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1.
Ann Hematol ; 103(9): 3293-3301, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38494551

RESUMO

Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) with a poor prognosis, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment with curative potential. Ruxolitinib, a JAK1/2 inhibitor, has shown promising results in improving patients' symptoms, overall survival, and quality of life, and can be used as a bridging therapy to HSCT that increases the proportion of transplantable patients. However, the effect of this and similar drugs on HSCT outcomes is unknown, and the reports on their efficacy and safety in the peri-transplantation period vary widely in the published literature. This paper reviews clinical data related to the use of JAK inhibitors in the peri-implantation phase of hematopoietic stem cell transplantation for primary myelofibrosis and discusses their efficacy and safety.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Inibidores de Janus Quinases , Nitrilas , Mielofibrose Primária , Pirazóis , Pirimidinas , Mielofibrose Primária/terapia , Mielofibrose Primária/tratamento farmacológico , Humanos , Inibidores de Janus Quinases/uso terapêutico , Nitrilas/uso terapêutico , Pirimidinas/uso terapêutico , Pirazóis/uso terapêutico , Aloenxertos , Janus Quinase 2/antagonistas & inibidores , Janus Quinase 1/antagonistas & inibidores
2.
J Environ Sci (China) ; 138: 650-659, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38135428

RESUMO

Massive waste aluminum scraps produced from the spent aluminum products have high electron capacity and can be recycled as an attractive alternative to materials based on zero-valent iron (Fe0) for the removal of oxidative contaminants from wastewater. This study thus proposed an approach to fabricate micron-sized sulfidated zero-valent iron-aluminum particles (S-Al0@Fe0) with high reactivity, electron selectivity and capacity using recycled waste aluminum scraps. S-Al0@Fe0 with a three-layer structure contained zero-valent aluminum (Al0) core, Fe0 middle layer and iron sulfide (FeS) shell. The rates of chromate (Cr(VI)) removal by S-Al0@Fe0 at pH 5.0‒9.0 were 1.6‒5.9 times greater than that by sulfidated zero-valent iron (S-Fe0). The Cr(VI) removal capacity of S-Al0@Fe0 was 8.2-, 11.3- and 46.9-fold greater than those of S-Fe0, zero-valent iron-aluminum (Al0-Fe0) and Fe0, respectively. The chemical cost of S-Al0@Fe0 for the equivalent Cr(VI) removal was 78.5% lower than that of S-Fe0. Negligible release of soluble aluminum during the Cr(VI) removal was observed. The significant enhancement in the reactivity and capacity of S-Al0@Fe0 was partially ascribed to the higher reactivity and electron density of the Al0 core than Fe0. More importantly, S-Al0@Fe0 served as an electric cell to harness the persistent and selective electron transfer from the Al0-Fe0 core to Cr(VI) at the surface via coupling Fe0-Fe2+-Fe3+ redox cycles, resulting in a higher electron utilization efficiency. Therefore, S-Al0@Fe0 fabricated using recycled waste aluminum scraps can be a cost-effective and environmentally-friendly alternative to S-Fe0 for the enhanced removal of oxidative contaminants in industrial wastewater.


Assuntos
Cromatos , Poluentes Químicos da Água , Ferro/química , Águas Residuárias , Alumínio , Poluentes Químicos da Água/química , Cromo/química
3.
J Immunol ; 206(9): 2160-2169, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33863788

RESUMO

IL-27, a heterodimeric cytokine of the IL-12 family, has diverse influences on the development of multiple inflammatory diseases. In this study, we identified the protective role of IL-27/IL-27R in host defense against Chlamydia muridarum respiratory infection and further investigated the immunological mechanism. Our results showed that IL-27 was involved in C. muridarum infection and that IL-27R knockout mice (WSX-1-/- mice) suffered more severe disease, with greater body weight loss, higher chlamydial loads, and more severe inflammatory reactions in the lungs than C57BL/6 wild-type mice. There were excessive IL-17-producing CD4+ T cells and many more neutrophils, neutrophil-related proteins, cytokines, and chemokines in the lungs of WSX-1-/- mice than in wild-type mice following C. muridarum infection. In addition, IL-17/IL-17A-blocking Ab treatment improved disease after C. muridarum infection in WSX-1-/- mice. Overall, we conclude that IL-27/IL-27R mediates protective immunity during chlamydial respiratory infection in mice by suppressing excessive Th17 responses and reducing neutrophil inflammation.


