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1.
Sensors (Basel) ; 24(11)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38894435

RESUMO

This article proposes a distributed intelligent Coordinated Multi-Point Non-Orthogonal Multiple-Access (CoMP-NOMA) collaborative transmission model with the assistance of reconfigurable intelligent surfaces (RISs) to address the issues of poor communication quality, low fairness, and high system power consumption for edge users in multi-cellular networks. By analyzing the interaction mechanisms and influencing factors among RIS signal enhancement, NOMA user scheduling, and multi-point collaborative transmission, the model establishes RIS-enhanced edge user grouping and coordinates NOMA user clusters based on this. In the multi-cell RIS-assisted JT-CoMP NOMA downlink transmission, joint optimization of the power allocation (PA), user clustering (UC), and RIS phase-shift matrix design (PS) poses a challenging Mixed-Integer Non-Linear Programming (MINLP) problem. The original problem is decomposed by optimizing the formulas into joint sub-problems of PA, UC, and PA and PS, and solved using an alternating optimization approach. Simulation results demonstrate that the proposed scheme effectively reduces the system's power consumption while significantly improving the system's throughput and rates.

2.
Transl Androl Urol ; 13(5): 699-707, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38855609

RESUMO

Background: Although ureteral stents are a well-established and commonly used method for renal drainage, the ureteral stent-related symptoms (SRSs) they cause in patients cannot be ignored. It is currently unclear whether mirabegron has a place in the treatment of SRSs. Our study aims to systematically evaluate the efficacy and safety of mirabegron in treating SRSs in adult patients. Methods: Through a systematical search of multiple scientific databases before August 2023, we performed a systematic review and meta-analysis of the primary outcomes of interest according to the PRISMA. Analysis was performed under multivariate random-effects network models and effects of drugs was ranked with surface under the cumulative ranking curves (SUCRA) probabilities. Results: Sixteen studies involving 2,002 patients were included. All regimens (including mirabegron, solifenacin, and tamsulosin) were significantly better than placebo in urinary symptoms. Solifenacin was associated with more adverse drug events than mirabegron and tamsulosin. The SUCRA values showed that mirabegron was the best in the outcomes of body pain (71.5%), sexual matters (76.4%), and adverse events (70.5%). Solifenacin was the best in the outcomes of urinary symptoms (73.1%), general health (81.0%), and work performance (85.1%). Tamsulosin had the lowest rate of all outcomes. Conclusions: Compared with traditional drugs for relieving SRSs, mirabegron performs best in terms of alleviating body pain, sexual matters, and adverse events, with little difference in urinary symptoms and general health. Further high-quality prospective double-blinded randomized controlled trials (RCTs) are required to provide sufficient evidence supporting our observations.

3.
Exp Ther Med ; 27(4): 150, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38476922

RESUMO

Current cancer treatments target tumor cells; however, the tumor microenvironment (TME) induces therapeutic resistance, tumor development and metastasis, thus rendering these treatments ineffective. Research on the TME has therefore concentrated on nonmalignant cells. Cancer-associated fibroblasts (CAFs) are a major TME component, which contribute to cancer progression due to their diverse origins, phenotypes and functions, including cancer cell invasion and migration, extracellular matrix remodeling, tumor metabolism modulation and therapeutic resistance. Standard cancer treatment typically exacerbates the senescence-associated secretory phenotype (SASP) of senescent cancer cells and nonmalignant cells that actively leak proinflammatory signals in the TME. Therapy-induced senescence may impair cancer cell activity and compromise treatment responsiveness. CAFs and SASP are well-studied in the formation and progression of cancer. The present review discusses the current data on CAF senescence caused by anticancer treatment and assesses how senescence-like CAFs affect tumor formation. The development of senolytic medication for aging stromal cells is also highlighted. Combining cancer therapies with senolytics may boost therapeutic effects and provide novel possibilities for research.

