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1.
Pestic Biochem Physiol ; 199: 105769, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38458678

RESUMO

The discovery of safe, effective, and selective chemical algicides is the stringent need for the algicides development, and it is also one of the effective routes to control cyanobacteria harmful algal blooms and to meet the higher requirements of environmental and ecological. In this work, a series of novel bromo-N-phenyl-5-o-hydroxyphenylpyrazole-3-carboxyamides were rationally designed as pseudilin analogs by bioisosteric replacement and molecular hybridization strategies, in which the pyrrole unit of pseudilin was replaced with pyrazole and further combined with the dominant structural fragments of algicide diuron. The synthesis was carried out by a facile four-step routeincluding cyclization, amidation, transanulation, and halogenation. The biological activity evaluation on AtIspD, EcIspD, Synechocystis sp. PCC6803 and Microcystis aeruginosa FACHB905 revealed that most compounds had good EcIspD and excellent cyanobacteria inhibitory activity. In particular, compound 6bb exhibited potent algicidal activity against PCC6803 and FACHB905 with EC50 = 1.28 µM and 0.37 µM, respectively, 1.4-fold and 4.0-fold enhancement compared to copper sulfate (EC50 = 1.79 and 1.49 µM, respectively), and it also showed the best inhibitory activity of EcIspD. The binding of 6bb to EcIspD was explored by molecular docking, and it was confirmed that 6bb could bind to the EcIspD active site. Compound 6bb was proven to be a potential structure for the further development of novel algicides that targets IspD in the MEP pathway.


Assuntos
Herbicidas , Microcystis , Synechocystis , Simulação de Acoplamento Molecular , Inibidores Enzimáticos/farmacologia , Synechocystis/química , Synechocystis/metabolismo , Herbicidas/farmacologia
2.
BMC Nephrol ; 24(1): 293, 2023 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-37794407

RESUMO

BACKGROUND: Parathyroid carcinoma and parathyromatosis are very rare diseases in patients on hemodialysis. Its pathogenesis, clinical features, preoperative diagnosis, and surgery are challenging. We describe a rare case of recurrent hyperparathyroidism due to synchronous parathyroid carcinoma and parathyromatosis. CASE PRESENTATION: A 46-year-old Chinese woman was diagnosed with end-stage renal disease and received regular hemodialysis. Four years later, she experienced discomfort due to itching and was diagnosed with drug-resistant secondary hyperparathyroidism. Parathyroidectomy was performed, and her parathyroid hormone (PTH) levels were reduced. The pathology also revealed that the four nodules were parathyroid nodular hyperplasia without evidence of malignancy. Five years after surgery, the right subcutaneous nodule and left inferior nodule were detected by multiple imaging modalities, and the nodules were accompanied by recurrence itching and elevation of PHT. A complete resection of two nodules was performed, and the patient was diagnosed with parathyroid carcinoma and parathyromatosis. At 8 months postsurgery, her PHT and serum calcium levels were stable, and there were no signs of recurrence. CONCLUSIONS: This is a rare case of synchronous parathyroid carcinoma and parathyromatosis in a patient with secondary hyperparathyroidism after parathyroidectomy. We suggest meticulous handling of parathyroid hyperplasia to avoid rupture and spillage during surgery, and precise pro-operation location by multiple imaging modalities is crucial for successful parathyroidectomy.


Assuntos
Hiperparatireoidismo Primário , Hiperparatireoidismo Secundário , Neoplasias das Paratireoides , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/cirurgia , Hiperplasia/patologia , Glândulas Paratireoides/diagnóstico por imagem , Glândulas Paratireoides/cirurgia , Glândulas Paratireoides/patologia , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/cirurgia , Hiperparatireoidismo Secundário/complicações , Hiperparatireoidismo Secundário/diagnóstico por imagem , Paratireoidectomia/efeitos adversos , Diálise Renal/efeitos adversos , Prurido , Recidiva , Hormônio Paratireóideo
3.
Toxicol Appl Pharmacol ; 446: 116045, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35526792

RESUMO

Xylitol is a hygroscopic compound known to protect nasal cavity against bacteria. It has also been developed into nasal spray and evaluated as a potential candidate drug for respiratory diseases. Consequently, it is necessary to study its inhalation toxicity. Based on our previous study on its subacute inhalation toxicity, this study aimed to investigate the safety of xylitol inhalation for long-term use. According to the OECD Test Guideline 413, Sprague-Dawley rats were randomly divided into six groups and exposed with different concentrations of xylitol aerosol or air. After exposure for 90-day, the recovery groups were continued to observe for a recovery period of 28-day. No significant changes in body weight were observed between sham and xylitol groups. Several significant differences in hematological, clinical chemistry, bronchoalveolar lavage fluid were observed, which either had no dose-effect relationship for both male and female rats or were restored during the recovery period. Finally, except for high dose group of xylitol, two rats showed a small amount of inflammatory exudate in alveolar and bronchial cavities, which was restored in the recovery period. The rest of rats showed no obvious difference. For the recovery groups, no significant difference was observed between these two groups. In conclusion, the no observable adverse effect level (NOAEL) of xylitol in our subchronic inhalation toxicological experiments was 2.9 mg/L, which indicated that xylitol for rats' long-time inhalation is tolerant and safe.


