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1.
Mol Med Rep ; 29(6)2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38639190

RESUMO

Traumatic Brain Injury (TBI) represents a significant public health challenge. Recovery from brain injury necessitates the collaborative efforts of various resident neural cells, predominantly microglia. The present study analyzed rat and mouse RNA expression micro­arrays, high­throughput RNA sequencing and single­cell sequencing data sourced from public databases. To construct an inflammation regulation network around TYRO protein tyrosine kinase­binding protein (TYROBP), to evaluate the role of TYROBP in cell death after TBI. These findings indicate that following TBI, neurons predominantly communicate with one another through the CXC chemokine ligand (CXCL) and CC chemokine ligand (CCL) signaling pathways, employing a paracrine mechanism to activate microglia. These activated microglia intensify the pathological progression of brain injury by releasing factors such as tumor necrosis factor α (TNF­α), vascular endothelial growth factor and transforming growth factor ß via the NF­κB pathway. Cells co­culture experiments demonstrated that neurons, impaired by mechanical injury, interact with microglia through non­contact mechanisms. Activated microglia secrete cytokines, including TNF­α, CXCL­8 and CCL2, which trigger an inflammatory response and facilitate neuronal apoptosis. TYROBP gene knockout in microglia was demonstrated to reduce this interaction and reduce neuronal cell apoptosis rates.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Lesões Encefálicas Traumáticas , Microglia , Animais , Camundongos , Ratos , Apoptose , Lesões Encefálicas Traumáticas/metabolismo , Inflamação/metabolismo , Ligantes , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Proteínas Tirosina Quinases/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
2.
Aging (Albany NY) ; 16(5): 4670-4683, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38446592

RESUMO

Surgery and anesthesia are vital medical interventions, but concerns over their potential cognitive side effects, particularly with the use of inhalational anesthetics like sevoflurane, have surfaced. This study delves into the neuroprotective potential of Echinatin against sevoflurane-induced neurotoxicity and the underlying mechanisms. Echinatin, a natural compound, has exhibited anti-inflammatory, antioxidant, and anticancer properties. Sevoflurane, while a popular anesthetic, is associated with perioperative neurocognitive disorders (PND) and neurotoxicity. Our investigation began with cellular models, where Echinatin demonstrated a significant reduction in sevoflurane-induced apoptosis. Mechanistically, we identified ferroptosis, a novel form of programmed cell death characterized by iron accumulation and lipid peroxidation, as a key player in sevoflurane-induced neuronal injury. Echinatin notably suppressed ferroptosis in sevoflurane-exposed cells, suggesting a pivotal role in neuroprotection. Expanding our research to a murine model, we observed perturbations in iron homeostasis, inflammatory cytokines, and antioxidants due to sevoflurane exposure. Echinatin treatment effectively restored iron balance, mitigated inflammation, and preserved antioxidant levels in vivo. Behavioral assessments using the Morris water maze further confirmed Echinatin's neuroprotective potential, as it ameliorated sevoflurane-induced spatial learning and memory impairments. In conclusion, our study unveils Echinatin as a promising candidate for mitigating sevoflurane-induced neurotoxicity. Through the regulation of ferroptosis, iron homeostasis, and inflammation, Echinatin demonstrates significant neuroprotection both in vitro and in vivo. These findings illuminate the potential for Echinatin to enhance the safety of surgical procedures involving sevoflurane anesthesia, minimizing the risk of cognitive deficits and neurotoxicity.


Assuntos
Chalconas , Ferroptose , Éteres Metílicos , Síndromes Neurotóxicas , Ratos , Animais , Camundongos , Sevoflurano/toxicidade , Éteres Metílicos/farmacologia , Éteres Metílicos/toxicidade , Antioxidantes/farmacologia , Animais Recém-Nascidos , Ratos Sprague-Dawley , Homeostase , Inflamação/metabolismo , Hipocampo/metabolismo
3.
Heliyon ; 10(6): e27294, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38509875

RESUMO

Breast cancer is a multifaceted and diverse illness that impacts millions of people globally. Identifying the underlying causes of BRCA and creating efficient treatment plans are urgent. Necroptosis is widely involved in cancer development. However, the specific roles of necroptosis in cancer immunotherapy of breast cancer have not been explored. In this study, we aim to establish the connection between necroptosis and immunotherapy in BRCA. TCGA, METABRIC, GSE103091, GSE159956, and GSE96058 were included for bioinformatics analysis. NMF and CoxBoost algorithms were used to develop the necroptosis-related patterns and model, respectively. A necroptosis-related model was developed and determined KLRB1 as a critical tumor suppressor by in vitro validation. The mutation characteristics, immune characteristics, and molecular functions of KLRB1 were explored. We further examined how necroptosis-related KLRB1 functions in BRCA as a powerful tumor suppressor and regulates the activity of macrophages by in vitro validation, including CCK8, EdU, and Transwell assays. KLRB1 was also revealed to be an immunotherapy determinant.