Assuntos
Inflamação/imunologia , Interleucinas/imunologia , Neutrófilos/imunologia , Receptores de Interleucina/imunologia , Animais , Chlamydia muridarum/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Interleucina/deficiência , Células Th17/imunologia
4.
J Immunol ; 206(7): 1586-1596, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33608454

RESUMO

The IL-21/IL-21R interaction plays an important role in a variety of immune diseases; however, the roles and mechanisms in intracellular bacterial infection are not fully understood. In this study, we explored the effect of IL-21/IL-21R on chlamydial respiratory tract infection using a chlamydial respiratory infection model. The results showed that the mRNA expression of IL-21 and IL-21R was increased in Chlamydia muridarum-infected mice, which suggested that IL-21 and IL-21R were involved in host defense against C. muridarum lung infection. IL-21R-/- mice exhibited less body weight loss, a lower bacterial burden, and milder pathological changes in the lungs than wild-type (WT) mice during C. muridarum lung infection. The absolute number and activity of CD4+ T cells and the strength of Th1/Th17 responses in IL-21R-/- mice were significantly higher than those in WT mice after C. muridarum lung infection, but the Th2 response was weaker. Consistently, IL-21R-/- mice showed higher mRNA expression of Th1 transcription factors (T-bet/STAT4), IL-12p40, a Th17 transcription factor (STAT3), and IL-23. The mRNA expression of Th2 transcription factors (GATA3/STAT6), IL-4, IL-10, and TGF-ß in IL-21R-/- mice was significantly lower than that in WT mice. Furthermore, the administration of recombinant mouse IL-21 aggravated chlamydial lung infection in C57BL/6 mice and reduced Th1 and Th17 responses following C. muridarum lung infection. These findings demonstrate that IL-21/IL-21R may aggravate chlamydial lung infection by inhibiting Th1 and Th17 responses.


Assuntos
Infecções por Chlamydia/imunologia , Chlamydia muridarum/imunologia , Interleucinas/metabolismo , Pulmão/imunologia , Receptores de Interleucina-21/metabolismo , Subpopulações de Linfócitos T/imunologia , Células Th1/imunologia , Células Th17/imunologia , Animais , Feminino , Inflamação , Espaço Intracelular , Camundongos , Receptores de Interleucina-21/genética , Fator de Transcrição STAT3/genética , Transdução de Sinais , Proteínas com Domínio T/genética
5.
Int J Mol Sci ; 24(17)2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37686375

RESUMO

The incidence of Chlamydia trachomatis respiratory infection is increasing, and its pathogenesis is still unclear. Pyroptosis, as a mode of inflammatory cell death, plays a vital role in the occurrence and development of Chlamydia trachomatis respiratory infection. In this study, the potential pyroptosis-related genes involved in Chlamydia trachomatis respiratory infection were identified by constructing a mouse model of C. muridarum infection combined with bioinformatics analysis. Through in-depth analysis of the RNA sequencing data, 13 differentially expressed pyroptosis-related genes were screened, including 1 downregulated gene and 12 upregulated genes. Gene ontology (GO) analysis showed that these genes mainly regulate inflammatory responses and produce IL-1ß. Protein-protein interaction network analysis identified eight hub genes of interest: Tnf, Tlr2, Il1b, Nlrp3, Tlr9, Mefv, Zbp1 and Tnfaip3. Through quantitative real-time PCR (qPCR) analysis, we found that the expression of these genes in the lungs of C. muridarum-infected mice was significantly reduced, consistent with the bioinformatics results. At the same time, we detected elevated levels of caspase-3, gasdermin D and gasdermin E proteins in the lungs of C. muridarum-infected mice, demonstrating that Chlamydia trachomatis infection does induce pyroptosis. We then predicted nine miRNAs targeting these hub genes and constructed a key competitive endogenous RNA (ceRNA) network. In summary, we identified six key pyroptosis-related genes involved in Chlamydia trachomatis respiratory infection and constructed a ceRNA network associated with these genes. These findings will improve understanding of the molecular mechanisms underlying pyroptosis in Chlamydia trachomatis respiratory infections.


