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1.
Inflamm Res ; 73(7): 1173-1184, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38739197

RESUMO

OBJECTIVE AND DESIGN: To elucidate Sirt1's role in gouty arthritis inflammation and its potential mechanisms. MATERIAL: Constructed murine models of gouty arthritis and conducted THP-1 cell experiments. TREATMENT: 1 mg of MSU crystals injected into mice ankle joints for a 72-h intervention. After a 3-h pre-treatment with Sirt1-specific inhibitor (EX527) and agonist (SRT2104), inflammation was induced for 21 h using lipopolysaccharide (LPS) plus MSU crystals. METHODS: We assessed gouty arthritis severity through joint inflammation index, swelling, and hematoxylin and eosin (H&E) staining, and measured CD68 mononuclear macrophages and Sirt1 expression in synovial tissue via immunohistochemistry. ELISA, NO assay, RT-qPCR, Flow cytometry, and Western blot were utilized to examine macrophage inflammatory factors, polarization, reactive oxygen species(ROS), MAPK/NF-κB/AP-1 and Nrf2/HO-1 pathways proteins. RESULTS: Significant joint swelling, synovial tissue edema, and inflammatory cell infiltration were observed. CD68 mononuclear macrophages and Sirt1 expression were elevated in synovium. Sirt1 activation decreased inflammatory factors, M1 polarization, and ROS generation. Sirt1 activation reduced p38/JNK phosphorylation, thereby inhibiting downstream NF-κB p65/AP-1 and enhancing Nrf2/HO-1, thus suppressing inflammation. CONCLUSIONS: Sirt1 alleviates M1 macrophage polarization and inflammation in gouty arthritis by inhibiting the MAPK/NF-κB/AP-1 pathway and activating the Nrf2/HO-1 pathway. Thus, activating Sirt1 may provide a new therapeutic target for gouty arthritis.


Assuntos
Artrite Gotosa , Heme Oxigenase-1 , Macrófagos , Fator 2 Relacionado a NF-E2 , NF-kappa B , Sirtuína 1 , Fator de Transcrição AP-1 , Animais , Artrite Gotosa/tratamento farmacológico , Artrite Gotosa/metabolismo , Artrite Gotosa/imunologia , Sirtuína 1/metabolismo , Sirtuína 1/genética , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/imunologia , Fator 2 Relacionado a NF-E2/metabolismo , Humanos , Masculino , NF-kappa B/metabolismo , Heme Oxigenase-1/metabolismo , Camundongos , Fator de Transcrição AP-1/metabolismo , Células THP-1 , Camundongos Endogâmicos C57BL , Inflamação , Transdução de Sinais/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Carbazóis , Proteínas de Membrana
2.
J Sep Sci ; 47(5): e2300871, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38471978

RESUMO

Postpartum hemorrhage can lead to a variety of maternal complications. Tao Hong Si Wu Decoction (THSWD) is a traditional Chinese medicine used for treating gynecological diseases. However, the active ingredients of THSWD and its pharmacological mechanism of treatment for postpartum blood stasis still remained unclear. In this study, 201 components were identified in THSWD ethanol extract using ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry, including 59 terpenoids and volatile oil, 61 Phenylpropanoids, 41 flavonoids, 22 alkaloids, and other 18 components. A total of 45 active compounds were identified in the blood and 33 active compounds were identified in the uterine. Taking the common components into the blood and into the uterus combined with network pharmacology. It was demonstrated that the active compounds can bind to the core target with good affinity through molecular docking. The results of this study will provide a reference for the quality control and pharmacodynamic material base research of THSWD.


Assuntos
Medicamentos de Ervas Chinesas , Feminino , Humanos , Simulação de Acoplamento Molecular , Medicamentos de Ervas Chinesas/química , Cromatografia Líquida , Período Pós-Parto , Cromatografia Líquida de Alta Pressão/métodos
3.
J Transl Med ; 21(1): 237, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-37005672

RESUMO

Eukaryotic cells are segmented into multiple compartments or organelles within the cell that regulate distinct chemical and biological processes. Membrane-less organelles are membrane-less microscopic cellular compartments that contain protein and RNA molecules that perform a wide range of functions. Liquid-liquid phase separation (LLPS) can reveal how membrane-less organelles develop via dynamic biomolecule assembly. LLPS either segregates undesirable molecules from cells or aggregates desired ones in cells. Aberrant LLPS results in the production of abnormal biomolecular condensates (BMCs), which can cause cancer. Here, we explore the intricate mechanisms behind the formation of BMCs and its biophysical properties. Additionally, we discuss recent discoveries related to biological LLPS in tumorigenesis, including aberrant signaling and transduction, stress granule formation, evading growth arrest, and genomic instability. We also discuss the therapeutic implications of LLPS in cancer. Understanding the concept and mechanism of LLPS and its role in tumorigenesis is crucial for antitumor therapeutic strategies.


