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1.
Cancer Lett ; 529: 53-69, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34979166

RESUMO

Dynamic miRNA alteration is known to occur in colitis-associated colon cancer (CAC), while the molecular mechanisms underpinning how miRNAs modulate the development from chronic inflammation to CAC is lacking. For the first time, we constructed knockout (KO) mice for individual miR-148/152 family members and entire miR-148/152 family. Based on these KO mice, we conduct the first comprehensive analysis of miR-148/152 family, demonstrating that deficiency of any member of miR-148/152 family aggravate colitis and CAC. Loss of individual miR-148/152 family members or full-family enhance MMP10 and MMP13 expression, causing disruption of intestinal barrier and cleaving pro-TNF-α into bioactive TNF-α fragments to activate NF-κB signaling, thereby aggravating colitis. Individual and full-family deletion also increase accumulation of IKKα and IKKß, resulting in further hyperactivation of NF-κB signaling, exacerbating colitis and CAC. Moreover, blocking NF-κB signaling exerts a restorative effect on colitis and CAC models only in KO mice. Taken together, these findings demonstrate deleting the full miR-148/152 family or individual members exhibit similar effects in colitis and CAC. Mechanically, miR-148/152 family members deficiency in mice elevates MMP10 and MMP13 to accelerate colitis and CAC via disrupting intestinal barrier function and activating NF-κB signaling, suggesting a potential therapeutic strategy for colitis and CAC.

2.
Behav Brain Res ; 416: 113535, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34416301

RESUMO

Reboxetine, the first selective norepinephrine (NA) reuptake inhibitor used in the treatment of depression, mainly acts by binding to the NA transporter and blocking reuptake of extracellular NA. Recently, some other pharmacological targets beyond the NA transporter are being demonstrated for reboxetine. Peroxisome proliferator activated receptor α (PPARα) is a member of the nuclear hormone receptor family of ligand-dependent transcription factors. Previous reports have demonstrated the role of hippocampal PPARα in the pathophysiology of depression. Here we assume that hippocampal PPARα may participate in the antidepressant mechanism of reboxetine. Therefore, the chronic social defeat stress (CSDS) model of depression, various behavioral tests, the western blotting and adenovirus associated virus (AAV)-mediated genetic knockdown methods were used together in the present study. Our results showed that repeated reboxetine treatment markedly restored the decreasing effects of CSDS on the expression of hippocampal PPARα, brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element binding protein (pCREB). Pharmacological blockade of PPARα notably prevented the antidepressant-like effects of reboxetine in the CSDS model. Furthermore, genetic knockdown of hippocampal PPARα also fully abolished the antidepressant-like effects of reboxetine in the CSDS model. Taken together, promoting the hippocampal PPARα expression participates in the antidepressant mechanism of reboxetine.

4.
Urol Int ; : 1-5, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34515252

RESUMO

OBJECTIVES: This study aimed to describe a novel double-sheath vacuum suction minimally invasive percutaneous nephrolithotomy (mini-PCNL) to overcome the deficiencies of the conventional procedure. PATIENTS AND METHODS: Between March 2019 and December 2019, 65 patients (37 males and 28 females) with a mean age of 41 years (range 23-69) underwent mini-PCNL with double-sheath vacuum suction. It consisted of an F20 Y-shaped sheath as an outer sheath and an F16 Y-shaped sheath as an inner sheath, in which the inner sheath was longer than the outer sheath. The oblique arm of the outer sheath and the inner sheath was connected to the perfusion inflow and the vacuum suction, respectively. A 550-µm holmium-YAG laser was introduced for stone fragmentation through the working channel of the mini-nephroscope, which was no longer connected to the perfusion fluid. RESULTS: All procedures were successful. Mean operation time was 50.2 min (range 39-83). Mean hemoglobin decrease was 5.2 g/L (range 1.0-15.5), and no patient needed a blood transfusion. One patient (1.5%) with low fever (<38°C) at day 1 had returned to normal at day 2 without administration of antibiotics. There were no Clavien grade 2-4 complications. Mean postoperative hospital stay was 2.4 days (range 2-6). The initial stone-free rate of PCNL was 81.53% (53 of 65 patients). One month after surgery, the final stone-free rate increased to 90.77% (59/65 patients). CONCLUSIONS: The double-sheath vacuum suction mini-PCNL is a safe and effective modality for large renal stones, which might increase the efficiency of stone extraction with low intrapelvic pressure.