Assuntos
Exposição por Inalação , Xilitol , Administração por Inalação , Aerossóis/toxicidade , Animais , Líquido da Lavagem Broncoalveolar/química , Feminino , Exposição por Inalação/efeitos adversos , Masculino , Ratos , Ratos Sprague-Dawley , Xilitol/toxicidade
4.
Ecotoxicol Environ Saf ; 247: 114262, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36327786

RESUMO

Volatile chlorinated hydrocarbons (VCHs) contaminated groundwater has a low indigenous microorganism population, and lack of nutrient substrates involved in degradation reactions, resulting in a weak natural remediation ability of groundwater ecosystems. In this study, based on the principle of degradation of VCHs by indigenous microorganisms in groundwater, and combined with biostimulation and controlled-release technology, we developed a starch-based encapsulated targeted bionutrient (YH-1) with easy uptake, good stability, controllable slow-release migration, and long timeliness for the remediation of groundwater contaminated by VCHs by indigenous microorganisms. The results showed that YH-1 is easily absorbed by microorganisms and can rapidly initiate itself to stimulate the microbial degradation of VCHs, and the degradation rate of various VCH components within 7 days was 82.38-92.38 %. The release rate of nutrient components in YH-1 increases with increasing VCH concentrations in groundwater; this could effectively prolong the action time of nutrient components, while also improving the degradation efficiency of pollutants with a sustained effect of more than 15 days. Simultaneously, owing to the fluidity, water solubility, and biodegradability of YH-1 in lithologic media, YH-1 injection did not cause blockage of the lithologic media in the aquifer. Through YH-1 stimulation, indigenous microorganisms grew rapidly in the underground environment, the diversity of microbial communities and the total number of species increased, and the correlation between genera strengthened. Simultaneously, YH-1 improved the ability of microbial community to convert inorganic electron donors/acceptors, thereby strengthening the co-metabolic mechanism between microorganisms. Additionally, there was a significant increase in the percentage of many microorganisms (e.g., Sphingomonas, Janthinobacterium, Duganella, etc.) that mediated the reductive dechlorination process and were redox inorganic electron donors/acceptors. This was conducive to the reductive dechlorination process of VCHs and achieved the efficient degradation of VCHs.


Assuntos
Antineoplásicos , Água Subterrânea , Hidrocarbonetos Clorados , Microbiota , Amido , Preparações de Ação Retardada , Nutrientes , Oxidantes
5.
Ecotoxicol Environ Saf ; 246: 114139, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36193588

RESUMO

The resistance mechanism of microbial communities in contaminated groundwater under combined stresses of aromatic hydrocarbons (AHs), NH4+, and Fe-Mn exceeding standard levels was studied in an abandoned oil depot in Northeast China. The response of environmental parameters and microbial communities under different pollution levels in the study area was discussed, and microscopic experiments were conducted using background groundwater with different AHs concentrations. The results showed that indigenous microbial community were significantly affected by environmental factors, including pH, TH, CODMn, TFe, Cr (VI), NH4+, NO3-, and SO42-. AHs likely had a limited influence on microbial communities, mainly causing indirect changes in the microbial community structure by altering the electron donor/acceptor (mainly Fe, Mn, NO3-, NO2-, NH4+, and SO42-) content in groundwater, and there was no linear effect of AHs content on the microbial community. In low- and medium-AHs-contaminated groundwater, the microbial diversity increased, whereas high AHs contents decreased the diversity of the microbial community. The microbial community had the strongest ability to metabolize AHs in the medium-AHs-contaminated groundwater. In the high-AHs-contaminated groundwater, microbial communities mainly degraded AHs through a complex co-metabolic mechanism due to the inhibitory effect caused by the high concentration of AHs, whereas in low-AHs-contaminated groundwater, microbial communities mainly caused a mutual transformation of inorganic electron donors/acceptors (mainly including N, S), and the microbial community's ability to metabolize AHs was weak. In the high-AHs-contaminated groundwater, the microbial community resisted the inhibitory effect of AHs mainly via a series of resistance mechanisms, such as regulating their life processes, avoiding unfavorable environments, and enhancing their feedback to the external environment under high-AHs-contaminated conditions.