4.
Molecules ; 29(2)2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38257322

RESUMO

Five artemisinin bivalent ligands molecules 4a-4e were designed, synthesized, and confirmed by 1H NMR, 13C NMR, and low-resolution mass spectrometry, and the bioactivities of the target compounds were investigated against four human tumor cell lines in vitro, including BGC-823, HepG-2, MCF-7, and HCT-116. The results showed 4a, 4d, and 4e exhibited significantly tumor cell inhibitory activity compared with the artemisinin and dihydroartemisinin; compound 4e has good biological activity inhibiting BGC-823 with an IC50 value of 8.30 µmol/L. Then, the good correlations with biological results were validated by molecular docking through the established bivalent ligands multi-target model, which showed that 4e could bind well with the antitumor protein MMP-9.


Assuntos
Artemisininas , Humanos , Simulação de Acoplamento Molecular , Artemisininas/farmacologia , Linhagem Celular Tumoral , Ligantes
5.
Environ Toxicol ; 39(3): 1140-1162, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37860845

RESUMO

Sulforaphane (SFN) has attracted much attention due to its ability on antioxidant, anti-inflammatory, and anti-apoptotic properties, while its functional targets and underlying mechanism of action on brain injury caused by acute carbon monoxide poisoning (ACOP) have not been fully elucidated. Herein, we used a systematic network pharmacology approach to explore the mechanism of SFN in the treatment of brain damage after ACOP. In this study, the results of network pharmacology demonstrated that there were a total of 81 effective target genes of SFN and 36 drug-disease targets, which were strongly in connection with autophagy-animal signaling pathway, drug metabolism, and transcription disorders in cancer. Upon the further biological function and KEGG signaling pathway enrichment analysis, a large number of them were involved in neuronal death, reactive oxygen metabolic processes and immune functions. Moreover, based on the results of bioinformatics prediction associated with multiple potential targets and pathways, the AMP-activated protein kinase (AMPK) signaling pathway was selected to elucidate the molecular mechanism of SFN in the treatment of brain injury caused by ACOP. The following molecular docking analysis also confirmed that SFN can bind to AMPKα well through chemical bonds. In addition, an animal model of ACOP was established by exposure to carbon monoxide in a hyperbaric oxygen chamber to verify the predicted results of network pharmacology. We found that the mitochondrial ultrastructure of neurons in rats with ACOP was seriously damaged, and apoptotic cells increased significantly. The histopathological changes were obviously alleviated, apoptosis of cortical neurons was inhibited, and the number of Nissl bodies was increased in the SFN group as compared with the ACOP group (p < .05). Besides, the administration of SFN could increase the expressions of phosphorylated P-AMPK and MFN2 proteins and decrease the levels of DRP1, Caspase3, and Casapase9 proteins in the brain tissue of ACOP rats. These findings suggest that network pharmacology is a useful tool for traditional Chinese medicine (TCM) research, SFN can effectively inhibit apoptosis, protect cortical neurons from the toxicity of carbon monoxide through activating the AMPK pathway and may become a potential therapeutic strategy for brain injury after ACOP.


Assuntos
Lesões Encefálicas , Intoxicação por Monóxido de Carbono , Medicamentos de Ervas Chinesas , Isotiocianatos , Sulfóxidos , Ratos , Animais , Simulação de Acoplamento Molecular , Monóxido de Carbono , Proteínas Quinases Ativadas por AMP , Farmacologia em Rede , Encéfalo
6.
Molecules ; 28(24)2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38138447