Assuntos
Infecções por Chlamydia , Chlamydia , MicroRNAs , Animais , Camundongos , Piroptose/genética , Gasderminas , Infecções por Chlamydia/genética , MicroRNAs/genética , Proteínas de Ligação a RNA
6.
Int J Mol Sci ; 24(16)2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37628738

RESUMO

Interleukin-21 and its receptors (IL-21/IL-21R) aggravate chlamydial lung infection, while macrophages (Mφ) are one of the main cells infected by chlamydia and the main source of inflammatory cytokines. Therefore, it is particularly important to study whether IL-21/IL-21R aggravates chlamydia respiratory infection by regulating Mφ. Combined with bioinformatics analysis, we established an IL-21R-deficient (IL-21R-/-) mouse model of Chlamydia muridarum (C. muridarum) respiratory tract infection in vivo, studied C. muridarum-stimulated RAW264.7 by the addition of rmIL-21 in vitro, and conducted adoptive transfer experiments to clarify the association between IL-21/IL-21R and Mφ. IL-21R-/- mice showed lower infiltration of pulmonary total Mφ, alveolar macrophages, and interstitial macrophages compared with WT mice following infection. Transcriptomic analysis suggested that M1-related genes are downregulated in IL-21R-/- mice and that IL-21R deficiency affects the Mφ-mediated inflammatory response during C. muridarum infection. In vivo experiments verified that in IL-21R-/- mice, pulmonary M1-type CD80+, CD86+, MHC II+, TNFα+, and iNOS+ Mφ decreased, while there were no differences in M2-type CD206+, TGF-ß+, IL-10+ and ARG1+ Mφ. In vitro, administration of rmIL-21 to C. muridarum-stimulated RAW264.7 cells promoted the levels of iNOS-NO and the expression of IL-12p40 and TNFα, but had no effect on TGFß or IL-10. Further, adoptive transfer of M1-like bone marrow-derived macrophages derived from IL-21R-/- mice, unlike those from WT mice, effectively protected the recipients against C. muridarum infection and induced relieved pulmonary pathology. These findings help in understanding the mechanism by which IL-21/IL-21R exacerbates chlamydia respiratory infection by promoting the proinflammatory effect of Mφ.


Assuntos
Infecções por Chlamydia , Chlamydia muridarum , Animais , Camundongos , Interleucina-10 , Fator de Necrose Tumoral alfa , Macrófagos
7.
Mediators Inflamm ; 2022: 4322092, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35693111

RESUMO

IL-21/IL-21R was documented to participate in the regulation of multiple infection and inflammation. During Chlamydia muridarum (C. muridarum) respiratory infection, our previous study had revealed that the absence of this signal induced enhanced resistance to infection with higher protective Th1/Th17 immune responses. Here, we use the murine model of C. muridarum respiratory infection and IL-21R deficient mice to further identify a novel role of IL-21/IL-21R in neutrophilic inflammation. Resistant IL-21R-/- mice showed impaired neutrophil recruitment to the site of infection. In the absence of IL-21/IL-21R, pulmonary neutrophils also exhibited reduced activation status, including lower CD64 expression, MPO activity, and neutrophil-produced protein production. These results correlated well with the decrease of neutrophil-related chemokines (KC and MIP-2), inflammatory cytokines (IL-6, IL-1ß, and TNF-α), and TLR/MyD88 pathway mediators (TLR2, TLR4, and MyD88) in infected lungs of IL-21R-/- mice than normal mice. Complementarily, decreased pulmonary neutrophil infiltration, activity, and levels of neutrophilic chemotactic factors and TLR/MyD88 signal in infected lungs can be corrected by rIL-21 administration. These results revealed that IL-21/IL-21R may aggravate the neutrophil inflammation through regulating TLR/MyD88 signal pathway during chlamydial respiratory infection.