Assuntos
Água Subterrânea , Hidrocarbonetos Aromáticos , Microbiota , Poluentes Químicos da Água , Biodegradação Ambiental , Poluentes Químicos da Água/análise , Água Subterrânea/química
6.
J Headache Pain ; 22(1): 129, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34711175

RESUMO

OBJECTIVES: In this study, we aimed to investigate the spontaneous neural activity in the conventional frequency band (0.01-0.08 Hz) and two sub-frequency bands (slow-4: 0.027-0.073 Hz, and slow-5: 0.01-0.027 Hz) in tension-type headache (TTH) patients with regional homogeneity (ReHo) analyses. METHODS: Thirty-eight TTH patients and thirty-eight healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (RS-fMRI) scanning to investigate abnormal spontaneous neural activity using ReHo analysis in conventional frequency band (0.01-0.08 Hz) and two sub-frequency bands (slow-4: 0.027-0.073 Hz and slow-5: 0.01-0.027 Hz). RESULTS: In comparison with the HC group, patients with TTH exhibited ReHo increases in the right medial superior frontal gyrus in the conventional frequency band (0.01-0.08 Hz). The between group differences in the slow-5 band (0.01-0.027 Hz) highly resembled the differences in the conventional frequency band (0.01-0.08 Hz); even the voxels with increased ReHo were spatially more extensive, including the right medial superior frontal gyrus and the middle frontal gyrus. In contrast, no region showed significant between-group differences in the slow-4 band (0.027-0.073 Hz). The correlation analyses showed no correlation between the ReHo values in TTH patients and VAS scores, course of disease and number of seizures per month in conventional band (0.01-0.08 Hz), slow-4 band (0.027-0.073 Hz), as well as in slow-5 band (0.01-0.027 Hz). CONCLUSIONS: The results showed that the superior frontal gyrus and middle frontal gyrus were involved in the integration and processing of pain signals. In addition, the abnormal spontaneous neural activity in TTH patients was frequency-specific. Namely, slow-5 band (0.01-0.027 Hz) might contain additional useful information in comparison to slow-4 band (0.027-0.073 Hz). This preliminary exploration might provide an objective imaging basis for the understanding of the pathophysiological mechanism of TTH.


Assuntos
Imageamento por Ressonância Magnética , Cefaleia do Tipo Tensional , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Lobo Frontal , Humanos , Cefaleia do Tipo Tensional/diagnóstico por imagem
7.
J Musculoskelet Neuronal Interact ; 19(4): 422-434, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31789293

RESUMO

OBJECTIVE: To investigate the expression profile of lncRNAs in bone and skeletal muscle of ovariectomized (OVX) rats. METHODS: Six-month-old female Sprague-Dawley (SD) rats were divided into OVX group (ovariectomized, n=12) and sham group (sham-operated, n=12). After 12 weeks, RNA-seq was used to analyze the differential expression of lncRNAs and mRNAs in femur and quadriceps between two groups. Dys-regulated expression of lncRNAs was confirmed by qRT-PCR. The cis and trans-regulatory functions were analyzed to determine their function and biological processes. Lastly, GO and KEGG analyses were performed to assess the biological relevance of genes in each profile. RESULTS: A total of 17 lncRNAs and 440 mRNAs were differentially expressed in the femur. Thirteen lncRNAs and 292 mRNAs were differentially expressed in the quadriceps. qRT-PCR results were in consistent with the RNA-seq data. Among them, ENSRNOT00000090777 was found in both femur and quadriceps samples. Bioinformatics analysis found that LNC_004549 participated in the differentiation of skeletal and skeletal muscle. CONCLUSIONS: The expression profile of lncRNAs was significantly altered in femur and quadriceps of OVX rat models, which may offer new insights into pathogenesis of osteoporosis and sarcopenia and potentially provide novel therapeutic targets.


Assuntos
Fêmur/metabolismo , Músculo Esquelético/metabolismo , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Animais , Biologia Computacional , Feminino , Perfilação da Expressão Gênica , Ovariectomia , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Análise de Sequência de RNA
8.
Int J Neuropsychopharmacol ; 20(6): 485-497, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28339691

RESUMO

Background: Z-guggulsterone, an active compound extracted from the gum resin of the tree Commiphora mukul, has been shown to improve animal memory deficits via activating the brain-derived neurotrophic factor signaling pathway. Here, we investigated the antidepressant-like effect of Z-guggulsterone in a chronic unpredictable stress mouse model of depression. Methods: The effects of Z-guggulsterone were assessed in mice with the tail suspension test and forced swimming test. Z-guggulsterone was also investigated in the chronic unpredictable stress model of depression with fluoxetine as the positive control. Changes in hippocampal neurogenesis as well as the brain-derived neurotrophic factor signaling pathway after chronic unpredictable stress/Z-guggulsterone treatment were investigated. The tryptophan hydroxylase inhibitor and the tyrosine kinase B inhibitor were also used to explore the antidepressant-like mechanisms of Z-guggulsterone. Results: Z-guggulsterone (10, 30 mg/kg) administration protected the mice against the chronic unpredictable stress-induced increases in the immobile time in the tail suspension test and forced swimming test and also reversed the reduction in sucrose intake in sucrose preference experiment. Z-guggulsterone (10, 30 mg/kg) administration prevented the reductions in brain-derived neurotrophic factor protein expression levels as well as the phosphorylation levels of cAMP response element binding protein, extracellular signal-regulated kinase 1/2, and protein kinase B in the hippocampus and cortex induced by chronic unpredictable stress. Z-guggulsterone (10, 30 mg/kg) treatment also improved hippocampal neurogenesis in chronic unpredictable stress-treated mice. Blockade of the brain-derived neurotrophic factor signal, but not the monoaminergic system, attenuated the antidepressant-like effects of Z-guggulsterone. Conclusions: Z-guggulsterone exhibits antidepressant activity via activation of the brain-derived neurotrophic factor signaling pathway and upregulation of hippocampal neurogenesis.