Assuntos
Neoplasias , Organelas , Humanos , Organelas/química , Organelas/metabolismo , Proteínas , Membrana Celular , Neoplasias/metabolismo , Carcinogênese/metabolismo
4.
Anal Bioanal Chem ; 415(8): 1437-1444, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36648546

RESUMO

Polybrominated diphenyl ethers (PBDEs) are considered emerging organic contaminants that attract more attention in the environment. Herein, online coupling of solid-phase microextraction and ultrahigh-resolution mass spectrometry was developed for rapid screening of eight PBDEs in water samples. This procedure was completed in 22 min, about 6 times faster than the routine workflow such as solid-phase extraction coupled with gas chromatography-mass spectrometry. Thermal desorption and solvent-assisted atmospheric pressure chemical ionization were developed for the effective coupling of solid-phase microextraction (SPME) with ultrahigh-resolution mass spectrometry (UHRMS), which contributed to the signal enhancement and made the methodology feasible for environmental screening. The limits of detection and quantification were 0.01-0.50 ng/mL and 0.05-4.00 ng/mL, respectively. The recoveries were 57.2-75.2% for quality control samples at spiking levels of 0.8-10 ng/mL (4-50 ng/mL for BDE209), with relative standard deviation less than 19.0%. Twelve water samples from different river sites near industrial areas were screened using the developed method. The results showed that BDE-209 was the dominant PBDE (1.02-1.28 ng/mL in positive samples), but its amount was lower than the human health ambient water quality criteria. Consequently, the developed method provides a rapid and reliable way of evaluating contamination status and risks of PBDEs in aqueous environment.

5.
Exp Cell Res ; 417(2): 113192, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35568072

RESUMO

BACKGROUND: The treatment of acute myeloid leukemia (AML) is developing towards "targeted therapy", which faces challenges such as low sensitivity and drug resistance. Therefore, targeted drugs need to be used in combination with other drugs to overcome clinical problems. OBJECTIVE: AML cells and animal models were used to determine the synergistic anti-leukemic effect of Dactolisib (BEZ235) and Venetoclax (ABT199) and explore its mechanism. METHODS: In vitro experiments, we used cell counting kit-8 (CCK8), flow cytometry, real-time quantitative PCR (qPCR), and Western blot to detect the anti-leukemic effects of ABT199 and BEZ235. In vivo experiments, female nude mice were injected subcutaneously with THP-1 cells to form tumors, evaluate the combined effect of ABT199 and BEZ235 by indicators such as tumor size, tumor weight, Ki67 and cleaved-Caspase3 staining. The mice's body weight and HE staining were used to evaluate the liver injury and adverse drug reactions. RESULTS: The combination of BEZ235 and ABT199 has a synergistic effect through promoting apoptosis and inhibiting proliferation. The BEZ235 increased the drug sensitivity of ABT199 by reducing the MCL-1 protein synthesis and promoted the degradation of MCL-1 protein, which is considered as the mechanism of reversing ABT199 resistance. Furthermore, the BEZ235 and ABT199 can synergistically enhance the inhibition of PI3K/AKT/mTOR pathway. CONCLUSION: The combination of BEZ235 and ABT199 exhibits a synergistic anti-tumor effect in AML by down-regulating MCL-1 protein.