RESUMO

Ampelopsis grossedentata is a valuable medicinal and edible plant, which is often used as a traditional tea by the Tujia people in China. A. grossedentata has numerous biological activities and is now widely used in the pharmaceutical and food industries. In this study, two new flavonoids (1-2) and seventeen known compounds (3-19) were isolated and identified from the dried stems and leaves of A. grossedentata. These isolated compounds were characterized by various spectroscopic data including mass spectrometry and nuclear magnetic resonance spectroscopy. All isolates were assessed for their α-glucosidase inhibitory, antioxidant, and hepatoprotective activities, and their structure-activity relationships were further discussed. The results indicated that compound 1 exhibited effective inhibitory activity against α-glucosidase, with an IC50 value of 0.21 µM. In addition, compounds 1-2 demonstrated not only potent antioxidant activities but also superior hepatoprotective properties. The findings of this study could serve as a reference for the development of A. grossedentata-derived products or drugs aimed at realizing their antidiabetic, antioxidant, and hepatoprotective functions.


Assuntos
Ampelopsis , Antioxidantes , Inibidores de Glicosídeo Hidrolases , alfa-Glucosidases , Ampelopsis/química , Antioxidantes/farmacologia , Antioxidantes/química , Flavonoides/química , Extratos Vegetais/química , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia
7.
Sci Rep ; 13(1): 20929, 2023 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-38017088

RESUMO

Bacillus is widely used in agriculture due to its diverse biological activities. We isolated a Bacillus velezensis SH-1471 from the rhizosphere soil of healthy tobacco, which has broad-spectrum antagonistic activity against a variety of plant pathogenic fungi such as Fusarium oxysporum, and can be colonized in the rhizosphere of a variety of plants. This study will further explore its mechanism by combining biological and molecular biology methods. SH-1471 contains a ring chromosome of 4,181,346 bp with a mean G + C content of 46.18%. We identified 14 homologous genes related to biosynthesis of resistant secondary metabolite, and three clusters encoded potential new antibacterial substances. It also contains a large number of genes from colonizing bacteria and genes related to plant bacterial interactions. It also contains genes related to environmental stress, as well as genes related to drug resistance. We also found that there are many metabolites in the strain that can inhibit the growth of pathogens. In addition, our indoor pot test found that SH-1471 has a good control effect on tomato wilt, and could significantly improve plant height, stem circumference, root length, root weight, and fresh weight and dry weight of the aboveground part of tomato seedlings. Therefore, SH-1471 is a potential biological control strain with important application value. The results of this study will help to further study the mechanism of SH-1471 in biological control of plant diseases and promote its application.


Assuntos
Bacillus , Rizosfera , Bacillus/genética , Bacillus/metabolismo , Bactérias/genética , Sequenciamento Completo do Genoma , Fungos/genética
8.
Pharm Biol ; 61(1): 1108-1119, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37462387

RESUMO

CONTEXT: Dihydromyricetin (DMY) is extracted from vine tea, a traditional Chinese herbal medicine with anti-cancer, liver protection, and cholesterol-lowering effects. OBJECTIVE: This study investigated the mechanism of DMY against hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Potential DMY, HCC, and cholesterol targets were collected from relevant databases. PPI networks were created by STRING. Then, the hub genes of co-targets, screened using CytoHubba. GO and KEGG pathway enrichment, were performed by Metascape. Based on the above results, a series of in vitro experiments were conducted by using 40-160 µM DMY for 24 h, including transwell migration/invasion assay, western blotting, and Bodipy stain assay. RESULTS: Network pharmacology identified 98 common targets and 10 hub genes of DMY, HCC, and cholesterol, and revealed that the anti-HCC effect of DMY may be related to the positive regulation of lipid rafts. Further experiments confirmed that DMY inhibits the proliferation, migration, and invasion of HCC cells and reduces their cholesterol levels in vitro. The IC50 is 894.4, 814.4, 467.8, 1,878.8, 151.8, and 156.9 µM for 97H, Hep3B, Sk-Hep1, SMMC-7721, HepG2, and Huh7 cells, respectively. In addition, DMY downregulates the expression of lipid raft markers (CAV1, FLOT1), as well as EGFR, PI3K, Akt, STAT3, and Erk. DISCUSSION AND CONCLUSION: The present study reveals that DMY suppresses EGFR and its downstream pathways by reducing cholesterol to disrupt lipid rafts, thereby inhibiting HCC, which provides a promising candidate drug with low toxicity for the treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Farmacologia em Rede , Receptores ErbB
9.
Zhongguo Zhong Yao Za Zhi ; 48(10): 2767-2780, 2023 May.
Artigo em Chinês | MEDLINE | ID: mdl-37282937