Assuntos
Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/metabolismo , Pregnenodionas/farmacologia , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fluoxetina/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Neurogênese/efeitos dos fármacos , Neurogênese/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
9.
Neurochem Res ; 42(10): 2698-2711, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28434164

RESUMO

Recently, the loss and dystrophy of hippocampal microglia induced by chronic unpredictable stress (CUS) has been reported to mediate the development of major depression in mice whose microglial cells were labeled with enhanced green fluorescent protein-conjuncted-CX3C receptor type 1. However, whether this happens in endogenous microglia with no genetic intervention remains unclear. Here, we addressed this issue in mice treated with different types of chronic stresses, including the CUS, chronic restraint stress (CRS) and chronic social defeat stress (CSDS). Results showed that the cellular numbers, process lengths, soma areas and activation markers of endogenous hippocampal but not cortical microglia, were markedly reduced by CUS, CRS and CSDS treatment. Administration of mice with two classical stimulators of microglia, lipopolysaccharide (LPS) or macrophage colony-stimulating factor (M-CSF), reversed the CUS-, CRS- and CSDS-induced reductions in endogenous hippocampal microglial numbers, and also improved the CUS-, CRS- or CSDS-induced behavioral abnormalities, including the increases in the immobile time in the forced swimming test and tail suspension test, the inhibition of sucrose preference, and the decrease in the time spent in the center of open field. Furthermore, inhibition of the initial activation of hippocampal microglia by minocycline pretreatment also reversed the reduction in hippocampal microglial numbers as well as the behavioral abnormalities induced by CUS, CRS and CSDS treatment. These results provide compelling evidences to show that different types of chronic stresses can trigger the loss of endogenous hippocampal microglia and restoration of microglial numbers may have therapeutic values in major depression.


Assuntos
Hipocampo/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Microglia/efeitos dos fármacos , Minociclina/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Transtorno Depressivo Maior/etiologia , Masculino , Camundongos , Neurônios/efeitos dos fármacos , Estresse Psicológico/fisiopatologia
10.
Pharmacology ; 99(3-4): 153-159, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28049198

RESUMO

Glutamate transporter-1 (GLT-1), a major glutamate transporter expressed in astrocytes, takes up excess glutamate from the micro-environment in order to prevent excitotoxicity. Drugs that increase GLT-1 expression may have therapeutic effects in disorders associated with neuronal excitotoxicity. 2,3,4',5-tetrahydroxystilbene 2-O-ß-D-glucoside (TSG), a monomer of stilbene from polygonummultiflorum, exerts neuroprotection in a range of experimental models such as Alzheimer's disease and brain ischemia. In this study, we evaluated the effect of TSG on GLT-1 protein expression in mouse primary-cultured astrocytes. Results showed that TSG markedly increased the GLT-1 protein expression level in mouse primary-cultured astrocytes in a dose- and time-dependent manner, and this increase was mediated by the activation of protein kinase B (Akt) but not by the activation of extracellular signal-regulated protein kinase 1/2. Furthermore, inhibition of cAMP response element-binding protein, but not nuclear factor kappa B, abolished the TSG-mediated increase in GLT-1 protein expression in cultured astrocytes. Collectively, these findings may provide novel insights into the mechanism for TSG in neuroprotection, and would help search new agents targeting neurodegenerative disorders associated with impaired astrocytic glutamate transporters.


Assuntos
Astrócitos/efeitos dos fármacos , Transportador 2 de Aminoácido Excitatório/biossíntese , Glucosídeos/farmacologia , Estilbenos/farmacologia , Regulação para Cima/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Astrócitos/metabolismo , Células Cultivadas , Regulação da Expressão Gênica , Glucosídeos/química , Camundongos , Camundongos Endogâmicos C57BL , Estilbenos/química , Regulação para Cima/fisiologia
11.
Pharmacology ; 97(5-6): 245-50, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26881748