5.
J Mol Biol ; 433(21): 167229, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34487791

RESUMO

Although RNA-binding proteins (RBPs) are known to be enriched in intrinsic disorder, no previous analysis focused on RBPs interacting with specific RNA types. We fill this gap with a comprehensive analysis of the putative disorder in RBPs binding to six common RNA types: messenger RNA (mRNA), transfer RNA (tRNA), small nuclear RNA (snRNA), non-coding RNA (ncRNA), ribosomal RNA (rRNA), and internal ribosome RNA (irRNA). We also analyze the amount of putative intrinsic disorder in the RNA-binding domains (RBDs) and non-RNA-binding-domain regions (non-RBD regions). Consistent with previous studies, we show that in comparison with human proteome, RBPs are significantly enriched in disorder. However, closer examination finds significant enrichment in predicted disorder for the mRNA-, rRNA- and snRNA-binding proteins, while the proteins that interact with ncRNA and irRNA are not enriched in disorder, and the tRNA-binding proteins are significantly depleted in disorder. We show a consistent pattern of significant disorder enrichment in the non-RBD regions coupled with low levels of disorder in RBDs, which suggests that disorder is relatively rarely utilized in the RNA-binding regions. Our analysis of the non-RBD regions suggests that disorder harbors posttranslational modification sites and is involved in the putative interactions with DNA. Importantly, we utilize experimental data from DisProt and independent data from Pfam to validate the above observations that rely on the disorder predictions. This study provides new insights into the distribution of disorder across proteins that bind different RNA types and the functional role of disorder in the regions where it is enriched.


Assuntos
Proteínas Intrinsicamente Desordenadas/química , RNA Mensageiro/química , RNA Ribossômico/química , RNA Nuclear Pequeno/química , RNA de Transferência/química , RNA não Traduzido/química , Proteínas de Ligação a RNA/química , Acetilação , Sítios de Ligação , Expressão Gênica , Humanos , Proteínas Intrinsicamente Desordenadas/genética , Proteínas Intrinsicamente Desordenadas/metabolismo , Metilação , Fosforilação , Ligação Proteica , Processamento de Proteína Pós-Traducional , Proteoma/genética , Proteoma/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Ribossômico/genética , RNA Ribossômico/metabolismo , RNA Nuclear Pequeno/genética , RNA Nuclear Pequeno/metabolismo , RNA de Transferência/genética , RNA de Transferência/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Ubiquitinação
6.
Mater Horiz ; 8(10): 2823-2833, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34486636

RESUMO

Whilst applying a coating layer to a polymer film is a routine approach to enhance the gas barrier properties of the film, it is counter-intuitive to consider that the gas barrier performance of the film would improve by ageing the coating dispersion for weeks before application. Herein, we report that the oxygen barrier performance of a 12 µm PET film coated with a dispersion of inorganic nanosheets in polyvinyl alcohol can be significantly enhanced by ageing this coating dispersion for up to 8 weeks before application. We found up to a 37-fold decrease in the oxygen transmission rate (OTR) of the PET coated film using aged dispersions of [Mg0.66Al0.33(OH)2](NO3)0.33 layered double hydroxide nanosheets (Mg2Al-LDH NS) in polyvinyl alcohol (PVA) compared to the film coated with an equivalent freshly prepared LDH/PVA dispersion. A limiting OTR value of 0.31 cc m-2 day-1 was achieved using the PET film coated with a 3 week aged LDH NS/PVA dispersion. X-ray diffraction experiments show that the degree of in plane alignment of LDH NS on the PET film surface increased significantly from 70.6 ± 0.6 to 86.7 ± 0.6 (%) (100% represents complete alignment of LDH NS platelets on the film surface) for the 4 week aged dispersion compared to the freshly prepared layer. We postulate that when the Mg2Al-LDH NS are aged in PVA the coiled PVA aggregates start to unwrap and attach onto the Mg2Al-LDH NS through hydrogen bonding and eventually form a hydrogen bonded ordered network that facilitates the alignment of nanosheet dispersions during the coating process. Our results suggest that the ageing of inorganic nanosheet dispersions in PVA or other potential hydrogen bonding adhesive systems could be a general approach to improve the alignment of the nanosheets on the polymer film surface once applied and thus improve their performance characteristics for barrier coating applications.

