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1.
Environ Sci Pollut Res Int ; 31(20): 29916-29929, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38594563

RESUMO

To elucidate the effects of long-term (20 years) afforestation with different woody plant species on the soil microenvironment in coal gangue polymetallic contaminated areas. This study analyzed the soil physicochemical properties, soil enzyme activities, soil ionophore, bacterial community structure, soil metabolite, and their interaction relationships at different vertical depths. Urease, sucrase, and acid phosphatase activities in the shallow soil layers increased by 4.70-7.45, 3.83-7.64, and 3.27-4.85 times, respectively, after the restoration by the four arboreal plant species compared to the plant-free control soil. Additionally, it reduced the content of available elements in the soil and alleviated the toxicity stress for Cd, Ni, Co, Cr, As, Fe, Cu, U, and Pb. After the long-term restoration of arboreal plants, the richness and Shannon indices of soil bacteria significantly increased by 4.77-23.81% and 2.93-7.93%, respectively, broadening the bacterial ecological niche. The bacterial community structure shaped by different arboreal plants exhibited high similarity, but the community similarity decreased with increasing vertical depth. Soils Zn, U, Sr, S, P, Mg, K, Fe, Cu, Ca, Ba, and pH were identified as important influencing factors for the community structure of Sphingomonas, Pseudarthrobacter, Nocardioides, and Thiobacillus. The metabolites such as sucrose, raffinose, L-valine, D-fructose 2, 6-bisphosphate, and oxoglutaric acid were found to have the greatest effect on the bacterial community in the rhizosphere soils for arboreal plants. The results of the study demonstrated that long-term planting for woody plants in gangue dumps could regulate microbial abundance and symbiotic patterns through the accumulation of rhizosphere metabolites in the soil, increase soil enzyme activity, reduce heavy metal levels, and improve the soil environment in coal gangue dumps.


Assuntos
Microbiologia do Solo , Poluentes do Solo , Solo , Solo/química , Carvão Mineral
3.
Acta Pharm Sin B ; 14(4): 1677-1692, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572095

RESUMO

Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment, significantly curtailing the efficacy of these treatments and, in some cases, resulting in fatal consequences. Despite identifying intestinal epithelial cell damage as a key factor in chemotherapy-induced mucositis, the paucity of effective treatments for such damage is evident. In our study, we discovered that Eubacterium coprostanoligenes promotes mucin secretion by goblet cells, thereby fortifying the integrity of the intestinal mucus barrier. This enhanced barrier function serves to resist microbial invasion and subsequently reduces the inflammatory response. Importantly, this effect remains unobtrusive to the anti-tumor efficacy of chemotherapy drugs. Mechanistically, E. copr up-regulates the expression of AUF1, leading to the stabilization of Muc2 mRNA and an increase in mucin synthesis in goblet cells. An especially significant finding is that E. copr activates the AhR pathway, thereby promoting the expression of AUF1. In summary, our results strongly indicate that E. copr enhances the intestinal mucus barrier, effectively alleviating chemotherapy-induced intestinal mucositis by activating the AhR/AUF1 pathway, consequently enhancing Muc2 mRNA stability.

4.
J Chem Phys ; 160(9)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38445735

RESUMO

Understanding the ignition and dynamic processes for the combustion of hydrate is crucial for efficient energy utilization. Through reactive force field molecular dynamics simulations, we studied the high-temperature decomposition and combustion processes of methane hydrates in a pure oxygen environment. We found that at an ignition temperature of 2800 K, hydrates decomposed from the interface to the interior, but the layer-by-layer manner was no longer strictly satisfied. At the beginning of combustion, water molecules reacted first to generate OH•, followed by methane oxidation. The combustion pathway of methane is CH4→CH3•→CH3O•→CH2O→HC•O→HCOO•→CO(CO2). During the combustion process, a liquid water layer was formed between melted methane and oxygen, which hindered the reaction's progress. When there is no heat resistance, oxygen will transform into radicals such as OH• and O•, which have faster diffusion rates, allowing oxygen to conveniently cross the mass transfer barrier of the liquid water layer and participate in the combustion process. Increasing the amount of OH• may cause a surge in the reaction. On the other hand, when significant heat resistance exists, OH• is difficult to react with low-temperature hydrate components, but it can transform into O• to trigger the oxidation of methane. The H• generated has a sufficient lifetime to contact high-temperature oxygen molecules, converting oxygen into radicals that easily cross the water layer to achieve mass transfer. Therefore, finding ways to convert oxygen into various radicals is the key to solving the incomplete combustion of hydrates. Finally, the reaction pathways and microscopic reaction mechanisms of each species are proposed.