RESUMO

Sickness behavior is a coordinated set of behavioral changes that happen as a response to acute infectious pathogens. Its well-known benefit is to reorganize the organism's priorities to cope with infection, but the uncontrolled development of sickness behavior may trigger negative feelings or chronic depressive events. This study aims at investigating the potential effect of pifithrin-µ, an inhibitor of heat shock protein 70 substrate binding activity, on lipopolysaccharide (LPS)-induced sickness response. C57BL/6J mice were submitted to the forced swimming test (FST), tail suspension test (TST), open field test (OFT) and light-dark box test. Food intake and body weight were also evaluated. The serum corticosterone level was measured using an ELISA kit. Treatment of mice with LPS (0.33 mg/kg, i.p.) markedly increased the floating and immobility time in the FST and TST, respectively, and depressed locomotor activity in the OFT. LPS administration prolonged the latency to first transition and reduced the total number of transitions in the light-dark box test. In addition, LPS induced anorexia and increased serum corticosterone levels. Pretreatment with pifithrin-µ (1 or 5 mg/kg) attenuated behavioral changes induced by LPS in the FST, TST, OFT and light-dark box test. Pifithrin-µ also prevented the formation of anorexia as well as the increase in serum corticosterone levels in LPS-treated mice. Our previous studies showed that pifithrin-µ prevents the production of pro-inflammatory factors in both microglia and macrophages. These findings presented here extend the role of pifithrin-µ beyond an anti-inflammatory molecule to a modulator of sickness behavior.


Assuntos
Comportamento Animal/efeitos dos fármacos , Comportamento de Doença/efeitos dos fármacos , Sulfonamidas/uso terapêutico , Animais , Corticosterona/sangue , Ingestão de Alimentos/efeitos dos fármacos , Comportamento Exploratório/efeitos dos fármacos , Elevação dos Membros Posteriores , Lipopolissacarídeos , Masculino , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Natação
12.
J Neuroinflammation ; 12: 189, 2015 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-26467650

RESUMO

BACKGROUND: Inducible nitric oxide synthase (iNOS) makes a great contribution to host defense and inflammation. In many settings, lipopolysaccharide (LPS) induces iNOS expression through activation of the inhibitor of κB-α (IκB-α)-nuclear factor-κB (NF-κB) cascade, whereas interferon-γ (IFN-γ) acts through Janus kinase (JAK)-signal transducer and activator of transcription 1 (STAT1) signals. Heat shock factor 1 (HSF1), a major regulator of heat shock protein transcription, has been shown to regulate the production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), but it remains obscure whether and how HSF1 affects iNOS induction. METHODS: Western blot was used to measure the protein expression. The mRNA level was measured by real-time PCR. Silence of HSF1 was achieved by small interfering RNA. Nitric oxide (NO) content and NF-κB binding activity were assayed by commercial kits. Chromatin immunoprecipitation (ChIP) was used to measure the binding activity of NF-κB and STAT1 to iNOS promoters. RESULTS: HSF1 inhibition or knockdown prevented the LPS- and/or IFN-γ-stimulated iNOS protein expression in cultured microglia. HSF1 inhibition blocked iNOS mRNA transcription. These inhibitory effects of HSF1 inhibition on iNOS expression were confirmed in brain tissues from endotoxemic mice. Further analysis showed that HSF1 inhibition had no effect on IκB-α degradation and NF-κB or STAT1 phosphorylation in LPS/IFN-γ-stimulated cells. The nuclear transport of active NF-κB or STAT1 was also not affected by HSF1 inhibition, but HSF1 inhibition reduced the binding of NF-κB and STAT1 to their DNA elements. In addition, HSF1 inhibition reduced NF-κB and STAT1 bindings to iNOS promoter inside the LPS/IFN-γ-stimulated cells. CONCLUSIONS: This preventing effect of HSF1 inhibition on iNOS mRNA transcription presents the necessary role of HSF1 in iNOS induction.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Microglia/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fatores de Transcrição/metabolismo , Aminopiridinas/farmacologia , Animais , Animais Recém-Nascidos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Relação Dose-Resposta a Droga , Fatores de Transcrição de Choque Térmico , Indazóis/farmacologia , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Ligação Proteica/efeitos dos fármacos , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/farmacologia , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/genética
13.
Oncol Res Treat ; 47(10): 474-483, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38934176

RESUMO

INTRODUCTION: Anal mucinous adenocarcinoma (AMAC) is an extremely rare form of anal cancer. Our objective was to examine the incidence, management, and prognostic factors of AMAC. METHODS: We analyzed age-adjusted incidence (AAI) rates over time and compared the prognosis of AMAC with anal squamous cell carcinoma (ASCC) and adenocarcinoma (AAC) using propensity score matching and Kaplan-Meier analysis. Patients were classified based on summary stage and treatments to determine cancer-specific survival. RESULTS: AAI of AMAC fluctuated within a narrow range (0.082-0.237 per million person-years) from 2000 to 2018. AMAC had a slight non-significant trend of worse prognosis than ASCC (p = 0.348) and a better prognosis than AAC (p < 0.01). Females made up a larger proportion of patients diagnosed with the distant disease (p < 0.05) and unmarried (p < 0.05) and somewhat less probably to need surgical removal (p < 0.01) and radiotherapy (p < 0.01). Elderly patients have lower rates of survival (p < 0.05). Localized stage was associated with better prognosis (p < 0.05). Surgery was associated with a tendency toward better survival (p = 0.095). CONCLUSIONS: AMAC exhibits a low incidence yet favorable prognosis compared to typical AAC and slightly worse compared to ASCC. Elderly age is associated with poorer prognosis, while localized stage indicates better prognosis. Surgery demonstrates a trend toward improved survival.