8.
Nat Commun ; 12(1): 4438, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290238

RESUMO

Identification of intrinsic disorder in proteins relies in large part on computational predictors, which demands that their accuracy should be high. Since intrinsic disorder carries out a broad range of cellular functions, it is desirable to couple the disorder and disorder function predictions. We report a computational tool, flDPnn, that provides accurate, fast and comprehensive disorder and disorder function predictions from protein sequences. The recent Critical Assessment of protein Intrinsic Disorder prediction (CAID) experiment and results on other test datasets demonstrate that flDPnn offers accurate predictions of disorder, fully disordered proteins and four common disorder functions. These predictions are substantially better than the results of the existing disorder predictors and methods that predict functions of disorder. Ablation tests reveal that the high predictive performance stems from innovative ways used in flDPnn to derive sequence profiles and encode inputs. flDPnn's webserver is available at http://biomine.cs.vcu.edu/servers/flDPnn/.


Assuntos
Biologia Computacional/métodos , Proteínas Intrinsicamente Desordenadas/química , Proteínas Intrinsicamente Desordenadas/metabolismo , Aprendizado de Máquina , Ligação Proteica , Análise de Sequência de Proteína
9.
Environ Sci Pollut Res Int ; 28(44): 62549-62561, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34212323

RESUMO

Tetracyclines are frequently detected in water bodies due to their widespread use in aquaculture and animal husbandry. A hydroponic experiment was conducted to explore the phytotoxic effects of Vallisneria natans (Lour.) Hare exposed to various concentrations of chlortetracycline (CTC) and oxytetracycline (OTC) (0, 0.1, 1, 10, 30, 50, and 100 mg/L) for 7 days (7 D) and 14 days (14 D), respectively. The results showed that similar to OTC treatment for 7 D, the relative growth rates (RGR) and catalase (CAT) activity of V. natans, after 7 D of CTC exposure, decreased significantly at 10 mg/L and 30 mg/L, respectively. The content of soluble protein notably decreased when CTC ≥ 10 mg/L and OTC ≥ 30 mg/L. The hydrogen peroxide (H2O2) content was significantly stimulated when OTC ≥ 10 mg/L, while it hardly changed when exposed to CTC. After 14 D, the malondialdehyde (MDA) and H2O2 contents of V. natans were significantly higher than those of the control group under a high concentration of OTC (≥ 30 mg/L), but they did not change significantly under a high concentration of CTC. The activity of polyphenol oxidase (PPO), under CTC treatment after 14 D, showed first a significant increase then decreases; the maximum value (125% of the control) was noticed at 10 mg/L CTC, while it remained unchanged when exposed to OTC. The soluble protein content significantly decreased at 10 mg/L CTC and 0.1 mg/L OTC, respectively. The RGR, CAT, and peroxidase (POD) activities, similar to OTC treatment after 14 D, decreased evidently when CTC was 10 mg/L, 30 mg/L, and 0.1 mg/L, respectively. CTC and OTC harm the chlorophyll content of V. natans after 14 D, and the reductions of chlorophyll a and carotenoid were more pronounced than chlorophyll b. The results suggest that CTC and OTC both have a negative effect on the growth of V. natans, and OTC can cause oxidative damage in V. natans but CTC harms the metabolism process without inducing oxidative damage. Overall, the toxicity of OTC to V. natans is stronger than that of CTC.


Assuntos
Clortetraciclina , Lebres , Oxitetraciclina , Animais , Clorofila A , Clortetraciclina/toxicidade , Peróxido de Hidrogênio , Oxitetraciclina/toxicidade
10.
Environ Sci Pollut Res Int ; 28(43): 61115-61127, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34169418

