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1.
Exp Cell Res ; 422(1): 113433, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36423659

RESUMO

Although most cells are mononuclear, the nucleus can exist in the form of binucleate or even multinucleate to respond to different physiological processes. The male accessory gland of Drosophila is the organ that produces semen, and its main cells are binucleate. Here we observe that CTP synthase (CTPS) forms filamentous cytoophidia in binuclear main cells, primarily located at the cell boundary. In CTPSH355A, a point mutation that destroys the formation of cytoophidia, we find that the nucleation mode of the main cells changes, including mononucleates and vertical distribution of binucleates. Although the overexpression of CTPSH355A can restore the level of CTPS protein, it will neither form cytoophidia nor eliminate the abnormal nucleation pattern. Therefore, our data indicate that there is an unexpected functional link between the formation of cytoophidia and the maintenance of binucleation in Drosophila main cells.


Assuntos
Carbono-Nitrogênio Ligases , Drosophila , Animais , Masculino , Carbono-Nitrogênio Ligases/genética , Carbono-Nitrogênio Ligases/metabolismo , Núcleo Celular/metabolismo , Citoesqueleto/metabolismo , Drosophila/metabolismo
2.
Int J Gynecol Pathol ; 42(2): 212-216, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35639370

RESUMO

The fetal gut-like phenotype can be found in yolk sac tumors and adenocarcinomas with enteroblastic differentiation (AEBDs). We report a cervical yolk sac tumor in a 44-yr-old woman. The tumor has similar morphology, immunophenotype, and molecular features to the AEBD of the digestive system. The tumor showed a glandular-predominant growth pattern, composed of columnar cells with clear glycogen-rich cytoplasm. The microcystic/reticular architecture or Schiller-Duval bodies were not found in the tumor. Immunohistochemically, the tumor cells were positive for p16, glypican-3 (GPC3), spalt-like transcription factor 4 (SALL4), CDX-2, and p53. TP53 mutation was identified by next-generation sequencing, and human papillomavirus (HPV) 35 was detected by HPV DNA polymerase chain reaction. In the present case, the adenocarcinoma cells in the superficial cervical glandular epithelium and the nonclear glandular components proved the existence of somatic components. The positivity of p16 and HPV also supports that the present case originates from an HPV-associated adenocarcinoma. The yolk sac tumor should be thought of as "germ cell differentiation" from a somatic carcinoma. This kind of yolk sac tumor arising from somatic-type adenocarcinoma in the female genital tract may be the counterpart of AEBD in the digestive tracts and adenocarcinomas with fetal gut-like morphology in other organs. The tumor might be more aggressive than conventional adenocarcinoma, pathologists should highlight the existence of the enteroblastic component in the pathologic report.


Assuntos
Adenocarcinoma , Tumor do Seio Endodérmico , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Tumor do Seio Endodérmico/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Diferenciação Celular , Adenocarcinoma/patologia , Glipicanas
3.
Bioorg Med Chem ; 73: 117033, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36202064

RESUMO

Targeted protein degradation using proteolysis-targeting chimeras (PROTACs) has emerged as an effective strategy for drug discovery, given their unique advantages over target protein inhibition. The bromodomain and extra-terminal (BET) family proteins play a key role in regulating oncogene expression and are considered attractive therapeutic targets for cancer therapy. Considering the therapeutic potential of BET proteins in cancer and the marked attractiveness of PROTACs, BET-targeting PROTACs have been extensively pursued. Recently, BET-targeting PROTACs based on new E3 ligases and novel strategies, such as light-activated, macrocyclic, folate-caged, aptamer-PROTAC conjugation, antibody-coupling, and autophagy-targeting strategies, have emerged. In the present review, we provide a comprehensive summary of advances in BET-targeting PROTACs.


Assuntos
Neoplasias , Humanos , Ácido Fólico , Neoplasias/tratamento farmacológico , Proteólise , Ubiquitina-Proteína Ligases/metabolismo
4.
Anal Chem ; 92(19): 13327-13335, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32794762

RESUMO

The ability to track interfacial dynamics of a single nanoparticle at the solution-solid interface is crucial for understanding physical, chemical, and biological processes, but it remains a challenge. Here, we demonstrated a plasmonic imaging technique that can track unlabeled nanoparticles at the solution-solid interface with high spatial and temporal resolutions. This technique is based on particle-induced interferometric scattering of a surface plasmonic wave, which results in a high vertical sensitivity. Using this ability, we tracked the trajectories of a single nanoparticle interacting with a surface, measured the hydrodynamically hindered diffusion of nanoparticles, and revealed the surface chemistry-dependent behavior of nanoparticles at the interface. The application for tracking formation of membranes from a lipid vesicle was demonstrated, indicating the potential for investigating a broad range of nano-objects at interfaces in a complex environment.