4.
Front Neurol ; 14: 1292260, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38053796

RESUMO

Background: In critically ill patients, transcutaneous oxygen saturation (SpO2) upon admission is typically associated with in-hospital mortality. Nevertheless, the available information for patients with non-traumatic subarachnoid hemorrhage (SAH) is limited. In our study, our objective was to assess the correlation between SpO2 levels and mortality among patients diagnosed with severe SAH. Methods: In this study, we extracted data from the Medical Information Marketplace in Intensive Care (MIMIC-IV) database, which comprises information on critically ill patients. By employing matching ICD-9 and ICD-10 codes, we identified 3,328 patients diagnosed with SAH. Every individual who was admitted to the intensive care unit (ICU) had their SpO2 data and various covariates, including age, sex, diagnosis, and duration of stay, recorded upon admission. Subsequently, the patients were categorized into three distinct groups according to their SpO2 levels: low (≤95%), moderate (95-98%), and high (≥98%). To investigate the association between percutaneous oxygen saturation and mortality in patients with severe SAH, logistic regression, and cubic spline models were utilized. The main outcomes of interest were 28- and 90-day mortality rates. Additionally, subgroup analyses were conducted to evaluate these correlations and assess the consistency of interactions. Results: A cohort of 864 patients diagnosed with non-traumatic SAH was included in this study. The correlation between SpO2 and mortality displayed a U-shaped curve when utilizing a finite cubic spline function (non-linearity < 0.001), with the nadir in the probability of in-hospital death at 96%. Mortality at 28 and 90 days showed an inverse correlation with SpO2 < 96% (adjusted odds ratio [OR], 0.8; 95% confidence interval [CI], 0.67-0.95, and 0.76; 95% CI, 0.6-0.96). Conversely, there was a positive correlation between percutaneous oxygen saturation (SpO2) levels of ≥96% and mortality rates at both 28 and 90 days (adjusted OR, 1.17; 95% CI, 1.02-1.35 and 1.2; 95% CI, 1.05-1.39). Conclusion: In patients with severe subarachnoid hemorrhage, the association between SpO2 and mortality at 28 and 90 days demonstrated a U-shaped pattern. When SpO2 levels were between 95 and 98%, both short- and long-term mortality rates were at their lowest. Patients with significant subarachnoid hemorrhage had a lower chance of survival when their SpO2 values were either high or low.

5.
Front Neurol ; 14: 1234080, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37780696

RESUMO

Objective: The study aimed to evaluate the relationship between serum sodium and mortality in critically ill patients with non-traumatic subarachnoid hemorrhage. Methods: This is a retrospective investigation of critically ill non-traumatic patients with subarachnoid hemorrhage (SAH) utilizing the MIMIC-IV database. We collected the serum sodium levels at admission and determined the all-cause death rates for the ICU and hospital. We employed a multivariate Cox proportional hazard regression model and Kaplan-Meier survival curve analysis to ascertain the relationship between serum sodium and all-cause mortality. In order to evaluate the consistency of correlations, interaction and subgroup analyses were also conducted. Results: A total of 864 patients with non-traumatic SAH were included in this study. All-cause mortality in the ICU and hospital was 32.6% (282/864) and 19.2% (166/864), respectively. Sodium levels at ICU admission showed a statistically significant J-shaped non-linear relationship with ICU and hospital mortality (non-linear P-value < 0.05, total P-value < 0.001) with an inflection point of ~141 mmol/L, suggesting that mortality was higher than normal serum sodium levels in hypernatremic patients. Multivariate analysis after adjusting for potential confounders showed that high serum sodium levels (≥145 mmol/L) were associated with an increased risk of all-cause mortality in the ICU and hospital compared with normal serum sodium levels (135-145 mmol/L), [hazard ratio (HR) = 1.47, 95% CI: 1.07-2.01, P = 0.017] and (HR = 2.26, 95% CI:1.54-3.32, P < 0.001). Similarly, Kaplan-Meier (K-M) survival curves showed lower survival in patients with high serum sodium levels. Stratified analysis further showed that the association between higher serum sodium levels and hospital all-cause mortality was stronger in patients aged < 60 years with a hospital stay of <7 days. Conclusion: High serum sodium levels upon ICU admission are related to higher ICU and hospital all-cause mortality in patients with non-traumatic SAH. A new reference is offered for control strategies to correct serum sodium levels.