Assuntos
Infecções por Chlamydia , Chlamydia muridarum , Subunidade alfa de Receptor de Interleucina-21/metabolismo , Animais , Imunidade , Inflamação/patologia , Interleucinas , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/metabolismo , Neutrófilos/metabolismo , Transdução de Sinais
8.
J Clin Lab Anal ; 36(11): e24751, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36305098

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin condition; however, little is known about the pathogenesis and serum biomarker of this disease. METHODS: Isobaric tagging for relative and absolute quantitation (iTRAQ) proteomic assay was adopted to identify and quantify the differentially expressed proteins (DEPs) in the serum of AD patients. Bioinformatic analysis, including GO, Reactome, GSEA, PPI, and ssGSEA analysis, were used to identified the enriched pathways, hub proteins and immune cells. The expression level and distribution of hub proteins were confirmed by ELISA and IHC. RESULTS: Sixty-six DEPs were identified with iTRAQ proteomic assay by analyzing serum from AD patients and normal subjects. GO and Reactome analysis shown the alternated pathway were mainly involved in immunity, oxidative stress, and actin cytoskeleton. The GSEA and PPI network analysis among the DEPs were carried out and identified Cofilin-1 and profilin-1 as the core components of this network. Additionally, the disruption of Th1/Th2/Th17 cell balance and the significantly reducing of Treg, MDSC, and γδT cells was also found in AD patients using the ssGSEA analysis. Further ELISA and IHC assay validated the significantly elevated expression of Cofilin-1 in AD patients. CONCLUSION: Our results suggested that Cofilin-1 may serve as a novel biomarker for AD diagnosis.


Assuntos
Dermatite Atópica , Proteômica , Humanos , Proteômica/métodos , Dermatite Atópica/diagnóstico , Recidiva Local de Neoplasia , Biomarcadores , Células Th17/patologia
9.
J Sep Sci ; 44(12): 2496-2503, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33857350

RESUMO

The volatile oil of Mentha haplocalyx is widely used in medicine, food, and cosmetics. However, a large amount of its residue after steam extraction of volatile oil is abandoned, resulting in a waste of resources. The method of aqueous two-phase flotation coupled with preparative high-performance liquid chromatography was established for the separation and purification of nonvolatile active compounds from Mentha haplocalyx for the first time. The parameters of the two-phase aqueous flotation were optimized. Under the optimal conditions including flotation solvent PEG 1000 aqueous solution (1:1, w/w), pH 5, (NH4 )2 SO4 concentration of 350 g/L in aqueous phase, N2 flow rate of 20 mL/min, and flotation time of 20 min, the flotation efficiency of linarin, hesperidin, and didymin was 82.24, 76.38, and 89.33%, respectively. The linarin and hesperidin with the high purities of 95.8 and 97.2%, respectively, were obtained by using preparative high performance liquid chromatography. The neuroprotective effect of linarin against H2 O2 -induced oxidative stress in rat hippocampal neurons was investigated. The experimental result indicated that linarin could alleviate H2 O2 -induced oxidative stress. The work indicated that the combination of aqueous two-phase flotation and preparative high performance liquid chromatography is a feasible and practical method for the purification of nonvolatile active substances from Mentha haplocalyx, which would provide a reference process for the comprehensive utilization of M. haplocalyx. Especially, linarin might be used as a good source of natural neuroprotectants.


Assuntos
Glicosídeos/farmacologia , Hesperidina/isolamento & purificação , Hipocampo/efeitos dos fármacos , Mentha/química , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Glicosídeos/química , Glicosídeos/isolamento & purificação , Hesperidina/química , Hipocampo/metabolismo , Peróxido de Hidrogênio/farmacologia , Estrutura Molecular , Neurônios/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Estresse Oxidativo/efeitos dos fármacos , Ratos , Água/química
10.
Arch Toxicol ; 95(5): 1621-1629, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33713148