Assuntos
Leucemia Mieloide Aguda , Fosfatidilinositol 3-Quinases , Animais , Apoptose , Compostos Bicíclicos Heterocíclicos com Pontes , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Leucemia Mieloide Aguda/tratamento farmacológico , Camundongos , Camundongos Nus , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sulfonamidas , Serina-Treonina Quinases TOR/metabolismo
6.
Int J Mol Sci ; 24(21)2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37958902

RESUMO

Prion diseases are a group of neurodegenerative diseases characterized by mitochondrial dysfunction and neuronal death. Mitophagy is a selective form of macroautophagy that clears injured mitochondria. Prohibitin 2 (PHB2) has been identified as a novel inner membrane mitophagy receptor that mediates mitophagy. However, the role of PHB2 in prion diseases remains unclear. In this study, we isolated primary cortical neurons from rats and used the neurotoxic prion peptide PrP106-126 as a cell model for prion diseases. We examined the role of PHB2 in PrP106-126-induced mitophagy using Western blotting and immunofluorescence microscopy and assessed the function of PHB2 in PrP106-126-induced neuronal death using the cell viability assay and the TUNEL assay. The results showed that PrP106-126 induced mitochondrial morphological abnormalities and mitophagy in primary cortical neurons. PHB2 was found to be indispensable for PrP106-126-induced mitophagy and was involved in the accumulation of PINK1 and recruitment of Parkin to mitochondria in primary neurons. Additionally, PHB2 depletion exacerbated neuronal cell death induced by PrP106-126, whereas the overexpression of PHB2 alleviated PrP106-126 neuronal toxicity. Taken together, this study demonstrated that PHB2 is indispensable for PINK1/Parkin-mediated mitophagy in PrP106-126-treated neurons and protects neurons against the neurotoxicity of the prion peptide.


Assuntos
Síndromes Neurotóxicas , Doenças Priônicas , Príons , Animais , Ratos , Mitofagia/fisiologia , Peptídeos/farmacologia , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
7.
BMC Genomics ; 22(1): 835, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34794394

RESUMO

BACKGROUND: A large number of variants have been employed in various medical applications, such as providing medication instructions, disease susceptibility testing, paternity testing, and tumour diagnosis. A high multiplicity PCR will outperform other technologies because of its lower cost, reaction time and sample consumption. To conduct a multiplex PCR with higher than 100 plex multiplicity, primers need to be carefully designed to avoid the formation of secondary structures and nonspecific amplification between primers, templates and products. Thus, a user-friendly, highly automated and highly user-defined web-based multiplex PCR primer design software is needed to minimize the work of primer design and experimental verification. RESULTS: Ultiplex was developed as a free online multiplex primer design tool with a user-friendly web-based interface ( http://ultiplex.igenebook.cn ). To evaluate the performance of Ultiplex, 294 out of 295 (99.7%) target primers were successfully designed. A total of 275 targets produced qualified primers after primer filtration, and 271 of those targets were successfully clustered into one compatible PCR group and could be covered by 108 primers. The designed primer group stably detected the rs28934573(C > T) mutation at lower than a 0.25% mutation rate in a series of samples with different ratios of HCT-15 and HaCaT cell line DNA. CONCLUSION: Ultiplex is a web-based multiplex PCR primer tool that has several functions, including batch design and compatibility checking for the exclusion of mutual secondary structures and mutual false alignments across the whole genome. It offers flexible arguments for users to define their own references, primer Tm values, product lengths, plex numbers and tag oligos. With its user-friendly reports and web-based interface, Ultiplex will provide assistance for biological applications and research involving genomic variants.


Assuntos
Reação em Cadeia da Polimerase Multiplex , Software , Primers do DNA/genética , Internet , Fluxo de Trabalho
8.
Plant Cell Environ ; 44(5): 1692-1706, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33554343

RESUMO

Arsenic stress causes rapid transcriptional responses in plants. However, transcriptional regulators of arsenic-induced gene expression in plants remain less well known. To date, forward genetic screens have proven limited for dissecting arsenic response mechanisms. We hypothesized that this may be due to the extensive genetic redundancy present in plant genomes. To overcome this limitation, we pursued a forward genetic screen for arsenite tolerance using a randomized library of plants expressing >2,000 artificial microRNAs (amiRNAs). This library was designed to knock-down diverse combinations of homologous gene family members within sub-clades of transcription factor and transporter gene families. We identified six transformant lines showing an altered response to arsenite in root growth assays. Further characterization of an amiRNA line targeting closely homologous CBF and ERF transcription factors show that the CBF1,2 and 3 transcription factors negatively regulate arsenite sensitivity. Furthermore, the ERF34 and ERF35 transcription factors are required for cadmium resistance. Generation of CRISPR lines, higher-order T-DNA mutants and gene expression analyses, further support our findings. These ERF transcription factors differentially regulate arsenite sensitivity and cadmium tolerance.