5.
Angew Chem Int Ed Engl ; 59(5): 1776-1785, 2020 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-31531917

RESUMO

Surface plasmon resonance microscopy (SPRM) is a versatile platform for chemical and biological sensing and imaging. Great progress in exploring its applications, ranging from single-molecule sensing to single-cell imaging, has been made. In this Minireview, we introduce the principles and instrumentation of SPRM. We also summarize the broad and exciting applications of SPRM to the analysis of single entities. Finally, we discuss the challenges and limitations associated with SPRM and potential solutions.


Assuntos
Técnicas Biossensoriais/métodos , Microscopia/métodos , Análise de Célula Única/métodos , Ressonância de Plasmônio de Superfície/métodos , Humanos
6.
Molecules ; 24(17)2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31454945

RESUMO

Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn) is rich in functional compounds such as rutin, quercetin, d-chiro-inositol, dietary fiber, and essential amino acids. Electric field (EF) treatment before sprout germination results in physiological and chemical changes, and some alterations might lead to positive applications in plant seeds. MTT assay showed that the effect of total flavonoids on human gastric cancer cell line MGC80-3 was significantly changed after EF treatment for different germination days (3-7 days). Among them, the total flavonoids of tartary buckwheat (BWTF) on the third day had the most obvious inhibitory effect on MGC80-3 (p < 0.01). In addition, flow cytometry evidenced that different ratios of quercetin and rutin had effects on the proliferation of MGC80-3. The same content of quercetin and rutin had the best effect, reaching 6.18 ± 0.82%. The anti-cancer mechanism was mainly promoted by promoting the expression of apoptotic proteins. The expression of Bax/Bcl-2 and caspase-8 in MGC80-3 cells was mediated by BWTFs. This study has good research value for improving the biological and economic value of tartary buckwheat.


Assuntos
Fagopyrum/fisiologia , Quercetina/farmacologia , Rutina/farmacologia , Neoplasias Gástricas/metabolismo , Caspase 8/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Fagopyrum/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Germinação , Humanos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Quercetina/isolamento & purificação , Rutina/isolamento & purificação , Neoplasias Gástricas/tratamento farmacológico , Proteína X Associada a bcl-2/metabolismo
7.
Lipids Health Dis ; 17(1): 165, 2018 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-30031400

RESUMO

BACKGROUND: Supplementation with Selenium (Se) has been shown to lower blood cholesterol and increase tissue concentrations of the antioxidant glutathione (GSH); however, the effects of Se supplementation, in combination with supplemental magnesium, on high fat-induced hyperlipidemia have not been studied. This study was designed to elucidate the effects of oral selenium and magnesium co-supplementation on antihyperlipidemic and hepatoprotective, antioxidative activities, and related gene expression in a hyperlipidemic rat model. METHODS: Forty male Sprague Dawley rats were divided into 4 groups: one group served as control group (CT), provided control diet; The other groups were made hyperlipidemic with high-fat diet; specifically, a high-fat diet group (HF); low-dose selenium (0.05 mg/kg·bw) + low-dose magnesium (5.83 mg/kg·bw) supplement high-fat diet group (HF + LSe + LMg) and high-dose selenium (0.10 mg/kg·bw) + high-dose magnesium (58.33 mg/kg·bw) supplement high-fat diet group (HF + HSe + HMg). The first 4 weeks of the experiment was a hyperlipidemia inducing period using high-fat diet and the following 8 weeks involved in selenium and magnesium co-supplementation. On day 0, 20, 40 and 60 of the intervention, lipid profile was measured. At the end of the 12-week experiments, final blood and liver samples were collected for the measurements of lipid profile, antioxidative indexes, pathological examination, and liver lipid metabolism related gene expression. RESULTS: The elevated levels of serum and liver total cholesterol (TC) and serum LDL-C induced by feeding high-fat diets were significantly reduced by low-dose Se and Mg co-supplementation. Both doses of selenium and magnesium co-supplementation notably decreased the blood and liver TG levels, liver function indexes ALT and AST and the ratio of TC/HDL-C and TG/HDL-C. In contrast, Se and Mg supplementation showed a substantial increase in Se-dependent glutathione peroxidase (GSH-Px) and SOD activities and an significant reduce of level of MDA of hyperlipidemic rats. Oil Red O staining showed that selenium and magnesium co-supplementation significantly reduced hepatic intracellular triacylglycerol accumulation. H&E staining also showed that selenium and magnesium co-supplementation can attenuate liver steatosis. Selenium and magnesium co-supplementation remarkably inhibited the mRNA expression level of hepatic lipogenesis genes liver X receptor alpha (LXRα),SREBP-1c and FASN (fatty acid synthase), regulated the mRNA expression levels of liver enzymes related to cholesterol metabolism, including the down regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) and the upregulation of cholesterol 7α-hydroxylase (CYP7A1) and lecithin cholesterol acyltransferase (LCAT) in the liver of hyperlipidemia rats. CONCLUSIONS: Oral selenium and magnesium co-supplementation inhibited an increase of lipid and liver profile and liver function index induced by a high-fat diet, and enhanced the activity of the antioxidant enzymes. Selenium combined with magnesium is a promising therapeutic strategy with lipid-lowering and antioxidative effects that protects the liver against hyperlipidemia.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Gluconatos/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Selenito de Sódio/farmacologia , Administração Oral , Animais , Antioxidantes/metabolismo , Peso Corporal/efeitos dos fármacos , Suplementos Nutricionais , Enzimas/genética , Enzimas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Gluconatos/administração & dosagem , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Ratos Sprague-Dawley , Selenito de Sódio/administração & dosagem
8.
Nephrology (Carlton) ; 23(2): 107-116, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28703918