5.
Nat Biotechnol ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336903

RESUMO

Dynamic 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) modifications to DNA regulate gene expression in a cell-type-specific manner and are associated with various biological processes, but the two modalities have not yet been measured simultaneously from the same genome at the single-cell level. Here we present SIMPLE-seq, a scalable, base resolution method for joint analysis of 5mC and 5hmC from thousands of single cells. Based on orthogonal labeling and recording of 'C-to-T' mutational signals from 5mC and 5hmC sites, SIMPLE-seq detects these two modifications from the same molecules in single cells and enables unbiased DNA methylation dynamics analysis of heterogeneous biological samples. We applied this method to mouse embryonic stem cells, human peripheral blood mononuclear cells and mouse brain to give joint epigenome maps at single-cell and single-molecule resolution. Integrated analysis of these two cytosine modifications reveals distinct epigenetic patterns associated with divergent regulatory programs in different cell types as well as cell states.

6.
Chemosphere ; 351: 141265, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38246497

RESUMO

Plant enrichment and tolerance to heavy metals are crucial for the phytoremediation of coal gangue mountain. However, understanding of how plants mobilize and tolerate heavy metals in coal gangue is limited. This study conducted potted experiments using Setaria viridis as a pioneer remediation plant to evaluate its tolerance to coal gangue, its mobilization and enrichment of metals, and its impact on the soil environment. Results showed that the addition of 40% gangue enhanced plant metal and oxidative stress resistance, thereby promoting plant growth. However, over 80% of the gangue inhibited the chlorophyll content, photoelectron conduction rate, and biomass of S. viridis, leading to cellular peroxidative stress. An analysis of metal resistance showed that endogenous S in coal gangue promoted the accumulation of glutathione, plant metal chelators, and non-protein thiols, thereby enhancing its resistance to metal stress. Setaria viridis cultivation affected soil properties by decreasing nitrogen, phosphorus, conductivity, and urease and increasing sucrase and acid phosphatase in the rhizosphere soil. In addition, S. viridis planting increased V, Cr, Ni, As, and Zn in the exchangeable and carbonate-bound states within the gangue, effectively enriching Cd, Cr, Fe, S, U, Cu, and V. The increased mobility of Cd and Pb was correlated with a higher abundance of Proteobacteria and Acidobacteria. Heavy metals, such as As, Fe, V, Mn, Ni, and Cu, along with environmental factors, including total nitrogen, total phosphorus, urease, and acid phosphatase, were the primary regulatory factors for Sphingomonas, Gemmatimonas, and Bryobacter. In summary, S. viridis adapted to gangue stress by modulating antioxidant and elemental enrichment systems and regulating the release and uptake of heavy metals through enhanced bacterial abundance and the recruitment of gangue-tolerant bacteria. These findings highlight the potential of S. viridis for plant enrichment in coal gangue areas and will aid the restoration and remediation of these environments.