6.
Anal Biochem ; 677: 115252, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37488002

RESUMO

BACKGROUND: 11-Dehydro-thromboxane B2 (11-dehydro-TXB2) is the final stable metabolite of thromboxane A2 (TXA2) and is involved in thrombus formation. Patients with membranous nephropathy (MN) are prone to thromboembolism events. METHODS: Time-resolved fluorescence immunoassay (TRFIA) for 11-dehydro-TXB2 was established by indirect competitive method. The coated 11-dehydro-TXB2-BSA conjugate was used to bind the 11-dehydro-TXB2 antibody competitively to the 11-dehydro-TXB2 antigen in the samples, followed by Eu3+-labeled goat anti-mouse IgG antibody, to detect 11-dehydro-TXB2. This study measured 11-dehydro-TXB2 concentrations in serum samples from healthy individuals and patients with MN. RESULTS: The linear range of TRFIA was 16.38-2000 pg/mL, the sensitivity was 4.70 pg/mL, the average coefficients of variation from intra-assay and inter-assay were 3.50% and 4.95%, respectively, and the recovery was 99.38%. The serum level of 11-dehydro-TXB2 in patients with MN was significantly higher than that in healthy subjects (P < 0.05). The serum 11-dehydro-TXB2 concentration detected by TRFIA was highly consistent with that by ELISA (ρ = 0.900). DISCUSSION: This study successfully established a new highly sensitive method for the detection of 11-dehydro-TXB2 in serum. 11-Dehydro-TXB2 has great potential in evaluating the risk of thromboembolic events in patients with MN and is expected to be applied to other thromboembolic-related diseases.


Assuntos
Glomerulonefrite Membranosa , Humanos , Glomerulonefrite Membranosa/diagnóstico , Tromboxano B2/metabolismo , Ensaio de Imunoadsorção Enzimática , Anticorpos
7.
Bioresour Technol ; 385: 129394, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37369317

RESUMO

Aerobic granular sludge (AGS) has proved to be a promising biotechnology for microplastics wastewater treatment. However, polyacrylonitrile microplastics (PAN MPs), the most widely used plastic in textile materials, have not been investigated. Therefore, the effect of the neglected PAN MPs on AGS at different concentrations (1, 10, and 100 mg/L) was evaluated. The results indicated that PAN MPs with 1 and 10 mg/L concentrations had no obvious effect on granular stability and nutrient removal performance, but greatly promoted the secretion of EPS. Remarkably, the granule structure was severely damaged under 100 mg/L PAN MPs. Moreover, microbial community analysis showed that phylum Proteobacteria played a dominant role in resistance to PAN MPs. Metabolic analysis further revealed that genes related to denitrification pathway (nasA, nirK, nirS and norB) and membrane transport were significantly inhibited under PAN MPs stress. This study may provide additional information on the treatment of microplastics wastewater using AGS.


Assuntos
Microbiota , Esgotos , Esgotos/microbiologia , Microplásticos , Plásticos , Eliminação de Resíduos Líquidos , Reatores Biológicos , Aerobiose , Nitrogênio
8.
J Cardiovasc Dev Dis ; 10(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36661908