RESUMO

AIMS: Diabetic nephropathy (DN) is a severe microvascular complication frequently associated with type 1 and type 2 diabetes mellitus. The objective of this study was to estimate the effect between Apa I, Bsm I, Fok I and Taq I polymorphisms of the vitamin D receptor (VDR) gene and DN susceptibility. METHODS: Eligible case-control studies published updated to March 2017 were searched. The odds ratio (OR) and 95% confident intervals (CI) were used to calculate the strength of effect. RESULTS: Twelve articles were finally screened out, including 3954 diabetic patients and 1248 healthy controls. When compared with the diabetic patients without nephropathy, our results found that only the Bsm I polymorphism was associated with increased risk of DN under the allelic model (B vs. b: OR = 1.51, 95% CI = 1.03-2.20, P = 0.04) and dominant model (BB + Bb vs. bb: OR = 1.52, 95% CI = 1.00-2.31, P = 0.05). When compared with the healthy controls, our results showed that the Bsm I polymorphism was associated with the DN susceptibility under the allelic model (B vs. b: OR = 1.80, 95% CI = 1.12-2.91, P = 0.02), the homogeneous model (BB vs. bb: OR = 1.43, 95% CI = 1.03-1.98, P = 0.03), and the domain model (BB + Bb vs. bb: OR = 1.80, 95% CI = 1.06-3.05, P = 0.03); the Taq I variant was associated with increased risk of DN only under the heterogeneous model (Tt vs. tt: OR = 2.29, 95% CI = 1.04-5.03, P = 0.04). CONCLUSION: Our results suggested that B allele, and BB + Bb genotypes of Bsm I variant, Tt genotype of Taq I variant might be risk factors for DN. Future researches are still needed to identify our results.


Assuntos
Nefropatias Diabéticas/genética , Polimorfismo Genético , Receptores de Calcitriol/genética , Adulto , Idoso , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Medição de Risco , Fatores de Risco
9.
Zhongguo Zhong Yao Za Zhi ; 43(15): 3176-3183, 2018 Aug.
Artigo em Zh | MEDLINE | ID: mdl-30200715