RESUMO

Transarterial chemoembolization (TACE) has significantly improved overall survival (OS) of unresectable hepatocellular carcinoma (HCC) patients. Unfortunately, a portion of patients show no therapeutic responses to TACE. N6-methyladenosine (m6A) as well as its epigenetic writers, erasers, and readers play a crucial role in HCC development. However, it is still largely unclear how functional small nucleotide polymorphisms (SNPs) in m6A-regulating genes contribute to prognosis of TACE-treated HCC patients. In this study, potential functional SNPs were systematically evaluated to identify their roles in the prognosis of HCC patients after TACE in a Chinese Han population. Employing multiple databases, we successfully annotated 55 candidate SNPs. After genotyping these SNPs in our TACE cohort, we identified three genetic variants in YTHDC2 (rs6594732, rs10071816, and rs2303718) and one SNP in FTO (rs7202116) having statistically significant associations with the OS of HCC patients treated with TACE. For example, multivariate Cox proportional hazards model indicated that the rs7202116 GG genotype carriers had markedly shorter OS and an 87% increased death risk compared with the AA carriers after TACE therapy (P = 0.002). When investigating functional relevance of these SNPs, we observed an allelic regulation of rs7202116 on FTO expression in HCC tissue samples, with higher tumor suppressor FTO expression among the A allele carriers. Our findings reported the first evidence supporting the prognostic value of m6A reader YTHDC2 and m6A eraser FTO SNPs in TACE-treated HCC patients. Importantly, our data implicated that m6A-regulating genes may be targets to improve therapeutic strategy for unresectable HCC patients.


Assuntos
Adenosina/análogos & derivados , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Carcinoma Hepatocelular/genética , RNA Helicases/genética , Adenosina/metabolismo , Povo Asiático , Quimioembolização Terapêutica , Estudos de Coortes , Genótipo , Humanos , Neoplasias Hepáticas , Polimorfismo de Nucleotídeo Único , Prognóstico , Modelos de Riscos Proporcionais , Resultado do Tratamento
12.
Microorganisms ; 12(7)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-39065071

RESUMO

Chlamydia infections commonly afflict both humans and animals, resulting in significant morbidity and imposing a substantial socioeconomic burden worldwide. As an obligate intracellular pathogen, Chlamydia interacts with other cell organelles to obtain necessary nutrients and establishes an intracellular niche for the development of a biphasic intracellular cycle. Eventually, the host cells undergo lysis or extrusion, releasing infectious elementary bodies and facilitating the spread of infection. This review provides insights into Chlamydia development and host cell responses, summarizing the latest research on the biphasic developmental cycle, nutrient acquisition, intracellular metabolism, host cell fates following Chlamydia invasion, prevalent diseases associated with Chlamydia infection, treatment options, and vaccine prevention strategies. A comprehensive understanding of these mechanisms will contribute to a deeper comprehension of the intricate equilibrium between Chlamydia within host cells and the progression of human disease.

13.
Sci Rep ; 14(1): 2653, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302517

RESUMO

Collapse is a major engineering hazard in open-cut foundation pit construction, and risk assessment is crucial for considerably reducing engineering hazards. This study aims to address the ambiguity problem of qualitative index quantification and the failure of high-conflict evidence fusion in risk assessment. Thus, a fast-converging and high-reliability multi-source data fusion method based on the cloud model (CM) and improved Dempster-Shafer evidence theory is proposed. The method can achieve an accurate assessment of subway pit collapse risks. First, the CM is introduced to quantify the qualitative metrics. Then, a new correction parameter is defined for improving the conflicts among evidence bodies based on conflict degree, discrepancy degree and uncertainty, while a fine-tuning term is added to reduce the subjective effect of global focal element assignment. Finally, the risk assessment result is obtained according to the maximum affiliation principle. The method is successfully applied to Luochongwei Station, where the difference between the maximum value and the second largest value of the basic probability assignment is 0.624, and the global uncertainty degree is 0.087. Both values satisfy the decision evaluation condition; however, values of other methods only satisfy one or neither condition. In addition, the proposed method requires only four cycles to reach the steady state by fusing data of the same index, which has faster convergence compared with that of other methods. The proposed method has good universality and effectiveness in subway pit collapse risk assessment.