RESUMO

The chemical compositions of Rodgersia aesculifolia were isolated and purified using a combination of silica gel, reverse phase silica gel, Sephadex LH-20 column chromatography, and semi-preparative HPLC. The structures were determined according to the physicochemical properties and spectroscopic data. The MTT method and the ABTS kit were used to measure the cytotoxicity and antioxidant capacity of all isolates, respectively. Thirty-four compounds were isolated from R. aesculifolia and elucidated as stigmastane-6ß-methoxy-3ß,5α-diol(1), stigmastane-3ß,5α,6ß triol(2), ß-sitosterol(3), ß-daucosterol(4), stigmast-4-en-3-one(5), bergenin(6), 11-ß-D-glucopyranosyl-bergenin(7), 11-O-galloybergenin(8), 1,4,6-tri-O-galloyl-ß-D-glucose(9), gallic acid(10), 3,4-dihydroxybenzoic acid methyl ester(11), ethyl gallate(12), ethyl 3,4-dihydroxybenzoate(13), caffeic acid ethyl ester(14), p-hydroxybenzeneacetic acid(15), 4-hydroxybenzoic acid(16), 2,3-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)-propan-1-one(17), 3,7-dimethyl-2-octene-1,7-diol(18), crocusatin-B(19), neroplomacrol(20), geniposide(21), 3-hydroxyurs-12-en-27-oic acid(22), 3ß-trans-p-coumaroyloxy-olean-12-en-27-oic acid(23), aceriphyllic acid G(24), isolariciresinol(25), trans-rodgersinine B(26), cis-rodgersinine A(27), neo-olivil(28),(7S,8R)-dihydro-3'-hydroxy-8-hydroxy-methyl-7-(4-hydroxy-3-methoxy phenyl)-1'-benzofuranpropanol(29), 5,3',4'-trihydroxy-7-methoxyflavanone(30), quercetin 3-rutinoside(31), catechin-[8,7-e]-4ß-(3,4-dihydroxy-phenyl)-dihydro-2(3H)-pyranone(32), ethyl α-L-arabino-furanoside(33), and l-linoleoylglycerol(34). One new compound was discovered(compound 1), 25 compounds were first isolated from R. aesculifolia, and 22 compounds were first isolated from the Rodgersia plant. The results indicated that compounds 22-24 possessed cytotoxicity for HepG2, MCF-7, HCT-116, BGC-823, and RAFLS cell lines(IC_(50) ranged from 5.89 µmol·L~(-1) to 20.5 µmol·L~(-1)). Compounds 8-14 and 30-32 showed good antioxidant capacity, and compound 9 showed the strongest antioxidant activity with IC_(50) of(2.00±0.12) µmol·L~(-1).


Assuntos
Antioxidantes , Raízes de Plantas , Antioxidantes/farmacologia , Antioxidantes/análise , Sílica Gel/análise , Raízes de Plantas/química
10.
BMC Public Health ; 23(1): 289, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-36755324

RESUMO

BACKGROUND: Parents are significantly important in shaping the screen use of children within a family system. This study aimed to examine the associations of Chinese children's screen time (ST) over four years with parents' attitudes toward their own screen use and physical activities (PA) and health behaviors including their ST, PA, cigarette smoking, and alcohol drinking. METHODS: The current study utilized data from two waves (2011 and 2015) of the China Health and Nutrition Survey (CHNS), including 1,941 mother-father-child triads in 2011 and 2,707 mother-father-child triads in 2015 (with children aged 0-17-years-old). The ST of children and the parental attitudes and health behaviors were measured via self-report or proxy-report (for children under 6 years old) questionnaires. Pool-OLS regression models were used to assess the associations of parental attitudes and health behaviors with the ST of children. Moderation models were built to assess whether these associations depended on the gender, age, and family income of children, as well as whether paternal and maternal influences were moderated by the other parent. A multilevel cross-lagged panel model (CLPM) was used to assess parental influences on children's ST over four years. RESULTS: Paternal ST (ß = 0.09, p < 0.001), maternal ST (ß = 0.10, p < 0.001), and paternal alcohol drinking (ß = 0.30, p < 0.05) were positively associated with children's ST. In addition, maternal smoking had a positive association with girls' ST (ß = 0.53, p < 0.05). Moreover, the association between maternal ST and children's ST was observed to decline as family income increased (ß = -0.03, p < 0.001). Paternal ST had a larger positive association with children's ST when the ST of mothers exceeded 14 h/week (ß = 0.06, p < 0.05). Furthermore, lagged associations were found between paternal attitudes toward PA (ß = -1.63, p < 0.05) or maternal cigarette smoking (ß = 1.46, p < 0.05) and children's ST measured four years later. CONCLUSION: Children establish a healthy lifestyle within the family system. From the perspective of the healthy family climate, the current study suggests that future programs for reducing children's ST should be built through an integrative approach with special attention to parental attitudes and health behaviors.