RESUMO

To investigate the protective effect and relevant mechanism of Fuzi Lizhong decoction (FZLZD) on liver of rats with non-alcoholic fatty liver disease (NAFLD), totally 32 male SPF Wistar rats were randomly divided into 4 groups: control group, model group, Yishanfu (YSF) group (200 mg·kg⁻¹·d⁻¹) and FZLZD group (10 g·kg⁻¹·d⁻¹), with 8 rats in each group. Rat model of NAFLD was prepared through the intragastric administration with fat emulsion for 4 weeks. After the successful modeling, rats in each administration group were continuously administered for 4 weeks. After 8 weeks, the rats in each group were put to death, and the pathological changes in liver tissue were detected by HE staining. Automatic biochemical analyzer was used to detect fasting serum lipid levels (T-Chol, TG, LDL-C, HDL-C) and liver functions (ALT, TP, ALB) of rats in each group. The rat liver index was calculated by weighing method. Enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of inflammatory cytokines TNF-α and IL-6 in liver tissue. Real-time quantitative PCR (qRT-PCR) was used to detect the mRNA expressions of fat metabolism-related factors SREBP-1c and FASN in liver tissue. Western blot was used to detect the p-AMPK and p-NF-κBp65 protein expressions in liver tissue. The results of HE staining showed that compared with the control group, the pathological changes in liver tissue in the model group rats were obvious; specifically, the outline of hepatic lobule was unclear, the hepatic cells showed diffuse steatosis of adipose tissue, and were accompanied by inflammatory infiltration, nuclear condensation, coloring deep; compared with the model group, liver lesions of all of the treatment groups were significantly alleviated; especially, the FZLZD group showed the most significant degree of remission. The results of serum test showed that the levels of serum lipids (T-Chol, TG, LDL-C, HDL-C), liver functions (ALT, TP, ALB) and liver index in model group were significantly higher than those in control group (P<0.01); compared with the model group, the indexes of serum lipid and liver function of rats in each treatment group were significantly decreased (P<0.01), and those in FZLZD group were significantly decreased (P<0.05), while those in YSF group were not significantly changed. The results of ELISA and qRT-PCR showed that compared with the control group, the secretion levels of TNF-α, IL-6 and the mRNA levels of SREBP-1c and FASN in the liver tissue of model group rats were significantly increased (P<0.01); compared with model group, the secretion levels of TNF-α, IL-6 and the mRNA levels of SREBP-1c, FASN in liver tissue of rats in each treatment group were significantly decreased (P<0.01); compared with YSF group, the secretion levels of TNF-α and IL-6 and the mRNA levels of SREBP-1c and FASN in FZLZD group were significantly different (P<0.01). Western blotting showed that compared with the model group, the protein expression of p-AMPK in liver tissue of rats in FZLZD group was significantly increased (P<0.01), while the protein expression of p-NF-κBp65 was significantly decreased (P<0.01). FZLZD can significantly improve hepatic pathological changes, reduce serum lipid levels, promote liver function and liver index in NAFLD rats, which may be associated with the activation of the AMPK pathway and thereby the inhibition of the expressions of SREBP-1c and FASN, and the inhibition of the NF-κBp65 pathway and thereby the reduction of the release of inflammatory factors.


Assuntos
Adenilato Quinase/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Transdução de Sinais , Fator de Transcrição RelA/metabolismo , Animais , Ácido Graxo Sintase Tipo I/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
10.
Tumour Biol ; 39(5): 1010428317697568, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28459375

RESUMO

This study aimed to investigate the effects of long non-coding RNA ROR (regulator of reprogramming) on cisplatin (DDP) resistance in patients with non-small-cell lung cancer by regulating PI3K/Akt/mTOR signaling pathway. Human cisplatin-resistant A549/DDP cell lines were selected and divided into control group, negative control group, si-ROR group, ROR over-expression group, Wortmannin group, and ROR over-expression + Wortmannin group. MTT assay was used to determine the optimum inhibitory concentration of DDP. Quantitative real-time polymerase chain reaction and western blotting were applied to detect expressions of long non-coding RNA ROR, PI3K, Akt, and mTOR. Colony-forming assay, scratch test, Transwell assay, and flow cytometry were conducted to detect cell proliferation, migration, invasion, and apoptosis, respectively. Tumor-formation assay was performed to detect the growth of transplanted tumors. Long non-coding RNA ROR expression was high in human A549/DDP cell lines. Compared with the control and negative control groups, the mRNA and protein expressions of PI3K, Akt, mTOR, and bcl-2 decreased, whereas the mRNA and protein expression of bax and the sensitivity of cells to DDP significantly increased. Cell proliferation, migration, and invasion abilities decreased in the si-ROR and Wortmannin groups. In comparison with control and negative control groups, the mRNA and protein expressions of PI3K, Akt, mTOR, and bcl-2 increased, whereas the mRNA and protein expressions of bax decreased, the sensitivity of cells to DDP significantly increased, and cell proliferation, migration, and invasion abilities decreased in the ROR over-expression group. For nude mice in tumor-formation assay, compared with control and negative control groups, the tumor weight was found to be lighter (1.03 ± 0.15) g, the protein expressions of PI3K, Akt, mTOR, and bcl-2 decreased, and the protein expression of bax increased in the si-ROR group. Long non-coding RNA ROR may affect the sensitivity of lung adenocarcinoma cells to DDP by targeting PI3K/Akt/mTOR signaling pathway.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Proteína Oncogênica v-akt/genética , RNA Longo não Codificante/genética , Serina-Treonina Quinases TOR/genética , Células A549 , Animais , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cisplatino/administração & dosagem , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Humanos , Camundongos , Invasividade Neoplásica/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Longo não Codificante/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Exp Mol Pathol ; 100(1): 192-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26723864