Assuntos
Arabidopsis/metabolismo , Arsenitos/metabolismo , Cádmio/metabolismo , Testes Genéticos , MicroRNAs/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação para Baixo/genética , Regulação da Expressão Gênica de Plantas , MicroRNAs/genética , Mutação/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição/metabolismo
9.
Clin Lab ; 67(3)2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33739053

RESUMO

BACKGROUND: Deoxyribonuclease 1-like 3 (DNASE1L3) is an endonuclease associated with many autoimmune diseases and tumors. However, the serum DNASE1L3 level in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains unreported. Thus, this study compared the diagnostic value of DNASE1L3 and alpha-feto-protein (AFP) individually and in combination in HBV-related HCC. METHODS: The study population consisted of 88 patients with HBV-related HCC, 80 patients with HBV-related liver cirrhosis (LC) and 88 control subjects. The serum DNASE1L3 levels were measured using an enzyme-linked immunosorbent assay. The serum AFP was also assayed. RESULTS: Our data showed that the serum DNASE1L3 levels were significantly higher in patients with HBV-related HCC than in the healthy controls and patients with LC. When the two biomarkers were analyzed individually, the receiver operating characteristic curve analysis showed that the areas under the curve of DNASE1L3 and AFP were 0.898 and 0.866, respectively. When DNASE1L3 and AFP were combined, the area under the curve was 0.951. The sensitivities of DNASE1L3 and AFP were 72.73% and 74.81%, respectively, and the specificities were 93.18% and 92.05%, respectively, in the diagnosis of HBV-related HCC. The sensitivity of the two combined could be improved to 89.77%. However, no correlation was found between serum DNASE1L3 and AFP in HBV-related HCC patients (r = 0.005, p = 0.734). CONCLUSIONS: Serum DNASE1L3 has high sensitivity and specificity in the diagnosis of HCC. DNASE1L3 combined with AFP has higher sensitivity and can improve the diagnostic efficiency of HBV-related HCC.


Assuntos
Carcinoma Hepatocelular , Hepatite B , Neoplasias Hepáticas , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Endodesoxirribonucleases , Hepatite B/complicações , Hepatite B/diagnóstico , Vírus da Hepatite B , Humanos , Cirrose Hepática , Neoplasias Hepáticas/diagnóstico , Curva ROC , alfa-Fetoproteínas
10.
Neurochem Res ; 45(2): 278-294, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31792665

RESUMO

Cerebral ischemia-reperfusion injury is a complex pathophysiological process. Poly(ADP-ribose) (PAR) polymerase-1 (PARP-1)/apoptosis-inducing factor (AIF) signaling pathway-mediated apoptosis is one of the non-caspase-dependent cell death programs that are widely present in neurological diseases such as stroke. In our study, we aimed to conduct further research on the effects of Gualou Guizhi decoction (GLGZD) on the PARP-1/AIF signaling pathway in cell apoptosis after ischemia-reperfusion injury caused by middle cerebral artery occlusion (MCAO). The results showed that GLGZD administration for 7 days significantly ameliorated MCAO-induced neurological damage, limb paralysis and the pathological state of the ischemic cortex. GLGZD exerted its effects by significantly reducing the volume of ischemic cerebral infarction, increasing the number of Nissl-positive cells, and reducing neuronal apoptosis. Furthermore, Western blot analysis showed that GLGZD significantly inhibited the total protein expression of PARP-1, PAR, AIF and endonuclease G (Endo G) in the ischemic cortex and significantly increased the total protein expression of heat-shock protein 70 (Hsp70). On the one hand, the expression of PARP-1, AIF and Endo G protein in the nucleus significantly decreased while the expression of PAR nucleoprotein significantly upregulated. On the other hand, compared with the MCAO model group, the GLGZD-treated group showed a significantly reduced protein expression of PAR in mitochondria and significantly increased protein expression of mitochondrial AIF and Endo G. It was concluded that GLGZD had good therapeutic effects in MCAO model rats. These effects were closely related to GLGZD-mediated inhibition of ischemia-induced neuronal apoptosis by regulation of protein expression and translocation in the PARP-1/AIF signaling pathway.