Assuntos
Pais , Tempo de Tela , Masculino , Feminino , Humanos , Pré-Escolar , Recém-Nascido , Lactente , Criança , Adolescente , Mães , Comportamentos Relacionados com a Saúde , Atitude
11.
J Hazard Mater ; 441: 129836, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36088878

RESUMO

The Mn-based catalysts, with low cost and high activity, are believed to be the effective composites for eliminating in-door formaldehyde (HCHO), while the powdered form nanosized catalysts are hardly to apply for practical application. Herein, hetero-structure of nanosheets manganese oxide (MnO2) encapsulating N-doping graphene sphere (GS) were deposited in network-like sponge for constructing 3D catalyst. The prepared MnO2-GS-Sponge composite catalyst exhibited excellent performance for removing HCHO at room temperature compared with GS and commercial MnO2. The MnO2-GS with larger specific surface area (209.1 m2·g-1) was dispersed evenly in 3D network of sponge, which facilitated exposing more activate sites and achieving fast transport kinetics accelerating catalytic reaction for converting 97.1 % of 100 ppm of HCHO continuously to CO2 for 120 h. Moreover, rely on the chemisorption of amino groups on N-doping GS surface, HCHO could be enriched even at low concentrations and efficient elimination (from 1000 ppb to12 ppb, at 35 â„ƒ in 48 h). The average oxidation state and infrared spectra analysis suggested that abundant oxygen vacancies on MnO2-GS-Sponge could be identified as surface-active sites of converting HCHO into the intermediates of dioxymethylene and formate. This work might inspire the designing 3D composite material for potential application in other fields of environmental engineering or energy industrial.

12.
Materials (Basel) ; 15(19)2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36234174

RESUMO

In the process of Cr8 roller production, the phenomenon of coarse grain size and uneven grain size often appears, which makes the mechanical properties of the material decrease sharply. Accurate dynamic recrystallization model is the basis for predicting the change of grain size during thermal processing, and is an important basis for refining grain and improving material properties. In this study, the isothermal compression experiment was carried out on Cr8 alloy steel at 900-1200 °C and 0.005-0.1 s-1 by Gleeble -1500D thermal simulation compressor, and the stress dates of Cr8 alloy steel were obtained. According to experimental data, the Kopp dynamic recrystallization model of Cr8 alloy steel was established. The dynamic recrystallization volume fraction obtained by Kopp model was compared with that obtained by experiment at the same temperature and strain rate. The correlation value was 0.988, and the root mean square error (RMSE) was 0.053, which proved that the DRX model established was reliable. Through the secondary development of the program, the DRX model of Cr8 alloy steel was written into the software Forge® to verify the microstructure evolution model. The compression process of a cylindrical specimen of Cr8 alloy steel at 0.1 s-1 and 1050 °C was simulated, and the DRX microstructure evolution of the alloy was calculated. The comparison between the final grain size calculation results and the test metallographic photos of samples in different deformation zones shows the relative error of the grain size was less than 10.6%, indicating that the DRX model of Cr8 alloy steel can better predict the dynamic recrystallization of Cr8 alloy steel.