RESUMO

OBJECTIVE: The purpose of our study was to elucidate the impact of microRNA-126 (miR-126) targeting PIK3R2 gene on cell proliferation and apoptosis of rheumatoid arthritis synovial fibro-blasts (RASFs) by regulating PI3K/AKT signal pathway. METHODS: The synovial tissue samples of this study were from 55 RA patients undergoing joint replacement and 27 healthy people undergoing joint repair due to trauma. The target genes of miR-126 were collected by the TargetScan and PIK3R2 as the direct target gene of miR-126 was confirmed by dual-luciferase reporter assay system. Our experiment had five groups including the blank control, miR-126 mimic, miR-126 mimic control, miR-126 inhibitor and miR-126 inhibitor control groups. Additionally, real-time quantitative polymerase chain reaction (RT-qPCR), Western-Blot, cell counting kit (CCK-8) and flow cytometry were carried out in this study. RESULTS: Compared with healthy individuals, the RA patients had increased miR-126, but decreased PIK3R2 mRNA expressions in the synovial tissues. Pearson correlation analysis indicated that miR-126 expression was negatively correlated with PIK3R2 mRNA expression (all P<0.05). When compared with the blank group respectively, the miR-126 mimic group had raising cell proportions in S and G2/M phases with reduced rate of cell apoptosis, while the miR-126 inhibitor group had raising cell proportions in G0/G1 and G2/M phases with increased rate of cell apoptosis (all P<0.05). Besides, compared with the blank control group, the miR-126 mimic group had declined expression of PIK3R2 protein with ascended expression of PI3K and p-AKT (all P<0.05), while the miR-126 inhibitor group had increased expression of PIK3R2 protein with decreased expression of PI3K and p-AKT (all P<0.05). CONCLUSION: Our study demonstrated that down-regulation of miR-126 may indirectly inhibit PI3K/AKT signaling pathway to disrupt the imbalance between growth and death of RASFs by targeting PIK3R2, which may be clinically helpful to find therapeutic strategies directed toward miR-126 function for RA patients.


Assuntos
Apoptose/fisiologia , Artrite Reumatoide/patologia , Proliferação de Células/genética , Fibroblastos/metabolismo , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/genética , Transdução de Sinais , Adulto , Idoso , Apoptose/genética , Artrite Reumatoide/genética , Regulação para Baixo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genética , Adulto Jovem
12.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 34(12): 1487-91, 2014 Dec.
Artigo em Zh | MEDLINE | ID: mdl-25632751

RESUMO

OBJECTIVE: To study the effect of Bushen Tongdu Capsule (BTC) on RANK/RANKL/ OPG pathway of collagen induced arthritis (CIA) rats, thereby laying theoretic evidence for treating rheumatic arthritis (RA) by Chinese medicine. METHODS: RA model was induced by CIA. Totally 42 rats were randomly divided into six groups, i.e., the normal control group, the model group, the low dose BTC (BSL) group, the medium dose BTC (BSM) group, the high dose BTC (BSH) group, and the Tripterygium Glycosides (TG) group, 7 in each group. BTC at the daily dose of 120, 240, and 480 mg/kg was given by gastrogavage to rats in the BSL, BSM, and BSH group respectively from the 13th day of modeling. TG at the daily dose of 24 mg/kg was given by gastrogavage to rats in the TG group. All medication was given once daily, 2 mL each time. Two mL normal saline was administered to rats in the normal control group and the model group. All medication lasted for 18 days. Samples were taken at day 31. The TRAP section of the ankle joint was fixed in 10% formalin for TRAP stain. Serum levels of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), and macrophage colony-stimulating factor (M-CSF) were detected using ELISA. RESULTS: Compared with the normal control group, positive reactions of pathological ankle joint section, inflammation, and osteoclasia degree were significantly improved in the model group, serum levels of RANKL and M-CSF were up-regulated, levels of OPG and OPG/RANKL were significantly lowered (all P < 0.01). Compared with the model group, positive reactions of pathological ankle joint section, inflammation, and osteoclasia degree also significantly decreased in the BSH group and the TG group (all P < 0.01). RANKL and M-CSF were significantly down-regulated in each medicated group, while levels of OPG and OPG/RANKL were significantly up-regulated (all P < 0.01). Compared with the TG group, M-CSF was lower, but levels of OPG and OPG/RANKL were significantly up-regulated in the normal control group (all P < 0.01). RANKL and M-CSF were significantly up-regulated, while levels of OPG and OPG/RANKL were significantly down-regulated in the model group and each BS group (all P < 0.01). CONCLUSION: BTC could relieve bone damage of CIA rats possibly through regulating and controlling osteoclasts.