Assuntos
Adenocarcinoma Mucinoso , Neoplasias do Ânus , Pontuação de Propensão , Humanos , Neoplasias do Ânus/terapia , Neoplasias do Ânus/mortalidade , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/patologia , Feminino , Masculino , Adenocarcinoma Mucinoso/terapia , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/epidemiologia , Adenocarcinoma Mucinoso/patologia , Pessoa de Meia-Idade , Idoso , Prognóstico , Incidência , Adulto , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Taxa de Sobrevida , Estimativa de Kaplan-Meier , Estadiamento de Neoplasias , Programa de SEER
14.
Sci Total Environ ; 948: 174596, 2024 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-38997023

RESUMO

The study embarked on a comprehensive examination of the evolution and diversity of microorganisms within long-term leachate pollution environments, with a focus on varying depths and levels of contamination, and its linkage to soil characteristics and the presence of heavy metals. It was observed that microbial diversity presented distinct cross-depth trend, where archaeal communities were found to be particularly sensitive to alterations in soil depth. Noteworthily, Euryarchaeota increased by 4.82 %, 7.64 % and 9.87 % compared with topsoil. The abundance of Tahumarchaeota was successively reduced by 5.79 %, 9.58 %, and 12.66 %. The bacterial community became more sensitive to leachate pollution, and the abundance of Protebacteria in contaminated soil decreased by 10.27 %, while the abundance of Firmicutes increased by 7.46 %. The bacterial genus Gemmobacter, Chitinophaga and Rheinheimera; the archaeal genus Methanomassiliicoccus and Nitrosopumilus; along with the fungal genus Goffeauzyma, Gibberella, and Setophaeosphaeria emerged as pivotal biological markers for their respective domains, underpinning the biogeochemical dynamics of these environments. Furthermore, the study highlighted that geochemical factors, specifically nitrate (NO3--N) levels and humic acid (HA) fractions, played crucial roles in modulating the composition and metabolic potential of these communities. Predictive analyses of functional potentials suggested that the N functional change of archaea was more pronounced, with anaerobic ammonia oxidation and nitrification decreased by 15.78 % and 14.62 %, respectively. Overall, soil characteristics alone explained 57.9 % of the total variation in the bacterial community structure. For fungal communities within contaminated soil, HMs were the primary contributors, explaining 46.9 % of the variability, while soil depth accounting for 6.4 % of the archaeal variation. This research enriches the understanding of the complex interrelations between heavy metal pollution, soil attributes, and microbial communities, paving the way for informed strategies in managing informal landfill sites effectively.


Assuntos
Archaea , Microbiota , Microbiologia do Solo , Poluentes do Solo , Instalações de Eliminação de Resíduos , Poluentes do Solo/análise , Microbiota/efeitos dos fármacos , Bactérias/classificação , Solo/química , Monitoramento Ambiental , Metais Pesados/análise , Fungos , Poluentes Químicos da Água/análise , China
15.
Chemosphere ; 363: 142833, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39002654

RESUMO

In this study, we examined the aging characteristics of polyethylene (PE) and polylactic acid (PLA) microplastics (MPs), examining the adsorption behaviors and mechanisms concerning Cd(II) and Cr(VI) under both single and binary systems. The results revealed that aging treatment changed the physicochemical properties of MPs. The aging mechanisms of PLA and PE MPs were shown to be similar by the 2D-FTIR-COS study. These mechanisms involve the formation of oxygen-containing functional groups through the combination of carbon chain breakdown and oxygen. Aged MPs had a greater ability to adsorb metal ions than pristine MPs, with PLA MPs outperforming PE MPs. After 30 days of aging, Cd(II) adsorption increased by 40.61 % and 25.49 % for PE and PLA MPs, respectively, while Cr(VI) adsorption increased by 37.50 % and 69.29 %, respectively. The adsorption ability of PE and PLA MPs with Cd(II) or Cr(VI) under binary systems was less than that under single systems, with Cd(II) exhibiting more adsorption competitiveness than Cr(VI). Humic acid (HA), ionic species and strength, solution pH, and adsorption of Cd(II) and Cr(VI) were found to be significantly correlated. Further investigation into the adsorption mechanisms of Cd(II) and Cr(VI) on PE and PLA MPs revealed that pore-filling, electrostatic interactions, complexation, and hydrogen bonding play important roles in the adsorption process. The study's conclusions are crucial for assessing the risk associated with concurrent contamination by metal ions and microplastics.