13.
Medicine (Baltimore) ; 101(41): e30741, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36254003

RESUMO

BACKGROUND: Gastric cancer (GC) is a malignant tumor originated from gastric mucosa epithelium. It is the third leading cause of cancer mortality in China. The early symptoms are not obvious. When it is discovered, it has developed to the advanced stage, and the prognosis is poor. In order to screen for potential genes for GC development, this study obtained GSE118916 and GSE109476 from the gene expression omnibus (GEO) database for bioinformatics analysis. METHODS: First, GEO2R was used to identify differentially expressed genes (DEG) and the functional annotation of DEGs was performed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The Search Tool for the Retrieval of Interacting Genes (STRING) tool was used to construct protein-protein interaction (PPI) network and the most important modules and hub genes were mined. Real time quantitative polymerase chain reaction assay was performed to verify the expression level of hub genes. RESULTS: A total of 139 DEGs were identified. The functional changes of DEGs are mainly concentrated in the cytoskeleton, extracellular matrix and collagen synthesis. Eleven genes were identified as core genes. Bioinformatics analysis shows that the core genes are mainly enriched in many processes related to cell adhesion and collagen. CONCLUSION: In summary, the DEGs and hub genes found in this study may be potential diagnostic and therapeutic targets.


Assuntos
Neoplasias Gástricas , Biomarcadores Tumorais/metabolismo , Biologia Computacional , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Prognóstico , Neoplasias Gástricas/genética
14.
Int J Mol Sci ; 23(20)2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36293167

RESUMO

The bladder is a target organ for inorganic arsenic, a carcinogen and common environmental contaminant found in soil and water. Urothelial carcinoma (UC) is the most common type of bladder cancer (BC) that develops into papillary or non-papillary tumors. Papillary tumors are mostly non-muscle invasive (NMIUC), easier treated, and have a better prognosis. Urothelial carcinoma can be molecularly sub-typed as luminal or basal, with papillary tumors generally falling into the luminal category and basal tumors exclusively forming muscle invasive urothelial carcinomas (MIUC). It is unclear why some UCs develop more aggressive basal phenotypes. We hypothesized that chronic arsenic exposure of a papillary luminal bladder cancer would lead to the development of basal characteristics and increase in invasiveness. We treated the human papillary bladder cancer cell line RT4 with 1 µM arsenite (As3+) for twenty passages. Throughout the study, key luminal and basal gene/protein markers in the exposed cells were evaluated and at passage twenty, the cells were injected into athymic mice to evaluate tumor histology and measure protein markers using immunohistochemistry. Our data indicates that chronic As3+- treatment altered cellular morphology and decreased several luminal markers in cell culture. The histology of the tumors generated from the As3+-exposed cells was similar to the parent (non-treated) however, they appeared to be more invasive in the liver and displayed elevated levels of some basal markers. Our study demonstrates that chronic As3+ exposure is able to convert a non-invasive papillary bladder cancer to an invasive form that acquires some basal characteristics.


Assuntos
Arsênio , Arsenitos , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Camundongos , Animais , Humanos , Carcinoma de Células de Transição/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Arsênio/toxicidade , Camundongos Nus , Carcinógenos , Solo , Água , Biomarcadores Tumorais/metabolismo
15.
Chin Herb Med ; 14(2): 210-233, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36117671

RESUMO

The genus Tetrastigma belongs to the Vitaceae family and contains over 100 species. This paper reviewed folk uses, chemical constituents, pharmacological activities, and clinical applications of the medicinal plants in the genus Tetrastigma. In addition, the paper also discussed the current problems for the further studies. Up to now, more than 240 compounds were reported from the genus Tetrastigma, covering 74 flavonoids, 14 terpenoids, 19 steroids, 21 phenylpropanoids, 14 alkaloids and others constituents. Among them, flavonoids are the major and the characteristic chemical constituents in this genus. Modern pharmacological studies and clinical practice showed that the extracts and chemical constituents of Tetrastigma species possessed wide pharmacological activities including antitumor, antioxidative, hepatoprotective, antiviral, anti-inflammatory, and analgesic activities. The information summarized in this paper provides valuable clues for new drug discovery and an incentive to expand the research of genus Tetrastigma.