RESUMO

The synthetic organic surfactants linear alkylbenzene sulfonate (LAS) and polycyclic aromatic hydrocarbon naphthalene (NAP), two common organic pollutants, are frequently detected in freshwater environments. However, the combined ecotoxicological risks associated with these pollutants have not been fully elucidated. The present study investigated the effects of individual and combined treatments of LAS and NAP on the growth and physiological responses of Spirodela polyrrhiza. The results showed that LAS was the main compound toxic to S. polyrrhiza in a dose-dependent manner. The peroxidase (POD) enzyme and catalase (CAT) enzyme are the main antioxidant enzymes protecting S. polyrrhiza from LAS stress. When exposed to NAP stress alone, only slightly reversible damage was observed as the exposure time was extended (14 days). The antioxidant enzyme systems (including superoxide dismutase (SOD), CAT and POD) showed positive responses. Synergistic effects were induced with LAS-NAP mixtures (≥ 5 + 5 mg L-1), and LAS played a major toxic role. The POD enzyme was a sensitive protective enzyme in duckweed during the joint exposure to LAS + NAP. The results indicate that LAS or NAP may cause serious damage to S. polyrrhiza and aggravate ecotoxicity in aquatic ecosystems.


Assuntos
Antioxidantes , Araceae , Ácidos Alcanossulfônicos , Ecossistema , Naftalenos
11.
Theranostics ; 11(15): 7337-7359, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34158854

RESUMO

Background: Hypoxia is a hallmark of the physical microenvironment of solid tumors. As a key factor that regulates tumor development and progression, hypoxia can reprogram the expression of multiple genes, whose biological function and molecular mechanism in cancer remain largely unclear. The mitochondrial ribosome protein family consists of nuclear-encoded mitochondrial proteins that are responsible for protein synthesis in the mitochondria. Methods: A high-throughput RNA sequencing assay was carried out to identify differentially expressed mRNAs between breast cancer tissues and adjacent normal tissues as well as breast tumors with metastasis and those without metastasis. Our clinical samples and TCGA database were analyzed to observe the clinical value of mitochondrial ribosome protein L52 (MRPL52) in human breast cancer. Potent hypoxia response elements in the promoter region of MRPL52 were identified and validated by chromatin immunoprecipitation and luciferase reporter assays. Functional experiments were performed using breast cancer cell lines with MRPL52 ectopic expression and knockdown cultured in a 20% or 1% O2 environment. Results: MRPL52 expression was upregulated in human breast cancer and was significantly associated with aggressive clinicopathological characteristics and a higher metastatic risk of breast cancer patients. We found that the overexpression of MRPL52 in breast cancer is induced by hypoxia-inducible factor-1 in response to hypoxic exposure. The role of MRPL52 in suppressing apoptosis and promoting migration and invasion of hypoxic breast cancer cells was demonstrated by our experimental evidence. Mechanistically, MRPL52 promoted PTEN-induced putative kinase 1 /Parkin-dependent mitophagy to remove oxidatively damaged mitochondria and prevent uncontrolled reactive oxygen species (ROS) generation, thus repressing activation of the mitochondrial apoptotic cascade. Additionally, MRPL52 augmented epithelial-mesenchymal transition, migration and invasion of hypoxic breast cancer cells by activating the ROS-Notch1-Snail signaling pathway. Benefited from this bidirectional regulatory mechanism, MRPL52 is responsible for maintaining ROS levels in a window that can induce tumorigenic signal transduction without causing cytotoxicity in hypoxic breast cancer cells. Conclusions: This work elucidates the molecular mechanism by which MRPL52 mediates hypoxia-induced apoptotic resistance and metastatic initiation of breast cancer, and provides new insights into the interplay between cancer and the tumor microenvironment.


Assuntos
Adaptação Fisiológica , Neoplasias da Mama/metabolismo , Fator 1 Induzível por Hipóxia/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Ribossômicas/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Hipóxia Celular/genética , Feminino , Humanos , Fator 1 Induzível por Hipóxia/genética , Células MCF-7 , Proteínas Mitocondriais/genética , Proteínas de Neoplasias/genética , Proteínas Ribossômicas/genética
12.
World J Urol ; 39(11): 4255-4260, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34032912