14.
Water Res ; 253: 121270, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38359598

RESUMO

Sulfidated zero-valent iron (S-ZVI) is an attractive material of permeable reactive barriers (PRBs) for the remediation of contaminated groundwater. However, S-ZVI is prone to be passivated due to the oxidation of reactive and conductive iron sulfide (FeSx) shell and the formation of inactive and non-conductive ferric (hydr)oxides, which serve as electron transfer barriers to hinder the electron flow from Fe° core to contaminants. This study thus proposed a novel approach for in-situ reactivation and reuse of micronsized S-ZVI (S-mZVI) in PRB using sulfate-reducing bacteria (SRB) enriched culture to realize long-lasting remediation of Cr(VI)-contaminated groundwater. S-mZVI were passivated after reactions with Cr(VI) due to the formation of electron transfer barriers (mainly inactive and non-conductive Fe(III) (hyd)oxides, which increased the polarization resistance from 16.38 to 27.38 kΩ cm2 and hindered the electron transfer from the Fe° core. Interestingly, the passivated S-mZVI was efficiently reactivated by providing the SRB-enriched culture and organic carbon within 12 h, and the Cr(VI) removal capacity of S-mZVI in the three use cycles increased to 37.4 mg Cr/g, which was 2.1 times higher than that of the virgin S-mZVI. After biological reactivation, the Rp of reactivated S-mZVI decreased to 12.30 kΩ cm2. SRB-mediated reactivation removed the electron transfer barriers via biotic and abiotic reduction of Fe(III) (hyd)oxides. Especially, the microbial Fe(III) reduction mediated by FmnA-dmkA-fmnB-pplA-ndh2-eetAB-dmkB protein family enhanced the Fe2+ release from the surface and the subsequent re-formation of reactive and conductive FeSx shell. A long-term PRB column test further demonstrated the feasibility of in-situ biological reactivation and reuse of S-mZVI for enhanced Cr(VI)-contaminated groundwater remediation. Within 64 days, the Cr(VI) removal capacity of S-mZVI in the four use cycles increased by 3.2 times, compared to the virgin one. The bio-reactivation using the SRB-enriched culture and sulfate locally-available in groundwater will reduce the chemical and maintenance costs associated with the frequent replacement of reactive ZVI-based materials. The PRB technology based on the bio-renewable S-mZVI can be a sustainable alternative to the conventional PRBs for the long-lasting and low-cost remediation of groundwater contaminated by oxidative pollutants.


Assuntos
Cromo , Água Subterrânea , Poluentes Químicos da Água , Ferro , Poluentes Químicos da Água/análise , Compostos Férricos , Óxidos , Sulfatos
15.
Water Res ; 249: 120940, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38071904

RESUMO

Conventional biological treatment processes cannot efficiently and completely degrade nitroimidazole antibiotics, due to the formation of highly antibacterial and carcinogenic nitroreduction by-products. This study investigated the removal of a typical nitroimidazole antibiotic (ornidazole) during wastewater treatment by a biological sulfidogenic process based on elemental sulfur (S0-BSP). Efficient and stable ornidazole degradation and organic carbon mineralization were simultaneously achieved by the S0-BSP in a 798-day bench-scale trial. Over 99.8 % of ornidazole (200‒500 µg/L) was removed with the removal rates of up to 0.59 g/(m3·d). Meanwhile, the efficiencies of organic carbon mineralization and sulfide production were hardly impacted by the dosed ornidazole, and their rates were maintained at 0.15 kg C/(m3·d) and 0.49 kg S/(m3·d), respectively. The genera associated with ornidazole degradation were identified (e.g., Sedimentibacter, Trichococcus, and Longilinea), and their abundances increased significantly. Microbial degradation of ornidazole proceeded by several functional genes, such as dehalogenases, cysteine synthase, and dioxygenases, mainly through dechlorination, denitration, N-heterocyclic ring cleavage, and oxidation. More importantly, the nucleophilic substitution of nitro group mediated by in-situ formed reducing sulfur species (e.g., sulfide, polysulfides, and cysteine hydropolysulfides), instead of nitroreduction, enhanced the complete ornidazole degradation and minimized the formation of carcinogenic and antibacterial nitroreduction by-products. The findings suggest that S0-BSP can be a promising approach to treat wastewater containing multiple contaminants, such as emerging organic pollutants, organic carbon, nitrate, and heavy metals.


