol was more likely to induce long-term renal impairment than iopromide, particularly among patients diagnosed with anemia and proteinuria and those taking antihypertensive medication and with additional contrast exposure. The all-cause mortality, however, showed no significant difference between iohexol and iopromide administration.


Assuntos
Anemia , Insuficiência Renal , Humanos , Iohexol/efeitos adversos , Angiografia Coronária/efeitos adversos , Angiografia Coronária/métodos , Meios de Contraste/efeitos adversos , Anti-Hipertensivos , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/epidemiologia , Proteinúria/induzido quimicamente , Ácidos Tri-Iodobenzoicos/efeitos adversos
16.
J Hazard Mater ; 476: 135098, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38970977

RESUMO

Next-generation sequencing (NGS) has revolutionized taxa identification within contaminant-degrading communities. However, uncovering a core degrading microbiome in diverse polluted environments and understanding its associated microbial interactions remains challenging. In this study, we isolated two distinct microbial consortia, namely MA-S and Cl-G, from separate environmental samples using 1,4-dioxane as a target pollutant. Both consortia exhibited a persistent prevalence of the phylum Proteobacteria, especially within the order Rhizobiales. Extensive analysis confirmed that Rhizobiales as the dominant microbial population (> 90 %) across successive degradation cycles, constituting the core degrading microbiome. Co-occurrence network analysis highlighted synergistic interactions within Rhizobiales, especially within the Shinella and Xanthobacter genera, facilitating efficient 1,4-dioxane degradation. The enrichment of Rhizobiales correlated with an increased abundance of essential genes such as PobA, HpaB, ADH, and ALDH. Shinella yambaruensis emerged as a key degrader in both consortia, identified through whole-genome sequencing and RNA-seq analysis, revealing genes implicated in 1,4-dioxane degradation pathways, such as PobA and HpaB. Direct and indirect co-cultivation experiments confirmed synergistic interaction between Shinella sp. and Xanthobacter sp., enhancing the degradation of 1,4-dioxane within the core microbiome Rhizobiales. Our findings advocate for integrating the core microbiome concept into engineered consortia to optimize 1,4-dioxane bioremediation strategies.

17.
Rev Neurosci ; 34(8): 899-914, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-37288945

RESUMO

Pain is a multifaceted process that encompasses unpleasant sensory and emotional experiences. The essence of the pain process is aversion, or perceived negative emotion. Central sensitization plays a significant role in initiating and perpetuating of chronic pain. Melzack proposed the concept of the "pain matrix", in which brain regions associated with pain form an interconnected network, rather than being controlled by a singular brain region. This review aims to investigate distinct brain regions involved in pain and their interconnections. In addition, it also sheds light on the reciprocal connectivity between the ascending and descending pathways that participate in pain modulation. We review the involvement of various brain areas during pain and focus on understanding the connections among them, which can contribute to a better understanding of pain mechanisms and provide opportunities for further research on therapies for improved pain management.


Assuntos
Encéfalo , Dor , Humanos , Manejo da Dor , Emoções , Sensibilização do Sistema Nervoso Central
18.
Pharmaceuticals (Basel) ; 16(11)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38004411

RESUMO

BACKGROUND: Inflammatory pain, characterized by sustained nociceptive hypersensitivity, represents one of the most prevalent conditions in both daily life and clinical settings. Aucubin, a natural plant iridoid glycoside, possesses potent biological effects, encompassing anti-inflammatory, antioxidant, and neuroprotective properties. However, its impact on inflammatory pain remains unclear. The aim of this study is to investigate the therapeutic effects and underlying mechanism of aucubin in addressing inflammatory pain induced by complete Freund's adjuvant (CFA). METHODS: The CFA-induced inflammatory pain model was employed to assess whether aucubin exerts analgesic effects and its potential mechanisms. Behavioral tests evaluated mechanical and thermal hyperalgesia as well as anxiety-like behaviors in mice. The activation of spinal glial cells and the expression of pro-inflammatory cytokines were examined to evaluate neuroinflammation. Additionally, RNA sequencing was utilized for the identification of differentially expressed genes (DEGs). Molecular biology experiments were conducted to determine the levels of the PINK1 gene and autophagy-related genes, along with PINK1 distribution in neural cells. Furthermore, mitophagy induced by carbonyl cyanide m-chlorophenylhydrazone (CCCP) was employed to examine the roles of PINK1 and mitophagy in pain processing. RESULTS: Aucubin significantly ameliorated pain and anxiety-like behaviors induced by CFA in mice and reduced spinal inflammation. RNA sequencing indicated PINK1 as a pivotal gene, and aucubin treatment led to a significant downregulation of PINK1 expression. Further GO and KEGG analyses suggested the involvement of mitochondrial function in the therapeutic regulation of aucubin. Western blotting revealed that aucubin markedly decreased PINK1, Parkin, and p62 levels while increasing LC3B expression. Immunofluorescence showed the predominant co-localization of PINK1 with neuronal cells. Moreover, CCCP-induced mitophagy alleviated mechanical and thermal hyperalgesia caused by CFA and reversed CFA-induced mitochondrial dysfunction. CONCLUSIONS: In summary, our data suggest that aucubin effectively alleviates CFA-induced inflammatory pain, potentially through triggering the PINK1 pathway, promoting mitophagy, and suppressing inflammation. These results provide a novel theoretical foundation for addressing the treatment of inflammatory pain.