Assuntos
Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Animais , Fator de Indução de Apoptose/metabolismo , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Medicamentos de Ervas Chinesas/química , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Masculino , Fármacos Neuroprotetores/química , Poli(ADP-Ribose) Polimerase-1/metabolismo , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
11.
Biochem Biophys Res Commun ; 487(2): 333-338, 2017 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-28412363

RESUMO

WD40 repeat protein WDR5 is a core component of the Set/MLL histone methyltransferase complex which catalyzes histone H3 Lys4 trimethylation and activates gene transcription in human cells. WDR5 promotes Set/MLL complex assembly and mediates the complex binding to Lys4-dimethylated histone H3 tail. Most earlier studies report that WDR5 exerts profound effects on various cellular and organismal processes mainly through epigenetic regulation of gene transcription. However, the functions of WDR5 in lung cancer remain largely unknown. Here, we report that WDR5 positively regulates p53 stability by inhibiting p53 ubiquitination in human lung cancer A549 cells. Overexpression of WDR5 dramatically increases p53 protein levels and its half-life in A549 cells, while depletion of WDR5 with WDR5-specific siRNAs significantly decreases p53 protein levels. We also observe that WDR5 is required for p53 induction in response to cisplatin treatment. Mechanistically, WDR5 colocalizes with p53 and inhibits p53 ubiquitination, resulting in p53 stabilization. Consequently, overexpression of WDR5 induces G1 phase arrest in A549 cells, and knocking down WDR5 by siRNAs reduces the population at G1 phase. Furthermore, p53 expression levels is at least in part determined by the p53 positive regulator WDR5 in some cancer cells. Taken together, these data suggest that WDR5 is directly involved in p53 signaling pathway. Our studies provide a new insight into WDR5 functions in A549 cells.


Assuntos
Cisplatino/uso terapêutico , Histona-Lisina N-Metiltransferase/metabolismo , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Ubiquitinação , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias Experimentais/patologia , Resultado do Tratamento , Ubiquitina/metabolismo , Proteínas Ubiquitinadas/metabolismo , Regulação para Cima
12.
Biochem Biophys Res Commun ; 488(4): 584-589, 2017 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-28528977

RESUMO

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms originating from the gastrointestinal tract with gain of function mutations in receptor tyrosine kinases KIT or platelet-derived growth factor receptor A (PDGFRA). The main effective treatment for GISTs is tyrosine kinase inhibitors, such as imatinib mesylate. However, GISTs respond to imatinib treatment eventually develop acquired resistance, which is a main obstacle for GISTs therapy. Therefore, it's urgent to have a better understanding of the mechanisms underlying the imatinib resistance in GISTs to develop novel therapeutic strategies. X-linked inhibitor of apoptosis (XIAP) is the most potent apoptosis inhibitor among the inhibitor of apoptosis protein (IAP) family members. Increased cellular expression of XIAP often leads to drug resistance in cancers. Here we report that XIAP is induced upon imatinb treatment in GIST882 cells, leading to imatinib-induced autophagy. Imatinib-induced autophagy was impaired in XIAP-knockout cells generated by CRISPR/Cas9 system demonstrated by the decreasing of LC3 lipidation. XIAP knockout sensitizes GIST882 cells to imatinib-induced apoptotic cell death, suggesting that XIAP protects GIST882 cells from imatinib-induced cell death by inducing autophagy. Thus, the resistance of the GIST882 cells to imatinib appears to be, in part, due to the increasing of XIAP and subsequent induction of autophagy.