RESUMO

BACKGROUND: Transthyretin cardiac amyloidosis (ATTR) is a life-threatening, debilitating disease caused by abnormal formation and deposit of transthyretin (TTR) protein in multiple tissues, including myocardial extracellular matrix. It can be challenging to diagnose due to the myriad of presenting signs and symptoms. Additionally, numerous TTR mutations exist in certain ethnicities. Interestingly, our patient was discovered to have a very rare Gly67Ala TTR mutation typically not found in individuals of Asian descent. Recent advances in cardiovascular imaging techniques have allowed for earlier recognition and, therefore, management of this disease. Although incurable, there are now new, emerging treatments that are available for symptom control of cardiac amyloidosis, making early diagnosis vital for these patients, specifically their quality of life. CASE SUMMARY: We outline a case of a 50-year-old Asian female who was initially hospitalized for nausea and vomiting and persistent orthostatic hypotension. She underwent a multitude of laboratory and imaging tests, resulting in a diagnosis of cardiac amyloidosis, which was confirmed to be due to a rare TTR mutation via genetic testing. CONCLUSIONS: Our objective is to describe various TTR mutations, existing diagnostic imaging modalities, and available treatments, as well as highlight the importance of early screening and awareness of cardiac amyloidosis, allowing for quicker diagnosis and treatment of this disease.

9.
Molecules ; 27(13)2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35807378

RESUMO

Compound Anoectochilus roxburghii (Wall.) Lindl. (A. roxburghii) oral liquid (CAROL) is a hospital preparation of A. roxburghii and Ganoderma lucidum (G. lucidum), which have hepatoprotective effects. Eight active components (five nucleosides/nucleobases and three triterpenoid acids) in CAROL, A. roxburghii, and G. lucidum were simultaneously detected by high-performance liquid chromatography−tandem mass spectrometry (LC−MS/MS). The multiple reaction monitoring (MRM) mode was applied for the detection of analytes. These eight compounds were separated well within 12 min and quantified using the internal standard working curve method. The method showed good linearity (R2 > 0.9935) and high sensitivity (limit of detection = 0.29 ng/mL). The analyte recovery ranged from 85.07% to 97.50% (relative standard deviation < 3.31%). The content of the target analytes in four batches of CAROL, and the raw materials of G. lucidum and A. roxburghii from the five regions was determined using this method. The contents of guanosine and ganoderic acid A in four batches of oral liquid were high and stabilized and could be recommended as quality markers (Q-marker) for CAROL. Simultaneous qualitative and quantitative analysis of nucleosides and triterpenoid acids in CAROL, A. roxburghii, and G. lucidum by LC−MS/MS based on the MRM model was reported for the first time. The proposed method provides a sensitive, rapid, and reliable approach for the quality control of Chinese medicinal products.


Assuntos
Orchidaceae , Reishi , Triterpenos , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Nucleosídeos , Orchidaceae/química , Controle de Qualidade , Reishi/química , Espectrometria de Massas em Tandem/métodos , Triterpenos/química
10.
Front Chem ; 10: 879402, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464209

RESUMO

Using two-dimensional (2D) heterostructure as photocatalyst for water splitting is a popular strategy for the generation of hydrogen. In this investigation, the first-principles calculations are explored to address the electronic performances of the 2D CdO/HfS2 heterostructure formed by van der Waals (vdW) forces. The CdO/HfS2 vdW heterostructure has a 1.19 eV indirect bandgap with type-II band alignment. Importantly, the CdO/HfS2 vdW heterostructure possesses an intrinsic Z-scheme photocatalytic characteristic for water splitting by obtaining decent band edge positions. CdO donates 0.017 electrons to the HfS2 layer in the heterostructure, inducing a potential drop to further separate the photogenerated electrons and holes across the interface. The CdO/HfS2 vdW heterostructure also has excellent optical absorption capacity, showing a promising role as a photocatalyst to decompose the water.