Assuntos
Cádmio , Cromo , Microplásticos , Poliésteres , Polietileno , Poluentes Químicos da Água , Poliésteres/química , Adsorção , Cádmio/química , Polietileno/química , Poluentes Químicos da Água/química , Microplásticos/química , Cromo/química , Substâncias Húmicas
16.
Chemosphere ; 349: 140951, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38101485

RESUMO

Salinity, a critical factor, could directly or indirectly affect the microbial community structure and diversity. Changes in salinity levels act as environmental filters that influence the transformation of key microbial species. This study investigates the adaptive characteristics of indigenous microflora in groundwater in relation to external organic pollutants under high salinity stress. A highly mineralized shallow groundwater in Northwest China was conducted as the study area, and six representative sampling points were chosen to explore the response of groundwater hydrochemical parameters and microflora, as well as to identify the tolerance mechanisms of indigenous microflora to combined pollution. The results revealed that the dominant genera found in high salinity groundwater contaminated with organic pollutants possess the remarkable ability to degrade such pollutants even under challenging high salinity conditions, including Halomonas, Pseudomonas, Halothiobacillus, Sphingomonas, Lutibacter, Aquabacterium, Thiomicrospira, Aequorivita, etc. The hydrochemical factors, including total dissolved solids (TDS), sulfide, nitrite, nitrate, oxidation reduction potential (ORP), NH3-N, Na, Fe, benzene series, phenols, and halogenated hydrocarbons, demonstrated a significant influence on microflora. High levels of sulphate and sulfide in groundwater can exhibit dual effects on microflora. On one hand, these compounds can inhibit the growth and metabolism of microorganisms. On the other hand, they can also serve as effective electron donors/receptors during the microbial degradation of organic pollutants. Microorganisms exhibit resilience to the inhibitory effects of high salinity and organic pollutants via a series of tolerance mechanisms, such as strengthening the extracellular membrane barrier, enhancing the synthesis of relevant enzymes, initiating novel biochemical reactions, improving cellular self-healing capabilities, responding to unfavorable environmental conditions by migration, and enhancing the S cycle for the microbial metabolism of organic pollutants.


Assuntos
Poluentes Ambientais , Água Subterrânea , Poluentes Químicos da Água , Monitoramento Ambiental , Salinidade , Poluentes Químicos da Água/análise , Água Subterrânea/química , Sulfetos
17.
Int J Biol Macromol ; 279(Pt 2): 135167, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39236944

RESUMO

How to solve the contradiction between the efficiency and adsorption rate of porous materials in adsorbing pollutants has always been one of the focus issues. In this study, the small landscape cypress trees structure like biomimetic of a hierarchical and dual morphology 3D porous HA-based aerogel was designed and synthesized to use humic acid (HA), pectin (PE) and chitosan (CTS) as raw materials, which it was formed by the disorderly overlapping of lamella composed of fiber networks in 3D space. Due to its special microstructure, it can be used like separation membrane, which allowing for rapid adsorption of pollutants in the water while the water flow passes through quick. In general, this work provides a new concept for owning fast adsorption rate and efficient adsorption of porous materials of preparation to use green method.


Assuntos
Quitosana , Géis , Substâncias Húmicas , Pectinas , Águas Residuárias , Poluentes Químicos da Água , Purificação da Água , Quitosana/química , Substâncias Húmicas/análise , Pectinas/química , Pectinas/isolamento & purificação , Águas Residuárias/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Adsorção , Purificação da Água/métodos , Géis/química , Porosidade
18.
Brain Imaging Behav ; 18(4): 819-829, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38512647

RESUMO

Previous studies have provided evidence of structural and functional changes in the brains of patients with tension-type headache (TTH). However, investigations of functional connectivity alterations in TTH have been inconclusive. The present study aimed to investigate abnormal intrinsic functional connectivity patterns in patients with TTH through the voxel-wise degree centrality (DC) method as well as functional connectivity (FC) analysis. A total of 33 patients with TTH and 30 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning and were enrolled in the final study. The voxel-wise DC method was performed to quantify abnormalities in the local functional connectivity hubs. Nodes with abnormal DC were used as seeds for further FC analysis to evaluate alterations in functional connectivity patterns. In addition, correlational analyses were performed between abnormal DC and FC values and clinical features. Compared with HCs, patients with TTH had higher DC values in the left middle temporal gyrus (MTG.L) and lower DC values in the left anterior cingulate and paracingulate gyri (ACG.L) (GRF, voxel-wise p < 0.05, cluster-wise p < 0.05, two-tailed). Seed-based FC analyses revealed that patients with TTH showed greater connections between ACG.L and the right cerebellum lobule IX (CR-IX.R), and smaller connections between ACG.L and ACG.L. The MTG.L showed increased FC with the ACG.L, and decreased FC with the right caudate nucleus (CAU.R) and left precuneus (PCUN.L) (GRF, voxel-wise p < 0.05, cluster-wise p < 0.05, two-tailed). Additionally, the DC value of the MTG.L was negatively correlated with the DASS-depression score (p = 0.046, r=-0.350). This preliminary study provides important insights into the pathophysiological mechanisms of TTH.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Vias Neurais , Descanso , Cefaleia do Tipo Tensional , Humanos , Imageamento por Ressonância Magnética/métodos , Cefaleia do Tipo Tensional/fisiopatologia , Cefaleia do Tipo Tensional/diagnóstico por imagem , Feminino , Adulto , Masculino , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Descanso/fisiologia , Mapeamento Encefálico/métodos , Adulto Jovem , Pessoa de Meia-Idade , Rede Nervosa/fisiopatologia , Rede Nervosa/diagnóstico por imagem
19.
Sci Total Environ ; 894: 164900, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37343867