Assuntos
Metais Pesados , Setaria (Planta) , Poluentes do Solo , Cádmio/farmacologia , Setaria (Planta)/metabolismo , Carvão Mineral , Urease , Metais Pesados/análise , Plantas/metabolismo , Fósforo/farmacologia , Bactérias/metabolismo , Enxofre/farmacologia , Solo , Fosfatase Ácida , Nitrogênio/farmacologia , Poluentes do Solo/análise
7.
Front Pediatr ; 11: 1272659, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37964816

RESUMO

Objective: This study investigates the feasibility of the indocyanine green-guided near-infrared fluorescence (ICG-NIRF) imaging technique in evaluating testicular blood flow during testicular torsion (TT) surgery in pediatric cases. Methods: We retrospectively analyzed the eight pediatric patients with TT who underwent surgery in our hospital between February and July 2023. The intraoperative two-step method of ICG-NIRF imaging and testicular incision was used to evaluate the testicular blood flow, followed by a selection of different surgical methods. The removed testes were pathologically examined after surgery, and all patients were followed up 1 month after surgery to evaluate testicular blood flow using gray-scale ultrasound and color Doppler flow imaging (CDFI). Results: Eight pediatric TT patients aged 1-16 years, with a median age of 11.5 years, were enrolled. Time from the onset ranged from 4 to 72 h (mean 26.13 ± 25.09 h). A total of eight testes were twisted, including four on the left side and four on the right side. The twisting direction of the testes was clockwise in four cases and counterclockwise in four cases. The rotation of torsion was 180°-1,080° (mean 472.5° ± 396°). There was no statistically significant difference in the imaging time between the four patients with testicular blood vessel imaging on both the torsional and normal sides (P > 0.05). The postoperative recovery was uneventful, with no complications during the follow-up period of 1 month. The postoperative histopathological results of three patients who underwent orchiectomy showed extensive hemorrhage, degeneration, and necrosis of the testicular tissue. Among the five patients who underwent orchiopexy, a gray-scale ultrasound and CDFI examinations showed uniform internal echo of the testes and normal blood flow signals in four patients. One patient with no testicular blood vessel imaging on the torsional side showed uneven internal echo of the testis and no blood flow signals. Conclusion: ICG-NIRF imaging is a feasible method to evaluate testicular blood flow during TT surgery. Testicular blood vessel imaging within 5 minutes after ICG injection might be the basis for testicular retention during TT surgery.

8.
Br J Pharmacol ; 180(8): 1072-1089, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36455594

RESUMO

BACKGROUND AND PURPOSE: Liver fibrosis is a critical risk factor for the progression from chronic liver injury to hepatocellular carcinoma. Clinically, there is a lack of therapeutic drugs for liver fibrosis. Previous studies have confirmed that GL-V9, a newly synthesized flavonoid derivative, exhibits anti-inflammatory activity, but whether it has anti-hepatic fibrosis actions remains unclear. This study aimed to investigate the anti-fibrotic activities and potential mechanisms of GL-V9. EXPERIMENTAL APPROACH: Bile duct ligation (BDL) and carbon tetrachloride (CCl4 ) challenges were used to assess the anti-fibrotic effects of GL-V9 in vivo. Mouse primary hepatic stellate cells (pHSCs) and the human HSC line LX2 also served as a liver fibrosis model in vitro. Cellular functions and molecular mechanism were analysed using senescence-associated beta-galactosidase staining, real-time PCR, western blotting, immunofluorescence, and co-immunoprecipitation. KEY RESULTS: GL-V9 attenuated hepatic histopathological injury and collagen accumulation, as well as decreasing the expression of fibrotic genes in vivo. GL-V9 promoted senescence and inhibited the expression of fibrogenic genes in HSCs in vitro. Mechanistic studies revealed that GL-V9 induced senescence by upregulating GATA4 expression in HSCs. Further studies confirmed that GL-V9 stabilized GATA4 by promoting autophagic degradation of P62. CONCLUSION AND IMPLICATIONS: GL-V9 exerted potent anti-fibrotic effects both in vivo and in vitro by stabilizing GATA4, thereby promoting the senescence of HSCs, and by avoiding its activation and ultimately inhibiting liver fibrosis. This action indicated that the flavonoid GL-V9 is a potential therapeutic candidate for the treatment of liver fibrosis.