Assuntos
Autofagia/efeitos dos fármacos , Mesilato de Imatinib/farmacologia , Regulação para Cima/efeitos dos fármacos , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Humanos , Células Tumorais Cultivadas
13.
Sensors (Basel) ; 16(12)2016 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-27897984

RESUMO

With the wide use of mobile sensing application, more and more location-embedded data are collected and stored in mobile clouds, such as iCloud, Samsung cloud, etc. Using these data, the cloud service provider (CSP) can provide location-based service (LBS) for users. However, the mobile cloud is untrustworthy. The privacy concerns force the sensitive locations to be stored on the mobile cloud in an encrypted form. However, this brings a great challenge to utilize these data to provide efficient LBS. To solve this problem, we propose a privacy-preserving LBS scheme for mobile sensing data, based on the RSA (for Rivest, Shamir and Adleman) algorithm and ciphertext policy attribute-based encryption (CP-ABE) scheme. The mobile cloud can perform location distance computing and comparison efficiently for authorized users, without location privacy leakage. In the end, theoretical security analysis and experimental evaluation demonstrate that our scheme is secure against the chosen plaintext attack (CPA) and efficient enough for practical applications in terms of user side computation overhead.

14.
Artigo em Inglês | MEDLINE | ID: mdl-38648006

RESUMO

Understanding the microbial community structure in soil contaminated with heavy metals (HMs) is a precondition to conduct bioremediation in mine soil. Samples were collected from a typical lead-zinc (Pb-Zn) mine to assess the microbial community structure of the HMs concentrated in the soil. The goal was to analyze the bacterial and fungal community structures and their interactions using the 16S rRNA genes and internal transcribed spacer high-throughput sequencing. Analyses at different sampling sites showed that contamination with HMs significantly reduced the bacterial richness and diversity but increased that of the fungi. The predominant bacteria genera of Acidobacteriales, Gaiellales, Anaerolineaceae, Sulfurifustis, and Gemmatimonadaceae, and predominant fungal genera of Sordariomycetes, Talaromyces, and Mortierella were assumed as HM resistant genera in Pb-Zn mining area. The pH effect on the bacterial and fungal communities was opposite to those of Cd, Pb, and Zn. This study offers comprehensive outlooks for bacterial and fungal community structures upon multiple HM stresses in the soil around a typical Pb-Zn mine area.

15.
Children (Basel) ; 11(5)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38790525

RESUMO

(1) Background: With autistic children's high pervasiveness of eating problems and inappropriate feeding behaviors by their caregivers, this study wanted to inspect the connection between caregivers' pressure to eat and food neophobia in these children. (2) Methods: Cross-sectional overview of 160 guardians of kids aged 2 to 7 years. After one-on-one questioning by the researcher, the collected information on the socio-demographic characteristics of the children with autism, caregiver feeding behavior, and new food neophobia (FN) scores was entered into the Questionnaire Star system. (3) Results: The mean FN score was 25.56 ± 6.46. The caregiver's pressure to eat positively related to children's FN (ß = 0.164 95% CI, 0.078, 2.163). In these children, we found a negative correlation between FN score and the frequency of vegetable intake (p ≤ 0.001), fruit intake (p ≤ 0.05), aquatic product intake (p ≤ 0.05), and dietary diversity score (p ≤ 0.01), and positively correlated with the frequency of snack intake (p ≤ 0.05). (4) Conclusions: Caregiver pressure to eat was positively associated with high levels of FN in Chinese kids with ASD, which in turn negatively impacted dietary quality. To improve eating habits, caregivers should reconsider their feeding strategies and avoid using forceful methods to ease food neophobia in these children.

16.
Nat Commun ; 15(1): 5170, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886341

RESUMO

The spatiotemporal regulation of inflammasome activation remains unclear. To examine the mechanism underlying the assembly and regulation of the inflammasome response, here we perform an immunoprecipitation-mass spectrometry analysis of apoptosis-associated speck-like protein containing a CARD (ASC) and identify NCF4/1/2 as ASC-binding proteins. Reduced NCF4 expression is associated with colorectal cancer development and decreased five-year survival rate in patients with colorectal cancer. NCF4 cooperates with NCF1 and NCF2 to promote NLRP3 and AIM2 inflammasome activation. Mechanistically, NCF4 phosphorylation and puncta distribution switches from the NADPH complex to the perinuclear region, mediating ASC oligomerization, speck formation and inflammasome activation. NCF4 functions as a sensor of ROS levels, to establish a balance between ROS production and inflammasome activation. NCF4 deficiency causes severe colorectal cancer in mice, increases transit-amplifying and precancerous cells, reduces the frequency and activation of CD8+ T and NK cells, and impairs the inflammasome-IL-18-IFN-γ axis during the early phase of colorectal tumorigenesis. Our study implicates NCF4 in determining the spatial positioning of inflammasome assembly and contributing to inflammasome-mediated anti-tumor responses.