RESUMO

To understand the response characteristics of indigenous microbial community in PAH-contaminated aquifers to the coexistence of microplastics. In this paper, we constructed a groundwater microecosystem using lithologic media collected from the field and subjected it to the stress of a polyethylene microplastics (PE-MPs) concentration gradient. By conducting adsorption experiments and 16S rRNA sequencing, we revealed the growth, structure, metabolism, and resistance mechanisms of the indigenous microbial community in the aquifer lithologic media exposed to varying levels of co-stress from PE-MPs and phenanthrene. Our findings suggest that the adsorption capacity of aquifer lithologic media for phenanthrene is significantly weaker than that of PE-MPs. Additionally, our observations indicated that small particle lithologic media had a greater adsorption capacity for phenanthrene than large particle lithologic media. The presence of PE-MPs was found to increase both the abundance and diversity of microbial communities, although the relationship was not linear with the content of PE-MPs. When exposed to the combined stress of PE-MPs and phenanthrene, the relative abundance of Proteobacteria decreased while that of Bacteroidetes increased. Several genera belonging to Proteobacteria (Aeromonas, Desulfovibrio, Klebsiella, Pantoea, and Microvirgula) and Bacteroidetes (Macellibacteroides and Bacteroides) occupied a central position in the microbial community interaction network and showed significant correlations with other genera. Furthermore, an increase in the proportion of genera capable of degrading various refractory organics was observed. The presence of PE-MPs increased the phenanthrene content in the aquifer lithologic media, thereby intensifying the inhibitory effect on indigenous microbial community in this environment. Despite an increase in the phenanthrene content of aquifer lithologic media due to the presence of PE-MPs, indigenous microbial community in this environment exhibited resistance to the combined inhibition of PE-MPs and phenanthrene through a series of resistance mechanisms. These mechanisms included strengthening the N-cycle process, enhancing metabolic capacity for phenanthrene, improving perception, response, and adaptation to changes in the external environment or intracellular state, modifying the transmembrane transport of the cell membrane to the substrate, and regulating life processes.


Assuntos
Microbiota , Fenantrenos , Hidrocarbonetos Policíclicos Aromáticos , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Microplásticos , Plásticos , Polietileno , RNA Ribossômico 16S , Fenantrenos/metabolismo
20.
Chemosphere ; 311(Pt 2): 137173, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36356804

RESUMO

The environmental conditions at a contaminated site will impact on the indigenous microbial communities, with implications for the removal of pollutants. An analysis of the characteristics of microbial communities in petroleum-contaminated groundwater can give insights into the relationships between microbial community and environmental factors, and provide guidance about how microbes can be used to remediate and regulate petroleum-contaminated groundwater. This study focuses on two petroleum-contaminated sites in northeast China, the physico-chemical-biological changes in petroleum-contaminated groundwater were analyzed, the response relationship between hydro-chemical indicators and microbial communities was characterized, and the bioindicator that can reflect the petroleum contamination status were established for environmental monitoring and management. The results showed that Proteobacteria was the dominant bacteria in petroleum-contaminated groundwater, with a relative abundance of 42.45%-91.19%. pH, TDS, DO, NO3-, NO2-, SO42-, NH4+, Al, and Mn have significant effects on microbial community. The effect of petroleum pollutants on microbial communities is not only related to the concentration and composition of the pollutants themselves, but also could indirectly affect microbial communities by changing the content of inorganic electron acceptor components such as iron, manganese, sulfate and nitrate in groundwater, and this indirect effect is significantly greater than the direct impact of pollutants on microbial communities. In petroleum-contaminated groundwater, the dominant genera (Polaromonas, Caulobacter) and microbial metabolic functions (methanol oxidation, methylotrophy, ureolysis, and reductive biosynthesis) of the indigenous microbial community can be used as bioindicators to indicate petroleum contamination status. The higher abundance of these bioindicators in petroleum-contaminated groundwater, the more serious petroleum pollution in groundwater.

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