11.
Eur J Med Chem ; 226: 113896, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34624825

RESUMO

Targeting neddylation pathway has been recognized as an attractive anticancer therapeutic strategy, thus discovering potent and selective neddylation inhibitors is highly desirable. Our work reported the discovery of novel cinnamyl piperidine compounds and their antitumor activity in vitro and in vivo. Among these compounds, compound 4g was identified as a novel neddylation inhibitor and decreased the neddylation levels of cullin 1, cullin 3 and cullin 5. Mechanistic studies demonstrated that compound 4g could inhibit the migration ability of gastric cancer cells and induce apoptosis partly mediated by the Nrf2-Keap1 pathway. Furthermore, in vivo anti-tumor studies showed that 4g effectively inhibited tumor growth without obvious toxicity. Collectively, the cinnamyl piperidine derivatives could serve as new lead compounds for developing highly effective neddylation inhibitors for gastric cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Cinamatos/farmacologia , Proteínas Culina/antagonistas & inibidores , Descoberta de Drogas , Piperidinas/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cinamatos/síntese química , Cinamatos/química , Proteínas Culina/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Piperidinas/síntese química , Piperidinas/química , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Relação Estrutura-Atividade , Células Tumorais Cultivadas
12.
J Healthc Eng ; 2021: 8605869, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34608415

RESUMO

OBJECTIVE: The study was to develop and externally validate a prognostic nomogram to effectively predict the overall survival of patients with stomach cancer. METHODS: Demographic and clinical variables of patients with stomach cancer in the Surveillance, Epidemiology, and End Results (SEER) database from 2007-2016 were retrospectively collected. Patients were then divided into the Training Group (n = 4,456) for model development and the Testing Group (n = 4,541) for external validation. Univariate and multivariate Cox regressions were used to explore prognostic factors. The concordance index (C-index) and the Kolmogorov-Smirnov (KS) value were used to measure the discrimination, and the calibration curve was used to assess the calibration of the nomogram. RESULTS: Prognostic factors including age, race, marital status, TNM stage, surgery, chemotherapy, grade, and the number of regional nodes positive were used to construct a nomogram. The C-index was 0.790 and the KS value was 0.45 for the Training Group, and the C-index was 0.789 for the Testing Group, all suggesting the good performance of the nomogram. CONCLUSION: We have developed an effective nomogram with ten easily acquired prognostic factors. The nomogram could accurately predict the overall survival of patients with stomach cancer and performed well on external validation, which would help improve the individualized survival prediction and decision-making, thereby improving the outcome and survival of stomach cancer.


Assuntos
Nomogramas , Neoplasias Gástricas , Humanos , Estadiamento de Neoplasias , Estudos Retrospectivos , Programa de SEER , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia
13.
Clin Biochem ; 96: 49-55, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34252448

RESUMO

BACKGROUND: The renal biopsy is an accurate and reliable gold standard for membranous nephropathy (MN) diagnosis. However, it is an invasive procedure involving the risk of hemorrhage or infection. Thus, an alternative approach that can facilitate the effective diagnosis and treatment monitoring of idiopathic membranous nephropathy (IMN) is urgently needed. METHODS: We established a dual-labeled time-resolved fluoroimmunoassay (TRFIA) to simultaneously detect phospholipase A2 receptor (PLA2R)-IgG4 and PLA2R-IgG antibodies. Utilizing this assay, we determined the ratio of autoantibodies in the serum of patients with different kidney diseases and normal controls. RESULTS: The sensitivity of TRFIA for detecting anti-PLA2R-IgG and anti-PLA2R-IgG4 was 0.12 µg/mL and 0.001 µg/mL, respectively. Human IgA did not interfere with the assay. Compared to anti-PLA2R-IgG alone, the positive rate of IMN could be increased from 86.5 % to 91.7 % through the combined use of anti-PLA2R-IgG4 and the PLA2R-IgG4/IgG ratio. In contrast, the false-positive rates for the detection of IgA nephropathy, lupus nephropathy, diabetic nephropathy, and minimal change nephropathy decreased from 25 to 50 % to 0 %. CONCLUSIONS: The dual-labeled PLA2R-IgG4/IgG-TRFIA for simultaneous detection of anti-PLA2R-IgG4 and anti-PLA2R-IgG will contribute to improved accuracy of IMN diagnosis.