Assuntos
Proteínas Adaptadoras de Sinalização CARD , Neoplasias Colorretais , Vigilância Imunológica , Inflamassomos , Espécies Reativas de Oxigênio , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Inflamassomos/metabolismo , Animais , Humanos , Camundongos , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Proteínas Adaptadoras de Sinalização CARD/genética , Espécies Reativas de Oxigênio/metabolismo , Progressão da Doença , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , NADPH Oxidases/metabolismo , NADPH Oxidases/genética , Camundongos Knockout , Interleucina-18/metabolismo , Camundongos Endogâmicos C57BL , Masculino , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Feminino , Fosforilação , Linhagem Celular Tumoral
17.
Int J Biol Macromol ; 258(Pt 1): 128520, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38040150

RESUMO

In this study, we developed an enhanced heterogeneous interface intelligent conductive hydrogel NH3 sensor for individualized treatment of infected wounds. The sensor achieved monitoring, self-diagnosis, and adaptive gear adjustment functions. The PPY@PDA/PANI(3/6) sensor had a minimum NH3 detection concentration of 50 ppb and a response value of 2.94 %. It also had a theoretical detection limit of 49 ppt for infected wound gas. The sensor exhibited a fast response time of 23.2 s and a recovery time of 42.9 s. Tobramycin (TOB) was encapsulated in a self-healing QCS/OD hydrogel formed by quaternized chitosan (QCS) and oxidized dextran (OD), followed by the addition of polydopamine-coated polypyrrole nanowires (PPY@PDA) and polyaniline (PANI) to prepare electrically conductive drug-loaded PPY@PDA/PANI hydrogels. The drug-loaded PPY@PDA/PANI hydrogel was combined with a PANI/PVDF membrane to form an enhanced heterogeneous interfacial PPY@PDA/PANI/PVDF-based sensor, which could adaptively learn the individual wound ammonia response and adjust the speed of drug release from the PPY@PDA/PANI hydrogel with electrical stimulation. Drug release and animal studies demonstrated the efficacy of the PPY@PDA/PANI hydrogel in inhibiting infection and accelerating wound healing. In conclusion, the gas-sensitive conductive hydrogel sensing system is expected to enable intelligent drug delivery and provide personalized treatment for complex wound management.


Assuntos
Quitosana , Polímeros de Fluorcarboneto , Polímeros , Polivinil , Animais , Hidrogéis/farmacologia , Pirróis
18.
Am J Health Behav ; 47(1): 13-20, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36945094

RESUMO

Objectives: In this study, examined the acoustic properties of affricates /t/ and /th/ in Mandarin Chinese, and analyzed the differences of the acoustic characteristics of these affricates produced by children with repaired cleft palate and normally developing children. We also explored the relationship between the affricates and high-front vowel /i/. Methods: We analyzed 16 monosyllabic words with alveolo-palatal affricates as the initial consonants produced by children with repaired cleft palate (N=13, Mean=5.9 years) and normally developing children (N=6, Mean age=5.3 years). We used several acoustic parameters to investigate the characteristics of these affricates, such as the center of gravity, VOT and the formants of vowels. Results: Compared with normally developing children, children with cleft palate exhibited a lower center of gravity for the 2 affricates /t/ and /th/. Data from the control group showed that the affricate /th/ had a significantly greater center of gravity than that of /t/. The accuracy of /t , th/ produced by speakers of cleft palate was significantly correlated with that of /i/ (r=0.63). High-front vowel /i/ is a significant index in diagnosing speech intelligibility which is more valuable than /a/ and /u/. There was a significant difference in F2 of vowel /i/ between children with cleft palate without speech therapy (CS1) and after speech therapy (CS2). After speech intervention, the accuracy of affricates produced by children with cleft palate was improved, the acoustic properties "stop + noise segments" appeared. Conclusion: Children with cleft palate can be distinguished better from children with normal development by 2 significant acoustic characteristics: center of gravity and VOT. As alveolo-palatal affricates /t , th/ and high-front vowel /i/ have a similar place of articulation, front-tongue-blade, their production accuracy can be improved mutually. The analysis showed that the articulation of Chinese /i/ has a higher frontal lingual position and less variability, which is more conducive to articulation training and improves the effect of cleft palate training. These findings provide a potential relationship on affricates /t, th/ and vowel /i/. Children with cleft palate have difficulty pronouncing the /t, t h/ and /i/. It is better to start with a vowel /i/, resulting in improvement in overall speech intelligibility.