Assuntos
Flavonoides , Células Estreladas do Fígado , Camundongos , Animais , Humanos , Flavonoides/farmacologia , Fator de Transcrição GATA4/metabolismo , Fator de Transcrição GATA4/farmacologia , Cirrose Hepática/metabolismo , Fígado/metabolismo , Fibrose
9.
Comput Math Methods Med ; 2022: 3482450, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35872951

RESUMO

Objective: Ureteropelvic junction obstruction (UPJO) represents to a leading cause of fetal hydronephrosis, which is associated with urinary tract infection (UTI) and urinary stone disease. This study is aimed at investigating risk factors of UTI in pediatric patients with UPJO after primary unilateral pyeloplasty. Methods: The records of a consecutive series of patients undergoing primary pyeloplasty at a single institution between June 2015 and November 2021 were retrospectively reviewed. Demographic and clinical characteristics, including age, gender, weight, height, body mass index (BMI), creatinine (Cr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), neutrophil ratio, lymphocyte ratio, neutrophil/lymphocyte ratio, renal pelvis anteroposterior diameter (APD), renal cortex thickness, caliectasis, open or laparoscopic pyeloplasty, and internal drainage or external drainage, were collected and analyzed. The incidence of postoperative UTI and its risk factors was analyzed. Results: A total of 504 patients were enrolled in the study, and they were classified into the UTI group (n = 188) and non-UTI group (n = 361). Univariate analysis of the incidence of UTI revealed that age, gender, weight, height, BMI, surgical modality, Cr level, BUN level, neutrophil ratio, lymphocyte ratio and neutrophil/lymphocyte ratio, renal cortex thickness, and postoperative drainage modality were associated with UTI incidence after pyeloplasty in pediatric patients with UPJO. Multivariate analysis revealed that male gender, <19 months, weight < 11.5 (kg), height < 83 (cm), BMI < 17.09, BUN > 4.08 (mmol/L), and internal drainage were risk factors of postoperative UTI in pediatric patients with UPJO. Conclusion: Our study demonstrated that male gender, <19 months, weight < 11.5 (kg), height < 83 (cm), BMI < 17.09, BUN > 4.08 (mmol/L), and internal drainage were risk factors of UTI in pediatric patients with UPJO after primary unilateral pyeloplasty, which may provide reference for prophylactic antibiotics for those patients with risk factors.


Assuntos
Hidronefrose , Laparoscopia , Obstrução Ureteral , Infecções Urinárias , Criança , Humanos , Hidronefrose/complicações , Hidronefrose/cirurgia , Pelve Renal/cirurgia , Masculino , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Obstrução Ureteral/cirurgia , Infecções Urinárias/complicações , Infecções Urinárias/cirurgia
10.
J Phys Chem B ; 126(2): 492-502, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34985263

RESUMO

Gas hydrates usually contain a certain number of empty cages that will both affect the hydrate stability and reduce the gas storage capacity. In this work, by MD simulations, we found that the hydrate stability is related to the cage occupancy, the empty cage types, and especially the distribution of empty cages. With the decrease of overall occupancy, the stability of hydrate becomes worse. Under the same overall occupancy, the more concentrated the empty cages are, the more unstable the hydrate is and hence the faster it decomposes. The methane molecules may migrate between distorted cages during the decomposition, resulting in a temporary increase in the stability of hydrate. Hydrates with different empty cage distributions show different decomposition mechanisms: when empty cages are concentrated, the melting rate is fast first due to the rapid decomposition of empty cages, but the remaining filled cages will reduce the melting rate; when empty cages are separated on the contrary, the early melting is slow because of the high local occupancy, and the following melting will be accelerated because of the high melting surface area. It indicates that the empty cage distribution plays a controlling role in hydrate decomposition kinetics at different stages.