Assuntos
Autoanticorpos/sangue , Glomerulonefrite Membranosa/sangue , Imunoglobulina G/sangue , Receptores da Fosfolipase A2/sangue , Fluorimunoensaio , Glomerulonefrite Membranosa/diagnóstico , Humanos , Sensibilidade e Especificidade
14.
Mol Med Rep ; 24(2)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34184086

RESUMO

A humanized anti­Toll­like receptor 4 (TLR4) monoclonal antibody (mAb) was previously produced using phage antibody library technology, and it was found that the mAb could effectively ameliorate lipopolysaccharide (LPS)­induced damage in macrophages. The present study investigated the protective effects exerted by the humanized anti­TLR4 mAb against LPS­induced acute kidney injury (AKI), as well as the underlying mechanisms. Female C57BL/6 mice were randomly divided into four groups (n=8 per group): i) Control; ii) LPS; iii) LPS + humanized anti­TLR4 mAb (1 µg/g); and iv) LPS + humanized anti­TLR4 mAb (10 µg/g). Serum creatinine, blood urea nitrogen, IL­6, TNFα and IL­1ß levels were then examined, followed by renal pathology assessment, immunohistochemical staining, reverse transcription­quantitative PCR and western blotting to assess apoptosis/survival/inflammation­related molecules and kidney injury molecule (KIM)­1. The humanized anti­TLR4 mAb successfully ameliorated LPS­induced AKI and renal pathological damage. The humanized anti­TLR4 mAb also dose­dependently suppressed LPS­induced elevations in serum IL­6, TNFα and IL­1ß, and decreased the renal expression levels of myeloid differentiation primary response 88 (MyD88), IKKα/ß, IκB, p65 and KIM­1. Compared with the LPS group, renal Bax and KIM­1 expression levels were significantly downregulated, and Bcl­2 expression was notably upregulated by the humanized anti­TLR4 mAb. Moreover, the humanized anti­TLR4 mAb also significantly decreased the protein expression levels of MyD88, phosphorylated (p)­IKKα/ß, p­IκB and p­p65 in the renal tissues compared with the LPS group. Therefore, the present study indicated that the anti­inflammatory effects of the humanized anti­TLR4 mAb against LPS­related AKI in mice were mediated via inhibition of the TLR4/NF­κB signaling pathway.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , NF-kappa B/antagonistas & inibidores , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Receptor 4 Toll-Like/imunologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Animais , Citocinas/sangue , Modelos Animais de Doenças , Feminino , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Proteínas I-kappa B/genética , Proteínas I-kappa B/metabolismo , Lipopolissacarídeos/toxicidade , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Proteína X Associada a bcl-2/metabolismo
15.
Pharmazie ; 76(5): 232-238, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33964998

RESUMO

Liver fibrosis is the result of long-term liver injury and has a high incidence worldwide. Protocatechuic acid (PCA) is ubiquitous in vegetables, nuts, brown rice and herbal medicines, which is reported to possess anti-asthmatic, anti-cancer, and anti-oxidation properties. Our research aimed to investigate the effect of PCA on liver fibrosis. In vitro, TNF-α-induced hepatic stellate cell (HSC) model was used to assess the anti-fibrosis effects of PCA. In vivo, mice were treated with thioacetamide (TAA) to develop liver fibrosis. Body weight, organ index, histological changes, and proteins alteration of factors associated with TGF-ß signaling pathway were used to assess the anti-fibrosis effects of PCA. Our results showed that PCA not only inhibited cell viability in TNF-α activated HSC-T6 cells in vitro, but also efficiently mitigated TAA-induced liver damage and fibrosis in vivo. Further experiments indicated that PCA played a protective role in liver fibrosis through regulation of the TGF-ß signaling pathway downregulating the protein expression of p-Smad2, p-ERK, c-Jun. In summary, our findings provide a pharmacological justification for the clinical application of PCA in preventing or treating liver fibrosis.