Assuntos
Fissura Palatina , Humanos , Criança , Pré-Escolar , Fissura Palatina/cirurgia , Fonética , Idioma
19.
Water Environ Res ; 95(4): e10867, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37041692

RESUMO

Accurate detection and analysis of arsenic pollutants are an important means to enhance the ability to manage arsenic pollution. Infrared (IR) spectroscopy technology has the advantages of fast analysis speed, high resolution, and high sensitivity and can be monitored by real-time in situ analysis. This paper reviews the application of IR spectroscopy in the qualitative and quantitative analysis of inorganic and organic arsenic acid adsorbed by major minerals such as ferrihydrite (FH), hematite, goethite, and titanium dioxide. The IR spectroscopy technique cannot only identify different arsenic contaminants but also obtain the content and adsorption rate of arsenic contaminants in the solid phase. The reaction equilibrium constants and the degree of reaction conversion can be determined by constructing adsorption isotherms or combining them with modeling techniques. Theoretical calculations of IR spectra of mineral adsorbed arsenic pollutant systems based on density functional theory (DFT) and analysis and comparison of the measured and theoretically calculated characteristic peaks of IR spectra can reveal the microscopic mechanism and surface chemical morphology of the arsenic adsorption process. This paper systematically summarizes the qualitative and quantitative studies and theoretical calculations of IR spectroscopy in inorganic and organic arsenic pollutant adsorption systems, which provides new insights for accurate detection and analysis of arsenic pollutants and arsenic pollution control. PRACTITIONER POINTS: This paper reviews the application of infrared spectroscopy in the qualitative and quantitative analyses of inorganic and organic arsenic acid adsorbed by major minerals such as ferrihydrite, hematite, goethite, and titanium dioxide, which can help identify and evaluate the type and concentration of arsenic pollutants in water bodies. In this paper, theoretical calculations of infrared spectra of mineral adsorbed arsenic pollutant systems based on density functional theory reveal the adsorption mechanism of arsenic pollutants in water at the solid-liquid interface and help to develop targeted arsenic pollution control technologies. This paper provides a new and reliable analytical detection technique for the study of arsenic contaminants in water bodies.


Assuntos
Arsênio , Arsenicais , Poluentes Químicos da Água , Arsênio/química , Adsorção , Compostos Férricos/química , Minerais/química , Espectrofotometria Infravermelho , Compostos Orgânicos , Poluentes Químicos da Água/química , Água , Espectroscopia de Infravermelho com Transformada de Fourier
20.
Heliyon ; 9(8): e17681, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37576257

RESUMO

Objective: The standard path of health education is a standardised health education method formulated according to the characteristics of the disease in question. This study aimed to explore the effect of traditional Chinese medicine (TCM) nursing combined with the health education standard path in terms of acute myeloid leukaemia (AML). Methods: Sixty patients with AML at Shijiazhuang Ping'an Hospital were recruited and divided into the control group (n = 30) and the intervention group (n = 30). Both groups received the same chemotherapy treatment, while the control group received routine nursing and the intervention group received a combined TCM-health education standard path intervention. The scores for the self-rating anxiety scale (SAS), Spitzer quality of life index (QLI), self-rating depression scale (SDS), awareness of TCM health education standard path content and nursing satisfaction were then compared. Results: The SAS and SDS scores of the patients decreased following the intervention, while the QLI score increased, with the intervention group significantly improved compared to the control group (P < 0.05). The awareness of TCM health education standard path content was significantly higher in the intervention group than in the control group (P < 0.05), and the nursing satisfaction was also higher in the former than in the latter (P < 0.05). Furthermore, the hospitalisation cost and length of stay were lower in the intervention group than in the control group (P < 0.05). There were no statistical differences in the median survival time between the intervention group and the control group (P > 0.05). Conclusion: The application of TCM combined with the health education standard path has an effect in terms of reducing patients' anxiety and depression, improving their awareness of health education content and enhancing their nursing satisfaction.

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