11.
J Environ Manage ; 305: 114400, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34995941

RESUMO

The soil ecological health risks and toxic effects of coal gangue accumulation were examined after 10 years of elm/poplar phytoremediation. The changes in soil enzyme activities, ionome metabolism, and microbial community structure were analyzed at shallow (5-15 cm), intermediate (25-35 cm), and deep (45-55 cm) soil depths. Soil acid phosphatase activity in the restoration area increased significantly by 4.36-7.18 fold (p < 0.05). Soil concentrations of the metal ions Cu, Pb, Ni, Co, Bi, U, and Th were significantly reduced, as were concentrations of the non-metallic element S. The repair effect was shallow > middle > deep. The soil community structure, determined by 16S diversity results, was changed significantly in the restoration area, and the abundance of microorganisms increased at shallow soil depths. Altererythrobacter and Sphingomonas species were at the center of the microbial weight network in the restoration area. Redundancy analysis (RDA) showed that S and Na are important driving forces for the microbial community distributions at shallow soil depths. The KEGG function prediction indicated enhancement of the microbial function of the middle depth soil layers in the restoration area. Overall, phytoremediation enhanced the biotransformation of soil phosphorus in the coal gangue restoration area, reduced the soil content of several harmful metal elements, significantly changed the structure and function of the microbial community, and improved the overall soil ecological environment.


Assuntos
Minas de Carvão , Poluentes do Solo , Biodegradação Ambiental , China , Carvão Mineral/análise , Solo , Microbiologia do Solo , Poluentes do Solo/análise
12.
Autophagy ; 18(7): 1673-1693, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34821530

RESUMO

ABBREVIATIONS: ALDOA: aldolase A; AMPK: AMP-activated protein kinase; ATG: autophagy related; ATG5: autophagy related 5; ATP: adenosine triphosphate; BMDMs: bone marrow-derived macrophages; CALCOCO2: calcium binding and coiled-coil domain 2; CASP1: caspase 1; CQ: chloroquine; FOXO3: forkhead box O3; IL1B: interleukin 1 beta; LPS: lipopolysaccharide; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MT: mutant; mtDNA: mitochondrial DNA; MTORC1: mechanistic target of rapamycin kinase complex 1; mtROS: mitochondrial reactive oxygen species; NLRP3: NLR family, pyrin domain containing 3; OPTN: optineurin; PBS: phosphate-buffered saline; PRKN/Parkin: parkin RBR E3 ubiquitin protein ligase; SN: supernatant; SQSTM1/p62: sequestosome 1; STK11/LKB1: serine/threonine kinase 11; TOMM20: translocase of outer mitochondrial membrane 20; ULK1: unc-51 like autophagy activating kinase 1; v-ATPase: vacuolar type H+-ATPase; WT: wild-type.


Assuntos
Autofagia , Inflamassomos , Proteínas Quinases Ativadas por AMP , Adenosina Trifosfatases , Autofagia/fisiologia , Caspase 1 , DNA Mitocondrial/metabolismo , Inflamassomos/metabolismo , Lipopolissacarídeos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ubiquitina-Proteína Ligases/metabolismo
13.
Mitochondrial DNA B Resour ; 6(12): 3352-3353, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790867

RESUMO

Cucumis melo L. var. agrestis Naud., commonly known as 'Field Muskmelon,' is an annual invasive weed in many parts of China. However, there is very little available information about the chloroplast genome of this species. Here, we first report and characterize its complete chloroplast genome sequence based on Illumina paired-end sequencing data. The complete plastid genome was 155,402 bp, which contained inverted repeats (IR) of 25,514 bp separated by a large single-copy (LSC) and a small single copy (SSC) of 86,287 bp and 18,087 bp, respectively. The complete chloroplast genome contains 133 genes, comprising 87 protein-coding genes, 37 tRNA genes, 8 rRNA genes and 1 pseudogene. The overall GC content of the plastome is 36.9%. The phylogenetic analysis of 16 selected chloroplast genomes demonstrated that C. melo var. agrestis Naud was close to congeneric species C. xhytivus.

14.
RSC Chem Biol ; 2(2): 441-449, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34458793

RESUMO

Single-cell profiling methods are developed to dissect heterogeneity of cell populations. Recently, multiple enzymatic or chemical treatments have been integrated into single-cell multi-omics profiling methods with high compatibility. These methods have been verified to identify rare or new cell types with high confidence. Single-cell multi-omics analysis can also provide tools to solve the complex regulatory network associated with genome coding, epigenome regulation, and transcripotome expression in a single cell. However, acquiring high-quality single-cell data still faces inherent technical challenges, and co-assays with some other layers of cell identify such as transcription factors binding, histone modifications etc., profiles need new technological breakthroughs to facilitate a more thorough understanding of a single cell. In this review, we summarize the recent advances of single-cell multi-omics methods and discuss the challenges and opportunities in this filed.