Assuntos
Hidroxibenzoatos/farmacologia , Cirrose Hepática/tratamento farmacológico , Animais , Linhagem Celular , Células Estreladas do Fígado/efeitos dos fármacos , Inflamação/metabolismo , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Ratos , Transdução de Sinais/efeitos dos fármacos , Baço/efeitos dos fármacos , Tioacetamida/farmacologia , Transaminases/sangue , Transaminases/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
16.
RSC Adv ; 11(48): 30373-30376, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-35480294

RESUMO

Immobilized whole-cells of Pichia pastoris harboring recombinant d-lactonase were entrapped in calcium alginate gels and used as an efficient biocatalyst for catalytic kinetic resolution of d,l-pantolactone. The immobilized whole-cell biocatalyst exhibited good catalytic stability, which was applied for stereospecific hydrolysis of d-pantolactone for up to 56 repeated batch reactions without obvious loss in the catalytic activity and enantioselectivity.

17.
Matrix Biol ; 95: 1-14, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33065248

RESUMO

The tumor microenvironment encompasses a complex cellular network that includes cancer-associated fibroblasts, inflammatory cells, neo-vessels, and an extracellular matrix enriched in angiogenic growth factors. Decorin is one of the main components of the tumor stroma, but it is not expressed by cancer cells. Lack of this proteoglycan correlates with down-regulation of E-cadherin and induction of ß-catenin signaling. In this study, we investigated the role of a decorin-deficient tumor microenvironment in colon carcinoma progression and metastasis. We utilized an established model of colitis-associated cancer by administering Azoxymethane/Dextran sodium sulfate to adult wild-type and Dcn-/- mice. We discovered that after 12 weeks, all the animals developed intestinal tumors independently of their genotype. However, the number of intestinal neoplasms was significantly higher in the Dcn-/- microenvironment vis-à-vis wild-type mice. Mechanistically, we found that under unchallenged basal conditions, the intestinal epithelium of the Dcn-/- mice showed a significant increase in the protein levels of epithelial-mesenchymal transition associated factors including Snail, Slug, Twist, and MMP2. In comparison, in the colitis-associated cancer evoked in the Dcn-/- mice, we found that intercellular adhesion molecule 1 (ICAM-1) was also significantly increased, in parallel with epithelial-mesenchymal transition signaling pathway-related factors. Furthermore, a combined Celecoxib/decorin treatment revealed a promising therapeutic efficacy in treating human colorectal cancer cells, in decorin-deficient animals. Collectively, our results shed light on colorectal cancer progression and provide a protein-based therapy, i.e., treatment using recombinant decorin, to target the tumor microenvironment.


Assuntos
Caderinas/genética , Neoplasias do Colo/tratamento farmacológico , Decorina/genética , Proteoglicanas/genética , Animais , Azoximetano/toxicidade , Fibroblastos Associados a Câncer/efeitos dos fármacos , Fibroblastos Associados a Câncer/patologia , Celecoxib/toxicidade , Neoplasias Associadas a Colite/induzido quimicamente , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Decorina/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Humanos , Camundongos , Metástase Neoplásica , Microambiente Tumoral/efeitos dos fármacos , beta Catenina/genética
18.
J Ethnopharmacol ; 264: 113249, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32810619