RESUMO

PURPOSE: To compare double-sheath vacuum suction minimally invasive percutaneous nephrolithotomy (DS-mini-PCNL) with vacuum-assisted mini-PCNL (VS-mini-PCNL) and to better define the potential benefits of DS-mini-PCNL. METHODS: Between July 2019 and May 2020, 117 patients with large radiopaque renal stones underwent mini-PCNL. Of these, 63 underwent DS-mini-PCNL and 54 underwent VS-mini-PCNL. For VS-mini-PCNL, a F20 Y-shaped sheath was used and the oblique arm of the sheath was connected to the vacuum suction. For DS-mini-PCNL, the oblique arm of a F20 Y-shaped sheath (the outer sheath) and a F16 Y-shaped sheath (the inner sheath) was connected to the perfusion inflow and the vacuum suction, respectively. A 550-µm holmium-YAG laser was used for stone fragmentation. RESULTS: Compared with VS-mini-PCNL group, DS-mini-PCNL group had significantly shorter operative time (35.78 ± 7.77 min vs. 44.56 ± 13.19 min; P = 0.000) and significantly lower fever rate (1.6% vs. 11.1%; P = 0.048). It was not significantly different between the two groups despite the higher initial stone-free rate seen for DS-mini-PCNL group relative to VS-mini-PCNL group (87.7% vs. 81.5%, P = 0.346). Auxiliary procedure rates were 4.8% (three patients) in DS-mini-PCNL group and 16.7% (nine patients) in VS-mini-PCNL group, with a significant difference (P = 0.034). The difference in the final stone-free rate between the two groups was rendered insignificant (93.8% vs. 89.1%, P = 0.510). CONCLUSIONS: DS-mini-PCNL is a safe and effective modality for large renal stones, which could increase the efficiency of stone extraction and decrease infectious complications compared with VS-mini-PCNL.

13.
J Phys Chem Lett ; 12(19): 4484-4489, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-33956459

RESUMO

Understanding the self-assembly mechanisms of amphiphilic molecules in solutions and regulating their phase behaviors are of primary significance for their applications. To challenge the reported direct phase transitions from nonlamellar to ordered lamellar phases, the self-assembly and phase behavior of the 1-hexadecyl-3-methylimidazolium chloride aqueous dispersions were studied using a strategy of isothermal incubation after the temperature jump. A disordered lamellar phase (identified as the lamellar liquid-crystal (Lα) phase), serving as an intermediate, was found to bridge the transition from a spherical micellar (M) phase to a lamellar-gel (Lß) phase. Meanwhile, the nonsynchronicity in the tail and headgroup regions of the ionic liquid surfactant during the transition process was also unveiled, with the former being prior to the latter. The in-depth understanding of the self-assembly mechanisms may help push forward the related applications in the future.

14.
Front Oncol ; 11: 630706, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968730

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney tumor worldwide. Analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases showed that the immune-related gene (IRG) hematopoietic cell signal transducer (HCST) could provide guidance for the diagnosis, prognosis, and treatment of ccRCC. The RNA-seq data of ccRCC tissues were extracted from two databases: TCGA (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga) and GEO (https://www.ncbi.nlm.nih.gov/geo/). Corresponding clinical information was downloaded from TCGA. Immune-related gene data were extracted from the IMMPORT website (https://www.immport.org/). Differential analysis with R software (https://www.r-project.org/) was used to obtain a prognosis model of ccRCC IRGs. The differences were combined with the clinical data to assess the usefulness of the HCST as a prognostic biomarker. Based on data obtained from the Oncomine (https://www.oncomine.org/), Human Protein Atlas (https://www.proteinatlas.org/), and PubMed (https://pubmed.ncbi.nlm.nih.gov/) databases, the expression levels of the HCST in ccRCC, clinical-pathological indicators of relevance, and influence on prognosis were analyzed. Regulation of the HCST gene in ccRCC was assessed by gene set enrichment analysis (GSEA). In TCGA/GEO databases, the high HCST expression in tumor tissues was significantly correlated to the TMN stage, tumor grade, invasion depth, and lymphatic metastasis (p < 0.05). The overall survival (OS) of patients with high HCST gene expression was significantly lower than that of patients with low HCST gene expression (p < 0.001). Multivariate Cox regression analysis suggested that the HCST expression level [hazard ratio (HR) = 1.630, 95% confidence interval (CI) = 1.042-2.552], tumor cell grade (HR = 1.829, 95% CI = 1.115-3.001), and distant metastasis (HR = 2.634, 95%, CI = 1.562-4.442) were independent risk factors affecting the OS of ccRCC patients (all, p < 0.05). The GSEA study showed that there was significant enrichment in cell adhesion, tumorigenesis, and immune and inflammatory responses in HCST high expression samples. Hematopoietic cell signal transducer expression was closely associated with the levels of infiltrating immune cells around ccRCC tissues, especially dendritic cells (DCs). In conclusion, the present study suggested that the HCST was interrelated to the clinicopathology and poor prognosis of ccRCC. High HCST expression was also closely correlated with the levels of tumor-infiltrating immune cells, especially DCs.