Assuntos
Artrite Experimental/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Animais , Inflamação , Fator Estimulador de Colônias de Macrófagos/metabolismo , Osteoclastos , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Ratos , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Tripterygium
13.
World J Gastrointest Oncol ; 16(2): 563-570, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38425401

RESUMO

BACKGROUND: Early adenocarcinoma mixed with a neuroendocrine carcinoma (NEC) component arising in the gastroesophageal junctional (GEJ) region is rare and even rarer in young patients. Here, we report such a case in a 29-year-old Chinese man. CASE SUMMARY: This patient presented to our hospital with a 3-mo history of dysphagia and regurgitation. Upper endoscopy revealed an elevated nodule in the distal esophagus 1.6 cm above the GEJ line, without Barrett's esophagus or involvement of the gastric cardia. The nodule was completely resected by endoscopic submucosal dissection (ESD). Pathological examination confirmed diagnosis of intramucosal adenocarcinoma mixed with an NEC component, measuring 1.5 cm. Immunohistochemically, both adenocarcinoma and NEC components were positive for P53 with a Ki67 index of 90%; NEC was positive for synaptophysin and chromogranin. Next-generation sequencing of 196 genes demonstrated a novel germline mutation of the ERCC3 gene in the DNA repair pathway and a germline mutation of the RNF43 gene, a common gastric cancer driver gene, in addition to pathogenic somatic mutations in P53 and CHEK2 genes. The patient was alive without evidence of the disease 36 mo after ESD. CONCLUSION: Early adenocarcinoma with an NEC component arising in the distal esophageal side of the GEJ region showed evidence of gastric origin.

14.
Clinics (Sao Paulo) ; 78: 100301, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37952443

RESUMO

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease closely linked to cardiovascular disease (CVD). This study aims to investigate the connection between early-stage NAFLD and atherosclerosis, as well as the correlation between liver fibrosis and coronary heart disease while exploring underlying inflammatory mechanisms. METHODS: In this retrospective study, the authors analyzed data from 607 patients who underwent both coronary computed tomography angiography (CCTA) and abdominal ultrasonography (US). Logistic regression was utilized to examine the association between NAFLD and atherosclerosis, while mediation analysis was conducted to explore whether inflammatory markers mediate the link between liver fibrosis and coronary artery disease. RESULTS: Among the 607 patients included, 237 (39.0 %) were diagnosed with NAFLD through ultrasonography. After adjusting for traditional cardiovascular risk factors, ALT, and AST, NAFLD demonstrated a significant correlation with carotid intimal thickening (1.58, 95 % CI 1.04‒2.40; p = 0.034) and non-calcified plaque (1.56, 95 % CI 1.03‒2.37; p = 0.038). Additionally, fibrosis predictive markers, including FIB-4 > 1.3 (1.06, 95 % CI 2.30‒5.00; p = 0.035) and APRI (6.26, 95 % CI 1.03‒37.05; p = 0.046), independently correlated with coronary heart disease after adjusting for cardiovascular risk factors. Conversely, among systemic inflammatory markers, only the neutrophil-to-lymphocyte ratio (NLR) and systemic inflammatory response index (SIRI) are independently associated with coronary heart disease. ROC curve analysis indicated that combining predictive fibrosis markers or inflammatory markers with traditional cardiovascular risk factors enhanced the predictive accuracy for coronary heart disease. Mediation analysis revealed that NLR fully mediated the effect of liver fibrosis on coronary heart disease. CONCLUSION: NAFLD is associated with carotid intimal thickening and non-calcified plaque, suggesting an increased cardiovascular risk. Furthermore, liver fibrosis independently increases the risk of coronary heart disease in the early-stage NAFLD population, and inflammation may play a fully mediating role in the effect of liver fibrosis on coronary heart disease. Early intervention is crucial for NAFLD patients to mitigate future major adverse cardiovascular events.