16.
Molecules ; 27(12)2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35744788

RESUMO

Two new A-ring contracted triterpenoids, madengaisu A and madengaisu B, and one undescribed ent-kaurane diterpenoid, madengaisu C, along with 20 known compounds were isolated from the roots of Potentilla freyniana Bornm. The structures were elucidated using extensive spectroscopic techniques, including 1D and 2D-NMR, HR-ESI-MS, ECD spectra, IR, and UV analysis. Moreover, all isolated constituents were evaluated for their anti-proliferative activity against RA-FLS cells and cytotoxic activities against the human cancer cell lines Hep-G2, HCT-116, BGC-823, and MCF-7. Ursolic acid and pomolic acid displayed moderate inhibitory activity in RA-FLS cells with IC50 values of 24.63 ± 1.96 and 25.12 ± 1.97 µM, respectively. Hyptadienic acid and 2α,3ß-dihydroxyolean-12-en-28-oic acid 28-O-ß-d-glucopyranoside exhibited good cytotoxicity against Hep-G2 cells with IC50 values of 25.16 ± 2.55 and 17.66 ± 1.82 µM, respectively. In addition, 2α,3ß-dihydroxyolean-13(18)-en-28-oic acid and alphitolic acid were observed to inhibit HCT-116 cells (13.25 ± 1.65 and 21.62 ± 0.33 µM, respectively), while madengaisu B and 2α,3ß-dihydroxyolean-13(18)-en-28-oic acid showed cytotoxic activities against BGC-823 cells with IC50 values of 24.76 ± 0.94 and 26.83 ± 2.52 µM, respectively, which demonstrated that triterpenes from P. freyniana may serve as therapeutic agents for RA and cancer treatment.


Assuntos
Diterpenos do Tipo Caurano , Potentilla , Triterpenos , Diterpenos do Tipo Caurano/química , Células Hep G2 , Humanos , Estrutura Molecular , Potentilla/química , Terpenos/farmacologia , Triterpenos/química , Triterpenos/farmacologia
17.
Front Public Health ; 10: 894741, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35719620

RESUMO

Background: In China, the figure for left-behind children (LBC) of migrants stood at 68. 77 million in 2015. Despite being seen as a whole in the last few decades, LBC today differ broadly in parental migrating status. This study focused on LBC with both parents migrating (BLBC), LBC with only mothers migrating (MLBC), LBC with only fathers migrating (FLBC), and previous LBC with one or both parents migrating (PLBC), separately. We aimed at exploring the extent to which LBC were being affected by each migrant parent on both mental health and risk behaviors. Methods: Data from 4,832 children were collected by a school-based survey in both rural and urban areas of China's Anhui province. Each participant anonymously completed a self-administered questionnaire containing the sociodemographics, the Strength and Difficulties Questionnaire (SDQ), the items from the Youth Risk Behavior Surveillance System (YRBSS), and Young's Internet Addiction Test for Chinese (YIAT-C). Data were analyzed using one-way ANOVA and the Chi-squared test. Associations were estimated by multiple linear regression and logistic regression analyses adjusted for several confounders. Results: The results suggested that BLBC (p < 0.001), MLBC (p < 0.05), FLBC (p < 0.01), and PLBC (p < 0.001) significantly scored higher for total difficulties along with emotional symptoms and conduct problems than never left-behind children (NLBC). Besides, BLBC, FLBC, and PLBC further reported a significantly higher rate of smoking (p < 0.001, p < 0.01, and p < 0.001, respectively) and drinking (p < 0.01, p < 0.05, and p < 0.01, respectively) than did NLBC. Also, MLBC appeared higher risks of smoking problems [OR = 2.31, 95% CI (1.45-3.69), p < 0.001] and the internet addiction [OR = 2.15, 95% CI (1.24-3.72), p < 0.01], when compared to NLBC. Conclusions: The findings provided insight into LBC within the different contexts of parental migrations and contributed to a better understanding of their specific and potentially persistent health risks. Correspondingly, the study highlighted the implications for differentiating LBC to capture the more vulnerable group and tailored interventions to prioritize.


Assuntos
Saúde Mental , Mães , Adolescente , Criança , China/epidemiologia , Estudos Transversais , Pai , Feminino , Humanos , Masculino , Assunção de Riscos
18.
J Oncol ; 2022: 2883404, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35368896