15.
Comput Struct Biotechnol J ; 19: 2597-2606, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34025946

RESUMO

A recent advance in the disorder prediction field is the development of the quality assessment (QA) scores. QA scores complement the propensities produced by the disorder predictors by identifying regions where these predictions are more likely to be correct. We develop, empirically test and release a new QA tool, QUARTERplus, that addresses several key drawbacks of the current QA method, QUARTER. QUARTERplus is the first solution that utilizes QA scores and the associated input disorder predictions to produce very accurate disorder predictions with the help of a modern deep learning meta-model. The deep neural network utilizes the QA scores to identify and fix the regions where the original/input disorder predictions are poor. More importantly, the accurate QUATERplus's predictions are accompanied by easy to interpret residue-level QA scores that reliably quantify their residue-level predictive quality. We provide these interpretable QA scores for QUARTERplus and 10 other popular disorder predictors. Empirical tests on a large and independent (low similarity) test dataset show that QUARTERplus predictions secure AUC = 0.93 and are statistically more accurate than the results of twelve state-of-the-art disorder predictors. We also demonstrate that the new QA scores produced by QUARTERplus are highly correlated with the actual predictive quality and that they can be effectively used to identify regions of correct disorder predictions. This feature empowers the users to easily identify which parts of the predictions generated by the modern disorder predictors are more trustworthy. QUARTERplus is available as a convenient webserver at http://biomine.cs.vcu.edu/servers/QUARTERplus/.

17.
J Tradit Chin Med ; 41(2): 194-202, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33825398

RESUMO

OBJECTIVE: To investigate the efficacy of an herbal formula of Bushen Jianpi ( BSJP) combined with sorafenib on hepatocellular carcinoma (HCC) in vitro and in vivo, and to study the underlying mechanisms of action. METHODS: BSJP, a mixture of 12 raw herbs, was extracted in 70% alcohol/30% water and freeze-dried into a powder. The in vitro effects of BSJP alone, sorafenib alone, and their combination on cell survival, apoptosis, and cell cycle distribution were evaluated in HCC cell lines HCCLM3, HepG2, and SMMC-7721. The expression of B-cell lymphoma-2 (Bcl-2), caspase-3, and caspase-9 in HCCLM3 cells was measured using Western blots after drug administration. The in vivo effects of BSJP and sorafenib were evaluated in a tumor surgical resection model using 4-week old male athymic BALB/c nude mice injected with HCCLM3 cells. Immunohistochemical analysis of tumor tissues was performed to evaluate the effects of BSJP alone, sorafenib alone, and their combination on the expression of caspase-3, caspase-9, and Bcl-2. RESULTS: BSJP decreased the survival rate of HCC cell lines, and the combination of BSJP and sorafenib further decreased the survival rate. BSJP significantly promoted cell apoptosis and blocked cell-cycle progression in HCCLM3, HepG2, and SMMC-7721 cells in a dose-dependent manner. Furthermore, the administration of BSJP and sorafenib inhibited the growth of HCCLM3 cell xenografts in nude mice, with no reduction in body weight. In vivo and in vitro experiments showed that BSJP combined with sorafenib could significantly decrease the expression of Bcl-2. CONCLUSION: Our findings suggest that the herbal formula of BSJP is a potential HCC antitumor agent.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/fisiopatologia , Medicamentos de Ervas Chinesas/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/fisiopatologia , Sorafenibe/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quimioterapia Combinada , Humanos , Masculino , Camundongos Endogâmicos BALB C
18.
Chin Med J (Engl) ; 134(11): 1345-1355, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33883408