Assuntos
Aterosclerose , Doença da Artéria Coronariana , Hepatopatia Gordurosa não Alcoólica , Placa Aterosclerótica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Estudos Retrospectivos , Aterosclerose/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Cirrose Hepática , Inflamação/complicações
15.
J Dig Dis ; 24(12): 660-670, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38100304

RESUMO

OBJECTIVE: To investigate the clinicopathological and prognostic significance of intestinal metaplasia (IM) in endoscopically resected early gastric carcinoma (EGC). METHODS: Altogether 136 consecutive cases with EGC resected by endoscopic submucosal dissection over 5 years were included and divided into the early gastric cardiac (EGCC; n = 60) and non-cardiac carcinoma (EGNCC; n = 76) groups. Goblet cell IM and subtypes were determined with histology and immunostaining. Recurrence-free survival (RFS) was compared among various IM groups. RESULTS: IM was identified in 128 (94.1%) EGC cases, including complete IM (n = 39), incomplete IM (n = 27), and mixed IM (n = 62). Incomplete IM was significantly more common in EGCC and exhibited a lower frequency of en bloc resection than the complete subtype. The frequency of synchronous or metachronous gastric tumor was significantly more common in EGCC with complete IM than in those with incomplete IM. Compared to EGC without IM, EGC with IM showed a significantly higher frequency of non-poorly cohesive carcinoma, en bloc resection, and non-eCuraC-1 grade. EGNCC with IM was significantly associated with negative resection margins and en bloc resection. The 5-year RFS was significantly lower in EGNCC patients with incomplete IM compared with those with mixed IM. The independent risk factors for RFS included tumor size >2 cm and eCuraC-1 grade. CONCLUSIONS: Subtyping IM in EGC helped predict endoscopic resectability, prognosis, and risk of synchronous or metachronous gastric tumor. The significance of IM differed between EGCC and EGNCC. Large studies with longer follow-up are warranted to validate our findings.


Assuntos
Carcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Endoscopia , Prognóstico , Carcinoma/cirurgia , Carcinoma/patologia , Metaplasia , Mucosa Gástrica/patologia , Estudos Retrospectivos , Resultado do Tratamento , Gastroscopia
16.
Virchows Arch ; 482(4): 789-795, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36414804

RESUMO

Salivary gland-type intraductal carcinoma (IC) is a rare malignant salivary gland neoplasm. Primary salivary gland-type IC has never been described in the lung. Herein, we present a primary pulmonary IC in a 63-year-old woman. The tumor originated in the bronchus wall of the right middle lobe. The tumor consisted of two histological types, intercalated component and oncocytic component. The intercalated component showed tubular/cystic pattern composed of column to cube-shaped cells and scattered mucous cells. The oncocytic component showed solid nests composed of large cells with abundant eosinophilic granular cytoplasm. Immunohistochemically, both histological components were positive for cytokeratin 7 (CK7), S-100 protein, SOX10, and mammaglobin. The rimming myoepithelial cells were highlighted by p63 and smooth muscle actin (SMA). The tumor cells were negative for androgen receptor (AR), HER-2, Dog-1, TTF-1, napsin A, GCDFP-15, and GATA3. In the present case, we detected KIAA1217::RET fusion via DNA-based next-generation sequencing (NGS) and RT-PCR, which established the diagnosis of IC at a molecular level. The present case expands the categories of bronchopulmonary salivary gland-type tumors.


Assuntos
Adenocarcinoma , Carcinoma Intraductal não Infiltrante , Neoplasias das Glândulas Salivares , Animais , Cães , Humanos , Biomarcadores Tumorais/análise , Brônquios/patologia , Carcinoma Intraductal não Infiltrante/patologia , Fusão Gênica , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/patologia
17.
Open Med (Wars) ; 18(1): 20230850, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38025537