RESUMO

Background: Renal cell carcinoma (RCC) affects the life quality of patients with advanced diseases despite good prognosis and exhibits abnormal lipid metabolism. Zinc oxide nanoparticles (ZONs) are metal oxide nanoparticles that are regarded as promising therapeutic candidate for multiple diseases. This study was for exploring the function of ZONs in RCC. Methods: We established in vitro cell model and in vivo xenograft model to determine the antitumor effect of ZONs. Cell viability and proliferation were evaluated via the cell counting kit-8 (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EDU) assay. Protein and RNA levels were checked by using immunohistochemistry (IHC) and qRT-PCR assay. ROS, malondialdehyde (MDA), triglyceride, and total cholesterol were quantified to assess lipid oxidation and synthesis. Oil red O staining was performed to check lipid droplets accumulation. The ACSL4 and miR-454-3p expression in tumor samples and normal tissues were evaluated. The luciferase reporter gene assay was performed for checking the interaction between miR-454-3p and ACSL4 3'UTR region. Results: ZONs suppressed the proliferation and viability of RCC cells both in vitro and in vivo. ZONs suppressed accumulation of ROS, MDA, triglyceride, total cholesterol, and lipid droplets in RCC cells, along with upregulated miR-454-3p. miR-454-3p targeted the 3'UTR region to suppress its expression. In patient samples, ACSL4 expression was notably elevated and indicated poor prognosis of RCC patients. Conclusion: ZONs treatment notably impeded proliferation, lipid accumulation, and oxidation in RCC cells, through upregulating miR-454-3p to suppression the function of ACSL4. Our data suggested that ZONs are promising and effective agent for RCC treatment.

19.
Front Oncol ; 12: 712475, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372039

RESUMO

Background: Breast cancer (BC) is the most common cancer and the fifth leading cause of cancer mortality with 685,000 deaths worldwide in 2020. Long non-coding RNAs (lncRNAs) are critical in BC carcinogenesis and progression. However, the functional roles and mechanisms of SLC16A1-AS1 in BC are unknown. Methods: The expression profile of SLC16A1-AS1 in BC patients was investigated using data from The Cancer Genome Atlas (TCGA) database and checked in 80 BC patients, followed by analyzing the prognostic value of SLC16A1-AS1 in the 80 BC patients. The biological functions of SLC16A1-AS1 were further examined in vivo and in vitro after overexpression of SLC16A1-AS1 in BC cells. Possible binding sites between SLC16A1-AS1 and miR-552-5p were predicted by miRDB and those between miR-552-5p and Wnt inhibitory factor-1 (WIF1) were predicted by miRanda, which were confirmed using dual-luciferase reporter assay with mutation. Spearman correlation assay was applied to evaluate the association between genes. Rescue experiments were further applied to investigate the molecular mechanisms involved. Results: Lower SLC16A1-AS1 expression in BC tissues was related to poor prognosis of BC patients. Upregulation of SLC16A1-AS1 suppressed BC cell viability, colony formation, invasion, and migration in vitro and growth in vivo via sponging miR-552-5p to release WIF1. Conclusion: SLC16A1-AS1 is a tumor suppressor in BC, and lower SLC16A1-AS1 expression is an indicator of poor prognosis in BC patients. SLC16A1-AS1 inhibits BC carcinogenesis and progression via the SLC16A1-AS1/miR-552-5p/WIF1 pathway. SLC16A1-AS1 represents a novel diagnostic, therapeutic, and prognostic target for BC management.

20.
BMC Infect Dis ; 22(1): 344, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35387590

RESUMO

BACKGROUND: The Yinzhou Center for Disease Prevention and Control (CDC) in China implemented an integrated health big data platform (IHBDP) that pooled health data from healthcare providers to combat the spread of infectious diseases, such as dengue fever and pulmonary tuberculosis (TB), and to identify gaps in vaccination uptake among migrant children. METHODS: IHBDP is composed of medical data from clinics, electronic health records, residents' annual medical checkup and immunization records, as well as administrative data, such as student registries. We programmed IHBDP to automatically scan for and detect dengue and TB carriers, as well as identify migrant children with incomplete immunization according to a comprehensive set of screening criteria developed by public health and medical experts. We compared the effectiveness of the big data screening with existing traditional screening methods. RESULTS: IHBDP successfully identified six cases of dengue out of a pool of 3972 suspected cases, whereas the traditional method only identified four cases (which were also detected by IHBDP). For TB, IHBDP identified 288 suspected cases from a total of 43,521 university students, in which three cases were eventually confirmed to be TB carriers through subsequent follow up CT or T-SPOT.TB tests. As for immunization screenings, IHBDP identified 240 migrant children with incomplete immunization, but the traditional door-to-door screening method only identified 20 ones. CONCLUSIONS: Our study has demonstrated the effectiveness of using IHBDP to detect both acute and chronic infectious disease patients and identify children with incomplete immunization as compared to traditional screening methods.


Assuntos
Dengue , Tuberculose , Big Data , Criança , China/epidemiologia , Humanos , Programas de Rastreamento , Tuberculose/diagnóstico
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