Assuntos
Reatores Biológicos , Ornidazol , Reatores Biológicos/microbiologia , Enxofre/metabolismo , Sulfetos/metabolismo , Antibacterianos , Carbono
16.
Cancer Lett ; 602: 217201, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39197582

RESUMO

Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancies worldwide. Oncogenic transcription factors (TFs) drive transcriptional reprogramming and tumorigenesis. The myc-associated zinc finger protein (MAZ) is one of the Myc family TFs. The role of MAZ in PTC pathogenesis is still largely unknown. Here, we report that MAZ profoundly promotes proliferation of PTC cells ex vivo and in vivo through activating MAPK signaling. We firstly profiled gene expression of PTC cells after silencing of MAZ. BRAF, KRAS and LOC547 were identified as important target genes of TF MAZ. In particular, TF MAZ bound to the promoters of BRAF or KRAS and significantly increased their transcription and expression levels. Meanwhile, MAZ could noticeably elevate LOC547 transcription and expression as a TF. High levels of LOC547 relocated ACTN4 protein from the nucleus to the cytosol, improved protein-protein interactions between ACTN4 and EGFR in the cytosol, enhanced ERK1/2 phosphorylation, activated the MAPK signaling and, thus, promoted PTC progression. Our data identify a previously underappreciated MAZ-controlled transcriptional reprogram and ERK1/2 activation via BRAF, KRAS and LOC547. Our data illustrate that activation of the MAZ-controlled axis promotes thyroid tumorigenesis. These insights would advance our knowledge of the role of TFs in cancer development and highlight the potential of TFs as future targets for treatments against cancers.

17.
Cancer Res ; 83(24): 4080-4094, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-37756562

RESUMO

Hepatocellular carcinoma (HCC) is one of the most lethal neoplasms and has a 5-year survival rate of only 18% in patients with metastatic diseases. Epigenetic modifiers and alterations, including histone modifications, long noncoding RNAs (lncRNA), RNA alternative splicing, and N6-methyladenosine (m6A) modification, are key regulators of HCC development, highlighting the importance of understanding the cross-talk between these biological processes. In the current study, we identified LINC01089 as a super enhancer (SE)-driven lncRNA that promotes epithelial-mesenchymal transition (EMT), migration, invasion, and metastasis of HCC cells in vivo and in vitro. The transcription factor E2F1 bound to a LINC01089 SE, promoting LINC01089 transcription and overexpression. LINC01089 interacted with heterogeneous nuclear ribonucleoprotein M (hnRNPM) and led to hnRNPM-mediated skipping of DIAPH3 exon 3. Knockdown of LINC01089 increased the inclusion of DIAPH3 exon 3, which contains an important m6A-modification site that is recognized by IGF2BP3 to increase DIAPH3 mRNA stability. Thus, LINC01089 loss increased DIAPH3 protein levels, which suppressed the ERK/Elk1/Snail axis and inhibited EMT of HCC cells. In conclusion, this study revealed cross-talk between different epigenetics modifiers and alterations that drives HCC progression and identified LINC01089 as a potential prognostic marker and therapeutic target for HCC. SIGNIFICANCE: LINC01089 is a super enhancer-driven long noncoding RNA that induces ERK signaling and epithelial-mesenchymal transition by regulating DIAPH3 alternative splicing that blocks N6-methyladenosine-mediated mRNA stabilization, establishing an epigenetic network that promotes hepatocellular carcinoma metastasis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Humanos , Processamento Alternativo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Transição Epitelial-Mesenquimal , Forminas/genética , Forminas/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
18.
J Exp Clin Cancer Res ; 42(1): 89, 2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37072811