RESUMO

BACKGROUND: Although increasing abnormal expression of circular RNAs (circRNAs) has been revealed in various cancers, there were a small number of studies about circRNAs in gastric cancer (GC). Here, we explored the expression and function of a novel circRNA, circ_0049447, in GC. METHODS: A total of 80 GC tissues and non-tumorous tissues were collected from the First Affiliated Hospital of China Medical University. And all cells were cultured with 10% fetal bovine serum and incubated at 37°C and 5% CO2. The expression of circ_0049447 was quantified by real-time polymerase chain reaction. The biological function of circ_0049447 on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) was evaluated by cell counting kit-8 (CCK-8), colony formation assay, transwell migration and invasion assay, and Western blotting. Luciferase report assay was used to verify the direct binding between circ_0049447 and predicted microRNA (miRNA). Furthermore, a xenograft mouse model was used to validate the function of circ_0049447 in vivo. RESULTS: We demonstrated that circ_0049447 was downregulated in GC (P < 0.001). The area under the receiver operating characteristic curve reached 0.838, while sensitivity was 82.3% and specificity was 77.2%. CCK-8 and colony formation assay showed that overexpression of circ_0049447 could inhibit the proliferation (P < 0.05). Transwell migration and invasion assay showed upregulated circ_0049447 could impede migration in GC cells (P < 0.05). In addition, overexpression of circ_0049447 could impede GC cell EMT. Upregulation of miR-324-5p in GC specimens and direct binding between miR-324-5p with circ_0049447 proven by luciferase reporter assay indicated that circ_0049447 may inhibit GC by sponging certain miRNA. CONCLUSION: Circ_0049447 acts as a tumor suppressor in GC through reducing proliferation, migration, invasion, and EMT, and it is a promising biomarker for diagnosis.


Assuntos
Neoplasias Gástricas , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , China , Transição Epitelial-Mesenquimal/genética , Camundongos , Neoplasias Gástricas/genética
19.
Prostate ; 81(9): 530-542, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33861464

RESUMO

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease in elderly men and is often accompanied by chronic inflammation. Macrophages (several subtypes) are the main inflammatory cells that infiltrate the hyperplastic prostate and are found to secrete cytokines and growth factors. The current study aims to explore the effect of M2a macrophages on the development of BPH via insulin-like growth factor 1 (IGF-1). METHODS: Human prostate tissues, prostate, and monocyte cell lines (WPMY-1, BPH-1, and THP-1) were used. THP-1 was polarized into several subtypes with cytokines. The expression and localization of IGF-1 and M2 macrophages were determined via immunofluorescent staining, quantitative real-time polymerase chain reaction, and Western blot analysis. Flow cytometry and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were used to investigate the effects of different subtypes of macrophages on prostate cells. IGF-1 in WPMY-1 and BPH-1 cells was silenced and cocultured with or without M2a macrophages. Cell proliferation, apoptosis, cell cycle, epithelial-mesenchymal transition (EMT), and fibrosis processes were examined. RESULTS: The polarized subtypes of macrophages were verified by amplifying their specific markers. M2a macrophages enhanced prostate cell proliferation more significantly and CD206 was more expressed in hyperplastic prostate. IGF-1 was localized in both epithelial and stromal components of prostate and upregulated in BPH tissues. M2a macrophages expressed more IGF-1 than other subtypes. Knockdown of IGF-1 in WPMY-1 and BPH-1 cells attenuated cell proliferation, promoted cell apoptosis, retarded cell cycle at the G0/G1 phase, and suppressed the EMT process in BPH-1 cells as well as the fibrotic process in WPMY-1 cells, which was reversible when cocultured with M2a macrophages. CONCLUSION: These data demonstrated that knockdown of IGF-1 expression in cultured BPH epithelial and stromal cells reduces proliferation and increases apoptosis. These effects are reversed by coculture with M2a macrophages.

20.
ISA Trans ; 116: 30-45, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33563465

RESUMO

An integrated control scheme composed of modified nonlinear disturbance observer and predefined-time prescribed performance control is proposed to address the high-accuracy tracking problem of the unmanned aerial vehicles (UAVs) subjected to external mismatched disturbances. By utilizing the transformation technique that incorporates the desired performance characteristic and the newly predefined-time performance function, the original controlled system can be transformed into a new unconstrained one to achieve the fixed-time convergence of the tracking error. Then, by virtual of the transformed unconstrained system, a modified nonlinear disturbance observer (NDO) which possesses fast convergence speed is established to estimate the external disturbance. With the application of the precise estimation value to compensate the normal control design in each back-stepping step, a novel composite control scheme is constructed. The light spot of the proposed scheme is that it not only has the superior capability to attenuate unknown mismatched disturbances, but also can guarantee that the output tracking errors converge to their prescribed regions within predefined time. Finally, simulation studies verify the effectiveness of the proposed control scheme.

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