15.
Br J Haematol ; 195(2): 267-275, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34409610

RESUMO

The expression of GGCT (γ-glutamyl cyclotransferase) is upregulated in various human cancers. γ-glutamyl cyclotransferase enzyme activity was originally purified from human red blood cells (RBCs), but the physiological function of GGCT in RBCs is still not clear. Here we reported that Ggct deletion in mice leads to splenomegaly and progressive anaemia phenotypes, due to elevated oxidative damage and the shortened life span of Ggct-/- RBCs. Ggct-/- RBCs have increased reactive oxygen species (ROS), and are more sensitive to H2 O2 -induced damage compared to control RBCs. Glutathione (GSH) and GSH synthesis precursor l-cysteine are decreased in Ggct-/- RBCs. Our study suggests a critical function of Ggct in RBC redox balance and life span maintenance through regulating GSH metabolism.


Assuntos
Eritrócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , gama-Glutamilciclotransferase/metabolismo , Anemia/genética , Animais , Antioxidantes/metabolismo , Cisteína/metabolismo , Ensaio de Imunoadsorção Enzimática/métodos , Eritropoetina/metabolismo , Feminino , Deleção de Genes , Glutationa/metabolismo , Masculino , Metabolômica/métodos , Camundongos , Modelos Animais , Fenótipo , Esplenomegalia/genética , Regulação para Cima/genética
16.
Nat Commun ; 12(1): 4249, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253716

RESUMO

5-Hydroxymethylcytosine (5hmC) is an important epigenetic mark that regulates gene expression. Charting the landscape of 5hmC in human tissues is fundamental to understanding its regulatory functions. Here, we systematically profiled the whole-genome 5hmC landscape at single-base resolution for 19 types of human tissues. We found that 5hmC preferentially decorates gene bodies and outperforms gene body 5mC in reflecting gene expression. Approximately one-third of 5hmC peaks are tissue-specific differentially-hydroxymethylated regions (tsDhMRs), which are deposited in regions that potentially regulate the expression of nearby tissue-specific functional genes. In addition, tsDhMRs are enriched with tissue-specific transcription factors and may rewire tissue-specific gene expression networks. Moreover, tsDhMRs are associated with single-nucleotide polymorphisms identified by genome-wide association studies and are linked to tissue-specific phenotypes and diseases. Collectively, our results show the tissue-specific 5hmC landscape of the human genome and demonstrate that 5hmC serves as a fundamental regulatory element affecting tissue-specific gene expression programs and functions.


Assuntos
5-Metilcitosina/análogos & derivados , Genoma Humano , Especificidade de Órgãos/genética , 5-Metilcitosina/metabolismo , Sequência de Bases , Sítios de Ligação/genética , Metilação de DNA/genética , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Fatores de Transcrição/metabolismo
17.
Cancer Lett ; 515: 73-85, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34052330

RESUMO

Dietary fiber intake helps to maintain gut homeostasis. Fiber deficiency causes commensals to utilize mucins as an energy source to destroy mucus layer, thus promoting susceptibility to inflammatory bowel disease. Here, we reported that oroxylin A, a natural flavonoid, ameliorated low-grade colonic inflammation caused by fiber deficiency, alleviated colitis, and further prevented colitis-associated colon cancer in mice. The anti-inflammatory effect of oroxylin A was due to its alteration of gut microbiota. We found that the levels of Eubacterium coprostanoligenes was significantly increased by oroxylin A and the colonized Eubacterium coprostanoligenes significantly protected against colitis and carcinogenesis in colon of mice. Together, our results in this study suggest that oroxylin A may reduce the susceptibility to intestinal diseases by increasing the level of Eubacterium coprostanoligenes which could provide a therapeutic alternation for the treatment of intestinal diseases.