RESUMO

BACKGROUND: Gastric cancer remains the leading cause of cancer death in the world. It is increasingly evident that long non-coding RNAs (lncRNAs) transcribed from the genome-wide association studies (GWAS)-identified gastric cancer risk loci act as a key mode of cancer development and disease progression. However, the biological significance of lncRNAs at most cancer risk loci remain poorly understood. METHODS: The biological functions of LINC00240 in gastric cancer were investigated through a series of biochemical assays. Clinical implications of LINC00240 were examined in tissues from gastric cancer patients. RESULTS: In the present study, we identified LINC00240, which is transcribed from the 6p22.1 gastric cancer risk locus, functioning as a novel oncogene. LINC00240 exhibits the noticeably higher expression in gastric cancer specimens compared with normal tissues and its high expression levels are associated with worse survival of patients. Consistently, LINC00240 promotes malignant proliferation, migration and metastasis of gastric cancer cells in vitro and in vivo. Importantly, LINC00240 could interact and stabilize oncoprotein DDX21 via eliminating its ubiquitination by its novel deubiquitinating enzyme USP10, which, thereby, promote gastric cancer progression. CONCLUSIONS: Taken together, our data uncovered a new paradigm on how lncRNAs control protein deubiquitylation via intensifying interactions between the target protein and its deubiquitinase. These findings highlight the potentials of lncRNAs as innovative therapeutic targets and thus lay the ground work for clinical translation.


Assuntos
RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Estudo de Associação Genômica Ampla , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo
19.
Pharmgenomics Pers Med ; 16: 229-238, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36970122

RESUMO

Introduction: Transarterial chemoembolization (TACE) is the commonly used therapy of unresectable hepatocellular carcinoma (HCC), though the prognosis of different TACE-treated HCC patients varies, which may be due to the heterogeneity of HCC tumors caused by genetic variants and epigenetic changes such as RNA editing. There is dysregulated RNA adenosine-to-inosine (A-to-I) editing in HCC and RNA-edited genes are involved in the epigenetic process. It remains unclear how genetic variants of RNA editing genes affect the prognosis of HCC cases treated by TACE. Methods: In this study, we examined 28 potentially functional single-nucleotide polymorphisms (SNPs) of four RNA editing genes (ADARB1, ADAR, ADARB2 and AIMP2) in two independent TACE patient cohorts. Results: We found that ADARB1 rs1051367 and rs2253763 polymorphisms were markedly associated with the prognosis of HCC cases who received TACE in both cohorts. In HCC cells, the rs2253763 C-to-T change in ADARB1 3'-untranslated region attenuated its binding with miR-542-3p and allele-specifically elevated ADARB1 levels. Consistent with this, patients carrying the rs2253763 C allele showed reduced ADARB1 expression in cancer tissues and notably shorter survival after TACE therapy in comparison with individuals with the T allele. Ectopic ADARB1 profoundly enhanced the efficacy of oxaliplatin, one of the common TACE chemotherapeutic drugs. Discussion: Our findings highlighted the value of ADARB1 polymorphisms as prognostic markers in TACE therapy for HCC patients. Notably, our findings revealed that targeting the ADARB1 enzyme may be a promising therapeutic strategy in combination with TACE for HCC cases.

20.
Microorganisms ; 11(3)2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36985179

RESUMO

Chlamydia trachomatis usually causes mucosal infections, bringing considerable morbidity and socioeconomic burden worldwide. We previously revealed that IL-27/IL-27R mediates protection against chlamydial invasion by promoting a protective Th1 response and suppressing neutrophilic inflammation. Here, we used the mouse model of Chlamydia muridarum (C. muridarum) respiratory infections to further investigate the impact of IL-27 signaling in the DCs-regulated immune response, since an elevated IL-27/IL-27R expression in DCs was identified following chlamydial infection. An adoptive transfer of Chlamydia muridarum-stimulated DCs to wild-type mice approach was subsequently used, and the donor-DCs-promoted resistance with a higher Th1 response against chlamydial infection was attenuated when DCs lacking IL-27R were used as donor cells. Flow cytometry analysis revealed the suppression of IL-27 signaling on DCs phenotypic maturation. A further functional maturation analysis of DCs revealed that IL-27 signaling restricted the protein and mRNA expression of IL-10 from DCs following infection. Thus, these findings suggest that IL-27 signaling could support the Th1 response via inhibiting IL-10 production in DCs, thus mediating the protective host defense against chlamydial respiratory infection.

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