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Triple-negative breast cancer (TNBC) has a poorer prognosis than other subtypes due to its strong invasion and higher risk of distant metastasis. Traditional Chinese medicine (TCM) and natural medicine have the unique advantages of multitargets and small side-effects and may be used as long-term complementary and alternative therapies. AIM OF THE REVIEW: The present article summarizes the classical signaling pathways and potential targets by the action of TCM and natural medicine (including extracts, active constituents and formulas) on TNBC and provides evidence for its clinical efficacy. METHODS: The literature information was acquired from the scientific databases PubMed, Web of Science and CNKI from January 2010 to June 2020, and it was designed to elucidate the internal mechanism and role of TCM and natural medicine in the treatment of TNBC. The search key words included "Triple negative breast cancer" or "triple negative breast carcinoma", "TNBC" and "traditional Chinese medicine" or "Chinese herbal medicine", "medicinal plant", "natural plant", and "herb". RESULTS: We described the antitumor activity of TCM and natural medicine in TNBC based on different signaling pathways. Plant medicine and herbal formulas regulated the related gene and protein expression via pathways such as PI3K/AKT/mTOR, MAPK and Wnt/ß-catenin, which inhibit the growth, proliferation, migration, invasion and metastasis of TNBC cells. CONCLUSION: The inhibitory effect of TCM and natural medicine on tumors was reflected in multiple levels and multiple pathways, providing reasonable evidence for new drug development. To make TCM and natural medicine widely and flexibly used in clinical practice, the efficacy, safety and mechanism of action need more in-depth experimental research.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Produtos Biológicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Medicina Tradicional Chinesa/métodos , Transdução de Sinais/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/metabolismo , Produtos Biológicos/metabolismo , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/tendências , Feminino , Humanos , Medicina Tradicional Chinesa/tendências , Transdução de Sinais/fisiologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo
19.
Clin Exp Nephrol ; 24(12): 1162-1176, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32779058

RESUMO

BACKGROUND: ESRD (End-stage renal disease) treatment is a comprehensive medical process and requires numerous serological biochemical tests (SBTs) in diagnosis. To reduce these invasive, expensive, cumbersome, and time-consuming SBTs, there is a need to develop an alternative serological biochemical composition evaluation method. Bioelectrical impedance analysis (BIA) is affected by body's chemical and physical components, which might be correlated with serological biochemical composition and can be potentially used to evaluate biochemical composition in hemodialysis patient treatments. In this work, the relationship of classic and specific bioelectrical impedance vector analysis (BIVA) with major serological biochemical indexes in maintenance hemodialysis (MHD) patients was examined. METHODS: Bioelectrical and biochemical datasets were measured from 280 women and 408 men and formed 3872 effective biochemical-bioelectrical records in total. Statistical analysis was performed. RESULTS: The results show that BIVA vectors have strong relationship with phosphorus, hemoglobin, and PTH in both male and female groups. Strong correlation was also observed between Ca, albumin, CHOL, LDLC, and BIVA vectors in the male group. In the female group, a significant correlation was observed between classic BIVA values and NT-proBNP. SVM models are effective for classifying biochemical indexes. CONCLUSIONS: The obtained correlations and SVM classification models imply that BIVA can be used as a preliminary tool to evaluate and classify the degree of anemia, malnutrition, fluid overload, and mineral and bone disorder (MBD) in MHD patients by reducing the number of SBTs.


Assuntos
Anemia/diagnóstico , Composição Corporal , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Desnutrição/diagnóstico , Estado Nutricional , Diálise Renal , Adulto , Idoso , Anemia/sangue , Anemia/fisiopatologia , Biomarcadores/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Estudos Transversais , Impedância Elétrica , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/fisiopatologia , Masculino , Desnutrição/sangue , Desnutrição/fisiopatologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Adulto Jovem
20.
Materials (Basel) ; 13(11)2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32516901

RESUMO

In order to better understand the damage tolerance of reinforced composite plates, the impact damage of the reinforced composite plates was investigated under low-velocity impact test. The experimental results show that the impact of different positions and energies causes different degrees of damage to the specimens, including but not limited to ply fracture, internal delamination of the skin, and debonding of the stiffeners and skin. After impacting, the specimens were tested in an axial compression. The results show that the ultimate bearing capacity of the specimen is also affected by different forms of impact. The impact point has the greatest influence on the specimen while it locates at the intersection of longitudinal and transverse bars. Compared with the intact specimen, the ultimate load carrying capacity was reduced by 16.83% and 44.02%, while the specimen impacted by 15 J and 30 J, respectively. The compression failure mode of the damaged specimen is mainly the breakage of the stiffeners and the delamination of the skin.

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