Assuntos
Flavonoides/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Animais , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Fibras na Dieta , Suscetibilidade a Doenças , Feminino , Inflamação/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL
18.
Cell Biol Toxicol ; 37(1): 97-111, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33126266

RESUMO

Multiple myeloma has always been an important health problem in human beings due to its high morbidity, high mortality, and lack of effective therapeutic drugs. This study investigated the anticancer effect and mechanism of the newly synthesized small molecule compound CPUC002 on multiple myeloma. Our results confirmed that CPUC002 inhibited proliferation and induced G0/G1 cell cycle arrest in multiple myeloma cells. Moreover, CPUC002 also induced apoptosis by mitochondrial pathway and exogenous pathway. In mechanism, CPUC002 triggered apoptosis by stabilizing p53 in NCI-H929 cells which expressed wt-p53. Knockdown of p53 partially suppressed CPUC002-induced apoptosis. This suggests that there are other molecular mechanisms underlying CPUC002's antitumor effect. Further studies showed that the CPUC002 also inhibited the STAT3 signaling pathway, while knockdown of STAT3 abolished CPUC002-induced apoptosis and cell cycle arrest. In vivo, CPUC002 has significant antitumor activity through the same mechanism as our in vitro studies, and is highly safe in xenograft models. Together these findings indicate that CPUC002 induces apoptosis and G0/G1 cell cycle arrest in multiple myeloma cells by stabilizing p53 and inhibiting the STAT3 signaling pathway.


Assuntos
Apoptose , Pontos de Checagem do Ciclo Celular , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fase G1/efeitos dos fármacos , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Modelos Biológicos , Estabilidade Proteica/efeitos dos fármacos , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Redox Biol ; 29: 101392, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31926620

RESUMO

Emerging evidence suggests that oroxylin A exhibits antitumor effects by inducing cell apoptosis. However, the involved molecular mechanisms have not been elucidated. Here we report that the apoptosis induced by oroxylin A was dependent on p62-mediated activation of caspase-8 in hepatocellular carcinoma cells. Furthermore, oroxylin A also caused p62/SQSTM1 proteolysis at Asp329 by activating caspase-8. Further studies confirm that mutation in p62 (D329H and D329G) was resistant to oroxylin A-mediated p62 cleavage and apoptosis. Due to the absence of the KIR domain that interacts with Keap1, the cleaved p62 reduced the stability of Nrf2, thereby causing oxidative stress and increasing ROS levels. In vivo, p62 similarly contributed to oroxylin A-exerted antitumor effect in xenograft model inoculated SMMC-7721 tumor. In conclusion, our findings indicated that oroxylin A triggered apoptosis through caspase-8 activation and p62/SQSTM1 proteolysis.


Assuntos
Apoptose , Fator 2 Relacionado a NF-E2 , Caspase 8/genética , Caspase 8/metabolismo , Flavonoides , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Proteólise , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismo
20.
Chemphyschem ; 20(19): 2553-2565, 2019 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-31448514

RESUMO

The decomposition process of methane hydrate in pure water and methanol aqueous solution was studied by molecular dynamics simulation. The effects of temperature and pressure on hydrate structure and decomposition rate are discussed. The results show that decreasing pressure and increasing temperature can significantly enhance the decomposition rate of hydrate. After adding a small amount of methanol molecules, bubbles with a diameter of about 2 nm are formed, and the methanol molecules are mainly distributed at the gas-liquid interface, which greatly accelerates the decomposition rate and gas-liquid separation efficiency. The radial distribution function and sequence parameter analysis show that the water molecules of the undecomposed hydrate with ordered ice-like configuration at a temperature of 275 K evolve gradually into a long-range disordered liquid structure in the dynamic relaxation process. It was found that at temperatures above 280 K and pressures between 10 atm and 100 atm, the pressure has no significant effect on hydrate decomposition rate, but when the pressure is reduced to 1 atm, the decomposition rate increases sharply. These findings provided a theoretical insight for the industrial exploitation of hydrates.

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