19.
Sci Total Environ ; 871: 161680, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36682558

RESUMO

Predatory myxobacteria are keystone taxa in the soil microbial food web that potentially regulate soil microbial community structure and ecosystem functions. However, little is known about the community assembly processes of myxobacteria in typical farmland soils over large geographic scales, in addition to their relationship with soil multi-nutrient cycling. Here, we used high-throughput sequencing techniques and phylogenetic null modeling analysis to investigate the distribution patterns and assembly processes of myxobacteria communities, in addition to interactions between myxobacteria communities and soil multi-nutrient cycling. Anaeromyxobacter (28.5 %) and Haliangium (19.6 %) were the dominant myxobacteria genera in all samples, and myxobacteria community similarities exhibited distinct distance-decay relationships. Stochastic processes (~77.8 %) were the dominant ecological processes driving the assembly of predatory myxobacteria communities over large geographical scales and under three fertilization regimes. Myxobacteria community structure was influenced by geographic factors (location and climate), soil factors (soil pH, soil organic carbon, total nitrogen, and total potassium), and fertilization, with myxobacteria community assembly being more sensitive to geographic factors. Organic-inorganic combined fertilization (NPKM) increased the proportions of deterministic processes in myxobacteria community assembly. Moreover, myxobacteria community assembly and diversity were closely associated with soil multi-nutrient cycling. Hence, myxobacteria phylogenetic α-diversity represented by NTI index is a potential bioindicators for soil multi-nutrient cycling. Overall, our findings comprehensively reveal the mechanisms of assembly of myxobacteria communities in soils over large geographic scales, and provide a theoretical basis for further research on the role of predatory bacteria on soil nutrient cycling in agro-ecosystems.


Assuntos
Microbiota , Myxococcales , Solo , Fazendas , Filogenia , Carbono , Microbiologia do Solo
20.
J Hazard Mater ; 458: 131993, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37423134

RESUMO

The limited bioavailability of polycyclic aromatic hydrocarbons (PAHs) in soils poses a challenge for their biodegradation. We hypotheses soapwort (Saponaria officinalis L.) as a factory in-situ providing biosurfactant, which could effectively promote the BaP removal by exogenous or native functional microbes. Rhizo-box and microcosm experiments were conducted to analyze the phyto-microbial remediation mechanism of soapwort, a plant that excretes biosurfactants known as saponins, and combined with two exogenous strains (P. chrysosporium and/or B. subtilis) for benzo[a]pyrene (BaP)-contaminated soils. The results revealed that the natural attenuation treatment (CK) BaP achieved only a 15.90% BaP removal rate after 100 days. In contrast, soapwort (SP), soapwort-bacteria (SPB), soapwort-fungus (SPF), soapwort- bacteria - fungus (SPM) mediated rhizosphere soils treatments yielded removal rates of 40.48%, 42.42%, 52.37%, and 62.57%, respectively. The analysis of the microbial community structure suggested that soapwort stimulated the introduction and native functional microorganisms, such as Rhizobiales, Micrococcales, and Clostridiales, which contributed to BaP removal via metabolic pathways. Furthermore, the efficient BaP removal was attributed to saponins, amino acids, and carbohydrates, which facilitated mobilization, solubilization of BaP, and microbial activity. In conclusion, our study highlights the potential of soapwort and specific microbial strains to effectively remediate PAH-contaminated soils.


Assuntos
Microbiota , Hidrocarbonetos Policíclicos Aromáticos , Saponaria , Saponinas , Poluentes do Solo , Benzo(a)pireno/metabolismo , Poluentes do Solo/metabolismo , Solo/química , Saponaria/metabolismo , Microbiologia do Solo , Biodegradação Ambiental , Hidrocarbonetos Policíclicos Aromáticos/análise
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