RESUMO

To investigate the effect of adipose-derived stem cells (ASCs) transplantation on radiation-induced lung injury (RILI), Sprague-Dawley rats were divided into phosphate-buffered saline (PBS) group, ASCs group, Radiation + PBS group, and Radiation + ASCs group. Radiation + PBS and Radiation + ASCs groups received single dose of 30 Gy X-ray radiation to the right chest. The Radiation + PBS group received 1 mL PBS suspension and Radiation + ASCs group received 1 mL PBS suspension containing 1 × 107 CM-Dil-labeled ASCs. The right lung tissue was collected on Days 30, 90, and 180 after radiation. Hematoxylin-eosin and Masson staining were performed to observe the pathological changes and collagen fiber content in the lung tissue. Immunohistochemistry (IHC) and western blot (WB) were used to detect levels of fibrotic markers collagen I (Collal), fibronectin (FN), as well as transforming growth factor-ß1 (TGF-ß1), p-Smad 3, and Smad 3. Compared with the non-radiation groups, the radiation groups showed lymphocyte infiltration on Day 30 after irradiation and thickened incomplete alveolar walls, collagen deposition, and fibroplasia on Days 90 and 180. ASCs relieved these changes on Day 180 (Masson staining, P = 0.0022). Compared with Radiation + PBS group, on Day 180 after irradiation, the Radiation + ASCs group showed that ASCs could significantly decrease the expressions of fibrosis markers Collal (IHC: P = 0.0022; WB: P = 0.0087) and FN (IHC: P = 0.0152; WB: P = 0.026) and inhibit the expressions of TGF-ß1 (IHC: P = 0.026; WB: P = 0.0152) and p-Smad 3 (IHC: P = 0.0043; WB: P = 0.0087) in radiation-induced injured lung tissue. These indicated that ASCs could relieve RILI by inhibiting TGF-ß1/Smad 3 signaling pathway.

18.
ACS Appl Mater Interfaces ; 14(19): 22658-22665, 2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35503924

RESUMO

Dissolution of nanoparticles is an environmental interfacial process that affects the transformation of nanoparticles. Understanding the dissolution processes of nanoparticles is important to predict their fate in the aquatic environment. However, studying nanoparticle dissolution kinetics is still challenging since dissolution is usually coupled with nanoparticle aggregation. Here, we probed the dissolution process of Ag nanoparticles at the single-particle level by surface plasmon resonance microscopy. The single-particle imaging capability enabled us to classify Ag nanoparticles, measure the dissolution dynamics of single nanoparticles, and correlate the aggregation size with oxidation activity. Moreover, we studied the dual effect of natural organic matter on the dissolution of Ag nanoparticles and validated this result with real natural freshwater. Our study provides new insights into the dissolution of Ag nanoparticles, and this technique can be extended for other nanomaterials to evaluate their fate in aquatic environments.

19.
Nat Commun ; 13(1): 7869, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36550149

RESUMO

Studying the localized electrocatalytic activity of heterogeneous electrocatalysts is crucial for understanding electrocatalytic reactions and further improving their performance. However, correlating the electrocatalytic activity with the microscopic structure of two-dimensional (2D) electrocatalysts remains a great challenge due to the lack of in situ imaging techniques and methods of tuning structures with atomic precision. Here, we present a general method of probing the layer-dependent electrocatalytic activity of 2D materials in situ using a plasmonic imaging technique. Unlike the existing methods, this approach was used to visualize the surface charge density and electrocatalytic activity of single 2D MoS2 nanosheets, enabling the correlation of layer-dependent electrocatalytic activity with the surface charge density of single MoS2 nanosheets. This work provides insights into the electrocatalytic mechanisms of 2D transition metal dichalcogenides, and our approach can serve as a promising platform for investigating electrocatalytic reactions at the heterogeneous interface, thus guiding the rational design of high-performance electrocatalysts.

20.
J Hazard Mater ; 427: 128210, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-34999401

RESUMO

Polyvinyl chloride (PVC) is one of the most commonly used plastics. The treatment and recycling of PVC waste is still challenging, due to its non-biodegradability, low thermal stability, high Cl content and low product value. In this study, a one-pot method was developed to upcycle PVC into valuable carbon materials, pipeline-quality pyrolysis gas and chlorides. The well-designed process included dechlorination by Cl-fixative (ZnO or KOH), carbonization of dechlorinated polyenes, and modification of carbon materials in sequence. ZnO and KOH converted 84.48% and 94.15% of total Cl into corresponding chlorides, respectively. CH4 and H2 accounted for 81.87-99.34 vol% of pyrolysis gas with higher heat values of 30.11-32.84 MJ m-3, which can be used as substitute natural gas. As high as 83.13% of the C element was converted into carbon materials. The morphology, structure and property of carbon materials can be modified by different Cl-fixatives. Millimeter-scale carbon spheres with mono-dispersity and porous carbon with a high specific surface area of 1922 m2 g-1 were obtained when ZnO and KOH were added, respectively. Moreover, the reaction mechanisms of PVC with Cl-fixatives were also deciphered through thermogravimetric analysis and thermodynamic simulation.

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